ISSN:0365-6217    

DOI:10.1039/AR95148FP001

出版商:RSC    

年代:1951

数据来源: RSC

摘要:

ERRATAVOL. 4'7, 1950.Page Line125 33 for (C,H,PtCl,), read (C2H,),PtC12.125 35 for Pt(Hal),ZAsR, read Pt(Hal),,ZAsR,.125 38 for r(C,H,),P,,PtC121, ?%ad r(C,H,),P,PtCI,I,.229 25 for Glocking read Glockling.Copyright reserved by the Chemical Society

ISSN:0365-6217    

DOI:10.1039/AR9514800006

出版商:RSC    

年代:1951

数据来源: RSC

摘要:

ANNUAL REPORTSON THEPROGRESS OF CHEMISTRY.GENERAL AND PHYSICAL CHEMISTRY.1. THE QUANTUM THEORY OF VALENCY.Introduction.-In the last few years increasing interest has been taken inthe application of quantum mechanics to chemistry. Most of the work inthis field has been concerned with one or other of the following problems :(a) the calculation of bond lengths, bond angles, heats of formation, anddipole moments of relatively simple molecules, ( b ) the interpretation of mole-cular spectra in terms of a scheme which will apply to large as well as to smallmolecules, and ( c ) the construction of theories which will explain howchemical rate constants and equilibrium constants are affected by structuralchanges in the species involved. Of the papers on quantum chemistrypublished in the last year or so, the greater number describe the applicationof standard methods to particular molecules or systems.To the organicchemist the most interesting work of this kind has been the application of themolecular-orbital theory to conjugated systems. The papers on this subjectcan be divided roughly into those concerned with the internal approxima-tions of the theory,l and those which apply it to particular types of re-action.2* 3* The former class of papers are chiefly of technical interest andraise no essentially fundamental questions in theoretical chemistry ; and theapplications of the theory, which promise to give us a semi-quantitativetheory of organic reaction^,^ are reviewed elsewhere in this volume.6 Thissection will therefore be devoted to recent progress in the more fundamentaltheory of chemical bonding.Work in theoretical spectroscopy, on whichan excellent review article has just a~peared,~ will only be referred toin so far as the excited states of molecules are relevant to their chemicalbehaviour .R. Daudel, C. Sandorfy, C. Vroelant, P. Yvan and 0. Chalvet, Bull. SOC. chim.,1950,17, 66; F. H. Burkitt, C. A. Coulson and H. C. Longuet-Higgins, Trans. FaradaySOC., 1951,47,553; J . de Hem, Phil. Mag., 1951,41, 370; M. G. Evans and J. de Hem,Trans. Paraday Soc., 1951, 47, 681, 801.a R. D. Brown, J., 1951,1612,1950,1955,2391,2670,3129.* B. Pullman et al., J . Chim. phys., 1951, 48, 356, 359.H. C. Longuet-Higgins, J . Chem. Phys., 1951,18,265,275,283.H. C.Longuet-Higginsand G. W. Wheland, Ann. ReviewsPhys. Chem., 1960,1,133.6 M. J. S. Dewar, this volume, p. 112. ' L. G. S. Brooker and W. T. Simpson, Ann. Reviews Phya. Okm., 1951.2, 1218 GENERAL AND PHYSICAL CHEMISTRY.In classifying theoretical work, it is convenient to distinguish between(i) the application of standard methods to new (or old) problems, (ii) theinvention of new theoretical ideas and methods, and (iii) purely mathematicalwork, without which it may be impossible to apply theory a t all. We willdiscuss (iii) first.Mathematical Work.-For many-electron systems the Schroedingerwave equation cannot be solved exactly, and it is always necessary toapproximate the wave function by some over-simplified function of theelectronic co-ordinates. I n order to assess the energy corresponding to suchan approximate wave function, one must take account not only of the kineticenergy of the electrons and their potential energy in the field of the nuclei,but also of their mutual repulsion energy, averaged over the various con-figurations according to their probability of occurrence.It is these electron-repulsion integrals which are always the most difficult to evaluate mathe-matically, and this is one reason why they have received so much attentionin the theoretical literature.The exact form which the integrals take depends, of course, on the typeof wave function which is used to describe the atomic or molecular system.As a rule the wave function is written as an anti-symmetric sum of terms, eachterm representing a situation in which each electron is assigned to a definiteatomic orbital on a particular atom.(This is true of the LCAO molecular-orbital method as well as of the Heitler-London or valence-bond method.)A detailed description of the types of integral which occur in such treatmentswould be out of place here; suffice it to say that in the last year or so im-portant new methods have been devised for evaluating them,g and an exten-sive programme of calculation has been started a t the University of Chicagointended to fill the more important gaps which still remain in the theoreticalliterature.10 The mathematical analysis is inevitably involved, and this hasled Mueller and Eyring l1 to discuss the possibility of replacing some of themore complicated integrals by weighted averages of simpler ones with promis-ing results.Adopting a slightly different approach, Boys l2 has suggestedthe use of atomic orbitals which are not of the conventional Slater type, butare derived from Gaussian functions by differentiation. He has applied theseideas successfully to the ground state of the beryllium atom, but it is uncer-tain a t present whether his procedure will converge sufficiently rapidly whenused for more complex systems, especially molecules. I n three recentpapers l3 he has developed some general theorems on the integrals of anti-symmetric wave functions, but his theory has not yet reached the point a twhich results of chemical interest can be derived.R.G. Parr and B. L. Crawford, J. Chem. Phys., 1948,16, 1049.* M. P. Barnett and C. A. Coulson, Phil. Trans., 1951, A, 243, 225, 234.10 C. C. J. Roothaan, Ann. Reports Spec. Lab. Uniu. Chicago, 1951, No. 2 ; K. Ruden-l1 C. R. Mueller and H. Eyring, J. Chem. Phys., 1951,19,934; see also K. Rudenberg,l2 S. F. Boys, Proc. Roy. SOC., 1950, A, 200,542; A , 201, 125.lS Idem, ibid., 1951, A , 206, 489; A , 207, 181, 197.berg, ibid., No. 3 .ibid., p. 1433LONGUET-HIGGINS : THE QUANTUM THEORY OF VALENCY. 9A rather different kind of paper is one by Carlson and Rushbrooke l4 onthe expansion of a Coulomb potential in spherical harmonics ; it seems likelythat the mathematical result which they establish will prove useful in thetheory of intermolecular forces.Current Theories of the Chemicd Bond.-Having disposed somewhatbriefly of the purely mathematical developments, we may now consider howfar present theories of valency have been able to guide our understanding ofbond properties in the last year or so.A most valuable source-book for recent work in this field is the report ofthe Royal Society Discussion on bond lengths and bond energies, held inMarch 1950.15 This discussion brought to the surface most of the out-standing problems of valence theory.One of these problems is the relationbetween the theoretical idea of ionic character, the semi-empirical concept ofelectronegativity, and experimental quantities such as bond-dissociationenergy and dipole moment. A paper by Warhurst l6 presents very clearlythe contrast between the logical dificulties and empirical successes of thetheory of ionic-covalent resonance. In another paper Cottrell and Sutton,17studying a simplified system of two electrons and two nuclei of equal or un-equal charge, come to the conclusion that there is no real contradictionbetween Pauling’s adjacent charge rule and Gordy’s empirical rule connectingelectronegativities and bond strength. They find that a transfer of positivecharge between initially equal nuclei leads to a decrease in the purely covalentpart of the binding energy, and that this is largely due to the decreased inter-nuclear repulsion, and unconnected with changing ionic character of the bond.This fact clarifies the basis of Pauling’s electronegativity scale, and lendssupport to Walsh’s views on polarity and bond strength.Cou1son,18 in acritical survey of the method of ionic-covalent resonance, discusses some ofthe theoretical difficulties in applying the method. It is dacult to assessthe energies to be associated with the covalent and ionic parts of the wavefunction, and the exchange integral between these two parts ; and if, as usual,the orbitals forming the bond are hybridised, both the atomic radius and theeffective electronegativity will be very sensitive to the degree of hybridisation.Calculations of dipole moment by the ionic-covalent method are especiallyuntrustworthy, because of the decisive role of unshared pairs; and theadditivity of bond properties is blurred by non-independence, partial de-localisation, and possibly also “ curvature ” of the bonds.Indeed “ themore closely we try to describe a molecule, the less clear-cut becomes ourdescription of the constituent bonds ! ” Coulson suggests that we need toclarify the relation between hybridisation and ionic resonance in order tounderstand the real origin of asymmetric charge distributions. Moffitt l9confirms the necessity of specifying the valence state before electronegativitiescan be defined theoretically.l4 B. C. Carlson and G. S. Rushbrooke, Proc. Camb. PhiE. Soc., 1951,46,626.l 5 Proc. Roy. SOC., 1951, A , 20’9, 1-136; Nature, 1950,165, 908.l6 E. W. Warhurst, Proc. Roy. Soc., 1951, A , 207,32.l7 T. L. Cottrell and L. E. Sutton, ibid., p. 49.la C.A. Coulson, ibid., p. 63. la W. E. Moffitt, ibid., p. 7410 UENERAL AND PHYSICAL CHEMISTRY.The second group of papers in the symposium is devoted to moleculescontaining mobile as well as localised electrons. Lennard-Jones 2O gives asurvey of the development of molecular-orbital theory, and shows that thesimple molecular-orbital theory of mobile electrons has given us a remarkablysuccessful interpretation of conjugated systems, both a t rest and in reaction.A paper by Longuet-Higgins 21 shows how the theory accounts for the effectof conjugation on heterolytic dissociation energies,. and brings out the factthat the topmost electron or electrons in a mobile shell play a speciallyimportant role in chemical reactions. Coulson 22 gives a survey of the theoryof unsaturated bond lengths.Recent accurate work by Robertson23 andothers on aromatic hydrocarbons has shown that " bond order " is a validconcept, but that there are limits to the accuracy with which it is possibleto predict bond lengths from calculated bond orders. It is possible to im-prove bond-length calculations somewhat by taking into account differencesin resonance integral and by allowing for configurational interaction (seebelow), but these refinements are laborious, and only alter the calculated bondlengths by about O-OOSA,. The present theory seems to be the best com-promise between accuracy and manageability, and is probably reliable toabout 0.02A.Various other papers which have appeared recently suggest that thestandard methods of studying electronic structure have now been stretchedto their limit, and that for further progress to be made some new ideas wil€be required. One difficulty which arises in molecular-orbital theory, forexample, and one which has been recognised by several independent workers,is that it is by no means correct to assign the electrons in a molecule to con-stant orbitals, even when due account is taken of the indistinguishabilityof the electrons. There seems to be substantial interaction between differentelectronic configurations of the same symmetry, and each electronic state isa mixture of different configurations in comparable proportions.The mostthorough investigations of this effect have been a study of ethylene by Parrand C r a w f ~ r d , ~ ~ of benzene by Parr, Craig, and of naphthalene byJacobs,26 of cyclobutadiene by and of butadiene by Coulson andJacobs.Z8 Walsh and Matsen 29 have made calculations on H,, and Taylor 30on H,.The general conclusions emerging from these studies, especiallyabout the upper electronic states, are depressing. It seems that within theframework of the method configurational interaction must be taken into20 (Sir) J. E. Lennard-Jones, Proc. Roy. SOC., 1951, A, 207, 75.21 H. C. Longuet-Higgins, ibid., p. 121.2 2 C. A. Coulson, ibid., p. 91 ; see also C. A. Coulson, R. Daudel and J. M. Robertson,24 R. G. Parr and B. L. Crawford, J . Chem. Phys., 1948,16,526.25 R. G. Pam, D. P. Craig, and I. G. Ross, ibid., 1950,18, 1651.26 J. Jacobs, Proc.Phys. SOC., 1949, A, 62, 710.2 7 D. P. Craig, Proc. Roy. SOC., 1950, A, 202,498.28 C. A. Coulson and J. Jacobg, ibid., 1951, A , 206, 287.2g A. D. Walsh and F. A. Matsen, J. Chem. Phys., 1951,19, 526.ibid., p. 396. 23 J. M. Robertson, Proc. Roy. SOC., 1951, A, 207, 101.R. Taylor, Proc. Phys. Soc., 1951, 44, 249LONGUET-HICQMS : THE QUANTUM THEORY OF VALENCY. 11account in order to secure even the correct sequence of energy levels. Themagnitude of the interaction is sensitive to the exact values of certain ‘‘ manycentre integrals ”, which at one time were hoped to be negligible. The extentof the interaction can be partly reduced by modifying the basic molecularorbitals, but it is not nearly eliminated ; and most unfortunately, there appearto be no simple rules for determining in advance which configurations willinteract most atrongly with one another.In the words of Coulson, Craig,and Jacobs :31 “ This is a melancholy position, suggesting very strongly thatprogress . . . must be looked for in some entirely new technique.” As yet,however, configurational interaction has not severely disturbed our theoryof the ground state, except in hypothetical molecules such as cyclobutadieneand other ‘‘ pseudoaromatic ” compounds.32New Contributions tovalence Theory.-Although there are difficulties whenthe method of molecular orbitals is applied to the excited states of molecules,for reasons outlined in the last paragraph, its relative success in describingthe ground state has led various authors to try to recast the theory in amathematically more precise form, in the hope of obtaining a better under-standing of saturated as well as unsaturated systems.An apparent weaknessof the molecular-orbital theory is that, as each electron is regarded as movingover the whole molecule, it is difficult to obtain from the theory the rules ofstereochemistry, or to understand the remarkable constancy of bond pro-perties in a series such as the paraffin hydrocarbons. Lennard-Jones, Hall,and Pople, in an impressive series of papers published over the last few yearsF3have attempted to supply this deficiency of the theory, and in doing so havedrawn attention to some important principles in stereochemistry. Theirfundamental assumption (in common with Roothaan 36) is that the electronsof a molecule, at least in its ground state, can be adequately described by ananti-symmetrised product of one-electron wave functions-in other words,that the electrons move more or less independently, subject to the Pauliexclusion principle.Now an anti-symmetrised product of molecular orbitalsmay be written in the form of a determinant; and determinants have theproperty of being unchanged in value if their rows or columns are subjectedto an orthogonal transformation. This abstract mathematical fact has thefollowing implication, which has been known for many years but neverdeveloped in much detail; if, on the one hand, we describe the methanemolecule (say) by asserting that there are two electrons in each molecularorbital (one symmetric and three degenerate), and if, on the other hand, weprefer to say that there are two electrons in each of four equivalent orbitalscompounded out of the four non-localised ones, then these two descriptionsare physically identical, as they correspond exactly to the same total wavefunction.However, in the former description the electron-repulsion energy(which must have the same total value in both descriptions) appears partly31 C. A. Coulson, D. P. Craig and J. Jacobs, Proc. Roy. Soc., 1951, A, 208, 297.3a D. P. Craig, J., 1951, 3175.33 (Sir) J. E. Lennard-Jones, G. G. Hall and J. A. Pople, Proc. Roy. Soc., 1949, A ,198,1, 14; 1960, A , 202,166,166,323,336; 1961, A , 205,357,541 ; A , 210,19012 GENERAL AND PHYSICAL CHEMISTRY.as coulombic repulsion energy and partly as exchange energy between themolecular orbitals, whereas in the latter description it appears almost entirelyas coulombic repulsion energy between the equivalent orbitals.Lennard-Jones, Hall, and Pople conclude that a more intuitively satisfactory descrip-tion of the ground state is given by the equivalent orbital formulation, andthis description leads more naturally to the approximate constancy of bondproperties in homologous series. Their argument stresses the importanceof interelectronic repulsions in determining valency angles, and the role ofunshared pairs in maintaining stereochemical configurations, a role whichwas recognised by Sidgwick and Powell 34 some years ago in a heuristic surveyof the experimental evidence.The electronic structure of the diboranemolecule 35 and similar systems has also been satisfactorily interpreted interms of equivalent (three-centre) orbitals, and even double and triple bondsmay for certain purposes be adequately regarded as consisting of two or threeequivalent ‘‘ bent ” bonds.Another, independent, development of what may be called the “self-consistent molecular-orbital theory ” is due to R ~ o t h a a n . ~ ~ He obtains thesame set of equations as Lennard-Jones for the best wave function of thedeterminantal type (these equations are identical with the Hartree-Fockequations for atoms), but pays particular attention to the problem of obtain-ing the component molecular orbitals in LCAO form; that is, he sets out tofind the best ones that can be constructed out of a given set of atomic orbitals.Mathematically his theory is very elegant, but in view of Coulson and Jacobs’swork 28 there are doubts whether it goes far enough ; even if the best mole-cular orbitals are used configurational interaction cannot be ignored, and ifthis is to be taken into account one might as well begin from the simpler“ inconsistent ” orbitals-the final result must be the same.3’ Nevertheless,the self-consistent molecular-orbital method has been applied with encourag-ing results to some unsaturated systems : to cis- and trans-butadiene byParr and M~lliken,~~ who obtain good values for the lower excitation energiesand ionisation potentials and find the trans-form to be 0-12 ev more stablethan the cis-isomer ; to carbon dioxide by M~lligan,3~ who calculates the firsttwo ionisation potentials, but confines his calculations to a single internucleardistance ; and to allene by Parr and Taylor,40 who calculate the ground-stateenergy as a function of twist, and conclude that the ethylene-allene twistingfrequency ratio should be rather greater than d2, in disagreement with themost recent experimental assignments.A rather different approach to the theory of chemical bonding is beingadopted by Mulliken41 and by Macc011.~~ These authors suppose, with34 N. V.Sidgwick and H. M. Powell, Proc. Roy. SOC., 1940, A , 176, 153.s5 H. C. Longuet-Higgins, J. Chim. phys., 1949, 46, 275.36 C. C. Roothaan, Rev.Mod. Physics, 1951, 23, 69.37 H. C. Longuet-Higgins, Proc. Phys. Soc., 1948, A , 60, 270.38 R. G. Parr and C. A. Mulliken, J . Chem. Phys., 1950, 18, 1338.3s J. F. Mulligan, ibid., 1951,19,347,1428.41 R. S. Mulliken, J. Amer. Chem. SOC., 1950, 72,4493.42 A. Maccoll, Trans. Faraday Soc., 1950, 46, 369.40 R. G . Parr and R. Taylor, ibid., p. 497LONQUET-HIGBINS : THE QUANTVM THEORY OF VALENCY. 13P a ~ l i n g , ~ ~ that “ of two orbitals in an atom the one that can overlap more withan orbital of another atom will form the stronger bond ”, but instead oftaking the angle-dependent factor of the orbital as a measure of its bond-forming power they prefer, reasonably enough, the overlap integral betweentwo orbitals as a measure of the strength of the bond between them.Thiscorrelation between bond strength and overlap integral does not, of course,follow rigorously from the wave equation; but Mulliken works out the con-sequences of the hypothesis, using already tabulated values of resonanceThedifference between first- and second-row atoms in their readiness to formmultiple bonds may be attributed to the greater “ strength ” of sigma bondsin the second row; the relative shortness of polar bonds can ,be correlatedwith a theoretical “ polarity index ”, in harmony with the work of Schomakerand Stevenson ; 45 and intermolecular energies may be understood semi-quantitatively in terms of overlap integrals. In a more recent paper46Mulliken extends the theory to s-p hybrid orbitals, and shows that in assistingbond formation ‘ I a little hybridisation goes a long way ”.In thefirst 47 he classifies the different types of hybridisation which occur in thefirst short period, calculates the term values of these hybridised “ valencestates ”, and applies the results to carbon, nitrogen, and oxygen.I n thesecond paper 48 he shows how the electronegativities of these atoms dependon their state of hybridisation, and clarifies the concept of ‘‘ lone-pair ”electrons. He also discusses the effect of hybridisation on the dipole momentsand quadrupole coupling constants of molecules. The recent accumulationof data on quadrupole constants 49 should soon make it possible to check theseideas quantitatively.Other papers on a rather smaller scale include one on directed valency inthe first short period,50 in which the authors associate the relative directionsof the bonds with the most probable configuration of the valency electronsin the isolated atom (as determin%d from an antisymmetrised wave functionfor the atomic state of maximum multiplicity).This idea, though intuitive,is highly suggestive, and a rather similar discussion of directed valence hasbeen given by Lesnik 51 in Russia. It seems to be more helpful than thesomewhat arbitrary construction of orthogonal hybrids from s, p , d, . . .atomic orbitals, a process which leads to too many po~sibilities.~~ Theand succeeds in interpreting several experimental facts.On the subject of hybridisation, Moffitt has published two papers.43 L.S. Pauling, “ Nature of the Chemical Bond,” p. 76, Cornell, 1940.4 4 R. S. Mulliken, C. A. Rieke, D. Orloff and H. Orloff, J . Chem. Phys., 1949,17, 1248.4 5 V. Schomaker and D. P. Stevenson, J. Amer. Chem. Soc., 1941,63, 97.4 6 R. S. Mulliken, J . Chem. Phys., 1951,19, 900, 912.4 7 W. E. Moffitt, Proc. Roy. SOC., 1950, A , 202, 534.4 8 Idem, ibid., p. 548.61 A. G. Lesnik, J . Phys. Chem., U.S.S.R., 1949, 22, 541. The Reviewer is indebted6z G. H. Duffey, J . Chem. Phys., 1949, 17, 196, 1328; 1950, 18, 128, 510, 746, 943,4g W. Gordy, J . Chem. Phys., 1951,19,792.J. W. Linnett and A. J. Po6, Trans. Furuday SOC., 1951,47,1033.to Dr. Harrison Shull for a translation of this paper.1444; 1951,19, 92, 553, 96314 GENERAL AND PHYSICAL CHEMISTRY.hydrogen molecule has had a good deal of attention : Frost and Braunstein 53have tried their method of “ correlated molecu1a.r orbitals ” on it, but arepessimistic about the possibility of using the method for more complex mole-cules; Lewinson and Kimball 54 have studied H, by the Wigner-Seitz cellmethod, obtaining binding energies considerably greater than the observedvalue ; and Hoare and Linnett,55 using a 4-parameter variation function dueto Hirschfelder and Linnett, 56 have discussed the relative importance ofpotential and kinetic energy changes in the process of bond formation.I n apaper on the interaction between the two electrons of an electron-pair bond,Lennard- Jones and Pople 57 recommend the inclusion in the wave function ofterms possessing lower geometrical symmetry than the ordinary molecular-orbital function.By using Hirschfelder and Linnett’s 56 calculations on thehydrogen molecule they find that allowance for the tendency of the electronsto be at opposite ends of the bond lowers the estimated bond energy by about20%, but that allowance for their being on opposite sides of the internuclearaxis makes a difference of only about 4%. The hydrogen molecule-ion hasbeen investigated by Pritchard and Skinner 58 in terms of hybridised hydro-gen-atom eigenfunctions. They find that the ground-state energy is accur-ately given by a 1s-2p hybrid function, but the derived bond length and forceconstant are less accurate. For excited states of similar bonding the forceconstants and internuclear distances appear to be related approximately byBadger’s rule.A recent, original attempt to break away from traditional techniques hasbeen made by Berlin 59 in a paper on “Binding regions in diatomic molecules”.He re-establishes a result due to Hellmann 6o and FeynmanY61 later criticisedby Coulson and Itcan be demonstrated rigorously from the Schroedinger equation and theBorn-Oppenheimer approximation that the net electrostatic force on anynucleus due to all the other nuclei is equal and opposite to the force exertedby the electron cloud regarded as a rigid, classical, charge distribution.Thismakes it possible to divide the space around the nuclei into binding and anti-binding regions defined completely by the relative charges on the nuclei.Applications of this idea are promised in later papers.Platt 63 has alreadymade use of much the same notion in predicting interatomic distances andforce constants in the diatomic hydrides. The only, though rather drastic,assumption that he needs in order to obtain good agreement with experimentabout the forces acting on a nucleus in a molecule.53 A. A. Frost and J. Braunstein, J . Chem. Phys., 1951,19, 1133.54 V. A. Lewinson and G. E. Kimball, ibid., p. 690.5 5 M. F. Hoare and J. W. Linnett, Trans. Paruday SOC., 1950,46, 885.5 6 J. 0. Hirschfelder and J. W. Linnett, J . Chem. Phys., 1950, 18, 130.5 7 (Sir) J. E. Lennard-Jones and J. A. Pople, Proc. Roy. Soc., 1951, A , 210, 190.5 8 H. 0. Pritchard and H. A. Skinner, J., 1951, 945.59 T.Berlin, J . Chem. Phys., 1951, 19, 208.60 H. Hellmann, “ Quantenchemie,” p. 285, Leipzig, 1937.61 R. P. Feynman, Phys. Review, 1939, 56,340.62 C. A. Coulson and R. P. Bell, Trans. Fu~uduy SOC., 1945,41, 141.63 J. R. Platt, J . Chem. Phys., 1950, 18, 932LONQUET-HIGUMS : THE QUANTUM THEORY OF VALENCY. 15is that the electronic charge distribution is the same in the hydride as in theunited atom. St present the success of this approximation is as mysteriousa B it is gratifying.Perhaps the most promising work on molecular energy levels which hasappeared lately, and which seems to offer the best hope of an improved quan-titative theory, is that of Moffitt 64 on interatomic forces in general, and theoxygen molecule in particular. Moffitt begins by recognising the logicalnecessity of introducing configurational interaction into the usual method ofanti-symmetrised molecular orbitals, when it is applied to many-electronsystems ; but, as he points out, this refinement, while destroying many of themost satisfactory qualitative features of the theory, does not give a sufficientimprovement in the quantitative results, as judged against experiment.Ina careful and detailed study of the oxygen molecule, for which accurate dataare available on no fewer than five spectroscopic states, he finds that even therefined theory gives very bad results ; and he associates this theoretical fail-ure with the inability of the theory to give a correct account of the energylevels of the monatomic systems 0, 0+, and 0-.It is not surprising that atheory which is inadequate for interpreting atomic spectra should fail in pre-dicting energy levels; and he suggests that the proper function of a theoryof molecular states is not to predict their energies from first principles, but toassess that part of the energy which is due to interaction between the atoms.For the former task the atomic-orbital theory is quite inadequate, but it islikely to be much better suited to the latter type of calculation. This isbecause the atomisation energy of a molecule is only a small fraction, some-times a very small fraction, of the energy required to dissociate it into nucleiand electrons, so that an atom retains much of its characteristic electronicstructure, so to speak, even when i t is in chemical combination.Guided bythis idea, Moffitt succeeds in accounting almost quantitatively for the posi-tions of the low-lying states of the oxygen molecule, by the simple device ofarranging that when the atoms are infinitely separated the energy shallamume its spectroscopically determined value for two oxygen atoms. Theperformance of the theory is thereby improved out of all recognition, and it isfound, incidentally, that configurational interaction plays a relatively insigni-ficant role. There is hope that the same method will be applicable to morecomplex molecules; but it will have to be checked against other simplesystems first.Other Work.-There have been many applications of quanta1 methods tospecific chemical problems in the last year.Mention should be made of twointeresting papers by Mulliken on molecular complex formation. I n thefirst 6s he gives a quantum-mechanical interpretation of the binding forcesand absorption spectra of the complexes formed between the halogens andaromatic or oxygen-containing solvents. He gives grounds for supposingthat in the aromatic complexes the halogen molecule lies on top of the aro-matic ring, whereas in the ether complexes, for example, the halogen atoms64 W. E. Moffitt, Proc. Roy. SOC., 1951, A , 210,245.6 5 R. 5. Mulliken, J. Amer. Chem. SOC., 1960, 72, 60016 GENERAL AND PHYSICAL CHEMISTRY.are both attached by rather stronger forces to the oxygen atom. The absorp-tion band of the benzene complex near 3000 A is considered to be essentiallythe same as the forbidden 2600-A absorption in benzene itself, but madeallowed by the close presence of the iodine molecule, which destroys thehexagonal symmetry.It is also possible, however, that this band representsan intermolecular charge-transfer spectrum, due t o the transfer of an electronfrom the benzene to the halogen. In his second paper 66 Mulliken outlinesfurther the theory of such charge-transfer spectra, and suggests why theyfrequently occur in complexes between electron-donor and electron-acceptormolecules.Pople, 67 applying quantitatively some ideas of Lennard- Jones andPople,6* has given a new theoretical description of the structure of water, andhas derived the radial distribution function from the assumption tha't, thehydrogen bonds are bent before they are broken.He interprets quanti-tatively the discontinuity in density at the freezing point, and the observeddielectric constant curve for water.Longuet-Higgins, Rector, and Platt 69 have.attempted an interpretation ofthe electronic structure of the porphyrin nucleus. They find that there is apiling up of electrons on the nitrogen atoms for purely geometrical reasons,and connect this with the great stability of the system. They also give ittentative interpretation of the electronic spectra of porphyrins.Everard and S ~ t t o n , ~ ~ in a series of papers on polarisation in conjugatedsystems, review theories of interaction between unsaturated hydrocarbonresidues and substituent groups, and conclude that in addition to the short-range classical inductive effect there is also a long-range component whichmust have a non-classical origin.The theory is, however, not yet a quantita-tive one.S i m p ~ o n , ~ ~ in a discussion of the polyenes, suggests that a large fraction ofthe conjugation energy in butadiene is due to internal dispersion forces be-tween the easily polarised double bonds. It is not clear whether this inter-pretation is fundamentally different from the delocalisation theory of con-jugation, or not.H. C. L.-H.2. MOLECULAR STRUCTURE.Electronic Spectra.-A Discussion on Spectroscopy and MolecularStructure was held by the Faraday Society in September, 1950, and has nowbeen published. An excellent survey of fundamental research in molecular66 R.S. Mulliken, J . Chem. Phys., 1951,19, 514.67 J. A. Pople, Proc. Roy. SOC., 1951, A , 205, 163.6g H. C. Longuet-Higgins, C. W. Rector, and J. R. Platt, J . Chem.Phys., 1950,18,1174.70 K. B. Everard and L. E. Sutton, J., 1951, 2816, 2817, 2818, 2821, 2826.71 W. T. Simpson, J . Amer. Chem. SOC., 1951, 73, 5363.(Sir) J. E. Lennard-Jones and J. A. Pople, ibid., p. 155MCDOWELL : MOLECULAR STRUCTURE. 17spectra was given by Pearse a t the Joint Commission for SpectroscopySymposium held a t Cambridge in September, 1950, and this has now beenpublished together with the other papers read a t this meeting.lConsiderable interest has been shown recently in the pro-duction of diffraction gratings in England.Merton has discussed methodsof ruling gratings and new methods of copying a plane grating have beendescribed in detail.3 Two interesting papers describe methods for studyingultra-violet spectra at very low temperatures?, Naish has described aphotomultiplier attachment for use with prism spectrographs.The predissociation in the upper state of the Lyman-Birge-Hopefield band of nitrogen has been investigated under high resolu-tion.' This observation is thought to eliminate the value of 8.565 ev for thedissociation energy of the nitrogen molecule but does not allow a decisionbetween the values of 7.373 and 9.756 ev. The mechanism of excitation ofthe C311u state of nitrogen has been discussed by Nicholls.* Very accuratevalues for the molecular constants of the ground state of the iodine moleculehave been obtained by Rank and B a l d ~ i n , ~ who have measured the green-line resonance series with high precision.A new band system of the iodinemolecule has been observed in the region 2785-2750 A.l0 New studies onthe spectra of K,ll and S212 have also been reported, and an emission bandof Cd, has been found at 2212 A.13A band system which had previously l4 been assigned to the CH moleculehas been shown l5 to be due to HgH+. Two new sequences of the system311 - 3X of the NH molecule have been observed in the explosive decom-position of hydrazoic acid.16 Schuler l7 has continued his studies of thetransition probabilities of the OH(2C+) molecule, and Gaydon and Wolfhard l*have observed a weak predissociation in OH bands from discharge tubes andfrom the reaction zone of an oxy-acetylene flame a t low pressure, and also tosome extent in the flame at atmospheric pressure.Studies of the absorption spectra of gaseous hydrogen fluoride haveTechnique.Diatomic molecules.1 R.W. B. Pearse, J. Opt. SOC. Amer., 1951,41,148.a (Sir) Thomas Merton, Proc. Roy. SOC., 1950, A , 201, 187.3 G. D. Dew and L. A. Sayce, ibid., 1951, A, 207, 278.4 R. N. Beale and E. M. F. Roe, J. Sci. Instr., 1951, 28, 109.5 R. L. Sinsheimer, A. F. Scott, and J. R. Loofbourow, J . Biol. Chem., 1950,187,299.6 J. M. Naish, J. Sci. Instr., 1951, 28, 138.7 A. E. Douglas and G. Herzberg, Canadian J. Phys., 1951, 29, 294.8 R. W. Nicholls, Nature, 1951,167, 31.9 D.H. Rank and W. M. Baldwin, J. Chem. Phys., 1951,19, 1210.10 P. Venkateswarlu, Phys. Review, 1951, 81, 821.l1 S. P. Sinha, PTOC. Phys. SOC., 1950,63, A , 952.l2 S. M. Naud6 and H. Vergleger, 2. Physik, 1950, 128, 173.13 W. R. S. Garton, Proc. Phys. SOC., 1951,64, A , 430.l4 M. W. Feast, ibid., p. 592.l6 F. C. McDonald, Phys. Review, 1927, 29, 212.l6 G. Pennetier, Compt. rend., 1951, 282, 817.l7 K. E. Schuler, J. Chem. Phys., 1951,19, 858; 1950,18,1466.la A. G. Gaydon and H. G. Wolfhard, Proc. Roy. SOC., 1951, A , 208, 6318 GENERAL AND PHYSICAL CHEMISTRY.shown that there is continuous absorption below 1650 A.19 Andrews andBarrow 2o have reported further work on the two bands attributed to the CFmolecule, one occurring at 2240 A and the other in the region 1970-2200 A.Two interesting papers 21y22 have appeared on the spectra of XF molecules,where X is C1, Br, or I.Schumacher, Schmitz, and Brodersen 21 have studiedCIF and have found that the limit of convergence of the excited state is21 512 & 5 cm.-l. A predissociation is evident a t 21 257 cm.-l and this isassumed to indicate C1(2P,,2) and F(2P,12) as the dissociation products. Thedissociation energy of the molecule into unexcited atoms is given as 2.62 evor 60.2 kcal./mole. Durie’s 22 work on the emission spectra of IIF and BrFshows that these spectra, which occur in the visible region, probably arisefrom a 3110+ -+ lC transition. Birge-Sponer extrapolations for the upperstates of these molecules lead to two dissociation energies depending onwhether the molecules dissociate to give a normal F atom and an excitedBr or I atom or vice versa.A consideration of the available information leadsto the view that the 3110+ state must dissociate to give an excited Br(2P,,2)or I(zPl/2) atom and a normal F(2P,12) atom. This is contrary to the modeof dissociation assumed by Schumacher, Schmitz, and Brodersen. It shouldbe noted, however, that in the case of CIF, if it is assumed that the dissoci-ation process is ClF(311,+) = C1(2P,,2) + F(’P3/2), this leads to a value ofD(C1F) = 2.557 ev, so that until further accurate data are available it isdifficult to decide between these two processes. It may be noted here thatthe value of D,(ClF) = 60.2 kcal./mole leads to a value of D,(F,) = 33.3 -&1 kcal./moleZ3 which is in good agreement with the recently determinedexperimental value of 37.7 k~al./mole,~~ and the estimates by Evans, War-hurst, and Whittle.25Migeotte and Rosen 26record spectra in the region 2000-4000 A ; Feast 27 has photographed thespectra between 2000 and 13000 A a t low dispersion and under high dis-persion, and Tanaka, Seya, and MoriZ8 have found new absorption bandsin the extreme ultra-violet region from 1380 t o 1650 A.Porter 29 has applied the method of flash photolysis 30 to the study of thespectra of CIO, SH, and SD, and has estimated values for the dissociationenergies of these radicals.Other diatomic molecules of interest which have19 J. Romand and E. Safary, Compt. rend., 1950, 231, 1050; E.Safary, J. Romand,and B. Vodar, J . Chem. Phys., 1951,19, 379.20 E. B. Andrews and R. F. Barrow, Proc. Phys. SOC., 1951,64, A , 481.21 H. J. Schumacher, H. Schmitz, and P. H. Brodersen, Anal. Asoc. Quim. Argentina,2a R. A. Durie, Proc. Roy. SOC., 1951, A , 207, 388.23 H. J. Schumacher, Anal. Asoc. Quim. Argentina, 1950, 38, 113.24 R. N. Doescher, J . Chern. Phys., 1951,19, 1070.2 5 M. G. Evans, E. Warhurst, and E. Whittle, J., 1950, 1524.26 P. Migeotte and B. Rosen; Bull. SOC. roy. sci., Liege, 1950, 19, 343.27 M. W. Feast, Canadian J . Res., 1950, 28, A , 408.28 Y. Tanaka, M. Seya, and K. Mori, J . Chem. Phys., 1951,19,979.20 G. Porter, Discuss. Faraday SOC., 1950, 9, 60.Several workers have studied the NO molecule.1950, 38, 93.Idem, Proc. Roy.SOC., 1950, A, 200, 284MCDOWELL : MOLECULAR STRUCTURE. 19been studied are BS,31 GaF:2 InF,33 SiF,34 HgIn,35 ZnBr,36 A1Br,37 AlCl,38and GaBr.39Further investigation 40 of the ultra-violet absorp-tion spectrum of the gaseous system NO-NO,-H,O, previously studied byMelvin and Wulf and by Newitt and Outridge, seems to prove the existenceof gaseous HNO,. A study of the NO-NO,-D,O system has enabled Porter 41to confirm that the band system between 3100 and 3900 A is due to the HNO,molecule. Porter has detected the expected isotope shift and has given apartial interpretation of the band structure. This proof of the existence ofgaseous HNO, is most interesting in view of the recent postulates that thismolecule is produced in reactions of NO, with NO and H20F2 and with acet-aldeh~de.4~A vibrational analysis of the hydrocarbon-flame bands has been given byMurphy and S ~ h o e n , ~ ~ and Vaidya 45 has detected the isotope effect in thesebands in the spectra of the flame from the reaction of deuterioacetylene withatomic oxygen.This shows that hydrogen is present in the emitter andsupports identification of the latter as HCO ; 46 the spectrum of this radicalhas been found in the emission from a discharge through f0rmaldehyde.4~The analysis of the fluorescence spectrum of HCHO and DCDO has been dis-cussed by Brand.48 Schuler and Reinebeck 49 have found several new bandsin the glow discharge of benzene vapour which they attribute t o radicals. Atpressures above 2 mm.they observe a continuum a t 3 4 0 0 4 4 0 0 . ~ with amaximum intensity at about 3700 A which they suggest might be due toa triplet-singlet transition. It will be recalled that the benzene phosphor-escence band at 3400 ,& has been identified as a triplet-singlet band 50 andassigned as a lAi, - 8B,, t r a n ~ i t i o n . ~ ~Near-ultra-violet spectra of a number of compounds in the liquid and thevapour state have been reported during the past year. Saksena and Kagar-31 P. B. Zeeman, Canadian J. Phys., 1951,29,336.32 D. Wetti and R. F. Barrow, Nature, 1951,168, 161.34 W. H. Dove11 and R. F. Barrow, Proc. Phys. SOC., 1951,64, A, 98.35 R. L. Penbrick, Phys. Review, 1951, 81, 89.36 C. Ramasastry and K. Sreeramamurty, Proc. Nut.Inst. Sci. India, 1950, 16, 307.37 D. Sharma, Astrophysical J., 1951, 113, 219.38 Idem, ibid., p. 210.3g E. B. Andrews and R. F. Barrow, Proc. Phys. SOC., 1950,63, A, 957.40 P. Tarte, Bull. SOC. chim. Belg., 1950, 59, 365.41 G. Porter, J. Chem. Phys., 1951,19, 1278.4 2 L. G. Wayne and D. M. Yoat, ibid., p. 41.43 C. A. McDowell and J. Thomas, Trans. Paraday SOC., 1950,46, 1030.4 4 G. M. Murphy and L. Schoen, J. Chem. Phys., 1951,19,1214.4 6 W. M. Vaidya, Proc. Phys. SOC., 1951,64, A , 428.46 P. J. Dyne and D. W. G. Style, Discuss. Paraday Sac., 1947,2,159.4 7 H. Schuler and L. Reinebeck, 2. Nuturforsch., 1950, 5, 604.4 8 J. C. D. Brand, J. Chem. Phys., 1951,19, 377.49 H. Schuler and L. Reinebeck, 2. Naturforsch., 1951, 6, A , 160.6o G.N. Lewis and M. Kasha, J. Amer. Chem. SOC., 1944,66,2100; 1945,6'4, 997.61 H. Schull, J. Chem. Phys., 1949,17, 295 ; D. S. McCIure, J . Chem. Phys., 1949,17,Polyutomic molecules.a3 Idem,ibid.665, 90520 GENERAL AND PHYSICAL CHEMISTRY.ise 52 have examined oxalyl chloride. The influence of temperature on theabsorption spectra of benzene and diphenyl has been studied by Almamyand Laemmel.53 Other compounds studied include ben~aldehyde,~~ chloro-phenol,55 benzotrifluoride, m- and p-fluorobenzotrifluoride, and o-, m-, andp - flu or ot oluene .In last year’s Report wementioned that an accurate method of measuring intensities in the vacuumultra-violet region was urgently required. It is pleasing, therefore, to beable to report that during this year several workers have suggested promisingmethods.Johnson, Watanabe, and Tonsey 57 have described a methodwhich uses an IP21 photomultiplier to measure the fluorescence of varioussubstances. Sodium salicylateis probably the most useful substance studied, for the quantum efficiency ofits fluorescence is approximately independent of wave-length over the range900-2300 8. A rather different approach to the solution of this problemhas been made by Packer and Lock 58 who have used a thermocouple tomeasure spectral intensity in the region 900-26OOA. They find that athermocouple with a sensitivity of 1.6 p.v/pw is adequate for the recordingof most spectra a t a band width of 14 A.Other technical developments in the vacuum ultra-violet region whichmight be noted are the monochromator described by Tonsey, Johnson,Richardson, and T ~ r a n , ~ ~ and the use of compressed argon as a solvent in theSchumann region.60The absorption spectrum of sulphur hexafluor-ide has been investigatedby Nui, Moe, and Duncan 61 down to 600 d.They have been unable todetermine the ionization potential of this compound because the SP6+ ion isunstable and the first ionization observed is that due to the process SP, --+SF,+ + 2e. This is in agreement with electron-impact studies.62 Teeganand Walsh 63 have examined the absorption spectrum of 1 : l-dichloroethyl-ene in the region 2100-1100 A and find evidence of two types of transitions :( a ) transitions of an electron initially present in the x-orbital of the C=Cbond, and ( b ) transitions of an electron initially present in an orbital largelylocalized around one of the chlorine atoms.A Rydberg series is foundamongst the (a) transitions which leads to an ionization potential of 9.46ev, whilst the ( b ) transitions appear to converge to a limit which yields aAbsorption spectra in the vacuum ultra-violet.This is satisfactory down to a t least 850 A.f e52 B. D. Saksena and R. E. Kagarise, J . Chem. Phys., 1951,19,999.53 F. Almamy and H. Laemmel, Helv. Chim. Aota, 1950,33,2092; 1951,34,462.54 S. Imanishi, J . Chem. Phys., 1951, 19, 389.65 C. Ramasastry, Current Sci., 1951, 20, 65.5 6 W. T. Cave and H. W. Thompson, Discuss. Furaduy Xoc., 1950, 9, 35.5 7 F. S. Johnson, K. Watanabe, and R. Tonsey, J . Opt.SOC. Arner., 1951,41, 702.58 D. M. Packer and C. Lock, ibid., p. 699.50 R. Tonsey, F. S. Johnson, J. Richardson, and N. Toran, ibid., p. 698.6o S. Robin, J. Romand, and B. Oksengorn, Compt. rend., 1950,231, 689.61 T. Y. Nui, G. Moe, and A. B. F. Duncan, J . Chem. Phys., 1951,19, 71.82 V. H. Dibeler and F. L. Mohler, J . Res. N.ut. Bur. Stand., 1948, 40, 25.63 J. P. Teegan and A. D. Walsh, Tram. Furuduy Soc., 1951,47, 1MCDOWELL : MOLECULAR STRUCTURE. 21value of 10.4 ev for the ionization potential. The far ultra-violet spectrumof keten has been found to resemble that of ethylene in the region 1830-1300 8; Rydberg series are found which lead to an ionization potential of9.60 ev which is thought to relate to the removal of an electron from thex-orbital of the CO group.Recently Parr and Taylor 65 have given a, verycomplete molecular-orbital treatment of the allene molecule and have com-puted the ionization potential to be 10.4 ev. Sutcliffe and Walsh 66 havereported that they have investigated the absorption spectrum of this com-pound in the far ultra-violet and have observed two Rydberg series whichconverge to practically the same limit at 10.19 ev. The agreement betweenParr and Taylor's theoretical value and this experimental value is mostsatisfactory. Vacuum ultra-violet spectra and ionization-potential datahave been published 67 for benzene, toluene, ethylbenzene, isopropylbenzene,o-, m-, and p-xylenes, phenol, fluorobenzene, benzotrifluoride, o-, m-, andp-fluorotoluene, m-fluorobenzotrifluoride, naphthalene, and 2-methyl-naphthalene.Kasha 68 has given an interesting sum-mary of the results obtained from a study of the emission spectra of complexmolecules.The spectra of unsaturated systems have been used to classify 69molecules as isoconjugate, i.e. molecules with the same number and geo-metrical arrangement of x-electrons, and uariconjugate sequences which areseries of unsaturated molecules in which the binding of some of the x-electronsand the appearance of the spectra slowly change. Platt 70 has introducedthe concept of" spectroscopic moment " as a measure of the added intensityproduced in a molecule by substitution. An interesting application 71 ofthis is its suggested use to determine experimentally whether in a moleculewith a centre of symmetry certain ambiguously assigned transitions areg+gorg+u.Two important papers have appeared on the experimental detection offorbidden triplet-singlet transitions in pyridine 72 and naphthalene, anthra-cene, and phenanthrene.73Raman Spectra.-Interest in the study of Raman spectra at low tempera-tures continues and recently two cryostats 749 75 have been described.Per-haps one of the most interesting of recent developments in the technique ofRaman spectroscopy has been the introduction by Welsh, Cummings, andStansburg 76 of a multiple-reflection tube for use with gases. The efficiencySpectra of aromatic compounds.64 W. C. Price, J. P. Teegan, and A. D. Walsh, J., 1951, 920.6 s R. G. Pam and G.R. Taylor, J. Chem. Phys., 1951,19,497.6 6 L. H. Sutcliffe and A. D. Walsh, ibid., p. 1210.6 7 V. J. Hammond, W. J. Price, J. P. Teegan, and A. D. Walsh, Discuss. FarudaySOC., 1950, 9, 53. M. Kasha, ibid., p. 14.Idem, ibid., p. 1418.J . R. Platt, J. Chem. Phys., 1951, 19, 101.'O Idem, ibid., p. 263.72 C. Reid, ibid., 1950,18, 1673.74 W. T. Taylor, A. L. Smith, and H. L. Johnson, J. Opt. SOC. Amer., 1951,41,91.75 B. Rice, J. M. Barredo, and T. F. Young, J . Amer. Chem. SOC., 1951,75, 2306.76 H. L. Welsh, C. Cummings, and E. J. Stansburg, J . Opt. SOC. Amer., 1951,41,712.7s D. S. McClure, ibid., 1951,19, 67022 GENERAL AND PHYSICAL CHEMISTRY.of the Raman tube is increased by multiple reflection from concave mirrors.The intensity of light entering a spectrograph from the Raman tube is in-creased by the factor l/(l-E) where R is the reflectivity of the mirrors.Another method of increasing the intensity of the light from a Raman tubehas also been suggested by White.77Gases.Germanium tetrafluoride has been studied at a pressure of 1-8atm., and two bands at 737-1 and 738.4 em. have been observed.78 Andry-chuk 79 has published full details of the Raman spectrum of fluorine. Thetriplet of ammonia at 3300 cm.-l has been further investigated under highdispersion, and no fine structure has been observed.80By using the multiple-reflection technique described above in conjunctionwith a grating, Stiochaff, Cummings, St. John, and Welsh have investi-gated the rotational structure of the v3 Raman band of methane.They haveresolved 68 lines and evidence was found for all but one (O+) of the fifteensub-branches which were predicted by Teller 82 in his theory of the Coriolisinteractions in tetrahedral molecules.Xolutions. Raman spectroscopic data for aqueous solutions of NaH,PO,,KH,PO,, HPO,, NaPO,, K4P207, K2Na2P207, and Na,H,P,O,, have beenpublished by Hannoick and H ~ f f m a n n . ~ ~ Studies of the degree of depolariz-ation of the lines in the Raman spectrum of oxalic acid solutions 84 lead tothe view that oxalic acid has a trans-structure. A comprehensive study ofthe Raman spectra of solutions of metallic nitrates 85 at various concentra-tions shows that the nitrate ion experiences some deformation as the concen-tration increases.This is indicated by the v3 deformation frequency of theion, which occurs about 1370-1390 cm.-l, splitting into two components asthe concentration is increased.Crystals. A large number of papers have recently been published on theRaman spectra of both inorganic and organic crystals. Most of the modernwork is carried out with single crystals, and perhaps the most interestingdevelopment has been Krishman’s refinement of Rasetti’s method of studyingthe Raman spectra of crystals. In this type of spectra besides the bandsdue to the characteristic vibrations of the molecules or ions which areobserved in the liquid phase, one also finds low frequency Raman lines whichare characteristic of the vibrations of the crystal lattice. An excellent reviewof the lattice vibrations of crystals and their study by Raman spectroscopyhas recently been given by Kastler.86 In collaboration with Rousset 87 this7 7 J.U. White, J . Opt. SOC. Amer., 1950, 40, 803 (A); 1951, 41, 732.‘ 8 A. D. Caunt, L. M. Short, and L. A. Woodward, Nature, 1951,168,557.79 P . Andrychuk, Canadian, J. Phys., 1951,29, 151.8o A. Mardhand, Compt. rend., 1951, 232, 395.81 B. P. Stiocheff, C. Cummings, G. B. St. John, and H. L. Welsh, Phys. Review,83 T. J. Hannoick and P. 0. Hoffmann, J . Chern. Phys., 1951,19, 708.84 R. Meripan and L. Berdet, Compt. rend., 1951,232, 1022.8 6 A. Kastler, 2. Elektrochem., 1950, 54, 501.87 A. Kastler end J. Rouaset, Phys. Review, 1947, 71, 455.1951, 84, 593. 82 E. Teller, Hand- zd. Jahrbuch Chem.Phys., 1934, 9, l i .J. P. Mathieu and M. Lousbury, Discuss. Faraday SOC., 1950, 9, 196MCDOWELL : MOLECULAR STRUCTURE. 23author has shown how investigations of the low frequency lines in the Ramanspectra of crystals give direct information about the torsional frequenciesof the ions and molecules in the crystal lattice. Amongst the inorganiccompounds which have been investigated in the crystalline state recently arepotassium hydrogen carbonate,88 potassium chlorate,sg calcium sulphateysOammonium chloride,g1 potassium dihydrogen phosphate,92 ap~plyllite?~lithium ammonium tartrate,94 sodium ammonium and varioussalt hydrates.96 The relative intensities of the Stoke and anti-Stoke linesin the Raman spectra of various crystals have been measured by Nara~anan.~'The following organic compounds have been studied in the crystallinestate : na~hthalene,~ * 100 diphenylmethane , loo diphen yl ether? loodipheny1,lW anthracene,lo0 p-dichlorobenzene, lol h e ~ a m e t h y l e n e t e t r a m i ~ ~ butyl bromide, butylamine, and butan01.10~ The Raman spectrum of solidpolystyrene has been reported.lo4Rotational Isomerism.-Raman-spectroscopic measurements which aremost useful in investigating cases of rotational isomerism Io5 have beenapplied to the cases of 1 : 2-dibromoethane lo6 and oxalyl ch10ride.l~~ Inthe former case, Neu and Gwinn have interpreted their results as showingthat the higher energy form of 1 : 2-dibromoethane has symmetry C,.Saksena and Kagarise lo' have calculated a value of 2.8 kcal./mole from theirRaman data for the heat of the reaction : oxalyl chloride (C&) + oxalylchloride (C,u).General Raman spectra of hydrocarbons and derivatives have beenrecorded by Braun, Sponer, and Fenske,lo8 and similar data for varioushydrocarbons have also been given by Cleveland and P o r ~ e l l i . ~ ~ ~ TheRaman spectrum of benzaldehyde has been studied by Chiorboli and Gual-L. Couture-Mathieu, J. Phys. Radium, 1950,11, 541.as C. S. Kumari, Proc. Ind. Acad. Sci., 1950, 32, A, 177.R. S. Krishman and C. S. Kumari, ibid., p. 105.9 1 J. P. Mathieu, It. M. Aguirre, and L. Couture-Mathieu, Compt. rend., 1951,232,318.92 P. S. Narayanan, Proc. Ind. Acad. Sci., 1951, 33, A, 240.93 Idem, Current Sci., 1951, 20, 94.s4 C. S.Kumari, Proc. Ind. Acad. Sci., 1951, 33, A , 236.e5 V. M. Padmanabham, ibid., p. 184.96 J. P. Mathieu, Compt. rend., 1950, 231, 896.s7 P. S. Narayanan, Proc. Ind. Acad. Sci., 1951, 33, A, 97.98 A. N. Ray, Indian J. Phys., 1950,24, 539.s9 I. Ichishima and S. Mizushima, J. Chem. Phys., 1950,18, 1686.loo A. Fruhling, Ann. Phys., 1951, 6, 401.lol B. D. Saksena, J. Chem. Phys., 1950,18, 1653.lo* L. Couture-Mathieu, J. P. Mathieu, J. Cremer, and H. Poulet, J. Chim. phye.,lo3 S. B. Sanyal, Indian J. Phys., 1950, 24, 378.lo* Ann Palin, J. Phys. Colloid Chem., 1951, 55, 1320.lo6 Ann. Reports, 1950, 47, 17.lo6 J. T. Neu and W. D. Gwinn, J . Chem. Phys., 1950,18, 1642.lo' B. D. Saksena and R. E. Kagarise, ibid., 1951,19, 987.lo8 W. G. Braun, D.F. Sponer, and M. R. Fenske, Analyt. Chem., 1950,22, 1074.lo9 F. F. Cleveland and P. Porcelli, J. Chem. Phys., 1950,18, 1459.1951, 48, 124 GENERAL AND PHYSICAL CHEMISTRY.dandi who have also studied mixtures of acetophenone and benzalde-hyde.lll Hydrogen bonding in acetoxime has been studied by Caughlan,Tartar, and Lingafelter. 112 Tetramethyldiborane has been investigated byRice, Barredo, and Young 75 who interpret their results as indicating evidencefor a hydrogen-bridge structure such as is now postulated in diborane.Molybdenum and tungsten hexafluorides have been shown to have an octa-hedral structure.l13Matossi has shown that the depolarization factor for a Raman line can becalculated in terms of the polarizabilities of atoms in a molecule.114In€ra-red Spectra.-Technique. The adaptation of a Beckman ultra-violet spectrophotometer by replacing the normal photocell with a leadsulphide cell and by using interrupted radiation has provided lZ5 an instru-ment with a resolving power of better than 0.005 p in the region 0.7 to 2.1 p.Several new double-beam instruments 116 and two fast scanning spectrometershave been described.l17 An interesting development has been the adoptionof a Faby-Perot interferometer for use with an infra-red spectrometer.llsWalsh, and Rochester and Martin have discussed 119 possible methods ofimproving the performance of a Littrow type infra-red spectrometer.Amat 120and others 121 have considered the problem of the effect of slit width on thedetermination of the intensity of an absorption band.Strong 122 has published an excellent article describing the historicaldevelopment and direction of current research on infia-red spectroscopes.The same author in collaboration with Taylor and Rupert 123 has describedan incandescent tungsten source for the infra-red region which is two tofour times as intense as the conventional globar over the rock saltregion.Plyler and Peters 12* have published wave-length tables of several absorp-tion bands of polystyrene, 1 : 2 : 4-trichlorobenzene, methanol, methane,carbon dioxide, and water over the range 1.5-24p which are sufficientlyP.ChiorboIi and G . Gualandi, Ann. chim., 1951,41, 172.ll1 Idem, ibid., p. 177.lI2 C. N. Caughlan, H. V. Tartar, and E. C. Lingafelter, J.Amer. Chem. SOC., 1951,113 K. N. Tanner and A. B. F. Duncan, ibid., p. 1164.11* F. Matossi, J . Chem. Phys., 1951, 19, 1007.115 W. Kaye, J . Opt. Xoc. Amer., 1951,41, 277.116 K. S. Tetlow, J. McAuslan, K. J. Brimley, and W. C. Price, J. Xci. Instr., 1951,117 E. F. Daly, Nature, 1950,166, 1072; P. J. Wheatley, E. R. Vincent, D. L. Roten-11* J. H. Jaffe, Nature, 1951, 168, 381.lle A. Walsh, Nature, 1951, 167, 810; J. C. 0. Rochester and A. E. Martin, ibid.,120 G. Amat, Compt. rend., 1951, 232, 1752.121 A. R. Philpotts, W. Thain, and P. G. Smith, Anulyt. Chem., 1951,23, 268.122 J. Strong, Physics Today, 1951, 4, 14.1z3 J. H. Taylor, C. S. Rupert, and J. Strong, J . Opt. SOC. Amer., 1951, 41, 626.1z4 E. K. Plyler and C. W. Peters, J.Rm. Nut. Bur. Stand., 1950,45, 462.73, 1180.28, 161 ; F. M. Rugg, W. L. Calvert, and J. J. Smith, J. Opt. SOC. Amer., 1951,41,32.berg, and G. R. Cowan, J . Opt. Xoc. Amer., 1951,41, 665.1951,168, 785MCDOWELL : MOLECULAR STRUCTURE. 25accurate for use in calibrating prism spectrometers. In this connection wemay note two recent methods of calibrating spectrometers. 125Cells for use a t liquid-air temperatures 126 and a t elevated temperatures 12'have been described. Plyler and Phelps 128 have given data on the trans-mission of a crystal grown from highly purified caium bromide which seemsto be suitable for use in the region 25-40~.An excellent detailed theoretical treatment of the vibration-rotational energy levels of molecules has been given by N i e l ~ e n , l ~ ~ who'hasalso discussed 130 the problem of the anomalous intensity distribution ofrotational lines in certain fundamental 6ands in the infra-red spectra of tri-atomic molecules. A means of quickly making vibrational assignments hasbeen given by Bernstein.131 This author has also calculated the change invibration frequencies due to changes in the mass, geometry, and potential-energy constants of a molecule.132Numerous calculations on force constants with different types of potential-energy functions have appeared.Amongst those recently discussed we notethe following : carbon tetrafluoride,133 silicon t e t r a f l ~ o r i d e , ~ ~ ~ , ammoniaand arsine,l35 cy~lohexane,~~~ linear triatomic molecules, 13' substitutedethylenes,13* and molecules with the symmetry D2h and its subgroups.139Bond-bond interactions in linear and angular molecules have been discussedby Duchesne and Burnelle.140 The vibrations of an infinitely long chain ofCH, groups have been considered by Kellner 141 who has attempted an inter-pretation of the infra-red spectrum of polythene.A discussion of the CH,vibrational frequencies in paraffins has also been given by Barrow 142 and byBrown, Sheppard, and Simp~0n.l~~Recently there has been considerable interest in the infra-redspectra of crystals particularly at low temperatures. In general these spectraare different from those of the corresponding substances in the liquid or gaslZ5 A. E. Martin, J. Opt. SOC. Amer., 1951, 41, 56; W. Guy and J.H. Towler, J. Sci.Instr., 1951, 28, 103.126 L. F. H. Bovey, J. Opt. SOC. Amer., 1951,41, 381.12' L. Brown and P. Holliday, J. Sci. Instr., 1951, 28, 27.lZ8 E. K. Plyler and F. P. Phelps, J. Opt. SOC. Amer., 1951,41, 209.129 H. H. Nielsen, Review Mod. Phys., 1951,23,90.130 Idem, Phys. Review, 1951,83, 838.131 H. J. Bernstein, J. Chem. Phys., 1950,18, 1682.132 Idem, Canadian J . Chem., 1951,29, 284.133 J. W. Linnett and D. F. Heath, J. Chem. Phys., 1951,19, 801.134 F. L. Voely, A. G. Weister, and F. F. Cleveland, ibid., p. 1084.135 L. Burnelle and J. Duchesne, ibid., 1950,18, 1300.136 M. Lamandie, C m p t . rend., 1950, 231, 1292.13' W. J. 0. Thomas, J. Chem. Phys., 1951,19, 1162.lS8 P. Torkington, Proc. Roy. SOC., 1951, A , 206, 17.139 H.H. Giinthard, Helu. Chim. Acta, 1950, 33, 1823.140 J. Duchesne and L. Burnelle, J. Chem. Phys., 1951,19, 1191.141 L. Kellner, Proc. Phys. SOC., 1951, 64, A, 521.14z G. M. Barrow, J . Chem. Phys., 1951,19, 345.143 J. Brown, N. Sheppard, and D. M. Simpson, Discws. Faraday Soc., 1950,Theoretiad.Crystals.9, 26126 GENERAL AND PHYSICAL CHEMISTRY.phase. These changes may be due to a number of factors of which perhapsthe most important are (a) the molecular symmetry may be perturbed bythe crystalline potential field which has not the symmetry of the moleculebut instead the local symmetry of the site group or unit cell ; (b) the molecularvibrations may be perturbed by coupling with identical molecular systems,with the symmetry of the coupling appropriate to the space group.Severalpapers on the theoretical interpretation of crystal spectra have been pub-lished 144 recently and an excellent review has been given by Honig.145Amongst crystalline compounds whose infra-red spectra have recently beendetermined are the following : hydrogen sulphide and deuterium sulphide, 146ammonia and trideuteri~arnmonia,~~~ c a l ~ i t e , l ~ ~ metallic acetylacetonates,l49and sodium and potassium fluorob~rates.~~~ Further study 151 of the absorp-tion and reflection spectra of the ammonium halides has confirmed previousconclusions 152 that there is no evidence for free rotation in these crystals.Several years ago Ketelaar 153 proposed a double minimum potential-energy field to explain his experimental results on the infra-red spectrum ofpotassium hydrogen fluoride.More recently a very complete discussion ofthis problem has been given by Pitzer and Westerum 154 who show that thethermodynamical and spectroscopic data can be explained by assumingthat the HF,‘ ion has a linear structure with a single potential-energy mini-mum, the hydrogen having its equilibrium midway between the two fluorineatoms. Ketelaar and Vedder’s 155 results show that in the reflection spec-trum obtained with polarized light with the electric vector perpendicular tothe rotational axis there are two absorption bands and with the electricvector parallel to the axis there is only one band as required by Pitzer andWesterum’s theory. Further work by Newman and Badger 156 and by Cot6and Thompson 157 confirms and extends the results of Ketelaar and Vedder.There is little doubt therefore that Pitzer and Westerum’s theory is correct.Amongst organic compounds which have been studied in the crystallinestate by means of polarized infra-red radiation are adipic acid,158 N-acetyl-g l y ~ i n e , l ~ ~ and diket~piperazine.~~~, 159144 F.Matossi, J . Chem. Phys., 1951,19, 161 ; J. J. Hrostowski and G. C. Pimentel,145 D. F. Honig, Discuss. Faraday Xoc., 1950, 9, 115.148 J. B. Lohman, F. P. Reding, and D. F. Honig, J . Chem. Phys., 1951,19, 252.14’ F. P. Reding and D, F. Honig, ibid., p. 594.148 J. Louisfert, Compt. rend., 1950, 230, 1154.149 J. Lecomte, Discuss. Faraduy Xoc., 1950, 9, 125.150 G. L. Cot6 and H.W. Thompson, Proc. Roy. Xoc., 1951, A, 210, 217.151 L. F. H. Bovey, J . Chem. Php., 1950,18, 1684.152 L. F. H. BoveyandG. B. B. M. Sutherlmd, ibid., 1949,17, 843; E. L. Wagner15s J. A. A. Ketelaar, Rec. Trav. chim., 1941,60, 523; J . Chem. Phy8., 1941, 9, 775.154 K. Pitzer and E. F. Westerum, ibid., 1947,15,526; J . Amer. Chem. SOC., 1949,71,156 R. Newman and R. M. Badger, ibid., p. 1207.15’ G. L. Cot6 and H. W. Thompson, Proc. Roy. SOC., 1951, A, 210,206.158 E. J. Ambrose, A. Elliott, and R. H. Temple, Proc. Roy. XOC., 1961, A, 206,192.158 R. Newman and R. M . Badger, J . Chem. Phys., 1961,19,1147.ibid.; p. 661 ; R. Newman and R. S. Halford, ibid., 1950,18, 1276.and D. F. Honig, ibid., 1950,18, 296, 305.1940. 155 J. A. A. Ketelaar and W.Vedder, J . Chem. phys., 1951,19,654MCDOWELL : MOLECULAR STRUCTURE. 27Intensity measurements. The absolute intensity of an absorption band isdefined as Ai = J adv = - (l/PZ) 1 In (I/Io)dv (where E is the absorptioncoefficient, v the frequency, P the pressure of the gas, Z the length of gas cell,and I/Io the fraction of light transmitted by the cell) ; the integral is takenover the whole band. To obtain correct absolute intensities from observedtransmission curves, errors caused by rapid variations in transmissions overa, single slit width must be eliminated. Wilson and Wells 160 have shownthat it is possible to overcome these errors by (a) using narrow slits to givehigh spectral resolution, (b) adding a foreign non-absorbing gas to pressure-broaden the individual rotational lines, and ( c ) taking spectra of the absorbinggas at successively smaller partial pressures.Once the absolute intensity of a band, Ai, is known the change in dipolemoment as the molecule executes a certain vibration can be calculated.Therelation between Ai and the change in dipole moment with a particularnormal mode is Ai = (Nn/3C) I av/aQi 12 so that once the normal vibrationsand normal co-ordinates of the molecule can be calculated we can estimatea@/&,, the change in dipole moment with the change in a particular bondlength ari.Molecules for which absolute intensity measurements, and 8p /arg forcertain normal modes, have recently been obtained by the above method are :nitrous oxide,161 cyanogen,162 cyanogen chloride,162 carbon monoxide,163carbon disulphide,164 carbonyl s ~ l p h i d e , ~ ~ ~ , 165 and acetylene.166 Fromstudies of the self-broadening 166 of rotational lines ‘it has also been shownthat reliable estimates of absolute intensities can be obtained, and Pennerand Weber have applied such measurements to determine quantitativevalues for line widths.They have compared these measurements withothers obtained when the rotational lines are broadened by a foreigngas.167 Francis 168 has determined the absolute intensities of somecharacteristic bands of ketones and esters. The influence of foreign gasesa t high pressure on the 3-3-p band of methane has been studied.169Crawford and Dinsmore 170 have discussed further the theory of theintensities of vibrational bands of diatomic molecules.Internal Rotation and Rotational Isomerism.-Tnfra-red studies ofdimethylzinc , dimethylmercury, and dimethylcadmium under high resolution160 E.B. Wilson and A. J. Wells, J. Chem. Phys., 1946, 14, 578; see also A. M.161 H. J. Callomon, D. C. McKean, and H. W. Thompson, Proc. Roy. SOC., 1951,162 E. R. Nixon and R. C. Cross, J. Chem. Phys., 1950,18, 1316.163 S. S. Penner and D. Weber, ibid., 1951, 19, 807.16* D. Z. Robinson, ibid., p. 881.166 H. J. Callomon, D. C. McKean, and H. W. Thompson, Proc. Roy. Soc., 1951166 S. S. Penner and D. Weber, J. Chem. Phys., 1951, 19, 817, 974.16‘ Idem, ibid., pp. 1351, 1361.lg9 H. L. Welsh, P. E. Pashler, and A. F. Dunn, ibid., p. 340.170 B. L. Crawford and H.L. Dinsmore, ibid., 1960, 18, 1682.Thorndike, A. J. Wells, and E. B. Wilson, ibid., 1947,15, 157.A , 208, 332.A , 208, 341.16* S. A. Francis, ibid., p. 84228 QENERAL AND PHYSICAL CHEMISTRY.in the 3p region have enabled Boyd, Williams, and Thompson 171, 172 toshow that in these molecules there is essentially free internal rotation of themethyl groups. Powley and Bernstein 173 have described a dilute-solutionmethod of studying rotation isomerism which, when applied to halogenatedethanes, yields results in good agreement with those obtained from measure-ments on the gaseous compounds. Brown and Sheppard have discussedrotational isomerism in 2-meth~lbutane,l~~ 2 : 3-dimethylbutane,17* 1 : 2-dibr~moethane,~~~ 1 : 4-dibromobutane, 175 n-propyl and n-butyl bromide,175and n-butyl, n-hexyl, and n-octyl alcoh01.l~~ Infra-red and Raman spectro-scopic studies 176 indicate that crystalline hydrazine at low temperature isalmost entirely in a trans-configuration. The possibility of rotational iso-merism in methyl- and dimethyl-hydrazine has been discussed.177GeneraE. Nielsen 178 has given an extensive analysis of the two lowfrequency fundamental bands in arsine and shows that it is probable that thedoubling of the &-branch is only an apparent one which is due to the natureof the convergence of the &-branch caused by a Coriolis resonance perturba-tion. In the case of phosphine 179 it is also suggested that the doubling isonly an apparent one and arises from similar causes.The long-path technique has been used by Herzberg and Herzberg lSoto study the spectrum of nitrous oxide below 1 .2 ~ ; they give a very completeanalysis of the spectrum. Other molecules which have been studied by thistechnique are HCNO, lS1 CH3*CF3,1S2 and CD3C=CH.ls3 The vibrational-rotation bands a t 4 . 5 ~ bf the nitrous oxide spectrum have been studied underhigh resolution by Thompson and Williams lS4 whose analysis leads to valuesof certain spectroscopic constants in excellent agreement with those obtainedby Herzberg and Herzberg.lso The infra-red spectra of 15N14N160 and14N15N160 have been recorded,ls5 and two new absorption bands have beenfound by Taylor.186The fine structure of the fundamental and f i s t overtone of the vibrational-rotational spectrum of ClF lS7 has been determined.Other diatomic mole-171 D. R. J. Boyd, H. W. Thompson, and R. L. Williams, Discus?. Faraday Soc.,172 Idem, Nature, 1951, 167, 766.173 J. Powling and H. J. Bernstein, J. Amer. Chem. Soc., 1951, 73, 1815.174 J. K. BrownandN. Sheppard, J. Chem. Phys., 1951,19, 976.175 Idem, Discuss. Faraday Soc., 1950, 9, 144.176 E. L. WagnerandE. L. Burgozdy, J. Chern. Phys., 1951,19, 1210.l" D. W. E. Axford, G. J. Janz, and K. E. Russell, ibid., p. 704.178 H. H. Nielsen, Discuss. Faraday SOC., 1950, 9, 85.179 Idem, ibid.lSo G. Herzberg and L. Herzberg, J. Chern. Phys., 1950,18, 1551.lS1 C. Reid, ibid., p. 1544.R. D. Cowan, G. Herzberg, and S. P. Sinha, ibid., p. 1538.le3 G. Herzberg, A. V. Jones, and L. C.Leitch, ibid., 1951,19, 136.H. W. Thompson and R. L. Williams, Proc. Roy. Soc., 1951, A , 208, 326.le5 J. Bigeleisen and L. Friedman, J. Chem. Phys., 1950, 18, 1656.J. H. Taylor, ibid., 1951, 19, 1314.A. H. Nielsen and E, A. Jones, ibid., p. 1117.1950, 9, 154MCDOWELL : MOLECULAR STRUCTURE. 29cules studied include OH l g 8 and N0.1g9 High resolution measurementshave been made on water lgo and deuterium oxide,lgl hydrogen s ~ l p h i d e , ~ ~ ethylene,lg3 acetylene,lg4 ammonia lg5 and carbonyl fluoride.lg6In the infia-red spectrum of boron trichloride lg7 certain bands exhibitdoubling due to isotope effects ; isotope effects have also been studied lg8 inD12CN, and D13CN. The spectra of nitrosyl chloride,lS9~ 201 fluoride,200 andbromide 201 have been examined and frequency assignments made.Phos-phorus in the solid and vapour, and in carbon disulphide solution has beenstudied.202 Other simple molecules which have been studied are : F20,203C1,O and C102,204 HOCl and DOCl,,05 HCN0,206 and HCNS.207 The polymerbands of hydrogen fluoride vapour have been investigated.208 Lagemannand Jones 209 and Edelson and McAfee 210 have independently reported onthe infra-red spectrum of sulphur hexafluoride, and Sheline 211 has studiedI n view of the continuing large number of compounds studied in detail byinfia-red spectroscopic methods it is no longer possible in a report of thistype adequately to discuss them. For many of the compounds very completeassignments have been made and in a great number of cases a normal co-ordinate treatment has been carried out.Amongst the work reported duringthe period under review we may note the following : 1 : l-dideuterioethyl-ene,212 dia~omethane,~~~ dideuteriodia~omethane,~~~ borine carbony1,214Fe, (CO) 12lE8 G. A. Hornbeck and R. C. Herman, J. Chem. Phys., p. 512.laS A. L. Smith, W. E. Keller, and H. L. Johnston, ibid., p. 189.lDo K. K. Jones, P. C . Cross, and P. A. Giguhre, ibid., p. 1086.lgl R. Mathis, J . Phys. Radium, 1951, 12, 51.lDz R. H. Noble, J . Chem. Phys., 1951, 19, 799; H. L. A11m and P. C. Cross, ibid.,lg3 E. K. Plyler, ibid., p. 658.lD4 E. E. Bell and H. H. Nielsen, ;bid., 1950, 18, 1382.lo5 D. L. Wood, E. E. Bell, H. H. Nielsen, Proc. Nut. Acad. Xci., 1950, 36, 497.lg6 A.H. Nielsen, J . Ghem. Phys., 1951,19, 99.ID7 R. E. Scruby, J . R. Lacher, andJ. D. Park, ibid., p. 386.lD8 W. S. Richardson, ibid., p. 1213.lB8 A. G. Pulford and W. Walsh, Trans. Faraday Xoc., 1951,4'4, 347.201 W. G. Burns and H. J. Bernstein, ibid., p. 1669.202 H. J. Gutowsky and C. J. Hoffman, J . Amer. Chem. SOC., 1950,72, 575.203 E. A. Jones, J. S. Kirby-Smith, P. T. H. Woltz, and A. H. Nielsen, J . Chem. Phys.,z04 K. Hedberg, ibid., p. 509.205 K. Hedberg and R. M. Badger, ibid., p. 508.20B G. Herzberg and C. Reid, Discuss. Faraduy Soc., 1950,9, 92.$07 L. H. Jones and R. M. Badger, J . Chem. Phys., 1950,18, 1511.208 R. D. Shelton and A. H. Nielsen, ibid., 1951, 19, 1312.209 R. T. Lagemann and E. A. Jones, ibid., p. 534.210 D. Edelson and K.B. McAfee, ibid., p. 1311.211 R. K. Sheline, J . A m r . Chem. SOC., 1951, 73, 1615.212 J. E. Lancaster, R. G. Inskeep, and B. L. Crawford, J . Chem. Phys,, 1951, 19, 661.213 W. H. Fletcher and D. A. Ramsay, ibid., p. 456.814 R. D. Cowan, ibid., 1960,18, 1101.p. 140.E. A. Jones and P. J. H. Woltz, J . Chem. Phys., 1950,18, 1516.1951, 19, 33730 GENERAL AND PHYSICAL CHEMISTRY.2 : 3-dibromo-2 : 3-dimethylb~tane,~l~ 2 : 2 : 3 : 3-tetramethylbutane,215chloroacetyleneY2l6 chlorodeuterioacetylene,216 de~terioethylene,~l7 halogen-substituted methanesY2l8 bromochlorofluoromethane,21g methyl halides,220trichloromethanes,221 methyl 1 : 1 : 1 -trichloroethane,2B, 2241 : 1 : l-trifl~oroethane,~~~ 1 : 3 : 5-trifluoroben~ene,2~~ neopentane and tetra-methylsilane and their monodeuterio-derivatives,227 chloroform,228 trichloro-silaney228 ethyleneMicrowave Spectra.-During the past five years microwave spectroscopy,which deals with that region of the electromagnetic spectrum between a fewmillimetres and about 10 em.has attained considerable importance in thestudy of molecular structure. This extremely powerful method providesmuch information not only about the rotational levels of simple moleculesin the gas phase, but also on rotational magnetic moments in polyatomicZeeman effects in m01ecules,2~~ nuclear quadrupole rn0ments,~34dipole moments, and internal-rotational centrifugal distortion,236isotopic effects in molecules, and the exchange of rotational energy oncollision .237It is not possible adequately to survey this rapidly expanding field indetlail here ; several excellent review articles are available 238 which discuss a tlength different aspects of the subject and we shall only mention briefly someof the main achievements of the past few years.The great advantage which this method offers over all other spectroscopicones available for investigating molecular structure is the enormously high216 F.F. Cleveland, J. 33. Lamport, and R. W. Mitchell, J . Chem. Phys., p. 1320.216 W. S. Richardsonand J. H. Goldstein, ibid., p. 1314.217 C. Courtoy, M. de Hemptinne, and M. V. Migeotte, ibid., 1951,19, 137.218 E. K. Plyler and W. S. Benedict, J . Res. Nat. Bur. Stand., 1951,46, 202.219 E. K. Plyler and M. A. Lamb, ibid., p.382.220 R. Mathis, J . Phys. Radium, 1951,12, 550.221 J. R. Madigan and F. F. Cleveland, J . Chem. Phys., 1951,19,119.222 P. Venkateswarlu, ibid., p. 293.224 M. Z. El-Sabban, A. G. Msister, and F. F. Cleveland, ibid., p. 855.226 J. Rud Nielsen, H. H. Claassen, and D. L. Smith, ibid., 1950,18, 1471.226 J. Rud Nielsen, C. Y. Liang, and D. L. Smith, Discuss. Paraday SOC., 1950,9,177.227 D. H. Rank, B. D. Saksena, and E. R. Shull, ibid., p. 187.s28 T. G. Gibian and D. S. McKinney, J . Amer. Chem. Soc., 1951, 73, 1431.229 H. H. Giinthard, B. Messikommer, and M. Kohler, Helv. Chim. Acta, 1950,33,1809.230 H. W. Thompson and W. T. Cave, Trans. Faraday SOC., 1951,47,946.231 Idem, ibid., p. 951. 232 C. K. Jen, Phys. Review, 1951,81, 197.233 K.B. McAfee, Phys. Review, 1950, 78, 340.z34 C. H. Tomes and B. P. Dailey, J . Chem. Phys., 1949,17, 782.235 B. P. Dailey, H. T. Minden, and R. G. Shulman, Phys. Review, 1949, 75, 1319;D. R. Lide and D. K. Coles, ibid., 1950, 80, 91 1 ; H. T. Minden, J. M. Mays, and B. P.Dailey, ibid., 1950, 78, 347; D. G. Burkhard and D. M. Dennison, ibid., 1951, 84,408.230 ethylene imine,231 and ethylene ~ u l p h i d e . ~ ~ ~223 Idem, ibid., p. 298.Zs6 R. E. Hillger and M. W. P. Straudberg, ibid., 1951, 83, 575.237 B. Bleaney, Reports Progr. Phys., 1946-47, 11, 178.z3* W. Gordy, Rev. Mod. Physics, 1948, 20, 668; Coles, Advances in Electronics,1950, 2, 300; D. H. Whiffen, Quart. Reviews, 1950, 4, 131; M. Freyman, R. Freyman,and J. Le Bot, J . Phys. Radium, 1948, 9, 1 ; B.Bleaney, Reports Progr. Phys., 194G47,11, 178; E. B. Wilson, Annual Review Phys. Chem., 1951,2,151MCDOWELL : MOLECULAR STRUCTURE. 31resolving power possible; spectral lines as close as 4 x cm.-l can beseparated.2s It is therefore possible by microwave techniques to observein molecules such phenomena as the Stark effect, Zeeman effect, the splittingdue to nuclear quadrupole effects, and a great many phenomena not other-wise detectable.Molecular geometry. Perhaps the most important information onmolecular structure from the chemists' viewpoint has been obtained bystudies of the Stark effect. The necessary apparatus has been described byseveral workers.240It should perhaps be mentioned that these applications of microwavetechniques are restricted to molecules with a permanent dipole moment,though oxygen is an exception for in this case a microwave spectrum is madepossible because of its paramagnetism.The theory of the microwavespectrum of oxygen is due to Van Vleck,24l and recently Anderson, Johnson,and Gordy242 have observed a single resonance absorption peak at 2.5 mm.wave-length which they identify as one predicted earlier by Van Vleck. Themicrowave magnetic resonance spectrum of oxygen has also been studiedrecently by Beringer and Castle,243 and here it is noteworthy that Talley andNielsen 244 have recently suggested that though deuterioacetylene has nopure rotational spectrum, because it has no dipole moment, it is neverthelesspossible that several vibrational-rotational lines arising from differencefrequencies may be observable in the microwave region.One consequence of the high resolving power of these techniques and thehigh degree of accuracy with which the frequencies in the microwave regioncan be measured, is to furnish extremely accurate values for certain molecularparameters.From these it is possible to calculate bond lengths and certaindetails of molecular geometry with high accuracy. In the case of bond-length calculations, etc., the accuracy is limited by the accuracy with whichPlanck's constant is known.One very interesting recent example of the application of microwavemethods is the work of C0rnwe11,~~~ who states that his observations of themicrowave spectrum of bromodiborane indicate clearly that the moleculeis not planar, and that the bridge hydrogen atoms are above and below theplane containing the other atoms.Molecules whose structure has beenpartially or wholly determined recently by the application of microwave tech-niques include the following : carbon sulphur nitrogenm9 C. H. Tomes, A. N. Holder, and F. R. Merritt, Phys. Review, 1948, '74, 1113;S. Geschwind, H. T. Minden, and C. H. Tomes, ibid., 1950,78, 174.240 K. B. McAfee, R. H. Hughes, and E. B. Wilson, J. Xci. Imtr., 1949, 20, 822;A. H. Sharbaugh, ibid., 1950,21, 120.841 J. H. Van Vleck, Phys. Review, 1947, 71,413.24a R. S. Anderson, C. M. Johnson, and W. Gordy, ibid., 1951,83,1061.243 R. Beringer and J. G. Castle, ibid., 1951, 81, 82.244 R. M. Tally and A.H. Nielsen, J . Chem. Phys., 1951,19, 805.245 C. D. Cornwell, ibid., 1950, 18, 1118.246 0. R. Gillam, C. M. Johnson, and W. Gordy, Phys. Review, 1950, 78, 140. "' M. H. S h e t z , J . Chern. P h y ~ . , 1951, 19, 93832 GENERAL AND PHYSICAL CHEMISTRY.ammonia,249 mono- and di-deuteri~ammonia,~~~ phosphine,251a r ~ i n e , ~ ~ ~ ~ t i b i n e , ~ ~ ~ phosphorus t r i ~ h l o r i d e , ~ ~ ~ arsenic tri~hloride,~53 nitrosylchloride ,2 54 br omog ermane , t r ifluor osilane ,2 ethylene oxide F57 ethylenes ~ l p h i d e , ~ ~ ~ keten,258 methanol,259 methyl chloride,260 methyl bromide,261methyl fluoride,262 methyl cyanide,263 methyl i ~ o c y a n i d e , ~ ~ ~ methanethiol,264tert. - butyl chloride,266 tert. - butyl bromide,26 tert. - butyl iod-ide,266 ~yanoacetylene,~~~ l-ohloro-lifluoroethylene,268 3 : 3 : 3-trifluoro-p r ~ p y n e , ~ ~ ~ ~ 270 isocyanic acid,271, 272 and formicA set of most useful tables giving the frequencies and intensities of micro-wave absorption lines, assignments of quantum numbers, moments of inertia,dipole moments, quadrupole coupling moments, etc., for 40 compounds havebeen compiled by Kisliuk and T0wnes.2~~Dipole moments.The application of Stark-effect measurements on mole-cules enables dipole moments to be calculated with high precision, since thetheory of the Stark effect for many types of molecular model is known andthe appropriate quantum-mechanical formule may be applied to the dataobtained from experimental studies. The change in energy of the levels of asymmetrical-top molecule, having adipole moment, in an electric field of poten-tial E, is given by an expression which involves p2E2 multiplied by a factorwhich is a function of various rotational quantum numbers K , J , and 2 M ;248 K.B. McAfee, Phys. Review, 1951, 82, 971.249 R. K. Coles, W. E. Good, J. K. Bragg, and A. H. Sharbaugh, ibid., 1951, 82, 877.250 M. T. Weiss and M. W. P. Straudberg, ibid., 1951, 81, 286; 1951, 83, 567.251 C. C. Wromis and M. W. P. Straudberg, ibid., 1951, 81, 798.252 P. Kisluik and C. H. Tomes, J . Chem. Phys., 1950,18, 1109.z53 Idem, ibid.254 W. J. Pietenpol, J. D. Rogers, and D. Williams, Phys. Review, 1951, 83, 431.255 A. H. Sharbaugh, B. S. Prichard, V. G. Thomas, J. M. Mays, and B. J. Dailey,256 J.Sheridan and W. Gordy, J . Chem. Phys., 1951,19, 965.257 G. L. Cunningham, A. W. Boyd, R. G. Rogers, W. 0. Gwinn and W. E. Le Van,2 5 8 B. Bak, E. Krudsen, M. E. Stanberg, and J. Rastrup-Andersen, Phys. Review,259 R. H. Hughes, W. E. Good, andD. K. Coles, ibid., 1951, 84, 418.260 J. Matlock, G. Glockler,D.R. Bianco,and A. Roberts, J. Chem. Phys., 1950,18,332.261 J. R. Simmons and W. 0. Swan, Phys. Review, 1950,80, 289.262 D. K. Coles and R. H. Hughes, ibid., 1949, 76, 858.263 M. KessIer, H. Rusig, R. Trambarulo, and W. Gordy, ibid., 1950,79, 54.264 T. M. Shaw and J. J. Windle, J . Chem. Phys., 1951,19, 1063.265 R. R. Unterberger, R. Trambarulo; and W. V. Smith, ibid., 1950, 18, 565.2E6 J. Q. Williams and W. Gordy, ibid., p. 994.267 A.A. Westenberg and E. B. Wilson, J . Amer. Chem. SOC., 1950,72, 199.J. K. Bragg, J. C, Madison, and A. H. Sharbaugh, PTby8. Review, 1950,77, 148.269 W. E. Anderson, R. Trambarulo, J. Sheridan, and W. Gordy, ibid., 1951, 82, 58.270 J. N. Shoolery, R. G. Shulman, W. F. Sheehan, V. Schomaker, and D. M. Yost,271 L. H. Jones, J. N. Shoolery, R. G. Shulman, and D. M. Yost, ibid., 1950,18,990.372 C. I. Beard and B. P. Dailey, ibid., 1951,19, 275.2'5 W. J. Pietenpol, J. D. Rogers, and D. Williams, Phys. Review, 1950, 78, 480.274 P. Kisliuk and C. H. Tomes, J . Res. Nut. Bur. Stand., 1950, 44, 611.ibid., 1950, 79, 189.ibid., p. 676.1950, 79, 190.J . Chem. Phys., 1951,19, 1364MCDOWELL : MOLECULAR STRUCTURE. 33an expression can thus be deduced for the frequencies of the Stark pattern ofthe molecule, and once the quantum numbers for the transitions have beencorrectly assigned, the product p2B2 can be calculated.Determination of Eleads to a very accurate value for the dipole moment p. By this methodvery accurate values for the dipole moments of a large number of moleculeshave been obtained. Some recently reported results are deuterium hydrogensulphide 275 1-02 5 O - O ~ D , methanethiol 264 1-22D, ammonia 249 1.468O ~ O O ~ D , ethylene oxide 257 1 . 8 8 ~ , ethylene sulphide 257 1 . 8 4 ~ , and 3 : 3 : 3-trifluoropropyne 2695 270 2.36 & 0.04~.An important recent development of the determination of dipole momentsof molecules from Stark-effect data is due to Burkhard and Dennison276who have given an extensive discussion of the theory of this effect in methylalcohol and equations from which they compute the components of thedipole moment parallel and perpendicular to the symmetry axis. Theyobtain the results pll = 0.893 x 10-l8 e.s.u.and pl = 1.435 x 10-l8 e.8.u.Nuclear quadrupole couplingconstants are of considerable interest t o chemists for they yield informationabout valency. This effect arises from the interaction of the quadrupolemoment, &, of a nucleus and the second derivative of the electrical potential,a2V/az2, at the nucleus due to all molecular changes outside the nucleus.Townes and Dailey Z3* have shown that the quadrupole moment is character-istic of a particular nucleus and is a measure of the departure of the particularnuclear charge distribution from spherical symmetry.Electrons in closedshells about the nucleus or in an s-type orbit for which, of course, the eigenfunction is spherically symmetrical, will not contribute to the variation ofenergy with nuclear orientations, or to that at the nucleus. Electrons ind- or higher orbitals should also be of small importance because of their lowpenetration power at the nucleus. A p-type orbital has the necessary varia-tion of charge distribution with angle and because it gives the electron con-siderable probability of being near the nucleus, the hyperfine splitting ob-served in the microwave spectrum is mainly due to the amount of p-orbitalcharacter of the valence electrons.Nuclear quadrupole coupling constants, which are defined by e&(a%/az2),have been determined for a large number of atoms in molecules and have beenused to provide information about electron distributions about chemicalConsiderable informationconcerning potential-energy barriers hindering free rotation about singlebonds can now be derived by mi’crowave spectroscopy.In excited torsionalstates molecules will have slightly different effective moments of inertia andso Stark-effect studies enable weak satellite lines to be detected near the nor-mal rotational lines. Measurements of the position and intensities of theseNucZear quudrupole eflects and valency.bonds.234,268,277,278,336Internal torsional potential-energy barriers.R. E. Hillger and M. W. P. Straudberg, Phys.Review, 1951,83, 575.276 D. G. Burkhard and D. M. Dennison, ibid., 1951, 84,408.e77 A. A. Westenberg, J. H. Goldstein, and E. B. Wilson, J . Chem. Phys., 1949,17,1319.278 J. H. Goldstein and J. D. Bragg, Phys. Review, 1949,75, 1453.REP.-VOL. XLVIII. 34 GENERAL AND PHYSICAL OHEMISTRY.satellites enable the height of the potential-energy barrier to be calculatedaccurately. These measurements also yield information about the shape ofthe barrier. Recent studies along these lines have yielded extensive informa-tion of the barriers hindering free rotation in rneth~lsilane,~'S methyl al-C O ~ O ~ , ~ ~ ~ l : l : l -trifluoroethane,280 methyltrifluorosilane,2a19 282 and acet-aldehyde .283Dipole Moments.-The Debye theory 284 of polar molecules, which is satis-factory for the determination of the dipole moment of gaseous polar molecules,leads to certain difficulties when applied to the determination of dipolemoments, p, of polar molecules dissolved in non-polar liquids. Thus, thedipole moments as determined in dilute solution, psoln., are often dependent onthe solvent used, and the solvent effect, Ap (= psoln.- pga,), is generallynegative, though several compounds are known for which a positive solventeffect is observed. In all cases, however, the solvent effect is dependent onthe dielectric constant of the solvent.In the past, several attempts have been made to evolve a theory of thesolvent effect 285, 286, 287 but none of these has been wholly satisfactory.During the past year new attempts have been made to understand the reasonsfor the solvent effect.In two cases the authors have successfully developednew theories which seem to account for the observed magnitudes and signsof Ap. These also point to new methods of calculating the dipole moment ofpolar molecules from measurements on dilute solutions, which lead to valuesin agreement with those obtained from gas-phase experiments.Ross and Sack 288 and Scholte 289 pointed out certain inadequacies in theDebye theory when applied to polar liquids and proceeded to base theirrespective theories on developments of Onsager's views. Both approachesare rather similar in that the authors tend to abandon the idea of a spherical-cavity model, and instead base their calculations on an ellipsoidal cavity,i.e.they take the shape of the molecule into consideration. Ross and Sackderive the expression :where E is the dielectric constant, n the refractive index, and 4, the so-calledinternal-field function, is defined by the equation, P = E + 4n<P, for theinternal field within an ellipsoidal cavity in a uniformly polarized medium,where E is the applied field and P is the polarization. The application of270 D. R. Lide and D. I(. Coles, Phys. Review, 1950, 80, 911.280 B. P. Dailey, H. T. Minden, and R. G. Shulman, ibid., 1949,75, 1319.281 H. T. Minden, J. M. Mays, and B. P. Dailey, ibid., 1950,78, 347.28a J. Sheridan and W. Gordy, J . Chem. Phys., 1951,19, 965.283 C. L. Baird, quoted by E. B. Wilson, Ann. Review Phys.Chem., 1951,2, 151.2134 P. Debye, " Polar Molecules ", 1929, Reinhold, New York.285 ( S i r ) C. V. Raman and K. S. Krishnan, Proc. Roy. Xoc., 1928, A , 117, 589.z8% K. Higasi, Sci. Papers Inst. Phys. Chem. Res., Tokyo, 1936, 28, 284.a87 F. C. Frank, Proc. Roy. SOC., 1935, A , 152, 171.lsS T. G. Scholte, Rec. Trav. chim., 1961, 70, 60.I. G. Ros8 and R. A. Sack, Proc. Phys. Soc., 1950,63, B, 893MCDOWELL : MOLECULaR STRUCTURE. 36equation (1 ) to data for polar molecules in benzene solutions leads to values ofpsoln./pgas which are in very good agreement with those observed. Bydifferentiating equation (1) the authors show that the sign of &/at (whereS = psoh./ptgas) is determined by the expression (c2 + 2n2)E - c2. They arethus able to show that their theory predicts the correct variation of Ap withdielectric constant of the solvent.Scholte on the other hand derives an expression from which the dipolemoment of a polar molecule dissolved in a non-polar liquid can be evaluated.This equation is applied to data on dilute solutions of chloroform, chloro-benzene, and nitrobenzene, in a large number of non-polar solvents, and inevery case the value of p calculated is in excellent agreement with that ob-tained from gas-phase experiments.A rather interesting point is brought outin Scholte’s paper. He has calculated the dipole moment of the above threecompounds from solution data by using the theories of Debye, and Onsagerand Bottcher, and also his own treatment for the cases of spherical and ellip-soidal cavities.In the following table, which is taken from his paper, theresults of these calculations are shown and compared with the value of p fromgas-phase data.Values of p from dilute-solution dataCompound Debye Bottcher spherical ellipsoidal gas data,Onsager- Scholte Scholte p fromCHCl, ............... 1 . 14 1-2 1.09 1 *04 0.95-1-05C,H,Cl ............ 1 *55 1-55 1-52 1.69 1.70C6H,*NOz ......... 3.93 3.76 3-84 4.31 4.22These data leave little doubt that the treatment based on an ellipsoidalcavity leads to more correct results. When these are considered in con-junction with Ross and Sack’s results, one can agree with these authors that“. . . an extension based on Onsager’s approach appears to be promisingenough to render unnecessary a re-interpretation of apparent dipole momentsfiguring in Debye’s formula ”.It should be mentioned here that Smith andWitten 290 have also shown that there are indications that approaches whichare not based on the Clausius-Mosotti-Debye model give the best correlationwith non-polar solvents. In this connection, however, it should be notedthat a development of the Clausius-Mosotti-Debye viewpoint, in which thereaction field is considered, has led to an expression 291 from which values ofp can be calculated which are in good agreement with those determined fromgas-phase experiments. In this theory the spherical-cavity model is retainedand the shape of the polar molecule is ignored.The variation of dipole moment with state for n-propyl- and n-butyl-amine has been examined by Barclay, Le Fbvre, and Smythe; 292 it is foundthat these compounds have a positive solvent effect in benzene.The resultsare discussed in terms of Barclay and Le FBvre’s empirical relation.293 Auds-zso J. W. Smith and L. B. Witten, Trans. Paraday SOC, 1951, 47, 1304.282 G. A. Barclay, R. J. W. Le FBvre, and B. M. Smythe, Trans. Pa~aday Soc.,H. Koren and E. Treiber, 2. Naturforsch., 1951,6a, 206.951, 47, 357.G. A. Barclay and R. J. W. Le FBvre, J., 1950, 65636 GENERAL AND PHYSICAL CHEMISTRY.ley and Goss 294 have considered the effect of solvent on the molecular re-fraction and polarization of n-paraffins.L. E. Sutton and his school have recentlyshown how considerable information about the stereochemistry of complexorganic molecules can be obtained from dipole-moment measurements.Inthe course of very extensive studies they have elucidated the stereochemistryof dihydrotetra~ines,~~~ aromatic ethers,296 2 : 5-dibromo-1 : 4-di-tert.-butyl-benzene,297 and shown 298 that a-and p-salicylides are not stereoisomers butare the only known forms of di- and tri-salicylide~,~~~ respectively.Other applications of stereochemical interest have been made by LeFBae and his colleagues to 2 : Z’-azopyridine,3OO and 2 : 2’-di~yridyl.~OlFischer 302 has discussed the stereochemistry of the tetrahydroglyoxalinering in the light of dipole-moment measurements.In an extensive series of publications, Sutton and his collaborators havediscussed the polarization of conjugated systems as influenced by sterichindrance, positional isomerism, and substitution.303Amongst the compounds whose dipole moments have recentlybeen determined the following may be noted : ethylene ~ u l p h i d e , ~ ~ ~ 2 : 2-dibromopropane,305 a-phenyl-ketones,306 some fluorine-containing organic308 aryl polysulphide~,~~~ metallic chelateketen and its derivati~es,~lr aromatic a m i n e ~ , ~ l ~ tropolone and relatedcompounds,3l? derivatives of hydroxybenzoic aromatic compoundscontaining iodineY3l5 and derivatives of diphenylmethan~l.~~~Electron Diffraction.-A few years ago Shaffer, Schomaker, and Pauling 317proposed a method for the adaptation of punched card calculation techniques2Q4 A.AudsleyandF. R. GOSS, J., 1950, 2989.2Q6 P.G. Edgerley and L. E. Sutton, J., 1950, 3394.2Q(r K. B. Everard and L. E. Sutton, J., 1951, 16.sS7 H. Koford, L. Kumar, and L. E. Sutton, J., 1951, 1790.2Q8 P. G. Edgerley and L. E. Sutton, J., 1950, 1019.PQQ W. Baker, W. D. Ollis, and T. S. Zeelley, Nature, 1949,164, 1049; J., 1951, 201.300 R. J. W. Le F h r e and W. Worth, J., 1951, 1814.3O1 P. E. Fielding and R. J. W. Le FBvre, J., 1951, 181 1.302 E. Fischer, J . Chem. Phys., 1951, 19, 395.303 K. B. Everard, L. Kumar, and L. E. Sutton, J., 1951, 2807; K. B. Everard andL. E. Sutton, J., 1951, 2816, 2817, 2818, 2821, 2826.304 H. H. Giinthard and T. Gaumann, Helv. Chim. Acta, 1950, 33, 1985.305 H. A. Smith and L. E. Line, J . Amer. Chem. SOC., 1950,72, 5434.*O6 E. L. Alpen and W.D. Kimler, ibid., p. 5745.3O7 P. E. Brown and T. de Vries, ibid., 1951,73, 1811.30* J. H. Gibbs and C. P. Smyth, ibid., p. 515.C. C. Woodrow, M. Carmack, and J. G. Miller, J. Chem. Phys., 1951,19,951.310 R. G. Charles and H. Freisen, J . Amer. Chem. Soc., 1951, 73, 5223.311 C. L. Angyal, G. A. Barclay, A. A. Hukins, and R. J. W. Le FBvre, J., 1951,2583.312 E. G. Cowley, Nature, 1951, 168, 705.s13 M. Kubo, T. Nozre, and Y. Kurita, ibid., 1951, 167, 688.314 C. S. Copeland and M. W. Rigg, J . Amer. Chem. SOC., 1951,73,3584.916 C. G. Le FBvre and R. J. W. Le FBvre, J., 1950, 3373.316 D. Cleverdon and J. W. Smith, J., 1951, 2321.817 P. A. Shaffer, V. Schomaker, and L. Pauling, J . Chem. Phy8., 1946,14,669.Xtereochemicul applications.GeneralMCDOWELL : MOLECULAR STRUCTURE.37to electron-diffraction computations. Recently Amble, Anderson, andVierwoll318 have devised yet another method using this technique for cal-culating radical distributions in electron-diffraction studies. These pro-cedures enable a great saving of labour t o be made; e.g., Amble, Anderson,and Vierwoll state that certain calculations which required about 25 hours'work on an electrical calculating machine can be done in 1 Q hours by thepunched card method. It thus becomes possible to compute more accuratelyintensity- and radial-distribution curves. In the case of a compound whosestructure is difficult to determine unambiguously from a few assumed models,it should be possible by the punched card technique to include many moremodels and so enable a more thorough interpretation of the diffraction data.The punched card technique has recently been used in the calculation ofthe radial-distribution function for 1 : 1 : 1 -trifluoropropyne.319 Mostelectron-diffraction data have been obtained by using intensity- and radial-distribution functions of the type originally introduced by Pauling andBr0ckway.3~~ Recently, however, several workers have used more elaboratedistribution functions of the type.. . ?P- rD(r) = C I(q) exp (-aq2) sin-p mas.p = l , 2 . . . 10This form of radial-distribution funct'ion wa.s first used by Stosick321 andby Degard and S~hornaker.~~~ A theoretical derivation of this form of thefunction was later given by Debye ; 323 and Vierwoll 324 has recently discussedthe advantages achieved by the use of such a function.In general it may besaid that the inclusion of the term exp( - up2) makes interference effects dueto thermal motion of the atoms less conspicuous and tends to remove falsepeaks, particularly at large values of q. Consequently the values ob-tained for bond lengths, etc., tend to be more accurate. Recent structureswhich have been studied by using the above type of radial-distributionfunction are : acetyl chloride, bromide, and 1 : 1 : 1-trifluoro-propyne 319 and diborane 326 (see below).Mackle and Sutton 327 find that the radial-distribution curves for acet-aldehyde and crotonaldehyde furnish evidence for the coexistence of planarand s-cis- and s-trans-isomers in both compounds.The same authors 328have re-examined carbon suboxide by the electron-diffraction method and318 E. Amble, P. Anderson, H . Vierwoll, Acta Chim. Scand., 1951, 5, 931.310 J. N. Shoolery, R. G. Shulman, W. F. Sheehan, V. Schomaker, and D. M. Yost,320 L. Pauling and L. 0. Brockway, J . Amer. Chem. Soc., 1935,57, 2684.321 A. J. Stosick, ibid., 1939, 61, 1130.322 C. Degard and V. Schomaker, quoted by P. W. Allen and L. E. Sutton, see ref.325 ; C. Degard, Bull. SOC. roy. sci., Lidge, 1938, 13, 770.323 P. Debye, J . Chem. Phys., 1941,9,55.324 H. Vierwoll, Acta Chim. Scand., 1947, 1, 120.326 P. W. Allen and L. E. Sutton, Trans. Faraday SOC., 1951, 47, 236.326 K. Hedberg and V. Schomaker, J . Amer. Chem. Soc., 1951,73, 1482.327 H.Mackle and L. E. Sutton, Trans. Paraday SOC., 1951,47, 691.s2s Idem, ibid., p . 937.J . Chem. Phys., 1951,19, 136438 GENERAL AND PHYSICAL UHEMISTRY.have tested certain nonlinear models but conclude that their results indicatethat appreciable deviation from linearity is unlikely.Diborane has been the subject of an extensive investigation by Hedbergand Schomaker326 who have also re-studied ethane. They were able toeliminate the ethane model for diborane and confirm the bridge structure forthis compound, the results for which are : <Hbond-B- -Hbond = 121-5 &= 1.334 & 0.027 A.Davies and Thomas 329 have examined various models for the carboxylgroup in the light of known electron-diffraction data and conclude that astructure with rl = r(C=O) = 1.239 b; rz = r(C-0) = 1.402 andO-C-0 = 125.25" provides an acceptable representation of both electron-diffraction and infia-red and Raman spectroscopic data.Other compounds which have been studied include germanium tetra-fluoride,330 1 : l-dichloro- and 1 : l-dibr0mo-ethane,3~~ halogenated meth-anes,3a2 p e n t a b ~ r a n e , ~ ~ ~ and methyl and ethyl Studies of difiac-tion of electrons by thin liquid films of silicones, hydrocarbons, and othercompounds have been made.3357.5" ; B- B = 1.770 & 0.013 A; B-Hbond = 1.187 & 0.03 A ; B-HbridgeAC. A.McD.3. THE MECHANISM OF CHEMICAL CHANGE.The study of the mechanism and kinetics of chemical reactions is of vitalimportance to the essential understanding of the fundamentals of bothstability and reactivity, and in the many fields of the application of chemistrysuch as hydrocarbon cracking and synthesis, combustion, high polymersand plastics, and explosives.It is evident from the volume of work beingpublished that interest in this field is increasing. In writing this Reportit is our intention to refer to the general trends and developments which aretaking place in reaction kinetic studies rather than to attempt to cover allpublications which have appeared during the year. The numerous studiesof the mechanism of organic and biochemical reactions in which it is nowbecoming more general to express rates in terms of order of reaction, fre-quency factor, and activation energy will not be summarised since this is doneelsewhere in this Report.Many of the different fields of experimentalapproach now overlap to a great extent, and where a common principle isinvolved, as for example in the study of radical reactions by thermal orphotochemical methods, the policy has been followed of grouping all in-329 M. Davies and W. 0. Thomas, Research, 1951, 4, 484; Discuss. Faraday SOC.,1950, 9, 333.330 A. D. Caunt, H. Mackle, and L. E. Sutton, Trans. Faraday Soc., 1951,47,943.a31 Y. Morino, M. Kimura, and M. Yamaka, J . Chern. SOC., Japan, 1949, 'SO, 449.332 M. Kimura, Chem. Research, Japan, 1951, 9, 53.333 K. Hedberg, M. E. Jones, and V. Schomaker, J. Amer. Chem. SOC., 1951,73, 3539.334 M. Kimura, J . Chem. SOC., Japan, 1950, 71, 18.335 C. W. Lufrey, F. S. Palubinskas, and L.R. Maxwell, J . Chem. Phys., 1951,19,217.336 W. Gordy, ibid., p. 792BAWN : THE MEUHANISM OF CHEMICAL CHANGE. 39vestigations under the general heading of the subject under study. Similarly,the section on isotopic effect refers only to those reactions in which the effectof isotopes on the rates has received attention and not to straightforwardtracer applications.Kinetics of Homogeneous Reactions.Although no new principles and theories have emerged recently, con-siderable progress has been made in the application of quantum theories tochemical reactivity, particularly in aromatic and conjugated systemswhere x electrons determine properties. In its application to saturatedmolecules and radicals quantum theory has not been so successful, but inLennard-Jones's new treatment by the method of equivalent orbitals (seep.11) we may have the beginnings of such an approach.As the knowledge of the mechanism of chemical reactions advances it isbecoming increasingly clear that in the majority of reactions the overallchange is built up of a series of elementary processes, each of which occurswith the minimum of atomic or electronic rearrangement. A large portionof the work carried out during the year has been devoted to the determina-tion of the detailed steps and of their kinetics. The results have beenformulated in terms of the familiar reaction velocity equations, and a con-siderable list of the frequency factors and activation energies of the elemen-tary reactions of atoms and radicals with one another and with moleculesmay now be compiled.2 This information forms the basis of the true under-standing of chemical reactivity, and certain generalisations regarding therelations between reactivity and structure have been formulated.For instance, in certain classes of bimolecular reaction a close parallelismhas been noted between the change in activation energy of the reaction( A E ) and the change in the bond dissociation energy (AD).For example,in the reaction of atomic sodium with a range of organic halides and thehomopolar reaction of halogen atoms with hydrocarbons,4 and in the hydro-gen abstraction reaction of the radical R0,- with unsaturated hydrocarbon^,^it has been found that the simple linear form AE = aAD is true.Thereactions of methyl radicals with 10 alkanes have been shown by A. F.Trotman-Dickenson to obey this relationship with a - &. A similarformulation for a series of atom amd alkyl radical reactions with hydrocarbonshas been suggested by Tikhomirova and Voevodskii who, expressing theirresults in the form AE = A - aAH, show that cc is a constant characteristicC. A. Coulson, Research, 1951, 4, 307; H. C. Longuet-Higgins, Proc. Boy. SOC.,1951, A , 20'7, 121.a M. G. Evans, Discuss. Faradtzy SOC., 1951, 10, 1 ; M. Szwarc and E. W. R. Shacie,J . Chem. Phys., 1951, 19, 1309.M. Polanyi and M. G. Evans, Trans. Paraday SOC., 1938,32, 1933; 1938,34,11.H. Steiner and H. R. Watson, Discuss. Faraday SOC., 1947,2,88.J . L. Bolland, Quart. Reviews, 1949,3, 1.A.F. Trotman-Dickenson, Discuss. Farachy SOC., 1951,10, 112.V. V. Tikhornirova and N. N. Voevodskii, Doklady Alcad. Nauk. S.S.S.R., 1951,79, 99340 CENERAL AND PHYSICAL CHEMISTRY.of each elementary type of reaction, e.g., H atom or CH, radical, whereas Ahas a characteristic value for the series. Extensive measurements by E. C.Kooyman * show that in the case of hydrogen extraction from hydrocarbonby the CC13 radical is largely determined by the heat of reaction.The transition-state treatment of reaction velocity is based on the assump-tion that the reaction does not disturb the Maxwell-Boltzmann equilibriumdistribution to an appreciable extent. This point has been doubted by somekineticists, although theoretical studies have shown that the error in thefailure to attain equilibrium is probably small.A new approach to thisquestion has been made by I. Prig~gine,~ using the modern theory of gases,and he has concluded that the equilibrium theory is justified for reactionsoccurring without heat change. For exothermic reactions the equilibriumis perturbed and this increases the measured rate. The reverse is true withendothermic reactions, and both of these effects vanish when a sufficientamount of inert gas is present in the reaction system. The perturbationeffects are in any case small and will not change the rate by an appreciablepercentage. It may, therefore, be assumed that the transition state theoryis in most cases satisfactory.Bond-dissociation Energy Measurements.*-Several new determinations ofbond-dissociation energies have been made which are of importance tochemical kinetics.A direct determination of the heat of dissociation offluorine lo from equilibrium pressure measurement gives AE = 37-7 & 0.4kcal. (759-1115' K), a value close to that deduced from other considerations.llThe successful determination of the mechanism of the thermal andphotobromination of methane and ethane gave reliable estimates of theC-H and C-C bond dissociation energies in these molecules. The homo-geneous photo- and thermal bromination of neopentane has now been foundto proceed through an analogous atom and radical mechanism,12 and leadsto a value of the C-H bond dissociation energy in neopentane of 95.5 kcal.,some 6 kcal.lower than in methane and 3 kcal. lower than in ethane.Calculation from the appearance potential data in the dissociation ofmethane by electron impact l3 leads to a value of D(CH-H) in methyleneof 88 kcal./mole or less than 93 kcal. depending on whether one assumesD(CH,-H) in methyl as 92 kcal./mole or <87 kcal./mole.By a similar method C. A. McDowell and J. W. Warren l4 conclude thatthe upper limit to D(CH,-H) is 3.45 5 0.2 e.v. and that D(CH-H) 3-4 & 0-3e.v. The appearance potentials of C,H,+, C,H,+, C,H,+, and C,H,+ in theI. Prigogine, J. Phys. Colloid Chem., 1951,55, 765.* E. C. Kooyman, Discuss. Paraday SOC., 1951,10, 163.10 R. N. Douscha, J . Chem. Phys., 1951,19,1070.l2 E. I. Hormats and E. R. van Artsdalen, J. Chem.Phys., 1951,1Q, 778.l4 C. A. McDowell and J. W. Warren, Discuss. Farachy Soc., 10, 26.* In Ann. Reports, 1950, 4'7, 35, the value of h 0 - 0 ~ ascribed to Walsh was incor-rectly quoted. Walsh actually deduced DRO-OH = 56 kcal., in agreement with deter-minations from other sources and the value of 64 kcal. quoted referred to the 0-0 bondenergy in H,O,.l1 Ann. Reports, 1950,47,24.F. H. Field, ibid., p. 793BAWN : THE MECHANISM OF CHEMICAL CHANGE. 41mass spectra of a number of branched alkanes have been measured byStevenson 14a which, with the appropriate thermochemical data, lead toD(C,H,-H) = 4.07Several other new determinations in which the bond dissociation energyis equated to the activation energy of a unimolecular dissociation will bereferred to in the following section.First-order and Unimoleculaz Reactions.-The understanding of uni-molecular reactions has for some time occupied an important place in reactionkinetic theory, and although many supposedly unimolecular decompositionshave now been shown to be chain reactions, yet several new examples havebeen reported.On the theoretical side, S. W. Benson l5 has shown thata discrepancy of lo3 exists between the frequency factor applicable to anabsolute reaction rate theory and those consistent with the Lindemanncollision hypothesis. He criticises the absolute rate theory on the groundsthat it over-simplified the situation by assuming that the act of decom-position of a complex molecule can be described in terms of the rupture ofthe single bond which is associated with the normal co-ordinates.M.Szwarc,l6 on the other hand, from a survey of a number of dissociationprocesses in which a single bond is broken, all having frequency factorsbetween 1012 and 1014 sec.-l, shows that in a series of similar decompositionssuch as the substituted benzyl bromides, the frequency factor is not affectedby the molecule as a whole but by the character of the reacting centre. Heconcludes that the rate of flow of energy inside the molecule is not therate-determining step.F. J. Stubbs and Sir Cyril Hinshelwood,17 from kinetic studies of thethermal decomposition of the paraffinic hydrocarbon and the observedvariation of activation energy with pressure, conclude that in a complexmolecule there may be kinetically different modes of activation, correspond-ing to different relations between total energy in the molecule, energy in thecritical location, and the decomposition probability of the energised molecule.The normal theory of unimolecular decomposition may need amplification toexplain their observation and the authors suggest an approach to this problem.An interesting example of a true unimolecular reaction has been foundin the thermal dissociation of acetic anhydride into keten and acetic acid 18which occurs over the temperature range 280-650" according to the rate lawk = 1.10l2 ea4 5001RT sec.-l.Several independent studies have been made ofthe first-order dissociation of the simple nitroalkanes,lg it being agreed thatthe initial process is the breaking of the R-NO, bond.Further studieshave also been recorded of the first-order dissociation of aliphatic and aro-0.1 e.v., and D(C,Hgkrt--H) = 3.88 & Q.1 e.v.140 D. P. Stovenson, Discuss. Faraday Soc., 10, 35.1s S, W. Benson, J . Chem. Phys., 1951,19, 802.16 M. Szwarc, J . Phys. Colloid Chem., 1951, 55, 939; M. Szwarc and C. H. Lieght,1 7 F. J. Stubbs and ( S i r ) Cyril Hinshelwood, Discuss. Paraday SOC., 1951,10, 129.18 M. Szwarc and J. Murawski, Trans. Paraduy SOC., 1951,47,269.10 T. L. Cottrell, T. E. Graham, and T. J. Reid, ibid., p. 584; J. L. Hillenbrand andM. L.Kilpatrick, J . ChemPhys., 1951,19,381; C.Frejacques,Compt.rend., 1950,231,1061.Nature, 1951, 16'9, 48642 GENERAL AND PHYSICAL CHEWTRY.matic bromides.20 In all these cases the frequency factor appears to benormal and the observed activation energy is assumed to represent the heatof dissociation of the bond which is ruptured.For a series of substitutedbenzyl bromides the effect of substituents, in sharp contrast to ionic reaction,is very small.20 The decomposition of propylene 21 has also been shown tobe a first-order homogeneous reaction, the primary process most probablybeing C,H, CH, + C2H2*. Although the thermal decomposition ofethylene oxide 22 is approximately of first order, the rate at 400" is reducedto 40% of its normal value by the addition of propylene, a known chain-stopping substance. The activation energies of the uninhibited and of theinhibited reaction are 57.4 and 52.7 kcal.jmole, respectively.Continuing their investigation of the kinetics cif dehydrochlorinationreactions, Barton and his co-workers 23 have reported that the decompositionreactions of 1 : 1 : 2 : 2- and 1 : 1 : 1 : 2-tetrachloroethanes and 2 : 2'-di-chlorodiethyl ether, although all homogeneous and obeying a first-orderrelationship, are of the radical-chain type. m-Propyl chloride and n-butylchloride on the other hand have been shown to be unambiguous examples ofunimolecular decompositions.The pyrolysis of dibenzyl 24 has been discussed by C. Horrex and S. E.Miles in terms of the primary dissociation into benzyl radicals. The first-order reaction constant obeyed the relationship k = ed8 W'RT and theenergy of activation was assumed to represent the central C-C bond dissoci-ation energy.This was shown to be consistent with a resonance energy of24.5 kcal. for the benzyl radical.The extent to which the surface enters into the mechanisms of thermaldecompositions is one of the prominent and puzzling questions which cannotalways be satisfactorily answered. Conditions of experiment determinethe effect of surface and it is generally agreed that it is in the lowest tem-perature range in which the reaction rate can be measured that the surfaceeffect is important. At higher temperatures the reaction may becomeessentially homogeneous and there may well exist a transition region betweenheterogeneous and homogeneous types in which reaction chains may start atthe surface and go out into the body of the gas and are stopped a t the surface.F.0. Rice and K. F. Herzfeld 25 have developed a kinetic expression for thistype of reaction and show that much information may be obtained from astudy of the effect of surface : volume ratio. The thermal decompositionof nitric acid vapour 26 is heterogeneous at low temperatures but is pre-20 C. H. Leigh, A. H. Sehon, and M. Szwarc, Proc. Roy. SOC., 1951, A , 209, 97; A.MaccolI and P. T. Thomas, J . Chem. Phys., 1951,19, 977.8 1 K. U. Ingold and F. J. Stubbs, J., 1951, 1749.28 K. H. Mueller and W. D. Walter, J . Amer. Chem. SOC., 1951, 73, 1458.2s D. H. R. Barton and K. E. Howlett, J., 1951,2033; D. H. R. Barton, A. J. Head,*4 C. Horrex and S. E. Miles, Di8Cus8. Furuduy SOC., 1951, 10, 187.25 F.0. Rice and K. F. Herzfeld, J . Phya. Colloid Chem., 1951,55,975.86 H. C. Johnston, L. Foerning, Ya Sheng, and G. H. Messerly, J . Amer. Chem. SOC.,and R. Williams, ibid., p. 2039.1951, 73, 2319BAWN: TEE MECHANISM OF CHEMI0A.L CEUNQE. 43dominantly a fast homogeneous first-order reaction a t about 400°, the initialreaction being decomposition to nitrogen peroxide and a hydroxyl radical.The initial process in the pyrolysis of diborane 27 has been shown to be thereaction B,H, -> 2BH,, followed by reaction between BH, and unreacteddiborane to give a series of intermediate products. The homogeneousdecomposition of dioxalan28 does not conform to any simple order and re-action seems to follow two courses : C3H,O,---r CH,O + CH,*CHO orCO, + C,H, + H, a t approximately equal rates.The inhibition by nitricoxide and propylene indicates the occurrence, at least in part, of a radicalchain.L. A. Wall and W. J. Moore z9 showed that in the pyrolysis of 50 : 50mixtures of ethane and hexadeuteroethane at 3 10-600" extensive isotopemixing occurs in the products and this was interpreted in terms of a free-radical mechanism. The nitric oxide-inhibited reaction showed decreasedisotope mixing. The fully inhibited decomposition of paraffinic hydro-carbon has been shown by Hinshelwood and his co-workers 30 to be a mole-cular rearrangement rather than a chain reaction. In these reactions theproportions of the hydrocarbons-methane, ethane, and propane-formed areindependent of temperature and pressure and the relative probability ofrupture decreases with distance from the end of the carbon chain. Methaneand ethane are the predominant saturated products, and it is suggestedthat rupture at a given linkage is associated with the electronic symmetryof these molecules.The extensively studied decomposition of nitrous oxide is of unusualinterest since it is the simplest molecule capable of unimolecular dissociationwhere activation is supplied by collision.Previous measurements made overa very wide range of concentrations have shown anomalies. These data havebeen critically examined by H. C. Johnston,31 who has shown that all diffi-culties are removed if the measurements are corrected for a heterogeneousfirst-order decomposition which is important a t low concentrations. Thedata thus corrected are those of a straightforward unimolecular reactionand satisfy the theory of Rice and Ramaperger, who assume four effectiveoscillators-which is the number of normal modes of vibration of the nitrousoxide molecule.The decomposition of dinitrogen pentoxide, which for a long time wasthought to be a unimolecular process, is now known to be a complex reaction,and the mechanism proposed by R.A. Ogg,32 which is consistent with first-order kinetics, has been largely substantiated by recent work. The reactionbetween dinitrogen pentoxide and nitric oxide, which was assumed to bethe rapid secondary step in the decomposition, has been further studied by27 J. K. Bragg, L. V. McCarty,andF.J. Norton, J. Amer. Chem. SOC.,~. 2134; R. P.2s W. B. Guenther and W. D. Walter, ibid., p. 2127.20 L. A. Walland W. J. Moore, ibid., p. 2840.30 K. U. Ingold, F. J. Stubbs and C. N. Hinshelwood,Proc. Roy. Soc., 1951, A , 208,285.31 H. C. Johnston, J. Chem.Phys., 1951,19,663. s8 R.A. Ogg,ibid., 1950,18,672.Clark and R. N. Pease, ibid., p. 21 3244 GENERAL AND PHYSICAL CHEMISTRY.Johnston and his co-workers 33 who have found that over 6 105-fold range ofpressure the initial reaction rate is that of the elementary unimolecularreaction N205 ---- NO, + NO,. Both the high-pressure first-order limitand the second-order limit of a unimolecular reaction have been attained.This investigation explains the anomalies long associated with the N,O,decomposition and a detailed analysis has been made by H.C. JohnstonNof the mechanism of four kinetic systems involving N,05, some of which havebeen extensively studied. He has shown that the kinetics may be expressedin terms of eight reactions which are believed to be the elementary steps :N205 + M T N205* + MN205* --- NO, + NO,N205* + M -r N,05NO, + NO, ---- NO + 0, + NO,NO + NO, --- 2N0, + 0 3 7 $- O,The central feature of these mechanisms is the rapid attainment of theequilibrium N,05 NO, + NO,, and this equilibrium constant and sevenof the eight reaction velocity constants have been evaluated. H. C. John-ston and H. C. Crosby35 have shown that the gas-phase reaction betweennitric oxide and ozone-NO + 0, .- NO, + 0, + 48 kcal., which is fasterthan 'the reaction between nitric oxide and oxygen-was of first order withrespect t o each of the reactants and obeys the rate law k: = 8.0 e-2500* 300'RTC.C.mole-lsec.-l. The rate was determined by measurement of the absorp-tion of light by the nitrogen dioxide, a method also employed by L. G.Wayne and D. Yost 36 t o follow the reaction between nitric oxide, nitrogendioxide, and water (NO + NO, + H,O --- ZHNO,). Half lives as short as0.014 sec. were observed, and the rate was kinetically consistent with amechanism involving termolecular collisions. A similar third-order lawwas confirmed by H. C. Johnston and L. W. Slentz 37 for the classical reactionbetween nitric oxide and oxygen. No trend in the rate constants was observedin going from high to low pressures.Isotopic EXects.-The relative rates of reactions of isotopes provide avaluable means both for studying mechanisms and for testing theories ofchemical kinetics.The study of the products of electronic bombardment of deuteratedhydrocarbons permits of the determination of both the number and thetypes of the various isotopic species present in a system, thus affording ameans of using stable isotopes for the study of homogeneous mechanisms.Also, the dissociation of a hydrocarbon into various fragments on electronbombardment is an example of a true unimolecular dissociation and onewhich throws light on the primary act of decomposition.The mass spectraof a number of deuterated methanes, ethane, and propane have been deter-33 R.L. Mills and H. C . Johnston, J . Amer. Chem. SOC., 1951,73, 938; H. C. Johnston34 H. C. Johnston, ibid.. p. 4542.35 H. C. Johnston and H. C . Crosby, J . Chem. Phys., 1951,19, 799.36 L. G. Wayne and D. Yost, ibid., p. 41.37 R. C. Johnston and L. W. Slentz, J . Amer. Chem. SOC., 1951,73, 2948.and R. L. Pirenne, ibid., p. 4763BAWN : THE MECHANISM OF CHEMICAL CELANGE. 45mined by D. 0. Schissler, S. 0. Thompson, and J. T u r k e v i t ~ h , ~ ~ who havegiven a quantitative explanation of the observed mass spectra of the deu-terated methanes. The isotopic effects in mass spectra of various isotopicpropanes and butanes have been attributed by D. P. Stevenson39 to thesmall differences in zero-point energy of the alternate dissociation products.Mass-spectra studies of the dissociation probabilities of chloroform anddeuteriochloroform 40 show that the probability of dissociation of the C-Hbond in CHCS is three times that of the C-D bond in CDCI,.The prob-ability of removing chlorine is only slightly affected by deuterium substitu-tion. The relative rates of the reactions of hydrogen and tritium hydridewith chlorine a t four temperatures have been measured by W. M. Jones 41and discussed in terms of the transition-state theory. The ratio of thespecific rate constants of H, and HT is R = 1-35 Zt: 0-03e552* 7/RT.Additional experimental data have been obtained on the fractionationof carbon isotopes in decarboxylation reactions.42 Comparison betweenexperimental results and theory of the absolute rate is still not entirelysatisfactory and much depends on the particular model selected for thetransition-state complex.Calculation of the equilibrium constants K p for the isotopic exchangereaction between methane and carbon tetrachloride (exchange 35Cl and37Cl) and for the reaction between H,O and D,S have been made by V.M.Tate~skii.~3 The ratio of the shift of the isotopic abundance of carbon andnitrogen isotopes in the solution equilibrium of hydrogen cyanide in aceticacid has been experimentally observed as 1-7 & 0-3 in close agreement withthe theoretical yield of 1.81.44The very high separation factor of 100 which can be realised in theadsorption and desorption of hydrogen on silicaat 20.37"~ isattributed to thetunnel effect .45Measurements by R.P. Bell and E. IF'. Caldin 46 of the velocities of thebase-catalysed decomposition of nitramide and partly deuterated nitramidein anisole show that quantum-mechanical leakage of the proton through theenergy barrier is not the controlling mechanism in the temperature range0-45". It is possible that this effect may be detectable at much lowertemperatures.E. Whalley4' has pointed out that the effect of separation of isotopesby thermal diffusion may cause serious changes of concentration in certain38 D. 0. Schissler, S. 0. Thompson, and J. Turkevitch, Discuss. Famday Soc., 1951,4o V. H. Dibelier and R. B. Bernstein, J . Chem. Phys., 1951,19, 404.41 W. M. Jones, ibid., p. 78.43 J. Bigeleisen and T. L. Allen, ibid., p.760; E. A. Evans and J. A. Huston, ibid.,43 V. M. Tatevskii, Zhur. Fiz. Khim., 1951, 25, 261.4 4 E. W. Becker and W. Vogell, 2. Physik, 1951,130, 124.4 5 P. Harteck and G. A. Milkonian, Naturwiss., 1950, 31, 450.4 6 R. P. Bell and E. F. Caldin, Trans. Furaduy SOC., 1951,47,60.4 7 E. Whalley, ibid., p. 816.10, 46. 39 D. P. Stevenson, ibid., p. 35.p. 1214; A. Roe and M. Hellman, ibid., p. 66046 GENERAL AND PHYSICAL CHEMISTRY.types of physical measurement. He has also shown *8 that it should bepossible to analyse three-component mixtures such as H2-HD-D, by partialseparation in a thermal diffusion column.Atom and Free-radical Reactions.-Recent advances in the analysis ofchain reactions have been made possible by the accurate determination ofthe concentration of the radical taking part in the rate-determining step ofthe reaction.In this way the rates of many inter-radical reactions as wellas of the reaction of radicals with molecules have been determined. Theseanalyses are based for the most part on the determination of the concen-tration of the active intermediate by using intermittent radiation to initiatethe reaction.A direct observation of the rate of recombination of iodine atoms hasbeen made by Davidson et al. 49 by dissociating iodine molecules in the presenceof inert gas by a short impulse of light, the iodine molecule concentrationbeing followed as a function of time by a photometric method. The value ofthe constant k in d[12]/dt = k[II2M at 25" was 4.5 x 109.The reaction of atomic hydrogen with acetylene 50 has been found to beof first order in the concentration of both atomic hydrogen and C,H2 at 17"and occurs with E = 1.5 kcal.and a steric factor of 4 x 10-4. A newmeasurement has been reported of the kinetics of the ortho-para-hydrogenconversion by hydrogen atoms.51 The results are shown to give betteragreement with the transition-state theory than with the collision hypo-thesis.The study of the bimolecular reactions of sodium atoms with the halogensand inorganic and organic halides has played an important part in thedevelopment of the general theory of chemical reactivity. The study ofthese reactions is still being actively pursued by the Manchester School and areview of the more recent work has been published by E.W a r h ~ r s t . ~ ~Many of the rates of reaction of elementary radicals with molecules havebeen reported as a quotient or ratio of rate constants. This arises becausethe result is usually obtained from the rates of competing reactions of thesame radical. Often the comparison is with the rate of recombination of theradical, and so an aecurate measurement of the recombinationrate is importantfor the evaluation of the absolute rates of many radical reactions. Usingthe rotating-sector technique in the photochemical decomposition of acetoneand dimethylmercury, together with an accurate measurement of themethane formed (as a measure of the methyl radical stationary concen-tration), R. Gomer and G. B. Kistiakowsky 53 deduce a rate constant forthe recombination of methyl radicals of 4.5 x 1013 C.C.mole-l sec.-l andE = 0 & 700 cal. regardless of the radical source. Using the photolysis48 E. Whalley, Trans. Faraday SOC., 1951, 47, 129.40 N. Davidson, R. Marshall, A. E. Marsh, and T. Carrington, J . Chem. Phys., 1951,60 J. R. Dingle and D. J. Le Roy, ibid., p. 1632.61 M. van Meersche, Bull. SOC. chim. Belg., 1951,60, 99.62 E. Warhurst, Quurt. Reviews, 1952, V, 44.58 R. Gomer and G. B. Kistiakowsky, J . Chem. Phys., 1961,19,86.19, 1311BAWN : THE MECHANISM OF CHEMICAL CHANGE. 47of diethylmercury as a source of ethyl radicals, K. J. Ivin and E. W. R.Steacie 54 have measured the rates of the reactionsC2H5+ C2H5 7 C2H4+ CgH6 . . - (1)The observed activation energy difference E,-E2 was 0-8 5 2 kcal.andE2 > 0.65 kcal./mole. The corresponding frequency factors were (1-57-12)x 1013 and (1.65-5.0) x 1013 mole-1 C.C. sec.-1 according to the limitingvalues of the activation energies selected.Much interest still centres on the magnitude of the steric factor of free-radical reactions. If the recombination rate of methyl radicals is taken as4-5 x 1013 mol-l C.C. sec.-1, then hydrogen abstraction reactions of methylradical with hydrocarbons and other molecules would have a steric factorof the order of 104.G5 The recombination of methyl radicals and iodineatoms has been examined theoretically by R. A. Marcus and 0. K. Rice,56who show that the steric factor of recombination and the effect of pressureon the rate mutually depend on the nature of the activated complex.Forvariously assumed complexes it is tentatively inferred that the collisionefficiency for recombination increases from ca. 0.001 to 0.01 as the pressureincreases from 20 mm. to infinity. Considerable information has nowaccumulated about the activation energies of methyl-radical reactions withsaturated and unsaturated hydrocarbons, ethers, and aldehydes, althoughthe facts are as yet insufficient for broad generalisations to be made.55, 66R. E. Dodd 57 has published full details of his work on the decompositionof acetaldehyde by intermittent illumination. The rate constants found forthe propagation and the termination reactions, k, and k,,CH3 + CH,*CHO 7 CH4 + CO + CH3 Ic2 1 k3CH3+CH3 7 C2H6CH3+CHO -/ CH4+COwere k, = 1012.8 f 042/Te-10 700 f 500/RT and k - 1013.8 f OSd&-SOO f 800/RT3 -mole-l C.C.sec.-l, both frequency factors corresponding to the maximumcollision frequency of a bimolecular reaction. The choice between thealternative termination reactions is uncertain although Dodd and J. D.Waldron 58 have since reported the formation of ethane in this reaction, andthis they regard as strong evidence for methyl-radical recombination as theterminating step.L. Bateman, J. L. Bolland, and G. Gee,S9 from a mathematical analysis64 K. J. Ivin and E. W. R. Steacie, Proc. Roy. SOC., 1951, A , 208, 25.66 R. Gomer and G. B. Kistiakowsky, J . Chem. Phys., 1951, 19, 8 5 ; E. W. R.Steacie and A. F. Trotman-Dickenson, J.Phys. Colloid Chem., 1951,55, 908; R. Gomerand L. M. Dorfman, J . Chem. Phys., 1951,19, 136.68 R. A. Marcus and 0. K. Rice, J. Phys. Colloid Chem., 1951,55, 894.67 R. E. Dodd, Trans. Faraday Soc., 1951,47, 56.68 R. E. Dodd and J. D. Waldron, Nature, 1951,167, 655.6D L. Bateman, J. L. Bolland, and G. Gee, Trans. Farday SOC., 1951, 47, 274; L.Bateman and G. Gee, ibid., p. 155 ; L. Bateman, G. Gee, A. L. Morris, and W. F. Watson,DbCW8. paTccda?/ BOG., 1961, 10, 25048 GENERAL AND PHYSICAL CHEMISTRY.and by measurements of the photochemical pre- and after-effects forolefinic oxidations at high and low oxygen pressures, have evaluated thevelocity constants of the propagation and termination reactions. Theresults agree with those determined by the sector techniquee6* By furtherrefinements of the experimental techniques the relative importance of thethree termination processes 2R, R + RO, and 2R0, to give non-initiatingproducts have been determined and it has been shown that cross terminationbetween unlike radicals is relatively more favoured in the more reactiveolefins .The vividly coloured free radical N’W-diphenyl-N-picrylhydrazyl, whichgives stable solutions in a wide range of organic solvents, reacts readily withfree radicals formed by thermal dissociation of peroxides and azo-com-pounds.The reaction is accompanied by a colour change and has beenused by C. E. H. Bawn and S. F. Mellish 61 to determine the rate ofdissociation of benzoyl peroxide and 2 : 2’-azobis(isobutyronitrile) .The kinetics of the autoxidation of aldehydes which have been deter-mined in several laboratoriesinitiation and propagation :RCHO 7R*CO* + 0, --i=-R.CO*O*O* + RGHO --i-support the following general mechanism forRCO* (photo; thermal; or metalion-catalysed initiation)} propagation R*CO-O*O-R*CO*O*OH + R*CO*I n the case of decanal H.R. Cooper and H. W. Melville 62 have used themethod of inhibitors and intermittent illumination to determine the velocityconstants of the various steps. The results support a radical-radicaltermination reaction. I n the trace-metal-catalysed autoxidation of acet-aldehyde, C. E. H. Bawn and J. B. Williamson63 have shown that theterminating step is the reaction of the RO,* radical with the peroxideformed.W. A. Waters and C. Wickham-Jones,6* from studies of theretardation of the autoxidation of benzaldehyde by m-cresol, conclude thatthe cresol acts as a chain-transfer agent and that chain termination involvesthe destruction of p-tolyl radicals, principally by dimerisation.Although the reaction CH, + H, -7 CH, + H has received much atten-tion in the past, since it is the simplest of the hydrogen-extraction reactionsof free radicals, the activation energy E , and the steric factor 8, for thereaction are still disputed. From a careful analysis of earlier work and fromrecent experimental results on the photolysis of dimethylcadmium in thepresence of hydrogen and the photolysis of acetone and acetaldehyde in thepresence of deuterium and an equimolar mixture of hydrogen and deuterium,R.D. Anderson, S. Davison, and M. Burton 65 conclude that E, = 13 kcal.6o L. Bateman and G. Gee, Proc. Roy. SOC., 1948, A , 195, 376, 391.61 C. E. H. Bawn and S. F. Mellish, Trans. Furuday SOC., 1951, 47, 1216.62 H. R. Cooper and H. W. Melville, J., 1951, 1984, 1994.63 C. E. H. Bawn and J. B. Williamson, Trans. Furuduy Soc., 1951, 47, 721, 735.64 W. A. Waters and C. Wickham-Jones, J., 1951, 812.* 6 R. D. Anderson, S. Davison, andM. Burton, Discuss. Faraduy Soc., 1951,10, 136BAWN: THE MECHANISM OF CHEMICaL CHANGE. 49and 8, = 10-2. E. W. R. Steacie and A. F. Trotman-Dickenson 66 have alsoreviewed the data on this reaction and conclude that the best work gaveE , = 8.8 kcal. and S1 = (4 & 2) x lo3.No satisfactory reason for theserious discrepancies in these conclusions is apparent.Quantitative radical chemistry has been recently extended by measure-ments of the reactivities of unsaturated hydrocarbons towards CCl, radicals.The photochemically induced reaction between bromotrichloromethane andcyclohexane 67 has been shown to occur according to the following mechanismCC1,Br + h v - CCl, + Br . . . . . (1)cc13-\-/ r\ + CC1,Br c7- CCl,-/-) -+ CC13 . . (3)/ Br >-E C l , ---- C,C&The activation energy and temperature-independent factor (7 x lo5) arelower than usual for addition reactions of this type. E. C. Kooyman68has measured the reactivity of 22 saturated and unsaturated hydrocarbonstoward the CC13 radical and has discussed the effect of structure on thereactivity of the a-methylenic groups.Polymerisation Reactions.-New determination have been made of therate constants of the polymerisation of styrene and methyl acrylate byusing the sector techniq~e.~~ Strong evidence was adduced for the ter-mination reaction by couRling of radicals rather than by disproportionation.A similar conclusion has been reached by F.R. Mayo, R. A. Gregg, andM. S. Matheson 70 from studies of chain-transfer measurements in thepolymerisation of styrene. The overall kinetics of the methyl-radicalinduced polymerisation of gaseous butadiene have been measured by D. MVolmanIf the condition for application of the sector technique, vix., the squareroot dependence of the rate on the intensity of the incident radiationis not satisfactory, then an alternative method of measurement ofthe concentration of active entities is necessary and several have beendeveloped by Melville and his co-~orkers.~~ The principle of some of66 E.W. R. Steacie and A. F. Trotman-Dickenson, J. Phys. CoEloid Chem., 1951,55, 908; J . Chenz. Phys., 1951,19, 163, 169.67 H. W. Melville, J. C. Robb, and R. C. Tutton, Discuss. Paraday Soc., 1951,10, 154.6 8 E. C. Kooyman, ibid., p. 163.M. S. Matheson, E. E. Auer, E. B. Bevilacqua, and E. J. Hart, J. Amer. Chem. SOC.,who deduces an activation of chain propagation of 2.6 kcal.1951, 73, 1700, 5395.'* F. R. Mayo, R. A. Gragg, and M. S. Matheson, ibid., p. 1691.71 D. H. Volman, J . Chem. Phys., 1951,19, 668.72 T.G. Majury and H. W. Melville, Proc. Roy. SOC., 1951, A , 205, 323,496 (dielectric-constant method); N. Grassie and H. W. Melville, ibid., 1951, A, 207, 288 (refracto-metric method) ; G. M. Burnett, Trans. Farday Soc., 1950, 46, 333 (dilatometry)50 GENERAL AND PHYS1CA.L CHEMISTRY.these methods is to follow the course of the reaction before the stationarystate is established, that is, before the rate of removal of radicals becomesequal to their production. Kinetics of the non-stationary state have beendeveloped, and in polymerisation reactions it has been found necessary, inorder to evaluate the kinetic lifetime of the radical, to discriminate in timeto 1 m-sec. and in reaction to one part in lo6 or lo7. Several ways have beenused to achieve this end in liquid phase systems, viz., measurement of changeof physical properties such as (1) volume change ; (2) refractive-indexchange (by interferometry) ; (3) dielectric-constant change.These veryelegant experimental developments, which have been used to measure thevelocity coefficients of polymerisation of styrene, vinyl acetate, methylacrylate, methyl methacrylate, and butyl acrylate, should be applicableto the study of non-stationary behaviour in many chain reactions in whichchange can be instigated by means of radiation.Polymerisation reactions can most conveniently be initiated by freeradicals formed by thermal and photo-dissociation of suitable organicmolecules or by electron-transfer processes upon which the important redoxinitiation method is based.A further development in the latter class ofreaction has been the use of ion-pair complexes Fe3+X-(X = OH, C1, N3,etc.) which on absorption of light undergo electron transfer, liberating thefree radical X,73 or by electron transfer from reducing ions such as c h r o m ~ u s . ~ ~A newer development has been the initiation of polymerisation by catho-dic reduction. Thus the polymerisation of methyl methacrylate can beinduced by electrolytic reduction of aqueous solutions of the monomer, andthe availability of the initiating hydrogen atoms seems to be correlated withthe cathodic overvoltage.75 Adsorption of hydrogen by certain metals isthought to be associated with a chemisorbed fib of hydrogen atoms, andmetals loaded with hydrogen either electrically or by chemisorption initiatepolymerisation, although the efficiency is low compared with the totalhydrogen released.76 The cathodic decomposition of formic acid at a plati-num surface also induces polymerisation, although only a small fraction ofthe formic acid decomposed is able to function as initiator.M. Kolthoffand L. F. Perstandig 77 have also demonstrated the initiation of polymerisa-tion by the electrolytic reduction of the peroxy-compounds hydrogenperoxide, potassium persulphate, and cumene hydroperoxide.Electron-transfer Reactions in Solution.I n recent years our understanding of the mechanism of electron-transferreactions has considerably increased owing largely to the increased experi-mental study of these reactions. These investigations fall into two broadgroups according as the process is a simple electron transfer between ions,73 M.G. Evans, M. Santappa, and N. Uri, J . Polymer Sci., 1951, 17, 243.74 F. S. Dainton and D. G. L. James, J . Chim. phyeique, 1951,48,1.75 G. Parravano, J . Amer. Chem. Soc., 1951,73, 628.76 Idem, ibid., 1950, 72, 5546.77 M. Kolthoff and L. F. Ferstmdig, J. PoZymer Sci., 1961, 6, 663BAWN: THE MECHANISM OF CHEMICAL CHANGE. 51e.g., Ce4+ + Fe++ - Ce+++ + Fe+++, or whether the transfer is accom-panied by the breaking of a homopolar bond such asFe++ + HO*OH -7 Fe+++ + OH- + OHThe former class of reaction has been extensively studied by the use ofradioactive isotopes, particularly when the exchange occurs between valencystates of the same element.New experimental investigations of the reaction of ferrous and ferricions with hydrogen peroxide 78 have revealed several new features incom-patible with the details of the Haber and Weiss chain mechanism.Thereaction of HO, with hydrogen peroxide, hitherto generally accepted, hasbeen shown to play no part in the reaction, and the oxygen evolution reactionis now ascribed to the interaction of HO, with Fe+++. Cupric ions have apronounced effect on the system. The general mechanism now proposedfor the ferrous ion reaction isFe++ + H,O, -% Fe+++ + OH- + OHFe++ + OH .-/ Fe+++ + OH-Fe++ + HO, - Fe+++ + H0,-Fe+++ + H02 -= Fe++ + 0, + HCu+ + Fe+++ -- Cu++ + Fe++H,O,+ OH - H2O + HO2CU++ + HO2 7 CU+ + 0 2 + H+The ratio of the velocity constants for the reaction of the OH radical has beenevaluated, and a more reliable velocity constant IC, for the initial reactionhas been given as k, = 4.45 x 108e9400'RT l.mole-lsec.-l.The kinetics of the ferric ion-catalysed decomposition have been deducedon the basis of the above mechanism. These lead to three different kineticexpressions depending on R, the ratio of the concentration of hydrogenperoxide and ferric ion.By experimental studies at high and low valuesof R it has been found that the results are, in general, in quantitative agree-ment with the above reaction mechanism, and the kinetics of some of theintermediate steps have been determined. The ferric salt-catalysed reactionhas also been discussed by V.S. Ander~en,'~ and his results are broadly inagreement with the above mechanisms.Kinetic measurements by J. H. Baxendale, H. R. Hardy, and L. H. Sut-cliffe 8o on the reactions of ferric ion with hydroquinol and ferrous ion withbenzoquinone indicate that the following reaction mechanism holds :Fe+++ + QH- =+ Fe++ + QHFe+++ + Q- + Fe++ + QValues of several of the individual velocity and equilibrium constants havebeen determined.1951, 47, 462, 591.QH =e Q-+H+W. G. Barb, J. H. Baxendale, P. George, and K. R. Hargrave, Tram. Faraduy Soc.,79 V. S. Andersen, Acta Chem. Scand., 1950,4, 914.J. H. Baxendale, H. R. Hardy, and L. H. Sutcliffe, Tram. Faraday SOC., 1951,47,96352 UENERAL AND PHYSICAL CHEMISTRY.J. W. L. Fordham and H. L. Williams have studied the decompositionof cumene hydroperoxide, and the primary mechanism was shown to bethe formation of the radical C,H,*CMe,*O* which splits off CH, to giveacetophenone.The rate constants of the primary reaction as obtainedfrom kinetic studies in the presence of oxygen, viz., -d[Fe++]/dt = 2kl[Fe++][RO*OH], can be represented by the equation k, = 3-9 x lO9e-l10O0/RT1.mole-l sec.-l. In the presence of acrylonitrile and in the absence of oxygenit has been found that the ferrous iron disappears by a bimolecular reactioninvolving Fe++ and the hydroperoxide, and the rate constant obtainedagrees closely with that quoted above.I n dilute aqueous solutions of acrylonitrile the oxidation of Fe++ by per-sulphate occurs according to the equationFe++ + S,O,-- -+ Fe+++ + SO,-* + SO,--and with a rate at infinite dilution given by ko = 1.0 x 1011e-12000/RTl.mole-lsec.-l. This reaction has also been studied by Kolthoff et aZ.,82who find that the reaction induces the oxidation of ethyl alcohol toacetaldehyde. Halogen ions and acrylonitrile suppress the inducedoxidation.H.L. Allen 83 has determined the kinetics of the oxidation of oxalateion by persulphate catalysed by silver. A trace of cupric ion has been foundto have a pronounced catalytic effect.P. Davis, M. G. Evans, and W. C. E. Higginson 84 have presented evidencethat the NH, radical is the intermediate in the reduction of hydroxylaminein acid aqueous solutions and postulate that the primary reduction reactionwith metal ions isMn+ + HO*NH3+ 7 M'n+l'+ + NH, + (OH- + H+)The NH, radicals have been shown to initiate vinyl polymerisation and toattack various organic substrates.The rate-determining step in the decomposition of water by cobalticions has been shown to be the electron-transfer reaction between cobalticand hydroxyl ions, and the kinetics of this reaction have been workedThe cobaltic ion has been shown to be a very powerful oxidising agent underconditions in which the water reaction is suppressed, and the kinetics of thecobaltic ion-initiated oxidation of formic acid, formaldehyde, and severalalcohols have been determined.86 I n all cases the rate-determining processwas shown to be the electron-transfer process leading to the formation offree radicals.The dynamic equilibrium between the oxidised and reduced form of(+)-Os(dipy),++ and (-)-Os(dipy),+++ as measured by change of optical81 J.W. L. Fordham and H. L. Williams, J. Arner. Chem. Soc., 1950,72,4465 : 1951,73, 1634.82 I. M. Kolthoff, A. I. Medalia, and H. P. Raaen, ibid., p. 1733.83 H. L. Allen, ibid., p. 3589.84 P. Davis, M. G. Evans, and W. C. E. Higginson, J., 1951, 2563.86 C. E. H. BawnandA. G. White, J., 1951,331. Idem, J., 1951, 339, 343BAVirN: THE MECHANISM OF CHEMICAL CHANGE. 53rotation showed that the exchange rate was very rapid at room temperat~re.~~The rate was greater in 2~-ammonium sulphate solution than in acetone-water mixtures, and these effects were related to the dielectric constant ofthe medium. Mixtures of solution of both ions showed that no interactionabsorption occurred in the region 4000-7000 8.Isotopic Exchange Reactions.-Among the newer tools for studying therates of mechanism of chemical processes, the application of radioactiveisotopes has been wide and fruitful.In particular, this method is mostvaluable for studying the kinetics of the transfer of electrons between theions of a metal in different oxidation states. Such studies give informationnot only on factors determining reaction rates but also on oxidation-reduc-tion reactions in general and on the nature of ionic species existing in solution.The exchange between Tl+ and Tl+++ was shown Po be a first-orderreaction,88 the rate of which decreases as the hydrogen-ion concentrationdecreases. It was established that the higher-valency species undergoingexchange was TIOH++, the activation energy and entropy of the reactionbeing 14-7 kcal.and 32 cal.deg. /mole, respectively. The exchange reactionbetween the two oxidation states of cerium 89 also follows a first-order lawbut in this case the rate depended on the Ce4+ concentration as well as onthe nature of the medium. The results were tentatively interpreted interms of an excited electronic state of cerous cerium. Using spectro-photometric and radiochemical methods, C. I. Browne, R. P. Craig, andN. DavidsongO have shown that the coloured intermediate species in thereactions between Sn++ and Sn++++ is a dimeric complex. The homogeneousthermal exchange in hydrochloric acid obeyed the rate lawR = [Sn++][Sn++++] x 4.5 x lO7e-10 800'RT Lmole-lmin.-l.The second-order kinetics was consistent with the assumption that the slowstep in the reaction was the electron transfer.The photochemical reaction 91had a quantum efficiency of 0-2 and was brought about by light absorbed bythe dimeric complex. The electron transfer between Fez+ and Fe3+ in 0 . 4 63.0M-perchloric acid takes about one hour to go t o c~rnpletion.~~Several investigations have been made of the exchange between man-ganese compounds of different ~ a l e n c y . ~ ~ , 949 95 Adamson 95 and Zimmermanand Libby,94 using radioactive manganese, have shown independently thatthe exchange reaction between manganate and permanganate is too fast tobe measured in alkaline solution, and conclude that it is the electrons ratherthan the manganese atoms which are exchanged.In acid solutions a com-8 7 F. P. Dwyer, E. C. Gyarfas, and D. P. Mellor, Nature, 1950,166, 746; F. P. Dwyer8 s G. Harbottle and R. W. Dodson, J . Amer. Chem. SOC., 1951, 73, 2443.90 C. I. Browne, R. P. Craig, and N. Davidson, ibid., p. 1946.O1 R. P. Craig and N. Davidson, ibid., p. 1951.O2 R. H. Betts, H. S. A. Gilmour, and R. H. Leigh, ibid., p. 4978.O3 P. Jordan, Helv. Chim. Acta, 1951, 34, 699.n4 L. Zimmerman and W. F. Libby, J . Amer. Chem. Soc., 1950,72, 3808.OS A. W. Adamson, J . Phys. Colloid Chem., 1951,55, 293.and E. C. Gyarfas, ibid., p. 481.J. W. Gryder and R. M. Dodson, ibid., p. 2890li4 GENERAL AND PHYSICAL CHEMISTRY.plete but measurable exchange reaction occurred.Heavy-metal cations insolution exist in the hydrated form, and by the use of oxygen isotopes J. P.Hunt and H. Taube 96 have shown that the exchange of the hydration shellof A13+, Ga3+, and Th4+ is complete within 3 min. in acid solution at 25".The rate of exchange with (2113' and Fe3+ is slower, but with all cations thedistribution of the oxygen isotopes in the final solution is noticeably differentfrom random, the cation showing greater affinity for l 8 0 .Radioactive sulphur has been used in studying the mechanism of thereaction of sulphur and the exchange between the many anionscontaining sulphur, and between colloidal sulphate precipitates and sulphateand thiosulphate ions.98 The transfer of the outer sulphur atoms of S,O,--to SO,-- occurs readily a t 60-100" 99 according to the bimolecular law,k = 2.3 x 106e-14 500/RT l.mole.-l sec.-l.The exchange occurs by collisionof the ions to give rO-S-S-S-O] as the activated complex. Studies ofacid-base exchange reactions of (NMe,),S,O, and SOC1, and SOBr, in liquidsulphur dioxide show that the base yields SO3-- and the acids SO++.lOoThe proton-exchange reaction between ammonia and ammonium ionin liquid ammonia has been found to be relatively fast.101 Kinetic studies ofthe slower exchange reaction between D20 and NH,+ have shown that therate is determined by the hydrolysis of the ammonium ion to the rapidlyexchangeable free amrnonia.lo2The readily available radioactive halogens, bromine and iodine, havebeen used extensively to study the exchange reaction between halogen ionand alkyl and aryl halides in various solvents.The kinetics of the followingreactions have been measured : exchange between (a) propyl bromide andsodium bromide in alcoholic solution,lo3 (b) inorganic iodides and butyliodide in methyl cyanide,lo4 (c) lithium chloride and p-nitrobenzyl chloridein dioxan-water s0lutions,~0~ (d) ally1 iodide and sodium iodide,lo6 (e)iodine ion and iodobenzene, and m- and piodonitroben~ene,~07 (f) bromideion and substituted phenyl and benzyl bromides in anhydrous ethylenediacetate,los (9) iodine and derivatives of pyridine co-ordinated unipositiveiodine complexes of the general type IPyC0,R in pyridine.log0 0 - 4L o 096 J.P. Hunt and H. Taube, J . Chem. Phys., 1951,19, 602.9' R. Muxart, Compt. Tend., 1940,231, 1489.99 D. P. Ames and J. E. Willard, J . Amer. Chem. SOC., 1951,73,164.R. Muxart, B. Boxarden, P. Daudel, and P. Winger, J . Chim. physique, 1950,47,606.loo R. E. Johnson, T. H. Morris, and J. L. Huston, ibid., p. 3052.101 C. J. Nyman, Si Chang Fung, and H. W. Dodgen, ibid., p. 1033.102 A. I. Brodakii and L. V. Sulema, Doklady Akad. Nauk., U.S.S.R., 1950,74, 513.Io3 V. B. Miller, M. B. Neiman, and Y. M. Shapovalov, ibid., 75, 419.104 G. W. Hodgson, K. G. V. Evans, andC. A. Winkler, CanadianJ. Chem., 1951,29,60.106 J. W. Hackett and H. C. Thomas, J . Amer. Chem. SOC., 1950, '72, 4962.Io6 S.May,P.Daudel, J. Schottey,M. Sarauf,andA.Vobaure, Compt.rend., 1951,232,727.107 A.M. Kristjanson and C. A. Winkler, Canadian J . Chem., 1951, 29, 154.lo* S. Sugdenand J. B. Willis, J., 1951, 1360.109 J. Kleinberg and J. Sattizahn, J . Amer. Chem. SOC., 1951, 73, 1865BAWN: THE MECHANISM OF CHEMICAL CHANGE. 55W. H. Johnston and W. F. Libby have studied the gaseous exchangereactions between chlorine and hydrogen chloride. The reaction is pre-dominantly heterogeneous at room temperature but the photochemicalreaction is very rapid, showing that chlorine atoms exchange rapidly withboth hydrogen chloride and chlorine molecules.Ionic Reactions in Solution.There has been much discussion lately concerning medium effects onreaction kinetics in the liquid phase. The theory of primary salt effects onreaction rates put forward by Brernsted in 1922 has been generally acceptedand shown to be applicable to all types of ionic reactions. Exceptions tothe theory have usually been found on closer examination to be due tosome peculiarity of the system being studied.In a paper on the rates ofionic reaction in aqueous solution, A. R. Olson and R. T. Simonson 111have re-examined the influence of salt on the reaction between COB~(NH~)~++and Hg++ and have concluded that in a reaction between ions of the samecharge, the rate is not dependent on the ionic strength of the solution butthat the significant effect is the concentration and character of the ions ofsign opposite to that of the reactants. A relationship proposed by the authorsnot based on ionic strength but on the concentration of ions of oppositesign to the reactants has been applied to other reactions.This new pointof view will need careful study. There is no doubt that in certain casesspecific effects may be more important than general interionic attraction, butbefore a change of viewpoint can be accepted, a very careful considerationwill have to be given to the many reactions which have been successfullyinterpreted in terms of the theory of salt influence being determined by thesquare-root of the ionic strength.E. A. Guggenheim and L. A. Wiseman 112 have made a careful and de-tailed study of the magnitude of kinetic salt effects in the inversion ofsucrose. They find that sucrose at a concentration of 30 g./L is hydrolysedby single strong acids at 24-68' -+ 0.05" and at molarities up to 0.2 accordingto a fist-order law and that the rate constant is related to the molarity of theacid by the formula E , (min.-l) = 6.95 X 103c.10B~c where Bj is a constant deter-mined by the anion.In mixed strong acids E , (min.-l) = 6.95 x 103C,.10WCj,where C , is the molarity of the strong acid and Cj the molarity of eachanion. The results were shown to be in accordance with Brransted's principleof specific interaction. In solutions containing bi-univalent and ter-univalentsalts a further negative salt effect of the multivalent cations was observed andthis increased with their valency. This effect indicated that the principle ofspecific interaction became detectably inaccurate a t high ionic strengths.The acid-catalysed reaction between hydrogen peroxide and iodide ions,which had previously been reported as having no salt effect and was thusregarded as anomalous from the standpoint of the Brernsted theory, has been110 W.H. Johnston and W. F. Libby, J . Amer. Chem. SOC., 854.111 A. R. Olson and R. T. Simonson, J . Chern. Phys., 1949,17,1167.112 E. A. Guggenheim and L. A. Wiseman, Proc. Roy. SOC., 1950, A, 205, 1756 QENERAL AND PHYSICAL CHEMISTRY.re-examined by F. Bell, R. Gill, D. Holden, and W. F. K. Wynne-Jones,l13who show that at low concentration the reaction obeys the Bronsted theory,and the results, which agree with those of previous workers, indicate aprimary salt effect in dilute solution. The result implies that for reactionsbetween ions of opposite sign a decrease in velocity constant occurs withincrease in ionic strength.R.P. Bell and G. M. Waind 114 have shown from kinetic measurements ofthe alkaline hydrolysis of carbethoxymethyltrimethyIammonium iodidethat the reaction shows a primary salt effect and is retarded by calcium andbarium ions. This retardation is accounted for by the formation of CaOH+and BaOH+, and the results derived agree quantitatively with the dissoci-ation constant of CaOHf obtained in other ways.The electrolytic effects of sodium, chlorine, calcium, strontium, andlanthanum ions on the kinetics of the bromoacetate-thiosulphate reactionin a propyl alcohol-water mixture of dielectric constant 30 have beenmeasured by F. G. Ciapetta and H. M. T0m1inson.l~~ They observed amaximum in the velocity constant with bivalent and tervalent cations, andthe large electrolyte effect of lanthanum ion was ascribed to ion-associationeffects.P.A. Long, W. F. McDevit, and F. B. Dunkle 116 have made a compre-hensive study of salt effect on the hydrolysis of y-butyrolactone in dilutesolution, and report measurements of the effect of salts on (a;) the hydrolysisand equilibrium between the lactone and its hydrolysis product y-hydroxy-butyric acid, ( b ) the activity coefficient of both product and reactant asdetermined by distribution experiments, (c) the rate of the acid-catalysedhydrolysis of the laclone, and ( d ) the rate of the reverse reaction of lactoneformation. They conclude that in general the logarithm of the activitycoefficient and the logarithm of the hydrolysis equilibrium constant varylinearly with the first power of the ionic strength.In certain cases there is adeparture from linearity at high ionic strength. The results are shown to bein very poor agreement with the Debye theory of salting out and withKirkwood’s theory of the effect of ions on the activity coefficient of dipolarmolecules. From the kinetic results it is concluded that Bronsted’s equationis adequate for these reactions.A. R. Olson and P. V. Youle117 have determined the two catalyticconstants for the hydrolysis of y-butyrolactone by the following bases :carbonate, phosphate, and tetraborate ions. The separate catalytic co-efficients, but not their sum, fit the Bronsted relation.It is suggestedthat the occurrence of simultaneous multiple-ion reactions may contributeto the frequently observed curvature of the plot of log kB against log KHB.11s F. Bell, R. Gill, D. Holden, and W. F. K. Wynne-Jones, J . Phys. Colloid Chem.,114 R. P. Bell and G. M. Waind, J., 1950,1979.115 F. G. Ciapetta and H. M. Tomlinson, J . Phys. Colloid Chem., 1951,55, 429.11’ A. R. Olson and P. V. Youle, J . Amer. Chem. Soc., 1951, 73, 2468.1951, 55, 874.F. A. Long, W. F. McDevit, and F. B. Dunkle, ibid., p. 813BAWN : TEE MECHANISM OF CHEMICAL CHANGE. 67It is well known that in certain classes of reaction showing general acid-base catalysis large deviations are encountered in the application of Brm-sted's relation connecting catalytic powers of a series of acids and bases fora given reaction with their acidic or basic dissociation constants.A generalaccount of the deviations resulting from change of chemical structure hasbeen given by R. P. Bell 118 and suggestions have been put forward for theseapparent anomalies.It was suggested by C. G. Swain ll9 that reactions that are catalysed byacids and bases normally take place by a ternary mechanism in which thesubstrate is attacked simultaneously by an acid and a base, and he hassupported this viewpoint by consideration of the results on the enolisation ofacetone and the mutarotation of glucose in aqueous solution. The hydrationof acetaldehyde, which exhibits general catalysis by acids and bases, has beenused by R.P. Bell and J. C. Clunie 120 as a test of this hypothesis. By com-parison of their observed rate results in acetate buffers at 0" with the rateequation required by Swain's method they conclude that the data may beaccounted for satisfactorily without the added term k[HAc][Ac-] whichaccounts for the ternary mechanism. They conclude that it would be un-wise t o assume either a binary or a ternary mechanism for acid-base catalysedreactions in general and that each type of reaction must be investigatedseparately.Bell and his co-workers 121, 122 have continued their studies of the base-catalysed decomposition of nitramide. Using five primary and seven tertiarybases as catalysts, they find that for each class there is a relationship betweencatalytic power and basic strength, and that tertiary bases are more powerfulcatalysts than primary bases of the same strength.A detailed studyof the decomposition of deuterated nitramide has already been referred toas showing no evidence for proton tunnelling. Calcium, barium, and zincions have been shown by R. P. Bell and G. M. Waind 123 t o retard specificallythe decomposition of nitramide catalysed by anions of carboxylic acids, andthis is accounted for in terms of the partial formation of species such asC,H,*CH(OH)*CO,Ca+ and [O,C*CH,*CH( OH)*CO,]Ca.The rate of iodination of 2-carbethoxycyclohexanone in aqueous buffersolution has been found to be of first order with respect to ester, zero orderwith respect to iodine, and to be catalysed by anions of carboxylic acids.124The catalytic constants of four carboxylic acids obey the Brernsted relation-ship with an exponent a = 0.67.The value of c( is shown to conform to theregularities previously established for a series of ketones and esters.Although the cations of the halogens are now frequently invoked asagents in halogenation reactions, little evidence has so far been produced118 R. P. Bell, J . Phys. Colloid Chem., 1951, 55, 885.llg C. G. Swain, J. Arner. Chem. SOC., 1950, 72, 4578.l*O R. P. Bell and J. C. Clunie, Nature, 1951, 167, 362.121 R. P. Bell and G. L. Wilson, Trans. Faraduy Soc., 1950, 46, 407.laa R. P. Bell and E. F. Caldin, ibid., 1951, 47, 50.123 R. P. Bell and G. M. Waind, J., 1951, 2357.I a 4 R. P. Bell and G.L. Goldsmith, Proc. Roy. Xoc., 1952, A , 210, 32268 GENERAL AND PHYSICAL CHEMISTRY.for their existence in measurable concentration in aqueous solutions. Theo-retical considerations 125 show that although the base Hal+ cannot exist inappreciable concentration the b ydrated cation H20Hal+ is much more stable.That the iodine cation H,OI+ is only one in which an appreciable proportionof the halogen is present in the positively charged state has been shown byR. P. Bell and E. Gelles 125 by electrometric studies of aqueous solutionsof iodine in the presence of varying concentrations of silver salts and acid.The acid-catalysed chlorination of sodium toluene-o-sulphonate by hypo-chlorous acid with sulphuric and perchloric acids as catalysts has beenshown by D.H. Derbyshire and W. A. Waters 126 to be a second-orderreaction, the mechanism of which involves either Clf or HOCl,+. Thereaction between chloral hydrate and bromine 12' in aqueous solutionwhiph is retarded by Br- ion proceeds according to the equationCCl,=CH(OH)*O- + Br, '7 CCl,*COO- + 2H+ + 2Br-with an activation energy of 15 830 cal. The straightforward bimolecularreaction CH31 + OH- -7 CH,*OH + I- has been studied at 60" and74.8" and the rates correspond to an activation energy of 23.1 & 0.5 kca1.128The rate-determining steps in the uncatalysed reduction of iodine bytitanous salts have been shown by C. E. Johnston and S. Winstein129 to bethe reactions of between TiOH++ and I, and between TiOH++ and I,-.K. J. Morgan, M.G. Peard, and C. F. Cullis l30 have reconsidered the mech-anism of the complex iodate and iodide reaction and have devised a reactionscheme, based on a series of simple steps and involving the dissociationconstant of iodic acid, which agrees with experiment.The reaction between hydroperoxides and iodine is extensively used todetermine the former and it is known that the rate of the reaction is depen-dent on the structure of the hydroperoxide and on the solvent medium used.Kinetic measurements by R. D. Cadle and H. Huff 131 on the reaction ofpotassium iodide with hydrogen peroxide, methyl, ethyl, and tert.-butylhydroperoxide have been reported. In all cases the reactions are pseudo-first-order and independent of pH in the range P - 7 .Kinetic measurements have been reported on the decomposition ofmalonamic and acetonitrolic acid.133 The rate of decomposition of theformer at concentrations of 0.01-0.1~ and over the pH range 0-8-4-33was consistent with the mechanism that only un-ionised molecules undergodecomposition.The decomposition of acetonitrolic acid into acetic acid andnitrous oxide in dilute sulphuric acid was of first order with respect to theconcentration of both the reactant and the oxonium ion.126 R. P. BellandE. Gelles, J . , 1951, 2734.126 D. H. Derbyshire and W. A. Waters, J., 1951, 73.12* H. A. Puente, Anal. Asoc. Quim. Argentina, 1950,88, 355.129 C. E. Johnston and S. Winstein, J . AWT. Chem. SOC., 1951,73, 2607.130 K. J. Morgan. M. G. Peard, and C. F. Cullis, J., 1951, 1865.R.D. Cadle and H. Huff, J . Phys. CoZZoid Chem., 1950, 54, 1191.132 G. A. Hall, J . Amer. Chem. SOC., 1950, 72, 4709.133 A. Maschke and A. Mirna, Monutsh., 1951, 82, 84.A. N. Kappanna and B. R. Deoras, J . Indian Chem. SOC., 1950, 27, 91BAWN: THE MECHANISM OF CHEMICAL CHANGE. 591. M. Kolthoff and I. K. Miller 134 have investigated the decompositionof persulphate ion in aqueous solution and provide evidence that reactionoccurs through the rupture of the 0-0 bond to give two SO4*- free radicals.These react either with the water to liberate oxygen or by an acid-catalysedreaction involving the unsymmetrical rupture of the 0-0 bond of the HS,O,-ion to form SO4*- and HS04-. In dilute solution the SO4-- radical reactsreadily to form oxygen and sulphuric acid but in 2-5~-perchloric or sul-phuric acid it hydrolyses to give H2S05.The activation energies for thecatalysed and the uncatalysed decomposition of the S20,-- ion are 26.0and 35.5 kcal., respectively. The oxygen liberated in the uncatalysedreaction comes from the water, but in the acid-catalysed reaction from theS20,-- ion.The kinetics of the reactions of nitrous acid with ammonia and methyl-amine have been investigated by J. H. Dusenburg and R. E. Powell.135In each case the rate of nitrogen evolution obeyed the second-order relationd[N2]/dt = k[HNO,][X], where X = NH4+ or CH3*NH2+, and the ratedetermining step was suggested to be that between the NO+ ion and theammonia or methylamine molecule.Photochemistry and Radiation Chemistry.Atom-photosensitised Reactions.-The study of mercury-photosensitiseddecomposition of organic molecules has been mainly directed towardsthe elucidation of the reactions of the radicals formed in the primary process.The Hg3P, photosensitised decomposition of ethane and propane 136 at hightemperatures has been explained in terms of the formation and thermaldecomposition of the ethyl and propyl radicals produced, vix.,C3H7 - C3H, + H or CH, + C,H,The activations of the first decompositions are estimated as 20 and 38 kcal.,respectively, and that for the ethyl radjcal as 39.5 kcal.Similar studieswith butane and isobutane 137 have shown that both reactions above 250"produce butyl radicals. The decomposition of mercury-excited ethylenehas been shown by B.de B. Darwent to be a heterogeneous reactionand the excited molecules have an average life of lo4 sec. The Hg3P,photosensitised decomposition of methylcyclohexane 139 a t 29-35" giveshydrogen, cyclopentenes, and a heavy fraction. The reaction was assumedto occur via the initial splitting of the C-H bond to give a hydrogen atomwhich then initiates a reaction chain. The initial decomposition of thecorresponding reaction with methyl chloride lp0 a t 72-328" gave chlorineatoms and a methyl radical, both of which then underwent further reaction134 I. M. Kolthoff and I. K. Miller, J . Amer. Chem. SOC., 1951, 73, 3055.135 J. H. Dusenburg and R. E. Powell, ibid., p. 3266.la6 S. Bywater and E. W. R. Steacie, J . Chem. Phys., 1951,19, 319, 326.13' Idem, ibid., p.172. las B. de B. Darwent, ibid., p. 285.130 M. Schlochauer-and H. E. Gunning, ibid., p. 474.140 C . R. Masson and E. W. 3%. Steacie, ibid., p. 183.CzH5 7 C,H,+'H60 GENERAL AND PHYSICAL CHEMISTRY.with the methyl chloride. The experimental results of Phibbs and Darwenton the photosensitised decomposition of methyl alcohol and methyl etherhave been recalculated by A. F. Trotman-Dickenson, 141 who concludesthat the difference between activation energies of the decomposition of theradical formed and that of dimerisation is 29 kcal. for methyl alcoholand 19 kcal. for methyl ether. The frequency factors of both reactions wereabnormally low.Photo- and Thermal Reactions of Aldehydes and Ketones.-In a detailedstudy of the photolysis of formaldehyde at a wave-length of 3130 8, J.G.Calvert and E. W. R. Steacie 142 showed that the rate of hydrogen formationwas proportional to the light intensity. The rate was accelerated by theaddition of formaldehyde and inert gas with equal efficiency and was notinhibited by nitric oxide or propylene. The reaction was fully explainedin terms of the mechanism :H,CO+hv -7 HCO+H. . , . . (1)H+H*CO 7 H,+CO . . . . . (2)H*CO -7 H+CO . . . . . (3)The activation energy of (2) and of (3) was E2<5 and E3<13 kcal., respec-tively. The high-temperature photolysis of acetaldehyde has been shown byDanby et to be a chain reaction of considerable length, the mainproducts being hydrogen and ethane in comparable amounts.This resultwas explained in terms of the reaction of the formyl radical according to themechanismCH3CHO + hv -7 CH4 + COCH,+ HCO*CH3 + CHs*CHO ---i- CH4 + CH3 + COO2CH3 -7 C2HGH*CO -7 H + C O *H + CH,*CHO -7 H, + CH3 + COOH + H -7 H2According to P. D. Zemansky and M. Burton,144 the photolysis of acetalde-hyde at 140" yielded CH, and CO in almost equal proportions. Fullydeuterated aldehyde gave similar results but at a lower rate; this wasascribed to the zero-point energy differences of the two aldehydes. In thepyrolysis of mixtures of the isotopic aldehydes it was shown that primaryproduction of radicals plays an important part, and the results were con-sistent with the view that pyrolysis proceeds by a chain mechanism of theRice-Herzfeld type with a chain length o f -100 at 465".L. A. Wall andW. J. Moore145 find that the pyrolysis of acetaldehyde and tetradeutero-1 4 1 A. F. Trotman-Dickenson, J. Chem. Phg8., 261.142 J . G. Calvert and E. W. R. Steacie, ibid., p. 176.143 C. J. Danby, A. S. Buchanan, and J. H. S. Henderson, J . , 1951, 1426; A. S.144 P. D. Zemansky and M. Burton, J . Phys. Colloid Chem., 1951,55,949.145 L. A. Wall and W. J. Moore, ibid., p. 965.Buchanan, ibid., p. 2317BAWN: THE MECHANISM OF CHEMICAL CHANCE. 61acetaldehyde at 500" yields isotopically mixed methanes even in the earlystages of the reaction, and this lent support to a free-radical chain ratherthan an intramolecular mechanism.The thermal decomposition of acetaldehyde has also been discussed byBril and others 146 who favour a free-radical chain mechanism with bi-molecular initiation, although the possibility of EL molecular mechanismcannot be ruled out.The results obtained by F. E.Blacet and J. G. Calvert 14' for the de-composition of the butaldehydes in the vapour phase and a t various wave-lengths are in agreement with it chain mechanism which is consistent withthe primary processesCH3*CH,-CH2 + CHOLCH, + CH,-CH,-CHOCH3*CH,*CH,*CHO + h v - rC2H4 + CH,*CHO(CH ) CH + CHOCH,*CH*CHO (CH,),CH*CHO + h v <cH33;This reaction mechanism leads to an activation energy for the decom-position of the formyl radical of 14 kcal. The chain character was con-firmed by a study of the reaction with iodine of the radicals produced.Using the mirror technique for the determination of free radicals T.J.Szworski and M. Burton 14* showed that the pyrolysis of propaldehyde a t850-950" produced methyl and ethyl radicals, the latter predominating.The increase in the ratio CH3/C,H5 with temperature was attributed tosecondary reactions of the ethyl radical, notably with hydrogen atoms formedin the reaction.A critical examination of the well-known photochemical decompositionof acetone to give methyl radicals has been made by A. J. C. Nichol~on,l~~who concluded that the existing theories of the production of methane andethane are valid provided the temperature be above loo", the concentrationof the acetone above l0l8 moles/c.c., and the adsorbed light intensity above10125 quanta/sec.Under these conditions the reactioncan be assigned a value for E of 9.6 kcal. Nicholson also considered thecorrection for effects of diffusion of radicals into and out of the light beam inexperiments where the light does not fill the reaction cell. A critical andvaluable discussion of wall effects and other factors which affect the reliabilityof conclusions about the rates of radical reactions. has been written byW. A. Noyes.lsoPhoto-reactions of Other Organic Molecules.-A close relationship hasbeen shown to exist between isomerisation and addition in the photochemical146 K. Bril, P. Goldfinger, M. Letort, H. Matty, and N. I. Clause, Bull. SOC. chim.Belg., 1950, 59, 263.14' P. E. Blacet and J. G. Calvert, J. Amer. Chem. Soc., 1951, 73, 661.140 A.J. C. Nicholson, ibid., p. 3981.lSo W. A. Noyes, J . Phys. Colloid Chem., 1951,55, 925.CH3 + CH3*CO*CH3 -7 CH, + CH3*CO*CH2*T. J. Szworski and M. Burton, ibid., p. 319462 GENERAL AND PEYSICAL CHEMISTRY.reaction of bromine with cis- and truns-1 : 2-dichloroethylene.151 Althoughthis relationship is independent of the oxygen content of the mixture, bothof the separate reactions are strongly influenced by oxygen.It has been observed by W. H. Hamell and R. H. Schuler 152 that thephotodecomposition of methyl and ethyl iodide a t wave-length 2557 A inthe presence of added radioactive iodine is accompanied by isotopic exchange.I n cyclohexane, cyczohexene and cyclohexyl iodide are the main products, andthis result is consistent with the initial formation of an iodine atom anda hot alkyl radical in the initial decomposition.C.J. Johnson and H. A. Taylor 153 have shown the previously postulatedmechanism for the rate of hydrogen and ammonia production in the photo-lysis of methylamine to be untenable, and they discuss the evidence forethylenediamine as an intermediate in this reaction.The photodecomposition of di-tert.-butyl hydroperoxide vapour a t tem-peratures of 25-75' forms methane, ethane, ethylene, acetone, and tert.-butyl alcohol. At low light intensities the major product is methane.The mechanism of the reaction has been discussed by L. M. Dorfmann andZ. W. S a l ~ b e r g , l ~ ~ who show that there is no evidence for a chain reactionat room temperature although short chains occur a t higher temperatures.Rapid reaction between chlorine and toluene vapour has been observedby M.Ritchie and W. I. H. Winning 155 to take place thermally and underthe action of light of wave-lengths 3650 and 4060 A a t room temperature.The thermal reaction obeys a second-order relationship in agreement withthe postulate that benzyl chloride and hydrogen chloride are the sole pro-ducts of the reaction. The quantum efficiency of the photo-reaction is ofthe order of 8 x lo4. A high value has also been observed by these authors 156for the quantum efficiency of the chlorination of methane (2 x lo3 a t press-ures of methane and chlorine of 45 mm.). The results are interpreted interms of a chain mechanism in which the chain ending involves the formationof Cl, molecules, vix.C12 + hv '7 c1+ c1 C1 + CH, - CH3Cl + ClC l + CH, CH3+ HC1 CH3+ Cl, '7 CH3C1 +ClC1+ C1, + M - CI, + M C13 + C13 - 3c1,Both of the above chlorination reactions are strongly inhibited by oxygen.An examination of the photo-reaction between chlorine and chloroform lS7has shown that two chain-ending processes operate.The three-body reaction2C1, + C1, 2CC1, predominates, but the observed dependence of rate onthe chloroform concentration and the deviation from a 2/r;tbsrelationship a t161 J. A. A. Ketelaar, P. F. van Velden, G. H. J. Broers, and H. R. Gersmann, J. Phys.Colloid Chem., 1951,55, 987.16s W. H. Hamell and R. H. Schuler, J . Amer. Chem. SOC., 1951,73,3466.153 C. J. Johnson and H.A. Taylor, J . Chem. Phys., 1951,19, 613.164 L. M. Dorfmann and Z. W. Salzburg, J . Arner. Chem. Soc., 1951,73,256.186 M. Ritchie and W. I. H. Winning, J., 1950, 3579.166 Idem, ibid., p . 3683.167 W. I. H . Winning, Tram. E"araday SOC., 1951,47, 1084BAWN : THE MECHANISM OF CHEMICAL CHANUE. 63high intensities point to the wall-removal of chlorination as a second ter-minating process.Some interesting results on the quenching of anthracene fluorescence,excited by light of wave-length 3650 8, have been presented by E. J. Bowenand W. S. Metcalfe.158 In the vapour phase, oxygen, sulphur dioxide, andcarbon tetrabromide quench a t every collision but in dilute paraffin solutionthe quenching is controlled by (a) diffusion together of the excited andquencher molecules, and (b) static quenching in which light is absorbed byanthracene molecules contiguous to the quencher molecules.Radiation Chemistry.-Recent work has given considerable support tothe view that free hydrogen atoms and hydroxyl radicals are the principalspecies liberated in water by ionising radiation.It is not always easy todifferentiate between the subsequent reactions initiated by these radicals,and E. (7. Hart 159 has shown that in the X-ray induced oxidation of formicacid the effect of the hydroxyl radical can be increased 50-fold by additionof low concentrations of hydrogen peroxide. Under these conditions theeffect of the hydrogen atom is very small and the chain initiation is determinedalmost entirely by the OH radicals.A further contribution to the radio-chemistry of ferrous sulphate solution has been made by Hart,lG0 whopresents new results of the yield ratio R = Fe,,+++/Fe,,,.+++. Reportedvalues of this ratio vary between 2.55 and 4.0, and Hart shows that theoreticalvalues of less than 4.0 are possible on the accepted ferrous sulphate oxidationmechanism. Using 6oCo X-rays and tritium P-rays, he found the values ofR to be 2.86 and 2.59, respectively. H. A. Dewhurst 161 has shown thataliphatic alcohols have a considerable accelerating effect on the X-ray oxid-ation of ferrous sulphate solutions. This he ascribed to the reaction of theOH radical with the alcohol to give the radical R*CH*OH which by inter-action with oxygen forms a hydroperoxide which in turn brings about theoxidation of two or more Fe2+ ions.This effect is suppressed by chlorineions as a result of the electron-transfer reaction1C1- + OH + H+ 7 C1 + HZOthe chlorine atom liberated reacting with Fe2+ ion rather than with thealcohol.The rate of decomposition of hydrogen peroxide by 2 M.e.v. X-rays wasshown by E. Johnson 162 to be proportional to the square root of the initialperoxide concentration. The hydrogen formed was believed to arise fromthe water and not the hydrogen peroxide. P. Bonet-Maury and M. Lefort 163from similar studies conclude that hydrogen peroxide is decomposd byX-rays and y-rays by two independent mechanisms.The hydroxyl radicals liberated from water by X-rays have been shownlS8 E. J. Bowen and W.S. Metcalfe, Proc. Roy. SOC., 1951, A, 206, 437.lse E. J. Hart, J . Amer. Chem. SOC., 1951, 73, 1891.la H. A. Dewhurst, J . Chem. Phys., 1951,19, 1328.16a E. Johnson, ibid., p. 1204.lBo Idem, ibid., p. 08.P. Bonet-Maury and M. Lefort, Nature, 1950, 166, 98164 QENERAL AND PHYSICAL CHEMISTRY.to hydroxylate benzoic,acid and to convert sodium cholate into 3a : 12a-dihydro-7-ketocholanic acid.165 The latter reaction shows the close parallel-ism between biological oxidation and those produced by penetrating radiationin aqueous solutions. In a similar manner the action of X-rays leads tohydroxylation of nitrobenzene and benzoic acid in aqueous solution.166 I nthe former reaction the proportion of the o-, m-, and p-nitrophenols formedwas similar to those produced by the action of the Penton reagent, thusconfirming the free-radical character of the reaction.Purther evidence hasbeen forthcoming that both high-energy electrons and X-rays initiatepolymerisation of vinyl monomers and the overall reactions show all thecharacteristics of the normal polymerisation chain reaction.167T. J. Sworski, R. R. Hentz, and M. Burton 16* have compared the photo-chemical and radio-chemical reactions of several aromatic hydrocarbons.The vapour-phase photolysis was interpreted in terms of methyl-radicalproduction by a primary splitting of the C-C bond p to the benzene ring andhydrogen production via rupture of the C-C bonds p and y to the benzenering. Data on the liquid-phase photolysis show almost complete suppressionof hydrocarbon formation.Liquid-phase irradiation of these compoundswith 1.5 M.e.v. electrons indicated that the process characteristic of theexcitation of the x electrons of the aromatic ring may make a relativelygreater contribution to the overall radiolysis than previously reported fortoluene, ethylbenzene, isopropylbenzene, and tert.-butylbenzene. Decom-position ensues from the highly excited state of the x electron system andgives products similar to those of the vapour-phase photolysis.Catalysis and Surface Chemistry.The considerable progress which has been made in the field of contactcatalysis and surface chemistry during recent years has proceeded primarilyfrom the development of experimental methods of determination of thesurface areas of catalysts and the application of the electronic theory of thesolid state to the problem of surface behaviour.The subject was reviewedin detail in the previous reports,169 and in continuing to record progressparticular emph?sis will be given to recent work on the kinetics and mech-anism of surface processes.Adsorption and Surface Studies.-The B.E.T. method of surface-areadetermination has been shown to give consistent and reproducible results,and recent work has confirmed this technique as a sound semi-empiricalmethod. The theory also explains qualitatively many features of gasadsorption, but the basic assumptions on which it rests are not in agreementwith the current viewpoints of the non-uniformity of the catalyst surface184 H.Loebl, G. Stein, and J. Weiss, J., 1951,405.166 M. Keller and J. Weiss, J., 1951, 25.166 H. Loebl, G. Stein, and J. Weiss, J., 1950, 2704; 1951, 405.1 6 7 J. V. Schmutz and E. J. Lawton, Science, 1951, 113, 718; W. Mund and P.168 T. J. Sworski, R. R. Hentz, and M. Burton, J. Amer. Chem. SOC., 1951, 73, 1-998.169 F. C. Tompkins, Ann. Reports, 1960, 47, 64-67.Huykens, Bull. Acad. roy. BeFge, Classe sci., 1950, 36, 610BAWN: TBE MECHANISM OF CHEMICAL OHANQE. 65and of the forces of interaction between adsorbed molecules. As a con-sequence, many attempts have been made to refke the theory. For sigmoid-shaped isotherms characteristic of multilayer adsorption on non-poroussolids the B.E.T. theory generally predicts an adsorption which is too smallat low pressures and too large in the multilayer region approaching satur-ation. The deviation a t low pressures is probably due to non-homogeneityof the adsorbing surface, but in the higher pressure region the theory is a tfault in that it assumes that the energy of adsorption for the firstmonolayer is unique and that for all succeeding layers it is the energy ofliquefaction. G.D. Halsey 170 has previously criticised the theory on thegrounds that extension of the attractive forces emanating from the surfaceto higher layers cannot be ignored. W. G. McMillan and E. Teller,171 byincluding this effect and also factors due to the surface tension of the solid,have derived an isotherm valid in the region of multilayer adsorption.The theoretical basis of the B.E.T.and the Huttig isotherm has also beenconsidered by R. M. Barrer,172 who concludes that the latter is consistentwith a succession of layers in a potential field in which vertical interactionbetween sorbate molecules in successive layers is ignored but that lateralinteractions are included. It is thus complementary to the B.E.T. isotherm,which omits lateral interactions. R. M. Barrer and A. B. Robins 173 con-sidered that there is little prospect of rendering either of the models satis-factory and they make a new approach to multilayer adsorption, using thevan der Waals equation of state for adsorbed gases. In this way both lateraland vertical interaction between sorbed molecules are approximately allowedfor, and in many types of isotherms good qualitative agreement betweentheory and experiment is obtained.The various theories of adsorptionhave been discussed by G. F. Huttig and 0. Theimer,174 who, using a modifiedand expanded form of the Langmuir isotherm, have proposed a compromiseequation between the Huttig and B.E.T. isotherms which they claim fits theexperimental data better than either equation. G. F. Huttig, H. Schreiner,and R. Klein 175 have also discussed the experimental basis for the determin-ation of isotherms suitable for comparison with theory. The various types ofrealisable isotherms have also been examined by D. C. Jones 176 who com-pares the B.E.T. and Langmuir equations. New adsorption equations havebeen proposed for multilayer adsorption by G.D. H a l ~ e y , ~ ~ ~ using a London-type law for the dispersion forces with an exponential distribution of absorb-ing centres, and for low-pressure adsorption by M. A. Cook, D. H. Pack, andA. G. Oblad,178 who employ a new'type of adsorption potential associated170 G. D. Halsey, Discuss. Paraday SOC., 1950, 8, 54.171 W. G. McMillan and E. Teller, J. Phys. Colloid Chem., 1951, 55, 17 ; W. G.17s R. M. Barrer and A. B. Robins, Trans. Faraday Soc., 1951, 47, 773.174 G . F. Huttig and 0. Theimer, Kolloid Z., 1950, 119, 69.176 G. F. Huttig, H. Schreiner and R. Klein, ibid., p. 157.176 D. C. Jones, J . , 1951, 126,1464; D. C. Jones and E. W. Birks, J., 1951, 1127.G. D. Halsey, J . Amer. Chem. SOC., 1951, 73, 2693.M. A. Cook, D. H. Pack, and A.G. Oblad, J . Chem. Phys., 1951,19, 367.REP.-VOL. XLVIII. CMcMillan, J. Chem. Phys., 1951,19, 25. 172 R. M. Barrer, J., 1951, 187466 GENERAL AND PHYSICAL CHEMISTRY.with surface strain. Good agreement with experiment is claimed in bothcases.The study of the thermal properties of adsorbed films is useful in pro-viding thermodynamic data which are of value in testing the theory ofadsorption and also for obtaining direct information concerning the state ofthe adsorbed film. An important consideration is the mobility 01 theadsorbed gas in the surface film, and ordinarily it is assumed that the adsorbedphases of the permanent gas are mobile a t low temperatures. T. L. Hill 179has shown theoretically that a transition from a localised to a mobile filmshould occur at low temperatures, but measurements of the heat capacityof physically adsorbed gas on titania a t 90'9 do not provide evidence forthis transition.More recent and direct measurements l80 on the same surfacebetween 14" and 2 5 " ~ and a t higher temperatures show that the heat capacityrises to values much larger than given by theory, and this is attributed to thecomplicated effect of heterogeneity of the surface. Other measurements 181 ofthe thermal properties of gases adsorbed on rutile show that the B.E.T. or anyother simple theory is inadequate to predict a set of thermodynamic properties.Accurate measurements of the adsorption of nitrogen on a single-crystalcopper surface by T. N. Rhodinla2 showed that the apparent numbersof copper atoms per nitrogen molecule were 14-2-21, 2-7-24, and 3.3for the 110, 100, and 111 faces, respectively. The differential heat ofadsorption shows a maximum a t monolayer coverage, and it is estimatedthat the true surface area may be determined with an error of 5 6% by low-temperature adsorption measurements.Evidence continues to accumulate to show that the surface of the catalystis at least in part non-uniform in activity, and the older concept of activecentres re-interpreted in terms of the modern ideas of the solid state thusseems firmly established. Measurements of heats of adsorption of gases onmetals and other solids usually show that the initially adsorbed gas evolvesconsiderably more heat per molecule than gas taken up when the surface ispartly covered.Although this observation is usually taken as evidence ofthe heterogeneity of the surface, great care is necesssary in analysing thedata before any definite conclusion can be reached because, as pointed outby many workers, a differential heat of adsorption is to be expected even on anon-uniform surface purely as a result of the tendency of adsorbed moleculesin adjoining positions to repel one another. F. C. Tompkins and D. M.Young 183 observed a definite trend in the heats of adsorption of carbonmonoxide, nitrogen, argon, and oxygen on calcium iodide at low temperaturesin the range of 0.2-0.8 coverage, and the initial decrease in heat of adsorp-tion observed with the last three gases with coverage (mutual interaction1'9 T.L. Hill, J . Chem. Phys., 1946,14, 441.180 J. Morrison, J. M. Los, and J. E. Drain, Trans. Paraday SOC., 1951, 47, 1023.lS1 J. G. Aston, G. J. Szasz, and G. L. Kington, J . Amer. Chem. SOC., 1951, 73,182 T. N. Rhodin, ibid., 1950, 72, 4343, 5691.lS3 F. C. Tompkins and D. M. Young, Trans. Paraday SOC., 1951,47, 77.1937; G. L. Kingtonand J. G. Aston, ibid., p. 1929BAWN : THE MECHANISM OF CHEMICAL CHANGE. 67forces being attractive would result in an increase in heat) was attributed tonon-uniformity of the surface.A direct experimental proof of the heterogeneity has been carried outby covering one part of the surface with one form of adsorbate and anotherpart with an isotopic form. If the surface is heterogeneous the portion ofthe adsorbate added first should be desorbed last.If, on the other hand,the ease of desorption is determined by purely molecular interaction amongthe adsorbed molecules on a homogeneous surface, the ratio of two isotopicspecies throughout the desorption would be equal. Using this procedurewith radioactive carbon monoxide, J. T. Kummer and P. H. Emmett la4show that iron catalysts behave as if they were half homogeneous and halfheterogeneous. I n a similar manner, R. P. Eischens lE5 has shown that amonolayer of 14CO adsorbed on reduced iron exchanges readily with normalcarbon monoxide only on portions of the surface.The problem of the rate of adsorption on a surface whose sites havedifferent adsorption energies has been treated theoretically by G.D. Halsey,l86who evaluates the case of a continuously non-uniform surface, having awhole spectrum of adsorption energies. He applied his theory to theresults of H. S. Taylor and S. C. Laing (who,from a study of the adsorptionof hydrogen on zinc oxide at different temperatures, have shown that thesurface was energetically heterogeneous), and concluded that the results canbe explained by assuming a continuously non-uniform surface.It is clear that the forces of the bonding in chemismption will depend onthe nature of the adsorbent and the adsorbate, and it was a natural develop-ment that some relationships would be sought between the structure of thesolid and its catalytic activity. Furthermore, besides an understanding of thedifference in behaviour between ionic and molecular crystals and metals, theenhanced activity of certain solids such as the transition metals or alloysmust be sought in terms of the electronic properties of the solid.Theadvances in current ideas of this new approach were excellently summarisedin a number of papers to the Faraday Society Discussion on HeterogeneousCatalysis.la8Much of the recent fundamental progress may also be attributed to useof a " clean " surface, in the form of either wire or film. Using evaporatedtungsten films, Sir Eric Rideal and B. M. W. Trapnell lag have studied thechemisorption of oxygen and carbon monoxide over a wide range of tem-peratures. The chemisorption proceeded without appreciable activationenergy, and the equilibrium gas pressures as the surface compound was firstformed were extremely small even above room temperature.The initialprimary rapid uptake of oxygen and carbon monoxide was used to determinethe film area and the results agreed within 5%. The heat of adsorption bylE4 J. T. Kummer and P. H. Emmett, J . Amer. Chem. SOC., 1951,73, 2886.ls5 R. P. Eischens, J . Chem. Phys., 1951,19, 377.lS6 G. D. Halsey, J . Phys. Colloid Chem., 1951, 55, 21.lS7 H. S. Taylor and S. C. Laing, J . Amer. Chem. SOC., 1947, 69, 1306.lE8 Discuss. Faraday SOC., 1950, 8.la9 Sir Eric Rideal and B. M. W. Trapnell, Proc. Roy. SOC., 1951, A, 205, 40968 GENERAL AND PHYSIUAL UHEMISTRY.carbon monoxide decreased rapidly with increasing amount adsorbed, and atvery low values a second adsorbed layer formed.The first and the secondlayer formation have been shown to be a continuous rather than a stepwiseprocess. The chemisorption of hydrogen 190 gave a densely packed layer andwas reversible even at liquid-air temperatures. The results were verysimilar to those with carbon monoxide, except that second layer formationdid not occur to any measurable extent. From measurements of the rate ofchemisorption of hydrogen on reduced copper, T. Kwan and M. Kujiraiconcluded that adsorption was not localised on active centres but that allsites on the surface area were equally capable of adsorbing gas.There is much evidence for the view that on certain hydrogenatingcatalysts, the adsorbed hydrogen may be ionised. Other metals and alloyshave the property of dissolving hydrogen.Thus measurements of the elec-trical resistance isotherms on the hydrogen-palladium system show that thehydrogen is held in solution as protons.lg2 The incomplete d shells of thepalladium become filled when the ratio of HjPd atoms in solid solution is0.6. M. A. Garstens 193 has shown that with powdered titanium containing536% of hydrogen, the hydrogen was free above 2 3 5 " ~ but at 2 1 5 " ~ theproton motion in the solid was frozen. W. Himmler 19* has shown that thesolubility of a hydrogen in metal may be considerably modified by alloying;e.g., zinc, tin, and aluminium decrease but nickel and platinum increase thesolubility of hydrogen in copper. The results are explained in terms of theinfluence of the added metal on the electron availability.By measurementof changes of electrical resistance two different mechanisms have been shownto be operative in the adsorption of hydrogen and ethylene in tungstendi~u1phide.l~~ Below 250" normal chemisorption occurs but at highertemperatures solubility in the lattice takes place.Kinetics.-Dispute still continues concerning the mechanism of thecatalytic reactions involving the activation of hydrogen, vix., the para-hydrogen conversion and the hydrogenation and exchange reaction of thesimple hydrocarbons. Several reviews of these studies have appeared duringthe last few years 1g6 and only the additional contributions will be referredto in this report. From studies of the chemisorption of hydrogen in tung-sten, B.M. W. Trapnell lg7 claimed that the ortho-para-hydrogen reactionoccurred according toG. D. Halsey,lg8 on the other hand, from a review of the assembled data for2W+p-H, =+ 2WH + 2W+o-H,190 B. M. W. Trapnell, Proc. Roy. SOC., A , 206, 36.191 T. Kwan and M. Kujirai, J . Chem. Phys., 1951,19, 798.198 P. Wright, Proc. Phys. SOC., 1950, A , 63, 727.193 M. A. Garstens, Phya. Rev., 1951, 81, 288.194 W. H i d e r , 2. physikal Chem., 1950,195,244.195 H. Friz, 2. Elektrochem., 1950, 54, 538.186 D. E. Eley, " Advances in Catalysis," Academic Preas, 1948, New York, Vol. I,197 B. M. W. Trapnell, Proc. Roy. SOC., 1951, A , 206, 36.198 G. D. Halsey, Trans. Paraday SOC., 1951,47,649.pp. 157-195; Quart. Reviews, 1949,111,209; J. Phys. Colloid Chem., 1951,55,1017BAWN : THE MEOHANISM OF CHEMICAL C W Q E .69the conversion on clear tungsten surfaces concluded that the exchangeoccurred between chemisorbed hydrogen atoms and molecular hydrogenadsorbed on van der Waals sites of varying energy. Measurements byD. E, Eley and A. Couper lQ9 on a series of palladium-gold alloys have shownthat vacant d orbitals in the metal are essential for the low-temperaturecatalysis, and it is suggested that they bond the chemisorbed hydrogenatom M-H. The reaction is postulated as occurring through an H, complexaccording toM-H+p-H, H-H-H a o-H2+MHMThe mechanism of the hydrogenation of ethylenic double bonds on metalsurfaces such as nickel has been the subject of much investigation, and thevarious proposed mechanisms have been summarised by D.E. Eley.200In an attempt to distinguish between the mechanisms, G . H. Twigg201studied the hydrogenation on a nickel surface a t -78" with a mixture of(a) H, + D, and (b) H, + HD + D,. His results showed that the samemixtures of deuterated ethanes was produced in the two experiments and wasdifferent from an equimolar mixture of C,H, and C,H,D2, leading to theunequivocal conclusion that addition of hydrogen to the double bond doesnot take place in a single act but that the hydrogen molecule is first splitinto atoms which are then added one at a time. He proposed a mechanismfor the reaction in which the hydrogen is not adsorbed directly in the catalystbut only through reaction with a chemisorbed ethylene molecule to form anethyl radical and an adsorbed hydrogen atom.Mass-spectroscopic analysisof the products of the deuterium-ethylenereaction on a nickel wire catalyst 202are in agreement with Twigg's findings.A systematic study of the catalytic hydrogenation of ethylene and otherhydrocarbons in evaporated porous metal films of the transition elementshas been reported by 0. Bee~k.~O~ He proposed the following mechanism:'' Depending on the heat of adsorption for ethylene, initial irreversiblepoisoning by acetylenic adsorption complexes, formed by self-hydrogenationof ethylene, renders the surface more or less inactive for hydrogenation.On the remaining part of the surface the overall rate of reaction is determinedby the reaction of adsorbed ethylene (non-dissociative) with adsorbedhydrogen with an apparent activation energy of 10.7 kcal.for metals ofGroup VIII. Strong evidence is presented that a third type of a fast reactionwith low activation energy is also involved. This reaction is thought not tonecessitate empty crystallographic sites for the separate adsorption of ethy-lene, but of being able to form the activated state on a surface alreadycovered with hydrogen."These observations brought out the surprising complexity of this appar-ently simple reaction and emphasised the influence of chemical properties10e D. E. Eley and A. Couper, Discuss. Faraday Soc., 1950,8, 172.*O0 D. E. Eley, ibid., p. 99. 801 G. H. Twigg, ibid., p. 152.*O* J. Turkevitch, F. Bonner, D. Schider, and P.Ima, ibid., p. 363.'O* 0. Beeck, ibid., p. 11870 GENERAL AND PHYSICAL CHEMISTRY.(electronic configuration) and physical properties (crystal parameters) ofthe catalyst on the rate of reaction. The facts discovered by Beeck will haveto be taken into account in any theory of ethylenic hydrogenation, and itappears that no single chemical mechanism will completely explain the ex-perimental observations.I n a paper on the catalysed reactions of unsaturated hydrocarbons withhydrogen and deuterium, T. I. Taylor and V. H. Dibelier 204 review pastwork on hydrogenation, double-bond shift, cis-trans-isomerisation, and deu-terium exchange, and present new results on the nickel-catalysed hydro-genation, isomerisations, and deuterium exchange reactions of the butenes.These authors show that hydrogen or deuterium is necessary for double-bond migration and that the breaking of a hydrogen or deuterium bond isinvolved in the rate-controlling step.Each time the double bond shifts,a deuterium atom enters the butene molecule and this is explained on thebasis of a " hydrogen switch " mechanism. The rate-controlling step forhydrogenation is shown to be different from that of exchange and double-bond migration and this is explained in terms of a mechanism involvingthe half-hydrogenated st ate.J. Turkevitch, D. Schissler, and R. Irsa205 show that the exchangereaction of deuterium and ethylene on a nickel wire a t 90" proceeds morerapidly than the addition reaction, and make the surprising discovery that thereaction of ethylene and deuterium gives a completely light ethane. Theresults suggest that ethylene hydrogenation is effected by the hydrogen thatwas previously on another ethylene molecule and only indirectly by thehydrogen molecule.The exchange reaction of methane and deuterium on evaporated nickelcatalysis has been studied by C.Kemba11.206 All four deuterated methanesare formed a t temperatures of 206-255'. The surface area of the filmswas determined by measurements of the adsorption of D,, which was in-stantaneous. Two types of reaction are distinguished : ( a ) the productionof CH,D with EI = 24 kcal., and ( b ) the formation of the higher deuteratedcompounds with E,, = 32 kcal., and the suggested mechanism is that intype I reaction methane is adsorbed as CH, + H, and in type I1 as CH,.The value of stable and radioactive isotopes in the study of catalyticreactions has been discussed by F.Bonner and J. Turkevitch 207 who haveused 14C to study the reaction between carbon and carbon dioxide. Theirresults are interpreted in terms of a mechanism which postulates a rapidreaction of the carbon dioxide with the surface to give an oxygenated surfaceand radioactive carbon monoxide, followed by a subsequent slow decom-position of the surface compound to give a second molecule of carbonmonoxide which is non-radioactive.Several independent investigations have been reported during the year204 T. I. Taylor and V. H. Dibelier, J. Phys. CoEZoid Chem., 1951, 55, 1036.205 J.Turkevitch, D. Schissler and R. Irsa, ibid., p. 1078.206 C. Kemball, Proc. Roy. Soc., 1951, A , 207, 539.207 F. BOMer and J. Turkevitch, J . Amer. Chem. SOC., 1951, 73, 561BAWN : THE MECHXNISM OF CHEMICAL CHANGE. 71on the catalytic decomposition of ammonia and related reactions. J. P.McGeer and H. S. Taylor208 observed that dissociative adsorption on rhen-ium begins at 250". Hydrogen is measurably adsorbed at - 196" to 330", andnitrogen adsorbed at -196" to 150" is slow in equilibrating and diflicult todesorb. Isotopic exchange between NH, and D,, H, and D,, and H,O andD, occurs on rhenium between 0" and 100" but the isotopes of nitrogenexchange readily only above 500". Carefully reduced iron synthetic ammoniacatalysts also bring about an exchangeof the nitrogen, and thereaction isvery sensitive to the thoroughness of reduction of the catalyst. The additionof hydrogen accelerates the isotopic exchange with nitrogen over both ironand rhenium catalysts, whereas traces of water act as poisons. The ex-change reaction was also very sensitive to traces of oxygen, and this andother findings provide convincing evidence for the non-uniform activity ofthe surface.From these observations it appeared that rhenium and ironcatalysts have much in common and that the ammonia decompositionoccurs similarly on both surfaces. The rate of exchange of 15N, and 14N2over iron catalysts has been shown by T. Kummer and P. H. Emmett 209to be explicable if all the nitrogen evaporated from the surface is completelyequilibrated with respect to nitrogen exchange.The reaction is markedlyaccelerated by hydrogen, and in agreement with the above results smalltraces of surface oxides poison the catalyst severely for isotopic exchange.The rate of ammonia decomposition on iron-type catalysts 210 has beenshown t o be the same for pure iron, iron containing 3% of alumina, and ironplus 3% of alumina and 2% of K,O. The exchange reaction betweenammonia and deuterium singly-promoted iron catalyst has been followed byJ. Weber and K. J. Laidler 211 by measurements of the microwave absorptionof the gases, and from a detailed kinetic study they conclude that exchangeoccurs between the absorbed species of both molecules.The catalytic decomposition of ammonia on tungsten and molybdenumfilaments 212 (610-820") showed similar kinetic characteristics.Theadsorption of nitrogen from the gas phase was negligible and the activesurface was entirely covered with hydrogen atoms and molecular ammonia.On platinum 213 at 650-750" the rate of decomposition was independent ofthe partial pressure of ammonia and was inhibited by both of the productsto about the same extent.Space does not permit of a review of the important developments in thestudy of the adsorption and catalysis on oxide surfaces or the related problemof the oxidation of metals and it is hoped to include these topics in a futureReport.Solid Reactions.-In many solid reactions we are concerned with the samebasic processes as occur in the substrate during catalytic reactions.Addi-208 J. P. McGeer and H. S. Taylor, J . Amer. Chern. SOC., 2743.aos T. Kummer and P. H. Emmett, J . Chern. Phys., 1951,19, 289.210 R. Brill, ibid., p. 1047.a18 N. Nagasko and S . Miyazaki, ibid., p. 134.211 J. Weberand K. J. Laidler, ibid., p. 381.S. Miyazaki, J . Chem. Soc. Japan (Pure Chem. Sect.), 1949, 70, 37372 GENERAL AND PHYSICAL CHEMISTRY.tional effects make their appearance and it is now necessary to consider thedecomposition of molecules in the surface which gives rise to the formationof a new solid phase and also reaction at the interface so created.Many solid reactions of the type Asolid -/ Bsohd + Cgas start at apoint on the surface of the solid, and when the new interface has grown to asufficient size the nuclei visible under the microscope have characteristicshapes, e.g., the alums.As Garner and his co-workers 214 have shown, thenuclei formed on the dehydration of hydrates may grow abnormally slowlyin the initial phases, and R. S. Bradley215 has recently suggested that thismay be due to the effect of the dehydrated phase on the activation energynecessary for the escape of water molecules. In certain exothermic decom-positions, e.g., of potassium azide and mercury fulminate, there are novisible signs of nucleation and the crystals colour throughout. With leadazide and barium azide visible nuclei are formed at the surface, and the lawsgoverning their production and growth have been established. A newexample of the latter class has been reported by W.E. Garner 216 on the de-composition of lithium aluminium hydride, LiAlH, LiH + A1 + l$H2,in which the spherical nuclei formed increase in area as the square of the time.J. Kawana217 has observed that in the reaction of hydrogen with calciumthe nuclei of CaH form after a finite induction period and then grow at arate proportional to their boundary area. The corresponding reaction withdeuterium is 1Sy0 slower than that of hydrogen. Possible mechanisms of theformation and the growth of nuclei during the decomposition of crystallinesolids have also been considered in a general manner in terms of surfacemigration and the lattice energies of the reactant and product by J. Y.Macdonald.21J. G. N. Thomas and F. C. Tompkins 219 have recently put forward a newmechanism for the thermal and photo-decomposition of barium azide.Theyconsider that nucleus formation is determined by the production of P centreswhich by interaction with vacant anion sites acquire mobility and so aggre-gate to form more stable double P centres or nuclei. Nucleus growthinvolves the decomposition at the metal-salt interface and the nitrogenproduced diffuses through the crystal instead of by the process of internalelectrolysis which has been postulated by Mott. It is shown that theactivation energy for the growth of small nuclei is higher than that fornuclei of visible size. In the photo-decomposition below 45" the nitrogenevolution varies as the square of the light intensity and thus the ultimatedecomposition involves two azide radicals.The results are explained bydecomposition proceeding through the reaction of neutral excitons rather thancharged azide radicals. Above 45" the rate was proportional to the intensity214 W. E. Garner and J. A. Cooper, Trans. Furuday Soc., 1936, 32, 1739; G. P.Acock, W. E. Garner, J. Milsted, and H. J. Willavoys, Proc. Roy. SOC., 1947, A,'189, 508.215 R. S. Bradley, Tram. Faruday SOC., 1951,47,630.216 W. E. Garner, Chern. und Ind., 1951, 1010.217 J. Kawana, J . Chern. SOC. Japan (Pure Chem. Sect.), 1950, '91, 494, 654.218 J. Y. Macdonald, Trans. Furuduy SOC., 1951, 4'9, 860.2lS J. G. N. Thomas and 3'. C. Tompkins, Proc. Roy. Soc., 1961, A , 210,111 ; A, 200,660LONUUET-HIQUINS : THE STATISTICAL THEORY OF SOLUTIONS.73of light, and this is consistent with a reaction of an exciton created byabsorption of light with an azide group produced by partial electron transferfrom an azide ion adjacent to a growing metallic nucleus.The decomposition of some inorganic azides which melt before explodinghas been shown by A. D. Yoffe Z20 to result from self-heating in the liquid.It is suggested that the self-heating is due to retention of the hot productsof the decomposition-either active nitrogen or excited nitrogen molecules-near the liquid surface.The kinetics of the decomposition of mercurous formate,221 nickel for-mate,222 and potassium chlorate 223 have been followed by pressure measure-ments, and the rate laws determined. The first obeys first-order reactionkinetics but the last two decompositions show chain characteristics and canbe satisfactorily represented by the Prout-Tompkins equation.Observation of the exchange of 13CO, between dolomite and calcitedecomposed a t 700" shows that interchange occurs between calcium andmagnesium in oxides formed by reaction with gaseous carbonC .E. H. B.4. THE STATISTICAL TaEORY OF SOLUTIONS.Introduction.-As electrolytes and solutions of polymers will be discussedin a future report, and as metallic and colloidal solutions are subjects inthemselves, consideration will be restricted here to recent work on non-electrolyte solutions in which the molecules are not too disparate in size.The statistical theory of solutions is concerned with two complementaryproblems : (1) to calculate the thermodynamic and other properties of theassembly from the intermolecular forces ; and (2) to obtain detailed inform-ation about the molecular interactions from the observed thermodynamicproperties.In general it is easier to predict macroscopic properties frommicroscopic ones than vice vema ; for example, the measured virial coefficientsof gases do not enable us to decide whether the repulsive part of the inter-molecular potential is proportional to r-8, r-12, or some other steep functionof r, and substances of such different shape and flexibility as methane andn-butane obey the same reduced equation of state to a good approximation.lThe usual procedure in calculating thermodynamic properties is thereforeto assume a definite molecular model and to compare its theoretical implic-ations with the results of experiment, rather than to work deductively fromthe experimental facts.Liquid Solutions.-Since Hildebrand's classical work: theoretical work ona20 A.D. Yoffe, Proc. Roy. Soc., A , 208, 188.BB1 G. A. Miller and G. W. Murphy, J . Amer. Chem. Soc., 1951,73, 1871.s2s L. Bircumshaw and J. E. Edwards, J., 1950, 1800.A. Glasner and A. E. Simche, Bull. SOC. chim., 1951,233.324 R. A. W. Haul, L. H. Stein, and J. D. Louw, Nature, 1951,167,241.J. A. Beattie and W. H. Stockmayer, J . Chem. Phys., 1942,10,473. ' See J. H. Hildebrand and R. L. Scott, " The solubility of non-electrolytes,'' 3rdedn., Reinhold, New York, 195074 UENERAL AND PHYSICAL CHEMISTRY.nonelectrolyte solutions has generally been based on some geometricalmodel of the liquid state, of which the most popular has been the quasi-crystalline or lattice modeL3 In the simple lattice theory, it is assumed thatthe energy of interaction between nearest neighbours is a fixed quantity,depending only on their chemical nature. This model lends itself to mathe-matical treatment, and has been used for interpreting the properties ofwhat Hildebrand describes as ‘‘ regular solutions.” A ‘‘ regular solution ”in Hildebrand’s sense is one in which the entropy of mixing is given by theequationas for an ideal solution; the heat of mixing and the non-ideal free energy ofmixing are therefore equal, and are given by Hildebrand’s theory asA s = --(x~logxA +xglOgx~) .. . . (1)AxG = AXH = (2/Ea - ~/EB)~XAXB . . . . (2)when the two components are of equal molar volume, where E A and E Bare the intermolecular energies per mole of the two components. (If themolar volumes are unequal, Hildebrand replaces mole fractions by volumefractions and takes volume averages.) These equations and their moregeneral forms have been found to account very well for solubility relation-ships in non-polar solutions, but less well for entropies of solution. Thesame applies to the equations obtained from the simple lattice theory;they describe well the dependence of free energy on composition, but not ontemperature or pressure. Recent work has therefore been directed towardsa better understanding not only of free energies of mixing, but also non-idealentropies and volumes of mixing.One type of solution for which the non-ideal entropy is large is a mixtureof molecules of very different size.The lattice theory of such solutions isbased on the assumption that each molecule of one kind occupies a singlelattice site, while each molecule qf the other kind occupies a number ofdifferent sites. The entropy is then evaluated essentially by counting thenumber of different configurations which are compatible with this condition(for a given composition), and is thus supposed to be essentially geometricalin origin. Entropies of mixing calculated in this way are found to begreater than the ideal value, in good agreement with the data for polymersolutions; and there can be little doubt that for such solutions the under-lying physical picture is essentially correct.However, the situation is less satisfactory when the two componentsare nearly equal in size. I n such a case the non-ideal entropy cannot begeometrical in origin, and must be traced to some other cause.E’or suchsolutions the lattice theory interprets the non-ideal entropy of mixing in thefollowing manner :Let WAA, WAB, and WBB be the energies of interaction between pairs ofSee R. H. Fowler and E. A. Guggenheim, “ Statistical thermodynamics,” ch. 8,* See A. R. Miller, “ The theory of solutions of high polymers,” Oxford UniversityCambridge University Press, 1939.Press, 1948LONGUET-HIGIGINS : THE STATISTICAL THEORY OF SOLUTIONS. 75adjacent molecules in a solution of A and B.Then, if w = 2wAB - WAA - WBBis appreciable compared with kT, there will be a tendency for like molecules(or unlike, as the case may be) to cluster together in the lattice. I n effect,the distribution of molecules on the lattice sites is no longer random, and theentropy of mixing will be less than the ideal value. Actually, the theorypredicts values of AxX which are often much smaller than the experimentalvalues, and are even of incorrect sign when the observed non-ideal entropy ispositive. Guggenheim,5 recognising this dilemma, ' has pointed out thatagreement may be obtained artificially by allowing w to vary with temper-ature, but this generalisation merely introduces another unknown para-meter into the theory, and also spoils the simplicity of the model.Prigogineand Garikian have clarified the situation somewhat by using a vibrating-lattice model of the Lennard-Jones and Devonshire type ; they find that thevariation of intermolecular-vibration frequency with composition is a muchmore important factor than non-random mixing ; but their calculated non-ideal entropies are still invariably negative.Now by purely thermodynamic reasoning it is possible to show that thenon-ideal entropy and volume of mixing are related to the non-ideal freeenergy of mixing by the equationsIn order to calculate entropies and volumes it is therefore necessary tohave a reliable expression for the free energy not only as a function of com-position but also of temperature and pressure.This fact appears to havebeen overlooked in the older work; for example, there is no guarantee thatHildebrand's equations (1) and (2) will be even thermodynamically consistent.It was therefore urgently necessary to have an exact theory of a t least onekind of non-ideal solution, independent of the uncertainties of a geometricalmodel and known to be thermodynamically self-consistent. Longuet-Higgins has recently put forward such a theory.' For solutions in whichthe interactions between the different species differ only slightly, and areof the same functional form (" conformal solutions "), his theory ismathematically exact. The key result is the expression for the non-idealentropy of mixing, namelywhere Eo is the intermolecular energy of either component, and d A B is asmall numerical constant , defined precisely in terms of the intermolecularenergy curves of the three pairs of components, AA, BB, and AB.For aliquid, E, is equal to RT minus the latent heat of vaporisation, Q,, and itsvariation with temperature may be determined experimentally. Differenti-ation of equation (4) with respect to temperature or pressure then givesAX8 = - (i3/aT),AxH and AxF = (a/ap)rAXG . . (3)AxG = EodaBxaxB + terms of higher order . . . (4)A X G : A W A X V = RT - Q,: dQ, - R : - T V , ~ , . . dTE. A. Guggenheim, Trans. Puruduy Soc., 1948,45, 1066. ' I. Prigogine end G. Garikian, Physicu, 1950,16, 239. ' H. C. Longuet-Higgins, Proc. Roy. SOC., 1951, A , 205, 24776 GENERAL AND PHYSICAL CHEMISTRY.where Vo is the molar volume of the reference component and a0 its coeffi-cient of thermal expansion.These relationships involve no theoreticalparameters, and may therefore be verified experimentally. They are foundto agree well with experiment over a much wider range than the validity ofthe assumptions on which they are based, which is mysterious but satis-factory. In particular, the theory of conformal solutions gives an interpre-tation of the fact that free energies and entropies of solution often go handin hand, as was observed by Bells and others some time ago. The factthat no statistical model is required means that the theory can be appliedto gaseous mixtures as well as liquids; and recently it has been used forinterpreting the phase diagram of mixtures of carbon dioxide and ethylenein the critical region, with very encouraging results.A still more general theory of solutions is being developed by Kirkwoodand Buff.lo They show that the derivatives of the chemical potentialswith respect to concentrations, partial molar volumes, and compressibilitymay be expressed in terms of integrals of the radial distribution functionsof the several types of molecular pairs present in the solution.However,the evaluation of these radial distribution functions presents formidablemathematical difficulties, and as yet the theory has not yielded any experi-mentally verifiable results.For solutions in which the molecules are of approximately the same size,but differ substantially in their intensities of interaction, the higher orderterms in equation (4) will undoubtedly become important.Brown andLonguet-Higgins l1 have discussed these higher terms and have shown thattheir evaluation is impossible without recourse to a model or to a radialdistribution function for a pure liquid. The refined theory therefore en-counters the same mathematical obstacles as does that of Kirkwood andBuff.lo The importance of these higher terms has been confirmed experi-mentally by Prigogine and Mathot,12 who find that the system carbontetrachloride-neopentane shows positive deviations from Raoult's law, butthat the volume of mixing is negative. This behaviour is inconsistent withthe first-order theory of conformal solutions, and they interpret it in termsof the oscillating-lattice model, obtaining good agreement between theoryand experiment.Other papers of the last year on liquid solutions have mostly been concernedwith the mathematical consequences of the lattice model.The geometricalfactor in athermal solutions has been investigated by McGlashan,13 whogives an improved calculation of the " configurational entropy '' ofmixtures of molecules occupying one and two lattice sites. Guggenheimand McGlashan 14 have shown the unimportance of the interaction betweenR. P. Bell, Tram. Faraday SOC., 1937,33,496.D. Cook and H. C. Longuet-Higgins, Proc. Roy. SOC., 1951, A, 209, 28.l o J. G. Kirkwood and F. P. BufF, J . Chem. Phys., 1951,19,774.11 W. B. Brown and H. C. Longuet-Higgins, Proc.Roy. SOC., 1951, A , 209, 416.12 I. Prigogine and V. Mathot, in press.l3 M. L. McGlashan, Tram. Paraday Soc., 1961,47, 1042.l4 E. A. Guggenheim and M. L. McGlashan, &id., p. 929LONGUET-HIQGFINS : THE STATISTICAL THEORY OF SOLUTIONS. 77next-nearest neighbours in calculations of the free energy as a functionof the parameter w (see above); and the same authors l5 have shown howit is possible to improve upon the quasi-chemical approximation applied topairs of sites, by considering a quasi-crystalline mixture as a system of nearlyindependent triplets or quadruplets of sites on a close-packed lattice. Thequalitative results obtained by these approximations differ only slightly ;but McGlashan l6 has found that the third approximation is necessary toaccount satisfactorily for the order-disorder transitions occurring in the solidalloys of copper and gold.Whether these minor rehements of the theoryhave any real significance for liquids, where the lattice model itself is a grossapproximation, is very much open to question. Even hydrocarbon solutions,which would be expected to conform best with the lattice theory, behave ina manner which is not consistent with Guggenheim’s theory of configur-ational entropy. Mathot l7 has shown that the configurational entropy ofmixing of two constituents, when every molecule occupies the same numberof lattice sites, should have the same value as for an ideal solution. On theother hand, he finds that tetraethylmethane-octane and hexane-cyclohexanemixtures have a considerable non-ideal entropy, and further, that this is ofthe wrong sign to be attributed entirely to the energy of mixing.He con-cludes that the motions of the individual molecules must not be overlookedin the calculation of thermodynamic properties, and that a more sophisticatedtheory, such as that of Prigogine and Clarikian,g is required.Mixed Gases.-Probably the most useful contribution to the theory ofmixed gases in the last year has been a paper by Guggenheim and Mc-Glashan l8 on mixed virial coefficients. At sufficiently low pressures anymixture of two gases will obey the equation of stateAs these authors point out, there is no experimental or theoretical justific-ation for taking B,, , to be the arithmetic mean of B,, and B,: 2, and suggestan alternative way of calculating Bl,2, based on a generalisation of theprinciple of corresponding states.This principle suggests that the forcesbetween nonpolar molecules are of approximately the same functional form,as assumed in the theory of conformal solutions. By making a reasonableassumption about the relation of the “ unlike ” to the “ like ” interactionenergies, Guggenheim and McGlashan are led to a formula for B,,, whichinvolves only the properties of the pure components, and contains no arbitraryparameters. The values so calculated for a number of gas mixtures agreewith the experimental data within the errors of measurement, and com-pletely confbm the assumptions on which they are based.A very interesting subject for theoretical work is the solubility of solidsin gases, on which experimental material is now becoming available.Al6 E. A. Guggenheim and M. L. McGlasham, Proc. Roy. Soc., 1951, A , 206, 335.l7 V. Mathot, Bull. SOC. chim. Belg., 1950, 59, 111.M. L. McGIashan, to appear in Guggenheim, “ Mixtures ”, Oxford, 1952.E. A. Guggenheim and M. L. McGlashan, Proc. Roy. Soc., 1951, A , 206, 44878 QENERAL AND PHYSICAL CHEMISTRY.paper by Robin, Vodar, and Bergeon l9 gives a very brief discussion of thisproblem for the case in which the pressure is low enough for clusters of morethan two molecules to be negligible. The extremely high solubility ofnaphthalene in ethylene 2o in the critical region of the latter suggests, how-ever, that this approximation will have to be improved upon; but no treat-ment has yet been given of such complicated systems.H.C. L.-H.5. COLLOIDS AND SURFACE CHEMISTRY.Coagulation, Stability, and Theories of Lyophobic Colloids.-The modernchemical concepts on the subject of colloid coagulation are contained in adiscussion on the double-layer theories.1 Determinations of the rates ofprecipitation of hydrophobic solutions in statu nascendi of silver chloride,bromide, and iodide by various neutral electrolytes have been reported.2.3The electrical double layer was the subject of a discussion by the FaradaySociety,ll and remains a topic in which important advances are beingmade.* Discussion and experiment are still somewhat divided over thegeneral applicability of the Gouy and the Stern view of the electrical doublelayer, the former representing the counter ions as point charges whilst thelatter allows for their finite dimensions.Both theories assume the surfaceto be a uniformly charged impenetrable film, though this is almost certainlynot so. Following Verwey and Overbeek’s t h e ~ r y , ~ Levine has publishedfurther papers 6-9 on the application of the Stern theory of the doublelayer.10 In particular in Levine’s treatment the need for inclusion ofmore terms in the expression for the mutual free energy of two plates isindicated. The expression derived, which can also be obtained fromLippmann’s equation, contains three terms, one of which is identical with thatderived by Verwey and Overbeek.The two other terms are not necessarilynegligible. An interionic attraction theory has been applied to the diffuselayer around colloid particles.12 On the other hand, Davies l3 has discussedthe distribution of ions under a charged monolayer and shown the potentialat a charged interface (water-oil or water-air) to be a function of the ionicstrength of the aqueous phase; this potential has been determined by fourdifferent, independent methods. By comparison of the rates of desorptionof lauric acid and laurate ions it is shown that the Gouy equations for thelP S. Robin, B. Vodar, and R. Bergeon, Compt. r e d . , 1951, 232, 2189.*O G. A. M. Diepen and F. E. C. Scheffer, J. Amer. Chem. SOC., 1948,70,4081.1 E. A. Hauser, J. Phys. Colloid Chem., 1951, 55, 605.J Idem, ibid., p.1567.B. Tezak, E. Matijevic, and K. Schulz, ibid., p. 1557.E. J. W. Verwey and J. T. G. Overbeek, “ Theory of the stability of lyophobicIdem, Proc. Camb. Phil.Soc., 1951,47,217.Ann. Reports, 1950, 47, 79.colloids,” 1948, Elsevier.6 S. Levine, J. ColloidSci., 1951,6,1.8 Idem, ibid., p. 230. Q Idem, Proc. Phys. Soc., 1951, 64, 287.l2 A. L. Loeb, J. Colloid Sci., 1951, 6, 75.lo 0. Stern, 2. Elektrochem., 1924, 30, 508.11 Trans. Faraday Soc., 1951,47,409.l3 J. T. Davies, Proc. Roy. SOC., 1951, A, 208, 224LAWRENCE AND MILLS: COLLOIDS AND SURFACE CHEMISTRY. 79electrical potential a t a surface may be applied to ionised monolayers onsolutions of ionic strength as high as 2 ~ . The Gouy equations are also verifiedby it study of ionised films on solutions on very low ionic strength.Theseresults are compatible with the Stern view at fairly high electrical potentials.Elimination of the electrical potential from the four independent equationsyields six new relationships applicable to ionized monolayers, one of whichis an equation of state for charged films. According to this, for long-chainions on very dilute solutions and for moderate areas per ion, a charged gaseousfilm should obey the equation x ( A -A,) = 3kT. The effect of addedelectrolyte is discussed, together with equations suggested by previous in-vestiga t ors.By way of application of the electrical double-layer theory to emulsionsthe distribution of potential at an interface between two immiscible liquidshas been studied for the system of an adsorbed surface-active ion and theelectrolyte distributed in both phases.14Surface Activity.-Hansen 15 has considered theoretically the basic con-cepts involved in the application of surface thermodynamics to solid-gasand solid-liquid interfaces.The use of radioactive tracers for measurementof adsorbed substances at liquid-air interfaces has been continued,l6-l9soft p-emitters, cc-emitters, and isotopes with radio-active recoil atomsbeing used; the isotopes include 393, 14C, and 45Ca.20 The dependence ofsurface activity on the molecular weight of fractionated poly(methacry1icacid) 21, 22 has been investigated by a drop-weight method, the surface activitydecreasing with increasing molecular weight at constant concentration, and A yvarying inversely with the square root of the degree of polymerisation (n,600-7,800 ; N, 51,800--670,000).The thickness of the polymer film wasestimated to be of the order of the mean diameter of randomly coiled mole-cules and, owing to the coexistence of monolayer and adsorbed molecules, apotential barrier has been postulated between the hypercoiled dissolvedmolecules and the flattened stretched molecules in the monolayer. Else-where23 the free-acid collector theory has been shown to yield a linearrelation between contact angle and the absolute surface coverage forpotassium xanthate on galena.Interfacial-tension measurements by the simple yet accurate pendant-drop technique 24-26 have been made at elevated temperatures (30-200")l4 E.J. W. Verwey, Proc. K. Ned. AEad. Wet., 1950, 53, 376.l5 R. S. Hansen, J. Phys. Colloid Chem., 1951, 55, 1195.l7 G. Aniansson and 0. Lamm, Nature, 1950,165, 357.l9 A. P. Brady and D. J. Sally, J . Amer. Chem. Soc., 1948, 70, 914.2o G. Aniansson, J. Phys. Colloid Chem., 1951, 55, 1286.21 A. Katchalsky and H. Eisenberg, J. Polymer Sci., 1951, 6, 145.22 A. Katchalsky and I. Miller, J . Phys. Colloid Chem., 1951, 55, 1182.23 H. E. Wadsworth, R. G. Conrady, and M. A. Cook, ibid., p. 1219.24 J. M. Andreas, E. A. Hauser, and W. B. Tucker, J . Phys. Chem., 1938,42, 1001.26 H. W. Douglas, J. Sci. Instr., 1950,27, 67.26 S. Fordham, Proc. Roy. SOC., 1948, A , 194, 1.E. Hutchinson, J . Colloid Sci., 1951, 4, 600.L.K. Dixon, A. J. Weith, Jnr., A. Argyle, and D. J. Sally, ibid., 1949, 163, 84580 GENERAL AND PHYSICAL CHEMISTRY.and pressures (1-680 atm.) for the systems benzene-water and n-decane-water.27 Surface-tension determinations at lower temperatures ( - 100" to40°) by using the capillary-rise technique have been reported for carbonylsulphide.28Bulk Properties of Micellar Colloids.-The maxima and minima in the plotsof the degree of dissociation against concentration for soap solutions belowand near the critical concentration for micelle formation, as demonstratedby pH measurements by Powney and Jordan,29 have been accounted fortheoretically ; in two papers 30~31 the essential quantitative requirements ofthese curves are accounted for by simple molecular considerations, on theassumption that hydrolysed fatty acid is distributed between the anionicmicelles (with their gegenions) and the bulk aqueous solution, and by postu-lating the aggregation of fatty acid molecules at concentrations lower thanthe critical value.The formation of acid soap of approximately 1 : 1 'ratioof fatty acid to soap at the critical concentration is shown to be a conse-quence of this treatment, and the quantitative effects of solubilised alcoholpredicted. Estimates of AH and AX for the equilibrium soap molecule insolution and in spherical micelles have been made, and the influencingfactors considered. Subsequently 32 the maxima and minima have beenattributed to free acid and anion in sub-micelle particles, and in which thesurface equilibria are involved in determining the concentration abovesurface saturation.Calculation indicates that it is possible to have up to75% of the soap as sub-micellar and micellar particles at the concentrationcorresponding to the minimum in the plot of the degree of dissociation againstconcentration. The experiments indicate surface phase transitions at thetemperature given by Adam32a for the transition from a condensed to aliquid expanded state on a weakly acid substrate; the surface film would begaseous, with strong interaction, on a strongly alkaline substrate. Calcula-tions show appreciable free acid in the surface film even at high pH. Thebehaviour on hydrolysis is demonstrated by means of a model, and thenquantitatively applied to sodium palmitate, sodium oleate, and sodiummyristate solutions.The results predict both the experimental variationsof the degree of dissociation and the temperature coefficient.Work continues to be published on the application of the Iaw of massaction to micelle formation in solutions of colloidal electrolytes : experi-mental evidence indicates that the law holds not only for single micellarspecies but also for their distribution, favouring the formation of largeaggregates, the bound counter-ions tending to a limiting value as theelectrolyte concentration in~reases.~32 7 A. S. Michaels and E. A. Hauser, J . Phys. Colloid Chem., 1951, 55, 408.28 J. R. Partington and H. H. Neville, ibid., p. 1550.2D J. Powney and D. 0.Jordan, Trans. Faraday SOC., 1938,34,363.3O G. Stainsby and A. E. Alexander, ibid., 1949, 45, 585.3 l Idem, ibid., 1950, 46, 587.32 M. A. Cook, J . Phys. Colloid Chem., 1951, 55, 383.*aa " The physics and chemistry of surfaces," 3rd edn., Oxford University Press.33 M. J . Vold, J . Colloid Sci., 1950, 5, 506LAWRENCE AND MILLS: COLLOIDS AND SURFACE CHEMISTRY. 81Some thermodynamic properties of detergents have been measured bya modification of Hills and Baldes’s vapour-pressure apparatus, “ matched ”thermistors being used in an A.C. bridge ; 340 35 activity coefficients and molalrelative heats are thus deduced.The effect of solutions of salts (e.g., sodium and calcium chlorides) on non-ionic surface-active agents has been reported ; whilst the alkali-metalsalts usually salt-out non-ionic surface agents, the salts of the heavy metalssalt-in the colloids, and a crystalline complex of the agent, calcium chloride,and water has been isolated.Co-ordination of the agent with hydratedcalcium ions both in solution and at the solid-liquid interface is suggested.38A plea has been made for a rational unit of adsorption, namely the“ Gibbs ” (1 Gibbs represents 10-1O mole per sq.In another paper38 on soap hydrates, dehydration isobars have beendetermined and X-ray photographs of stages in the dehydration are given.This topic, particularly in respect to the sodium soaps, has been the subjectof much work which has not been discussed previously in these reports. Thefield is still confused; four clearly defined crystalline forms of soaps havebeen demonstrated by one set of workers; 39 others claim a multiplicity ofpolymorphic forms and hydrates differentiated in most cases by only minordifferences of X-ray diffraction patterns or small irregularities or inflectionsin heating and cooling curves.40, 41* 42 In all the work an absence of adequateanalytical control of the amounts of water present is noticeable.Concen-trated aqueous soap systems have been examined in the liquid-crystallineregion but the position is again confused ; both fibrous and lamellar structureshave been claimed; 43*44 there has been a singular reluctance to study theflow birefringence of the liquid-crystalline systems although the opticaleffects at very moderate rates of shear are most striking.So1ubilisation.-Since this subject was reviewed in 1948,46 there has beenless activity; but the demonstration that a long X-ray spacing can be givenby a solution of spherical micelles and that such a spacing cannot be re-garded as proof of a laminar micelle 4 6 p 4 7 p 4 8 is an important achievement.Much confusion still results from the large number of papers whose authors34 A.P. Brady, H. Huff, and J. W. McBain, J . Phys. Colloid Chem., 1951,55, 304.35 H. Huff, J. W. McBain, and A. P. Brady, ibid., p. 31 1.s* T. M. Doscher, G. E. Myers, and D. C. Atkins, Jnr., J . Colloid Sci., 1951, 6, 223.37 J . Phys. Colloid Chem., 1951.38 W. 0. Milligan, G. L. Bushey, and A. L. Draper, J . Phys. Colloid Chem., 1951,55,44.30 R.H. Fergusson, F. B. Rosevear, and R. C . Stillman, Ind. Eng. Chem., 1943,35,1005.40 J. Buerger, L. B. Smith, F. V. Ryer, and J. E. Spike, Proc. Nat. Acad. Sci., 1945,41 J. W. McBain, M. J. Vold, and S . A. Johnston, J . Amer. Chem. Soc., 1941, 63, 1000.4 2 R. D. Vold, J . Phys. Chem., 1945,49, 315.43 R. D. Vold and M. J. Heldman, J . Phys. Colloid Chem., 1948, 52, 148.4 4 D. G. Dervichian,R. S. Titchen,and H. J. van der Berg, Bull.Soc.chim., 1950,17,632.4 6 Ann. Reports, 1948, 45, 33.4 c R. W. Mattoon, R. S. Steams, and W7, D. Harkins, J . Chem. Phys., 1947,15, 209.4 7 G. S. Hartley, Nature, 1949, 163, 767.4 8 M. I,. Corrin, J . Chem. Phys., 1948,16, 844.31, 22682 GENERAL AND PHYSICAL CHEMISTRY.accepted the laminar micelle uncritically and interpreted all solubilisationon a simple picture of the micelle opening like a concertina, H.B. Klevenshas given a good review of the experimental results while, in general, notdiscussing the controversial points.49 He concludes that “ solubilisationand hydrotropy and related phenomena are essentially similar solubilityprocesses and that this concept of similarities can much better explain theexisting data than the use of minor differences which may be found in thesevarious phenomena.’’ “ Threetypes of solubilisation are illustrated. . . . These are (1) adsorption by themicelle usually on or near the soap-water interface ; (2) incorporationinto the hydrocarbon centre of the micelle, and (3) penetration into thepalisade layer of the micelle.” The first class he regards as a doubtful onebut suggests that phenols may be solubilised in this way.Presumably thiswould also include the low molecular-weight alcohols whose behaviour differsfrom their higher homologues in effect upon the X-ray spacings of solutionsof sodium dodecyl ~ u l p h a t e . ~ ~ Class (2) involves hydrocarbon solubilisat ionin which the solute molecules are not oriented with respect to the soap-waterinterface and “ possibly not oriented in the hydrocarbon-like micelle centre.’’I n class (3) the solubilised molecules are ‘‘ oriented fairly perpendicularly tothe water interface with the hydrocarbon portion of the molecule penetratingbetween the hydrocarbon chains of the soap molecules and lying fairlyparallel to them.”If the references to orientation are omitted, the distinction between thetypes becomes identical with that postulated by Lawrence in 1937.51Hartley in his classical paper on the solubilisation of trans-azobenzene insolutions of cetylpyridinium salts explicitly mentions the non-polar characterof azobenzene.and the liquid state of the interior of the m i ~ e l l e . ~ ~ Themechanism of entry of a molecule containing a polar group is essentially thatof such a molecule penetrating into an insoluble monolayer as described innumerous cases by the Cambridge workers, especially J. H. Schulman. Itwill be noted that Klevens, following Harkins, speaks of high adhesionenergy of a long-chain alcohol to water whereas the English workers havepostulated adhesion to the polar group of the soap by hydrogen bonding.Recent work tends to support the idea of the existence of the two typesof solubilisation.J. W. McBain and P. H. Richards 53 found that solubilisa-tion of octyl alcohol and benzaldehyde was greatly depressed by sodium orpotassium chloride in contrast to hydrocarbons. H. B. Klevens 54 reached asimilar conclusion from a study of the effects of potassium chloride, sulphate,and ferrocyanide on the solubility of heptane and octyl alcohol in potassiummyristate solutions. Salts reduce solubility of polar solutes and increasethat of hydrocarbon^.^^He then contradicts this view by saying :49 Chem. Reviews, 1950, 47, 1.50 W. D. Harkins and R. Mittelman, J . Colloid Sci., 1949,4, 367.5 1 A.S. C. Lawrence, Trans. Faraday SOC., 1937,33,819 ; Ann. Reports, 1940,37,108.62 G. S. Hartley, J., 1938, 1968.63 J . Amer. Chem. SOC., 1948, 70, 1338. 54 Ibid., 1950, 72, 3780.I. M. Kolthoff and W. Stricks, J . Phys. Colloid Chem., 1949, 53, 424LAWRENCE AND MILLS : COLLOIDS AND SURFACE CHEMISTRY. 83J. W. McBain and 0. A. Hoffman 56 found no evidence for a laminarmicelle in four colloidal detergents, one of which was a 20y0 solution of a bilesalt ; these authors conclude that the long spacing from the solubilisedsystems is from a Hess (bimolecular leaflet) micelle, but solubilisation ofdimethyl phthalate, which is said to occur by attachment to external polargroups, is considered to involve breakdown of the Hess micelle. Sodiumbenzene-, p-cymene- , and xylene-sulphonate solubilise polar and non-polarsubstances; 57 and even simpler substances, such as sodium butyrate,hexanoate, heptanoate, and decanoate, in aqueous solution solubilisehydrocarbons.58 P.A. Windsor 59 has also shown that sodium butyrate andisobutyrate possess solubilising properties.Those factors which increase the amount of colloid in a solution, that is,which reduce the micelle-formation critical concentration (cm), such as theaddition of salts 60 or decrease of temperature, usually increase the solubilis-ing power. Klevens 61 has shown that log em = A + nB for any homo-logous series (n is the number of carbon atoms in the chain, B is an empiricalconstant and A is another constant which varies with the nature of the seriesand with temperature).The addition of compounds containing polar groups, e .g.phenols, alcohols,and amines, greatly increases the solubilisation of hydrocarbons by soapsolutions.The straightforward issue, whether the micelle is solid or liquid, willprobably be resolved by recognition that it may be either ; that it begins as aliquid but that, if the molecule solubilised in it is large enough and of thecorreot shape, the interior of the micelle can be solid solution or para-crystalline. The solubilisation of non-polar molecules might for clarity benamed “ intramicellar solubilisation ” and the type where the solute moleculecontains a polar group, “ interaction solubilisation.” The relative importanceof the interior and the exterior of the micelle upon its phase state is not yetclear nor is it yet proved whether the interaction leading to a crystalline statemust always involve the transition of spherical to laminar micelle.Thework of Dervichian, reported earlier, is of particular interest here in that hiscomplexes of soaps and a variety of other substances were frequently‘‘ smectic.” 62 herecognises three regions above the micelle-formation critical concentration :( a ) electrolyte absent (shorter-chain soaps in all range of concentration orlonger-chain soaps a t lower concentrations only) ; ( b ) a moderate amount ofelectrolyte present, and (G) longer-chain soaps a t higher concentrationswithout electrolyte and all soaps with more electrolyte than is present inclass ( b ) .He concludes that the best interpretation of the facts is that theW. Philippoff 63 has recently reviewed the evidence :5 6 J . Phys. Colloid Chem., 1949, 53, 39.5 7 H. S. Booth and H. E. Everson, I n d . Eng. Chem., 1949, 41, 2627.58 R. Durand, Cornpt. rend., 1948, 226, 409.59 Trans. Faraday SOC., 1948, 44, 376 et seq.62 D. G. Dervichian and M. Joly, Bull. SOC. Chim. biol., 1946, 28, 426.0. A. Hoffman, J . Phys. Colloid Chem., $950, 54, 421.Discuss. Faraday SOG., 1951, 11, 96.Ibid., 1948, 52, 13084 a ENERAL AND PHYSICAL OHEMISTRY.micelle is a bimolecular leaflet of about 50 molecules, partly ionised andhydrated ; X-ray diffraction is caused by mutually orientated micelles.The question most rarely asked and most pertinent is whether we arejustified at all in speaking of a shape or a structure of the micelle as if it werea static tiny crystal. The micelles must be in kinetic equilibrium with themolecularly dispersed soap; it is highly improbable that a micelle is everbroken down to single molecules entirely as the energy required would betoo large. There must then be a statistical concentration of fragments ofmicelles: these have never been detected but it is not easy to see anymethod for their unequivocal detection. There is no reason for regardingthe interior of the micelle as anything but liquid : if the micelle is a crystallinebi-molecular leaflet, it must be held in regular arrangement by the polarend-groups, possibly hydrogen-bonded together laterally by water mole-cules. There is not however satisfactory evidence for such a crystallinemicelle. Debye 64 has suggested that in solutions of alkyltrimethylam-monium bromides the micelles are rod-shaped with the molecules orientedradially, but these results have been criticised particularly with respect tothe very large micellar weights determined.65 Little work has been reportedon Debye’s light-scattering method which seemed to be so promising in thesoap field ; dodecylamine hydrochloride and some homologues have beenexamined 66-the micelle-formation critical concentration was found toagree with the value obtained by other methods and to correspond with amolecular weight of 17,300 ; the presence of O-O46~-sodium chloride increasedthis value to 37,200. Increase of chain length increases the critical con-centration and, also, the number of molecules in the micelle. A laminarmicelle is postulated to explain the results. Debye and Cashin 67 havediscussed the effect of small refractive-index differences between solvent andsolute on light scattering.Emulsions.-Richardson has reviewed data on the formation and stab-ility of emulsions.68 Emulsification was carried out by injecting a stream ofone liquid at high velocity into the other stationary one; an ultrasonicmagnetostriction generator fitted on to the nozzle increased the dispersionwithout altering the velocity of efflux. Jellinek 69 has discussed particle-size distribution. Stability has been discussed by a number of workers :D. Dervichian and F. Lachampt 70 point out that the adsorbed emulsifyinglayer must have certain physical properties at the working temperaturewhich require the film to be in the condensed mesomorphic state; on theother hand, wetting agents must give non-organised fluid films. A. S. C.Lawrence 71 has suggested that the value of the interfacial tension decidesonly the amount of work required to break up the disperse phase and that it64 P. Debye and E. W. Anacker, J. Phys. Chem., 1951, 55, 644.65 D. A. I. Goring, P. Johnson, and N. K. Adam, Discuss. Paraclay Doc., 1951,11,151.66 P. Debye, Chem. WeeEbl., 1948, 44, 337.67 P. Debye and W. M. Cashin, J . Chern. Phys., 1951,19, 510.6 8 E. G. Richardson, J. Colloid Sci., 1950, 5, 404.69 H. H. G. Jellinek, J . SOC. Chem. Ind., 1950, 09, 225.70 BUZZ. SOC. Chim., 1946, 13, 486. 71 J . Boc. Chem. I n d . , 1948, 615LAWRENCE AND MILLS: COLLOIDS AND SURFACE CHEMISTRY. 85has nothing t o do with the stability of the system. The function of theemulsifying layer is to render ineffective collisions due to Brownian motion;such an energy barrier may be electrical, mechanical, or surface tension(such as the differential wetting of fine powder emulsifiers), but stability(except in the case of hydrosols) requires lateral high cohesion in the emulsify-ing layer. The anomalous viscosity of emulsions is attributed to the workrequired to deform the protected drops according to the picture of flowconditions suggested by C. F. G o ~ d e v e . ~ ~ * 73 It has been suggested that thesolution of surface-active emulsifying agent should be thixotropic. 74 E.Hutchinson has measured the interfacial tensions of solutions of n-octylalcohol in benzene against aqueous solutions of sodium dodecyl sulphate bythe sessile-drop method, and has calculated the surface excess of the twoadsorbed components ; 75 no evidence of complex formation was observed.Interfacial tensions against cyclohexane, chlorobenzene, and nitrobenzenewere measured, and differences of the expansion of the detergent film werefound with these liquids, the greatest condensation occurring with nitro-benzene. Measurements of the adsorption of potassium laurate and ofsodium dodecyl sulphate a t the water-n-decane interface, and data for four-component systems containing cholesterol are reported.'Sa These authorsconclude that in the latter molecular interaction a t the interface isunimportant in the determination of the value of interfacial tension.However L. Desalbres, who examined the surface tension of solutions ofvarious concentrations of sodium dodecyl sulphate in the presence of equi-molecular proportions of terpineol, dihydro-a-terpineol, or cyclohexan01,~~observed that these alcohols depressed the interfacial tension, and minimawere obtained with the last two compounds.R. Matalon 77 has shown that there is spontaneous emulsification of aNuj ol solution of cholesterol in aqueous sodium dodecyl sulphate with muchreduced concentration of the soap when salts such as sodium chloride andcopper sulphate are added to the aqueous phase. Stability of the emulsionsvaries with salt concentration and the valency of the added cation. Xyleneis spontaneously emulsified in O.l-O~S~-aqueous solutions of dodecylaminehydrochloride. Inequalities of interfacial tension are considered to be thecause of the emulsification.It is obvious that the various cases of " spontaneous " emulsificationreported in recent years are misnamed. The system can be an emulsiononly insofar as there is some interfacial tension between the phases; if thisis reduced to zero, miscibility results. Certain interesting results follow ifthe interfacial tension is very small, especially in those not infrequentcases where a small interfacial tension is accompanied by a very large72 Trans. Famday Soc., 1939, 35, 342.73 A. C. S. Lawrence and W. Killner, J. I n s t . Petrol., 1948, 34, 821.74 L. Y a Kremney, Colloid J., U.S.S.R., 1948, 10, 18.76 J . Colloid Sci., 1948, 3, 413.750 E. G. Cockbain and A. I. McMullen, Trans. Faraday SOC., 1951,47, 322.16 Bull. SOC. chim., 1950, 17, 26. 7' Trans. Faraday SOC., 1950, 40, 67486 GENERAL AND PHYSICAL CHEMISTRY.viscosity or viscoelasticity. Any shearing of such a system in preparation,stirring, or removal of a specimen or the mounting of it on glass mustinvolve distortion of spherical drops, and any such distortion involves somedegree of orientation and anisotropy. Once in existence, the restoringforce of the small interfacial tension has to operate against a veryhigh resistance to relaxation. The " spontaneous " process, if not due toextraneous disturbances or to a myelin-figure mechanism (activated byosmotic flow), could be similar to the emulsion-like systems formed by binarymixtures just below their consolute temperature, where local internalfluctuations of temperature cause a relatively large change of phase com-position, e.g. phenol-water mixtures. 78The light-scatteringmethod gives 100400 A as the diameter of the droplets. Alkylpoly-ethylene oxides in light petroleum have been used and small amounts ofwater added ; peculiar viscous and birefringence results were found whichthe authors explain as due to a variety of micelles. The function of thewater is the hydrogen bonding of ethylene oxide chains.80 Electricalconductivity measurements have been made of solutions of dodecylaminehydrochloride in water-organic solvents.8183 which were not available in this country during the war,on the rate of breaking of water-in-oil emulsions are of a rather specialinterest because they give a treatment which, although not entirely satis-factory, does explain the autocatalytic form of a slow sedimentation process.Where the rate of Stokes sedimentation becomes important compared withthe Brownian velocity, i.e. when the particles are approaching one anotherat a rate comparable with the collision Brownian-movement velocity, thereis obviously an effective increase of concentration and the process isautocatalytic. 71" Soluble oil '' type systems are reported again.79TwoA. S. C. L.0. s. M.C. E. H. RAWN.A. S. C. LAWRENCE.H. C. LONGUET-HIGGINS.C. A. MCDOWELL.0. S. R~ILLs.78 E. K. Ridealand A. K. Goard, J., 1925,127, 780, 1668.70 J. Schulman and J. A. Friend, J. Colloid Sci., 1949,4, 97.81 A. W. Ralston and E. N. Eggenburger, J. Phys. Colloid Chem., 1948, 52, 1494.82 A. Dobrowsky, Kolloid Z., 1941, 95, 286.83 E. L. Lederer, ibid., 1935, 71, 61.J. H. Schulman, R. Matalon, and M. Cohen, Discuss. Furuduy SOC., 1951,11, 117

ISSN:0365-6217    

DOI:10.1039/AR9514800007

出版商:RSC    

年代:1951

数据来源: RSC

摘要:

INORGANIC CHEMISTRY.ON the occasion of the Diamond (75th) Jubilee of the American ChemicalSociety, an interesting picture has been drawn of Inorganic Chemistry asit is to-day and of the way in which “ the past quarter century has witnessedthe transition of inorganic chemistry from an almost purely descriptivesubject to one in which all the modern developments of chemistry and physicshave found applications.”Typical of the use of new methods has been the preparation of a large andgrowing number of simple and complex inorganic compounds in which thevalencies of the constituent atoms are “ anomalous ”. This field has beenreviewed2 especially in connection with compounds of the elements of thefirst transition series and of several of the A-subgroup members of the first tofourth groups.Other reviews on special topics that have appeared during the year includethose on “ The Addition Compounds of Olefines with Mercuric Salts,’’ on“ The Germanes and their Organo Derivatives,”on “ The Stabilities of Complex Compounds,” and on “ Solvent Extractionand its Applications to Inorganic Analysis.”’ The last is a technique whichis coming into increased use, not only for analysis, but also for the large-scale preparation of pure inorganic compounds : the now well-known etherextraction method for the purification of uranyl nitrate is a case in point.Group 1.-The extension of alkali-metal superoxide formation to includesodium was noted last year.8 been obtained of theexistence also of a lithium superoxide, stable at -78” and formed by the rapidoxidation of the metal in liquid ammonia solution. The light-absorption ofsuch lemon-yellow solutions is similar to that of oxidised solutions of sodiumand potassium, which are known to form superoxides under the same con-ditions.The so-called alkali-metal ‘‘ ozonates ” have also received attention.lOThe deeply coloured products of the ozonisation of potassium and caesiumhydroxides are soluble in liquid ammonia; that of sodium hydroxide isinsoluble.Analytical and magnetic data seem to indicate that these com-pounds have essentially the composition MO,, with one unpaired electron,and decompose on storage or on gentle warming, to give the superoxide andoxygen.on “ Nitrosyl Chloride,”Evidence has nowL.F. Audrieth, I n d . Eng. Chem., 1951,43, 269.W. Klemm, Angew. Chem., 1951, 63, 396.J. Chatt, Chem. Reviews, 1951, 48, 7.L. J. Beckham, W. A. Fessler, and M. A. Kim, ibid., p. 319.A. R. Burkin, Quart. Reviews, 1951, 5, 1.H. M. Irving, ibid., p. 200.0. H. Johnson, ibid., p. 259.Ann. Reports, 1950, 47, 99, ref. 11.@ J. K. Thompson and J. Kleinberg, J. Amer. Chem. SOC., 1951,73, 1243.lo T. P. Whaley and J. Kleinberg, ibid., p. 7988 INORCIANIU OHEMISTRY.The amides of the alkali metals are commonly prepared by catalyticdecomposition of their liquid-ammonia solutions by, e.g., ferric nitrate. Amethod has been described l1 for the preparation of pure potassamide, freefrom oxygen or traces of catalyst, by the use of a platinum catalyst in aclosed system.I n the preparation of pure czsium, use has been made l2 of the sparingsolubility of cesium chloroantimonite in glacial acetic acid.Several new co-ordination compounds of the " coinage " metals have beenreported.Complex compounds of bivalent copper with triethylenetetra-mine 13-with which it forms only a 1 : 1 complex-and of univalent copperwith the di(tertiary arsine) chelate group o-phenylenebisdimethylarsine 14have been examined. Attempts to prepare compounds in which the latterchelate group was co-ordinated to a cupric ion were unsuccessful.An investigation l5 of the structure of the blue and the brawn form of thecuprous-cupric complexes of methyldiphenylarsine, formerly believed t o begeometric isomers with an empirical formula Cu2C13,3AsPh2Me, has shownthat the arsine is present as arsine oxide and that the empirical formula ofthe blue form is actually Cu3C1,,4AsPh2Me0 with a structural formulaprobably [Cu(AsPh,MeO),] [CuCl,],.The brown form contains a smallamount of cupric chloride (5-10%) probably as a polymerised CuC13-anion, which causes the difference in colour.A further contribution has been made to the question of the nature ofsolid argentic oxide.16 It is reported that an oxide of bipositive silver con-taining 99-4-99+3% of Ago has been prepared by the anodic oxidation of a10% solution of silver nitrate, followed by decomposition with boiling waterof the black crystalline nitrate complex, of the composition Ag,NO,,,formed at the anode. If this oxide were indeed the oxide of a bipositivesilver ion, one would expect it to be paramagnetic, or diamagnetic if it werean argentous peroxide.The preparation was actually found t o be diamag-netic (a similar observation was made by S. Sugden nearly 20 years ago 17),but it does not appear to be a peroxide since it is reported not to yield hydrogenperoxide on acidification. On the other hand, the black crystalline nitratecomplex is paramagnetic, as is also the solution of Ago in concentratednitric acid. It would seem therefore that the diamagnetism is a feature ofthe solid state.The solvent power of aqueous solutions of silver, mercury, and cuproussalts for the lower olefins is well known. Liquid complexes have now l8been prepared between anhydrous silver nitrate and propylene or but-1 -enecontaining over 1.3 mols.of olefin per mol. of silver nitrate. The complexesl1 J. de Postis and L. Liiemann, Compt. rend., 1951, 233, 867.l2 G. Thomaa, Ann. Chim., 1951, 6, 367.Is H. B. Jonassen and A. W. Meibohm, J . Phys. Colloid Chem., 1951, 55, 726.l4 A. Kabesh and R. S. Nyholm, J., 1951,38.l6 A. B. Neiding and I. A. Kazarnovskii, Doklady Akad. Nauk. S.S.S.R., 1951, 78,l7 J., 1932, 161.l5 R. S. Nyholm, J., 1951, 1767.713; Chem. Abs., 1951,45, 8385.A. W. Francis, J . Amer. Chem. SOC., 1961, 73, 3709FAIRBROTHER. 89are not very stable and may be resolved into their components by warmingor reduced pressure.Chloro- and bromo-auric acids, HAuC1, and HAuBr,, react with ethylene-diamine and propylene-1 : 2-diamine, to give complex compounds with oneor two diamine molecules per atom of gold.lg These compounds may losea proton from one of the co-ordinated amine groups and behave as acids.The compounds [Au(en),]Br, and [Au(en - H)]Br,, where en - H representsthe anion resulting from the removal of a proton from an amine group, havebeen isolated.Gold(II1) forms a series of compounds with 2 : 2'-dipyridyland 1 : 10-phenanthroline, but in each case only one bidentate molecule isco-ordinated to a single gold atom.Group II.-Conflicting views appear in the literature regarding thenature and stabilities of the hydrates of beryllium sulphate. The systemBeS0,-H,S0,-H20 has now been re-investigated 2o and it has been shownthat a t ordinary temperatures the stable solid phase is the tetrahydrateBeS04,4H,0. At 89.0" a transition into solution and BeS04,2H,0 takesplace, the dihydrate being the stable form above this temperature : noevidence of the formation of a monohydrate was found.Magnesium dihydride has been prepared by the pyrolysis of magnesiumdialkyls, or by the reaction of these with diborane.Diethylmagnesium andexcess of diborane in ether give Mg(BH,),, whilst magnesium bromide andlithium aluminium hydride, or MgH, and aluminium chloride, in ether, giveMg(A1H4),.21Reduction of the metal alkyls by lithium aluminium hydride in etherealsolution has also been used z2 for the preparation of magnesium hydride andof the hydrides of beryllium, zinc, and cadmium. Zinc and cadmiumhydrides were obtained in a pure condition by this method, but those ofberyllium and magnesium retained traces of the solvent ether. The hydridesof beryllium, zinc, and cadmium are less stable than magnesium hydride :cadmium hydride undergoes rapid decomposition at 0".Zinc hydride decom-poses very slowly a t room temperature, though it can be heated at 50" fora short time without evident decomposition, whilst beryllium hydride beginsto lose hydrogen at 125". Beryllium and zinc hydrides react with diboraneto give Zn(BH,), and Be(BH,),, respectively.An examination 233 24 of the conditions of formation of basic magnesiumchloride between 50" and 175" has revealed the formation of several new well-defined basic salts within this temperature range.In an attempt 25 to prepare alkaline-earth superoxides by a metatheticalreaction between potassium superoxide and barium nitrate in liquid-ammonialo B.P. Block and J. C. Bailar, J. Amer. Chem. SOC., 4722.2o A. N. Campbell, A. J. Sukava, and J. Koop, ibid., p. 2831.21 E. Wiberg and R. Bauer, 2. Naturforsch., 1950, 5, B, 396, 397.22 G. D. Barbaras, C. Dillard, A. E. Finholt, T. Wartik, K. E. Wilzbach, and H. I.a3 L. Walter-LBvy and Y. Bianco, Cornpt. rend., 1951, 232, 730.24 Y. Bianco, ibid., p. 1108.s6 E. Seyb, Jr., and 3. Kleinberg, J. AMP. Chem. SOC., 1951, 73, 2308.Schlesinger, J. Amer. Chem. SOC., 1951, 73, 458590 INORGANIC CHEMISTRY.solution, it has been found that these reactants evolve oxygen and form amixed superoxide-peroxide :Ba(NO,), + 4K02 = K,Ba(0,)20, + 2KNO, + 0,analogous to the mixed, so-called sesquioxides Rb406 and Cs,O,.Sub-stitution of sodium superoxide for potassium superoxide leads mainly to theformation of barium peroxide, whilst in the case of strontium nitrate, bothsuperoxides lead to the formation of strontium peroxide.A crystalline barium chloride metaphosphate, with the compositionBa4P,01,C1,, has been prepared 26 by the passage of chlorine gas over bariumorthophosphate-carbon briquettes at 800". Examination of its propertiesindicates that it is an association of barium, metaphosphate, and chlorideions, rather than a chlorophosphate.A study27 of the 25" isotherm of the system Ba(IO,),-BaC12-H,Osystem has demonstrated the formatidn of an incongruently soluble hydrateddouble salt with the probable formula Ba( IO3),,BaC1,,2H,O.By the introduction of a polar substituent (e.g., OH, NH,, CO,H, orSO,H) into the 5-position of 8-hydroxyquinoline, which in its unsubstitutedform is very widely used in analytical work for the preparation of insolublecomplexes with a variety of metal ions, it becomes possible to prepare com-plexes of only slightly less stability but which are more soluble in water andtherefore capable of being studied in aqueous solution.For example,288-hydroxyquinoline-5-sulphonic acid forms stable co-ordination compoundswith several metal ions. The covalent nature and tetrahedral distributionof the bonds in its zinc complex, Zn(cgH6S04N)2, has been demonstrated bythe optical resolution of its strychnine salt in pyridine solution.Zinc ion has also been shown 29 to form complex compounds with 1 : 10-phenanthroline, containing 1, 2, or 3 molecules per zinc ion.To this may beattributed the interference of traces of zinc when iron is determined colori-metrically with this reagent.The composition of the familiar black solid obtained when ammonia isadded to a mercurous salt has been re-in~estigated.~~ It is found that theaction of 0-1N-aqueous ammonia on mercurous nitrate or perchlorate maybe described by the equation :where X- is NO,- or Clod-, and that in addition to free mercury theprecipitate contains the ammonolysed salts Hg,N*NO,, Hg2NC10,,Hg,NCl,H,O, and HgNH,Cl.A number of complex compounds of mercuric halides with diarylselen-oxides have been prepared.,l pp'-Diethoxydiphenyl and pp'-dimethoxy-diphenyl selenoxides and dibenzoselenophen oxide form solid addition com-2Hg2++ + X- + 4NH4*OH = 2Hg + Hg2NX + 3NH4+ + 4H2Oz 8 F.R. Hartley and A. D. Wedsley, J . Amer. Chem. SOC., 1951, 73, 1599.so I. M. Kolthoff, D. L. Leussing, and T . S . Lee, ibid., p . 390.31 E. S. Gould and J. D. McCullough, ibid., p. 3196.J. E. Ricci, ibid., p. 1375.S. D. Arora, W. N. Lipscomb, and M. C. Sneed, ibid., p. 1015.28 J. C. I. Liu and J. C . Bailar, Jr., ibid., p. 5432FAIRBROTHER. 91pounds with mercury(I1) chloride and bromide. The last two also form solidcompounds with mercury(I1) iodide.The two mercurous arsenates, Hg,As,08 and Hg,As,O,, have been pre-pared.32 They are decomposed into the corresponding mercuric salts andfree mercury when heated in a vacuum at 300".The chemistry of mercury(I1) bromide as an ionising solvent 33 has beencarried a stage further.Determination of the molecular weights of anumber of solutes in molten mercury(I1) bromide 34 gives the cryoscopicconstant of this solvent (m. p. 238.5") as 37-45' per mol per 1000 g. of HgBr,.Sulphur appears to dissolve as s8. Like mercuric oxide, the sulphide, selenide,and telluride are potential electrolytes in mercury(I1) bromide : the tellurideis a fairly strong electrolyte in contrast to the oxide, which is very weak.Potentiometric titrations with gold electrodes have been carried out with the"acid " (HgBr)ClO, against the "bases " AgBr and T1Br.The ionicproduct in molten HgBr, at 250" is [HgBr+][Br-] = 2 xGroup III.-The hydrogen-bridge structure of the diborane molecule nowseems fairly well established. Additional evidence in ihs favour has beenobtained from a re-investigation of the structure of diborane and ethane bythe electron-diffraction method,35 which has eliminated the ethane-like model,and from the Raman spectrum of tetramethyldib~rane.~~The most favourable conditions for the isolation of pentaborane from theproducts of pyrolysis of diborane 37 and the determination of its molecularstructure have received attention. Both a re-consideration 38 of electron-diffraction data and an X-ray diffraction study of the crystalline solid39lead to a tetragonal pyramidal structure in which, it is suggested, the inter-atomic binding is of a " metallic " type.Addition compounds of trimethylboron with n-propyl-, n-butyl-, n-amyl-,and n-hexyl-amine have been prepared,40 and their dissociation in the gaseousphase examined : the heats of dissociation increase fairly regularly withchain length, to a limit of approximately 18.5 kcal.A study of the stereochemistry of tercovalent boron 4 1 has suggested thatsome major differences between the chemistry of substituted amines R3N,and of borines, R,B, may arise from the planar configuration of the boronvalency bonds as compared with the pyramidal configuration of nitrogen.Further studies have been made of the reactions of the dimethylamino-boron h y d r i d e ~ .~ ~32 H.Guhrin and R. Bouitrop, Compt. rend., 1951, 232, 65.33 Ann. Reports, 1950, 47, 101, ref. 24.34 G. Jander and K. Brodersen, 2. anmg. Chem., 1951,264,57, 76, 92.55 K. HedbergandV. Schomaker, J. Amer. Chem. Soc., 1961,73, 1482.36 B. Rice, J. M. Gonzalez Barredo, and T. F. Young, ibid., p. 2306.37 L. V. McCarty and P. A. Di Giorgio, ibid., p. 3138.38 K. Hedberg, M. E. Jones, and V. Schomaker, ibid., p. 3538.39 W. J. Dulmage and W. N. Lipscomb, ibid., p. 3539.40 H. C. Brown, M. D. Taylor, and S. Sujishi, ibid., p. 2464.41 H. C. Brown and E. A. Fletcher, ibid., p. 2808.42 A. B. Burg and C. L. Randolf, Jr., ibid., p. 95392 INORGANIC CHEM'ISTRY.Borazole (B3N3H6), which was originally prepared by the action of heaton diborane diammoniate, has now 43 been prepared by the action of lithiumborohydride on ammonium chloride at about 300", in the absence of solvents.The ability of boron trifluoride to ionise a neutral oxygen-containingmolecule and to form a complex anion with the negative oxygen-containingfragment, which is illustrated by the ethyl ethoxyfluoroborate structure ofboron trifluoride ethyl etherate, C2H5(BP3*OC2H,),44 is shown also by thebehaviour of the 1 : 1 addition compound of boron trifluoride with aceticacid as acetoxytrifluoroboric acid, H(BF,*O*CO*CH3),45~ 46 and of BF3,H20and BF3,2H20, which have now been prepared in a pure crystalline form 47(m.p.5-9-6.0" and 6.2"), as H+(BF,*OH-) and (H,O+)(BF,*OH-) respectively.Evidence for the formation and hydrolysis of HBF3*OH as an intermediatestage in the hydrolysis of boron trifluoride has also been given by kineticstudies 48 and it has been suggested that the slow formation of HBF, in thisprocess takes place by the reaction :HBF,*OH + HF = HBF, + H20The behaviour of difluorodihydroxyboric acid, H3B02F2, towards thehalogenating agents phosphorus frichloride, pentachloride, pentabromide,and tri-iodide and thionyl chloride has been examined.49 No reaction wasobserved with phosphorus trichloride : with the remaining reagents thereactions were characterised by the formation of boron trifluoride or boronphosphate, or both.By the careful addition of anhydrous ethylene chlorohydrin to borontrifluoride at -78", bis-2-chloroethoxyboron chloride and tris-2-chloroethylborate are 0btained.~0By the reaction of metal chlorides MeC1, with lithium aluminium hydride,mixed hydrides are obtained : 51MeC1, + nLiAIH, = Me(A1H4), + nLiClI n this manner, the aluminium hydrides (" alanates ") of beryllium, magnes-ium, aluminium, gallium, indium, and thallium(rI1) have been prepared.The stabilities of these compounds in each periodic group decrease withincreasing atomic radius : e.g., Tl(UH4)3 decomposes even below -115",but aluminium " alanate," Al(AlH,),, presumably aluminium hydride, isstable above 100".A similar series of the corresponding gallium compounds(" gallanates ") has been prepared by the use of lithium gallium hydride.Two gaseous oxides of aluminium have been identified in equilibrium withaluminium-aluminium trioxide mixtures 52 a t high temperatures : A120 is43 G.W. Schaeffer, R. Schaeffer, and H. I. Schlesinger, J . Amer. Chern. SOC., 1951,73, 1612.45 N. N. Greenwood, R. L. Martin, and H. J. Emelkus, J., 1951, 1328.46 N. N. Greenwood and R. L. Martin, ibid., p. 1795.4 7 Idem, ibid., p. 1916.50 D. R. Martin and L. S . Mako, J . Amer. Chern. Soc., 1951, 73, 2674.51 E. Wiberg, Angew. Chern., 1951, 63, 485.m L. Brewer and A. W. Searcy, J . Am?. Chem. Soc., 1951, 73, 6808.44 Ann. Reports, 1950, 47, 102, ref. 32.48 C. A. Wamser, J . Amer. Chern. SOC., 1951, 73, 409.L. H. Long and D. Dollimore, J., 1951, 1608FAIRBROTHER. 93evolved when aluminium trioxide is heated with aluminium or anotherreducing metal, and A10 appears to be the principal compound vaporisedfrom Al2O, alone, the b.p. of which is 3800" -J= 200" K.The equilibrium and rate of formation of aluminium monochloride by thereaction AlCl, + 2A.l = 3AlC1 have been investigated 53 by measuring theamount of aluminium carried forward in the vapour phase when aluminiumtrichloride vapour is passed over heated aluminium.The diffraction of X-rays by fused aluminium trichloride shows that thedimeric structure A12Cls, which is well known to exist in the vapour at theboiling point, is also present in the liquid phase.54Further work 55 on the exchange of radio-chlorine between solid alumin-ium chloride and organic chlorides has shown that this exchange can takeplace, even in the absence of a solvent, as a heterogeneous reaction on thesurface of the aluminium chloride.The presence of the ion AlC1,- in solid NaAlC1, has long been assumed :experimental evidence of its existence has recently been obtained from theX-ray analysis of the crystal structure of NaA1C14.56By a detailed study of the hydrogen chloride-aluminium chloride systemunder a variety of conditions, including temperatures as low as -120",57 andas high as 195" under a pressure of nearly 2 atmos~heres,~8 it has been shownconclusively that the free acid HAlCl,, frequently assumed to be formed inFriedel-Crafts catalyses using aluminium chloride, does not exist, at allevents in any concentration which can be detected.The relative stabilities of several aluminium bromide complex compoundsin benzonitrile 59 and nitrobenzene 6o solutions have been examined.An almost pure crystalline aluminium sulphide A12S, has been preparedby direct combination of the elements, followed by heating a t 1150" in avacuum to remove traces of uncombined aluminium, and subsequent slowcooling of the melt.61The co-ordination compounds of trimethylgallium with all the trimethylderivatives of the group VB elements from nitrogen to antimony and withall the dimethyl derivatives of the group VIB elements from oxygen totellurium have been prepared.62 A study of the dissociation of these com-pounds indicates a regular decrease of donor properties in the sequenceN > P > As > Sb > Bi and an irregular decrease in the sequence0 > Se > S = Te.Electrometric titrations and studies of the hydrolysis of tervalentgallium show that the Gas+ ion is somewhat more acidic than the In3+ ionm A.S . Russell, K. E. Martin, and C. N. Cochran, J. Amer. Chem. SOC., 1951,73, 1466.64 R. L. Harris, R. E. Wood, and H. L. Ritter, ibid., p. 3151.6 6 M. Blau and J. E. Willard, ibid., p. 442.6 6 N. C. Baenziger, Acta Cryst., 1951, 4, 216.67 H. C. Brown and H. Pearsall, J. Amer. Chem. SOC., 1951, 73, 4681.& * R. L. Richardson and S. W. Benson, ibid., p. 5096.IB R. E. VanDyke and T. S. Harrison, ibid., p. 402. 6o Idem, ibid., p. 575.62 C. E. Coates, J., 1951, 2003. J. Flahaut, Compt. rend., 1951, 232, 33494 INORGANIC CHEMISTRY.and that the hydrolysis of Ga3+ is governed by the formation of GaOH++ions.63from the polarographic reduction ofIn3+ in the presence of chloride ions, of the existence of two complex ionsInCl,+ and InC1,- : the latter is relatively unstable and exists only in solutionsof high chloride-ion content'.Pure thallous hypophosphite has been prepared (m.p. 114" & 0.5", corr.).At temperatures even below the m. p., some decomposition occurs, and onbeing heated in air the salt slowly liquefies, probably through oxidation tothallous phosphite, T1H2P0, (m. p. 70").65Lanthanons.-The steady development of improved methods of separationand purification of the lanthanons, both by ion-exchange methods and byfractional precipitation in the presence of complexing agents, continues.It has been found 66 that a more efficient separation can be achieved byan ion-exchange resin of high capacity than by one of low : gram quantitiesof erbium, holmium, and dysprosium, of a purity greater than 99%, havebeen separated by the use of Nalcite HCR resin.The use of salts of ethylenediamine-NNN'N'-tetra-acetic acid 67 and ofantipyrine 68 for the separation mainly of the heavier lanthanons has beenextended to include the use of the former for the separation also of some ofthe lighter members of the series.69Ceric nitrate may be readily extracted from a solution containing nitricacid (5-6~) by peroxide-free ether, in the form of the soluble complexH,[Ce(NO,),] or a mixture of this with H[Ce(NO,),,H,O] 70.The lanthanontervalent nitrates are inappreciably extracted under the same conditions.The oxides of quadrivalent praseodymium and terbium, the latter in apure form, have been obtained by the action of atomic oxygen (from anelectrodeless discharge) on the lower oxides.71Group IV.-It has been known for a long time that graphite is able toocclude, between its layer planes, a variety of other atoms and moleculeswith the resultant formation of " lamellar compounds." Several new com-pounds of this type have recently been described, Compounds with chromylchloride and chromyl fluoride are formed when graphite is warmed with thehalide in q~estion,'~ and an examination of the equilibrium pressure of potas-sium over the system potassium-graphite a t various temperatures up to 400"has indicated the existence of two additional potassium compounds KC24and KC4,.73 Measurements of the dissociation pressures of C,M and C24M(where M = K, Rb, Cs) have shown that the stabilities of these alkali-metalSome evidence has been obtained63 T.Moeller and 0. L. King, J . Phys. Colloid Chem., 1950, 54, 999.64 J. A. Schufle, M. F. Stubbs, and R. E. Whitman, J . Amer. Chem. SOC., 1951,?'3,1013.6 6 W. A. Jenkins and D. M. Yost, ibid., p. 2945.6 6 F. H. Spedding, E. I. Fulmer, J. E. Powell, T. A. Butler, and I. S. Yaffe, ibid., p. 4840.6 7 J.K.Marsh, J., 1950,1819; J . , 1951,1461. 68 Idem, J., 1950,577; J . , 1951,1337.6g R. C. Vickery, J., 1951, 1817. 70 A. W. Wylie, J., 1951, 1474.71 D. M. Gruen, W. C. Koehler, and J. J. Katz, J. Amer. Chem. SOC., 1951,73, 1475.72 R. C. Croft and R. G. Thomas, Nature, 1951, 168, 32.7a A.Hhrold, Compt. rend., 1951, 232, 838FAIRBRO THER . 95compounds increase with the atomic mass of the alkali meta1.V4 Some ideaof the nature of the bonding in these compounds has been obtained from astudy of the physical properties of the compounds C,K and C,Br.75 Themarked diamagnetism of graphite, associated with its 7c electrons, is absentin both compounds; in fact, C8K is considerably more paramagnetic thansolid potassium itself, and both compounds are better conductors of electricitythan pure graphite.Reactions between solid refractory carbides can take place a t hightemperatures to yield a new compound and free carbon; a t a temperatureabove 1920", titanium carbide (Tic) reacts with boron carbide (B,C) to givetitanium boride (TiB,), carbon, and a higher boride of unknown com-position.7sInvestigation of the structure of thorium carbide (ThC,), by X-ray andneutron d i f f r a c t i ~ n , ~ ~ has shown that it contains C-C groups, but the C-Cdistance (1.5 b) is too great for these to be acetylene ions ; moreover, ThC,yields exclusively methane on hydrolysis.A metallic type of structure,with essentially covalent binding, has been suggested : compressed thoriumcarbide powder possesses an electrical conductivity comparable with that ofpowdered thorium itself.When acetylene is passed into a solution of sodium or lithium in anhydrousammonia, the weakly dissociated acetylides C,HNa and C,HLi are produced. 78On evaporation of the ammonia, these acetylides readily undergo spon-taneous decomposition into the impure carbides Na,C, and Li,C, containingmore or less acetylene and ammonia-the lithium acetylide being too un-stable to be isolated in the solid state without decomposition, even a t-33.5".On the other hand, the corresponding barium compound, whenheated in a vacuum a t 120", gives a highly reactive product which consists ofsome 97 yo of barium carbide, B+,. 79A new approach to the study of the important carbon-carbon monoxide-carbon dioxide equilibrium has been made with the aid of 14C used as afracer.*O The results obtained are in agreement with the mechanismsuggested by earlier workers, according to which a carbon dioxide moleculeapproaches the carbon surface, drops one of its oxygen atoms, and evaporatesas carbon monoxide, leaving an oxygenated carbon surface from which asecond molecule of carbon monoxide is slowly desorbed.A number of new organo-silicon and halogeno-organo-silicon compoundshave been prepared.8174 A.H6rold, Compt. rend., 1951, 232, 1484.76 F. R. M. McDonnell, R. C. Pink, and A. R. Ubbelohde, J., 1951, 191.7 6 H. M. Greenhouse, 0. E. Accountius, and H. H. Sisler, J . Amer. Chem. SOC.,7 8 E. Masdupuy and F. Gallais, Compt. rend., 1951, 232, 1935.7* Idem, ibid., p. 1837.*O F. Bonner and J. Turkevich, J . Amer. Chem. Xoc., 1951,73, 561.*l R. V. Lindsey, ibid., p. 371 ; H. H. Anderson, D. L. Seaton, and R. P. T. Rudnicki,ibid., p. 2144; H. H. Anderson, ibid., p. 2351; R. E. Scott and K. C. Frisch, ibid., p.2599 ; J.E. Noll, J. L. Speier, and B. F. Daubert, ibid., p. 3867.1951, 73, 5086. 7 7 E. B. Hunt and R. E. Rundle, ibid., p. 477796 INORQANIU CHEMISTRY.When silicon tetrafluoride is circulated over glass wool at 430" or overanhydrous sodium silicate at 720-730", a slow reaction takes place andpolymerised fluorosiloxanes are obtained.8,In order to clarify the relationships between the chemical propertiesand molecular structures of the complex silicates, the synthesis has beenattempted of a number of silicates with polymeric anions of known structureby the hydrolysis of neutral monosilicates and condensation of the simpleanions to more complex structures by the elimination of water.83Hydrothermal methods have been used to prepare synthetic crystallinehydrated calcium silicate 84 and lithium aluminosilicates.85Pure germanium may be freed from the arsenic with which it is almostalways associated in Nature, by the fractional distillation of the tetrachloridethrough an efficient column.86Both germanium and tin tetraiodides can be prepared from their tetra-chlorides by the action of ethyl iodide in the presence of aluminium chlorideor bromide : with tin the yield is quantitative, whilst with germanium thereaction is slower and the yield much less.*'Several hypophosphites of bivalent tin have been prepared, viz.,Sn(H2P0,),,6H,0 ; Sn(H,PO,), ; 3Sn(H,P0,),,SnC12 ; and Sn(H2P0,)2,SnC1z.88A study has been made of the binary systems of stannic bromide, stanniciodide, and trichlorosilane with some aliphatic ethers.89 The results are inaccord with Pfeiffer's observation that the apparent ability of the tin tetra-halides to form addition compounds with ethers decreases with increasingradius of the halogen atom.As a preliminary step in the study of the stabilities of stannic halidecomplexes with a variety of ligands, accurate measurements have been madeof the vapour pressures and heats of vaporisation of stannic chloride, bromide,and iodide.g0Titanium trifluoride has been prepared 'by several different reactions.91It is a dark blue compound (occasionally with a somewhat reddish tint), ischemically resistant, and is stable when heated in air for a short time, be-ginning to sublime in absence of air at 900".A convenient method of preparation of anhydrous titanium trichlorideand tribromide in good yield and purity has been described, in which thetetrahalide is refluxed and reduced in the vapour phase with hydrogen on thesurface of a tungsten filament at 1000-1 100°.92The equilibria in the system BaO-TiO, have been investigated on82 J.Goubeau and H. Grosse-Ruyken, 2. anorg. Chem., 1951,264,230.83 E. Thilo, Angew. Chem., 1951, 63, 201.84 L. Heller, J., 1950, 3682; L. Heller and H. F. W. Taylor, J., 1951, 2397.8 6 R. M. BarrerandE. A. D. White, J., 1951, 1267.W. H. Nebergall and R. H. Walsh, J. Amer. Chem. Soc., 1951,73,4043.8 8 D. A. Everest, J., 1951, 2903.89 H. H. Sisler, E. E. Schilling, and W. 0. Groves, J. Amer. Chem. Soc., 1951,73, 426.DO A. Kabesh and R.S. Nyholm, J., 1951, 3245.92 J. M. Sherfey, J . Res. Nat. Bur. Stand., 1951, 46, 299.86 F. Sebba, J., 1951,1975.P. Erlich, Angew. Chem., 1951, 63, 485FAIRBROTHER. 97samples weighing less than 1 mg. heated in a micro-furnace. Four definitecompounds have been reported, wix., BaTi,O,, BaTi,O,, BaTiO,, andBn,TiO,. The molten barium oxide mixtures attacked molydenum andplatinum with the formation of BaMoO,, Ba,Pt,O,, and Ba3Ti,Pt0,.93A simple method for the separation of zirconium and hafnium on a labora-tory scale has been developed which depends on the use of dilute sulphuricacid for the fractional elution of the ions adsorbed on a cation-exchange resin.94Further work has also been published on the separation of these twoelements by anion exchange, hydrochloric acid-hydrofluoric acid mixtures 95and concentrated hydrochloric acid 96 being used as eluents.The solubility of hafnium dioxide in water has been measured by a tracertechnique ; it varies from 2.3 mg.of HfO, in 100 g. of water at 35" to 4.7 mg.a tA series of double sulphates of the type RSO,,Zr(SO,),, where R is Mg,Zn, Cd, Co, or Mn, has been prepared by heating zirconium nitrate with thebivalent metal sulphate in concentrated sulphuric acid. The double sulphatesare soluble in a small amount of water but are hydrolysed when heated withexcess .98Further work has been published on the zirconium alkoxide~.~~Group V.-The conditions under which ammonium amalgam is formedwhen a solution of ammonium sulphate is electrolysed with a mercurycathode have been examined.loO At room temperatures, amalgams areformed when the pH of the solution is greater than about 4 : increase oftemperature above 50" or the addition of a few drops of ammonium sulphideprevents amalgam formation.The behaviour of the ammonium radicaldischarged at a mercury cathode is initially very similar to that of potassium.When ammonium aluminium alum is crystallised from a solution whichcontains free sulphuric acid, the crystals are defective in NH,+ contentalthough the SO,- content is almost unchanged. This observation has led lolto an investigation of the quaternary system H,0-S0,-Fe,03-(NH,),0, fromwhich it has been concluded that H,Of ions can effect an isomorphous sub-stitution with the similar-sized NH4+ ions in the crystal lattice.In the well-known Raschig process for the preparation of hydrazine, thesuccessive reactions are carried out in aqueous solution.It has now beenshown lo2 that chlorine, diluted with an inert gas, will react with anhydrousammonia to give chloroamine in good yield, and that this in turn will undergoammonolysis in considerable excess of anhydrous ammonia to give hydrazine.Interest in the production of hydrazine has been greatly stimulated in93 W. 0. Statton, J . Chem. Phya., 1951,19,33.94 B. A. J. Lister, J., 1951, 3123.O 6 E. H. Huffman and R. C . Lilly, J . Amel.. Chem. Soc., 1951,73, 2902.96 E. H. Huffman, G. M. Iddings, and R. C . Lilly, ibid., p. 4474.9 7 R. A. Cooley and H. 0. Banks, ibid., p. 4022.O B S. R. Patel, ibid., p. 2958.D. C. Bradley and W. Wardlaw, J., 1951, 280; see also Ann. Reports, 1950,47,108,lo0 R. J. Johnston and A. R. Ubbelohde, J., 1951, 1731. ref. 97a.lol N. V. Shiskin, Zhur. Obahchei Khirn., 1951, 21,456; Chem. Abs., 1951,45, 6115.loa R. Mattair and H. H. Sisler, J . Amer. Chem. SOC., 1951, 73, 1619.REP.-VOL. XLVIII. 98 INORGANIC CHEMISTRY.recent years by its potentialities as a speciality fuel. I n consequence, thequestion of its stability becomes of paramount importance. Not only is itcatalytically decomposed by traces of certain metals, but it also undergoesautoxidation in air. This autoxidation has been found to be greatlyaccelerated by minute traces of copper, and it has been shown that substanceswhich will reduce the concentration of copper ion by the formation of highlyinsoluble or complex compounds, will stabilise both dilute and highly con-centrated solutions of hydrazine.lo3A considerable amount of work has been carried out recently on the pro-perties of, and electrolytic reactions in, liquid dinitrogen tetroxide.lO4 It hasbeen shown that a number of reactions in this solvent, involving nitrosylcompounds and nitrates, may be interpreted on the basis of the solventionisation N204 -f- NO' + NO,-. The action of metallic zinc on dinitrogentetroxide produces an evolution of NO and the formation of a compoundinsoluble in the liquid N204 which has a composition Zn(N03),,2N204 andwhich on being heated loses N204 and gives pure anhydrous zinc nitrate.Acloser examination of the mechanism of this reaction shows that below 14"the reaction is chiefly an electrolytic one, involving an electron transfer fromthe zinc to [lNO+][NO,-] pairs, but that a t higher temperatures a reactionbetween molecular N,O, and the surface atoms of the zinc may be involved.Some reactions of the nitrosyl (or nitrosonium) ion, NO+, in liquid sulphurdioxide solution have also been studied : with iodides, NO is produced,105and with azides N,O. lo6A study of the system SO,-N,O,-H,O has indicated the existence of twoadditional phases, vix., 6S03,N,0,,2H20 and 4S03,N20,.lo7Liquid phosphorus can be supercooled and kept indefinitely in the liquidform at room temperatures.lo8 When crystallisation is induced in the super-cooled liquid the solidification spreads through the mass with a high velocity,which depends on the degree of supercooling : at 21.3" a linear speed of 210cm.per second was observed.logAlkali-metal phosphides with compositions Li2P, Na2P, and K3P2 areformed when the solutions of the respective metals in anhydrous ammonia aretreated with white phosphorus.l1° An examination of the properties of thecompound with the empirical formula Na,P, suggests that it is probablydimeric and may be considered formally as the sodium salt of the liquidhydride of phosphorus P,H4 (biphosphine) .ll1lo3 L. F. Audrieth and P. H. Mohr, I n d . Eng. Chem., 1951,43, 1774.104 C. C. Addison, J. Allen, H. C. Bolton, and J. Lewis, J., 1951, 1289; C. C. Addison,H.C. Bolton, and J. Lewis, ibid., p. 1294 ; C. C. Addison, C. P. Conduit, and R. Thompson,ibid., pp. 1298, 1303; C. C. Addison, J. Lewis, and R. Thompson, ibid., p. 2829; C. C.Addison and J. Lewis, ibid., p. 2833 ; C. C. Addison, J. Lewis, and R. Thompson, ibid.,p. 2838; C. C. Addison and J. Lewis, ibid., p. 2843.lo5 F. Seel, A. K. BOCZ, and J. Nbgrhdi, 2. anorg. Chem., 1951,264, 298.l o 6 F. Seeland J. NbgrBdi, ibid., p. 311.108 J. H. Hildebrand and G. J. Rotariu, J. Amer. Chem. SOC., 1951, 73, 2524.log R. E. Powell, T. S. Gilman, and J. H. Hildebrand, ibid., p. 2525.110 E. C. Evers, ibid., p. 2038.111 E. C. Evers, E. H. Street, Jr., and S. L. Jung, ibid., p. 5088.lo7 R. Pascard, Compt. rend., 1951,232,621FAIRBROTHER. 99A comparison of the stabilities of the BF3, SO,, and SO, addition productsof trimethylphosphine oxide, with the corresponding addition products oftrimethylamine oxide, leads to the conclusion that the oxygen atom inPMe30 is a somewhat weaker electron donor than the oxygen in a trialkyl-amine oxide.l12Studies of equilibria in aqueous phosphate solutions include those of thesystemsCa2+-H+-P0,3+-H20 andNH,+-P043+-H20 and ofAg,O-P,05-H,0.Some further work has also been carried out on the constitution and chemistryof the condensed (p01y)phosphates.l~~Anhydrous vanadium trichloride has been prepared by a new methodwhich involves the action of iodine monochloride on vanadium metal.l15The formation and stabilities of the complex ions VSCN++ and VOSCNf,which are formed in aqueous solution between vanadium(II1) and vana-dium(1v) and thiocyanate ion, have been studied spectrophotometrically.Work has been carried out on the separation of niobium and tantalum byanion-exchange meth0ds,~~7 124 and by making use of the greater stability ofthe niobium-oxalic acid complexes as compared with those of tantalum forthe preparation of pure niobium compounds by the fractional extraction ofthe mixed niobium-tantalum oxides with a mixture of hydrochloric andoxalic acids.l17Anhydrous niobium trichloride and tribromide have been prepared in apure state by reduction of the pentahalides by hydrogen at 400" and 500",respectively.Both trihalides can be sublimed, but disproportionation ofthe tribromide into pentabromide and metal takes place above 900°.118The vapour pressures of niobium and tantalum pentafluorides have beenmeasured over a range of temperatures up to their normal boiling points.Niobium pentafluoride appears t o undergo a polymorphic transition, withsudden change of volume, a t about 20" below its melting point, so that aspecimen which has been melted and allowed to solidify in a glass tube canrarely be remelted without fracture of the tube.Both pentafluorides behaveas Friedel-Crafts type ~ata1ysts.l~~Stable niobium and tantalum phosphates are formed as amorphoushydrated precipitates when a potassium niobate or tanfalate solution re-spectively is treated with an excess of phosphoric and nitric acids. Thehydrated precipitates lose water and become crystalline on ignition.120The method of preparation of sulphates of metals of high valency involving112 A.B. Burg and W. E. McKee, J . Amer. Chem. SOC., 1951, 73,4590.113 R. Flatt, G. Grunisholz, and S. Chapuis-Gottreux, Helv. Chim. Acta, 1951, 34,114 D. Laforgue-Kantzer, Ann. Chim., 1950, 5, 819 ; Th. Pitance, Bull. Centre Belge683 ; R. Flatt and G. Grunisholz, ibid., p. 692.Etude et Document. Earn, 1950,8,471; Chem. Abs., 1951,45, 6112.V. Gutmann, Monatsh., 1950, 81, 1155.116 S. C. Furman and C. S. Garner, J . Amer. Chem. Soc., 1951, 73, 4528.11' H. SchBfer and C. Pietruck, 2. anorg. Chem., 1951, 264, 106.11* C. H. Brubaker, Jr., and R. C. Young, J . Amer. Chem. SOC., 1951, 73, 4179.llD F. Fairbrother and W. C. Frith, J., 1951, 3051.lZo R.B. Hahn, J . Amer. Chem. Xoc., 1951,73, 5091100 INORGANIC CHEMISTRY.theuse of a solution of sulphur trioxide in sulphuryl chloride 121 has been appliedto the preparation of Nb,O(SO,), and Ta,(S0,)5.122 Whether the metalatom in these compounds however is really a multivalent ion or is attached bymainly covalent bonds to surrounding oxygen atoms, must still be in question.A promising new source of protactinium, which should be capable ofyielding gram quantities of the element, has been found in the aqueous wasteof the Mallinckrodt process for the extraction of uranium from pitchblendeconcentrates. This waste contains between 25 and 50% of the protactiniumoriginally present in the raw material.123Experiments on the separation of niobium, tantalum, and zirconium inhydrochloric-hydrofluoric acid mixtures by anion-exchange resins, with useof tracer techniques, have also been extended'to include the separation ofprotactinium .The chemistry of protactinium, and in particular the relative stabilitiesof its several oxidation states, is of especial interest in connection with theposition of the element as a possible member of an actinon series.It hasbeen shown125 that protactinium(v) in acid solution is reduced to thequadrivalent state, the principal analytical reactions of which have beendescribed. Some reactions of quinquevalent protactinium have also beenstudied 126 on a 20-mg. preparation of pure Pa205.As a, proof of the six-fold co-ordination of antimony in potassium(" pyro ")antimonate K[Sb( OH),], six new hexahydroxoantimony ammineshave been prepared by replacement of K+ by cobalt, chromium, or copperammines of known constitution,127 vk., [sb(oH),]3[Co(NH3),],3H20 ;[sb(oH),]2[co(NH3),c1],H20; [Sb(oH),][Co(NH3)4C204] ;[Sb(OH),]3[Cr(NH3),],2H20; [Sb(oH)6][Co(NH3)4C03],1'5H,0;and [sb(oH),]2TCu(NH3),1,2.5H20.BiO( OH) ,BiON03 in 0.005-0.2~-nitric acid shows that the reactionA study of the solubilities of the two basic bismuth nitrates BiONO, andBiON03(solid) + 2H+ = Bi3+ + NO,- + H20accounts completely for the solubility of bismuthyl nitrate in dilute nitricacid, and that the ion Bi(OH)++ is not formed in appreciable quantities.128Group VI.-The semi-crystalline structure of liquid water and the absencetherein of any definite species of associated water molecules are supportedby measurements of the rate of its self-diffusion, a t temperatures between1" and 55", using both D2160 and H2180 as tracers.129121 E.Hayek and A. Engelbrecht, Monatsh., 1949, 80, 640.122 E. Hayek and K. Hinterauer, ibid., 1951, 82, 206.18s R. Elson, G. W. Mason, D. F. Peppard, P. A. Sellers, and M. H. Studier, J . Amer.Chem. SOC., 1951, 73,4974. 124 K. A. Kraus and G. E. Moore, ibid., p. 2900.135 M. Hai'ssinsky and G. Bouissibres, Bull. SOC. chim., 1951, 146.las Idem, ibid., p. 557127 G. Spacu and C . Nisculescu-Schreher, Acad. Rep. Populare Romdne Bul. Stiint, A ,1948,1,41; Chem. Abs., 1951,45, 8387.138 D. F. Swinehart and A. B. Garrett, J . Arne.r. Chern. SOC., 1951, 73, 607.la@ J.H. Wang, ibid., pp. 610, 4181FAIRBROTHER. 101An X-ray study of the crystal structure of solid hydrogen peroxide hasindicated an angle of about 97" between the O-H and the 0-0 bonds, andof 94" for the angle between the 0-0-H ~ 1 a n e s . l ~ ~It is apparently possible to replace one of the sulphur atoms in theoctagonal ring of the S, molecule by the imide group. The resulting, prob-ably cyclic, compound S,NH is formed to the extent of 10% of the sulphurinvolved, and along with N,S, when dry ammonia gas is passed into a solu-tion of sulphur monochloride in carbon tetrach10ride.l~~between sulphur trioxideand sulphur dioxide in the liquid state in contrast to the exchange of labelledoxygen which takes place under similar conditions suggests that thelatter exchange takes place through an exchange of oxide ions interactingas a Lewis-acid and a Lewis-base, wiz., SO, + SO,-;fSO++ + SO,' orSO, + ZSO, SO++ + S,O,-, but not undergoing an oxidation-reductioninteraction. This is a similar mechanism to that postulated by G.Jander 13*to account for the observed electrical conductivity of sulphur trioxide inliquid sulphur dioxide.Radio-sulphur (35S) has also been used to study the rate of exchangebetween solvent sulphur dioxide and the " base" tetramethylammoniumpyrosulphite and between the sulphur dioxide and the two " acids " thionylchloride and thionyl br01nide.l~~ In the first case the exchange of sulphuris extremely rapid, but in the last two extremely slow. From this it may beconcluded that whilst the " base " yields sulphite ions in liquid sulphurdioxide solution, the " acids " yield negligible amounts of thionyl ions.Since the previous results 132 indicate that the concentration of sulphite ionsin liquid sulphur dioxide, derived from its self-ionisation, is very small, it hasbeen suggested that the exchange takes place through a direct oxygen-ionexchange between the sulphur dioxide and the sulphite base : SO,' + 80,zSO, + 80;. This leads to a concept of an acid-base system in liquid sulphurdioxide involving mobile oxygen ions, as an alternative to the self-ionisationinto thionyl and sulphite i0ns.l3~The oxidation of sulphurous acid by oxides of manganese, by ferric andcupric salts, and by molecular oxygen has been studied.137 There is evidenceto show that the oxygen reacts in the form of ionic complexes such as[O,+SO,]- and [IO,+S,O,]- and that the greatly increased rate of oxidationin the presence of manganous ion may be caused by the formation of acomplex oxygen-manganous sulphite ion such as [ O,+Mn( SO,)$ whichthen rapidly undergoes rearrangement to [Mn(SO,),]" and breaks up withthe formation of fresh sulphite complexes.The absence of isotopic exchange of sulphur130 S.C. Abrahams, R. L. Collin, and W. N. Lipscomb, Acta Cryst., 1951,4,16.131 M . Goehring, H. Herb, and W. Koch, 2. anmg. Chem., 1951,264, 137.laa J. L. Huston, J . Amer. Chem. SOC., 1951, 73, 3049.133 S. Nakata, J . Chem. SOC. Japan, 1943, 64, 635. 134 Naturwiss., 1938, 26,793.135 R.E. Johnson, T. H. Norris, and J. H. Huston, J . Amer. Chem. SOC., 1951,73,3052.la* G. Jander and K. Wickert, 2. physikal. Chem., 1936, A , 178, 57.la' H. Bassett and W. G. Parker, J., 1951, 1540102 INORGANIC CHEMISTRY.A number of aqueous molybdate systems have been investigated:Ag,MoO,-AgN03-H,O, AgzMo04-Na,Mo04-H,O, MgMo0,-MgC1,-H,O,M~MoO~-N~,SO,-H,O.~~~ From the first two it emerges that pure silvermolybdate can be prepared- by the precipitation reaction between silvernitrate and sodium molybdate, and forms neither double compounds norsolid solutions with the reactants.Oxalatomolybdic acid (Mo03C,0,H,,3H,0) and its sodium and bariumsalts (Mo03C,04Na,,3H,0 and MoO,C,O,Ba) have been prepared. 139A study of some phosphomolybdate solutions has shown that the phospho-molybdate ions are less stable than phosphotungstate ions but that equili-brium in the solutions is more rapidly established.The existence of colour-less phospho-l-molybdate and phospho-25molybdate ions has been demon-strated : the former is stable only in the pH range 4-6.140Purther work has been carried out on the preparation and properties ofthe alkali-metal tungsten bronzes,l4l9 several of which have been preparedin a pure form and analysed chemically and by X-ray diffra~ti0n.l~~ Theresults of these analyses have confirmed the view that these compounds may bedescribed by the general empirical formula M,W03, where x is less than unity.Uranium and the Tram-uranic Elements.-Uranium hydride has for sometime been thought to possess a " bridge-type " structure.143 It has now beenshown,144 by neutron diffraction, that the hydrogen atoms are arranged inthe form of distorted tetrahedra, equidistant from four uranium atoms witha hydrogen-uranium separation of 2.32 A.Such an interatomic distancewould mean that the hydrogen atoms are located in large holes in the uraniumstructure with a radius about three times the '' normal " radius of hydrogen.The electronic configuration of uranium in its lower oxidation states, i.e.,whether the valency electrons which still remain attached to the uraniumatom occupy 5f or 6d levels, or both, is of especial interest. The magneticsusceptibilities of the chlorides, bromides, and iodides of ter- and quadri-valent uranium have been measured over the temperature range 77-550" H.The results, except for the case of uranium trichloride, for which the actualassignment presents some difficulty, show that the codgurations of ter- andquadri-valent uranium are 5f2, 6d1 and 5f re~pective1y.l~~ The suscepti-bilities of solid solutions of uranium tetrafluoride diluted with the isomorphousdiamagnetic thorium tetrafluoride have also been measured, over the temper-ature range 90-350" K.146 At all dilutions the susceptibility of theuranium(1v) ion obeys the Weiss-Curie law, and at infinite dilution theextrapolated susceptibility and the magnetic moment of this ion are closeto those which would be expected for two unpaired electrons in the 5f level.l 3 8 J.E. Ricci and W. F.Linke, J. Amer. Chem. Soc., 1951,73, 3601, 3603,3607.139 M. Murgier and M. Sall6, Compt. rend., 1951, 232, 1558.l40 P. Souchay and J. Faucherre, Bull. SOC. chim., 1951, 355.141 E. 0. Brimm, J. C. Brantley, J. H. Lorenz, and M. H. Jellinck, J. Amer. Chem.142 A. Magnkli and B. Blomberg, Acta Chem. Scand., 1951, 5, 372.143 R. E. Rundle, J. Amer. Chem. SOC., 1947,69,1719.145 J. K. Dawson, J., 1951, 429.SOC., 1951, 73, 5427.144 Idem,ibid., 1951,73,4172.146 Idem, ibid., p. 2889FAIRBROTHER. 103These results may be contrasted with those obtained for the correspondingsolid solutions of the dioxides,14' which have been interpreted as evidencethat the two unpaired electrons are to be assigned to the 6d rather than tothe 5f level.A study of the phase diagram of the CaO-UO, system over the temper-ature range 1650-2300" c.indicates the existence of a eutectic mixturemelting a t 2080" & 20" and containing 45 moles yo of UO,, and the formationof two compounds, Ca,U04 and CaUO,, at or below 1750°.148Some evidence has been presented to suggest that the yellow precipitate,with an empirical formula U04,xH20, obtained when hydrogen peroxide isadded to a solution of a uranyl salt and usually known as uranium peroxide,may in reality be uranyl peruranate, and not a true peroxide of sexavalenturanium; 149 e.g., the composition of the product obtained by drying theprecipitate at room temperature in a current of air may be represented as(U02)2U08,9H20.The solubility of uranyl nitrate in water, from the incongruent m.p. ofthe hexahydrate- a t about 60" to the melting point of the dihydrate at 184",has been re-investigated. The results show a lower solubility than mostpublished data and also an incongruent m. p. of the trihydrate at 84.67".The system is thermally stable up to 184", above which the dihydrate decom-poses with evolution of oxides of nitrogen. 150A comprehensive investigation has also been carried out on ternarysystems uranyl nitratewater-organic solvent for a series of alcohols, ethers,and ketones. l5Some interesting possibilities in the field of synthetic element formationare afforded by the use of stripped carbon ions (C6+) in the cyclotron. Thecharge : mass ratio of these ions (obtained, e.g., when carbon dioxide isadmitted into the accelerating chamber) is very similar to that of He2+ ionsor deuterons as ordinarily used, whilst the energy of the carbon ions is aboutsix times that of deuterons under similar operating conditions. Carbon ionswith an energy of 120 Mev have been produced,152 and californium isotopeshave been obtained by irradiating natural uranium with C6+ ions:2 3 W ( 12C,6n)244Cf, 238U( 12C,4n)246Cf.153 It would appear that a similarreaction between C6+ and neptunium and plutonium should lead to elementswith atomic numbers 99 and 100 respectively, and with americium andcurium to 101 and 102.Naturally occurring plutonium has been separated chemically from a147 Ann. Reports, 1950, 47, 116, ref. 164.148 K. B. Alberman, R. C. Blakey, and J.S. Anderson, J., 1951, 1352.149 G. Tridot, Compt. rend., 1951, 232, 1215; cf., however, Ann. Reports, 1950, 47,150 W. L. Marshall, Jr., J. S. Gil1,and C. H. Secoy, J . Amer. Chem. Xoc., 1951,73,1867.151 L. I. Katzin and J. C. Sullivan, J. Phys. Colloid Chem., 1951, 55, 346.152 J. F. Miller, J. G. Hamilton, T. M. Purnam, H. R. Hammond, and G. B. Rossi,163 A. Ghiorso, S. G. Thompson, K. Street, Jr., and G. T. Seaborg, ibid., 1951,81,154.117, ref. 167.Phys. Rev., 1950, 80, 486104 INORGANIO CHEMISTRY.number of ores 154 and from the waste products of a process using naturaluranium.155 The ratio of plutonium to uranium present in pitchblende,of widely varying uranium content, remains fairly constant at about 10-11 : 1 ,which appears to be too high to be the result solely of neutrons from thespontaneous fission of uranium, and it has been suggested that additionalneutrons reacting with the 238U present may have been formed by the(a, n) reaction between the more energetic a-particles from the uraniumseries and the light elements present in the ore.The magnetic susceptibilities of plutonium trifluoride and plutoniumtrichloride have been measured over the temperature range 90-600" K.The results, which show a similarity to the magnetic properties of samarium,offer further evidence that the electronic structure of plutonium(m) involves5f5 e1e~trons.l~~Metallic neptunium and americium, the former on a milligram scale l 5 7and the latter in amounts of 40 -200 have been prepared by reductionof the trifluorides with barium metal, and a number of their propertiesexamined. Neptunium has a density of 19.5 & 0.5 whereas the '' heavier "americium has a density of only 11.7 -+ 0.3.This increase in atomic volumeis in striking resemblance to that of europium, which has a density of 5.2, ascompared with 6.9 and 7.9 of its neighbours samarium and gadolinum,respectively .A number of anhydrous americium compounds have been prepared, allwith the exception of the dioxide having an oxidation state of 3+.159 Thechlorides, bromides, and iodides of this and other actinon elements can bevery conveniently prepared by reaction of the appropriate oxide or fluoridewith the aluminium halide in question.Further evidence of the existence of a 5 + oxidation state of americiumhas been obtained by the hypochlorite oxidation of americium(m) in potas-sium carbonate solution.16*The availability of milligram amounts of 241Am from the prolongedneutron irradiation of p1utonium,l6l has made possible the production ofmicrogram amounts of curium by the neutron irradiation of americiumtrioxide,162 i.e., 241Am(n, y)242Am & 242Cm. The americium and curiumwere separated by means of an ion-exchange resin and further purified andisolated as the fluoride and hydroxide. 242Cm is an a-emitter with a half-lifeof 162 days.Nicrogram specimens of metallic 242Cm have been prepared by reduction154 C. A. Levine and G. T. Seaborg, J . Amer. Chem. SOC., 1951,73,3278.156 D. F. Peppard, M. H. Studier, M.V. Gergel, G. W. Mason, J. C. Sullivan, and1 5 6 J. K. Dawson, C. J. Mandelberg, and D. Davies, J., 1951, 2047.157 E. F. Westrum, Jr., and L. Eyring, J . Amr. Chem. SOC., 1951, 73, 3399.lti8 Idem, ibid., p . 3396.160 L. B. Werner and I. Perlman, ibid., p. 495.J. F. Mech, ibid., p. 2529.15* S . Fried, ibid., p. 416.A. Ghiorso, R. A. James, L. 0. Morgan, and G. T. Seaborg, Phys. Rev., 1950,162 L. B. Werner and I. Perlman, ibid, 1951,73,5215. 78,472FAIRBROTHER. 105of the trifluoride with barium metal vapour, at 1275”.lS3 The globules ofmetallic curium remained bright in dry nitrogen for some time after theirpreparation, but gradually tarnished, and after the lapse of 24 hours werefound to be badly corroded. This great reactivity has been attributed to theradioactivity of the curium, which is sufficient to maintain the specimen at atemperature above that of its surroundings.Group VII,-The fluorination of several volatile chlorides of silicon andphosphorus has been carried out by heating them under reflux withammonium fluoride : 164 the method appears to be particularly suitablefor the preparation of the monofluoride chlorides.Gaseous fluorine and cobalt fluoride have been used to carry out thefluorination of several nitrides and cyanides.lS5Some new complex fluorides, KCrOP,, AgCrOF,, and KMnF,, have beenobtained by the action of bromine trifluoride on potassium and silver di-chromates and on potassium permanganate respectively.Nitrosoniumhexafluorovanadate, NOVF,, is obtained by the interaction of nitrosylchloride, vanadium pentoxide, and bromine trifluoride.lS6that antimony pentachloride and phosphorus penta-chloride react with chlorine-saturated arsenic trichloride to form the complexchlorides AsCl,,SbCl, and AsCl,,PCl,. This reaction is of interest becausearsenic does not readily form a pentachloride, and it may be that thesecompounds may be formulated for example as [AsCl4][SbC1,].The exchange of radio-chlorine between hydrogen chloride and gaseouschlorine is slow in the gas phase and is catalysed by ordinary glass surfaces.A rapid photochemical exchange takes place, probably through the formationof chlorine atoms, which exchange rapidly both with the chlorine moleculesand with the hydrogen chloride.16*The behaviour of molten iodine monochloride and of iodine monobromideas electrolytic dissociating solvents and as inorganic chlorinating andbrominating agents, respectively, has been the subject of several papers.169Acid-base reactions have been carried out, for example, between alkali-metalchlorides, which form “bases” such as K+ICl,-, and the “acids” TiCl,, SnCl,,VCI,, SbCl,, and NbCI,.Neutralisation reactions in iodine monobromide,however, are limited by the scarcity of compounds which will act as “ acids ”which may be correlated with the general instability of complex bromides.The interest shown in halogen addition compounds and the chemistry ofunipositive halogen compounds is increasing.It has been shown that both iodine and bromine form molecular complexeswith na~htha1ene.l’~ As with benzene, iodine forms the stronger complex.It is reported16s J.C. Wallmann, W. W. T. Crane, and B. B. Cunningham, Phys. Rev., 1950,7S, 493.164 C. J. Wilkins, J . , 1951, 2726.113~ G. E. Coates, J. Harris, andT. Sutcliffe, J., 1951, 2762.166 A. G. Sharpe and A. A. Woolf, J., 1951, 798.167 V. Gutmann, Monatsh., 1951, 82, 473.16* W. H. Johnston and W. F. Libby, J . Amer. Chem. SOC., 1951,73, 854.169 V. Gutmann, 2. anorg. Chem., 1951,264, 151, 169; Monatsh., 1951,82, 156, 280.N. W. Blake, H. Winston, and J.A. Patterson, J. Amer. Chem. SOC., 1961,73,4437106 INORGANIC CHEMISTRY.Spectrophotometric studies have shown that molecular iodine also formsa 1 : 1 complex with dioxan in carbon tetrachloride solution.171A comparison of the absorption spectra of positive iodine compoundsdissolved in ~ y r i d i n e , l ~ ~ with that of molecular iodine itself in pyridine,supports the view that the reaction 21, + Py.J- IPy+ + I,- takes place, asdoes also the fact that when molecular iodine is dissolved in pyridine i twill undergo isotopic exchange with the iodine of a positive iodine compoundwhatever the nature of the anion in the ~omp1ex.l~~ Positive iodine com-pounds? which are colourless themselves, dissolve in pyridine to give golden-yellow solutions.A study of the thermodynamic stability of the iodine cation in aqueoussolution 174 shows that this is governed essentially by the equilibriumconstants of the reactions : (1) I, + H,O; H,OI+ + I- ; (2) H,OI+ +H,O f HOI + H30+ ; Theequilibrium constants of (1) and (2) are respectively 1 x 10-11 and 3 x 10-2,and for any cationic iodine t o remain in the aqueous solution, it is necessaryfor reaction (3) to be sufficiently slow.It has been shown that both iodine and bromine are absorbed fromabsolute-alcoholic solution by a cation-exchange resin, in the form of uni-valent positive halogen ions, and may be removed as salts by addition of theappropriate acid, if the activity of hydrogen ion in the solution is sufficientt o effect the exchange.175 A similar series of exchange reactions has beencarried out with the halogen nitrates.176The trifluoroacetyl hypohalites, CF,*CO*OBr and CF,*CO*OI, which canbe prepared by the addition of an equimolar amount of the free molecularhalogen to a solution of silver trifluoroacetate in an organic solvent, may beused as a source of positive halogen ions.177A study of the structure of tetramethylammonium pentaiodide revealsthe presence in the crystal of V-shaped 1,- ions, probably with two different1-1 distances.It has been suggested that these polyiodide ions result fromthe interaction of a single iodine ion with two highly polarisable iodinemolecules.178Evidence has been obtained that the familiar oxidation of sodium thio-sulphate by iodine in potassium iodide solution occurs in steps and does nottake place immeasurably fast : 179 an initial very rapid reaction leads to theformation of S2031- and iodide ion. If the iodide concentration in the solu-tion is relatively high, as it usually is in practice, the S2031- then reacts at a1 7 1 J.A. A. Ketelaar, C. van de Stolpe, and H. R. Gersmann, Rec. Trav. chim.,1951, 70, 499.172 R.A. Zingaro,C. A.VanderWerf, and J. Kleinberg, J . Amer. Chem. Soc., 1951,73,88.1 7 3 J. Kleinberg and J. Sattizahn, ibid., p. 1865.174 R. P. Bell and E. Gelles, J., 1951, 2734.1 7 5 T. Kikindai and M. Csasel, Compt. rend., 1951, 232, 1110.1 7 6 H. Brusset and T. Kikindai, ibid., p. 1840.1 7 7 A. L. Henne and W. F. Zimmer, J . Amer. Chem. Soc., 1951,73,1362.1 7 8 R. J. Hach and R. E. Rundle, i b i d . , p. 4321.179 A. D. Awtrey and R. E. Connick, ibid., p. 1341.(3) 3HOI + 3H20 = 10,- + 21- + 3H,O+FAIRBROTHER. 107measurable rate, with the re-formation of iodide ion, S,O,I- + 21- =S203= + 13-, giving the correct stoicheiometry of the reaction.At lowiodide-ion concentrations the S,O,I- is oxidised by iodine to give sulphateand iodide.Several ternary systems involving silver iodate and alkali-metal iodates,ammonium iodate, and silver nitrate have been examined : silver iodateforms an incongruently soluble pyroiodate AgIO,,I,O, in excess of iodic acid. 180The equilibrium between the complexes which manganese(m) formswith pentane-2 : 4-dione (acetylacetone) has been studied spectrophoto-metrically.181 When trispentanedionemanganese(II1) in aqueous solutionis subjected to varying acidity, it changes reversibly to a bispentanedione-diaquo-complex, the colour changing from a coffee-brown in neutral solution,through a golden-yellow t o a greenish-yellow at a pH of about 3.Rhenium trioxide has been prepared in almost quantitative yield bythermal decomposition of the addition product of rhenium heptoxide withdioxan, which apparently has the composition Re2(), ,3C4H802.182 When thetrioxide is heated, it disproportionates, without loss of oxygen, into rheniumheptoxide and dioxide : 3ReO3 = Re,O, + ReO,.A somewhat unstable rhenium nitride, with a 0 9+c?..- - r - - &_- %$, maximum nitrogen content corresponding to ReNWd3,has been prepared by passage of ammonia gas over \fly@hedral in which holes the nitrogen of a cubic atoms are face-centred located in the rhenium octa- o=()=* aA!\ammonium per-rhenate or rhenium trichloride a t300-350".The compound is an interstitial nitridestructure : the solubility of nitrogen in the hexagonalrhenium structure is only very ~ma11.l~~A number of metallic salts of per-rhenic acidhave been prepared and studied.ls4Group VIII.-The molecular structure of ironblack crystals when a solution of iron enneacarbonyltetracarbonyl (I), which is obtained as dark green orin toluene is heated to 90" and allowed to cool, has 6'been derived from a study of its absorption spectrais a sequel to the study of the infra-red absorptionof iron penta- and ennea-carbonyl which has been shown to lead tosubstantially the same conclusions regarding the structures of these moleculesas electron diffraction and X-ray diffraction, respectively.186o.E/\, ''O,'* - - ***O.C - - * - - -&4* 8in the infia-red, visible, and ultra-violet .185 This (1.)180 J. E. Ricci and I. Amron, J . Amer. Chm. Xoc., 1951, 73, 3613.181 G. H. Cartledge, ibid., p. 4416.182 H. Neehamkin, A. N. Kurtz, and C. F. Hiskey, ibid., p. 2828.183 H. Hahn and A. Konrad, 2. anorg. Chem., 1951,264, 174.184 W. T. Smith, Jr., J . Amer. Chem. SOC., 1951,73, 77; W. T. Smith, Jr., and G.E.R. K. Sheline, ibid., p. 1615.186 R. K. Sheline and K. S. Pitzer, ibid., 1950, 72, 1107.Maxwell, ibid., p. 658108 INORGAN10 OHEMISTRY.The familiar red ferric thiocyanate, which for 20 years has been thoughtt o dissolve in organic solvents as the dimer E’e2(CNS),,187 has been shown t obe present in ether and alcohol in the form of single molecules only : it is notsoluble in pure benzene.188 By using the distribution of ferric thiocyanatebetween ether and water, it has been shown that all complexes between theferric and thiocyanate ions from Fe(CNS)2+ to E’e(CNS)63- occur.189The composition and stability of the yellow iron(II1)-sulphosalicylatecomplex ion, formed in neutral and alkaline solution, has been studied polaro-graphically and found to contain three triply-ionised sulphosalicylate ions toeach ferric ion, Fe[O,S*C,H,( o)*co*o]36-.No evidence was found forcomplex-ion formation between iron( 11) and sulphosalicylate ions.190X-Ray powder diffraction patterns indicate that the mixed halideFeBrCl,, which is formed by the action of bromine on ferrous chloride, isisostructural with FeCS and FeBr, and approximates closely to what a solidsolution of these two halides would be expected to be.191Catecholdisulphonic acid gives with iron( III) salts, two blue complexes,Fe[C6H202( SO,)( SO,H)] and Fe[C,H202( a violet complex anionFe[C,H2O2( and a red complex anion Fe[C6H202(so3)]39-.I n thepresence of nitrilotriacetate ions, mixed complexes are f0rmed.1~~The equilibrium constants and redox potentials of iron(I1) and iron(m)complexes with nitrilotriacetate and ethylenediamine-NNN’N’-tetra-acetateions and the association of these chelating agents with a number of bivalentcations, including those of iron(n), cobalt(@, and nickel@), have also beenmeasured. lg3Magnetic-susceptibility measurements 19* have shown that the aqueouscobalt(II1) ion is a t the most only very slightly more paramagnetic than theaqueous aluminium(II1) or gallium(1n) ions, and therefore must be present inthe form of a penetration complex of the same electronic type as the hexam-minocobalt(II1) ion, [CO(NH,),]~+.Some further progress lg5 has been made towards the correlation of absorp-tion spectra with the geometric isomerism of cobalt (111) complex compounds.From an examination of the absorption spectra of cis- and trans-[Co en2( SCN),]C1,H20 and [Co(NH,),SCN]SO, it is concluded that thethiocyanato specific absorption bands of the trans-forms of cobalt(1n)complexes have longer wave-lengths than those of the cis-f0rms.19~Absorption measurements in the visible region have demonstrated the187 H.I. Schlesinger and H. B. Van Valkenburgh, J. Amer. Chem. Soc., 1931,53,1212.188 K. M. Mitchell and J. Y. Macdonald, J., 1951, 1310.189 J. Y. Macdonald, K. M. Mitchell, and A. T. S. Mitchell, J., 1951, 1574.190 C. V. Banks and J. H. Patterson, J. Amer. Chem. SOC., 1951,73, 3062.191 N. W. Gregory, ibid., p. 5433.198 G. Schwarzenbach and A. Willi, HeZv. Chim. Acta, 1951, 34, 528.lS3 G. Schwarzenbach and J. Heller, ibid., p p . 576, 1889; G. Schwarzenbach and194 H. L. Friedman, J. P. Hunt, R. A. Plane, and H. Taube, J. Amer. Chem. Soc.,lD6 Y. Shimura, J . Amer. Chem. SOC., 1951, 78, 6079.33. Freitag, ibid., p. 1492.1951, 73, 4028. lg6 Ann. Reports, 1950, 47, 124, ref. 242FAIRBROTHER. 109stepwise formation of the thiocyanatocobalt complexes [Go( SCN)J2+, wheren = 1, 2, 3 and 4, the value of n depending on the concentration of thio-cyanate ion.When n = 1, 2, or 3, the co-ordination number of the cobaltis 6 and the solution is red ; when n is 4, the co-ordination number changes to4 and is accompanied by a change of colour to blue.lg7A number of complex dicyanobisethylenediaminocobalt (111) compoundshave also been prepared.lg8A comparison of the polarographic reduction of cis- and trans-dinitro-tetramminocobalt(II1) chlorides in chloride, tartrate, and citrate solutions,shows that the cis- is reduced much more readily than the tyans-isomer.lQ9In the sytem BaO-NiO, two compounds have been identified, viz.,Ni0,BaO which is black, stable in air, orthorhombic, and melts at 1250", andthe grey-green Ni0,3BaO which is hexagonal, unstable in air, and melts at1 160°.200When nickel monoxide is heated with barium peroxide, the compoundBaNiO, and intermediates with compositions between Ba,Ni308 andBa,Ni,O,, with a continuously varying oxygen content, are obtained.201The preparation of pure nickelous oxide has been described, and itssolubility in aqueous ammonia determined.202 When a saturated solutionin 10N-ammonia is diluted with alcohol and kept in a closed vessel, crystallinemauve needles of Ni(NH,),(OH), separate.These lose ammonia on beingremoved from the mother-liquor, with the formation of the cobalt-bluetetrammine Ni(NH,),( OH), which in turn decomposes into nickeloushydroxide and ammonia .203Some complex quadrivalent nickel compounds have been prepared by theaction of oxidising agents on the tervalent compound [NiCl,(o-phenylenebis-dimethylarsine),]Cl. Chlorine and ceric sulphate give deep green compoundswhich are easily reduced; concentrated nitric acid gives an intensely bluesolution from which aqueous perchloric acid precipitates the deep blueNiC12(diarsine),(C10,),. The corresponding bromide NiBr,(diarsine),(ClO,),,which is green, is similarly prepared by the action of nitric and perchloricacids on the tervalent bromide complex.204When hydrazine is added to a solution of a nickel salt, a deep blue colouris formed, and if the solution is at all concentrated a red-violet solid complexmay soon be precipitated.Many of these complexes-depending on theparticular salt of nickel-are relatively insoluble.The nitrate is moresoluble and spectrophotometric studies have been made of its solutions.205It is reported that the perchlorate, even in dilute aqueous solution, showsa dangerous tendency to explode.206197 M. Lehn6, Bull. SOC. chim., 1951, 76.198 P. RiLy and B. Sarma, J . Indian Chem. Xoc., 1951,28, 59.198 H. F. Holtzclaw, Jr., J . Amer. Chem. SOC., 1951, 73, 1821.200 J. J. Lander, ibid., p. 2450.202 R. Paris, Compt. rend., 1951, 232, 840.203 Idem, ibid., p. 1421.206 E. C. Gilbert and W. H. Evans, J . Amer. Chem. Xoc., 1951,73, 3516.PO* B. Maiasen and G. Schwarzenbach, Helv. Chim. Acta, 1951, 34, 2084.J. J. Lander and L. A. Wooten, ibid., p. 2452.204 R. S. Nyholm, J., 1951, 2602110 INORGANIC CHEMISTRY.The compositions and structures of the borides and silicides of the sixplatinum metals have been studied over the whole range of compositions ofthe twelve systems involved.207It has been shown 208 that potassium ruthenocyanide can be oxidised inaqueous solution by strong oxidising agents : the estimated molar potentialof the ruthenicyanide -ruthenocyanide couple is +046 ;t 0.05 v.The effects of temperature and concentration of reactants on the reactionbetween sodium nitrite and dichlorodiamminopalladium(rr) have been in-ve~tigated.2~~ Cold concentrated palladium solutions containing chlorideion favour the, formation of the cis-dinitrodiamminopalladium(II), whichslowly reacts in solution with ammonia and nitrite ion to form the trans-isomer.The first preparation of optically active tervalent hexacovalent osmiumcompounds has been achieved by the oxidation of the resolved enantio-morphic forms of the corresponding osmium(I1) complex ; the dark green(+)- and (-)-forms of tris-2 : 2’-dipyridylosmium(11) dichloride have beenoxidised anodically or by chlorine, and the tervalent enantiomorphous formsisolated as red crystalline perchlorates, Os( dipy),( ClO,),,H,O .210A number of halogen-bridged compounds of the type (11) have beenprepared (where M = P, As, or Sb).No evidence of geometrical isomerismhas been observed in this series of complexes, ofwhich only the trans-forms were obtained. On thebasis of the observed stabilities of these com-pounds, the co-ordinating affinity of the severalto be in the order :Pr,M c1k / hpt/Ptc1 ’ ‘ c1 /’ hMPr3 ligands towards platinous chloride is considered(11.)PPr, > AsPr, > SbPr, > NPr, > BiPr3.,l1Improved methods have also been devised for the preparation of tertiaryphosphine, arsine, and stibine complex compounds of platinous chloride.212Further evidence has been presented 213 that d-electrons from the centralmetal atom take part in complex formation with certain ligands. To thisend, complex formation by phosphorus trifluoride, where the stronglyelectronegative fluorine should enhance the effect of the d-electrons ascompared with the trialkylphosphines, was studied. Phosphorus trifluoridedoes not form complexes with boron trifluoride or aluminium compounds,which have no d-electrons available, but forms two volatile stable compoundswith platinous chloride, (PF,),PtCl, and (PF3,PtCI2),, which are very similarto the corresponding carbonyl compounds,Phosphorus trifluoride does not combine with freshly reduced nickel, evenunder pressure, but up to half of the CO in nickel tetracarbonyl can be re-*07 J. H. Buddery and A. J. E. Welch, Nature, 1951, 167, 362.208 D. D. DeFord and A. W. Davidson, J . Amer. Chem. SOC.. 1951,73, 1469.200 H. B. Jonassen and N. L. Cull, ibid., p. 274.210 F. P. Dwyer and E. C. Gyarfas, ibid., p. 2322.211 J. Chatt, J., 1951, 652.213 J. Chatt and B. A. Williams, J., 1951, 3061.212 J. Chatt and R. G. Wilkins, J . , 1951, 2532FAIRBROTHER. 111placed by PF, by passage of the compounds through a heated tube : thereaction isA convenient method has been described for the preparation of trimethyl-platinum compounds which starts from the readily accessible and non-hygroscopic cis-dipyridinotetrachloroplatinum. The latter compound ismuch easier to prepare than anhydrous platinum tetrachloride, and is obtainedalmost quantitatively when sodium chloroplatinate is refluxed with therequisite amount of pyridine in aqueous solution.214F. FAIRBROTHER.214 M. E. Foss and (the late) C. S. Gibson, J., 1951, 299

ISSN:0365-6217    

DOI:10.1039/AR9514800087

出版商:RSC    

年代:1951

数据来源: RSC

摘要:

1. INTRODUCTION.THIS year’s Report represents the final stage in implementing the change-overto true Annual Report form and we hope that the present framework willprove satisfactory in the future. It seems appropriate to make special men-tion in the Introduction of the most outstanding developments of the yearunder review.On the theoretical side, considerable progress has been made in applyingthe quantum theory to the prediction of chemical reactivity; another note-worthy feature is the postulation of ionic intermediates of non-classicalstructure in organic reactions. An outstanding advance in stereochemistryis the rigid proof by X-ray crystallographic methods of the correctness ofFischer’s guess at the absolute configuration of tartaric acid and, therefore,in principle, of all other asymmetric molecules.I n the aliphatic field there have been interesting developments in thechemistry of the polyacetylenes ; a further achievement of the year has beenthe synthesis of the much debated vitamin 4.This has been a vintage yearfor steroid synthesis and, perhaps because of the current interest in cortisone,has seen two independent total syntheses of non- benzenoid steroids, includingcholesterol, the non-benzenoid hormones, and cortisone ; there have alsobeen important developments in the chemistry of the triterpenes and of thetropolone group of non- benzenoid aromatic compounds. Among thealkaloids, biogenetic considerations have been extended to the cinchonaseries, which is now linked with the yohimbine group by the recognition ofcorynantheine as a “ missing link ’’ between these two large families.A theoretical consideration of the coiling possibilities of peptide chains hasled to the postulation of completely new configurations of the peptide back-bone in protein molecules, which agree well with the experimental findingsand seem likely to throw a completely new light on protein chemistry; onthe experimental side, patient work has led to the establishment of the de-tailed arrangement of more than two-thirds of the amino-acid residues ininsulin.A.W. J.H. N. R.2. THEORETICAL ORGANIC CHEMISTRY.A. Basic Theory.-Work on the application of the quantum theory tochemical problems has been developing in the past year in three maindirections.First, attempts have been made to refine the theoreticaltreatment ; these are described elsewhere. Secondly, the standard MDEWAR : THEORETICAL ORGANIC CHEMISTRY. 113(molecular orbital) and VB (valence bond) methods have been used tocalculate the specific properties of individual compounds ; these calculations,which have followed conventional lines, are of great interest but naturallythey do not lead to any general principles and space does not permit adetailed survey. Attention may be drawn to the work by A. and B. Pullmanand their collaborators on the properties of fulvenes and thermochromicethylenes,2a and on acenaphthenes 2b and diamagnetic susceptibility,3 byP. and R. Daudel and their collaborators on photochemical and exchangereactions,4 and by R. D.Brown on various addition reactions (discussedlater in this Report). Thirdly, attempts have been made t o derive generaltheoretical principles either by calculating the properties of ranges of relatedcompounds and finding empirical correlations with their structure, or bymethods of direct approximation.Chemical reactivity has been related, on the one hand, to the orders ofbonds, the charge distributions, and the polarisabilities of atoms, inmolecules; and, on the other, to energy differences between the reactantsand transition states. The latter approach is more fundamental thoughmore diilicult, the former having little direct theoretical justification.Several investigations have shown, however, that both lead in most casesto similar concl~sions,~~ and reasons have been given 5b for the exceptions.This work is important since it removes the necessity for consideringchemical reactivity under several apparently independent headings.The basic problem of theoretical organic chemistry is the prediction ofthe way in which a given change in structure (e.g., introduction of asubstituent or replacement of carbon by a hetero-atom) will influence itsreactivity.As indicated above, attempts have been made to discuss suchproblems by calculating the properties of specific molecules ; but correlationsbetween structure and reactivity for molecules in general can be deducedfrom such calculations only on an empirical basis. A method is needed bywhich the variations of molecular properties with respect to changes inmolecular structure can be calculated.So far, the only method of thiskind has been the so-called resonance theory based on the VB approxima-tion but derived from it by intuitive simplification rather than rigorousargument.' Owing to this intuitive element and lack of any quantitative1 For a review of this work and its application to chemical problems see A. Pullman(a) Bull. Soc. Chim., 1951, 18, 661, 669,681,684, 693, 697, 702,707; (b) J . Chim.8 J . Phys. Radium, 1951,12, 652, 717; Compt. rend., 1951,233, 1035.4 Bull. Xoc. chim., 1951, 18, 132.(a) R. Daudel, C. Sandorfy, C. Vroelant, P. Yvan, and 0. Chalvet, ibid., 1950, 17,66; C. Sandorfy end P. Yvan, ibid., p. 131 ; M. ROUX, ibid., p. 861 ; 0. Chalvet, ibid.,p.862 ; ( b ) F. H. Burkitt, C. A. Coulson, and H. C. Longuet-Higgins, Trans. Paraday Soc.,1951, 47, 553.and B. Pullman, " Les Theories Electroniques de la Chimie Organique," Paris, 1952.physique, 1951, 48, 359.See G. W. Wheland, '' The Theory of Resonance," John Wiley, 1944.7 The neglect of excited structures is particularly questionable ; see A. Pullman andB. Pullman, Experientia, 1946, 2, A , 364114 ORGANIC CHEMISTRY.basis,8 the resonance theory has been more successful in the interpretationof known facts than in the prediction of new phenomena.Some years ago C. A. Coulson and H. C. Longuet-Higgins showed howsuch variations could be calculated in the MO approximation by regardinga change in the structure of a mesomeric molecule as a perturbation andapplying the known techniques of perturbation theory.The two mostimportant results related the total energy E of a molecule to changes inthe coulomb term (uT) of a given atom r, or the resonance integral (pTs) of agiven bond rs : . . .where q T is the x-electron charge density a t atom r and prs is the bond orderof the x-component of the rs bond.I n order to use these results, however, it is necessary to have some simpleapproximate method for calculating the charge distributions, etc., inmolecules. Theanalysis applies only to altermnt mesomeric compounds,11 i.e., compoundsin which the conjugated atoms can be divided into two sets, “starred”and ‘(unstarred,” such that no two atoms of like type are directly linked.(The definition excludes compounds such as fulvene, pyrrole, and azulene,which have odd-membered rings.) In an odd alternant compound, i.e., onewith an odd number of conjugated atoms such as the ally1 radical or aniline,the more numerous set is to be the (‘ starred ” one.Now it can be shown l1that in an even alternant hydrocarbon, the x-electrons are uniformlydistributed, so that q T = 1 at all positions. It follows that alternant hydro-carbons should be non-polar, as of course they are, in contrast to non-alternant hydrocarbons such as fulvene or azulene which have appreciabledipole moments.12 It also follows from equation (1) that the change intotal x-electron energy when a carbon atom is replaced by a hetero-atomshould be approximately the same for any alternant hydrocarbon; since asingle resonance form of such a hydrocarbon will also be alternant, theenergy of the hydrocarbon, and of any resonance form of it, will be changedequally by replacing carbon by a hetero-atom.Consequently, the resonanceenergy of an alternant heterocyclic compound should be the same as that ofthe isoconjugate (i.e., corresponding aromatic) hydrocarbon, as is known tobe the case. It can be shown likewise that the basicity of all monoaza-derivatives of alternant hydrocarbons should be similar,12 as indeed theyare, and 13a that heterocyclic compounds and isoconjugate hydrocarbonsshould show similar light absorption (due to x-x transitions), as they d0.13b8 The counting of resonance structures as a measure of stability has no basis inVB theory ; the fact that this questionable procedure works in practice can be explainedonly by an argument0 Proc.Roy. Soc., 1947, A , 191,39; A , 192,16; 1948, A , 193,447,456; A , 195,188.This has now been found 10 by H. C. Longuet-Higgins.based on MO theory.10 J. Chem. Phys., 1950,18, 265, 275, 283.11 C. A. Coulson and S. Rushbrooke, Proc. Cumb. PhiE. SOC., 1940,36,193.1s G. W. Wheland and F. W. Mann, J. Chem. Phys., 1949,1’7,264.13 (a) M. J. S. Dewar, J., 1950, 2329; ( b ) cf. G. M. Badger, R. S. Pearce, and R.Pettet, J., 1951, 3199DEWAR : THEORETICAL ORGANIC CHEMISTRY. 115In a neutral odd alternant hydrocarbon residue, Le., a radical such asally1 or benzyl, one MO is singly occupied by the odd unpaired electron.Itcan be shown l1 that this non-bonding MO does not contribute t o the bindingenergy of the molecule, electrons in it having the same energy (to theapproximation of simple MO theory) as those in carbon Zp atomic orbitals.The non-bonding orbital in such a system is confined to the starred atoms.It is easily seen that these are the atoms which appear as radical centres inthe principal resonance forms of the molecule; since radical activity isassociated with the odd electron, both treatments predict it to appear a tthe starred atoms ; e.g., in the benzyl radical :(MO) (Resonance)It can be shown l1 that the x-electron distribution in an odd alternanthydrocarbon radical is uniform; since a corresponding ion differs from theradical only in having one more or one less electron in the non-bonding MO,the formal charge in such an ion must then be distributed over the starredatoms only, in agreement with resonance theory.Thus in the benzyl anionor the isoconjugate aniline, the op- (but not the rn-) positions are negativelycharged.Calculation of the coefficients of an NO, i.e., the contributions ofindividual atomic orbitals to it, is usually laborious; but by a fortunatechance the coefficients of non-bonding MO’s can be found extremely simplyby a rule due to H. C. Longuet-Higgins.lO The rule is that the sum of thecoefficients at the starred atoms adjacent to a given unstarred atomvanishes; it enables the ratios of all the coefficients to be calculated, andtheir absolute values are then found by normalising the MO ( L e ., equatingthe sum of the squares of the coefficients to unity). For example, in thep-naphthylmethyl radical :a -2a4a2 + (2a)2 + (3a)2 = 1 ; a = 17-lI2- a*aSince the charge density at each atom due to an electron in a given MI0 isproportional t o the square of the corresponding coefficient, the chargedistribution in odd alternant hydrocarbon ions can be found very simply.The charge distribution in the odd alternant hydrocarbon ion beinggiven, the energy changes due to replacement of carbon by hetero-atoms canbe calculated approximately from equation (1). In this way the chemistryof a family of isoconjugate compounds can be correlated. Aromaticsubstitution is a good example.1° Consider a-substitution in naphthalen116 ORUANIC CHEMISTRY.by an ionic reagent X.It is usually assumed l4 that in the transition statethe a-carbon atom becomes tetrahedral and is removed from conjugation,and that the rate of substitution can be correlated with the x-electron energydifference E between the initial and the transition state. Let the chargedensity at carbon atom r be qT in naphthalene and 4,’ in the transition state ;then, in analogous substitution of an isoconjugate heterocyclic compound(e.g., quinoline), where carbon atom r is replaced by a hetero-atom of coulombterm ap, the corresponding energy difference E‘ will be given [from equation(1>1 by :E’ = E + cc, (qT - PI’). . . . . . . (2)Now, naphthalene is an alternant hydrocarbon in both its normal andits transition state; therefore, the charge density at each position in theformer, and a t each unstarred position in the latter, is unity.At starredpositions, the charge density in the transition state is less than unity jf Xis an electrophilic reagent, and greater than unity if X is nucleophilic, bythe fraction of the formal charge a t the corresponding atom. This fractionis given by the square of the corresponding coefficient in the non-bonding NO; the coefficients are given below. To a first approxima-tion then, a hetero-atom will not affect substitution at positions of likeparity l5 to itself, but will repress electrophilic substitution, and acceleratenucleophilic substitution, a t positions of opposite parity ; for, in the formercase 471 < qT, in the latter 431 > qT in equation (2), and, the greater is E’, thegreater the overall activation energy and the slower the reaction.Theseconclusions agree qualitatively with those of current resonance theory,since the charge distributions ascribed to the transition state are qualitativelysimilar, but the new treatment allows the effects to be estimated semi-quantitatively ; for instance, the acceleration of nucleophilic substitutionshould be greatest in the 2 : 4-positions of quinoline and the l-position ofisoquinoline, as it is well known to be. A second-order effect of the hetero-atom on positions of like parity to itself can be ascribed l6 t o the inductiveeffect of the hetero-atom, which raises the electron affinity of the adjacentring carbon atoms (and so affects their coulomb terms and makes them inturn accelerate nucleophilic and retard electrophilic substitution of positionsof opposite parity to themselves, i.e., of like parity to the hetero-atom).To complete this approach to theoretical chemistry, some method isneeded for comparison of different (anisoconjugate) sets of isoconjugatecompounds with one another. Thus, to calculate the quantity E inequation (2), a method is required for comparing two anisoconjugatesystems, namely, the parent (even) hydrocarbon and the (odd) transitionstate.Such a method has been found l7 in the application of perturbationtheory to a modification 18 of the usual MO method. The basic result isthat, if an even alternant hydrocarbon RS is formed by fusion together of14 G.W. Wheland, J . A m y . Chem. SOC., 1932, 64, 900.1 5 Two starred or two unstarred atoms are said to be of like parity ; a starred and an1 7 Idem, in the press. la Idem, Proc. Carnb. Phil. Soc., 1949, 45, 038.unstarred atom of opposite parity. M. J. S. Dewar, J., 1949,463DEWAR : THEORETICAL ORGCANIU CHEMISTRY. 117two odd alternant radicals R and S [e.g., (CHPh:), from 2CH2Ph., analogouslyto naphthalene from benzene and butadiene], then the difference in totalx-electron energy between RS and (R + S) is given approximately by :where p is the (empirical) C-C resonance integral, am, b,, etc., are coefficientsof the non-bonding MO's of R and S, respectively, a t atoms m, r, etc., and thelinkage between R and S in RS is through atom m in R to atom z in S,atom n in R to atom s in S, etc.In the case of aromatic substitution,R can be taken as the transition state and S as the atom a t which substitu-ion occurs; the energy difference E in equation (2) is then givenapproximately by :where a, and a, are non-bonding MO coefficients at the carbon atomsadjacent to S in the parent hydrocarbon. Thus, in naphthalene the non-bonding MO coefficients for the two types of transition state are :AE = 2p (ambf + anbs + . . . .) , . . . (3)E = 2p (a, + a,) . . . . . . . (4)-a&Taa -2a-a 2aa = 11-112; E = 6g . 11-1/2 a = 8-112; E = 6fi . S-1PClearly E is less for substitution at the cc-position, which accordingly takesplace more readily than that at the p-position.(Note that the MO theorypredicts identical orientation, etc., for substitution in alternant hydro-carbons by reagents of all types, since the transition states for substitutionby electrophilic, radical, and nucleophilic reagents differ only in the numberof electrons occupying the non-bonding orbital, and all three therefore havethe same total n-electron binding energy. This identical orientation is wellknown experimentally ; thus, naphthalene is substituted in the a-positionby electrophilic reagents, by radicals such as phenyl, and by nucleophilicreagents such as sodamide.)In this way a complete theory of organic chemistry can be developedwhich is less qualitative and on a better basis than current treatments.Ithas been shown l9 that this approach must lead in general to qualitativelythe same conclusions as does the resonance theory.An analogous simplification of VB theory by use of perturbation methodshas been devised by H. Hartmann20 and refined by C. Vroelant andR. Daudel; 21 it permits bond orders, etc.,22 and total x-electron bindingenergies 23 to be estimated for hydrocarbons in a very simple way. Althoughit cannot be applied to systems containing hetero-atoms, or to the estimationM. J. S. Dewar and H. C. Longuet-Higgins, t o be published.to 2. Natwrforsch., 1947, 2, A , 259, 263.Bull. Soc. chirn., 1949, IS, 36, 217.*3 M. Roux and R. Daudel, ibid., p. 1260 ; 0. Chalvet, R. Daudel, and M. ROUX, ibid.,2f 0. Chalvet, ibid., 1950, 17, 571.1961, 18, 143118 ORGANIC CHEMISTRY.of charge distributions, it should prove very useful in its own sphere wherethe corresponding MO techniques are less satisfactory.B.Non-classical Ions.-The existence of non-classical structures invarious reaction intermediates is now well recognised ; e.g., in electrophilicaddition to olefins the intermediate ions have triangular configurations 24which cannot be represented satisfactorily by classical bond structures. Suchions can be represented in VB or resonance terminology as hybrids ofclassical structures, e.g. :X+5 c-c X+ /x + + x\ c-c f3 c--c tJ c=c(Resonance) (MO)but this representation is not very satisfactory since it cannot account forthe limitation of the phenomenon to electrophilic addition (the intermediatesin radical or nucleophilic addition show only behaviour characteristic ofalkyl radicals or anions).I n the corresponding MO description above,25X is held by a dative bond in which the donor pair of electrons are thex-electrons of the olefin, which play a part analogous to that of the unsharedpair of electrons on nitrogen in the formation of typical donor complexessuch as amine oxides; analogy suggests that the phenomenon should bemarked only when X is an acceptor (electrophilic group) with a vacantorbital, and the analogy is confimed by an approximate MO treatmentwhich shows that but one of the MO's in the system is bonding, so that onlya pair of electrons can be accommodated. Similar x-complexes should beformed also by the x-electrons in more complex molecules, e.g., aromatichydrocarbons ; the application of these ideas to a variety of chemical problemshas been recently reviewed.26 An interesting confirmation is provided bythe crystal structure 27 of the AgCIOpC,H, complex; the Ag+ ions areeach x-bonded to the mid-points of edges of two benzene rings, thetwo Ag+ ions associated with a given benzene molecule being attached toopposite edges on opposite sides of the plane of the ring.Arguments basedon resonance theory had led to the prediction that Ag+ would be attachedsymmetrically to the mid-point of the ring. The observed lateral attachmenthad been correctly predicted from NO considerations.26Since a simple x-complex from an olefin is isomeric with two classicalcarbonium ions, and indeed is normally postulated as an intermediatein the apparent interconversion of such ions (Wagner-Meerweinrearrangements) ?2* the question naturally arises of the relative stability ofthe three isomers, i.e., of :--t 6'\ + 5 + /R RC,--Cb c,-cb c,-c,t C Ann.Reports, 1950, 47, 133.26 Bothdescriptionsare equivalent, but the MO description seems themoreilluminating.26 M. J. S. Dewar, BuZZSoc. chim., 1951,18C, 71c.27 R. F. Rundle and H. J. Goring, J . Amer. Chem. SOC., 1950,72,5337.2 8 Ann. Reports, 1950, 47, 143DEWAR : THEORETICAL ORGANIC CHEMISTRY. 119The possibilities are indicated by the four curves of Fig. 1, where totalenergy is plotted against the position of R relatively to C, and cb.Curve (a) represents one limiting case where the x-complex is an energymaximum or transition state; curve ( d ) the opposite extreme where onlythe x-complex is stable.In ( b ) and (c) all three forms are stable but in ( b )the x-complex is the least stable and in ( c ) the most stable. Addition ofelectrophilic reagents t o olefins should give the most stable forms of theintermediate cations ; stereochemical evidence 24 shows those to ben-complexes, implying that the systems are of type (c) or (d). No cases areknown of type (a) or (b), and it seems likely that x-complexes are in generalmore stable. than isomeric carbonium ions. Consider now the formation ofthe cations by X,l heterolysis of R-C,--C,-X. If the ion is of type (c),FIG. 1.it will be formed fist in a classical configuration, and whether or notrearrangement occurs will depend on the life of the ion and on the potentialbarrier separating it from the x-complex.In any case the possibility ofsubsequent rearrangement may affect neither the rate nor the stereo-chemistry of the reaction. If, however, the ion is of type (d), rearrangementto the x-complex should accompany heterolysis of the C-X bond; this willact as a " driving force " in the reaction which should therefore take placeunusually rapidly ; also the stereochemistry of the starting material shouldbe retained since R will approach C b from the side opposite to X.A number of reactions are now known 29 which show such accelerationand retention of configuration. These include the neighbouring groupeffects described by Winstein et U E ., ~ ~ the solvolyses of isobornyl chloride andcamphene hydrochloride 26* 30 and of 2-phenyl-1 -methylpropyl toluene-p-2s Some examples were described in a Colloquium on the Walden Inversion andMolecular Rearrangements at Montpellier, 1949 ; see Bull. SOC. chim., 1951,18, 1-144c.ao F. Brown, E. D. Hughes, C. K. Ingold, and J. F. Smith, Nature, 1951,168, 65120 ORGAWIO CHEMISTRY.sulphonate,3l and of exo-norbornyl chloride.32 These experiments showthat the systems with R = Br, I, or Ph are of type (d), and those withR = C1 of type ( c ) . If R = alkyl, the systems are of type (d) only if theclassical structures are rendered unstable by ring strain.Still more complicated structures are found in the intermediate cationsin 8,l reactions of cyclopropylmethyl, cyclobutyl, exo-norbornyl and dehydro-exo-norbornyl derivatives.The rates of solvolysis of cyclopropylmethyl andcyclobutyl chlorides are unexpectedly high, as the following table shows.33Relative rates of solvolysis in 50% EtOH.Temp. Me*CH:CH*CH,Cl b H , C l @- - 1.7 - 50" 1.1 4590" - 0 41 15 100It would have been expected that cyclopropylmethyl chloride wouldundergo solvolysis more slowly than crotyl chloride, whereas the ring-straineffect noted later would lead one to expect a very low rate for cyclobutylchloride. Furthermore, cyclopropylmethyl chloride and cyclobutyl chloridegave identical mixtures of products, suggesting that both solvolyses involvea common intermediate cation C,H,+ ; similar products were also obtainedby deamination of the corresponding a m i n e ~ .~ ~ J. D. Roberts andR. H. Mazur35 have shown by tracer methods that the three methylenegroups in this ion are equivalent; it must therefore have a tetrahedralconfiguration which can be formulated nicely in MO theory as (I). Thebasal carbon atoms are linked by a three-centre bond formed by mutualoverlapping of three sp3 hybrid orbitals, and the electrons are just sufficientto occupy all the bonding orbitals completely. It follows that the corre-sponding radical would contain one electron in an antibonding orbital ; and,in fact, no such rearrangements are observed in the case of the cyclopropyl-methyl or cyclobutyl radical.33 Roberts 36 has suggested an alternativepyramidal structure (indicated in 11) by analogy with the recentlyestablished 37 structure for B,H,.This structure seems less likely than (I)since in it two electrons would occupy antibonding orbitals, and the analogywith B5Hg is probably s~perficial.~~J. D. Roberts and C. C. Lee 39 have studied the solvolysis intermediatefrom exo-norbornyl p-bromobenzenesulphonate labelled with 14C. Their31 D. Cram, J . Amer. Chem. SOC., 1949,71,3836.38 S. Winstein and D. S . Trifan, ibid., p. 2953; Abstr. 119th Meeting h e r . Chem.33 J. D. Roberts and R. H. Mazur, J . Amer. Chem. Soc., 1951,73, 2509, 3542; J. D.34 J. D. Roberts and V. C. Chambers, ibid., p . 3176.36 Announced at the Symposium on Reaction Mechanisms at the New York Meeting37 K.Hedberg, M. E. Jones, and V. Schomaker, J . Amer. Chem. SOC., 1951,73, 3538;38 This appeared in discussion with Dr. H. C. Longuet-Higgins.39 J . Amer. Chem. SOC., 1951, 73, 5009.he., 1951, 53M, 54X.Roberts and V. C. Chambers, ibid., p . 5034.35 Ibid., p. 3543.of The American Chemical Society, September, 1951.W. J. Dulmage and W. N. Lipscomb, ibid., p. 3539DEWAR : THEORETI(3AL ORGAN10 OHEMISTRY. 121results are incompatible with the mechanism suggested by S. Winstein andD. S. TrifanF2 in which the intermediate ion is considered to have the singlex-complex structure (111). The results show that an ion of " triangular "r 1+configuration (IV), and yet another intermediate, possibly (V), must occur,if only as intermediates in the mutual interconversion of different structuresof type (111).S.Winstein, H. M. Walborsky, and K. Schreiber40 have studied theacetolysis of the dehydronorbornyl derivatives (VI), (VII), and (VIII)(X = p-C,H,Br*SO,=O) as models for the cholesterol-cyclocholesterolrearrangement. The relative rates a t 25" were 7000 : 2000 : 1, (VIII)reacting at about the same rate as cyclohexyl p-bromobenzenesulphonate.This shows that rearrangement to some non-classical ion must act as adriving force in the acetolyses of (VI) and (VII).At any rate the reaction is one of considerable complexity.x(VIII)C. Mechanism of Aliphatic Substitution.-S. Winstein, E Grunwald, andH. W. Jones,,la and C. G. Swain and W. T. Lang~dorf,~lb have put forwardarguments that the S,l and the SN2 reactions are not quaLitatively distinctbut merely extremes of a graded series.This was suggested as a possibilityby E. D. Hughes, C. K. Ingold, et u E . ~ ~ but was not pursued. The crucialquestion is whether a borderline reaction takes place by two distinct (#,I40 J . Amer. Chem. SOC., 1950, 72, 6795.4% J., 1935, 236, 244; 1948, 2060; Trans. Faraday SOC., 1941,37, 657.41 Ibid., 1951, 73, (a) 2700, (b) 2813122 ORGANIC CHEMISTRY.and &2) concurrent mechanisms, or only by one mechanism of intermediatetype. Winstein et al. argue that the effects of changing the solvent on therate of reaction form a graded series as one proceeds from “ typical ” XN2reactions to “ typical” SNl reactions; Swain and Langsdorf argue from theeffects of substituents on the rates of substitution in benzyl halides, togetherwith an analysis of the meaning of Hammett’s a-constant.In this connexionthe earlier observations by P. D. Bartlett and R. W. Nebel 43a and C. G. Swainet al. 43b should be noted, that the solvent appears in the kinetic equationseven for “ genuine ” SNl reactions. All these arguments are suggestive, ifinconclusive.Recently W. von E. Doering and A. Streitwieser 44 have reported a studyof the X,1 methanolysis of optically active 1-ethyl-3-methyl-n-butylhydrogen phthalate in mixed solvents which threw new light on the problem.The product was partly racemised and partly inverted, as is usual in X,1reactions, and the proportions of inverted products were :Added solvent None MeNO, MeCN7-7 - MeOH, mol.yo ......... 100 81 33 14 81 32 14Inversion, yo ............ 60 42 10 0 44 24 14Since the solvent enters into the kinetics of SNl these resultssuggest strongly that the intermediate ion is not a simple carbonium ion butis of the type (IX) with both phthalate (P) and solvent (S) covalently bondedby lobes of a 21, orbital of the central planar carbon atom. In pure methanol,where S = MeOH, (IX) can break down directly to P- and inverted ROMe.Alternatively, MeOH may replace P by lateral (SN1) attack, to give thesymmetrical (X) and consequently a racemic final product. In the mixedsolvents the analogue of (IX) may be formed with S = MeNOz or MeCN;these cannot break down to stable solvolysis products until either P or S hasbeen replaced by MeOH.Since either may be so replaced, the productsare more highly racemised.Now the structure (IX) is of the type normally ascribed to the transitionstate of an 8 N 2 reaction. This suggests that the difference between X,1 andij”2 reactions lies only in the stability, not in the structure, of the inter-mediate (IX). The transition from one type to the other is illustrated byconventional potential energy curves in Fig. 2, where energy is plotted43 (a) J. Amer. Chem. Xoc., 1940, 62, 1345; ( b ) ibid., 1948, ‘SO, 1119, 2989; 1949, 71,On the basis of this work Swain has described substitution reactions as termolecular.44 Abstr. 119th Meeting Amer. Chem. SOC., 1951. 4 5 ~ .965DEW= : THEORETICAL ORUANIC CHEMISTRY. 123against a reaction co-ordinate for the nucleophilic replacement AB + C- +A- + BC:Reaction co-ordinate - FIG.2.It is evident that, as the intermediate (IX) becomes more stable, the transi-tion state moves to lower values of the reaction co-ordinate, i.e., toconfigurations where the BC bond has less and less strength. Since thedifference in B-C bond energy between the transition states from twodifferent reagents C- is likely to be roughly proportional to the total valueof this bond energy, differences in reactivity between reagents should becomeless and less45 the smaller the B-C bond energy in the transition state,ie., the more stable the intermediate (IX). The extreme case corresponds,of course, to the SN1 reaction, where the difference in reactivity betweendifferent reagents becomes negligible.This picture accommodates all theknown facts about the flNl-flN.2 complex of reactions and does so withoutany fundamental duality of mechanism; if it is correct, carbonium ions donot exist as such, being either x-complexes or compounds (IX) of" pentacovalent " carbon.This conclusion would be scarcely surprising, since compounds such asstannic chloride, which certainly should have much lower electrophilicreactivity than carbonium ions, are completely co-ordinated in donorsolvents ; and E. A. Braude and J. A. Coles 46 have shown that even themuch more stable ally1 cation is co-ordinated in water, when it is formed asan intermediate in anionotropic rearrangements, since the stereochemistryof the starting material is retained during the rearrangement.D.Strain Effects in Substitution.-This subject has been recently re-viewed4' and, apart from an interesting interpretation of entropy effects in45 An argument of this kind has been used to interpret the different products obtainedfrom mesomeric ions with reagents of differing reactivity; M. J. S . Dewar, Discuss.Faraday SOC., 1947, 2, 261. 4 6 J., 1951, 2085.See also Ann. Reports, 1949, 46, 115. 4 7 E. D. Hughes, Quart. Reviews, 1951, 5, 245124 ORQAKIO OHEMISTRY.substitution due to restricted rotation of alkyl attention need bedrawn only to one new feature, the effect of ring strain. In SN2 substitutionson carbon, the central carbon atom has approximately ty2 hybridisation inthe transition state ; in SN1 reactions hybridisation is intermediate betweengp2 and sp3.In both cases the carbon bond angles to the three passivegroups are greater than in the tetrahedral initial state. If then the carbonatom is contained in a 3-, 4-, or 5-membered ring, the ring strain is greaterin the transition state than in the initial state, and reaction should thereforetake place less readily than in the case of an open-chain analogue. Theeffect should increase with decreasing ring size, and should be greater for8N2 reactions where the change in hybridisation in forming the transitionstate is greater. The argument is due to H. C. Brown et al., who havesuggested the term " I-strain " for the effe~t.4~ The substitution reactionsof cyczopropane derivatives, and the EN2 reactions of cydobutane derivatives,are indeed extremely slow, but since the 8,l solvolyses of cyclobutanederivatives are fast for reasons considered earlier, and since further specialeffects must be postulated 50 t o account for the reactivities of derivativesof the higher cycloparaffins, the concept as such seems to be of limitedutility,E.Molecular Rearrangements.-( 1) pseudo-Rearrangeme~~s. A truemolecular rearrangement is usually understood to be one in which an internalmigration occurs by a, process which cannot be formulated in terms ofsuccessive " ordinary " reactions. In this sense the Favorskii reaction,the conversion of a-halogeno-ketones into carboxylic acids by alkali, mustnow be regarded as a pseudo-rearrangement, since tracer studies 51 on thereaction of 2-chlorocycZohexanone with alkali have shown the mechanism tobe a simple cyclisation (&2) to a cydopropanone derivative, followed byhydrolysis :c1c>=o OH- + 4 CP=O + c1- @co2HThe Rowe rearrangement has also been shown 52 to take place by successivereactions not involving group migration. The reaction of a-halogeno-sulphones with bases to give olefins and sulphur dioxide probably involves 53a 3-membered annular sulphone intermediate analogous to the cyclo-propanone in the Favorskii reaction.These results reopen the possibilitythat other reactions now formulated as Wagner-type rearrangements mayinvolve similar cyclic intermediates. At any rate such mechanisms can nolonger be accepted without experimental verification.413 A.0. Evans and S. D. Hamman, Trans. Faraday SOC., 1951,47, 25.4O J . Amer. Chem. SOC., 1950, 72, 2926; 1951, 73, 212.50 H. C. Brown, R. S. Fletcher, andR. B. Johanneson, ibid., 1951,73,212.5 1 R. B. Loftfield, Abstr. 119th Meeting Amer. Chern. Soc., 1951, 4 8 ~ .62 W. R. Vaughan, D. I. McCane, and G. J. Sloan, J. Amer. Chem. SOC., 1951,73,2298.5 1 F. G. Bordwell and G. D. Cooper, ibid., p. 5187DEWAR : THEORETICAL ORGANIC CHEMISTRY. 125The acid-catalysed rearrangement of phenylhydroxylamine must alsobe regarded as a pseudo-rearrangement, since Y. Y u k a ~ a , ~ ~ ~ and H. F. Heller,E. D. Hughes, and C. K. Ingold 54b have found it to involve nucleophilicattack by solvent :The timing of the various processes telescoped together in the aboverepresentation is not yet known.(2) Aromatic rearrangements.In the Fischer indole synthesis catalysedby zinc chloride, 2 : 6-dichlorophenylhydrazones give 5 : 7-dichloroindolederivatives, one chlorine atom migrating; 55 but with stannous chloride ascatalyst, only 7-chloroindoles are formed, one chlorine atom being removed.56This implies 56 thatZnC1, /)cl Snc1, A+--- I I VH3 --* I I n l R\/\NH*N=CR \A /c1 C1 NHthe chlorine atom migrates in a positive reducible form,since chlorine is removed neither from the reactant nor from 5 : 7-dichloro-indoles by stannous chloride. Since, moreover, no migration of chlorine tosolvent molecules is observed when the reaction is carried out in presence ofreactive nucleophilic substances such as p - c r e ~ o l , ~ ~ the rearrangement mustbe genuinely intramolecular.This evidence supports strongly the x-complexinterpretation 26 of such rearrangements, the ion never being detached butremaining covalently bound to the x-electron cloud of the benzene ringduring migration. A similar mechanism accounts well for the formation of(XII), but not the dibromo- or dichloro-analogues, when (XI) is ~hlorinated.~'OH OH OH OH(XI) (XI*)(3) Bznxidine rearrangement. The rearrangement of hydrazobenzenehas been investigated 58 and the second-order dependence on acid strengthconfirmed; the diphenyline : benzidine ratio is independent of the rate of54 (a) J. Chem. SOC. Japan, Pwe Chem. Sect., 1950, 71, 647, 603; ( b ) Nature, 1951,66 C.S. Barnes, K. H. Pausacker, and W. E. Badcock, J., 1951,730.66 R. B. Carlin, Abstr. 119th Meeting h e r . Chem. Soc., April, 1961.6 7 H. J. denxertog, Rec. Trav. chim., 1951, 70, 363.168, 909.R. B. Carlin, R. G. Nelb, and R. C. Odioeo, J . Amer. Chem. Soc., 1961,75, 1002126 ORGANIC CHEMISTRY.rearrangement. It has been pointed out 26 that no mechanism involvingfission and recombination will account for the course of the reaction. Aparticularly cogent argument is the fact that although 2 : 2’-diphenyl- and4-phenyl-hydrazobenzenes rearrange normally to a diphenyline and asemidine respectively, 4 : 4‘-diphenylhydrazobenzene does not rearrange a tall; no steric effects could arise in the latter case if the reaction were nottruly intramolecular, but they would be expected between the p-phenylgroups in an intermediate x-complex since the rings in diphenyl are normallynon-coplanar ; no hindrance need appear in the x-complex from 2 : 2’-di-phenylhydrazobenzene. The second-order dependence on acidity could beinterpreted 26 in terms of a doubly charged x-complex formed fromPh*NH,*NH,-Ph, but the chemical evidence suggests strongly that the tworings in the intermediate play different parts and that the intermediate istherefore not symmetrical.An alternative 26 explanation is that theformation of the x-complex from the monosalt of hydrazobenzene isreversible, and that it can undergo conversion into benzidine only by unionwith a proton to complete the second amino-group.If, as seems reasonable,the latter step is rate determining, the kinetics would approximate to secondorder in acid strength. Obvious kinetic consequences would follow in caseswhere the second step became fast ; and the semidine rearrangement, whereone NH group remains intact, would be expected on this basis to show first-order dependence on acid.+ +(4) Migratory aptitudes. D. Y. Curtin and P. I. Pollak 59 have foundthat different products are formed from the two racemates of the ethanol-amine derivatives (XIII) on pinacolic deamination ; one gives (XIV) with\ - /H Ar\ - ArPh-C C-Ph Ar*CO*CHPh, Ph*CO*CHArPh Ph-C CH,*NH,HO/ \NH, HO/(XIII) W V ) (XV) WVI)migration of Ph, the other (XV) with migration of Ar. These results areindependent of the nature of the aryl group Ar, unlike the correspondingdeamination of (XVI), where the product formed is determined purely bythe relative migratory aptitudes of Ar and Ph.Since H.I. Bernstein and F. C. Whitmore 6o have shown that inversionoccurs in pinacolic deamination a t the carbon atom attached to NH, in thestarting material, it is evident that group migration in such reactions mustaccompany heterolysis of the C-N2+ bond in the intermediate diazonium ion ;Pollak and Curtin point out that if, as seems likely, the product of heterolysisis a x-complex and not a carbonium ion, the two x-complexes corresponding6s J. Amer. Chem. SOC., 1950, 72, 961; 1951, 73, 992. 6o Ibid., 1939, 61, 1324DEWAR : THEORETICAL ORGANIC CHEMISTRY. 127to the two possible modes of rearrangement of a given racemate of (XIII)will be derived from a cis- and a trans-stilbene respectively, e.g.:Ar’andThe course of the reaction might then be determined by the fact that cis-stilbene, through .steric hindrance to coplanarity, is less stable than trans-stilbene. that the stereochemistry of the tworacemates of (XIII) conforms to this suggested mechanism.Similar stereospecificity has been found 62 in the pinacol-pinacolinrearrangements of w s o - and racemic butane-2 : 3-dio1, and in correspondingreactions of the related oxides and 3-chlorobutan-2-01s. It is likely thatmany of the discrepancies in order of migratory reactivity observed in variousreactions are due to similar steric factors.(5) Rearrangements of radicals and anions.The rearrangement ofcarbanions, of which the Stevens 63 rearrangement is the best known, havebeen studied by C . R. Hauser and S. W. Kantor,a who find evidence that thereactions are of S,1 type as H. B. Watson G5 had postulated. The rearrange-ments of triarylmethoxy-radicals 66 are probably similar. Both thesereactions are analogous to the Wagner rearrangements of ‘‘ carbonium ions,”except that there is no evidence that the triangular intermediates in themare other than transition states; in MO terminology such an intermediateis a x-complex which is rendered unstable by the presence of one or twoelectrons in an antibonding MO.The acid-catalysed conversion of triarylmethyl peroxides into diary1ketones and phenols by acid probably involves 66v 67 a heterolysis rearrange-ment analogous to the pinacol-pinacolin rearrangement :It has indeed been shownAr,C=O*OR + H+ --+Ar Ar+5 H O --+ Ar2C-0 -3 (Ar,C-OAr)+ --bAr2C0 + ArOH crNote that since the 0-0 bond is broken heterolytically, the rearrangementis one of a structure analogous to a carbonium ion, not to a radical; this isconfirmed by the fact that in peroxides of mixed triarylmethyls the order ofmigratory aptitude corresponds to that found in typical Wagner rearrange-ments, whereas in the rearrangements of the triarylmethoxy-radicals formedby homolysis the order of migratory aptitudes is quite different.81 D.Y . Curtin, E. E. Harris, and P. I. Pollak, J . Amer. Chem. SOC, 1951,73, 3453.62 E.R. Alexander and D. C. Dittmer, ibid., p. 1665.See J. L. DunnandT. S. Stevens, J . , 1934,279.64 J . Amer. Chem. SOC., 1951, 73, 1437.6 5 “ Modern Theories of Organic Chemistry,” Oxford, 1941, p. 205.6 8 P. D. Bartlett and J. D. Cotman, J . Amer. Chern. SOC., 1950, 72, 3095; M. S.Kharasch, A. G. Poshkus, A. Foro, and W. Nudenberg, J . Org. Chem., 1951,16, 1458.t17 M. S. Kharasch and J. G. Burt, J . Org. Chem., 1951, 16, 105128 ORGANIC CHEMISTRY.F. Oxidation.-F. W. Westheimer and his collaborators 68 have shown thatthe chromic acid oxidation of isopropyl alcohol to acetone takes place byE,2 elimination from an isopropyl chromate :B~H-CMe,-O--CrO,H --+ BH+ + Me,CO + Hero3-(The subsequent reactions of the quadrivalent chromium have also beenstudied.)Similar mechanisms have been postulated 69 for the oxidation of alcoholsby quatervalent manganese, formed as an intermediate in the reduction ofpermanganate by hydrogen peroxide, and for the oxidations of glycols bythe Criegee and Malaprade 71 It seems likely that oxidations ofalcohols by reagents other than free radicals proceed in general by similarelimination of a reduced form of the oxidant from an intermediate ester orether. (The Criegee and Malaprade reactions do not involve intermediatefree radicals.71)G.Aromatic Substitution.-( 1) Electrophilic substitution. Nitration hasbeen studied in detail by E. D. Hughes, C. K. Ingold, and theircollaborator^.^^ Three types of reaction are distinguished. With highlyreactive substrates in aqueous nitric acid, nitration takes place bybimolecular reaction with nitracidium ion ( H2N03+) ; nitro-compounds maysimultaneously be formed by nitrosation and oxidation of the nitroso-derivative.With dinitrogen pentoxide in aprotic solvents, nitration takesplace again by bimolecular reaction and large positive salt effects show thata highly polar intermediate is formed, possibly of the type (ArH*NO,)+(NO,)-.In concentrated sulphuric acid the nitrating agent is the free nitronium ionNO,+ ; the reactions involved are :/--nH+ + HNO, $ H,O+ NO2+(3>_ NO,+ + ArH 14) (ArH*N02)+(ArH*NO,)+ + B -% ArNO, + BH+With unreactive substrates such as 2 : 4-dinitrotoluene reaction (5) is slowand rate-determining, and the overall kinetics are of third order, involving[ArH], [NO,]', and [B], where the base B can be HS0,-, HS207-, or H,SO,.With rather more reactive substrates, reaction ( 5 ) becomes fast andreaction (3) rate-determining; the kinetics are then of second order,involving (ArH) and (NO,+).With fully reactive substrates reaction (3)also becomes fast, and the rate is then independent of the concentration ofthe substrate.** See F. Holloway, M. Cohen, and F. W. Westheimer, J . Amer. Chem.Soc., 1951,73,65.*O J. H. Merz, G. Stafford, and W. A. Waters, J., 1951,638.' 0 F. R. Duke, J . Amer. Chem. SOC., 1947,69,2885,3054.71 M. S. Khamsch, H. N. Friedlander, and W. H. Urry, J . Org. Chem., 1949,14, 91.78 J., 1950, 2400, 2441, 2462, 2467, 2628, 2657, 2678DEWAR : THEORETICAL ORGANIC CHEMISTRY.129The existence of a stable intermediate (ArH-NO,)+ was first postulatedon theoretical grounds l6 to explain the third-order kinetics of the nitrationof dinitrotoluene, it being suggested that ArH might combine with NO,+ toform a x-complex. The existence of some such intermediate is indicated bysalt effects in the nitration of toluene 72 qhich is of second-order type, andby the absence of an isotope effect 73 when tritiotoluene is nitrated (whichshows that the C-H bond broken in the reaction is still effectively intact inthe transition state).The electrophilic nature of halogenation reactions has been confirmed byD. H. Derbyshire and W. A. Waters 74 who find that chlorination andbromination by hypochlorous and hypobromous acids are acid-catalyged ;the active agent must be either (H,OHal)+ or perhaps free C1+ or Br+ ions.R.P. Bell and E. Gelles 75 have shown that the equilibrium concentrationsof these cations in acid solutions of hypochlorous or hypobromous acid mustbe extremely small.Interesting orientation effects have been observed by E. Ochiai,M. Katada, and their collaborators in the nitration of pyridine and quinolineoxides ; v6 both react readily, to give 4-nitro-derivativea, unlike the parentheterocylic compounds or their quaternary salts where the cxy-positions areselectively deactivated to electrophilic substitution. The explanation ofthis anomaly is seen when it is realised that the oxides are isoconjugate withphenoxide ions, the group - 0- being strongly op-directing in both cases :The conjugation of the oxygen with the ring is indicated by the unusualstability of these oxides to reduction.At the same time the positivequaternary nitrogen atom in the oxide exerts a very strong +E effect,activating the ay-positions to nucleophilic substitution ; for instance, thenitro-group in 4-nitropyridine oxide can be readily displaced as NO,- bynucleophilic reagents such as MeO-.76 These reactions emphasise the needfor relating reactivity to the reIative resonance energies in the initial and thetransition state, rather than to static properties (e.g., charge distribution)in the initial state; the grouping 0-N< can stabilise transition states forccy-substitution by both electrophilic and nucleophilic reagents, the initialcharge density a t the ay-positions being quite irrelevant.A similar situationmay arise in the case of the nitroso-group which also seems 77 to show bothstrong +E and strong - E activity.Orientation effects of theoretical interest have been observed in the acid--73 L. Melander, Nature, 1949, 163, 599; ArEiv Kemi, Min., Qeol., 1950, 2, 211.74 J., 1951, 73, 564. 75 J., 1951, 2734. 7 6 J . Pharm. SOC. Japan, 1943,63, 307.But see D. L1. Hammick and W. S. Illingworth, J., 1930,2358.REP.-VOL. XLVIII. 130 ORGANIC CHEMISTRY.catalysed dehydration of dihydro-1 : 2-diols from aromatic hydrocarbon^.^^These reactions are presumably of E,1 type, in which case the intermediateshave the structures of Wheland-type transition states l4 for (hypothetical)electrophilic substitution of the parent hydrocarbon by OH+ ; e.g.:The hydroxyl group surviving in the h a 1 phenol is in fact a t the positionmore readily substituted in cases where the relative rates of substitutionare known (e.g., 1 : 2-dihydronaphthalene-1 : 2-diol gives a-naphthol) ; andthese reactions should therefore provide information concerning relativereactivities a t positions in hydrocarbons where the rates of substitutioncannot be found directly.The proportions of isomers formed whennitrobenzene is arylated by aryl radicals have been investigatedquantitatively 79 and the op-directing effect of NO,, a +E group, in radicalsubstitution has been confirmed. The proportion of o : rn : p isomers in theproduct was roughly 6 : 1 : 3.The formation of large amounts of theo-isomer is interesting; the ortho-position is more reactive than the para inelectrophilic substitution of nitrobenzene l6 and also, as a rule, in nucleo-philic substitution (see below). The hydroxylation of nitrobenzene byradicals also takes place 8o mainly a t the oppositions, although in this casethe o : p ratio is less, and much more m-isomer is formed. However themechanism of the hydroxylation is by no means established, and it may wellinvolve removal of a hydrogen atom or electron from the aromatic substrateby the hydroxyl radical, rather than normal substitution, via addition ofhydroxyl.(3) Nucleophilic substitution. The nucleophilic replacement of halogenfrom o- and p-halogenonitrobenzenes by piperidine has been studied and thegreater reactivity of the o-isomers This indicates that theposition ortho to NO, is the more strongly activated, although the situationmay be complicated l6 by hydrogen bonding between the reagent and thenitro-group in the transition state for o-substitution.Nucleophilic replacement of halogen by piperidine is faster a t hightemperatures (165-200") in 2- than in 1 -halogenonaphthalenes,s2 but thetemperature coefficients indicate that the reverse would be true at roomtemperature.Reactivity is greater in 1-halogeno-2-nitronaphthalenes than(2) Free-radical substitution.See G. M. Badger, J., 1949, 2497.7O D. F. De Tar and H. J. Scheifele, J . Amer. Chem. Xoc., 1951,73, 1442 ; D. H. Hey,A.Nechvatal, and T. S. Robinson, J., 1951, 2892.H. Loebl, G. Stein, and J. Weiss, J., 1949, 2074; 1950, 2704.*l N. B. Chapman, R. E. Parker, and P. W. Soanes, Chem. and Ind., 1951, 148;82 E . Berliner, M. J. Quinn, and P. J. Edgerton, J . Amer. Chem. SOC., 1950,72,5305.J. A. Brieux and V. Deulofeu, ibid., p. 971DEWAR : THEORETICAL ORGANIC CHEMISTRY. 131in the 2-halogeno-1 -nitronaphthalenes, possibly because of steric hindranceto coplanarity of the nitro-group in the latter.W. Bradley and his collaborators 83 have shown that the amination andhydroxylation of benzanthrone and analogous polycyclic quinones are nucleo-philic substitution reactions; he has also found evidence 84 for an entirelynovel mode of reaction in which a base abstracts a hydrogen atom from thering, giving an anion.The anion may then attack a second molecule ofsubstrate to give a dimeric product. For instance, the synthesis ofviolanthrone is represented as follows :+ Benzanthrone /\A/\- K+ .->+KOH + 1 II I II\A/\/II/\\N\/II 0 0\A/\/II0I10The final stage probably involves a repetition of the removal of hydrogenby the base, followed by cyclisation. The intermediate ion probablyapproximates in structure to a state in which the carbon atom initiallyattacked has become bivalent, the charge residing mainly//\ on oxygen, Le., as inset. The formation of binuclearI 11 products may then take place by dimerisation of suchions, rather than by nucleophilic attack on benzanthrone (,, I itself. It would be interesting to see whether the inter-mediate can show the electrophilic activity to be expected0- from bivalent carbon and condense with nucleophilicring systems such as phenols or dimethylaniline.The reaction is particularly interesting in view of the possibility thata similar abstraction of hydrogen (or an electron) may be the first step insome radical substitutions.The postulation of bivalent carbon no longer seems heretical since severalreactions apparently involving it are now known; e.g., the Reimer-Tiemann and related reactions of chloroform in presence of alkali whereCC1, is an intermediate; 85 the condensation of methylene radicals, formed83 J., 1948, 1175, 1746; 1949, 2712; 1951, 2129.84 W.Bradley, and G. V. Jadhov, J ., 1948, 1622.86 J. Hine, J. Amer. Chem. SOC., 1950, 72, 2438./v\A1 11 \qH 132 ORGANIU OHEMISTRY.by photolysis of diazomethanes, with aromatic hydrocarbons to give cyclo-heptatriene derivatives ; 86 and the alkaline hydrolysis of certaina-substituted propargyl halides.87H. Tropo1one.-Tropolone has been studied theoretically (MO approxi-mation), and the bond orders, charge distribution, resonance energy, lightabsorption, and orientation of substitution have been calculated.88Tropolone gives y-derivatives 89 on nitrosation, nitration, or coupling withdiazonium salts; this is in agreement with predictions based on thecalculation of the energies of Wheland-type transition states,l4 but notwith those based The formation of a-bromo-derivatives takes place via intermediate complexes, and the preferentiala-substitution in this case can be ascribed to molecular rearrangements ofO-halides (cf.the formation of o-nitroanilines by rearrangement of N-nitro-anilines, and the explanation given in ref. 26). The light absorption of tropo-lone derivatives agrees very well withwith the calculated dipole mornent.8*6 Tropolone has, as expected,88 anapproximately symmetrical ring in which all the bonds are of nearly thesame length as those in benzene; 91 this is interesting since the resonancetheory would predict a long OC-CO bond. The observed resonance energy(28.6 kcal./mole) 920f tropolone is less than that calculated (-45), but thismay be due to neglect of oxygen-oxygen repulsion in calcu- f,-+-*-y o- lation of the resonance energy from the heat of combustion.The parent cycloheptatrienone has been prepared 93 andfound to be highly polar in agreement with the idea thatit should approximate to the zwitterionic structure with an " aromaticsextet " of electrons in the ring.Calculation by the MO method 94 confirmsthe analogy with pyrone.I. Reactions involving Cyclic Transition States.-R. D. Brown 95 has calcu-lated the loss in resonance energy of a range of hydrocarbons when theycombine with maleic anhydride, and has shown that the loss in resonanceenergy can be quantitatively correlated with the stability of the adduct.Since a similar correlation exists between this " paralocalisation " energyand the rate of reaction, it seems likely that the transition state resemblesthe product of reaction rather than the initial state ; that is, that the transi-tion state in the Diels-Alder reaction is cyclic, as advocated earlier byon static charge distribution.and so does the found-- 2-86 W.von E. Doering and L. H. Knox, J. Amer. Chm. SOC., p. 2305.88 (a) M. J. S. Dewar, Nature, 1950, 166, 790; (b) Y. Kurita and M. Kubo, Bull.89 The chemistry of tropolone is discussed elsewhere in these Reports.9 1 J. M. Robertson, J., 1951, 1222.92 G. R. Nicholson, quoted by J. W. Cook, A. R. Gibb, R. A. Raphael, and A. R.Somerville, J., 1951, 507.93 H. J. Dauben and H. J. Ringold, J . Amer. Chem. SOC., 1951, 73, 876; W. von E.Doering and F. L. Detert, ibid., p. 877.94 R. D. Brown, J., 1951, 2670.G.F. Hennion and D. E. Maloney, ibid., 1951, 73, 4735.Chem. SOC. Japan, 1951,24,13.Y. Kurita, T. Nozoe, and M. Kubo, Bull. Chem. SOC. Japan, 1951,24, 10.95 J., 1950, 691, 2730; 1951, 1612, 3129DEWAR : THEORETICAL ORGANIC CHEMISTRY. 133M. G . Evans 96a and by B. J. F. Hudson and R. Robinson,96b the reactiontaking place in one step :Similar calculations suggest 97 that osmium tetroxide oxidations of olefinsand aromatic hydrocarbons to cis-diols also involve one-step additionswith cyclic transition states, the mode and ease of addition to aromaticsystems being correctly predicted on this basis.Cyclic transition states have been postulated for a large number of otherreactions in recent years, on evidence of varying weight, and space does notpermit an adequate review here.Some recent examples where suchmechanisms seem strongly indicated are the Chugaev reaction g8 (dehydrationof alcohols by loss of hydrogen sulphide and carbonyl sulphide from theirxanthates), the Passerini reaction 99 (R-CHO + R*NC + R”*CO,H --+R’*NH*COCHR.O*OCR”), the reaction of diphenyldiazomethane withcarboxyhc acids to give diphenylmethyl esters,100 and the internal allylicrearrangements of various ally1 derivatives .lolJ. Decarboxylation and Decarbony1ation.-Three mechanisms ofdecarboxylation of carboxylic acids are now recognised.lo2 First, if R- isa stable mesomeric carbanion, decarboxylation of the acid R*CO,H mayoccur by S,1 loss of carbon dioxide from the conjugate anion. The bestexamples of this mechanism are the decarboxylation of pyridinecarboxylicacids and related acids, where D.L1. Hammick and his collaborators lo3 haveisolated the aldol condensation products of the intermediate anions withcarbonyl compounds.Secondly, the eIectrophilic replacement of (CO,H)+ from the acid, orof CO, from its conjugate anion, may take place by bimolecular SE2 reaction ;this occurs in acids with the grouping R:C’*CO,H, where R+ is a stablemesomeric cation, the reaction resembling electrophilic substitution inaromatic compounds :R:b=CO,H + H+ + 6-hH-C02H --+ R h H + CO, + H+<JA recent example, where both the acid and its conjugate anion undergo 5,2replacement by H+, is the decarboxylation of 2 : 4 : 6-trihydroxybenzoicacid. lo4Thirdly, in molecules with a double bond Py to the carboxyl group, such9 6 (a) Trans.Paraday Xoc., 1939, 35, 824; (b) J., 1941, 715.O 7 R. D. Brown, J., 1950, 3249.O 8 E. R. Alexander and A. Mudrak, J . Amer. Chem. Soc., 1951, 73, 59.O9 R. H. Baker and D. Stanonis, ibid., p. 699.loo J. D. Roberts, W. Watanabe, and R. E. McMahon, ibid., p. 760.lol W. G. Young, S. Winstein and H. L. Goering, J . Amer. Chem. SOC., 1951,73, 1958.lo* H. Schenkel and M. Schenkel-Rudin, Helv. Chim. Acta, 1948, 31, 514.lo3 J . , 1937, 1724; 1939, 809; 1949, 173, 659.lo4 B. R. Brown, W. W. Elliott, and D. L1. Hammick, J., 1949, 1384134 ORGANIC CHEMISTRY.as p-keto-acids, vinylacetic acids, etc., decarboxylation may occur byintramolecular reaction through a cyclic transition state.This mechanismwas first proposed by Westheimer and Jones lo5 to explain the decarboxyla-tion of acetoisobutyric acid :H\o --+ Me-C' ---+ Me-C Me-C\The decarbonylations of certain carboxylic acids are probably relatedreactions, taking place in acids R*CO,H when R+ is a stable cation.losHere reaction takes place by electrophilic removal of hydroxyl :/OH +co, H.. .,, /,o -----.-- -. p/ \.. CMe, ---I CO %Me2 CMe,--COc 3 RCO-OH H+ -+ R d O -+ R + + C O 3 R*OHThe details of the reaction are not quite certain since there is evidence lo'that in some cases two or more protons are involved.(1)The theoretical possibility that a merocyanine dye might approximate soclosely to the extreme zwitterionic structure that a decrease in the dielectricconstant of the medium would actually increase the degeneracy of the dyeand exert a bathochromic effect has been realised experimentally.lo8(2) The peculiar behaviour of thermochromic spirans has now been satis-factorily interpreted log in terms of an equilibrium between colourlesscyclic cis-structures and coloured merocyaninoid trans-structures, e.g.:K. Co1our.-Only a few recent developments can be outlined here.C i S(3) The colours of basic dyes have been studied by the MO method and rulesfound relating them to chemical structure.l1° These confirm earlierqualitative speculations ll1 but also introduce the idea that electromericsubstituents or additional hetero-atoms in a cyanine dye should have dis-similar effects a t positions of like or opposite parity to the terminal basicgroups.that conjugation of two even alternantsystems necessarily has a bathochromic effect; but this is not necessarilyso in odd alternant systems where hypsochromic shifts are often observed(4) It has been shownlo5 J . Amer. Chem. SOC., 1941, 63, 3283.lo6 M. J. S. Dewar, " The Electronic Theory of Organic Chemistry," Oxford, 1949,~. 108.lo7 W. W. Elliott and D. L1. Hammick, J., 1951, 3402.lo* I. I. Levkoev, N. N. Svestrikov, and E. B. Lifshits, Doklady Akad. Nauk.S.S.S.R., 1950, 74, 275; L. G. S. Brooker et al., J. Amer. Chern. Soc., 1951, 73, 5326,5332, 5350, 5356; E. B. Knott, J., 1951, 3033. For a theoretical discussion aee W. T.Simpson, J . Amer. Chem. SOC., 1951, 73, 5359. lo9 E. B.Knott, J., 1951, 3038.ll1 See ref. 106, p. 295. 110 M. J. S. Dewar, J., 1950, 2329CAMPBELL : STEREOCHEMISTRY. 135and also predicted by the MO method.2 ( 5 ) An interesting empirical ruleconnecting colour and light absorption in a wide range of dyes has beendiscovered by E. B. Knott.l12M. J. S. D.3. STEREOCHEIMSTRY.It is appropriate that a preliminary announcement of the determinationof absolute configuration should come from the van’t Hoff Laboratory of theUniversity of Utrecht. Professor Bijvoet and his collaborators have exam-ined sodium rubidium tartrate by means of zirconium Ku rays which excitethe rubidium atom and have shown that it is possible to differentiate betweenthe diffracting model and its mirror image. The principle involved is illu-strated in Fig.1 in which (a) and ( b ) show the diffraction by atoms in crystalsrelated as object and mirror image. The phase differences are the same except(a) (4FIG. 1.’Equal phase differences (except for sign) for model and inversion in the same directionBy introducing a phase-lag in the scattering of one of the atoms, this of diffraction.equivalence i s removed.for sign and the resultant interference effect in (a) and (b) is identical. Whena phase lag is introduced into the scattering process by exciting atom A bythe use of X-rays of appropriate wave-length, because A-P is the longerpath in (a) and the shorter in ( b ) , the diffraction intensities differ in (a) and( b ) , and it becomes possible to decide between the diffracting model and itsmirror image.The authors find that natural dextrorotatory tartaric acidhas the configuration assigned to it by Fischer (Fig. 2). Full details of themethod and results are promised shortly.As the configuration of D( +)-tartaric acid is now a reality, the configura-tion of those compounds, which have been related to tartaric acid by chemicaltransformations not directly involving the asymmetric carbon atom, is alsosatisfactorily settled, and the use of a “ standard substance,” D( +)-glycer-aldehyde, becomes unnecessary. Nevertheless confusion can still arise when112 J., 1951, 1024, 1028, 1586.1 J, M. Bijvoet, A. F. Peerdeman, and A. J. van Bommel, Nature, 1951,168, 271.* Reproduced, by permission, from Nature, 1951, 168, 272136 ORGANIU CHEMISTRY.HO--HH--OHH of glyceraldehyde.If the order of groups is clockwise when viewed fromthe side opposite to H (or the group correlated with H) the configuration isD, and if anticlockwise L (Fig. 3). The symbols D and L refer to the con-figuration about a specific atom which must be numbered or lettered. Forexample, natural dextrorotatory tartaric acid is accorded the D-configurationfor both carbon atoms by the sequence rule and named ED : a‘wtartaric acid,There is wide agreement between the suggested notation and the conventionsin general use, but the original paper must be consulted for details.CHO II H-C-OHCH,*OH r B H r-1 c - - - - - - - -- - - - - - - - - - - - - - - -\OH \ DCHz*OHFIU. 3.Configurational relations have been established chemically betweenD( +)-phenylalanine and ( +) -2-amino-1 -phenylpropane, between L-tyrosineand ( - )-2-amino-1 phydroxyphenylpropane and between L( -) -proline and( -)-2-methylpyrrollidir~e,~ and the configuration of chloramphenicol (Chloro-H.N. Rydon, Ann. Reports, 1950,47, 150; C. Buchanan, Nature, 1951,167, 689.R. S. Cahn and C. K. Ingold, J., 1952, 612.P. Karrer and E. Ehrhardt, Helv. Chim. Acta, 1951, 34, 2202.* Reproduced, by permission, from Nature, 1951,168, 272CAMPBELL : STEREOCHEMISTRY. 137mycetin) has been correlated with that of nor-$-ephedrine by chemical intercon-versions involving stereospecific 0 -+N acyl migrati~n.~ The chain ofrelations between (-)-lactic acid and (-)-mandelic acid has been completedY6so that the previous tentative assignment of (-)-mandelic acid to the D-series is proved correct.The study of the asymmetric enzymic synthesis of amino-acid anilides asa method of resolving the DL-acids has been continued.’ The optimum con-ditions, such as concentration of papain and activator, pH, and time, requiredfor the quantitative synthesis of the L-N-acylaminoanilides according to thereactionDL-R=CO*NH*CHR’*CO,H + Ar*NH, ----+ L-RCO*NH-CHR‘*CO*NH~ + D-R*CO*NH*CHR’*CO,Hhave been established for a wide range of DL-amino-acids, and informationon the influence of R and R’ on the rate of anilide and phenylhydrazideformation,lO and therefore on the stereospecificity of the reaction, has beenobtained.The reverse process of asymmetric hydrolysis of the N-acyl-amido-acids by hog-kidney acylase 11 constitutes another useful method ofresolution, though N-acetylproline and other acids lacking peptide hydrogenare resistant to the enzyme.The four stereoisomers of isoleucine have beenobtained by this method l2 which has also been applied successfully to a-amino-acids not occurring naturally, such as the chloroacetyl derivative of2-aminoheptanoic acid * and the amides of 2-amino-octanoic and -dodecanoicacids.13 A further example of the versatility of biological tools is the use ofD- and L-amino-acid oxidases and of bacterial decarboxylases l4 for thequantitative determination of the contamination of one optical isomer by itsenantiomer. It is claimed that the presence of one part of D-alanine in 1000parts of the L-isomer can be determined in this way, and all the opticallyactive amino-acids prepared by asymmetric enzymic hydrolysis, and capableof examination by this method, have been proved to contain less than 0-1 %of the enantiomer.D. D.De Witt and A. W. Ingersoll15 have called attention to the easewith which pure N-acetyl-L-leucine ma ybe prepared from technical leucine(available as a by-product in the manufacture of sodium glutamate) and haveEnzymeG. Fodor, J. Kiss, and I. Sallay, Nature, 1951, 167, 690; J., 1951, 1858.K. Mislow, J . Amer. Chem. Xoc., 1951,73,3954. Cf. Ann. Reports, 1949,46,186.* D. G. Doherty and A. E. Popenoe, J . Biol. Chem., 1951,189,447; H. T. Huanga N. F. Albertson, ibid., p. 452. See also E.Waldschmidt-Leitz and K. Kuhn,lo E. L. Bennett and C. Niemann, J . Amer. Chem. SOC., 1950, 72, 1798; W. H.l1 J. P. Greenstein et al., J. Biol. Chem., 1949, 179, 1169; 1950,182, 451.l2 I d e m , ibid., 1951,188, 647.,l3 C. G. Baker and A. Meister, J . Amer. Chem. Soc., 1951,73, 1336.l4 A. Meister, L. Levintow, R. B. Kingsley, and J. P. Greenstein, J . Biol. Chemand C. Niemann, J . Amer. Chem. SOC., 1951,73,475.2. physiol. Chem., 1950, 285, 23.Schuller and C. Niemann, ibid., 1951, 73, 1644.1951,188, 535. l6 J . Arner. Chem. Xoc., 1951, 73, 3359.* Geneva notation (C0,H = 1)138 ORGANIC CHEMISTRY.used it to resolve (-i-)-a-fenchylamine obtained from ( j-)-fenchone by amodified Leuckart synthesis.16 ( +)-a-Fenchylamine separates as the leastsoluble salt (SO-SS%) and the crude (-)-amine regained from the moresoluble salt is purified by recrystallisation of the salicylidene derivative andsubsequent hydrolysis.The advantages of (+)- and (-)-a-fenchylamines asresolving agents have been demonstrated by the successful resolutions ofN-acetyl derivatives of a series of DL-amino-acids.The essential principle of garlic, alliin, l8 and its three optically active iso-mers have been synthesised by A. Stoll and E. Seebe~k.1~ The compound isof interest because it contains two centres of asymmetry, a carbon and asulphur atom, and is the first example of its kind. 8-Allyl-L-cysteine (I) isoxidised by hydrogen peroxide to a mixture of the two diastereoisomericsulphoxides, [a]: +29.3" (in water), which is separable by careful crystallis-ation from aqueous acetone into the less soluble ( +)-8-allyl-L-cysteine sul-phoxide (11), [a]: +63.2", identical with natural alliin, and the (-)-SO isomer, [a],, -60.7" :NH2 I NH2 I H A +CH&CH*CH,*S*CH,*C-CO,H _Lf CH,:CH*CH,-S--CH,-C-CO,HI +AIliinase I (11) 1 I H H (1)CH,:CH*CH,-S-S-CH,*CH:CH, + NH, + CH,*CO*CO,H II 08-AlIyl-D-cysteine7 obtained by resolution of N-formyl-DL-cysteine by meansof brucine, is similarly converted into the (+)- and the (-)-sulphoxide. Theisomers containing the D-cysteine residue are unaffected by alliinase 2o but theenzyme shows less specificity towards the configuration of the sulphoxidegroup, for (IIb) is hydrolysed as shown, though much less rapidly than (IIa).(&)-Methyl hydrogen P-methylglutarate has been resolved 21 into enantio-mers [the la3vorotatory isomer being configurationally related to D( +)-glyceraldehyde, by means of certain assumptions additional to the Fischerconvention] which undergo the Kolbe electrolytic reaction without racemisa-tion of the asymmetric centre in the p-position to the carboxyl group.22Electrolysisofthesodiumsalt of D( -)- or L( +)-CO,H*CH,*CHMe.CH,-CO,Me*in methanol gives, after hydrolysis, good yields of the optically pure (-)- and(+)-PP-dimethylsuberic acids, [ ~ ] l D 9 ' ~ &13.2" (c, 5% in dioxan), whereas thel6 A.W. Ingersoll et al., J . Amer. Chem. Xoc., 1936, 58, 1808.l7 L. R. Overbury and A. W. Ingersoll, ibid., 1951,73,3363 ; W. A. H. Huffmann andl 8 A.Stoll and E. Seebeck, Helv. Chim. Acta, 1948, 31, 189.l9 Idem, Experientia, 1950, 6, 330; Helv, Chim. Acta, 1951, 34, 481.2o Idem, ibid., 1949, 32, 197.21 S. Stallberg-Stenhagen, A r k i v K e m i , Min., Geol., 1948,25, A , No. 10.22 ( a ) Idem, Arkiv K e m i , 1950, 2, 95; (b) R. P. Linstead, J. C. Lunt, and B. C. L.A. W. Ingersoll, ibid., p. 3366.Weedon, J., 1950, 3333.* For the special symbols D and L, see J . , 1950, 3331CAMPBELL : STEREOCHEMISTRY. 139product obtained from the sodium salt of the racemic half ester is a mixtureresulting from a (' crossed " coupling to give the meso-diester and from sym-metrical coupling to give the racemic diester ; the acid obtained on hydrolysisis separable by fractional crystallisation into meso- p p-dimethylsuberic acid,m.p. 105", and the racemic form, m. p. 79-79-5". I n consequence of thisretention of configuration, a useful method has become available for the syn-thesis of optically pure branched-chain fatty acids, some of which are ofbiological interest. For example, electrolysis of a mixture of L(+)- orD( -)-(methyl hydrogen P-methylglutarate) with acetic, propionic, or butyricacid yields the optically active 3-methyl-pentanoic, -hexanoic, or -heptanoicacid respectively,22a and (+)- and (-)-tuberculostearic acids [L( +)- andD( -)-10-methyloctadecanoic acids] have been obtained 23a by two anodicsyntheses as follows :Me*[CH2]6*C02H + L( +) -HO,C*CH,*CHMe*CH,*CO,Me(1) Kolbe electrolysis,(2) hydrolysisD( +) -Me*[CH,],*CHMe*CH,*CO,HD( +)-Me*[CH,],*CHMe*CH,CO,H + HO,C*[CH,],*CO,Me(1) Kolbe electrolysis, - ~(-)--e*[CH,l,*CHMe*CCH21**CO2HSimilarly, an unsymmetrical electrolytic coupling of D( +)- or L( -)-3-methylundecanoic acid with the monomethyl ester of sebacic acid yieldsD( +)- or L( -)-ll-methylnonadecanoic a~id,,~b neither of which is identicalwith phytomonic acid, the branched-chain acid, C20H4002, isolated by Velickfrom the fat of Phytomonas tumefaciens.Two preliminary notices 24 describe an interesting phenomenon entitled'( configurational activity." Using ( &->-[Ni(dip~)~]I~ (111), which exists inoptically labile enantiomers (half-life, 15 minutes a t 17") less soluble than theracemic form, Dwyer shows that it is apparently possible to effect a partialresolution by merely adding an optically active anion or cation to.an aqueoussolution of the racemic form.For instance when (111) is dissolved in l+yoaqueous solutions of ammonium (+)-bromocamphorsulphonate or ( -)-quinine hydrogen sulphate or ( +)-[Co(en),]C13 a t 5" and immediately pre-cipitated by the addition of sodium iodide, the least soluble fraction is dextro-rotatory, m5461 +O.lO", and the most soluble is hvorotatory. If the solutionis kept a t 20" for a day, the rotation moves in the hvo-direction and fractionalprecipitation yield's first an inactive iodide and then a lzevorotatory iodide.Apparently the asymmetric electric field of the added optically active ioninteracts preferentially with one of the anfimeric ions of the optically labilesystem (111), increasing the activity coefficient of this ion and rendering itless soluble by the solubility-product principle ; similar activity changes witha non-ionic species, trisacetonylacetonecobalt, have also been observed. Itshould be noted that the added asymmetric cations cannot form diastereoiso-(b) R.Cavanna and S.Stallberg-Stenhagen, A t t i Accad. nazl. Lince?:, Meni. Classe sci. 8s. mat. emat., 1950, 3 (No. Z), 31.b23 (a) R. I?. Linstead, J. C. Lunt, and B. C. L. Weedon, J., 1951, 1130;24 F. P. Dwyer et al., Nature, 1951,167, 1036; 168, 29140 ORGANIC CHEMISTRY.merides with (111), and in this connection the authors refer to the work ofP. Pfeiffer and K. Q ~ e h 1 , ~ ~ suggesting that, here, the extreme optical labilityof the system studied prevented the isolation of optically active solid.Evidence obtained from ultra-violet and visible absorption spectra of aseries of thioindigo dyes indicates that in solution in benzene or chloroformcis- and trans-forms exist in an equilibrium which is dependent on temper-ature and on illumination.26 The greatest change in the visible absorptionspectrum of thioindigo occurs on irradiation with light of A >520 mp, i.e., Acorresponding to the first long-wave absorption band of the dye.Moreover, abenzene solution, after a period of irradiation, may be chromatographicallyseparated on silica gel into the more strongly adsorbed unstable cis- and themore readily eluted stable trans-form, the former orange-yellow and the latterPh, ,CO*Ar H\ ,CO*ArC’ \(IVU) c---/ \ /’ \HH NRIH C/\ H PhAr I H C\C- C’ (IW/ \ / \ Ph N HRAr .1I H CPh /\H1 fast ’ Ar I * H C,..+-NPh Ph’LNph :* !-&Ph \Ph” H (VII) H” Ph( V I 4 (VIb)purple-red.Absorption spectra have also provided evidence 27 that thestable forms of diazosulphonates, Ar*N:N*SO,K, on exposure to ultra-violetlight or to sunlight undergo a partial reversible conversion into the labileforms, although some irreversible decomposition also occurs. The similaritiesand differences in the spectra of the isomeric forms are of the same type asBer., 1932, 65, 560; 1933, 66, 415; Ann. Reports, 1933, 30, 263; Quart. Reviewe,1947,1,309. as G. M. Wyman and W. R. Brode, J . Amer. Chem.SOC., 1951,73,1487.2 7 H. C. Freeman and R. J. W. Le Fdvre, J . , 1951, 415CAJYWBELL : STEREOCHEMISTRY. 141those observed in the spectra of cis- and trans-diazocyanides and -azobenzenes.Indeed, all the evidence obtained by examination of compounds containingthe -N:N- linkage z8 points to the probable existence of geometrical isomersand constitutes further argument in favour of Hantzsch's original hypothesis.cis-Cinnamoyl chloride has been prepared 29 and used in a study of relativereactivities, along with ally1 chloride and cis- and trans-but-2-enyl chloride.30Evidence from phase equilibria and from spectroscopic and kinetic data leadsto the view31 that the cis-di-iodoethylene recorded in the literature is aeutectic mixture of cis- and trans-forms.Separation of the isomers has notyet been accomplished.The isomeric ethyleneimine ketones (acylaziridines) 32 have been assignedcis- and tram-configurations on the basis of absorption-spectral and chemicaleviden~e.~S The isomer which has the characteristic CO absorption band atlower frequency in both the infra-red and the ultra-violet region is assignedthe tram-configuration (IVb). The form (IVb) reacts readily with phenyl-hydrazine in ethanol and acetic acid at room temperature, giving a substitutedpyrazoline (VIb), whereas (IVa) reacts very slowly and yields (VII) ; inter-mediate hydrazones (Va and b ) have not been isolated. The suggestedmechanism of the reaction, illustrated above, shows that formation of thefive-membered heterocyclic ring is sterically hindered in (Va) but not in(Vb), and that (VIa), if formed, will have NHR and H in the trans-positionand elimination of NH,R will be facilitated.Prolonged heating with acid isnecessary to convert (VIb) into (VII). Interesting results emerge from thereaction of phenyl-lithium or Grignard reagents with (IVa and b), and all fourracemic carbinols expected from the three asymmetric carbon atoms present,when R in R-MgX differs from Ar, have been isolated. Here the evidencefor the correctness of the assignment of cis- and trans-configuration is moredifficult to assess but seems reasonable. It is of interest that no isomerismcontingent on the presence of tervalent nitrogen has been detected.Following the discovery that a- and P-disalicylides are, not stereoisomers,but di- and tri-~alicylides,~~ a study of the dipole moments of these compoundsand the corresponding o-, m- and p-cresotides has been ~ndertaken.3~ a-Salicylide, the dimer, is shown to possess the cis-configuration (VIIIa), havingp 6.26 D-a transform (VIIIb) would have p = 0.Di-o-cresotide has sub-stantially the same dipole moment, 6.34 D, because the methyl groups are insuch a position as to produce a resultant moment of zero. In the di-m- and di-p-cresotides the methyl groups increase the moments to 6.74 and 6.67 D respec-tively, values which agree well with those calculated from the geometry of themodels. For the trisalicylides which have a twelve-membered ring, fourpossible extreme configurations are considered.Of these the planar con-28 R. J. W. Le F6vre et al., J., 1814, 1977, 2743.20 L . F. Hatch and H. E. Alexander, J. Amer. Chem. Soc., 1950,72,5643.30 L. F. Hatch and S. S. Nesbitt, ibid., 1951, 73, 358.31 S. I. Miller and R. M. Noyes, ibid., p. 2376.33 N. H. Cromwell ef al., ibid., 1951, 73, 1044, 2803.34 W. Baker et al., J., 1951, 201, 209.36 P. G. Edgerley and L. E. Sutton, J., 1951, 1069.32 N. H. Cromwell, ibid., 1949, 71,708142 ORGANIC CHEMISTRY.figuration is excluded because a model shows it to be sterically impossible,but, since the calculated dipole moments of the other three are all much higher(VIIIa)than the values found experimentally, the molecule is considered to take up aconfiguration as nearly planar as steric hindrance allows.Optical activity is frequently useful as a diagnostic property for theelucidation of reaction mechanisms and an example is found in the acidhydrolysis of acetals, in which hemiacetal formation has been postulated asthe first and rate-determining step.36 However, hydrolysis of acetaldehyde(+)-di-( l-methylheptyl) acetal with aqueous phosphoric acid a t 100” yieldsoptically pure (+)-octanol 37 and consequently an intermediate methyl-heptyl carbonium ion is unlikely, and an aldehyde carbonium ion (IX) isproposed. Cyclic acetals and esters of (-)-butane-2 : 3-diol also yield un-racemised diol on hydr~lysis.~~ In the cleavage of optically active sec.-butyl methyl ether with hydrogen bromide 39 (equimolecular proportions)a t 50°, the methyl-oxygen bond is broken and unracemised sec.-butyl alcoholis obtained.Similar cleavage in acetic acid as solvent yields sec.-butylacetate with retained configuration and 88% of the possible activity. On theother hand, cleavage by acetyl chloride cafalysed by stannic chloride breaksthe Bus-0 bond yielding sec.- butyl chloride with inverted configurationand 50% racemised. J. Kenyon and his collaborators have extended theirstudy 40 of the hydrolysis of esters of optically active secondary alcohols andin recent papers *l have examined the tendency to alkyl-oxygen fission inesters of cyclohexylphenyl-, methyl-2-naphthyl-, and methyl-2-thienyl-carbinols. The effect of electron-releasing or -withdrawing groups in pro-moting alkyl-oxygen fission in esters ig admirably illustrated by comparisonof the behaviour of ( - )-p-methylthio- and the corresponding p-methylsul-phonyl-diphenylmethyl hydrogen phthalate on alkaline hydrolysis.Exten-sive racemisation occurs on hydrolysis of the methylthio-compound, whereas,36 L. P. Hammett, ‘‘ Physical Organic Chemistry,” McGraw-Hill, New York, 1940,304.36 H. K. Garner and H. J. Lucas, ibid., p. 5497.30 R. L. Burwell, L. M. Elkin, and L. G. Mawry, ibid., 1951, 73, 2428.40 Ann. Reports, 1946, 43, 165.37 J. M. O’Gorman and H. J . Lucas, J . Amer. Chem. SOC., 1950,72, 5489.41 J. Kenyon et al., J., 1951, 376. 380, 385WALKER : GENERAL METHODS. 143under similar conditions optically pure carbinol is obtained from the methyl-sulphonyl analogue.42Partly asymmetric Meerwein-Ponndorf reductions 43 and the isolation ofsec.-butyl alcohol, [a],, +2.5", from the reduction of ethyl methyl ketonewith lithium aluminium hydride in the presence of (+)-camphor 44 have beenbriefly announced.A more extensive study 45 deals with the extent of partialasymmetric synthesis originating in the interaction of phenylmagnesiumbromide with Me*CO*[CH,]~~CO,C,,H, 9-( -) (series 1) and of met,hyl-magnesium bromide with Ph*CO*[CH,],-C02Cl,H,9- ( - ) (series 2) wheren = 0 , 2 , 3 , 4 , and 8 and C1,H,, = menthyl. (+)-Hydroxy-acids are obtainedin series 1, and the (-)-acids in series 2, and the extent of asymmetric syn-thesis is 18 and 20% respectively when n = 0, and 12.5 and 16.6% whenn = 2. Lactones, [a]& -2-5" and +243", are obtained when n = 3, buthere the extent of asymmetric synthesis cannot be estimated as the opticallypure lactones are unknown ; and when n = 8 the hydroxy-acids obtained areoptically inactive.As it is unlikely that the carbonyl group can be stereo-specifically polarised,46 the authors have suggested that here, and also in theReformatsky rea~tion,~' the transition states, which precede the formation ofthe Grignard complex, are of a diastereoisomeric type, having differentenergies of formation. Consequently t'he reaction proceeds preferentiallyby the route with the lower activation energy, and a partial asymmetricsynthesis results. It is concluded that this disparity gradually decreases asn in series 1 and 2 increases, and vanishes when n = 8.I.G. M. C.4. GENERAL METHODS.Reduction and Hydrogenation.-Lithium aluminium hydride. The out -standing advance in recent years in general methods used in organic chemistryhas undoubtedly been the introduct'ion of lithium aluminium hydride and itscongeners. The general principles underlying the use of these substances, inparticular lithium aluminium hydride itself, have previously received atten-tion in these Reports and elsewhere,2 and the present Report deals with someof the more novel applications described during the year. In the case of asubstance so widely used as lithium aluminium hydride it is prudent to notethat its use is not without hazard and an attempt to reduce the diamide ofperfluorosuccinic acid to the diamine was attended by a violent explosion,4 2 J.Kenyon et al., J., 1951, 382.43 W. von E. Doering and R. W. Young, J. Amar. ClzenL. SOC., 1950, 72, 631.4 4 A. A. Bothner-By, ibid., 1951, 73, 846.4 5 E. E. Turneret aZ., J., 1951, 3219, 3223, 3227.4 6 Idem, J., 1941, 538; 1949, 5169. 4 7 Idem, J . , 1949, 3365.Ann. Reports, 1948,45, 122; 1949,46, 140; 1950,47, 154.W. G. Brown, Org. Reactions, 1951, 6, 469.Ref. 2, p. 489; G. Barbaras, G. D . Barbaras, A. E. Finholt, and H. I. Schlesinger,J . Arner. Chem. SOC., 1948, 70, 877144 ORGANIC CHEMISTRY.traceable to formation of a complex of the amide with the hydride.4 Froma wide range of evidence, it has been suggested that the rate-determiningstep in reductions with lithium aluminium hydride is a bimolecular nucleo-philic substitution by a (possibly complex) hydride Direct proof hasnow been provided for the presence of ions in the ethereal solution of lithiumaluminium hydride, and it is suggested that there is an equilibrium in solu-tion :AlH,9 H9 +AlH,and that the function of the ether is to co-ordinate with the aluminium hydrideand facilitate the forward reaction.6 It may be noted that the hydrogen ofsodium borohydride does not exchange with the hydrogen of water.' A newreagent has been described in the solution obtained from lithium aluminiumhydride and " Carbitol " (diethylene glycol monoethyl ether, which is a stablereducing agent a t temperatures up to the boiling point of " Carbitol " (-ZOO"),and the vigorous reaction generally observed in the hydrolysis of the excess oflithium aluminium hydride is avoided : this reagent reduces acenaphthyleneto acenaphthene but the solution obtained by dissolving the hydride inn-butanol has no such action on acenaphthylene.8Several anomalous reductions with lithium aluminium hydride have beenreported.Thus, brucine affords a new reduction product, dehydrobrucidine,in which reduction of the amide group to the carbinol-amine has occurredand has been followed by loss of water; on the other hand, strychnine, a-and (3-colubrine, as well as dihydrobrucine, are reduced in the expectedmanner of amides, giving respectively strychnidine, a- and p-colubridine,and dihydrobr~cidine.~ The implicit reduction of brucine to the carbinol-amine stage is in line with the reduction of lactams, generally, to amino-aldehydes with lithium aluminium hydride and to oxygen-free amineswith excess of the reagent.lO A further example is found in the productionof 3-hydroxy-4-methyl-2 : 2-diphenylmorpholine (11; X = OH) as an inter-mediate in the reduction of 3-keto-4-methyl-2 : 2-diphenylmorpholine (I) to4-methyl-2 : 2-diphenylmorpholine (11; X = H).l1 When the open-chainanalogue (111) of (I) was reduced, the expected product (IV) was obtainedtogether with 3-dimethylamino-1 : 1 -diphenylpropanol (V), produced byG C bond fission and a rearrangement for which analogies are available.llSimilarly, rj-2'-piperidylpropionodimethylamide (VI ; X = 0) yielded 2-3'-dimethylaminopropylpiperidine (VI ; X = H2), and octahydro-3-keto-pyrrocoline (VII; X = 0) afforded octahydropyrrocoline (VII; X = H,)and a substance showing reactions of an amino-aldehyde, though identityAnon., Chem.Eng. News, 1951,29, 3042.etc etc.Lactones.-P. D. Bartlett and his co-workers l7 have dealt with themechanisms involved in the formation and reactions of @-lactones and anumber of authors have dealt with further additions, e.g., of carboxylic acids,anhydrides, and acid chIorides,lB of ammonia and amines,lg of compoundscontaining active methine and methylene groups 2o including indole,,l and11 Chem. and Ind., 1951, 719.l3 W. E. Parham and H. E. Holmquist, J . Amer. Chem. Soc., 1951, 73, 913; C. W.l4 Idem, ibid., p. 5270.113 R. R. Whetstone and S. A. Ballard, ibid., p.5280; cf. this vol., p. 164.l7 J . Amer. Chem. SOC., 1950,72,4867; 1951,73, 4273,4275.l8 T. L. Gresham, J. E. Jansen, and F. W. Shaver, ibid., 1950,72,72.l9 T. L. Gresham, J. E. Jansen, F. W. Shaver, R. A. Bankert, and F. T. Fiedorek,2o T. L. Gresham, J. E. Jansen, F. W. Shaver, M. R. Frederick, and W. L. Beears,l2 Ann. Reports, 1950, 47, 226.Smith, D. G. Norton, and S. A. Ballard, ibid., p. 5267.Idem, ibid., p. 5273.ibid., 1951, 73, 3168.ibid., p. 2345. z1 J. Harley-Mason, Chem. and Ind., 1951, 886212 ORUANIC CHEMISTRY.of dimethyl sulphide,22 to P-propi~lactone,~~ now available commercially inAmerica.The chemistry of the naturally occurring picrotoxin is particularlycomplex because of the ease with which it and its various degradationproducts undergo rearrangements.H. Conroy 24 has recently advanced aformula for picrotoxinin, C1,Hl,O,, which with picrotin, CI5H1,O,, forms theaddition compound picrotoxin. The close relationship between picrotoxininand picrotin has been discussed.25 The first structurally significant productstobe obtained by relatively mild methods 26 were the keto-acids (V) and (VI)isolated by the action of alkalis on picrotoxinin, a-dihydropicrotoxinin, ora-dihydropicrotoxininic acid, and more recently from neopicrotoxinin 27 alsoobtainable from p i ~ r o t i n . ~ ~ Conroy 24 has degraded dihydro-a-picro-toxininic acid to picrotoxadiene (VII) which he recognised as an opticallyactive form of cis-8 : 9-dihydro-8-rnethyl-5-isopropylindane and this wasconfirmed by synthesis.Consideration of the course of this degradation led-0-'*.2; (VIII)to the partial structure (VIII), and the total structure (IX) was deduced frominfra-red studies on picrotoxinin as well as its isomeric hydrolysis products,picrotoxic acid (X) and picrotoxininic acid (XI), and the reactions of thesecompounds with periodat e./O\CO-C--QH0 MeI CH,\\)\/OHHO(,CO,H I--CMe:CH,Sulphur Ring Systems.-Thiophens and thiophans. Methods of formationof thiophen and thiophan rings have been reviewed.28 Saturated cyclicsulphur compounds are often obtained from the deacetylation of acetylated22 N. F. Blau and C. G. Stuckwisch, J . Amer. Chem. Soc., 1951,73, 2355.23 Ann. Reports, 1949, 46, 149.86 8. N. Slater and A. T.Wilson, Nature, 1951, 167, 324.26 E . Schlittler et al., Helu. Chim. Acta, 1947, 30, 403, 2102; 1949, 32, 1855, 1860;a * D. E. Wolf and K. Folkers, Org. Reactions, 1951, 6, 410.24 J . Amer. Chem. SOC., 1951, 73, 1889.1950, 33, 902. 27 S. N. Slater, J., 1949, 806JOHNSON : HETEROCYCLIU COMPOUNDS. 213thiols if there is a suitably placed hydroxyl or carbonyl group which willpermit cyclisation to O C C W , ~ ~ e.g. :C)H,--CH*SHHS*CH,*CH(SH)*CH,*CH,*OAc .--+ CH, CH,\S/Although Wolff-Kishner reductions of keto-thiophans proceed normally,3oClemmensen reductions cause ring fission with the formation of sulphides.3lNitrogen Ring Systems.-Recent reviews have dealt with the nitration ofnitrogen heterocyclic with nucleophilic substitution of hetero-cyclic ay~tems,3~ and with cyanine dyes.34The recognition of a number of heterocyclic ringsystems for which no single satisfactory formula, using the normal covalentvalency bonds, can be written, has led W.Baker and his colleagues35 topropose the term '' mesoionic " for such compounds, of which sydnone (XII)Mesoionic structures./\A I It I\/\N'\ -0h - 0 P,,.""" \N---C:NPh YA/\ I II I(XIII) (XIV) \A/.'."To(XI11(XV) (XVI) (XVII)is a typical example. The & formulation suggested by J. C. E. Simpson 36has been adopted for these aromatic-type hybrid structures derived from anumber of contributing ionic forms. Many such compounds exist, e.g.,nitron (XIII) and Besthorn's red (XIV) ; e.g.s37 and others, e.g., the 2-substituted benzotriazoles (XV; X = NR), benzofurazan (XV; X = 0),etc., are considered to be '' partially mesoionic " as the covalent o-quinonoidforms (e.g., XVI) are contributing structures.The physical properties ofthese mesoionic compounds, e.g., dipole moments 38 and infra-red ~pectra,3~*O J. S. Harding, L. W. C. Miles, and L. N. Owen, Chem. and Ind., 1951, 887; L.Bateman and R. W. Glazebrook, ibid., p. 1093 ; E. E. van Tamelen, J . Amer. Chem. Soc.,1951,73,3444.H. Schmid and E. Grob, Helv. Chim. Acta, 1948,31, 360.31 H. Schmid and E. Schetzler, ibid., 1951, 34, 894.32 K. Schofield, Quart. Reviews, 1960,4, 382.s3 J. F. Bunnett and R. E. Zahler, Chem. Reviews, 1951, 49, 273.34 F. M. Hamer, Quart. Reviews, 1950, 4, 327.3 5 W. Baker el al., J., 1945, 267 ; 1949, 307 ; 1950, 1542 ; 1951, 289.36 J., 1946,95.38 R.A. W. Hill and L. E. Sutton, J., 1949, 746.39 J. C. Earl, R. J. W. Le FBvre, A. G. Pulford, and A. Walah, J., 1961,2207.3 7 B. R. Brown and D. L1. Hammick,J., 1950, 629214 ORaANIC CHEMISTRY.support these formulations. A number of compounds in the older literature,which were considered to have structures now known to be sterically im-possible, have been re-formulated as mesoionic compounds, e.g., the dihydro-endothiothiadiazoles (XVII) 4O and the anhydro-compounds derived from(2-pyridy1thio)acetic acid and the corresponding quinolyl derivatives(XVIII) 41 (if unsubstituted in the 8-position).\ /CH,*CH,*CO(XVIII) F I X )R*IIJ*CH(CO,Et),COCHC~*R~Trimethylemirnine (azetidine) ; p-lacturns.The first claim of the naturaloccurrence of the azetidine ring has been made for the antibiotic nocardaminefor which the structure (XIX) has been advanced.42 The four-memberedring was postulated on the basis of the products of acid hydrolysis. Papersby J. C. Sheehan and his co-workers have given full details of their two newroutes to p-lactams. The cyclisation of a-chloroacetamidomalonic esters(XX) 43 has been shown to be general for N-substituted a-halogenoacyl-aminomalonic esters.44 The second method, which leads to @-lactamscontaining a substituted 3-amino-group as in penicillin, comprises theaddition of a diacylaminoacyl chloride to a Schiff's base : 45CO-TRFH-CHR'yoc1 flRYH2 + CHR' __f/N\ co co /N\ co yoIn order to obtain the free 3-amino-p-lactam, the phthaloyl group, whichcan be removed later by the action of hydrazine, was used to protect the freeamino-grouping, and the reaction was extended to thia~olines.~~ When therequired product contained the 3-phenylacetamido-grouping as in benzyl-penicillin, the amino-group could be protected as the 5-phenyloxazolidine-2 : 4-dione 47 or 2-benzylideneoxazolidine-4 : 5-dione (as in XXI) 48 ring40 W.Baker, W. D. Ollis, A. Phillips, and T. Strawford, J . 1951, 289.41 G. F. Duffin and J. D. Kendall, ibid., p. 734.42 A. Stoll, J. Rem, and A, Brack, HeZv. Chim. Acta, 1951,34, 862.43 J. C. Sheehan and A. K. Bose, J . Amer. Chem. Xoc., 1950, '72,5158.4 4 Idem, ibid., 1951,73, 1761.4s J. C. Sheehan and J. J. Ryan, ibid., p.1204.4 6 J. C. Sheehan et al., ibid., pp. 4367,4373.47 J. C. Sheehan and G. D. Laubach, .&bid., p. 476248 J. C. Sheehan and E. J. Corey, ibid., p. 4756JOHNSON : HETEROCYCLIC COMPOUNDS. 215system which gave the phenylacetamido-group directly on h ydrogenolysisor on treatment with benzylamine respectively, e.g. :Ph I P co-co P\ co-co \>N*CH,*COCI + PhR CH2 -+ >N-CH-F vH2N-CH, -k CO-N-CH, *6HPh CHPh (XXI)b F € * . N H ,EtO,C*CH, CH,*CH,*CO,Et 7% EtO,C\ I I I M e / Ph*CH,-CO-NH*VH-$! 7H2NH (XXII) CO-N-CH,Pull details have now been published 49 of the 5-phenylpenicillin synthesisreferred to in last year's Report.50The rearrangement of pyrroles in the presence of a strong baseand a di- or tri-halogenomethane to give 3-substituted pyridines proceedsbest with pyrryl-lithium but the yield of pyridines is still very Thetotal synthesis of the uroporphyrin b2 molecule has been achieved 53 althoughthe product seems to be a mixture of isomers. The synthesis of the por-phyrin was carried out by standard methods from the pyrrole (XXII),prepared by the use of benzyl acetoacetate in the initial Knorr synthesis.54The structure of the various pyrrolines has been considered by a number ofauthors and a study of the infia-red spectra 55 has shown that in general thereduction of pyrroles gives a mixture of the A3- and either the A1- or A2-pyrrolines.Cyclisation of y-chloro-nitriles 56 gives A1-pyrrolines, a con-clusion also reached on the basis of the reaction of the products with methyl-magnesium iodide.5' The structures of certain alleged A2-pyrrolines, e.g.,4-phenyl-A2-pyrroline 58 and dihydroni~otyrine,~~ have been revised to theA3-isomers on the basis of ozonolysis,60 ultra-violet absorption spectra, andbehaviour on hydrolysis.61The high-temperature catalytic methods for the preparationPyrroEes.Indoles.49 J.C. Sheehan and G. D. Laubach, J . Amer. Chem. Soc., 1951, 73, 4376.6o Ann. Reports, 1950, 47, 239.61 E. R. Alexander, A. B. Herrick, and T. M. Roder, J . Amer. Chem. Soc., 1950,63 Ann. Reports, 1950, 47, 278; R. E. H. Nicholas and C. Rimington, Biochem. J.,53 S. F. MacDonald, Chem. and Ind., 1951, 1092.5 5 G. G. Evans, J . Amer. Chem. SOC., 1951, '93, 5230.5 6 J. B. Cloke, L. H. Baer, J. M. Robbins, and G.E. Smith, ibid., 1945,67, 2155.5 7 P. M. Maginnity and J. B. Cloke, ibid., 1951, 73, 49.5 8 H. P. L. Gitsels and J. P. Wibaut, Rec. Trav. chim., 1941, 60, 50.59 E. Spiith, J. P. Wibaut, and F. Kesztler, Ber., 1938, 71, 100.6o F. E. King, J. R. Marshall, and P. Smith, J . , 1951, 239.61 J. P. Wibaut and H. C. Beyerman, Rec. Trav. chim., 1951, 70, 977; A. Eisner et72, 2760.1951, 50, 194.64 Idem, ibid., p. 759.al., J . Amer. Chepn. SOC., 1049,71, 1341 ; 1950,78, 1719216 ORGANIC CHEMISTRY.of certain oxygen and sulphur heterocyclic ring syatems 62 have been extendedto the dehydrocyclisation of aromatic anils and o-alkylanilines to indoles andq~inolines.~~ 1 : 3-Dialkylindoles may be conveniently obtained by theaction of Grignard compounds on 1 -alkylgramine mefhiodides.64The 5 : 6-dihydroxy-derivatives of indole are of interest as intermediatesin the conversion of tyrosine into melanin and the various stages in theconversion have been examined by several authors. Tyrosine is thought 65to be converted through 3 : 4-dihydroxyphenylalanine (DOPA) into,successively, a red quinonoid oxidation product, 5 : 6-dihydroxyindole-2-carboxylic acid, 5 : 6-dihydroxyindole, the corresponding o-quinone, andfinally melanin.The oxidation of 3 : 4-dihydroxyphenylalanine is parallelledby the formation of adrenochromeG6 (XXIII) from adrenaline and thesimilar formation of a number of anal0gues.6~ The supposed naturaloccurrence of a quinone of this type 68 (“ halla-readily rearrange in the presence of zinc ions,70 onhydrogenation, or even when k e ~ t , ~ 1 to derivativesMe (xxlll) of 5 : 6-dihydroxyindole.Other synthetic routes tothe 5 : 6-dihydroxyindoles are available and have been developed byA. Robertson and his co-w0rkers.7~ Model experiments on the reactionsof quinones and indoles have led to a tentative structure for melanin.73As a result of some synthetic studies in the strychnine field Sir R. Robin-son and J. E. Saxton ‘4 have made the interesting observation that thecondensation of skatole with acetonylacetone gives 1 : 5 : 8-trimethyl-2 : 3-benzopyrrocoline (XXIV). Indole itself reacts differently but thenature of the product is not known.chrome ”) has been dispr~ved.~~ These quinonesB. Witkop and J. B. Patrick have now provided full details of theformation and Wagner-Meerwein rearrangements 75 of the spiro-+indoxyl62 C.Hansch et al., J . Amer. Chern. SOC., 1948, 70, 1561, 2495; 1949, 71, 943;Ind. Eng. Chem., 1950,22,2114. 63 Idem, J . Amer. Chem. SOC., 1951,73,704,3080.64 H. R. Snyder, E. E. Eliel, and R. E. Carnahm, ibid., p. 970.6 6 H. 8. Raper et al., Biochem. J . , 1927,21, 89; 1930,24, 239.67 J. D. Bu’Lock and J. Harley-Mason, J., 1951, 712; H. Sobotka, J. Austin, et al.,6 8 F. P. Mazza and G. Stolfi, Arch. mi. biol., 1931,16, 183.6s J. D. Bu’Lock, J. Harley-Mason, and H. S. Mason, Biochern. J., 1950,47, XxXii.70 P. Fischer, G. D&ouaux, H. Lambot, and J. Lecomte, Bull. SOC. chim. Belge,7l Idem, J . , 1950, 1276; 1951, 712; J. Austin, J.D. Chanley, and H. Sobotka,72 J., 1948,2223 ; 1949,2061 ; 1951,2029,2426.73 J. D. Bu’Lock and J. Harley-Mason, J., 1951, 751.74 J., 1950, 3136. 76 J . Amer. Chem. Soc., 1951, 73, 713, 1558.J. Harley-Mason, J., 1950, 1276.J . Amer. Chem. SOC., 1951,73, 3077, 5299.1950, 59, 72; J. D. Bu’Lock and J. Harley-Mason, J., 1951, 2248.J . Amer. Chem. SOC., 1951,73,2395JOHNSON : HETEROCYCLIC COMPOUNDS. 21 7(XXV) which is obtained as one of the products from the action of alkali ontetrahydrocarbazole hydropero~ide.5~ Other cases of this type of reactionhave been discussed fully by these and include the rearrangementof the alkaloid quinamine to isoquinamine which is a substituted ind~xyl.'~New preparations of indolylacetic acid have been described 78 which de-pend on Fischer-type syntheses from succindialdehyde or the aldehydo- ester.Among other important naturally occurring indole compounds, the structureof the compound responsible for the vasoconstrictor activity of serum 79has been confirmed as 5-hydroxytryptamine by its synthesis from Ei-benzyl-oxyindole by standard methods.** Another route to ~~-p-3-oxindolylalanine(XXVI) has been described on p.166.Although there has been no further clarification of the total structure ofthe antibiotic gliotoxin, the structure of the degradation product C,,H8N,0S,obtained by the action of methanolic potassium hydroxide,Bl has beenconfirmed as the thiohydantoin (XXVII) by two total syntheses 82 andanother of the corresponding h y d a n t ~ i n .~ ~ The view that the 3-hydroxy-indoline-2-carboxylic acid nucleus occurs in gliotoxin and its dethio-derivativeis strengthened by comparisons with model compounds of this type.84The novel formation of carbazoles by the cyclisation of2-azidodiphenyls by heat or by ultra-violet irradiation s5 has been extendedto the synthesis of a- and y-carbolines and certain related nuclei.86Stereospecific studies on the formation ofoxazolines from p-amino-alcohols and the course of the subsequent hydrolysisof the products have been widely used in structural determinations and arewell illustrated in the recent cf.87 complete cycle of asymmetric trans-formations in the threonine series.88 When the oxazoline is formed by theaction of thionyl chloride on the acylamino-alcohol inversion occurs at the76 J . Amer.Chern. SOC., 1951, 73, 2196, 2641.7 7 G. Bendz, C. C. J. Culvenor, L. J. Goldsworthy, K. S. Kirby, and (Sir) R. Robinson,J., 1950, 1130; B. Witkop, J . Amer. Chem. SOC., 1950,72, 2311.7 8 S. W. Fox and M. W. Bullock, &id., pp. 2754, 2756, 5155.Carbaxoles.Oxazolines ; oxazolidines.M. M. Rapport et al., Science, 1948, 108, 329; J . Biol. Chem., 1948, 176, 1243;*O K. E. Hamlin and F. E. Fischer, J . Amer. Chem. SOC., 1951, 73, 5007 ; M. E.81 J. D. Dutcher, J. R. Johnson, and W. F. Bruce, ibid., 1945,67, 1736.82 J. A. Elvidge and F. S. Spring, J., 1949, S 135 ; J. R. Johnson and J. B. Buchanan,133 J. D. Dutcher and A. Kjaer, ibid., p. 4139.84 J. R. Johnson and J. H. Andreen, ibid., 1950, 72, 2862.8 6 P.A. S. Smith and B. B. Brown, ibid., 1951,73, 2435.86 P. A. S . Smith and J. H. Boyer, ibid., p. 2626.87 Ann. Reports, 1949,46, 188; 1950,47, 173.D. F. Elliott, J., 1949, 589; 1950, 62.1949,180, 961.Speeter, R. V. Heinzelmann, and D. I. Weisblat, ibid., p. 5514.J . Amer. Chem. SOL, 1951, 73, 3749218 ORUANIC CHEMISTRY.carbon bearing the oxygen atom with little or no racemisation,e-g-~ 89f90 andsimilar conclusions have been reached from studies of cyclic acylamino-a l c h ~ l s , ~ ~ , 92 although cis-2-benzamidocyclohexanol did not give an oxazoline :1 H ~ - NI &H$For the preservation of configuration at both asymmetric centres duringoxazoline formation, the p-amino-alcohol is treated with an imino-ester.This applies to the 2-aminocyclohexanol (cis- and trans-) and cis-2-amino-cyclopentanol series 91,93 as well as to the aliphatic compounds.88 From apractical point of view in the threonine series, the conversion of the cis-into the trans-oxazoline by the action of alkali results in a much improvedyield of L-threonine 88 as the acid hydrolysis of the oxazoline proceeds withoutinversion. Resolution of the DL-trans-oxazoline acid gave the L-form(XXVIII), and furthermore the D-form, also isolated, could be inverted byusing the above reactions.Similar conversions have been used for thepreparation of the isomers of 2-hydroxy-1 : 2-diphenylethylamine.90R \,/OHHC--d >+c<paPh$lp-Y" HN/ \o(XXIX) (XXVIII) MeCOR acid COR/c< >-< HN >c-These transformations are related to the acyl migrations which occur soreadily in the p-amino-alcohol series, and cyclic intermediates are involved,probably oxazolines in the acid migration (N-acyl 4 O-acyl) and cyclicesters (XXIX) in the alkaline migration (O-acyl + N-acyl).The oxazolinesthemselves 94 can be hydrolysed to O-acyl or N-acyl derivatives by acid oralkali respectively. Recent studies of acyl migrations have led to theassignment of configurations to the ephedrine isomers,95 and to chloram-8s J. Attenburrow, D. F. Elliott, and G. F. Penny, J . , 1948, 310; E. M. Fry, J . Org.Chem., 1949, 14, 887.J. Weijlard, K. Pfister, E. F. Swanezy, C. A. Robinson, and M. Tishler, J . Amer.Chem. SOC., 1951, 73, 1216.Dl W. S . Johnson and E. N.Sehubert, ibid., 1950, 73, 2187.98 G. E. McCasland and D. A. Smith, ibid., 1951, 73, 2190; G. Fodor and J. Kiss,93 G. E. McCasland and E. C. Horswill, J. A m r . Chem. Soc., 1951, 73, 3744.94 R. H. Wiley and L. L. Bennett, Chem. Reviews, 1949,44,457.s6 L. H. Welsh, J. Amer. Chem. Soc., 1947,69, 128; 1949, 71, 3500; G. Fodor et al.,J., 1948,885 ; J. Org. Chem., 1949,14,337 ; H. Bretschneider and K. Biernann, Molzatsh.,1950, 81, 31.Research, 1951, 4, 382JOHNSON : HETEROCYCLIC COMPOUNDS. 219phenicol g6 which has a configuration corresponding to that of (-)-nor-$-ephedrine, a conclusion previously deduced from optical rotational data.97In the cyclic series configurations have been assigned, on the basis of similarconsiderations, to the acyl derivatives of the 2-aminocyclohexanols 91,92,98and of the various in0samines.9~ Similar attempts in the p-phenylserineseries have not been successful 100 but other methods are also available forthe determination of configuration of p-amino-alcohols, e.g., a study of thedissociation constants as used by V. Prelog and 0. Hafliger lol in their elegantstudy of quinine and its isomers.Studies of the infra-red and ultra-violet spectra of the products obtainedfrom the reaction of p-amino-alcohols and carbonyl compounds Io2 revealthat they are frequently Schiff's bases and not oxazolidines as often sup-posed. It is now doubtful if any oxazolidine of well-established purity andstructure bearing no substituent on the nitrogen atom is known. Methodsfor the preparation of oxazolid-2-ones have been assessed 103 and, as thesecompounds can be readily obtained from p-amino-alcohols by reaction withurea, they have also been used, like the oxazolines, for the assignment ofsteric configurations.104 The decomposition of the N-nitroso-oxazolid-2-ones can yield a variety of products, including acetylenes, depending on thenature of the s u b s t i t u e n t ~ .~ ~ ~Thiaxoles lo6 ; thiaxolines ; thiaxolidines. The preparations of %,Io74-,Io79 lo* and 5-thiazolylalanines lo9 have been carried out by standardamino-acid type syntheses.The colourless compound obtained together with thiochrome by the actionof heat on aneurin disulphide I10 has been shown to be the thiazolone (XXX)and is no longer regarded as an intermediate in the aneurin-thiochromeconversion.lll The structure was confirmed by synthesis 112 either from4-amino-5-aminomethyl-2-methylpyrimidine, carbon oxysulphide, and 3-s6 G.Fodor, J. Kiss, and I. Sallay, J., 1951, 1858.97 M. C. Rebstock, H. M. Crooks, J. Controulis, and Q. R. Bartz, J . Amer. Chem. SOC.,1949, 71, 2458.See alsoE. E. van Tamelen, J . Amer. Chem. SOC., 1951, 73, 5773.99 G. E. McCasland et al., ibid., 1949, 71, 637; 1951, 73, 2295; L. Anderson andH. A. Lardy, ibid., 1950, 72, 3141; T. Posternak, HeZv. Chim. Acta, 1950, 33,1597.loo K. Vogler, ibid., p. 211 1 ; E. D. Bergmann, H. Bendas, and W. Taub, J., 1951,2673.lol Helv. Chim. Acta, 1950, 33,' 202 1.lo2 G. R. McCasland and E. C. Horswill, J . Amer. Chem.Soc., 1951,73,3923; L. W.lo4 G. Fodor and K. Koczka, Research, 1951, 4, 381; W. J. Close, J. Org. Chem.,lo5 M. S. Newman and A. Kutner, J. Amer. Chem. SOC., 1951,73,4199.lo8 R. H. Wiley, D. C. England, and L. C. Behr, Org. Reactions, 1951, 6, 367.lo' R. G. Jones, E. C. Kornfeld, and K. C. McLaughlin, J . Amer. Chem. SOC., 1950,log F. C. Brown, H. Erlenmeyer, and E. Sorkin, HeZv. Chim. Acta, 1951,34, 1654.110 0. Zima and R. R. Williams, Ber., 1940, 73, 941.ll1 P. Sykes and A. R. Todd, J., 1961,634.G. Fodor and J. Kiss, ibid., 1950, 72, 3495 ; Acta Chimica, 1951,1, 130.Daasch, ibid., p. 4523.1951,15, 1131.103 W. J. Close, ibid., p. 95.72, 4526. lo8 W. T. Caldwell and S. M. Fox, ibid., 1951, 73, 2935.11* P. Sykea, ibid., p. 2507220 ORGANIC CHEMISTRY,acetoxy-1 -chloropropyl methyl ketone by acid treatment or by acid cyclisationof the intermediate (XXXI).cf- l13A new method for the stepwise degradation of peptides l14 has been out-lined by H.G. Khorana 115 who separates the terminal amino-acid as thethiazolidione by reaction of the amino-group with O-ethyl S-methyl xanthate.But-2-yne-1 : 4-diol has been used in anew histamine synthesis 116 and full details have now appeared of theergothioneine synthesis and related reactions.l17 The chemistry of thebenziminazoles 118 and hydantoins 119 has been reviewed. The biologicalimportance of various condensed glyoxeline (e.g., purine and benziminazole)glycosides 120 has led to new synthetic methods, and J. Dsvoll and B. A.Lowy 121 recommend the use of the chloromercuri-derivatives of the purinesfor condensations with the acetohalogeno-sugars with subsequent deacetyl-ation.Syntheses of adenosine, guanosine, and crotonoside 122 were describedas well as of benziminazole glycosides.123Pyridifies ; piperidines. The extensive researches of the Amsterdamschool have been reviewed by J. P. W i b a ~ t . ~ ~ ~ Two tetramethylpyridineshave been isolated from coal tar 125 and pentamethylpyridine has beenobtained 1z6 by the stepwise reduction of the readily available collidine-3 : 5-dicarboxylic ester. The lithium aluminium hydride reduction of theester groups in this reaction proceeds normally with pyridine esters 127,128although pyridine itself is reduced.129 p-Picoline, like the a- and y-isomers,can be alkylated with the lower alkyl halides in liquid ammonia in thepresence of sodamide.130 The Chichibabin synthesis of substituted pyridines,Glyoxalines ; benximinuxoles.113 T. Matsukawa and T. Iwatsu, J. Pharm. SOC. Japan, 1950,70, 32.11* Cf. Ann. Reports, 1950, 47, 164.116 Chem. and Imd., 1951, 129; cf. this vol., p. 245.116 C. F. Huebner, J. Amer. Chem. SOC., 1951, 73, 4667; M. M. Fraser and R. A.117 H. Heath, A. Lawson, and C. Rimington, J., 1951, 2215, 2217, 2220, 2223; see118 J. B. Wright, Chem. Reviews, 1951,48, 397. 119 E. Ware, ibid., 1950, 46, 403.12* G. W. Kenner, “ Fortschritte der Chemie Organischer Naturetoffen,” 1951, Vol.121 J. Amer. Chem. SOC., 1951, 73, 1650.183 J. Davoll and G. B. Brown, ibid., p.5781.la6 H. B. Nisbet and A. M. Pryde, Nature, 1951,167, 862; 168, 832.126 P. Karrer and M. Mainoni, J . Amer. Chem. SOC., 1951,34, 2151.1 2 7 R. G. Jones and E. C. Kornfeld, ibid., p. 107.12* H. S. Mosher and J. E. Tessieri, ibid., p. 4925; A. Cohen, B.P. 631,078; Chem.lao H. C. Brown and W. A. Murphey, J . Amer. Chem. SOC., 1961,73,3308.Raphael, J., 1952, 226.also Ann. Reports, 1950,47, 176.VIII, p. 96.12% Idem, ibid., p. 3174.124 Chim et Ind., 1950, 63, 609.Abs., 1950, 44, 5397. 12s P. de Mayo and W. Rigby, Nature, 1950,166, 1076JOHNSON : HETEROCYCLIC COMPOUNDS. 22 1including arylpyridines and polypyridyls, from carbonyl compounds andammonia has been developed by R. L. Frank and his c01leagues.l~~ 2-Aminopyridines may be obtained from the condensation of imino-ethers oramidines with p-dicarbonyl and recommended routes t o 3-133and 4-aminopyridine 134 have been published. Use of hydrogen peroxideand sulphuric acid 135 for the oxidation of 2- and 4-aminopyridines to thecorresponding nitro-compounds has been applied in a number of othercases.13* The relative ease with which pyridine oxide undergoes nitration 13'has been developed into a useful route to the 4-substituted pyridines as thenitro-group of 4-nitropyridine N-oxide can be readily reduced 138 or replacedby alkoxyl, hydroxyl, halogen, e t ~ ., l ~ ~ and the oxide group subsequentlyremoved by reduction. Another route to the 4-substituted pyridines is thesubstitution reactions of the acylpyridinium salts 140 and W.von E. Doeringand W. E. McEwen have provided further examples by proving that thecrystalline product from the reaction of pyridine, benzoyl chloride, andacetophenone 142 has the structure (XXXII), and the related product frompyridine, acetic anhydride, and acenaphthenone is (XXXIII) .(XXXII)OAcCH,*OH(XXXIV)There is general agreement that the preparation of Grignard derivativesfrom the halogeno-pyridines requires special conditions 143 and even then isnot always satisfactory, but the alternative lithium compounds are readilyprepared.lU131 J . Amer. Chem. Soc., 1949,71,2629; 1950,72,4182,4184; Org.Synth., 1950,30,41.193 C. F. H. Allen and C. N. Wolf, Org. Synth., 1950,30, 3.134 A. Albert, J., 1951, 1376.135 A. Kirpal and W. Bbhm, Ber., 1931, 64, 767; 1932, 65, 680.Is6 H.J. den Hertog, C. Jouwersma, A. A. van der Wal, and E. C. C. Willebrands-Schogt, Rec. Trav. chim., 1949,68,275; R. H. Wiley and J. L. Hartman, J . Amer. Chem.SOC., 1951, 73,494.13' H. J. den Hertog and J. Overhoff, Rec. Trav. chim., 1950, 69, 468; E. Ochiai,E. Hayashi, et al., J . Pharm. SOC. Japan, 1947,67,79, 157.138 E. Ochiai and I. Suzuki, ibid., p. 158.13* M. Katada, ibid., p. 61 ; E. Hayashi, ibid., 1950, 70, 145 ; H. J. den Hertog andW. P. Combe, Rec. Trav. chim., 1951, 70, 581. Many of the earlier Japanese papers onthis subject have been abstracted recently, see Chem. Abs., 1951, 45, 5151-5154, 8367,140 Cf. J. P. Wibaut and J. F. &em, Rec. Trav. chim., 1941,60, 119 ; E. Koenigs andl 4 2 L. Claisen and E.Haase, Ber., 1903,36, 3674.143 J. P. Wibaut et al., Rec. Trav. chim., 1940,59,973; 1950,69,1048; 1951,70, 989.144 D. W. Adamson and 5. W. Billinghurst, J., 1950, 1039; H. E. French and K.Sears, J . Amer. Chem. Xoc., 1951, 73, 469; A. P. de Jonge, H. J. den Hertog, and J. P.Wibaut, Rec. Trav. chim., 1951, 70, 989.A. Dornow et al., Ber., 1940, 73, 542 ; 1951,84, 296.8525-8529, 9536-9541.E. Ruppelt, Annalen, 1934,509, 142. 141 J . Amer. Chem. Soc., 1951, 73, 2104222 ORGANIC UHEMISTRY.The chemistry of vitamin B, (Xxmv) still continues to attract attentionand the Lilly research group have described 127 a new synthesis dependingon the lithium aluminium hydride reduction of the corresponding dicarboxylicester, which was obtained by an improved method.145 The condensation ofethyl hydroxymethyleneoxaloacetate (XXXV) and acetylacetone iminegave the compound (XXXVI) together with the ammonium salt of (XXXV).(XXXm) was cyclised with sulphuric acid to the pyridine acid-ester(XXXVII; R = Et, R’ = COMe) and then by the Schmidt reaction gavethe amino-pyridine (XXXVII; R = H, R’ = NH,).Nitrous acid thengave the hydroxypicolinedicarboxylic acid required for the final reduction.C0,HEtO,C*f*CO*CO,Et EtO,C*g*CO*CO,EtCH*OH CH*NH*CMe:CH-COMe(XXXV) (XXXVI)(XXXVII)The use of ethyl ethoxymethyleneoxaloacetate in the initial condensation,or even in certain cases the hydroxymethylene compound, gave rise t o2 : 3 : 5 : 6-tetrasubstituted pyridines.l*, In another approach to pyridoxin,A.Cohen 147 has studied the Dieckmann cyclisation of carbalkoxyalkyl-aminoitaconic esters (XXXVIII) (from the condensation of a-amino-esterswith acylsuccinic esters) but found that the products were the pyrrolinones(XXXIX) unless the nitrogen atom was substituted. Related condensationshave been described by C. A. Grob and P. Ankli.14*(XXXVIII) (XXXIX) (XL)Codecarboxylase (synthesis 149) has been proved to be the 5-monophos-phate ester (XL) of pyridoxal by its general reactions, the non-identity withthe 3-m0nophosphate,~~* and the demonstration of the free aldehydegroup 151 by the preparation of derivatives and degradation products. 152Pyridoxamine 5-phosphate 153 has been oxidised to codecarb~xylase.~~~Technical piperidine may contain up to 20% of 1 : 2 : 5 : 6-tetrahydro-145 R.G. Jones, J . Amer. Chem. SOC., 1951, 73, 5244, 5610.148 E. M. Boltorff, R. G. Jones, E. C. Kornfeld, and M. J. Mann, ibid., p. 4380.147 J., 1950, 3005; E. C. Barell Jubilee vol., p. 71 (Basle, 1946).148 Helv. Chim. Acta, 1949, 32, 2010; 1950, 33, 273.148 I. C. Gunsalus, W. W. Umbreit, W. D. Bellamy, and C. E. Foust, J . Biol. Chem.,1945, 161, 743; D. Heyl, E. Luz, S. A. Harris, and K. Folkers, J . Amer. Chem. SOC.,1951, 73, 3430; M. Viscontini, E. Ebnother, and P. Karrer, Helv. Chim. Acta, 1951, 34,1834,2198. 160 D. Heyl, S. A. Harris, etal., J . Amer. Chem. SOC., 1951,73,3430,3434.161 Cf. J. Baddiley, E. M. Thain, and E. Rodwell, Nature, 1951,167, 556.lSa D. Heyl, E. Luz, and S. A! Harris, J . Amer. Chem.SOC., 1951, 73, 3437.163 D. Heyl, E. Luz, S. A. Harris, and K. Folkers, ibid., p. 3436; M. Viscontini,lS4 A. N. Wilson and S. A. Harris, J . Amer. Chem. SOC., 1951, 73, 4693.C. Ebnother, and P. Karrer, Helv. Chim. Acta, 1951, 34, 2199JOHNSON : HETEROCYCLIC COMPOUNDS. 223~ y r i d i n e . l ~ ~ A convenient preparation of N-alkylpiperidines by hydro-genation of pyridine quaternary salts in the presence of a base is reportedby J. A. Barltrop and D. A. H. Tay10r.l~~ In a series of papers,15' N. J.Leonard and his collaborators have shown that whereas the Wolff-Kischnerreduction of cyclic a-amino-ketones including p-piperidones is normal, theClemmensen reduction is generally accompanied by rearrangement involvingcontraction of the ketonic ring and is independent of substitution on thea-carbon atom :CH,Clemmensen H,V---p%H,C, ,CHEt j .H,C, ,,CHfCH2],-MeNMe NMeWith exocyclic ketones, ring fission occurred, e.g. :CH, CH2+ H27/ \QHzH2C, CH,*CH,*MeH2F/ \QH2H,C, ,,CH*COMeNMe NHMeThe scope and mechanism of these reactions were thoroughly examined andprevious anomalies in the literature reinterpreted. Similar rearrangementshave also been observed in electrolytic reductions of a-amino-ketones in30% sulphuric acid with a cadmium cathode.The chemistry of the 4-hydroxyquinolines has been re-viewed.158 The preparation of 6-substituted 3-bromoquinolines can beeffected by the condensation of 2 : 2 : 3-tribromopropaldehyde with theappropriate p-substituted aniline or NN-dialkylaniline ; 159 without thep-substituent a number of by-products are also formed.Some light on themechanism of this reaction comes from a later paper 16* in which it is shownthat the same reaction using 2-alkyl-2 : 3-dibromopropaldehydes yields6-substituted 3-alkylquinolines, e.g. :Quinolines.CH*N09155 W. H. Davies and L. L. McGee, J., 1950, 678. 156 J., 1951,108.J . Amer. Chem. SOC., 1949, 71, 3089, 3094, 3098, 3100; 1950, 72, 3632, 4931;1951,73, 5210; cf. G. R. Clemo, R. Raper, and H. J. Vipond, J., 1949, 2095.Is* R. H. Reitsema, Chem. Reviews, 1948, 43, 43.159 R. H. Baker, S. W. Tinsley, D. Butler, and B. Riegel, J. Amer. Chem. Soc., 1950,72, 393; F. Weygand and W. Rupp, Ber., 1950,83,455.la* F. Weygand and E. Frank, Ber., 1951,84, 619224 ORGANIC CHEMISTRY.The unusual reaction between 2-methylisoquinolinium iodide and nitro-methane in the presence of a base resulting in the formation of 2-nitro-naphthalene in up to 25% yield has prompted the investigation of the samereaction with 1-methylquinolinium iodide. 162 The product, 1 : 4-dihydro-1-methyl-4-nitromethylenequinoline (XLI), was obtained in the highestyield in the presence of a dehydrogenating agent, e.g., nitrobenzene.There still remains some confusion regarding the nature of quinaldoinand quinaldil.B. R. Brown and D. L1. Hammick 163 obtained a compound,m. p. 266-267", which was identical with the product obtained fromquinoline-2-aldehyde and potassium cyanide with subsequent oxidation(cf. benzoin --+ benzil), and for which they advanced a structure of meso-ionic 35 type.C. A. Buehler and J. 0. Harris,164 however, regard the com-pound as the true quinaldil and the crystal structure 165 seems to favourthis view. The nature of a second compound, m. p. 175", also formulatedas quinaldil is ,still unknown. The potent trypanocidal drug, " An-trycide " 167 (XLII), is a substituted 4 : 6-diamino-l : 2-dimethylquinoliniumsalt.(XLII) (XLIII)isoQuinoZines. 1 -isoQuinolones have been obtained by the cyclisation ofsubstituted o-carbamoyl-w-chlorostyrenes 168 (e.g., XLIII). The preparationof 3 : 4-dihydroisoquinolines by the Bischler-Napieralski reaction and oftetrahydroisoquinolines by the Pictet-Spengler method have been re-viewed. 69Further contributions have been made to the elucidationof the precise structures of the tautomeric 2- and/or 4(6)-hydroxy-, -amino-,and -memapto-pyrimidines.Infia-red spectral data have been provided 170and the ultra-violet spectra have also been studied.171 J. R. Marshall andJ. Walker used monosubstituted pyrimidines at controlled pH's as isclearly desirable and conclude from the ultra-violet absorption spectra andPyrimidines.161 N. J. Leonard and G. W. Luebner, J . Amer. Chem. SOC., 1949, 71, 3405.162 N. J. Leonard, H. A. de Walt, and G. W. Luebner, ibid., 1951, 73, 3325.163 J . , 1950, 628.165 D. R. Davies and H. M. Powell, Nature, 1951,168, 386.166 F. Linsker and R. L. Evans, J . Amer. Chem. SOC., 1946,68, 947.167 F. H. S. Curd and D. G. Davey, Brit. J .Pharm. Pharmacol., 1950,5, 25.168 G. Berti, Gaxxetta, 1951, 81, 868.160 W. M. Whaley and T. R. Govindachari, Org. Reactions, 1951, 6, 74, 151.170 I. R. Brownlie, J., 1950, 3062; E. R. Blout and M. Fields, J . Amer. Clzem. Xoc.,1950,72,479.1 7 1 L. F. Cavalieri, A. Bendich, et al., ibid., 1948, 70, 3875; 1950, 72, 2587; A.Maggiolo and P. B. Russell, J., 1951, 3297; see also J. M. Hearn, R. A. Morton, andJ. C . E. Simpson, ibid., pp. 3318, 3329, for similar studies in the quinoline, quinazoline,and chnoline series.164 J . Amer. Chem. SOC., 1950, 72, 5015.172 Ibid., p. 1004JOHNSON : HETEROUYCLIC COMPOUNDS. 225other physical properties that the keto-form is favoured in the hydroxy-and mercapto-pyrimidines but the situation with the aminopyrimidines isless clear.Recent preparative work in the field of the monosubstitutedpyrimidines has filled in many and includes an improvedmethod for pyrimidine itself. 175 Many of these preparations involvecatalytic dehalogenation during the hydrogenation, and magnesium oxide isthe preferred base for this purpose 174,175 although D. Shapiro 176 recom-mends zinc and ammonium chloride in the presence of Raney nickel, as thereducing agent. Aryl-lithium compounds may be used for the directphenylation of ~yrimidines,l~~ which can also be effected by the Gombergreaction ; 175 phenyl-lithium is similarly effective with other heterocyclicsy~tems,l7~ including pyrazine. 179qHO NH,J.0(XLVI)An important series of antimalarials based on substituted 2 : 4-diamino-5-arylpyrimidines has been developed 180 and the most promising compoundso far described is 2 : 4-diamino-5-p-chlorophenyl-6-ethylpyrimidine (XLIV).The antimalarial research which led to the development of (( Paludrine ”and related compounds has been reviewed by F.L. Rose in a Tilden lecture.l*lThe demonstration that (‘ Paludrine ” is transformed in the animal bodyinto another more active compound lS2 has been followed by its isolationand establishment of its structure as the dihydrotriazine (XLV),18a whichbears an obvious close relation to the 2 : 4-diamino-5-arylpyrimidines.Pyraxines and quinoxulines. The formation of 3 : 5-disubstituted2-aminopyrazine 1 -oxide by the condensation of a-amino-nitriles with1 7 3 M. P. V. Boarland and J.F. W. McOmie, J. 1961, 1218; D. J. Brown, Nature,1950,165, 1010; J. SOC. Chem. Ind., 1950, 69, 353; A. Maggiolo and P. B. Russell, J.,1951,3297.174 N. Whittaker, ibid., p. 1565. 176 B. Lythgoe and L. S. Rayner, ibid., p. 2323.1713 J . Amer. Chem. SOC., 1951, ‘73, 3526.1 7 7 T. D. Heyes and J. C. Roberts, J., 1951,328; W. K. Detweiler and E. D. Amstutz,170 B. Klein and P. E. Spoerri, J. Amer. Chem. SOC., 1951, 73, 2949.180 I. M. Rollo, Nature, 1951, 168, 332 ; G. H. Hitchings et aE., Brit. J. Pharm.,1951,6, 185; J. Amer. Chem. SOC., 1951,73,3753,3758,3763; B. H. Chase, J. P. Thurs-ton, and J. Walker, J., 1951, 3439.188 F. Hawkinget al., Natwe, 1947,159,409; Brit. J. Pharm. Pha~macol., 1948,3, 320.183 H. C. Carrington, A. F. Crowther, D.G. Davey, A. A. Levi, and F. L. Rose,J. Amer. Chem. SOC., 1951, 73,5451. R. Gaertner, Chem. Reviews, 1949, 45, 495.181 Ibid., p. 2770.Nature, 1951, 168, 1080.REP.-VOL. XLVIII. 226 ORGANIC CHEMISTRY.oximinomethyl ketones 184 has been developed into a total synthesis of rac.-deoxyaspergillic acid (XLVI) from DL-leucine nitrile and P-methyl-a-o~imino-n-valeraldehyde.~~~ This synthesis thus establishes the structureof aspergillic acid as the 1-oxide of (XLVI). A somewhat related synthesishas been used for 2-aminoquinoxaline, namely, cyclisation of N-cyano-methyl-o-phenylenediamine, itself obtained by the action of hydrogencyanide and formaldehyde on o-phenylenediamine.186Pterins 187 and jlavins. As with the pyrimidines, a number of simplemonosubstituted pteridines have been prepared and their physical properties,including spectra, recorded.188 The method of synthesis of dihydropter-idines 187, lS9 depending on the condensation of 4-chloro-5-nitropyrimidinesand a-amino-esters or -ketones with subsequent cyclisation has been studiedindependently by W.R. Boon and W. G. M. Jones l90 and has been extendedto a further xanthopterin synthesis.191 Preliminary studies on the synthesisof pteridine 8-glycosides have been reported.lg2Among the naturally occurring pterin colouring matters, chrysopterinand mesopterin lg3 are probably identical with 9-methylxanthopterin andisoxanthopterin lg4 respectively, and ichthyopterin lg5 is probably 2-amino-6 : 9-dihydroxy-8-pteridinylacetic acid.lg6 R.Tschesche and F. Korti lg7have also synthesised erythropterin lg8 (XLVII) from 7-acetonyl-4 : 6-diacetoxy-2-aminopteridine by a series of operations involving only theacetonyl group. In another preparation 2 : 5 : 6-triamino-4-hydroxyyrim-Bra ; -CH,*CO*CH, godc/ -CH( OAc)*CO*CH,OHNP\/]2 /\ II ,'C\(UH);C(OH)*CHH N ' N N/(XLVII)idine was condensed with the ethoxalyl derivative of diacetoxyacetone,EtO,C*CO-CH( OAc)*CO*CH,*OAc. Variations on the pterorhodin (XLVIII)synthesis,lgg Le., the oxidative coupling of xanthopterin and 7-methyl-lS4 W. Sharp and F. S. Spring, J., 1951, 932.lS5 G. T. Newbold, W. Sharp, and F. S. Spring, ibid., p. 2679.lS6 K. Phter, A. P. Sullivan, J. Weijland, and M. Tishler, J. Amer. Chem. SOC.,lB8 A. Albert et al., Chena.and I n d . , 1951, 187; J., 1951, 494.lBo J., 1951, 96, 591.lQ2 H. S. Forrest, R. Hull, H. J. Rodda, and A. R. Todd, ibid., p. 1.lS3 C. Schijpf and E. Becker, Annalen, 1933,507, 266 ; 1936,524,49.lS4 R. Tschesche and F. Korte, Ber., 1951, 84, 641.lB5 R. Hiittel and G. Sprengling, Annalen, 1943, 554, 69.lS6 R. Tschesche and F. Korte, Ber., 1951, 84, 801.lB7 Ibid., p. 77. lSB R. Purrmann and F. Eulitz, Annulen, 1948,559, 169.lSB P. B. Russell, R. Purrmann, W. Schmitt, and G. H. Hitchings, J . Amer. Chem.1951, 73, 4955. 18' Ann. Reports, 1950, 47, 241-245.M. Polonovski, M. Pesson, and A. Puister, Compt. rend., 1950, 230, 2205.lB1 W. R. Boon and T. Leigh, ibid., p. 1497.Soc., 1949, 71, 3412SOHNSON : HETEROCYCLIC COMPOUNDS.227xanthopterin, have led to the preparation of a number of the so-calledpteridine reds.200The folic acid group has been reviewed by G. Emerson and K. Folkers 201and there have been a number of new contributions to the chemistry offolinic acid which is one of a group of factors with greater ability to preventthe toxicity of inhibitory folic acid analogues than folic acid itself. Thepreparation of a synthetic compound, folinic acid SF or leucovorin, withthese properties has been achieved 202 by the reduction of formylfolic acidwith subsequent autoclaving or alkali-treatment , or alternatively byreduction of folic acid in the presence of compounds which can yield onecarbon atom. Degradative and synthetic studies on folinic acid SF(leucovorin) 203 have led to its formulation 204, 205 as (XLIX), Fi-formyl-5 : 6 : 7 : 8-tetrahydropteroylglutamic acid.There is some evidence that10-formyl-5 : 6 : 7 : 8-tetrahydropteroylglutamic acid (tetrahydrorhizopteroyl-glutamic acid) may rearrange t o (XLIX) with the intermediate form-ation of a di- or tetra-hydroglyoxaline ring, as occurs on the action ofacids on l e ~ c o v o r i n . ~ ~ ~ Leucovorin has " citrovorum factor " activity 206but is not identical with the " citrovorum factor " 207 which has been isolatedfrom liver as the crystalline barium salt.208OH OHNew syntheses of lyxoflavin 209 depend on the intermediate formation ofN-lyxityl-4 : Ei-dimethylaniline and thenceforwacrd follow the normal flavinsyntheses as elaborated for riboflavin.Lyxoflavin has been shown 210to have growth-promoting properties and is stated to occur naturally.2111951, 34, 1029, 2155.73, 1979; cf. ref. 187.and W. Shive, ibid., p. 3067.200 P. Karrer et al., Helv. Chim. Acta, 1949, 32, 423, 1689; 1950, 33, 39, 557, 1233;202 E. H. Flynn, T. J. Bond, T. J. Bardos and W. Shive, J . Amer. Chem. SOL, 1951,203 M. May, T. J. Bardos, F. L. Barger, M. Lansford, J. M. Ravel, G. L. Sutherland,204 A. Pohland, E. H. Flynn, R. G. Jones, and W. Shive, ibid., p. 3247.205 D. B. Cosulich, B. Roth, J. M. Smith, M. E. Hultquist, and R P. Parker, ibid.,206 H. P. Broquist, M. J. Fahrenbach, J. A. Brockman, E. L. R. Stokstad, and T. H.20* Idem, ibid., p. 5510.2oD D. Heyl, E. C. Chase, F. Koniuszy, and K. Folkers, ibid., p.3826; T. S. Gardner,210 G. A. Emerson and K. Folkers, J . Amer. Chem. Soc., 1951, 73, 2398, 5383.211 E. S. Pallares and H. M. Garza, Arch. Biochem., 1949,22, 63.201 A m . Rev. Biochem., 1951, 20, 574.p. 5006.Jukes, ibid., p. 3535. 207 M. Silverman and J. C. Keresztesy, ibid., p. 1897.E. Wenis, and J. Lee, Arch. Biochem., 1951, 34, 98228 ORUANIC OHEMISTRY.Triaxines. An extensive series of papers 212 describes a variety of sub-stitution reactions of cyanuric chloride. K. Schogl and G. Korger 213 haveprepared some 1 : 2 : 4-triazines.Alkaloids.-The first of a series of five volumes on " The Alkaloids " waspublished in 1950214 as well as a " Fortschritte der Alkaloidchemie ".215An extensive survey of the infra-red spectra of many of the common alkaloidshas also been published.216The mild reduction of amides to aldehydes with lithiumaluminium hydride has been used in another hygrine (L) synthesis,217 byreduction of l-methyl-2-pyrrolidone followed by condensation of the productwith acetone dicarboxylic acid.Cuscohygrine was also isolated from theproduct, and analogous reactions starting with l-methyl-2-piperidone gavemethylisopelletierine, and with octahydro-3-ketopyrrocoline (LI) gave(probably) a polymer of p-2-piperidylpropaldehyde (LII),218 the structureadvanced for pelletierine.Simple bases.Lupin group. This group has been reviewed219 and the absolute con-figurations of a number of the C,, lupin alkaloids have been determined.220isoQuinoZine group. Recent synthetic approaches to morphine have beendiscussed by E.S. Stern.221 The unknown A7-deoxycodeine (LIII) has beenprepared from toluene-p-sulphonylcodeine by reduction with lithiumaluminium hydride,222 and converted into A'-deoxymorphine by demethyl-ation with pyridine hydrochl~ride.~~~ A8-Deoxycodeine was obtainedsimilarly from toluene-p-sulphonylneopine.In the benzylisoquinoline series improved routes to papaverine and itscongeners have been reported 224 and three independent syntheses of (&)-a n J. T. Thurston, J. R. Dudley, F. C. Schasfer, et al., J. Amer. Chem. SO~., 1951,73,2981,2984,2986,2990,2992,2996,2999,3004,3007 ; M. A. Spielman, W. J. Close, andI. J. Wilk, ibid., p. 1775.214 Ed. : R. H. F. Manske and H. L. Holmes, Academic Press, New York, 1950.alS A.-G.Boit, Berlin, 1950.216 L. Marion, D. A. Ramsey, and R. N. Jones, J. Amer. Chem. SOC., 1951,73,305.217 F. Galinovsky, A. Wagner, and R. Weiser, Monatsh., 1951, 82, 551.218 F. Galinovsky and R. Weiser, Experkntia, 1950, 6, 377; J. A. King, J . Org.219 F. Galinovsky, " Fortschritte der Chemie Organischer Naturstoffen," 1951,8,245.220 L. Marion and N. J . Leonard, Canad. J . Chem., 1951,29, 355; Bee also L. Mariona22 H. Rapoport and R. M. Bonner, J . Amer. Chem. SOC., 1951, 73, 2872; P. Karrer223 H. Rapoport and R. M. Bonner, J. Amer. Chm. SOC., 2951,73,5486.213 Monatsh., 1951, 82, 799.Chem., 1951,16, 1100.et al., ibid., pp. 13,22,297.and G. Widmark, Helv. Chim. Acta, 1951,34,34.221 Quart. Reviews, 1961, 5,405.H. Galat, ibid., p.3664; H. Wahl, Bull. SOC. chim., 1950, 17, 680; 1951, 18, ~ 1 JOHNSON : HETEROCYCLIC COMPOUNDS. 229coclaurine (LIV) have been announced 225 using benzyl or O-carbethoxy-groups to protect the free hydroxyl groups. The ability of sodium inliquid ammonia to split aromatic ethers has been applied with signal successby the Japanese school to the degradation of the bisbenzylisoquinolineswhich are converted into two monobenzylisoquinoline fragments. Therotation of the fission products enables the configuration of the two asym-metric centres of the original alkaloid to be determined and this has beenapplied to both isotetrandrine 226 (LV) and tetrandrine 227 ofthe oxyacanthinetype and to cycleanine 228 of the bebeerine or tubocurarine type of bisbenzyl-Csoquinolines .R.H. F. Manske has continued his structural studies in the isoquinolineand related alkaloid groups and has confirmed the structures of coreximine(LVI) (a member of the protoberberine class) by the synthesis229 of itsdiethyl ether, and of glaucentrine (LVII) by the synthesis of its ethyl ether.230Cularine 231 (LVIII), and its N-demethyl derivative cularimine, are benzyl-isoquinolines containing ether bridges.325 J. Finkelstein, J . Amer. Chem. SOC., 1951, 73, 550; K. Kratzl and G. Billek,Monatsh., 1951,82,568 ; M. Tomita, K. Nakaguchi, and S. Takagi, J. Pharm. SOC. Japan,1951,71, 1046. 226 M. Tomita, E. Fujita, and F. Murai,ibid., pp. 226, 1035.229 J. Amer. Chem. SOC., 1950, 7'2,4796; 1951,79, 5144.231 R. F.H. Manske, ibid., 1950, 72, 55.227 E. Fujita and F. Murai, ibid., p. 1039.230 Ibid., p. 3751.Idem,ibid.,p. 1043230 ORGANIC CHEMISTRY.Erythrina group. The a- and p-erythroidines differ from the other closelyrelated members of this group, and the structural features are not quite sowell established. p-Erythroidine is a tertiary base containing one 0-methyl group (no C-methyl or N-methyl) and a lactone group. Oxidativedegradation has yielded derivatives of hemipinic acid and 3-methoxy-phthalic acid. Considerations of the various reactions of the alkaloid haveled F. Koniuszy and K. Folkers 232 to propose (LIX) containing a dihydro-benzenoid ring, as the structure. The action of sulphuric acid caused lossof methanol with the aromatisation of ring A in demethoxyerythroidine.More vigorous acid treatment 233 of p-erythroidine forms apo- p-erythroidinecontaining an exocyclic methylene group and formulated by the Americanauthors as (LX).Other workers 234 feel that these structures may requiremodification and C. Lapihe and Sir R. Robinson235 prefer to representp-erythroidine as (LXI), on the grounds that the formation of a basefrom the Hofmann degrad-/\A\/‘p=2containing the partial structure I ]Iation of dihydro- p-erythroidine 234 indicates the presence of the group-O*CO*CH,*bH*N< in the alkaloid. The rearrangement to apo- (3-erythro-idine on this basis was discussed.R = R’ = H = ErysopineR or R’ = H ErysovineM~OI,)~:A-CH, A / 1 V C 3 H 2 R’OI Bo//\/j A II R’ or R = Me 1 Erysodine\/’\/N\qoMeI c i l ~-\,/ RR’ = CH, = ErythralineThe remaining alkaloids of the Erythrina group contain a commonnucleus and differ only in the nature of the substituents: erysopine(C1,Hl,03N ; 20H, lOMe), the isomeric erysovine and erysodine (C,BH,103N ;10H, ZOMe), all of which give “ erysotrine ” on methylation (ClgH23O3N;30Me).236 Also in this class is erythraline (Cl8HI9O3N; CH,O,, 1OMe)I IO g 3 2 (LXII)(LXI)232 F.Koniuszy and K. Folkers, J . Amer. Chem. XOG., 1950, 72, 5579.233 Idem, ibid., 1951,73, 333; G. L. Sauvage and V. Boekelheide, ibid., 1950,72,2062.234 V. Boekelheide and E. Agnello, ibid., 1951, 73, 2286.235 Chem. and Ind., 1951, 650.236 F. Koniuszy, P. F. Wiley, and K. Folkers, J . Amer. Chem. SOC., 1949, 71, 875;R.A. Labriola, V. Deulofeu, and B. Berinzaghi, J . Org. Chem., 1951,16, 90JOHNSON : HETEROCYCLIC COMPOUNDS. 231which gives a dihydro-derivative, er~thramine.~~' Largely on the basis ofthe permanganate oxidation of these alkaloids to derivatives of 4 : 5-di-hydroxyphthalimide, and the formation of indole on fusion with potassiumhydroxide, the Merck group put forward the structures (LXII), again contain-ing dihydrobenzenoid rings. Treatment of erythraline, erysopine, or eryso-vine with hydrogen bromide gave upoerysopine 238 (CI,H,50,N ; 20H)which was stated to be formed by loss of methanol and aromatisation ofring D. A synthetic compound containing this ring system and corre-sponding to a hexahydroapoerysotrine (ring D saturated) has been de-scribed.239 An extensive reinvestigation of these compounds 240 has led to acomplete revision of their structures.upoErysodine and upoerythraline,which were also obtained by the action of hydrogen halides on the parentalkaloids, were fairly strong bases and contained three conjugated doublebonds, i.e., the two conjugated double bonds (which spectral data indicatedwere in different rings) of the original molecule and a third formed by theloss of methanol. On the other hand, apoerysopine had only the basicityof an aromatic amine and its ultra-violet absorption spectrum indicated theformation of a new benzenoid ring. Other objections were also raised to thestructures (LXII) : (1) the product from a double Hofmann degradation ofupoerysopine, and subsequent hydrogenation was formulated 238 as 2'-dimethylamino-2-ethyl-4 : 5-dimethoxydibenzyl but it contained two C-methyl groups ; (2) the high specific rotation of the upo-alkaloids would notbe expected from molecules such as (LXII; with ring D aromatic) whichshould be flat ; (3) dehydrogenation of (LXII) should readily produce com-pounds of the dehydrolaudanosoline type but this has not been observed.Accordingly the alkaloids have been reformulated as (LXIII).The acidrearrangement to the upo-compounds takes place in two stages, first tocompounds of the type (LXIV), e.g., upoerysodine and upoerythraline, andthen to upoerysopine (LXV) which by Hofmann degradation and hydro-genation gives (LXVI ; 2C-Me). The Hofmann degradations of tetra-hydroerysotrine and fetrahydroerythraline have also been interpreted on thisbasis .241Indole group.Quinamine. The structure (LXVII) for quinaminepreviously advanced by V. Prelog and his co-workers 242 on the basis of itsreduction to cinchonamine with lithium aluminium hydride has been modifiedto (LXVIII) by B. Witkop 243 because of the reconversion of cinchonamineinto quinamine (full experimental details not yet available) with diluteperacetic acid and the established course of oxidations in the indole series.244Corynalztheim. Schemes for the biogenesis of the yohimbine and237 K. Folkers and F. Koniuszy, J . Amer. Chem. SOC., 1940, 62, 1673; V. Prelog,K. Wiesner, H G. Khorana, and G. W. Kenner, Helv. Chim. Acta, 1949,32,453.238 K. Folkers, F.Koniuszy, and J. Shavel, J. Amer. Chem. SOC., 1951, 73, 589.239 K. Wiesner et al., Canad. J . Res., 1950, 28, B, 234, 745.240 M. Karmack, B. C. McKusick, and V. Prelog, Helv. Chim. Acta, 1951, 34, 1601.241 G. W. Kenner, H. G. Khorana, and V. Prelog, ibid., p. 1969.242 Ibid., 1950,33, 150; Ann. Reports, 1949,46, 203.243 B. Witkop, J . Amer. Chern. SOC., 1950, 72, 2311. 244 Idem, ibid., p. 1428232 ORGANIC CHEMISTRY.Strychrtos alkaloids245 have been extended to the Cinchona group and arestrengthened by the elucidation of the structure of corynantheine (LXIX)which is a biogenetic " missing link " between cinchonamine and yohimbine.CH2 CH2CH CH (LXIV)Hofmann ;H,(LXIII ; R and R' as in LXII)(LXVII) 'C'H,These biogenetic relations have proved of considerable value in the elucid-ation of structures of new alkaloids. Corynantheine is quite closely related totwo other alkaloids, serpentine and alstonine (see below), and all three yield thesame product, ~orynanthryine,2*~ alstyrine,2*' or coryline,248 formulated 249CH,as (LXXI ; R = Et). On this and other degradative evidence and the claimthat corynantheine contains one C-methyl group, Karrer 250 has postulatedthat the alkaloid is pentacyclic and although the exact nature of the ring Ewas not clarified; it was stated to be a cyclopentene ring containing onemethoxy-, one C-methyl, and one carbomethoxy-substituent .Theseconclusiqns have not been accepted by V. Prelog, M.-M. Janot, and R.245 Ann. Reports, 1950, 47, 197.248 M.-M.Janot and R. Goutarel, Ann. Pharm. franc., 1949, 7 , 648 ; P. Karrer and247 T. M. Sharp, J., 1938, 1353.248 M.-M. Janot and R. Goutarel, Compt. rend., 1947,225, 1371 ; 1949,229, 360.249 P. Karrer and P. Enslin, Helv. Chim. Acta, 1950,33, 100.a50 P. Karrer et al., ibid., p. 802; 1951, 34, 993.P. Enslin, Helv. Chim. Acta, 1949, 32, 1390JOHNSON HETEROCYCLIC COMT’OUNDS. 233Goutarel 251 who formulate corynantheine as a tetracyclic compound notcontaining a C-methyl The fact that neither corynantheine norcorynantheal (LXX; R = CHO) contains a C-methyl group althoughcorynanthean (LXX; R = Me), obtained from (LXX; R = CHO) byWolff-Kishner reduction, contains one C-methyl is evidence for the presenceof the aldehyde group in corynantheal. Moreover, as corynantheal isreadily obtained from corynantheine with loss of carbon dioxide by theaction of dilute acids, the presence of an enol ether of a p-keto-acid derivative,RO,C*d:b*OR’, is indicated in corynantheine and this is supported by theultra-violet absorption spectrum.Corynanthean (LXX; R = Me), but notits dihydro-derivative, gives formaldehyde on ozonolysis and this supportsthe presence of the C-methylene group, which gives rise to one of the threeethyl groups of corynanthyrine. This ethyl group cannot be the p-indolesubstituent because the ultra-violet absorption spectrum of corynantheineis not consistent with the presence of a 3-vinylindole grouping. Hencethe vinyl group must be a substituent of ring D and corynantheine must betetra- and not penta-cyclic. The position of the substituents in ring D wasdetermined from the structure of de-ethylcorynanthyrine (LXX; R = H)which accompanies corynanthryine in the products of selenium dehydrogen-ation.As the oxygenated side-chain of corynantheine would be lost pre-ferentially, the vinyl group is probably p to the nitrogen atom in coryn-antheine (LXIX) which thus bears a striking resemblance to cinchonamineas well as to yohimbine.ICHICH\ / \CHMe\, / \MeO,C*v 1 CH E CH2MeO,C*?H 7H2(LXXIII) CH2-0 CH,---O (LXXIV)Serpentine and ahtonine. These alkaloids have much in common withcorynantheine, although they are coloured, and are quaternary P-carbolinesof the same anhydronium base type as sempervirine253 and tetradehydro-y ~ h i m b i n e . ~ ~ ~ From the general properties of these compounds they areformulated as (LXXII), ring E being (LXXIII) in serpentine255 and(LXXIV) in alstonine 256 which contains an aP-unsaturated ester grouping.261 Compi?.r e d . , 1950,231, 152; 1951,232, 1305.252 Helv. Chim. Acta, 1951, 34, 1207; Bull. SOC. chim., 1951, 18, 588.263 Ann. Reports, 1949, 46, 205.2 5 5 E. Schlittler and H. Schwarz, Helv. Chim. Acta, 1950, 33, 1463.256 R. C. Elderfield and A. P. Gray, J . Org. Chem., 1951,16,506.254 H. Schwarz, Experienfia, 1950, 6, 330234 ORGANIC CHEMISTRY.H. Schwarz and E. Schlittler 257 have studied the physical and chemical (e.g.,hydrogenation) behaviour of a number of synthetic quaternary p-carbolinesand have discussed the structural changes in solutions of varying pH's.This compound isolated from Cryptolepis triangularis isthe first violet-coloured alkaloid to be described and is also an anhydroniumbase. It has been shown 258 to be a quaternary 8-carboline and the yellowhydriodide proved to be identical with the methiodide of quindoline (LXXV)and the base itself to be identical with the methylquindolanol of I?.Fichterand R. B ~ e h r i n g e r . ~ ~ ~ The present formulation (LXXVI) is preferred to the$-base structure of the earlier workers. Crytpolepine was converted intoquindoline by the action of selenium at 300".Cryptokpine.Me ,Me(LXXV) (LXXVI)Gekemine. Earlier work on this alkaloid, C,,H,,O,N,, has been sum-marised by V. Prelog and his co-workers 260 who have provided furtherdegradative evidence and have been able to advance a plausible structure.Distillation with zinc or dehydrogenation had yielded indole derivatives,but a study of the spectra of gelsemine and its lithium aluminium hydridereduction product led M.Kates and L. Marion261 to postulate a pp-disub-stituted oxindole structure for the alkaloid. Of the remainder of themolecule, the second nitrogen atom carried a methyl group, and the secondoxygen atom was inert, probably as an ether. Gelsemine itself, containing noC-methyl group but one double bond, gave a dihydro-derivative which con-tained one C-methyl group ; hence the presence of a C-methylene group andtherefore four more rings in the gelsemine molecule was inferred.On thisand other evidence M. S. Gibson and Sir R. Robinson262 advanced thestructure (LXXVII) for the alkaloid :CH,-CH/ i\ CH,--CH-CH 0 CH,/ \ / / 1 MeN C--cx7X = C, N, or 0.n = 0, 1, or 2.(LXXVIII)257 Helv. Chim. Acta, 1951, 34, 629.258 E. Gellkrt, Raymond-Hamet, and E. Schlittler, ibid., p. 642.259 Ber., 1906, 39, 3932 ; 1907, 40, 3478 ; 1910, 43, 3489.260 R. Goutarel, M.-M. Jsnot, V. Prelog, R. P. A. Sneedon, and W. I. Taylor, Helv.Chim. Acta, 1951, 34, 1139.261 J . Amer. Chem. SOC., 1950,72, 2308; Canad. J . Chern., 1951,29,37.26a Chem. and Ind., 1951, 93RYDON : MACROMOLECULES. 235This formula has been modified by the Paris-Zurich school 260 who confirmedthe presence of the oxindole nucleus and the C-methylene grouping but also,from a study of the action of bromine on gelsemine, established that therelative position of these two features of the molecule was as represented in(LXXVIII).Largely on biogenetic grounds cf- 262 the partial formula wasdeveloped to (LXXIX) ; and in a later paper 263 the results of the Hofmann0------h-- 7 CH ,--CH/H2-CH-CH/ \\ /CH-A CH--CI 1r-V- \\\/\ NH Po CHZ(LXXIX)H(LXXXI)\. H CH2-CH2/ C-C-CH 1 MeN\ ;C----CH,\CHZI /v - 0 \ /CH, H-CH,I I 1 \\\/\ NH CHZCH, H I / \/I \ / /\ 7-CH-Cdegradations of the methiodides of gelsemine and its di- and octa-hydro-derivatives, which gave the de-N-methyl bases, e.g., (LXXXII), each con-taining an extra but inert double bond, were used to afford a completestructure for gelsemine (LXXX) or (LXXXI) as viewed in perspective.A. W.J.9. MACROMOLECULES.Polysacchaxides.A valuable method of estimating reducing end-groups of polysaccharides,using the radioactive indicator 14C, has been developed by Isbell ; 1 treatmentwith Na14CN yields the cyanohydrin which is hydrolysed to the hydroxy-acid; this is isolated by means of an ion-exchange resin and estimated bymeans of its radioactivity. The use of sodium and liquid ammonia for the263 R. Goutarel, M.-M. Janot, V. Prelog, and R. P. A. Sneedon, HeZv. Chim. Ada,1951, 34, 1962, H. S . Isbell, Xcience, 1951, 113, 532236 ORUANIO OHEMISTBY./h \ I\"" I/ HO I H OHrHO* H, 0explanation in the sugar case; clearly great careis necessary to avoid errors from this cause.Non-nitrogenous Polysacchazides.-Work con -tinues on the fine structure of starch; 7 thepresenceof the 6-a-branching point in amylopectinhas been put on a firmer basis by the isolationof crystalline p-isomaltose octa-acetate from theacetolysis products.8 A careful study of the0HO* H, 0/ \ eighteen-glucose glycogen reported by earlierworkers lo was not encountered.The infra-reRYDON : MACROMOLECULES. 237grass rhizomes (Triticum repens L.) is more complicated and has a highly-branched structure made up of D-fmctofuranose residues, about half thelinkages being 2 : 1 and the remainder 2 : 6 ; the whole system is terminatedby a sucrose residue.13 The Jerusalem artichoke (HeEianthw twheroms L.)and other composites contain a whole series of glucose-terminated fructo-sans (I), ranging in complexity from sucrose to inulin.14The soluble laminarin of Laminaria digituta resembles the insoluble incontaining 20 D-glUCOpyl3nOSe units linked 8-1 : 3 ; the difference between thetwo polysaccharides is at present unexplained.l5 Other polysaccharideswhich have, been investigated include slippery-elm mucilage,ls black-wattlegum,17 pear cell-wall xylany18 mesquite gum,lg and three polysaccharides ofbacterial origin.2*Nitrogenous Polysaccharides.-Details have now been published 22 of thework leading to the hyaluronic acid structure given in the last Report;Z2this structure has been confirmed by the isolation of a crystalline hyalo-biuronic acid, made up of py-ranose D-glucuronic acid and D-glucosamine,by enzymic and mild alkaline hydr~lysis.~~The following structure has been proposed for heparin on the basis ofperiodate oxidation experiments : 24r HO*$!H,A second anticoagulant @-heparin, in which galactosamine replaces glucos-amine, has been found to accompany normal heparin.25Aminoff and Morgan 26 have carried out a most painstaking investigationof the periodate oxidation of the human blood-group A substance; theirresults indicate three different modes of linkage of the fucose residues andcall for a minimum '' average " building unit of four galactose, four fucose,l3 P.C. Arni and E. G. V. Percival, J., 1951, 1822.14 J. S. D. Bacon and J. Edelman, Biochem. J . , 1951,48, 114.l5 E. G. V. Percival and A. G.Ross, J., 1951, 720.l6 E. L. Hirst, L. Hough, and J. K. N. Jones, J., 1951,323.l7 A. M. Stephen, J., 1951,646.19 F. Smith, J., 1951, 2646.2O P. W. Kent, J., 1951,364; P. N. HobsonandH. Nasr, J., 1951,1855; E. E. Evans11 K. H. Meyer, J. Fellig, and E. H. Fischer, Helu. Chim. Acta, 1951,34, 939; R. W.83 Ann. Repwte, 1950, 47, 248.2s M. M. Rapport, B. Weissmann, A. Linker, and K. Meyer, Nature, 1951, 168, 996.24 M. L. Wolfrom, R.. Montgomery, J. V. Karabinos, and P. Rathgeb, J . Amer. Chem.a s R. Marbet and A. Winterstein, Helv. Chim. Acta, 1951,34, 2311.as D. Aminoff and W. T. J. Morgan, Biochem. J., 1951,48, 74.S. K. Chanda, E. L. Hirst, and E. G. V. Percival, J . , 1951, 1240.and J. W. Mehl, Science, 1951,114, 10.Jeanloz and E. Forchielli, J.Bid. Chem., 1951, 190, 537.Soc., 1950, 72, 6796238 ORGANIC CHEMISTRY.four N-acetylglucosamine and four N-acetylgalactosamine residues ; serineand threonine do not occupy terminal positions in the molecule. Mild acidhydrolysis of hog blood-group A and 0 substances liberates aspartic acid,glutamic acid, lysine, serine, threonine, and glycine ; on a molar basis asparticacid accounts for hdf of the liberated amino-acids and it is suggested that thesubstances contain peptide chains with alternate aspartic acid residue^.^'Some interesting work on yeast invertase by E. H. Fischer and his col-leagues 28 forms a suggestive bridge between the polysaccharides and theproteins. The highly purified enzyme contains 70% of polysaccharide butis electrophoretically homogeneous at pH above 4, splitting into an inactivepolysaccharide and an active protein-polysaccharide complex at lower pH.The whole of the polysaccharide can be removed by adsorption on bentoniteat pH 2.9 but the enzyme activity is then lost. The polysaccharide is madeup of about 48 mannose residues linked a-1 : 3 and it is concluded that theenzyme is a labile protein stabilised by this mannan.Proteins and Polypeptides.Proteins.-Electron-microscopy continues to yield information on the sizeand shape of large protein molecules; thus, it has been concluded from astudy29 of dried droplet sprays that the particles of tobacco-mosaic virusare rod-like end-to-end aggregates of unit particles 298 mp in length with amolecular weight of 49 x lo6.Studies of viscosity and osmotic pressure 30lead to the conclusion that the cyclopeptide chain 31 of tropomyosin is heldby intra-molecular cross-linkages to give a monomeric particle 385 long and14.5 A wide ; the monomer polymerises in aqueous solution and exists in theunpolymerised form only in the presence of urea or of salts in high con-centration.Amino-end-group determination, with the aid of fluorodinitrobenzene,32has been applied to many proteins. In two instances no end-group wasfound and it seems likely that the proteins concerned, vix., tropomyosin andmyosin 31 and c0llagen,3~ have cyclopeptide structures ; as Bailey 31 pointsout, this type of structure has not previously been established with certainty,the case of ovalbumin being complicated by the presence of carbohydrate.In more normal cases, three histidine amino-end-groups have been found ingliadinF4 one lysine in l y ~ o z y m e , ~ ~ and tyrosine and cystine in oxytocin; 3627 H.van Vunakis and E. A. Kabat, J . Amer. Chem. SOC., 1951,73, 2977.2 8 E. H. Fischer and L. Kohtes, Helv. Chim. Acta, 1951, 34, 1123; E. H. Fischer,29 R. C. Williams and R. L. Steere, J . Amer. Chem. SOC., 1951, 73, 2057; R. C.30 T.-C. Tsao, K. Bailey, and G. S . Adair, Biochem. J., 1951, 49, 27.31 K. Bailey, ibid., p. 23.33 J. H. Bowes and J. A. Moss, Nature, 1951,168, 515.34 Z. Koroc, Magyar Kem. Folyoirat, 1950, 56, 131.36 F. C. Green and W. A. Schroeder, J . Amer. Chem. SOC., 1951, 73, 1385.36 H. Davoll, R. A. Turner, J.C. Pierce, and V. du Vigneaud, J . Biol. Chem., 1951,L. Kohtes, and J. Fellig, ibid., p. 1132.Williams, R. C. Backers, and R. L Steere, ibid., p . 2062.32 F. Sanger, ibid., 1945,39,507.193, 363RYDON : MACROMOLECULES. 239in the last case the conclusion was confirmed by Levy's method 37 and alsoby finding tyrosine and alanine as end-groups in the desulphurised protein.Two new methods for the determination of amino-end-groups havebeen devised. One 38 of these employs l3l1-labelled p-iodobenzenesul-phony1 chloride as the marking agent; hydrolysis of the marked proteingives a mixture of amino-acids with the marked sulphonyl derivative,1311*C,H,*S02-NH=CHR*C02H, of the amino-end-group, which can readilybe separated and estimated. By this method, insulin was found to containone glycine and one phenylalanine, horse haemoglobin two valine, andrabbit-muscle aldolase two proline residues as amino-end-groups ; the resultswith insulin and the haemoglobin are in qualitative agreement, but quantit-ative disagreement, with those of Sanger, who found two glycine and twophenylalanine end-groups in insulin 32 and six valine in horse h~moglobin,~~and it seems likely that the iodobenzenesulphonyl residues are not whollyretained under the conditions of hydrolysis. The other method 40 involvesmicrobiological estimation of all the amino-acids in hydrolysates of the pro-tein and of its phenylureido- or phenylthioureido-derivative, thus givingthe amino-end-group by difference ; the method has so far only been appliedto small peptides.A satisfactory method for the determination of carboxyl end-groups isbadly needed as a complement to the fluorodinitrobenzene method for deter-mining amino-end-groups ; two methods for this purpose have been described.The more promising 41p 42 involves reduction of the protein methyl ester withlithium borohydride in tetrahydrofuran 41 or of the protein itself with lithiumaluminium* hydride in 4-ethylmorph0line,4~ followed by hydrolysis ; thecarboxyl end-group appears as the corresponding amino-alcohol :.. . CO*NH*CHR*CO,H --+ . . . CO*NH*CHR*CH,*OH --+. . . C02H + H2N*CHR-CH2*OHThis can be estimated by periodate oxidation and identified by chromato-graphy. Applied to insulin, this procedure shows two alanine and twoglycine carboxyl end-groups.The other method 43 is a modification of theprocedure of Schlack and Kumpf; 44 when applied to insulin it revealedalanine as a carboxyl end-group but the yield was poor and the method clearlyrequires further work.The painstaking and brilliantly executed researches of Sanger on theconstitution of insulin 45 are rapidly approaching completion. In the year3 7 A. L. Levy, J., 1950, 404.38 S. Udenfriend and S. F. Velick, J. Biot. Chem., 1951, 190, 733.39 R. R. Porter and F. Sanger, Biochem. J., 1951, 42, 287.40 S. W. Fox, T. L. Hurst, and K. F. Itschner, J . Amer. Chem. SOC., 1951, 73, 3573.41 A. C. ChibnallandM. W. Rees, Biochem. J., 1951,48, xlvi.42 C. Fromageot, M. Jutisz, D. Meyer, and L. Penasse, Biochem. Biophys.Acta,44 I?. Schlack and W. Kumpf, 2. physiol. Chem., 1926,154, 125.4 5 Ann. Reports, 1948, 45, 283; 1950, 47, 250.46 F. Sanger and H. Tuppy, Biochem. J., 1951, 49, 463, 481.1950,6, 283. 43 S. G. Waley and J. Watson, J., 1951, 2394240 ORGANIC CHEMISTRY.under review the full structure of the two phenylalanine-terminated, or B,peptide chains has been established 46 as :H,N - phenylalanine - valine - asparagine - glutamine -histidine - leucine-cystine-glycine-serinehistidine-leucine-va~ne-glutamic acid-alanine-leucine-tyrosine-leucine-valine-cystine-glycine-glutamic acid-arginine-glycine-phenylalanine-phenylalanine- tyrosine - threonine -proline -lysine-alanine-CO,HThis is a most remarkable achievement and completion of the structure ofinsulin now requires only the determination of the arrangement of the twentyresidues in the glycine-terminated, or A, chains, in which the arrangement ofthe five residues at the amino-end is already known.As Sanger and Tuppy 46point out, " an examination of the structure . . . fails to reveal any simpleperiodic arrangement of the residues, nor is it possible to formulate anygeneral principles which might govern the order of amino-acids along theprotein chains " : the authors draw attention to the clustering of (relatively)non-polar residues in the sequence -phenylalanine-phenylalanine-tyrosine-and -1eucine-tyrosine-leucine-valine- and the two occurrences of the pairs-histidine-leucine-, -cysthe-glycine- and -1eucine-valine- as the sole (andvery slight) indications of chemical non-randomness in the structure.Itis clear that the idea of some sort of periodicity in the amino-acid constitutionof proteins, originated by Bergmann and Niemann?' has no foundationin fact and remains of interest only as an illustration of the human urgeto seek for order in Nature.It has long been abundantly clear that the properties of native proteinscannot be explained solely on the basis of their formulation as straightforwardpeptide chains joined by disulphide and other cross-linkages. Closely similarX-ray diffraction patterns, conforming to one or other of three characteristictypes (a, p, and collagen), are given.by proteins of very variable amino-acidcomposition and it is evident that there is some regularity of structurewhich is independent of the side-chains and must, therefore, arise fiom thecoiling or folding of the peptide backbones.The year under review has seenmajor developments in this field which are likely to lead to the abandonmentof the view hitherto accepted on this matter ; 48 although this new work isbeing fully treated in the section on Crystallography, it is so important that itseems proper to discuss it briefly here from the organic chemical viewpoint.The first proposal to abandon the Astbury-Bel148 structure for the a-proteins came from the Courtauld who adopted the structure (11),which had already been advanced in various guises by other^,^^^^^ to account4 7 M. Bergmann and C. Niemann, Science, 1937, 86, 187.48 W.T. Astbury and F. 0. Bell, Nature, 1940,145,421 ; 1941,147, 696.49 C. H. Bamford, W. E. Hanby, and F. Happey, Proc. Roy. Xoc., 1951, A , 205,30; E. J. Ambrose and A. Elliott, ibid., p. 47; idem, ibid., 206, 206; idem, ibid., 208,76; cf. idem, Nature, 1949-1950,163-166, passim.6O M. L. Huggins, Chem. Reviews, 1943,32, 195.61 H. Zahn, 2. Naturforsch., 1947, 2, b, 104; T. Simanouti and S. Mizushima,Bull. Chem. Soc., Japan, 1948, 21, 1 ; 5. Mizushima, T. Simanouti, M. Tsuboi, T. Sugita,and E. Kato, Nature, 1949,164,918RYDON : MACROMOLECULES. 241for their work on infka-red absorption and X-ray diffraction by polypeptidesand proteins. Although this ribbon-like structure has several advantages,notably the ease with which it undergoes secondary folding and with whichit may be stretched to the extended p-form without rotation of the side-(11)chains, it has been severely criticised, especially by Pauling and C ~ r e y , ~ ~who point out that it involves too much distortion of the necessarily planaramide groups and linear hydrogen bonds to be energetically acceptable.Although clearly untenable in the light of this criticism, it has had consider-able importance as a stimulus to further work, especially on the behaviour ofproteins and polypeptides in hydrogen-bonding and non-hydrogen-bondingsolvents; a remarkable outcome of this work has been the discovery of awater-soluble a-form of silk.53Bragg, Kendrew, and Perutz 64 made a systematic study of all the possiblemodes of coiling of a peptide chain with an integral number of amino-acidresidues in each turn of the helix and compared the resulting structureswith the X-ray crystallographic findings on hamoglobin and myoglobin ;the best fit was obtained with the Astbury-Bell structure 48 but this was notsufficiently good to allow any definite conclusion to be drawn.This unsatisfactory state of affairs has been ended as a result of thecalculations of Pauling, Corey, and Branson 55 who abandoned the restric-tion, introduced by hug gin^,^^ limiting likely structures to those containingan integral number of amino-acid residues in each helical turn.Employingas sole, but rigid, restrictions the accepted interatomic distances and co-valency angles, the planarity of the amide system, and the linearity of the-N-H-O-hydrogen bond, and assuming that the maximum possible numberof intra-molecular hydrogen bonds would be formed, they arrived at twosatisfactory helical structures ; one of these was derived by coiling structure(111) to give 3.7 residues per complete helical turn and the other by coiling52 L.Pauling and R. B. Corey, Proc. Nat. Acud. Sci., 1951,37, 241.68 E. J. Ambrose, C. H. Bamford, A. Elliott, and W. E . Hanby, Nature, 1951,64 Sir Lawrence Bragg, J. C. Kendrew, and M. F. Perutz, Proc. Roy. Soc., 1950, A ,s6 L. Pauling, R. B. Corey, and H. R. Branson, Proc. Nat. A d . Sci., 1951,37, 206.167, 264. .203, 321242 ORGANIC CHEMISTRY.(IV)(IV) t o give 5.1 residues per turn; it will be seen that in both structures *every -CO- and -NH- group is hydrogen-bonded to give 13-membered ringsin the 3.7 residue helix and 16-membered rings in the 5.1 residue helix.FIG.1 -f FIG. 2 tDrawings of these two configurations, taken from Pauling, Corey, andBranson's paper, are shown in Figs. 1 and 2. It is concluded that the 3.7residue helix occurs in the a-forms of the fibrous proteins and synthetic* In (111) and (IV) the curved bonds represent hydrogen bonds of the type T-"-.'R -N C-Reproduced, by permission, from Proc. Nut. Acad. Sci., 1951, 37, 206RYDON : MACROMOLECULES. 243polypeptides and in the globular proteins, while the 5-1 residue helix mayoccur in supercontracted keratin and myosin. In other papers 5 6 9 52 theexcellent agreement of the observed X-ray crystallographic data with thosepredicted from the 3.7 residue helix is demonstrated.In a further important paper Pauling and Corey 57 advance a new struc-ture, the " pleated sheet," for the @-form of the fibrous proteins.The wayin which this differs from the older structure is most clearly seen by com-paring the diagrammatic structures (V) and (VI) which represent the old andnew p-structures respectively :I I II IH i, H II I I CHR\cHR/N\c/ \N/C\CHR/N\C/I1I0iI b H (V0 4 III II CHR / CHR \C/N\CHR/c\N/ \C/N\I9I1 I IIA perspective drawing, taken from Pauling and Corey's paper, is shown inFig. 3. This " pleated sheet " structure can be easily ,converted into the3.7 residue helical structure and it is suggested that this conversion may bethe process involved in the contraction of muscle.58 In other papers 59 thestructures of feather rachis keratin, hair, muscle, and globular proteins are66 L.Pauling and R. B. Corey, Proc. Nut. Acud. Sci., 1951, 37, 235.67 Idem, ibid., p. 251. 68 Idem, ibid., p. 268. 6s Idem, ibid., pp. 256, 261, 282244 ORGANIC CHEMISTRY.discussed in the light of the new configurations. A fuller discussion of thesepapers and of a proposed new collagen structure is given elsewhere.These new ideas are clearly of the greatest importance for protein chem-istry, and it is pleasing to note that, so far as the 3.7 residue helix is con-cerned, they have already passed the first test of a new theory, uix., theprediction of new phenomena which have been experimentally verified.61At this stage the Reporter may perhaps be allowed to abandon traditionalobjectivity in order to make two points of his own. It is clear that anygeneral structure of this type must accommodate the detailed findings re-lating to the arrangement of the amino-acid residues in the peptide chains.Sanger’s latest work on insulin 46 requires the two B-chains to be linked tothe adjacent A-chains by disulphide bridges twelve residues apart ; suchbridges must, presumably, emerge from the same side of the helix and it isFIG. 3.*easy to verify from Fig.. 1 that this is possible, in more than one way, for the3.7 residue helix. Sanger’s findings on the A-chains of insulin are awaitedwith some impatience since these chains are each linked by two disulphidebridges to another A-chain and by two more to a B-chain; the fitting to-gether of the four peptide chains of insulin with disulphide bridges at thespacings required by the chemical evidence will provide a rather stringenttest for the new theory.Ithas seemed for some time that too rigid a specification of the backbonecoiling might prove to be incompatible with the known capacity of y-globulinto assume antigenically different forms while retaining the unmodifiedarrangement of the amino-acid residues required by theory 62 and to someextent confirmed by e~periment.~~ The 3.7 residue helix seems capable ofThe Reporter’s second point is more general.80 L. Pauling and R. B. Corey, Proc. Nut. Acod. Sci., 1951, 87, 272.61 M.F. Perutz, Nature, 1951, 167, 1053; H. E. Huxley and M. F. Perutz, ibid.,82 L. Paiiling, J . Amer. Chem. SOC., 1940, 62, 2643.63 R. R. Porter, Biochem. J., 1950, 46, 473.* Reproduced, by permission, from Proc. Nat. Acad. Sci., 1961, 87, 261.p. 1054; L. Pauling and R. B. Corey, ibid., 1951, 168, 550; M. F. Perutz, ibid., p . 653RYDON : MACROMOLECTJLBS. 245overcoming this difiiculty since it may, so to speak, be transposed into manydifferent keys by starting the helix with the same amino-acid but at geo-metrically different points; it may not be too bold to regard Pauling andCorey’s diagram of muscle contraction (Fig. 4 of ref. 58) as a picture of anti-body formation on a ‘‘ pleated sheet ” template; partial blocking of thetemplate by the antigen or its “ remembered ” impress would clearly lead tothe required transposition with formation of a modified, antigenic, y-globulindiffering only in this respect from the normal product.Interesting information related to denaturation has emerged from a, studyof the induction of gels in protein solutions by the action of urea ; 64 the ureaappears to act by breaking hydrogen bonds and so enabling -SH groups toreact with intramolecular -S-S- bridges, each of which is converted into anintermolecular bridge with liberation of a new -SH; continuation of thechain-process gives rise to an -S-S- cross-linked framework, thus :s-s-s-s-S HS-S Is-s-s-s-s-s-SHResults consistent with this view have been obtained in a study of the actionof 2-mercaptoethanol on lysozyme in the presence of urea; 65 addition ofiodoacetamide brings about alkylation of the -SH groups as they are formedand yields a product, not cross-linked but alkylated, of about the samemolecular weight as the starting material indicating that the lysozyme mole-cule consists of a single peptide chain with intramolecular -S-S- cross-link-ings (cf.Green and Schroeder s5).Polypeptides.-Li has published 66 a complete amino-acid analysis ofadrenocorticotrophic hormone (ACTH) isolated from sheep pituitary ; G7this apparently homogeneous product contains about 160 amino-acid residuers,indicating a molecular weight of 22,600; there seems to be nothing singulaxin the amino-acid composition. In conformity with earlier work,6* it isfound that brief acid hydrolysis increases the hormone activity; it hasbeen shown 69 by a combination of paper chromatography and displacementchromatography on charcoal using a new method 70 that the average mole-cular weight of the most active fraction is about 2000.64 C.Huggins, D. F. Tapley, and E. V. Jensen, Nature, 1951, 167, 592.6s H. Fraenkel-Conrat, A. Mohammed, E. D. Ducay, and D. K. Mecham, J . Amer.67 C. H. Li, H. M. Evans, and M. E. Simpson, J . Biol. Chem., 1943,149,413.6 8 C . H. Li, J . Amer. Chem. SOC., 1950, 72, 2815.69 C. H. Li, A. Tiselius, K. 0. Pedersen, L. Hagdahl, and H. Carstensen, J. BioE. Chem.,Chem. SOC., 1951,73, 626. 66 C. H. Li, ibid., p. 4146.1961,190, 317. 70 A. Tiselius and L. Hagdahl, Acta Chem.Xcand., 1950, 4, 394246 ORGANIC CHEMISTRY.Interesting data have been obtained on the polypeptide antibiotic, sub-tilin, from Bacillus subtilis. This substance is remarkable 'in containingmeso-lanthionine 71 which has never before been isolated from a protein orpolypeptide not previously treated with alkali, and an unidentified diamino-dicarboxy-sulphide, C7H,,0,N2S. 72 A thorough amino-acid analysis 73shows the remainder of the molecule (mol. wt. 3500) to be made up of onlythirteen L-amino-acids ; it is noteworthy that arginine, cyst(e)ine, histidine,methionine, serine, threonine, and lysine are absent.The Lossen rearrangement of hydroxamic acids has been applied 74 tothe synthesis of macromolecular polypeptides as follows, the polymerisationbeing ascribed to the formation of the N-carboxy-anhydride (IX) from theisocyanate (VIII) produced by rearrangement of the acyl-hydroxamic acid(VII) :p 2 H H,N*OH /C02H Ph.COC1 /CO2H'C02Et \R*CH ___f R*C,H ---+ RGHCO*NH*OH \CO*NH*O*COPh(VII)J(n,F::C.8*1/co-0 /CO,H[*NH*CHR*CO*]n +-- [ R*CH \NH-io] - pTNc0 ] +Ph*Co2H(IX) (VIII)The well-established N-carboxyamino-acid anhydride method 75 has beenapplied to the preparation of p~lyphenylalanine,~~ polycystine, 77 polyasparticacid,78 and p~lyarginine,~~ and copolymers of glutamic acid with lysine 80and aspartic acid.8lNucleic acids.Estimation of adenine, guanine, cytosine, and thymine in deoxypentose-nucleic acids from salmon sperm 82 and a number of bacteria and viruses 839 84has shown these bases to be present in various proportions; the sugar ofsalmon sperm nucleic acid has been provisionally identified as 2-deoxy-7 1 G. Alderton and H. L. Fevold, J . Amer. Chem. SOC., 1951, 73,463.72 G. Alderton, unpublished data quoted in ref. 73.'3 J. C. Lewis and N. S . Snell, J . Amer. Chem. SOC., 1951,73, 4812.74 C. D. Hurd and C. M. Buess, ibid., p. 2409 ; C. D. Hurd and L. Bauer, ibid., p. 4387.75 Ann. Reports, 1949,46, 225; 1950,47, 251.7 6 J. W. Breitenbach and F. Richter, MulcromoE. Chem., 1950,4, 262.7 7 H. W. Jones and H. P. Lundgren, J . Amer. Chem. SOC., 1951,73,5465.78 M. Frankel and A. Berger, J . Org. Chem., 1951, 16, 1513; A. Berger and E.79 E. Katchalski and P. Spitnik, ibid., p. 3992.81 D. Coleman, J., 1951, 2294.82 E. Chargaff, R. Lipschitz, C. Green, and M. E. Hodes, J . BioE. Chem., 1951,192,223.83 J. D. Smith and G. R. Wyatt, Biochem. J., 1951,49, 144.84 R. Markham and J. D. Smith, ibid., p. 401.Katchalski, J . Amer. Chem. SOC., 1951, 73, 4084.8. Akabori, H. Tani, and J. Noguchi, Nature, 1951,167, 160RYDON : MACROMOLECULES. 247ribose.82 The component nucleotides of calf thymus deoxypentosenucleicacid have been isolated by enzymic hydrolysis followed by ion-exchangechromatography. 855-Methylcytosine has been found to be a fairly common minor constituentof deoxypentosenucleic acids. It was isolated by Cohn 86 from calf thymusdeoxypentosenucleic acid and identified chromatographically and spectro-scopically, while Dekker and Elmore 87 isolated it from wheat-germ deoxy-pentosenucleic acid and identified it as ,the hydrochloride and picrate. Theextensive studies of Wyatt 88 have shown 5-methylcytosine to occur inrelatively small amount in all the animal deoxypentosenucleic acids exam-ined and in one plant acid, and to be absent from the bacterial and viral acidsinvestigated ; it was not found in any pentosenucleic acids.Clark, Todd, and Zussman 89 have provided welcome new evidence forthe p-configuration of the natural ribonucleosides.conclude, from light-absorption data, that the glycosidic linkage in thedeoxyribonucleosides is of the same type, i.e., p, as that in the ribonucleosidesand have also shown, by periodate oxidation that the pentose is present inthe furanose form.Considerable attention has been given to the position of the phosphoricacid residues in the nucleotides isolated from nucleic acids by mild methodsof hydrolysis. It has been found 919 92 that all the nucleotides from pentose-nucleic acids appear in the two isomeric forms first encountered in the caseof adenylic acid.93 The two cytidylic acids from yeast pentosenucleic acidhave been obtained in crystalline form ; 94 neither reduces periodate and forthis, and other, reasons they are regarded as the 2’- and 3’-phosphates. Theappearance of these two isomerides has been ascribedg5 to the opening inboth possible directions of a cyclic 2’ : 3’-phosphate formed during the courseof the hydrolysis ; nucleotides containing such a cyclic structure have beenencountered in enzymic hydrolysates of pentosenucleic acids.96- 97 Cohnand Volkin 92 have also isolated 5’-isomerides of adenylic, guanylic, uridylic,and cytidylic acids from enzymic hydrolysates of calf liver pentosenucleicacid and it seems clear that the pentose residues in pentosenucleic acids maycarry, or at least be isolated carrying, phosphoric acid residues in all the three(2’-, 3‘-, and 5‘-) available positions. Enzyme studies 98 show that the nu-cleotides isolated from calf thymus deoxypentosenucleic acid g 5 are all 5’-phosphates.a6 E. Volkin, J. X. Khym, and W. E. Cohn, J. Amer. Chem. SOC., 1951,73, 1533.86 W. E. Cohn, ibid., p. 1539.a8 G. R. Wyatt, Biochem. J., 1951, 48, 581, 584.89 V. M. Clark, A. R. Todd, and J. Zussman, J., 1951, 2952.90 L. A. Manson and J. P. Lampen, J. Biol. Chem., 1951,191,87.9 1 W. E. Cohn, J. Amer. Chem. SOC., 1950,72, 1471, 2811.92 W. E. Cohn and E. Volkin, Nature, 1951,167, 483.93 Cf. Ann. Reports, 1950, 47, 262.94 H. S. Loring and N. G. Luthy, J . Amer. Chem. SOC., 1951, 78, 4215.95 D. M. Brownand A. R. Todd, J., 1952, 44, 52.g6 R. Markham and J. D. Smith, Research, 1951,4,344.9 7 Idem, Nature, 1951,168,406.Manson and LampenC. A. Dekker and D. T. Elmore, J . , 1951,2864.98 C. E. Carter, J. Amer. ChemlSoc., 1951, ‘93,1637248 ORGANIC CHEMISTRY.A start has been made on the isolation of oligonucleotides by mild hydro-lysis of nucleic acids 97*99 as an essential step towards determining thearrangement of the component nucleotides in the nucleic acids themselves.The nature of the internucleotide linkages in the nucleic acids 100 is farfrom being settled. Overend, Stacey, and Webb lol conclude, from a studyof the Feulgen reaction during the course of enzymic hydrolysis of deoxy-pentosenucleic acid, that additional labile bonds, involving the attachmentof phosphate residues at Cil, of the deoxypentose, are present in the highlypolymerised acids. Ronwin lo2 has proposed the new type of structure(X), with a " core " similar to that present in phosphoric oxide, for bothpentose- and deoxypentose-nucleic acids.n k I BThe structure appears to agree well with the X-ray data. It requires oneprimary phosphate dissociation for each nucleotide residue, which is inagreement with the accepted findings for the deoxypentosenucleic acids butnot with those for the pentosenucleic acids; the discrepancy in the last-named case is ascribed to the heterogeneity of the products used in thetitration experiments.Discussion of other macromolecules is postponed.H. N. R.A. J. BIRCH.I. G. M. CAMPBELL.M. J. S. DEWAR.A. W. JOHNSON.H. N. RYDON.J. WALKER.B. C. L. WEEDON.L. N. OWEN.88 A. H. Gordon and P. Reiohard, Biochern. J., 1951,48, 569; J. A. Little and G. C.101 W. G. Overend, M. Stacey, and M. Webb, J., 1951, 2450.lo2 E. Ronwin, J . Amer. Chem. Soc., 1951, 73, 5141.Butler, J . Biol. Chem., 1951, 188, 695. loo Ann. Reports, 1950, 47, 263

ISSN:0365-6217    

DOI:10.1039/AR9514800112

出版商:RSC    

年代:1951

数据来源: RSC

摘要:

1. INTRODUCTION.THIS year’s Reports continue the policy of attempting to cover some fieldsof biochemistry rather than giving special reviews on selected topics. Thereviews on microbiology, nutrition, enzymes, and hormones included in lastyear’s Reports are supplemented by the present issue. The attention ofchemists is drawn to the publication Annual Reviews of Biochemistry inwhich the subject is covered in a more comprehensive and specialisedmanner than can be attempted here.E. B.2. IMMUNOCHEMISTRY.Immunology was last reviewed in Annual Reports in 1940. Since then,very much work has been done; only that done since 1946 will be reviewedhere and only the more strictly chemical aspects will be considered; allergyand complement will be omitted. Readers are referred to reviews by Kabat,Grabar and Mayer and surveys by Kabat and W~rmall.~ Importantbooks have been published by Kabat and Mayer (methods and general),Doerr (general), Burnet and Fenn,6 van Hepingen,’ Burger,s Grabar,Qand Ponder,lO and a review by Stacey.ll A new and much enlarged editionof H.Schmidt’s l2 “ Fortschritte der Serologie ” is appearing in parts.Articles on immunology have appeared in Advances in Protein Chemistry(Treffers),13 “ Chemistry and Biology of Proteins ” (Haurowitz),l4 The1 E. A. Kabat, Ann. Rev. Biochem., 1946,15, 505; P. Grabar, ibid., 1950, 19, 453;2 E. A. Kabat, J . Immunol., 1943, 47, 513.3 A. Wormall, Brit. Med. Bull., 1948, 5, 333.* E. A. Kabat and M. M. Mayer, “ Experimental Immunochemistry,” C. C.Thomas,5 R. Doerr, “ Die Immunit&tsforschung,” Springer, Vienna, 1949-50.6 F. M. Burnet and F. Fern, “ The Production of Antibodies,” Maernillan & Co.,M. M. Mayer, ibid., 1951, 20, 415.Springfield, U.S.A., 1948.Melbourne, 1949.W. E. van Heyningen, “ Bacterial T o x ~ , ” Blackwell, Oxford, 1950.M. Burger, “ Bacterial Polysaccharides,” C. C. Thomas, Springfield, U.S.A., 1950.P. Grabar, “ Les Globulins du Serum Sanguin,” Masson & Cie., Pans, 1947.lo E. Ponder, “ Haemolysis,” Grune and Stratton, New York, 1948.11 M. Stacey, Quart. Reviews, 1947,1, Nos. 2 and 3.1 2 Dietrich Steinkopff, Frankfurt /Main.l3 H. P. Treffers, Adv. Protein Chem;, 1944,1, 70.l4 F. Haurowitz, “ Chemistry and Biology of Proteins,” Academic Press Inc., NewYork, 1950250 BIOCHEWSTRY.Enzymes (Marrack),15 “ Research in Medical Science ” (Kabat),l6 and“ Amino Acids and Proteins ” (Campbell and Lanni).17The mechanism of formation was discussed a tthe Royal Society of Medicine.18 Dickey l9 has prepared silica gels whichadsorb dyes specifically; this may be analogous to the formation of anti-bodies.The relation of antibody formation to the state of nutrition has beenstudied.Diabetic patients, whose serum albumin is low, form less thannormal amounts of antibody (measured as agglutin-N), and the amountsare not related to the amount of serum y-globulin.20 The amount of anti-toxin formed by Schick-positive patients suffering from wasting diseases inresponse to injection of diphtheria toxin is not less than that formed bycontrols and may be very high when the y-globulin content is high.20a Titresof agglutinins in the serum of patients with low serum albumin, after injec-tion of typhoid vaccines,21 and of malnourished persons in Germany, afterinjection of fowl red blood cells and tobacco mosaic virus,22 were less thanin the serum of normal controls after the same stimuli.Patients withhypoproteinaemia, idiopathic or nutritional, with low or absent y-globulin,formed little or no 24I n much of the work on the effects of ACTH and cortisone on the amountsof circulating antibody, the antibody has been measured by agglutinin titreswhich are affected by non-specific factors. Those who have measured theantibody by the amount of precipitatable nitrogen or the neutralization oftoxin have found that ACTH and cortisone do not increase and may reducethe amount of circulating antibody.25Wolfe and Dilks 26 have studied the formation of antibodies by variousspecies of birds.Domestic fowls, pheasants, partridges, and owls form largeamounts of antibody; some can be detected in the serum 24 hours afterinjection of antigen. Ducks form little antibody, and guinea fowls, turkey,Antibodies.--Pormation.l5 J. R. Marrack, in The Enzymes, 1950,1,343, Eds., J . B. Sumner and K. Myrbiick,l6 E. A. Kabat, in “ Research in Medical Science ” p. 120, Eds., E. Green and W. E.1 7 D. Campbell and F. Lanni, “ Amino Acids and Proteins,” 2nd edn., D. M. Green-18 C. 0. Stallybrass, Proc. Roy. SOC. Med., 1949, 43, 137.10 F.H. Dickey, Proc. Nat. Acad. Sci., 1949, 35, 227.2o J. A. Flick, S. Ketterer, and M. G. Wohl, Fed. Proc., 1950, 9, 382.20a H. Batch, J . Immunol., 1950, 64, 397.a2 P. H. GeI1, Med. Res. Council Special Rep. No. 275, 1951, p. 193.z3 B. Schick and K. W. Greenbaum, J . Pediat., 1945, 27, 241 ; E. G. Krebs, J . Lab.24 E. A. Kabat, J . Lab. Chin. Med., 1949,34, 1066.25 H. W. Eisen, M. M. Mayer, D. H. Moore, and H. C. Stoerck, Proc. SOC. Exp. Biol.,N . Y . , 1947, 65, 301 ; E. E. Fischel, M. Le May, and E. A. Kabat, J . Immunol., 1949,61,89; J . de Vries, ibid., 1950, 6 5 , l ; M. Bjorneboe, E. E. Fischel, and H. Stoerch, J . Ezp.Med., 1951, 93, 37.Academic Press Inc., New York.Knox, MacMillan & Co., New York.berg, C. C. Thomas, Springfield, U.S.A., 1951, p.649.M. G. Wohl, J. G. Reinhold, and A. S. B. Rose, Arch. Int. Med., 1949, 83, 402.Clirt. Med., 1946, 31, 851.26 H. R. Wolfe and E. Dilks, J . Immunol., 1949, 61, 251MARRACK : IMMUNOCHEMISTRY. 251and pigeons none. Heidelberger and his colleagues2' have studied theformation of antibodies by human beings after injection of pneumococcalpolysaccharides; up to 100 pg. of antibody-N per ml. may be found in theserum 3-8 years after the injection. Antibodies against Rh-antigens maypersist for many years after sensitization.28The sera of human beings after vaccination with Bact. typhosum maycontain 30-40 pg. and after typhoid fever 60-190 pg. of O-agglutinin-Nper ml.; rabbit antisera may contain 160 pg. The agglutinin titre risesfaster than the amount of a g g l ~ t i n i n .~ ~ Rabbit antisera against Staph.aureus may contain 0.68-1 -04 mg. of agglutinin-N per ml. with agglutinationtitres of 1/250 to 1 /1024,30 and rabbit antisera against Staph. albus 0-35 mg.The sera of horses immunized with diphtheria toxoid differ from those ofrabbits in failure to form precipitates with antigen in the zone of antibodyexcess (flocculation curve). Treffers, Heidelberger, and Freund 32 studiedthe relation of the type of antibody formed after injection of rabbit serum-globulin and -albumin by subcutaneous, intracutaneous, and intravenousroutes. After intravenous injection incomplete antibodies were formed,but eventually an antiserum was obtained which gave a typical precipitationcurve, without a prozone, with rabbit globulin. After intra- and sub-cutaneous injections flocculating sera against both albumin and globulinwere obtained.A precipitating serum, without prozone, was obtained byintravenous injection of pneumococcal nucleoprotein. Gitlin and his col-leagues 33 injected alum-precipitated human albumin into a horse's veinsand obtained incomplete antibody ; after intramuscular injection, theyobtained a flocculating antiserum. It appears that the type of antibodymay depend on the route of immunization. However, flocculating antiseraare obtained after both subcutaneous and intravenous injection of diphtheriaanatoxin ; 34 and Perez 35 obtained flocculating antibodies against pigglobulin after immunizing horses by either subcutaneous or intravenousinjection.Complexes formed by " mustard gas " with proteins do not give rise toprecipitins unless combined with p h ~ s p h a t e .~ ~ The formation of antibodiesagainst simple chemical substances depends on the ratio of the reactivity27 M. Heidelberger, C. M. MacLeod, R. C. Hodges, W. G. Bernhard, and M. M.Dilapi, J. Exp. Med., 1947, 85, 227 ; M. Heidelberger, C. M. MacLeod, and M. M. Dilapi,ibid., 1948, 88, 369; M. Heidelberger, M. M. Dilapi, M. Siegel, and A. W. Walter, ibid.,1950, 62, 535.Z 8 P. Speiser and J. Schwartz, Wien. K l i n . Wochenschr., 1950, 52, 772; A. S. Wiener,R. Nappi, and E. B. Gordon, Blood, 1951,6, 799.of ~/m1.31J. Gurevitch and E. Ephrati, J. Immunol., 1947, 55, 37.30 M.J. Kahnke, ibid., 1950,65, 707. 31 H. Umezawa, Jap. Med. J., 1948, 55, 89.32 H. P. Treffers, H. Heidelberger, and J. Freund, J. Exp. Med., 1947, 86, 83; M.33 D. Gitlin, C. S. Davidson, and L. H. Wetterlow, J. Immunol., 1949, 63, 415.34 M. Faure, R. Larny, andM. H. Coulon, Ann. Inst. Pasteur, 1948, '74, 19.s 5 J. J. Perez and C. Mazureke, Compt. rend. SOC. biol., 1950, 144, 1639.36 D. S. Fleming, A. M. Moore, and G. C. Butler, Biochem. J., 1949, 45, 546.Heidelberger, ibid., 1947, 86, 77262 BIOOHEMISTRY.with protein-NH, groups to the rate of hydr~lysis.~~ Loiseleur and Levy38claim to have demonstrated antibodies in the sera of animals that had re-ceived injections of substances of low molecular weight, repeated at shortintervals; when the injected substance is added to the serum or globulinof the serum, the viscosity and, in some cases, the turbidity are increased.Goebel et ~ 1 .~ ~ modified the methodof recovering antibody from precipitates formed by anti-pneumococcalhorse serum and polysaccharide. About 30% of the antibody was recovered,65--82% of this being precipitable by antigen.Haurowitz and his colleagues 40 dissolved precipitates formed by azo-proteins with the corresponding rabbit antibodies, or with rabbit antibodiesto the homologous native protein, in acid and 5% sodium chloride solution;on neutralisation and dilution a precipitate was formed, consisting of antigenwith part of the antibody. Part of the antibody, up to 66% of which wasprecipitable by antigen, remained in solution. Campbell and his col-leagues 41 used rabbit antiserum against sheep serum-proteins coupled withdiazotized p-aminophenylarsonic acid, formed a precipitate with a synthetichaptea, dissolved this in sodium arsanilate solution, and removed the haptenby acidification and fractional precipitation with &-sodium chloride.Theyclaimed yields of 63-97% ; 71-98% of the material WM specifically pre-oipitatable. The recovered antibody was electrophoretically. homogeneous,with the mobility of y-globulin ; the molecular weight by osmotic pressurewas 136,000 to 144,000, and by other methods 158,000.Sternberger and Pressman 42 precipitated the antibody in a rabbitantiserum against bovine serum-albumin by adding bovine serum-albumincoupled with diazotised p-aminophenylarsonic acid.They dissolved theprecipitate in aqueous calcium hydroxide and removed the azo-protein on asuspension of calcium aluminate. About 30% of the antibody was re-covered; nearly all of this was precipitable by bovine albumin. Stern-berger and Petermann43 studied the effects that this treatment mighthave on the antibody. The mobility, sedimentation constant, and viscosityof rabbit y-globulin were not affected if the pH was not brought above 11.4.At pH 12.4 structural changes occurred in less than 3 minutes a t 25" (cf.Svedberg 44). Campbell et C C Z . ~ ~ attached bovine serum-albumin to cellulose,absorbed antibody on a column of this product, and eluted it with weak acid.Eisen and Karush46 obtained antibodies to azoproteins from the com-a7 P.H. Gale, C. R. Harington, and R. Michel, Brit. J . Exp. Path., 1948, 29, 578.58 J. Loiseleur and M. Levy, Ann. Inst. Pasteur, 1947, 73, 116; J. Loiseleur, ibid.,39 W. F. Goebel, P. J. Olitsky, and A. C. Saenz, J . Ezp. Med., 1948,87,445.40 F. Haurowitz, S. L. Tekman, M. Bilan, and P. Schwerin, Biochem. J., 1947, 41,4 1 D. Campbell, R. H. Blaker, and A. B. Pardee, J . Arner. Chem. SOC., 1948,70,2496.4 2 L. A. Sternberger and D. Pressman, J . Immunol., 1950, 65, 65.43 L. A. Sternberger and H. C. Petermann, ibid., 1951,67, 207.44 T. Svedberg, Trans. Faraday SOC., 1950,26, 740.45 D. Campbell, E. Luescher, and S. G. Lemann, PTOC. Nut. Acad. Sci., 1951,37, 576.4% W. Eisen and F. Karush, J . Arner. Chem. SOC., 1949,71, 363.Recovery from specific precipitates.1950, 78, 1.304; F.Haurowitz, L. Etili, and S. Tune, Bull. SOC. C h k . biol., 1948, 30, 220MARRACK : IMMUNOCHEMISTRY. 253pound of antibody with azotized stromata of red blood cells (Landsteinerand Van der Scheer 47) ; yields were low. Not less than 90% of the re-covered antibody was precipitatable by antigen. Campbell and Lanni l7discuss methods of recovering antibodies from precipitates formed byovalbumin and azoproteins with antisera.Northrop and Goebel 48 separateda crystalline protein from horse antiserum against Type I pneumococcus byprecipitation with potassium hydrogen phthalate , followed by precipitationwith ammonium sulphate. This protein was completely precipitated byHI and formed no precipitate with SII, but its protective value per pg.wasabout 20% of that of antibody recovered from a specific precipitate; theamount of precipitate formed with rabbit antiserum against horse serumwas considerably greater than that formed by recovered antibody.Deutsch and his colleagues have prepared globulin fractions from human,horse, and cow sera. The distribution of antibodies is summarized in theTable. The yl-globulin of human serum contains about 30% of componentwith 820r = 185 ; the lighter portion has components with Sz0w = 7 and 98.No 188 component was found in the y2-globulin.49 In horse serum andcow serum32 the isoelectric point of y2-globulin is on the alkaline side ofthat of the 7,-globulin. The L320w of the y,-globulin of horse serum is slightlymore than 7 s and that of the y,-globulin slightly less.In cow immuneserum the Xz0w of both yl- and y,-globulin is 7.4s; some 188 componentwas found in the yl-globulin, although none was found in normal cow serum.There appears to be no difference between yl-globulin, and T-globulin.Isolation from antiserum ; properties.Species AntibodyMan Typhoid, O-agglutininIs0 haemagglutininTyphoid, H-agglutininInfluenza-A, neutralizing antibodyH . pertussis antibodyDiphtheria antitoxinRabbit Diphtheria antitoxinSerum fractiony,-Globulin 6oy,-Globulin, heavy fraction 617,-Globuliny,-Globuliny,-Globuliny,-Globulin 62y,-Globulin 64cow Br. abortusagglutinin and bactericidin y,-Globulin, bactericidin moreneutralizing Mainly y,-globulin 53Horse Tetanus antitoxin T-globulin (yl-globulin), y,-globulin,soluble 63Newcastle virus :haemagglutination inhibiting Mainly y,-globulin 68and a /I-globulin fraction 64Smith and his colleagues have studied the composition and properties ofthe globulin fractions of serum and of cow colostrum that contain antibodies47 I(.Lendsteiner and J. van der Scheer, J . Exp. Med., 1936, 63, 321.48 J. H. Northrop and W. F. Goebel, J. Ben. Physiol., 1942, 32, 705.dB H. F. Deutsch and J. C. Nichol, J . Biol. Chem., 1948,176, 797.6o H. F. Deutsch, R. A. Alberty, and L. J. Gosting, J. Biol. Chem., 1946,165, 21.61 H. F. Deutsch, R. A. Alberty, and W. J. Williams, J . Immunol., 1946,56, 183.6a M. Cohn and A. M. Pappenheimer, Jnr., ibid., 1949,8s, 291.61 E.L. Smith and T. D. Cterlough, J . Biol. Chem., 1947,167, 679.E. L. Hess and H. F. Deutsch, J . Amcr. Chern. Soc., 1949,71, 1376254 BIOCHEMISTRY.(reviewed by Smith 55). The immune globulin of colostrum differs fromp-lactoglobulin ; it resembles T-globulin and differs from y-globulin ofplasma in isoelectric point and mobility.56 The ultra-violet absorptioncurve of T-globulin differs from those of plasma y-globulin and colostrumg l ~ b u l i n . ~ ~ ~ The amino-acids have been estimated.57, 57a The y-globulinsof horse and cow plasma contain more basic amino-acids than do the T-globulins ; human serum contains fractions resembling the y-globulin andT-globulin. Hansen, Potter, and Phillips 57a also find that the mobility ofthe immune globulin of colostrum is higher than that of y-globulin of serum.They estimated amino-acids in this globulin and found larger amounts oftryptophan than were found by Smith and his colleagues.Smith and Gerlough 54 found that the antitoxin in horse antiserum againsttetanus toxin is in the T- and the y-globulin fraction and in a water-solublep-globulin. The sedimentation constants of the main components of theglobulin fractions from cow, horse, and human sera are about 7 8 ; smallamounts of 108 components were found, but no 208 components.55"Different types of anti-Rh antibodies have been separated by dialysis,58bdifferential solubility in salt so1utions,68a and electrophoresis con~ection.~8bAntibodies against protein and against determinant groups in antiserumagainst azo-proteins have been separated by electrophoresis conve~tion.~~Magnuson and his colleagues 6o found that the antibody in syphiliticserum that immobilises Tr.paZEidum is in the same serum fraction as theisoagglutinins and the anti-haemophilic globulin of high molecular weight.Syphilitic antibody does not seem to differ antigenically from normal humanserum globulin.6*a Human y-globulin inhibits the agglutination of Rh-positive cells sensitized with incomplete anti-Rh serum by anti-human-globulin serum (Coombs's reaction) ; Wiener and his colleagues inferredthat the antibody is a y-globulin and used this inhibition to demonstrate thepresence of y-globulin in cerebrospinal fluid and saliva and its absence fromurine and semen.It is notusually found that antibodies derived from different species have a commonantigenic specificity by virtue of being antibodies against the same antigen.Antibodies are globulins and can therefore serve as antigens.5 5 E.L. Smith, J . Dairy Sci., 1948, 31, 127.55a E. L. Smith and D. M. Brown, ibid., 1950, 183, 247.5 6 E. L. Smith, J . Biol. Chem., 1946, 164, 345.5Ga E. L. Smith and N. H. Coy, ibid., p. 367.5 7 E. L. Smith, 1%. D. Greene, and E. Bartner, ibid., p. 359.570 R. G. Hansen, R. L. Potter, and P. H. Phillips, ibid., 1947, 171, 229.5 8 E. Witebsky and J. F. Mohn, J . Lab. Clin. Med., 1948,33, 1353, 1361, 1369.5Su J. M. Hill, G. Haberman, and R. Guy, Amer. J . Clin. Path., 1949, 19, 134.58b J. R. Cann, R.A. Brown, D. C. Gajdusek, J. S. Kirkwood, and P. Sturgeon,59 J. R. Cam, D. H. Campbell, R. A. Brown, and J. G. Kirkwood, J . Amer. Chem.60 H. T. Magnusson, H. Tauber, C. Macleod, and W. Garson, J . Clin. Invest., 1951,30,61 A. S. Wiener,M. A. Hyman, and L. Handman, Proc. SOC. Exp. Biol. Med., 1949,71,96.J . Immunol., 1951, 66, 137.SOC., 1951, 73, 4611.659. GOa S. D. Henriksen, J . Immunol., 1947, 55, 153MARRACK : IMMUNOCHEMISTRY. 255However, Laporte and his colleagues 6, prepared an antiserum by injectingsheep red blood cells, sensitized with horse haemolysin, into sheep; thisinhibited lysis of sheep red blood cells both by horse sheep-cell-haemolysinand by rabbit sheep-cell-haemolysin; but it did not inhibit lysis of ox redcells by rabbit ox-cell-haemolysin.The two sheep-cell-haemolysins, unlikeother horse- and rabbit-serum proteins, have a common antigenic feature.Porter 63 found by the fluorodinitrobenzene method that normal rabbity-globulin and rabbit antibody against ovalbumin contain only one freea-amino-group per molecule. The terminal amino-acids, determined bySanger's m e t h ~ d , ~ ~ ~ are alanine, leucine, valine, and aspartic acid ; all thehistidine reacts with fluorodinitrobenzene.Loveless 64 heated sera at 37" for several hours in order todistinguish the heat-stable " blocking " antibody (formed by allergic per-sons after treatment with allergen) from the heat-labile reagin. However,the effect of heat on human antibodies varies considerably. Agglutininsagainst Bact.dys. Shiga are lost when heated at 65" for 20 minutes, whereasthe incomplete antibodies are not affected ; the agglutinins against typhoidVi-antigen are not lost on being heated.65 The incomplete anti-Rh anti-bodies are more stable than the complete antibodies.58, 66 Heidelbergerand his colleagues 27, G7 found that human precipitins, reacting with pneumo-coccal polysaccharides, may be partly or completely lost when heated at57" for 30 minutes. They recommend that the complement of human serashould be removed by means of a heterologous antigen-antibody reactionand not by heat.The antitoxic sera of human beings, monkeys, and guinea pigs heated at56" for a short time no longer form precipitates with diphtheria toxin;their neutralizing titre is but slightly reduced.52 The heated antitoxin isprecipitated quantitatively when it is mixed with unheated rabbit antitoxinand then treated with toxin.Purified human antitoxin y,-globulin, thathas been heated alone, still flocculates with toxin, bu not if it has beenheated with crude albumin or normal human serum; crystalline albuminhas little effect. Also heated normal serum, added to the 7,-globulin, delaysthe formation of a precipitate on addition of toxin. On the other hand,Schuhardt and his colleagues found that a " blocking " antibody in thesera of persons infected with Br. abortus might be destroyed by being heatedat 56" for 15 minutes, whereas the agglutinin and incomplete antibodydetected by the Coombs reaction might be unaffected.Follensby and Hooker 69 heated horse antiserum against haemocyaninfor 20-30 minutes at 68-70'; the amount of protein precipitable from62 R.Laporte, L. Hardre de Looze, and P. Roulier, Ann. Inst. Pasteur, 1950,79, 381.63 R. R. Porter, Biochem. J., 1950, 46, 473.64 M. H. Loveless, J. Immunol., 1940, 38, 25; Amer. J . Med. Sci., 1947, 214, 559.6 6 W. T. J. Morgan and H. Schutze, Brit. J . Exp. Path., 1946, 27, 286.66 L. K. Diamond and N. Abelson, J. Clin. Invest., 1945,24, 122.6 7 M. Heidelberger and M. M. Dilapi, J. Immunol., 1948, 61, 153.1313 E. M. Follensby and S. B. Hooker, J. Immunol., 1947, 55, 205.EfjCect of h a t .F. Sanger, ibid., 1945, 39, 507.V. T. Schuhardt, H. W. Woodfin, and K. C. Knolle, J. Bact., 1951,61, 299256 BIOCHEMISTRY.the serum by antigen was not reduced, but the amount of antigen neededto produce the maximum precipitate was much less than that needed byunheated serum.Heated rabbit antisera did not form precipitates withantigen and delayed the precipitation of unheated antibody and antigen.By short treatment with pepsin, precipitating antibody can be recoveredfrom the non-precipitating complexes formed by heat .70Effects of enzymes. Rabbit and horse antisera against H . pertussis canbe treated with pepsin at pH 4 or 1.3 for 24 hours at 37" without loss ofantitoxins; the ability to fix complement is lost.71 Harms 72 gives detailsof the concentration of antitoxins by treatment with pepsin. Pope andStevens 73 consider that the enzyme that splits diphtheria antitoxin into anactive and an inactive fraction is of the cathepsin type and find that crystalsof pepsin and trypsin contain an enzyme of this type.When the complexformed by tobacco mosaic virus and antibody is digested with pepsin," stubs " of the digested antibody are left combined with the antigen.74Porter 63, 74a studied hydrolysis of the y-globulin of rabbit antiserumagainst ovalbumin by various methods. After treatment with trypsin andwith pepsin a t pH 3 for 16 hours the globulin was still precipitated byantigen. After treatment with 0.2~1-sodium dodecyl sulphate for 2 hours itneither precipitated nor inhibited. An inhibitor which appeared tohave a molecular weight of about 100,000 was obtained with pepsin atpH 1.5 for 16 hours.Papain-hydrogen cyanide a t pH 8 produced aninhibitor of molecular weight of about 40,000 which appeared to have thesame terminal alanine group as the original antibody. Further treatmentwith amino-peptidase gave on one occasion a dialysable inhibitor. Noinhibitor or precipitin was obtained by hydrolysis of the antigen-antibodyprecipitate; Porter suggests that " stubs " of hydrolysed antibody remainattached to " stubs " of hydrolysed antigen (cf. Malkiel 74). Streptokinase,plasminogen activated by streptokinase, lecithinase, and hydrogen peroxidehave no effect on the reaction of human antitoxic sera with diphtheriaant it oxin.Introduction of small amounts of iodine intoantibodies has little effect on the amount of precipitate formed with anti-gen.75976 Masouredis and his colleagues 77 found no difference between theprecipitation curves of native antibody and antibody containing about1.3 atoms of iodine per molecule.However, the figures given by Pressmanand Sternberger 78 suggest that some antibody is lost and some aggregationEffects of other treatments.70 A. Kleckowski, Brit. J . Exp. Path., 1950, 31, 145.7 1 I. A. Parfentjev and E. Virion, J . Immunol., 1948, 60, 167.12 A. J. Harms, Biochem. J., 1948, 42, 390.78 C. G. Pope and M. F. Stevens, Brit. J . Exp. Path., 1951,323,314.74 S. Malkiel, J . Immunol., 1950,64,197. 14* R. R. Porter, Bwchem. J., 1950,46,479.'5 G. E. Frmcis, W. Mulligan, and A. Wormall, Nature, 1951, 167, 748; E. C,7 6 S. Cohen, Fed. Proc., 1950, 9, 380; J .Immunol., 1951, 67, 339.7 7 S. P. Massowedis, L. R. Melchior, and D. C. Koblick, J . Immunol., 1951, 66, 3.7 * D. Pressman and L. H. Sternberger, J. Amer. Chem. Soc., 1950,72, 2226.Kooyman and D. Campbell, J. Amer. Chem. SOC., 1948,70, 1293MARRACK : IMMUNOCHEMISTRY. 257occurs when the number of atoms introduced is of the order of 7. Whenthe number of atoms per molecule of globulin is over 15, less precipitate isformed with antigen.It is frequently assumed that the number of atoms or substituent groupsintroduced will be the same in all the protein molecules of a treated serumor globulin fraction. However, Butement,79 and Pressman and Stern-berger,7s calculate the distribution of molecules containing m atoms ofiodine when the average number of atoms per molecule is n.Pressman and Sternberger 78 found that the antibody precipitated byantigen from an iodinated preparation of rabbit antiserum globulin (con-taining about 75%.of y-globulin) contained less iodine per g. than did thebulk of the globulin. This difference was not found by Massouredis andhis colleague^,^^ when the amount of iodine added per molecule was less.Cohen80 also found that antibody of horse anti-pneumococcal serum isiodinated at the same rate as the rest of the globulin fraction. The couplingof 15 p-diazophenylarsonic acid groups to a Rh antibody molecule does notdestroy the combining power of the antibody, although the agglutinin titremay be reduced.81Treatment with periodate destroys the specific activity of horse antibodyto Type I11 polysaccharides, ribonuclease, and western equine encephalo-myelitis ~ i r u s .3 ~ The antigenicity of the immune globulin is retained butthat of the virus is lost. Treatment of proteins with periodate has con-siderable further effects on the amino-acids of proteins besides oxidising thehydroxyl groups of serine and threonine.*2Reduction of disulphide (-S-S-) groups of antibody against ovalbuminwith thioglycollate (mercaptoacetate) delays, but does not abolish, theformation of a precipitate with antigen. If the thioglycollate is dialyzedoff, the antibody is re-oxidised and the precipitation time returns to itsoriginal value.66The rate of inactivation of antitoxic globulin, measured by the neutral-ization of toxin, by 8M-urea is minimal at pH 6.2-7.4.Sodium sulphateprotects, but sodium and calcium chloride promote, inactivation ; inactiv-ation may be due to liberation of thiol gr0ups.8~ The rate of inactivationis independent of the concentration of antibody. Complexes that do notinvolve inactivation may be formed.found that antisera from which lipoids had been extractedin the cold would not form precipitates with antigen; on treatment ofantisera with ninhydrin the ability of rabbit (but not horse) antisera toTayeau et7s F. D. S . Butement, Nature, 1948,161, 731; J., 1949, 408.81 R. R. A. Coombs, L. S. Mynors, and G. Weber, Brit. J . Exp. Path., 1950,31, 640;82 W. F. Goebel and G. E. Perlmann, J . E x p Med., 1949,89,479.83 G. S. Wright and V.Shomaker, J . Biol. Chem., 1948,175,169; J. Amer. Chem. SOC.,84 F. Tayeau, F. Fause, E. Neuzel, and R. Pautrizel, Comp. rend. SOC. biol., 1947,S. Cohen, Ped. Proc., 1950,9, 380; J. Immunol., 1951, 67, 339.R. R. A. Coombs, L. S. Mynors, and F. Wild, J . Path. Bact., 1951, 63, 179.1948, 70, 356.141, 191.REP.-VOL. XLVIII. 258 BIOCHEMISTRY.form precipitates was restored. They inferred that formation of a precipit-ate was a question of solubility. Krueger and Heidelberger 85 extractedlipoids from horse antisera which had been kept for several years and foundthat they still formed precipitates with antigen if the mixture was kept longenough and centrifuged fast enough. Orlansky 86 also found that extractedold horse anti-pneumococcal serum formed a precipitate with antigen ;but extracted fresh rabbit-antisera did not do so even when kept for severaldays in the cold and centrifuged fast.Delsal et aLS7 suggest that the lossof ability to be precipitated is not due to loss of lipoid but to an effect ofthe alcohol used for extraction.Combining groups. Pressman and Sternberger 88 found that haptensprotect antibodies from the effects of iodination. Phenylarsonic acid pro-tects the homologous antibody and antibody against diazobenzoic acidproteins ; benzoic acid protects the homologous antibody only. As only thetyrosine, histidine, and cysteine residues are affected when the number ofiodine atoms introduced is small, it appears that these residues may beessential parts of the combining groups.Porter 63 found that one histidineresidue in the precipitate formed by ovalbumin with rabbit antibody isnot available for combining with fluorodinitrobenzene, although all thehistidine residues of y-globulin-containing antibody and of ovalbumin areavailable. It appears that histidine forms part of the combining group ofthe antigen or of the antibody molecule.Investigations into the transfer are reviewed byParish. 89 The protection of newborn calves against B. coli septicaemiadepends on the ingestion of the aqueous phase of colostrum.g0 A smallquantity only is required; heating the aqueous phase at 63" for 30 minutesdoes not destroy the protective power.g0a Protection against white scoursdepends on the amount of antibodies against K-antigens of Bact.coli in thecolo~trum.~~ The appearance of y-globulin in the serum after ingestion ofcolostrum can be shown 91a by Kunkel's zinc sulphate test.92 If colostrumis ingested more than 24 hours after the birth of the calf, it has no effecton the protein of the s e r ~ r n . ~ ~ ~ 9 * The mobility of the component thatappears in a calf's serum after colostrum is greater than that of normalTransfer to offspring.86 R. C. Krueger and M. Heidelberger, J. Exp. Med., 1950,92, 383.B 6 E. Orlansky, Thesis, London, 1951.87 J. L. Delsal, Bull. SOC. Chim. biol., 1949, 31, 122; J. L. Delsal, J. J. Perez, and88 D. Pressman and L. Sternberger, J. Immunol., 1951,66, 609.88 H. J. Parish, Brit. Med. J., 1951,1, 1164.90 R. Aschaffenburg, S.Bartlett, S. K. Kon, P. Terry, S. Y. Thompson, D. M.DOa R. Aschaffenburg, S. Bartlett, S. K. Kon, D. M. Walker, C. Briggs, E. Cotchin,91 C. Briggs and R. Lovell, Brit. J. Nutrit., 1951, 5, 349, 350.91a R. Aschaffenburg, J. Dairy Sci., 1949,3, 200.82 H. G. Kunkel, Proc. SOC. Exp. Biol. Med., 1948, 66, 217.83 R. G. Hansen and P. H. Phillips, J. Biol. Chem., 1947,171, 223.94 E. L. Smith and A. Holm, ibid., 1948, 175, 349.K. Laporte, ibid., 1950,32,219.Walker, C. Briggs, E. Cotchin, and R. Lovell, J. Dairy Sci., 1949,3, 187.and R. Lovell, ibid., p. 196MARRACK : IMMUNOCHEMISTRY. 269y-globulin. As the calf gets older, the mobility of the slow globulin com-ponent falls.94 The antibodies absorbed from colostrum go up the lymphaticduct .95New light has been shed on the passage of antibodies from mother tofetus in those species in which this occurs during intrauterine life, by aseries of studies of rabbits by Brambell and his colleagues.Antibodies passfrom the lumen of the uterus into the yolk sac of an S&day foetus, beforethe foetal circulation is established; they pass from yolk sac to foetus bythe yolk-sac splanchnopleur.96 In the 24-day foetus, antibodies pass bythe uterine lumen and yolk-sac splanchnopleur to the fetal circulation ; 97they are not transmitted by the allanto-chorionic placenta. Evans-blue,adsorbed on serum albumin, passes from maternal circulation into the yolksac; the fluid in the yolk sac contains the same number and distribution ofprotein components as the serum.98 In the later part of pregnancy theyolk-sac splanchnopleur admits rabbit antibodies, but little or no ox orhorse antibodies ; the selection is not a matter of molecular weight.It issuggested that the process of selection depends on an active cellular process.99Antibodies from the amnion are swallowed and found in the stomach of the24-day fetus.lo0 This selective transfer was found by Cohen; lo1 hetero-logous y-globulin is transferred from mother to foetus more slowly thanhomologous antibody and does not rise to the same concentration in foetalserum.The concentration of homologous antibodies in the serum of humanbabies is above that in their mother’s ~ e r ~ m . ~ * ~ ~ ~ ~ ~ The selection betweenhomologous and heterologous antibodies is again not a matter of size;Hartley lo4 finds that antitoxin molecules, homologous or heterologous,reduced in size by hydrolysis, are not transferred from mother to foetus(human or guinea pig), whereas untreated homologous antibodies are trans-ferred.The rate of disappearance of antibodies can be deduced from therate of decline of antibodies, thus passively acquired, in the fetal circulation.Barr, Glenny, and Randall lo2 found that the concentration in serum fell tohalf that in cord blood in 10 days; after this the half-life was 4i weeks.Wiener lo5 criticised the use of cord blood and concluded that, if allowancewas made for increase of plasma volume, the antibody declined steadilywith it half-life of about 30 days.O 5 R. 8. Comline, H.E. Roberts, and D. A. Titchen, Nature, 1951,167,561.O 6 F. W. R. Brambell, W. A. Hemming, and W. T. Rowlands, Proc. Roy. Soc., 1948,97 F. W. R. Brambell, W. A. Hemming, M. Henderson, and H. J. Parry, ibid., 1949,98 F. W. R. Brambell and W. A. Hemming, J . Physiol., 1949,108,177.O9 F. W. R. Brambell, W. A. Hemming, and W. T. Rowlands, Proc. Roy. SOC., 1950,loo F. W. R. Brambell, W. A. Hemming, C. L. Oakley, and W. T. Rowlands, ibid.,lo2 M. Barr, A. T. Glenny, and K. J. Randall, Lancet, 1949,11, 324.lo3 H. Vignes, R. Richou, and P. Ramon, Rev. ImmunoE., 1948, 2, 1.lo4 P. Hartley, Monthly Rev. Min. Health, 1948, 7, 45; Proc. Roy. SOC., 1951, B.,By 135,390.136, 131.B., 137, 239.1951,138,195. lol S. G. Cohen, J . Infect. Dis., 1950, 87, 291.138, 499.lo5 A. S. Wiener, J . Exp. Med., 1951, 94, 213260 BIOCHEMISTRY.Buxton lo6 found that if hens were immunized intravenously with 8.puhrum, incomplete antibody passed into the egg yolk, but agglutinins didnot. If hens were immunized intramuscularly or subcutaneously, noantibody passed into the yolk.Antigens.-Antigenic substances. An electrophoretically homogeneousantigen that elicits antibodies has been made from M . tubercuZosis.lO7 Itconsists mainly of polysaccharide, containing glucose and glucosamine ;freed from lipoid, it gives a precipitate with antiserum. A protein and apolysaccharide have been prepared from tuberculin ; the polysaccharidegives the haemagglutination reaction, and the protein the typical reactionof tuberculin.lO* A polysaccharide-lipoid complex of Serratu mrcescem(Chrmbacterium prodigwsum) is antigenic ; the complexes of differentstrains differ immunologically.10g It is suggested that the complex containstwo factors, one toxic and the other antigeni~.~O~a The development ofprotective antibody has been studied.logb Antigens have been made fromBact.typhosum ; a polysaccharide Vi-antigen reacts only with anti-Vlsera; different preparations of 0 antigen cross-react with it to varyingdegrees.ll0 Type I pneumococcal polysaccharide has been fractionated ;a preparation was obtained that gave a single electrophoretic and a singleultra - centrifuge peak.The glomeruli contain the antigen which elicits nephrotoxic antisera.l12, 113The antigen is not extracted by saline, alcohol, acid, alkali, or diethyleneglycol; it is extracted after digestion with trypsin.Antiserum to leci-thinase of CZ. Wekhii inhibits the action of the enzyme ~ompetitive1y.l~~Precipitates formed by D-glyceraldehyde 3-phosphate dehydrogenase withantiserum retain about 10 yo of their activity ; inhibition of enzyme is lessif DPN is added first.l15 The antiserum does not cross-react with hexo-kinase from the same strain of yeast, nor with muscle D-glyceraldehyde3-phosphate dehydrogenase ; this antiserum inhibits the fermentation ofglucose by yeast extract, but not that by living yeast cells.l16 Antisera108 A. Buxton, Nature, 1951,168, 657.107 F. B. Seibert, M. Stacey, and P. W. Kent, Biochem. Biophys. Acta, 1949, 3, 632;108 A.Lamensans, P. Grabar, and J. Bretez, Comp. rend., 1931,230, 1967.109 H. J. Creech, M. A. Hamilton, and I. C. Diller, Cancer Res., 1948, 8, 318; H. J.Creech, M. A. Hamilton, E. T. Nishimura, and R. F. Hankwitz, jnr., ibid., p. 330.1OSa D. R. A. Wharton and H. J. Creech, J . Immunol., 1949, 62, 135.P. W. Kent, J., 1951, 364.H. J. Creech, R. F. Hankwitz, jnr., and D. R. A. Wharton, Cancer Res., 1949,110 P. Grabar and M. H. Oudin, Ann. Inst. Pwteur, 1947, 73, 627; P. Grabar and111 R. A. Alberty and M. Heidelberger, J . Amer. Chem. Soc., 1948, 70, 211.112 D. H. Solomon, J. W. Gardella, H. Finger, F. M. Dethier, and J. W. Ferrebee,113 L. R. Cole, W. J. Cromartie, and D. W. Watson, Proc. SOC. Exp. Biol. Med.,116 E . G. Krebs and V. A. Najjar, ibid., 1948, 88, 569.11' E.G. Krebs and R. R. Wright, J . Biol. Chem., 1951,192, 55.9, 150; H. J. Creech and R. F. Hankwitz, jnr., ibid., p. 589.P. Corvazier, ibid., 1951, 80, 255.J . Exp. Med., 1949, 90, 267.1951, 77, 498. 11* P. C. Zamecnik and F. Lipmann, J . Exp. Med., 1947,87, 395MARZLACK : TMMUNOCHEMISTRY. 261against yeast hexokinase l1 and carboxylase 118 also inhibit fermentationof glucose. The deoxyribonuclease of streptococci and of pancreas differantigenicaUy.119 Collagen alone, coupled to diazobenzenesulphonic acid, orcoupled through benzidine to human serum globulin did not give rise toantibodies.120 No evidence was found of antibodies to collagen in the serumof patients whose diseases were characterised by fibrinoid necrosis.Foetal and adult haemoglobin which differ immuno1ogically,l2l differ interminal amino-acids7122 content of amino-acids,lB ultra-violet absorptioncurves, and electrophoretic mobility ; 123a differences have been reviewedby Leeks and Worman.124 Ferritins of different species cross-react but areimmunologically different ; they differ in isoelectric point .125 Dextranforms a precipitate with antisera to Type I1 and Type XX pneumococci.Antiserum to partly hydrolyzed dextran passively sensitises guinea pigs toanaphylactic shock.126Cross-reactions of different strains of viruses have been studied.Strainsmay appear immunologically identical although their amino-acids differ.Modi$ed antigens. Plakalbumin is formed from ovalbumin by theaction of an enzyme of B.subtiZis,12s with the loss of a glutamic and anaspartic acid residue; 129 it does not precipitate all the antibody from anantiserum against ovalbumin ; 129a different preparations differ immuno-logically. l30 Partial deamination and change of disulphide to thiol groupsappear to have little effect on the reaction of ovalbumin with antisera.131Proteins coupled with diazo-compounds have been widely used in immuno-logical work and it has been assumed that their molecular weights have notbeen altered; the sedimentation constants of the greater part of such azo-proteins may be unchanged but some faster-sedimenting material is formed.132Serum albumin treated with periodate does not form a precipitate withantiserum against untreated albumin.82 Wetter and Deutsch 133 studiedthe effects of acetylation, esterification, iodination of ovomucoid, and of117 R.E. Miller, V. Z. Pasternak, and M. G. Sevag, J . Bact., 1949,58, 621.11* V. Z. Pasternak, M. G. Sevag, and R. E. Miller, ibid., 1951,61, 189.119 M. McCarty, J . Exp. Med., 1949, 90, 543.120 B. H. Waksman and H. L. Mason, J . Immunol., 1949,63,427.121 R. R. Darrow, S. Nowakavsky, and M. H. Austin, Arch. Path., 1940,31, 873.12) R. R. Porter and F. Sanger, Biochem. J., 1948, 42, 287.lZ3 J. Wyman, Adv. Protein Chem., 1948, 4, 420.123a G. H. Beaven, H. Hoch, and E. R. Holiday, Bwchem. J., 1951,49, 374.124 H. Leeks and I. J. Worman, Amer. J . Med. Sci., 1950,219,684.lZ5 A. Mazur, I. Litt, and E. Shorr, J . Biol. Chem., 1950,187, 473.126 E.J. Hehre and J. Y. Sugg, Fed. Proc., 1950, 9, 383.Iz7 S. Malkiel, J . Immunol., 1947, 5'4, 43; 1948,60, 255.K. Linderstrom-Lang and M. Ottesen, Nature, 1947,159, 807.1z9 N. Eeg-Lamen, K. Linderstrom-Lang, and M. Ottesen, Arch. Biochem., 1948,19,310.129a M. Kaminski and P. Grabar, Bull. SOC. Chim. biol., 1949, 31, 684.130 P. Grabar and M. Kaminski, ibid., 1950,32, 620.131 M. Heidelberger and P. H. Maurer, Ped. Proc., 1950, 9, 383.132 D. Gitlin,H.Latta, W.H.Batchelor, and C. A. Janeway, J . Immunol., 1951,66,461.133 L. R. Wetter and H. F. Deutsch, Arch. Biochem., 1950,28,399 ; R. 0 Pmdhommeand P. Grabar, Bull. SOC. Chirn. bwl., 1947,29, 122262 BIOCHEMISTRY.coupling with diazo-compounds, on the amount of precipitate formed withantiserum; and Grabar and Kaminski 130 studied the effects of conversionto plakalbumin, diazotization, acetylation, denaturation by heat and shakingand of ultrasonic vibration.Proteins that no longer have the absorptionbands of aromatic rings are still antigenic.133 Malkiel 134 considers thatantigenic groups are uncovered by ultrasonic vibration of virus. Klecz-kowski 135 has studied the ratios of serum to bushy stunt virus that, onbeing heated, form complexes that do not form precipitates with antiserumto bushy stunt virus. After treatment of red blood cells with trypsin andother enzymes, they are agglutinated by incomplete anti-Rh antibodies ;fresh antigenic groups may be uncovered by this treatment.136Antisera have been made against sheep serumproteins coupled with diazotised p-aminosuccinanilic acid l3’ and 4-amino-phthalic acid.138 From the effects of various haptens on the amounts ofprecipitate formed by the antisera with ovalbumin azo-compounds, it isinferred that the normal configuration of succinanilic acid is cis, and thatthe two negatively charged groups of the phthalate ion are attracted byone or two positively charged groups of the antibody molecule.Crossreactions between benzanthryl-carbamido-proteins have been ~tudied.13~Antisera may contain considerable amountsof antibodies to small impurities in the antigen used for immunization.These may be detected (a) by study of precipitation in the zone of antigenexcess and ( b ) by Oudin’s method.By method (a) rabbit antisera against 6 times recrystallised ovalbuminand against ovomucoid may contain antibodies against other constituents ofegg white.140 Rabbit antiserum against conalbumin prepared by ethanolfractionation may contain considerably larger amounts of antibodies toother constituents ; horse antiserum against 3 times recrystallized ovalbuminmay contain more anti-conalbumin than anti-o~albumin.~~~ Rabbit andguinea pig antitoxic sera contain antibodies against bacillary proteins otherthan diphtheria toxin; antisera made by immunizing human beings withpurified toxin contain antibody to the toxin only.52 Pope and his col-leagues 1 4 l found [methods (a) and (b)] that toxic filtrates of C. diphtheria,P.W.8 strain, contain a t least 24 antigens and that routine peptic-refinedantitoxins contain corresponding antibodies.Other antigens besides theactual C. Wekhii a-toxin appear to form precipitates with the a n t i t 0 ~ i n . l ~ ~Method (b) has shown antibodies against 5 antigens in serum against4 times recrystallized ovalbumin; against 2 in serum against 5 times re-Synthetic antigens.Detection and measurement.134 S. Malkiel, J, Immunol., 1947, 57, 51.135 A. Kleczkowski, Biochem. J., 1949, 44, 573.136 W. E. Wheeler, A. L. Luhby, and M. L. L. Scholl, J. Immunol., 1950, 65, 39.137 D. Pressman and L. Pauling, J. Amer. Chem. Soc., 1949, 71, 2893.13* D. Pressman, J. H. Bryden, and L. Pauling, ibid., 1948, ‘90, 1352.139 H. J. Creech, E. L. Oginsky, and F. S. Cheever, Cancer Res., 1947,7, 290.140 M. Cohn, L.R. Wetter, and H. F. Deutsch, J. Imrnunol., 1949,61, 283.141 C. G. Pope, M. F. Stevens, E. A. Caspary, and E. L. Fenton, Brit. J. Exp. Path.,1-32 W. E. van Heyningen and E. Bidwell, Biochem. J., 1950,48, 42. 1951, 32, 246MARRACR : IMMUNOCHEMISTRY. 263crystallized horse albumin ; against 1 only in sera against Armour's crystallhebovine serum albumin; 143(a) against 4 in antiserum against p-lacto-globulin ; lU(b) against 3 antigens in anti-serum against ragweed pollenextract; l44 against 2 antigens in serum against timothy grass pollenextract .I45 There is evidence of antibody against more than one antigenin the precipitation curves with ragweed pollen extract.146The possible presence of such antibodies should be taken into accountwhen effects are attributed to incomplete antibodies, e.g., by Sherman et~ 1 .l ~ ' and by Miller and Cam~be11.l~~When more than antigen and antibody are present the relation betweenantigen and antibody precipitated may fit Heidelberger and Kendall'sequation : 149y = 2R - R2x21-A . . . . (1); or r = 2 8 - R2x/A . . . . (2)where y = antibody in the precipitate, r = ratio of antibody precipitatedto antigen added, R = value of this ratio at the equivalence point, x = anti-gen added, and A = total antibody in the antiserum. Agreement with thisequation cannot be taken as evidence that one antigen only is reacting withone antigen. Evidence of the presence of more than one antigen should besought in the zone of antigen excess.150This formation of antibodies against minor constituents of the antigenhas a bearing on the immunological detection and measurement of antigens.The measurement of y-globulin is complicated by special difficulties : (1) Thesample used for immunization probably contains other antigens ; (2) y-globulin is not a homogeneous substance ; 8 components of bovine y-globulinhave been distinguished by convection-electrophoresis ; 151 yl- and y2-globulins of human serum differ as antigens ; the T- and the y-globulinsof sera of horses immunized.with tetanus toxin differ as antigens, but cross-react; 152 (3) globulins may differ in electric charge without differing anti-genically, and vice versa.Immunological estimates of the y-globulin content of human serum areoften considerably higher than electrophoretic estimates.153-155 This dis-143 (a) J. Munoz and E. L. Becker, J . ImmumZ., 1950,65, 47; ( b ) H. F. Deutsch, J .144 E. L. Becker and J. Munoz, Proc. SOC. Exp. Biol. Med., 1949, 72, 287.145 J. R. Marrack, Internat. Arch. Allergy Appl. Immun., 1951,2, 264.146 S. C. Bukantz, M. C. Johnston, and S. Hampton, J . Allergy, 1949, 20, 1.14' W. B. Sherman, A. E. 0. Menzel, and P. M. Seebohm, J . Exp. Med., 1950,93,191.148 H. Miller and D. H. Campbell, Ann. Allergy, 1947, 5 , 236.160 M. C o b , L. R. Wetter, and H. F. Deutsch, J . Immunol., 1950,64,381.lS1 J. R. Cam, R. A. Brown, and J. G. Kirkwood, J . Biol. Chem., 1949,181, 161.lSla H. F. Deutsch, R. A. Alberty, L. J. Gosting, and J. W. Williams, J . Immunol.,152 B.V. Jager, E. L. Smith, B. Bernhisch, and L. A. Jager, J . Immunol., 1950,65,lS4 B. V. Jager, E. L. Smith, M. Nickerson, and D. M. Brown, J . Biol. Chem.. 1948,Biol. Chem., 1949, 90, 543.M. Heidelberger and F. E. Kendall, J . Exp. Med., 1935, 61, 563.1947, 56, 183.311.176, 1177.153 F. E. Kendall, J . Clin. Invest., 1937, 16, 921.165 B. V. Jager and E. L. Smith, J . Clin. Invest., 1951, SO, 652264 BIOCHEMISTRY.crepancy may vary with the sera tested and the antiserum used for testing ;the antisera may react with human sera from which y-globulin has beenremoved, and Oudin's method may show more than one antibody other thanthat against y-gl0b~lin.l~~ Cohn and his colleagues found evidence of morethan one antigen in preparations of y,-globulin that Kabat and Murray,156and Jager and his had considered homogeneous.However,Kabat and Murray found no evidence by Oudin's method of more than oneantibody against globulin in their a n t i ~ e r a . 1 ~ ~In those cases 157, 162 in which immunological and electrophoretic estimatesagreed, the antisera used may have contained antibody to y-globulins only.Immunological methods have been used to detect and measure manyantigens. Estimates of the albumin content of serum have agreed withelectrophoretic estimates over a wide range of albumin concentrations ; 15*but discrepancies up to 16% may occur. Albumin has been determined innormal urine.159 The synthesis of serum albumin by liver slices has beendemonstrated.160 The concentrations of albumin and y-globulin in cere-brospinal fluid,W 162 and of y-globulin in the serum of a patient with idio-pathic hypoproteinaemia,162 have been measured.Antigenic differenceshave been found between the abnormal y-globulins in serum of patientswith multiple myelomatosis ; 163 these proteins also differ in physicalproperties.The immunological relations of a serum protein that formed a gel oncooling 164 and of the proteins involved in the thymol-turbidity reactionhave been studied.15' The proteins (acute-phase proteins) that occur inthe serum of human beings, monkeys, and rabbits in the early stages ofinfections, after injection of vaccines and after injuries, have been measuredimmunologically with rabbit 165 and fowl antisera.la6 This protein forms aprecipitate with the C-polysaccharide of pneumococci ; the preparation ofthe polysaccharide that forms a precipitate with the rabbit protein differsslightly from that of the polysaccharide which forms a precipitate with166 E.A-Kabat and J. P. Murray, J . BioE. Chem., 1950,182,251.167 J. R. Marrack, R. G. S. Johns, and H. Hoch, Brit. J . Exp. Path., 1950, 31, 36.16* B. F. Chow, F. Hornburger, S. De Biase, and M. L. Peterman, J . Lab. Clin. Med.,1948, 33, 1052; D. Gitlin, C. S. Davidson, and L. H. Wetterlow, J . Immunol., 1949, 63,413; B. V. Jager, T. B. Schwartz, E. L. Smith, M. Nickerson, and D. M. Brown, J . Jab.Clin. Med., 1950, 35, 76.lSs J. R. Marrack and R. G. S. Johns, Biochem. J . , 1950,47, xxxi.180 T. Peters, jnr., and C. B. Anmen, J .Biol. Chem., 1950,182, 171.161 E. A. Kabat, M. Glusman, and V. Knaub, Amer. J . Med., 1948, 4, 653; E. A.Kabat, D. A. Freedman, J. P. Murray, and V. Knaub, AmeT. J . Med. Sci., 1950,219, 55.lsa E. A. Kabat, A. Wolf, A. E. Bezer, and J. P. Murray, J . Exp. Med., 1951,93,615.183 F. H. Wuhrmann, C. Wunderly, and A. Hassig, Brit. J . Exp. Path., 1950, 31,507; F. H. Wuhrmann, C. Wunderly, and P. de Nicola, 2. Klin. Med., 1950, 147, 73;H. G. Kunkel, R. J. Slater, and R. A. Good, Proc. SOC. Exp. Biol. Med., 1951,76, 190.184 H. C. Lucey, E. Leigh, H. Hoch, J. R. Marrack, R. A. Kekwick, and E. R.Holiday, Brit. J . Exp. Path., 1950, 31, 380.166 H. C. Anderson and M. McCarty, J . Exp. Med., 1950, 93, 25; H. F. Wood andM. McCarty, J . Clin. Inuest., 1951,30, 616MARRACK : IMMUNOCHEMISTRY.265the human protein.166 The human protein has been crystallized.167 Thealbumin of cow’s milk appears to be identical with serum albumin; 167ap-lactoglobulin is a contaminant of milk albumin but is distinct from anycomponent of serum.l67&The iron-storing protein, ferritin, has been determined in various organsof dogs 168 and in horses’ intestines.169 It has been shown to be immuno-logically similar to the vasodepressor substance formed in the livers of dogssuffering from shock after bleeding ; the vasodepressor is inhibited by anti-serum to ferritin.168 Removal of the iron (forming apoferritin) does notaffect the reaction with antiserum.168The amounts of ovalbumin, c~nalburnin,~~~ ovomucoid,133 and lyso-zyme 170 found immunologically in egg white agree with amounts found byother methods.Hen serum albumin is not identical with conalbumin (asclaimed by Hektoen and Cole 171). The amounts of conalbumin and oval-bumin in the serum of laying hens, non-laying hens, cocks, and chick embryoshave been measured.172 Preparations of virus grown in eggs contain con-siderable amounts of chick embryo proteins ; formalinized virus reacts withantisera to formalinized ovalbumin, ovoglobulin, hen serum albumin, andglobulin.172~ The precipitation curves of extracts of Br. melitensis, Br.abortus, and Br. suis with homologous and heterologous antisera suggest thepresence of a common antigen and minor antigens.173 Phenol extracts ofB. anthracis contain several antigens ; none of these precipitates the protectiveantibody.17*Blood Group Substances.-Reviews of work up to 1947 and 1948 are givenby Morgan 175 and Kabat.176 Blood group substances are recognized bytheir ability to inhibit agglutination of red blood cells of the correspondinggroup by the corresponding agglutinins.They have, t o a varying degree,two serological properties : (1) inhibition of lysis of sheep red cells byrabbit anti-A sera (Ly); (2) formation of precipitates with horse TypeXIV antipneumococcal sera (XIV). Certain animal sera agglutinate group0 red cells preferentially. It was supposed that these reacted with thespecific 0 antigen, the product of the O-gene; substances prepared fromvarious sources inhibit this agglutination and have been called 0 groupsubstances.Genuine human anti-0 sera have now been found; agglutin-166 H. C. Anderson and M. McCarty, J. Exp. Ned., 1951,93, 25.167 M. McCarty, ibid., 1947,85,491.1670 €3. D. Polis, H. W. Shmukler, and J. H. Custer, J . Biol. Chem., 1950, 187, 349.167b E. J. Coulson and H. Stevens, ibid., p. 355.16* A. Mazur and E. Shorn, ibid., 1950,182, 607.169 B. W. Gabrio and K. Solomon, Proc. SOC. Exp. Biol. Med., 1950, 75, 124.17* L. R. Wetter and H. F. Deutsch, J. Biol. Chem., 1951, 192, 237.1 7 1 L. Hektoenand A. C. Cole, J. Inf. Dis., 1928,42, 1.17% M. E. Marshall and H. F. Deutsch, J. Biol. Chem., 1951,189, 1.1724 L. L. Engel and R. Randall, J. Immunol., 1947, 55, 325, 331.173 S. J. Silverman and S. S. Elberg, &bid., 1950, 65, 163.174 A.Staub and P. Grabar, Ann. Inst. Pasteur, 1947,73, 1.175 W. T. J. Morgan, Experientia, 1947, 3, 7.1 7 6 E. A. Kabat, Bact. Reviews, 1949,13, 1872 66 BIOCHEMISTRY.ation of 0 red cells is not inhibited by the so-called O-substance and mostof the so-called anti-0 sera are not specific for the product of the 0-gene.177lt is considered that the so-called O-substance is a basic substance presentto varying degrees in all human red cells, and Morgan and Watkinssuggest that the O-substance should be renamed H-substance. This nameis used in this review in place of O-substance. Morgan and Watkins 177and Grubb 178 discuss the relationships of the A, B, and 0 agglutinogens.Preparations from individual hog stomachs may have A activity, H activity,or both activities ; 1793 lS0 preparations from ovarian cysts of group A womenhave A activity only.lsl Methods of preparation of A-substance arereported by Brown et uZ.lS2Human A substances prepared from saliva, amniotic fluid, and stomachcontain similar amounts of reducing sugar, hexosamine, and acetyl groups ;they resemble hog-stomach A substance.l S 3 By paper chromatography itwas found that human A substances contain hexosamine, galactose ;mannose and fucose; mannose was not found in hog-stomach A substancebut in varying amounts in A substance from other s0urces.~8* HumanA substance contains both glucosamine and galactosamine.184a Acidhydrolysis of human A substance increases the reducing power and liberatesfucose.lS5 Kabat and his colleagues estimated the amount of fucose inA- and H-substances from various sources : 186 that from human salivacontains most and that from cattle stomach least.lS7 It is inferred that thepolysaccharide component consists of long chains with fucose a t the ends(as found by Bray et ~ Z .1 ~ 8 ) . The simplest polysaccharide unit of humanA-substance from ovarian cysts is composed of L-fucose, D-galactose, andN-acetyl-D-hexosamine ; a t least eleven amino-acids can be detected ;threonine occurs in larger proportion than in most proteins.lSg Vunakisand Kabat found six amino-acids set free from blood group substances;they suggest that part of the group substance may be a peptide chain withaspartic acid residues in alternate positions.l90Blood group substances from cow stomachs resemble those from hog andW. T. J. Morgan and W. M. Watkins, Brit. J . Exp. Path,, 1948,29, 159.1 7 8 R. Grubb, Acta Path. Micr. Scand., 1949, Suppl. LXXXIV.17@ A. Bendich, E. A. Kabat, and A. E. Bezer, J. Exp. Med., 1946,83,485.la0 A. Bendich, E. A. Kabat, and H. Baer, J . Amer. Chem. SOC., 1947,69,263.lal D. Aminoff, W. T. J. Morgan, and W. M. Watkins, Nature, 1946,158, 874.lea D. H.. Brown, E. L. Bennett, G. Holtzmann, and C . Niemann, Arch. Biochem,la3 E. A. Kabat, A. Bendich, A. E. Bezer, and S. M. Beiser, J . Exp. Med., 1947,85,685.la* S. M. Partridge, Biochem. J . , 1948,42, 251.184O D. Aminoff and W. T. J. Morgan, Nature, 1948,162,579.la6 Idem, Biochem. J., 1948,43, xxxvi.la6 ( a ) E.A. Kabat, H. Bmr, A. E. Bezer, and V. Knaub, J . Exp. Med., 1948,88,43;1947, 13, 421.( b ) H. Baer, E. Dische, and E. A. Kabat, ibid., p. 59.E. A. Kabat, R. L. Day, and V. Knaub, Ped. Proc., 1950,9,376.lea H. G. Bray, H. Henry, andM. Stacey, Biochem. J., 1946,40, 124.18@ D. Aminoff, W. T. J. Morgan, and W. M. Watkins, ibid., 1950,46, 426.lB0 H. van Vunakis and E. A. Kabat, J. Amer. Chem. Soc., 1951,73,2977MARRACK : IMMUNOCHEMISTRY. 267human sources.191 Substances from horse stomach contained less hexos-amine and reducing sugar and more total and non-hexosamine-N than dosubstances from other species. B-Group substance from human saliva re-sembles other human and hog group sub~tances.1~~ H-Substance from hogstomach resembles the A - s ~ b s t a n c e .~ ~ ~ The enzyme of CZ. WeZchii (Type B)filtrates that inactivates human H-substance differs from that which destroysthe A- and B-~ubstances.~94 Le-Group substances are inactivated by CZ.Welchii filtrates that do not inactivate H-substance.lg5Kabat and his colleagues 179y l S o 9 lS3, lg6, lg7 have studied the quantitativeserological reactions of blood group substances in three ways : (1) by com-paring the amounts of antibody in an antiserum against a group substance" G, " that is precipitated by G, and a similar substance, " G2 " ; (2) bycomparing the amount of GI and G, needed to precipitate a given amountof antibody from anti-Gl serum; and (3) by finding how much of Gl andG, are precipitated by antiserum. The glucosamine 179 or methylpentose lg7of the antigen serves as a marker ; the marker is measured in the precipitateand the proportion precipitated is calculated.Data from (1) and (2) maybe regarded as measures of the degree of serological resemblance betweenG, and G,, although more of G, than of G, may be needed to precipitate agiven amount of antibody if G, contains substances, other than G,, thathave not given rise to antibodies. This last point is settled by method (3).In estimations of glucosamine or methylpentose precipitated, corrections aremade for the solubility of the precipitate and for the apparent glucosamineor methylpentose content of the antibody protein in the precipitate. Theapparent glucosamine and methylpentose contents of human y-globulinhave been estimated ; l98 the correction for protein methylpentose mayamount to 30% of the tota1.1g7 The estimation of glucosamine in the pres-ence of relatively large amounts of protein has been criticized,lg9 and Holz-mann and Niemann200 consider that group A substances extracted fromhog stomachs are not homogeneous.The upshot of investigations by thethree methods is that human A-substance from saliva or ovarian cysts isserologically very similar to hog stomach A-substance and that most or allof the hexosamine and methylpentose in these substances is in material thatacts as antigen. Horse and cattle substances are less closely related to hogstomach A-substance. It is significant that A-substance from hog stomachand that from human ovarian cyst react similarly with an antibody in thelgl S.M. Beiser and E. A. Kabat, J . Amer. Chem. SOC., 1949,71, 2274.lQ2 H. Baer, E. A. Kabat, and V. Knaub, J . Exp. Med., 1950,91, 105.lg3 H. Baer, E. A. Kabat, and A. E. Bezer, J . Amer. Chem. SOC., 1947,69, 2163.lQ4 W. T. J. Morgan, Nature, 1946,158, 759; M . J. Stack and W. T. J. Morgan, Brit.lQ5 R. Grubb and W. T. J. Morgan, Brit. J . Exp. Med., 1949,30, 198.lg6 E. A. Kabat and A. E. Bezer, J . Exp. Med., 1945, 82, 207; E. A. Kabat, A.lQ7 E. A. Kabat, H. Baer, and V. Knaub, ibid., 1949,89, 1.lQ8 S. M. Beiser and E. A. Kabat, J . Amer. Chem. SOC., 1951,73, 3501.lQ9 R. G. S. Johns and J. R. Marrack, Biochem. J . , 1951, 50, xvii.J . Exp. Path., 1949, 30, 470.Bendich, and A. E. Bezer, ibid., 1946, 83, 477.S.Holtzmann and C. Niemann, J . Amer. Chem. SOC., 1950, 72, 2048268 BIOCHEMISTRY.serum of a woman immunized by human A-substance absorbed from afcetus in utero.201 B-Substance from cattle stomachs forms precipitates withhuman antisera against horse stomach B-substance but not with antiseraagainst hog or human B-substance. Antisera against cattle stomachB-substance form precipitates with all group substances prepared fromcattle.202Preparations of blood group substances and, presumably, molecules ofthese substances may have more than one serological specificity, and thesespecificities may be independent. Treatment with dilute acid destroys theactivity of human A-substance measured by inhibition of isoagglutination,whereas the haemolytic inhibition (Ly) is in~reased.18~ Crude extracts ofCZ.Wekhii destroy the first activity, but not the second; a purified enzymedestroys both activities.lg4 Substances with either A, B, H, AH, or BHactivity prepared from cattle have little Ly activity. Various samples ofblood group substances form precipitates with horse Type XIV anti-pneumococcal sera ; this activity and isoagglutination vary inde-pendently.lg2, 203 Morgan’s preparations of A-substance from ovarian cystsdid not form precipitates with Type XIV anti-sera.lsg There is an inverserelation between the degree of reaction with the Type XIV anti-sera andthe fucose content of hog A- and H-substances but not of human or cattle,A-, B-, and H-substances.la6 On acid hydrolysis of these substances,fucose is split off and reaction with anti-XIV sera increased, while the iso-agglutinin activity is lost .lS6 (b), The ratio of minimal amounts of humanH-substance that will inhibit the agglutination of 0 red cells by a serumto the minimal amount of hog H-substance that will inhibit agglutinationby the same serum varies with the serum (human, rabbit anti-human-H,eel, chicken anti-Shiga, goat anti-Shiga, or cow) used.204 A lipoprotein(called elinin) obtained from stromata of red blood cells carries the A, B,and Rh activities of the ~ells.~O~ A claim to be able to isolate Rh-groupsubstance 206 has not been confirmed.207Labelled Antigens and Antibodies.-Many investigations have been madewith labelled antigens and antibodies.In particular, advantage has beentaken of the possibility of introducing a radioactive isotope into an antigenor antibody molecule with little or no change in serological properties.Antibodies and protein antigens, labelled with a small amount of 1311, reactlike untreated protein and are stabIe.79,208~209 The specific reactions ofaol E.A. Kabat, H. Baer, R. L. Day, and V. Knaub, J . Exp. Med., 1950,91,433.20* E. A. Kabat, A. Bendich, A. E. Bezer, and V. Knaub, J . Exp. Med., 1948,87,295.104 E. F. Annison and W. T. J. Morgan, Nature, 1950,165, 884.205 M. Moskowitz, W. B. Dandliker, M. Calvin, and R. S. Evans, J . Immunol., 1950,65,383 ; W. B. Dandliker, M. Moskowitz, B. H. Zinn, and M. Calvin, J . Amer. Chern. SOC.,1950,72,5587.207 C. C. Price, D.H. Read, T. J. Bardos, and C. Chen, J . Arner. Chem. SOC., 1948,70,3527; C. Howe and R. Rustigian, J. Immunol., 1950, 64, 505; F. Stratton and P. H.Renton, Lancet, 1950,1, 328; D. A. Osborn, J . Clin. Path, 1951,4, 470.208 H. M. Eisen and A. G. Keston, J . Immunol., 1949,63, 71.S. M. Beiser and E. A. Kabat, Fed. Proc., 1950, 9, 377.B. B. Carter, J . Irnmunol., 1949,61, 79.W. C. Knox and F. C. Endicott, ibid., 1950,65,523W R A C K : IMMUNOCHEMISTRY. 269protein coupled with a label by an azo-link are modified; also the azo-compounds are less stable.208 Methods of labelling with radioactive isotopesare described in individual papers and in a paper by Francis et aZ.209aColoured antigens have been made by attaching dyes, particularlyEvan's-blue, to proteins by an a~o-link.~lO-~l* These disappear rapidly fromthe plasma; they are taken up by reticulo-endothelial cells.The half-lifein the tissues is 2-7 days; 214 some colour may be detectable for severalmonths; after 2 days the antigen in the cytoplasm of liver cells still fixescomplement in the presence of antiserum.210Proteins labelled with 1311 have been injected into veins and their disposalhas been f~llowed.~l~ Estimates of the concentration of labelled bovineserum albumin made by radioactivity agree with estimates made withantiserum up to the seventh day; after this, there is evidence of iodinewithout the protein.209 The decline of concentration of heterologous globulinin the plasma runs parallel to that of homologous globulin up to about thefifth day; after this, the homologous globulin content continues to fall a tthe same rate as before, while the heterologous globulin disappears216 Elimination of heterologous protein antigen from the cir-culation of non-immunized animals takes place in three stages : distributionduring the first day, steady decline for about 4 days, and then rapid decline.Injection of antibody is followed by a rapid fall.If an animal has beenimmunized before with the same protein, and antibodies are present in thecirculation, the antigen is completely removed in 3 days; if it has beenimmunized beforehand, but no detectable antibody is present in the circula-tion, rapid elimination begins after 2 days. On the other hand, if theanimal is X-rayed and formation of antibody thereby inhibited, eliminationafter 7 days resembles elimination of homologous protein.The appearanceof circulating antibody coincides with the disappearance of the antigen.Shortly after injection into sensitized guinea pigs, labelled bovine y-globulinand ovalbumin are specially localized in the bronchial fibrousLater, the labelled proteins are not retained or concentrated in any tissues.214When antibody is present the antigen is rapidly broken down, as shown bythe iodine split 0ff.215Labelled serum albumin persists in the circulation longer than serumglobulin ; 214y 217 no localization or retention was found, but the maximumzogo G. E. Francis, W. Mulligan, and A. Wormall, Nature, 1951, 167, 748.zlo H. Kruse and P.D. McMaster, J . Ezp. Med., 1949,90, 425.811 P. D. McMaster and H. Kruse, Fed. Proc., 1950, 9, 387.alz H. Latta, D. Gitlin, and C. A. Janeway, Arch. Path., 1951, 51, 260.21s D.Gitlin,H.Latta,W.H.Batchelor,andC.A. Janeway, J. Immunol., 1951,66,451.a14 S. G. Bukantz, F. J. &ton, G. J. Dammin, and D. W. Talmadge, Fed. Proc.,1951, 10, 404.z16 F. J. Dixon, S. G. Bukantz, G. J. Dammin, and D. W. Talmadge, Fed. Proc.,1951, 10, 553 ; D. W. Talmadge, F. J. Dixon, S. C. Bukantz, and G. L. Dammin, ibid.,p. 421.zlr Idem, J . Immunol., 1951, 67, 243; S. Warren and F. Dixon, Amer. J. Med. Sci.,1948, 216, 136; F. Dixon and S. Warren, ibid., 1950, 319, 414.11' H. Latta, J. Immunol., 1951,66,635.270 BIOCHEMISTRY.sensitivity of the method was not used.217 Crampton and Haurowitz218found that labelled iodoprotein antigens were first fixed in the microsomesof the liver and, later, in the mitochondria and nuclei; radioactivity couldbe detected in mitochondria after 29 days.219 Heterologous y-globulin canbe detected in the liver by an anaphylactic test up to 70 days after injection.211Wormall and his colleagues 220* 221 have prepared vitellin and lipovitellinlabelled with 32P from the eggs of hens that had received injections of 32Pas inorganic phosphate. A large proportion of labelled lipovitellin, injectedinto veins of mice, was found in the lungs 2 minutes after injection; later, alarge proportion of the 32P was found in the liver.222 Labelled vitellin andserum proteins labelled by phosphorylation with 32POCl, also accumulatedin the lungs and liver.223 Tobacco mosaic virus labelled with 32P injectedintraperitoneally into mice is concentrated mainly in the liver.Almost allthe virus is gone by the sixteenth day.224Coons and Kaplan 225 have improved the method of making a fluorescentantibody by conjugating the proteins of antisera with fluorescein isocyanate.The fluorescent antibodies have been used to trace the distribution and lifeof bacterial polysaccharides 226 and foreign proteins 227 injected intravenouslyinto mice. These antigens appear in high concentration in phagocytic cells,in hepatic cells, and in cells of kidney tubules. Egg albumin disappearswithin a few hours, serum albumin in about 2 days, and y-globulin in abouta week.Protein antigens or degradation products are seen in cell nuclei(cf. ref. 219). Polysaccharides persist for months. Rickettsiae of epidemictyphus and Rocky Mountain spotted fever can be detected with fluorescentantibodies in the cells of liver and spleen of infected cotton rats and the gastro-intestinal tracts of infected lice,228 and mumps virus in the parotids andbrains of infected monkeys.229 Sk Virus and Theiler’s GD VII straincannot be detected; nor can poliomyelitis virus be found in monkey spinalcord or brain, or in tissue cultures from human skin and brain.230 A shortreview is given by Coons.230 Similar fluorescent antibody was used to locatepig ACTH in the cytoplasm of cells of pig’s pituitary.231Injected antibodies, homologous or heterologous, are removed from the218 C.F. Crampton and F. Haurowitz, Science, 1950,112, 300.21D F. Haurowite, C. F. Crampton, and R. Sovinski, Fed. Proc., 1951,10, 560.220 J. C. Boursnell, H. M. Dewey, G. E. Francis, and A. Wormall, Nature, 1947, 160,222 T. E. Banks, G. E. Francis, K. J. Franklin, and A. Wormall, ibid., 1950,47, 374.2e3 T. E. Banks, J. C. Boursnell, H. M. Dewey, G. E. Francis, R. Tupper, and A.22p R. L. Libby and C. R. Madison, J. Immunol., 1947,55, 15.22s A. H. Coons and M. H. Kaplan, J . Exp. Med., 19m, 91, 1.OZ6 M. H. Kaplan, A. H. Coons, and H. W. Deane, ibid., p. 15; A. G. S. Hill, H. W.227 A. H. Coons, E. H. Leduc, and M. H. Kaplan, ibid., 1951,93,173.228 A. H. Coons, J. C. Snider, F. S. Cheever, and E. S.Murray, ibid., 1950,91, 31.22s T. H. Chu, F. S. Cheever, A. H. Coons, and J. G. Daniels, Proc. Xoc. Exp. Biol.230 A. H. Coons, Fed. Proc., 1951,10, 558.831 J. M. Marshall, J . Exp. Med., 1951, 94, 21.339. 221 G. E. Francis and A. Wormall, Biochem. J., 1948, 42, 469.Wormall, ibid., 1948, 43, 518.Deane, and A. H. Coons, ibid., 92, 35.Med., 1951, 76, 571MARRACK : IMMUNOCHEMISTRY. 271circulation at about the same rate as other y-globulin. Kooyman andCampbell 232 found evidence that rabbits incorporated some 14C-labelledleucine, injected intraperitoneally , into injected homologous antibody ; theradioactivity of antibody, formed by the rabbit itself, increased up to36 days after the last injection of antigen, 24 days after the last injection of[14C]leucine. The life of antibodies made by rabbits in response to injectedtobacco mosaic virus is not more than 7 da~s.22~Pressman and his colleagues233 have studied the localization of anti-kidney and anti-lung antibodies labelled with 1311. Anti-kidney antibodiesare fixed in kidneys, lungs, and liver.234 Radiographs show that anti-kidneyantibodies and also anti-lung and anti-ovalbumin antibodies are localized inthe g l o m e r ~ l i .~ ~ ~ , ~ ~ ~ The life of the anti-ovalbumin antibodies in the glo-meruli is much shorter than that of those of anti-kidney and anti-lung anti-bodies; the fixed anti-kidney and anti-lung antibodies are protected fromthe usual process of metab0lism.2~7 The antibodies are fixed in the kidneywithin 18 minutes after injection.236 Mouse kidney is not saturated by15 mg.of anti-kidney globulin.238 Homogenates of kidney and lung absorbfrom anti-kidney serum much of the antibody that is localized in the kid-ney.237 The absorbed antibodies can be eluted with weak alkali, but notwith saline or weak a ~ i d . ~ ~ ~ ~ The eluted antibodies are fixed specifically bythe tissues from which they are eluted.239 Better auto-radiographs can begot by using antibodies labelled by coupling with diazotized sulphanilic acidcontaining 35S.240 These investigations have been reviewed by Pressman.241The precipitates formed by antigen and antibody do not carry downunrelated proteins ; this has been shown with lipovitellin labelled with32P 221?242 and with serum proteins labelled with l3lI.'6 When antigen,antibody, or both are labelled, the amounts of each can be estimated inspecific precipitates.Proteins labelled with 1311, lipovitellin anti-gens 220s 221, 2423 243 labelled with 32P, proteins labelled with 15N " nitrogenmustard " 244 and with 35S " mustard gas sulphone " (bis-2-chloroethylsulphone) 245 have been used. The ratio of pho~pholipid-3~P to p r ~ t e i n - ~ ~ P232 E. C. Kooyman and D. Campbell, J. Amer. Chem. Soc., 1948,70, 1293.233 D. Pressman and G. Keighley, J. Immunol., 1948, 59, 141.234 D. Pressman, ibid., 1949, 63, 375.235 D. Pressman, R. F. Hill, and C. W. Foote, Science, 1949,109, 65.2s6 D. Pressman, H. N. Eisen, and P. J. Fitzgerald, J. Immunol., 1950, 69, 281.237 H. N. Eisen, B. Sherman, and D.Pressman, ibid., 65, 543.238 D. Pressman and H. N. Eisen, ibid., 64, 270.2380 H. N. Eisen and D. Pressman, ibid., p. 487.299 D. Pressman and B. Sherman, Fed. Proc., 1951,10,416.a40 D. Pressman, H. N. Eisen, M. Siegel, P. J. Fitzgerald, B. Sherman, and A. Silver-242 C. E. Francis and A. Wormall, Biochem. J., 1950,47, 380.243 T. E. Banks, G. E. Francis, W. Mulligan, and A. Wormall, Biochem. J., 1951,244 V. C. E. Burnop, D. E. Richards, W. M. Watkins, and A. Wormall, Nature, 1951,245 J. C. Boursnell, H. M. Dewey, G. E. Francis, and A. Wormall, ibid., 1947, 160,stein, J . Immunol., 1950, 65, 559. 241 D. Pressman, Fed. PTOC., 1951,10,568.48, 180; Nature, 1950, 165, 111.168, 251.339; G. E. Francis, W. Mulligan, and A. Wormall, Biochem.J., 1950, 48, xxxvi272 BIOCHEMISTRY.in precipitates formed by lipovitellin with antisera is higher than in thelipovitellin added, suggesting that the serum contains antibodies againstthe phospholipid.221, 243, 246 Antibodies labelled with 13lI have been779 243 The amount of antibody calculated from radioactivity wasslightly less than that calculated from estimations of nitrogen.76 Themolecular ratio of antigen to antibody in precipitates formed by lipovitellin(labelled with 32P) and antibody (labelled with 1311) is very high.243The effect of hapten on the amount of precipitate formed by iodinatedprotein with antisera was No appreciable amount of inhibitorwas found in precipitates ; it was concluded that antibodies are univalent.Mechanism and Quantitative Aspects.- Valency of antibodies.Eisen andKmush 46 measured the amount of hapten bound by purified antibody andconcluded that one antibody molecule can combine with 2 molecules ofhapten. The number of antigen molecules combined with an antibodymolecule when antigen is in great excess has been calculated from theelectrophoretic patterns ; 248, 249 the number is over 1 and there is evidenceof a compound of 2 molecules of antigen to one of antibody. The maincomponent detected by the ultra-centrifuge corresponds to this compound.249The agglutination reaction described by Coombs et seems to involveantibodies with two valencies. Lanni and Campbell251 could find noevidence of antibody molecules which combined with two different antigens.Further experiments have favoured the specificity of the second stage ofagglutination reaction ; quantitative aspects of the theory are disc~ssed.~~2Heidelberger andKendall 149 found that in some cases the plot of the ratio, antibody precipit-ated : antigen added, against antigen was a straight line [equation 2 (p.263)].When special care had been taken to ensure that only one antigen-antibodysystem was involved, or when either antigen or antibody was labelled, thislinear relation was found in some instances, viz. : diphtheria toxin withhuman, monkey, or rabbit antisera freed from antibodies against bacillaryprotein ; 52 ovalbumin with rabbit antiserum ; 140 human serum albuminwith iodinated rabbit antiserum, except when x was small.78 Less good fitwas obtained in the systems bovine serum albumin with rabbit antiserurn,l43or rabbit antiserum with ferritin, which could be estimated by the ironcontent and was precipitated completely in the region of antibody excess.168This linear relation has been found in the reaction of rabbit-antisera withQuantitative relations between antibody and antigen.t 4 6 G.E. Francis and A. Wormall, Nature, 1950, 47, 380.94’ T. E. Banks, C. E. Francis, W. Mulligan, and A. Wormall, Biochem. J., 1951,48,$48 J. R. Marrack, H. Hoch, and R. G. S. Johns, J . Gen. Microbiol., 1949, 3, xxviii;S. J. Singer and D. H. Campbell, Fed. Proc., 1951,10, 418; J . Amer. Chem. SOC.,$50 R. R. A. Coombs, M. H. Gleeson-White, and J. G. Hall, Brit. J . Exp. Path.,952 H.Umezawa, Jap. Med. J., 1948, 1, 51, 58, 89; K. W. McKerns and 0. F.xxxvi, 371.Biochem. J., 1951, 48, xxi; Brit. J . Exp. Path., 1951, 32, 212.1951, 73, 3543.1951, 82, 195.Denstedt, Canad. J . Res., 1949, 27, E , 164.261 F. Lanni and D. Campbell, Stanford Med. Bull., 1948, 6, 97MaRRACH : IMlvIUNOCHEMISTRY. 273human and horse y-globulin; 1529154 but good fits were found when T wasplotted against d. The equations are not applicable to virus-antiviruss~stems,25~ The precipitin reaction of botulinus toxin with antiserum iscomplicated by non-specific precipitation of serum proteins by the toxin.254Antigens precipitate both a-globulin and y-globulin from antisera pre-pared in domesti'c fowls; 254a the amount of precipitate is much increased ifthe concentration of salt is raised.255 Kabat et al.have made quantitativestudies on anaphylaxis.256 Those made up to 1947 have been summarizedin a convenient form by Kabat.257Results of thermodynamic studiesare given in the following Table; data for binding of orange I by ox serumalbumin are given for comparison.Thermodynamic and kinetic aspects.Kcal . /mole Cal . /mole/I A\ degreeSystem AF" AHo AS" KHsemocyanin ; horse anti-serum 261 40Arsanil-azo-bovine serumglobulin ; rabbit anti-serum 210 about -8.5 - 2 21 106-107Sulphanil-azo -ovalbumin ;rabbit antiserum 21nAnthranil-azo -bovine serumglobulin ; rabbit anti-serum 262Agglutinogens of red bloodcells ; human isoagglutino-gens 258A10AlAA2A,Hapten; rabbit antibody 4 5Orange I ; bovine serumalbumin 263- 8.5- 9.3- 8- 9- 3- 7.7- 6-36- 4.7 to- 4-4- 2.8 21 ¶,about - 70andabout $ ofthis- 21, - 34 2-4 x 107 (40)0.4 x 107 (370)3-5 x 105- 3.91 8.75 9.93 x 104 (50)6-16 x lo* (25")0-19 (25")- 3.50 3.26 0.29 (5")The results given for the isoagglutinin system 258 are calculated on theassumption that all red blood cells to which more than a standard number ofantibody molecules are attached are agglutinated ; a special technique isused to estimate free antibody.In estimating the equilibrium constant,Kabat's absolute figures 259 for the amount of agglutinin in serum were used.The combination of agglutinin and red blood cells is reversible.260 Boyd253 S. Malkiel and W. M. Stanley, J .Imrnuml., 1947,47, 31.254 C. Lamanna and B. W. Doak, ibid., 1948, 59, 231.2540 H. F. Deutsch, J. C. Nicol, and M. Cohn, ibid., 1949,63, 195.256 M. Goodman, H. R. Wolfe, and S . Norton, ibid., 1951, 66, 225.256 E. A. Kabat, G . S . CofKn, and D. J. Smith, ibid., 1947, 56, 377; E. A. Kabatand B. Benacerref, ibid., 1949,62, 97; B. Benacerraf and E. A. Kabat, ibid., 1950,64, 1.257 E. A. Kabat, Amer. J . Med., 1947,3, 535.258 S. Fillitti Wurmser, Y. Jacquot-Armand, and R. Wurmser, J . Chim. phys., 1950,260 S. Fillitti Wurmser and Y. Jacquot-Armand, Arch. Sci. Physiol., 1947, 1, 151.47, 419. 25p E. A. Kabat and A. E. Bezer, J. Exp. Med., 1945,82,207274 BIOCHEMISTRY.et aZ.261 assumed a " reasonable " value of AF" = -10 and got a negativeAX".The two values of AH" given for the antigen anthranil-azo-bovineserum globulin are for firmly and loosely bound antibody. Those for orange Iare for strong and weak dye-albumin bonds.Bowman, Mayer, and Kapp 264 consider that in haemolysis by antisera inpresence of excess of complement, the compound antibody-red cell is disso-ciable and the antibody is transferred from one cell to another, thus actinglike an enzyme.The plots of degree of haemolysis against complement, when complementis not in excess, are sigmoid; this has been ascribed to differences insusceptibilities of the red cells. Albert and Baldwin265 suggest that it maybe due to probability effects alone in a suspension of identical cells.Levine et aZ.266 find a linear relation between log time of flocculation andlog concentration in a mixture of equivalent amounts of toxin and antitoxin.This relation holds for the data of Duncan 267 and of Naylor.268 Thekinetics and equilibrium of reaction between antigens and antibodies havebeen studied by light-scattering methods.Goldberg and Campbell 269consider that all the reactions are bimolecular. Gitlin and Edelhoch 270find that the reaction between horse antibody and antigen is reversible inthe zone of antigen excess but very slowly reversible in the zone of antibodyexcess.Aggregation of dyes. Pardee and Swingle2'l found, in agreement withBoyd and Behnke,272 that the azo-dyes, which Pauling and his colleagues 273had found to form precipitates with antisera, are aggregated in aqueoussolution.Pardee and Pauling found that these compounds are stronglyadsorbed by precipitates formed by an unrelated antibody and antigen andincreased the amount of protein precipitated. Karush 263 has pointed outthat large proportions of various organic compounds added to serum areadsorbed by the albumin and that this affects the quantitative aspects ofreactions between antibody and inhibiting or precipitating dyes. This hasbeen confirmed by Pardee and P a ~ l i n g . ~ ~ ~ It follows that the calculations byPauling and his colleagues,273 based on the results of experiments in whichthese dyes were added t o whole serum, are invalid. Those concerned withinhibition are invalid for one reason-the adsorption of the inhibitor on the261 W.C. Boyd, J. B. Coun, D. C. Gregg, G. B. Kistakowsky, and R. M. Roberts, J .BWZ. Chem., 1941,139,787. F. Haurowitz and L. Etili, Fed. Proc., 1949, 8, 404.363 F. Karush, J . Amer. Chem. Soc., 1949, 72, 2705.864 W. M. Bowman, M. M. Mayer, and H. J. Kapp, J . El~l~l~l~l~l~l~l~l~l~l. Med., 1951,94, 87.266 R. A. Albert and R. L. Baldwin, J . Immunul., 1951,66, 725.266 L. A. Levine, L. Wyman, and G. Edsall, ;bid., 1949,63, 219.2137 J. T. Duncan, Brit. J . Exp. Path., 1934,15, 28.268 C. R. E. Naylor, J . Hyg., 1948, 46, 131.269 R. J. Goldberg and D. H. Campbell, J . Immunol., 1951,66, 79.270 D. Gitlin and H. Edelhoch, ibid., 1951, 66, 67.271 A. B. Pardea and S. M. Swingle, J . Amer. Chem. SOG., 1949,71, 148.372 W. C. Boyd and J. Behnke, Science, 1944,100, 13.273 L.Pauling, et al., J . Amer. Chem. SOG., 1942,63, 3003, 3011, 3015; 1943,65, 728;1944,66, 784; 1948,67, 1003. 274 A. B. Pardee and L. Pauling, ibid., 1949,71, 143MARRACK : IMMUNOCHEMISTRY. 275albumin-and those concerned with the amount of precipitate formed bydye with antiserum for three reasonsthe polymerization of the dye, theadsorption of the dye on albumin, and the co-precipitation of inert protein.Eisen and Karush 46 comment on the large amount of antibody recovered byCampbell et aL41 It is possible that some of this apparent antibody wasinert protein precipitated and re-precipitable by the azo-dye used.According to Pardee and Pauling 274 non-aggregating amides, with morethan one determinant group per molecule, form precipitates with antisera,whereas those with one determinant group per molecule do not.Rothen 275 has published a series of papers in whichhe claimed to show that combination of antigens and antibodies and actionsof enzymes are due to long-range forces.He spread films of antigen orsubstrate, covered these with layers of inert substances, and found that thetotal thickness of the layers increased when antiserum was poured over thefilm of antigen or that there was evidence of breakdown of substrate whenenzyme was poured over the layers. This was criticized by Karush andSiegel 276 on the grounds that the films are uneven, and Iball 277 suggestedthat aggregation of antigen and antibody start at holes in the inert layers(cf. Astbury and Bell 278) and that this aggregation causes cracks.Singer 279also considered that the layers may have irregularities which would not bedetected by Rothen's technique and that diffusion may take place throughholes. Trurnit 280 has found evidence that proteins may be leached outthrough these layers and that the precipitates formed by antibody with theleached-out antigen are deposited on the film.Carroll 281 finds that serum albumin is protected from the action of pepsinwhen its molecules are partly covered by adsorbed orange I and considersthis evidence that the pepsin does not act through long-range forces. Mar-rack l5 suggests that, even when no inert layers intervene, the antibody isnot deposited as a layer on the layer of antigen, but that antigen and antibodyaggregate as usual.Theoretical.Morales et aZ.282 have suggested that the combination ofmultivalent antigens with univalent antibodies is affected by interactionbetween adjacent antibody molecules or effects of translation and rotation.Motales and Botts 283 discuss the packing of antibody molecules on antigenmolecules, both being assumed to be spherical.Methods.-Methods of detecting the presence of more than one antigenin a preparation, or more than one antibody in a serum, have been intro-Long-range forces.275 A. Rothen, Adv. Protein Chem., 1947, 3, 135; J . Biol. Chem., 1947, 168, 75;276 F. Karush and B. M. Siegel, Science, 1948,108, 107.2 7 7 J. Iball, ibid., 1949, 109, 18.2'8 W. T. Astbnry and F. 0. Bell, Nature, 1938,142, 33.27@ S.J. Singer, J . Biol. Chem., 1950, 182, 189.281 B. Carroll, J . Amer. Chem. Xoc., 1950, 72, 2763.282 M. F. Morales, J. Botts, and T. L. Hill, ibid., 1948, 70, 2339.283 M. F. Morales and J. Botts, J . Chem. Phys., 1948,16, 587.J . Arner. Chem. SOC., 1948, 70, 2732.H. J. Trurnit, Science, 1950, 111, 1276 BIOCHEMtSTBY.duced ; 28p these depend on the solubility of antigen-antibody precipitates inexcess of antigen. If antigen diffuses from a solution into a gel which con-tains antibody, an advancing band of precipitate is formed, followed by aclear zone. If the solution contains more than one antigen and the gelmore than one antibody, more than one band is formed. The theory of themethod is discussed .285Forms of this method have been used for examining ovalbumin, bovine,and horse serum albumin,l&(a) human y-globulin,l55,156 p-lactog1obuliny143(b)pollen extracts, 145 cytochrome c,286 egg white constituents,287 anddiphtheria toxin 141 with corresponding antisera. The optimum-proportionsmethod has been further studied.Z68Measurement of ultra-violet light absorption has been used for measure-ment 288 and analysis 289 of antigen-antibody precipitates.Measurement oflight scattering has been used for study of kinetics of the r e a c t i ~ n . ~ ~ ~ ~ 270 Theaccuracy of estimations of antigen-antibody compounds by turbidimetryhas been studied and the method has been used for estimation of serumalbumin.290 Precipitates have been measured by Nessler’s reagent, by thebiuret method, and with ninhydrin ; the methods have been compared.292A falling-drop method has been proposed.293 Coombs and his colleaguesdescribe a method of recognising and titrating antibodies against chemicalsubstances by an agglutination reaction.81J. R.M.3. NICOTINIC ACID.The development of a number of techniques for the estimation of thevarious compounds connected directly or indirectly with nicotinic acid hasgreatly enhanced the knowledge of the metabolic pathways and biogenesisof this vitamin.For the chemical estimation of nicotinic acid or of compounds convertibleinto it, the original Konig reaction is generally used, which involves re-action of the pyridine ring with cyanogen bromide and coupling of the fissionproduct with an aromatic atmine.A number of amines have been suggested :284 M. J. Oudin, Cmpt. rend., 1946,222, 115; Ann. In&. Pasteur, 1948, 74, 30, 109;S. D. Elek, Brit. Med. J., 1948, 1, 493; 0. Ouchterlony, Acta. Path Microbial. Scad.,1948, 25, 186 ; Lancet, 1949, I, 346.285 M. J. Oudin, Compt. rend., 1949,228, 1890.286 E. L. Becker and J. Munoz, J . Immunol., 1949,63, 173.287 M. Kaminski and 0. Ouchterlony, Bull. SOC. Chim. biol., 1951, 33, 158.288 D. Gitlin, J . Immunol,, 1949, 62, 437.I;. A. Leone, and A. Boyden, ibid., 1948,58, 169.289 H. N. Eisen, ibid., 1948,60, 77.A. Boyden, E. T. Bolton, and D. Gemervy, ibid., 1947, 57, 211; E. T. Bolton,291 B. F. Chow, J . Biol. Chem., 1947,167, 751.29* H. C. Kunkel and G. M. Ward, J . Biol. Chem., 1950,182,597.a9!3 M.Lipton, J . Immunol., 1948, 59, 249KODICEK : NICOTINIC ACID. 277aniline , 1 met ol , p - aminoace t ophenone ,3 p - aminopr opiophenone ,4 ort ho-f0~.la,5 procaine,G and others. The great number of papers on this subjectintroducing various modifmations, the discussion of which is outside thescope of this review, indicates that the chemical methods have certaindisadvantages which still have to be overcome and therefore microbiologicalprocedures have gained general acceptance.’Nicotinumide has been estimated colorimetrically and differentiated fromnicotinic acid by comparison of their respective reaction rates.8 More recentlyfluorometric procedures 8a have been worked out which allow the estimationof nicotinamide in biological materia1.Q Animal tissues appeared to containall or almost all their nicotinoyl derivatives in the form of nicotinamide,either bound in the form of pyridine nucleotides or free.On the otherhand, a number of cereals seemed to contain only nicotinic acid, either infree form or bound to unknown substance^.^ Kynurenine and S-hydroxy-kynurenine appear to interfere with the fluorometric estimation of nicotin-amide but this interference can be eliminated by the use of synthetic ion-exchange resins.1°In the.urine l1 of animals, a number of metabolites have been reportedto appear, such as nicotinuric acid, N‘-methylnicotinamide,12 1 : 6-dihydro-6-keto-N’-methylpyridine-3-carboxyamidey~~ and in faeces of chicks di-nicotinoylornithine. l4 N’-dlethyZniwtinamide was found to be an importantmetabolite of nicotinic acid following the discovery by Najjar and Wood l5that a fluorescent compound F, was formed in the urine of subjects givennicotinic acid.This compound Fz proved t o be a derivative of ”-methyl-nicotinamide, obtained when the latter was treated at alkaline pH withbutanol,16 acetone,17 or ethyl methyl ketone.ls It seems that all pyridineM. Swamhathan, Nature, 1938,141, 830.a E. Bandier and J. Hald, Biochem. J., 1939, 33, 264.a L. J. Harris and W. D. Raymond, ibid., p. 2037.ti R. G. Mrtrtinek, E. R. Kirch, and G. L. Webster, J . Biol. Chem., 1943,149,245.C. Klatzkin, F. W. Norris, and F. Wokes, Analyst, 1949, 74, 447.E. C. Barton-Wright and R. G. Booth, Lancet, 1944, I, 565; P. C. Dennis andFor collected refs.see E. E. Snell, “ Vitamin Methods,” Academic Press, Inc.,F. W. Lamb, Id. Eng. Chem. AnuZ., 1943, 15, 352; D. Melnick and B. L. Oser,J. V. Scudi, Science, 1946, 103, 567; E. Kodicek, Analyst, 1947, 72, 385.H. G. Rws, Analyst, 1949,74, 481.N.Y., 1950, Vol. I, p. 327 ; W. N. Norris, Ann. Repwts, 1944,41,258.ibid., p. 355.a D. K. Chaudhuri and E. Kodicek, Biochem. J., 1949, 44, 343; E. Kodicek andD. K. Chaudhuri, Bull. SOC. chim. biol., 1949, 31, 249.lo M. Kato and H. Shimizu, Science, 1951,114, 12.l1 For collected refs. see P. Ellinger and M. M. A. Kader, Bwchem. J . , 1949,44, 77.l3 Cf. J. R. P. O’Brien, Ann. Reports., 1944,41,252.l4 W. J. Dam and J. W. HUB, ibid., p. 121.l5 V. A. Najjar and R. W. Wood, Proc. SOC.Exp. Biol. Med., 1940,M, 386.l6 J. W. Huff and W. A. Perlzweig, Science, 1943, 97, 538.l7 Idem, J . Biol. Chem., 1947,167, 157.W. E. Knox and W. I. Grossmann, J . Bwl. Chem., 1946,166, 391 ; 1947,168, 363.K. J. Carpenter and E. Kodicek, Biochem. J., 1950,48, 421278 BIOCHEMISTRY.compounds which have a carboxyamide group in position 3 and a substitutedring nitrogen (cf. XXI) will fluoresce under these conditions. This provedto be so with pyridine nucleotides l9 and with the betaine .of "-methyl-nicotinuric acid. l8 These compounds can be differentiated from N'-methyl-nicotinamide by chromatographic adsorption on " Decalso " columns. l8 Forthe estimation of 1 : 6-dihydro-6-keto-N'-rnethyZpyridine-3-carboxyamide, fluoro-metric 2o and colorimetric 21 procedures have been developed.Recently paper-chromatographic methods have been described whichallow the separation and identification of tertiary nicotinoyl and quaternarypyridinium compounds.For the former, the Konig reaction is applied tochromatograms, using benzidine 22 or p-aminobenzoic acid 23 as the aromaticamine reagent, and for the latter the ethyl methyl ketone condensation hasbeen used to detect the pyridine nucleotides and nucleosides, "-methyl-nicotinamide and the betaine of N'-methylnicotinuric acid.23Biological Studies.-A new impetus in the research on the metabolism ofnicotinic acid was given by the finding that rats which were able to surviveon diets apparently devoid of nicotinic acid, were made deficient whengiven diets containing 9% of casein and 40% of maize.24 The deficiencymanifested itself in depressed growth and the animals developed a rough furcoat , stained with reddish porphyrin-like material.These symptoms werealleviated and the growth rate restored to normal by the addition of nicotinicacid in amounts of 0 . 6 1 . 5 mg.% of the diet. When the casein content wasraised to 15-20~0, the maize diets were no longer pellagragenic. Since thisresult could not be explained by the dietary content of nicotinic acid and themain difference was in the low tryptophan and lysine content, Krehl andhis co-workers 25 tested supplementation with these amino-acids. Whileadministration of lysine had no effect, tryptophan in amounts of 50 mg.%of the diet cured the deficiency.However the efficiency of tryptophancompared, on a wt./wt. basis, to that of nicotinic acid was in a ratio ofabout 50 : 1.A careful and complete study of these effects was made in a series ofpapers by the Wisconsin group.26 It was found that the type of carbo-hydrate in the diet affected the development of the defi~iency.~' Thusreplacement of sucrose by dextrin, glucose, or maize starch corrected partlyor sometimes completely the growth depression which resulted from feedingmaize diets. It has been suggested that these effects are due to alterationsin the synthesis of the vitamin by the intestinal microflora. There isChem., 1947,167, 169.19 N. Levitas, J. Robinson, F. Rosen, J. W. Huff, and W. A. Perlzweig, J . Bid.20 F. Rosen, W.A. Perlzweig, and I. G. Leder, ibid., 1949,179, 157.21 W. I. M. Holman and D. J. de Lange, Bwchem. J., 1949, 45, 559; Nature, 1950,22 C. F. Huebner, Nature, 1951,167, 11 9.23 E. Kodicek and K. K. Reddi, ibid., 168, 475.24 W. A. Krehl, L. J. Teply, and C. A. Elvehjem, Science, 1945,101, 283.25 W. A. Krehl, L. J. Teply, P. S. Sarma, and C. A. Elvehjem, ibid., p. 489.Z 6 For collected refs. see W. A. Krehl, " Vitamins and Hormones," 1949, Vol. VII, 11 1.27 W. A. Krehl, P. S. Sarma, L. J. Teply, and C. A. Elvehjem, J . Nutrit., 1946,31,85.165, 112, 604RODICEK : NICOTINIC ACID. 279evidence that the amount of fat in the diet may also alter the course of thedeficiency ; an addition of 30% of lard to maize diets resulted in normalgrowth of rats even without supplementation with nicotinic acid.28 Thiscomplicated interrelation between the various constituents of the dietshows the precarious balance needed to produce symptoms of deficiency inthe rat.Nevertheless, when the original maize diet of the Wisconsinworkers is used, the depressing effect on growth can be demonstrated withoutfail. A similar diet, but containing still less casein, 3.6%, was used recentlyin an attempt to induce more severe symptoms of deficiency and to studythe possibility of using the rat for quantitative assays of the anti-pellagravitamin.29 Well-graded dose-response curves were obtained, but in viewof “ interaction between different factors (tryptophan, nicotinamide, proteinlevel) it was possible only to compare the overall ‘ antipellagric ’ activity offood preparations.”Amino-acid hbalance.-The studies of Krehl and his co-workers haveshown that the deficiency in the rat could be also induced by certain otherprotein diets which had a low tryptophan content and were of poor nutritivequality.Thus diets containing 15% of wheat gluten or 10% of gelatin27were as effective in producing a deficiency syndrome as were maize diets.From these and later studies, the Wisconsin workers advanced the conceptof the amino-acid imbalance : 30 “ That an imbalance of amino-acids resultsin an increased tryptophan (or niacin) requirement, and therefore poorgrowth, is shown by the fact that rats will grow reasonably well on rationswhich contain the same amount of tryptophan and which also contain awell balanced protein.”This hypothesis is supported by further findings of the growth-retardingeffect of diets containing 9% of casein and 6% of gelatin or 3% of ~ein.~OSimilarly, the incorporation, into 9%-casein diets, of 2 % of acid-hydrolysedproteins, such as casein, egg albumin, and fibrin, in which the tryptophanhad been destroyed, resulted in a deficiency.In search of the particularamino-acids responsible for this effect, glycine fed a t a level of 2% with a9 %-casein-sucrose diet, and also a combination of amino-acids consistingof tyrosine, phenylalanine, leucine, valine, and glycine, produced a retard-ation of growth curable by nicotinic acid. However, the amounts necessaryto produce an amino-acid imbalance were much higher than would be foundnaturally in proteins.More convincing are the findings of Hankes et aL31that DL-threonine and phenyl-DL-alanine in amounts similar to those foundin 2% acid-hydrolysed casein, namely 0.078 and 0.104%, produced a de-ficiency in rats curable by nicotinic acid. Lyman and Elvehjem32 foundrecently that the presence in the diet of the sulphur-containing amino-acids,28 W. D. Salmon, J . Nutrit., 1947, 33, 155.30 W. A. Krehl, L. M. Henderson, J. DeLa Huerga, and C. A. Elvehjem, J . Biol.Chem., 1946,166,531 ; L. M. Henderson, T. Deodhar, W. A. Krehl, and C. A. Elvehjem,ibid., 1947,170, 261.L. V. Hankes, L. M. Henderson, W. L. Brickson, and C. A. Elvehjem, ibid., 1948,174, 873.L. J. Harris and E. Kodicek, Brit.J . Nutrit., 1950, 4, xiii.31 R. L. Lyman, and C. A. Elvehjern, J. Nutrit., 1951, 45, 101280 BIOCHEMISTRY.cystine or methionine, is necessary to obtain a growth depression with 6%of gelatin, when added to 9%-casein diets. The effect of cystine has beenexplained by the development of a cystine deficiency before the tryptophanbecame the limiting amino-acid. A mixture of amino-acids simulating 6%of gelatin produced a depression of growth similar to that obtained with thenatural protein, suggesting that an amino-acid imbalance was responsible forthese effects.The studies of the Maryland group 33 have shown that chicks can also bemade deficient by feeding them on diets low in nicotinic acid and supple-mented with maize, gelatin, or zein.An amino-acid mixture simulatinggelatin inhibited the growth of chicks and this seemed to be largely due to acombined effect of glycine, arginine, and alanine, suggesting again theinfluence of an amino-acid imbalance.34 Feeding of nicotinic acid reversedcompletely the inhibition of growth. However, the effects of a number ofother amino-acids, namely lysine, tyrosine, phenylalanine, methionine,isoleucine, and valine, which were efficient growth-inhibitors, were not greatlyinfluenced by the addition of nicotinic acid to the diet.35The amino-acid imbalance was f i s t thought to interfere with the synthesisof nicotinic acid by intestinal bacteria. However, the subsequent findingthat the conversion of tryptophan into nicotinic acid occurs in the animalbody itself, led to a widening of the hypothesis to embrace both the hostand the intestinal flora.The amino-acid imbalance may well operate inndural diets, although it is difficult at present to explain fully by this conceptthe pellagragenic effect of maize. The evidence is still too circumstantialthough it is true that Groschke et aZ.a6 found that chick pellagra could beproduced by an amino-acid mixture simulating zein. In contrast to this,Kodicek 37 observed that zein retained its pellagragenic effect for rats evenwhen " improved " by a number of amino-acids reported to be limiting inthe protein.38Toxic Factors.-There is at present not much experimental evidence thata " toxic " factor exists in maize, nevertheless intensive research on thisline is still continuing.39 A structural analogue of nicotinic acid, 3-acetyl-pyridine, was found to produce a nicotinic acid deficiency in mice40 andaggravate such a deficiency in dogs.4l More recently Woolley has beenable to prepare a chloroform extract of maize which in mice produced areduced growth rate and deficiency symptoms curable by nicotinic acid.42a3 G.M. Briggs, J . Biol. Chem., 1945, 161, 749; G. M. Briggs, A. C. Groschke, andR. J. Lillie, J. Nutrit., 1946, 32, 659.34 A. C. Groschke and G. M. Briggs, J. Biol. Chem., 1946,165,739.35 J. 0. Anderson, G. F. Combs, A. C. Groschke, and G. M. Briggs, J. Nutrit., 1951,3~3 A. C. Groschke, J. 0. Anderson, and G. M. Briggs, PTOC. SOC. Exp. Bid. Med..38 D. Kligler and W. A. Krehl, J.Nutrit., 1950, 41, 215.39 H. Chick, Lancet, 1933, 225, 341 ; Nutrit. Abstr. Rev., 1951, 20, 523.4* D. W. WoolIey, J . BioZ. Chem., 1945,157, 455.4 1 D. W. Woolley, F. M. Strong, R. J. Madden, and C. A. Elvehjem, ibid., 1938,124,45, 345.1948, 68, 564. 37 E. Kodicek, Biochem. J., 1951, 48, viii.715. 4% D. W. Woolley, ibid., 1946, 163. 773KODICEK : NICOTINIO ACID. 281The factor responsible for these effects has, however, not yet been identified.A structural analogue of tryptophan, 3-indolylacetic acid which is present inconsiderable amounts in maize, has been reported to cause a growth retard-ation, but further experiments have shown that it was not responsible forthis effect .& Cooperman et ~ 1 . ~ ~ recently made the interesting observationthat the toxic effect of borrelidin, a crystalline antibiotic obtained from theculture broth (maize-steep liquors) of certain streptomyces, could be partlyovercome by supplementation with nicotinic acid or tryptophan.Intestinal Synthesis.-There is a certain amount of evidence that syn-thesis of nicotinic acid by intestinal bacteria supplements the requirementsof the host organism.It is, however, still uncertain to what extent thisadditional supply is important and whether it applies to all species. Theeffect of different carbohydrates, in altering the response of the animal topellagragenic diet~,~7 may be cited in favour of microbial synthesis of thevitamin and its availability to the host. The studies of Ellinger 45 andothers46 also lend support to this concept.Since it has been shown byexperiments in vitro that the intestinal flora may also destroy nicotinicit appears that the problem of vitamin supplies from intestinalbacteria is more complex and has to await further elucidation.The Relation between Tryptophan and Nicotinic Acid.-Although it wasnoted as early as 192248 that the amino-acids tryptophan and cystineimproved patients suffering from pellagra, the main significance of theeffect of tryptophan was only realized 23 years later from experiments onrats (Krehl et ~ 1 . ~ ~ ) . Soon afterwards Rosen et ~ 1 . ~ ~ showed that administra-tion of tryptophan to rats resulted in an increased urinary excretion ofderivatives of nicotinic acid and they advanced the hypothesis that trypto-phan may act as a biological precursor of nicotinic acid.The conversion oftryptophan into nicotinic acid seems to occur in a number of animal species,such as the horse, pig, chick, turkey, and man,50 in micro-organisms (seebelow), and indeed in green leaves 51 and in the maize embryo.52It was first suggested that tryptophan exerts its effect on the intestinalflora, but more recent results support the view that the synthesis of nicotinicacid occurs in the body of the animal. Thus injections of tryptophan causedan immediate rise of nicotinic acid derivatives in the urine of the rat 53 and43 E. Kodicek, K. J. Carpenter, and L. J. Harris, Lancet, 1946,251,491 ; 1947,253,616.4 4 J. M. Cooperman, S . H. Rubin, and B. Tabenkin, Proc. SOC.Exp. Biol. Med.,45 P. Ellinger, Biochem. J., 1946, 40, 31 ; 1947, 41, 308; Nature, 1947,160, 675.4 6 L. V. Hankes, L. M. Henderson, W. L. Brickson, and C. A. Elvehjem, J . Biol. Chem.,47 R. Benesch, Lancet, 1945,248, 718.4 8 J. Goldberger and W. F. Tanner, U.S. Pub. Health Repts., 1922,37,462.49 F. Rosen, J. W. Huff, and W. A. Perlzweig, J . Biol. Chem., 1946,163, 343.1951, 76, 18.1948,174, 873.For collected refs. see S. E. Snyderman, K. C. Ketron, R. Carretero, and L. E. Holt,Proc. SOC. Exp. Biol. Med., 1949,70, 569.51 F. G. Gustafson, Science, 1949, 110, 279.52 A. Nason, ibid., 109, 170. 63 J. M. Hundley, Fed. Proc., 1949, 8, 386282 BIOCHEMISTRY.of man.50 Even in absence of the entire intestinal tract the synthesis ofnicotinic acid from tryptophan takes place.54 Moreover the tissues of achick embryo 55 and liver slices 56 can convert tryptophan into nicotinicacid.That the part played by the intestinal flora may be also of someimportance is indicated by the effect of varying the dietary carbohydrates 27and of administration of succinoylsulphathiazole.26Studies with Moulds and Bacteria.-An important advance in the under-standing of the mechanism of the tryptophan-nicotinic acid conversion wasmade by studies with lower organisms. Mutant strains of Neurosporu werefound which could grow when supplied with tryptophan or nicotinic acid 57and their requirements were equally met by the tryptophan metabolitekynurenine. Soon afterwards Bonner 58 observed that 3-hydroxyanthranilicacid could replace these compounds.Mitchell and Nyc 59 put forward atentative scheme for the conversion of tryptophan into nicotinic acid inwhich kynurenine, 3-hydroxykynurenine, and 3-hydroxyanthranilic acidserve as intermediates. Intensive research in the past 3 years, carried outmainly by Bonner, Mitchell, Nyc, and their co-workers, confirmed the originalhypothesis. The proven and possible intermediates are shown in the annexedscheme, where the substances merely postulated are enclosed in squarebrackets. Less detailed information exists for the metabolic pathways inthe animal body, as will be discussed below.It has been shown that tryptophan undergoes a similar conversion incertain species of Pseudomonas 6o and Xanthomonas pruni,61 while in mutantstrains of Aspergillus 3-hydroxyanthranilic acid seems to be formed directlyfrom anthranilic acid.62 On the other hand, several lactic acid bacteria,yeasts, and Proteus vulgaris 63 have lost the ability to synthesize nicotinicacid from tryptophan.I n this respect they resemble certain animal organ-isms, namely Tetrahymena gelei a and Dro~ophiZa.~~As mentioned before, tryptophan(111) was shown to be converted by moulds into kynurenine (VI). N -Formylkynurenine (V) is formed from tryptophan by a coupled peroxidase-oxidase system in liver homogenates and (V) is split by the enzyme formylaseinto kynurenine (VI).66s 67 There is a postulated intermediate formed from54 L. M. Henderson and L. V. Hankes, Proc. SOC. Exp. Biol. Med., 1949,70,26 ; J .M.Hundley, ibid., p. 592.55 B. S. Schweigert, H. L. German, and M. J. Garber, J . Biol. Chem,. 1948,174, 383.66 W. W. Hurt, B. T. Scheer, and H. J. Deuel, jnr., Arch. Bwchem., 1949, 21, 87.57 G. W. Beadle, H. K. Mitchell, and J. F. Nyc, Proc. Nut. Acad. Sci., 1947, 33, 155.'5 8 D. M. Bonner, ibid., 1948, 34, 5. 59 H. K. Mitchell and J. F. Nyc, ibid., p. 1.6o R. Y. Stanier and M. Tsuchida, J . Bacteriol., 1949,58,45.131 D. Davis, L. M. Henderson, and D. Powell, J . Biol. Chem., 1951,189,543.62 G. Pontecorvo, Biochem. SOC. Symp., 1950, No. 4, p. 40.63 B. E. Volcani and E. E. Snell, Proc. SOC. Exp. Biol. Med., 1948, 67, 511.64 G. W. Kidder, V. C. Dewey, M. B. Andrews, and R. B. Kidder, J. Nutrit., 1949,65 J. Schultz and G. T. Rudkin, Fed.Proc., 1948, 7, 185.6 6 W. E. Knox, K. Mero, W. I. Grossmann, and V. H. Auerbach, ibid., 1949,8, 214.6 7 W. E. Knox and A. H. Mehler, J . Biol. Chem., 1950,187,419,431.Tryptophun-kynurenine conversion.37, 521KODICEK : NICOTINIC ACID. 283tryptophan (111) by the action of peroxidase in presence of hydrogen per-oxide and it was thought to be p-2-oxindolylalanine (XIV). However,recently Sakan and Hayaishi 68 proved that this compound was not anintermediate, at least for Pseudomonas spp. Similar conclusions were reachedby Dalgliesh et from studies on the urinary excretion of tryptophanmetabolites in rats. Knox et al. 6 7 3 G9 suggested that the unknown inter-mediate could be 2 : 3-dihydro-2 : 3-dihydroxytryptophan (IV), formed fromScheme of conversion of tryptophan into nicotinic acid.(Modified from Bonner andYanofsky. 73)tryptophan by the addition of peroxide, and (IV) in turn by dehydrogen-ation and ring opening could give formylkynurenine (V). This suggestionwill need experimental verification. In Neurospora, it has been establishedthat tryptophan can be resynthesized from kynurenine via anthranilic acid(I) and indole (11), thus producing, apart from nicotinic acid formation, a'' cycle " on its own 70 (see scheme). A mutant of Neurospora, the strainN-3 which cannot synthesize nicotinic acid, is unable to utilize kynurenine6 8 T. Sakan and 0. Hayaishi, J . Biol. Chrn., 1950, 186, 177.6g C. E. Dalgliesh, W. E. Knox, and A. Neuberger, Nature, 1951,168, 20.70 F. A. Haskins and H.K. Mitchell, Proc. Nat. Acad. Sci., 1948, 35, 500284 BIOCHEMISTRY.and accumulates a substance which has been identified as Na-acetylkynurenine(XV).71 It is of interest that this substance was found in the urine ofpyridoxine-deficient rats, together with Na-acetyl-3- hydroxykynurenine. 69Kynurenine-3-hydroxyanthranilic acid conversion. 3-Hydroxykynurenine(VII), which occurs in Nature,72 was shown to be able to replace nicotinicacid in a number of strains of Neuro~pora.~~ It is therefore acceptedas an intermediate, although definite proof of its place in the scheme is still(XVI)lacking.73 The formation of 3-hydroxyanthranilic acid (IX) from (VII) ispossibly mediated by the enzyme kyn~reninase,~g which seems to have asa prosthetic group pyridoxal phosphate.74 Dalgliesh, &ox, and Neu-berger 69 suggest that by transamination reactions a diketo-acid (VIII) isformed which may be split into 3-hydroxyanthranilic acid (IX) and alanine.This possible intermediate reaction in the tryptophan-nicotinic acid con-version would explain the interaction of pyridoxine which evidently occursbefore the formation of 3-hydroxyanthranilic acid.75The final phase ofthe conversion, namely that of 3-hydroxyanthranilic acid (IX) into nicotinicacid (XIII), is the least explored. The remarkable formation of the pyridinefrom a benzene ring has been proved by experiments with Neurospora 7 6 3 7 7and labelled intermediate~.7~ It has been suggested by Bonner and Yanof-sky 77 that the benzene ring of 3-hydroxyanthranilic acid (IX) is split in the3 : 4-position and an unstable aliphatic intermediate (X) is formed whichundergoes decarboxylation (to XII) and subsequent ring closure to nicotinicacid (XIII).Makino et ~ 1 . ~ ~ suggested, from studies on liver slices, that3 : 4-dihydroxyanthranilic acid (XVI) is an intermediate formed as theoxidation product, before cleavage of the benzene ring. It is, however,uncertain if that is so, since Mitchell 8o found it to be inactive for Neurospora.The discovery that quinolinic acid (XI) is excreted by rats, after adminis-tration of tryptophan or of 3-hydroxyanthranilic acid,81 led to intensive3-E€ydroxyanthranilic acid-nicotinic acid conversion.71 C. Yanofsky and D. M. Bonner, Proc. Nut. Acad. Sci., 1950, 36, 167.73 A.Butenandt, W. Weidel, and H. Schlossberger, 2. Naturforsch., 1949,4, b, 242 ;Y. Hirata, K. Nakanishi, and H. Kikkawa, Science, 1950, 112, 307.78 D. M. Bonner and C. Yanofsky, J . Nutrit., 1951,44, 603.74 A. E. Braunshtein, E. V. Goryachenkova, and T. S. Pashkina, Biokhimiyu, 1949,75 L. M. Henderson, I. M. Weinstock, and G. B. Ramasarma, J . Biol. Chem., 1951,7 7 D. M. Bonner and C. Yanofsky, Proc. Nat. Acad. Sci., 1949, 35, 576.7 8 C. Yanofsky and D. M. Bonner, J . Biol. Chem., 1951,190, 211.79 K. Makino, F. Itoh, and K. Nishi, Nature, 1951,167, 115.so Cf. H. K. Mitchell, “ Vitamins and Hormones,” 1950, Vol. VIII, p. 144.81 L. M. Henderson, J . BioZ. Chem., 1949,178, 1005.14, 163.189, 19. 76 L. M. Henderson, ibid., 1949, 181, 677KODICEK : NICOTINIC ACID.285studies of its metabolism in mutants of Ne~rospora.~~,~~ Henderson 81advanced the hypothesis that quinolinic acid was an intermediate in theconversion of tryptophan into nicotinic acid by undergoing “ oxidativeopening of the benzenoid nucleus in the 3 : 4-position and reclosure throughthe amino-group ” (see scheme). However, the activity of quinolinic acidon a molar basis is far below that observed with 3-hydroxyanthranilic acid ornicotinic acid and it was therefore suggested by Bonner and Yanofsky 77that quinolinic acid may be an alternative end product and not a directintermediate. Recently, Bokman and Schweigert 82 reported that theyhave obtained spectrophotometric evidence for the formation, by rat liverslices, of an intermediate between 3-hydroxyanthranilc acid (IX) andquinolinic acid (XI). It is supposed to be a compound of a quinonetype.Animal Studies.-The scheme for conversion of tryptophan into nicotinicacid seems, in the main, to hold good for higher organisms but the exactsteps which lead to the formation of nicotinic acid in the animal body areless certain and critical proof has yet to be obtained.The identification ofintermediates in the animal metabolism has proved to be more difficult andless direct than in studies on unicellular organisms. Thus the metabolismin rats, which were the main experimental animals, is complicated by thetype of diets and other factors which have been discussed on previous pages.The methods used for exploring the animal metabolism can be sum-marized as follows :(1) Various compounds supposed to take part in the conversion wereadministered to animals, and the urinary excretion of nicotinoyl metaboliteswas determined.Conclusions derived from such expFriments give valuable,but indirect, proof, and the statement by Kallio and Berg 83 may be citedhere, that “ evidence based on metabolite excretion does not always providea safe criterion as to relative utility for growth.’’(2) The relative efficiency of the different postulated precursors inenhancing the growth of nicotinic acid-deficient animals seems to be oneof the most important proofs which have to be required before a compoundis accepted as a possible intermediate. Nevertheless, to exclude the possi-bility of indirect effects a cautious interpretation is often warranted.(3) Studies with isolated tissues provide a useful tool which may elucidatea number of intermediate reactions.However, metabolic studies in vitrodo not reproduce fully the complex conditions existing in the body and sidereactions may appear which do not occur or are minimized in vivo.(4) The most convincing proof of the existence of intermediate steps isprovided by isotopic studies. At the same time, the appearance of labelledintermediates need not.necessarily indicate their relative importance in themetabolism as some may be end products of side reactions. More rigorousproof is needed, such as administration of the labelled intermediate and deter-mination of the fate of the label.This has been done in many instances,82 A. H. Bokman and B. S . Schweigert, Arch. Biochem., 1951, 23, 270.R. E. Kallio and C. P. Berg, J . Bio2. Chem., 1949,181,333286 BIOCHEMISTRY.but experiments with labelled kynurenine, 3-hydroxykynurenine, or quinol-inic acid are still lacking.Regard being had to the above considerations, the animal studies can bediscussed on the basis of the scheme on p. 283 as follows : The identity oftryptophan as the biological precursor of nicotinic acid for a number ofspecies (see p. 287) has been conclusively proved by growth and excretionstudies 26 and from isotopic experiments carried out mainly by Heidel-berger and his co-workers. a4, 85 N-Formylkynurenine (V), though formedby liver preparations of several animal species,67 has proved inactive ingrowth tests.86 Similarly, kynurenine (VI) has given contradictory results.It does not improve the growth of nicotinic acid-deficient rats 86 and noincreased excretion of N’-methylnicotinamide was found on its administra-t i ~ n .~ ’ The latter result is contradicted by the significant increases observedby Kallio and Berg.83 Most powerful support for the participation ofkynurenine in the conversion scheme in animals is supplied by isotopicstudies 84 where labelled kynurenine was found in rabbits and rats afteradministration of [P-14C]-~~-tryptophan and after administration of 15N-labelled indole.8s Furthermore it has been shown that kynurenine can beformed in vitro by liver preparations from tryptophan via formylkynurenine.67The conflicting results may be due to the labile nature of kynurenine,’3nevertheless the position of the latter in the tryptophan-nicotinic acid con-version in animals is still uncertain. The finding of Na-acetylkynurenine(XV) in the urine of rats 69 (see p. 284) could indicate either that (XV) isa detoxication product or that “ acetylation may be a mechanism by whichthe body directs the chain of metabolic reactions.’’ 89 Since N“-acetyl-kynurenine had no effect on the growth of nicotinic acid-deficient rats,86it seems to be an end product rather than an intermediate. It is practicallycertain that 3-hydroxyanthranilic acid (IX) is a direct intermediate. Itimproves growth of deficient rats,W and increases the urinary excretionof N’-methylnic~tinarnide.~~ The growth response obtained with 3-hydroxy-anthranilic acid is of the order of that obtained with tryptophan.Sub-cutaneous 90, 92 or intraperitoneal 86 injection proved to be more effectivethan oral administration, suggesting that the intestinal flora was not involved.The conversion of 3-hydroxyanthranilic acid into nicotinic acid willprobably involve a number of intermediates also in the animal organism.However, so far only quinolinic acid (XI) has been implicated and no othercompound has been found which would possess growth-promoting activityChem., 1949,179, 143.C. Heidelberger, M. E. Gullberg, A. F. Morgan, and S . Lepkowsky, J . Biol.8s C. Heidelberger, E. P. Abraham, and D.Lepkowsky, ibid., p. 151.86 W. A. Krehl, D. Bonner, and C. Yanofsky, J . Nutrit., 1950, 41, 159.F. Rosen, J. W. Huff, and W. A. Perlzweig, ibid., 1947, 33, 561.R. W. Schayer, J . Biol. Chem., 1950,187, 777.H. K. Mitchell, J. F. Nyc, andE. D. Owen, J . Biol. Chem., 1948,175, 433.89 C. E. IDalgliesh, Qmrt. Reviews, 1951, 5, 227.O 1 P. W. Albert, B. T. Scheer, and H. J. Deuel, jnr.? ibid., p. 479.O2 0. Wiss, G. Viollier, and M. Muller, Helv. Chim. Acta, 1950, 33, 771KODICEK : NICOTINIC ACID. 287for deficient animals. Thus isocinchomeronic acid (XVII), which could bea possible intermediate if the benzenoid ring of 3-hydroxyanthranilic acid(IX) would split in the 2 : 3-position, did not improve the growth of deficientratsYg3 nor did 6-hydroxynicotinic acid (XVIII) .94Quinolinic acid (XI) appears in the urine after oral or intraperitonealadministration of tryptophan or of 3-hydroxyanthranilic acid *l, 95 andimproves the growth of nicotinic acid-deficient 86 but its efficiency islower than that of tryptophan or of 3-hydroxyanthranilic acid. Rat liverslices or homogenates 96,97 convert the latter but not kynurenine or trypto-(XVIII)phane into quinolinic acid.No indication was found that liver slices couldconvert quinolinic acid into nicotinic acid.96 It can be said that quinolinicacid has a place in the tryptophan metabolism of animals but in view of itslow activity it is more likely “ a product of a side reaction than a directintermediate in the conversion of tryptophan to nicotinic acid.” 86The Effect of Other B-Vitamins.-It has been shown that pyridoxine isintimately connected with the metabolism of tryptophan (for collected refs.see ref.75). Pyridoxine-deficient rats excrete, after a dose of tryptophanor, kynurenine, smaller amounts of nicotinoyl derivatives than do normalanimals. Administration of 3-hydroxyanthranilic acid had no such effect ,indicating that its pathway is not influenced by pyridoxine. Similar find-ings were observed in riboflavin deficiency. Henderson et aZ. 75 interpretedthe effects of pyridoxine deficiency as involving an impaired function ofkynureninase whose prosthetic group appears to be pyridoxal phosphate(see p. 284). The resulting biochemical block would cause an impairedconversion of 3-hydroxykynurenine (VII) into 3-hydroxyanthranilic acid(IX) with the subsequent accumulation of xanthurenic acid (XIX) from(VII)...c(XX)The biochemical lesion due to a riboflavin deficiency is most likelysituated between kynurenine (VI) and hydroxykynurenine (VII) 75 since,according to Porter et riboflavin deficiency had little influence on theexcretion of kynurenine or xanthurenic acid, but increased four-fold theexcretion of kynurenic acid (XX).93 L. V. Hankes and C. A. Elvehjem, Proc. SOC. Exp. Biol. Med., 1950,73, 550.94 E. Kodicek and K. K. Reddi, 1951, unpublished results.95 L. M. Henderson and H. M. Hirsch, J . Biol. Chem., 1949, 181, 667.96 L. M. Henderson and G. B. Ramasarma, ibid., p. 687.97 B. S. Schweigert and M. M. Marquette, ibid., p. 199.C.C. Porter, I. Clark, and R. H. Silber, Arch. Biochem., 1948,18, 339288 BIOCHEMISTRY.The following schematic representation, adapted from Henderson et uZ.,'~summarizes the possible sites of the action of pyridoxine and riboflavin :(XX) Kynurenic acid (XIX) Xanthurenic acid 1' Riboflavin 1'(IX) .1Tryptophan + Kynurenine ~-> 3-Hydroxykynurenine(VIIJ I+Kpureniunse O 9(111) (vl) ~K,,,,,,(I) Anthranilic acid 3-Hydroxyanthranilic acidNicotinic acidl/+ alanine g9Quinolinic acid - - --+.1N'-MethylnicotinamideThat the rat seems to convert tryptophan also into anthranilic acid andalanine can be seen from the accumulation of alanine in the liver and fromthe formation of anthranilic acid by liver preparation^.^^ It is, however,evident thrtt this is only an alternative pathway, not directly connectedwith the tryptophan-nicotinic acid conversion, since anthranilic acid iscompletely devoid of any growth-promoting activity for nicotinic acid-deficient 93Further Fate of Nicotinic Acid in Mammals.-Tryptophan seems to be animportant precursor of the nicotinamide moiety in pyridine nucleotidesof red blood cells loo and liver tissue.lol Ling et a1.lo0 found that intravenousinjections of tryptophan caused an increase of pyridine nucleotides in theerythrocytes of normal, but not of pyridoxine-deficient, rats.Injections ofnicotinic acid produced increases in both the normal and the deficientanimals. The pyridine nucleotide content of liver after administration oftryptophan, nicotinic acid, and its amide was studied by Elvehjem and hisc o - w o r k e r ~ .~ ~ ~ - ~ ~ ~ They showed that tryptophan and nicotinic acid wereequally effective in raising the level of pyridine nucleotides in livers ofdeficient rats, while nicotinamide was slightly less active when added tothe diets. A single large dose of nicotinamide, given by stomach tube,produced significantly higher levels than either tryptophan or nicotinic acid.Pyridoxine deficiency lo* had no effect on the response of liver pyridinenucleotides to the administration of tryptophan. It is at present difficult tointerpret these results which seem to contradict the finding that the effectBs 0. Wiss and I?. Hatz, Helv. Chim. Acta, 1949,32, 532.loo C. T.Ling, D. M. Hegsted, and F. J. Stare, J. Biol. Chem., 1948, 174, 803.lol J. N. Williams, jm., P. Feigelson, and C. A. Elvehjem, ibid., 1950, 187, 597.loa J. N. Williams, jnr., P. Feigelson, 5. S. Shahinian, and C. A. Elvehjem, ibid.,lo3 P. Feigelson, J. N. Williams, jnr., and C. A. Elvehjern, Proc. SOC. Ezp. Biol. Med.,*O* J. N. Williams, jnr., P.Feigelson, S. S. Shahinian, and C. A. Elvehjem,ibid.,76,441.1951, 189, 659.1951,78, 34KODICEK : NICOTINIC ACID. 289of tryptophan on erythrocytes is influenced by pyridoxine deficiency.loOFurthermore the in vitro experiments of Kohn and Klein,lo5 and of Leiferet aE.,l06 should be taken into account. These authors have shown thatnicotinic acid was taken up by red blood cells ifi vitro and converted into anon-diffusible form Io6 or factor V ( coenzymes),105 while nicotinamide wastaken up, but did not raise the factor V content.The urinary excretion of nicotinic acid metabolites has been studiedextensively.11 Apart from 1 : 6-dihydro -6- keto-37'-meth ylp yridine-3 -carb -oxyamide 13,20,21 and N'-methylnicotinamide,12 a number of tertiarynicotinoyl compounds have been reported to be excreted, such as nicotinuricacid, nicotinic acid, and its amide, but their identification was based oncomplicated and indirect differentiation procedures.The recent applicationof tracer techniques has permitted a more critical study of excretory pro-ducts. Hundley and Bond lo7 found that almost the entire "-methyl-nicotinamide excretion in rats was derived from a dose of 13C-labelled nico-tinic acid, indicating that in presence of excess of nicotinic acid there is littleformation of N'-methylnicotinamide from tryptophan or other sources.The recent synthesis of radioactive nicotinic acid and nicotinamide with 14Cin the carboxyl group lo* allowed Roth et aZ.Io9 to study the fate of the labelafter administration of the radioactive compounds to mice.It was foundthat about 15% of the radioactivity, fixed in the tissues, appears as exhaled14C0,. Six radioactive metabolites were found in the urine of the rat, dog,hamster, and mouse after an injection of labelled nicotinic acid.l1° I n therat, the following five were identified : N'-methylnicotinamide, 1 : 2-di-hydro-6-keto-N'-methylpyridine-3-carboxyamide, nicotinuric acid, nicotinicacid, and nicotinamide. The identity of the sixth metabolite is still un-known.After an injection of nicotinamide,l1° the same radioactive meta-bolites were found, with the exception of nicotinuric acid.The recent development of paper-chromatographic techniques 23 allowedthe separation of urinary metabolites without recourse to isotopic pro-cedures. m Since the chromatographic methods did not detect a-substitutedpyridine compounds, such as quinolinic acid or the pyridone of "-methyl-nicotinamide, only the quaternary pyridinium compounds of the type (XXI)and tertiary nicotinoyl compounds were identified.The results obtained on rat urines were essentially in agreement withthe isotopic studies on rats by Leifer et aZ.l1° I n man, nicotinuric acidappeared after ingestion of nicotinic acid, but not of nicotinamide.Freenicotinic acid was found in the urine of those subjects who experienced avasodilatory reaction after taking a dose of nicotinic acid. The administra-Io5 H. I. Kohn, and J. R. Klein, J. Biol. Chem., 1939,130, 1.Io6 E. Leifer, J. R. Hogness, L. J. Roth, and W. Langham, J . Amer. Chem. SOC.,J. M. Hundley and H. W. Bond, J. Biol. Chem., 1948,173, 513.log A. Murrray, W. W. Foreman, and W. Langham, Science, 1947,106, 277.log L. J. Roth, E. Leifer, J. R. Hogness, and W. H. Langham, J. Biol. Chem., 1948,110 E. Leifer, L. J. Roth, D. S. Hogness, and M. H. Corson, ibid., 1951,190, 596.ll1 K. K. Reddi and E. Kodicek, Biochem. J., in preparation.REP.-VOL. XLVIII.K1948,70, 2908.176, 249290 BIOCHEMISTRY.tion of nicotinamide resulted only in a small rise of the urinary nicotinamideexcretion, and tryptophan had no effect on the excretion of tertiary nicotinoylcompounds. After ingestion of nicotinic acid, its amide, or tryptophan, theN’-methylnicotinamide excretion was significantly increased, but no otherpyridinium compounds of the type (XXI) could be found in the urine.ll1cc Bound ’’ Nicotinic Acid.-It has been observed that alkaline hydrolysisof certain cereals gives higher chemical values for apparent nicotinic acidthan simple water extraction. The increase was attributed to the presenceof “ an unknown substance, giving the cyanogen-p-aminoacetophenonereaction, which was more strongly bound and liberated only after hydrolysiswith NaOH.” The presence of this chromogenic substance was con-firmed by a number of workers.l13 Krehl and Strong 114 produced evidencewhich indicated that the substance, called by them “precursor,” was anunknown derivative of nicotinic acid consisting of the nicotinoyl radicalattached to a constituent bearing functional groups which rendered theentire molecule acidic and water-soluble.I n microbiological tests, Lacto-bacillus arabinosus l l 4 5 115 and L. cusei 116 could only partly utilize the pre-cursor. The total nicotinic acid contents were obtained after hydrolysiswith alkali or strong mineral acids. By using this differentiation procedure,it was found that some milling fractions of wheat, dehydrated p o t a t 0 , ~ ~ ~ ~ ~ 1 rice, barley, rye brans, maize meal, and maize bran seemed to contain aform of ‘‘ bound ” nicotinic acid.The “ precursor ” present in wheat branappears to be different from that in potatoes,l15 rye bran, or maize bran.l16On the other hand, wheat germ does not seem to contain ‘‘ bound ’’ nicotinicacid 114,115 and its nicotinoyl content is possibly derived from coenzymes,yielding in treatment nicotinamide, but not nicotinic acid.g However,since the methods of differentiation are necessarily indirect, little or noinformation is available about the identity or concentration of these nico-tinoyl derivatives.The precursor present in wheat bran has been purified 170-fold 117 andthe resulting brown powder contained about 30 mg. of nicotinic acid per g.in “ bound ” form.It was readily soluble in 70% ethanol or water, andshowed a blue fluorescence and a characteristic absorption spectrum. Itcontained glucose and traces of amino-acids,ll7 and its nicotinoyl constituentdid not move on paper-~hromatograms,~3 indicating that the nicotinic acidwas bound to residual substances insoluble in the solvents tested. Since thepreparation gave a positive Millon’s test 117 and a strongly positive test forphenols with diazotized p-nitroaniline, 118 it is possible that polyphenolicsubstances are present either as impurities or as a constituent of the molecule.11% E. Kodicek, Biochem. J., 1940, 34, 712.113 H. A. Waisman and C. A. Elvehjem, I d . Eng. Chem. Anal., 1941,13,221; B.L.Oser, D. Melnick, and L. Siegel, Pood. Ind., 1941, 13, 66; E. E. Snell and L. D. Wright,J . BWZ. Chem., 1941,139, 675. 114 W. A. Krehl and F. M. Strong, ibid., 1944,156, 1.115 E. Kodicek and C. R. Pepper, J . @en. Microbiol., 1948, 2, 306.116 K. M. Clegg, E. Kodicek, and S. P. Mistry, Biochem. J . , 1952,50, 326.117 D. K. Chaudhuri and E. Kodicek, Nature, 1950,165, 1022.118 E. Kodicek, 1950, unpublished resultsKODICEK : NICOTINIC ACID. 291The “ bound ” form present in wheat bran seems to be unavailable torats 119 and chicks,l*O but dogs appear to be able to utilize it.120 The fullbiological activity of nicotinic acid can be released by hydrolysis with weakalkali, as has been shown on a purified precursor preparation, wheat, barley,and rice brans.119 Maize when hydrolysed with sodium hydroxide 37also seems to improve the nicotinic acid-deficiency in rats, but a largeproportion of the diet, vix., 40%, bas to be replaced by hydrolysed material.This result is not as easily interpreted as the results with wheat and other brans,since constituents other than the “ bound ” nicotinic acid could have beenaltered.Nevertheless, it can be said that ‘‘ the pellagra-producing maize canbe changed by alkaline digestion into a pellagra-preventive foodstuff. Thisis most likely due to the liberation of free nicotinic acid from its boundform, but other factors may also be involved.” 37 Further investigation isneeded to show the form or forms in which nicotinic acid is present in maizebefore any definite conclusions can be drawn.In any case, the non-avail-ability of nicotinic acid would not fully explain the pellagragenic effect ofmaize and it does not exclude the possibility that imbalance of amino-acidsor other (toxic ?) factors are involved.The curative effect on rat pellagra of alkali-treated maize has been con-firmed by Laguna and Carpenter 121 who used maize treated with lime waterin the manner that is being used for cooking the Mexican maize dish ‘‘ tor-tilla.” These tests were evidently done to investigate the possibility whetherthe custom of cooking maize in lime water has any connection with the lowincidence of pellagra in Mexico. I n contrast to their results, Krehl et aL3has previously observed that dried tortillas, prepared according to the methoddescribed by Cravioto et aZ.,lZ2 were as pellagragenic as untreated maize.Krehl26 suggested that the traditional Mexican drink “ pulque ” containsnicotinic acid and, consumed in reasonable amounts, could contribute asignificant proportion of the daily requirement of this vitamin.The differ-ing results of these two groups of workers are difficult to explain; they maypossibly be due to variation in the strength of lime or in the duration oftreatment of the maize.It is not known if the ‘‘ precursor ” in wheat products is available to man.Doubts whether it is available have been expressed by Kodicek 112 andBrown et aZ.123 An interesting finding, suggestive of the same inter-pretation was made by H01man.l~~ He studied the urinary excretion ofnicotinic acid metabolites in groups of German children who lived for 44months on diets which contained comparable amounts of white or whole-meal flour or white flour enriched with synthetic B-vitamins to the level of119 D.K. Chaudhuri and E. Kodicek, Biochem. J., 1950,47, xxxiv.120 W. A. Krehl, C. A. Elvehjem, and F. M. Strong, J. BioE. Chem., 1944,156, 13.121 J. Laguna and K. J. Carpenter, J. Nutrit., 1951,45, 21.12% R. 0. Cravioto, R. K. Anderson, E. E. Lockhart, F. P. Miranda, and R. S. Harris,123 E. B. Brown, J. M. Thomas, and A. F. Bina, J. BWZ. Chem., 1946,162,221.124 See R. A. McCance and E. M. Widdowson, Medical Research Council SpecialScience, 1946, 102, 91.Report Series, in the press292 BIOCHEMISTRY.wholemeal flour.He found that the excretion of metabolites, especiallythat of 1 : 2-dihydro-6-keto-N’-methylpyridine-3-carboxyamide, was con-siderably lower in children eating wholemeal flour than in those consumingthe enriched flour. The excretion of the former group tended t o be nearlyas low as that of the ‘‘ white flour ” group, suggesting that the nicotinicacid in the wholemeal flour was not readily absorbed.E. K.4. THE PRUTEASES.The proteolytic enzymes are widely distributed and have been detectedin numerous tissues and organisms but comparatively few have been isolatedas pure preparations. Most of the detailed studies of their specificity andother properties have been confined to pepsin and the pancreatic proteases,particularly those from beef pancreas.This is due in part to their highcontent in this organ but largely to the excellent preparative methodsdevised by Northrop, Kunitz, and Herri0tt.l Recently, however, a numberof proteases have been purified, and in some cases crystallised, after isolationfrom such micro-organisms as yeast,2 streptococcus group A,3 Clostridiumwelchii? and Aspergillus 0r2ae.~ andchymopapain have been crystallised and no crystalline preparations ofcathepsins, amino-peptidases, or dipeptidases have yet been reported. Manyof the last enzymes have been partly purified (see E. L. Smith G. C. Popeand Stevens found a cathepsin-like enzyme as an impurity in crystallinepepsin and, though they have obtained pepsin free from it, they were notable to purify the cathepsin itself.This impurity, which was found also inpapain and even in trypsin and chymotrypsin after many recrystallisations,is apparently responsible for the hydrolysis of horse antitoxin by theseenzymes at pH about 4.Many studies of specificity have been carried out with the proteases, anda considerable volume of data on the rates of hydrolysis or inhibiting powerof di- and tri-peptides, together with their analogues and derivatives, isavailable, A beginning has also been made in examining how far the enzymicspecificities, as determined with small substrates, are reflected in theirbehaviour when hydrolysing proteins. P. Desnuelle, M. Rovery, and G.Bonjour 10 used end-group techniques to determine which peptide bondswere broken in the peptic digestion of haemoglobin and ovalbumin, and1 J. H.Northrop, M. Kunitz, and R. M. Herriott, “ Crystalline Enzymes,” ColumbiaOf the plant proteases, only papainUniv. Press, New York, 1948.M. J. Johnson, J . Biol. Chern., 1941,137, 575.S . D. Elliott, J . Exp. Med., 1950, 92, 201.E. Bidwell and W. E. van Heyningen, Biochern. J., 1948,42,140.W. G. Crewther and F. G. Lennox, Nature, 1950,165,680.E. F. Jansenand A. K. Balls, ibid., 1941,137, 459.“ The Enzymes,” Academic Press Inc., New York, 1951, Vol. I, Part 2.6 A. K. Balls and H. Lineweaver, J . Biol. Chern., 1939,130, 669.9 Brit. J . Exp. Path., 1951, 32, 314. lo Biochirn. Biophys. Acta, 1950, 5, 116PORTER : THE PROTEASES. 293concluded that a broad specificity was shown with both substrates, but thisis possibly due to the cathepsin impurity referred to above.g F.Sangerand H.Tuppy,ll in the course of their investigation of the amino-acidsequence in the phenylalanine chain of insulin, found that trypsin and chymo-trypsin, when digesting this polypeptide of 30 amino-acid residues, showedthe same specificity which Bergman had found with dipeptides. Pepsinagain gave a much less specific hydrolysis. The much more powerful actionof trypsin on denatured than on native proteins l2 shows, however, that theconfiguration of the substrate may become important with larger molecules.Using small substrates, Neurath and his collaborators made the sur-prising discovery that trypsin,13 chymotrypsin,14 and carboxypeptidase l5will all hydrolyse ester and hydrazide bonds at least as rapidly as similarpeptide and amide linkages, The work detailing the specificity requirementsof these three pancreatic proteases has been reviewed by H.Neurath andG. W. Schwert.lG For hydrolysis to take place adsorption of the substrateon to the enzyme surface must occur and the kinetic studies with manysubstrates and inhibitors have shown that steric factors are critical to within1-2 A. Support was also given for the belief that hydrogen and electro-static bonding is responsible for the enzyme-substrate complex formation,van der Waals forces becoming important when the closest fit occurs.Somewhat similar work with cholinesterase has been interpreted in terms ofthe composition of the enzymic active centre but no such attempt has yetbeen made with the proteolytic enzymes.E. L.Smith l7 has put forward a theory to explain the role of metals whichare known to be essential for the hydrolytic action of amino-peptidases anddipeptidases. He postulates that, of the bonds between enzyme andsubstrate, a t least two are through the metal, the bonds from the metal tosubstrate being on either side of the labile bond and of sufficient strength todistort it. This distortion leads to decrease in the free energy of the activa-tion and permits catalytic hydrolysis by hydrogen and hydroxyl ions. Thistheory is a more specific development of older views on the mode of action ofmetal enzymes and is largely based on a comparison of the chelating powersof peptides with their rates of hydrolysis by different exopeptidases.Inaccord with this theory Smith claimed that carboxypeptidase was a mag-nesium enzyme because it was inhibited by several metal poisons and theash of a well-dialysed preparation contained appreciable amounts of thismetal. H. Neurath and G. de Maria,l* however, have criticised the evidencepurporting to show that metal poisons do in fact inhibit the enzyme. Ithas been suggested recently that trypsin is a calcium enzyme l9 but thel1 Biochem. J., 1951, 49, 481.l2 F. Haurowitz, M. Tunca, P. Schwerin, and V. Goksu, J . Biol. Chem., 1945,157,621.l3 G. W. Schwert, H. Neurath, 5. Kaufman, and J. E. Snoke, ibid., 1948,172,221.S. Raufman, G. W. Schwert, and H. Neurath, Arch.Biochem., 1948,17, 203.l5 J. E. Snoke, G. W. Schwert, and H. Neurath, J . Biol. Chem., 1948,175, 7.l6 Chem. Reviews, 1950, 46, 69,Is J . Biol. Chem., 1950, 186, 653.1' Proc. Nat. Acad. Sci., 1949, 35, 80.L. Gorini, Biochim. Biophys. Acta, 1951, 7, 318294 BIOCHEMISTRY.evidence is not yet convincing. At present it is not certain that metals canplay an important part in proteolysis except that by the amino-peptidasesand certain dipeptidases.The concept of enzymesubstrate complex formation has been challengedby A. Rothen 2o in the case of trypsin. He found that this enzyme coulddestroy the power of unimolecular films of serum albumin to combine withthe specific antisera even when several inert barrier films separated thetrypsin solution from the serum albumin.The significance of this work asevidence that long range forces may operate in proteolysis has been ques-tioned 21s22s23 and Rothen 24 has recently summarised his own position. Inthis latter article, a suggestion is put forward that long range forces betweentrypsin and its substrate may be responsible only for a motivated diffusiontowards each other, the subsequent catalysis occurring at short range as theoverwhelming weight of other evidence suggests. M. Hanig 25 has, however,described an experiment where the hydrolysis of haemoglobin by trypsinoccurred through a membrane impermeable to both proteins. In this caseno measure of the thickness of the membrane was obtainable.The occurrence of different proteins, found together and with apparentlythe same enzymic activity, has been reported in several cases, for example,pepsin 26 and ribon~clease.~~~ 28 Chymotrypsin, however, appears t o be themost remarkable example of this multiplicity of form.Two precursors havebeen isolated and crystallised, and six forms of the active enzyme have beenfound. Chymotrypsinogen B,29 which differs from chymotrypsinogen insolubility and crystalline form, is activated by trypsin, giving chymotrypsinB. On the other hand, chymotrypsinogen may, according to the conditionsof activation, yield 5 or 6 forms of active enzyme. Thus under the conditionsemployed by Kunitz, the principle product from tryptic activation ofchymotrypsinogen is a-chymotrypsin 30 but, from the mother-liquor fromthe crystallisation of this enzyme, two further enzymes (p and y) wereisolated.31 These three enzymes show very similar specificities, pH optima,and activities, but differ somewhat in crystalline form, solubility, and stabilityto different conditions of denaturation.It has further been found by C. F.Jacobsen32 that if the activation of chymotrypsinogen is carried out at 0"in the presence of much larger amounts of trypsin than were used by Kunitz--enough to cause formation of maximum enzyme activity in 1 hour-thentwo further and different chymotrypsins are produced. These were not20 J . Amer. Chem. SOC., 1948. 70. 2732.zz S. J. Singer, J . Biol. Chem., 1950,182, 189.z3 H. J. Trurnit, Science, 1950, 112.z6 Proc. SOC. Exp. Biol. Med., 1950,73, 381.86 V.Desreux and R. M. Herriott, Nature, 1939, 144, 287.97 C. H. W. Him, W. H. Stein, and S . Moore, J . Amer. Chem. SOC., 1951,73, 1893.2 8 A. J. P. Martin and R. R. Porter, Bwchem. J . , 1951,49, 215.30 M. Kunitz and J. H. Northrop, J . Gen. PhyswZ., 1935,18, 433.31 M. Kunitz, ibid., 1938, 22, 207.33 Compt. Rend. Trav. Lab. Carlsberg, Sdr. Chim., 1947, 25, 325.a1 J . Iball, Science, 1949, 109, 18.24 Helv. Chim. Acta, 1950, 33, 834.K . D. Brown, R. E. Shupe, and H. Lakowski, J . Biol. Chem., 1948,173,99PORTER : THE PROTEASES. 295isolated, but correlation of the peptide bonds broken with resultant activityled to the following interpretation of his results. The fist product underhis conditions is x-chymotrypsin, which has 2-5 times the specific activity ofthe a-enzyme.This product is unstable and the tryptic splitting of onemore bond produces &chymotrypsin, 1.5 times more active than the a-enzyme. Simultaneously, the autocatalytic splitting of four bonds in othermolecules of the x-enzyme led to formation of a-enzyme. If, however, theprotease from B. subtilis is used for activation,33 rather than trypsin, chymo-trypsinogen gives yet another enzyme which bears some resemblance tochymotrypsinogen B.New estimates of the molecular weights of both chymotrypsinogens andsome of the chymotrypsins have been made and all give lower values thanwere orginally found. Sedimentation and diffusion data 34, 35, 36 give forboth zyrnogens and the B and the a-enzyme 22,000-23,000, whereas lightscattering and osmotic pressure experiments 37 led to the value of 27,000 fora-chymotrypsin.There seems little doubt that the precursors and enzymeshave about the same molecular weight, though B- and a-chymotrypsinreversibly associate t o form dimers. This is in agreement with the verysmall amounts of non-protein-nitrogen which have been observed to beproduced during activation. It seems that the peptide bonds which aresplit in the zymogen must be nearly terminal and hence release only smallpeptides, or that the original molecule is cyclic so that peptide bonds may beopened without fragmentation. A very recent note 38 describing the estima-tion of N-terminal amino-acids in chymotrypsinogen and a-chymotrypsinsuggests that the precursor is cyclic and that there may be 1-3 terminalgroups in the enzyme.Difficulties, such as the possible adsorption ofpeptides, even in many times recrystallised enzyme, and the continualautocatalytic degradation, make interpretation of the results with a-chymo-trypsin uncertain.The remarkable power of very low concentrations of diisopropyl fluoro-phosphonate (D.F.P.) to inhibit acetylcholinesterase 39 has been found toextend to certain other esterases.40 Jansen and his associates have foundthat trypsin and chymotrypsin are also inhibited by D.F.P. and are making adetailed study of the reaction with ~hymotrypsin.~~ Inhibition of thisenzyme is complete when 1 mol. of D.F.P. reacts with 1 mol. of enzyme. Inthe reaction hydrogen fluoride is liberated, and phosphorus and the di-isopropyl radical are bound to the protein.As diisopropyl phosphate has no33 A. Abrams and C. F. Jacobsen, Compt. Rend. Trav. Lab. Carlsberg, Sdr. Chim., 1951,27, 447.36 G. W. Schwert and S. Kaufman, ibid., p. 807.36 E. L. Smith, D. M. Brown, and M. Laskowski, ibid., 191, 639.37 E. F. Jansen, M.-D. Fellows Nutting, and A. K. Balls, ibid., 1949, 179, 201.38 P. Desnuelle, M. Rovery, and C. Fabre, Compt. rend., 1951,233, 1496.39 E. D. Adrian, W. Feldberg, and B. A. Kilby, Rept. Great Britain Ministry of41 E. J. Jansen, M.-D. Fellows Nutting, R. Jang, and A. K. Balls, ibid., 1949, 179,34 G. W. Schwert, J . Biol. Chem., 1951,190, 799.Supply, 1942, No. 2, 3.189; idem, ibid., 1950,185, 209.4O E. C. Webb, Biochem.J., 1948,42, 96296 BIOCHEMISTRY.inhibitory action it is presumed that condensation with a protein group hasoccurred. The modified enzyme may be recrystallised, dialysed, andfreeze-dried without change in the content of the inhibitor, confirming thatit is strongly bound. Chymotrypsinogen does not bind D.F.P., nor do anyof the constituent amino-acids or an acid hydrolysate of the enzyme. Thissuggests that an unusual group is responsible for the reaction with D.F.P.and that the reactive group appears on activation of the zymogen. As only1 mol. of inhibitor destroys the activity of 1 mol. of enzyme it is probablethat the reactive grouping is in or near the active centre. It is conceivablethat the condensation is followed by some secondary effect, such as a localchange in the configuration of part of the molecule, and that this is responsiblefor the loss of activity.However, the substituted enzyme has been crystal-lised and there has been no detectable change in physical properties, so thatthis seems unlikely. Various analogues of D.F.P. react with chymotrypsinin a similar mannerj2The influence of reagents with a known specificity for different polargroups of a protein has been investigated further. Thus trypsin may beacetylated without loss of enzyme activity 43 but is then no longer inhibitedby the egg white inhibitor, now identified as ovorn~coid.~~ It has thereforebeen concluded that amino-groups of the trypsin are essential for combinationwith ovomucoid but not for enzyme activity.Acetylation now permitstrypsin to be assayed in the presence of its i n h i b i t ~ r . ~ ~ The use of otherreagents 43 suggests that indole, amide, and possibly hydroxyl and guanidino-groups are essential for tryptic activity, while amino-, phenolic, glyoxaline,and disulphide groups are not.It has been found that a-chymotrypsin may be oxidised with periodateto give a protein which is still enzymically active and may be crystal-lised.46 Some non-protein-nitrogen is formed during oxidation, and reducingagents such as cysteine cannot reverse the reaction. This reaction is ofparticular interest as the proteolytic activity is reduced to 35% of theoriginal value while the esteratic power falls to only 65%. This is the firstexample of chemical differentiation between the two properties which areconsidered to originate from the same active centre of the enzyme and theauthors suggest that in the multipoint attachment of substrate to enzymeone point necessary for protease but not esterase function may be oxidisableby periodate.I n pepsin 47 and chymotrypsin 48 the amino-groups are not necessary foractivity but, with both, phenolic groups are essential.Groups essential for42 B. S, Hartley and B. A. Kilby, Nature, 1950,166,784 ; J. H. Fleisher, B. J. Jandorf,W. H. Summerson, and D. P. Norton, Fed. Proc., 1950,9,171; E. F. Jansen, A. L. Curl,and A. K. Balls, J. Biol. Chem., 1951, 190, 557.43 H. Fraenkel-Conrat, R. S. Bean, and H. Lineweaver, ibid., 1949,177, 385.44 H. Lineweaver and C.W. Murray, ibid., 1947,171, 565.4 5 H. Lineweaver, H. Fraenkel-Conrat, and R. S. Bean, ibid., 1949, 177, 205.4 6 R. M. Herriott, J. Cen. PhysioZ., 1936, 19, 283.4 7 I. W. Sizer, J . Biol. Chem., 1945,160, 547.4 8 E. F. Jansen, A. L. Curl, and A. K. Balls, ibid., 1951,189, 671ROBINSON AND WARREN : STEROID HORMONES. 297the trypsin-inhibitory action of ovomucoid have been studied in detail 43and a preliminary investigation has been begun with other trypsin inhibitors.This already suggests that these inhibitors, so diverse in origin, size and otherproperties, owe their inhibitory power to different groupings, and thereforepresumably their specific effect on trypsin arises from essentially differentmechanisms.It is regretted that the brevity of this report has permitted only slightreference to the large volume of interesting work on the proteases which hasbeen published in the last two or three years.R.R. P.5. STEROID HORMONES.During recent years workers in the field of steroid hormones have beenvery well served by the publication of numerous books, monographs, andreview articles. Authoritative articles on steroid hormones have beencollected and edited by Pincus and Thimann.l Reports of the AnnualLaurentian Conference 2 have included expert summaries on special topicsas well as stimulating accounts of work in progress. Similar publicationsare now appearing from CIBA Foundation Conferences dealing with steroidhormone^.^ Methods of hormone assay, including the biological and thechemical assay of steroid hormones, have been fully treated in a recent bookedited by em men^.^ What promises to be the first of a series of reportsfrom an Annual Steroid Conference dealing with steroids in experimentaland clinical practice has now a~peared.~ In view of the wealth of suchpublications in this field the present report is confined to discussion of recentwork on selected topics.Steroids in Urine.-Methods for isolation of urinary neutral 6 andphenolic steroids have been reviewed. Evidence has continued to accumu-late that the steroids of normal human urine are present almost entirely inthe conjugated form and that only very small amounts of any of the sub-stances so far investigated are excreted in the free form.An earlier report 8that free estrogen was present in the urine of pregnant women at full-terml, G.Pincus and K. V. Thimann, “ The Hormones,” Academic Press, N.Y., Vol. I ,“ Recent Progress in Hormone Research,” Academic Press, N.Y., Vols. I-VI,‘‘ Isotopes in Biochemistry,” “ Steroid Hormones and Tumour Growth,” ‘‘ Meta-C. W. Emmens (Editor), “ Hormone Assay,”Academic Press, N.Y., 1950.A. White (Editor), “ Steroids in Experimental and Clinical Practice,” The BlakistonCo., Toronto and Philadelphia, 1951.H. L. Mason, “ Recent Progress in Hormone Research,” 1948, Vol. 111, p. 103 ; H. L.Mason and W. W. Engstrom, Physiol. Rev., 1950,30,321; S. Lieberman and K. Dobriner,op. cit., p. 91 ; S. Lieberman, D. K. Fukushima, and K. Dobriner, J . Bid. Chem., 1950,182, 299; L.L. Engel, op. cit., 1950, Vol. V, p. 335. ’ L. L. Engel, “ Recent Progress in Hormone Research,” 1950, Vol. V, p. 335 ; G. A.Grant and D. Beall, op. cit., p. 307.1948; Vol. 11, 1950.1946-51.bolism of Steroids and their Estimation,” Churchill, London, 1951.S . L. Cohen, G. F. Marrian, and M. Watson, Lancet, 1935, I, 674298 BIOCHEMISTRY.has been re-investigated by Clayton and Marrian who now attribute theearlier result to contamination of the urine with glucuronidase present inblood clots and amniotic fluid. In the androgen group, Dingemanse and hercolleagues lo have isolated 6-hydroxy-3 : 5-cychandrosten-17-0ne whichthey believe to be excreted in the free form. When heated with acid thissubstance is converted into dehydroisoandrosterone.Methods of I.Iydrolysis.-It has long been recognised that a number ofsteroid substances occurring in extracts of acid-hydrolysed wines are artifactsin the sense that they do not occur in fresh urine but arise during hydrolysis.The continued improvements in methods of isolation and estimation haveincreased the troublesomeness of these artifacts and have intensified the searchfor methods of hydrolysis which will not give rise to them.The only typesof steroid conjugates so far isolated from human urine are glucuronides andsulphates and most effort has been put into a search for new methods ofcleavage of such compounds.Since sulphates are hydrolysed by acid at low temperatures, acidificationof urine to pH 1, followed by prolonged ether-extraction at room temper-ature, has been advocated.ll Steroid sulphates are rapidly hydrolysed bydioxan.12 (Estrogen sulphates can be split by phenolsulphatase.13 Marrianand his colleagues l4 acidified urine to pH 1 and determined the amounts offormaldehydogenic steroids extractable after different times. They recognisetwo types of conjugate : acid-labile and acid-stable.Acid hydrolysis of glucuronides requires a higher temperature thanhydrolysis of sulphates and this procedure is especially liable to produceartifacts.This has been clearly rec.ognised for some years and in earlierwork l5 crude preparations of liver glucuronidase were employed for splittingglucuronides. Current interest in corticoid excretion and the occurrence ofvery acid-labile compounds in this group of substances l4 has promptedintensive investigation of enzymic hydrolysis.Bacterial glucuronidasehas been shown l6 to liberate a large proportion of keto-steroids, oestrogens,and formaldehydogenic steroids. Similar preparations have been used forsplitting pregnanediol gl~curonide.1~ Yields of reducing steroids onenzymic hydrolysis three- to five-fold greater than on acid hydrolysis arereported.l* With beef spleen glucuronidase 10-30 times as much form-Q B. E. Clayton and G. F. Marrian, J. E.ndocrinol., 1950,6,332.10 E.Dingemanse, L. G. Huis in't Veld, and S. L.Hartogh-Katz,Nature, 1948,162,492.11 8. Lieberman and K. Dobriner, op. cit., Vol. 111, p. 91.1s G. A. Grant and D. Beall, op. cit., 1960, Vol. V, p. 307.13 H.Cohen and R. W. Bates, Endocrinology, 1949,44, 317.14 J. Y. F. Patterson, R. I. Cox, and G. F. Marrian, Biochem. J., 1950, 46, xxix;J. Y. F. Patterson and G. F. Marrian, Biochem. J., 1951, 48, xxxiii; G. F. Marrian, J.Endocrinol., 1961, 7, lxix.N. B. Talbot, J. Ryan, and J. K. Wolfe, J. Biol. Chem., 1943,151, 607.18 H. J. Buehler, P. A. Katzman, P. P. Doisy, and E. A. Doisy, Proc. SOC. Ezp.BioZ. Med., 1949, 72, 297; H. J. Buehler, P. A. Katzman, and E. A. Doisy, Fed. PTOC.,1950, 9, 157.17 B. W. L. Brooksbank, and G. A. D. Haslewood, Bwchem. J., 1950,47, 36.1 8 R. A. Kinsella, jnr., R. J. Doisy, and J. H. Glick, jnr., Fed. Proc., 1950,9, 190ROBINSON AND WARREN : STEROID HORMONES. 299aldehydogenic material is obtained l9 as on hydrolysis at pH 1.Whether allof the increase in formaldehydogenic material consists of steroid compoundsis still undetermined.Separation Methods.-Girard reagents continue to be the mainstay ofketonic steroid separations. Recommended procedures for small-scaleseparation of ct- and p-hydroxy-steroids with digit onin continue t o appear.20Hydrogen phthalates and hydrogen succinates are useful derivatives in theC,, series, but the necessity for alkaline conditions in their preparationprecludes their use with alkali-labile corticoids.Adsorption chromatography on alumina has been widely used21 forseparation of urinary steroids. Silica gel and magnesium silicate have beenused for the same purpose.22 Zaffaroni and his co-workers 23 applied paperchromatography to keto-steroids in the form of their hydrazones withGirard reagent T.They found that the number of carbonyl groups was theoverwhelming factor in determining R, values. In later work the samegroup 24 developed methods for paper chromatography of adrenocorticalsteroids in microgram quantities. The separation of steroids on alumina-impregnated paper has been described.25 CEhtrogens may be separated asdiazo-derivatives on paper chromatograms.26 Reversed-phase chroma-tography on < < Celite ” columns with aqueous methanol as stationary and12-hexane as mobile phase has been employed for steroid separations.27Kritchevsky and Tiselius 28 have reported successful separations of freeketo-steroids by reversed-phase chromatography on silicone-treated paperwith a water-ethanol-chloroform solvent.Localisation was achieved byspraying with the Zimmermann reagent. The slow-running androstanedione(RF 0.25) acts as reference standard. Good separation between isomericpairs is achieved (androsterone, R, 0-420 ; isoandrosterone, R, 0627).Engel and his colleagues 29 have made an intensive study of the applicationof counter-current distribution to the separation of natural estrogens.19 A. C. Corcoran, I. H. Page, and H. P. Dustan, J. Lab. CEin. Med., 1950, 36, 297;R. I. Cox and G. F. Marrian, Biochem. J., 1951, 48, xxxiii ; S. L. Cohen, Fed. Proc.,1951,10, 173; J. BioE. Chem., 1951,192, 147.2O W. R. Butt, A. A. Henly, and C. J. 0. R. Morris, Biochem. J., 1948,42,447.21 E. Dingemanse, L.G. Huis in% Veld, and B. M. De Laat, J. Clin. Endocrinol.,22 G. Pincus and L. P. Romanoff, Fed. Proc., 1950,9, 101.23 A. Zaffaroni, R. B. Burton, and E. H. Keutmann, J. Biol. Chem., 1949,177, 109.24 Idem, Science, 1950, 6, 111; Fed. Proc., 1950, 9, 250; J . Biol. Chern., 1951, 188,26 I. E. Bush, Nature, 1950, 166, 145; J . PhysioE., 1951, 112, lop.a 6 E. Heftmann, Science, 1950,111, 571.27 W. R. Butt, P. Morris, C. J. 0. R. Morris, and D. C. Williams, Biochem. J., 1951,28 T. H. Kritchevsky and A. Tiselius, Science, 1951, 114, 299.29 L. L. Engel, “ Recent Progress in Hormone Research,” 1950, Vol. V, p. 335 ; L. L.Engel, W. R. Slaunwhite, jnr., P. Carter, and I. T. Nathanson, J . Biol. Chem., 1950,185,265; W. R. Slaunwhite, jnr., L. L. Engel, P.C. Olmsted, and P. Carter, ibid., 1951,191,627; L. L. Engel, W. R. Slaunwhite, jnr., P. Carter, and P. C. Olmsted, ibid., p. 621.1946,6, 535; A. M. Robinson and F. Goulden, Brit. J. Cancer, 1949, 3, 62.763. H. Reich, D. H. Nelson, and A. Zaffaroni, ibid., 1950,187,411.49, 435300 BIOCHEMISTRY.Methods of Ana,lysis.-l7-Ketu-steroids. The most widely used method fordetermination of 17-keto-steroids is still the original methodY3* or modificationsthereof, based on the Zimmermann reaction. I n a study of the groupsnecessary for maximum colour development in this reaction, Marlow 3 lshowed that the C,l,,-keto group with adjacent CH, is essential. Wilson 32investigated the relative chromogenicity of various keto-steroids. Of theindividual components making up the total 17-keto-steroid complex of urineextracts, dehydroisoandrosterone has always been of peculiar interest becauseof its possible adrenal origin.Attempts a t specific estimation of thissubstance in the presence of other components were begun some years ago 33and have been continued. The reaction described by Munson and hiscolleagues 34 has been employed ~linically.~~ Jensen 36 has used the bluecolour shown by dehydroisoandrosterone in sulphuric acid for its estimation.The estimation of steroid alcohols in urinary extractslags considerably behind that of ketonic steroids. Engel 37,38 has invest-igated a method of estimation based on measurement of the colour producedby hydrogen dinitrophthalates of the steroid alcohols in methanolic alkali.In recent years various methods have been advocatedfor the determination of corticoids in urines.At present this field is one ofintense activity mainly because of a general realisation of the unsatisfactorynature of any of the methods thus far devised. That most commonly usedconsists in extraction of urine, with or without mild hydrolysis, with organicsolvents followed by assay of the extracts biologically or by chemical methodsdepending on reducing power or the amount of formaldehyde generated byperiodic acid oxidation. Agreement among the results obtained by the threetypes of assay is not to be expected. Proof of this is furnished by the recentisolation from urine of four steroids which are biologically inactive but havethe reactive groups involved in the chemical assays, i.e., 3% : 17a : 21-tri-hydroxypregnane-11 : ZO-di~ne,~~ 3a : l l p : 17a : 21-tetrahydroxypregnan-20-one,4* 3p : 2I-dihydroxypregn-5-en-20-0ne~~~ and 17a : 21 -dihydroxy-pregnane-3 : 11 : 20-tri0ne.~~ The present situation of chemical assay ofurinary corticoids thus resembles that arising in chemical estimations ofSteroid alcohols.Cortiwsteroids.30 N.H. Callow, R. K. Callow, and C. W. Emmens, Biochem. J., 1938, 32, 1312;3 1 H. W. Marlow, ibid., 1950, 183, 167.32 H. Wilson, Fed. Proc., 1950, 9, 246.33 G. Pincus, Endocrinology, 1943,32, 176; J. Patterson, Lancet, 1947,253,580.34 P. L. Munson, M. E. Jones, P. J. McCall, and J. F. Gallagher, J. Biol. Chem.,35 R. L. Landau, K. Knowlton, and K.Lugibihl, J. CZin. Invest., 1950,29, 829.3 6 C. C. Jensen, Nature, 1950, 165, 321; Acta Endocrinol.,.l950, 4, 140, 374.37 L. L. Engel, op. cit., p. 335.38 L. L. Engel, H. R. Patterson, H. Wilson, and M. Schinkel, J. BWZ. Chern., 1950,39 S. Lieberman, L. B. Hariton, and K. Dobriner, Fed. Proc., 1950, 9, 196; J. J.4 O S. Lieberman, L. B. Hariton, M. B. Stokem, P. E. Studer, and K. Dobriner, ibid.,A. F. Holtorffand F. C. Koch, J. Biol. Chem., 1940,135, 377.1948, 176,73.183,47.Schneider, ibid., 10, 244.10, 216. 4 1 J. J. Schneider, ibid., p. 244ROBINSON AND WARREN : STEROID HORMONES. 301urinary 17-keto-steroids, namely, that close correlation with biological assayis not to be expected but that search is made for empiric relations betweenthe amounts of certain closely related substances excreted and physiologicalor pathological conditions.This approach, which is the natural one, isalready entering on its second phase, namely, identification and estimationof individual components. As has already been noted,14 a major problemin the isolation or estimation of urinary corticoids is that of hydrolysis andextraction, I n urine corticoids appear to be present in more than one formof conjugation.423 43 I n addition, indications have been obtained of thepresence of a free formaldehydogenic steroid which is not egciently extractedby chloroform unless special precautions are taken.43 Marrian 43 has recentlydescribed available methods for the hydrolysis of the conjugated adreno-cortical steroids in urine as so unsatisfactory that it is doubtful whetherresults of any real quantitative significance can be obtained by their use.Methods of measuring reducing and formaldehydogenic steroids havebeen r e ~ i e w e d .~ ~ , ~ ~ Increased sensitivity in formaldehyde determinations,compared with the usual distillation method, has been claimed by the use ofConway diffusion ~ n i t s . 4 ~ Dichloromethane in a continuous extractor hasbeen advocated as an efficient solvent."6 A number of studies have appearedcomparing different assay methods. Venning 47 compared the reduction(copper) with the formaldehydogenic method and found the reductionmethod more variable. Wick and his colleagues48 found that the form-aldehydogenic method gave values considerably higher (6-8 times) thanbioassay by glycogen deposition.In a similar comparison of reducingmethods and bioassay Sprechler 49 found the chemical values to be 8-10times those obtained biologically. A new colour reaction for steroids withdihydroxyacetone side chains which may be used for their estimation hasbeen described. 50QCstrogens. I n connection with their study of counter-current distribu-tion in the separation of oestrogens 29 Engel and his colleagues employedfluorometric determinations (which have been reviewed 37). A fluorometricmethod has also been applied to urine extracts by Bates and Cohen.51When a solution of a steroid estrogen is heated in a mixture of phenoland sulphuric acid, cooled, diluted with water, and reheated, a pink colourhaving an absorption maximum a t 520 mp develops.52 Since Kober firstdescribed this reaction many attempts have been made to apply it to the42 A.M. Robinson and J. M. Norton, J. EndocrinoZ., 1951, 7 , 321.43 G. F. Marrian, ibid., p. lxix.4 4 L. P. Romanoff, J. Plager, and G. Pincus, Emdocrinology, 1949,45, 10.4 5 G. T. Bassi1 and A. M. Hain, Nature, 1950, 165, 525.4 6 G. Pincus and L. P. Romanoff, Fed. Proc., 1950, 9, 101.4 7 E. H. Venning, Trans. 1st Conf. Metabolic Interrelations, 1949, p. 167.4 8 A. N. Wick, E. Pecka, jnr., and R. Medz, J. Clin. Endocrinol., 1950,10, 84.4n M. Sprechler, Acta Endocrinol., 1950, 4, 205.C. C. Porter and R. H. Silber, J. BWZ. Chem., 1950,185, 201.51 R. W. Bates and H. Cohen, Endocrinology, 1950,47, 166, 182.5B S.Kober, Bwchem. Z., 1931, 239, 209302 BIOCHEMISTRY.chemical assay of urinary ce~trogens.~~ The major problem is that ofinterfering chromogens which produce brown pigments. Of the proceduresso far published that of Stevenson and Marrian 54 is probably the best. Morerecent discussions of the Kober test have been given by Jayle and hiscolleagues,55 and Stimmel has applied this reaction to hydrogen phthalatesof cestradiol and cestratriol. 56Pregmnediol. In 1936 Venning and Browne discovered that pregnanedioloccurs in human pregnancy urine as a glucuronide which could be isolated asa crystalline sodium salt.57 Based on this observation a relatively simplegravimetric determination of pregnanediol as its glucuronide was devised.58This method rapidly found widespread acceptance.Heard and his col-leagues 59 showed that the glucuronic acid is conjugated at CQ) in this com-pound and the substance was proved to be a p-glucuronide.6° In spite ofthese advances in characterisation of the glucuronide, however, severalgroups of workers reported that they failed to find more than about 70% ofthe theoretical amount of pregnanediol on acid hydrolysis of ‘( sodiumpregnanediol glucuronide.” Marrian and his colleagues therefore undertookan extensive investigation of the so-called ( ( sodium pregnanediol glucur-onide ” prepared from human pregnancy urine. Their results showed thatthis was a mixture containing approximately 20 % of sodium 3cc-hydroxy-pregnan-20-one glucuronide.61, 62In 1941 Astwood and Jones 63 described a new method for the quantitativedetermination of urinary pregnanediol as the free steroid.This wasdeveloped by Talbot and his colleagues who estimated the purified preg-nanediol by the yellow colour it develops in concentrated sulphuric acid.More recently Marrian and his c.olleagues have devised a refined version ofthis method which permits determination of pregnanediol with a reasonabledegree of accuracy at a level of 2 mg. per day, and this has been used duringthe past few years in their extensive investigations of the fate of progesteronein normal and diseased states.65Steroids isolated from Urine.-Extensive reviews and tabulations of53 G. A. D. Haslewood, “ Hormone Assay,” Academic Press, N.Y., 1950, p.443.54 M. F. Stevenson and G. F. Marrian, Biochem. J., 1947,41,507.56 M. F. Jayle, 0. Crdpy, and 0. Judas, BUZZ. SOC. Chim. bioZ., 1949,31, 1592.66 B. F. Stimmel, Fed. Proc., 1950, 9, 235.67 E. H. Venning and J. S. L. Brome, Proc. SOC. Expt. BWZ. Med., 1936,34, 792.6 8 Idem, J . Biol. Chem., 1937,119,473 ; 1938,126,595.59 R. D. H. Heard, M. M. Hoffman, and G. E. Mack, J . Biol. Chem., 1944,155, 607.60 C. F. Huebner, R. S. Overman, and K. P. Link, ibid., p. 615.61 G. F. Marrian and N. Gough, Biochem. J., 1946,40, 376.62 E. S. Sutherland and G. F. Marrian, ibid., 1947,41, 193.63 E. B. Astwood and G. F. S. Jones J . BWl. Chem., 1941,137, 397.6 4 N. B. Talbot, R. A. Berman, E. 4. Machachlan, and J. K. Wolfe, J . CZin. Endo-crinol., 1941, 1, 668.6 5 I.F. ,Sommerville and G. F. Marrian, J. EndocrinoZ., 1949, 6, ix; Biochem. J.,1950, 46, 285, 290; G. F. Marrian, “ Recent Progress in Hormone Research,” 1949,Vol. IV, p. 3; I. F. Sommerville, G. F. Mamian, J. J. R. Duthie, and R. J. G. Sinclair,Lancet, 1950, I, 116ROBINSON AND WARREN : STEROID HORMONES. 303steroid substances isolated from urine have appeared comparativelyrecently.66 Mention will, therefore, only be made of some recent isolations.Normal human urine contains small amounts ofcompound E (17 : 21-dihydroxypregn-4-ene-3 : 11 : 20-trione) and largerquantities of compound F (11 : 17 : 21-trihydroxypregn-4-ene-3 : 20-dione).Administration of ACTH (adrenocorticotrophic hormone) increases the ex-cretion of compound F.Compound F has been isolated from the urine of apatient with Cushing’s syndrome,67 from that of a patient with rheumatoidarthritis under treatment with ACTH and from urines of post-operativepatients,68 or of cancer patients undergoing ACTH therapy.69Crystalline compound E has been isolated from the urine of normalsubjects 7O and from patients with rheumatoid arthritis or Addison’sdisease treated with cortisone 68 (17 : 21-dihydroxypregn-4-ene-3 : 11 : 20-trione acetate). Closely related metabolites have also been isolated,3a : 17a : 21-trihydroxypregnene-11 : 20-dione (tetrahydro-E) by Schneider 71and by Lieberman and his colleague^,^^ and 3a : 17a-dihydroxypregnene-11 : 20-dione (21-deo~yfetrahydro-E).~~Other new urinary steroids with an oxygen function atCtll, include 3a-hydroxypregnane-l l : 20-di0ne,~~ 3a : 20a-dihydroxypreg-n a n - l l - ~ n e , ~ ~ ll-ketoandrosterone,73 3a : 17/3-dihydroxy~tiocholan-11-one,7311 -hydroxyandro~terone,~* and 3a-hydroxyandrost-9-en-17-one. 74Among recent work in the group of C,, compounds without an oxygenfunction a t C(ll) may be mentioned Klyne’s demonstration that Marrian’strio1 75 is pregnane-3a : 17a : 20a-trio1 76 and the same author’s proof thatthe uranes are homo-compounds.77 Two new triols have been isolated,pregn-5-ene-3P : 17a : 20~-trio1 78 and pregn-5-ene-3p : 16a : 20a-tri01.~~ Sixof the thirteen steroids isolated from adrenal hyperplasia urine by Miller andDorfman 74 were C,zl, compounds.C,, Compounds.In this group, recent isolations include androstane-Compounds E and I?.C,, Compounds.*6 K.Dobriner, S. Lieberman, and C. P. Rhoads, J. Biol. Chem., 1948,172, 241 ; K.Dobriner, S. Lieberman, C. P. Rhoads, R. N. Jones, V. Z. Williams, and R. B. Barnes,ibid., p. 297; S . Lieberman and K. Dobriner, op. cit., Vol. 111, p. 71; H. L. Mason,op. cit., p. 103.67 H. L. Mason and R. G. Sprague, J . Biol. Chem., 1948, 175, 451 ; R. G. Sprague,A. B. Hayles, M. H. Power, H. L. Mason, and W. A. Bennett, J . Clin. Endocrinol.,1950, 10, 289. 68 H. Mason, J. Biol. Chem., 1950,182, 131.6s S. Lieberman, L. B. Hariton, and K. Dobriner, Fed. Proc., 1950,9, 196.70 J. J. Schneider, Science, 1950, 111, 61.71 Idem, Fed. PTOC., 1950, 9, 224; J . Biol. Chem., 1950, 183, 365.72 K. Dobriner, S. Lieberman, H.Wilson, B. Ekman, and C. P. Rhoads, “ PituitaryAdrenal Function,” Amer. Assoc. Advancement of Science, Washington, D.C., U.S.A.,1951, p. 158.7s S. Lieberman, D. K. Fukushima, and K. Dobriner, J. BWZ. Chem., 1950,182, 299.7 4 A. M. Miller and R. I. Dorfman, Endocrinology, 1950, 46, 514.76 G. C. Butler and G. F. Marrian, J . Biol. Chem., 1937,119, 565; 1938,124,237.7 6 W. Klyne, Biochem. J., 1949, 45, viii.78 H. Hirschmann and F. B. Hirschmann, J . Biol. Chem., 1950,187, 137.7s Idem, ibid., 1950,184, 269.7 7 Idem, Nature, 1950,166, 659304 BIOCHEMISTRY.3a : 16a : 17P-tri01,~~ 3-P-hydroxycetio-cholan- 17-one, 81 androst - 1 -ene-3 : 17-dione. 81 Androst- 16-en-3a-01 has beenisolated from the “pregnanediol-like glucuronide ” of men’s urine.82Steroid Hormones in Blood.-There has been growing realisation during thepast few years that the detection and estimation of steroid hormones andtheir metabolites in blood is probably the most important current problemin steroid biochemistry. The chief incentive to the immense labour whichhas been devoted to the pursuit of urinary metabolites has been the hope ofobtaining indirectly some knowledge of the state of the steroid hormones inthe blood and tissues. With the increasing refinement of analytical tech-niques the difficulties and dangers of this approach t o the problem havebecome more apparent. As an example of the difficulties the metabolism oftestosterone (assumed to be the testicular hormone) may be cited. It haslong been known that administration of testosterone leads to increasedexcretion of both androsterone and hydroxycetiocholanone.Attempts toascribe these urinary metabolites solely to the metabolism of testosteroneare, however, vitiated by the demonstration that dehydroisoandrosteroneadministration leads to increased excretion of the same two steroids. Afurther example of a different type is the lack of evidence that a high rate ofexcretion of pregnanediol (a demonstrable metabolite of progesterone) isassociated with a high level of progesterone in blood or tissues.The detection*and estimation of steroid hormones in the blood is aformidable problem. Present evidence suggests that they are present inextremely low concentrations. Also, there are indications that some a t leastof these substances are closely associated with protein in the form of lipo-protein complexes.This alone suggests that great difficulty may be en-countered in the extraction of the steroids as a preliminary to their identi-fication and estimation. At the present stage only brief mention will bemade of some recent attacks on this problem.Although Hooker and Forbes 83 by a highly sensitive bioassay reportedvalues of 5.3 pg. of progesterone per ml. of human pregnancy blood, Buttand his colleagues,8* using a method based on solvent partition, partitionchromatography, and polarographic determination which they estimatedcould detect progesterone at levels above 0.1 pg./ml., failed to find pro-gesterone in 13 samples of human pregnancy blood.Progesterone wasdetected in 2 samples of umbilical cord blood. Hoskins 85 failed to detectprogesterone in the plasma of pregnant women by ultra-violet spectrometry.Nelson et aE.S6 isolated compound F from adrenal vein blood of dogscetiocholane-3a : 16a : 17P-tri01,~~80 S. Lieberman and K. Dobriner, 1950 Abstract Amer. Chem. SOC. 117th Meeting, 1%.81 K. Dobriner and S. Lieberman, “ A Symposium on Steroid Hormones,” Univ.82 B. W. L. Brooksbank and G. A. D. Haslewood, Biochem. J., 1950,47, 36.83 C. W. Hooker and T. R. Forbes, Endocrinology, 1949,44, 61.S4 W. R. Butt, P. Morris, C. J. 0. R. Morris, and D. C. Williams, Biochem. J., 1951,8 6 A. L. Hoskins, jnr., Proc. Soc. Expt. Biol. Med., 1950,73,439.8 6 D. H. Nelson, H.Reich, and L. T. Samuels, Science, 1950, 111, 578.Wisconsin Press, Madison, Wisconsin, 1950, p. 46.49, 434ROBINSON AND WARREN : STEROID HORMONES, 305treated with ACTH. The blood was extracted with chloroform or ether,and the extract partitioned between hexane and 70% ethanol. Theethanolic fraction was chromatographed on magnesium silicate-" Celite "columns and eluted with chloroform containing progressively increasingconcentrations of ethanol. Ultra-violet spectrometry was used for recognition.More recently the same workers have proposed a general method for the deter-mination of 17-hydroxycorticosteroids 87 based on Porter and Silber's colourreaction 88 adapted as a micro-method. Reich et aLS9 have confirmed theisolation of compound F which could be recognised by paper chromat~graphy.~OSteroid Hormones and Enzymes.-During recent years increasing atten-tion has been paid to the'interaction between steroid substances and enzymesystems. On the one handthere is the necessity to identify the enzymes involved in the interconversionsand metabolism of the known steroid hormones in the tissues, and on theother the search for possible sites of action of steroid hormones on knownenzyme systems involved in intermediary metabolism.Current canons ofbiochemical faith suggest that the latter is the most direct line of attack onthe unsolved problem of the mechanism of action of steroid hormones. This is,of course, an empiric approach and since no clear picture has yet; emerged briefmention only will be made of a few of the systems that have been investigated.Kochakian and Robertson 9 l studied the action of adrenal corticalsteroids on arginase activity.Cortisone increased the activity of this enzymein the liver and the kidney of mice, but compound A (21-hydroxypregn-4-ene-3 : 11 : 20-trione) had no effect. Hayano et aLg2 found that deoxy-corticosterone alone of 32 steroids tested inhibited D-amino-acidoxidase.Umbreit and Tonhazy 93 found that the proline-oxidising enzyme wasaffected by cortisone. The same authors 94 investigated the adenylatesystem. There have been a number of recent reports on the influence ofcorticoids on carbohydrate systems. Chiu 95 and Chiu and Needham 96investigated the influence of cortisone, deoxycorticosterone, and compoundA on rat and rabbit liver slices and found increased glycogen content withoutalteration in oxygen uptake. Verzhr and his colleagues have shown thatcorticoids without a C,,,,-oxygen function have important effects in carbo-hydrate metabolism.97 Dirscherl et aLS8 have made detailed investigationsTwo aspects of this problem may be recognised.87 D. H. Nelson, private communication.sB H. Reich, D. H. Nelson, and A. Zaffaroni, ibid., 187, 41 1.91 C. D. Kochakian and E. Robertson, ibid., 190, 481.92 M. Hayano, R. I. Dorfman, and E. Y . Yamada, ibid., 1950, 186, 603.93 W. W. Umbreit and N. E. Tonhazy, ibid., 1951, 191, 249.94 Idem, ibid., p . 257.96 C. Y. Chiu and D. M. Needham, Nature, 1949,164,790; Biochem. J., 1950,46, 114.9 7 A. Sass-KortsBk, F. C. Wang, and F. VerzBr, Amer. J . Physiol., 1949, 159, 256;F. C. Wang and F. VerzBr, ibid., p. 263; F . Verzitr and F. C. Wang, Nature, 1950, 165,114; F. C. Wang, ibid, p. 277; E . Leupin and F. Verzk, Biochem. J . , 1950,46,562.98 W. Dirscherl and K. H. Hauptmann, Biochem. Z., 1950, 320, 199; W. Dirscherland W. Knuchel, ibid., p. 228.C. C. Porter and R. H. Silber, J . Biol. Chem., 1950,185, 201.R. B. Burton, A. Zaffaroni, and E. H. Keutmann, ibid., 1951,188, 763.95 C. Y . Chiu, Biochem. J., 1950,46, 120306 BIOCHEMISTRY.of the effect of Estrogens and androgens on respiratory and glycolyticsystems. Hayano et aLg9 found that certain steroids inhibit the oxygenconsumption of liver, kidney, and brain slices.The most outstanding work on the enzymes responsible for the metabolismof steroid hormones is that of Samuels and his colleagues on the metabolismof testosterone which has been reviewed by Samuels.loO These workers havedemonstrated that mammalian livers contain enzymes which will converttestosterone into compounds without the ap-unsaturated ketone structure ora C,,,,-carbonyl group. They recognise a t least three enzyme systems. Onesystem, catalysing the oxidation of the C,,,,-alcohol group to a ketone, re-quires diphosphopyridine nucleotide (DPN) as a cofactor. A second appearsto act preferentially on the androst-4-ene-3 : 17-dione so formed, destroyingthe conjugated double bond system. The cofactor for this reaction has notbeen identified. A third system, with citrate specifically as cofactor, actsdirectly on testosterone, to destroy conjugation in ring A. Few tissues otherthan liver metabolise testosterone. Kidney was the only other tissue foundwith significant activity. When kidney slice or kidney mince is incubatedwith testosterone there is a significant disappearance of the ap-unsaturatedgroup. The 17-keto-steroidsformed are equal to the ap-unsaturated groups destroyed. Recently, Westand Samuels lol have reported enzyme systems involved in testosteronecatabolism in kidney of dog, rabbit, and guinea pig. The principle action inall three species was oxidation of the C,,,,-hydroxyl group to a ketone. DPNwas a cofactor in the dog and guinea pig but not in the rabbit. The sameoxidative system appeared to act on any C,, 17-hydroxy steroid with analcohol or ketone group at position 3. The reaction could be reversed in thepresence of acids of the Krebs cycle. They summarise the reactions so farknown to be involved in testosterone metabolism as follows :The rate is about one-third of that for liver.17-OH-compounds (4 Citrate (B) DPNwithout Testosterone Androstenedione-GEGz&- 1 a/honjugation J (c) UnknownAndrosterone andand its isomers 1 Non-17-ketosteroidswithoutajLconjugationBiosynthesis of Steroid Hormones.-The dramatic clinical effects obtainedwith cortisone and ACTH in recent years have stimulated efforts to solvelong-standing problems connected with the biosynthesis of adrenocorticalhormones. These involve the questions of how many of the 28 specificsteroids isolated from adrenal tissue lo2 are actually secreted by the gland,8Q M. Hayano, S. Schiller, and R. J. Dorfman, Endocrinology, 1950, 46, 387.loo L. T. Samuels, “ Recent Progress in Hormone Research,” 1949, Vol. IT, p. 65 ;L. T. Samuels, “ A Symposium on Steroid Hormones,” Univ. Wisconsin Press,Madison, Wisconsin, 1950, p. 241.lol C. D. West and L. T. Samuels, J . Biol. Chem., 1951,190, 827.lo% T. Reichstein and C. W. Shoppee, “ Vitamins and Hormones,” 1943, Vol. I, p. 346ROBINSON AND WARREN : STEROID HORMONES. 307what are their precursors and how are they elaborated, and how does ACTHparticipate in the corticosteroidogenic mechanism.Pincus and his collaborators initiated experiments some six years agodesigned to answer these questions and have now presented a report of theirresults.lo3 Their general method consists of the study of corticosteroido-genesis in isolated perfused adrenal glands with or without added ACTH.Much of their earlier work was devoted to the elaboration of the necessarytechniques, but already results of great significance are being obtained.Perfusion of blood containing ACTH through isolated ox adrenals leads tothe release of a t least 15 a-ketol steroids. A number of these have beencharacterised by paper chromatography. Compounds A and F compriseabout 60% of the total steroids.The perfusion of adrenals with known steroids but without added ACTHwas also studied. It was found that the gland could effect ll-p-hydroxyl-ation of both C,, and C,, steroids. The data suggested that 17-hydroxy-corticosterone (compound F) and corticosterone are the end products of thecorticosteroid synthetic system and that the natural route might be (a)degradation of the cholesterol side chain to produce the ketol side chain,( b ) ap-unsaturation in ring A, and ( c ) introduction of aSince deoxycorticosterone and corticosterone were not hydroxylated a tC(l,) on perfusion, the possibility was considered that the presence of a C(21)-hydroxyl group might be an inhibitory factor in C,,,,-hydroxylation. Sup-port for this view was obtained when the perfusion of progesterone orpregnenolone led to the production of C,,,,-hydroxylated derivatives.Pincus and his colleagues tentatively suggest that pregnenolone orprogesterone is the key intermediate. The hydroxylation mechanismappears to be independent of ACTH and they suggest that the action of thissubstance is primarily concerned with the conversion of cholesterol intopregnenolone.The biosynthesis of cholesterol itself and its metabolic conversion into bileacids and pregnanediol have been reviewed by Bloch.lo4group.A. M. R.F. L. w.E. BOYLAND.E. KODICEK.J. R. ~MBRRAcK.R. R. PORTER.A. M. ROBINSON.I?. L. WARREN.103 0. Hechter, A. Zaffaroni, R. P. Jacobsen, H. Levy, R. W. Jeanloz, V. Schenker,lo4 K. A. Bloch, “ A Symposium on Steroid Hormones,” Univ. Wisconsin Press,and G. Pincus, “ Recent Progress Hormone Research,” 1951, Vol. VI, p. 215.Madison, Wisconsin, 1950, p. 33

ISSN:0365-6217    

DOI:10.1039/AR9514800249

出版商:RSC    

年代:1951

数据来源: RSC

摘要:

ANALYTICAL CHEMISTRY.1. INTRODUCTION.ANALYTICAL chemistry may be regarded either as one of the oldest or asone of the newest branches of chemistry. This anomaly, among other things,renders the preparation of an Annual Report on the progress of analyticalchemistry a formidable task. As P. J. Elving has pointed out in a consider-ation of current trends, it was much easier, 20 or 30 years ago, to definewhat is meant by the term “ analytical chemistry ” than it is to-day. If hisdefinition is accepted, of “ all techniques and methods for obtaining inform-ation regarding the composition, identity, purity and condition of samplesof matter in terms of the kind, quantity and groupings of atoms and mole-cules, as well as the determination of those physical properties and behaviourwhich can be correlated with these objectives,” the field to be covered ismuch vaster than the space available, or, indeed, the time and energy of oneor a few individuals will permit.It will be recalled that for the past few yearsannual reviews of most, though not all, recognised fields of analytical chemis-try have appeared,2 and these have, on each occasion, been compiled by morethan a dozen writers, and have occupied over 100 pages. Where one hasalmost 100 elements to deal with, together with the unnumbered classes oforganic compounds, and where the techniques available may be listed (inpart) under a series of 40 headings ranging from absorption spectrometry tozymometry,3 it is obvious how far science has moved from the qualitativeanalysis and the volumetric and gravimetric methods of the earlier part ofthis century.The chemical analyst must be prepared to apply any one ofthese techniques to any one of the elements or compounds or to the infinitevariety of mixtures that is possible ; the analytical chemist must not only befamiliar with the theory of these but must be able to select, correlate, com-pare, and improve the methods available, and must be alive to the applic-ations of still further physicochemical methods and techniques. In con-sequence of this complexity, a Report of this type cannot be completelycomprehensive, even if confined to the strictly “ pure ” as distinct from the“ applied ” field ; and the selection made, no matter how careful the Reportermay be, must in some degree reflect his prejudices.On surveying the extensive literature, perhaps the most striking pointthat emerges is not the amount of information but, as many authors have,indeed, been quick to stressY4 the lack of information that exists in so manyinstances.It has been said that when the number of publications dealingwith the details of any one analytical method begins to increase markedlyit is probably an indication of a lack of fundamental information regardingthe method. Although the number of authors who realise the necessity1 Analyt. Chem., 1950, 22, 411.4 See e.g., A. R. Burkin, Quart. Reuiews, 1951, 5, 1.a Ibid., 1949, 21, 2 ; 1950, 22, 2; 1951,23, 2.E. J. Serfass, R. G. Steinhardt, and F. C. Strong, ibid., 1950, 22, 966WILSON : INTRODUCTION.309of obtaining such information is increasing, it is still not nearly greatenough. For the proper progress of any science the proportion of basicresearch to ad hoc research should be very high. A survey of recent worksuggests that in analytical chemistry ad hoc research still bulks much toolarge for the health of the science. This is to be deplored if for no otherreason than that there is a natural resulting tendency on the part of outsidersto regard all analytical work as ad hoc, and to assume that once it becomesfundamental it is no longer analytical chemistry. But looking furtherthan the. reputation of the science, there is the additional consequence thatlack of fundamental knowledge causes a multiplication of superficialinvestigations. It is not surprising, therefore, that it is so difficult, as lastyear’s Reporter stres~ed,~ to distinguish major advances! or even to indicatetrends.A classification into sections of all the analytical publications appearingover the past year shows a high preponderance dealing with (1) colorimetricand absorptiometric techniques, and (2) that heterogeneous collection oftechniques usually classed under a blanket -heading of “ chromatographicand similar separations.” In the first field it is clear that the absorptiometer,now firmly established as a laboratory tool, will always appeal because of themany advantages it possesses.There is still much room for selection and forthe discovery of new reagents. There is also much scope for a propercomparison and evaluation of existing methods.The second field mentioned is in process of intensive and enthusiasticcultivation.It is not a simple matter to assess the value of many of thevariants proposed and it is probable that, just as in the early history of otheranalytical techniques, some years must pass before the methods achieve aproper and uninflated importance. Chromatography proper, and the applic-ation of partition methods to organic analysis (and in particular to bio-chemical investigations), have already proved their worth over wide ranges :and certain others of the techniques have a more limited but still high value.It may, however, be deduced that ion-exchange methods, and partition andextraction methods, perhaps in novel forms, hold high promise for the solutionof an extensive variety of problems in the future. Again, the importanceof a fundamental examination of separation processes such as are involvedin these techniques is only beginning to be realised, and this realisation isexpressed clearly in several valuable contributions during the past year.In connexion with an earlier remark concerning absorptiometry, thisintroduction might conclude with a comment on the necessity for unbiassedassessment of analytical methods.The fact that an author has thought outa new procedure which works is by itself hardly sufficient excuse for public-ation of the method, at least in an extended form. The procedure should beshown clearly to be superior to other procedures already existing for the samepurpose.It may be felt that comparison of other people’s methods in orderto choose the most reliable is inferior to or less important than devising newmethods of one’s own. But the enormous extent of the experimental liter-F. R. Cropper, Ann. Reports, 1950, 47, 373310 ANALYTICAL CHEMISTRY.ature on analytical methods must cause us to examine the validity of thisviewpoint. There is, at any rate, a clear case for increased use of statisticalinvestigation as one of the major concerns of the analytical chemist at thepresent time, and it is pleasant to note that attention to this has not beenlacking in the past year.2. GENERAL.The progress of analytical chemistry for the years 1900-1950 has beenreviewed.6 P.J. Elving has discussed the basic stages in analytical processes;that is, sampling, separation of the desired constituent in a measurable state,the measurement, and finally, the calculation and interpretation of thenumerical value thus obtained. He distinguishes between non-discriminatorymeasurements such as that of mass, and discriminatory methods which dealwith such processes as the recording of the absorption spectrum by a spectro-photometer. In a further paper he has discussed the importance of hetero-geneous equilibria in analytical chemistry, particularly as related to problemsof separations as used a t present, and with respect to future developments.The selection and nature of standards for analytical purposes has beenconsidered in general by G.D. Beal,g and particular types of standards andstandardisation procedures for different branches of analytical chemistryhave been discussed.10-22 Trishydroxymethylaminomethane has beenproposed as an acidimetric standard.23 A method for the preparation ofcarbonate-free sodium hydroxide solution, using an ion-exchange resin, hasbeen described.24 A report has been given of the keeping properties ofvolumetric solutions.25 Specifications for microchemical reagents havebeen published.26The increasing importance of the application of statistical methods toanalytical chemistry has been emphasised by the publication of a seriesof lectures specially directed to the analytical chemist,27 and by the subse-quent meeting 28 which was held to provide an opportunity for further6 A.Lassieur, Chim. anal., 1951, 33, 216. Analyt. Chern., 1950, 22, 962.Ibid., 1951, 23, 1528. Ibid., 1951, 23, 1202.10 H. V. Farr, A. Q. Butler, and S. M. Tuthill, ibid., p. 1534.11 E. Wichers, ibid., p. 1537.la V. A. Stenger, ibid., p. 1540.1 4 B. F. Scribner and C. H. Corliss, ibid., p. 1548.1 5 A. H. Thomas and C. S. Mills, ibid., p. 1553.1 6 W. A. Kirklin and W. W. Becker, ibid., p. 1556.1 7 F. D. Tuemmler, ibid., p. 1559.18 L. E. West, ibid.,p. 1562.80 R. Belcher and R. Goulden, I d . Chem., 1950, 26, 451.8 1 E. Kahane and S. Korach, Chim. anal., 1951, 33, 11.28 L. Nicholas, J. Plant&, and R. BureI, ibid., p. 268.83 J. H. Fossum, P. C. Markunas, and J. A. Riddick, AnuZyt. Chem., 1951, 23, 491.24 C.W. Davies and G. H. Nancollas, Nature, 1950,165, 237.85 B. W. Durham, J. Chem. Educ., 1951,28, 387.8 6 Anon., Analyst, 1951, 76, 671.27 D. R. Read, Roy. Inst. Chem. Monog., No. 1, 1951.lS H. A. Bright, ibid., p. 1544.C. 0. Willits, ibid., p. 1565.E. C. Wood, D. J. Finney, 0. L. Davies, and D. R. Read, Nature, 1951,168, 1072WILSON: GENERAL. 311discussion of this topic. M. Vignau 29 describes the general application ofstatistics to analytical problems. The use of simplified statistics for a smallnumber of observations has been describedFO and a comparison has beenmade of criteria, for the rejection of measurements.31 S. E. Hermon andE. C. Mills 32 have compared the precision of photometric and polarographicprocedures for aluminium and magnesium against classical wet methods.A somewhat similar comparison has been carried out for manganese.33 Astatistical analysis of three absorptiometric methods for iron 34 has also beenmade.The application of statistical methods to a series of repeatedindependent titrations has been de~cribed.~~ Statistical studies of spectro-graphic source units,36 of the spectral analysis of plant ash,37 and of thephotometric determination of sodium, lithium, and potassium in glass 38 havebeen described. The analysis of metals and alloys39 and biological assaymethods 40 have also been studied from the standpoint of statistics. A statist-icalinvestigation has been made of precision and accuracy in the chemicalanalysis of silicate rockstl and methods suitable for the design and inter-pretation of inter-laboratory studies of test methods have been describedj2Advances in inorganic microchemistry have been reviewed by P.W.West,a the review including qualitative analysis, volumetric and gravimetricanalysis, colorimetric methods, and various forms of separation. A. J.Haagen-Smit 44 has discussed the contribution of microanalysis to analyticalchemistry.Reagents.-R. Belcher and R. Goulden 45 have reviewed the applicationsof a selection of new analytical reagents. The compounds termed “ Com-plex~nes,”~~ first Erought to the attention of analytical chemists in 1946,47have received a considerable amount of attention. These compounds,ethylenediaminetetra-acetic acid (EDTA or “ enta ”) and related substances,have been used in a number of ways.F. L. Hahnt8 making use of a titrationprocedure for determination of calcium and magnesium, with bromothymol-blue as indicator, uses the sodium or ammonium salt for the determinationof hardness of water. With murexide as indicator, small amounts of calcium29 Chim. Analyt., 1950,32, 156, 185.30 R. B. Dean and W. J. Dixon, Analyt. Chem., 1951, 23, 636.31 W. J. Blaedel, V. W. Meloche, and J. A. Ramsay, J . Chem. Educ., 1951, 28, 643.32 Metullurgia, 1950, 42, 220.34 L. K. Reitz, A. S. O’Brien, and T. L. Davis, Analyt. Chem., 1950, 22, 1470.35 J. E. Kerrich, S . Afr. Ind. Chem., 1950, 4, 134.36 H. T. Shirley, A. Oldfield, and H. Kitchen, J . Iron Steel Inst., 1950, 166, 329.37 A.C. Oertel, Aust. J . Appl. Sci., 1950,1, 259.36 E. J. Broderick and P. G. Zack, Analyt. Chem., 1951,23, 1455.39 E. Scheur and F. H. Smith, Chem. and Id., 1951,60.40 J. 0. Irwin, J . Pharm. Pharmucol., 1950, 2, 737.4 1 W. G. Schlecht, Analyt. Chem., 1951, 23, 1568.42 G. Wernimont, ibid., p. 1572.43 Analyt. Chem., 1951, 23, 51.I d . Chem., 1950,26, 522.G. Schwarzenbach, W. Biedermann, and F. Bangerter, HeZv. Chim. Actcc, 1946,33 J. 0. Lay, J . Iron Steel Inst., 1951, 16’9, 42.4 4 J . Chem. Educ., 1951, 28, 496.46 Ann. Reports, 1950, 47, 374.48 Analyt. Chim. Acta, 1950, 4, 583. 29, 811312 ANALYTICAL CHEMISTRY.may be determined in plant material.49 Magnesium in leather may be deter-mined 50 by titration in the presence of Eriochrome-black T.Manganeseis determined oxidimetrically by ferricyanide, making use of the " Complex-one " for separation from other metals.51 The coloured complex with man-ganese may also be used for the determination of the element.52 Sulphateion in water samples 53 and calcium in biological fluids 54 may be determinedvolumetrically. Certain of the lanthanons have been separated by J. K.Marsh 55 and by R. C. V i ~ k e r y . ~ ~ The dissociation constant of the complexwith nickel has been rnea~ured,~' and F. W. Kerckow 58 describes a volumetricmethod for the determination of EDTA.E. S. Tinovskaya 59 has reported the solubilities of the 8-hydroxyquinolinederivatives of aluminium, ferric iron, zinc, copper, and magnesium undervarious conditions, and has calculated the solubility products.The com-plexes of silver with the same reagent have been investigated60 withoutfinding any evidence for the compound of Ag(I1) formerly reported. J. P.Phillips and H. P. Price 61 have studied certain complexes with 8-hydroxy-quinaldine, and have compared the values of the solubility products which theydetermined with those for the corresponding " oxine " complexes and thecorresponding hydroxides. They conclude that the stabilities are parallel inthe three series of compounds. M. Borrel and R. Piiris 62 have determined thecompositions of some 8-hydroxy-2-methylquinoline complexes and comparedthese with corresponding data for the derivatives of ~ x i n e . ~ ~ The structuresof some metallic derivatives of 8-hydroxyquinoline-5-sulphonic acid havebeen in~estigated.~~Exchange reactions of some 4-co-ordinated nickel complexes including thecomplex with dimethylglyoxime have been examined.65In an important review of our knowledge of the stabilities of metal-organic complexes, Burkin points out that there is a grave lack of factualinformation and of experimental methods capable of providing the basisfor the formulation of satisfactory theories of the structure and behaviourof these complexes.The present knowledge of bond strengths and the exist-ing methods of investigating the formation of complexes are described byhim. V. I. Kuznetsov 66 discusses some theoretical bases for the formation49 A. C. Mason, A.R.E. Mulling Res. Sta., 1950, 122.50 C. H. Spiers, J .Xoc. Leather Trades Chem., 1950, 34, 289.51 R. Pfibil and V. Simon, Coll. Trav. chim. Tchkcosl., 1949, 14, 454.5z R. PPibil and E. Hornychova, ibid., 195.0, 15, 457.53 J. R. Munger, R. W. Nippler, and R. S. Ingols, Analyt. Chem., 1950, 22, 1455.54 I. J. Greenblatt and S. Hartman, ibid., 1951, 23, 1708.5 5 J., 1950, 1819; 1951, 1461, 3057. 5 6 J., 1951, 1817.5 7 C . M. Cook and F. A. Long, J . Amer. Chem. SOC., 1951,73, 4119.5 8 2. anal. Chem., 1951,133, 281. 59 J . Anal. Chem., U.S.S.R.; 1950, 5, 345.6o B. P. Block, J. C. Bailar, and D. W. Pearce, J . Amer. Chem. SOC., 1951,7'3, 4971.61 Ibid., p. 4414. 62 Analyt. Chim. Acta, 1951, 5, 573.63 Ibid., 1950, 4, 267.64 J. C. I. Liu and J. C. Bailar, J . Amer. Chem. SOC., 1951, 73, 5432.6 5 N.F. Hall and B. R. Willeford, ibid., p. 5419.6 6 J . Anal. Ch,em., U.S.S.R., X951, 6, 139WILSON : INORGANIC QUALITATIVE ANALYSIS. 313of coloured complexes, and draws parallels between the action of organicreagents containing hydroxyl and hydrolysis, the action of reagents containingthe thiol group and the formation of sulphides, and the action of amine-nitrogen and the formation of ammoniates. M. D. E. Jonckers 67 surveys awide range of organic reagents and makes certain deductions regarding theprobable action of organic compounds in the field of complex formation.The preparation, properties, and uses of derivatives of dithiocarbamicacid have been reviewed.68 Mention has been made elsewhere in this Report(pp. 317,326) of uses of substituted benzidines.In addition to such uses, thesensitivities of a number of these towards oxidising agents have beenreported,69 and 3-methylbenzidine and 3 : 3'-diethylbenzidine have beenrecommended in preference to o-dianisidine as indicators for the volumetricdetermination of gold.70 Benzidine has also been recommended as it pre-cipitant for silicot~ngstate.~~ A number of these compounds precipitatemolybdenum and tungsten. 1 -Amino-4-p -aminophenylnaphthalene permitsthe separation of tungsten from m~lybdenum.~~ In hydrochloric acid,benzidine can be used as a qualitative test or as a colorimetric reagent forceric ions.73Among miscellaneous organic gravimetric reagents may be mentionedpenicillin G as a precipitant for a large number of p-mercapto-acetamidoacetanilide for the gravimetric determination of mercuric mercuryand ammonium benzoate for the precipitation of Sn, Ti, Zr, Th,Bi, and Ce,76 nitrosophenolphthalein as a precipitant for Cu, Ni, Co, Zn, Mn,Fe**, Fe.'., Pb, Hg", and Pd.77An investigation of conditions for precipitation of thiosulphate as thetriethylenediamine complex, which has been recommended for microscopicidentification, has been carried and the requirements for decreasingthe solubility of the complex are detailed.3.INORGANIC QUALITATIVE ANALYSIS.The solubilities of the sulphides of As, Sb, and Sn have been studied witha view to improving the separation of these by hydrochloric acid, and suitableconditions are re~ommended.~~ A scheme of analysis, based on that ofNoyes and Bray but converted to the semimicro-scale, has been proposed 80for the separation and semi-quantitative estimation of the cations of the6 7 Chim.anal., 1950, 32, 207, 249.69 R. Belcher and A. 3. Nutten, J., 1951, 546. 7O Ibid., p. 550.71 M. NardelIi, Ann. Chim. Roma, 1950, 40, 490. 72 Idem, ibid., p. 1516.73 T. K. S. Murthy and B. S. V. R. Rao, J . Indian Chem. SOC., 1950,2'7,383.74 H. Malissa, Mikrochem., 1951,38, 120.7 5 F. Buscar6ns and F. CapitAn, AWE. Pis. Quim., 1950,46, B, 569.'13 A. Jewsbury and G. H. Osborn, Analyt. Chim. Acta, 1949, 3, 642.7 7 J. Konecny, Mikrochem., 1950, 35, 384.78 J. H. Gast and F. L. Aldrich, J . Arner. Chem. SOC., 1951,73, 3037.79 C. H. Sorum and H. A. Wolf, J . Chem. Educ., 1950,2'7, 614.8o C. C.Miller and R. J. Magee, J., 1951, 3188.P. Chabrier and G. Nachmias, Bull. Xoc. chim., 1950,17, D, 51314 ANALYTIUAL CHEMISTRY.alkaline-earth and alkali-metal groups. The use of potassium ethyl xanthateinstead of hydrogen sulphide in the schematic qualitative analysis of thecations has been proposed.81 In a micro-scheme 82 which includes W, Ti,No, and Zr in addition to the common cations, hydrogen sulphide is dis-pensed with, and the principal insoluble groups are the chlorides, the sulph-ates, and the hydroxides. Microscopic examination of the mercurithio-cyanates is utilised for final identification of a number of the cations, eitherseparately or occurring in conjunction. Spot-test procedures are proposedfor the identtfication of nickel alloys and s t e e 1 ~ , ~ ~ , 8 ~ and of fibre ash.85isoQuinoline has been shown to produce readily identifiable crystals with anumber of inorganic cations.86In the schematic separation of cations, the phosphate ion may be removedas titanium 88 but precipitation is not complete with niobiumor tantalum, which also form insoluble phosphates.89 Schematic identi-fication of anions is described by 5.M. Odekerken.90Methods for representing the sensitivities of analytical reactions havebeen proposed and c r i t i c i ~ e d . ~ ~ - ~ ~ Absolute and practical sensitivities forthe reactions listed by P. E. Wenger and Y. Rusconi 94 have been tab~lated.~5P. W. West and W. C. Hamilton 96 investigated the sensitivities of a series ofreactions as affected by the type of paper on which the tests were carried out,and reported that the values for different papers may differ by a factor of 100.New or improved tests have been reported for a variety of ions : ger-manium,97 fluoride?* orthophosphate,gg~ 100 metaphosphate,lOl ar~enate,~~’ lo2sulphide and other sulphur ions,lo3 sulphite and other reducing ions,lMnitrate and nitrite,lo5 nitrite and sulphamate,l06 cyanide,l07 borate,lo881 L.R. Chaves Lavin, Informac. Quim. Analit., 1951, 5, 98.88 M. C. Alvmez Querol and C. L. Wilson, Mikrochem., 1951, 36/37, 224.83 H. B. Lea, Met. Abstr., 1951,18, 620.85 N. A. Math, Amer. Dyestu8s Rep., 1951, 40, 44.86 H. F. Schaeffer, Analyt. Ghem., 1951, 23, 1674.87 A. J. Nutten, Analyt. Chim. Acta, 1950,4, 340.88 A.J. Nutten and W. I. Stephen, ibid., 1951, 5, 448.R. B. Hahn, J . Amer. Chem. SOC., 1951,73,5091.90 2. anal. Chem., 1950,131, 165. O1 F. L. Hahn, Mikrochem., 1951,38,26.92 H. Malissa, Analyt. Chim. Acta, 1950,4,1; Mikrochem., 1950,35,266 ; 1951,38,33.93 J. Gillis, ibid., p. 50.94 “ RQactifs pour 1’Analyse Qualitative Minerale,” 4th Rep., Paris, 1950.9 5 H. Malissa, Mickrochem., 1951, 38, 33.9 7 G. Brauer and H. Renner, 2. anal. Chem., 1951,133,401.98 W. R. Crandall, Analyt. Chem., 1950, 22, 1449.99 I. P. Ryazanov and L. V. Churmanteeva, J. Anal. Chem., U.S.S.R., 1951, 6, 49.100 E. Van Dalen and G. De Vries, Analyt. Chim. Acta, 1951, 5, 238.101 R. Neu, 2. anal. Chem., 1950,131, 102.108 G. Brauer and H. Renner, ibid., 1951,134, 9.103 L.P. Pepkowitz and E. L. Shirley, Analyt. Chem., 1951, 23, 1709.104 J. A. Lundin, J . Chem. Educ., 1951, 28, 122.105 H. Barnes, Analyst, 1951, 76, 666.106 R. C. Brasted, J. Chem. Educ., 1951, 28, 592.107 A. R. Hickinbotham, Analyst, 1950, 75, 502.108 J. A. Gautier and P. Pignard, Mikrochem., 1951, 36/37, 793.84 P. Reboul, Chim. et Ind., 1950,64,574.Ibid., 1951, 38, 100WILSON : INORGANIC URAVIMETRIC ANALYSIS. 315silicate ,lo9 lithium ,110 calcium, ll1 magnesium,110 zinc, 112 cadmium, 113copper,l14, 115 mercury,114 gold,ll6 aluminium,llO lanthanons,l17 indium,11gmanganese,llg iron,115,120,121 cobalt,ll4,122,123 chromiurn,l24 tin,125,126 vana-dium,127,C. E. White l30 recommends the use of fluorescence phenomena asconfirmatory tests for Al, Zn,'B, Na, Be, T1, and Th, The fluorescence of anumber of rarer elements is described by H.Haberlandt,131 and the fluores-cence of a wide range of salts of 8-hydroxyquinoline has been observed andr e ~ 0 r d e d . l ~ ~The applications of catalytic reactions to microanalysis have beenreviewed, discussed, and classified by P. W. W e ~ t . 1 ~ ~ The reaction betweenazide and iodine, which is catalysed by thiocyanate, has been used 134 as aspot test for the detection of this ion, and may be applied to its microdeter-mination by a gas-volumetric method.135and palladium, platinum, and rhodium. 1294. INORGANIC GRAVIlYIETRIC ANALYSIS.Balances and Weights.-An isothermal balance chamber, in which thetemperature may be controlled to k0.1" and maintained within 10" of roomtemperature, has been described.136 The adaptation of a chemical balancefor precision weighing has been described by A. A. Hills.137 Developmentsin the design of microchemical balances have been reviewed and discussed.13glog E. van Dalen and G. de Vries, Analyt. Chim. Acta, 1950,4, 235.110 W. Schneider, Arch. Pharm., 1950, 283, 248.M. V. Davis and F. H. Heath, J . Chem. Educ., 1950,27, 626.112 J. T. Dobbins and H. H. Norman, ibid., p. 604.113 H. J. Rahn, 2. anal. Chem., 1950,131, 263.114 V. Hovorka and L. DiviiS, Coll. Trav. chim. Tchdcosl., 1950, 15, 589.G. A. Bottomley, Analyst., 1950, 75, 501.116 F. L. Hahn, Mikrochem., 1951, 38, 136.117 0. Neunhoeffer, 2. anal. Chem., 1951,132, 91.118 G. J. Sutton, J .Aust. Chem. Inst., 1950,17,249.ll9 V. Hovorka and Z. Holzbecher, Coll. Trav. chim. Tchdcosl., 1950,15, 281.120 M. Cefola, W. S. Andrus, B. R. Mieeioli, and L. K. Yanowski, Mikrochem.,121 K. B. Berg and F. Reimers, Dansk Tidsslcr. Farm., 1950,24,315.122 S. Gordon and J. M. Schreyer, Analyt. Chem., 1951, 23, 381.123 A. J. Llacer and J. A. Sozzi, Mikrochem., 1951, 36/37, 239.lZ4 P. W. West and L. Granatelli, ibid., 1951,38, 63.lZ5 A. V. Pizarro, Analyt. Chim. Acta, 1951, 5, 529.126 M. Bourson, Chim. anal., 1951, 33, 134.12' P. W. West and L. J. Conrad, Mikrochem., 1950,35,443.12@ D. E. Ryan, ibid., p. 167.130 J . Chem. Educ., 1951, 28, 369.132 H. Zocher, F. Feigl, and C. Torok, Monatsh., 1950, 81, 274.133 Analyt. Chem., 1951, 23, 176.134 P.Senise, Mikrochern., 1951, 36/37, 206.136 W. S. Castor and F. Basolo, J . Chem. Educ., 1951, 28, 380.137 Canadian J . Phys., 1951, 29, 245.138 G. F. Hodsman, Roy. Inst. Chem. Monog. No. 4, 1950, 5 ; Mikrochem., 1951,1950, 35, 439.R. Belcher, A. J. Nutten, and W. I. Stephen, Analyst, 1951, '76, 431.131 Mikrochem., 1951, 36/37, 1075.136 Idem, ibid., p. 210.36/37, 133316 ANALYTICIAL CHEMISTRY.The maintenance of microchemical balances, and the methods of determiningand comparing their precisions are also de~cribed.1~~ Quartz-fibre microgrambalances of various types have been constructed. That of F. C. Edwardsand R. R. Baldwin 140 is magnetically controlled. J. K. Dawson and M. W.Lister 141 use a balance based on that of P. L. Kirk and his co-workers 142 asa magnetic susceptibility balance.A similar balance, with a beam ofsimple construction, has been used 143 for the gravimetric determination ofmicrogram quantities of inorganic ions. The design of microgram balancesis reviewed at the same time, and the method of construction of the beamassembly has been given in detail. A magnetic suspension balance anda radioactive electronic balance 145 both have a sensitivity of g.In a study of the corrosion resistance of analytical weights, P. 33. Biggand F. H. Burch 146 conclude that the most satisfactory material is highlypolished 25 yo Cr-20 %Ni stainless steel, but other materials which are almostas satisfactory are quoted. Zirconium fractional weights withstood aconstant-weight test over a period of 18 months.l4' The construction ofmicrochemical balance riders from aluminium foil instead of from wire isrecommended.148 A method of verifying the rider markings on a balancehas been described.149 The behaviour of polystyrene weighing bottles hasbeen examined.150Methods of Analysis.-The progress of inorganic gravimetric analysisduring 1950 has been reviewed by F.E. Beamish and W. A. E. McBryde.lS1On the basis of thermal analysis, C. Duval 152 has recommended silver nitrateas precipitant for cyanide, silver nitrate or nickel sulphate-pyridine forthiocyanate, silver nitrate or semicarbazide for cyanate, and silver nitriteor benzidine for ferrocyanide, but has been unable to recommend a suitablegravimetric reagent for ferricyanide. The determination of phosphate asthe strychnine-molybdate complex has been examined and suitable conditionsfor its use re~0mmended.l~~ W.Dewald and H. Schmidt 154 describe aprocedure for the estimation of pyrophosphate and hexametaphosphate inthe presence of each other. Thioformamide has been recommended by E.Gagliardi and A. Loidl 155 as a precipitant for arsenic, both for its directgravimetric estimation in acid solution, and for its estimation in the presenceof copper, which is first removed by the same reagent in acetic acid solution.139 D. W. Wilson, Roy. Inst. Chem. Monog. No. 4, 1950, 16.140 Analyt. Chem., 1951, 23, 357.142 I d . Eng. Chem. Anal., 1947,19, 427.143 H. El. Badry and C . L. Wilson, Roy. Inst. Chem. Monog. No.4 , 1950, 23.144 J. W. Beams, Phys. Rev., 1950, 78, 471.145 I. Feuer, Milcrochem., 1950, 35, 419.146 Nature, 1950,165, 201 ; Brit. J . Appl. Phys., 1951, 2, 126.147 W. M. Thornton and E. S . Hauber, J . Franklin Inst., 1950,250,39.148 L. E. Brown, Analyt. Chem., 1951, 23, 388.149 W. M. Thornton, Mikrochem., 1950, 35, 431.150 C. T. Douwes and J. F. Reith, AnaEyt. Chim. Acta, 1951, 5, 459.151 Analyt. Chem., 1951, 23, 59.153 W. Heimann and A. Heimann-Geierhaas, 2. anal. Chem., 1951,133, 255.154 Ibid., 1951, 134, 17, 86.141 J., 1950, 2177.152 Analyt. Chim. Acta, 1951, 5, 508.155 lbid., 1951,132, 33, 274WILSON INORGANIC GRAVIMETRIC ANALYSIS. 317T. Dupuis and C. Duval 156 conclude that Ag,S, As&&, PbS, HgS, S,CaSO,, PbSO,, benzidine sulphate, and strychnine persulphate are suitableweighing forms for the gravimetric determination o f sulphur.Substitutedbenzidines as precipitants for sulphate have also been investigated,15' butnone has been found to be more satisfactory than benzidine itself. R.Belcher and R. Goulden 15* conclude that estimation as barium sulphate isthe most accurate method of sulphate determination. Procedures have beenproposed to avoid interference by small amounts of iron 159 and molybdatein the estimation of sulphate as barium su1phate.l6Orecommendthe following weighing forms for deftermination of the halogens : for fluorine,bismuth trifluoride, triphenylstannic fluoride, lead chlorofluoride, anduranium oxyfluoride ; for chlorine, silver chloride and nitron perchlorate ;for bromine, silver bromide ; for iodine, silver, cuprous and palladous iodideand silver iodate.The lead chlorofluoride method has, however, beenreported on unfavourably by other workers.162 C. Duval and U. M. Doan lmhave also examined the thermolysis curves of lead selenate and selenium asprecipitated by a variety of reducing agents. They recommend for thegravimetric determination the methods which make use of stannous chlorideand lead nitrate. Selenium may be determined, after conversion into sele-nium bromide, by precipitation with hydroxylamine hydrochloride, or,in stainless steels, by precipitation with hydroxylamine hydrochloride andhydrochloric acid.165 U. M. Doan and C. Duval 166 find that no gravimetricmethod for tellurium is completely satisfactory, the most useful being pre-cipitation with vanadyl sulphate, precipitation by hexamethylenetetramineas tellurium dioxide, or precipitation as lead tellurate.H. Bode 16' proposestetraphenylarsonium chloride as a precipitant for tellurium.An improved method for the precipitation of silica by gelatin is describedby M. H. Jenkins and J. A. V. Webb.16* Gravimetric reagents for germanium,which can be used on the micro-scale with the application of empirical con-version factors, are combinations of molybdate or tungstate with cinchonine,pyridine, or 8-h ydroxy quinoline. 169A. C. Mason 170 has described a method of preparing sodium cobaltinitriteas a finely divided suspension in ethanol which is stable and can be usedsatisfactorily for the determination of small amounts of potassium by theFrom thermogravimetric studies, T.Dupuis and C. Duval156 Analyt. Chim. Acta, 1950, 4, 623.15' R. Belcher and A. J. Nutten, J., 1951, 544.159 0. Milner and W. M. McNabb, Analyt. Chim. Acta, 1950,4, 386.160 Shu-Chuan Liang and Tien-Hui Shen, J . Chinese Chern. Soc., 1951,18, 37.161 Analyt. Chim. Acta, 1950, 4, 615.162 J. H. Saylor, C . H. Deal, M. E. Larkin, M. E. Tavenner, and W. C . Vosburgh,164 H. J. Bridger and R. W. Pittmann, J . , 1950, 1371.165 N. S. Mott, Foundry, 1950,78, Feb., 121 ; J . Iron Steel Inst., 1951,167, 237.166 Analyt. Chim. Acta, 1951, 5 , 569.lB7 2. anal. Chem., 1951,134, 100.lBS F. Hecht and G. Bartelmus, Milerochem., 1951, 36/37, 466.170 Analyst, 1951, 76, 176.158 I d .Chem., 1951, 27, 295.ibid., 1951, 5, 157. lB3 Ibid., p. 566.lB8 Analyst, 1950, 75, 481318 ANALYTICAL CHEMISTRY.silver potassium cobaltinitrite method. The zinc uranyl acetate methodfor the determination of sodium has been modified.171, 172 The necessity forproducing the triple acetate at temperatures above 4-6" when potassium ispresent has been stressed.173 Potassium may be precipitated as potassiumtetraphenylboron. 174A method has been devised, utilising the formation of fluoroberyllates,for the removal of fluoride interference in the determination of calcium infl~0rspar.l~~ Strontium may be separated from calcium by conversion intochloride in butyl Cellos01ve.l~~ Methods for overcoming the effects ofinterfering elements in the estimation of small amounts of magnesium incast iron as pyrophosphate have been desdibed.177 The sulphate, ammoniumphosphate, cyanamide, mercurithiocyanate, oxalate, 5-bromoanthranilate,oxinate, and quinaldinate are suitable weighing forms for zinc.178 It hasbeen recommended 179 that in the estimation of cadmium as sulphide pre-cipitation should be carried out from perchloric acid solution to avoid copre-cipitation of impurities. Quantitative precipitation of cadmium may beachieved by thioacetamide.lsO Mercury may be precipitated by thioacet-amide, as Hg,S,C12 or, with excess of reagent, as sulphide.lS1 Thermalanalysis suggests that only 4 precipitants, out of 21 examined for mercury,are acceptable : lS2 thionalide, Reinecke's salt, biguanidine chloride, andpropylenediamine. A method using o-phenanthroline as a precipitant formercury has been described.lS3Copper may be separated from arsenic and estimated as cupric sulphide.ls4Conflicting reports regarding the satisfactory determination of copper withdithiocarbamidohydrazine have ap~eared.18~9 lS6 An improved method forthe determination of copper with salicylideneimine has been proposed.l87Twelve methods for the determination of silver have been chosen on thebasis of thermal analysis.ls8 Estimation as silver iodide in lubricating oilshas been found satisfactory.1sg Mercaptobenzothiazole in ammoniacalsolution has been recommended as a new gravimetric reagent for silver.lg0171 W. McCamley, T.E. L. Scott, and R. Smart,CAnaZyst, 1951,76, 200.171 N. Urban and A. Stechern, Biochem. Z., 1951, 301, 388.173 M. F. Harrison, Biochem. J., 1951,48, 283174 P. Raff and W. Brotz, 2. anal. Chem., 1951, 133, 241.175 F. Feigl and A. Schmffer, Analyt. Chem., 1951, 23, 351.176 K. A. Kobe and W. L. Motsch, ibid., p. 1498.177 W. Westwood and R. Presser, Analyst, 1951, '96, 191.178 M. de Clerq and C. Duval, Analyt. Chim. Acta, 1951, 5, 282.179 G. Denk and F. Denk, 2. anul. Chem., 1950,130,383.180 H. Flaschka and H. Jakobljevich, Andyt. Chim. Acta, 1950, 4, 602.181 Idem, ibid., 1951, 5, 152.183 M. E. Hall and G. M. Smith, Analyt. Chem., 1951, 23, 1181.184 E. Gagliardi and A. Loidl, 2. anal. Chem., 1951, 132, 87, 274.185 N. A. Raju and K. Neelakmtam, J .Sci. Ind. Res. India, 1951,10, B, 97.186 J. Gupta and R. Srinivasm, ibid., p. 98.187 A. P. Terentev and E. G. Rukhadze, J . Anal. Chem., U.S.S.R., 1951,6, 186.188 Y. Marin and C. Duval, Analyt. Chim. Acta, 1950,4, 393.189 T. D. Parks and L. Lykken, Analyt. Chem., 1950, 22, 1505.190 I. Ubddini and L. Nebbia, Ann. Chim. Roma, 1951,41, 181.C. Duval and Nguyen Dat Xuong, ibid., p. 494WILSON : INORGANIC GRAVIMETRIC ANALYSIS. 319Thermal analysis of gold precipitates indicates citarin, thiophenol, or quinolas suitable gravimetric reagents.lglImproved procedures for the determination of aluminium as oxide,lg2-lMas sulphate,lD5 and as 8-hydroxyquinoline complex lQ6 have been described.The determination of aluminium oxide in aluminium may be achieved bysubliming the metal as trichloride.197 Scandium may be determined as the8-hydroxy quinoline complex.198 Thallium may be precipitated as a complexdichromate and converted into the chromate.199Conditions for the determination of manganese as pyrophosphate havebeen determined.2m,201 Separation of rhenium from the elements of thehydrogen sulphide group, and determination as a complex with nitron, havebeen successfully achieved.202 Improved conditions for the precipitation offerric hydroxide in a quickly filterable and washable form have been detailedby D. K o ~ z e g i . ~ ~ ~ . Cobalt may be determined as the mercurithiocyanate.204The determination of nickel by precipitation with salicylideneimine has beendescribed,lS7 and the determination with cycloheptane-1 : 2-dione dioximehas been adapted to the micro-~cale.~~~Molybdenum may be determined by precipitation with m-nitrobenzoicacid.206 Chrysoidine R and Bismark-brown have been recommended 207 asgood precipitants for tungsten in acid media.The precipitation of vanadiumwith tannin 20* and the co-precipitation of protactinium with titanium inorder to separate it from interfering elements 209 have been described.Procedures which are in accordance with the B.S.I. method for theestimation of tin in steels and overcome interference by tungsten, depend 210either on the complexing of the tungsten with citric acid, or on hydrolyticprecipitation of the tungsten. Lead, first separated by double precipitationof the lead nitrate-thiourea complex, or electrolytically from its alloys, maybe redissolved and then determined by precipitation as lead chromate.211lgl P.Champ, P. Fauconnier, and C. Duval, Analyt. Chim. Acta, 1951,5, 277.lQ2 R. F. Innes and W. L. Sheppard, J . SOC. Leather Trades Chem., 1950, 34, 460.IQ3 E. C. Mills and S. E. Hermon, Metal Ind., London, 1950, 76, 343.lg4 E. T. Saxer and E. W. Jones, Blast Puma., 1951,39,445,476, 549.IQ6 T. Gaspar y Arnal and J. Miner Liceaga, Anal. Pis. Quim., 1950,66, 299.Ig6 J. L. Kassner and M. A. Ozier, J . Amer. Ceram. Soc., 1950, 33, 250.I@' P. Urech, R. Sulzberger, and E. Schaad, Chimia, 1950,4, 233.IQS L. Pokras and P. M. Bernays, Analyt. Chem., 1951, 23, 757.lg9 0. L. Forchheimer and R. P. Epple, ibid., p. 1445.zoo V.Njegovan and B. Morsan, 2. anal. Chem., 1950,131, 187.201 S. Lj. Jovanovid. and V. M. Jovanovi6, Bull. SOC. chim. Belgrade, 1950, 15, 107.ao2 W. Geilmann and H. Bode, 2. anal. Chem., 1951,132, 260; 133, 177.203 Ibid., 1950, 130, 401.204 F. Sierra and F. C&rceles, Anal. Pis. Quim., 1951, 47, B, 281, 341.206 R. C. Ferguson, R. C. Voter, and C. V. Banks, Nikrochem., 1951, 38, 11.zo6 M. Venkataramaniah and B. S. V. R. Rao, 2. anal. Chem., 1951,133, 248.207 Shu-Chuan Liang and Kan-Nan Chang, J . Chinese Chem. SOC., 1951,18, 25.208 L. L. Colin, J . Chem. SOC. 8. Afr., 1950, 50, 314.209 M. R. Sales Grade, Rev. Quim. apl., 1950,1, 184.Methods of Analysis Committee, J . Iron Steel Inst., 1951,168, 61.C. C. Miller and L. R. Currie, Analyst, 1960, 75, 467, 471320 ANALYTICAL CHEMISTRY.Conversion into the basic lead chromate is preferred by F.C. Guthrie andJ. T. The most suitable conditions for precipitation of lead assulphate are discussed by L. P. Adamovich and K. G. P a r f e n ~ v a . ~ ~ ~ Leadmay be estimated as chloride in butanol-HC1 solution.214 Thioacetamidehas been recommended for the precipitation of lead sulphide which mayeither be dried and weighed, or preferably converted into ~ u l p h a t e . ~ ~ ~A detailed procedure for the precipitation of titanium by cupferron andsubsequent ignition is applicable to the determination of titanium in per-manent-magnet alloys.216 The varying compositions of titanium phosphatesprecipitated under a range of conditions have been studied.217 Titaniummay be precipitated completely by tannin.218 Zirconium may be separatedby precipitation with hydrazine ~ u l p h a t e , ~ ~ ~ phthalic acid,220 tannin,221fumaric acid,222 m-tolyloxyacetic or mandelic 225 I n eachcase the precipitate is ignited to the oxide for final weighing.Precipitationas the arsenate 226 may be used to separate zirconium from iron, aluminium,thorium, and cerium, and the precipitate may then either be redissolved andfinally precipitated by ammonia for ignition to the oxide, or ignited directly,the weighing form then being (ZrO),As,O,. Zirconium-hafnium mixturesmay be determined by p-bromomandelicSeparations of thorium from lanthanons and from uranium have beenstudied by Rao and his co-workers, who recommend o-chlorobenzoicacid,228, 231 o- and p-aminobenzoic a ~ i d s , ~ z ~ o-toluic acid and acetylsalicylicacid,230 m-nitrobenzoic and cinnamic a ~ i d , ~ ~ ~ t 233 the precipitate ineach case being converted into the oxide as weighing form.A critical examination of various gravimetric methods for vanadium hasshown that the most reliable methods are those depending on precipitation212 J .Appl. Chem., Lond., 1951,1,109.214 S. Kallmann, Analyt. Chem., 1951, 23, 1291.215 H. Flaschka and H. Jakobljevich, Analyt. Chim. Acta, 1950, 4, 606.216 B.S.I. Specif., 1951, No. B.S. 1121, Pt. 17.217 V. I. SpitsynandE. A. Ippolitova, J. Anal. Chem., U.S.S.R., 1951, 6, 5.218 A. Purushottam and B. S. V. R. Rao, Rec. Trav. chim., 1951, 70, 555.219 C. Venkateswarlu and B.S. V. R. Rao, J. Indian Chem. SOC., 1950, 27, 395.220 A. Purushottam and B. S. V. R. Rao, Analyst, 1950, 75, 684.Z 2 1 Idem, ibid., p. 555.222 M. Venkataramapiah and B. S. V. R. Rao, ibid., 1951,76, 107.223 Idem, Analyt. Chem., 1951, 23, 539.524 G. Gavioli and E. Traldi, Metall. ital, 1950, 42, 179; J . Iron Steel Inst., 1951,226 A. A. Astanina and E. A. Ostroumov, J. Anal. Chem., U.S.S.R., 1951, 6, 27.226 I. Sarudi, 2. anal. Chem., 1950, 131, 416.227 R. B. Hahn, Analyt. Chem., 1951, 23, 1259.228 B. R. L. Rao and B. S. V. R. Rao, J. Indian Chem. SOC., 1950,27, 457.22% D. S. N. Murthy and B. S. V. R. Rao, ibid., p. 459.230 B. R. L. Rao and B. S. V. R. Rao, ibid., p. 569.231 T. K. S. Murthy, B. R. L. Rao, and B. S. V. R. Rao, ibid., p.610.239 C. Venkateswarlu and B. S. V. R. Rao, ibid., p. 638.233 C. Venkateswarlu, A. Purushottam, and B. S. V. R. Rao, 2. anal. Chem., 1951,213 J . Anal. Chem., U.S.S.R., 1950,5,339.167, 167.133, 251WILSON : INORGANIC GRAVIMETRXO ANALYSIS. 321by mercurous nitrate or cupferron and final weighing as the pentoxide.2aMethods for the estimation of niobium are discussed, and a procedure hasbeen proposed for the estimation of the element in complex alloys notcontaining tungsten.235 An indirect method depending on conversion intochlorides, weighing, and reconversion into oxides and reweighing, has beendevised for the estimation of niobium and tantalum in the presence of eachother .236The contamination of a number of precipitates by coprecipitation, whenorganic reagents are used, was found to be more marked in general than ifinorganic precipitants were employed.237 Coprecipitation has also beenexamined with special reference to the precipitation of silver chloride and ofammonia with Nessler's reagent .238 A procedure to reduce coprecipitationof iron and aluminium, thus giving a more satisfactory iron precipitate, hasbeen de~cribed.~~9 The values of pH a t which the sulphides of Cd, Zn, Ni,and Co begin to precipitate have been measured.240The advantages, for gravimetric analysis, of precipitation from homo-geneous solution have been described by H.H. Willard,241 who gives anumber of examples to illustrate the use of this technique. The precipit-ation of calcium, strontium, and barium as sulphates by the decompositionof dimethyl ~ u l p h a t e , ~ ~ ~ of basic ferric formate by the hydrolysis of urea,2Gand of zinc by the decomposition of ethyl oxalate 244 have a quantitativeapplication.The nature and behaviour of barium sulphate precipitates havebeen investigated by means of the electron microscope.245Thermal analysis procedures and apparatus have been described by W.van T ~ n g e r e n , ~ ~ ~ and by F. Burriel Marti and C. Barcia G~yanes.~*' Thermalanalysis curves are given by C. Duval 248 for the precipitates recommendedby Donau for the gravimetric determination of 38 metals and 7 non-metals,and the methods are discussed critically. Differential thermal analysis,as applied to the analysis of such material as clays, has been described inA suitable apparatus for extending the method to other subst,anceshas been proposed.250234 A.Morette, Bull. Soe. chim., 1950, 17, 526.235 R. B. Golubtsova, J . Anal. Chem., U.S.S.R., 1951, 6, 34.236 H. SchBfer and C. Pietruck, 2. anorg. Chem., 1951,264,2.237 P. W. West and L. J. Conrad, Analyt. Chim. Acta, 1950, 4, 561.23* F. Reimers and K. R. Gottlieb, Acta Pharm. int., 1950, 1, 139.239 N. Gandolfo, R. C. Super. Sanit., 1951,14, 57.240 P. J. Galm6s and C. Mataix, AJinidad, 1950, 27, 401.241 Analyt. Chem., 1950, 22, 1372.242 9. J. Elving and R. E. van Atta, ibid., p. 1375.243 H. H. Willard and J. L. Sheldon, ibid., p. 1162.244 E. R. Caley, L. Gordon, and G. A. Simmons, ibid., p. 1060.p4s R. B. Fischer, Analyt.Chem., 1951, 23, 1667.246 Chem. Weebblad, 1950, 46, 847.247 Anal. 3%. Quim., 1951, 47, B, 73.248 Mihoehem., 1951, 36/37, 425; Analyt. Chem., 1951, 23, 1271.a60 C. J. Penther, S . T. Abrams, and F. H. Stross, Analyt. Chem., 1951, 23, 1459.REP.-VOL. XLVIII. LR. E. Grim, Ann. N . Y . Amd. Sci., 1951, 53, 1031322 ANALYTICAL CHEMISTRY.5. INORGANIC VOLUMETRIC ANALYSIS.General =agents.-The uses for volumetric purposes of bromine 251~ e r i c , ~ ~ ~ , 253 iodate and p e r i ~ d a t e , ~ ~ ~ mercurous,255-259 hypochlorite andm a n g a n i ~ , ~ ~ ~ ferrate,255 t i t a n ~ u s , ~ ~ ~ chromous,260percupric,260 chloramine-T,262 and p-mercaptoacetamidoacetanilide solu-tions have been described.Methods of Analysis.-Small amounts of chloride may be determined byprecipitation as the silver salt, reduction of the precipitate to silver, solutionof the metal, and titration of the solution with dithi~one.~6~ Total chlorinein inorganic salts is determined by fusion with potassium hydrogen sulphateand manganese dioxide in a standard carbon-hydrogen train, collection of theevolved chlorine as chloride, and titration with silver nitrate.265 An ultra-micro-method for chloride has been proposed.266 The course of the iodo-metric bromide determination by means of cyanogen bromide 267 is discussedby E.Shulek and E. Pungor.268 An improved procedure is described whichextends the method to a wide variety of bromine-containing materials.269Hypobromite can be estimated iodometrically in the presence of hypo-chlorite.270Determination of iodine by thiosulphate has been extended to the deter-mination of small amounts of iodine in chloride,271 and a new method hasbeen devised for determining the end-point when iodine in a chloroformlayer ceases to mask the fluorescence of a chloroform-soluble dye.272 Themechanism of the reaction of iodine with tetrathionate has been studied inconnection with the thiosulphate t i t r a t i ~ n .~ ' ~ The ceric sulphate-arseniousacid method has been adapted to the rni~ro-scale.~~~ A number of modi-fications of the estimation of fluoride with thorium nitrate have been251 J. D'Ans and J. Mattner, Angew. Chem., 1951,63, 45.252 C. C. Guardia, AJinidad, 1950,27,454.25P R. Belcher and R. Goulden, Ind. Chem., 1950, 26, 352.255 Idem,libid., 1951, 27, 107.256 W.Pugh, S. Afr. Ind. Chem., 1950,4, 182.25' R. Belcher and T. S. West, Analyt. Chim. Actu, 1951, 5, 260, 268, 472, 474, 546.268 H. Flaschka, Mikrochem., 1950, 35, 473.259 F. Burriel Marti and F. Lucena Conde, Anal. F k Quim., 1951, 47, B, 257.260 R. Pallaud, Chim. anal., 1951, 33, 181.261 G. Beck, Mikrochem., 1950, 35, 169; 1951, 36/37, 245; 38, 152.262 S. A. Repin and 0. S. Lobakhina, J . Anal. Chem., U.S.S.R., 1951, 6, 39.263 F. Buscarbns and F. Capithn, Anal. Pis. Quim., 1950,48, B, 569.264 G. Iwantscheff, Angew. Chem., 1950,62, 361.265 W. A. James and R. E. Belser, Analylt. Chem., 1951,23, 1037.266 R. Viswanathan, Biochem. J., 1951, 48, 239.267 E. Shulek, Analyt. Chim. Acta, 1948, 2, 74; E.Shulek and P. Endroi, ibid.,269 E. Shulek, J. Laszlovszky, L. G. MolnBr, andE.Zapp,Z.anaZ. Chem., 1951,134,161.270 E. Shulek and P. Endroi, Analyt. Chim. Acta, 1951, 5, 245, 252.271 J. D'Ans and T. Kanakowsky, Angew. Chem., 1950, 62, 168.272 K. Brandt and H. Dahlenborg, Acta Chem. scand., 1950, 4, 582.275 A. D. Awtrey and R. E. Connick, J . Amer. Chem. SOC., 1951,73, 4546.274 A. Lein and N. Schwartz, Analyt. Chem., 1951, 23, 1507.263 J. P. Watson, Analyst, 1951,76, 177.1951, 5, 245, 252. Z68 Ibid., p. 137WILSON : INORGANIC VOLUMETRIC ANALYSIS. 323proposed.275-278 H. Ballczo and 0. Kaufmann 278 recommend thatmethylene-blue be added to the alizarinsulphonate indicator to produce amarked sharpening of the end-point. Fluoride may be titrated withzirconium oxychloride solution, sodium alizarinsulphonate being used asindicator.2'9 Distillation losses in the fluoride determination have beeninvestigated.280Volumetric methods have been described for the estimation of hypo-nitrite,2g1 nitrite in the presence of hyponitrite,282 nitrite in nitricand nitrate in water and soils.2s4 Nitrate may also be determined indirectlyby reduction to ammonia, precipitation of ferrous hydroxide from ferrousammonium sulphate, and estimation of the unprecipitated iron by a perman-ganate titration : 285 this method eliminates many interferences.Catalyticreduction by hydrogen followed by volumetric estimation is recommendedby E. van Dalen.286Phosphate may be determilied by titration with standard bismuthoxyperchlorate solution with thiourea as indicator,287 by precipitation asquinoline phosphomolybdate, solution of this in standard alkali, and titrationwith standard acid,288 or by precipitation with glycine and standard silvernitrate solution and estimation of the excess silver.28g Arsenic may beprecipitated as the element, and redissolved in standard iodine,290 or otheroxidising agent ,291 the excess of oxidant then being determined.Conditionsfor the iodine-arsenic reaction are discussed on a theoretical basis by M. C.Alvarez Quer01,~~~ and experimental conditions, particularly of pH, aredetermined. Arsenic may be distilled from insecticides as the trichloridefor subsequent determinati~n.~~~In the volumetric determination of sulphur by titration of sulphate withbarium chloride, using tetrahydroxybenzoquinone or sodium rhodizonate asindicator, R.N. Walter 294 recommends the photometric detection of theend-point for improved accuracy. The tetrahydroxybenzoquinone-indicatormethod has been extended to cement.295 An iodometric method, through275 T. von Fellenberg, Mitt. Lebensmitt.-Untersuch. Hyg., 1951, 42, 158.276 J. A. Brabson, J. P. Smith, and A. Darrow, J . Assoc. 08. Agric. Chem., 1950,277 F. A. Smith and D. E. Gardner, Arch. Biochem., 1949, 29, 311.278 Mikrochem., 1951, 38, 237. 279 H. von Zeppelin, Angew. Chem., 1951,63,281.280 W. H. MacIntire, L. S. Jones, and L. J. Hardin, J . Assoc. 08. Agric. Chem., 1950,281 T. M. Oza, N. L. Dipali, and V. T. Oza, J . Indian Chem. Soc., 1950,27,409.282 Idem, ibid., 1951, 28, 15.284 W.Leithe, Mikrochem., 1951, 36/37, 265.285 Z. G. Szab6 and L. Bartha, Nature, 1950, 166, 309.286 Analyt. Chim. Acta, 1951, 5, 463.287 J. E. Salmon and H. Terrey, J., 1950, 2813.288 H. N. Wilson, Analyst, 1951, 76, 65.289 I. Ubeldini and F. Guerrieri, Chim. e Ind., 1951, 33, 436.290 Y. Kakita, Sci. Rep. Res. Inst. TBhoku Univ., 1950, 2, 255, 477.lZ9l Idem, ibid., p. 483.a93 Shui-Lwen Hwang and Kuang-Ti Yen, J . Chinese Chem. SOC., 1951,18, 85.294 Analyt. Chem., 1950,22,1332.33, 457.33, 653.283 R. C . Brrtsted, Analyt. Chem., 1951, 23, 980.292 Inform. Quim. Analit., 1950, 4, 157.295 Anon., Cement Lime Manuf., 1950, 23, 122324 ANALYTICAL CHEMISTRY.chromate, is described by K. Elsermann and G.W u n d e r l i ~ h . ~ ~ ~ Sulphide 297is determined by absorption of evolved hydrogen sulphide in hypochlorite andtitration of the excess. Selenium may be separated by distillation as itsdibromide, and trapping of this compound, which is then estimated bytitration with standard thiosulphate solution.298 Selenium and telluriumhave been determined volumetrically in copper after precipitation by stannouschloride .299The application of a factor in the volumetric determination of potassiumby precipitation as cobaltinitrite and titration of the precipitate with anoxidising agent is discussed by W. Doden and H. R o d e ~ k . ~ ~ New volu-metric determinations of potassium are based on precipitation of a doublecadmium potassium ferrocyanide and estimation of excess of ferrocyanide,301or on addition of standard aminosulphonic acid to precipitated cobaltinitriteand estimation of the excess of reagent by titration with sodium nitrite,starch-iodide being used as an external Determination of sodiumby the zinc uranyl acetate precipitation, and titration by aid of a mixedphenolphthalein-bromothymol-blue indicator is described by R.Belcher andA. J. N~tten.~O~ The precipitate may also be titrated with titanouschl0ride.3~~ The use of a lead reductor in this determination has beendescribed.305A method for calcium depends on precipitation of calcium picrolonateand estimation of the excess of picrolonic precipitant by titration withcetylpyridinium bromide, either methylene-blue or bromophenol-bluebeing used as indicator in a two-phase system.306 Magnesium may beprecipitated as oxalate followed by a permanganate t i t r a t i ~ n , ~ ~ ~ or byprecipitation with oxine, solution of the precipitate in standard hexanitrato-cerate, and estimation of the excess by a ferrous titration.308The estimation of zinc with potassium ferrocyanide has been studied.309$ 310Mercury in copper is treated with stannous sulphate, distilled into acidpermanganate, and determined by titration with dithizone solution.311An iodine-thiosulphate standard method may be used for the deter-mination of copper either in the absence of antimony or, by a suitable,296 2.anal. Chem., 1951, 134, 96.297 J. A. Kitchener, A. Liberman, and D. A. Spratt, Analyst, 1951,76, 509.29s J.S. McNulty, E. J. Center, and R. M. MacIntosh, Analyt. Chem., 1951,23,123.299 F. D. L. Noakes, Analyst, 1951, 76, 542.300 Bwchem. Z., 1950, 320, 413.801 I. V. Tananmv and A. S. Kozlov, J . Anal. Chem., U.S.S.R., 1951,6,149.302 M. Goehring and J. Schlaich, 2. anal. Chem., 1949,129, 319.303 Amlyt. Chim. Acta, 1950, 4, 595.3O4 W. McCamley, T. E. L. Scott, and R. Smart, Analyst, 1951,76, 200.so* C. C. Waahbrook, Analyst, 1950, 75, 621.307 V. E. Elias, Monit. Farm. Terap., 1951, 57, 23.SO9 D. ZivanoviE, Bull. SOC. chim. Belgrade, 1950, 15, 91.310 Y. Oka and T. Kanno, Sci. Rep. Res. Inst. TGhoku Univ., 1950, A , 2,802.311 W. L. Miller and L. E. Wachter, Analyt. Chem., 1950, 22, 1312.W. M. McNabb, J. F. Hazel, and H. F. Dantro, Awlyt.Chem., 1951,23, 1325.H. W. Spier, KZin. Wochenschr., 1951, 29, 85WILSON : INORGANIC VOLUMETRIC ANALYSIS. 325modification, in its presence.312 Copper in solutions containing 80% ofacetone may be titrated with a carbon tetrachloride solution of dithizone, astable emulsion being f0rmed.3~~ Aluminium may be precipitated as thebenzoate and reprecipitated as the oxinate for volumetric determinati~n.~l*A rapid determination of iron which is not subject to interference bytitanium depends on reduction by zinc and oxidation of titanium by mercuricchloride.315 Details are given3l6 of the preparation of silver for a silverreductor. A micro-reductor burette is described by H. Flaschka 317 whichmay be used for the determination of iron. The normal filing of the reductortube is cadmium amalgam, but in use of titanous solution gas bubbles mayform on standing.This may be overcome by titrating with cuprous solutionobtained by reduction of cupric solution with silver powder, or by reductionof titanic solution containing potassium or ammonium sulphate with leadpowder. Iron may also be estimated by titration with ceric sulphate, ferricsolutions first being reduced by thiosuIphate,318 or by titration withvanadium(11) solution.319 I n an indirect method for iron in the form offerrate, the sample is added to chromium trichloride solution, and the Cr(v1)produced is titrated with standard ferrous solution, sodium diphenylamine-sulphonate being used as indicator.320 The effect of halide ions in the reduc-tion of ferric iron by stannous ion has been investigated by F.R. Duke andR. C. P i n k e r t ~ n . ~ ~ ~A standard method forthe determination of chromium in ferro-chromium has been p~blished.3~~The titration with vanadium recommended by Meites 319 may also be used forthe determination of Cr(vr). Molybdenum may be titrated with lead nitrate,filter-paper impregnated with carminic acid or cochineal tincture being used asa spot indicator.324Germanium may be titrated as mannitogermanic acid.325 Methods forthe estimation of tin in highly alloyed steels are discussed critically, and astandard method based on titration of stannous tin with iodate is proposed.326The volumetric determination of lead with ammonium molybdate is discussed,and methods for ensuring accurate results are detailed.327 Potassium thio-318 B.S.I.Specif., 1951, No. B.S. 1728, Pt. 1.313 R. Delavault and R. Irish, Compt. rend., 1951, 232, 2318.314 G. W. C. Milner and 5. Townend, Analyst, 1951,76,424.31ti G. Norwitz, Metallurgia, 1951, 43, 154.316 J. L. P. Wyndham, S. Afr. Ind. Chem., 1951,5,73.317 Mikrochem., 1951, 36/37, 269; 38, 15; Analyt. Chim. Acta, 1950, 4, 242.318 R. Lang and I. Furstenau, 2. anal. Chem., 1951,133, 163, 331.319 L. Meites, J. Chem. Educ., 1950, 27, 458.320 J. M. Schreyer, G. W. Thompson, and L. T. Ockerman, Analyt. Chem., 1950, 22,321 J . Amer. Chem. SOC., 1951,73, 3045.322 H. A. Laitinen and L. W. Burdett, Analyt. Chem., 1951, 23, 1268.323 B.S.I. Specif,, 1951, No. B.S. 1121, Pt, 18.324 A.Castiglioni and M. Nivoli, 2. anal. Chem., 1951, 133, 161.326 K. J. Cluley, AnaZyst, 1951, 76, 517.328 Methods of Analysis Committee, J . Iron Steel Inst., 1950, 165, 190.817 H. Enzfelder, Berg- u. Hiittenw. Monatsh., 1960,95,141; Met. Abstr., 1951,18,473.Cobalt has been determined i~dometrically.~~~691, 1426; J. M. Schreyer and L. T. Ockerman, ibid., 1951,23, 1312326 ANALYTICAL CHEMISTRY.cyanate and stannous chlbride is recommended as an indicator for thistitrati0n.~28Titanium may be estimated in the presence of niobium by reduction withmetallic powder and titration with standard ferric solution in a carbondioxide atmosphere.329 Titanium in the presence of iron may be estimatedby using standard vanadate sol~tion.3~~ Vanadyl and vanadate presenttogether may be estimated by precipitation of both forms with sodiumhydrogen carbonate and acetone, followed by estimation of vanadate bytitration with ferrous sulphate and subsequent conversion of the vanadylform into vanadate and a further titration ; 331 barium diphenylaminesul-phonate is used as indicator.Photometric deiermination of the end-pointin the h a 1 titration with permanganate when determining vanadium byferrous sulphate-ammonium persulphate has been recommended 332 as givinghigher accuracy.Palladium is estimated333 by adding excess of standard cyanide anddetermining the excess through treatment with solid mercuric oxide t oliberate alkali equivalent to the palladium. Iridium 334 is converted intothe iridichloride and titrated with standard potassium ferrocyanide or,preferably, quinol, o-dianisidine being used as indicator.Indicators.-0. TomiGek 335 has provided a valuable collection of data,hitherto widely scattered, on indicators of all classes.New indicators foracid-base titrations have been reviewed and discussed by A. J. Nutten336and by R. Belcher and R. G~ulden.~~’ G. Manelli and E. Martini 338 reportthat the leuco-base of gallamine-blue has two pH ranges as an acid-baseindicator, vix., 2-3 and 7-9.Nutten 339 and Belcher and Goulden 340 also review redox, adsorption,fluorescent, and other classes of indicators. A wide range of adsorptionindicators for various determinations has been examined critically byG. Manelli and M. L. R o s s ~ , ~ ~ ~ and the mechanism of the colour changes hasbeen in~estigated.3~~ Xylene-cyanol E’F has been investigated 343 as aredox indicator in ceric sulphate titrations.R. Belcher and S. J. Clark344have described the use of p-ethoxychrysoidine as a reversible indicator in thetitration of arsenious solutions with sodium iodate. Naphthidine 345 and328 A. Kutzelnigg, 2. a w l . Chem., 1949,129, 382.38s F. Bischoff, Mikrochem., 1951, 36/37, 251.330 L. E. MacCardle and E. R. Schaffer, Analyt. Chem., 1951, 28, 1169.331 A. Morette and G. Gaudefroy, Compt. rend., 1950, 231, 408; Bull. SOC. chim.,332 R. F. Goddu and D. N. Hume, Analyt. Chem., 1950,22,1314.333 F. Burriel and F. Pino, Anal. Pis. Quim., 1951, 47, B, 261.334 G. Milazzo and L. Paoloni, Monatsh., 1950, 81, 155.335 “ Chemical Indicators,” transl.A. R. Weir, London, 1951.336 Metallurgia, 1950, 42, 216.338 Ann. Chim. Roma, 1951, 41, 68.340 Ind. Chem., 1951, 27, 82.342 E. Shulek and E. Pungor, Analyt. Chim. Acta, 1950, 4, 213.343 H. M. Tomlinson, 0. T. Aepli and H. M. Ebert, Analyt. Chem., 1951,23, 286.344 Anulyt. Chim. Acta, 1950,4,580.1951, 18, 73.337 Ind. Chem., 1951, 27, 33.33D Metallurgia, 1950, 42, 271, 407.3 4 1 Ann. Chim. Roma, 1950,40, 163, 166, 175.345 R. Belcher and A. J. Nutten, J., 1951,648WILSON : INORGANIC VOLUMETRIC ANALYSIS. 3273 : 3’dimethylnaphthidine 346 can be used as reversible indicators for thetitration of zinc with ferrocyanide, and either 3-methylbenzidine or 3 : 3’-diethylbenzidine 347 for the estimation of bromide or iodide with silver,proving more satisfactory than benzidine or the usual adsorption indicators.G.Milazzo and L. Paolini 348 describe the use of o-dianisidine as an indicatorfor the titration of free chlorine or bromine in water, the titration of gold oriridium with quinol, the titration of iridium with ferrocyanide, and thetitration of ferrocyanide and zinc with permanganate. The copper complex ofthe same compound has been recommended 349 in the determination of silverwith thiocyanate or the determination of bromide or iodide argentometrically.The ferric iron complex may be used similarly 350 for the titration of silverwith chloride, as may the ferric complexes with,benzidine and tolidine. Thecopper-benzidine and copper-t olidine complexes may be used 351 in silver-thiocyanate titrations.Cacothelin acts as a redox indicator in the systemferric iron-thi~sulphate,~~~ and this permits estimation of iron and copperoccurring together.353 Difficulties in the use of Eriochrome-black T ando-dianisidine have been 0vercome.3~4 NN’-Substituted benzidines may beused 355 in the titration of ferrous iron and ferrocyanide with cerate.Two-colour indicators for the titration of fluoride with thorium havebeen critically examined by H. H. Willard and C. A. H o I - ~ o ~ , ~ ~ ~ who reportpurpurinsulphonate, alizarin-red S, eriochromcyanin-R, dicyanoquinizarin,and chrome azurol-S to be the most satisfactory. The same authors357recommend morin and quercetin as fluorescent indicators for this titration.In the titration of mercurous with chloride or bromide, telxaiodophenol-sulphonphthalein has been found to give good results.358 The ferric com-plexes with benzidine, tolidine, and o-dianisidine may be used satisfactorilyfor titration of mercurous solution with bromide.359 Azide may be titratedby silver in the same way as halogens, sodium fluorescein being used asindicator; or rhodamine-6G may be used, in which case the end-point isobserved in ultra-violet F.Kenny and R. B. Kurtz 361 recommenda mixture of luminol and hzmoglobin as a chemiluminescent indicator foracid-base titrations with a light emission at pH 6.5, and they describe 362a suitable light-tight box for observing the end-point of this and othertitrations made with chemiluminescent indicators.346 R.Belcher, A. J. Nutten, and W. I. Stephen, J., 1951, 1520.347 R. Belcher and A. J. Nutten, ibid., p. 547.348 Milcrochem., 1951, 36/37, 255.349 F. Sierra and J. Hernandez Cafiavate, Anal. Pis. Quim., 1950, 46, B, 557; 1951,36a F. Sierra and E. Monllor, ibid., 1950, 46, B, 319.353 Idem, ibid., 1951, 47, B, 239.364 H. Flaschka and W. Schoniger, 2. anul. Chem., 1951, 133, 321.365 R. N. Adams and E. M. Hammaker, Analyt. Chem., 1951,23,744.356 Ibid., 1950, 22, 1190; C. A. Horton, MicroJiZm Abstr., 1951, 11, No. 1, 31.367 Ibid., p. 1194.35s F. Sierra and J. A . Shnchez, Anal. Pis. Quim., 1951, 47, B, 446.360 R. Haul and G. Uhlen, 2. anal. Chem., 1949, 129, 21.361 Analgt. Chem., 1951, 23, 339.47, B, 277.350 Idem, ibid., p. 439. 361 Idem, ibid., p. 269.368 R. C. Mehrotra, 2. anal. Chem., 1950,130, 390.362 Idem, ibid., p. 382328 ANALYTICAL CHEMISTRY.6. CLASSICAL ORGANIC ANALYSIS.General.-Methods for the characterisation of organic compounds 363 andfor micro-elemental and group analysis and the determination of specificcompounds 364 have been reviewed.Qualitative.-Qualitative tests for carbon,365 halogens,366 nitrogen,367and silicon 3683 369 in organic compounds have been described. Methods havebeen proposed for the identification of lactic a~id,~'O a~enaphtbene,~71 nico-tine,372 ~alicylamide,~~~ a m i n e ~ , ~ ~ ~ primary aromatic a m i n e ~ , 3 ~ ~ amines andN-nitr~amines,~~~ aromatic nitro- and nitroso-compounds,377~ 3'8 aldehydesand ketones,379381 methoxy- and etho~y-groups,~8~ acetyl com-pounds,384 methylenedioxy- phenols ,3 86 amino~acids,3~~ pyri-dine derivatives,3ss silicon-organic and plastics and resins.389392Quantitative.-I?.Martin 393 has described a method for the determinationof sulphated ash which depends on the inclusion of sulphur dioxide in anoxygen stream. The accuracy of organic microelemental analysis has beenexamined by W. Kir~ten,~9* who reports unfavourably on the claims fre-quently made in published work. The same author 395 has described improve-ments in the microchemical determination of the elements in organiccompounds, with particular reference to the methods for halogens, sulphur,363 R. L. Peck, Analyt. Chem., 1951, 23, 97.364 C.L. Ogg and C. 0. Willits, ibid., p. 47.365 L. P. Pepkowitz, ibid., p. 1716.366 M. JureEek and F. Muiik, Coll. Trav. chim. Tchdcosl., 1950, 15, 236.3 6 7 L. E. Brown and C. L. Hoffpauir, Analyt. Chem., 1951, 23, 1035.368 H. Gilman and G. N. R. Smart, J. Org. Chem., 1950,15, 720.369 A. P. Kreshkov and V. A. Bork, J. Anal. Chem., U.S.S.R., 1951,16, 78.370 R. A. McAllister, Analyst, 1951, 76, 238.371 G. Ya. Vanag and E. A. Zalukaeva, J. Anal. Chem., U.S.S.R., 1950, 5, 315.3'2 L. Feinstein and E. T. McCabe, Analyt. Chem., 1951, 23, 385.373 F. Hernhndez Guti6rrez and F. Pulido Cuchi, Analyt. Chim. Acta, 1951, 5, 450.574 K. W. Wilson, F. E. Anderson, and R. W. Donohoe, Analyt. Chem., 1951,23,1032.3 7 5 G. R. Lappin, J. Chem. Educ., 1951,28, 126.376 H.M. Curry and J. P. Mason, J. Amer. Chem. SOC., 1951, 73, 5041.377 H. Gilman and T. N. Goreau, ibid., p. 2939.3 7 8 L. S. Nelson and D. E. Laskowski, Analyt. Chem., 1951, 23, 1495.3 x 1 A. Castiglioni, 2. anal. Chern., 1950,131, 113.380 R. Opfer-Schaum, Angew. Chem., 1950, 62, 144.381 M. Viscontini and J. Meier, Helv. Chim. Acta, 1950,=, 1773.J. L. E. Erickson, J. M. Dechary, and M. R. Kesling, J. Amer. Chem. SOC., 1951.383 C. J. de Wolff, A. L. 0. M. Smithuis, and A. F. C. Sterk,Pharm. Weekblad, 1951,73, 5301.86,429. 384 C. J. de Wolff, ibid., p. 273.38638738838939039 1393396 -Idem, ibid., p. 335.M. S. Dunn and W. Drell, J. Chem. Educ., 1951, 28,480.J. V. Harispe and Mme. Harispe, Compt. rend., 1950, 231, 701.H. Nechamkin, J.Chem. Educ., 1951,28, 97.J. Contreras Berrojo, Inform. Quim. Analit., 1951, 5, 7.R. Castle, Chem. and Id., 1951,129.Mikrochem., 1951, 36/37', 660.Mikrochem., 1951, 36/37, 609; Analyt. Chim. Acta, 1951, 5, 272.3 a 6 L.S.Malowan, Milcrochem., 1951,38,212.392 A.Bischoff, Industr. Vern., 1950,4,200.394 Analyt. Chim. Acta, 1951, 5, 489WILSON : CLASSICAL ORGANIC ANALYSIS. 329and oxygen. Volumetric methods for the determination of elements inorganic compounds have been reviewed by W. T. Smith and R. E. buck el^.^^^Improvements have been described in methods for the determination ofcarbon and hydr0gen.3~7-400 A rapid method has been described by G.Ir~gram.~Ol Combustion may be carried out over a chromium oxidecatalyst.m2 Manganese dioxide is recommended as an absorbent for nitrogenoxides.m3 A statistical study has been made of factors in the microdetermin-ation of carbon and hydrogen, and it is reported 404 that the most importantof these are the size of sample and the treatment of absorption tubes beforeweighing. R.Belcher and R. Goulden 405 describe-the modifications necessaryfor the determination of carbon and hydrogen in fluorine-containing com-pounds. Factors affecting the determination of carbon and hydrogen bycombustion in oxygen, and of oxygen by reduction with hydrogen arediscussed by M. L. Ch~pin.~O~ G. W. Perold407 has examined methods ofcompensating for adverse atmospheric conditions when weighing absorptiontubes. Methods for the direct determination of oxygen have been describedand d i s c u s ~ e d .~ ~ ~ ~ 40~-412Modifications of the Preg1,413 Zimmermann+14 spiral-tube,415, 416 andbomb methods 417, 418 for sulphur have been proposed. A standard specifica-tion has been proposed for Carius micro-combustion tubes.4lQ Methods forselenium in organic compounds have been described.420¶ 421Nitrogen determination in oils has been systematically investigated by anumber of laboratories.422425 Improvements in the Dumas method for the396 Analyt. Chem., 1951, 23, 66.se7 M. P. Charest, P. Koch, and A. Gagnon, Rev. Canad. Biol., 1951, 9, 422.398 W. Kirsten, Mikrochem., 1951, 36/37, 217.399 H. Wagner, ibid., p. 634.402 P. N. Fedoseev and M. M. Pavlenko, J . Anal. Chem., U.S.S.R., 1950,5,296.403 R. Belcher and G.Ingram, AnaZyt. Chim. Acta, 1950, 4, 118, 401.404 C. L. Ogg, C. 0. Willits, C. Ricciuti, and J. A. Connelly, Analyt. Chem., 1951,406 Chim. anal., 1951, 33, 12.408 A. 0. Maylott and J:B. Lewis, Analyt. Chem., 1950, 22, 1051.409 H. W. Deinum and A. Schouten, Analyt. Chim. Acta, 1950, 4, 286.410 P. Gouverneur, M. A. Schreuders, and P. N. Degens, ibid., 1951,5, 293.411 M. Dundy and E. Stehr, Analyt. Chem., 1951, 23, 1408.412 V. A. Campanile, J. H. Badley, E. D. Peters, E. J. Agazzi, and F. R. Brooks,413 W. Padowetz, Mikrochem., 1951, 36/37, 648.414 G. Bussmann, Helv. Chim. Actu, 1950,33,1566.415 H. Wagner and F. Buhler, Mikrochem., 1951, 36/37, 641.416 F. Huffman and F. Zinneke, 2. anal. Chem., 1951,132, 175.417 R. K. Seigfriedt, J. S.Wiberley, and R. W. Moore, Analyt. Chem., 1951,23, 1008.41* R. N. Walter, ibid., 1950, 22, 1332.419 Cttee. for Stdn. of Microchemical Apparatus, A.C.S., Anulyt. Chem., 1951,23,1689.420 E. Kahane and S . Korach, Mikrochem., 1951, 36/37, 781.421 E. S. Gould, Analyt. Chem., 1951, 23, 1502.422 J. S. Ball and R. van Meter, ibid., p. 1632.423 G. R. Lake, P. McCutchan, R. van Meter, and J. C. Ned, ibid., p. 1634.424 R. van Meter, C. W. Bailey, and E. C. Brodie, ibid., p. 1638.426 R. T. Moore, P. McCutchan, and D. A. Young, ibid., p. 1639.400 J. Unterzaucher, ibid., p. 706. 401 Ibid., p. 690.23, 911. 405 Mikrochem., 1951, 36/37, 679.407 S. Afr. I d . Chem., 1951, 5, 38.ibid., p. 1421330 ANALYTICAL CHEMISTRY.determination of nitrogen have been described.4m, 426-431 B.Wurzschmittdescribes a method for determining nitrogen simultaneously with hydrogen.A variety of catalysts for Kjeldahl digestions has been proposed.*444Digestion in a sealed tube is recommended by L. M. White and M. C. Long,445and by J. Remy and J. Pitiot .446 Improvements in the distillation apparatushave been put forward by V. Klingmuller,447 M. Levy and M. SapirYM8 D. L.Shepard and M. B. Jacobs,449 D. B. William~,4~O and A. P. de Groot andJ. C. A. M i g h ~ r s t . ~ ~ ~ J. Ploquin 452 and W. J. Wingo, 0. L. Davis, and L.Anderson453 draw attention to errors that may occur in the titration pro-cedure. C. 0. Willits and C. L. Ogg 454 report on a series of test analysescarried out by the micro-Kjeldahl method, and consider these statistically.A method which does not require distillation after digestion depends onaddition of hypobromite and determination of the Diffusionmethods for the determination of nitrogen have been described by H.Hughes 456 and by P. L.Kirk.457 An investigation has been made 458 of theabsorption of ammonia from a gas stream, and the observations have beenapplied to the determination of organic nitrogen.Modified methods for comb~stion-tube,4~~, 459 Cari~s,4~0,4~~ and bomb 462465426 G. W. Perold, S. Afr. Ind. Chem., 1951, 5, 42.427 A. Dirscherl and H. Wagner, Milcrochem., 1951, 36/37, 628.4z8 A. Dirscherl, W. Padowetz, and H. Wagner, ibid., 1951, 38, 271.42Q W. Kirsten, Ind. Eng. Chem. Anal., 1947,19, 925.430 P. D. Sternglanz, R.C. Thompson,and W. L. Savell, Analyt. Chem., 1951,23,1027.431 E. F. Shelberg, ibid., p. 1492.433 M. Marzadro, R.C.Inst. Super Xanit., 1950, 13, 702.434 I. Ribas and F. L. Capont, Anal. 3%. Quim., 1950,46, B, 581.436 F. Koch, 2. anal. Chem., 1950, 131, 426.437 J. de la Rubia Pacheco, F. Blasco L6pez-Rubio, and J. Garrido MArquez, Inform.438 M. C. Marquez, Industr. y Quim., 1950, 12, 162.439 G. E. Secor, M. C. Long, M. D. Kilpatrick, and L. M. White, J . Assoc. 08. Agric.441 P. Dupuy, ibid., p. 836.442 M. B. Jacobs, J . Amer. Pharm. ASSOC., 1951, 40, 151.043 M. Marzadro, Mikrochem., 1951, 36/37, 671.444 C.H. Vanetten and M. B. Wiele, Analyt. Chem., 1951, 23, 1338.445 Ibid., p. 363.447 2. anal. Chem., 1950, 131, 17.449 J . Amer. Pharm. Assoc., 1951,40,154.451 Chem.Weekblad, 1951, 47, 219.453 Analyt. Chem., 1950, 22, 1340.456 H. W. Harvey, Analyst, 1951,76,657.457 Analyt. Chem., 1950, 22, 611.458 E. van Dalen, Anulyt. Chim. Acta, 1951, 5, 563.45Q H. W. Safford and G. L. Stragand, Analyt. Chem., 1951,23,520.460 L. M. White and G. E. Secor, ibid., 1950, 22, 1047.461 L. M. White and M. D. Kilpatrick, ibid., p. 1049.482 R. LQvy, Mikrochem., 1951, 36/37, 741.463 F. Martin, ibid., p. 653.485 E. J. Agazzi, T. D. Parks, and F. R. Brooks, Analyt. Chem., 1951.23. 1011.432 Milcrochem., 1951, 36/37, 614.D. W. A. Roberts, Canadian J . Res., 1950, 28, C, 745.Quim. Analit., 1950, 4, 166, 192.Chem., 1950, 33, 872. d40 J. Ploquin, CompLrend., 1951,232,164.446 Bull. SOC. Chim. biol., 1951, 33, 405.448 Bull SOC.chim. Biol., 1951, 33, 198.460 Waterandsewage Wks., 1951,98,87.462 Compt. rend., 1950, 231, 1066.464 J . Assoc. 08. Agric. Chem., 1950,33,179.456 J . Chem. Educ., 1951, 28, 195.464 B. Wurzschmitt, ibid., p. 769WILSON : CLASSICAL ORGANIC: ANALYSIS. 331methods for the determination of halogens have been described. V. E.Stewart 466 proposes sodium carbonate as an ashing fixative, and calciumoxide is recommended by H. J. Schenck and M. P ~ e l l . 4 ~ ~ Chlorine may bedetermined in coal by a rapid method using Eschka mixture for the decom-position.468 Potassium is recommended for the decomposition of organichalogen compounds by G. Kainz.469 The micro-estimation of iodine by theLiepert method has been modified by M.K. Zacherl and W. S t o ~ k l . ~ ~ Combustion methods for fluorine in organic compounds have beendescribed.471, 472 I n the estimation of fluorine by a bomb method the elementis finally determined as lead chlor~fluoride.~~~A micro-method for phosphorus has been described.474Volumetric methods for the determination of functional groups havebeen reviewed,396 and S. Siggia 475 discusses the place of functional-groupdetermination in the identification of organic compounds. Quantitativeprocedures have been devised for the analysis of some organic substances bycatalytic hydrogenation.476 A method based on rates of reaction has beenapplied477 to the analysis of mixtures of esters, olefins, and carbonyl com-pounds.Specific methods have been proposed for the determination of paraffins,478olefin hydrocarbons,479 unsaturation,48*-482 saponification nurnber~,4~~hydroxy-compounds,484 ethanol,4s5 tertiary alcohols,486 glycer01,4~~, 488peroxides,489491 citric acid,492 lactic acid,493 higher n-fatty long-chain466 J .Assoc. Off. Agric. Chem., 1950, 33, 214.468 Anon., Brit. Coke Res. Ass., 4th Rep., Panel I; J . Iron Steel Inst., 1951,168,228.469 Mikrochem., 1951, 38, 124.471 H. S. Clark, AnaEyt. Chem., 1951, 23, 659.472 R. R. Rickard, F. L. Ball, and W. W. Harris, ibid., p. 919.473 R. Belcher and J. C. Tatlow, AnaEyst, 1951, 76, 593.4 7 4 Y . Tsuzuki, M. Miwa, and E. Kobayashi, AnuZyt. Chem., 1951,23, 1179.476 Ibid., p. 667.4 7 6 E. C. Dunlop, Ann. N.Y. Acad. Sci., 1951,53, 1087.4 7 7 T.S. Lee and I. M. Kolthoff, ibid., p. 1103.478 W. Leithe, Analyt. Chem., 1951, 23, 493.479 A. R. Glasgow, J . Res. Nut. Bur. Stand., 1951, 46, 43.480 J. F. Mead and D. R. Howton, Analyt. Chem., 1950, 22, 1204.481 W. Schoniger, Mikrochem., 1951, 38, 132.482 H. Boer and E. C. Kooyman, Analyt. Chim. Acta, 1951, 5, 550.483 F. L. Hahn, ibid., 1950, 4, 577.484 S. Siggia and I. R. Kervenski, Analyt. Chem., 1951, 23, 117.485 H. Goetzke, Deutsch. Lebensmitt. Rundsch., 1950, 46, 276.486 0. R. Gottlieb, Industr. Parfum., 1950, 5, 447.487 R. Colson, ibid., 1951, 6, 115.488 R. B. Bradbury, Mikrochem., 1951,38, 114.489 I. M. Kolthoff and A. I. Medalia, Analyt. Chem., 1951,23, 595.490 J. Mattner and R. Mattner, 2. anal. Chem., 1951, 134, 1.491 D.Barnard and K. R. Hargrave, Analyt. Chim. Acta, 1951, 5, 476.493 A. Buffa, Ann. Chim. Roma, 1950, 40, 617.493 K. Lang and K. Pfleger, Mikrochem., 1951,36/37, 1174.494 G. T. Barry, Y . Sato, and L. C. Craig, J. Biol. Chem., 1951,188, 299.467 Kunststoff, 1951, 41, 192.470 Ibid., p. 278332 ANALYTICAL CHEMISTRY.hydroxamic aconitic and itaconic f~rfuraldehyde,4~~, 498carbonyl gr0ups,4~~, 500 amines,501 keto-alcohols,502 acetone,503, 504 vanillin,505alkaloids and amine~,~O6 phenols,507 sulph~xides,~O~ reducing sugars,509, 510pentoses and pentosans.497,498 A bibliography has been compiled on resinanaly~is.~ll7. INSTRUMENTAL METHODS.A wide variety of instrumental methods of analysis has been discussedby a number of authors.512-516 The second volume of Berl’s book 517completes an extensive and valuable collection of advanced monographs oninstrumental and other techniques in analytical chemistry.R. G.Steinhardt and E. J. Serfass 518 have proposed the use of X-rayphotoelectron spectra for chemical analysis, and have described a spectro-meter suitable for application to atomic surface analysis. Typical metallicspectra are illustrated.Electrodeposition.-Analytical techniques based on electrochemicaldeposition methods have been reviewed and critically studied, and theapparatus and devices for determinations and separations ~onsidered.~l~-~~Apparatus for maintaining potential control during depositions a t definitepotentials for such purposes as analytical separations has been d e s ~ r i b e d , ~ ~ ~ 495 E.T. Roe and D. Swern, Analyt. Chem., 1950,22, 1160.496 K. Lauer and S. M. Makar, ibid., 1951, 23, 587.497 L. Brissaud, A. Roudier, P. Lhoste, and L. Eberhard, Mt?m. Sew. c h h . l’dtat,490 W. Schoniger, and H. Lieb, Mikrochem., 1951, 38, 165.W. Schoniger, H. Lieb, and K. Gassner, 2. anal. Chem., 1951,134,188.601 S. Siggia, J. G. Hanna, and I. R. Kervenski, Analyt. Chem., 1950, 22, 1295.502 A. Chaney and M. J. Astie, J. Org. Chem., 1951, 16, 57.1950, 35, 57. 408 L. Brissaud and G. Perriot, Chim. Analyt., 1950, 32, 241.A. Ileceto and A. Malatesta, Ann. Chim. Roma, 1950,40, 494.A. Bennett, L. G. May, and R. Gregory, J. Lab. Clin. Med., 1951, 37, 643.505 L. K. Sharp, Analyst, 1951, 76, 215.506 D. Koszegi and E. Salg6,Z. anal.Chem., 1950,130, 403.507 H. Zahn and A. Wiirz, ibid., 1951, 134, 183.508 D. Barnard and K. R. Hargrave, Analyt. Chim. Acta, 1951, 5, 536.L. J. Heidt and K. A. Moon, J. Amer. Chem. SOC., 1950, 72, 4130.510 P. Bevillard, Bull. Soc. chim., 1950,17, 1298.511 E. V. Smith and T. P. G. Shaw, T.A.P.P.I., 1951,34, No. 5, 123A.512 G. D. Patterson and M. G. Mellon, Analyt. Chem., 1951, 23, 101.513 P. E. Klopsteg, Rev. Sci. Instr., 1951, 22, 216.614 F. Gutmann, J. Brit. Instn. Radio Engrs., 1950, 10, 194.515 Idem, Bull. Brit. Sci. Instr. Res. Ass., 1950, 5, 244.516 G. Charlot, Rev. Metall., 1950, 47, 528.517 W. G. Berl (Ed.), “ Physical Methods in Chemical Analysis,” Vol. 11, New York,519 R. Belcher and R. Goulden, Ind. Chem., 1951, 27, 204, 249.520 S.E. Q. Ashley, Analyt. Chem., 1950, 22, 1379.521 A. Lassieur, Chim. anal., 1950, 32, 79, 103.522 E. B. Thomas and R. J. Nook, J . Chem. Educ., 1950,27, 217.523 J. J. Lingane and S. L. Jones, Analyt. Chem., 1950,22, 1169.524 F. W. Chambers, J. Sci. Instr., 1950, 27, 292.s8s R. W. Lamphere, Analyt. Chem., 1951, 23, 258.’1951. 518 Analyt. Chem., 1951, 23, 1585WILSON : INSTRUMENTAL METHODS. 333and also an improved mercury cath0de.~,6 The separation of milligram andmicrogram amounts of elements by electrodeposition is considered, the diffi-culties involved are pointed out ,521 and methods for overcoming themdiscussed. 527Methods for the determination of specific elements have been proposedas follows : zinc, as a measure of zinc oxide extracted from the metal; 528copper occurring in conjunction with arsenic, silver, lead, and bismuth; 529gold ; 530 aluminium, using a mercury cathode ; 531 thallium ; 532 cobalt afterprecipitation as potassium cobaltinitrite ; 533 tin after separation as meta-stannic acid or sulphide ; 534 lead ; 535, 536 antimony ; 537 and bism~th.~~8> 539Coulomeb.-A titration coulometer making use of the electrode reactionsof VO,” is stated to be more accurate and more rapid than the normalsilver c ~ u l o m e t e r .~ ~ A constant current supply for coulometric titrations 541and an electromechanical integrator to replace the chemical coulometer 542have been described. A sensitive method, derived from amperometrictitration procedure, has been devised for indicating more clearly the end-pointin coulometric titrations.543 Coulometric titrations with electrically generatedceric ion may be applied 544 to the titration of ferrous solutions. Vanadiummay be determined after reduction with sulphite ion followed by oxidationwith ~ermanganate.~~~ Acids and bases may be titrated with externallygenerated H’ or OH’ ions which are subsequently delivered, in a speciallydesigned apparatus, to the titration The coulometric titration ofacids is also described by W.N. Carson and R. Ko,547 and 8-hydroxyquinolinemay be titrated with electrically generated bromine.548PolaromapW.-Polarographic apparatus and methods have been exten-sively reviewed, and new advances d i s ~ u s s e d . ~ ~ - ~ ~ ~ A dropping-mercury526 E.J. Center, R. C. Overbeck, and D. L. Chase, Analyt. Chem., 1951, 23, 1134.627 L. B. Rogers, ibid., 1950, 22, 1386. 628 G. H. Osborn, Analyst, 1951, 76, 114.529 G. Norwitz, 2. anal. Chem., 1950, 131, 410, 412; Analyst, 1950, 75, 551 ; 1951,76, 236; Metallurgia, 1951, 43, 46; Analyt. Chim. Acta, 1951, 5, 197.530 Idem,ibid.,p. 332. 531 J.KinnunenandB.Merikanto,AnaEyt. Chem., 1951,23,1690.532 G. Norwitz, Analyt. Chim. Acta, 1951, 5, 518.533 S. Kallmann, Analyt. Chem., 1950, 22, 1519.534 G. Norwitz, 2. anal. Chem., 1950,131, 266.635 Idem, Analyst, 1951, 76, 113; Metallurgia, 1951,43, 46.536 H. P. Mollenhower, J. Soc. Glass Tech., 1950, 34, 254.5 3 7 G. Norwitz, Analyt. Chem., 1951, 23, 386.538 Idem, Analyst, 1950, 75, 473; Analyt. Chim.Acta, 1951, 5, 195,539 C. Goldberg, Metallurgia, 1950, 42, 108.640 V. S. Syrokomsky and T. I. Nazarova, J. Anal. Chem. U.X.S.R., 1951, 6, 15.641 C. N. Reilley, W. D. Cooke, and N. H. Furman, Analyt. Chem., 1951, 23, 1030.5 4 2 J. J. Lingme and S. L. Jones, ibid., 1950, 22, 1220.543 W. D. Cooke, C. N. Reilley, and N.H. Furman, ibid., 1951, 23, 1662.544 N. H. Furman, W. D. Cooke, and C. N. Reilley, ibid., p. 945.545 N. H. Furman, C. N. Reilley, and W. D. Cooke, ibid., p, 1665.546 D. D. DeFord, J. N. Pitts, and C. J. Johns, ibid., pp. 938, 941.547 Ibid., p. 1019. 548 W. N. Carson, ibid., 1950, 22, 1565.54u T. D. Parks and L. Lykken, ibid., p. 1444.550 J. J. Lingane, ibid., 1951,23,86. 551 P-Delahay, Analyt. Chim. Acta, 1951,5,129.562 0. H. Muller, “The PoIarographicMethod of Analysis,” 2nd edn.,Easton,Pa., 1951334 ANALYTICAL CHEMISTRY.electrode 553 and a dropping-amalgam electrode 554 have been described.Advantages of vibrating dropping-mercury electrodes, and new methodsof obtaining vibration, are disc~ssed.~5~ W.Furness 556 proposes a modifiedapparatus for determining the rate of mercury flow from a dropping-mercuryelectrode. The effects of drop weight as a function of drop time 557 and ofionic strength 558 on diffusion current have been measured by Meites, and thetheoretical implications discussed. The choice of capillaries for electrodesis discussed by 0. H. Muller.559 P. Delahay and J. E. Strassner have derivedan equation 560 for irreversible polarographic waves, and have applied this tothe reduction of iodate ion, examining some experimental factors that mightinfluence the rate of the electrode processes. Some effects of adsorptionprocesses on polarographic waves have been studied."l Differential polaro-graphic titrations have been discussed.562 I. M.Kolthoff and D. Leussing 563have examined the use of micro-wire electrodes for polarography. Thesuccessful use of a stationary platinum micro-electrode has been described. 564P. Silvestroni 5135 has found the polarographic behaviour of oxygen a t thesurface of solutions to differ from that in the interior. The polarographicbehaviour of arsenic 566 and of antimony 567 has been studied. Polarographicmethods have been proposed for the estimation of elemental sulphur, bydissolution in methanol-pyridine ; 5 6 8 3 569 for potassium, indirectly throughprecipitation with dipicrylamine ; 570 and for 572 Comprehensivestudies of the complexes of zinc and cadmium with itr rate,^^^ and of cadmiumwith thiocyanate 574 have been made.Zinc, cadmium, and copper may bedetermined in silver-base all0ys.~7~ Procedures are described for thedetermination of zinc,576 578 and aluminium.576 Indium isfirst extracted as the 8-hydroxyquinoline complex before determination66s W. C. Cooper and M. M. Wright, Analyt. Chem., 1950, 22, 1213.664 N. H. Furman and W. C. Cooper, J . Amer. Chem. SOC., 1950, 72, 5667.666 D. A. Berman, P. R. Saunders, and R. J. Winzler, Analyt. Ckem., 1951, 23, 1040.666 Analyst, 1951, 76, 178.6 6 8 Ibid., p.4257.660 J . Amer. Chem. SOC., 1951, 73, 5219.661 M. Loshkarev and A. Kryukova, J . Anal. Chem. U.S.S.R., 1951, 6, 166.662 C. N. Reilley, W. D. Cooke, and N. H. Furman, Analyt. Chem., 1951,23, 1223.663 2. anorg. Chem., 1950, 262, 160.664 D. B. Julian and W. R. Ruby, J . Amer. Chem. SOC., 1950, 72, 4719.Ric. mi., 1950, 20, 1291.666 D. Cozzi and 8. Vivarelli, Analyt. Chim. Acta, 1951, 5, 215.667 Idem, {bid., 1950, 4, 300. 668 M. E. Hall, Analyt. Chem., 1950, 22, 1137.669 F. C. J. Poulton and L. Tarrant, J . Appl. Chem. Eond., 1951,1, [i], 29.570 D. Monnier, Z. Besso, and P. E. Wenger, Helw. Chim. Acta, 1951, 34, 433.671 V. Semerano and E. Gagliardo, Analyt. Chim. Acta, 1950, 4, 422.5 5 7 L. Meites, J . Amer. Chem. SOC., 1951, 73, 3724.6 5 9 Analyt.Chem., 1951, 23, 1175.A. S. Bogorad and S. N. Aleksandrov, J . Anal. Chem., U.S.S.R., 1951, 6, 101.L. Meites, J . Amer. Chem. SOC., 1951, 73, 3727.674 D. N. Hume, D. D. DeFord, and G:C. B. Cave, ibid., p. 5323.676 E. G. Ford, Canadian J . Tech., 1951, 29, 61.676 H. W. Hodgson and J. H. Glover, Analyst, 1951, 76, 706.677 L. C. Copeland and F. S . Griffith, Analyt, Chem., 1950, 22, 1269.678 W. Stross, Metallurgia, 1951, 43, 145WILSON INSTRUMENTAL METHODS. 335polarographically. 579 The polarographic behaviour of various oxidationstates of rheni~m,~8* of ferric citrate complexes,573 of the ferric-sulphosalicylicand of the ferric-hydrogen peroxide system 582 have been made.Iron may be determined polarographically in zinc ores,571 and cobalt, afterseparation as trioxalatocobaltate(m) 583 or as dithizone comple~.~W Methodshave also been described for molybdenum 585, 586 and for lead.577, 587 I.M.Kolthoff and E. P. Parry 588 have studied the peroxy-compounds of molyb-denum(vI), tungsten@), and vanadium(v) . Tin has been determinedpolarographically.576 The polarographic behaviour of this element is muchimproved in the presence of traces of tetraphenylarsonium chloride. 589 Thestandardisation of curves for lead according to the solution viscosity has beendescribed by P. Rutherford and L. A. Cha.590 Polarographic determinationof titanium has been preferred to a colorimetric method.591 F. L. English 592describes a method for the determination of platinum. The simultaneousdetermination of copper, cadmium, nickel, and zinc in bearing metals may bemade polar~graphically.~~~ The polarograph may be applied to the deter-mination of traces of a wide variety of elements in rocks 594 or in industrial~ a s t e s .5 ~ ~ It has also been used in the determination of organic mercurycompounds 596 and in the petroleum industry.597Polarography as applied to organic compounds has been discussed.598The method has been used to study and determine dimeth~lamine,~~~acetone,600 benzil,601 mixtures of dichloro- and trichloro-acetic acids,602mono- and di-nitroxylene~,~~~ nicotine,6M and benzoyl peroxide and cumenehydroperoxide. 605B. E. Gordon and L. C. Jones have examined a separation method based5 7 9 G. W.C.Milner, Analyst, 1951,76,488.580 C.L. Rulfs and P. J. Elving, J . Amer. Chem. SOC., 1951, 73, 3284, 3287.5 8 1 C. V. Banks and J. H. Patterson, ibid., p. 3062.5*2 I. M. Kolthoff and E. P. Parry, ibid., p. 3718.583 I. M. Kolthoff and J. I. Waters, Analyt. Chem., 1950, 22, 1422.684 F. Ender and H. Steeg, Biochem. Z., 1951,301, 426.5 8 5 M. Stepien, Prace Badawcze Glownego Inst. Metal. Odlewn., 1950, No. 2, 89;587 R. Portillo and P. Sanz Pedrero, Anal. Pis. Quim., 1951, 47, B, 413.5 8 8 J . Amer. Chem. SOC., 1951, 73, 5315.68s I. M. Kolthoff and R. A. Johnson, Analyt. Chem., 1951, 23, 574.590 Ibid., p. 1714.ss2 Ibid., 1950, 22, 1501.s94 S. MiholiE, J., 1950, 3402; Mikrochem., 1951, 36/37, 393.s95 P. G. Butts and M. G. Mellon, Sewage and Industr. Wastes, 1951, 23, 59.5s6 R.Benesch and R. E. Benesch, J . Amer. Chem. SOC., 1951, 73, 3391.597 P. W. West and C. H. Hale, Petrol Re$ner, 1950, 29, 109; U.S. Bur. Min., 1950P. J. Elving, J. C. Komyathy, R. E. VanAtta, Ching-Siang Tang, and I. RosenJ . Iron Steel Inst., 1951, 168, 114. 586 G. P. Haight, Analyt. Chem., 1951, 23, 1505.ssl R. P. Graham and J. A. Maxwell, ibid., p. 1123.sfis B. Rodewald, 2. anal. Chem., 1950, 131, 81.Synth. Liq. Fuels Abstr., 3, No. 5, 42.thal, Analyt. Chem., 1951, 23, 1218. 6s9 F. L. English, ibid., p. 344.601 E. Gagliardo, Ric. sci., 1950, 20, 1282. 6oo P. Zuman, Nature, 1950, 165, 485.602 P. J. Elving and Ching-Siang Tang, AnaZyt. Chem., 1951, 23, 341.603 C. H. Hale, ibid., p. 572.604 Y . Rusconi, D. Monnier, and P. E. Wenger, AnaZyt.Chim. Acta, 1951, 5, 222.605 P. A. Giguere and D. Lamontagne, Canadian J . Chem., 1951,29,54336 ANALYTICAL UHEMISTRY.on differences in partition coefficient, as applied to the polarography ofmixtures of similar compounds, and report on the applicability of the methodto mixtures of acetaldehyde and its homologues.606 B. Drake has proposedthe use of the polarograph as an automatic method for recording proteinconcentrations in chromat~graphy.~~~Amperometric Titrations.-Recent apparatus and methods for ampero-metric titration have been reviewed.549 Vibrating electrodes have been usedin the amperometric titration of thiosulphate, iodine, arsenic, and anti-mony.608 Amperometric titration methods have been proposed for theestimation of fluoride,6og chloride,610 phosphorus,611 zinc,612 copper,563, 612-615silver, 6143 iron, 616 nickel, thallium, 63, l4 chromium, 618 vanadium, l6and tungsten.614 Perrocyanide may be determined by titration withhexamminocobalt(m) chloride.619Nicotine,620 p-aminosalicylic acid,621 and cystine and cysteine 622 mayalso be determined amperometrically .Potentiometric !l!itrations.-Potentiometric titration methods have beenreviewed,549, 623 and newly developed reagents for use in potentiometric titr-ations 624 and pH meters 625 critically examined.G. Gran 626 describes anaccurate graphical method for determining the end point in potentiometrictitrations. A. Schleicher 627 discusses the errors arising from internal resistanceduring acid-base titrations.Calome1,6281 629 arsenic,630 and antimony 631electrodes have been described. G. Duyckaerts 632 has studied potentio-metric titrations carried out under steady polarisation.Potentiometric titration methods have been described for the deter-606 Analyt. Chem., 1950, 22, 981.6os E. D. Harris and A. J. Lindsey, Analyst, 1951, 76, 647, 650.609 H. G. Petrow and L. K. Nash, Analyt. Chem., 1950,22, 1274.610 I. M. Kolthoff and P. K. Kuroda, ibid., 1951, 23, 1306.611 R. N. Boos and J. B. Conn, ibid., p. 674.61* A. A. Zanko and L. I. Panteleeva, J . Anal. Chem., U.S.S.R., 1951, 6, 109.613 A. Liberti and E. do Cesaris, Ann. Chim. Roma, 1950, 40, 593.614 R. Kalvoda and J. Z-jka, Coll. Trav. Chim. Tchdcosl., 1950, 15, 630.616 T. D. Parks and L. Lykken, Analyt.Chem., 1950, 22, 1503.616 Idem, ibid., p. 1505.617 G. A. Butenko, G. E. Bekleshova, and E. A. Sorochinsky, J . AnaZ. Chem.,618 T. D. Parks and E. J. Agazzi, Analyt. Chem., 1950,22, 1179.1319 H. A. Laitinen and L. W. Burdett, ibid., 1951, 23, 1265.620 G. De Angelis, Ric. sci., 1951, 21, 62.621 W. Liberti, Atti Accad. Lincei, 1950, 8, 608.622 I. M. Kolthoff and W. Stricks, Analyt. Chem., 1951, 23, 763.623 N. H. Furman, {bid., p. 21.684 R. Belcher and R. Goulden, I n d . Chem., 1951, 27, 157, 178.616 G. I. Hitchcox, Mfr. Chem., 1951, 22, 93.686 Actu Chem. Scand., 1950, 4, 559.688 G. Gran and B. Altkin, Acta Chem. Scand., 1950, 4, 967.6g* G. J. Hills and D. J. G. Ives, Nature, 1950, 165, 530.630 A. A. Mousa, Analyst, 1951, 76, 96.Acta Chem.Scand., 1950, 4, 554.U.S.S.R., 1951, 8, 105..637 2. anal. Chem., 1950,131, 245.A. A. Scherbakov, J . Anal. Chem., U.S.S.R., 1951, 6 , 157.Analyt. Chim. Acta, 1951, 5 , 233WILSON : INSTRUMENTAL METHODS. 337mination of boron,633 br0mide,~3~~ 637, 638 nitrate,640sulphite, thiosulphate and sulphide,al sodium,a2 silveryM4-indium,M5 thallium,M6 tin,a3 titanium,a7 r n ~ l y b d e n u m , ~ ~uranium,BQS bismuth,650 and vanadium. a7A potentiometric method on the micro-scale for organic acids has beendescribed by W. Ingold,"l and E. B. G. Cameron 652 recommends a potentio-metric determination of reducing sugars. A quantitative procedure forcopolymer analysis by potentiometric titration in aqueous or in anhydrousmedia has been described.653Condnctimetric titrations.-P.Delahay 654 discusses the electrocheniicalphenomena occurring during " dead-stop " titrations, and deduces theconditions under which the method can be applied. C. Gensch and G.Jander 655 have described a conductimetric determination of the ammoniacontent of complex ammines, through which the metal content of cadmium,nickel, and zinc complexes may be determined. Conditions are described forthe conductimetric titration of potassium with lithium tetraphenylb~ron,~~~and of magnesium with barium hydroxide.656Apparatus for carrying out high-frequency conductimetric titrations,and the application of these titrations to suitable determinations, have beende~cribed.~~'-~~O The high-frequency titration of chloride with mercuricnitrate and of beryllium with alkali 662 is advocated. High-frequency63s G.H. Bush and D. G. Higgs, Analyst, 1951, 76, 683.634 F. Sierra and 0. Carpena, Anal. Fis. Quirn., 1950, 46, B, 627, 688.636 McD. Duxbury, Analyst, 1950, 75, 679.636 I. M. Kolthoff and P. K. Kuroda, Analyt. Chem., 1951, 23, 1304.637 F. Sierra and 0. Carpena, Anal. Pis. Quim., 1951, 47, B, 547.638 P. Wade, Analyst, 1951, 76, 606.63D F. Sierra and 0. Carpena, Anal. 2%. Quim., 1951,47, B, 345.640 M. P. Etheredge, J . Assoc. Off. Agric. Chem., 1950, 33, 262.641 A. D. Miller, J . Anal. Chem., U.S.S.R., 1951, 6, 71.642 R. Belcher and A. J. Nutten, Analyt. Chim. Acta, 1950, 4, 595.643 J. J. Lingane and C. Auerbach, Analyt. Chem., 1951,23, 986.F. Sierra and 0. Carpena, Anal.P i g . Quim., 1951, 47, B, 215.645 W. A. E. McBryde and M. L. Cluett, Canadian J . Res., 1950,28, B, 788.646 E. Bertorelli and A. Tunesi, Ann. Chim. Roma, 1951, 41, 34.647 A. Rius Mir6 and C. Alfonso Diaz-Flores, Anal. Pis. Quim., 1950,46, B, 289.648 C. V. Banks, U.S. Atomic Energy Comm. Rep., AECD-2735 ; Nuclear Sci. Abstr.,84n W. R. Grimes, U.S. Atomic Energy Comm. Rep., AECD-2804; Nuclear Sci.661 Mikrochem., 1951, 36/37, 276.663 Proc. Qd. SOC. Sug. Cane Technol., 1950, 17th Conf., 217.13~3 E. R. Garrett and R. L. Guile, J . Amer. Chem. SOC., 1951, 73, 4533.G54 Analyt. Chim. Acta, 1950, 4, 635.666 A. P. Toropov and G. B. Pasovskaya, J . Anal. Chem., U.S.S.R., 1951, 6, 115.657 J. L. Hall and J. A. Gibson, Analyt. Chem., 1951, 23, 966.658 W.J. Blaedel and R. V. Malmstadt, ibid., 1950, 22, 1413.65D G. G. Blake, Analyst, 1950,75,689; 1951,76,241; Chem. and Ind., 1951, 59.661 W. J. Blaedel and H. V. Malmstadt, Analyt. Chem., 1950, 22, 1410.662 K. Anderson and D. Revinson, ibid., p. 1272.1950, 4, 15.Abstr., 1950, 4, 368. 660 A. I. Busev, J . Anal. Chem., U.S.S.R., 1951, 6, 178.665 2. anal. Chern., 1950, 131, 89.W. van Tongeren, Chem. Weekblad, 1951, 47, 281338 ANALYTICAL CHEMISTRY.titration of calcium and magnesium has been applied 663 to the determinationof the total hardness of water.Analyses depending on the direct determination of concentration havebeen carried out, direct high-frequency measurements with a heterodyneoscillator being used rather than conductimetric titration, and small samplesof water-benzene-ethyl methyl ketone mixtures have been rapidly andquantitatively analysed.664Colorimetry and Absorptiometry.-Instruments for absorptiometry andtheir applications have been reviewed,665, and there is an extensivereview 667 of absorptiometric techniques and methods applicable to inorganicanalysis. J. W. Nicholas 668 describes a null-point, variable-aperturephotoelectric instrument. The conditions of maximum precision of threecommercially available instruments have been determined.669 A graduatedstrip filter can be used to convert a photoelectric colorimeter into a spectro-photometer.670 J. W. Nicholas and F. F. Pollak 671 describe a new cementfor light filters, to be used instead of Canada balsam.The transmissioncurves of a number of solution filters have been des~ribed.6~~The effective wave-length of a colorimetric system is defined,673 and 20colorimeters have been examined in respect of this definition. The prin-ciples of precision colorimetry have been discussed.674A. Boettcher and E. Hellwig 675 have discussed the problems arising inbinary systems where the colorimetric determination of each of the compo-nents suffers interference from the other, and have devised a method bywhich, in such a system, the composition of any sample can be read froma calibration curve. Absorptiometric schematic methods have been putforward for the analysis of 677 ores containing zinc, lead, vanadium,and and chromium, nickel, cobalt, and copper,679 and metalsin sewage and industrial wastes.680For individual elements new and improved procedures have been devised163 F.W. Jensen, G. M. Watson, and L. G. Vela, AnaZyt. Chem., 1951,23, 1327.664 P. W. West, T. S. Burkhalter, and L. Broussard, ibid., 1950,22,469 ; P . W. West,T. Robichaux, and T. S. Burkhalter, ibid., 1951,23, 1625.C . H. Giles, J . SOC. Dyers Col., 1950, 66, 615.666 A. G. Jones, Ind. Chem., 1951,27, 13.667 E. B. Sandell, “ Colorimetric Determination of Traces of Metals,” 2nd edn.,669 C. F. Hiskey, J. Rabinowitz, and I. G. Young, Analyt. Chem., 1950, 22, 1464.870 E. J. King and W. Weedon, Biochem. J., 1951, 48, Proc. lxi.13~1 J . Sci. Instr., 1951, 28, 23.672 A. M. Robinson and T. C. J. Ovenston, Analyst, 1951,76,416.673 G.Righini, Chim. e Id., 1951, 33, 91.674 C. F. Hiskey and I. G. Young, Analyt. Chem., 1951, 23, 1196.6 7 5 2. anorg. Chem., 1950, 263, 39.676 A. Berger, J. Pirotte, R. Muylle, and A. Juliard, BUZZ. Soc. chim. Belg., 1950, 59,677 J. S. Argila, Informac. Quim. analit., 1950, 4, 197.678 Y. Murakami, Chem. Age, 1951, 64, 356.679 J. Aubry and G. Laplace, Bull. SOC. chim., 1951, 18, 204.680 P. G. Butts, A. R. Gahler, and M. G. Mellon, Sewage and Industr. Wastes, 1950,London and New York, 1950. 668 Metallurgia, 1951, 43, 95.465.22, 1543; MetaZ Pinish, 1951, 49, 50-SON : INSTRUMENTAL METHODS. 339as follows : chloride, indirectly by liberation of an equivalent amount ofiodate and estimation through the starch-iodide blue,681 by liberation of anequivalent amount of chromate and estimation of this by reduction t ochromic ion,6g1 by conversion through silver chloride into colloidal silversulphide.6*2 Chlorine in tap water may be estimated by the yellow colourdeveloped by o-tolidine and sodium a r ~ e n i t e .~ * ~ Iodide may be determinedby liberation of iodine and estimation of the starch-iodide blue or the colourof a carbon disulphide solution ; fluoride by decolorisation of peroxytita-nate solution,685 or of solutions of ferric bromide, 686 or by zirconium-alizarinreagent ; 687 nitrate by nitration of phenoldisulphonic acid ; 688-690 nitrite bya modification of the Griess-Ilosvay method ; 691 azide by its interference withthe Griess-Ilosvay reaction ; 692 phosphate by molybdate-vanadate 693, 694or by molybdenum-blue ; 695-702 arsenic by molybdenum-blue ; 703 hydrogenperoxide by catalytic liberation of iodine from potassium iodide ; 704 sulphideby formation of methylene-blue ; 705 sulphate by addition of excess of bariumchloride, precipitation of the excess of barium as chromate, and reductionof the chromate to chromium(1n) by sodium metabisulphite ; 706 thiocyanateby ferric thiocyanate ; 707 tellurium as the iodo-tellurite complex ; 708 borateby turmeric; 709 silicate as silicomolybdate 710, 711 or as molybdenum-681 F.de A. Bosch Arfio and J. de la Rubia Pacheco, Anal. Fis. Quim., 1951, 47,68z P. K. Kuroda and E. B. Sandell, Analyt. Chem., 1950,22, 1144.683 M. J. Taras, Water and Sewage Wks., 1950,97, 404.684 F.de A. Bosch Ariio and J. de la Rubia Pacheco, Anal. Pis. Quim., 1951,47, B,685 S. Koritnig, 2. anal. Chem., 1950, 131, 1.687 J. P. Boonstra, Rec. Trau. chim., 1951, 70, 325.dm J. E. Eestoe and A. G. Pollard, J . Sci. Food Agric., 1950, 1, 266.M. J. Taras, Analyt. Chem., 1950, 22, 1020.6g0 C. M. Johnson and A. Ulrich, ibid., p. 1526.6g1 H. Barnes and A. R. Folkard, Analyst, 1951,76, 599.6ga H. Lees, Biochem. J., 1950,47, Proc. xliv.6g3 E. A. Epps, Analyt. Chem., 1950, 22, 1062.6s4 B. Ljunggren, Suenska Mejeritidn., 1950, 42, 332.605 H. J. Atkinson, R. F. Bishop, and R. Levick, Sci. Agric., 1950,30, 61.6S6 L. Marimpietri, V. Morani, and A. Gisondi, Ann. Staz. chim.-agr., Roma, 1950,6g7 U. T. Hill, Analyt. Chem., 1951, 23, 1496.600 W.Radmacher and W. Schmitz, Brennstoff-Chem., 1950, 31, 233.700 G. Norwitz and I. Norwitz, Metallurgia, 1950, 42, 219.701 L. Emster, R. Zetterstrom, and 0. Lindberg, Acta Chem. Scand., 1950, 4, 942.'02 B. L. Griswold, F. L. Humoller, and A. R. McIntyre, Analyt. Chem., 1951,23, 192.703 H. Poh1,Z. anal. Chem., 1951,134,177. 704 D. J. Savage, Analyst, 1951,76,224,705 R. H. Wright, M. A. Schoening, and A. M. Hayward, T.A.P.P.I., 1951, 34, 289.706 J. de IaRubia PachecoandF. Blasco L6pez-RubioYInform. Quim. anal., 1950,4,119.'07 F. Goldstein, J . Biol. Chem., 1950, 187, 523.'08 R. A. Johnson and F. P. Kwan, Analyt. Chem., 1951,23, 651.'0° J. de D. Guevard, Monit. Farm., 1951,57, 45.7 1 O W. J. Miller, J . Amer. Oil Chem. SOC., 1950, 27, 348.By 419.263, 331.686 K.Erler, ibid., p. 103.SBr. 3, No. 24.M. Rockstein and P. W. Herron, ibid., p. 1500.R. Guenther and R. H. Gale, Analyt. Chem., 1950, 22, 1510340 ANALYTICAL CHEMISTRY.blue ; 7129 713 germanium with hematoxylin and hydrogen peroxide,714 bymolybden~m-blue,~~5 or by 2 : 3 : 7-trihydroxy-9-phenyl-6-fluorone ; 716potassium by diazotisation using the cobaltinitriteY717 or by dipicryl-amine; 718-720 sodium by zinc uranyl acetate 721 or magnesium uranylacetate ; 722 calcium by precipitation as oxalate and decolorisation of cericsolution,723 by m~rexide,'~~ by chloranilic or by picrolonic acid ; 726barium by the chromate-metabisulphite reaction ; 706 beryllium by quin-alizarin v27 or by sulphosalicylic acid; 728 magnesium by coupling the 8-Titan-yellow, 7329 733 or by p-nitrobenzeneazo-1 -naphthol ; 734 zinc by dithi-zone 735,736 or by sodium diethyldithi~carbamate.~~~ Millimicrogramquantities of zinc have been estimated by d i t h i ~ o n e .~ ~ ~ Mercurous ion maybe estimated by the chromate-metabisulphite method, 706 or by perchlorate,the absorption being measured in the ultra-violet region; 739 mercuric ionhydroxyquinoline complex with diazotised sulphanilic acid, 729-731 b Yby dithizone ; 740 copper by sodium diethyldithi~carbamate,~~'* 741-747 b Y712 Brit. Iron and Steel Res. ASSOC., Methods of Analysis Cttee., J . Iron Steel Inst.,714 H. Newcornbe, W. A. E. McBryde, J. Bartlett, and F. E. Beamish, Anulyt. Chem.,716 L. Erdey and A. Bodor, 2. anal. Chem., 1951, 134, 81.717 C.L. Whittles and R. C. Little, J . Sci. Food Agric., 1950, 1, 323.718 M. Y . Shawarbi, Mikrochem., 1951, 36/37, 366.719 J. Colin, Bull. SOC. Chim. biol., 1951, 33, 394.720 W. Reimann, 2. physiol. Chem., 1951, 287, 210.721 W. McCamley, T. E. L. Scott, and R. Smart, Analyst, 1951, 76, 200.722 P. Trinder, ibid., p. 596.723 A. H. Cornfield and A. G. Pollard, J . Sci. Food Agric., 1951, 2, 135.724 H. Ostertag and E. Rinck, Compt. rend., 1950, 231, 1304.726 F. J. H. Mackereth, Analyst, 1951, 76, 482.727 G. W. Marks and H. T. Hall, U.S. Bur. Min., 1950, Rep. Invest. 4741.728 H. V. Meek and C . V. Banks, Analyt. Chem., 1950,22, 1512.729 Z. StolcovQ and M. Friml, Listy Cukr., 1951,67,33; Sug. Ind. Abstr., 1951,13,91.730 P. Pignard, Bull.SOC. Chim. biol., 1950, 32, 401.7s1 A. E. Willson, Analyt. Chem., 1951, 23, 754.m A. H. Cornfield and A. G. Pollard, J. Sci. Food Agric., 1950,1, 357.733 M. Orange and H. C. Rhein, J . Biol. Chem., 1951,189, 379.734 F. Farhan, Mikrochem., 1950, 35, 560.736 H. Wolff, Biochem. Z . , 1950, 320, 291.7s7 S. Ventura and E. J. King, Biochem. J., 1951, 48, lxi.738 B. G. Malmstrom and D. Glick, Analyt. Chem., 1951,23, 1699.73s W. C. E. Higginson, J., 1951, 1438.740 C. Stein, J . Assoc. 08. Agric. Chem., 1950, 33, 409.7 4 1 K. C. Beeson and R. L. Gregory, ibid., p. 819.742 J. A. V. Webb, 8. A&. Id. Chem., 1950, 4, 189.743 F. C. J. Poulton and M. E. Tunnicliffe, Trans. Inst. Rubber Ind., 1950, 26, 235.744 Y. Murakami, Bull. Chem. SOC., Japan, 1950, 23, 99.745 E.C. Mills and S. E. Hermon, Analyst, 1951, 76, 317.746 K. Kimura and Y. Murakami, Mikrochem., 1951, 36/37, 958.747 D. R. Perrin, F. R. Lightfoot, and G. M. Moir, J. Dairy Res., 1951,18, 77.1950,165, 430.1951,23, 1023.713 C. Ferrari, Mikrochem., 1951, 36/37, 585.H. J. Cluley, Analyst, 1951, 76, 523, 530.M. le Peintre, ibid., p. 968.738 H. Barnes, Analyst, 1951, 76, 220WILSON : INSTRUMENTAL METHODS. 3412 : 2'-diquinoly1,748,749 by dithio-oxamide, 751 by benz~inoxime,~~~ byhydrogen peroxide in the presence of alcoholic pyridine, resorcinol, andpyrarnidone,753 or by ferr~cyanide.?~~ In connection with the absorptio-metric determination of silver by p-dimethylaminobenzylidenerhodanine,the solubility product of the complex has been determined.755 Gold may beestimated by dithizone 756 or by p-dimethylaminobenzylidenerhodanine ; 757aluminium by aurintri~arboxylate,~~~, 761 by 8-hydroxyq~inoline~~~~ or byeriochromcyanine-R ; 760 manganese as permanganate by oxidation withperiodate 762 or with per~ulphate,~63 or by the use of pp'-tetramethyldiamino-diphenylmethane ; 764 iron by t h i ~ c y a n a t e , ~ ~ ~ , 765-767 by 1 : l ' - d i ~ y r i d y l , ~ ~ ~by quinaldic acid,769.by triphenylmethylarsonium thiocyanate,770 or bythioglycollic acid.771 A large number of colorimetric methods for the deter-mination of iron have been reviewed by T. s. We~t.77~ An investigation intothe action of sodium citrate on the formation of Prussian-blue has givenguidance for the conditions necessary for the production of true rather thancolloidal solutions.773 Cobalt may be determined by o-nitroso-p-~resol,~~~as tetraphenylarsonium cobaltothiocyanate, 774 or by direct measurement ofthe colour of the solution in concentrated hydrochloric P.W. Westand C. G. de Vries 776 have studied the formation of the cobalt-thiocyanateblue colour, and suggest a mechanism for this. Nickel may be estimated bydimethylglyoxime,777,778 by p-isothioureidopropionic or by cyclo-748 J. Hoste, A. Heiremans, and J. Gillis, Mikrochem., 1951, 36/37, 349.749 J. Gillis, J. Hoste, and E. Fernkdez-Caldas, Anal. Pis. Quim., 1951, 47, B, 327.750 W. L. Miller, I. Geld, and M. Quatinetz, Analyt. Chem., 1950, 22, 1572.751 P. W. Wright, J. SOC. Chern. Id., 1950, Suppl.Issue 2, S 69.75* K. W. Nance, Anulyt. Chem., 1951, 23, 1034.76s J. Storck, Ann. Pharm. franc., 1951, 9, 247.764 V. N. Podchaynova, J. Anal. Chern. U.S.S.R., 1951, 6, 191.766 E. B. Sandell and J. J. Neumayer, Analyt. Chim. Acta, 1951, 5, 445.766 R. S. Young, Analyst, 1951, 76, 49.767 S . Natelson and J. L. Zuckermann, Analyt. Chem., 1951, 23, 653.768 R. F. Innes and W. L. Sheppard, J. SOC. Leather Trades Chem., 1950,34, 460.760 J. L. Kassner and M. A. Ozier, Analyt. Chern., 1951,23, 1453.760 F. Pohl, 2. anal. Chem., 1951, 133, 322.761 A. C. Rolfe, F. R. Russell, and N. T. Wilkinson, J. Appl. Chem., Lond., 1951, 1,763 G. Gattorta, Ann. Staz. chim.-agr., Roma, 1950, SBr. 3, No. 34.764 W. Prodinger and A. Gurski, Mikrochern., 1951, 36/37, 580.766 C.Goldberg, Metal Ind., Lond., 1950, 76, 451.766 W.Sack,Z.anal.Chem., 1950,131,13.768 A. C. Mason, A.R.E. Mulling Res. Sta., 1950, 124.769 A. K. Majumdar and B. Sen, J. Indian. Chem. SOC., 1950,27, 245.770 F. P. Dwyer and N. A. Gibson, Analyst, 1951,76, 548.A.Mayer and G. Bradshaw, ibid., p. 715. 7 7 8 Metallurgia, 1951,43,204,260,311.773 M. Kohn, Analyt. Chim.'Acta, 1951, 5, 525.774 H. E. Affspmng, N. A. Barnes, and H. A. Potratz, Anulyt. Chem., 1951,23,1680.775 A. C. Zettemoyer and W. C. Walker, Amer. Ink Maker, 1950,28, 69.7 7 6 Analyt. Chern., 1951, 23, 334.777 W. L. Miller and G. Norwitz, Amer. Foundry, 1950,18, No. 4,67 ; Met. Abstr., 1951,7 7 8 C. Goldberg, Amer. Foundry, 1950,18, No. 1,66; Met. Abstr., 1950, IS, 203.779 L.J. Uhlig and H. Freiser, Analyt. Chem., 1951, 23, 1014.170. 76a J. A. Corbett, Analyst, 1950, 75, 475.7 6 7 G.NorwitzandI.Norwitz,ibid.,p. 268.18,544342 ANALYTICAL CHEMISTRY.heptane-1 : 2-dione d i o ~ i m e . ~ ~ ~ High percentages of nickel may be estimatedaslthe p e r c h l ~ r a t e . ~ ~ ~ The effect of foreign-salt concentration on the accuracyof the determination of nickel in plating solutions has beenChromium has been determined by diphenylcarbazide ; 783-785 molybdenumby hydrogen per0xide,~~~5 787 by thiocyanate-stannous ~hloride,~ss by thethiocyanate complex stabilised by 2-butoxyethan01,7~~ by the catalytic effecton the reduction of malachite-green by titanous solution,7Q0 bypyrocate~hol,~~~and by phenylhydrazine hydrochloride ; 792 molybdenum and tungsten bytoluenedithiol ; 793 tungsten by thiocyanate-stannous chloride ; 794 uraniumby oxalohydroxamic acid 795 or by potassium thiocyanate ; 796 radium-D,radium-E, and polonium by dithizone; 797 lead by the chromate-meta-bisulphite reaction,706 by dithizone,798-800 or by di-2-naphthyldithizone ;titanium by hydrogen peroxide,s01 or as the 8-hydroxyquinoline complex withhydrogen peroxide; SO2 zirconium by the zirconium-alizarin lake SO3 or bychloranilic acid; vanadium by o-phenanthroline or by benzoyl-phenylhydroxylamine ; niobium and tantalum by pyrogallol ; 807 palla-dium by dithizone ; 756 palladium and rhodium by 2-mercapto-4 : &dimethyl-thiazole ; iridiumby perchloric-phosphoric-nitric acid mixture ; 810 osmium by thiourea ; 811ruthenium by dithio-oxamide.812platinum by dithizone 756 or by stannous chloride ;780 R.C . Ferguson and C . V. Banks, Analyt. Chem., 1951, 23, 1486.781 R. Bastian,ibid., p. 580.783 P. F. Urone and H. K. Anders, Analyt. Chem., 1950,22, 1317.784 Y. Murakami, Bull. Chem. Soc., Japan, 1950, 23, 157.786 A. Gottlieb and F. Hecht, Mikrochem., 1950, 35, 523; A. Gottlieb, ibid., 1951,787 H. J. Evans, E. R. Purvis, and F. E. Bear, ibid., p. 1568.788 F. N. Ward, Analyt. Chem., 1951, 23, 788.789 E. Knuth-Winterfeldt, Acta Chem. Scad., 1950, 4, 963.790 T. Shiokawa, Sci. Rep. Res. Inst. TGhoku Univ., 1950, [A], 2, 770.791 S. Seifter and B. Novic, Analyt. Chem., 1951, 23, 188.792 G. H. AyresandB. L. Tuffle, ibid., p. 304.796 A.K. Dasgupta and J. Gupta, J . Sci. Id. Res., India, 1950,9, B, 237.796 M. Gerhold and F. Hecht, Mikrochem., 1951,36/37, 1100.782 G. C . H. Stone, Metal Finish., 1951,49, No. 2,44.38, 142. 786 G. Telep and D. F. Boltz, Analyt. Chem., 1950, 22, 1030.79g H. G. Short, Analyst, 1951,76,710.H. Freund, M. L. Wright, and R. K. Brookshier, ibid., p. 781.G. Boussibres and C. Ferradini, Analyt. Chim. Acta, 1950, 4, 610.G. W. C. Milner and J. Townend, ibid., 1951, 5, 584.R. Vesterberg and 0. Sjoholm, ibid., 1951, 38, 81.799 R. Vesterberg, Mikrochem., 1951, 36/37, 967.801 B.S.I. Specif., 1951,No. B.S. 1121, Pt. 17. K. Gardner, Analyst, 1951,76,485.803 R. Guenther and R. H. Gale, U.S. Atomic Energy Comm. Rep. KAPL-305, 1950;804 B. J. Thamer and A.F. Voigt, J . Amer. Chem. SOC., 1951, 73, 3197.808 S. C. Shome, Analyt. Chem., 1951, 23, 1186.807 H. GotG and Y. Kakita, Sci. Rep. Res. Inst. TGhoku Univ., 1950, 2, 249.D. E. Ryan, Analyst, 1951, 76, 310, 731.809 G. H. Ayres and A. S . Meyer, Analyt. Chem., 1951, 23, 299.810 G. H. Ayres and Q. Quick, ibid., 1950, 22, 1403.811 F. P. Dwyer and N. A. Gibson, Analyst, 1951,76, 104.812 G. H. Ayres and F. Young, Analyt. Chem., 1950, 22, 1277, 1281.Nuclear Sci. Abstr., 1950, 4, 417.A. Gottlieb, Mikrochem., 1951, 36/37, 370. WILSON : INSTRUMENTAL METHODS. 343The preparation of pure dithizone solutions of known concentration maybe controlled abs~rptiometrically.~~~In organic compounds nitrogen may be determined colorimetrically byNessler 's reagent ,8l* phosphorus with molybdate-vanadate ,815 and sulphurby conversion into methylene-blue.816 Colorimetric methods have beenproposed for the determination of oxalic acidJ817 picric acid,818 linoleic andlinolenic acidsJ819 methanol,s20 ethanol,s21 glycero1,822 f~rfuraldehyde,~~~formaldehyde,824-826 carbonyl phenols,828 rneth~lamine,~~~he~amethylenetetramine,~~~ diacylamine~,~~~ amino-acids,m2 urea,833 pen-t 0 s e s ~ ~ ~ P ~ 5 a~enaphthylene,s~~ benzene,837 anthracene,s38 m-dinitrobenzeneand ~-trinitrobenzene,8~~ and quino1.840s 841Nephe1ometry.-The nephelometer described by A.C. Mason 842 can beused over a wide range of concentrations and deviates little from linearityat higher turbidities. Nephelometric methods have been proposed forpotassium,sa calcium and magnesium,s@ cadmium,846 and zincand lead.s47J.Haslam and D. C. M. Squirrel1 848 have given directions for the prepar-ation from Perspex of permanent turbidimetric standards for chloridedetermination.S. S. Cooper and M. L. Sullivan, Analyt. Chem., 1951, 23, 613.814 J. F. Thompson and G. R. Morrison, ibid., p. 1153.816 W. R. Simmons and J. H. Robertson, ibid., 1950, 22, 1177.816 H. Roth, Mikrochem., 1951, 36/37, 379.817 R. S. Pereira, ibid., p. 398.81s T. P. Hilditch, C. B. Patel, and J. P. Riley, Analyst, 1951, 76, 81.820 A. Mariani, R. C. Inst. super. Sanit., 1950,13, 154.821 M. B. Williams and H. D. Reese, Analyt. Chem., 1950,22, 1556.822 S . C. HarveyandV. Higby, Arch. Biochem., 1951, 30, 14.823 L. Fuchs, Monatsh., 1950,81,70.836 M.Tanenbaum and C. E. Bricker, ibid., p. 354.82s L. Segal, ibid., p. 1499.828 A. J. Singer and E. R. Stern, ibid., p. 1511.829 A. A. Olmsby and S. Johnson, J . BioZ. Chem., 1950,187, 711.830 F. Montequi Diaz de Plaza, And. Pis. Quim., 1951,47, B, 135.831 J. B. PolyeandP. L. Tardew, Analyt. Chem., 1951,23, 1036.832 A. M. Smith and A. H. Agiza, Analyet, 1951, 76, 623.833 H. 0. Halvorson and M. 0. Schultze, J . Biol. Chem., 1950,186, 471.834 M. V. Tracey, Biochem. J., 1950,47,433.836 G. L. Miller, R. H. Golder, and E. E. Miller, Analyt. Chem., 1951, 23, 903.836 M. Kaufman and A. F. Williams, Analyst, 1951, 76, 109.837 D. M. Buis and H. Jansen, Pharm. Weekblad, 1951,86, 357.838 F. P. Hazlett, R. B. Hannan, and J.H. Wells, AnaZyt. Chem., 1950, 22, 1132.83g K. Cruse and R. Mittag, 2. anal. Chem., 1950, 131, 273.840 R. Belcher and W. I. Stephen, Analyst, 1951, 76, 46.841 R. Belcher and T. S. West, Analyt. Chim. Acta, 1951, 5, 699.842 Analyst, 1951, 76, 172.844 A. Valls-Conforto, Rev. clin. esp., 1950, 37, 186.846 J.de 1aRubiaPacheco and F. Blasco L6pez-Rubio,Inform. Quim. Analit., 1951,5,1,646 R. Fabre, R. Truhaut, and C. Boudhe, Ann. Pharm. franp., 1951, 9, 30.847 Y. Murakami, Bull. Chem. Soc., Japan, 1950, 23, 150.848 Biochem. J., 1951, 48, 48.818 R. Stohr and F. Scheibl, ibid., p. 362.824 E. W. Rice, AnaEyt. Chem., 1951,23,1501.827 G. R. Lappin and L. C. Clark, ibid., p. 541.843 Idem, ibid., p. 176344 ANALYTICAL CHEMISTRY.Turbidimetric methods of determining the end-point in the titration ofsodium-potassium of and of zinc 851 have beendescribed.Theblue fluorescence given by flavonol in sulphuric acid has been used for thequantitative estimation of zirconium.853Emission Spectrography.-The apparatus employed in spectrochemicalanalysis has been reviewed.854 It has been suggested 855 that a better" signal-to-noise " ratio can be obtained in the direct-current arc by replacingthe air round the arc by either argon or helium. The atmosphere round thearc has also been modified by J.Y. Ellenburg and L. E. Owen.85s Anelectrode holder for operating arc or spark in an atmosphere of controlledpressure has been described,857 and A. T. E. W. Claffy and J. G.Schumacher 859 and L. E. Owen J.F.Woodruff 861 has published a description of a technique for producing bri-quetted samples of drillings, millings, or grindings. .The method of concentrating trace elements by precipitation withorganic reagents before spectrochemical analysis has been extended byR. L. Mitchell,s62 Burriel-Marti and his co-w0rkers,~6~ and by G. Gorbachand F. Pohl.864 R. Pieruccini 865 describes the concentration of nickel andcobalt by co-precipitation with iron sulphide.General spectrochemical methods have been described for the analysis ofmiscellaneous materials,866 copper or lead being used as internal buffer in ad.c. arc. The technique of successive additions has been used by N. W. H.Addink.B67 The use of sodium nitrate as matrix has been recommendedas a method capable of extension to the determination of a largenumber of elements.868 Lithium tartrate has been recommended as abuffer .869General reviews of spectrochemical analysis in metallurgy have849 Z.Blaszkowska, Roczn. Chem., 1950, 24, 193.850 H. Frey, 2. anal. Chem., 1951, 133, 328.852 W. C. Alford and H. J. H. Daniel, AmEyt. Chem., 1951,23, 1130.853 W. C. Alford, L. Shapiro, and C. E. White, ibid., p. 1149.854 M. 9. Coheur, Rev. MLt., 1950, 47, 531.855 B. L. Vallee, C. B. Reimer, and J. R. Loofbourow, J. Opt. SOC. Amer., 1950, 40,857 T. Hugo, S. M. Naud6, and H. Verleger, Rev. Sci. Instr., 1951, 22, 210.8 5 8 Analyt. Chem., 1951, 23, 209.860 Analyt. Chem., 1950, 22, 1581.862 Mikrochem., 1951, 36/37, 1042.863 F. Burriel Marti and J.Rdrez-Muiios, AnaE. Fis. Quim., 1951, 47, B, 201;F. Burriel-Martl, J. Ramirez-Mufios, and E. FernAndez Caldas, ibid., p. 429 ; F. Burriel-Marti and J. Ramirez-Mufios, Analyt. Chim. Actu, 1950, 4, 428; Mikrochem., 1951,36/37, 495.Fluorimetry.-A photoelectric fluorimeter has been de~cribed.8~2have described electrode cutters.851 Idem, ibid., 1951, 132, 276.751. 856 Analyt. Chem., 1951, 23, 1512.859 Rev. Sci. Instr., 1950, 21, 575.8B1 J . Opt. SOC. Amer., 1950, 40, 192.864 Ibid., p. 486; 1951, 38, 258.81313 E. K. Jaycox, AnaEyt. Chem., 1950, 22, 1115.867 Rec. Trau. chim., 1951, 70, 155.S 6 8 V. G. Perry, W. M. Weddell, and E. R. Wright, Anulyt. Chem., 1950, 22, 1516.869 H. G. Schrenk and H. E. Clements, ibid., 1951, 23, 1467.865 Ibid., 1951, 36/37, 522WILSON : INSTRUMENTAL METHODS.345appeared,87*, 871 and general methods in steel analysis have been describedand disc~ssed.87~-~~5 The estimation of carbon 87% 877 and phosphorus 878 insteels, and of magnesium in cast iron879 has also been described. Thetechniques used in the analysis of non-ferrous metals have been reviewed anddiscussed.880 J. P. Puenzieux 881 has described the spectrochemical deter-mination of aluminium, zinc, and silicon in magnesium alloys, and the con-ditions for reproducible determination of the minor elements in aluminium-zinc-magnesium alloys have been described.882 Gallium has been estimatedspectrographically in al~minium.~8~ A spectrographic method is reportedfor the estimation of iron, magnesium, and manganese in titanium metal.Spectrographic techniques in the oil industry have been described andexamined critically.885 Simple sparking of powdered clays with copperoxide as internal standard enables reproducible results to be obtained formajor constituents, but is not suitable for trace elements or for the alkalimetals where an intermittent arc must be used on a solution of the clay in asulphuric-hydroffuoric acid mixture.886 Copper rather than graphite shouldbe used as the electrode in determining lanthanons by the intermittent-arctechnique.887 Spectrographic methods have been described for the analysisof archzological bronzes,888 impurities in catalyst rnaterial~,88~ and tracesof metals in ~ i l ~ . ~ ~ ~ ~ ~ ~ ~ Beryllium has been estimated in air-dust samples870 J.M. Pouvreau, Rec. Me’tall., 1950, 47, 515.871 R. Castro, ibid., p. 521.873 P. R. Irish, Amer. Inst. Min. Met. Eng., Elect. Furn. Steel Conf. Proc., 1949, 7,110; M. L. Windle, and W. H. Magrun, ibid., p. 119; D. G. Schoffstall, ibid., p. 122;A. C. Hale, ibid., p. 124; J . Iron Steel Inst., 1951, 168, 112, 113.874 G. Monnot, #roup. Avance. Me‘th. d’Anul. spectrog. Prod. dtallurg., 12th Congr.,1950, 85; J . Iron Steel Inst., 1951, 167, 466.876 J. F. Young, Iron Age, 1951,168, No. 2, 91.877 F. Malamand, Group. Auance. Mdth. d’AnaE. spectrog. Prod. mktallurg., 12th878 A. Hans, ibid., 1950, 166, 118.87s T. J. Hugo, J . S. Afr. Chem. Inst., 1950, 3, 17.880 D. M. Smith, Inst. Min. Metall. Symp. Refining Non-ferrous Metals, 1949, Pre-881 Helv.Chim. Acta, 1951, 34, 615.882 T. Nuciari, Alluminw, 1949, 18, 476; Met. Abstr., 1951, 18, 619.883 F. Farhan, Mikrochem., 1950, 35, 564.884 M. J. Peterson, Anulyt. Chem., 1950, 22, 1398.R. 0. Clark et al., Analyt. Chem., 1951, 23, 1348; E. L. Gunn, ibid., p. 1345;J . W. Anderson and H. K. Hughes, ibid., p. 1358; J. Hansen, P. Skiba, and C. R.Hodgkins, ibid., p. 1362; C. M. Gambrill, A. G. Gassmann, and W. R. O’Neill, ibid.,p. 1365.C. G. Carlsson and J. T. M. Yu, J . Iron Steel Inst., 1950, 166, 273.R. Breckpot and C . Gobert, Bull. SOC. chim. Belq., 1950, 59, 102.Congr., 1950, 59; J . Iron Steel Inst., 1951, 16’7, 465.print 1 ; Met. Abstr., 1950, 17, 526.886 J. Gillis and J. Eeckhout, Silicates Industr.Bruxelles, 1950, 15, 213.887 J. A. C . McClelland, Analyst, 1950, 75, 392.88n D. D. Harmon and R. G. Russell, Analyt. Chem., 1951, 23, 125.8s1 E. H. Melvin and J. E. Hawley, J . Amer. Oil Chem. SOC., 1951,28, 346.M. Van Doorselaer, Mikrochem., 1951, 36/37, 513.M. T. CarlsonandE. L. Gunn, ibid., 1950,22, 1118346 ANALYTICAL CHEMISTRY.after removal of other elements by precipitation with oxine and then pre-cipitating the beryllium as hydroxide.892Nitrogen has been estimated in organic compounds by using the CN bandhead,Sg3 and halogens, sulphur, and selenium have been determined byexcitation in a high-frequency discharge.894R. W. Murphy and H. K. Hughes 895 describe an auxiliary optical systemwhich enables the simultaneous recording of two spectral ranges on a Littrow-type instrument.D. D. Harmon has devised a slide-rule which permits rapidevaluation of plates by relating the calibration and working curves,896 andA. J. Mittledorf 897 an index block made of Perspex for easy identification ofthe spectrograms on a plate during examination in a comparator. A. Hans 898discusses the advantages of the line-breadth photometric method forquantitative analysis, with special reference to the analysis of steel, cast iron,and zinc.Direct-reading spectrochemical methods using photomultiplier tubes ininstruments of the “ Quantometer ” type have been described by a numberof P. Coheur and A. Hans 903 have utilised photomultipliertubes to record the first-order spectrum, and a camera to record simultane-ously the second-order spectrum.Background corrections in spectrograms have been discussed by A.C.Oertel 904 and by E. Roux and C . H ~ s s o n . ~ ~ ~ Scale-readinggo6 andrecording 907 densitometers have been described.L. G. Young and J. M. Berriman 908 describe a solution spark technique,where the solution is contained in a porous graphite cup in the upper electrode,for the determination of the major constituent of a solution. It has beenclaimed 909 that increased sensitivity and reproducibility are obtained byusing a small auxiliary gas flame in a spark discharge, the gas being fed inthrough a channel in one of the electrodes.General apparatus Flame photometry has been critically reviewed.g10* 91189% G. E. Peterson, G. A.Welford, and J. H. Harley, Analyt. Chem., 1950, 22, 1197.893 L. D. Frederickson and L. Smith, ibid., 1951, 23, 742.894 A. Gatterer, Mikrochem., 1951,38137,476. 896 J . Opt. SOC. Amer., 1950,40,779.8D6 Analyt. Chem., 1950, 22, 1227. 897 Ibid., 1951, 23, 1055.898 Group. Avance. Mkth. d’Anal. spectrog. Prod. mdtallurg., 11th Congr., 1949, 51 ;Idem, Zoc. cit., p. 105; M. F. Hasler, ibid., p. 113; R. Breckpot, ibid., p. 99; J .L. W. Orr, MicroJilm Abstr., 1950, 10, No. 3, 189.R. W. Callon and L. P. Charette, AnaZyt. Chem., 1951, 23, 960.J . Iron Steel Inst., 1950, 166, 165; Met. Abstr., 1950, 17, 751.Iron Steel Inst., 1951,167,466.901 J. M. Naish, J. Sci. Instr., 1951, 28, 138.9O3 Group. Avance. Me’th. d’Anul. spectrog. Prod. me’tallurg., 11th Congr., 1949,45; J .9O4 Austr.J . Appl. Sci., 1950, 1, 152.906 Compt. rend., 1950,231,770. 9O6 J. C. Delaney, J . Opt. Soc. Amer., 1950,40,787.*08 Nature, 1950, 166, 435.Iron Steel Inst., 1950,166,165.W. N. Brown and W. B. Birtley, Rev. Sci. Instr., 1951, 22, 67.E. SBnchez Serrano and L. Jimeno Martin, Anal. Fb. Quim., 1950, 46, B, 617;47, B, 175. 910 A. G. Spencer, Lancet, 1950, 249, 623.911 W. G. Schrenk, Analyt. Chem., 1950, 22, 1202WILSON : INSTRUMENTAL METHODS. 347and methods,912 simple 913-916 and integrating 917 flame photometers, and aglass atomiser 918 have been described. E. Dunker and H. Passow 919 discussmethods for increasing the accuracy of flame photometry. Methods havebeen proposed for the determination of lithium,920 s o d i ~ m , ~ ~ ~ - ~ ~ * potas-sium,9=29,931,932 calcium,92% 930,933,934 and magnesium.925 The method hasalso been applied to the determination of the alkali metals and alkaline-earthmetals in minerals 935 and inVisible and Ultra-violet Absorption.-A bsorption spectrometry in thevisible 937 and in the ultra-violet 938 region has been reviewed, and there hasbeen increasing application of ultra-violet investigations to the inorganicfield. The limits of accuracy are examined,939 and apparatus for work a ttemperatures down to -165" is described.940 R.H. Munch 941 discussesultra-violet photometers and the checks which must be applied to them.Suitable constructions for hydrogen-discharge tubes providing an ultra-violetcontinuum have been prop0sed.9~~1 943 The purification of solvents, both forultra-violet and for infra-red work, has been surveyed by M.P e ~ t e m e r , ~ ~ and methods for a number of these are given in detail.Infra-red Absorption.-The field of infra-red spectroscopy in analyticalchemistry has been reviewed.945 The errors involved, and the relative merits918 A. R. Robinson, K. J. Newman, and E. J. Schoeb, AnaEyt. Chem., 1950,22,1026.913 G. K. McGowan and J. Smart, Biochem. J., 1951, 49, xxxi.914 A. M. Robinson and T. C . J. Ovenston, Analyst, 1951,76,416.91S L. Leyton, ibid., p. 723.916 W. G. Schrenk and F. M. Smith, Anulyt. Chem., 1950,22, 1023.917 J. A. Ramsay, S. W. H. W. Falloon, and K. E. Machin, J . Sci. Instr., 1951,28,75.918 J. Benotti and A. DeTore, J . Lab. Clin.Med., 1950, 36, 763.921 R. L. Shirley, J . Assoc. Off. Agric. Chem., 1950, 33, 805.922 W. A. Seay, 0. J. Attoe, and E. Truog, Soil Sci., 1951, 71, 83.923 D. A. Brewster and C. J. Clausen, Iron Age, 1950, 166, No. 18, 88.gZ4 J. Smit, C. T. J. Alkemade, and J. C. M. Verschure, Biochem. Biophys. Acta, 1951,926 J. G. Brown, 0. Lilleland, and R. K. Jackson, Proc. Amer. Soc. Hort. Sci., 1950,D27 W. M. Wallace, M. Holliday, M. Cushman, and J. R. Elkinton, J . Lab. Clin. Med.,Q2s F. M. Biffen, Analyt. Chem., 1950, 22, 1014. 929 C. L. Fox, ibid., 1951, 23, 137.Q30 G. H. Osborn and H. Johns, AnaZyst, 1951,76,410.Qsl 0. W. Ford, J . Assoc. Off. Agric. Chem., 1950, 33, 268.932 G. Ehrlin-Tamm, Acta Chem. Scand., 1950,4, 1317.933 J. W. Severinghaus and J.W. Ferrebee, J . Biol. Chem., 1950,187, 621.934 R. H. Heidel and V. A. Fassel, Analyt. Chem., 1951, 23, 784.s3s S. B. Knight, W. C. Mathis, and J. R. Graham, ibid., p. 1704.936 A. L. Conrad and W. C . Johnson, ibid., 1950,22,1530.937 M. G. Mellon, ibid., 1951, 23, 2.939 A. Luszczak, Mikrochem., 1951,36137, 532.940 R. N. Beale and E. M. F. Roe, J . Sci. Instr., 1951, 28, 109.941 Ind. Eng. Chem., 1950,42, No. 10, A 61.942 S. K. Battacharye, Indian J . Phys., 1950, 24, 109.943 N. A. Finkelstein, Rev. Sci. Instr., 1950, 21, 509.944 Angew. Chem., 1951, 63, 118.Biochem. Z . , 1950, 32, 152. 920 E. Wilberg, Z . anal. Chem., 1950, 131, 405.6, 508 ; Chem. Weekblad, 1951,47, 23.56, 12.1951, 37, 621.926 N. Gammon, Soil Sci., 1951, 71, 211.838 E.J. Rosenbaum, ibid., p. 12.945 R. C . Gore, Andyt. Chem., 1951,23, 7348 ANALYTICAL CHEMISTRY.of various types of instruments, have been discussed by D. Z. Robinson.946The principles and construction of a variety of infra-red spectrographs andspectrometers have been d i s ~ u s s e d . ~ ~ ~ - ~ ~ ~ Calibration procedures aredescribed by W. Guy and J. H. Towler 955 and by A. E. Martin.956 Low-temperature 957 and high-temperature 958 cells, and a method for water-proofing rock-salt for cells by evaporating selenium on to the walls 959 havebeen described. It is claimed that addition of triethylamine to carbondisulphide or carbon tetrachloride improves these as solvents for some studiesin the infra-red.960Infra-red analysis has been applied to hydrocarbons,961s 962 long-chainfatty acids, esters, and alcohols,g63 trans-octadecenoic acids, esters, andalcohols,964 diethylene glycol dinitrate and nitroglycer01,~~~ substitutedbenzene derivatives,966, 967 o- and m-cresol in the p - i ~ o r n e r , ~ ~ ~ cis- andtn;cns-decahydronaphthalene~,~~~ epoxy-compounds,970 hydroperoxides andperoxides,971 guanidines and related and pharmaceuticalproducts .973The frequencies of C-H bonds in a wide range of sulphur- and oxygen-containing compounds have been studied.974 By grinding minerals finely,mixing the particles to a paste with isopropanol, and applying this paste as athin film to a rock-salt window, it has been found possible to determine theabsorption spectra of the minerals, and thus to identify them.975 A powdertechnique may also be applied to organic substances which are insoluble incommon solvents,976 and the method is capable of being applied quantitatively,947 W.Siebert, 2. Elektrochem., 1950,54,512.949 E. F. Daly, Nature, 1950, 166, 1072.946 Ancslyt. Chern., 1951, 23, 273.948 G. J. Minkoff, Fuel, 1950, 29, 228.950 R. L. Chapman and R. E. Torley, Analyt. Chem., 1950,22,987.951 R. A. Oetjen and L. C. Roess, J . Opt. SOC. Amer., 1951,41, 203.952 K. S. Tetlow, J. McAuslan, K. J. Brimley, mdW. C.Price,J.Sci. Instr., 1951,28,161.953 F. K. Rugg, W. L. Calvert, and J. J. Smith, J . Opt. SOC. Amer., 1951,41, 32.954 N. C. Jamison, T. R. Kohler, and 0. G. Koppius, Analyt. Chem., 1951,23, 551.955 J . Sci. Instr., 1951,28,103.g 5 6 A. E. Martin, J . 0pt.Soc. Amer., 1951,41,56.g5' R. B. Holden, W. J. Taylor, and H. L. Johnston, ibid., 1950,40, 757.0 5 * L. Brown and P. Holliday, J . Sci. Instr., 1951, 28, 27.959 S. Anderson, W. J. Anderson, and M. Krakowski, Rev. Sci. Instr., 1950, 21, 574.g60 J. S. Ard and T. D. Fontaine, Analyt. Chem., 1951, 23, 133.962 A. Evans, R. R. Hibbard, and A. S. Powell, ibid., 1951, 23, 1604.963 0. D. Shreve, 111. R. Heether, H. B. Knight, and D. Swern, ibid., 1950, 22, 1498.g64 Idem, ibid., p. 1261. 965 S. Pinchas, ibid., 1951, 23, 201.966 C. W. Young, R. D. DuVall, and N. Wright, ibid., p. 709.9 6 7 L. N. Ferguson and A. J. Levant, ibid., p. 1510.968 0. E. Knapp, H. S. Moe, and R. B. Bernstein, ibid., 1950, 22, 1408.969 J. Seidman, ibid., 1951, 23, 559.970 0.D. Shreve, M. R. Heether, H. B. Knight, and D. Swern, ibid., p. 277.971 Idem, ibid., p. 282.9 7 2 E. Lieber, D. R. Levering, and L. J. Patterson, ibid., p. 1594.973 T. V. Parke, A. M. Ribley, E. E. Kennedy, and W. W. Hilty, ibid., p. 953.974 A. Pozefsky and N. D. Coggeshall, ibid., p. 1611.975 J. M. Hunt, M. P. Wisherd, and L. C. Bonham, ibid., 1950, 22, 1478.076 G. Pirlot, Bull. SOC. chirn. Be&., 1950, 59, 327.J. D. Stroupe, ibid., 1950, 22, 1125WILSON : INSTRUMENTAL METHODS. 349even in cases where Beer’s law does not apply, or where mixtures with over-lapping absorption bands are being examined.Mass-spectrum Analysis.-The mass spectrograph has been applied to thequalitative analysis of hydrocarbon mixt~res,~7~ and the isotope contributionsof hydrocarbons are tabulated, mass-spectrum peaks of almost 300 compoundsbeing roughly classified by magnitude.Methods have been published forthe analysis of low concentrations of vapours in air,978 and the determinationof small traces of paraffins in their monodeuterated derivatives.979 R. E.Honig 980 describes a procedure using preferential ionisation of certainion species to enable determinations of traces to be carried out, even wherethe impurity pattern is normally masked by that of the main constituent.Chemical Microscopy.-L. Kofler 981 discusses microscopical methods inmicrochemistry, dealing specially with the characteristics of crystals whichmay readily be determined as an aid in the identification of crystallinematerial.Apparatus for heating materials under the microscope has beend e s ~ r i b e d .9 8 ~ ~ ~ ~ Applications have been reported of apparatus of this kindto the fusion analysis of sterols,985 the identification and separation of plantproducts 986 and pharmaceutical ~ o m p o u n d s , ~ ~ ~ ~ 988 the determination ofthe melting points of crystals which melt with decompo~ition,~~~ the studyof salt hydrates,990 the obtaining of melting-point diagrams for binarythe determination of critical mixing temperatures 992 by methodssimilar to, or derived from, those described by L. Kofler and A. K ~ f l e r . ~ ~ Cold stages for the ordinary microscope994~995 and for use in conjunctionwith a metallurgical polarising microscope 996 have also been described.Optical crystallographic data have been reported for a series of aliphaticdicarboxylic and for nitrog~anidine,~~~ xanthoto~in,~g~ tetrazole,lmS77 S.M. Rock, AnaZyt. Chem,, 1951, 23,261.s78 G. P. Happ, D. W. Stewart, and H. F. Brockmyre, ibid., 1950, 22, 1224.97s D. P. Stevenson and C. D. Wagner, J. Amer. Chem. SOC., 1950, 72, 5612.s80 Analyt. Chem., 1950, 22, 1474.982 H. Hilbck, ibid., p. 307.983 D. G. Grabar and W. C. McCrone, J. Chem. Educ., 1950, 27, 649.s84 E. F. Westnun and L. Eyring, J. Amer. Chem. SOC., 1951, 73, 3399.s86 V. Gilpin, AnaZyt. Chem., 1951, 23, 365.986 D. Markovib, Mikrochem., 1951, 36/37, 1158.ss* M. Brandsttitter and G. Breuer, Arch. Phurm., 1950, 283, 253.Oa9 L. Kofler and H. Sitte, Monatsh., 1950, 81, 619.ssO A.Kofler, Mikrochem., 1951, 36/37, 302.ssl L. Kofler and H. Winkler, Monatsh., 1950, 81, 746.992 R. Fischer, Mikrochem., 1951, 36/37, 296.se3 L. Koffer and A. Kofler, “ Mikromethoden zur Kennzeichnung organischer Stoffess4 W. Kofler, A. Kofler, and L. Kofler, Mikrochem., 2951, 38, 218.s96 R. G. Rhodes, J. Sci. Instr., 1950, 27, 333.s96 J. C. Monier and R. J. Hocart, ibid., p. 302.s s p R. N. Castle, Mikrochem., 1951, 38, 92.OS8 W. C. McCrone, Analyt. Chem., 1951, 23, 205.sss J. Krc, ibid., p. 389.s81 Mikrochem., 1951, 36/37, 283.s87 F. Ludy-Tenger, ibid., p. 882.und Stoffgemische,” Innsbruck, 1948.loo0 W. C. McCrone, D. Grabar, and E. Lieber, ibid., p. 543350 ANALYTICAL CHEMISTRY,sodium metaborate dihydrate,l sodium stannate,2 di-p-tolylseleniumdibromide? chrysene? 1 : 8-dinitrona~hthalene,~ tetrachlorophthalic anhy-dride,6 cis-terpineol hydrate, and cis-terpineol.88.PHYSICAL SEPARATION METHODS.Chromatography.-The progress of chromatographic adsorption analysishas been re~iewed,~ and two important books on the topic have recentlyappeared.103 11 L. Deibner l2 has described methods for the activation ofclays for chromatographic work, and methods for determining the degreeof activation which is required. D. F. Mowery l3 has devised a method ofair-blowing powdered adsorbents so as to give better columns. The use ofpacked papers to form adsorbent columns has been described,14,15 andalumina-impregnated filter-paper has also been recommended.l6¶ 17 L.Rutter l* treats filter-paper with cetyltrimethylammonium bromide solutionto render it suitable for the chromatography of colloidal electrolytes. Talc incombination with powdered glass or Super-Cel l9 and tricalcium phosphate 2ohave been recommended as adsorbents.The specificity of chromatographicadsorbents has been studied.21 The fluorescence of chromatographedpetroleum products and analytical uses of this have been reported.22 H.Brockmann and E. Beyer 23 describe a method for the detection of adsorptionzones by making use of the quenching of the fluorescence of the columnmaterial, which may be alumina treated with a strongly fluorescing materialsuch as 3-hydroxypyrene-5 : 8 : 10-trisulphonic acid. Other fluorescentzone indicators may be used in the same way.24 W.S. Wise 25 has recom-mended the mixing of the sample to be chromatographed with silica gel, thewhole being then packed over a filter-paper disc which lies on top of thecolumn proper. Strip chromatograms may be prepared on glass stripscoated with adsorbent material.26 A self-supporting column, made of a1 J. Krc, Analyt. Chem., 1951, 23, 806.3 G. J. Neuerberg and W. C. McCrone, ibid., p. 1042.J. Krc, ibid., p. 922.(I Idem, ibid., p. 1339.Idem, ibid., p. 1718.10 H. G. Cassidy, “ Technique of Organic Chemistry, Vol. V.matography,” New York, 1951.l1 L. Zechmeister, “ Progress in Chromatography,” New York, 1951.18 Chim. anal., 1951, 53, 18.14 S. Rosebeek, Chem. Weekblad., 1950, 46, 813.W. L. Porter, Analyt. Chem., 1951, 23, 412.l6 S.P. Datta, B. G . Overell, and M. Stack-Dunne, Nature, 1949,164, 673.l7 I. E. Bush, ibid., 1950, 166, 445.I@ R. M. Hanson and C. W. Gould, Analyt. Chem., 1951,23,670.to S . M. Swingle and A. Tiselius, Biochem. J . , 1951, 48, 171.21 A. L. LeRosen, P. H. Monaghan, C. A. Rivet, and E. D. Smith, Analyt. Chem.,2r J. A. Schuldiner, ibid., p. 1676.24 D. W. Criddle and R. L. LeTourneau; Analyt. Chem., 1951,23, 1620.2S Analyst, 1951, 76, 316.s6 J. G. Kirchner, J. M. Miller, and G . J. Keller, Analyt. Chem., 1951, 23, 420.Idem, ibid., p. 675.W. C. McCrone, ibid., p. 1188.Idem, ibid., p. 1523.@ H. H. Strain, ibid., p. 25.Adsorption and Chro-l3 J . Amer. Chem. Soc., 1951, 73, 5047.la Ibid., p. 273.1951, 23, 730.2s Angew.Chem., 1951,63, 133WILSON : PHYSICAL SEPARATION METHODS. 351suitable adsorbent mixed with plaster of Paris, which renders detection andseparation of fractions much easier than if a glass envelope is used, has beendescribed by J. M. Miller and J. G. I i i r ~ h n e r . ~ ~ A sectioned tube,28 andautomatic apparatus for collecting fractions of equal volume 29-31 aremethods used to simplify separation of components of mixtures.Chromatography has been applied to the qualitative and quantitativedetermination of radioactive materials.32 Radioactive phosphorus hasbeen detected on a column by means of a Geiger-Muller Othermethods recommended for following separations on columns or in the collectedfractions are refractive-index measurements on the effluent ,34 and observationof infra-red, visible, or ultra-violet absorption or refle~tion.~~ R.H. Miillerand D. L. Clegg 36 describe a photometric method for recording automaticallythe results of paper chromatography.The chromato-graphy of small volumes of gas, carried in a hydrogen stream through asilica or carbon column, and analysed on emergence by thermal conductivity,has been described by E. Cremer and R. Muller.38 The separation of inorganiccations by conversion into organo-metallic complexes with sodium diethyl-dithiocarbamate, and chromatography of the complexes on an aluminacolumn, has been achieved by A. K. Al-Mahdi and C. L. Wils0n.~9 Afterseparation, the individual ions may be estimated colorimetrically bystandard procedures.Chromatographic procedures have been described for hydrocarbons intar, by a column heated to 500°,40 liquid hydrocarbon mixtures, by dis-placement analysis on a silica gel column,41 volatile fatty acids$2 methylester fractions from mineral oils in oil emulsions,44 aldehydes andketones after formatione of the 2 : 4-dinitrophenylhydrazone~~ andalcohols after conversion into the 3 : 5-dinitrobenzoates.*5 E.D. Smith andA. L. LeRosen46 have carried out a comprehensive investigation of theeffect of a variety of factors such as side-chain length and nature of adsorbentGases may be chromatographed on activated ~harcoal.~'27 Analyt. Chem., 1951, 23, 428.a8 H. Gault and C. Ronez, Bull. Xoc. chim., 1950, 17, 597.49 J. 0. Harris, Chem. and Ind., 1951,255.30 A.T. James, A. J. P. Martin, and S. S. Randall, Biochem. J., 1951,49,293.31 D. F. Durso, E. D. Schall, and R. L. Whistler, Ana.Zyt. Chem., 1951, 23, 425.32 R. Lindner, 2. Elektrochem., 1950, 54, 421.33 J. C. Boursnell, Nature, 1950, 165, 399.34 C. D. Hurd, G. R. Thomas, and A. A. Frost, J . Amer. Chem. SOC., 1950,72, 3733.36 Z. J. Harvalik, Analyt. Ghem., 1950, 22, 1149.36 Ann. N . Y . Acad. Sci., 1951, 53, 1108.37 C. G. B. Hammar, Svensk Kem. Tidskr., 1951, 63, 125.38 Mikrochem., 1951, 36/37, 533. 39 Ibid., p. 218.40 M.Vahrman,Nature, 1950,165,404. 41 S.G.Blohm,Mikrochem., 1951,36/37,322.d2 L. L. Ramsey and S. M. Hess, J . Assoc. Off. Agric. Chem., 1950,33, 848.43 H. A. Schuette and S. dal Nagore, J . Amer. Oil Chem. SOC., 1951, 28, 229.44 L.Kierstead, J . Assoc. Off. Agric. Chem., 1950, 33, 770.46 R. G. Rice, G. J. KelIer, and J. G. Kirchner, AnaEyt. Chem., 1951, 23, 194.4 8 Ibid., p. 732352 ANALYTICAL CHEMISTRY.on the chromatography of methyl ketones. terpenes,26 51and porphyrins 52 have also been separated chromatographically.Ion Exchange.-Ion exchange separations have been reviewed,53s5 and theanalytical applications of this method of separation have received particularattention.56, 57 T. R. E. Kressman 58 has advocated the use of filter-paperimpregnated with ion-exchange resins, or preparation of the resins themselvesas membranes.Ion-exchange separations have been applied to the determination of freea~idity,~g phosphate in foods after ashing, 6o arsenic in insecticides, 61 andpotassium,62, 63 to the separation of the l a n t h a n o n ~ , ~ ~ ~ 7 the isolation ofcobalt,68,69 the separation of titanium from iron,70 of iron from aluminium,71of zirconium and niobium oxalate complexes,72 and of zirconium and haf-n i ~ m . ~ ~ It is reported 74 that in the separation of zirconium, hafnium,niobium, and tantalum as chloro-complexes, good separations of hafniumfrom tantalum and of zirconium from niobium are possible.Ion exchange,in its simplest form, has been used for the separation of bromide and iodideon a lead chloride column.75In the organic field, separations by ion-exchange resins have been appliedto amino-acids,76 the purification of reducing sugars,77 monosaccharides as47 D. F. Mowery, J .Amer. Chem. SOC., 1951, 73, 5049.d8 M. L. Wolfrom and W. L. Shilling, ibid., p. 3557.49 I. Vavruch, Listy Cukr., 1949-50, 66, 249 ; Sugar Ind. Abstr., 1950, 12, 228.50 R. T. Holman, J . Amer. Chem. Soc., 1951,73, 1261, 3337,5289.61 R. T. Holman and W. T. Williams, ibid., p. 5285.52 R. E. H. Nicholas, Biochem. J . , 1951, 48, 309.63 E. R. Tompkins, Analyt. Chem., 1950,22,1352.5 5 R. Kunin and R. J. Myers, “ Ion Exchange Resins,” New York, 1950.56 J. Schubert, Analyt. Chem., 1950, 22, 1359.5 7 R. Wickbold, 2. anal. Chem., 1951, 132, 241.50 L. M. Orlova, J . Anal. Chem. U.S.S.R., 1950,5, 370.60 S. Kubo and C. Tsutsumi, Bull. Chem. SOC., Japan, 1950, 23, 187.61 J. T. Odencrantz and W. Rieman, Analyt. Chem., 1950, 22, 1066.6% G. Gabrielson and 0.Samuelson, Svensk Kem. Tidskr., 1950,62, 221.63 J. A. Dean, Analyt. Chem., 1951, 23, 202.64 F. H. Spedding, E. J. Fulmer, J. E. Powell, T. A. Butler, and I. S. Yaffe, J . Amer.6 6 E. H. Huffman and R. L. Oswalt, ibid., 1950, 72, 3323.66 F. H. Spedding and J. L. Dye, ibid., p. 5350.67 G. H. Higgins and K. Street, ibid., p. 5321.68 J. A. Dean, Analyt. Chem., 1951, 23, 1096.60 F. T. Fitch and D. S. Russell, ibid., p. 1469.70 Y. Yoshino and M. Kojima, Bull. Chem. SOC., Japan, 1950, 23, 46.7 1 H. Teicher and L. Gordon, Analyt. Chem., 1951,23,930.72 R. E. Wacker and W. H. Baldwin, U.S. Atomic Energy Comm. Rep. ORNL-637,73-B. A. J. Lister, J., 1951, 3123.74 E. H. Huffman, G. M. Iddings, and R. C. Lilly, J . Amer. Chem. SOC., 1951,73,4474.7 6 B.MiliEevi6, Bull. SOC. chim. Belgrade, 1950, 15, 167.76 8. M. Partridge and R. C. Brimley, Biochem. J., 1951,48, 313 ; 49, 153.7 7 K. T. Williams, A. Bevenue, and B. Washauer, J . Assoc. 08. Agric. Chem., 1950,54 R. Kunin,ibid., 1951,23,45.5 8 Nature, 1950, 165, 568.Chem. SOC., 1951, 73, 4840.1950; Nuclear Sci. Abstr., 1950, 4, 469.33, 986WILSON : PHYSICAL SEPARATION METHODS. 353borate complexes,78 adenosine polypho~phates,~~ fruit acids,80 pectins,81alkaloids,82 and yeast component^.^^ It is reported that a highly pure formof the analytical reagent morin can be prepared from natural sources bypurification on a cation-exchange resin.84 Analysis of Nylon-type polymersthrough ion-exchange separations has been described.85Extraction Processes.-A valuable review of solvent extraction and itsapplication to inorganic analysis has been given by H.M. Irving.86 Pointingout that the recent advances in the chemistry of radioactive elements andrelated fields would not have been possible withdut extensive application ofextraction processes, he goes on to discuss the liquid-liquid partition ofinorganic substances of which no comprehensive survey then existed.Dealing with extraction for removal and extraction for fractionation, hediscusses factors which favour solvent extraction, and draws examples bothfrom simple inorganic substances and from organometallic complexes.Stressing the paucity of information in this field, he outlines future usefullines of investigation. Liquid-liquid extraction has also been discussed byC.G0lumbic.~7The practical applications of extraction have been reviewed in theirgeneral aspects,s8s 89 and in respect of the determination of metals.g0, 91 Specialconsideration has been given to the particular case of countercurrente x t r a c t i ~ n . ~ ~ , ~ ~ A method has been described for the measurement of verylarge or very small partition coefficient^.^^ Apparatus for extraction hasbeen de~cribed.~~-lO~78 J. X. Khym and L. P. Zill, J . Amer. Chem. Soc., 1951, 73, 2399.7D W. E. Cohn and C. E. Carter, ibid., 1950,72, 4273.so J. B. Wilson, J . Assoc. Off. Agric. Chem., 1950, 33, 995.81 L. Anyas-Weisz and H. Deuel, Mitt. Lebensmitt.-Untersuch. Hyg., 1951,42, 91.82 A. Jindra and J. Pohorsky, J . Phrm.Pharmacol., 1951,3, 344.Bs R. A. Bolomey and L. Wish, U.S. Atomic Energy Comm. Rep., ORNL-627,1950;84 Q. L. Morris, T. B. Gage, and S. H. Wender, J . Arner. Chem. Soc., 1951, 73, 3340.8s J. Haslam and M. Clasper, Analyst, 1951,76,33. 8 6 Quart. Reviews, 1951, V , 200.88 L. C. Craig, ibid., p. 41.89 G. H. Morrison, ibid., 1950, 22, 1388.O0 E. Abrahamczik, Mikrochem., 1951, 36/37, 104.91 T.S.West,Metallurgia, 1951,43,41. 92 R.Rometsch,HeEv. Chirn.Acta, 1950,33,184.93 C. Golumbic, Amer. Chem. Soc., 1950,118th Meeting Abstr., 71-Q; U.S. Bur. Min.,1950, Sypth. Liq. Fuels Abstr., 3, No. 6, 44.OP C. Golumbic and S . Weller, Analyt. Chem., 1950, 22, 1418.O 5 B. J. Herian and L. A. Moignard, Chem. and Ind., 1951, 358.g6 R.GBrard,Chim.analyt., 1950,32,155.O 8 J.H. Cannon, J . Assoc. Off. Agric. Chem., 1950, 33, 934.F. Dobson and S. S . Randall, Bwchem. J., 1951,49, 399.Nucliar Sci. Abstr., 1950, 4, 469.Analyt. Chem., 1951, 23, 1210.g 7 A.W.Hemmings, Analyst, 1951,76,117.loo M. Beroza, Analyt. Chem., 1951, 23, 1055.lol G. H. Lathe and C. R. J. Ruthven, Biochem. J., 1951,48, Proc. lix.lo2 M. W. Kies and P. L. Davis, Fed. Proc., 1950, 9, 189.lo3 H. L. Lochte and H. W. H. Meyer, Analyt. Chem., 1950,22, 1064.lo4 J. M. Connolly and G. Oldham, Analyst, 1951, 76, 495.lo5 L. C. Craig, W. Hausmann, E. H. Ahrens, and E. J. Harfenist, Analyt. Chem.,1951, 23, 1236.REP.-VOL. XLVIIC. 354 ANALYTICAL CHEMISTRY.Extraction processes have been applied to 5 : 7-dichloro-8-hydroxy-quinoline derivatives of lanthanons,lo6 to the extraction of available man-ganese in soils by ammonium acetate and ammonium acetate-quinol,l07 andto the extraction of chromium as perchromate by ethyl acetate.108Partition Chromatography.-The theory of counter-current liquid-liquidseparation as it takes place in partition chromatography has been theoretic-ally considered by several authors, and has enabled comparisons to be madebetween theoretical deductjons and practical finding^.^^^-^^^ The analyticalspecificity of the method has been considered.l12 A particular study hasbeen made of paper chromatography, to investigate the influence of capillarityand geometric factors.l13 Liquid-gas partition chromatography, with useof a moving nitrogen phase and a stationary liquid phase, has been examinedby A.T. James and A. J. P. Martin.l14 Reversed phase work, on a chlorinatedrubber supporting medium 115 or on a Pyrex-glass powder medium,l16 hasbeen investigated. A conductivity method of registering changes in theaqueous phase 30 and apparatus and methods for filter-paper chromatographyhave been described. 117-120 H. Weil 121 has discussed industrial applicationsof the technique.Partition chromatography has been applied to the analysis of glyceroland related compounds,122 aliphatic semicarbazones, 123 acids and theirlo6 T. Moeller and D. E. Jackson, Analyt. Chm., 1950, 22, 1393.l o 7 G. Gattorta, Ann. Sper. agr., 1950, 4, 789.lo8 R. K. Brookshier and H. Freund, Analyt. Chem., 1951,23, 1110.loo L. C. Craig, ibid., 1950, 22, 1346.110 R.Allouf and M. Macheboeuf, Compt. rend., 1951,232,2440.111 M. W. Kies and P. L. Davis, J . Biol. Chem., 1951, 189, 637.11* G. D. Gregory and L. C. Craig, Ann. N . Y . Acad. Sci., 1951, 53, 1015.118 R. H. Muller and D. L. Clegg, Analyt. Chem., 1951, 23, 396.11* Biochem. J., 1951, 48, Proc. vii.115 S. M. Partridge and T. Swain, Nature, 1950, 166, 272.116 M. W. Partridge and J. Chilton, ibid., 1951, 167, 79.1 1 7 E. Kawerau, Biochem. J., 1951,48, 281.118 A. J. Singer and L. Kenner, Analyt. Chem., 1951, 23, 387.ll9 G. Toennies and J. J. Kolb, ibid., p. 823.120 L. B. Rockland, J. L. Blatt, and M. S. Dunn, ibid., p. 1142.121 Chim. et Id., 1950, 64, 432.122 A. C. Neish, Canadian J . Res., 1950,28, B, 535.123 G.Di Modica and C. Spriano, -Ann. Chim., Roma, 1951, 41, 64.124 L. M. Marshall and F. D. Drew, Fed. Proc., 1950, 9, 199.126 L. A. Liberman, A. Zaffaroni, and E. Stotz, J . Amer. Chem. SOC., 1951,126 K. T. Zilch and H. J. Dutton, Analyt. Chem., 1951,23, 775.127 J. B. Stark, A. E. Goodban, and H. S. Owens, ibid., p. 413.128 H. J. Nijkamp, Analyt. Chim. Acta, 1951, 5, 325.1 Z 9 L. L. Ramsey, J . Assoc. Ofl. Agric. Chem., 1950, 33, 1010.13O D. N. Gore, Chem. and Ind., 1951, 479.1 3 1 V. 8. Govindarajan and M. Sreenivasaya, CUTT. Sci., 1950,19,43, 269.133 M. Renard, Bull. SOC. chim. Belg., 1950, 59, 34.133 R. J. Zahner and W. B. Swann, Analyt. Chem., 1951, 23, 1093.lS4 R. L. Hossfeld, J . Amer. Chem. Soc., 1951, 73, 852.73, 1387WILSON : PHYSICAL SEPARATION METHODS.355deri~atives,l~Pl~~ 134 amino-acids and related c o m p o ~ n d s , ~ ~ ~ sugars and related c o m p o ~ n d s , ~ ~ ~ - ~ ~ ~ miscellaneous nitrogenous bases,175-1s0136 R. J. Block, Analyt. Chem., 1950, 22, 1327.136 S. Ishii and T. Ando, Bull. Chem. SGC., Japan, 1950, 23, 172.137 R. A. Boissonnas, Helv. Chim. Acta, 1950, 33, 1966, 1972, 1975.138 L. Fowden and J. R. Penney, Nature, 1950,165, 846.C. G. HedBn, ibid., 166, 999.140 L. Novellie, ibid., p. 1000.141 C. E. Dalgliesh, ibid., p. 1076.142 T. Wieland, 2. Elelctrochem., 1950, 54, 412.143 A. J. Landua, R. Fuerst, and J. Awapara, Analyt. Chem., 1951, 23, 162.144 E. F. McFarren, ibid., p. 168.145 A. R. Patton and P. Chism, ibid., p. 1683.1413 T. Wieland and L.Wirth, Angew. Chem., 1951, 63, 171.147 S. Blackburn and A. G. Lowther, Biochem. J., 1951, 48, 126.148 L. Fowden, ibid., p. 327.148 A. E. Bender, ibid., Proc. xv.lSo S. Blackburn, Chem. andInd., 1951,294.161 J. E. DeVay, Wen-Hua Chang, and R. L. Hossfeld, J . Amer. Chem. SOC., 1951,lS2 F. Lionetti, J . Chem. Educ., 1951, 28, 152.lS3 H. Brockmann and H. MUSSO, Naturwiss., 1951, 38, 11.154 A. Polson, P. J. Van Rooy, and E. J. Marrais, Onderstepoort J . Vet. Res., 1951,lS5 P. Shu, Canadian J . Res., 1950,28, B, 527.lS6 J. E. Stone and M. J. Blundell, ibid., p. 676.lS7 L. Hough, J. K. N. Jones, and W. H. Wadman, J., 1950, 1702.lS8 J. G. Buchanan, C. A. Dekker, and A. G. Long, ibid., p. 3162.lse I. Vavruch, Listy Cukr., 1949-50,66, 299; Sugar Ind.Abstr., 1950,12, 244.160 R. B. Duff and D. J. Eastwood, Nature, 1950, 165, 848.1131 W. E. Trevelyan, D. P. Procter, and J. S. Harrison, ibid., 166, 444.lB2 R. A. Laidlaw and S. G. Reid, ibid., p. 476.163 L. Boggs, L. S. Cuendet, I. Ehrenthal, R. Koch, and F. Smith, ibid., p. 520.113~ L. Novellie, ibid., p. 745.1~ E. F. McFarren and H. R. Rutkowski, Amer. Chem. Soc. 119th Meeting, 1951,lB6 H. C. S. de Whalley, N. Albon, and D. Gross, Analyst, 1951, 76, 287.167 A. Jeanes, C. S. Wise, andR. J. Dimler, Amlyt. Chem., 1951,23, 415.ld8 E. F. MacFarren, K. Brand, and H. R. Rutkowski, ibid., p. 1146.168 E. F. Annison, A. T. James, and W. J. T. Morgan, Biochem. J . , 1951,170 J. K. Bartlett, L. Hough, and J. K. N. Jones, Chem. and Id., 1951, 76.171 P.S. Rao and R. M. Beri, Curr. Sci., 1951,20, 99.172 C. Gustafsson, J. Sundman, and T. Lindh, Finnish Paper and Timber J., 1951,173 0. Schindler and T. Reichstein, Helv. Chim. Acta, 1951, 34, 108.174 R. Weidenhagen, Zucker, 1951, 4, 275; Sugar Ind. Abstr., 1951, 13, 108.176 R. M. Reguera and J. Asimov, J . Amer. Chem. SOC., 1950,72, 5781.176 M. Lederer, Nature, 1950, 165, 529.177 R. Munier and M. Machebceuf, Compt. rend., 1950, 230, 1177.17* D. J. Lussmann, E. R. Kirch, and G. L. Webster, J . Amer. Pharm. ASSOC., 1951,179 C. F. Huebner, Nature, 1951, 167, 119.180 J. B. Schute, Pharm. Weekblad, 1951, 86, 201.73, 4977.25, 31.Div. of Biol. Chem., Abstr. 41C; Sugar Ind. Abstr., 1951,13, 74.48, 477.B, 33, 1.40, 368356 ANALYTICAL CHEMISTRY.proteins and related c o m p o ~ n d s , ~ ~ ~ - ~ ~ ~ and a variety of miscellaneousproducts, mostly of natural origin.1'34-201This is a convenient place to refer to so-called partition chromatographyof inorganic ions.The nature of this means of separation is not yet clear,but the processes are obviously more complex than those found in theorganic field. Schematic analysis of cations has been proposed, makingextensive use of the techniques.202 Methods for separating alkali metalsand alkaline-earth metals in mixtures have been described by C. C. Millerand R. J. Magee.203 Cation separations have also been described by otherworkers.2°4-210 Determinations of zinc,212 gold,213, 214 and uranium 215 bythis method have been proposed. I n connection with this technique theinvestigation of the solubilities of metal salts in binary solution systems of aninorganic-organic nature, such as alcohol-ammonia, may indicate a profitableline of investigation.216Separation of ions by this method has been used before polarographicdetermination.211Anion separations have been described by Pollard, McOmie, and Elbeih 217lal B. Magasmik, E.Vischer, R. Doniger, D. Elson, and E. Chargaff, J . Biol. Chem.,lS3 R. Markham and J. D. Smith, Biochen;. J., 1951, 49, 401.lS4 U. Hamberg and V. S. von Euler, Acta Chem. Xcand., 1950, 4, 1185.la6 P. B. Baker, F. Dobson, and A. J. P. Martin, Analyst, 1950,75,651.lS6 E. C. Spaeth and D. H. Rosenblatt, Analyt. Chem., 1950, 22, 1321.lS7 J. F. Nyc, J. B. Garst, H.B. Friedgood, and D. M. Maron, Arch. Biochem., 1950,la* P. Simonart and Kwang-Yu Chow, Bull. SOC. chim. Belg., 1950, 59, 417.lag F. Cacioppo and G. La Grutta, Bull. Xoc. ital. Biol. sper., 1950, 26, 1011.lgo V. Kocher, R. Karrer, and H. M. Muller, Int. Rev. Vitamin Res., 1950, 21, 403.lgl A. G. Renfrew and P. C. Platt, J . Amer. Pharm. ASSOC., 1950, 39, 657.lea S. M. Shea, Nature, 1950, 165, 729.lQ4 T. B. Gage, C. D. Douglas, and S. H. Wender, Analyt. Chem., 1951, 23, 1582.lg6 H. A. Nash and A. R. Smashey, Arch. Biochem., 1951,30, 237.le6 R. J. Boscott, Biochem. J., 1951, 48, xlvii.lg7 F. Brown and K. L. Baxter, Chem. and Ind., 1951, 633.lea W. 0. James and N. Kilbey, J . Pharm. Pharmacol., 1951, 3, 22.lQg 0. Th. Schmidt and R. Lademann, Annalen, 1951,571,41.zoo H.Zahn and H. Wolf, Melliand Textilber., 1951, 32, 317.201 J. Sternberg, J. Colas, and T. Kahn, Milcrochem., 1951, 36/37, 942.2oz F. H. Pollard, J. F. W. McOmie, and I. I. M. Elbeih, J . , 1951, 466, 470; F. H.2os Ibid., p. 3183.206 W. R. Walker and M. Lederer, ibid., p. 191.207 A. Lacourt, G. Sommereyns, E. De Geyndt, and 0. Jacquet, Milcrochem., 1951,A. Lacourt, G. Sommereyns, and G. Wantier, Compt. rend., 1951, 232, 2426.1950, 186, 37. 18z J. I. M. Jones and S. E. Michael, Nature, 1950, 165, 685.29, 219.lg3 J. S. Harrison, Analyst, 1951, 76, 77.Pollard, J. F. W. McOmie, and H. M. Stevens, ibid., pp. 771, 1863.204 M. Lederer, Analyt. Chim. Acta, 1951, 5, 185.SO6 E. C. Martin, ibid., p. 511.36/37, 117. 2os A.Lacourt, G. Sommereyns, and E. De Geyndt, ibid., p. 312.210 C. Romano, Boll. SOC. ital. Biol. 5per., 1950, 26, 604.zll J. A. Lewis and J. M. Griffiths, Analy.st, 1951, 76, 388.z12 J. R. Bishop and H. Liebmann, Nature, 1951, 167, 524.p13 J. R. A. Anderson and M. Lederer, Analyt. Chim. Acta, 1951, 5, 321.z14 N. F. Kember and R. A. Wells, Analyst, 1951, 76, 579.216 F. H. Burstall and R. A. Wells, ibid., p. 396.$17 F. H. Pollard, J. F. W. McOmie, and I. J. M. Elbeih, J., 1951,470.H. Barber and D. Ali, Mikrochem., 1951,38, 194WILSON : MISCELLANEOUS. 357and by W. S. DeLoach and C. Drinkard.218 The separations of fatty acidsas anions of sodium or ammonium salts which have been described219-223must be considered to be more allied to this technique than to normalchromatographic separation or even to partition chromatography, as prob-ably also is the separation of acids in ethanolic ammonia solution.224 W.A.Reeves and T. B. Crumpler 225 have separated oxine complexes of a numberof metals on paper, and D. E. Laskowski and W. C. McCrone 226 have chro-matographed inorganic solutions of cations on paper impregnated with oxine.It is probable that in these investigations the mechanism is yet another thanthat operating in the separation of simple ions, and may be more allied totrue chromatography of organometallic compounds.Electrophoresis.-Apparatus for electrophoretic separations has beendescribed by a numb& of ~ o r k e r s , ~ ~ ' - ~ ~ l and methods for following the separ-ations by optical means have been discussed.232, 233 Two-dimensional electro-phoresis, that is, electrophoresis on paper, has been considerably devel-oped.234-239 Electrophoresis in a glass-powder column 24* and in agarmedia 241 has also been described.9.MISCELLANEOUS.Radiochemical Analysis.-The application of radioactive isotopes, theanalytical methods that have been developed, and instrumental methods ofmeasurement have been reviewed.242 The isotope-dilution method has beenapplied to biological materials.243 0. Giibeli and W. Kolb 244 discuss thequantitative analysis of radioactive substances by activity measurements, andhave applied the method, by measurement of radon and thoron, to the218 J . Chem. Educ., 1951,28, 461.22* F. Brown and L. P.Hall, Nature, 1950,166, 66.221 E. R. Hiscox and N. J. Berridge, ibid., p. 522.222 F. Brown, ibid., 1951, 167, 441.223 E. P. Kennedy and H. A. Barker, AnaZyt. Chem., 1951,23, 1033.224 A. G. Long, J. R. Quayle, and R. J. Stedman, J., 1951, 2197.a2s Aruzlyt. Chem., 1951, 23, 1576.227 W. Geissen, B. Schuler, and H. F. Schuster, KZin. Wochenschr., 1950, 28, 751.228 A. J. Rutgers, L. Facq, and L. J. van der Minne, Nature, 1950, 166, 100.22n H. Michl, Monatsh., 1951, 82, 23.230 M. Tschapek and R. E. Ruhstaller, KolZoid-Z., 1951, 121, 74.231 R. A. Kekwick, J. W. Lyttleton, E. Brewer, and E. S . Dreblow, Biochern. J . ,233 L. G. Longsworth, AnaZyt. Chem., 1951, 23, 346.234 E. L. Durrum, J . Colloid Sci., 1951, 6, 274.236 E. L. Durrum, J . Amer.Chem. Soc., 1950,72, 2943; 1951,73,4875.237 V. Schwarz, Nature, 1951, 167, 404.238 T. Wieland and L. Wirth, Angew. Chem., 1950, 62, 473.23s H. H. Strain and J. C. Sullivan, Analyt. Chem., 1951, 23, 816.240 H. Haglund and A. Tiselius, Acta Chem. S c a d , 1950,4, 957,241 Q. P. Peniston, H. D. Agar, and J. L. McCarthy, AmZyt. Chem., 1951,23, 994.242 C. L. Gordon, Analyt. Chem., 1951, 23, 81.243 M. Berenbom, H. A. Sober, and J. White, Arch. Biochem., 1950, 29, 369.244 HeZv. Chim. Acta, 1950,,33,~1526, 1534.219 F. Brown, Biochem. J., 1950, 47, 598.Ibid., p. 1579.1951, 49, 253. 232 H. J. Antweiler, Mikrochem., 1951, 36/37, 561.K. Wallenfels and E. von Pechmann, Angew. Chem., 1951,63,44368 ANALYT1UA.L CHEMISTRY.determination of radium and thorium.J. W. Bremner 245 has determineduranium and thorium in rocks by use of a nuclear photographic plate.Radiochemical methods, with tracers, have been used to investigate thecompleteness of recovery of ash components from and for indicatingthe position of inorganic ions in paper chr~matography.~~ A. Langer 248 hasapplied radioactive silver to the determination of the end-point in argento-metric precipitation titration of halides. Bromides have been determinedby an activation-exchange reaction with methyl bromide in acetone.249Astatine has been determined in biological material 250 by co-precipitationwith tellurium, deposition on silver foil, and counting. Beryllium may bedetermined by its (7, n) phot~disintegration.~~~ Estimation of radioactivezinc is preceded by extraction by d i t h i ~ o n e .~ ~ ~ Oxalate has been foundmore satisfactory than carbonate for the precipitation 'of calcium for radio-active assay.253 Tantalum has been estimated 254 by neutron-activationanalysis.R. W. Dunn 255 has described electrochemical deposition methods for therecovery and estimation of the radio-isotopes of copper, silver, zinc, mercury,iron, and cobalt. Radio-tracer methods have been applied to the estimationof purines in nucleic acid analysis,256 the measurement of adsorption ofdissolved substances on liquid and the measurement of adsorptionon paper and glass surfaces.258The materials suitable for working surfaces in radiochemical laboratorieshave been critically d i s c ~ s s e d . ~ ~ ~ ~ 260 A storage cabinet,261 handling appara-tus,262-265 a pipetting device,266 a pipette,267 filtering apparatus,268 and avacuum evaporator 269 for use in conjunction with radioactive materialshave been described.Gas Analysis.-Apparatus and methods for gas analysis have been245 Proc.Phys. SOC., 1951, 64, A , 25.247 W. J. Frierson and J. W. Jones, ibid., p. 1447.248 Ibid., 1950, 22, 1288.360 W. M. Garrison, J. D. Gile, R. D. Maxwell, and J. G. Hamilton, AnaZyt. Chem.,251 A. M. Gaudinand J. H. Pannell, ibid., p. 1261.863 T. E. Banks, R. L. F. Tupper, and A. Wormall, Biochem. J., 1950,47,466.26s R. L. Shirley, R. D. Owens, and G. K. Davis, AnaZyt. Chem., 1950,22, 1003.264 J. V. P. Long, Analyst, 1951,76, 644.266 R. Abrams, Arch. Biochem., 1951, 30, 44.a57 G.Aniansson and 0. Lamm, Nature, 1950, 165, 357.w* T. Schonfeld and E. Broda, Mikrochem., 1951, 36/37, 537.259 P. C. Tompkins and 0. M. Bizzell, Ind. Eng. Chem., 1950, 42, 1469.S8O C. D. Watson, ibid., p. 1475.261 0. Kantorowicz, J . Sci. Instr., 1951, 28, 189.a63 Idem, ibid., p. 220.w4 J. W. Mitchell and P. J. Linder, Bot. Guz., 1950, 112, 126.265 A. B. Ritchie and W. T. Spragg, J . Sci. Instr., 1951, 28, 214.266 R. Beul e d J. Harkness, Nature, 1950,166, 403.367 A. J. Swallow, ibid., 1950,165, 249.266 J. J. Pinajian and J. M. Cross, AnaZyt. Chem., 1951, 23, 1056.26O C. W. Sherwin, Rev. Sci. Instr., 1951, 22, 339.L. 0. Morgan and S. E. Turner, AnaZyt. Chem., 1951,23, 978.a40 F. P. W. Winteringham, AnaZyst, 1950, 75, 627.1951, 23, 204.865 J .Lab. Clin. Med., 1951,37, 644.26s J. E. Sherwood, Rev. Sci. Instr., 1950, 21, 570WILSON : MISCELLANEOUS. 359reviewed.270 Apparatus has been described by H. H. Maliss~t,2~~D. J. LeRoy,273 and L. E. J. Roberts and P. C. D a ~ i d g e . ~ ~ ~K. Kordesch and A. Marko 275 have devised a method for the determin-ation of oxygen by means of a reversible oxygen electrode. Methods havebeen described for the determination of traces of oxygen in metallic bismuth 276and zirconium -277 The determination of superoxide by measuring the volumeof liberated oxygen,278 the analysis of gaseous mixtures of carbon monoxideand carbon dioxide,279 the gas-volumetric determination of nitrite and sulpha-mate by evolved nitrogen,zsO and an absorption system for the analysis ofhydrocarbon mixtures into ethylenic, aromatic, and saturated fractions 281have also been described. Amino-groups have been determined in fibroinby diazotisation and measurement of the evolved nitrogen.282Determination of Moisture.-Methods generally applicable to the deter-mination of moisture have been discussed and classified,283-286 and methodssuitable for application to the determination of moisture in coal 287 andrefrigerator oils 288 have been selected. The composition of the Karl Fischerreagent, and its preparation, standardisation, and use have been describ-ed.289-291 Limitations of the reagent have been discussed.292 A suitably littitration cabinet for use with the reagent has been devised.293 Moisture maybe determined colorimetrically in " dry " farm products such as cereals,2g4or electrically by measuring the permittivity at radio-fiequen~ies.~~~Sedimentation Analysis.-There are a few determinations in which theprecipitate formed has been estimated, not by weighing, but by measurementof the apparent volume after sedimentation by a standard procedure; e.g.,potassium may be precipitated as the cobaltinitrite 296 and iron as the270 L. K. Nash, Analyt. Ghem., 1951, 23, 74.a72 Ibid., p. 217.274 Atomic Energy Res. Establ. Rep. No. AERE-C/R470, 1950; Nuclear Sci.278 E. S. Funston and S. A. Reed, Analyt. Chem., 1951, 23, 190.277 J. K. Stanley, J. von Hoene, and G. Wiener, ibid., p. 377.278 E. Seyb and J. Kleinberg, ibid., p. 115.C. H. Toensing and D. S. McKinney, ibid., 1950, 22, 1524.W. N. Carson, ibid., 1951, 23, 1016.271 Mikrochem., 1951, 38, 268.273 Canadian J . Res., 1950, 28, B, 492.Abstr., 1950, 4, 414. 275 Mikrochem., 1951, 36/37, 420. '281 M. G. A. Vassiliev, Bull. SOC. chim., 1950, 17, 750.282 S. N. Beketovsky, J . Appl. Chem., U.S.S.R., 1950,23,444.283 L. Brissaud, Chim. anal., 1951,33,159. 284 A. H. Ward, J. Inst. Fuel, 1951,24,16.285 C. F. M. Fryd, Food Manuf., 1950,25, 275, 313, 374, 380.286 C. 0. Willits, Analyt. GhRm., 1951, 23, 1058; W. R. Fetzer, ibid., p. 1062; J.Mitchell, ibid., p. 1069; E. R. Weaver, ibid., p. 1076.287 E. G. Barber, J . Inst. Fuel, 1950, 23, 295.288 H. Umstlitter, Erd61 u. Kohle, 1951, 4, 28.290 A. G. Jones, Analyst, 1951, 76, 5.291 J. D. Neuss, M. G. O'Brien, and H. A. Frediani, Analyt. Ghem., 1951, 23, 1332.292 W. Ciusa and E. Moroni, Mikrochern., 1951, 36/37, 273.293 J. B. Whittum, Analyt. Chem., 1951, 23, 209.294 S. T. Dexter, Michigan Agric. Exp. Sta. Quart. Bull., 1948, 30, 422.295 A. T. S. Babb, AnaZyst, 1951, 76, 12.296 S. Campanile, Ann. Sper. agr., 1950, 4, 919.C. Ricciuti and C. 0. Willits, J. Assoc. Off. Agric. Chem., 1950,33, 469360 ANALYTIUAL CHEMISTRY.hydroxide.297 The relation between the volume of such a precipitate, its weight,and the shape and uniformity of the particles is discussed by H. Ch0mse.~9*Miscellaneous Methods.-The quantitative microanalysis of minerals hasbeen discussed by F. H e ~ h t . ~ ~ ~ A bibliographical summary of methods forthe chemical analysis of materials in the metallurgical industries has beenprovided.300 Miscellaneous collections of methods of analysis in the ferrousmetals industries,3°1306 in the analysis of non-ferrous m e t a l ~ , 3 ~ ~ ~ ~ ~ and inelectroplating solutions 313,314 may be mentioned. A colIection of papersdealing with the analytical chemistry of thorium, uranium, and other radio-active elements 315 describes the solution of a wide variety of problemsconnected not only specifically with these elements, but with the whole rangeof analytical chemistry.Education.-Since, as stated on p. 308, analytical chemistry may in someways be regarded as a very young branch of Chemistry, and since there havebeen outstanding changes in the field in the last 25 years, many writers havelatterly been concerned to examine the whole problem of the teaching ofanalytical chemistry as related to these advances. Consequently, some ofthe publications of this nature in the past year are mentioned. Requirementsof, and general problems in the teaching of the subject have been dis-The teaching of instrumental analysis has also been consideredas a separate pr~blem.~ls Important trends in the academic presentationof chemistry have been listed by D. G. Nicholson.31g These include the grow-ing use of semimicro-techniques , the elimination of hydrogen sulphide inqualitative analysis, the application of Kjeldahl techniques dispensing withdistillation, instruction in applied electronics, the introduction of paperchromatography, ion-exchange and radio-tracer techniques, and the extensionof the teaching of instrumental analysis. These, then, are the branches inwhich, it is considered, sufficient advance has recently been made to warranttheir inclusion in teaching courses in analytical chemistry.317CECIL L. WILSON.z97 M. Tagliabue and B. Alessandro, Electroplating, 1951, 4, 49.298 Mikrochem., 1951,36137, 1026.300 M. Jean, Chim. anal., 1950, 32, 133, 162, 179, 213.301 K. Swoboda, Mikrochem., 1951, 36/37, 813.303 J. S. Ponce, Informac. Quim. analit., 1950, 4, 193.303 T. Heczko, Mikrochem., 1951,36137, 825.304 H. F. Beeghly, Alzalyt. Chem., 1951, 23, 228.306 B.Bagshawe, Chem. Age, 1951,64,447. SO6 R.Kraaus,Z.anal. Chem., 1951,133,414.307 J . W. Price, Metallurgia, 1950,42,263. 508 G. Norwitz and I. Norwitz, ibid., p. 405.309 C, Goldberg, Poundry, 1950, 78, No. 9, 234; Met. Abstr., 1950,18, 288.310 C. Golding, Iron Age, 1950,166, No. 3,87. 311 G. Norwitz, Analyst, 1951,!76,314.312 R. S. Young, Analyt. Chim. Acta, 1950, 4, 366.313 L. Silverman, Metal Finish, 1950, 48, No. 5, 59; No. 7, 50.314 K. E. Langford, Electroplating, 1950, 3, 166.s16 " Analytical Chemistry of the Manhattan Project," U.S. Atomic Energy Com-316 R. W. Bremner, J . Chem. Educ., 1951, 28, 391.318 L. G. Bassett, J. H. Harley, and S. E. Wiberley, &id., p. 466.319 Amlyt. Chem., 1951, 23, 815.29s Ibid., p. 1083.mission, edit. C. J. Rodden, New York, 1950.317 L. Lykken, ibid., p. 440

ISSN:0365-6217    

DOI:10.1039/AR9514800308

出版商:RSC    

年代:1951

数据来源: RSC

摘要:

CRYSTALLOGRAPHY.IN the last two reports on progress in crystallography an attempt was madeto cover systematically the main contributions of X-ray analysis during3-4 years in the general fields of inorganic and organic chemistry. Thisyear only very limited space for a report was available, and we planned touse this to give a short general account of compounds of high molecularweight which were omitted from earlier reports and which fall principallywithin the biological field of interest. However, the past year has seen suchimportant developments in one section of this field, that of the study of pro-teins, .that it has seemed better to concentrate on the discussion of proteinstructures only.There is one event in crystallographic research this year that deserves aseparate mention, the determination for the first time of the absolute con-figuration of an optically active compound, sodium rubidium D-tartrate, byBijvoet, Peerdeman, and van Bomme1.l It has often been stated thatX-ray analysis cannot distinguish between optical isomers ; this statementis true for analysis carried out under the usual experimental conditions.Itdepends upon the fact that X-ray reflexions from opposite crystal faces,hkZ and i.Lkl, normally have intensities equal in magnitude though not inphase, whether the crystal is actually centrosymmetrical or not. But it hasalso long been known that this equality may be destroyed in an asymmetricstructure if these are present in the crystaI atoms which have an absorptionedge near the wave-length of the incident X-rays, because these introduce aphase change on scattering which has the same sense for both hkZ and hlclreflections.2 Bijvoet realised that this effect could be exploited to derive theabsolute arrangement in space of the atoms surrounding an anomalouslyscattering atom in an asymmetric s t r ~ c t u r e .~ He and his co-workers selectedfor study sodium rubidium D-tartrate, a salt which is isomorphous withRochelle salt and the sodium ammonium tartrate originally studied byPasteur. They have shown that the intensity changes which occur whenthis salt is examined with zirconium K , X-rays (which have a wave-lengthclose to the rubidium absorption edge) can be correlated with one particularconfiguration in space of the D-tartrate ion, namely that shown on p.136.This configuration is identical with that chosen by Emil Fischer for the usualchemical convention. And it is highly satisfactory that recent calculationson optical rotatory power4 have also reached the same conclusion, thatFischer’s convention corresponds to reality.1 J. M. Bijvoet, A. F. Peerdeman, and A. J. van Bommel, Proc. K . Ned. Akad. Wet.,M. von Laue, Ann. Physik, 1916,50, 33 ; D. Coster, K. S. Knol, and J. A. Prim,J. M. Bijvoet, Proc. K . Ned. Akad. Wet., 1949, 52, 313.J. G. Kirkwood, personal communication.1951, By 54, 3 ; Nature, 1951,168, 271.2. Physik, 1940, 63, 345362 CRYSTALLOGRAPHY.Perhaps not altogether logically, it does add to the confidence with whichwe approach the problem of the structure of the complex molecules that occurin Nature that, at least, we now know which way round in space are arrangedmany of the units from which they are built.D.C . H.Structure of Proteins and Related Compounds.During 1951 a synthesis has been achieved of several hitherto discon-nected lines of work and has borne rich fruit over the entire field. It hadlong been suspected that the great majority of naturally occurring proteinfibres contain polypeptide chains folded to about half the length of a fullyextended chain, and recent X-ray analyses of haemoglobin and myoglobinsuggested the presence of similarly folded proteins in globular proteins.The structure of this so-called a-fold was unknown; it was uncertain, more-over, whether this fold occurred so frequently because it represented thestate of lowest free energy of a bare chain, or whether it was due to inter-action between side-chains; whether the fold could be formed by a singleisolated chain or only by an assembly of chains, or whether perhaps the foldwas imposed upon the chains by the “ templates ” of the synthesising enzymesin the cell.Studies of synthetic polypeptides which form folded chainsapparently-similar in structure to the naturally occurring proteins have nowshown clearly that the a-fold represents the state of lowest free energy ofan isolated -CO-CH,-NH- chain, and have also proved that this fold isheld together by hydrogen bonds between CO and NH groups orientedapproximately parallel to the chain axis.These results had an important influence on current ideas about the natureof the a-fold; its structure, however, was not solved by direct X-ray andspectroscopic analysis of synthetic polypeptides or of natural proteins, butby a purely stereochemical approach due to Pauling and Corey, which maywell be regarded as a climax of Pauling’s work on the nature of the chemicalbond and his early recognition of the importance of resonance in interatomicforces.Accurate studies on the structure of amino-acids and small peptides,which had been pursued in their laboratory a t Pasadena since 1939, ledPauling and Corey to formulate certain stereochemical conditions to whichpolypeptide chains should conform. By rigorous application of these con-ditions Pauling, Corey, and Branson were able to reject all but a very smallnumber of the seemingly endless variety of possible chain configurations asstereochemically unstable, and to select one particular form of helical chain,which they called the a-helix, as a possible structure of the a-fold.WhenBamford, Hanby, and Happey ’s X-ray work on synthetic polypeptidesappeared early in 1951, Pauling and Corey immediately recognised that theX-ray diffraction patterns from two of the folded polypeptides could beexplained on the basis of this helical chain, and they also found suggestivecorrelations with the published X-ray patterns from fibrous proteins andhaemoglobin .The announcement of Pauling, Corey, and Branson’s discovery led thPERUTZ . 363Reporter to predict an X-ray reflexion, hitherto observed in only one proteinfibre, which should appear universally if the a-helix were really present inall fibres of the a-type and in haemoglobin, and this prediction was borneout by experiment.Though this did not by itself prove the correctnessof the helical chain, it excluded all models previously proposed, and inci-dentally led to the discovery that many synthetic polypeptides and proteinfibres give X-ray diffraction patterns at far higher angles than had previouslybeen suspected, sometimes with reflexions extending to spacings of less than1 A. This discovery in turn opened the way to a more rigorous test of pro-posed structures than had been possible before. A synthesis of the newexperimental methods with a comprehensive theoretical treatment of theproblem of X-ray scattering by a helical chain has now led to confirmationof the structure of a-polypeptides proposed by Pauling and Corey.Amongglobular proteins X-ray evidence for the presence of the a-helix was found inhaemoglobin and serum albumin ; spectroscopic evidence which is suggestive,but less definite, was found also in insulin and chymotrypsinogen.The Report includes accounts of further advances in the X-ray study ofhaemoglobin and of an analysis of ribonuclease, a protein of low molecularweight which gives exceptionally good X-ray photographs. p-Keratin andcollagen are also considered, as well as those still larger structures whichform the link between chemistry and cytology, such as muscle fibrils andnucleo-proteins.Structures of amino-acids and small peptides were reviewed in last year’sR e p ~ r t .~ No review of protein structure has appeared in these volumes inrecent years, but reviews published elsewhere have described developmentsup t o the end of 1950,6 so that only the most recent work need be discussedhere.Amino-acids and Small Peptide%-The list of amino-acids and peptidesof known structure now includes glycine,’ DL-alanine,S ~-threonine,gL-h ydrox yproline, lo m-serine, l1 glycylgly cine, l2 cysteinylglycine, l3glycylglycylglycine,l* and NN’-diglycyl-~-cystine.~4 Of this year’s croponly L-hydroxyproline and cysteinylglycine have been published in full.Zussman’s structure of L-hydroxyproline,lo deduced from Fourier pro-jections on two ldutually perpendicular planes, shows the (20,- and OHti Ann.Reports, 1950, 47, 446.D. Crowfoot Hodgkin, Cold Spring Harbor Symp., 1950, 14, 6 5 ; Ann. Rev. Bio-chem., 1948, 17, 115; M. F. Perutz, Research, 1949, 2, 52; R. B. Corey, Ann. Rev.Biochem., 1951, 20, 131.G. Albrecht and R. B. Corey, J . Amer. Chem. SOC., 1939,61, 1087.H. A. Levy and R. B. Corey, ibid., 1941,63,2095.D. P. Shoemaker, J. Donohue, V. Schomaker, and R. B. Corey, ibid., 1950,72,2328.J. Zussman, Acta Cryst., 1951, 4, 72, 493.11 R. E. Shoemaker, J. Barieau, J. Donohue, and Chia-Si Lu, J . Amer. Chem. SOC.,in the press; reported at Int. Congress of Cryst., Stockholm, 1951.l2 E. W. Hughes and W. J. Moore, J . Amer. Chem. Soc., 1949, 71, 2618; A.B. Bis-was, E. W. Hughes, and J. N. Wilson, ibid., in the press; reported at Int. Congress ofCryst., Stockholm, 1951. l3 H. B. Dyer, Acta Cryst., 1951, 4, 42.l4 E. W. Hughes, in the press; reported a t Int. Congress of Cryst., Stockholm, 1951364 CRYSTALLOGRAPHY,groups in trans-positions, in agreement with Neuberger.15 A three-dimensional structure analysis by Donohue and Trueblood is also understoodto be complete. l6 Cysteinylglycine-sodium iodide shows two featureswhich differ from those of glycylglycine and related compounds.13 Thebond between the a-carbon and the peptide nitrogen atom is abnormallyshort (1.33, compared with 1.49 for a single bond), and the atoms immediatelylinked to the peptide bond are not in one plane.It will be interesting tosee whether these anomalies persist on further refinement of the structure.Tspes of Protein Fibre.-Astbury’s extensive X-ray studies of fibrousproteins led him to believe that they fell into three main structural categories,exemplified by p-keratin which contained extended chains, a-keratin whichcontained chains coiled or folded to about half their fully stretched length,and collagen. The principal features of their X-ray patterns are shown inTable 1.One interesting newcomer to Astbury’s group of a-fibres is tropomyosinwhose structure is described by Tsao, Bailey, and Adair as a single cyclicpolypeptide chain resembling ‘‘ a deflated bicycle tube ” and having a mole-cular weight of 53,000. This protein exists in a fibrous and a crystallineform, and the crystals consist of 90% of liquid.Bacterial flagella areanother recent addition.l* The individual flagella are only 150 A thick, butthey nevertheless give remarkably detailed X-ray diffraction patterns whichhave some interesting features in common with those of muscle.TABLE 1.a-Fibres p-Fibres CollagenSpacings of strong- Meridian 5*1-5.4 ; 3.07-3.65 2.85est reflexions (A) 1.47-1*50Equator 9.7-12.5 9.7; 4.5 10-4(in j-keratin) (dry)3300 1_ 3335 Lbands in infra-red Funda- 1640 I 1660 Idichroism 1545 1 152511 1548114830 4825 II 486511(cm.-l! and sign of mentalationation 1:; 4600 4530 4590 1_Principal absorptisnOvertone Combin-(1 strong absorption parallel to fibre axis.L 39 ,, normal ,, ,,Synthetic Polypeptides. X-Ray Patterns and Ma-red AbsorptionSpectra.-The polypeptide-chain hypothesis of protein structure is not basedon any single piece of conclusive evidence, but rather on an extensive edificeof consistent observations ; this edifice has been greatly strengthened by therecent studies of synthetic polypeptides.Darmon and Sutherland l9 werel6 A. Neuberger, Adv. Protein Chem., 1948, 4, 297.l7 T.-C. Tsao, K. Bailey, and G. S . Adair, Biochem. J., 1951,49, 27.l8 W. T. Astburg and C . Weibull, Nature, 1949, 163, 280; C. Weibull, ibid., 1950,l9 S. E. Darmon and G. B. B. M. Sutherland, J.-Amer. Chem. SOC., 1947,69, 2074.J. Donohue and K. N. Trueblood, J . Amer. Chem. SOC., in the press.165, 482PERUTZ . 365the first to show the similarity between the infra-red absorption spectraof a polypeptide and those of natural keratin in the 3- and the 6-p region.The first report of a polypeptide giving an X-ray pattern of the a-type camefrom Brown, Coleman, and Farthing.20 Since then an important study ofthe infra-red absorption spectra of synthetic polypeptides and natural pro-teins has been carried out by Ambrose and Elliott.21 The polymers wereprepared by Bamford, Hanby, and Happey 22 who also recorded their X-raydiffraction patterns.Poly(methy1 and benzyl L-glutamate) can be prepared in two distinctstructural forms : films cast from m-cresol or chloroform give X-ray patternsand infra-red spectra similar to those of natural proteins of the a-type suchas hair or myosin; films cast from formic acid, which disrupts hydrogenbonds, show similarities with Nylon and natural silk in which the chains areknown to be fully extended.Of five prominent infi.a-red absorption fie-quencies, one can be assigned to NH stretching, one to NH deformation, oneto CO stretching, and, in the overtone region, one to an NH and one to a COcombination mode. Three of the bands show large frequency shifts betweenthe a- and the @-forms and can thus serve to identify the type of chain con-figuration in a polypeptide or protein, even if no oriented preparation isavailable. Unlike the bands in the fundamental region, the combinationbands in the overtone region are not obscured by water and can serve toidentify the chain configuration of proteins in aqueous solution or in wetcrystals. With their help, the unfolding of chains during.protein denatur-ation can for instance be followed.The NH stretching frequency at 3300 cm.-l is characteristic for hydrogen-bonded NH groups ; no absorption is observed a t the frequency characteristicfor free NH groups. It is particularly interesting that the NH stretchingfrequency remains unchanged when poly( benzyl glutamate) is dissolved inchloroform a t a concentration of less than 0.05%, where it can be shown thatthe molecules are isolated from each other. The spectrum of such a solution,moreover, is of the a-type. This means that each NH must be bonded to aCO within the same chain and rules out models of the type proposed byAstbury and Bell,23 where only one-third of the hydrogen bonds are made.The existence of an a-fold in such dilute solution also shows that it representsthe state of minimum free energy of the isolated chain itself and is quite inde-pendent of interaction between chains.Even polyglycine, when dispersedin dilute solution in polystyrene, forms chains of the a-type, thus provingthat the fold is a property of the main -CO-CH2-NH- chain, rather than beingformed as a consequence of the attractions between side-chains. The lattermerely seem to favour the formation of the a-fold by making it more difficultA summary of the results is given in Table 1.ao Quoted by W. T. Astbury, C. E. Dalgliesh, S. E. Darmon and G. B. B. M. Suther-land, Nature, 1948, 162, 596.p1 E. J.Ambrose and A. Elliott, Proc. Roy. Soc., 1951, A , 205, 47.; 206, 192, 206;208, 76; E. J. Ambrose, A. Elliott, and R. B. Temple, ibid., 1949,199, 183.2* C. H. B d o r d , W. E. Hanby, and F. Happey, ibid., 1951,205,30.28 W. T. Astbury and F. 0. Bell, Nature, 1941,147, 696366 CRYSTALLOGRAPHY.for the main chains to approach each other, thus preventing cross-linkagebetween CO and NH groups of different main chains.Further important results were obtained by the examination of thin filmsof oriented polypeptides in polarised infra-red light; by this method thedirection of the transition moment of a chemical bond can be found and itsapproximate orientation with respect to the fibre axis determined. For eachabsorption band, the relation between the direction of maximum absorptionand the orientation of the bond is checked empirically by examination ofsubstances of known structure such as diketopiperazine or Nylon.By thismethod Ambrose and Elliott found the NH and CO bonds in proteins of the@-type to be normal to the fibre axis, in accordance with the generallyaccepted picture of cross-linkage between neighbouring chains ; in the a-typethis orientation was reversed, the bonds now being approximately parallelto the fibre axis (see Table 1). However, in the best oriented a-polypeptidesthe dichroic ratio of the NH stretching frequency at 3300 cm.-l is 14 : 1 whilethat of the CO stretching frequency a t 1660 cm.-l is only 2.6 : 1. If inter-preted literally, this would imply that the NH bond is oriented very nearlyparallel to the chain axis, while the CO bond should make an angle of at least36" with that axis.24 This great difference is not borne out by the geometryof a-helix described below, with which the infra-red data are otherwise inaccord.Ambrose and Elliott's results can be applied to distinguish a- from P-proteins and to find the orientation of the polypeptide chains in either.Thushair and porcupine quill were found to contain substantial fractions of poorlyoriented protein of the P-type, and feather keratin a fraction of disorienteda-protein. Pure a-spectra were found only among homogeneous proteinssuch as haemoglobin, insulin, or chymotrypsinogen. As would be expectedfrom its X-ray diffraction pattern, collagen gives an infra-red absorptionspectrum which is different from that of either a- or @-fibres, though itresembles the latter as far as the orientation of the hydrogen bonds normal tothe chain axis is concerned (Table 1).It is interesting that Astbury's divisionof proteins into three structural types according to their X-ray patterns hasnow found a corollary in the three corresponding types of absorption fre-quencies and dichroic properties discovered by Ambrose and Elliott.Structure of the a-Chain.-The work on synthetic polypeptides had animportant influence on our conceptions of the a-fold. At the beginning of1951, before most of this work had been published in detail, three main typesof model were under consideration. The simplest was the ribbon-like 2,or aII chain originally proposed by Zahn and since favoured by severalauthors, in which the CO group of each residue is hydrogen-bonded to theNH group of a neighbouring residue, forming a succession of seven-memberedrings.21922925 This model was favoured by Ambrose and Elliott, because itappeared to fit their spectroscopic results and also by Bamford, Hanby, and24 I.F. Trotter, personal communication.26 H. Zahn, 8. Naturfwsch., 1947, 26, 104; S. Mizushima, T. Simanouti, M. Tsuboi,T. Sugita, andE. Kato, Nature, 1949, 164, 918PERUTZ. 367Happey, even though it would not fit their X-ray photographs of a-poly-peptides (they attributed unexplained reflexions to the presence of a secondphase 22). Next was the model of Astbury and Bell 23 in which only everythird CO group is hydrogen-bonded, forming a thirteen-membered ring withan NH group three residues further along the chain; this was effectivelyruled out by Ambrose and Elliott's results on polypeptides.Zahn's andAstbury's models both have twofold screw axes, and all the atoms of the mainchain are more or less confined to one plane. A fundamentally differenttype of chain is a helix in which successive turns are held together by hydrogenbonds. The first such model was constructed by Taylor 26 and Huggins:'and several other helices were later discovered by Bragg, Kendrew, andPerutz 28 who published a comprehensive review of all possible models witha crystallographic repeat of about 5 8, as seemed to be demanded by theX-ray data.On the evidence available to them at the time, however, theywere unable to select any one of these models as stereochemically the mostattractive or in the best accord with experiment.Pauling, Corey, and Branson29 approached the same problem from adifferent point of view, disregarding X-ray data from proteins in the firstinstance and attempting to build the chain with the lowest free energy, anapproach which was vindicated by the properties of the synthetic polypep-tides described in the preceding section. For this purpose they adoptedfour bold and stringent stereochemical conditions which any possible modelwould have to satisfy; these were based in part on X-ray analyses of simplepeptides and related compounds, and in part on intuitive reasoning : (1)all residues must be in equivalent positions ; (2) all amide groups must bestrictly planar, on account of resonance between (I) and (11) ; (3) all hydrogenc\ -+/H(I) ON c\C-N/H \c -O/ ,c-yc (11)bonds must be made ; (4) the vector from the nitrogen atom t o the hydrogen-bonded oxygen atom must not be more than 30" from the direction of theNH bond when the NH-0 distance is 2.72 8.Adoption of the first threecriteria restricted the choice to five possible models. Three of these wereeliminated by the fourth criterion and a fourth model, known as the y-helix,was recently excluded by a further set of stereochemical restrictions postulatedby Pauling and Corey in connection with the p-structure.30Thehelix is made of a succession of planar amide groups hinged on the or-carbonatoms and held together by hydrogen bonds which form thirteen-memberedrings linking the CO group of one residue to the NH group of the third residueThis left one structure, shown in Fig.1 and named the " a-helix ".H. S . Taylor, Proc. Amer. Phil. SOC., 1941, 85, 1.47 M. L. Huggins, Chern. Reviews, 1943,32, 195.88 W. L. Bragg, J. C. Kendrew, and M. F. Perutz, Proc. Roy. SOC., 1950, A , 203, 321.L. Pauling, R. B. Corey, and H. R. Branson, Proc. Amer. Acad. Sci., 1951,57,206.so L. Pauling and R. B. Corey, ibid., p. 729368 CRYSTALLOGRAPHY.along the chain. It is related to the tetragonal " 4,, " helix first built byKendrew (his Fig. 12),28 from which it is derived by a slight tightening of theturns; this makes the peptide groups planar and reduces the number ofresidues per turn from 4 to 3.6 or 3.7.If the a-helix is compared to a spiralstaircase with the residues as steps, then the height of each step is 1.5 A andthe height of each turn 5.4 8, making 3.6 steps per turn. It takes 18 steps orFIG. 1.(a) The a-helix. ( b ) Plan of a-helix.(Reproduced, by permission, from PTOC.Amer. Acad. Sci., 1951, 3'4, 207, 208).five turns until a step is found exactly in a vertical line above the startingpoint. The a-helixthus differs from all structures previously considered in not having a crystallo-graphic repeat of 5 Any one side-chain is surrounded bysix others, branching from a-carbon atoms which are spaced 4, 5, and 6from the a-carbon atom at the centre.The side chains branching from thea-carbon atoms which are closest together protrude in different directions ;only those branching off from a-carbon atoms 5 and 6 apart are actualneighbours. If the helix is sliced open lengthways, unrolled, and spreadHence the true " repeat " pattern is 18 X 1.5 = 27 8.along its axisPERUTZ. 369out on paper, with the residues represented by letters, the arrangement issomewhat as follows :With side-chains of different kinds, this arrangement will form a most intri-cate pattern of chemical forces, and if two such chains combine the patternswould have to interlock in three dimensions. This may be the stereochemicalmeaning of protein specificity.Evidence Relating to the a-Helix.-In a series of three further papers 31Pauling and Corey discuss the experimental evidence in favour of the a-helix,comparing calculated X-ray diffraction effects with published X-ray data forsynthetic polypeptides, fibrous proteins, and haemoglobin.The first papercontains a brilliant re-interpretation of Bamford, Hanby, and Happey 's X-rayphotographs of poly-(y-methyl L-glutamate) .22 By assigning to the methylester a hexagonal unit cell with a = 11-96 and c = 27.5 8, the positions ofall 13 recorded reflexions are accounted for. This unit cell contains onerepeat pattern of the a-helix, consisting of 18 residues in 5 turns, and givesapproximately the right density. The structure is also in agreement withthe rough intensity values of seven equatorial reflexions recorded by Bam-ford et al.A similar attempt to interpret the X-ray pictures of the corre-sponding benzyl ester was handicapped by the fact that Bamford, Hanby,and Happey's list included two equatorial reflexions, since found to bespurious,32 which forced Pauling and Corey to assign to this ester a wrongunit cell.33 Even so, ,the agreement between calculated and observedequatorial reflexions was encouraging.Pauling and Corey's attempts to explain the X-ray pattern of hair andporcupine quil131 are less convincing than their analysis of the syntheticpolypeptides. These fibres are mixtures of different proteins, includingsome of the P-type,21s 34 and their X-ray patterns cannot be fully accountedfor on any single-structure hypothesis. A large part of the relevant paper 31is devoted to a discussion of the sharp and detailed X-ray pattern obtainedby Lotmar and Picken35 from a muscle which had been kept for a year.Pauling and Corey show that an arrangement of a-helices, each of them com-pressed to an elliptical cross-section, gives good agreement of calculated5 1 L.Pauling and R. B. Corey, Proc. Amer. Acud. Sci., 1951, 37, 241, 261, 282.32 M. F. Perutz, 1951, unpublished.33 C. H. Bamford and W. E. Hanby, Nature, 1951, 168, 340.34 (a) F. Happey, Nature, 1950, 166, 397; J. L. Farrant, A. L. F. Rees, and E. H.Mercer, Nature, 1947, 159, 535; (b) M. F. Perutz, ibid., 1951, 168, 653.86 W. Lotmar and L. E. R. Picken, Helw. Chim. Actu, 1942, 25, 538370 CRYSTALLOGRAPHY.and observed intensities of this “ crystalline ” muscle.Bear and Cannan 36have since produced evidence that the Lotmar-Picken pattern is caused, notby protein, but by an unknown substance of small molecular weight whichcrystallises in muscle on prolonged storage.Pauling and Corey’s third paper 31 compares the results of Perutz’s three-dimensional Patterson synthesis of haemoglobin 37 with those to be expectedfor the cc-helix, showing a suggestive correlation with the spacing of subsidiarypeaks along the “ central rod ” of the vector structure and also with theobserved radial distribution function. I n the Reporter’s experience, how-ever, tests of this kind tend to be somewhat insensitive to the precise modelthat is chosen as a basis for comparison, and the same kind of agreementmight possibly have been obtained with one of the other helices.28The cc-helix carried conviction by its intrinsic beauty as a structure andby the agreement with the X-ray data of poly(methy1 L-glutamate).Onthe other hand, the paucity of reflexions from the synthetic polypeptideslisted by Bamford et ul., on which Pauling and Corey had to base their com-parisons, the spurious nature of the Lotmar-Picken pattern (of which theReporter had heard in advance of publication), and the insensitivity of thehaemoglobin data to the precise type of model examined, all suggested theneed for some stringent test which would exclude alternative structures.These considerations led the Reporter to predict that the 3-6-residue helix, ifpresent in all proteins and polypeptides of the or-type, should give rise to areflexion a t 1.5 A spacing from planes perpendicular to the fibre axis, corre-sponding to the axial repeat of residues along the chain.None of the modelspreviously considered would give a reflexion at that spacing. For the re-flexion to appear, the fibre axis would have to be inclined at equal angles of31” to the incident and the diffracted rays, and the Reporter argued that itsgeneral presence might have been overlooked because photographs werenormally taken only with the X-ray beam at right angles to the fibre axis.A reflexion at this spacing had previously been observed by MacArthur inAfrican porcupine quill and noted in support of the a-helix by Paulingand C ~ r e y , ~ l but, in view of the chemical and structural complexity of por-cupine quill, this observation by itself did not seem decisive.The Reporter’s prediction was borne out by experiment .34h 39 I n poly-(y-benzyl L-glutamate), where conditions for its appearance were thought tobe particularly favourable, a powerful reflexion a t 1.50 A spacing was foundon the meridian.A less intense, but clearly defined, reflexion a t the samespacing was found in horse hair, wool, and muscle, and a weaker, less-defined,reflexion in crystalline haemoglobin. When hair was stretched to the (3-form the reflexion disappeared. Since the reflexion was first reported, ithas been found in all fibres of the a-type where investigators have looked forit (Table 2).R. S. Bear and C.M. M. Cannan, Nature, 1951,168,684.I. MacArthur, Nature, 1943,152, 38.M. F. Perutz, ibid., 1951,169,1053; H. E. Huxley and M. F. Perutz, ibid., p. 1054.37 M. F. Perutz, Proc. Roy. SOC., 1949, A , 195, 474PERUTZ . 37 1A fibre can give a strong meridional reflexion at a reciprocal spacing of1/x only if the Fourier transform of the chain molecule itself has a largevalue there and if this region of the transform coincides with a reciprocallattice point. For this to be possible, the chain must have a repeat of patternc = nx, where n is an integer. Thus a fibre with c # 1-5n A cannot give astrong meridional reflexion a t 1.5 A, even if neighbouring chains are dis-placed by 1.5 A or by some other distance along the fibre axis. The appear-ance of the reflexion in all fibres of the a-type therefore excludes models withc # 16n 8, but in theory a t least does not prove the a-helix.I n practice itcan be shown that chains with n # 1 are ruled out by the intensities of theequatorial reflex ion^.^^ There remains the possibility that several chainmodels exist with a repeat of c = 1.5 A. However, attempts a t buildingalternative models show that it is difficult, if not impossible, to constructany stereochemically satisfactory structure with an axial repeat of 1.5 ,kother than the a-helix.TABLE 2. Fibres giving the 1-5 A rejlexion.Fibre Spacing in ASynthetic polypeptides (* 0.01 A)Poly-(y-methyl L-glutamate) 40 1.50Poly-(y-benzyl L-glutamate) 30 1.50 *Homogeneous proteinsEpidermin 4 1 1-49Myosin 34b 1.50Tropomyosin 1.49Fibrin 41 1-49Biological fibresHair 39Muscle 3sBacterial flagella 411.501-491.49* Several other a-polypeptides, including copolymers of different amino-acids, showstrong meridional reflexions at 1.47-1.50 8, but detailed data have not yet beenpublished.40Pauling and Corey calculated the Fourier transform of the a-helix in theequatorial plane and used it for comparison with observed intensities.Quiterecently Cochran, Crick, and V ; ~ n d , ~ ~ calculated the three-dimensional Fouriertransform (or continuous scattering function) of a single atom repeated atregular axial intervals of 1.5 A along a helix with an axial distance of 5-4 Abetween turns. Their theory leads them to predict the relative strength ofthe different layer lines in an X-ray photograph of such a helical chain.Atthe same time Bamford and co-workers4* prepared several new samplesof polypeptides, including a highly crystalline specimen of poly- (y-methylL-glutamate). With this specimen, and by employing the improved techniquesused by Bunn 43 and by the Reporter, Bamford et aL40 increased the numberC. H. Bamford, L. Brown, A. Elliott, W. E. Hanby, and I. F. Trotter, Nature,1952,169, 357.4 1 W. T. Astbury, personal communication.48 W. Cochran and F. H. C. Crick, Nature, 1952, 169, 234; W. Cochran, F. H. C. Crick,43 C. W. Bunn and E. V. Garner, Proc. Roy. SOC., 1947, A , 189, 39.and V. Vand, Acta Cryst., in the press372 CRYSTALLOGRAPHY.of reflexions of the methyl ester from 13 to 28, and obtained similarlyimproved photographs of other polymers.The relative intensities of thelayer lines, and particularly the positions of the large number of absentlayer lines, are in such striking agreement with the mathematical predictionsof the theory as to leave no doubt that the structure of synthetic polypeptidesof the a-type is based on a helix of 18 residues in 5 turns and 27 A, or a helixwhich approximates to this very closely. A Fourier projection of the methylester on the equatorial plane is shown in Fig. 2.40 It contains volcano-shaped peaks, and the diameter of their annular maxima is in exact agreementwith the a-helix.FIG. 2.Linear section through Fourier projection of poly- (y-methyl L-glutamate).The radialdistances of the different atoms from the centre of the chain are marked on the abscissa.(Reproduced, by permission, from Nature, 1952, 169, 357.)Fibrous proteins do not give as good diffraction patterns as syntheticpolypeptides. However, the occurrence of the 1.5 A reflexion and thesimilarity of the infra-red spectra with those of synthetic polypeptides indicatethat these proteins contain either the a-helix or a chain of very similar structure.Globular Proteins.-The three-dimensional Patterson synthesis of horsemethaemoglobin contains rod-like maxima of high vector density whichindicate polypeptide chains of the a-type running parallel to the crystallo-graphic a axis.37 The arrangement of the chains as seen in end-on pro-jection forms the subject of an X-ray study by Bragg, Howells, and Perutz.44Whatever the precise chain model, the electron density in the main-COTH-NH- chain is greater than in the volume occupied by the side chains,and one would therefore expect the main chains to appear as prominentpeaks of high electron density in an end-on projection (e.g., Fig.2). As afirst approximation, such a projection can be treated mathematically asthough it consisted of point atoms, and standard methods of X-ray analysiscan be used to fmd their positions. It was found that the chains could not44 W. L. Bragg, E. R. Howells, and M. F. Perutz, Acta Cryst., 1962,5, 136PERUTZ . 373be arranged in the four layers suggested by one-dimensional Fourier pro-jections 45 and that agreement of calculated and observed intensities could beobtained only with an uneven number of layers.Fig. 3a shows the arrange-ment of chains in a single molecule as deduced by trial and error, with threeheavy central and two light outer layers of chains ; Fig. 3b shows the arrange-ment of two molecules in the face-centred unit cell, and 3c the Fourier pro-jection. The highest peaks in the projection correspond to overlappingchains, the lower ones to single chains. One of the encouraging features ofthe projection is its simplicity, and the fact that it remains unaltered at vari-ous stages of swelling and shrinkage of the crystal. On the other hand, theheight of the peaks in absolute electron units is only one-third of that expectedfor parallel chains running straight through the entire molecule.Theauthors suggest that a considerable fraction of the molecule must be takenup by chains turning corners, or running in directions other than the a-axis.The same conclusion was reached independently by Crick 46 on the groundthat the absolute height of the rod-shaped peaks in the three-dimensionalPatterson synthesis is too low. Comparisons of the observed heights withthose calculated for various idealised models led Crick to the view thatchains may not continue in a straight line for longer than 16A, i.e., one-quarter of the length of the molecule, before turning a corner.Two other observations suggest that haemoglobin, though containingor-helices which run parallel to the a axis, does not consist entirely of helicesrunning in that direction.The 1.5-A reflexion from a haemoglobin crystalis fainter and less distinct than expected from a simple model of straightparallel chains. The position of the CO combination band in the overtoneregion a t 4600 cm.-l, which Ambrose and Elliott found both in haemoglobincrystals and in solutions, is consistent with a pure cr-structure.21 On theother hand, the dichroism of the NH combination band, although of theright sign and orientation for a-helices running parallel to the a-axis, is weakerthan it would be expected to be on the basis of a simpleThe external form of the haemoglobin molecule is considered in twopapers by Bragg and P e r ~ t z . ~ * When salt solution is substituted for wateras the medium surrounding a haemoglobin crystal, a few reflexions of loworder are reduced in intensity, while high orders are little affected.The saltenters the liquid surrounding the molecules in the crystal, reducing the con-trast in density between protein and liquid. Absolute measurements ofthe changes in F values are used to determine the outer shape of the hydratedhorse methaemoglobin molecule which is not penetrated by the salt. It isconcluded that its width is 55 A in the b and the c direction and its lengthca. 65 or 80 A in the a direction of the crystal. The larger of these values isexcluded by measurement of the intensities in one of the other forms ofhaemoglobin, considered in the second paper, where it is shown that a hydrated4 5 J.Boyes-Watson, E. Davidson, and M. F. Perutz, Proc. Roy. SOC., 1947, A , 191, 83.46 F. H. C. Crick, Acta Cryst., in the press.47 A. Elliott and E. J. Arnbrose, Discuss. Faraday SOC., 1950, 9, 246.4 R W. L. Bragg and M. F. Perutz, Acta Cryst., in the press374 CRYSTALLOGRAPHY.molecule of the overall dimensions 55 x 55 x 65 A is consistent with theunit-cell dimensions and symmetry of nine other forms of mammalian haemo-globin, except in the case of foetal sheep haemoglobin which appears to have adifferent structure. The dimensions of the hydrated haemoglobin moleculeproposed by Bragg and Perutz are slightly different from those of the earliercylindrical mode1.45 The arguments which had led t o the choice of thatc sinflc sinpIll11 I l l I l l I l l , I I I I I 1 ( c )0 10 20AFIG.3.Overlapping chains are shaded.(Reproduced, by permission, from Acta Cryst., 1952, 5, 136.)Distribution of chains in single haemoglobin molecule.View of unit cell.Fourier projection of unit cell. Contours are drawn at intervals of 1 el/AaPERUTZ . 375model had been based on changes in relative intensities and on an analysis ofone crystal form only. The later approach 48 led to more definite conclusionsboth because absolute intensities were used and because data from a largevariety of different crystal forms were considered together. Data on thecrystal structure of human haemoglobin were obtained during an X-ray studyof sickle cell anzemia haemoglobin by Perutz, Liquori, and E i r i ~ h . ~ ~ Thishaemoglobin has an isoelectric point slightly different from the normal 50and a much lower solubility in the reduced state,51 yet no differences either inunit-cell dimensions or in the relative intensities of normal and sickle cellhaemoglobin could be found. It seems that slight differences between thechemical constitutions of two proteins may pass undetected by X-ray methods.A thorough X-ray study of ribonuclease, a protein of unusually low mole-cular weight (14,000), has been begun by Carlisle and Sco~loudi.~~ Theirfirst paper confirms the unit-cell dimensions and symmetry originally deter-mined by F a n k ~ c h e n , ~ ~ and describes Patterson and tentative Fourier pro-jections on the principal planes. The space group is P2, with only two mole-cules in the unit cell and a comparatively short b axis ; the crystals give muchmore detailed X-ray patterns than any protein so far examined, with distinctspots extending to spacings of less than 1 8.The results are best discussedin relation to the preliminary three-dimensional Patterson synthesk54This shows a rod-like vector peak passing through the origin in the directionof the c axis, with subsidiary peaks spaced at intervals of 5.4 A along thelength of the rod, and suggests the presence of chains of the a-type runningparallel to the c axis. However, the strong reflexions in the 10-8 regionwhich produce the simple system of peaks in the Fourier projection ofhaemoglobin (Fig. 3) do not appear in ribonuclease, and both Patterson andFourier projections show that the structure must be more complex.Thedimensions of the molecule are tentatively estimated at 30 x 10 x 48 A.The infra-red dichroism of the crystals, measured by Ambrose and Elliot, isin qualitative agreement with the presence of chains of the cr-type runningparallel or at a small angle to the c axis.Pauling and Corey’s comparison of observed and calculated radial distri-bution functions in haemoglobin 31 has been followed by a similar, but rathermore detailed, comparison of these functions in serum albumin by Riley andA r ~ ~ d t . ~ ~ Their experimental curve was obtained by extremely careful re-cording of the X-ray scattering from a powdered sample of bovine serumalbumin, and extends to a spacing of 0.83 8, whereas Perutz’s haemoglobindata, on which Pauling and Corey’s comparison was based, do not extendbeyond 2 - 8 8 .The agreement between the observed function and thatcalculated for the a-helix is suggestive, particularly if it is borne in mind that4s M. F. Perutz, A. M. Liquori, and F. Eirich, Nature, 1951,167, 929.61 M. F. Perutz and J. M. Mitchison, Nature, 1950,166, 677.62 C. H. Carlisle and H. Scouloudi, Proc. Roy. SOC., 1951, A , 207, 496.63 I. Fankuchen, J . Gen. Physiol., 1941, 24, 315.64 C. H. Carlisle, reported at Int. Congress of Cryst., Stockholm, 1951.66 D. P. Riley and U. Arndt, Nature, 1952,169, 138.L. Pauling, M. A. Itano, S. J. Singer, andI. C. Wells, Science, 1949,110, 543376 CRYSTALLOGRAPHYPERUTZ. 377neither in this nor in Pauling and Corey’s original comparison was anyaccount taken of the side chains beyond the @-carbon atom.This elegantmethod of testing proposed models of protein structure has the advantage ofbeing quick and simple and of not needing crystalline material; it will beinteresting t o see how sensitive it is to the precise model of chain which isused as a basis for the calculations.@-Structures.-In one of their seven papers on polypeptide chain structurePauling and Corey also proposed a “ pleated sheet ” of extended chains asthe structure of Further stereochemical studies have now ledthem to withdraw this and to replace it by two remarkably beautiful new“ pleated sheets,” which have a single chain model in In boththe sheets, neighbouring chains are cross-linked by hydrogen bonds at adistance of 4.7 A, in agreement with the distance which Bunn and Garnerfound for Nylon.43 Neighbouring chains point the same way in one of thesheets and opposite ways in the other (Fig.4). Pauling and Corey selectthis new model by placing restrictions on the rotation around the N-Cb andand the CO-C, bonds. They postulate free-energy minima for chain con-figurations in which one of the tetrahedral bonds of the a-carbon atom is inthe same plane as the amide group, and examine the 36 different permutationsA t o m conJined to one plane in four alternative polypeptide chain structures.(111) Fully extended chain as in polyglycine ; all the main chain atoms are in one plane.(IV) Planar unit used in building the chain model for the pleated sheet.Broken linesshow the bonds which are not in the plane of the paper and which form the links with the nexta&de groups.Thebroken lines have the same meaning as in (IV).(V) and (VI) Planar units used in building two alternative versions of the a-helix.which this condition implies. They find four possible structures (111)-(VI) ; in each of these, eight atoms surrounding the amide bond are confinedto one plane. (111) is a fully extended chain as found in silk fibroin and poly-glycine; (IV) is the structure of the pleated sheets; (V) and (VI) are twoalternative modifications of the a-helix, differing only by the arrangement ofthe @-carbon atoms. (V) appears to be more stable than (VI), as it does notinvolve close proximity between the oxygen of the carbonyl group and theS-carbon atom.5~ L.Pauling, and R. B. Corey, PTOC. Amer. A d . Sci., 1951,3’9, 251378 CRYSTALLOURAPHY.If the absolute configuration of L-amino-acids is chosen in accordancewith the results of Bijvoet et aZ.,l configuration (V) can be shown to correspondto a right-handed helix. (This would be the mirror image of the modelreproduced in Fig. 1.) The large increase in dextrorotation observed byRobinson and Bott 57 when poly-(y-benzyl L-glutamate) is converted fromthe p- into the a-form may be due to the transition from a straight chain toa right-handed helix.A model of feather keratin,58 of which two-thirds consists of a-helicesand one-third of pleated sheets of the type now withdrawn, was discussedbetween Pauling and Corey 59 and the Reporter; 34b it appears that thismodel has now been abandoned.Following a suggestion by Bunn, a revised unit cell of polyglycine hasbeen proposed by Astbury.60 The cell dimensions suggest a hydrogen-bonded structure of fully extended chains, close packed as in Nylon, withneighbouring chains pointing opposite ways.Collagen.-This, the protein of bone, skin, tendon, and connective tissue,differs from other protein fibres in many of its properties.It has little exten-sibility, swells laterally, and forms characteristic fibrils with a principaltransverse spacing of 640 8, visible under the electron-microscope. Its low-angle X-ray pattern shows a series of sharp lines on the meridian, correspond-ing to the orders of the 640 A spacing.Unlike other fibrous proteins, col-lagen shows no low angle reflexions on the equator, which indicates that itconsists of single long-chain units rather than of strings of globular particles.Bear and Bolduan 61 found that the lateral spread of the meridional reflex-ions is consistent with an assembly of long, very thin scattering units con-taining nodes of high density, the nodes in neighbouring units being displacedby different distances along the fibre axis.The high-angle equatorial reflexions of collagen appear to correspond toa close-packed structure of circular cylinders, spaced 12A apart in drytendon. It can be shownthat a unit cell of (12 X 12 X sin 60" X 2-85) ,k3 would contain approxi-mately three residues of average weight, and this argument forms the basisof a new structure of collagen proposed by Pauling and Corey.62 Theiringenious model consists of three helical chains intertwined like a rope andheld together by hydrogen bonds between them.The structure has a repeatof 2-85 A per residue, gives rough agreement with the observed intensitiesof four equatorial reflexions, and would explain the swelling properties, theinextensibility, and the infra-red dichroism of collagen. Stability of thestructure depends on the regular sequence of prolines or hydroxyprolinesa t every third residue along the chain, for which there is as yet no evidence.The gross amino-acid content, lately redetermined by Bowes and Kenten,shows less than one-quarter of the residues to be proline and hydroxypro-The principal meridional reflexion is a t 2-85 A.67 C.Robinson and M. J. Bott, Nature, 1951,168, 325.68 L. Pauling and R. B. Corey, Proc. Amer. Acad. Sci., 1951, 37, 256.59 Idem, Nature, 1951, 168, 550.61 R. S. Bear and 0. E. A. Bolduan, Acta Cryst., 1950,3, 326.I2 L. Pauling and R. B. Corey, Proc. Amer. Acad. Sci., 1951,37, 272.8o W. T. Astbury, ibid., 1949, 163, 722PERUTZ. 379line.63 Partial hydrolysis of gelatin with isolation of di- and tri-peptidescould establish whether the structure is chemically possible.Further X-ray evidence relating to the structure of collagen has beencollected by Huxley and Perutz.64 By tilting the fibre axis with respect tothe X-ray beam and by using short wave-length radiation they discoveredfour new meridional reflexions at spacings of 1.45, 0.98, 0.76, and 0*60&corresponding to the second-fifth orders of the fundamental spacing of2-85 A.The overwhelming strength of the 2.85 A reflexion, and the factthat the observed meridional reflexions are all higher orders of the 2-85 Aspacing, appear to exclude models which do not have a repeat of 2-85 A perresidue. As far as their spacings are concerned, the new meridional reflexionsare therefore in agreement with the structure proposed by Pauling andCorey; on the other hand, they exclude models in which the residues repeatat intervals of 2-85/3 8, such as that recently proposed by Bear ; this modelresembles the y-helix of Pauling et aL29 and was put forward on the groundthat collagen fibres were occasionally observed to show long-range extensi-bility under the electron-microscope.65 A comparison of the intensities ofthe newly discovered reflexions with those calculated for Pauling andCorey’s model is in progress.New electron-microscope results from Highberger, Gross, and Schmitt G6throw an interesting light on the association of the protein molecules incollagen fibres. It had been known for some time that the collagen of cer-tain forms of coqnective tissue dissolves in dilute acid to yield a clear viscoussolution. If neutral electrolyte is added to such a solution a fibrous pre-cipitate is produced which shows the same striations and axial period asnative collagen. Highberger et al.have found that the addition of muco-protein to such a filtrate produced a new type of regenerated collagen fibrewith an axial period of 2400A instead of the usual 640A. Mucoproteinfrom several different sources appeared to have the same effect, including themucoprotein normally contained in collagen itself, provided that its con-centration was sufficiently enriched above the normal. Closer analysisshowed that the type of fibril formed depended on the ratio of mucoproteinto collagen present in the filtrate.67 If the ratio was 1 : lo5 or less, theregenerated collagen formed a structureless gel. At a ratio of 1 : 1000,normal collagen fibres appeared, at 1 : 100 a mixture of normal and “ longspacing ” fibres, and a t 1 : 10 long-spacing fibres only.Great interestattaches to these results, especially in view of the abnormalities in collagen-ous tissue associated with rheumatoid arthritis. Thus rheumatoid nodulesin affected joints tend to show amorphous structureless fibrils partly replac-ing the collagen fibrils normally found there 6* and, significantly, an abnormal63 J. H. Bowes and R. H. Kenten, Biochem. J., 1948, 43, 358.64 H. E. Huxley and M. F. Perutz, in the press.66 R. S. Bear, 75th Anniv. Meeting, Amer. Chem. SOC., Sept., 1951.66 J. H. Highberger, J. Gross, and F. 0. Schmitt, Proc. Amer. Acud. Sci., 1951,37,286.67 F. 0. Schmitt, 75thAnniv. Meeting, Amer. Chem. SOC., Sept., 1951.68 H. J. Kellgren, J. Ball, W. T. Astbury, R. Reed, and E. Beighton, Nature, 1951,168, 493380 CRYSTALLOGRAPHY.mucoprotein fraction appears in the serum of patients suffering from thisdisease .69Muscle.-As a result of electron-microscope studies by Hall, Jakus, andS~hmitt,~* and Draper and H ~ d g e , ~ l we now have a beautifully detailedpicture of the fine structure of the striated muscle fibre.This appears as along tube of about 0.l-mm. thickness, with a thin wall made of an intricatelacework of collagen and other protein fibrils. The tube is sub-divided intoseparate compartments about 1 in length by a regular sequence of trans-verse membranes connected to the outer wall; about 90% of the volume ofthe compartments seems to be filled with an aqueous solution containinginorganic salts, and presumably some of the metabolic enzymes and theirsubstrates; the remaining 10% is occupied by the protofibrils, long pro-tein strands about 150 A thick, which stretch through several compartments.There is evidence that the strands contain a compound of two fibrous pro-teins, actin and myosin, which are thought to be the contractile elements ofmuscle.Morgan, Rosza, Szent-Gyorgyi, and Wyckoff 72 have recentlyfound that fixed and dried preparations of rabbit muscle, examined in trans-verse section under the electron-microscope, show signs of a regular array ofprotofibrils arranged in hexagonal close-packing ; the electron-micrographsby Draper and H ~ d g e , ~ l on the other hand, suggested that the protofibrils arearranged in a single layer around the outer wall of muscle fibrils, secondarytubes, 1 p thick, which would make up the muscle fibre.As a tool in biology, the electron-microscope has the drawback thatspecimens have to be dead, fixed, and dried.Using a new X-ray micro-diffraction technique, Huxley 73 has recently obtained interesting inform-ation on the arrangement of the protofibrils in wet, living muscle. Low-angle photographs of frog sartorius or rabbit muscle, taken with a slitparallel to the fibre axis, show three equatorial lines corresponding to the firstthree reflexions from a hexagonal array of cylindrical particles 450 A apart.When muscle is dried, this pattern gives way to one from a correspondingarray of particles 150 A apart. These results suggest that in living musclethe protofibrils are separated by liquid and spaced out in a regular hexagonalclose-packed array, reminiscent of the wet gels of tobacco mosaic virusobserved by Bernal and F a n k ~ c h e n .~ ~ On drying, this array collapses,giving place to that observed by Morgan et al. in the electron-microscope.If the distance between neighbouring protofibrils in wet muscle is 450 A, asindicated by Huxley’s results, their array must fill the entire muscle fibril,rather than merely covering the wall as suggested by Draper and Hodge; 71it would be impossible otherwise to account for the known actomyosin con-tent of muscle. Draper and Hodge’s electron-micrographs also show trans-verse striations which cross the protofibrils and are spaced 250450 A apart,60 H. Laurell, personal communication.70 C.E. Hall, M. A. Jakus, and F. 0. Schmitt, Biol. Bull., 1946, 90, 32.71 M. H. Draper and A. J. Hodge, Austral. J . Exp. Bid. Med. Sci., 1949, 27, 465.72 C. Morgan, G. Rosza, A. Szent-Gydrgyi, and R. W. G. Wyckoff, Science, 1950,111,73 H. E. Huxley, Discuss. FaTaday SOC., in the press.74 J. D. Bernal and I. Fankuchen, J . #en. Physiol., 1941, 25, 1 11.201PERUTZ . 381dependent on the state of contraction. By taking microphotographs ofliving muscle with a slit normal to the fibre axis Huxley has now discoveredseveral orders corresponding to a meridional repeat of 430 A, including thereflexions a t higher angles which have been found in dried muscle by Mac.Arthur 38 and Bear 75 and appear to correspond to a secondary repeat of 54 d.These had been interpreted by Astbury as arising fkom the actin c~mponent.~~While Huxley's low-angle microtechnique has revealed axial periodicitiesin living muscle of the order of 1/20 p, which must belong to a level oforganisation involving large groups of protein molecules, Huxley andPerutz,39 using a large dried specimen of the same muscle and tilting the fibreaxis with respect to the X-ray beam, found the periodicity of 1.5 d, corre-sponding to the repeat of amino-acid residues along some of the polypeptidechains within that group. The reflexion is presumably due to the myosincomponent, since it was also found in dried films of purified myosin.s4bThe reflexion is strongest in stretched, dried muscle, weaker in the relaxed,and very feeble in muscle dried in the contracted state; this confirms theresults of Astbury and Dickinson 77 who found that muscle shows the cc-keratin pattern at all stages of extension and contraction, and that con-traction brings about a disorientation of the normal pattern rather than achange in the spacing of any of the a-keratin reflexions.Interpreted liter-ally, this would mean that myosin maintains the a-helix configuration bothin relaxed and contracted muscle. However, as Huxley has pointed out, nocertain deductions can be made unless X-ray photographs can be takenduring an actual twitch.Pauling and Corey recently postulated that polypeptide chains in relaxedmuscle have a p-configuration and coil to form a-helices on c~ntraction.~~Their theory was criticised by Huxley and Perutz 39 because it was incom-patible with the results just described; Pauling and Corey then modifiedit, making the contractile elements such that they do not contribute to theX-ray diffraction pattern, which means that their new theory is not subjectto verification by X-ray meth0ds.5~ The idea of muscle contraction as p-atransformation has been in the minds of many previous investigators, andthe difficulties that have led them to abandon this simple and attractivesolution apply with equal force to Pauling and Corey's model.Nucleoproteins and Nucleic Acids.-Structural studies of tobacco mosaicvirus, which had remained dormant since the classical X-ray work of Bernaland Fank~chen,~~ were recently revived by the discovery of small hexagonalcrystals in the leaf hair cells of virus-infected plants.78 These crystals canbe identified as nucleoprotein by their ultra-violet absorption spectrum.They are positively birefringent, and have the remarkable property of givingBragg reflexions with visible light.There are two types : one gives Braggreflexions in unpolarised light, at an angle corresponding to a repeat ofR. S . Bear, J . Amer. Chem. SOC., 1945, $7, 1625.7 0 W. T. Astbury, Nature, 1947,160, 388. '' W. T. Astbury and S. Dickinson, Proc. Roy. Soc., 1950, B, 129, 307.'* M. H. F. Wilkins, A. R. Stokes, W. E. Seeds, and J. Oster, Nature, 1950,166, 127382 CRYSTALLOGRAPHY.3200-4000 A ; the other gives Bragg reflexions only between crossed nicolsand can be shown to contain a helical arrangement of particles with a repeatpattern of about 3000 A.The crystals evidently consist of layers of close-packed, rod-shaped virus particles, possibly interleaved with layers of water.Doubt has sometimes been expressed whether the well-known rod-shapedvirus particles originally discovered by Stanley were not an artefact formedduring purification. The properties of these interesting crystals and theearlier demonstration of sheaves of virus particles within infected cells 79dispose of this uncertainty.The crystals just described are the f i s t example of rod-shaped virusparticles forming a three-dimensional lattice ; the other plant viruses whichcrystallise seem to be very nearly spherical and tend to form lattices whichare either cubic or a t least simulate cubic symmetry. One of these is tobacconecrosis virus which exists in the form of several different strains. An X-ray study of a single crystal of one of the strains showed it to be triclinic,with two non-equivalent molecules in the unit Electron-micrographsof crystals of another strain seemed to indicate an approximately cubicclose-packed lattice.81 By an X-ray study of dried crystals of this samestrain Cowan and Crowfoot 82 have now demonstrated that these crystalsare also triclinic, with cell dimensions related to those of the first strainexamined by X-rays, and derived by distortion of a cubic face-centred lattice.The triclinic character of the lattice is evidence that the virus particle has aspecific internal structure and a shape which is not exactly spherical.Structural studies of nucleic acid received a fresh impetus by the discoverythat fibres of sodium thymonucleate, when kept in air of 50% humidity,contain remarkably well-ordered crystallites.83 The fibres are negativelybirefringent, and show negative ultra-violet and infra-red dichroism, whichmeans that the nucleotides must be oriented approximately normal to thefibre axis. They also give a sharp and detailed X-ray diffraction pattern.In stretched fibres, the sign of the birefringence and of the infka-red dichroismis reversed, and the ultra-violet dichroism vanishes, which suggests thatnucleic acid is an extensible molecule. Wilkins et aZ.84 have since discovereda close relation between the X-ray pattern of the wet unstretched fibre ofsodium ribonucleate and that given by oriented preparations of livingsperms. If the structure of deoxyribonucleate in chromosomes should be thesame as in the purified fibres, it would be open to standard X-ray analysis. Thesolution of this structure is not yet in sight, but in view of the great progressrecently made with proteins the difficulties may not prove insurmountable.M. F. P.D. C. HODGKIN.M. 3’. PERUTZ.79 L. M. Black, C. Morgan, and R. W. G. Wyckoff, Proc. Soe. Exp. Biol. Med., 1950,81 R. W. G. Wyckoff, Acta Cryst., 1948, 1, 292.Ba P. Cowan and D. Crowfoot Hodgkin, Acta Cryst., 1951, 4, 160.8s M. H. F. Wilkins, R. J. Gosling, and W. E. Seeds, Nature, 1951,167, 759; M. Ja73, 119. 8o D. Crowfoot and G. M. J. Schmitt, Nature, 1945, 155, 504.Fraser and R. D. E. Fraser, ibid., p. 759. 84 M. H. F. Wilkins et al., in the press

ISSN:0365-6217    

DOI:10.1039/AR9514800361

出版商:RSC    

年代:1951

数据来源: RSC

摘要:

INDEX OF AUTHORS’ NAMES.Abdel-Akher, M.., 146, 183,Abelson, N., 255.Abraham, E. P., 286.Abrahamczik, E., 353.Abrahams, S. C., 101.Abrams, A., 295.Abrams, R., 358.Abrams, S. T., 321.Accountius, 0. E., 95.Acock, G. P., 72.Adair, G. S., 238, 364.Adam, N. K., 84.Adamovich, L. P., 320.Adams, R. N., 327.Adamson, A. W., 53.Adamson, D. W., 221.Addink, N. W. H., 344.Addison, C. C., 98.Adrian, E. D., 295.Aepli, 0. T., 326.Affsprung, H. E., 341.Agar, H. D., 357.Agazzi, E. J., 329, 330, 336.Agiza, A. H., 343.Agnello, E., 230.Aguirre, R. M., 23.Ahrens, E. H., 353.Akabori, S., 246.Akaishi, K., 190.Akroyd, P., 186.Aksnes, G., 154.Alberman, K. B., 103.Albert, A., 221, 226.Albert, P. W., 286.Albert, R. A., 274.Albertson, N.F., 137.Alberty, R. A., 253, 260,Albon, N., 355.Albrecht, G., 363.Aldag, H.-J., 158.Alderbon, G., 164, 246.Aldrich, F. L., 313.Aleksandrov, S. N., 334.Alessandro, B., 360,Alexander, A. E., 80.Alexander, B. H., 175, 183.Alexander, E. R., 127, 133,Alexander, H. E., 141.Alford, W. C., 344.Ali, D., 356.Aliminosa, L. M., 206.Alkemade, C. T. J., 347.236.263.215.Allen, C. F. H., 210, 221.Allen, H. L., 29, 52.Allen, J., 98.Allen, P. W., 37.Allen, T. L., 45.Allerton, R., 180.Allouf, R., 354.Alm, R. L., 145.Al-Mahdi, A. K., 351.Almamy, F., 20.Alpen, E. L., 36.Altkin, B., 336.Alvarez Querol, M. C., 314,Amat, G., 24.Amble, E., 37.Ambrose, E. J., 26,240,241,365, 373.Ames, D. E., 161.Ames, D. P., 54.Aminoff, D., 237, 266.Amron, I., 107.Amstutz, E.D., 225.Anacker, E. W., 84.Anchel, M., 158.Anders, H. K., 342.Andersen, V. S., 51.Anderson, A. G., 191.Anderson, F. E., 328.Anderson, G. W., 153.Anderson, H. C., 264, 265.Anderson, H. H., 95.Anderson, J. O., 280.Anderson, J. R. A., 356.Anderson, J. S., 103.Anderson, J. W., 345.Anderson, K., 337.Anderson, L., 172, 219, 330.Anderson, P., 37.Anderson, R. C., 205, 206.Anderson, R. D., 48.Anderson, R. K., 291.Anderson, R. S., 31.Anderson, S., 348.Anderson, W. E., 32.Anderson, W. J., 348.AndB, T., 189, 355.Andreas, J. M., 79.Andreen, J. H., 217.Andrews, E. B., 18, 19.Andrews, M. B., 282.Andrews, W. S., 315.Andrychuk, P., 22.Anfinsen, C. B., 264.Angyal, C.L., 36.323.383Aniansson, G., 79, 358.Ankli, P., 222.Annison, E. F., 268, 355.Antonucci, R., 205.Antweiler, H. J., 357.Anyas-Weisz, J., 353.Arai, T., 188, 190.Ard, J. S., 348.Arens, J. F., 221.Argyle, A., 79.Armitage, J. B., 157.Arndt, U., 375.Arni, P. C., 237.Arora, S. D., 90.Artsdalen, E. R. van, 40.Aschaffenburg, R., 258.Ashley, S. E. Q., 332.Asimov, J., 355.Asmis, H., 147.Asselineau, J., 163.Astanina, A. A., 320.Astbury, W. T., 240, 275,364, 365, 367, 371, 378,380, 381.Astie, M. J., 332.Aston, I. G., 168.Aston, J. G., 66, 146.Astwood, E. B., 302.Atkins, D. C., jun., 81.Atkinson, H. J., 339.Atkinson, R. O., 164.Atta, R. E. van, 321.Attenburrow, J., 218.Attoe, 0. J., 347.Aubry, J., 338.Audrieth, L. F., 87, 98.Audsley, A., 36.Auer, E.E., 49.Auerbach, C., 337.Auerbach, V. H., 282.Aulin-Erdtman, (Mrs.) G.,Austin, J., 216.Austin, M. H., 261.Awapara, J., 355.Awtrey, A. D., 106, 322.Axford, D. W. E., 28.Ayres, G. H., 342.Babb, A. T. S., 359.Babcock, J. C., 206.Bach, G., 191.Bachmruzn, W. E., 204.Backers, R. C., 238.Bacon, J. S. D., 236, 237.187384 INDEX OF AUTHORS’ NAMES.Badcock, W. E., 125.Baddiley, J., 152, 168, 222.Badger, G. M., 114, 130.Badger, R. M., 26, 29.Badley, J. H., 329.Baenziger, N. C., 93.Baer, E., 163, 164.Baer, H., 266, 267, 268.Baer, L. H., 215.Bagshawe, B., 360.Bailar, J. C., 89, 312.Bailar, J. C., jun., 90.Bailey, C. W., 329.Bailey, K., 238, 364.Baird, C. L., 34.Bak, B., 32.Baker, C.G., 137.Baker, P. B., 356.Baker, R. H., 133, 223.Baker, W., 36,141, 184, 191,Baldwin, E., 236.Baldwin, R. L., 274.Baldwin, R. R., 316.Baldwin, W. H., 352.Baldwin, W. M., 17.Ball, I?. L., 331.Ball, J., 380.Ball, J. S., 329.Ball, S., 150.Ballard, S. A., 165, 211.Ballczo, H., 323.Ballou, C. E., 182.Balls, A. K., 292, 295,296.Bamford, C. H., 240, 241,365, 369, 371.Bandier, E., 277.Bangerter, F., 311.Bankert, R. A., 211.Banks, C. V., 108, 319, 335,337, 340, 342.Banks, H. O., 97.Banks, T. E., 270, 271, 272,Barb, W. G., 51.Barbaras, G., 143.Barbaras, G. D., 89, 143.Barber, E. G., 359.Barber, H., 356.Barchet, H. M., 191.Barcia Goyanes, C., 321.Barclay, G. A., 35, 36.Bardet, L., 22.Bardolph, M.P., 175.Bardos, T. J., 227, 268.Barger, F. L., 227.Barieau, J., 363.Barker, G. R., 175.Barker, H. A., 357.Barker, S. A., 183.Barltrop, J. A., 186, 223.Barman, P., 184.Barnard, D., 331, 332.Barnes, C. S., 125, 196.Barnes, H., 314,329,340.213, 224.358.Barnes, N. A., 341.Barnes, R. A., 150.Barnett, M. P., 8.Barr, M., 259.Barredo, J. M., 21, 24.Barrer, R. M., 65, 96.Barrow, G. M., 25.Barrow, R. F., 18, 19.Barry, G. T., 331.Bartelmus, G., 317.Bartels-Keith, J. R., 186,Bartha, L., 323.Bartlett, J., 340.Bartlett, J. K., 355.Bartlett, P. D., 122, 127,Bartlett, S., 258.Bartner, E., 254.Barton, D. H. R., 42, 146,192, 194, 196, 199, 200.Barton-Wright, E. C., 277.Bartz, Q. R., 219.Bashford, V.G., 173, 178.Basolo, F., 315.Bassett, H., 101.Bassett, L. G., 360.Bassil, G. T., 301.Bastian, R., 342.Batch, H., 250.Batchelor, W. H., 261, 269.Bateman, L., 47, 48, 213.Bates, R. W., 298, 301.Batres, E., 204.Bauer, L., 246.Bauer, R., 89.Bawn, C. E. H., 48, 52.Baxendale, J. H., 51.Baxter, K. L., 356.Bayly, R. J., 236.Beadle, G. W., 282.Beal, G. D., 310.Beale, R. N., 17, 347.Beall, D., 298.Beamish, F. E., 316, 340.Beams, J. W., 316.Bean, R. S., 296.Bear, F. E., 342.Bear, R. S., 370, 378, 379,Beard, C. I., 32.Beattie, J. A., 73.Beaven, G. H., 261.Beck, G., 322.Becker, E., 226.Becker, E. L., 263, 276.Becker, E. W., 45.Becker, W. W., 310.Beckett, C. W., 192.Beckham, L. J., 87.Beears, W.L., 211.Beeck, O., 69.Beeghly, H. F., 360.Beeson, K. C., 340.Beets, M. G. J., 154.Behnke, J., 274.187.211.381.Behr, L. C., 219.Behringer, H., 165.Beighton, E., 380.Beiser, S. M., 266, 267, 268.Beketovsky, S. N., 359.Bekleshova, G. E., 336.Belcher, R., 310, 311, 313,315, 317, 322, 324, 326,327, 329, 331, 332, 336,337, 343.Belisle, J., 146.Bell, D. J., 183, 236.Bell, E. E., 29.Bell, F., 56.Bell, F. O., 240, 275, 365,367.Bell, R. P., 14, 45, 56, 57,58, 76, 106, 129.Bellamy, W. D., 222.Belleau, B., 146, 201.Belser, R. E., 322.Benacorraf, B., 273.Bendas, H., 219.Bender, A. E., 355.Bendich, A., 224, 266, 267,Bendz, G., 217.Benedict, W. S., 30.Benesch, R., 281, 335.Benesch, R. E., 335.Bennett, A., 332.Bennett, E.L., 137, 266.Bennett, L. L., 218.Bennett, W. A., 303.Benoit, G., 154.Benotti, J., 347.Benson, S. W., 41, 93.Benyon, J. H., 197.Berenbom, M., 357.Berg, C. P., 167, 285, 286.Berg, H. J. van der, 81.Berg, K. B., 315.Bergeon, R., 78.Berger, A., 246, 338.Bergmann, E. D., 188, 219.Bergmann, M., 151, 240.Bergstrom, E., 208.Beri, R. M., 355.Bringer, R., 31.Berinzaghi, B., 230.Berkoz, B., 146.Berl, W. G., 183, 332.Berlin, J., 204, 209.Berlin, T., 14.Berliner, E., 130.Berman, D. A., 334.Berman, R. A., 302.Bernal, J. D., 380, 381.Bernays, P. M., 319.Bernhard, H., 152.Bernhard, W. G., 251.Bernhisch, B., 263.Bernstein, H. J., 25, 28, 29,Bernstein, R. B., 45, 348.Bernstein, S., 205.268.126INDEX OF AUTHORS’ NAMES.385Beroza, M., 353.Berridge, N. J., 357.Berriman, J. M., 346.Berti, G., 224.Bertorelli, E., 337.Besso, Z., 334.Betts, R. H., 53.Beul, R., 358.Bevenue, A., 352.Bevilacqua, E. B., 49.Bevillard, P., 332.Beyer, E., 350.Beyerman, H. C., 215.Bezer, A. E., 264, 266, 267,268, 273.Bhattacharya, S. K., 347.Bianco, D. R., 32.Bianco, Y., 89.Bidwell, E., 262, 292.Biedermann, W., 311.Biemann, K., 218.Biffen, F. M., 347.Bigeleisen, J., 28, 45.Bigg, P. H., 316.Bijvoet, J. M., 135, 361.Bilan, M., 252.Bilham, P., 199.Billek, G., 229.Billeter, J. R., 200.Billinghurst, J. W., 221.Bina, A. F., 291.Birch, A. J., 200, 204, 210.Bircumshaw, L., 73.Birks, E. W., 65.Birtley, W. B., 346.Bischoff, A., 328.Bischoff, F., 326.Bishop, J.R., 356.Bishop, R. F., 339.Biswas, A. B., 363.Bizzell, 0. M., 358.Bjorneboe, M., 250.Blacet, F. E., 61.Black, L. M., 382.Blackburn, S., 355.Bladon, P., 171, 172, 176,Blaedel, W. J., 311, 337.Blake, G. G., 337.Blake, N. W., 105.Blaker, R. H., 252.Blakey, R. C., 103.Blasco L6pez-Rubio, F.,330, 339, 343.Blaszkowska, Z., 344.Blatt, J. L., 354.Blau, M., 93.Blau, N. F., 212.Bleaney, B., 30.Blindenbacher, F., 181.Blizzard, R. H., 146.Bloch, K. A., 307.Block, B. P., 89, 312.Block, R. J., 355.Blohm, S. G., 351.Blomberg, B., 102.177.REP.-VOL. XLVIII.Blomquist, A. T., 184.Blout, E. R., 224.Blundell, M. J., 355.Boarland, M. P. V., 225.BOCZ, A. K., 98.Bode, H., 317, 319.Bodor, A., 340.Bohm, W., 221.Boehringer, R., 234.Boekelheide, V., 191, 230.Boer, H., 331.Boettcher, A., 338.Boggs, L., 355.Bogorad, A.S., 334.Bohlmann, F., 157,158,159.Bohrer, J. C., 184.Boissonas, R. A., 153, 355.Boit, H.-G., 228.Bokelmann, E., 152.Bokman, A. H., 285.Bolduan, 0. E. A., 378.Bolland, J. L., 39, 47.Bolliger, H., 178, 180.Bolomey, R. A., 353.Bolton, E. T., 276.Bolton, H. C., 98.Boltorff, E. M., 222.Boltz, D. F., 342.Bommel, A. J. van, 135,Bompard, F., 209.Bond, H. W., 289.Bond, T. J., 227.Bonet-Maury, P., 63.Bonham, L. C., 348.Bonjour, G., 292.Bonner, D. M., 282, 283,284, 285, 286.Bonner, F., 69, 70, 95.Bonner, R. M., 147, 228.Boon, W. R., 226.Boonstra, J. P., 339.Boord, C.E., 156.Boos, R. N., 336.Booth, H. S., 83.Booth, R. G., 277.Bordwell, F. G., 124, 147.Bork, S., 158.Bork, V. A,, 328.Borrel, M., 312.Bosch Ariio, F. de A., 339.Boscott, R. J., 356.Bose, A. K., 214.Bothner-By, A. A., 143.Bott, M. J., 378.Bottomley, G. A., 315.Botts, J., 275.Boudhe, C., 343.Bouissitms, G., 100, 342.Bouitrop, R., 91.Bourne, E. J., 171,172,181,Boursnell, J. C., 270, 271,Bourson, M., 315.Bovey, J. L. F., 25, 26.361.183, 236.351.Bowen, E. J., 63.Bowes, J. H., 238, 379.Bowman, R. E., 160, 161.Bowman, W. M., 274.Boxarden, B., 54.Boyd, A. W., 32.Boyd, D. R. J., 28.Boyd, W. C., 274.Boyden, A., 276.Boyer, J. H., 217.Boyes-Watson, J., 373.Boys, S. F., 8.Brabson, J. A., 323.Brack, A., 214.Bradbury, R.B., 331,Bradley, D. C., 97.Bradley, R. S., 72.Bradley, W., 131.Bradshaw, G., 341.Brady, A. P., 79, 81.Bragg, J. D., 33.Bragg, J. K., 32, 43.Bragg, (Sir) L., 241, 367,Brambell, F. W. R., 259.Brand, J. C. D., 19.Brand, K., 192, 355.Brandstatter, M., 349.Brandt, K., 322.Branson, H. R., 241, 367.Brantley, J. C., 102.Brasted, R. C., 314, 323.Braude, E. A., 123, 150,Brauer, G., 314.Braun, W. G., 23.Braunshtein, A. E., 284.Braunstein, J., 14.Bray, H. G., 266, 313.Breckpot, R., 345, 346.Breitenbach, J. W., 246.Bremner, J. W., 358.Bremner, R. W., 360.Bretez, J., 260.Bretschneider, H., 218.Breuer, G., 349.Brewer, E., 357.Brewer, L., 92.Brewster, D. A., 347.Bricker, C. E., 343.Brickson, W.L., 279, 281.Bridger, H. J., 317.Bridson-Jones, F. S., 151.Brieux, J. A., 130.Briggs, C., 258.Briggs, G. M., 280.Bright, H. A., 310.Brigl, P., 178.Bril, K., 61.Brill, R., 71.Brimley, K. J., 24, 348.Brimley, R. C., 352.Brimm, E. O., 102.Brissaud, L., 332, 359.Brit. Iron and Steel Res.372, 373.191.kbsoc., 340.386 IXDEX OF AUTHORS’ NAMES.Brockman, J. A., 227.Brockmann, H., 162, 350Brockmyre, H. F., 349.Brockway, L. O., 37.Broda, E., 358.Brode, W. It., 140.Broderick, E. J., 311.Brodersen, K., 91.Brodersen, P. H., 18.Brodie, 33. C., 329.Brodskii, A. I., 54.Broers, G. H. J., 62.Brooker, L. G. S., 7, 134.Brooks, C. J. W., 199.Brooks, C. W., 146.Brooks, F. R., 329, 330.Brooksbank, B. W. L., 298,Brookshier, R. K., 342, 354.Broquist, H.P., 227.Brotz, W., 318.Brousmrd, L., 338.Brown, 365.Brown, B. B., 217.Brown, B. R., 133, 213, 224.Brown, D. H., 266.Brown, D. J., 225.Brown, D. M., 181,247,254,263, 264, 295.Brown, E. B., 291.Brown, F., 119, 356, 357.Brown, F. C., 219.Brown, G. B., 220.Brown, H. C., 91, 93, 124,184, 193, 220.Brown, J., 25.Brown, J. G., 347.Brown, J. K., 28.Brown, K. D., 294.Brown, L., 25, 348, 371.Brown, L. E., 316, 328.Brown, P. E., 36.Brown, R. A., 254, 263.Brown, R. D., 7, 132, 133,Brown, W. B., 76.Brown, W. G., 143, 144.Brown, W. N., 346.Browne, C. I., 53.Browne, J. S. L., 302.Brownlie, I. R., 224.Brubaker, C. H., jm., 99.Bruce, G. T., 172.Bruce, W. F., 217.Brusset, H., 106.Bryden, J.H., 262.Buchanan, A. S., 60.Buchanan, C., 156.Buchanan, J. B., 217.Buchanan, J. G., 355.Buchman, E. R., 148.Buchta, E., 150.Buckels, R. E., 329.Buckley, G. J., 151.Buckwalter, G. R., 150.,355.304.191.Buddery, J. H., 110.Budziarek, R., 198, 199Buehler, C. A., 224.Bueliler, H. J., 298.Buerger, J., 81.Buess, C. M., 246.Buff, F. P., 76.Buffa, A., 331.Buhler, F., 329.Buis, D. M., 343.Bukantz, S. C., 263, 269.Bollock, M. W., 217.Bu’ Lock, J. I-)., 216.Bunn, C. W., 371.Bunnett, J. P., 213.Burch, F. H., 316.Burdett, L. W., 385, 336.Burel, H., 310.Burg, A. B., 91, 99.Burge, €3. E., 184.Burger, M., 249.Burgmdy, E. L., 28.Burgstalhr, A. W., 210.Burkhalter, T. S., 338.Burkhead, D.G., 30, 33.Burkin, A. K., 87, 308, 312.Burkitt, F. H., 7, 113.Bunolle, L . , 25.Burnet, F. M., 249.Burnett, G. M., 49.Uurnop, V. C. E., 271.Burns, W. G., 29.Burriel Martl, F., 321, 322,Burstall, F. H., 356.Burt, J. G., 127.3urton, M., 48, 60, 61, 64.3urton, R. B., 299, 305.3urwel1, R. J., 142.3uscar6ns, F., 313, 322.3Usev, A. I., 337.3 u h , G. H., 337.3ush, I. E., 299, 350.3ushey, G. L., 81.3ussmann, G., 329.3utement, F. D. S., 257.3utenandt, A., 284.htenko, G. A., 336.3utter, A. Q., 310.3utler, D., 223.3utler, G. C., 248, 251, 303.3utler. K., 180, 182, 183.3utler, T. A., 94, 352.3utt, W. R., 299, 304.3utts, P. G., 335, 338.3uxton, A., 260.3ywater, S., 69.Jacioppo, F., 356.;adjot, P., 158.hdle, R.D., 58.>ahn, R. S., 136.Jaldin, E. F., 46, 57.Jaldwell, W. T., 219.;aley, E. R., 321.205, 206.326, 344.Callomon, H. J., 27.Callon, R. W., 346.Cnllow, N. H., 300.Callow, R. K., 209, 300.Calvert, J. G., 60, 61.Calvert, W. L., 24, 348.Calvin, M., 268.Campanile, S., 359.Campbell, A., 194.Campbell, .A. N., 89.Campboll, D., 250, 252, 253,356, 27 1, 272.Campbell, D. H., 254, 263,272, 274, 275.Cameron, E. B. G., 337.Campanile, V. A., 329.Cunn, J. R., 254, 263.Cmnan, C. M. M., 370.Cnnnon, J. H., 353.Cupitan, F., 313, 382.Sapont, F. L., 330.Zarceles, F., 319..:ardwell, H. M. E., 200.hrhart, H. W., 146.hrlin, Et. B., 125.=arlisle, C. H., 375.;adson, B. C., 9.>adson, M. T., 345.3arlsson, C.G., 345.hrmack, M., 36.>amahan, It. E., 216.Jarpena, O., 337.Jnrpenter, K. J., 277, 281,Jarretero, R., 281.hrrington, H. C., 225.:arrington, T., 46.2arroll. B., 275.:arson, W. N., 333, 359.:arstensen, H., 245.:tarter, B. B., 268.:artier, C. E., 247, 353.hrter, H. E., 164.>arter, P., 299.:artledge, G. H., 107.:ashin, W. M., 84.Jason, J., 163.:aspary, E. A., 262.:assel, M., 106.hssidy, H. G., 350.hstiglioni, A., 325, 328.:astle, J. G., 31.hstle, K., 328.:astle, R. N.. 349.:astor, W. S., 315.:astro, R., 315.hughlan, C. N., 24.:aunt, A. D., 22, 38.?aunt, D., 186.Javalieri, L. F., 224.Javtzlla, J. F., 196.Javanna, R., 139.hve, G. C. B., 334.Jave, W. T., 20, 30.hfola, M., 315.bnter, E. J., 324, 333.291INDEX OF AUTHORS’ NAMES.387Cha, L. A., 335.Chabrier, P., 313.Chalvet, O., 7, 113, 117.Chamberlin, E. M., 206.Chambers, F. W., 332.Chambers, V. C., 120, 184.Champ, P., 319.Chanda, S. K., 237.Chaney, A., 332.Chanley, J. D., 216.Channing, D. M., 151.Chantrenne, H., 151.Chapman, N. B., 130.Chapman, R. L., 348.Chapuis-Gottreux, S., 99.Charest, M. P., 329.Charette, L. P., 346.Chargaff, E., 246, 356.Charles, R. G., 36.Charlot, G., 332.Chase, B. H., 225.Chase, D. L., 333.Chase, E. C., 227.Chatt, J., 87, 110.Chaudhuri, D. K., 277, 290,Chaves Lavin, L. R., 314.Cbeever, F. S., 262, 270.Chemerda, J. M., 206.Chen, C., 268.Chia-Si Lu, 363.Chibnall, A. C., 239.Chick, H., 280.Chilton, J., 354.Ching-Siang Tang, 335.Chiorboli, P., 24.Chism, P., 355.Chiu, C.Y., 305.Chomse, H., 360.Chopin, J., 185.Chopin, M. L., 329.Chow, B. F., 264, 276.Christen, K., 197.Christensen, P. K., 156.Christiansen, R. G., 203.Chu, T. H., 270.Chu-Tsiu Liu, 191.Churmanteeva, L. V., 314.Ciapetta, F. G., 56.Ciusa, W., 359.Claassen, H. H., 30.Claffy, E. W., 344.Claisen, L., 221.Clark, H. S., 331.Clark, I., 287.Clark, L. C., 343.Clark, R. O., 345.Clark, R. P., 43.Clark, S. J., 326.Clark, V. M., 247.Clasper, M., 353.Class, J. B., 146.Claus, C. J., 146.Clause, N. I., 61.Clawen, C. J., 347.Clayton, B. E., 298.291.Clegg, D. L., 351, 354.Clegg, K. M., 290.Clements, H. E., 344.Clemo, G. R., 191, 196, 223.Cleveland, E.A., 183.Cleveland, F. F., 23, 25,ClevelaDd, J. H., 183.Cleverdon, D., 36.Cloke, J. B., 215.Close, W. J., 219, 228.Cluett, M. L., 337.Cluley, H. J., 325, 340.Clunie, J. C., 67.Coates, G. E., 93, 105.Cochran, C. N., 93.Cochran, W., 371.Cockbain, E. G., 85.Coffey, S., 151.Coffin, G. S., 273.Coggeshall, N. D., 348.Cohen, A., 220, 222.Cohen, H., 298, 301.Cohen, M., 86, 128.Cohen, S., 256, 257.Cohen, S. G., 259.Cohen, S. L., 297, 299.Coheur, P., 344, 346.Cohn, M., 253,262,263,273.Cohn, W. E., 247, 353.Colas, J., 356.Cole, A. C., 265.Cole, L. R., 260.Cole, W., 145.Coleman, 365.Coleman, D., 246.Coleman, G. H., 175.Coles, D. K., 30, 32, 34.Coles, J. A., 123.Coles, R. K., 32.Colin, J., 340.Colin, L. L., 319.Collin, R.L., 101.Colson, R., 331.Combe, W. P., 221.Combs, G. F., 280.Comline, R. S., 259.Conduit, C. P., 98.Conley, J. B., 210.Conn, J. B., 336.Connelly, J. A., 329.Connick, R. E., 106, 322.Connolly, J. M., 353.Conrad, A. L., 347.Conrad, L. G., 315, 321.Conrady, R. G., 79.Zonroy, H., 212.Contreras Berrojo, J., 328.Controulis, J., 204, 219.Cook, C. L., 157.Clook, C. M., 312.Zook, D., 76.Zook, J. W., 132, 185, 186,187, 188.Zook, M. A., 65, 79, 80.k o k e , W. D., 333,334.30.Cooley, R. A., 97.Coombs, R. R. A., 257,272,Coons, A. H., 270,Cooper, G. D., 124.Cooper, H. R., 48.Cooper, J. A., 72.Cooper, S. S., 343.Cooper, W. C., 334.Cooperman, J. M., 281.Cope, A. C,, 150, 188.Copeland, C. S., 36.Copeland, L.C., 334.Corbett, J. A., 341.Corbett, W. M., 172.Corcoran, A. C., 299.Corey, E. J., 214.Corey, R. B., 241, 243, 244,363, 367, 369, 377, 378.Corliss, C. H., 310.Cornfield, A. H., 340.Cornforth, J. W,, 166, 167,Cornforth, R. H., 166.Cornwell, C. D., 31.Corrin, M. L., 81.Corson, M. H., 289.Corvazier, P., 260.Costcr, D., 361.Cosulich, C. B., 227.Cotchin, E., 258.Cote, G. L., 26.Cotman, J. D., 127.Cottrell, T. L., 9, 41.Couch, D. H., 183.Coulon, M. H., 251.Coulson, C. A., 7, 8, 9, 10,11,12,14,39, 113, 114.Coulson, E. J., 265.Coun, J. B., 274.Couper, A., 69.Coutoy, C., 30.Couture-Mathieu, L., 23.Cowan, G. R., 24.Cowan, P., 382.Cowan, R. D., 28, 29.Cowley, E. G., 36.Cox, R. I., 298, 299.Coy, N.H., 254.Cozzi, D., 334.Craig, D. P., 10, 11.Craig, L. C., 331,353, 354.Craig, L. E., 184.Craig, R. P., 53.Cram, D., 120.Cram, D. J., 186.Crampton, C. F., 270.Crandall, W. R., 314.Crane, W. W. T., 105.Cravioto, R. O., 291.Zrawford, B. L., 8, 10, 27,Zrawhall, J. C., 166.Zreech, H. J., 260, 262.Zremer, E., 351.h m e r , J., 23.276.200.29388 INDEX OF AUTHORS’ NAMES.Cdpy, O., 302.Crewther, W. G., 292.Crick, F. H. C., 371, 373.Criddle, D. W., 350.Critchlow, A., 186.Croft, R. C., 94.Cromartie, W. J., 260.Cromwell, N. H., 141, 145.Crooks, H. M., 219.Cropper, F. R., 309.Crosby, H. C., 44.Cross, J. M., 358.Cross, L. H., 151.Cross, R. C., 27, 29.Crow, A. D., 186.Crow, W. D., 186.Crowfoot, D., 363, 382.Crowther, A.F., 225.Crumpler, H. R., 164.Crumpler, T. B., 357.Cruse, K., 343.Cuendet, L. S., 355.Cull, N. L., 110.Cullis, C. F., 58.Culvenor, C. C. J., 217.Curnmings, C., 21, 22.Cunningham, B. B., 105.Cunningham, G. L., 32.Curd, F. H. S., 224.Curl, A. L., 296.Currie, L. R., 319.Curry, H. M., 328.Curtin, D. Y., 126, 127.Curtius, T., 151.Cushman, M., 347.Custer, J. H., 265.Czajkowski, G. J., 148.Daasch, L. W., 219.Dahlenborg, H., 322.Dahn, H., 145, 191.Dailey, B. P., 30, 32, 33, 34.Dainton, F. S., 50.Dalen, E. van, 315,323,330.Dalgliesh, C. E., 166, 167,283, 286, 355, 365.Dal Nagore, S., 351.Daly, E. F., 24, 348.Dammin, G. J., 269.Danby, C. J., 60.Dandliker, W. B., 268.Daniel, H. J. H., 344.Daniels, J.G., 270.Dann, W. J., 277.D’Ans, J., 322.Dantro, H. F., 324.Darmon, S. E., 364, 365.Darrow, A., 323.Darrow, R. R., 261.Darwent, B. de B., 59.Dasgupta, A. K., 342.Datta, S. P., 350.Daubon, H. J., 132, 187.Dauben, W. G., 146, 201,Daubert, B. F., 95, 146.204.Daudel, P., 54, 113.Daudel, R., 7, 10, 113, 117.Davey, D. G., 224,225.Davidge, P. C., 359.Davidson, A. W., 110,Davidson, C. S., 251, 264.Davidson, E., 373.Davidson, N., 46, 53.Davies, C. W., 310.Davies, D., 104.Davies, D. R., 224.Davies, J. T., 78.Davies, M., 38.Davies, 0. L., 310.Davies, W. H., 223.Davis, A. C., 152.Davis, D., 282.Davis, G. K., 358.Davis, H. A., 176.Davis, M. V., 315.Davis, 0. L., 330.Davis, P., 52.Davis, P.C., 172.Davis, P. L., 353, 354.Davis, R. H., 162.Davis, T. L., 311.Davison, S., 48.Davoll, H., 238.Davoll, J., 180, 220.Davy, G. S., 198.Dawson, J. K., 102, 104,Dawson, T. L., 194.Day, R. L., 266, 268.Deal, C. H., 317.Dean, J. A., 352.Dean, R. B., 311.Deane, H. W., 270.De Angelis, G., 336.De Biase, S., 264.Debye, P., 34, 37, 84.De Cesaris, E., 336.Dechmy, J. M., 328.De Clerq, M., 318.De Ford, D. D., 110, 333,Degard, C., 37.Degens, P. N., 329.De Geyndt, E., 356.De Groot, A. P., 330.De Heer, J., 7.De Hemptinne, M., 30.Deibner, L., 350.Deinum, H. W., 329.De Jonge, A. P., 221.Dekker, C. A., 247, 355.De Laat, B. M., 299.Delahay, P., 333, 334, 337.De La Huerga, J., 279.Delaney, J. C., 346.De Lange, D.J., 278.De la Kubia Pacheco, J.,330, 339, 343.Delavault, R., 325.De Loach, W. S., 357.Delsal, J. L., 258.316.334.De Maria, G., 293.De Mayo, P., 220.Den Hertog, H. J., 125,221.De Nicola, P., 264.Denk, F., 318.Denk, G., 318.Dennis, P. C., 277.Dennison, D. M., 30, 33.Denstedt, 0. F., 272.Dent, C. E., 164.Deodhar, T., 279.Deoras, B. R., 58.De Postis, J., 88.Derbyshire, D. H., 58, 129.Deriaz, R. E., 179, 180, 181.Dhrouaux, G., 216.Dervichian, D. G., 81,83,84.Desalbres, L., 85.Desnuelle, P., 292, 295.Desreux, V., 294.De Tar, D. F., 130.Detert, F. L., 132, 187.Dethier, F. M., 260.De Tore, A., 347.Detweiler, W. K., 225.Deuel, H., 353.Deuel, H. J., jun., 282, 286.Deulofeu, V., 130, 230.Deutsch, H.F., 253, 261,262, 263, 265, 273.De Vay, J. E., 355.De Vries, C. G., 341.De Vries, G., 314, 315.De Vries, J., 250.De Vries, T., 36.Dew, G. D., 17.Dewald, W., 316.De Walt, H. A., 224.Dewar,M. J. S., 7, 114, 116,117, 118, 123, 132, 134,189.Dewey, H. M., 270, 271.Dewey, V. C., 282.De Whalley, H. C. S., 355.Dewhurst, H. A., 63.De Witt, D. D., 137.De Wolff, C. J., 328.Dexter, S. T., 359.Diamond, L. K., 255.Diaz-Flores, C. A., 337.Dibeler, V. H., 20, 45, 70.Dickey, F. H., 250.Dickinson, S., 381.Dickson, G. T., 188.Diehl, H. W., 177.Diels, O., 210.Dierner, G., 145.Diepen, G. A. M., 78.Di Giorgio, P. A., 91.Dilapi, M. M., 251, 255.Dilks, E., 250.Dillard, C., 89.Diller, I. C., 260.Dimler, R. J., 175, 176, 355.Di Modica, G., 354.Dingemanse, E., 298, 299INDEX OF AUTHORS’ NAMES.389Dingle, J. R., 46.Dinkloh, E., 183.Dinsmore, H. L., 27.Dipali, N. L., 323.Dirscherl, A., 330.Dirscherl, W., 305.Dische, E., 266.Dittmer, D. C., 127.Divig, L., 315.Dixon, F. J., 269.Dixon, L. K., 79.Dixon, W. J., 311.Djerassi, C., 146, 149, 204,206, 207, 208, 209, 210.Doak, B. W., 273.Doan, U. M., 317.Dobbins, J. T., 315.Dobriner, K., 210, 297, 298,300, 303, 304.Dobrowsky, A., 86.Dobson, F., 353, 356.Dodd, R. E., 47.Doden, W., 324.Dodgen, H. W., 54.Dodson, R. M., 53.Dodson, R. W., 53.Doering, W. von E., 122,132, 143, 185, 187, 221.Doerr, R., 249.Doescher, R. N., 18.Doherty, D. G., 137.Doi, K., 185, 186, 189.Doisy, E.A., 298.Doisy, P. P., 298.Doisy, R. J., 298.DoleiL, L., 194.Dollimore, D., 92.Doniger, R., 356.Donohoe, R. W., 328. .Donohue, J., 363, 364.Dorfman, L. M., 47, 62.Dorfman, R. I., 303, 305,Dornow, A., 221.Doscher, T. M., 81.Douglas, A. E., 17.Douglass, C. D., 356.Douglas, H. W., 79.Dousch&, R. N., 40.Douwes, C. T., 316.Dovell, W. H., 19.Drain, J. E., 66.Drake, B., 336.Draper, A. L., 81.Draper, M. H., 380.Dreblow, E. S., 357.Drefahl, G., 183.Drell, W., 328.Drew, F. D., 354.Drinkard, C., 357.Driver, A. P., 151.Driver, G. W., 151.Druker, L. J., 168.Drukker, E. A., 154.Ducay, E. D., 245.Duchesne, J., 25.306.Dudley, J. R., 228.Duff, R. B., 173, 355.Duff, S. R., 200.Duffey, G. H., 13.Dufiin, G.F., 214.Duke, F. R., 128, 325.Dulmage, W. J., 91, 120.Dulou, R., 197.Duncan, A. B. F., 20, 24.Duncan, J. T., 274.Dundy, M., 329.Dunker, E., 347.Dunkle, F. B., 56.Dunlop, A. P., 210.Dunlop, E. C., 331.Dunn, A. F., 27.Dunn, J. L., 127.Dunn, M. S., 328, 354.Dunn, R. W., 358.Dupont, G., 197.Dupuis, T., 317.Dupuy, P., 330.Durand, R., 83.Durham, B. W., 310.Durie, R. A., 18.Durrum, E. L., 357.Durso, D. F., 351.Dusenburg, J. H., 59.Dustan, H. P., 299.Dutcher, J. D., 217.Duthie, J. J. R., 302.Dutton, H. J., 354.Duval, C., 316, 317, 318,DuVall, R. D., 348.Du Vigneaud, V., 238.Duxbury, McD., 337.Duyckaerts, G., 336.Dwyer, F. P., 53, 110, 139,Dye, J. L., 352.Dyer, H. B., 363.Dyne, P. J., 19.Earl, J.C., 213.Eastham, J. F., 146, 201,Eastoe, J. E., 339.Eastwood, D. J., 355.Eberhard, L., 332.Ebert, H. M., 326.Ebine, S., 189, 190.Ebnother, E., 222.Edelhoch, H., 274.Edelman, J., 237.Edelson, D., 29.Edgerley, P. G., 36, 141.Edgerton, P. J., 130.Edsall, G., 274.Edwards, F. C., 316.Edwards, J. E., 73.Eeckhout, J., 345.Eeg-Larsen, N., 261.Eggenburger, E. N., 86.Ehrenthal, I., 355.Ehrhardt, E., 136.319, 321.341, 342.204.Erhardt, K., 167.Ehrlin-Tamm, G., 347.Eirich, F., 375.Eischens, R. P., 67.Eisen, H. N., 268, 271, 272,Eisen, H. W., 250.Eisen, W., 252.Eisenberg, H., 79.Eisner, A., 215.Ekman, B., 303.El Badry, H., 316.Elbeih, I. I. M., 356.Elberg, S. S, 265.Elderfield, R. C., 210, 233.Elek, S. D., 276.Eley, D.E., 68, 69.Elias, V. E., 324.Eliel, E. E., 216.Elkin, L. M., 142.Elkinton, J. R., 347.Ellenburg, J. Y., 344.Ellinger, P., 277, 281.Elliott, A., 26,240,241,365,Elliott, D. F., 166, 217, 218.Elliott, S. D., 292.Elliott, W. W., 133, 134.Ellis, G. P., 182.Elmore, D. T., 247.El-Sabban, M. Z., 30.Elsermann, K., 324.Elson, D., 356.Elson, R., 100.Elvehjem, C. A., 278, 279,280, 281, 287, 288, 290,291.Elvidge, J. A., 217.Elving, P. J., 308, 310,321,EmelBus, H. J., 92.Emerson, G. A., 227.Emmens, C. W., 297, 300.Emmett, P. H., 67, 71.Erlich, P., 96.Ender, F., 335.Endicott, F. C., 268.Endroi, P., 322.Engel, L. L., 265, 297, 299,Engelbrecht, A., 100.England, D. C., 219.English, F. L., 353.Engstrom, W.W., 297.Enslin, P., 232.Entwistle, N., 157.Enzfelder, H., 325.Ephrati, E., 251.Epple, R. P., 319.Epps, E. A., 339.Erdey, L., 340.Erickson, A. E., 206.Erickson, J. L. E., 328.Erilinne, D., 172.Erlenmeyer, H., 219.Erler, K., 339.275, 276.371, 373.335.300, 301390 INDEX OF AUTHORS’ NAMES.Ernster, L., 339.Eschenmoser, A., 194, 196.Esson, H. van, 154.Etheredge, M. P., 337.Etili, L., 252, 274.Eugater, C. H., 159.Euler, V. S. von, 356.Eulitz, F., 226.Evans, A., 348.Evans, A. G., 124.Evans, E. A., 45.Evans, E. E., 237.Evans, G. G., 215.Evans, H. G. V., 54.Evans, H. J., 342.Evans, H. M., 245.Evans, M. G., 7, 18, 39, 50,Evans, R. L., 224.Evans, R. M., 172.Evans, R. S., 268.Evans, W.H., 109.Everard, K. B., 16, 36.Everest, D. A., 96.Evers, E. C., 98.Everson, H. E., 83.Eyring, H., 8.Eyring, L., 104, 349.Fabre, C., 295.Fabre, R., 343.Facq, L., 367.Fahrenbach, M. J., 227.Fairbrothor, F., 99.Fairweather, D. A. W., 151.Falloon, S. W. H. W., 347.Fankuchen, I., 375, 380,Farhan, F., 340, 345.Fan, H. V., 310.Farrant, J. L., 369.Farrar, K. R., 160.Farthing, 365.Fassel, V. A., 347.Faucherro, J., 102.Fauconnier, P., 319.Faure, M., 251.Fause, F., 257.Faust, M., 159.Fawcett, J. S., 196.Feast, M. W., 17, 18.Feazel, C. E., 183.Fedoseev, P. N., 329.Feigelson, P., 288.Feigl, F., 315, 318.Feinstein, L., 328.Feldberg, W., 295.Fellenberg, T. von, 323.Fellig, J., 237, 238.Fonn, F., 249.Fenske, M.R., 23.Fenton, E. L., 262.Fenton, S. W.,. 160, 188.Ferguson, L. N., 348.Ferguson, R. C., 319, 342.Fergusson, R. H., 81.62, 133.381.Fernhdez-Caldas, E., 341,Ferradini, C., 342.Ferrari, C., 340.Ferrobee, J. W., 260, 347.Ferstandig, L. F., 50.Fessler, W. A., 87.Fetzor, W. R., 359.Feuer, I., 316.Feurer, M., 146.Fevold, H. L., 164, 246.Feynman, R. P., 14.Fichter, F., 234.Fiedorek, F. J., 211.Field, F. H., 40.Fielding, P. E., 36.Fields, M., 165, 224.Fieser, L. F., 140, 201, 204,Fieser, M., 201.Fillitti-Wurrnser, S., 273.Findlay, S. P., 144.Finger, H., 260.Finholt, A. E., 89, 143.Finkelstein, J., 229.FinkeLtein, N. A., 347.Finney, D. J., 310.Firmenich, It., 154.Fischel, E. E., 250.Fischer, E., 36, 151, 172,Fischer, E.H., 237, 238.Fischer, F. E., 146, 217.Fischer, H. 0. L., 169, 171.Fischer, P., 216.Fischer, R., 349.Fischer, R. B., 321.Fituh, F. T., 352.Fitzgerald, 1’. J., 271.Flahaut, J., 93.Flaschka, H., 318, 320, 322,325, 327.Flatt, H., 99.Fleisher, J. H., 296.Fleming, D. S., 251.Fletcher, E. A., 91.Flotcher, H. G., 146.Fletcher, H. G., jun., 176,Flotcher, R. S., 124, 184.Flotchor, W. H., 29.Flick, J. A., 250.Flynn, E. H., 227.Fodor, G., 137, 218, 219.Foerning, L., 42.Folkard, A. R., 339.Folkers, K., 146, 212, 222,Follcnsby, 14:. M., 255.Fontnine, T. D., 348.Footo, C. W., 271.Forbes, T. R., 304.Forbes, W. F., 150, 191.Forchheimer, 0. L., 319.Forchielli, E., 237.Ford, E. G., 334.344.205, 206.188.177, 182.227, 230, 231.Ford, 0.W., 347.Fordham, J. W. L., 62.Fordham, S., 79.Fordham, W. D., 160.Foreman, W. W., 289.Forker, R. F., 209.Foro, A., 127.Forrest, H. S., 226.Forziati, F. H., 236.Foss, M. E., 11 1.Fossum, J. H., 310.Foster, A. B., 172, 174, 176,Fourneau, E., 154.Foust, C. E., 222.Fowden, L., 355.Fowler, R. H., 74.Fox, C. L., 347.Fox, S. W., 217, 219, 239.Fraenkel-Conrat, H., 245,France, H. G., 146.Francis, A. W., 88.Francis, C. E., 271, 272.Francis, G. E., 256, 269,270, 271, 272.Francis, S. A., 27.Francis, W. C., 168.Frank, E., 223.Frank, F. C., 34.Frank, R. L., 221.Frank, V. S., 151.Frankel, M., 246.Franklin, K. J., 270.Franzen, V., 157.Fraser, J. B., 172.Fraser, M.J., 382.Fraser, M. M., 220.Fraser, R. D. E., 382.Frederick, M. R., 211.Frederickson, L. D., 346.Frediani, H. A., 359.Freedman, D. A., 264.Freeman, H. C., 140.Freeman, N. K., 163.Freisen, H., 36.Freiser, H., 341.Freitag, E., 108.Frejacques, C., 41.French, H. E., 221.FrBrejacquo, M., 18 1.Freund, H., 342, 354.Freund, J., 251.Frey, H., 344.Freyman, M., 30.Freyman, R., 30.Fried, J., 176.Fried, S., 104.Friedgood, H. B., 356.Fricdlrtnder, H. N., 128.Friedman, C. A., 204.Friedman, H. L., 108.Pricdman, T,., 28.Friedman, L. J., 210.Frimd, J. A., 86.Frierson, W. J., 368.180.296M D E X OF AUTHORS’ NAMES. 391Friml, M., 340.Frisch, K. C., 95.Frith, W. C., 99.Eriz, H., 68.Fromageot, C., 239.Frost, A.A., 14, 351.Fruhling, A., 23.Frwh, H. L., 182, 183.Fry, E. M., 218.Fryd, C. F. M., 359.Fuchs, L., 343.Fiirst, A., 190, 194.Fuerst. R., 355.Fiirstenau, I., 335.Fujiha, E., 229.Fukushima, D. K., 297,303Fulmer, E. I., 94.Fulmer, E. J., 352.Funston, E. S.. 359,Furman, N. H., 333, 334336.Furman, S. C., 99.Furness, W., 334.Gabrielson, G.. 352.Gabrio, B. W., 265.Gaertner, R., 225.Gaumann, T., 36.Gage, T. B., 353, 356.Gagliardi, E., 316, 318.Gagliardo, E., 334, 335.Gagnon, A,, 329.Gahler, A. R., 338.Gajdusek, D. C., 254.Galat, H., 228.Gale, P. H., 252.Gale, R. H., 339, 342.Galinovsky, F., 144, 228.Galkowski, T. T., 236.Gallagher, J. F., 300.Gallaghor, T. F., 146, 201,208, 209.Gallais, F., 95.GalmBs, P.J., 321.Gambrill, C. M., 345,Gandolfo, N., 321.Garber, M. J., 282.Gardella, J. W., 260.Gardner. D. E.. 323.Gardner, K., 342.Gardner, T. S., 227.Garikian, G., 75, 77.Garner, C. S., 99.Garner, E. V., 371.Garner, H. K., 142.Garner, W. E., 72.Garrett, A. B., 100.Garrett, E. R., 337.Garrido Marquez, J., 330..Garrison, W. M., 358. . Garson, W., 254.Garst, J. B., 356.Garstens, M. A., 68.Garton, W. R. S.. 17.Garza. H. M.. 227.Gascoigne, R. M., 197.Gaspar y Amal, T., 319.Gassmann, A. C., 345.Gesmer, K., 332.Gttst, J. H., 313.Gatterer, A., 346.Gattorta, G., 341, 354.Gaudefroy, G., 326.Gaudin, A. M., 358.Gault, H., 351.Gaittier, J. A., 314.Gavioli, G., 320.Gaydon, A. G., 17.Gee, G., 47, 48.Geilmann, W., 319.Geissen, W., 357.Geissman, T.A., 150.Geld, I., 341.Gell, P. H., 250.GellBrt, E., 234.Gelles, E., 58, 106, 129.Gemervy, D., 276.Gensch, C., 337.Gender, W. J., 162.George, P., 61.GGrard, R., 353.Gergel, M. V., 104.Gerhold, M., 342.Gerlough, T. D., 253.German, H. L., 282.Gerold, C., 148.Gersmann, H. R., 62, 106.Geschwind, S., 31.Ghiorso, A., 103, 104.Giancola, D., 205.Gibb, A. R., 132, 185, 186.Gibbs, J. H., 36.Gibitln, T. G., 30.Gibson, C. S., 111.Gibson, J. A., 337.Gibson, M. S., 234.Gibson, N. A., 341, 342.Gigubre, P. A., 29, 335.Gilbert, E. C., 109.Gile, J. D., 358.Giles, C. H., 338.Gill, J. S., 103.Gill, R., 56.Gillam, 0. R., 31.Gillis, J., 314, 341, 345.Gilman, H., 328.Silman, T.S., 98.3ilmour, H. S. A., 53.Jilpin, V., 349.Jinsberg, D. F., 210.>insburg, D., 188.3irardot. P. It., 144.>isondi, A., 339.Xtlin, D., 251, 261, 264269, 274, 276.Xtsels, H. P. L., 215.:Ittugow. A. R., 331.2lctsner, A., 73.>lazc?brook, K. W., 213.3leeson-Wtlits, M. H., 272.=Itmny, A. T.. 259.:lick, D., 340Glick, J. H., jun., 298.Glockler, G., 32.Glockling, F., 184, 191.Glover, J. H., 334.Glusman, M., 264.Goard, A. K., 86.Gobert, C., 345.Goddu, R. F:, 326.Goebel, W. F., 252,253,257.Gobhring, M., 101, 324.Goksu, V., 293.Goepp,. R. M., jun., 169,Goering,’ H. L., 133.Goetzke, H., 331.Gold, M. H., 168.Goldberg, C., 333,341, 360.Goldberg, R. J., 274.Goldberger, J., 281.Golder, R. H., 343.Goldfinger, P., 61.Golding, C., 360.Goldschmidt, S., 153.Goldsmith, G.L., 57.Goldstein, F., 339.Goldstein, J. H., 30, 33.Goldsworthy, L. J., 217.Golubtsova, R. B., 321.Golumbic, C., 353.Gomor, R., 46, 47.Gonzalez Barredo, J. M.,Good, P.. A., 264.Good, W. E., 32.Goodban, A. E., 354.Goodeve, C. F., 85.Goodman, I., 144.Goodman, M., 273.Goodwin, T. W., 150.Zorbach, G., 344.>ordon, A. H., 248.Sordon, B. E., 335.SordQn, C. L., 357.=ordon, E. B., 251.>ordon, L., 321, 352.:ordon, S . , 316.:ordy, W., 13, 30, 31, 32,>ore, D. N., 354.fore, R. C., 347,foreau, T. N., 328.>oring, D. A. I., 84.foring, H. J., 118.?iorini, L., 203.>oryachenkova, E. V., 284.aosling, R. J., 382.aoss, F. R., 36.171, 177.91.34, 38.Gosting, L.J., 253, 263.GotB, H., 342.Gottlieb, A., 342.Gottlieb, K. El., 321.Gottlieb, 0. R., 331.Goubeau, J., 96.Gould, C. W., 350.Gould, E. S., 90, 329.Goulden, F., 299392 INDEX OF AUTHORS’ NAMES.Goulden, R., 310, 311, 317,322, 326, 329, 332, 336.Goutarel, R., 232, 233, 234,235.Gouverneur, P., 329.Govindachari, T. R., 224.Govindarajan, V. S., 354.Grabar, D. G., 349.Grabar, P., 249, 260, 261,Graham, J. R., 347.Graham, R. P., 335.Graham, T. E., 41.Gran, G., 336.Granatelli, L., 315.Grant, G. A,, 298.Grassie, N., 49.Gray, A. P., 233.Green, C., 245, 246.Green, E., 250.Green, F. C., 238.Greenbaum, K. W., 250.Greenberg, D. M., 151, 164,Greenblatt, I. J., 312.Greene, R. D., 254.Greenhouse, H. M., 95.Greenlee, K.W., 156.Greenstein, J. P., 137.Greenwood, N. N., 92.Gregg, D. C., 274.Gregg, R. A., 49.Gregory, G. D., 354.Gregory, G. I., 164.Gregory, N. W., 108.Gregory, R., 332.Gregory, R. L., 340.Gresham, T. L., 211.Griffith, F. S., 334.Griffiths, J. M., 356.Grim, R. E., 321.Grimes, W. R., 337.Grimmel, H. W., 153.Griswold, B. L., 339.Grob, C. A., 164, 222.Grob, E., 148, 213.Groschke, A. C., 280.Grosheintz, J. M., 171.Gross, D., 355.Gross, J., 379.Grosse, A. V., 168.Gross-Ruyken, H., 96.Grossmann, W. I., 277Grove, J. F., 210.Groves, L. H., 191.Groves, W. O., 96.Grubb, R., 266, 267.Gruen, D. M., 94.Grunisholz, G., 99.Grunwald, E., 121.Grutta, G. L., 356.Gryder, J. W., 53.Gualandi, G., 24.Guardia, C.C., 328.Gubeli, O., 357.262, 265.250.282.:iinthard, H. H., 25,30,36,Zuenther, A., 153.henther, R., 339, 342.henther, W. B., 43.fubrin, H., 91.fuerrieri, F., 323.hevard, J. de D., 339.fuggenheim,E. A., 55, 74,195.75, 76, 77.fuile, R. L., 337.hllberg, M. E., 286.h n n , E. L., 345.hnning, H. E., 59.hnsalus, I. C., 222.fupta, J., 318, 342.furevitch, J., 251.hrin, S., 209.furski, A., 341.fustafson, F. G., 281.fustafsson, C., 355.h t , M., 146, 180, 181.hthrie, F. C., 320.htmann, F., 332.Zutmann, H., 199.htmann, V., 99, 105.htowsky, H. J., 29.3uy, R., 254.h y , W., 25, 348.Swinn, W. D., 23, 32.Jyarfas, E. C., 53, 110.Haagen-Smit, A. J., 311Haase, E., 221.Haberlandt, H., 315.Haberman, G., 254.Hach, R.J., 106.Hackett, J. W., 54.Hiifliger, O., 219.Hagdahl, L., 245.Hailund; H:, 357.Hahn, F. L., 311, 314, 315,Hahn, H., 107.Hahn, R. B., 99,314, 320.Height, G. P., 335.Hain, A. M., 301.Haissinsky, M., 100.Hald, J., 277.Hale, A. C., 345.Hale, C. H., 335.Halford, R. S., 26.Hall, C. E., 380.Hall, G. A., 58.Hall, G. G., 11.Hall, H. T., 340.Hall, J. G., 272.Hall, J. L., 337.Hall, L. P., 357.Hall, M. E., 318, 334.Hall, N. F., 312.Halsall, T. G., 150, 183, 198Halsey, G. D., 65, 67, 68.Halvorson, H. O., 343.Hamberg, U., 356.331.236.Iamell, W. H., 62.Iamer, F. M., 213.Iamilton, J. G., 103,358.Iamilton, J. K., 146, 183.Iamilton, M. A., 260.kmilton, W. C., 314.Iamlet, J.C., 160.Iamlin, K. E., 146, 217.Iammaker, E. M., 327.Iamman, S. D., 124.Iammar, C. G. B., 351.Iammett, L. P., 142.Iammick, D. L., 129, 133,Iammond, H. R., 103.Iammond, V. J., 21.Campton, S., 263.Ianby, W. E., 240, 241,365, 369, 371.Iandman, L., 254.lanig, M., 294.Gnkes, J. V., 281,282,287.1ankes, W. A., 279.lankwitz, R. F., jun., 260.h n n , R. M., 172, 177.lanna, C., 146.lanna, J. G., 332.lannan, R. B., 343.Sannoick, T. J., 22.Sans, A., 345, 346.lansch, C., 216.3ansen, J., 345.Hansen, R. G., 254, 258.Kansen, R. S., 79.Hanson, R. M., 350.Happ, G. P., 349.Happey, F., 240, 365,369.Karbottle, G., 53.Hardin, L. J., 323.Harding, J. S., 213.Hardre de Looze, L., 255.Hardy, H. R., 51.Harfenist, E.J., 353.Hargrave, K. R., 51, 331,Karington, C. R., 252.Harispe, J. V., 328.Harispe, (Mme), 328.Hariton, L. B., 300,303.Harkins, W. D., 81, 82.Harkness, J., 358.Harley, J. H., 346, 360.Harley-Mason, J., 211, 216.Harmon, D. D., 345, 346.Harms, A. J., 256.Harris, E. D., 336.Harris, E. E., 127.Harris, H., 164.Harris, J., 105.Harris, J. O., 196, 224, 351.Harris, L. J., 277, 279, 281.Harris, R. L., 93.Harris, R. S., 291.Harris, S. A., 222.Harris, W. W., 331.Harrison, J. S., 355, 356.134, 213, 224.332INDEX OF AUTHORS’ NAMES. 393Harrison, M. F., 318.Harrison, T. S., 93.Hart, E. J., 49, 63.Harteck, P., 45.Hartley, B. S., 296.Hartley, F. R., 90.Hartley, G. S., 81, 82.Hartley, P., 259.Hartman, J. L., 221.Hartman, S., 312.Hartmann, H., 11 7.Hartogh-Katz, S.L., 298.Hartree, E. F., 236.Harvalik, Z. J., 351.Harvey, H. W., 330.Harvey, S. C., 343.Haskins, F. A., 283.Haskins, W. T., 172.Haslam, J., 343, 353.Hasler, M. F., 346.Haalewood, G. A. D., 298,Hassel, O., 192.Hassid, W. Z., 236.Hassig, A., 264.Haszeldine, R. N., 168.Hatch, L. F., 141.Hatz, F., 288.Hauber, E. S., 316.Hauenstein, H., 180, 181.Haul, R., 327.Haul, R. A. W., 73.Hauptmann, K. H., 305.Hauptschein, M., 168.Haurowitz, F., 249,. 252,270, 274, 293.Hauser, C. R., 27.Hauser, E. A., 78, 79, 80.Hausmsnn, W., 353.Hawking, F., 225.Hawley, J. E., 345.Haworth, R. D., 164, 185,Haworth, (Sir) W. N., 236.Hayaishi, O., 283.Hayano, M., 305, 306.Hayashi, E., 221.Hayek, E., 100.Hayles, A.B,, 303.Hayward, A. M., 339.Hazel, J. F., 324.Hazlett, F. P., 343.Head, A. J., 42.Heard, R. D. H., 302.Hearn, J. M., 224.Heath, D. F., 25.Heath, F. H., 315.Heath, H., 167, 220.Hebbelynck, M. F., 149.Hecht, F., 317, 342, 360.Hechter, O., 209, 307.Heczko, T., 360.Hedberg, K., 29, 37, 38, 91,HedBn, C. G., 355.Heer, J,, 299.302, 304.186.120.Heether, M. R., 348.Heftmann, E., 299.Hegsted, D. M., 288.Hehre, E. J., 261.Heidel, R. H., 347.Heidelberger, C., 286.Heidelberger, H., 251.Heidelberger, M., 251, 255,258, 260, 261, 263, 272.Heidt, L. J., 332.Heilbron, (Sir) I. M., 152,Heimann, W., 316.Heimann-Geierhaas, A.,Heinzelmann, R. V., 146,Heiremans, A., 341.Hektoen, L., 265.Heldman, M.J., 81.Heller, H. F., 125.Heller, J., 108.Heller, L., 96.Hellman, M., 45.Hellmann, H., 14.Hellwig, E., 338.Hemming, W. A., 259.Hemmings, A. W., 353.Henbest, H. B., 150, 160.Henderson, J. H. S., 60.Henderson, L. M., 279, 281,282, 284, 285, 287, 288.Henderson, M., 259.Henly, A. A., 299.Henne, A. L., 106, 145, 168.Hennig, W., 192.Hennion, G. F., 132.Henriksen, S. D., 254.Henry, H., 266.Hentz, R. R., 64.Herb, H., 101.Herian, B. J., 353.Herling, F., 210.Herman, R. C., 29.Hermon, S. E., 311, 319,HernBndez Cafiavate, J.,Hedndez Gutihez, F.,HBrold, A., 94, 95.Herout, V., 196.Herrick, A. B., 215.Herriott, R. M., 292, 294,Herron, P. W., 339.Hershberg, E. B., 148.Hervey, A., 158.Herz, J.E., 204, 206.Herzberg, G., 17, 28, 29.Herzberg, L., 28.Herzfeld, K. F., 42.Herzog, H. L., 148.Hess, E. L., 253.Hess, S. M., 351.Heusler, K., 202.197.316.217.340.327.328.296.Hey, D. H., 130.Heyes, T. D., 225.Heyl, D., 222, 227.Heymann, H., 205, 206.Heyningen, W. E. van, 249,Hibbard, R. R., 348.Hickinbotham, A. R., 314.Higasi, K., 34.Higby, V., 343.Higgins, G. H., 352.Higginson, W. C. E., 52,Higgs, D. G., 337.Highberger, J. H., 379.Hilbck, H., 349.Hilbert, G. E., 176, 236.Hildebrand, J. H., 73, 98.Hilditch, T. P., 343.Hill, A. G. S., 270.Hill, H. W., 146.Hill, J. M., 254.Hill, R. A. W., 213.Hill, R. F., 271.Hill, T. L., 66, 275.Hill, U. T., 339.Hillenbrand, J. L., 41.Hillger, R.E., 30, 33.Hills, A. A., 315.Hills, G. J., 336.Hilty, W. W., 348.Himmler, W., 68.Him, J., 131.Hinreiner, E., 150.Hinshelwood, (Sir) c., 41,Hinterauer, K., 100.Hirata, Y., 284.Him, C. H. W., 294.Hirsch, H. M., 287.Hirschfelder, J. O., 14.Hirschmann, F. B., 303.Hirschmann, H., 303.Hirshberg, Y., 188.Hirst, E. L., 183, 236, 237.Hiscox, E. R., 357.Hiskey, C. F., 107, 338.Hitchcox, G. I., 336.Hitchings, G. N., 225, 226.Hoare, M. F., 14.Hobson, J. D., 186.Hobson, P. N., 237.Hocart, R. J., 349.Hoch, H., 261, 264, 272.Hockett, R. C., 177.Hodes, M. E., 246.Hodge, A. J., 380.Hodge, 5. E., 236.Hodges, R. C., 251.Hodgkins, C. R., 345.Hodgson, G. W., 54.Hodgson, H. W., 334.Hodsman, G. F., 315.Hoene, J.von, 359.Hoff, M. C., 156.Hoffman, C. J., 29.262, 292.340.43394 INDEX OF AUTHORS’ NANES.HHHHHHHHHH aHHHHHn[offman, M. M., 302.[offman, 0. A., 83.Ioffmann, P. O., 22.Ioffpauir, C. L., 328.lofmann, V., 145.:ogness, D. S., 289.:ogness, J. R., 289.:olden, B., 149.:olden, D., 56.:olden, R. B., 348.older, A. N., 31.‘oliday, E. R., 261, 264.‘olker, J. R . E., 197.olliday, M., 347.olliday, P., 25, 348.olloway, F., 128.olm. A.. 258.Holmin, R. T., 352.Holman, W. I. M., 278,291.Holmes, H. L., 228.Holmquist, H. E., 211.Holness, N. J., 199.Holt, L. E., 281.Holtermann, H., 200.HoltorfX, A. F., 300.Holtzclaw, H. F., jun., 109.Holtzmann, G., 266.Holtzmann, S., 267.HoIzbecher, Z., 3 15.Homburger, F., 264.Honeyman, J., 182.Honig, D.F., 26.Honig, R. E., 349.Hooker, C. W., 304.Hooker, S. P., 255.Hormats, E. I., 40.Horn, D. H. S., 167.Hornbeck, G. A., 29.Hornychova, E., 312.Horrex, C., 42.Horswill, E. C., 218, 219.Horton, C. A., 327.Hoskins, A. L., jun., 304.Hossfeld, R. L., 354, 355.Hoste, J., 341.Hougen, F. W., 167.Hough, L., 183, 237, 355.Hovorka, V., 315.Howard, G. A., 182.Howe, C., 268.Howells, E. R., 372.Howlett, K. E., 42.Howton, D. R., 162, 331.Hrostowski, J. J., 26.IIuang, H. J., 137.Huang, W.-Y., 204, 206.Huang-Minlon, 147.Huber, G., 185.Huber, H., 179.Huber, W. F., 161, 162.Hudson, B. J. F., 133.Hudson,C. S., 146,169,172,174, 176, 177, 180, 182,183.Huebner, C.F., 220, 278,302, 355.Huttel, R., 226.Huff, H., 58, 81.Huff, J. W., 277, 278, 281,Huffman, E. H., 97, 352.Huffman, F., 329.Huggins, C., 241, 245.Huggins, M. L., 240, 367.Hughes, E. D., 119, 121,Hughes, E. W., 363.Hughes, H., 330.Hughes, H. K., 345, 346.Hughes, I. W., 180.Hughes, R. H., 31, 32.Hugo, T., 344, 345.Huis in’t Veld, L. G., 298,Hukins, A. A., 36.Hull, R., 226.Hultquist, M. E., 227.Hume, D. N., 326, 334.Humiston, C. G., 164.Humoller, F. L., 339.Humphries, P., 210.Hundley, J. M., 281, 289.Hunt, E. B., 95.Hunt, J. M., 348.Hunt, J. P., 54, 108.Hunter, J. H., 148.Hurd, C. D., 246, 351.Hurst, T. L., 239.Hurt, W. W., 282.Husson, C., 346.Huston, J.,A., 45.Huston, J. H., 101.Huston, J. L., 54, 101.Hutchinson, E., 79, 85.Huttig, G.F., 65.Huxley, H. E., 244, 370,379, 380, 381.Huykens, P., 64.Hyman, M. A., 254.Ibrtll, J., 275, 294.Irhishima, I., 23.Iddings, G. M., 97, 352.Ikemi, T., 188, 189, 190.Ileceto, A., 332. aIllingworth, W. S., 129.Imanishi, S., 20.Ingersoll, A. W., 137, 138.Ingold, C. K., 119, 121, 125,Ingold, K. U., 42, 43.Ingold, W., 337.Lngols, R. S., 312.Ingram, G., 329.Cnhoffen, H. N., 158, 159,Cnnes, R. F., 319, 341.Cnskeep, R. G., 29.Ipatieff, V. N., 148.Ippolitova, E. A., 320.Iriarte, J., 209.Crish, P. R., 345.286.123, 125, 128.299.128, 136.209.Irish, R., 325.Irsa, P., 69.Irsa, R., 70.Irving, F., 151.Irving, H. M., 87, 353.Irwin, J. O., 311.Isbell, H. S., 182, 183, 235.Isherwood, F.A., 236.Ishii, S., 355.Ismay, D., 210.Itano, M. A., 375.It6, s., 190.I%oh, F., 284.Itschner, K. F., 239.Ives, D. J. G., 336.Ivin, K. J., 47.Twantscheff, G., 322.Iwatsu, T., 220.Jackson, D. E., 354.Jackson, R. K., 347.Jacobs, J., 10, 11, 12.Jacobs, M. B., 330.Jacobsen, C. F., 294, 295.Jacobsen, R, P., 307.Jacquet, O., 356.Jacquot-Armand, Y., 273.Jadhav, G. V., 131.Jaffe, J. H., 24.Sager, B. V., 263, 264.Jakobljevich, H., 318, 320.Jakus, M. A., 380.James, A. T., 351, 354, 355.James, D. G. L., 50.James, R. A., 104.James, W. A., 322.James, W. O., 356.Jamison, N. C., 348.Jander, G., 91, 101, 337.Jandorf, B. J., 296.Janeway, C. A., 261, 269.Jang, R., 295.Janot, M.-M., 232, 234, 235.Jansen, E.F., 292,295,296.Jansen, K., 343.Jansen, J. E., 211.Janz, G. J., 28.Jaycox, E. K., 344.Jayle, M. F., 302.Jean, M., 360.Jeanloz, R. W., 175, 176,182, 237, 307.Jeffries, P. R., 185.Jeger, O., 196, 197, 198,199,Jellinek, H. H. G., 84.Jellinek, M. H., 102.Jen, C. K., 30.Jenkins, D. M., 168.Jenkins, M. H., 317.Jenkins, W. A., 94.Jenny, E. F., 164.Jensen, C. C., 300.Jensen, E. V., 245.Jensen, F. W., 338.Jewsbury, A., 313..200INDEX OF AUTHORS' NAMES. 395Jimeno Martin, L., 346.Jindra, R. A., 353.Johannesen, R. B., 124,184.Johns, A. T., 183.Johns, C. J., 333.Johns, H., 347.Johns, R. G. S., 264, 267,Johnson, A. S., 186.Johnson, A. W., 186, 187,Johnson, C. J., 62.Johnson, C. M., 31, 339.Johnson, E., 63.Johnson, F.S., 20.Johnson, H. L., 21.Johnson, J. E., 146.Johnson, J. R., 217.Johnson, L., 148.Johnson, M. J., 292.Johnson, 0. H., 87.Johnson, P., 84.Johnson, R. A., 335, 339.Johnson, R. E., 54, 101.Johnson, S., 343.Johnson, W. C., 347.Johnson, W. S., 193, 203,Johnston, C. E., 58.Johnston, H. C., 42, 43, 44.Johnston, H. L., 29, 348.Johnston, J. D., 198, 199.Johnston, M. C., 263.Johnston, R. J., 97.Johnston, S. A., 81.Johnston, W. H., 55, 105.Joly, M., 83.Jonassen, H. B., 88, 110.Jonckers, M. D. E., 313.Jones, 134.Jones, A. G., 338, 359.Jones, A. V., 28.Jones, D. C., 65.Jones; E. A., 28, 29.Jones, E. R. H., 154, 156,157, 160, 198.Jones, E. W., 319.Jones, G. F. S., 302.Jones, H. W., 121, 246.Jones, J.I. M., 356.Jones, J. K. N., 168, 183,236, 237, 355.Jones, J. W., 358.Jones, K. K., 29.Jones, L. C., 335.Jones, L. H., 29, 32.Jones, L. S., 323.Jones, M. E., 38, 91, 120,Jones, P. G., 191.Jones, R. G., 219, 220, 222,Jones, R. N., 210, 228, 303.Jones, S. L., 332, 333.Jones, W. G. M., 226.Jones, W. M., 45.272.190.218.300.227.Jordan, D. O., 80.Jordan, P., 53.Jouwersma, C., 221.Jovanovid, S. L., 319.Jovanovid, V. M., 319.Judas, O., 302.Jukes, T. H., 227.Julian, D. B., 334.Julian, P. L., 145, 209.Juliard, A,, 338.Jung, S. L., 98.JureEek, M., 328.Jutisz, M., 239.Kabat, E. A., 238, 249, 250,264, 265, 266, 267, 268,273.Kabesh, A., 88, 96.Kader, M. M. A., 277.Kagarise, R. E., 20, 23.Kahane, E., 310, 329.Kahn, T., 356.Kahnke, M.J., 251.Kainz, G., 331.Kakita, Y., 323, 342.Kallert, W., 150.Kallio, R. E., 285, 286.Kallmann,. S., 320, 333.Kalvoda, R., 336.Kaminski, M., 261,262,276.Kan-Nan Chang, 319.Kanakowsky, T., 322.Kanno, T., 324.Kantor, S. W., 127.Kantorowicz, O., 358.Kaplan, M. H., 270.Kapp, H. J., 274.Kappanna, A. N., 58.Karabinos, J. V., 237.Karjala, S. A., 236.Karmack, M., 231.Karrer, P., 136, 147, 159,167, 172, 220, 222, 227,228, 232.Karrer, R., 356.Kerush, F., 252, 272, 274,Kasha, M., 19, 21.Kassner, J. L., 319, 341.Kastler, A., 22.Katada, M., 129, 221.Katchalski, E., 246.Katchalsky, A., 79.Kates, M., 234.Kato, E., 240, 366.Kato, M., 277.Katsura, S., 190.Katz, J.J., 94.Katzin, L. J., 103.Katzman, P. A., 298.Kaufman, M., 343.Kaufman, S., 293, 295.Kaufmann, O., 323.Kavanagh, F., 158.Kawana, J., 72.Kawerau, E., 354.275.Kaye, W., 24.Kazarnovskii, I. A., 88.Keighley, G., 271.Keilin, D., 236.Kekwick, R. A, 264, 357.Keller, G. J., 350, 351.Keller, M., 64.Keller, W. E , 29.Kellgren, H. J., 380.Kellner, L., 25.Kemball, C., 70.Kember, N. I?., 356.Kemp, A. D., 188.Kendall, F. E., 263, 272.Kendall, J. D., 214.Kendrew, J. C., 241, 367.Kennedy, E. E., 348.Kennedy, E. P., 357.Kenner, G. W., 151, 182,Kenner, L., 354.Kenny, F., 327.Kent, P. W., 180, 237, 260.Kenton, R. H., 379.Kenyon, J., 142, 143.Kerckow, F. W., 312.Keresztesy, J. C., 227.Kern, W., 152.Kerrich, J.E., 311.Kervenski, I..R., 331, 332.Kesling, M. R., 328.Kessler, M., 32.Keston, A, G., 268.Kesztler, F., 215.Ketelaar, J. A. A,, 25, 62,Ketron, K. C., 281.Ketterer, S., 250.Keutrnann, E. H., 299,305.Kharasch, M. S., 127, 128.Khorana, H. G., 152, 154,Khym, J. X., 247,353.Kidder, G. W., 282.Kierstead, L., 351.Kies, M. W., 353, 354.Kikindai, T., 106.Kilbey, N., 356.Kilby, B. A., 295, 296.Killner, W., 85.Kilpatrick, M. D., 330.Kilpatrick, M. L., 41.Kimball, G. E., 14.Kimler, W. D., 36.Kimura, K., 340.Kirnura, M., 38.King, E. J., 338, 340.King, F. E., 215.King, G. L., 94.King, J. A., 145, 228.King, W. H., 210.Kingsley, R. B., 137.Kington, G. L., 66.Kinnunen, J., 333.Kinsella, R. A,, jun., 298.Kirby, K.S., 217.220, 231.106.220, 231396 INDEX OF AUTHORS’ NAMES.Kirby-Smith, J . S., 29.Kirch, E. R., 277, 355.Kirchlof, W., 191.Kirchner, J. G., 350, 351.Kirk, J. C., 165.Kirk, P. L., 316, 330.Kirklin, W. A., 310.Kirkwood, J. G., 76, 254,Kirkwood, J. S., 254.Kirpal, A., 221.Kirsten, W., 328, 329, 330.Kise, M. A., 87.Kishi, H., 186.Kisluik, P., 32.Kiss, J., 137, 218, 219.Kistiakowsky, G. B., 46, 47,Kitahara, Y., 185, 186, 189,Kitasato, Z., 199.Kitchen, H., 311.Kitchener, J. A., 324.Kjaer, A,, 217.Klatzkin, C., 277.Kleczkowski, A., 256, 262.Klein, B., 225.Klein, (Miss) E. R., 196.Klein, J. R., 289.Klein, R., 65.Kleinberg, J., 54, 87, 89,106, 359.Kleis, J., 184.Klemer, A., 167, 183.Klemm, W., 87.Klevens, H.B., 82.Kligler, D., 280.Klingmiiller, V., 330.Klinkhammer, H. J., 188.Kloch, K., 209.Klopsteg, P. E., 332.Klyne, W., 303.Knapp, 0. E., 348.Knaub, V., 264, 266, 267,Knight, H. B., 348.Knight, J. D., 186.Knight, S. A., 196.Knight, S. B., 347.Knight, S. K., 196.Knol, K. S., 361.KnoIle, K. C., 255.Knott, E. B., 134, 135.Knowlton, K., 300.Knox, L. H., 132, 185.Knox, W. C., 268.Knox, W. E., 167, 250, 277,Kniichel, W., 305.Knuth-Winterfeldt, E., 342.KO, R., 333.Kobayashi, E., 331.Kobe, K. A,, 318.Kober, S., 301.Koblick, D. C., 256.Koch, F., 330.263, 361.274.190.268.282, 283.Koch, F. C., 300.Koch, G., 209.Koch, H. P., 187.Koch, P., 329.Koch, R., 355.Koch, W., 101.Kochakian, C.D., 305.Kocher, V., 356.Koczka, K., 219.Kodicek, E., 277, 278, 279,280, 281, 287, 289, 290,291.Koehler, L. H., 176.Koehler, W.-C., 94.Kolling, G., 209.Koenigs, E., 221.Koszegi, D., 319, 332.Kofler, A., 349.Kofler, L., 349.Kofler, W., 349.Koford, H., 36.Kohler, M., 30.Kohler, T. R., 348.Kohn, H. I., 289.Kohn, M., 341.Kohtes, L., 238.Kojima, M., 352.Kolb, J. J., 354.Kolb, W., 357.Kolp, D. G., 162.Kolthoff, I. M., 50, 52, 59,82, 90, 331, 334, 335, 336,337.Komyathy, J. C., 335.Kon, G. A. R., 199.Kon, S. K., 258.Konecny, J., 313.Konigstein, (Miss) M., 144.Koniuszy, F., 227,230, 231.Konrad, A., 107.Koop, J., 89.Kooyman, E. C., 40, 49,Koppius, 0. G., 348.Korach, S., 310, 329.Kordesch, K., 359.Koren, H., 35.Korger, G., 228.Koritnig, S., 339.Kornfeld, E.C., 219, 220,Koroc, Z., 238.Korte, F., 226.Koshland, D. E., 152.Kotake, M., 166.Kozlov, A. S., 324.Krakowski, M., 348.Kratzl, K., 229.Kraus, K. A., 100.Kraus, R., 360.Krc, J., 349, 350.Krebs, E. G., 250, 260.Krehl, W. A., 278, 279, 280,281, 286, 290, 291.Kremney, L. Y., 85.Kreshkov, A. P., 328,256, 271, 331.222.Kressman, T. R. E., 352.Krishman, K. S., 34.Krishnan, R. S., 23.Kristjanson, A. M., 54.Kritchevsky, T. H., 209,Krudsen, E.,, 32.Krueger, R. C., 258.Kruse, H., 269.Kryukova, A., 334.Kuang-Ti Yen, 323.Kubo, M., 36, 132, 188.Kubo, S., 352.Kuhn, K., 153.Kuhlen, L., 148.Kuhn, K., 137.Kuhn, R., 157, 158.Kuivila, H. G., 148.Kujirai, M., 68.Kumar, L., 36.Kumari, C.S., 23.Kummer, J. T., 67.Kummer, T., 71.Kumpf, W., 154, 239.Kunin, R., 352.Kunioka, E., 185, 189.Kunitz, M., 292, 294.Kunkel, H. C., 276.Kunkel, H. G., 258, 264.Kunori, M., 186, 190.Kurita, Y., 36, 132, 188.Kuroda, P. K., 336, 337,Kurtz, A. N., 107.Kurtz, P., 155.Kurtz, R. B., 327.Kutner, A., 219.Kutzelnigg, A., 326.Kuznetsov, V. I., 312.Kwan, F. P., 339.Kwan, T., 68.Kwang-Yu Chow, 356.Labriola, R. A., 230.Lachampt, F., 84.Lachner, J. R., 29.Lacourt, A., 356.Lademann, R., 356.Laemmel, H., 20.Laforgue-Kantzer, D., 99.Lagemann, R. T., 29.Laguna, J . , 291.Lahey, F. N., 196, 197.Laidlaw, R. A., 236, 355.Laidler, K. J., 71.Laing, S. C., 67.Laitinen, H. A,, 325, 336.Lake, G.R., 329.Lakowski, H., 294.Laland, S., 180, 182.Lamandie, M., 25.Lamanna, C., 273.Lamb, F. W., 277.Lamb, M. A,, 30.Lamberton, A. H., 168.Lmnbot, H., 216.299.339INDEX OF AUTHORS’ NAMES. 397Lamenmans, A., 260.L a m , O., 79, 358.Lamotagne, D., 335.Lamp,.B., 146.Lampen, J. P., 247.Lamphere, R. W., 332.Lamport, J. E., 30.Lancaster, J. E., 29.Landau, R. L., 300.Landauer, S. R., 155.Lander, J. J., 109.Landsteiner, K., 253.Landua, A. J., 355.Lang, G., 168.Lang, K., 331.Lang, R., 325.Langeland, W. E., 191.Langer, A., 358.Langford, K. E., 360.Langham, W., 289.Langley, R. W., 168.Langsdorf, W. T., 121, 122.Lanni, F., 250, 253, 272.Lansford, M., 227.Lapidre, C., 230.Laplace, G., 338.Laporte, K., 258.Laporte, R., 255.Lappin, G.R., 328, 343.Lardon, A., 149.Lardy, H. A., 172, 219.Larkin, M. E., 317.Larny, R., 251.Laskowski, D. E., 328, 357.Laskowski, M., 295.Lassieur, A., 310, 332.Laszlovszky, J., 322.Lathe, G. H., 353.Latta, H., 261, 269.Laubach, G. D., 214, 215.Laue, M. von, 361.Lauer, K., 332.Laurell, H., 380.Lavie, D., 188.Lawrence, A. S. C., 82, 84,Lawson, A., 167, 220.Lawton, E. J., 64.Lay, J. O., 311.Lea, H. B., 314.Leblond, C. P., 209.Le Bot, J., 30.Lecomte, J., 26, 216.Leder, I. G., 278.Lederer, E., 163.Lederer, E. L., 86.Lederer, M., 355, 356.Leduc, E. H., 270.Lee, C. C., 120.Lee, J., 227.Lee, T. S., 90, 331.Leeks, H., 261.Lees, H., 339.Le FBvre, C. G., 36.Le FBvre, R.J. W., 35, 36,140, 141, 213.85.Lefort, M., 63.Lehn6, M., 109.Leibner, G., 158.Leichssenring, G., 155.Leifer, E., 289.Leigh, C. H., 42.Leigh, E., 264.Leigh, R. H., 53.Leigh, T., 226.Lein, A., 322.Leitch, L. C., 28.Leithe, W., 323, 331.Le May, M., 250.Lennard-Jones, (Sir) J. E.,10, 11, 14, 16.Lennox, F. G., 292.Leonard, N. J., 223, 224,Leone, L. A., 276.Le Peintre, M., 340.Lepkowsky, S., 286.Lermann, S. G., 252.Le Rosen, A. L., 350, 351.Le Roy, D. J., 46, 359.Lesnik, A. G., 13.Lespieau, R., 173.Letort, J. G., 61.Le Tourneau, R. L., 350.Leumann, E., 159.Leupin, E., 305.Leussing, D., 90, 334.Le Van, W. E., 32.Levant, A. J., 348.Levering, D. R., 348.Levi, A. A., 225.Levick, R., 339.Levine, C.A., 104.Levine, H. H., 168.Levine, L. A., 274.Levine, S., 78.Levintow, L., 137.Levitas, N., 278.Levkoev, I. I., 134.Levy, A. L., 152, 239.Levy, H., 307.Levy, H. A., 363.Levy, M., 252, 330.LBvy, R., 330.Levy, (Miss) W. J., 151.Lew, B. W., 171.Lewinson, V. A., 14.Lewis, 0. N., 19.Lewis, J., 98.Lewis, J. A., 356.Lewis, J. B., 329.Lewis, J. C., 164, 246.Leyton, L., 347.Lhoste, P., 332.Li, C. H., 245.Liang, C. Y., 30.Libby, R. L., 270.Libby, W. F., 53, 55, 105.Liberman, A., 324.Liberman, L. A., 354.Liberti, A., 336.Liberti, W., 336.228.Lide, D. R., 30, 34.Lieb, H., 332.Lieber, E., 348, 349.Lieberman, S., 297, 298,300, 303, 304.Liebmann, H., 356.Lieght, C. H., 41.Lifshits, E. B., 134.Lightfoot, F.R., 340.Lilleland, O., 347.Lillie, R. J., 280.Lilly, R. C., 97, 352.Lindberg, O., 339.Linder, P. J., 358.Linderstrom-Lang, K., 261.Lindh, T., 355.Lindner, R., 351.Lindsey, A. J., 336.Lindsey, A. S., 194.Lindsey, R. V., 95.Line, L. E., 36.Linemann, L., 88.Lineweaver, H., 292, 296.Ling, C. T., 288.Lingafelter, E. C., 24.Lingane, J. J., 332, 333,Link, K. P., 182, 302.Linke, W. F., 102.Linker, A., 237.Linnell, W. H., 204.Linnett, J. W., 13, 14, 25.Linsker, F., 224.Linstead, R. P., 138, 139,Lionetti, F., 355.Lipmann, F., 260.Lipschitz, R., 246.Lipscomb, W. N., 90, 91,Lipton, M., 276.Liquori, A. M., 375.Lister, B. A. J., 97, 352.Lister, M. W., 316.Litt, I., 261.Little, J. A., 248.Little, R.C., 240.Liu, J. C. I., 90, 312.Liu, L. H., 184.Ljunggren, B., 339.Llacer, A. J., 315.Lobakhina, 0. S., 322.Lochte, H. L., 353.Lock, C., 20.Lock, M. V., 175.Lockhart, E. E., 291.Loeb, A. L., 78.Loebl, H., 64, 130.Loftfield, R. B., 124.Lohman, J. B., 26.Lohmar, R., 171.Loidl, A., 316, 318.Loiseleur, J., 252.Long, A. G., 355, 357.Long, F. A., 56, 312.Long, J. V. P., 358.337.161, 167.101, 120398 INDEX OF AUTHORS' NAMES.Long, L..H., 92.Long, M. C., 330.Long, R. F., 144.Longsworth, L. G., 357.Longuet-Higgins, H. C., 7,10, 12, 16, 39, 75, 76, 113,114, 115, 117, 120.Loofbourow, J. R., 17, 344.Lorenz, J. H., 102.Loring, H. S., 247.Los, J. M., 66.Loshkarev, M., 334.Lotmar, W., 369.Loudon, J. D., 185, 186,Louisfert, J., 26.Lounsbury, M., 22.Louw, J.D., 73.Loveless, M. H., 255.Lovell, R., 258.Lowenfeld, R., 181.Lowther, A. G., 355.Lowy, B. A., 220.Lucas, H. J., 142.Lucena Conde, F., 322.Lucey, H. C., 264.Luebner, G. W., 224.Ludy-Tenger, F., 349.Lueacher, . E . , 252.Lufrey, C. W., 38.Lugibihl, K., 300.Luhby, A. L., 262.Lundgren, H. P., 246.Lundin, J. A., 314.Lunt, J. C., 138, 139, 161.Lussmann, D. J., 355.Luszczak, A,, 347.Luthy, N. G., 247.Lutton, E. S., 162.Lutz, R. E., 146.Luz, E., 222.Lykken, L., 318, 333, 336,Lyman, R. L., 279.Lynen, F., 152.Lythgoe, B., 168, 180, 181,182, 183, 225.Lyttleton, J. W., 357.Mabis, A. J., 162.McAfee, K. B., 29, 30, 31,McAllister, R. A., 328,MacArthur, I., 370, 381.McAuslan, J., 24, 348.McBain, J.W., 81, 82, 83.McBryde, W. A. E., 316,McCabe, E. T., 328.McCall, P. J., 300.McCamley, W., 318, 324,McCance, R. A., 291.McCane, D. I., 124.MacCardle, L. E., 326.McCarthy, J. L., 367.188.360.32.337, 340.340.McCarthy, L. V., 43, 91.McCarthy, M., 261,264,265,McCasland, G. E., 218, 219McClelland, J. A. C., 345.McCloskey, C. M., 175.McClure, D. S., 19, 21.Maccoll, A., 12, 42.McCrone, W. C., 349, 350,McCullough, J. D., 90.McCutchan, P., 329.McDevit, W. F., 56.McDonald, F. C., 17.Macdonald, J. Y., 72, 108.MtcDonald, S. F., 215.McDonnell, F.< R. M., 95.McDowell, C. A., 19, 40.McEwen, W. E., 221.McFarren, E. F., 355.McGee, L. L., 223.McGeer, J. P., 71.MrGhie, J. F., 196.MacGillivray, R., 164.McGilvray, D.I., 236.McGlashan, M. L., 76, 77.McGowan, G. K., 347.Macheboeuf, M., 354, 355.Machin, K. E., 347.MacIntire, W. H., 323.MacIntosh, R. M., 324.McIntyre, A. R., 339.Mack, G. E., 302.McKean, D. C., 27.McKee, W. E., 99.McKellin, W. H., 147.Mackereth, F. J. H., 340.McKerns, K. W., 272.McKinney, D. S., 30, 359.Mackle, H., 37, 38.McKusick, B. C., 231.MacLachlan, E. A., 302.McLamore, W. M., 202.McLaughlin, K. C., 219.McLem, J., 198.Macleod, C., 254.MacLeod, C. M., 251.MrMahon, R. E., 133.MvMaster, P. D., 269.McMillan, F. A., 145.MacMillan, J., 210, 211.McMillan, W. G., 65.M. Mullen, A. I., 85.McLNabb, W. M,, 317, 324.McNulty, J. S., 324.McOmie, J. F.W., 184, 191,MacWilliam, I. C., 236.Madden, R. J., 280.Madigan, J. R., 30.Madison, C. R., 270.Madison, J. C., 32.Magasanik, B., 356.Magee, R. J., 313, 356.Maggiolo, A., 224, 225.Maginnity, P. M., 215,MagnBli, A., 102.357.225, 356.Magnussan, H. T., 254.Magrun, W. H., 346.Mainoni, M., 220.Maissen, B., 109.Majumdar, A. K., 341.Majury, T. G., 49.Makar, S. M., 332.Makino, K., 284.Mako, L. S., 92.Malamand, F., 345.Malatesta, A., 332.Malissa, H., 313, 314, 359.Malkiel, S., 256, 261, 262,Malkin, T., 164.Malmstadt, H. V., 337.Malmstrom, B. G., 340.Maloney, D. E., 132.Malowan, L. S., 328.Mancera, O., 207.Mandelberg, C. J., 104.Manelli, G., 326.Mann, F. W., 114.Mann, M. J., 222.Manske, R. H. F., 228, 229.Manson, L.A., 247.Manson, W. S., 198, 199.Marbet, R., 237.Marchand, A., 22.Marcus, R. A., 47.Mariani, A,, 343.Marignan, R., 22.Marimpietri, L., 239.Marin, Y., 318.Marion, L., 228, 234.Markham, R., 246,247,356.Marko, A., 359.Markovi6, D., 349.Marks, G. W., 340.Markunas, P. C., 310.Marlow, H. W., 300.Maron, D. M., 356.Marquette, M. M., 287.Marquez, M. C., 330.Marrack, J. R., 250, 263,264, 267, 272, 275.Narrais, E. J., 355.Marrian, G. F., 297, 298,299, 301, 302, 303.Karsh, A. E., 46.Harsh, C. A., 183.Harsh, J. K., 94, 312.Harshall, J. M., 270.Harshall, J. R., 215, 224.garshall, L. M., 354.Harshall, M. E., 265.Marshall, R., 46.Marshall, W. L., 103.Hartin, A. E., 24, 25, 348.Hartin, A. J. P., 294, 351,Hartin, D.R., 92.Nartin, E. C., 356.Hartin, F., 328, 330,Martin, K. E., 93.Hartin, R. H., 149.273.354, 356INDEX OF AUTHORS’ NAMES. 399Martin, R. L., 92.Martinek, R. G., 277.Martinez, H., 204, 208.Martini, E., 326.Marvel, C. S., 146.Marzadro, M., 330.Mmazumi, N., 157.Maschka, A., 58.Mmdupuy, E., 95.Meson, A. C., 312, 317, 341,Mason, G. W., 100, 104.Mason, H. L., 261, 297, 303.Mason, H. S., 216.Mason, J. P., 328.Mason, M., 167.Mason, R. G., 160.Masouredis, S. P., 256.Masson, C. R., 59.Mataix, C., 321.Matalon, R., 85, 86.Mstheson, M. S., 49.Mathieson, D. W., 204.Mathieu, J. P., 22, 23.Mathis, R., 29, 30.Mathis, W. C., 347.Mathot, V., 76, 77.Metijevic, E., 78.Matlin, N. A., 314.Metlock, J., 32.Matossi, F., 24, 26.Matsen, F.A., 10.Matsukawa, T., 220.Matsukuma, A., 189.Matsumoto, S., 186.Mattair, R., 97.Mattner, J., 322, 331.Mattner, R., 331.Mattoon, R. W., 81.Matty, H., 61.Maurer, K., 183.Maurer, P. H., 261.Maumkas, J., 164.Mawry, L. G., 142.Maxwell, G. E., 107.Maxwell, J. A., 335.Maxwell, L. R., 38.Maxwell, R. D., 358.May, E. L., 145.May, L. G., 332.May, M., 227..May, S., 54.Mayer, A., 341.Mrtyer, M. M., 249, 250,274.Mttylott, A. O., 329.Mayo, F. R., 49.Mayot, N., 188.Mays, J. M., 30, 32, 34.Mazur, A., 261, 265.Mazur, R. H., 120, 184.Mazureke, C., 251.Mazza, F. P., 216.Mead, J. F., 331.Meakins, G. D., 186.Mech, J. F., 104.Mecham, D. K., 245.343.Medalia, A. I., 52, 331.Medz, R., 301.Meek, H.V., 340.Maersche, M. van, 46.Mehl, J. W., 237.Mehler, A. H., 282.Mehltretter, C. L., 175, 183.Mehrotra, R. C., 327.Meibohm, A. W., 88.Meier, J., 328.Meikle, R. D., 209.Meister, A., 137.Moister, A. G., 30.Maites, L., 325, 334.Melander, L., 129.M dchior, L. R., 256.Metlies, R. L., 183.MAlish, S. F., 48.Mellon, M. G., 332, 335, 338,Mellor, D. P., 53.Melnick, D., 277, 290.Meloche, V . W., 311.Mel\ ille, H. W., 48, 49Meliin, E. H., 345.Menzel, A. E. O., 263.Mercer, E. H., 369.Merikanto, B., 333.Mero, K., 282.Merritt, F. R., 31.Merton, (Sir) T., 17.Merz, J. H., 128.Messerly, G. H., 42.Messikommer, B., 30.Metralfe, W. S., 63.Meter, R. van, 329.Meyer, A., 198.Meyer, A. S., 342.Meyer, D., 239.Meyer, H.W. H., 353.Meyer, K., 237.Meyer, K. H., 237.Miccioli, B. R., 315.Michael, S. E., 366.Micaheals, ,4. S., 80.Micheel, F., 167, 183.Michel, R., 252.Micheli, R. A., 146.Michl, H., 357.Miescher, K., 200, 204, 209.Migeotte, M. V., 30.Migeotte, P., 18.Migliorst, J. C. A., 330.Miholib, S., 335.Mijo\ib. M. V., 196.Milazzo, G., 326, 327.Miles, L. W. C., 213.Miles, S. E., 42.MiliEevi6, B., 352.Milkonian, G. A., 45.Miller, A. D., 337.Miller, A. M., 303.Miller, A. R., 74.Miller, C. C., 313, 319, 356.Miller, E. E., 343.Miller, G. A., 73.347.Miller, G. L., 343.Miller, H., 263.Miller, I., 79.Miller, I. K., 59.Miller, J. F., 103.Miller, J. G., 36.Miller, J. M., 350, 351.Miller, R.E., 155, 261.Miller, S. I., 141.Miller, V. B., 54.Miller, W. J., 339.Miller, W. L., 324, 341.Milligan, W. O., 81.Mills, C. S., 310.Mills, E. C., 311, 319, 340.Mills, R. L., 44.Milner, G. W. C., 325, 335,Milner, O., 317.Milsted, J., 72.Minden, H. T., 30, 31, 34,280, 281.Miner Lireaga, J., 319.Minkoff, G. J., 348.Minne, L. J. van der, 357.Miramontes, L., 210.Miranda, F. P., 291.Mirna, A., 58.Mislow, K., 137, 147.Mistrp, S. P., 290.Mitchell, A. T. S., 108.Mitchell, H. K., 282, 283,Mitchell, J., 359.Mitchell, J. W., 358.Mitchell, K. M., 108.Mitchell, R. A., 204.Mitchell, R. J., 344.Mitchell, R. W., 30.Mitchison, J. M., 375.Mittag, R., 343.Mittelman, R., 82.Mittledorf, A. J., 346.Miwa, M., 331.Miyazaki, S., 71.Mizushima, S., 23, 240, 366.Moe, G., 20.Moe, H.S., 348.Moeller, T., 94, 354.Mnffett, It. B., 148.Moffitt, W. E., 9, 13, 15.M )hammad, A., 245.MrJhler, F. L., 20.Rlohn, J. F., 254.Mahr, P. H., 98.Moignard, L. A., 353.Moir, G. M., 340.M llenhower, H. P., 333.Molnhr, L. G., 322.M naghan, P. H., 350.Monier, J. C., 349.Monllor, E., 327.Monnier, D., 334, 335.Monnot, G., 345.342.284, 286.Montequi Diaz de Plaza, F.,343400 INDEX OF AUTHORS’ NAMES.Montgomery, R., 173, 177,Moon, K. A., 332.Moore, A. M., 251.Moore, D. H., 250.Moore, G. E., 100.Moore, R. T., 329.Moore, R. W., 329.Moore, S., 294.Moore, W. J., 43, 60, 363.Morales, M. F., 275.Morani, V., 339.Morette, A., 321, 326.Morgan, A. F., 286.Morgan, C., 380, 382.Morgan, K.J., 58.Morgan, L. O., 104, 358.Morgan, W. T. J., 237, 255,265, 266, 267, 268, 355.Morgenthau, J. L., 146.Mori, K., 18.Morino, Y., 38.Moroe, T., 161.Moroni, E., 359.Morris, A. L., 47.Morris, C. J. 0. R., 299, 304.Morris, P., 299, 304.Morris, Q. L., 353.Morris, T. H., 54.Morrison, A. L., 144.Morrison, G. H., 353.Morrison, G. R., 343.Morrison, J., 66.Morsan, B., 319.Morton, R. A., 150, 224.Mosby, W. L., 145.Mosettig, E., 145.Mosher, H. S., 220.Moskowitz, M., 268.MOSS, J. A., 238.Motsch, W. L., 318.Mott, N. S., 317.Mousa, A. A., 336.Mowery, D. F., 350, 352.Mudrak, A., 133.Miiller, A., 190.Mueller, C. R., 8.Muller, H. M., 356.Mueller, K. H., 42.Muller, M., 286.Muller, 0.H., 333, 334.Miiller, R., 351.Muller, R. H., 351, 354.Muhlschlegel, H., 178.Mukai, T., 186, 189.Mukherjee, S., 180.Mukherji, S. M., 210.Mulholland, T. P. C., 210.Mulligan, J. F., 12.Mulligan, W., 256, 269, 271,Mulliken, C. A., 12.Mulliken, R. S., 12, 13, 15,Munch, R. H., 347.Mund, W., 64.178, 237.272.16.Munday, L., 191.Munger, J. R., 312.Munier, R., 355.Munoz, J., 263, 276.Munson, P. L., 300.Murai, F., 229.Murakami, Y., 338, 340,Murawski, J., 41.Murgier, M., 102.Murphey, W. A., 220.Murphy, G. M., 19.Murphy, G. W., 73.Murphy, R. W., 346.Murray, A,, 289.Murray, C. W., 296.Murray, E. S., 270.Murray, J. P., 264.Murthy, D. S. N., 320.Murthy, T. K. S., 313, 320.Musgrave, 0. C., 167.Musso, H., 152, 355.Muxart, R., 54.Muglle, R., 338.Muiik, F., 328.Myers, A.T., 344.Myers, G. E., 81.Myers, G. S., 161.Myers, R. J., 352.Mynors, L. S., 257.Myrback, K., 250.Nachmias, G., 313.Nagasko, N., 71.Nager, M., 168.Naish, J. M., 17, 346.Najjar, V. A., 260, 277.Nakaguchi, K., 229.Nakata, S., 101.Nakayama, Y., 186.Nakazaki, M., 187.Nance, J. T., 320.Nance, K. W., 341.Nancollas, G. H., 310.Nappi, R., 251.Narayanan, P. S., 23.Nardelli, M., 313.Nash, H. A., 356.Nash, L. K., 336, 359.Nason, A., 281.Yasr, H., 237.Natelson, S., 341.Nathanson, I. T., 299.NaudB, S. M., 17, 344.Naylor, C. R. E., 274.Yazarova, T. I., 333.Nebbia, L., 318.Xebel, I., 209.Nebel, R. W., 122.Nebergall, W. H., 96.Nechamkin, H., 107, 328.Nechvatal, A., 130.Yeedham, D.M., 305.Xeel, J. C., 329.Yeelakantam, K., 3 18.Nef, J. U., 169.342, 343.Neiding, A. B., 88.Neiman, M. B., 54.Neish, A. C., 354.Nelb, R. G., 125.Nelson, D. H., 299,304, 305.Nelson, J. A,, 191.Nelson, L. S., 328.Nesbitt, S. S., 141.Ness, A. T., 172.Ness, R. K., 146, 176, 182.Neu, J. T., 23, 314.Neuberger, A., 166, 167,Neuerberg, G. J., 350.Neumayer, J. J., 341.Neunhoeffer, O., 315.Neurath, H., 293.Neuss, J. D., 359.Neuzel, E., 257.Neville, H. H., 80.Newbold, G. T., 205, 206,Newcombe, H., 340.Newman, K. J., 347.Newman, M. S., 145, 219.Newman, R., 26.Newth, F. H., 174, 175.Nichol, J. C., 253.Nicholas, J. W., 338.Nicholas, L., 310.Nicholas, R. E. H., 215,Nicholas, S.D., 174.Nicholls, R. W., 17.Nicholson, A. J. C., 61.Nicholson, D. G., 360.Nicholson, G. R., 132.Nickerson, M., 263, 264.Nicol, J. C., 273.Nielsen, A. H., 28, 29, 31.Nielsen, H. H., 25, 28, 29.Nielsen, J. R., 30.Niemann, C., 137, 240, 266,Nijkamp, H. J., 354.Nippler, R. W., 312.Nisbet, H. B., 220.Nisculescu-Schreher, C.,Nishi, K., 284.Nishimura, E. T., 260.Nivoli, M., 325.Nixon, E. R., 27.Njegovan, V., 319.Noakes, F. D. L., 324.Noble, R. H., 29.NbgrQdi, J., 98.Noguchi, J., 246.Noll, J. E., 95.Nook, R. J., 332.Nord, F. F., 155.Norman, H. H., 315.Norman, (Miss) J. M., 184.Norris, F. W., 277.Norris, T. H., 101.Norris, W. M., 277.364. -226.352.267.100INDEX OF AUTHORS' NABfES.401Northrop, J. H., 253, 292,Norton, D. G., 211.Norton, D. P.. 296.Norton, F. J., 43.Norton, J. M., 301.Norton, S., 273.Norwitz, G., 325, 333, 339,Nomitz, I., 339, 341, 360.Novellie, L., 355.Novic, B., 342.Nowakavsky, S., 261.Noyea, R. M., 141, 313.Nozoe, T., 36, 132, 185, 186,188, 189, 190.Nuciari, T., 345.Nudenberg, W., 127.Nui, T. Y., 20.Nunn, J. R., 161.Nutten, A. J., 313,314, 315,317, 324, 326, 327, 337.Nutting, M.-D. F., 295.Nyc, J. F., 282, 286, 356.Nyholm, R. S., 88, 96,Nyman, C. J., 54.OakIey, C. L., 259.Oblad, A. G., 65.O'Brien, A. S., 311.O'Brien, J. R. P., 277.O'Brien, M. G., 359.Ochiai, E., 129, 221.Ockerman, L. T., 325.Ockrent, C., 164.Odekerkon, J. M., 314.Odencrantz, J. T., 352.Odioso, R.C., 125.O'ertel, A. C., 31 1, 346.Oetjen, R. A., 348.Ogg, C. L., 328, 329, 330.Ogg, R. A., 43.Oginsky, E. L., 262.O'Gorman, J. M., 142.Oka, Y., 324.Oksengorn, B., 20.Oldfield, A., 31 1.Oldham, G., 353.Olitsky, P. J., 252.Oliveto, E. P., 148.Ollis, W. D., 36, 184, 214.Olmsby, A. A., 343.Olmsted, P. C., 299.Ohen, S., 154, 210.Olson, A. R., 55, 56.O'Neill, A. N., 236.O'Neill, J. J., 167.O'Neill, W. R., 345.Opfer-Schaum, R., 328.Orange, M., 340.Orlansky, E., 258.Orloff, D., 13.Orloff, H., 13.Orlova, L. M., 352.294.341, 360.NOY88, W. A., 61.109.REP.-VOL. XLVIIT.Orr, L. W., 346.Osato, R. L., 153.Osborn, D. A., 268.Osborn, G. H., 313, 333Oser, B. L., 277, 290.Oster, J., 381.Ostertag, H., 340.Ostroumov, E.A., 320.Oswalt, R. L., 352.Ottar, B., 192.Ottesen, M., 261.Ouchterlony, O., 276.Oudin, M. H., 260.Oudin, M. J., 276.Ovenston, T. C. J., 338,Overbeck, R. C., 333.Overbeek, J. T. G., 78.Overbury, L. R., 138.Overell, B. G., 350.Ovorend, W. G., 170, 171,172, 174, 176, 177, 179,180, 181, 182, 183, 248.347.347.Overhoff, J., 221.Overman, R. S., 302.Owen, E. D., 286.Owon, L. E., 344.Owen, L. N., 171, 172, 176,Owens, H. S., 354.Owens, R. D., 358.Oza, T. M., 323.Oza, V. T., 323.Ozier, M. A., 319, 341.Pack, D. H., 65.Packer, D. M., 20.Paddock, N. L., 144.Padmanabham, V. M., 23.Padowetz, W., 329, 330.Page, I. H., 299.Palin, -A., 23.Pallares, E. S., 227.Pallaud, R., 322.Palmer, A., 183, 236.Pulubinskas, F.S., 38.Pannell, J. H., 358.Panteleeva, L. J., 336.Paoloni, L., 326, 327.Papa, D., 210.Pappenheimer, A. M., 253.Pardee, A. B., 252, 274,Parfenova, K. G., 320.Parfentjev, I. A., 256.Parham, W. E., 211.Paris, R., 109, 312.Parish, H. J., 258.Park, J. D., 29.Parke, T. V., 348.Parker, R. E., 130.Parker, R. P., 227.Parkor, W. G., 101.Parks, T. D., 318, 330, 333,177, 213.275.336.Pam, R. G., 8, 10, 12, 21.Parravano, G., 50.Parry, E. P., 335.Parry, H. J., 259.Parry, R. W., 144.Partington, J. R., 80.Partridge, M. W., 354.Partridge, S. M., 266, 352,Pascard, R., 98.Pashkina, T, S., 284.Pashler, P. E., 27.Pasovskaya, G. B., 337.Passow, H., 347.Pasternak, V. Z., 261.Patel, C. B., 343.Patel, S.R., 97.Patriok, J. B., 216.Patterson, G. D., 332.Patterson, H. R., 300.Patterson, J., 300.Patterson, J. A., 105.Patterson, J. H., 108, 335.Patterson, J. Y. F., 298.Patterson, L. J., 348.Patton, A. R., 355.Paul, R., 210.Pctuling, L., 36,37,241,243,244, 262, 274, 275, 307,369, 375, 377, 378.Pauling, L. S., 13.Pausackor, K. H., 125.Pauson, P. L., 186.Pautrizel, R., 257.Pavlenko, M. M., 329.Peacock, D. H., 164.Pearce, D. W., 312. .Pearce, R. S., 114.Peard, M. G., 58.Fearsall, H., 93.Pearse, R. W. B., 17.Pease, R. N., 43.Feat, S., 174.Pechmann, E. von, 367.Peck, R. L., 328.Pecka, E., jun., 301.Pedersen, K. O., 245.Peerdeman, A. F., 135, 361.Pelley, R. L., 145.Penasse, L., 239.Penbrick, P.L., 19.Peniston, Q. P., 357.Pennetier, G., 17.Ponney, J. R., 355.Penny, G. F., 218.Penther, C. J., 321.?epkowitz, L. P., 314, 328.'eppard, D. F., 100, 104.?epper, C. R., 290.'ercival, E. G. V., 236,'ereira, R. S., 343.'erez, J. J., 251, 258.'erlman, I., 104.'erlmann, G. E., 267.0364.PeMer, s. s., 27.237402 IPerlzweig, W. A., 277, 278,Perold, G. W., 330.Perrin, D. R., 340.Perriot, G., 332.Perry, V. G., 344.Perutz, M. F., 241, 244, 363,367, 369, 370, 372, 373,375, 379, 381.Pesson, M., 226.Pestemer, M., 347.Peterman, M. L., 264.Petermann, H. C., 252.Peters, C. W., 24.Peters, E. D., 329.Peters, T., jun., 264.Peterson, G. E., 346.Peterson, M. J., 345.Petrow, H. G., 336.Pettet, R., 114.Pfeiffer, P., 140.Plister, K., 218, 226.Pfleger, K., 331.Phelps, F.P., 25.Philippoff, W., 83.Phillips, A., 214.Phillips, J. P., 312.Phillips, P. H., 254, 258.Philpotts, A. R., 24.Picken, L. E. R., 369.Piepenbrink, H. F., 155.Pierce, J. G., 238.Pieruccini, R., 344.Pientenpol, W. J., 32.Pietruck, C., 99, 321.Pigman, W., 183.Pigman, W. W., 169.Pignard, P., 314, 340.Pimentel, G. C., 26.Pinajian, J. J., 358.Pinchas, S., 348.Pincus, G., 209, 297, 299,300, 307.Pines, H., 148.Pink, R. C., 95.Pinkerton, R. C., 325.Pino, F., 326.Pirenne, R. L., 44.Pirlot, G., 348.Pirotte, J., 338.Pitance, T., 99.Pitiot, J., 330.Pittmann, R. W., 317.Pitts, J. N., 333.Pitzer, K., 26, 107.Pitzer, K. S., 192.Pizarro, A. V., 315.Plager, J., 301.Plane, R.A., 108.Plant& J., 310.Platt, J. R., 14, 16, 21.Platt, P. C., 356.Plattner, P. A., 190, 191.Platzer, G., 158.Plaut, H., 155.Pliva, J., 156, 194, 196.281, 286.DEX OF AUTHORS’ NAMES.Ploquin, J., 330,Plyler, E. K., 24, 25, 29, 30.Podchaynova, V. N., 341.Po& A. J., 13.Pohl, F., 341, 344.Pohl, H., 339.Pohland, A., 227.Pohorsky, J., 353.Pokras, L., 319.Polanyi, M., 39.Polatnick, J., 158.Polen, P. B., 168.Polgar, N., 163.Polis, B. D., 265.Pollak, F. F., 338.Pollak, P. I., 126, 127.Pollard, A. G., 339, 340.Pollard, F. H., 356.Polonovski, M., 226.Polson, A., 355.Polya, J. B., 343.Ponce, J. S., 360.Ponder, E., 249.Pontecorvo, G., 282.Pope, C. G., 256, 262, 292.Popenoe, A. E., 137.Pople, J.A., 11, 14, 16.Porcelli, P.. 23.Porter, C. C., 287, 301, 305.Porter, G., 18, 19.Porter, R. R., 239, 244, 255,Porter, W. L., 350.Portillo, R., 335.Poshkus, A. G., 127.Posternak, T., 219.Potratz, H. A., 341.Potter, A. L., 236.Potter, R. L., 254.Poulet, H., 23.Poulton, F. C. J., 334, 340.Pouvreau, J. M., 345.Powell, A. S., 348.Powell, D., 282.Powell, H. M., 12, 224.Powell, J. E., 94, 352.Powell, R. E., 59, 98.Power, M. H., 303.Powling, J., 28.Powney, J., 80.Pozefsky, A., 348.Pradhan, M. K., 196.Prelog, V., 184, 193, 198,219, 231, 232, 234, 235.Presser, R., 318.Pressman, B. C., 172.Pressman, D., 252, 256,257,258, 262, 271.Pfibil, R., 312.Price, C. C., 268.Price, H. P., 312.Price, J.W., 360.Price, W. C., 21, 24, 348.Price, W. J., 21.Prichard, B. S., 32.Prigogine, I., 40, 75, 76, 77.256, 258, 261, 294.Prins, D. A., 179, 180, 181.Prins, H. J., 154.Prins, J. A., 361.Pritchard, H. O., 14.Procter, D. P., 355.Prodinger, W., 341.Prudhomme, R. O., 261.Pryde, A. M., 220.Puell, M., 331.Puente, H. A., 58.Puenzieux, J. P., 345.Pugh, W., 322.Puister, A., 226.Pulford, A. G., 29, 213.Pulido Cuchi, F., 328.Pullman, A., 113.Pullman, (Mrs) A., 188.Pullman, B., 7, 113, 188.Pungor, E., 322, 326.Purnam, T. M., 103.Purrmann, R., 226.Purushottam, A., 320.Purvis, E. R., 342.Quatinetz, M., 341.Quayle, J. R., 357.Quehl, K., 140.Quick, Q., 342.Quinn, M. J., 130.Raaen, K. P., 52.Rabinowitz, J., 338,Radmacher, W., 339.Raff, P., 318.Rahn, H.J., 315.Rajagopalan, S., 149, 205.Raju, N. A., 318.Ralph, B. J., 197.Ralston, A. W., 86.Ramage, G. R., 194.Raman, (Sir) C. V., 34.Ramasarma, G. B., 287.Ramasastry, C., 19, 20.Ramirez-Muiios, J., 344.Ramon, P., 259.Ramsay, D. A., 29, 228.Ramsay, J. A., 311, 347.Ramsey, L. L., 351, 354.Randall, K. J., 259.Randall, R., 265.Randall, S. S., 351, 353.Randolf, C. L., jun., 91.Rank, D. H., 17, 30.Rao, B. R. L., 320.Rao, B. S. V. R., 313, 319,Rao, P. S., 355.Raper, H. S., 216.Raper, R., 223.Raphael, R. A., 132, 163,173, 185, 186.Rapoport, H., 147, 228.Rapport, M. M., 217, 237.Rastrup-Andersen, J., 32.Rathgeb, P., 237.320INDEX OF AUTHORS’ NAMES. 403Ravel, J.M., 227.Ray, A. N., 23.Rly, P., 109.Raymond, W. D., 277.Raymond-Hamet, 234.Rayner, L. S., 225.Read, D. H., 268.Read, D. R., 310.Reboul, P., 314.Rebstock, M. C., 219.Rector, C. W., 16.Reddi, K. K., 278, 287, 289.Reding, F. P., 26.Reed, H. W. B., 184.Reed, R., 380.Reed, S. A., 359.Rees, A. L. F., 369.Rees, H. G., 277.Rees, M. W., 239.Reese, H. D., 343.Reeve, K. D., 183.Reeves, R. E., 178, 183,236.Reeves, W. A., 357.Reguera, R. M., 355.Reich, H., 149, 299, 304,Reichard, P., 248.Reichert, E., 152.Reichstein, T., 149, 179,180, 181, 306, 355.Reid, C., 21, 28, 29.Reid, S. G., 236, 355.Reid, T. G., 41.Reilley, C. N., 333, 334.Reimann, W., 340.Reimer, C. B., 344.Reimers, F., 315, 321.Reinebeck, L., 19.Reinhold, J.G., 250.Reith, J. F., 316.Reitsema, R. H., 223.Reitz, L. K., 311.RBmy, J., 330.Renard, M., 354.Renfrew, A. G., 356.Renner, H., 314.Renton, P. H., 268.Renz, J., 214.Repin, S. A., 322.Revinson, D., 337.Rhein, H. C., 340.Rhoads, C. P., 303.Rhodes, R. G., 349.Rhodin, T. N., 66.Ribas, I., 330.Ribley, A. M., 348.Ricci, J. E., 90, 102, 107.Ricciuti, C., 329, 359.Rice, B., 21, 24, 91.Rice, E. W., 343.Rice, F. O., 42.Rice, 0. K., 47.Rice, R. G., 351.Richards, D. E., 271.Richards, G. N., 175.Richards, P. H., 82.305.Richardson, E. G., 84.Richardson, J., 20.Richardson, R. L., 93.Richardson, W. S., 29, 30.Richou, R., 259.Richter, F., 246.Richtmyer, N. K., 172, 174,176, 177, 180.Rickard, R.R., 331.Riddick, J. A., 310.Rideal, (Sir) E. K., 67, 86.Ried, W., 156.Riegel, B., 223.Rieke, C. A., 13.Rieman, W., 352.Rigby, W., 149, 220.Rigg, M. W., 36.Riggs, N. V., 168.Righini, G., 338.Riley, D. P., 375.Riley, J. P., 343.Rimington, C., 167, 215,Rinck, E., 340.Ringold, H. J., 132, 149,Rist, C. E., 183.Ritchie, A. B., 358.Ritchie, M., 62.Ritter, H. L., 93.Ritter, J. J., 155.Rius Mir6, A., 337.Rivet, C. A., 350.Robb, J. C., 49.Robbins, J. M., 215.Robbins, W. J., 158.Roberts, A., 32.Roberts, D. W. A., 330.Roberts, H. E., 259.Roberts, J. C., 225.Roberts, J. D., 120, 133,Roberts, L. E. J., 359.Roberts, R. M., 274.Robertson, A., 197, 216.Robertson, E., 305.Robertson, J. H., 343.Robertson, J.M., 10, 132.Robichaux, T., 338.Robin, S., 20, 78.Robins, A. B., 65.Robinson, A. M., 299, 301,Robinson, A. R., 347.Robinson, C., 378.Robinson, C. A., 218.Robinson, D. Z., 27, 348.Robinson, J., 278.Robinson, (Sir) R., 133, 163,200, 204, 216, 217, 230,234.Robinson, T. S., 130.Rochester, J. C. O., 24.Rock, S. M., 349.Rockland, L. B., 354.Rockstein, M., 339.220.187, 208.184.338, 347.Rodda, H. J., 226.Rodden, C. J., 360.Rodeck, H., 324.Roder, T. M., 215.Rodewald, B., 335.Rodwell, R., 222.Roe, A., 45.Roe, E. M. F., 17, 347.Roe, E. T., 332.Roelen, O., 154.Roess, L. C., 348.Rogers, J. D., 32.Rogers, L. B., 333.Rogers, M. A. T., 210.Rogers, R. G., 32.Rogier, E. R., 184.Rolfe, A. C., 341.Rollo, I.M., 225.Romand, J., 18, 20.Romano, C., 356.Romanoff, L. P., 299, 301.Romero, M., 146.Rometsch, R., 353.Romo, J., 146, 204, 206,Ronez, C., 351.Ronwin, E., 248.Roothaan,C. C. J., 8,11,12.Rose, A. S. B., 250.Rose, F. L., 225.Rosebeek, S., 350.Roseman, S., 182.Rosen, B., 18.Rosen, F., 278, 281, 286.Rosenbaum, E. J., 347.Rosenblatt, D. H., 356.Rosenfeld, D. A., 174.Rosenfelder, W. I., 192.Rosonkranz, G., 146, 149,204, 206, 207, 208, 209,210.Rosenthal, I., 335.Rosevear, F. B., 81.Ross, A. G., 237.Ross, I. G., 10, 34.Rossi, G. B., 103.Rossi, M. L., 326.Rosm, G., 380.Rotariu, G. J., 98.Rotenberg, D. L., 24.Roth, B., 227.Roth, H., 343.Roth, L. J., 289.Rothchild, S., 165.Rothen, A., 275, 294.Roudier, A., 332.Roulier, P., 255.Rousset, J., 22.ROUX, E., 346.ROUX, M., 113, 117.Rovery, M., 292, 295.Rowen, J.W., 236.Rowlands, W. T., 259.Rubin, M., 148, 209.Rubin, S. H., 281.Ruby, W. R., 334209404 INDEX OF AUTHORS’ NAMES.Rudkin, G. J., 282.Rudnicki, R. P. T., 95.Rudenberg, K., 8.Rueff, L., 152.Ruff, S. U., 198.Rugg, F. K., 348.Rugg, F. M., 24.Ruhstaller, R. E., 357.Rukhadze, E. G., 318.Rulfs, C. L., 335. ’Rummert, G., 159.Rundle, R. E., 95, 102, 106.Rundle, R. F., 118.Rupert, C. S., 24.Rupp, W., 223.Ruppelt, E., 221.Rusconi, Y., 314, 335.Rushbrooke, G. S., 9.Rushbrooke, S., 114.Rusig, H., 32.Russell, A. S., 93.Russell, D. S., 352.Russell, F. R., 341.Russell, K. E., 28.Russell, M., 164.Russell, P.B., 224, 225,226.Russell, R. G., 345.Rustigian, R., 268.Rutgers, A. J., 357.Rutherford, P., 335.Ruthven, C. R. J., 353.Rutkowski, H. R., 355.Rutter, L., 350.Rutz, G., 170.Ruyle, W. V., 206.Ruzicka, L., 184, 196, 197,198, 199, 200.Ryan, D. E., 315,342.Ryan, J., 298.Ryan, J. J., 214.Ryazanov, I. P., 314.Rydon, H.N., 136,155,194.Ryer, F. V., 81.Sack, R. A,, 34.Sack, W., 341.Saenz, A. C., 252.Safary, E., 18.Saflord, H. W., 330.St. John, G. B., 22.Sekan, T., 166, 187, 283.Saksena, B. D., 20,23, 30.Sales Grade, M. R., 319.Salg6, E., 332.Sallay, I., 137, 219.Sall6, M., 102.Sally, D. J., 79.Salmon, J. E., 323.Salmon, W. D., 279.Salzburg, Z. W., 62.Samuels, L. T., 304, 306.Samuelson, O., 352.Shnchez, J.A., 327.SAnchez Serrano, E., 346.Sandell, E. B., 338, 339,341.Sandorfy, C., 7, 113.Sanger, F., 238, 239, 240,255, 261, 293.Santappa, M., 50.Sanyal, S. B., 23.Sane Pedrero, P., 335.Sapir, M., 330.Sarauf, M., 54.Sareen, K. N., 147.Sarett, L. H., 146, 149.Sarma, B., 109.Sarma, P. S., 278.Sarudi, I., 320.Sass-KortsAk, A,, 305.Sato, K., 190.Sato, Y., 331.Sattizahn, L., 54, 106.Saunders, P. R., 334.Sauvage, G. L., 230.Savage, D. J., 339.Savell, W. L., 330.Sax, K., 205.Saxer, E. T., 319.Saxton, J. E., 216.Sayce, L. A., 17.Saylor, J. H., 317.Schaad, E., 319.Schafer, E., 152.Schaefer, F. E., 228.Schafer, H., 99, 321.Schafer, W., 152.Schaeffer, A., 318.Schaeffer, G. W., 92.Schaeffer, H.J., 314.Schaeffer, R., 92.Schafer, J. G., 145.Schaffer, E. R., 326.Schaffer, R., 169.Schall, E. D., 351.Schayer, R. W., 286.Scheer, B. T., 282, 286.Scheer, J. van der, 253.Seheffer, F, E. C., 78.Scheibl, F., 343.Scheifele, H. J., 130.Schenck, H. J., 331.Schenkel, H., 133.Schenkel-Rudin, M., 133.Schenker, V., 307.Scherbakov, A. A., 336.Schetzler, E., 213.Scheur, E., 311.Schick, B., 250.Schiller, S., 306.SchiIling, E. E., 96.Schindler, O., 355.Schinkel, M., 300.SchinIe, R., 178.Schissler, D., 69, 70.Schissler, D. O., 45.Schlrtck, P., 154, 239.Schlaich, J., 324.Schlecht, W. G., 311.Schleicher, A., 336.Schlenk, H., 146.Schlenk, W., 156.Schlesinger, H. I., 89, 92,Schlittler, E., 212, 233, 234.Schlochauer, M., 59.Schlossberger, H., 284.Schlubach, H.H., 157.Schmeidler, G. A., 200.Schmid, H., 148, 213.Schmid, M. D., 178.Schmidt, E., 170.Schmidt, H., 249, 316.Schmidt, 0. T., 181, 356.Schmitt, F. O., 379, 380.Schmitt, G. M. J., 382.Schmitt, W., 226.Schmitz, H., 18.Schmitz, W., 339.Schmutz, J., 180.Schmutz, J. V., 64.Schneider, J. J., 300, 303.Schneider, W., 315.Schnieder, W. P., 206.Schnetzler, E., 148.Schoeb, E. J., 347.Schogl, K., 228.Schoen, L., 19.Schonfeld, T., 358.Schoniger, W., 327, 331,Schoening, M. A., 339.Schopf, C., 226.Schoffstall, D. G., 345.Schofield, K., 213.Scholl, M. L. L., 262.Scholte, T. G., 35.Schomaker, V., 13, 32, 36,Schottey, J., 54.Schouten, A,, 329.Schreiber, K., 121.Schreiner, H., 65.Schrenk, H.G., 344.Schrenk, W. G., 346, 347.Schreuders, M. A., 329.Schreyer, J. M., 315, 325.Schroeder, W. A., 238, 245.Schubert, E. N., 218.Schubert, J., 352.Schueler, F. W., 146.Schuler, H., 19.Schuette, €3. A., 351.Schufle, J. A., 94.Schuhardt, V. T., 255.Schuldiner, J. A,, 350.Schuler, B., 357.Schuler, K. E., 17.Schuler, R. H., 62.Schull, H., 19.Schuller, W. H., 137.Schulman, J., 86.Schulman, J. H., 82, 86.Schultz, J., 282.Schultze, M. O., 343.Schulz, K., 78.Schumacher, H. J., 18.Schumacher, J. G., 344.108, 143.332.37, 38, 91, 120, 363INDEX OF AUTHORS’ NAMES. 405Schuster, C., 154.Schuster, H. F., 357.Schute, J. B., 355.Schutze, H., 255.Schwartz, J., 251.Schwartz, N., 322.Schwartz, T.B., 264.Schwarz, H., 233, 234.Schwaw, V., 357.Schwarzenbach, G., 108,Schweigert, B. S., 282, 285,Schwenk, E., 146, 210.Schwerin, P., 252, 293.Schwert, G. W., 293, 295.Schwyzer, R., 147.Scott, A. F., 17.Scott, A. I., 186.Scott, 0. P., 188.Scott, R. E., 95.Scott, R. L., 73.Scott, T. E. L., 318, 324,Scouloude, H., 375.Scribner, B. F., 310.Scruby, R. E., 29.Scudi, J. V., 277.Seaborg, G. T., 103, 104.Searcy, A. W., 92.Searles, S., 210.Sears, K., 221.Seaton, D. L., 95.Seay, W. A,, 347.Sebba, F., 96.Secor, G. E., 330.Secoy, C. H., 103.Seebeck, E., 138, 167.Seebohm, P. M., 263.Seeds, W. E., 381, 382.Seel, F., 98.Segal, L., 343.Sehon, A. H., 42.Sehring, R., 151, 152.Seibert, F. B., 260.Seidman, J., 348.Seifter, S., 342.Seigfriedt, R.K., 329.Sellers, P. A., 100.Semerano, V., 334.Sen, B., 341.Senise, P., 315.Senoh, S., 166.Serfass, E. J., 308, 332.Seto, S., 186, 188, 189, 190.Sevag, M. G., 261.Severinghaus, J. W., 347.Seya, M., 18.Seyb, E., 359.Seyb, E., jun., 89.Shaffer, P. A., 36.Shalizadeh, F., 179, 180,Shahinian, S. S., 288.Shapiro, D., 225.Shapiro, L., 344.109, 311.287.340.181.Shapovalov, Y. M., 54.Sharbaugh, A. H., 31, 32.Sharma, D., 19.Sharp, L. K., 332.Sharp, T. M., 232.Sharp, W., 226.Sharpe, A. G., 105.Shavel, J., 231.Shaver, F. W., 211.Shaw, T. M., 32.Shaw, T. P. G., 332.Shawarbi, M. Y., 340.Shea, S. M., 356.Shechter, H., 165.Sheehan, J. C., 151, 214,Sheehan, W.F., 32, 37.Sheffield, E. L., 177.Shelberg, E. F., 330.Sheldon, J. L., 321.Sheline, R. K., 29, 107.Shelton, R. D., 29.Shen, T. Y., 154.Shepard, D. L., 330.Shephard, B. R., 167.Sheppard, N., 25, 28, 187.Sheppard, W. L., 319, 341.Sherfey, J. M., 96.Sheridan, J., 32, 34.Sherman, B., 271.Sherman, W. B.,.263.Sherwin, C. W., 358.Sherwood, J. E., 358.Shilling, W. L., 352.Shimizu, H., 277.Shimura, Y., 108.Shiokawa, T., 342.Shirley, E. L., 314.Shirley, H. T., 311.Shirley, R. L., 347, 358.Shiskin, N. V., 97.Shive, W., 227.Shmukler, H. W., 265.Shoemaker, D. P., 363.Shoemaker, R. E., 363.Shoemaker, V., 257.Shome, S. C., 342.Shoolery, J. N., 32, 37.Shoppee, C. W., 306.Shorr, E., 261, 265.Short, H. G., 342.Short, L.M., 22.Shreve, 0. D., 348.Shu, P., 355.Shu-Chuan Liang, 317, 319.Shui-Lwen Hwang, 323.Shulek, E., 322, 326.Shull, E. R., 30.Shulman, R. G., 30, 32, 34,Shupe, R. E., 294.Si Chang Fung, 54.Sidgwick, N. V., 12.Siebert, W., 348.Siegel, B. M., 275.Siegel, L., 290.215.37.Siegel, M., 251, 271.Sierra, F., 319, 327, 337.Siggia, S., 331, 332.Siiteri, P. K., 148.Silber, R. H., 287, 310, 305.Silverman, L., 360.Silverman, M., 227.Silverman, S. J., 265.Silverstein, A., 27 1.Silverstone, G. A., 198.Silvestroni, P., 334.Simanouti, T., 240, 366.Simche, A. E., 73.Simmons, G. A., 321.Simmons, J. R., 32.Simmons, W. R., 343.Simon, V., 312.Simonart, P., 356.Simons, C., 164.Simonson, R. T., 55.Simpson, D.M., 25.Simpson, J. C. E., 213, 224.Simpson, M. E., 245.Simpson, W. T., 7, 16, 134.Sinclair, R. J. G., 302.Singer, A. J., 343, 354.Singer, S. J., 272, 275, 294,Sinha, S. P., 17, 28.Sinsheimer, R. L., 17.Sirvetz, M. H., 31.Sisler, H. H., 95, 96, 97.Sita, G. E., 206.Sitte, H., 349.Sizer, I. W., 296.Sjoholm, O., 342.Skebelsky, M., 168.Skiba, P., 345.Skinner, H. A., 14.Slack, S. C., 148.Slater, R. J., 264.Slater, S. N., 212.Slates, H. L., 150, 159, 204.Slaunwhite, W. R., jun.,Slentz, L. W., 44.Sloan, G. J., 124.Smart, G. N. R., 328.Smart, J., 347.Smart, R., 324, 340.Smashey, A. R., 356.Smit, J., 347.Smith, A. L., 21, 29.Smith, A. M., 343.Smith, C. W., 211.Smith, D. A., 218.Smith, D. J., 273.Smith, D.L., 30.Smith, D. M., 345.Smith, E. D., 350, 351.Smith, E. L., 253, 254, 258,263, 264, 292, 293, 295.Smith, E. V., 332.Smith, F., 146, 174, 182,Smith, F. A., 323.375.299.183, 236, 237, 355406 INDEX OF AUTHORS: NAMES.Smith, F. H., 311.Smith, F. M., 347.Smith, G. E., 215.Smith, G. M., 318.Smith, H., 210.Smith, H. A., 36, 210.Smith, J. D., 246, 247, 356.Smith, J. F., 119.Smith, J. J., 24, 348.Smith, J. M., 227.Smith, J. P., 323.Smith, J. W., 35, 36.Smith, L., 346.Smith, L. B., 81.Smith, L. E., 236.Smith, L. I., 184.Smith, P., 215.Smith, P. A. S., 217.Smith, P. G., 24.Smith, S., 210.Smith, W. T., 329.Smith, W. T., jun., 107.Smith, W. V., 32.Smithuis, A. L. 0. M., 328.Smyth, C. P., 36.Smythe, B.M., 35.Sneed, M. C., 90.Sneedon, R. P. A., 234, 235.Snell, E. E., 277, 282, 290.Snell, N. S., 164, 246.Snider, J. C., 270.Snoke, J. E., 293.Snyder, H. R., 216.Snyderman, S. E., 281.Soanes, P. W., 130.Sober, H. A., 357.Sobotka, H., 216.Sorensen, N. A., 156, 158.Solms, U., 145.Solomon, D. H., 260.Solomon, K., 265.Soltzberg, S., 177.Somerville, A. R., 132, 186,Sommereyns, G., 356.Sommerville, I. F., 302.Sondheimer, F., 162, 163,Sorkin, E., 219.gorm, F., 194, 196.Sorochinsky, E. A., 336.Sorum, C. H., 313.Souchhy, P., 102.Sovinski, R., 270.Sowden, J. C., 169, 170.Sozzi, J. A., 315.Spacu, G., 100.Spath, E., 215.Spaeth, E. C., 356.Spedding, F. H., 94, 352.Speeter, M. E., 146, 217.Speier, J. L., 95.Speiser, P., 251.Spencer, A.G., 346.Spielman, M. A., 228.Spier, H. W., 324.190.202, 303.Spiers, C. H., 312.Spike, J. E., 81.Spitnik, P., 246.Spitsyn, V. I., 320.Spitzer, P. F., 209.Spitzer, R., 192.Spoerri, P. E., 225.Sponer, D. F., 23.Spragg, W. T., 358.Sprague, R. G., 303.Spratt, D. A., 324.Sprechler, M., 301.Sprengling, G., 226.Spriano, C., 354.Spring, F. S., 167, 197, 198,199, 205, 206, 217, 226.Squirrell, D. C. M., 343.Sreenivasaya, M., 354.Sreeramamurty, K., 19.Srinivasan, R . , 3 18.Stacey, M., 170, 179, 180,181, 182, 183, 236, 248,249, 260,266.Stack, M. J., 267.Stack-Dunne, M., 350.Stlillberg-Stenhagen, S.,138, 139, 161.Ytaeudle, H., 148.Stafford, G., 128.Stainsby, G., 80.Stallybrass, C.O., 250.Stanberg, M. E., 32.Stangk, J., 179.Stanier, R. Y., 282.Stanley, J. K., 359.Stanley, W. M., 273.Stanonis, D., 133.Stansburg, E. J., 21.Stare, F. J., 288.Stark, J., 167.Stark, J. B., 354.Statton, W. O., 97.Staub, A., 265.Stavholt, K., 158.Steacie, E. W. R., 39, 47,49, 59, 60.Steams, R. S., 81.Stechern, A., 318.Stedman, R. J., 357.Jteeg, H., 335.Steel, D. K. V., 186.Steere, R. L., 238.Stehr, E., 329.Stein, A., 190, 191.Stein, C., 340.Stein, G., 64, 130.Stein, L. H., 73.Stein, W. H., 294.Steiner, H., 39.Steinhardt, R. G., 308, 332.Steinkopff, D., 249.Stenger, V. A., 310.Stephen, A. M., 237.Stephen, W. I., 314, 315,stepien, M., 335.327, 343.Sterk, A. F. C., 328.Stern, E. R., 343.Stern, E.S., 228.Stern, O., 78.Sternberg, J., 356.Sternberger, L., 257, 258.Sternberger, L. A,, 252.Sternberger, L. H., 256.Sternglanz, P. D., 330.Stevens, 292.Stevens, H., 265.Stevens, H. M., 356.Stevens, M. F., 256, 262.Stevens, 'I?. S., 127.Stevenson, D. P., 13,41, 45,Stevenson, M. F., 302.Stevenson, R., 205, 206.Stewart, C. B., 162.Stewart, D. W., 349.Stewart, L. C., 172.Stewart, V. E., 331.Stillman, R. C., 81.Stimmel, B. F., 302.Stiochaff, B. P., 22.Stockmayer, W. H., 73.Stohr, R., 343.Stoerch, H. C., 250.Stokem, M. B., 300.Stokes, A. R., 381.Stokstad, E. L. R., 227.8tolcov8, Z., 340.Stolfi, G., 216.Stoll, A., 138, 167, 214.Stolpe, C. van de, 106.Stone, G. C. H., 342.Stone, J. E., 355.Storck, J., 341.Stork, G., 206, 207, 210.Stosick, A.J., 37.Stotz, E., 354.Stragand, G. L., 330.Strain, H. H., 350, 357.Strandberg, M. W. P., 30.Strasser, P. H. A., 197.Strassner, J. E., 334.Stratton, F., 268.Strawford, T., 214.Street, E. H., jun., 98.Street, K., 352.Street, K., jun., 103.Streibl, M., 196.Streitwieser, A., 122.Stricks, W., 82, 336.Strong, F. C., 308.Strong, F. M., 280, 290.Strong, J., 24.Stross, F. H., 321.Stross, W., 334.Stroupe, J. D., 348.Stubbs, F. J., 41, 42, 43.Stubbs, M. F., 94.Stuckwisch, C. G., 212.Studer, P. E., 300.Studier, M. H., 100, 104.349.32, 33INDEX OF AUTHORS' NAMES. 407Sturgeon, P., 254.Style, D. W. G., 19.Sucsz, A. C., 184.Sus, O., 153.Sugden, S., 54, 88.Sugg, J.Y., 261.Sugita, T., 240, 366.Sujishi, S., 91.Sukava, A. J., 89.Sulema, L. V., 54.Sullivan, A. P., 226.Sullivan, J. C., 103, 104,Sullivan, M. L., 343.Sulzberger, R., 319.Summerson, W. H., 167,Sumner, J. B., 250.S m e l l , G., 163.Sundman, J., 355.Sutcliffe, L. H., 21, 51.SutclifTe, T., 105.Sutherland, E. S., 302.Sutherland, G. B. B. M.,26, 364, 365.Sutherland, G. J., 227.Sutton, G. L., 315.Sutton, L. E., 9, 16, 36, 37,38, 141, 213,Sueuki, I., 221.Svedberg, T., 252.Svestrikov, N. N., 134.Swadesh, S., 210.Swain, C. G., 57, 121, 122.Swain, T., 354.Swallow, A. J., 358.Swaminathan, M., 277.Swan, G. A., 191.Swan, W. O., 32.Swanezy, E. F., 218.Swann, W. B., 354.Swern, D., 332, 348.Swinehart, D.F., 100.Swingle, S. M., 274, 350.Swoboda, K., 360.Sworski, T. J., 61, 64.Sykes, P., 219.Syrokomsky, V. S., 333.Seab6, Z. G., 323.Szase, G. J., 66.Szent-Gyorgyi, A., 380.Szwarc, M., 39, 41, 42.Tabenkin, B., 281.Tagliabue, M., 360.Takagi, S., 229.Takasu, I., 190.Talbot, N. B., 298, 302.Tally, R. M., 31.Talmadge, D. W., 269.Tamelen, E. E. van, 165,210, 213, 219.Tamm, C., 179, 181.Tanaka, Y., 18.Tananaev, I. V., 324.Tanenbaiim, M., 343.357.296.,Tani, H., 246.Tanner, K. N., 24.Tanner, W. F., 281.Tapley, D. F., 245.Taras, M. J., 339.Tarbell, D. S., 188.Tardew, P. L., 343.Tarrant, L., 334.Tartar, H. V., 24.Tarte, P., 19.Tatchell, A. R., 182.Tatevskii, V. M., 45.Tatlow, C. E. M., 181.Tatlow, J. C., 181, 331;Taub, D., 202, 203.Taub, W., 219.Taube, H., 54, 108.Tauber, H., 254.Taverner, M.E., 317.Tayeau, F., 257.Taylor, D. A. H., 209, 223.Taylor, G. R., 21.Taylor, H. A., 62.Taylor, H. F. W., 96.Taylor, H. S., 67, 71, 367.Taylor, J. H., 24, 28.Taylor, M. D., 91.Taylor, R.; 10, 12.Taylor, T. I., 70.Taylor, W. I., 186, 234.Taylor, W. J., 348.Taylor, W. T., 21.Teece, E. G., 179, 181.Teegan, J. P., 20, 21.Teicher, H., 352.Tekman, S. L., 252.Telep, G., 342.Teller, E., 22, 65.Temple, R. B., 365.Temple, R. H., 26.Teply, L. J., 278.Terentev, A. P., 318.Terrey, H., 323.Terry, P., 258.Tessieri, J. E., 220.Tetlow, K. S., 24, 348.Tezak, B., 78.Thain, E. M., 152, 168, 222.Thain, W., 24.Thamer, B. J., 342.Theimer, O., 65.Thilo, E., 96.Thimann, K.V., 297.Thomas, A. H., 310.Thomas, B. R., 196.Thomas, C. C., 151, 164,Thomas, E. B., 332.Thomas, G., 88.Thomas, G. R.., 162, 351.Thomas, H. C., 54.Thomas, J., 19.Thomas, J. G. N., 72.Thomas, J. M., 291.rhomas, P. T., 42.rhomas, R. G., 94.249, 250.Thomas, V. G., 32.Thomas, W. J. O., 25.Thomas, W. O., 38.Thompson, G. W., 325.Thompson, H. W., 20, 26,Thompson, J. F., 343.Thompson, J. K., 87.Thompson, R., 98.Thompson, R. C., 330.Thompson, S. G., 103.Thompson, S. O., 45.Thompson, S. Y., 258.Thompson, W. W., 148.Thor, C. J. B., 168.Thorndike, A. M., 27.Thornton, W. M., 316.Thurston, J. P., 225.Thurston, J. T., 228.Tibbs, J., 154.Tien-Hui Shen, 317.Tietjen, D., 145.Tikhomirova, V.V., 39.Tinovskaya, E. S., 312.Tinsley, S. W., 223.Tiselius, A., 245, 299, 350,357.Tishler, M., 150, 159, 204,206, 218, 226.Titchen, D. A., 259.Titchen, R. S., 81.Todd, A. R., 180, 182, 187,219, 226, 247.Toennies, G., 354.Toensing, C. H., 359.Torok, C., 315.TomiEek, O., 326.Tomita, M., 229.Tomkuljak, D., 172.Tomlinson, H. M., 56, 326.Tompkins, E. R., 352.Tompkins, F. C., 64, 66,72.Tompkins, P. C., 358.Tongeren, W. van, 321,337.I'onhazy, N. E., 305.I'onsey, R., 20.roran, N., 20.I'orkington, P., 25.rorley, R. E., 348.roropov, A. P., 337.rousey, R., 20.rouster, o., 165.Fowler, J. H., 25, 348.I'ownend, L., 325, 342.I'ownes, C. H., 30,31,32, 33.EIracey, M. V., 343.L'raldi, E., 320.L'rambarulo, R., 32.lhpnell, B.M. W., 67, 68.rreffers, H. P., 249, 251.rreiber, E., 35.L'reibs, W., 155, 188, 190,henner, N. R., 159.rrevelyan, W. E., 355.rrevoy, L. w., 144.27, 28, 30.191, 194408 INDEX OF AUTHORS’ NAMES.Tridot, G., 103.Trifan, D. S., 120, 121.Trinder, P., 340.Trippett, S., 183.Trotman-Dickenson, A. F.,39, 47, 49, 60.Trotter, I. F., 366, 371.Trueblood, K. N., 364.Truhaut, R., 343.Truog, E., 347.Trurnit, H. J., 275, 294.Truter, E. V., 161.Tsao, T.-C., 238, 364.Tschapek, M., 357.Tschesche, R., 226.Tsuiboi, M., 240, 366.Tsuchida, M., 282.Tsutsumi, C., 352.Tsuzuki, Y., 331.Tucker, W. B., 79.Tuemmler, F. D., 310.M e , B. L., 342.Tunca, M., 293.Tune, S., 252.Tunesi, A., 337.Tunnicliffe, M.E., 340.Tupper, R., 270.Tupper, R. L. F., 358.Tuppy, H., 239, 340, 293.Turkevitch, J.,45,69,70,95.Turner, E. E., 143.Turner, P. B., 151.Turner, R. A., 238.Turner, S. E., 358.Tuthill, S. M., 310.Tutton, R. C., 49.Twigg, G. H., 69.Twombly, G. H., 209.Tyree, J. T., 236.Ubaldini, I., 318, 323.Ubbelohde, A. R., 95, 97.Udenfriend, S., 239.Uhlen, G., 327.Uhlig, L. J., 341.Ulrich, A., 339.ULrici, B., 190.Umbreit, W. W., 222, 305.Umezawa, H., 251, 272.Umstiitter, H., 359.Unterberger, R. R., 32.Unterzaucher, J., 329.Urban, N., 318.Urech, P., 319.Uri, N., 50.Urone, P. F., 342.Urry, W. H., 128.Utzinger, H., 164.Vahrman, M., 351.Vaidya, W. M., 19.Valentin, F., 172.Vallee, B. L., 344.Valls-Conforto, A., 343.Vanag, G.Y., 328.TSOU, K.-C., 145.Van Atta, R. E., 335.Vand, V., 371.Van Dalen, E., 314.Van der Werf, C. A., 106.Van Doorselaer, M., 345.Van Dyke, R. E., 93. . Vanetten, C. H., 330.Van Rooy, P. J., 355.Van Valkenburgh, H. B.,Van Vleck, J. H., 31.Van Vunakis, H., 266.Van Zyl, G., 165.Vassiliev, M. G. A., 359.Vaughan, J. R., 153.Vaughan, W. R., 124.Vavruch, I., 352, 355.Vedder, W., 26.Vela, L. G., 338.Velden, P. F. van, 62.Velick, S. F., 239.Venkataramaniah, M., 319,Venkateswarlu, C., 320.Venkateswarlu, P., 17, 30.Venning, E. H., 301, 302.Ventura, S., 340.Verleger, H., 17, 344.Verschure, J. C. M., 347.Verwery, E. J. W., 78, 79.VerzBr, F., 305.Vesterberg, R., 342.Vickery, R. C., 94, 312.Vierwoll, H., 37.Vignau, M., 311.Vignes, H., 259.Vilkas, M., 197.Vincent, E.R., 24.Viollier, G., 286.Vipond, H. J., 223.Virion, E., 256.Vischer, E., 356.Viscontini, M., 222, 328.Viswanathan, R., 322.Vivarelli, S., 334.Vobaure, A., 54.Vodar, B., 18, 78.Voely, F. L., 25.Voevodskii, N. N., 39.Vogel, A., 200.Vogel, H., 171.Vogler, K., 219.Voigt, A. F., 342.Volcani, B. E., 282.Vold, M. J., 80, 81.Vold, R. D., 81.Volkin, E., 247.Volman, D. H., 49.Vosburgh, W. C., 317.Voser, W., 196.Voter, R. C., 319.Vroelant, C., 7, 113, 117.Vunakis, H. van, 238.Wacbter, L. E., 324.108.320.Vogell, w., 45.Wacker, R. E., 352.Wade, P., 337.Wadman, W. H., 355.Wadsley, A. D., 90.Wadsworth, H. E., 79.Wagner, A., 228.Wagner, C.D., 349.Wagner, E. L., 26, 28.Wagner, H., 329, 330.Wagner, R. B., 209.Wagner-Jauregg, T., 167.Wahl, H., 228.Waind, G. M., 56, 57.Waisman, H. A., 290.Waksman, B. H., 261.Wal, A. A. van der, 221.Walborsky, H. M., 121, 162.Waldron, J. D., 47.Waldschmidt-Leitz, E.,Waley, S. G., 154, 239.Walker, D. M., 258.Walker, J., 224, 225.Walker, W. C., 341.Walker, W. R., 356.Wall, L. A., 43, 60.Wallace, W. M., 347.Wallenfels, K., 158, 357.Wallmann, J. C., 105.Walsh, A., 24, 213.Walsh, A. D., 10, 20, 21.Walsh, R. H., 96.Walsh, W., 29.Walter, A. W., 251.Walter, R. N., 323, 329.Walter, W. D., 42, 43.Walter-LQvy, L., 89.Walz, D. E., 165, 176.Wamser, C. A., 92.Wang, F. C., 305.Wang, J. H., 100.Wantier, G., 356.Ward, A.H., 359.Ward, F. N., 342.Ward, G. M., 276.Wardlaw, W., 97.Ware, E., 220.Warhurst, E., 46.Warhurst, E. W., 9, 18.Warren, J. W., 40.Warren, S., 269.Wartik, T., 89.Washauer, B., 352.Washbrook, C. C., 324.Watanabe, K., 20.Watanabe, W., 133.Waters, J. I., 335.Waters, W. A., 48, 58, 128,Watkins, W. M., 266, 271.Watson, C. D., 358.Watson, D. W., 260.Watson, G. M., 338.Watson, H. B., 127.Watson, H. R., 39.Watson, J., 164, 239.137, 153.129INDEX OF AUTHORS' NAMES. 409Watson, J. P., 322.Watson, M., 297.Watson, W. F., 47.Waylmd, R. L., 146.Wayne, L. G., 19, 44.Weaver,'E. R., 359.Webb, E. C., 295.Webb, J. A. V., 317, 340.Webb, M., 248.Weber, D., 27.Weber, G., 257.Weber, J., 71.Webster, G. L., 277; 355.Weddell, W.M., 344.Weedon, B. C. L., 138, 139,160, 161, 167.Weedon, W., 338.Weibull, C., 364.Weidel, W., 284.Weidenhagen, R., 355.Weijlard, J., 218, 226..Wsil, H., 354.Weir, A. R., 326.Weisblat, D. I., 146, 217.Weiser, R., 144, 228.Weiss, J., 64, 130.Weiss, M. T., 32.Weissmann, B., 237.Weister, A. G., 25.Weith, A. J., jun., 79.Welch, A. J. E., 110.Welcher, A. D., 153.Welford, G. A., 346.Weller, S., 353.Wells, A. J., 27.Wells, I. c., 375.Wells, J. H., 343.Wells, R. A., 356.Welsh, H. L., 21, 22, 27.Welsh, L. H., 218.Wender, S. H., 353, 356.Wendler, N. L., 150, 159,Wendt, B., 156.Wenger, P. E., 314, 334,Wen-Hua Chang, 355.Wenis, E., 227.Werner, L. B., 104.Wernicke, E., 181.Wernimont, G., 311.West, C.D., 306.West, L. E., 310.West, P. W., 311, 314, 315,West, T. S., 322, 341, 343,Westhall, R. G., 164.Westenberg, A. A., 32, 33.Westheimsr, F. W., 128,Westrum, E. F., 26, 349.Westrum, E. F., jun., 104.Westwood, W., 318.Wetter, L. R., 261,262,263,204.335.321, 335, 338, 341.353.134.265.Wetterlow, L. H., 251, 264.Wetti, D., 19.Weygand, F., 145, 181,223.Whaley, T. P., 87.Whaley, W. M., 224.Whalley, E., 45, 46.Wharton, D. R. A., 260.Wheatley, P. J., 24.Wheeler, W. E., 262.Wheland, G. W., 7, 113,Whetstone, R. R., 165, 211.Whiffen, D. H., 30.Whistler, R. L., 351.White, A., 297.White, A. G., 52.White, C. E., 315, 344.White, E. A. D., 96.White, J., 357.White, J. U., 22.White, L.M., 330.Whiting, M. C., 154, 157.Whitman, R. E., 94.Whitmore, F. C., 126.Whittaker, N., 225.Whittle, E., 18.Whittles, C. L., 340.Whittum, J. B., 359.Wibaut, J. P., 215,220,221.Wiberg, E., 89, 92.Wiberley, J. S., 329.Wiberley, S. E., 360.Wichers, E., 310.Wick, A. N., 301.Wickbold, R., 352.Wicked, K., 101.Wickham-Jones, C., 48.Widdowson, E. M., 291.Widmark, G., 147, 228.Wieland, P., 204.Wieland, T., 151, 152, 355,Wiele, M. B., 330.Wiener, A. S., 251, 254, 259.Wiener, G., 359.Wiesner, K., 231.Wiggins, L. F., 170, 171,172, 173, 174, 175, 176,177, 178, 179, 180, 181.Wilberg, E., 347.Wild, F., 257.Wilds, A. L., 148.Wiley, P. F., 230.Wiley, R. H., 218, 229, 221.Wilk, I. J., 228.Wilkins, C. J., 105.Wilkins, M. H. F., 381, 382.Wilkins, R. G., 110.Wilkinson, N. T., 341.Willard, H. H., 321, 327.Willard, J. E., 54, 93.Willavoys, H. J., 72.Willebrands-Schogt, E. C.Willeford, B. R., 312.Willemart, A,, 158.114, 116.357.c., 221.Willi, A., 108.Williams, A. F., 343.Williams, B. A., 110.Williams, D., 32.Williams, D. B., 330.Williams, D. C., 299, 304.Williams, G., 204.Williams, H. L., 52.Williams, J. N., jun., 288.Williams, J. Q., 32.Williams, J. W., 263.Williams, K. T., 352.Williams, M. B., 343.Williams, R., 42.Williams, R. C., 238.Williams, R. L., 28.Williams, R. R., 219.Williams, V. Z., 303.Williams, W. J., 253.Williams, W. T., 352.Williamson, J. B., 48.Willis, J. B., 54.Willits, C. O., 310, 328, 329,Willson, A. E., 340.Wilson, A. N., 222.Wilson, A. T., 212.Wilson, B., 194.Wilson, C. L., 210, 314, 316,Wilson, D. W., 316.Wilson, E. B., 27, 30, 31,Wilson, E. H., 206.Wilson, G. L., 57.Wilson, H., 300, 303.Wilson, H. N., 323.Wilson, J. B., 353.Wilson, J. N., 363.Wilson, K. W., 328.Wilzbach, K. E., 89.Windle, J. J., 32.Windle, M. L., 345.Windsor, E., 164.Windsor, P. A., 83.Winger, P., 54.Wingo, W. L., 330.Winkler, C. A., 54.Winkler, H., 349.Winning, W. I. H., 62.Winstein, S., 58, 119, 120,121, 122, 133.Winston, H., 105.Winteringham, F. P. W.,Winterstein, A., 237.Winder, R. J., 334.Wirth, H., 359,Wirth, L., 355, 357.Wischinsky, H., 209.Wise, C. S., 355.Wise, W. S., 350.Wiseman, L. A., 55.Wish, L., 353.Wisherd, M. P., 348.Wiss, O., 286, 288.330, 359.351.32, 33, 34.358410 INDEX OF AUTHORS' NAMES.Witebsky, E., 254.Witkop, B., 216, 217, 231.Witten, L. B., 35.Wohl, M. G., 250.Wokes, F., 277.Wolf, A., 264.Wolf, D. E., 212.Wolf, H., 356.Wolf, H. A., 313.Wolfe, H. R., 250, 273.Wolfe, J. K., 298, 302.Wolff, H., 340.Wolfhard, H. G., 17.Wolfrom, M. L., 146, 171,173, 183,236, 237, 352.Woltz, P. J. H., 29.Wood, D. J. C., 177.Wood, D. L., 29.Wood, E. C., 310.Wood, H. B., 146, 183.Wood, H. F., 264.Wood, R. E., 93.Wood, R. W., 277.Woodfin, H. W., 255.Woodrow, C. C., 36.Woodruff, J. F., 344.Woods, R. J., 160.Woodward, L. A., 22.Woodward, R. B., 202, 203.Woolf, A. A., 105.Woolley, D. W., 280.Wooten, L. A., 109.Wormall, A., 249, 256, 269,270, 271, 272, 358.Worman, I. J., 261.Worth, W., 36.Wright, E. R., 344.Wright, G. S., 257.Wright, J. B., 220.Wright, L. D., 290.Wright, M. L., 342.Wright, M. M., 334.Wright, N., 348.Wright, P., 68.Wright, R. H., 339.Wolf, c. N., 221.Wright, R. R., 260.Wromis, C. C., 32.Wiirz, A., 332.Wuhrmann, F. H., 264.Wunderlich, G., 324.Wunderly, C., 264.Wurmser, R., 273.Wurzschmitt, B., 330.Wyatt, G. R., 246, 247.Wyckoff, R. W. G., 380,Wylie, A. W., 94.Wyman, G. M., 140.Wyman, J., 261.Wyman, L., 274.Wyndham, J. L. P., 325.Wynne-Jones, W. F. K.,382.56.Xuong, N. D., 318.Yaffe, I. S., 94, 352.Yamads, E. Y., 305.Yamaka, M., 38.Yamaki, K., 185.Yamane, K., 185, 189.Yanofsky, C., 283, 284,285, 286.Yanowski, L. K., 315.Ya Sheng, 42.Yoffe, A. D., 73.Yoshikoshi, A., 186.Yoshino, Y., 352.Yost, D., 44.Yost, D. M., 19, 32, 37, 94.Yotter, R., 168.Youle, P. V., 56.Young, C. W., 348.Young, D. A., 329.Young, D. M., 66.Young, F., 342.Young, G. T., 151.Young, I. G., 338.Young, J. F., 345.Young, L. G., 346.Young, R. C., 99.young, R. S., 341, 360.Young, R. W., 143, 153.Young, T. F., 21, 24, 91.Young, W. G., 133.Yu, J. T. M., 345.Yukawa, Y., 125. *Yvan, P., 7, 113.Zacherl, M. K., 331.Zack, P. G., 311.Zaffaroni, A., 209, 299, 305,Zahler, R. E., 213.Zahn, H., 157,240,332,356,Zahner, R. J., 354.Zalukaeva, E. A., 328.Zamecnik, P. C., 260.Zanko, A. A., 336.Zapp, E., 322.Zealley, T. S., 36.Zechmeister, L., 350.Zeeman, P. B., 19.Zemansky, P. D., 60.Zeppelin, H. von, 323.Zervas, L., 151.Zettemoyer, A. C., 341.Zetterstrom, R., 339.ZiegIer, K., 210.Zilch, K. T., 354.Zill, L. P., 353.Zillikens, P., 165.Zima, O., 219.Zimmer, W. F., 106.Zimmerman, L., 53.Zingaro, R. A., 106.Zinn, B. H., 268.Zinneke, F., 329.Zissis, E., 180.Zivanovib, D., 324.Zocher, H., 315.Zuckermann, J. L., 341.Zuidema, G. D., 165.Zuman, P., 335.Zussman, J., 247, 363..ZQka, J., 336.307, 354.366

ISSN:0365-6217    

DOI:10.1039/AR9514800383

出版商:RSC    

年代:1951

数据来源: RSC

摘要:

INDEX OF SUBJECTS.Absorptiometry, 338.Absorption spectroscopy, ultra-violet andvisible, 347.Acenaphthenes, 113.Acepleiadiene, 19 1.Acetals, acid hydrolysis of, 142.Acetaldehyde, autoxidation of, 48.cyclic, structures of, 172.decomposition of, 47.hydration of, 57.photolysis of, 60.pyrolysis of, 60.radial-distribution curves for, 37.thermal decomposition of, 61.Acetanilide, p-mercaptoacetamido-, asAcetic acid, indolyl-, preparation of, 21 7.Acetic anhydride, thermal dissociation of,Acetobromo-2-deoxy-sugars, 180.Acetoisobutyric acid, decarboxylation of,Acetone, photolysis of, 61.Acetonitrolic acid, decomposition of, 58.Acetoxime, hydrogen bonding in, 24.Acetyl hypohalites, trifluoro-, 106.Acetylene, reaction of atomic hydrogenAcetylides, alkali, 95.Acids, carboxylic, decarboxylation of, 133.analytical reagent, 313.41.134.with, 46.trifluoromethyl-, 168.fatty, and their derivatives, 160.saturated branched-chain, 161.unsaturated straight-chain, 161.straight-chain, 160.Acrylic acid, methyl ester, polymerisationAdipic acid, a-amino-, 164.Adrenals, perfused, corticosteroidogenesisAdrenochrome, 216.Adsorbents for chromatography, 350.Adsorption and surface studies, 64." Gibbs " unit of, 81." Alanates ", 92.Alanine, ~~-/3-3-oxindolyl-, 217.Alanines, thiazolyl-, 219.Albumin, serum, structure of, 375.Alcohols, oxidation of, 128.primary, hydrogenolysis of, 149.Aldehydes, autoxidation of, 48.photo- and thermal reactions of, 60.Aldolase, structure of, 239.Aliphatic compounds, 156.Alkali " ozonates ", 87.of, 49.in, 307.4Alkaline-earth superoxides, 89.Alkaloids, 228.Alkanes, nitro-, dissociation of, 41.n-Alkenes, inversion of con@uration of,Alkyl iodides, preparation of, 155.Alkylamines, l-methyl-, optically active,Allene, far ultra-violet absorption spectrumAlliin and its isomers, 138.(+)-Alliin, synthesis of, 167.Alstonine, 232, 233.Alstyrine, 232.D-Altromethylose, synthesis of, 180.D-Altrose, isopropylidene derivative, 175.Aluminium compounds, 92, 93.detn. of, 319, 325.Americium and its compounds, 104.Amides, alkoxyalkyl-, 167.substituted, from nitriles, 155.Amino-acid imbalance in diet, 279.Amino-acids, 164.crystal structure of, 363./3-Amino-alcohols, configuration of, 21 9.Amino-end-groups, detn.of, 239.a-Amino-ketones, cyclic, reduction of, 223.Ammonia, catalytic decomposition of, 71.Ammonium amalgam, formation of, 97.156.167.of, 21.Raman spectrum of, 22.iodide, carbethoxymethyltrimethyl-,pentaiodide, tetramethyl-, structure of,alkaline hydrolysis of, 56.106.Amperometric titration, 336.a- and /3-Amyrins, 197.Analysis, absorptiometric, 338.amperometric titration, 336,chromatographic, 350.partition, 354.colorimetric, 338.coulometric, 333.electrochemical, 332, 337.electrophoretic, 357.extraction, 353.fluorimetric, 344.gas, 358.inorganic gravimetric, 315.qualitative, 313.volumetric, 322.instrumental methods, 332.ion-exc hange, 352.mass-spectrum, 349.metallurgical, 360.microscopic, 349412 INDEX OF SUBJEUTS.Analysis, nephelometric, 343.organic, 328.elementary, 329.polarographic, 333.potentiometric titration, 336.radiochemical, 357.sedimentation, 359.spectroscopic, infra-red, ultra-violet,and visible, 347.spectrographic emission, 344.Analytical chemistry, 308.teaching of, 360.epiAndrosterone, 20 1.1 : 6-Anhydro-p-~-altrose, isopropylidenederivative, 175.2 : 5-AnhydroaZdehydoarabinose, 3 : 4-iso-propylidene derivative, 174.1 : 5-3 : 6-dihhydro-~-dulcitol, 176.1 : 6-Anhydro-a-~-galactofuranose, 176.6 : 6-Anhydroglucose, 1 : 2-isopropylidene1 : 5-Anhydrohexitols, 176.1 : 4-3 : 6-diAnhydroidito1, reactivity of,177.1 : 2-3 : 6-diAnhydro-~-mannitol, 4 : 5-iso-propylidene derivative, 176.1 : 4-3 : 6-diAnhydroma.nnito1, reactivityof, 177.2 : 6-Anhydro-a-methylaltroside, 174.1 : 5-Anhydropentitols, 176.1 : 4-Anhydrosorbitol, 173.1 : 4-3 ; 6-dihhydrosorbitol, reactivity of,Anhydro-sugars, 173./3-1 : 6-Anhydro-sugars, 175.3 : 4-Anhydro-~-talitol, 1 : 2-5 : 6-diiso-1 : 3-Anhydroxylitol, 2 : 4-methylene, 177.Anilides, L-N-acylamino-, enzymic syn-Anions, rearrangements of, 127.Anthracene fluorescence, quenching of,63.Anthranilic acid, 3-hydroxy-, formation of,and conversion into nicotinic acid, 284.Antibodies, 250.derivative, 173.177.propylidene derivative, 176.thesis of, 137.detection and detn.of, 262.effect of enzymes on, 256.effect of heat on, 255.effect of iodine on, 256.fluorescent, 270.labelled, 268, 271.quantitative relations of antigens with,transfer of, to offspring, 258.valency of, 272.antibodies serve as, 254.detection and detn.of, 262.labelled, 268.modified, 261.quantitative relations of antibodieswith, 272.synthetic, 262.thermodynamio and kinetic aspects of,273.272.Antigens, 260.Antigen-antibody precipitates, analysisof. 276.Antigenic substances, 260.Antimalarials, 225.Antimony, co-ordination compounds of,Antiserum, isolation of antibodies from,‘‘ Antrycide ”, 224.DL-Arabitol, synthesis of, 173.Argentic oxide, 88.Aromatic compounds, spectra of, 21.Arsenic, detn. of, 316, 323.Arsine, infra-red spectrum of, 28.cycZoArtenone, 200.Aspergillic acid, structure of, 226.Atomiser, glass, 347.Azetidine, 2 14.Azides, decomposition of, 73.Aziridines, acyl-, stereoisomerism of, 141.trans-Azobenzene, solubilisation of, 82.2 : 2’-Azobis(isobutyronitrile), decomposi-Azulenes, 190.Bacilli, tubercle, acids from, 163.Bacteria, antigens from, 260.282.Balances, 315.Barium azide, decomposition of, 72.carbide, 95.chloride metaphosphate, 90.Basseol, 197.Benzaldehyde, autoxidation of, 48.Raman spectrum of, 23.solubilisation of, 82.Benzanthrone, amination and hydroxyl-Benzene, electronic structure of, 10.interfacial tension of, with water,nitro-, arylation and hydroxylation of,vapour, electronic spectra of, 19.Benzenesulphonic acid, p-bromo-, e m -norbornyl ester, solvolysis of, 120.Benzidine rearrangement, 125.Benzidines, substituted, as analyticalreagents, 313.Benziminazoles, 220.Benzofurans, 210.Benzoic acid, ammonium salt, as anaIytical2 : 4 : 6-trihydroxy-, decarboxylation2 : 3-Benzopyrrocoline, 1 : 5 : 8-trimethyl-,216.Benzoq inone, reaction of, with ferrousions, 51.Benzothiazole, mercapto-, as reagent forsilver, 3 18.Benzoyl peroxide, dissociation of, 48.Benzoylbromo-sugars, reaction of, withmethanol, 182.100.253.tion of, 48.tryptophan-nicotinic acid conversion by,ation of, 131.80.by radicals, 130.N-substituted, as indicators, 327.reagent, 313.of, 133INDEX OF SUBJECTS.413Beryllium hydride, 89.Betulin, 199.Betulin-lupeol series, 198, 199.Birds, formation of antibodies by, 250.Bismuth nitrates, 100.Blood, steroid hormones in, 304.Blood-group substances, 237, 265, 267.Bond energies, 9.Bonds, chemical, theories of, 9.Bond-dissociation energy measurements,40.Borazole, 92.Boron trichloride, infra-red spectrum of,29.sulphate, hydrates, 89.oxide, oxidation by, J49.lengths, 9.compounds, 91, 92.organic compounds, 92.Borrelin, toxic action of, 281.a-Boswellic acid, 200.Bromides, aliphatic and aromatic, dis-Bronzes, spectrographic analysis of, 345.Butadiene, dimerisation of, 184.electronic structure of, 10.cis- md trans-isomers of, 12.polymerisation of, 49.10.sociation of, 42.cycZoButadiene, electronic structure of,Butaldehydes, decomposition of, 61.cycZoButy1 chloride, solvolysis of, 120.isoButyric acid, 8-amino-, 164.y-Butyrolactone, hydrolysis of, 56.Butyrospermol, 200.Cadmium, detn.of, 318.hydride, 89.dimethyl-, infra-red spectra of, 27.Caesium, preparation of, 88.Calcium, detn. of, 318, 324.silicate, hydrated, 96.Californium isotopes, 103.Carbanions, rearrangement of, 127.Carbazoles, 217.Carbides, refractory, 95.Carbon ions, stripped, use of, in cyclotron,isotopes, fractionation of, in decarboxyl-monoxide, chemisorption of, 67.dioxide, electronic structure of, 12.reaction of, with carbon dioxide, 70.Carbonium ions, rearrangement of, 127.Carbonyl sulphide, surface tension of, 80.Carboxyl end-groups, detn. of, 239.8-Carotenq synthesis of, 158.Carotenoids, 158.fl-Caryophyllene, derivatives of, 194.Caryophyllenic acid, 193.Catalysis, 64.Catalysts, heterogeneity of surface of, 66,67.Cellulose, structure of, 236.103.ation, 45.group, structure of, 38.acid-base, 57.Cephalin, ( + )-dimyristoyl-, -dipalmitoyl-,and -distearoyl-, 163.Ceric nitrate, extraction of, 94.Cerium, exchange between oxidationstates of, 53..Chemical change, mechanism of, 38.Chloramphenicol, 218.configuration of, 136.Chlorine, exchange reactions of, withfluoride, vibrational-rotational spec-reaction of, with chloroform and withChloroform, reaction of, with chlorine, 63.Cholesterol, biosynthesis of, 307.solutions, effect of salts on emulsi-fication of, 85.synthesis of, 200.Chromatograms, strip, 350.Chromatography, 350.partition, 354.Chromium, detn.of, 325.Chrysopterin, 226.Chymopapain, 292.Chymotrypsin, 293, 294, 295.inhibition of, by diisopropy1 fluoro-a-Chymotrypsin, oxidation of, with per-Chymo trypsinogens, 294, 295.cis-Cinnamoyl chloride, 141." Citrovorum factor ", 227.Clemmensen reaction, 148.Clovene, 195.Coal, detn. of moisture in, 359.Cobalt, complex compounds of, 108, 109.Cob~ltic ions, decomposition of water by,(-J)-Coclaurine, 229.Codecarboxylase, 222.Coenzyme A, hydrolysis of, 168.Collagen, structure of, 238, 378, 379.Colloids, 78.lyophobic, coagulation of, 78.micellar, bulk properties of, 80.hydrogen chloride, 55.trum of, 28.toluene, 62.phosphonate, 295.iodate, 296.detn. of, 319, 325, 341.52.Colorimetry, 338.Colour and constitution, 134.Combustion analysis, 329.Complex formation, molecular.15.Complexones, 3 1 1.Conductimetric titration, 337.Configurational activity, 139.Copper alloys with gold, order-disordertransitions in, 77.compounds, complex, 88.detn. of, 318, 324, 325.Coprecipitation in analysis, 321.Coreximine, 229.Coronene, 184.Corticosteroids, detn. of, 300.Cortisone, synthesis of,. 200, 203, 207.Coryline, 232.Corynantheal, 233.Corynanthean, 233414 INDEX OF SUBJECTS.Corynantheine, 231.Corynanthryine, 231.Coulometers, 333.Coulometry, 333.Crotonaldehyde, radihl-distribution curvesfor, 37.Cryostats,.21.Cryptolepine, 234.Cryptolepsis triangularis, cryptolepinefrom, 234.Crystals, infra-red spectra of, 25.Crystallography, 361.Cularimine, 229.Cularine, 229.Cumene hydroperoxide, decomposition of,52.Cumulenes, 158.Curium, 104.Cuscohygrine, 228.merocyanine dyes, 134.Cyanuric chloride, substitution reactionsof, 228.Cyclamen alcohol, 154.Cycleanine, 229.Cyclic systems, conformation of, 192.Cymarose, 18 1.D- and L-Cysteines, S-allyl-, 138.Cysteinylglycine-sodium iodide, crystalstructure of, 364.Cystine, synthesis of, 165.Cytidylic acids, 247.Cytosine, 5-methyl-, in deoxypentose-nucleic acids, 247.Deamination, pinacolic, 126.n-Decane, interfacial tension of, withDecarbonylation, 133.Decarboxylation, 133.cycZoDecyne, 184.Dehydrobrucidine, 144.Dehydronorbornyl derivatives, acetolysisof, 121.Densitometers, 346.6-Deoxy-~-altritol, synthesis of, 172.r-Deoxyaspergillic acid, synthesis of, 226.Deoxycodeines, 228.A 7-Deoxycodeine, 147.1 : 6-diDeoxydulcitol,1 : 6-dibromo-, tetra-acetyl derivative, 172.2-Deoxygalactose, 179.1-Deoxy-D-glucose, 1-fluoro-, reaction of,with a-amino-acids, 167.2-Deoxy-~-glucose, 170, 178, 179.6-Deoxy-~-glucose, 6-nitro-, 170.6-Deoxy-~-idose, 6-nitro, 170.1-Deoxy-D-mannitol, synthesis of, 172.3-Deoxy-a-methylaltroside, %amino-, 4 : 6-benzylidene derivative, 174.As-Deoxyneopine, 147.2-DeoxypentosesY Dische test for, 181.Deoxypentosenucleic acids, 246, 247, 248.2-Deoxy-~-ribose, 170, 179.Raman spectra of, 22.transition states, reactions involving,132.water, 80.Deoxyribosides, structure of, 181.Deoxy-sugars, 178.2-Deoxyxylose, 179.Detergents, colloidal, micelle structure in,thermodynamic properties of, 8 1.Deuterioacetylene, flame spectra of re-action with oxygen, 19.micro-wave spectrum of, 3 1.Deuterium, exchange reaction with ethyl-ene and with methane, 70.Dialdehydes, reaction of, with nitro-methane, 170.Dicycloalkyls, 184.o-Dianisidine as indicator, 327.Diazosulphonates, stereoisomerism of, 140.Dibenzopentalene, 19 1.Dibenzotropolone, 187.Dibenzotropones, 188.Dibenzyl, pyrolysis of, 42.Diborane, 91.83.bromo-, micro-wave spectrum of, 31.electronic structure of, 12.tetramethyl-, structure of, 24.pyrolysis of, 43.structure of, 38.Di-tert.-butyl hydroperoxide, photo-Dicresotides, 141.Diethyl ether, 2 : 2’-dichloro-, decomposi-Diginose, 18 1.Digitalose, synthesis of, 181.Digitoxose, synthesis of, 181.Dinitrogen monoxide, infra-red spectrumoxidation of unsaturated compoundsmon- and pent-oxides, decomposition of,43.dioxide, electronic spectra of, 18.tetroxide, liquid, reactions in, 98.decomposition of, 62.tion of, 42.of, 28.with, 150.Dioxalan, decomposition of, 43.Dipole moments, 32, 34.Diisopropyl fluorophosphonate, inhibitionof enzymes by, 295.Dicyclopropyl, 2-phenyl-, spectra, andchemical reactivity of, 184.1 : 5’4‘ : l-Diribofuranose anhydride, 175.Disalicylides, 141.Dodecylamine hydrochloride, electricalconductivity of solutions of, 86.micelle formation in, 84.Dyes, aggregation of, 274.Eburicoic acid, 197.Electrical double layer, 78.Electrodes, dropping-mercury, 334.Electrodeposition, analysis by, 332.Electron diffraction, 36.Electrons, mobile, molecular-orbitaltheory of, 10.Electron-transfer reactions in solution,Electrophilic substitution, 128.Electrophoresis, 3 57.50INDEX OF SUBJECTS. 415Emission spectrography, 344,Emulsification, 85.Emulsions, 84.Entropy of mixing, 75.Enzymes, reaction of, with steroid hor-mones, 305.Ergothioneine, synthesis of, 167.Erysodine, 230.upoErysodine, 231.Erysopine, 230.apoErysopine, 231." Erysotrine ", 230.Erysovine, 230.Er yt hraline , 2 30.apoErythreline, 231.Erythramine, 231.Erythrina alkaloids, 230.Q- and 8-Erythroidines, 230.Erythropterin, 226.Eschscholtzxanthin, 159.Esterases, inhibition of, by diisopropylEthane, 1 : 2-dibromo-, isomerism andwater-in-oil, breaking of, 86.fluorophosphonate, 295.Raman spectra of, 23.photo- and thermal bromination of, 40.Ethanes, tetrachloro-, decomposition of, 42.Ethyl iodide, photodecomposition of, 62.Ethylamine, 2-hydroxy-1 : 2-diphenyl-,isomers, 218.Ethylene, catalytic hydrogenation of, 69.1 : l-dichloro-, ultra-violet absorptioncis- and trans-1 : 2-dichloro-, reaction ofelectronic structure of, 10.exchange reaction with deuterium, 70.oxide, thermal decomposition of, 42.Ethylenes, thermochromic, 113.Ethylenediaminetetra-acetic acid, 31 1.Ethylenic bonds, hydrogenation of, 69.Euphol, 197.Extraction analysis, 353.( -J- )-a-Fsnchylamine, resolution of, 138.Ferric ions, reaction of, with hydrogenperoxide, 51.with quinol, 51.Ferritin, detn.of, 265.Ferrous ions, reaction of, with benzo-with hydrogen peroxide, 51.sulphate, radiation chemistry of, 63.Films, adsorbed, thermal properties of, 66.Flame photometry, 346.Flavins, 226.9-Fluorenylamine, N-methyl-N-a-(or /3)-naphthoyl-, 145.Fluorides, 105.Fluorimeter, photoelectric, 344.Fluorimetry, 344.Fluorination, 105.Fluorine, heat of dissociation of, 40.spectrum of, 20.bromine with, 62.quinone, 51.organic compounds, 167.Raman spectrum of, 22.Fluorosiloxanes, 96.Folic acid, 227.Folinic acid SF, 227.Force constants, 25.Formaldehyde, photolysis of, 60.reaction of, with unsaturated com-pounds, 154.Formic acid, mercurous and nickel salts,decomposition of, 73.Fruc tosans , 23 6.Fuel, hydrazine as, 98.Fulvenes, 1 13.Furans, 210." Gallanates ", 92.Gallium, trimethyl-, co-ordination com-pounds of, 93.Gas analysis, 358.Gases, chromatography of, on activatedcharcoal, 351.~-Fuc0-4-ketose, 172.mixed, 77.Raman spectra of, 22.solubility of solids in, 77.Gelsemine, 234.Germanium, detn. of, 317, 325.tetrafluoride, Raman spectrum of, 22.pure, 96.Girard reagents, 299.Glaucentrine, 229.Gliadin, structure of, 238.Gliotoxin, 2 17.y-Globulin, 244, 245.detn.of, 263.L-Glucomethylose, synthesis of, 180.L-GLUCOSB, 169.Glucuronides, hydrolysis of, 298.Glutaric acid, /3-methyl-, ( -+)-methylhydrogen ester, resolution of, 138.Glycogen, structure of, 236.Glycols, 167.Glyconic acids, reduction of, 183.Glyoxalines, 220.Glyoxime, dimethyl-, nickel complexesGold compounds, complex, 89.Graphite, " lamellar compounds " of, 94.Grignard reagents, preparation of, 184.Griseofulvin, structure of, 210.L-Gu~os~, 169.Gypsogenin, 200.Hzemoglobin, structure of, 239, 370, 373,Hafnium dioxide, solubility of, in water,Hair, proteins of, 366, 369." Hallachrome ", 216.Halogen compounds, 155.Halogens, detn. of, 317, 322, 331.action study, 54.Halogeno-sugars, 174.Hecogenin, 208.Helianthus tuberosus, fructosans from, 237.oxidation of, 128.with, 312.374.97.separation of, from zirconium, 97.radioactive, use of, in exchange-re416 INDEX OF SUBJECTS.j3-Lactams, 214.Lactones, 211.Laminaria digitata, laminarin from, 237.Laminarin, structure of, 237.Lanostadienol, structure of, 196.Lanostene, structure of, 196.Lanthanons, 94.Lead, detn. of, 319, 325.L-Leucine, N-acetyl-, preparation of, 137.Leucovorin, 227.l Light filters, 338.Heparin, structure of, 237.p-Heparin, 237.Heptadec-9-enoic acid, 161.cycZoHeptane-1 : 2-diones, dehydrogen-cycZoHeptatrienone, 132.B(trans) : 8(cis)-Herculin, 163.Heterocyclic compounds, 210.cycZoHexane, reaction with bromotri-cycZoHexanone, 2-carbethoxy-, iodination2-chloro-, reaction of, with alkali, 124.n-Hexapentacontanoic acid, 160.Hexapentaenes, 158.Hexitols, interconversion of, 173.Hinokitiol, 185.Hinopurpurins, 190.Homocaryophyllenic acid, 194.Homocyclic compounds, 184.Hormones, steroid, 297.biosynthesis of, 306.in blood, 304.ation of, 186.chloromethane, 49.of, 57.Humulene, 196.Hyalobiuronic acid, structure of, 237.Hyaluronic acid, structure of, 237.Hybridisation, 13.Hydantoins, 220.Hydrazine and its methyl derivatives,dithiocarbamido-, as reagent for copper,trimethyl-, 14 6.preparation of, 97.isomerism in, 28.318.Hydrazobenzene, rearrangement of, 125.Hydrazyl, N’N”-diphenyl-N-picryl-, re-Hydrides, mixed, 92.Hydrocarbons, 156.reactions of, 64.actions of, with radicals, 48.aromatic, photo- and radio-chemicalparafb, thermal decompositn.of, 41,43.Ramen spectra of, 23.Hydrogen, chemisorption of, 68.fluoride, gaseous, absorption spectra of,and of fluorides, 17, 18.ortho-para conversion of, 68.peroxide, acid-catalysed reaction ofdecomposition of, by X-rays, 63.reactions of, with ferric and ferroussolid, crystal structure of, 101.iodide with, 55.ions, 51.solubility of, in metals and alloys, 68.Hydrogenation, 143.Hydronopol, reduction of, 149.Hydroxylamine, phenyl-, rearrangementof, 125.reduction of, 52.Hygrine, 228.Hypobromous acid, bromination by, 129.Hypochlorous acid, chlorination by, 129.Hyponitrites, detn.of, 323.Ixnmunochemistry, 249.long-range forces in, 275.Indicators, 326.chemiluminescent, 3 2 7.fluorescent, 350.Indoles, 215.Indole alkaloids, 23 1.spiro-#-Indoxyl, 2 16.Infra-red spectroscopy, 24, 347.Inorganic ions, partition chromato-Insulin, structure of, 239, 244.Interferometer for infra-red use, 24.Invertase, yeast, 238.Iodates, 107.Iodide ions, acid-catalysed reaction ofhydrogen peroxide with, 55.Iodine atoms, recombination of, 46.mono-bromide and -chloride, reactionswith, 105.complexes with, 105, 106.electronic spectrum of, 17.reaction of, with sodium thiosulphate,graphy of, 356.106.Ion exchange, 352.Ions, non-classical, 1 18.Ionic reactions in solution, 55.8-Ionone, dehydrogenation of, 150.Iridium, detn.of, 326.Iron pentacarbonyl, structure of, 107.complex compounds of, 108.detn. of, 325, 341.exchange between oxidation states of,53.Isomerism, rotational, 23, 27.Isotopes in study of catalysis, 70.radioactive, in analysis, 357.reaction rates of, 44.separation of, by diffusion, 45.labelling with, 269.Isotope-exchange reactions, 53.a- and 8-Keratins, structure of, 364,Keten, far ultra-violet spectrum of, 21.Ketones, photo- and thermal reactions of,Keto-steroids, separation of, 209.17-Keto-steroids, detn.of, 300.Kinetics of reactions, 38, 68.Kynureninase, 284.Kynurenine, conversion of, into 3-377.60.hydroxyanthranilic acid, 284.formation of, from tryptophan, 282.~~-S-hydroxy-, synthesis of, 166INDEX OBLinoleic acid, synthesis of, 162.Liquids, polar, Debye theory and, 34.Lithium aluminium hydride as reducingagent, 143.decomposition of, 72.aluminosilicates, 96.borohydride, reduction by, 146.superoxide, 87.Lolium permne, “ fructosan ” from, 236.Lupin alkaloids, 228.Lysine, N-benzoyl-, 211.DL-Lysine, synthesis of, 165.Lysozyme, structure of, 238.Lyxoflavin, 227.Macromolecules, 235.Macrozamin, structure of, 168.Magnesium, detn.of, 318, 324.Maize, alhli-treated, for cure of pellagra,8-hydroxy-, synthesis of, 165.dihydride, 89.toxic factor in, 280.291.Malonamic acid, decomposition of, 58.Manganese, complexes of, 107.detn. of, 319.exchange between oxidation states of,53.dioxide, oxidation of, in light petroleum,149.Mannitol, hexa-acetyl derivative, reactionof, with hydrogen bromide, 171.D-Mannoheptoses, 169.L-Mannose, 169.Melanin, 216.Mercurous arsenates, 91.Mercury, detn. of, 318, 324.bromide as ionising solvent, 91.halides, complex compounds of, 90, 91.dimethyl-, infra-red spectra of, 27.Mesoionic compounds, 213.Mesopterin, 226.Metals, effect of, on hydrolysis by pept-idases, 293.Metallurgical analysis, 360.Metallurgy, spectrochernical analysis in,Methsemoglobin, structure of, 372.Methane, bromotrichloro-, reaction withexchange reaction with deuterium, 70.tris(hydroxymethy1amino)-, as acidi-nitro-, reaction of, with dialdehydes, 170.photo- and thermal bromination of, 40.Raman spectrum of, 22.Methyl alcohol, photosensitised decom-chloride, cyclopropyl-, solvolysis of, 120.ether, photosensitised decomposition of,iodide, photodecomposition of, 62.radicals, recombination of, 46.structure of, 84.344.cyclohexane, 49.metric standard, 310.position of, 60.60.Micelles, formation of, in colloidal solutions,80.IUBJECTS.417Microscopic analysis, 349.Migratory aptitudes, 126.Minerals, infra-red spectra of, 348.microanalysis of, 360.Moisture. See Water.Molecular geometry, 31.orbitals and valency, 11.rearrangements, 124.structure, 16.Molecules, diatomic, binding regions in, 14.electronic spectra of, 17.polyatomic, electronic spectra of, 19.Molybdates, 102.Molybdenum, detn. of, 319, 325.hemfluoride, structure of, 24.Monochromator, 20.Moulds, tryptophan-nicotinic acid con-version by, 282.Multiple-reflection tube, 21.Muscle, contraction of, 243.fibres, structure of, 380.living, fibre structure in, 380.Mycolic acids, 163.Mycolipenic acid-I ”, 163.Myosin, structure of, 238, 381.Myrtanol, reduction of, 149.Naphthalene, bromine and iodine com-plexes with, 105.electronic structure of, 10.solubility of, in ethylene, 78.Nephelometer, 343.Nephelometry, 343.Neptunium, 104.Nickel compounds and complexes, 109.detn. of, 319, 341.Nico tinamide, 2 7 7.N-methyl-, 277.Nicotinic acid, 276.* “ bound ”, 290.fate of, in animal body, 288.formation of, in animal body, 285.intestinal synthesis of, 281.metabolism of, 278.metabolites, urinary excretion of, 289.Nicotyrine, dihydro-, 215.Niobium compounds, 99.detn. of, 321.separation of, from tantalum, 99.Nitramide, base-catalysed decompositionof, 57.Nitramines, 168.Nitrates, detn.of, 323.Nitration, 128.Nitric acid vapour, thermal decompositionof, 42.Nitriles, 155.Nitrites, detn. of, 323.Nitrogen, adsorption of, on copper, 66.Raman spectra of, 22.detn.of, Kjeldahl, catalysts for, 330.electronic spectrum of, 17.organic compounds, 168.oxides, 98.electronic spectra of, 19.See also Dinitrogen oxides418 INDEX OF SUBJECTS.Nitrogen ring systems, 2 13.Nitrosyl halides, infra-red spectra of, 29.Nitrous acid, reactions of, with ammoniaand methylamine, 59.n-Nonatriacontanoic acid, 160.cycloNonyne, 184.19-Norprogesterone, biological activity of,19-Nortestosterone, biological activity of,Nuclear quadruple effects, 33.Nucleic acids, 246.structure of, 381.Nucleoproteins, structure of, 381.Nucleotides, 247.Nutrition, relation of antibody formationto, 250.oxide. See Dinitrogen monoxide.210.210.Octadecenoic acids, 161.cycZoOctane, 184.Octayne, 157.Octyl alcohol, solubilisation of, 82.CEstrogens, separation and detn.of, 299,301.(Estrone, synthesis of, 203.Oil industry, spectrography in, 345.Oils, detn. of moisture in, 359.detn. of nitrogen in, 329.L-Oleandrose, synthesis of, 181.Olefins, silver nitrate complexes with, 88.0 ligonucleo tides, 2 4 8.Organic analysis, qualitative and quanti-tative, 328.chemistry, theories of, 112.compounds, polarography of, 335.complexes, 155, 3 12.DL-Ornithine, synthesis of, 164.Osmium, complexes of, 110.Oxalic acid, Raman spectrum of, 22.Oxalatomolybdic acid, 102.Oxalyl chloride, isomerism and Ramanspectra of, 23.Oxazolidines, 217.Oxazolid-2-ones, 2 19.Oxazolines, 21 7.Oxidation, 128, 149.Oxides, cyclic, from alkaline hydrolysis ofOxygen, chemisorption of, 67.microwave spectrum of, 31.molecule, electronic structure of, 15.ring systems, 210.sulphates, 173.Oxytocin, structure of, 238.Palladium, detn.of, 326.“ Paludrine ”, 225.Papain, 292.Papaverine, 228.Pellagra, effect of treated and untreatedPelletierine , 2 28.Penicillin, 5-phenyl-, synthesis of, 215.Penicillin G as analytical reagent, 313.Pentaborane, 91.Pentalene, 19 1.maize on, 291.neoPentane, photo- and thermal bromin-Pentosenucleic acids, 248.Pepsin, 292.Pep tidases, effect of metals on hydrolysisby, 293.Peptides, crystal structure of, 363.synthesis and degradation of, 151, 220.Persulphate ions, decomposition of, 59.Petroleum industry, polarography in, 335.Phalloidine, hydrolysis of, 167.Phenolphthalein, nitroso-, as analyticalreagent, 313.Phosphates, detn.of, 316, 323.Phosphatides, and their derivatives, 163.Phosphides, alkali, 98.Phosphine, infra-red spectrum of, 28.Phosphorus, and its compounds, 98.detn. of, 331.Photochemistry, 59.Photometers, flame, 347.ultra-violet, 347.Photomultiplier, 20.tubes, 346.Photosensitised reactions, 59.Phthalic acid, l-ethyl-3-methyl-n-butylhydrogen ester, methanolysis of, 122.Phthalobisdimethylamide, reduction of,145.“ C,,-Phthienoic acid,” 163.Phthalobispiperidide, 145.Picrotin, 212.Picrotoxadiene, 212.Picrotoxic acid, 212.Picrotoxin, 212.Picrotoxinin, 212.Picrotoxininic acid, 212.Pinacol-pinacolin rearrangements, 127.Piperidine, nucleophilic substitution ofhalogen by, 130.Piperidines, 220.Pituitary, adrenocorticotrophic hormoneof, 245.Plakalbumin, 261.Platinum metals, complex compounds of,110, 111.Plutonium, 103.compounds, 104.Polarography, 333.Poly-(y-benzyl L-glutamate), structure of,Polyenes, electronic structure of, 16.Polyglycine, structure of, 378.Polymerisation reactions, 49.Poly(methacry1ic acid), mol.wt, andsurface activity of, 79.Poly(methy1 and benzyl L-glutamate),structure of, 365.Poly-(y-methyl L-glutamate), structure of,369, 372.Polypeptides, 245.synthetic, structure of, 364.Polysaccharides, 235.nitrogenous, 237.non-nitrogenous, 236.ation of, 40.Phthioic acid ’.’, 163.370INDEX OF SUBJECTS.419Poly-ynes, 156.Porcupine quill, proteins of, 366, 369.Porphyrin nucleus, electronic structure ofPotassamide, 88.Potassium chlorate, decomposition of, 73.16.detn. of, 317, 318, 324.hydrogen fluoride, infra-red spectrum ofPotential-energy barriers, internal tor.Potentiometric titration, 336.Precipitates, specific, recovery of anti.bodies from, 252.Pregnanediol, detn. of, 302.Pregnene-11 : 20-dione7 3a : 17a- di- andPregn-4-ene-3 : 20-dione, 11 : 17 : 21-tri-hydroxy-, 303.Pregn-5-ene-3/3 : 16a : 20u-trio1, 303.Pregn-5-ene-3p : 17a : 20a-triol, 303.Pregn-4-ene-3 : 11 : 20-trione,hydroxy-, 303.Prins reaction, 154.Progesterone, 209.Proline, L-hydroxy-, crystal structure of,Propaldehyde, pyrolysis of, 61.isoPropyl alcohol, oxidation of, 128.borate, reaction of, with aldehydes andPropylene, thermal decomposition of,42.Propyne, 1 : 1 : l-trifluoro-, radial-Protactinium, source of, and its separ-Proteases, 292.pancreatic, specificity requirements of,crystal structure of, 362.fibrous, structure of, 364.Elobular, 372.a-helix ” in, 367-372.labelled with lalI, 269.B-structures in, 377.structure and properties of, 240.26.sional, 33.3~ : 17a : 21-iPi-hydr0~y-, 303.17 : 21-di-363.ketones, 148.distribution function for, 37.ation, 100, 319.293.Proteins, 238.Pteridines, dihydro-, synthesis of, 226.Pterins, 226.Pterorhodin, 226.Euberulonic acid, structure of, 187.Pulque ”, nicotinic acid in, 291.Purpurogallin, preparation of, 186.Pyrans, 211.Pyrazines, 225.Pyrene, 184.Pyridine, 3-acetyl-, nicotinic acid deficiencyfrom, 280.Pyridines, 220.Pyridine-3-carboxyamide, 1 : 6-dihydro-6-detn.of, 278.Pyridinecarboxylic acidg, decarboxylationoxide, nitration of, 129, 221.keto -”-me th y l- , 2 9 2.of, 133.Pyridoxine, effect of, on metabolism ofPyrimidines, 224.Pyrroles, 215.Pyrrolines, structure of, 215.Pyrrolinones, 222.Quantum mechanics applied to chemistry,tryptophan, 287.7.of valency, 7.Quinaldil, 224.Quinaldine, 8-hydroxy-, as analytical re-agent, 312.Quinaldoin, 224.Quinamine, 231.Quinol, reaction of, with ferric ions, 5 1.Quinoline, 8-hydroxy-, as analytical re-agent, 312.oxide, nitration of, 129.Quinolines, 223.isoQuinoline alkaloids, 228.isoQuinolines, 224.l-isoQuinolones, 224.Quinoxalines, 225.theory, mathematics of, 8.Radiation chemistry, 59, 63.Radicals, free, initiation of polymerisationreactions with, 46.reaction rates of, with molecules, 46.rearrangements of, 127.Radioactive elements, analytical chemistrymaterials, chromatography of, 351.Radiochemical analysis, 357.Reactions, atomic, and free-radical, 46.first-order and unimolecular, 4 1.homogeneous, kinetics of, 39.involving cyclic transition states, 132.mechanism and kinetics of, 38.by, 50.of, 360.Reactivity and structure, 113.Reagents, 311, 322.Rearrangements, aromatic, 125.pseudo-Rearrangements, 124.Reduction, 143.by, 50.Reformatsky reaction, 155.Resins, ion-exchange, 352.Rhenium compounds, 107.Ribitol, synthesis of, 173.Riboflavin, effect of, on tryptophanmetabolism, 287.Ribonuclease, structure of, 375.Ribonucleosides, configuration of, 247.Rocks, polarography of, 335.Rotation, internal, 27.Salicylic acid, sodium salt, fluorescenceof, 20.larcosine, 164.Sarmentose, 181.Scandium, detn.of, 319.Schiff’s bases, 219.electrolytic initiation of polymerisationdetn. of, 319420 INDEX OISedimentation, 86.analysis, 359.Selenium, detn. of, 317, 324.Serpentine, 232, 233.Sesquiterpenes, 193.Siaresinolic acid, dihydro-, 199.Silica, precipitation of, by gelatin, 3 17.Silicates, 96.Silver, detn. of, 318.nitrate complexes, 88.reductor, 325.Soaps, “ smectic ” complexes of, 83.Soap hydrates, 81.solutions, concentration and dissoci-Sodium borohydride, reduction by, 146.cobaltinitrite, preparation of, 31 7.detn.of, 324.dodecyl sulphate, surface tension of, 85.thiosulphate, reaction of, with iodine,Sorbitol, and its triethylidene derivative,Solids, reactions of, 71.solubility of, in gases, 77.Solubilisation, 81.“ interaction ” and “ intramicellar ”,“ Soluble oil ” type systems, 86.Solutions, electron-transfer reactions in,ation in, 80.106.171.83.50.ionic reactions in, 55.liquid, 73.Raman spectra of, 22.statistical theory of, 73.Solvent effect, 34.extraction, 353.Spartiurn junceum, octadecme-1 : 18-diolfrom, 167.Spectra, electronic, 16.infra-red, 24.intensity measurements in, 27.micro-wave, 30.Raman, 21.vacuum ultra-violet, 20.Spectrograph, mass, 349.Spectrometers, calibration of, 25.Spectrophotometers, 338.Sphingine, derivatives of, 164.Sphingosine, and dihydro-, 164.Starch, structure of, 236.Stmk effect, 31.Steel, spectrochemical analysis of, 345.Stereochemistry and dipole moments, 36.Stereoisomerism, 135.Steroid alcohols, detn.of, 300.biosynthesis of, 306.in blood, 304.hydrolysis of, 298.in urine, 297.radioactive, biogenesis and metabolismof, 209.infra-red, 24.infra-red, 24.hormones, 297.Steroids, 200.SUBJECTS.Steroids, separation of, 299.unsaturated, reduction of, 148.Stipitatic acid, synthesis of, 186.Structure and reactivity, 113.Styrene, polymerisation of, 49.Substitution, aliphatic, 121.aromatic, 128.free-radical, 130.nucleophilic, 130.strain effects in, 123.Subtilin, 246.Succinimide, N-bromo-, brominrttion by,150.N-chloro-, oxidation by, 149.Sucrose, kinetic salt effect in inversion of,35.Sugar alcohols, polyhydric, 17 1.thio-derivatives of, 172.Sugars, 168.Sulphones, reduction of, 147.Sulphonyloxy-group, reactivity of, 172.Sulphur compounds, 101.synthesis of, 169, 183.trifluoroacetyl derivatives of, 181.detn.of, 317, 323.hemfluoride, infra-red spectrum of, 29.ultra-violet absorption spectrum of,radioactive, use of, in exchange-reactionstudy, 54.ring systems, 212.Sulphurous acid, oxidation of, by man-ganese oxides, 101.Surface activity, 79.chemistry, 64, 78.Sydnone, 213.L-Talomethylose, 180.Tantalum compounds, 99.Tartaric acid, sodium ammonium salt,D-Tartaric acid, sodium rubidium salt,D( +)-Tartaric acid, configuration of, 135,UD : a’D-Tartaric acid, 136.Tellurium, detn.of, 317, 324.Testosterone, metabolism of, 306.Tetradeuterioacetaldehyde, pyrolysis of,n- and iso-Tetrandrines, 229.Thallium, detn. of, 319.Thallous hypophosphite, 94.Thiazoles, 219.Thiazolidines, 2 19.Thiazolines, 219.diThiocarbamic acid, 313.Thioformamide as precipitant for arsenic,Thioglycopyranosides, desulphurisation of,Thioindigo, stereoisomerism of, 140.Thiophans, 212.20.detn. of, 321.separation of, from niobium, 99.stereoisomerism of, 135.crystallography of, 361.136.60.exchange between oxidation states of, 53.316.176INDEX OF SUBJECTS.421Thiophens, 212.endoThiothiadiazoles, &hydro-, 214.Thiourea complexes, 156.Thorium carbide, 95.Thujaplicins, 186.Thymonucleic acid, sodium salt, structureof, 382.Tin compounds, 96.detn. of, in steel, 319, 325.exchange between oxidation states of, 53.Titanium, detn. of, 320, 326.halides, 96.Tobacco viruses, mosaic, structure of, 238,Toluene, reaction of, with chlorine, 62.Toluene-p-sulphonic acid, esters, action ofToxic factors, 280.Transuranic elements, 102.Triazines, 228.Tricosanoic acid, r-3 : 13 : 19-trimethyl-,161.Trimethylene oxide, 210.Trisalicylides, 141.Triterpenes, 196. ((Triticum repens,Tropolone, 132.separation and detn. of, 320.381.necrosis, structure of, 382.lithium aluminium hydride on, 147.fructosan ” from, 237.addition of bromine to, 189./3-isopropyl-, substitution reactions of,conversion of, into benzenoid com-esters and ethers of, 190.substituted, interconversion reactions of,substitution in, 188.189.Tropolones, 185.pounds, 185.189.Tropomyosin, structure of, 238, 364.Tropone, 187.Trypsin, 293, 294.Tryptamine, 5-hydroxy-, 21 7.Tryptophan, conversion of, into kynur-inhibitors of, 297.enine, 282.into nicotinic acid, 283.DL-hydroxy-, preparation of, 166.relation of, with nicotinic acid, 281.(+)- and (-)-Tuberculostearic acids, 139.Tungsten bronzes, 102.Turbidimetric standards, preparation of,from Perspex, 343.Tyrosine, reactions of, 216.DL-Tyrosine, synthesis of, 165.Ultra-violet, vacuum, absorption spectraUltra-violet spectroscopy, 347.Uranium compounds, 102.Urea complexes, 156.Urine, detn. of corticoids in, 300.steroids in, 297, 302.Uronic acids, methylated, characterisationUroporphyrin, 215.Valency, theories of, 7, 11.Vanadium trichloride, anhydrous, 99.detn. of, 319, 320, 326.Violanthrone, synthesis of, 131.Virial coefficients of mixed gases, 77.Visnaginone, dihydro-, dehydrogenationof, 150.Vitamin A,, synthesis of, 159.Vitamin A,, structure of, 160 .Vitamin B,, 222.Volumetric analysis, inorganic, 322.Wastes, industrial, polarography of, 335.Water, detn. of, 359.Weights, 316.Wolff-Kishner reaction, 148.Wool fat, a-glycols in, 167.Zamene, 156.Zinc compounds, complex, 90.detn. of, 319.hexafluoride, structure of, 24.in, 20.of, 183.preparation of, 183.Karl Fischer reagent for, 359:structure of, 16, 100.detn. of, 318, 324.hydride, 89.dimethyl, infra-red spectra of, 27.detn. of, 320.separation of, from hafnium, 97.Zirconium compounds, 97

ISSN:0365-6217    

DOI:10.1039/AR9514800411

出版商:RSC    

年代:1951

数据来源: RSC