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ISSN:0365-6217    

DOI:10.1039/AR94441FP001

出版商:RSC    

年代:1944

数据来源: RSC

摘要:

ANNUAL REPORTSON THEPROGRESS OF CHEMISTRY.GENERAL AND PHYSICAL CHEMISTRY.1. SURFACE CHEMISTRY.THIS section is restricted to certain aspects of monolayers at mobile interfaceswhich have evoked interest in recent years and have not been dealt with inearlier Reports.l.2The reduction of surface tension by the monolayer, termed the “ surfacepressure,’’ and previously denoted by P, is now denoted by IT in conformitywith the revised nomenclature. The change in phase boundary potential,or “ surface potential,” is denoted by A V and is usually related to the mole-cular density (n, in molecules/cm?) by the Helmholtz equation AT‘ = 4mp,where p is the vertical component of the apparent dipole moment; A =1016/n, is the area (in a.2) occupied by each molecule in the surface.Themeasurement of surface pressure, surface potential, and mechanical pro-perties such as elasticity and rigidity have been outlined before.l,The Str2ccture of Momlayers.-Of the principal two-dimensional phaseswhose existence is well established, viz., gaseous, expanded, and condensed,the structure in the first two is now generally accepted. Gaseous filmsapproach the ideal relationship IIA = kT a t very low surface pressures(areas generally of the order 1000-10,000 A.2/molecule), and obey anequation of the Amagat type IT(A - A,) = skT a t higher pressures. Lang-muir’s explanation for the ‘‘ expanded ” type,ll3 which have no three-dimen-sional analogy and which obey the equation of state (II - IT,)(A - A,) = C,has been generally accepted. In this equation TI, allows for the (negative)spreading pressure of the chains, A, is the ‘‘ co-area ” of the polar head-group, and C a constant equal to kT for un-ionised groups? As pointedout below, this explanation has been strengthened by work upon insolublemonolayers a t the oil-water interface.Considerable discussion still centres, however, upon the condensed films.The 1I-A curves of condensed films of simple long-chain hydrocarbonderivatives generally consist of two approximately linear portions, the firstand more compressible part extrapolating to about 22-30 A?, dependingupon the nature of the head-group, and the second showing a very lowcompressibility and extrapolating to 20-21 ~ .2 in all cases. N. K. Adam tihas ascribed these to close-packed heads and close-packed chains respect-N.K. Adam, Ann. Reports, 1936, 33, 103.J. H. Schulman, i&id., 1939, 36, 94.I. Langmuir, J . Chem. Physics, 1933, 1, 756.J. Marsden and E. K. Rideal, J . , 1938, 1163.“ Physics and Chemistry of Surfaces,” 3rd Edition, 1941 (Oxford Univ. Press)6 GENERAL AND PHYSIUAL CHEMISTRP.ively, whereas W. D. Harkins and G. E. Boyd class them as liquid andsolid, and D. E. Dervichian claims that breaks occur at areas prescribedby the packing in the various three-dimensional crystalline forms, e.g.,at 18.5, 19.5, 20.5, 22, and 23.5 A . ~ in the case of fatty acids. Dervichian’semphasis upon a close correspondence between the two-dimensional con-densed film and the three-dimensional crystal has been strongly criticised,For instance, Harkins and Boyd8 point out that accurate n-A curves offatty acids do not show breaks at his predicted areas, and that the liquidcondensed phase cannot be crystalline (as postulated by Dervichian), sincetheir viscosity measurements exactly fit the theory of liquid monolayersdeveloped by W.J. Moore and H. E~ring.~ In the Reporter’s opinion lothe available evidence is strongly opposed to any such general thesis,lla conclusion supported by. subsequent work. Although a powerful inter-action between polar group and the aqueous substrate is necessary to obtainspreading, it seems unlikely that the magnitude and direction of the forcesinvolved would exactly compensate in all cases for those in the crystallinestate.In the very incompressible region the recent alternative suggestionthat the long-chains are vertically orientated and close-packed l2 is basedupon the agreement between the compressibility of the monolayer and oflong- chain hydrocarbons in bulk, and between the cross-sectional areasof the monolayer and of paraffins near their melting points (both 19-20A .~ ) , i.e., in what is believed to be their most nearly oomparable states.12This formulation is supported by surface-potential measurements uponethyl stearate, the apparent surface moment of which can only be satis-factorily explained on the basis of vertically orientated chains.12The structure of the more compressible region of condensed films doesnot seem to be so definitely established, different factors appearing to beoperative with different head-groups.12 For instance, in some cases, e.g.,p-hexadecylphenyl derivatives, C,,H,,*C,H,X, the limiting area is deter-mined by the “ size ” of the phenyl nucleus, since with X = -OH, -NH2,or -OCH, the limiting area remains constant at ca.25 A . ~ ; in others (e.g.,cis- and trans-unsaturated compounds) , the hydrocarbon chain packingseems to be the decisive factor, and in certain others hydrogen-bond form-ation between the head-groups lo. l3 (e.g., long-chain amides, acetamides,and ureas).is also controvereial. In the more compressible “ liquid ” region, all filmsso far studied behave as Newtonian liquids, the surface viscosity 7 obeyingthe equation, log r) = log q, + kII, as predicted by Moore and Eyringgfrom Eyring’s theory of the liquid state.It seems reasonable thereforeThe suggested classification of condensed films as “ liquid ” or “ solid ”6 J . Physical Chem., 1911, 45, 20. J . Chem. Physics, 1939, 7, 931.Ibid., 1938, 6, 391. Ibid., 1940, 8, 129.10 A. E. Alexander, Trans. Paraduy Soc., 1941, 57, 426.11 See also A. Q. Nasini and Q. Mattei, Obzzelta, 1940, 70, 697.12 A. E. Alexander, Proc. Roy. Soo., 1942, A, 178, 486. Is Idem, aid., p. 470ALEXANDER SWRFAUP) UEIEMISTBY. 7to term this region “liquid condensed,” but the use of the t a m “solidcondensed” for aZE films in the other condensed region is less justifiable.Here some films are quite mobile (e.g., methyl ketones and esters), othersdefinitely very rigid (e.g., heavy-metal soaps, ureas, and amides).Thelong-chain alcohols, acids (un-ionised) ,I4 and esters,15 exhibit anomaloussurface viscosity, and this is possibly general for all mobile films in thisregion, but to term these “ solid ” seems unnecessarily confusing. Withthe more rigid films a definite elastic modulus can be obtained by applyinga torque to a diso on the surface,16 or by rotating a disc in the liquid andobserving the motion of dust particles on the film.17Spreading and Phase Changes of Monolayers.-By means of the Clapeyronequation in the form h = T(aH/aT)(Ap - AB) it is possible to determinethe latent heat of spreading (A) from the crystal to the monolayer.l* (AFand As are areas occupied by film and solid respeotively.) Some veryaccurate II-A and IT-T measurements have been carried out recently forthis purpose by Harkins and his co-workers, with myristic and pentadecylicacids, and latent heats and entropies of spreading determined.lgSuch measurements lead naturally to a consideration of the thermo-dynamics of monolayers, such as the energy, entropy, and heats of spreadingand expansion, and the order of phase change~.~*~OThere has been much discussion recently concerning the fundamentalstability of duplex or multi-layers, such as are formed initially by a mixtureof an .inert oil containing an amphipathic compound a8 “ spreader.” Thishas some practical bearing upon the use of oil films in antimalarial measures,and in preventing the evaporation of water, as discussed below.Withsimple long-chain acids, alcohols, etc., it seems that the equilibrium systemconsists of monolayer and lenses, but with polymerised spreaders, or withcertain dyes in the aqueous phase, stable (or metastable) thick films couldbe obtained.21 It is probably very significant that in all such cases theinterfacial films are rigid. W. A. Zisman22 has recently made a verythorough study of the spreading of drops of an inert oil containing polarcompounds, on the lines first initiated by I. Langmuir and K. B. BlodgettF8and as expected, maximum spreading is induced by compounds ionised a tthe interface (e.g., acids on alkaline solutions).I* L. Fourt and W. D. Harkins, J . Physical Chem., 1938, 42, 897; G. E. Boyd andW. D. Harkins, J.Amer. Chem. SOC., 1939, 61, 1188; L. E. Copeland, W. D. Harkins,and G. E. Boyd, J . Chern. Physics, 1942,10, 357.lS A. A. Trapeznikov, Acta Physicochim. U.R.S.S., 1038, 9, 273; 1939, 10, 65;Dokhdy Akad. Nazclc. U.R.S.S., 1941,30,319.l6 H. Mouquin and E. K. Rideal, Proc. Roy. Soo., 1027, A , 114, 690; A. A.Trapeznikov and P. Rebinder, Compt. r e d . (Doklady) U.R.S.S., 1938, 18, 185.l7 A. E. Bresler and S. E. Bresler, J . Physiccrl Chem. U.S.S.R., 1940, 14, 1604.l@ W. D. Harkins and G. C. Nutting, J. Amer. Chem. Soc., 1939,61, 1702.*O W. D. Harkins, T. F. Young and G. E. Boyd, J. Cheni. Physics, 1940, 8, 964;a1 E. Hepann and A. Yoffe, Tram. B’ar&y Soc., 1942, 38,408; 1943, 89, 217.22 J. Chern. Physics, 1941,9,634,729,789. 28 J. Pranklin Inat., 1934,218,143.A.Cary and E. K. Rideal, Proc. Roy. Soc., 1926, A , 109, 301.W. D. Harkins and L. E. Copeland, ibid., 1942, 10, 2728 GENERAL LND PHYSICAL CHEMISTRY.The kinetics of spreading, both from liquid droplets and from crystals,have also been further examined in some detail. In the usual method theedge of the advancing film is indicated by a suitable inert powder and photo-graphed by means of a cine ~amera.2~ Another technique, attractive inthat it avoids the possibility of contamination by powders, uses a series ofair electrodes, connected to an oscillograph with photographic registration,and arranged so that the spreading film passes radially under each in turn.25Spreading at interfaces can also be followed by the latter method.These experiments show that boundary spreading is in general veryrapid indeed compared with dissolution from the interface, even withcomparatively soluble substances (see also below).The rapidity of spreadingof insoluble oils such as oleic acid has indeed been used to investigate thestructure of adsorbed 26#27Evaporation through Monolayers.-The influence of boundary layersupon the movement of molecules from one phase to another has been littleinvestigated save for the study of evaporation from a water surface, andthis has derived much of its impetus from the very practical problem ofretarding evaporation from lakes and reservoirs in arid regions, such asSouth Africa, Australia, and parts of Russia. Although the practicalproblem does not appear to have been satisfactorily solved, yet some veryinteresting results have emerged.211 28Monolayers alone being used, it is generally agreed that only condensedfilms are appreciably effective, possibly not so surprising in view of the largeenergy barrier at the interface.With long-chain alcohols, such as octadecyl,as much as 95% reduction can be obtained at high film pressures. Markedreductions can also be obtained by the use of duplex oil films several pthick, by using suitable polymers as spreaders.21 These films, as pointedout above, appear to be reasonably stable in the laboratory, but deterior-ate when subjected to atmospheric conditions such as rain, wind, anddust.Reactions in Monolayers.-The study of reactions at the air-waterinterface by means of the monolayer technique is due principally to Ridealand his co-workers. Reactions can be followed by change of area or ofsurface potential, usually at constant IT.In almost all cases a very markeddependence upon the molecular orientation at the interface is observed-a true " steric '' factor which may modify the reaction velocity by a powerof 10 or more.24 E.g., F. Ford and D. A. Wilson, J. Physical Chem., 1938, 42, 1051 ; E. H. Mercer,Proc. Physical SOC., 1939, 51, 561 ; W. von Guttenberg, 2. Physik, 1941,118,22.25 A. E. Alexander and T. Teorell, unpublished.26 J. W. McBain and W. V. Spencer, J. Amer. Chem. SOC., 1940,62,239.2 7 A. E. Alexander, Trans. Faraday SOC., 1942, 38, 54.28 N. I. Glazov, J . Physical Chem. U.S.S.R., 1938, 11, 484; F.Sebba and H. V. A.Briscoe, J . , 1940, 106, 114, 128; F. Sebba and E. K. Rideal, Trans. Paraday SOC.,1941, 37, 273; A. S. Kheinman, J . Physical Chem. U.S.S.R., 1940, 14, 118; S. I.Sklyarenko, M. K. Baranaev, and K. I. Mezhueva, ibid., p. 839; I. Langmuir and V. J.Schaefer, J . Fmnklin In&. 1943, 235, 119ALEXANDER : SURFACE CHEMISTRY. 9The oxidation of unsaturated compounds by dilute permanganate,outlined in an earlier Report,l has been further studied with triolein 29 andwith cis- and trans-unsaturated acids.4 Erucic and brassidic acids showvery clearly the greater ease of packing of the hydrocarbon chains in thetrans-compound (and hence of removal of the double bond from the aqueousphase), since the oxidation of brassidic acid (trans) can be almost completelyinhibited by increasing the surface pressure, whereas the cis- form (erucic)is but little affected.Closely related to the above, and showing a common sensitivity tomolecular orientation, is the oxidation and subsequent polymerisation ofmonolayers of drying oils, by atmospheric oxygen, ozone, or ~ermanganate.~~Certain other types of polymerisation, vix., pepsin-formalin, cadaverine-pepsin, and tetra-aminobenzidine-stearaldehyde, have also been followedin mono layer^,^^ and it is clear that the method offers considerable scope inthis direction.The hydrolysis of lactones 32 and esters 33 and the lactonisation ofhydroxy-acids 34 also provide several points of interest.The alkalinehydrolysis of esters shows particularly well how the velocity of interfacialreactions can be controlled by means of a true steric factor.For example,with an expanded Hm of ethyl palmitate the short ethyl chain lies on thesurface, and the reaction can proceed quite rapidly (k = 0-04 min.-l). Oncompression to the condensed state the short chain is forced beneath thesurface, thus screening the ester group and reducing the velocity constantIc to 0-005 min.-l. The change can be depicted as below :Ethyl palmitate Ethyl palmitate Octadecyl acetate(expanded). (condensed). (condensed).I / /“0p&#.. milli-Debyes 536A , A.= ............ > 72k, min.-l ......... 0.04pcalc., 9 , 9 , 525\CH3193198200.005502525230.152s R. Mittelmann and R.C. Palmer, Trans. Furuduy SOC., 1942, 38, 506.30 G. Gee and E. K. Rideal, Proc. Roy. SOC., 1935, A , 153, 116, 129; J., 1937,772;P. H. Faucett, Drugs, OiZs and Paints, 1939, 54, 13; A. G. Nasini and P. Ghersa, AttiXO Cong. intern. Chim., 1939,4,236; C . Ockrent and W. H. Banks, Nature, 1940,145,861 ;A. G. Nasini and G. Mattei, Gazzetta, 1941, 71, 302, 422.31 S. E. Bresler, D. L. Talmud, and M. F. Yudin, J. Physical Chem. U.S.S.R.,1940, 14, 801; Actu Physicochirn. U.R.S.S., 1941, 14, 71.32 R. J. Fosbinder and E. K. Rideal, Proc. Roy. SOC., 1933, A , 143, 61.33 A. E. Alexander and J. H. Schulman, ibid., 1937, A , 161, 11.5; A. E. Alexander34 F. Kogl and E. Havinga, Rec. Truv. chim., 1940, 59, 601.and E. K. Rideal, ibid., 1937, A , 183, 70.A 10 QBIKEBAL AND PHYSICIAL OHEMISTRY.The validity of these configurations was confirmed by the agreement betweenthe observed surface moments (v) and those calculated by the Thomson-Eucken vectorial summation method.With a long-chain acetate, on theother hand, it is clear from the above diagram that condensation affordsno such protection, and the reaction is still rapid (k = 0.15 min.-1).The lactonisation of monolayers of hydroxy-fatty acids on acid sub-strates has shown in one case (@-hydroxyethyloctadecylmalonic acid) arate some lo3-lo4 times greater than in solution a t the same pH; inanother case (y-hydroxystearic acid) reaction was slower in the film.34 Thelatter effect has been ascribed to steric hindrance, whereas the former maybe due either to a particularly favourable proximity of hydroxyl andcarboxyl groups, or to a higher concentration of hydrogen ions in the surfacelayer than in the bulk medium.The latter explanation may well be thecorrect one, since various workers, from other considerations, have suggestedjust such a difference between surface and bulk It would be interest-ing to see this finally established by this rather direct method.The monolayer technique enabled J. S. Mitchell and E. K. Ridea136 toinvestigate the effect of ultra-violet radiation upon proteins, using as astarting point . monolayers of stearanilide and other simple compoundscontaining the -CO*NH- link. The presence of the aromatic nucleusinduced photochemical hydrolysia, leaving a monolayer of stearic acid, atwave-lengths of 2483 A.and less, the apparent quantum efficiency and rateof reaction being very sensitive to the orientation of the aromatic chromophorwith respect to the surface. The eame authors later 37 described the effectof irradiating protein monolayers, which causes liquefaction of the originallygel films and an increase in surface pressure. The above work suggeststhat peptide links adjacent to each chromophoric side chain undergophotolysis, the liberated chromQphoric residue dissolving into the substrate.The preliminary results of an essentially similar investigation have beenpublished by D. C. Carpenter.38Finally, mention may be made of the monolayer technique to studythe halogenation of phenols, where reaction is well known to proceedextremely rapidly in some cases (e.g., phenol with free bromine).Mono-layers of p-hexadecylphenol were employed, and the kinetics of reactionwith hypohalous acid, free halogen, and trihalide ions determined.39Reactions with a half-life of as little as 40 seconds could be followed satis-factorily. The halogenation of long-chain unsaturated compounds, par-ticularly by iodine chloride, which is closely related to t h e above, has beenfollowed in similar manner by A. G . Nasini and G. Mattei.40Insoluble Monolayers at the O i d Water Interface.-It is only comparativelyrecently that any marked success has been achieved in the study of insoluble36 J. F. Danielli, Proc. Roy. SOC., 1937, B, 122, 155; G. S. Hartley and J. W. Roe,Trans. Faraday Soc., 1940, 36, 101.36 Proc.Roy. SOC., 1937, A , 159, 206.3’ Ibid., 1938, A, 167,342.s9 A. E. Alexander, J., 1938, 729.s8 Science, 1939, 89, 251.O0 Qazzetta, 1940, 70, 635ALEXANDER: SURFAOI UHEMIS!FRY. 11monolayers at oil-water interfaces. This has been due to the difiicultieuencountered and not to the lack of interest, since such interfacial films areclearly of more direct relevance to the biologist and emulsion chemist thanare those at air-water interfaces,Some preliminary II-A measurements were obtained by F. A. Askewand J. I?. Danielli,41 using a slightly modified Langmuir-Adam surfacebalance, and bromobenzene as the oil phase. Various compounds weremeasured (egg-albumin, a-aminopalmitic acid, a long- chain amide, and amethyl cellulose), but very great difficulties with leaks and contaminationwere found.The various methods which appeared promising, oiz., the modifiedsurface balance, detachment methods such as the maximum pull on a ringor frame, and the Wilhelmy plate, were explored by A.E. Alexander andT. Te~rell,~Z using benzene as the oil phase, but only the ring method wasfound suitable. The interface is formed in a large Pyrex dish, and the inter-facial tension (’yo) determined. By means of a micrometer syringe, a smallbut accurately-known volume of a solution of the compound under examin-ation is then expelled into the interface, and the new interfacial tension(7) determined as before. Hence the spreading pressure (II) due to the filmcan be found, since II = yo - y.The molecular density at the interfaceis then increased, and the II-A curve constructed, not by reducing the areaas with air-water monolayers, but by further injections of spreading solution.This technique avoids errors due to leaks and varying contact angles, andgives an accuracy equal t o that of the usual film balance for air-watermonolayers.By this means accurate H-A curves for six compounds a t the benzene-water interface were determined, vix., for gliadin , serum albumin, lecithin,Iysolecithin, k e ~ h a l i n , ~ ~ and sodium cetyl sulphate. The results showinteresting similarities and differences when compared with those givenby the same compounds at the air-water interface. For example, theI-I-A curves are of the vapour expanded type in all cases, as might be expectedfrom the presence of the oil medium, but on compression the moleculesreach the same ultimate paoking as a t the air-water interface (see alsoHeymann and Yoffe),21indicating that the oil is eventually squeezed outcompletely from the interface.Films of the above phospholipoids at theair-water interface are of the liquid expanded type, obeying Langmuir’sequation of state (11 - rI,)(A - A,) = C , and this was also found to holdfor their interfacial films. The change from an air-water to a bcnzene-water interface had no effect on A , or C, but eliminated no almost completely(s.g., from 12.8 to 0-05 dyne/cm. with lysolecithin). As pointed out above,these results provide direct support for Langmuir’s theory of expandedfilms at air-water interfaces.The mechanical properties of interfacial films (e.g., elasticity and viscosity),O1 Proc.Roy. SOC., 1936, A , 15S, 695; g’rans. Paraday Soc., 1940, 36, 785.4 2 Ibid., 1939, 85, 727.43 A. E. Alexander, T. Teorell, and 0. G. Aborg, &bid., p. 120012 GENERAL AND PHYSIUAL CHEMISTRY.can be determined by an oscillating needlet4 or by the rotating themethods developed for air-water interfaces being followed closely, but thedetermination of the change in phase-boundary potential (AT) is not yetentirely satisfactory. The difliculty here arises from the high resistanceof even a thin film of benzene or other suitable non-polar oil. Some pre-liminary results for using a very thin film of benzene, a largepolonium air electrode, and a Lindemann or valve electrometer, indicatethat for a given molecular density the dipole orientation and change in phaseboundary potential are the same at both air-water and oil-water interfaces.When a suitable technique for interfacial potentials has been finallyevolved, a systematic examination of insoluble interfacial monolayers willbecome possible.The oil-water shows certain advantages over the air-water interface : spreading is facilitated (e.g., proteins spread readily andcompletely), and ionised substances, such as soaps and detergents, arestabilised sufficiently to make measurements feasible. A clear under-standing of interfacial monolayers should help considerably towards theelucidation of certain problems of adsorbed films.Some Applications of Monolayer Techniques to Other Fields.--No surveyof recent advances in surface chemistry would be complete without out-lining some of the ways in which the study of monolayers has assistedproblems in other branches of science.I n addition to those mentionedabove and certain physical aspects recently there are numerousapplications to organic and physical chemistry, to classical colloidal systemssuch as emulsions, and finally to biology, a field in which the obviousapplicability of surface studies is only just beginning to make itself manifest.(a) Structure of complex organic molecules. The use of monolayermeasurements as an aid towards elucidating the structure of complexorganic molecules is well shown by several recent publications.Thepossibilities inherent in such a method had been indicated by the earlywork of Adam and his co-workers on sterols,5 and in general terms it canbe said that the technique can indicate not only the general shape of themolecule but also the relative positions of the polar groups. (One polargroup at least is necessary to ensure suitable spreading.) For example,a molecule composed of a complex ring system with two polar groups inclose proximity would probably give a condensed film, thus allowing adirect comparison between the monolayer area and that calculated frommodels of likely structures. If, however, these polar groups are widelyseparated, then the molecule tends to lie flat on the surface, giving a gaseousor expanded film.Recent work on these lines has dealt with cerin, friedelin, and relatedcompounds,47 lupane derivatives:* the constitution of quillaic and oleanolic4 4 A.E. Alexander, Trans. Faraday Xoc., 1941, 37, 117.4 5 P. F. Pokhil, J . Physical Chem. U.S.S.R., 1939, 13, 301.46 A. E. Alexander, Reports Prog. Physics, 1943, 9, 158.4 7 N. L. Drake and J. K. Wolfe, J . Arner. Chem. SOC., 1940, 62, 3018.4 8 P. Bilham, E. R. H. Jones, and R. J. Meakins, J., 1941, 761ALEXANDER : SURFACE CHEMISTRY. 13acids,49 and the position of the carboxyl group in certain triterpene acids.60S. Stallberg and E. Stenhagen, in a series of papersY5l have dealt with mono-layers of compounds with branched hydrocarbon chains, with the objectof elucidating the structure of phthioic acid s2 and other complex biologicalcompounds.I n this connection it is important to emphasise the value of the multi-layer technique for inducing crystallisation of complex organic molecules,soften intractable to ordinary methods, so that additional information fromX-ray analysis might become available.(b) Emulsions.Two fundamental papers 54 upon the formation, stability,and structure of oil-in-water and water-in-oil emulsions were based uponmonolayer studies at the air-water interface as detailed in an earlier Report.2With some two- component monolayers, such as cholesterol and sodiumcetyl sulphate, a marked molecular association, or “ complex ” formation,is found, as evidenced by the reduction of the surface or interfacial tension,and owing to this extremely low oil-water tension very stable emulsionsare formed on shaking a mixture of cholesterol in oil and sodium cetylsulphate in water.A charged interfacial monolayer, as given by the abovesystem for example, was found to promote oil-in-water emulsions, whereason discharge, as by addition of calcium ion to an ordinary soap, rigid filmsare produced which tend to link the oil droplets together, enclosing theaqueous phase and so forming the invert water-in-oil type.One phenomenon, which has arousedconsiderable discussion during the past decade is the anomalously slowrate of transfer of molecules from bulk solution to a freshly formed interface,generally termed “ surface ageing.” 55 Soaps and synthetic detergentsoften require several days for equilibration if their concentration is belowthat for micelle formation; if above it, equilibration is very rapid.Un-ionised amphipathic compounds such as alcohols and acids also show thesame slow accumulation, the anomaly increasing with the chain length.A recent examination from a new angle shows that the time factor isreduced by the presence of simple capillary-active substances (e.g. , ethylacetate), and eliminated at an oil-water interface, even when the oil phaseis only of molecular dimensions (e.g., oleic acid or ethyl laurate monolayers) .56These results appear to rule out earlier theories, which postulated electro-static potential barriers at the surface 57 or the formation of surface pellicles(c) The surface ageing of solutions.49 P.Bilham and G. A. R. Kon, J., 1941, 552.60 P. Bilham, G. A. R. Kon, and W. C. J. Ross, J . , 1942, 35.61 Svensk Kern. Tidskr., 1940, 52, 223; 1941, 53, 335; J. Biol. Chem., 1941, 139,62 N. Polgar and S i r R. Robinson, J., 1943, 615.63 For recent reviews, see refs. (2) and (46).54 J. H. Schulman and E. G. Cockbain, Trans. Faraday SOC., 1940, 36, 651, 661;55 For early references, see ref. (5).ti6 A. E. Alexander, Trans. Paraday SOC., 1941, 37, 15.6 1 K. S. G. Doss, Gurr. Sci., 1935, 4, 405; 1937, 5, 645; Kolloid Z., 1939, 86, 205;345; 1942,143,171 ; 1943,148, 685.T. P. Hoar and J. H. Schulman, Nature, 1943, 152, 102.cf. G. S. Hartley and J. W. Roe, Trans. Faraday SOC., 1940, 86, 10114 GENERAL AND PHYSICAL CHEMISTRY.more than unimolecular in thi~kness,~8 and it seems that the slow, rate-determining step is the penetration, into the surface layer, of the hydrophobicportion of the molecule.A slow accumulation is also observed with polar compounds in non-aqueous media, both t o the surface59 and to an aqueous interface.6O Inthese organic media it would appear that the apparent retardation arisesprimarily from the low concentration of solute present in the monomericform, since media favouring dissociation, such as nitrobenzene, show muchless anomaly than benzene or cycbhexane, where association is almostcomplete.61Closely related to the above is the remarkable stability of interfacialmonolayers of relatively soluble substances (e.g., sodium cetyl sulphate),and the slow rate of re-solution of an adsorbed monolayer on compression.O2It would thus appear that with the amphipathic type of molecule bothentrance into, and escape from, an interface are markedly hindered processes.The question ofthe structure of protein monolayers, which, despite a large amount ofinvestigation is by no means settled, and may assist in unravelling thestructure of globular and fibrillar proteins, has been approached recentlyfrom two new angles.Since the protein molecule appears to function normally only in thepresence of water, it seemed natural to examine the properties of its charac-teristic -CO*NH- group, with its tendency for hydrogen bonding,m in thepresence of an aqueous medium.Accordingly, monolayers of long chaincompounds containing this group, such as amides, acetamides, and ureas,were compared with those given by acetates, esters, and methyl ketoneswhich clearly cannot associate by intermolecular hydrogen bonding of thetype >CtO- - - -H-N<.The differences were most striking, and it seemsthat cross hydrogen bonding plays a very important part in condensedmonolayers of compounds containing the -CO*NH- group, tending to bringabout condensation and ~olidification.1~ The molecular packing and themechanical properties were also very sensitive to the pH of the subrstrate,and the effects of other reagents such as urea and thiocyanates, also knownto have a marked influence on native proteins, are being studied.The other method of approach 64 has been the study of monolayers oflinear polymers such as polyacrylates, polymethacrylates, nylons, etc.,the last being of considerable interest in view of their close similarity tothe polypeptide chain.All these compounds have known structures andthis has led to a clearer appreciation of the various factors which contributetowards the overall behaviour of protein monolayers.58 J. W. McBain and L. H. Perry, Ind. Eng. Chern., 1939,31,35.59 Idem, J . Arner. Chem. SOC., 1940, 62, 989.6o A. F. H. Ward and N. Tordai, Nature, 1944,154, 146.61 A. E. Alexander and E. K. Rideal, ibid., 1945,156, 18.fi2 A. E. Alexander, Trans. Faraday Soc., 1942, 38, 64.63 W. T. Astbury, ibid., 1940,36, 871.c p D. Crisp and E. K. Rideal, PTOC.Roy. SOC., A (in the press).(d) Structure of proteins and of protein monolayersHIINSEELWOOD : PHYSICOCHEMIUAL ASPHCTS OF BAUTERIAL GROWTH. 15(e) Some biological applications. J. H. Schulman and E. K. Rideal 65h w e used the technique of penetration t o form mixed monolayers,2 inparticular cholesterol with saponin or various synthetic detergents, in aninvestigation of haemolysis and agglutination. They have also 66 examinedthe adsorption on to protein monolayers of homologous series of biologicallyactive compounds (e.g., estrogenic stilbene derivatives), and related theseto their known biological effects.The mechanism of fat abaorption in the intestine has been studied byA. C. Frazer, H. C. Stewart, and J. H. Schulman,67 using emulsion systemsbased upon the monolayer and emulsion work mentioned above.Finally, mention may be made of investigations into tho anthelmintioand anti-bacterial action of soap-phenol mixtures, in which the biologicalactivity is in general accelerated by low concentrations of soap, but inhibitedby high concentrations.Surface- studies 6* show that the accelerationarises from complex formation between soap and phenol, enhancing thesurface activity of the mixture. The acceleration is a maximum at thecritical concentration for micelles, since a t higher soap concentrationscompetition between soap micelles and biological interface brings aboutprogressive inhibition of biological activity.It is hoped that this necessarily brief outline has indicated some of thetypes of problem which can be assisted by surface studies.A. E. A.2. SOME PHYSICOCHEMIUAL AEIPEUTS OF BACTERIAL GROWTH,Introduction.Bacteria are unicellular, without differentiated organs. I n suitablemedia they grow and multiply by binary division. They perform a widevariety of chemical feats in virtue of enzymes which are sometimes isolablefrom the cell but are more often integral parts of the structure. The cellcontents are not homogeneous, but the internal differences are of a fine-grained order.fs2*3 The material of the cell is largely a network of macro-molecular substances, the most important of which are proteins, permeatedby an aqueous solution in which substances of lower molecular weight c9ndiffuse about. Such a system presents certain possibilities, suggestedby analogy with non-living systems, and one may well wonder to whatextent these possibilities in fact help to explain the mechanisms which thecell actually uses.We will begin by mentioning certain analogies, and then, in the light ofthem, consider some of the phenomena of bacterial growth.In the first place, i t is probable that the various enzyme functions of a cell0 5 Proc.Roy. SOC., 1937, B, 132, 29.6 G Nature, 1939, 144, 100.e8 A. E. Alexander and A. R. Trim, ibid., 1944,154, 177.67 Ibid., 1942, 149, 167.G. Knaysi and S. Mudd, J. Bact., 1943, 45, 349.G. Piekarski, 2. Bakt., 1939, 144, 140.C. F . Robinow, Proc, Roy. Sac., 1942, B, 180, 29916 GENERAL AND PHYSICAL CHEMISTRY.depend upon specific protein textures, and that these textures are built upduring growth by heterogeneous.polycondensation reactions not whollyunlike those with which chemical kinetics has already made us familiar.In the cell, moreover, there is a complex scheme of linked processes, in whichstarting materials, often of the simplest kind, are built up stepwise to givecell material. There must be a whole series of reactions so linked that theproducts of one enzyme process Muse from one region of the cell to another,there to participate in further enzyme processes.all individual enzymes must thereforeincrease in amount during growth-and, to a first approximation, in aconstant ratio. This suggests the scheme for the fundamental growthreaction :enzyme + substrate =expanded enzyme + products available for further cell reactionsI n other words the enzymes expand as they do their work.There areanalogies for this kind of reaction in other parts of chemistry. The de-composition of arsine is catalysed by arsenic according to the scheme:solid arsenic + arsine = more solid arsenic + hydrogen. The essentialbasis for the catalysis here is the tendency of the regular lattice of thesolid arsenic to expand by the accretion of like units.4 This principle israther important. Proteins and other macromolecular structures constituteordered arrays, and when they expand by the addition of fresh fragments-after the manner of crystal growth-there will be a release of free energy.This can compensate decreases elsewhere, so that other products of greatchemical activity, possibly free radicals, could be released, capable of takingpart in further polycondensation reactions in other parts of the cell.The concentration in which intermediate products reach the next enzymeof a sequence depends upon the spatial distribution of matter in the cell.This applies even if the intermediates are not labile, since, if they are of lowmolecular weight, the process of loss from the cell by diffusion will be incompetition with that of utilisation by other enzymes.Thus we have the picture of a sequence of consecutive reactions, withrelative rates determined by spatial, as well as temporal factors, occurringin different regions between which transit of intermediate products is governedby the establishment of definite concentration gradients.These reactionslead to the expansion of various ordered arrays of macromolecular com-pounds. One problem confronting us is this : which, if any, of the character-istics of the bacterial cell are understandable in terms of the chemicalkinetics of spatio- temporally linked reaction sequences, and, indeed, interms of relative reaction rates of different enzyme processes ? A few of theoutstanding phenomena of bacterial growth will be discussed from this pointof view.In asequence of reactions of the kind envisaged, if all raw materials are suppliedti Cf. Topley and Wilson, “ Bacteriology.”Cells reproduce themselves :The first group of facts relate to the so-called growthC. N. Hinshelwood, J., 1939, 1203HINSHELWOOD : PHYSICOUHEMICAL ASPECTS OF BACTERIAL GROWTH.17from a constant environment, a steady state will be established in which allthe regions of the cell material expand at rates such that their relativeproportions remain unchanged. For some reason, unspecified at present, thecell divides when it exceeds a certain size. Each cell can go on growing at thesame rate as its parent. Hence the total number increases with timein geometrical progression according to the law n = n,,ekl, where no is theoriginal number and n the number a t time t , E being a constant. This lawis, in fact, rather closely followed (with understandable deviations) over aquite wide range of growth known as the logarithmic growth p h s e . Ulti-mately the supply of raw material becomes exhausted, or substances areformed which inhibit some stage or stages of the reaction sequence, andgrowth ceases.The cells may go on living but they enter what is calledthe stationary phase. During this, some of the intermediate products of thesequence are lost by decomposition or diffusion : more profound changes,fi8 NITime.Fxa. 1.Time.FIG. 2.possibly involving structural alterations in the proteins, may also occur.The result is that even if the cells are transferred to fresh media there may bea delay, known as the lag phase, before the steady state necessary for growthand division is re-established. The phases of the growth cycle are shown inFig. 1. (If the stationary phase is prolonged the cells die : the death ratewill not be considered a t present.) In Section 1 we shall deal briefly withvarious factors governing the length of the lag phase, the rate of growth inthe logarithmic phase, and the onset of the stationary phase.Having considered the initiation and maintenance of growth, we shouldlogically proceed to discuss cell division.This can be done a t present onlyin an imperfect manner, and it is not clear what is the appropriate physico-chemical model. However, various interesting and suggestive facts havecome to light which will be dealt with in Section 2.The various enzymes concerned in the sequence of growth processesare the seat of reactions possessing many characters in common with surfacereactions, and which must be susceptible to inhibition by substances havingaffinity for them.Enzymes will also be inhibited by agents which damag18 QENHIRAL AND PHYBICIAL UHEIKTSTRY.them structurally or deprive them of their substrates. These factors f0rt.nthe basis of various forms of drug action, some of which are considered inSection 3.One of the most striking characteristics of bacteria is their power ofadaptation. When cells which have been grown for some time in a givenmedium are transferred to a new one in which the necessary carbon or nitrogenis supplied in the form of compounds not present in the original medium,growth may be slow during the first few growth cycles, but gradually in-orease in rate in the manner illustrated (in a slightly idealised way) in Fig, 2.Similarly, in the presence of certain drugs there may initially be a verymarked deceleration of growth, but after a few growth cycles the cells becomeimmune and grow quite unhindered by the drug.This remarkable behaviour,apparently so typical of a living organism, can, hypothetically, be explainedin terms of an automatic adjustment of the enzyme balance in the cell : itbecomes, in fact, a study in relative reaction rates. If we consider thesequence of reactions by which various enzymes are synthesised, it is clearthat the rate of each one can respond to changes in the local concentrationof the intermediate supplied by the preceding enzyme of the series. If therelative rates of formation of two enzymes change, then the relative propor-tions of two types of cell material will change also, until a new state of balanceis attained.With suitable auxiliary assumptions this principle can be madeto explain various facts about adaptation. Some aspects of the vast subjectof adaptation are discussed in Section 4.1. Phases of the Growth Cycle.(a) The Lag Phase.-The sequence of cell reactions may begin with verysimple materials; for example, some bacteria grow well in media where theonly source of nitrogen is ammonia and the only source of carbon a simplecoqpound like glycerol. The compounds built up are of much greatercomplexity, and some organisms will not start to grow unless they are sup-plied with molecules of various specific kinds ready made.6 Among neoessarygrowth substances for various baoteria are glutamine,’ tryptophan,* uracil>nicotinic acid, thiamin and various amino-acids.Similar compounds aretherefore likely intermediates in the chain of processes occurring in cellswhich can start with simpler materials. Indeed, certain bacteria whichnormally demand tryptophan, an essential constituent of the protein, canadapt themselves to build it up, fist from indole and then from am-monia.8.1Ot11 Hence the order, ammonia, indole, tryptophan is indicated,and it depends simply upon the state of the cell enzymes whetber the earlier6 €3. C. J. G. Knight, “Bacterial Nutrition,” 1936.7 H. McIlwain, P. Fildes, U. P. Gladstone, and B. C. J. Gc. Knight, Biochem. J.,8 P. Fildes, G. P. Gladstone, and B. C. J. G. Knight, Brit.J . Exp. Path., 1933, 14,1939, 33,223.189. *G . M. Richardson, Biochem. J., 1936, 30, 2184.10 P. Fildes and B. C. J. G. fcnight, Brit. J . Exp. Path., 1933, 14, 343.11 P. Fildes, as., 1040, 21, 67HINSHELWOOD : PHYSICOCHEIHICAL ASPEOTS OF BACJT'ERIAL GROWTH. 19stages operate or whether they have to be by-passed. Very simple sub-stances indeed may be necessary for growth. One of the most interesting iscarbon dioxide. When a stream of air freed from this is passed throughcultures in some media, growth is delayed indefinitely.l2# l3, l4 Many cellsalso require inorganic ions; for instance, when glucose is used as carbonsource in presence of inorganic phosphate, the length of the lag phase maydepend markedly upon small concentrations of magnesium ions.15 Somesubstances used in growth are probably broken down in one departmentof the cell and passed on to another department for further processing.When 8taphylowccus aureus adapts itself to grow without ready-madealanine, it can simultaneously dispense with various other amino-acidswhich it normally demands.16 This may mean that the mechanisms whichare mobilised deal, not specifically with the individual amino-acids, but withactive fragments common to them all.During the early stages of the lag phase there is no apparent increasein cell substance ; later the cell volume increases and this is usually heraldedby an increased production of metabolites such as carbon di0xide.l'.l8# l9One of the obvious conclusions is that during the lag there must be establishedthe necessary concentrations and concentration gradients of the less complexintermediates.This is confirmed by the fact that the lag in simple artificialmedia is longer than in media like meat extract which contain a varied stockof ready-synthesised compounds. The simpler intermediates are diffusiblesubstances which not only pass from one part of the cell to another, but maybe easily lost into the surrounding medium. This comes to light in thequantitative study of the lag phase. We may take the example of Bact.Zactis cerogenes, which grows easily with glucose as carbon source and am-monium sulphate or amino-acids as nitrogen source. The following experi-ment is made : cells from a growing culture are transferred to a fresh supplyof the same medium and the length of the lag is determined (cf.Fig. 1).The lag proves to be a function of the age of the parent cells, i.e., the timebetween start of growth of the parent and the transfer to the new medium.When amino-acids are the eource of nitrogen, the result is as shown in Fig. 3,but with ammonium sulphate as source the relation illustrated in Fig. 4 isfound.20 The explanation of the minimum is as follows. In the ammoniumsulphate medium a diffusible intermediate escapes into the solution.Ordinarily cells transferred to a new medium carry with them a certainvolume of the original medium. In Fig. 4 the initial fall of the lag to aminimum is due to the increasing amounts of the intermediate transferredle G. P.Gladstone, P. Fildes, LtndiG. M. Richardson, Brit. J . Exp. Path., 1935,16,335.l8 S. Dagley and C. N. Hinshelwood, J., 1938, 1930.l4 W. Kempner and C. Schlayer, J . Bact., 1942, 43, 387.l5 R. M. Lodge and C. N. Hinshelwood, J., 1939, 1692.l6 G . P. Gladstone, Brit. J . Exp. Path., 1937, 18, 322.l7 G. Mooney and C.-E. A. Winslow, J . Bact., 1935, 30, 427.l 8 E. Huntingdon and C.-E. A. Winslow, ibid., 1937, 33, 123.lD C.-E. A. Winslow and I. J. Walker, Bad. Rev., 1939, 8, 1472o R. M. Lodge and C. N. Hinshelwood, J . , 1943, 21320 GENERAL AND PHYSICAL CHEMISTRY.with the cells. Actual filtered medium from the old culture lowers the lag ofa new culture. The lag of freshly transferred cells which have been washedfree of the old medium is much increased.Moreover, with the washed cellsthe lag depends in a marked degree on the actual number transferred, sincethey all form the diffusible intermediate and pour it into the medium to forma common store, and the more there are to contribute their quota the sooneris the critical concentration built up. A fairly satisfactory quantitativetheory of the lag under such conditions can be constructed with the aid of theassumptions (i) that the lag ends when the concentration, c, of some activesubstance in each cell reaches a critical value, c' ; (ii) that c is made up inthree ways, being expressed by c = av + Pnot + yt, where v is the volume ofthe old medium transferred, no the number of cells transferred, and a, p,and y are constants. The first term &presents the active substance trans-ferred with the old medium accompanying the cells, the second that builtup by them in time t in the new medium, and the third that built up in a givenAgeFIa.3.AgeFIG. 4.cell without help from the medium or from the other cells. The resultingexpression for the lag gives a reasonable account of its variation with separatechanges in v and no (which can be varied independently with washed cells).The variation of lag with no is specially striking : i t is not found when amino-acids are used instead of ammonium sulphate, since under these conditionsloss of the intermediate into the medium plays a less important part.Various qualitative references to the influence of the inoculum size on thelag occur in the earlier literat~re.~ Diffusible substances which leave the cellplay a part in the functioning of various specific enzymes such as deaminases,and dehydrogenases under conditions where these are not directly involvedin growth.21*22s23 To what extent the increases in lag on continued ageingof the cells (Figs.3 and 4) are due to simple decay or loss of active inter-mediates, and to what extent due to actual structural changes in the protein,is imperfectly known.The lag is a function of the concentrations of medium constituents,but does not vary rapidly with that of the ordinary food materials. It is21 J. Yudkin, Biochem. J., 1937, 31, 865.23 E. F. Gale and M. Stephenson, Biochem. J., 1938, 32, 392.23 D. D. Woods and A. R. Trim, ibi&., 1942,36, 50HINSHELWOOD : PHYSICOCHEMICAL ASPECTS OF BACTERIAL GROWTH.21specifically influenced by various drugs, and this influence is easily modifiableby adaptive changes in the cells in a way which will be considered later.(b) The Logarithmic Growth Phase.--& the end of the lag phase thesteady state is established, and the rate of increase of all the cell substanceat any moment becomes proportional to the amount present, i.e., dm/dt =km. In so far as division occurs when a standard size is reached (which isonly roughly true), this means that the number of cells increases in geometricalproportion with time, the number doubling in equal increments of a periodusually called the mean generation time. The constancy of the meangeneration time is an approximation : small deviations arise from severalcauses-consumption of the food materials, accumulation of inhibitors,non-survival of some of the newly formed cells, and variation in the meansize of cells formed at different stages.24 Quantitatively, however, theseTime,FIG.5.0 A C BFIG. 6.effects are usually quite small until the logarithmic phase approaches itsend. One or more of them then rapidly becomes serious and growth becomesslower and stops,25 often with what appears as considerable abruptness.The actual growth rate of a given organism varies widely, at least over atenfold range, according to the nature of the medium. The mean generationtime, at a given temperature, depends upon the relative amounts of the variouscell enzymes and upon the nature and concentration of the substratesprovided.The fist factor seems to govern the extraordinary way in whichcells modify themselves to utilise a given new substrate, a process calledtraining or adaptation. The course of the training process is instructiveand is illustrated in Fig. 5 . Bact. Zactis cerogenes accustomed to use glucoseas a carbon source is grown in a medium where the glucose is replaced byglycerol. At first the growth rate is low, but increases suddenly a t a certainstage of the logarithmic phase as a t the point When the experimentis repeated with cells already grown once in the new medium, this pointoccurs successively earlier, at a2, a3 . . . and finally passes below the range24 A. T. Henrici, Proc.SOC. Exp. Biol. Med., 1922, 20, 179; 1923, 21, 215, 343, 345.z 6 C. N. Hinshelwood, Biol. Rev., 1944, 19, 135.26 R. M. Lodge and C. N. Hinshelwood, Trune. Furuduy Soc., 1944,Qo, 67122 GIINERAL AND PHYSIUAL UHHMISTRY.of observation. The simplest interpretation of this is given in Fig. 6. Thecells may be assumed to utilise the new medium by two mechanisms, onewith a slower growth rate but a shorter lag, the other with a higher growthrate but a longer lag (as shown by the lines AX and BY, respectively).The latter represents a mechanism which utilises glycerol more efficientlybut is not originally in a state of mobilisation. The training consists in theprogressive reduction of the lag phase of this competing mechanism, aa shownby the movement of the second part of the growth curve from the positionBY to that CZ.The existence of what appear to be alternative and com-peting mechanisms comes to light in other connexions, e.g., in training toutilise new nitrogen sources, or to resist the action of sulphonamide drugs.27Any mode of growth involves a complex sequence of reactions, and the varietyof possible links in any such chain is shown by the number of substrates whichthe cells can use and the variety of reactions which they can provoke. Froma given starting point to the final cell materials a whole network of routes canbe imagined. For example, an amino-acid might be deaminated to giveammonia-used then just as though it were supplied from ammoniumsalts-or the entire amino-acid might be first incorporated and subsequentlytransformed.Two alternative growth modes might differ only in one or twoparticular links, yet might be of very different efficiency in utilising a givensubstrate. They would involve different enzymes, and the readiness withwhich one or the other would come into play would depend upon the pro-portion of the various enzymes present. Only when the cells are fullytrained to a given medium will the proportions be adjusted to give optimumgrowth and a simple logarithmic growth curve. (In fact, the logarithmicform of the growth curve is a good criterion of the degree of adaptationand of the extent to which the various cell processes are in balance.)Although the rates of particular reactions and the combination of re-actions used in the total growth sequence are modifiable by training, thereare well-defined limits to the adjustments possible.When adaptationhas gone to its limit the slowest step determines the overall rate of growth.The fact that there is probably a single rate-determining step is relevant to thequestion of the relation between rate and nature of substrate. The meangeneration time of Bact. Zactis cerogenes varies little for a series of amino-acids as nitrogen sources, so that presumably the step involving their utilisa-tion is not a rate-determining one, though in some other respects the be-haviour of different amino-acids may be very divergent.2s*29 On the otherhand, the rate of growth may vary widely according to the nature of thecarbon source.For one representative bacterium, a t least, the meangeneration time has been shown to be almost independent of the mediumpH-which is rather remarkable in view of the profound influence which2T D. S. Davies and C. N. Hinshelwood, Trans. Faraday Soc., 1943,39,431.28 S. A. Koser and L. F. Rettger, J . Infect. Dis., 1919,24,301; M. Sahyun, P. Beard,E. W. Gchultz, J. Snow, and E. Cross, i6id., 1936, 58,28 ; J. Gordon and J. W. M’Leod,J . Path. Bact., 1926, 29, 13.R. M. Lodge w d C. N. Hinshelwood, J., 1943,208HINSHELWOOD : PHYST~O(3HEMIUA.L ASPBCTS OR’ BAOTERIAL GROWTH. 23pH has on cell activities in general.30 Experimental data on the relationof growth rate to concentration of medium constituents are not very abundant.On the whole, however, it appears that over wide ranges of concentrationthe growth rate varies little, and only shows a marked falling off when theconcentration of the foodstuff becomes very small indeed.30* 31* s2 This canbe understood.The cell reactions resemble heterogeneous reactions,and their rates are probably related to concentration of substrate by anequation like that of an adsorption isotherm, rate = k c / ( l + bc), where ois the concentration and lc and b are constants. As soon as c exceeds acertain value, this expression becomes nearly constant, in a way familiarin the study of surface reactions. Since the scale of cell processes is a minuteone, the saturation limit may very well be reached early. (This is one of thereasons why the mean generation time remains nearly oonstant over thelogarithmic phase despite the consumption of food material.)L imifing factor -toxic ,productsf-- L imiting f a c t o r - /- exhaustionIIniiia/ co:7cn.o f food materia/.mFIU. 7.Time.Ra. 8.(c) The Stationary Phase ; Total Cell Population which the Medium willSupport.-One or other of several factors may, according to circumstances,be the limiting one in determining the end of the growth phase and themagnitude of the final population. When exhaustion of foodstuff is thelimiting factor, the population is directly proportional to the initial concen-tration of one of the medium constituents. Sometimes this linear relationholds over a certain range and then breaks down a t concentrations whereaccumulation of toxic products beoomes limiting, as shown in Fig.7.33The effects on the total final popuIation of growth inhibitors added tothe medium are various. One might have expected the inhibitors tolengthen the mean generation t i q e without affecting the final state : this,however, is seldom found. Alcohols,34 for example, not only decrease rateof growth but reduce the final population in nearly the same ratio. AdversepH reduces the final population without much affecting the rate at which30 R. M. Lodge and C. N. Hinshelwood, J., 1939, 1683.31 W. J. Penfold and D. Norris, J. Hyg., 1912,12,627.32 S. Dagley and C. N. Hinshelwood, J., 1938, 1930,33 R. M. Lodge and C. N. Hinshelwood, J., 1939, 1683.34 E. A. Poole and C. N. Hinshelwood, J., 1940,166524 GENERAL AND PHYSICAL CHEMISTRY.it is attained.30 Lag may be specifically affected without change in totalpopulation.16 Aeration of the medium may affect total population but notnecessarily growth rate.35# 29(d) The Phase of Decline.-Unless they are renewed by division, cellsdie, the death rate being increased by antiseptics, high temperatures, andvarious radiations.According to some observers, the number of survivorsat time t out of an initial population of No is given by the exponential decaylaw, N = Noe-U, where 1 is a constant (curve I in Fig. 8). Others maintainthat the true form of curve is more like that of I1 in the figure, and that Iis found only as an approximation observed over a certain range, andespecially when some of the cells have already died before the first measure-ments are made (as would be found if observation began a t the point a oncurve 11).The experimental decision of the question whether the exponentialcurve is indeed the ideal form seems to be not quite easy.36 An importanttheoretical question lies at the basis of the matter. If the death of a cellexposed to an unfavourable environment occurred after a definite time, thenumber of survivors would vary with time as in curve I11 : if the populationwere non-homogeneous initially, I11 would be rounded off to give IVY which,by assuming the appropriate frequency distribution of resistance could beadjusted to reproduce 11. A very special distribution could even change thecurve into I, but such a distribution would be improbable, since it wouldinvolve a maximum proportion of cells, not with the average resistance, butwith the very lowest resistance.If we accept the (controversial) fact thatI may in certain examples be accurately followed, and if we reject as im-probable the assumption of the very special initial distribution necessaryto explain i t in terms of the varying resistance theory, then some very interest-ing conclusions follow. The differential equation of I is - l / N . W/dt =constant, i.e., the probability of death for any individual in any givenelement of time is independent of the previous history, as in radioactivedecay. If death is caused by the presence of an antiseptic (for example),yet is independent of the time of exposure, it can only mean that a t somemoment a chance conjunction of events occurs exposing the cells to lethalinfluences which have not so far affected them.For the analogous actionof X-rays on the cells of Bact. coli, it has been suggested that the chanceevent is an encounter of a quantum of radiation with some localised sensitivesite in the celL37 This is a special hypothesis which leads to a result of thecorrect form, but the possible implications of the exponential law are of amore general character.2. Cell Division and Cell Morphology.Another phenomenon which seems to depend upon conjunctions of eventsCells do not all attain the same sizes6 0. Rahn and G. L. Richardson, J . Bact., 1942,44,321.36 A. J. Clark, “General Pharmacology”; cf.It. C. Jordan and S. E. Jacobs, J .37 D. E. Lea, R. B. Haines, and C. A. Coulson, Proc. Roy. A‘oc., 1936, B, 120, 47;is the division of the growing cell.Hyg., 1944,43,275.1937, 123, 1 ; J. A. Crowther, ibid., 1926, B, 100, 390HINSHELWOOD : PHYSICOCHEMICAL ASPECTS OF BACTERIAL GROWTH. 25before dividing : nor are the successive intervals of time between divisionsof individual cells precisely equal. They are distributed about a mean in anapparently random fashion. In experiments on Bact. lactis cwogenes at30°, 30% of the divisions occurred after intervals between 30 and 35 minutes,and 91% of the total occurred within the range 20-50 minutes. The dis-tribution was not far from symmetrical about a mean of 30-35 minutes.Very few cells had a fission time of more than double the mean.The varia-tion was, however, striking : it was not due to inhomogeneity of the strain,for daughter cells from an early division were not consistently different fromthe average.38Under certain conditions, divisions may be so much delayed that verylong filamentous or snake-like cells are formed.39~ 40* 41 In these conditionsthe size distribution becomes much more scattered than normal. The factorsconducive to long-cell formation with scattered size distribution are ( a ) thepresence of certain drugs which inhibit division without inhibiting growthto the same extent, and ( b ) the transfer of the cells to an unaccustomedgrowth medium, to which the growth and division functions adapt themselvesat different rate~.~20 43* 44With one coliform organism the distribution of cell sizes at a givenmoment has been found to follow approximately the law n(1) = e-lI5,where n(Z) is the number of cells of length greater than 1, and l i s the meanlength.This suggests that the attainment of a given size greater than themean is governed by a conjunction of probabilities statistically analogous tothat which permits a molecule to traverse a free path greater by an assignedfactor than the mean. The view has been put forward, on the basis of variousexperiments on Bact. lactis cerogenes, that two independent factors controldivision and elongation of the cell (the latter being diffusible into the medium)and that these two factors are separately modifiable by a d a p t a t i ~ n .~ ~3. The Influence of Drugs on Bacterial Growth.The influence of drugs on bacteria is varied : some act as general proto-plasmic poisons, some by interfering with specific members of the series ofenzyme reactions upon which growth depends. Some have specific effectson lag, mean generation time, or on cell division probability. Accordingto the evidence brought forward by Fildes and 0thers,4~* 461 47* 48e 49n 60* 6138 G. D. Kelly and 0. Rahn, J . Bact., 1932, 23, 147.3D E. W. Ainley Walker and W. Murray, Brit. Med. J., 1904, 2, 16.40 R. TunniclifF, J . Infect. D k , 1939, 64, 59.41 A. D. Gardner, Nature, 1940, 146, 837.42 C. N. Hinshelwood and R. M. Lodge, Proc. Roy. SOC., 1944, B, 132, 47.43 R. M. Lodge and C.Hinshelwood, Trans. Faraday SOC., 1943,39,420.4 4 G. H. Spray and R. M. Lodge, ibid., p. 426.4 6 P. Fildes, Brit. J . Exp. Path., 1940, 21, 315.4 6 D. D. Woods, ibid., p. 74.4 8 H. McIlwain, ibid., p. 148.61 G. P. Gladstone, Brit. J . Ezp. Path., 1939,20,189.4' H. McIlwain, ibid., p. 136.49 P. Fildes, ibid., 1941, 22, 293.H. McIlwain, Biochem. J., 1942, 86, 417speoific inhibitory actions are often exerted by substances which areatructurally related to normal metabolites of the cell. Their structure makesthem liable to be taken up by the enzymes in competition with the normalsubstrate, for whioh, however, they are in other respects not adequatesubstitutes. Competing pairs of substances in this sense are thiol compoundsand r n e r ~ u r y , ~ ~ aminobenzoic acid and sulphonamides,46 nicotinic acid andpyridine-3-sulphonic acid:* amino-acids and their sulphonic acid analogues,48and EO on.Only a few aspects of the extensive subject of drug action can be dealtwith here.(a) Influence of Drug Concentration on Antibacterial Action.-Much of theearlier 36 consisted of measurement4 on the rate at which disinfectantskilled cells, the death rate being expressed in the form acn, where a is constantand 12 is frequently a quite high power of the concentrakion c of the drug.This power law could hardly have a real theoretical significance and wouldseem to be an approximation for a law of rather different form.Suppose a.certain concentration, G ~ , of the drug oould be tolerated by the cell, beingdealt with by neutralising mechanisms of some kind : the death rate mightwell be proportional to c - co.Then we have :andlog rate = log const. + log ( c - co)d(1og rate)/dc = l / ( c - co)If we also write rate = acn, then d(1og rate)/dc = n/c, and comparison of thetwo expressions gives n = c/(c - cJ. If the tolerance is appreciable,c - co will be small over the range in which the first serious action of the drugis exerted, i.e., n will be large, though it would not appear constant overmore than a limited range. The tolerance to small concentrations which thisview implies is in fact observed in some cases. In the action of bacteriostaticagents such as proflavine (2 : 8-diaminoacridine sulphate) on the lag of coliformorganisms, the initial tolerance is not only observable but is t o be expectedtheoretically.Fig. 9 shows results found for proflavine and Bact. lacbiso~ogenes.6~ Each curve of the family corresponds to a strain of cells whichhas been repeatedly grown in presence of a certain concentration of the drug(see later). The form of the curves is explained as follows : the proflavineinterferes with the working of an enzyme which yields an intermediateconstituting the substrate of a second enzyme. The rate of working of thissecond enzyme is related to the concentration of the intermediate by anadsorption isotherm (Fig. 10). Normafiy, the concentration of intermediateprevailing in the cell has a value such as A,; it can be reduced to B beforeany inhibition is manifest, i.e., there will be a tolerance proportional toA,B, after which further drug oauses a fall in rate to, say, C. The cellswhich have been trained in presence of drug at higher concentrations havegreater reserves of the intermediate-forming enzyme, so that the concentration62 D.S. Davies, C. N. Hinshelwood, and J. M. G. Pryce, l'rane. Paraday SOC., 1945,in pressKINSH~WOOD : PKPSICOCHIOMICAL ASPECTS OF BAOTERIAL GROWTH. 27of the intermediate itself starts at values A,, A , . . . . ., with correspondinglygreater tolerances. If the curves in Fig. 9 were expressed in terms of a lawmaking the lag depend upon the nth power of the drug concentration, thenthe values of n would have to be high. Actually, the curves can be representedby a formula derived rationally from the above theory.The influence of various inhibitors on the mean generation time oansometimes be expressed quite well by a simple linear relation of growthrate and concentration : R = R,(1 - bc), where R is the growth rate inpresence of a concentration c of drug, Ro that with none, and b is a con&ankW(b) Drug Action and Structwe.-This subject cannot be dealt with indetail but reference should be made to a few general matters.Two effectsrCConcn. o f ihtcrrnediate .Prof/a vine concn.FIG. 9. FIG. 10.of structure have to be distinguished. In the first place, the partition of thedrug between the medium and the part of the cell where it acts will dependupon the structure of the drug molecule. In particular, it will show regularvariations during the ascent of a homologous series.54 Many quite largequantitative differences in drug action are explained away when varyingphase distributions are allowed for, e.g., by comparing actions at equivalentchemical potential^.^^ The antibacterial action of various phenole seems tobe related to the solubility of the phenol in olive oil (a possible model forcertain regions of the interior of the cell) .56 The inhibitory action of straight-chain aliphatic alcohols increases by a constant factor from one member ofthe homologous series to the next higher : this shows that each CHa grouphas its own contribution to make to the total effect, and indicates that theaction occurs in a part of the cell capable of attaching alcohol to its substanceby each link of the hydrocarbon chain.530 g4* 57.58The differences in antibacterial action of such classes of compound63 S.Dagley and C. N. Hinshelwood, J., 1938,1942.G4 K. H. Meyer, Trane. Paraday Soc., 1937,33,1062.6 5 J. Ferguson, Proc. Roy. Soc., 1939,B, 12'4,387.G' A. H. Fogg and R. M. Lodge, Tram. Paraday Soc., 1946, in press. '' F. W. Tilley and J. M. SoMer, J. Baot., 1926,12,303.5 R W. S. Stiles, " Introduotion t o Plant Physiology," 1936, p. 8128 GENERAL AND PHYSICAL CHEMISTRY.as sulphonamides, acridine derivatives, triphenylmethane dyes, and so oncan hardly be explained in this way. The actions depend upon the inter-vention of the drug at specific stages of the reactions involved in growth.The antibacterial action of substances related to known metabolites, alreadyreferred to, supports this view, for which further evidence is provided by thephenomenon of " cross training ".For example, Buct. Zuctis cerogenestrained to resist proflavine has also increased resistance to methylene- blue,but not to sulphonamide. When thoroughly trained to sulphanilamide, itwill resist sulphaguanidine and vice versa : but sulphonamide training doesnot immunise to proflavine. This offers yet another method of classifyingspecific inhibitory actions. On the other hand, with Stuphylocaccus uureuSnicotinamide antagonises not only sulphapyridine but quite unrelateddrugs It is also of interest to note that some antiseptics are statedt o cause death of cells before causing significant inhibition of several typicalenzymes of those cells.604.Bacterial Adaptation.One of the most remarkable properties of bacteria is their capacity forsuffering changes in morphology, biochemical and other characters and intheir power to withstand the action of certain drugs. These changes,though important and sometimes profound, are limited in amplitude in thesense that the main species characteristics are always preserved.61 Strepto-cocci are never transformed into coliform bacteria, though within the in-dividual groups continuous ranges of forms exist, all possibly, and somedemonstrably, intercoqvertible.62-66 A great deal of attention has beenpaid to the changes in the forms of colony in which bacteria grow on solidmedia. One initial type often gives rise to variants, sometimes stable,sometimes unstable,67* 68 the changed colony form being linked in varyingdegrees with other changes 69-74 in character.This phenomenon is often,though not very happily, referred to as bacterial dissociation. The adapta-tion of bacteria to utilise new food sources has already been mentioned.There is no reason to suppose that the development of the power to resist theaction of certain drugs is other than a special example of the operation of thegeneral adaptive mechanism.To illustrate some of the principles involved in adaptation we will con-6o M. A. Bucca, J . Buct., 1943, 46, 151.61 A. I. Virtanen, {bid., 1934, 28,447.62 P. Fildes, Brit. J . Exp. Path., 1927, 8, 219.63 L. W. Parr, Buct.Rev., 1939, 3, 1.64 C. Nyberg, K. Bonsdorff, andK. Kauppi, 2. Bukt., 1937,139,13.6s 0. Sievers, ibid., p. 27.6 7 P. Hadley, J . Infect. Dis., 1937, 80, 129.6 8 F. Farag6, 2. Bukt., 1934, 133, 139.69 H. B. Gillespie and L. F. Rettger, J . Bmt., 1939, 38, 41.7O C. S. Flynn and L. F. Rettger, ibid., 1934,28,1.71 M. I. Bunting, ibid., 1940,40,57,69; 1942,43,593.78 I. M. Lewis, ibid., 1934, 28, 619.74 L. W. Parr and M. L. Robbins, ibid., 1942, 43, 66.W. B. Wood and R. Austrian, J . Exp. Med., 1942,75, 383.e6 F. Neri, ibid., 1940, 146, 166.73 M. W. Deskowitx, ibid., 1937, 33, 349HINSHELWOOD : PHYSICOCHEMICAL ASPECTS OF BACTERIAL GROWTH. 29sider a, particular example in more detail. Bact. hctis cerogenes grown inpresence of prof3 avine acquires an immunity to the drug, the relation betweenlag and test concentration for strains trained at a series of concentrationsbeing shown in Fig.9.75 The differences in the spacing of the curves corre-spond almost exactly to the training concentration,T6 showing that thetraining consists in the graded response of the cell to the actual inhibition,rather than in the selection of an inherently resistant strain from a mixedpopulation of resistant and non-resistant cells.(The Reporter 77 has discussed some of the literature bearing on thequestion of adaptation versus selection. There seems to be good evidencethat adaptation is usually initiated by actual changes in individual cells.Naturally, when some of the cells have become adapted they will outgrowany unadapted cells, and in this sense selection must always be super-posed on any other adaptive mechanism.But it is the initiation of theprocess which is of greater interest from the physicochemical point ofview. Very varied opinions have been expressed about the subject inUnder favourable conditions the adaptation is very rapid, being completeafter a few cell divisions, though it does not occur during the lag phase itself,i.e., in the absence of any actual increase of cell substance. For the systemunder consideration the following simple model accounts for many of the facts.We assume an enzyme I whose total substance expands according to theequation h1/dt = k1x1. It gives an active intermediate which is partlyused by another enzyme, 11, and partly lost by diffusion. The intermediateattains in the region between the two enzymes a concentration c, such thatdc/dt = k ' l ~ l - E,cn - k,cx,/(l + bc) = 0.The term k,cn is the totalrate of loss by diffusion and is thus proportional to the total area of cell wall,i.e., to n, the number of cells. The total substance of enzyme I1 expandsa t a rate related to c by a Langmuir isotherm, so that the consumption of cfrom this cause is given by the term k3cx2/(l + bc). Assuming that celldivision waits until the amount of enzyme I1 per cell attains to some standardamount, i.e., that n = px,, we can easily solve the equations. The ratioxr/x2 tends on growth of the cells to a definite limit, whatever its initial value.If now a drug impairs the production of the intermediate so as to slow downthe synthesis of enzyme 11, the overall multiplication rate will be lowered.The ratio xJx2 will, however, expand as growth occurs, and c will rise, thisin turn causing an increase in the rate of growth of enzyme I1 until themultiplication rate returns to normal.The whole process constitutes anadaptation to the drug. There is, in fact, evidence that the enzymic40,397.general. 6 7 a 7+*1 17 6 D. S. Davies, C. N. Hinshelwood, and J. M. G. Pryce, Trans. Faruday SOC., 1944,76 Idem, ibid., 1945, in press. '' See ref. (26).'* E. W. Todd, Brit. J . Exp. Path., 1930,11,368.70 R. R. Mellon, J. Bact., 1942, 44, 1.8o A. C. Giese, {bid., 1943, 46, 323.81 D. S. Davies and C. N. Hinshelwood, Trans.Faraday SOC., 1943, 39,43130 GENERAL AND PHYSICAL UHXCMTSTRY.oonstitution of drag-resistant bacteria has been changed in variousways.82--85In the light of the hypothesis that adaptation coiisists in a change ofenzyme balance resulting directly from the modification of the relativereaction rates of different cell processes, it is possible to discuss the spontaneousloss of training which sometimes occurs on subsequent growth in the drug-free medium, the marked retention of the training which occurs in othercases, the induced reversion of trained strains caused by growth in presenceof other antibacterial agents, and similar problems.The above-mentioned model provides a reasonable expression for thelag-conoentration relation. If we assume that the increase of lag caused bythe proflavine is essentially due to the lowered rate of working of an enzymesuch as enzyme 11, this lowered rate being caused by a reduced concentrationof the active intermediate from its normal value cI1 t o a new value c, thenwe have the following equations :G = C ’ ~ - +(m), +(m) being some function of the drug concentration.L = A/& where L is the lag and R the rate of working of the enzyme, and A aconstant :From these we obtainR = k c / ( l + bc).1/(L - Lo) = k/A[c’le/+(m) - C’JWith proflavine, the experimental results are well represented with + (m) =fm, where f is a constant, corresponding to st virtually quantitative titration.The value of cfl for the various trained strains proves to be related to thetraining concentration P by the linear equation c ’ ~ = const.(54 + P).The effect of training is thus to restore c from the reduced value it hasinitially in presence of the drug to the original value it would have had foruntrained cells in the absence of any drug at all. Cells trained to methylene-blue also show increased resistance t o proflavine. The lag-concentrationcurves for methylene-blue are of a very markedly different shape, indicatinga different form for the function +(m). If the form of the latter is calculatedfrom the experimental results for untrained cells in presence of methylene-blue, then it can be used to predict how methylene-blue-trained cells shouldbehave both at other methylene-blue concentrations and in presence ofproflavine.Certain outstanding qualitative differences are correctlyaccounted for, and there is even a measure of quantitative agreement.86No more is to be claimed for the views just outlined than that theyillustrate the general sort of way in which adaptation may be related to82 W. P. Wiggert and C. H. Werkman, Biochem. J., 1939,33,1061.83 R. A. McKinney and R. R. Mellon, J. Infect. Dis., 1941, 68,233.M. Landy, N. W. Larkum, E. J. Oswald, and F. Streightoff, Scknce, 1943, 87,295.8 s E. H. Rennebaum, J . Bact., 1935,30,625.86 J. M. G. Pryce, D. S. Davies, and C. N. Hinshelwood, Trans. Farday SOC.,1945, in pressBARRER : ZEOLITES AS ABSORBENTS AXD MOLMCULAR SIEVES. 31kinetic principles. For more general ctocounts of adaptive enzymes, andin particular for the distinution which may be drawn between adaptiveand constitutive enzymes, reference should be made to the discussions ofJ.Yudkin 8' and of R. Dubos.88In contrast to hypotheses about the progressive modifioation duringadaptive changes of the enzyme balance of cells stand those views whiohrefer adaptation and variation to alternative possibilities presented to thecell a t the moment of division.89*90 Such views would acoount naturallyfor cases where variant forms are found to be produced in a stableratio,'l* 72s 73 and also for completely irreversible variations (whioh arebelieved to occur, though the evidence for complete irreversibility must benegative only) .67* 90Not very much is known about the nuclear apparatus of bacteria, orabout the way in which the cell proteins are organised.If there is somesort of centre of organisation, and if an abnormal mode of division occurs,it is quite conceivable that appreciable modification of the actual proteinpatterns is produced in the new cells. This might well lead to rather im-portant changes in properties. Perhaps, therefore, we might imagine thatsimple changes in the quantitative efficiency with which a given carbon ornitrogen source is utilised or in the resistance to a given drug can be explainedby nothing more profound than the automatic shift in enzyme balance ofthe kind just discussed. On the other hand, to explain rather more profoundchanges in qualitative character we must perhaps invoke changes in theprotein pattern dependent upon nuclear changes.The equation on p. 16provides a basis for the expansion of precisely those enzymes which are neededin the utilisation of a given foodstuff, so that shifts in enzyme balance arethe natural explanation of adaptive changes to new media.86*Spontaneous variations in bacteria occur : more frequent and moreprofound changes are caused by exposure to radiations such asThese changes probably involve activation energies (or local entropy de-creases) very unlikely to be provided under the normal oonditions of He.Still more profound changes in the fundamental patterns, of the kind whichwould distinguish one species from another, would involve activationenergies so high that they would only be available under conditions whichwould usually kill the cells.8 7 ~ 88* 91C.N. H.3. ZEOLITES AS ABSORBENTS AND MOLECULAR SIEVES.Certain minerals show remarkable occlusive properties, and because ofthe way in which they have influenced current views of sorption a surveyof these properties is opportune. Of all mineral occlusives, none are ao well87 Biol. Rev., 1938, 13, 93.s9 G. R. Reed, J . B d . , 1933, 25, 645.ea Bad. Rev., 1940, 4, 1.Cf. discussion by A. Haddow, A& Int. Union against Cancer, 1937,2, 376.Cf. G. S. Miriok, J . ESP. Med., 1943.78, 256.g a Cf. the discussion in E. Schroedinger, " Whet is Life Y ", 194432 GENERAL AND PHYSICAL CHEMISTRY.known as the zeolites.1 These crystalline minerals (Table I) should bedistinguished from amorphous gel zeolites and permutites used in watersoftening.They are aluminosilicates (R,R2‘)0,A&03,nSi0,,mH20, whereR = Ca, Sr, and Ba and R’ = Na, K. The ratio of base to A1203 is always1 : 1 and the ratio (A1 + Si) : 0 = 1 : 2. Although the minerals are wide-spread, massive deposits are not usually found. They are formed undercomparatively alkaline and probably stagnant conditions by the hydro-thermal alteration of older rocks and lavas at temperatures believed to lieas a rule between 100’ and 350°.2 Under more acid conditions hydrothermalreactions would largely yield clays.3 Zeolites, like clays, are frequentlyZeolite groupand zeolite.*Mwdenite group.YordeniteP tiloli teHeulandite group.HeulanditeBrewsteriteEpis tFbitePhzlzpslte group.PhilipsiteHarmotomeStilbiteGismonditeLaumontiteChabuzitc ptoup.ChabavteGlIIdhiteLevyniteFauj asiteNalrolite group.NatroliteScoleciteMesoliteThomsoniteEdingtoniteA?MZW.TABLE I.Some Typical Zeolites.Crystal chemicalX - F Sstudes,Probable ideal formula.ref. no. nature.(Ca,E1,Na3AI,Silo0,.,69H,0 - Robust three-dimensional- network Ca,KlNa,)A1,Si1,O,,,4H,O -CaAl SiIOlI,5H10(Sr C i Ba)Al Si6Ol6,5HSOLide deulandite(K,,Ca)AI s4011 44H10 9(K2,Ba)Al:Si5Ol4~5HaO 10 Robust thrAe-dimensional(Nal,Ca)A1,SiIO,.,6H10CaAllSi,O8,4HXOCaAI,Si40,,,4BI,0(Ca,Na,)AI,Si,O ,,,6H,O 8 Robust three-dimensional(Na,,Ca)A1,Si,01,,6H,0 - Robust t9ee-dimensionalCaAI,Si,Ol,,SH,O(Na,,Ca)A1,Si5O1,,1OHaO8, 8a Laminar structure - - - --- network - - - - -networknetwork - - - -Approx.interstitialvolumeavailableto H,O(c.c./g.).0.1350.1020-1480.1360.1550.1650.1410.1720.2060-1530.2140.2110.1840.281Chain structures with a.0.095rather weak cross-link- 0,138chain8NaAlSiO 2HOCaAl &,6,,$!tH?b0.1400.11NaCalAI,Si~0,0,6H10BaAlSiO 3H 0NaAl!Si,b 6:?Ha 6 ’ 14 Robust three-dimensional 0.078Betwken scolecite and natro- 12a, 12b, 12c ing oflr aluminosilicate 0.095-0.138litenetworkThe classiEcation is a modiEcation of that given by C. Dana 4 but the grouping m y still need revisionas more X-ray and crystal chemical data accrue The crystal Lhemical classiEcation in col. 4 is basedin part on X-ray data and in part on studies of the stability of the zeolite as an absorbent and towardsheating.0 Chemical formulae are ideal values, and isomorphous replacements of the type Ca $2Na orCaAl G NaSi may cause considerable modification of these formulae.‘Earlier data on sorption equilibria in zeolites are discussed by J.W. McBain,“ Sorption of Gases by Solids,” Routledge, 1932, Chap. 6. Some kinetic aspects aresummarised by Barrer, “Diffusion in and through Solids,” Cambridge Univ. Press,1941, Chap. 3.a Cf. Lindgren, ‘* Mineral Deposits,” McGraw Hill Book Co., 1919, p. 427.a F. Norton, Amer. Min., 1939, 24, 1; 1941, 26, 1. A survey of work on hydro-thermal formation of minerals, including zeolites and clays, is available up to 1937(G. Morey and C. Ingerson, J.Econ. Geol., 1937, 32, 607-761).“ A System of Mineralogy,” 6th Edtn.; see also W. Bragg, ‘‘ Atomic Structureof Minerals,” Oxford Univ. Press, 1937, Chap. 16.W. Milligan and H. Weiser, J. Physical Chem., 1937, 41, 1029; R. M. Barrer,pro^. Roy. Xoc., 1938, A , 167, 392, 406BLUtRER: ZEOLITES AS ABSORBENTS AND MOLECULAR SIEVES. 33highly hydrated (Table I), and they have a rather low density and refractiveindex which reflect this high water content. They have a well-developedproperty of base-exchange, which is, however, shared by other mineralswhich are not zeolites such as the sodalite-hauyne group of minemh,15ultramarine, and some clays.Like all silicates, zeolites are built by the union of Si04'"' tetrahedraby sharing one or more oxygen atoms with neighbouring tetrahedra.SomeSiO,"" tetrahedra are replaced by A10,""' tetrahedra, thus imparting anegative charge to the framework, which is neutralised by an electro-chemical equivalent of interstitial cations. The framework is alwayssufficiently open to enmesh also interstitial water molecules, and upon thisproperty depends their behaviour as occlusives. AS indicated in Table I,three kinds of anionic framework exist : 14 (i) Robust three-dimensionalahminosilicate network structures. (ii) Structures with ahminosilicatesheets rather weakly bonded to one another. (iii) Structures with ratherweakly cross-linked aluminosilicate chains.The zeolites lose their crystal water on heating, with a variable degreeof lattice shrinkage which is a minimum with the first kind of zeolite, andmay be large, or even amount to irreversible lattice collapse, in the case ofthe laminar or fibrous zeolites.5 From the present point of view the non-collapsing zeolites are the most important, for these not only regain theircrystal water readily, but may sometimes occlude other gases and vapoursin place of water.* The water or other molecules are situated in the sameCf.M. Hey, Min. Mag., 1932, 23, 51 ; A. Winchell, Amer. Min., 1925, 10, 90;1926, 11, 82.R. M. Barrer, Trans. Faraday SOC., 1944, 40, 555.J. Wyart, Bull. SOC. franq. Min., 1933, 56, 81; see also 8a W. H. Taylor, Proc.Roy. Soc., 1934, A , 145, 80.' J. Wyart and P. Chatelain, Bull. SOC. franc. Min., 1938, 61, 121.lo J. Sekawina and J.Wyart, ibid., 1937, 60, 139.l1 R. M. Barrer, unpublished data on the sorptive properties of harmotome.lZa W. H. Taylor, C. Meek, and W. Jackson, 2. Krist., 1933, 84, 373; 12b W. H.Taylor and R. Jackson, ibid., 1933, 86, 53; 12c M. Hey and F. Bannister, Min. Mag.,1932, 23, 51, 243, 305, 421, 483.l3 W. H. Taylor, ref. (8a).* Chabazite,l gmelinite,7 mordenite 7 and " active " analcite,16 all robust networkstructures (Table I), absorb non-polar gases, although not all robust network structureswill do so, and the property depends on the relative dimensLon of molecule and inter-stitial zeolitic channel. Laminar and fibrous zeolites, if not over-heated during out-gassing, may occlude small polar molecules such as ammonia in place of water, buthave not yet been found to occlude non-polar gases.17 reported thatharmotome could absorb hydrogen sulphide and ethyl alcohol in place of water, butfor the latter at least this report requires reinvestigation.11 In view of recent work onsorption by fibrous zeolites,6 it is also most unlikely that the fibrous zeolite thomsonitecould occlude glycol and isopropyl alcohol, as reported by M.Hey.19 In these caseseffects noted with larger organic molecules could have been due to selective removalof water from the liquid. M. Grandjean20 stated that levynite, gismondite, andharmotome could occlude mercury vapour. This is possible even for harmotome inview of the small radius of the mercury atom (-1.5 A.).Molecules which may replace water as constituents of the lattices of a number ofzeolites are given in Table V.l4 W.H. Taylor, 2. Krist., 1930, 74, 1.G. FriedelREP.-VOL. XLT. 34 GENERAL AND PHYSICAL CHEMISTRY.interstices as the interstitial cations, with which they are in close associ-afion.l39' Like these cations they may diffuse from one site to another,but whereas cations cannot leave the lattice unless their place is taken byan electrochemical equivalent of other cations (base-exchange) the waterand other molecules may do so, and thus form vagabondising constituentsof the crystal lattice. In this they recall the behaviour of hydrogen insolution in palladium, cerium, thorium, and other metals.', 21 The gas-zeolite system is best considered as an interstitial solid solution in whichthe occluded molecule interacts physically only with its environment,through dispersion, polarisation, and ion-dipole forces.21 The term " per-sorption " applied to gas-zeolite systems is inadequate and should bereserved for the irregular dispersion of the sorbate in the sorbent, as is thecase in charcoal or silica gel.As should characterise binary interstitial solid solutions in which theoccluded component is a vapour, most zeolites give a continuous sorption-desorption isotherm (Fig.1). This property is also reported z2 for water ina number of other crystalline substances, including MgPt( CN),, strychninesulphate, basic zirconium oxalate, oxalates of cerium and some rare earths,some flavanol derivatives, glucosides, and crystalline proteins.In addition,certain clays and other silicates,23 such as ~iloxene,~* will take up wateror ammonia continuously, probably within the crystal lattice, or betweenindividual aluminosilicate sheets.26Isotherms, Isobars, and Isosteres.-Typical isotherms, isobars, and iso-steres in zeolites are illustrated in Figs. 1, 2, and 3. A number of equationshave been suggested to describe the isothermals.26 The most successful ofthese are based upon kinetic or statistical models 27 and have the formp = constant x 0 / ( l - 0) . . . . (1)See W. H. Bragg, ref. (a), p. 265, for structural details of the hauyne-sodalitegroup.l6 R. M. Barrer and D. A. Ibbitson, Trans. FaracEay SOC., 1944, 40, 195, 206.1' R. M. Barrer, ref. (5).a1 R. M. Barrer, Trans. Faruday SOC., 1944, 40, 374.22 A list of references to work on crystals with zeolitic components, and crystalsgiving continuous sorption isothermals is given by McBain, ref.(1).z3 J. Sameahima and N. Morita, Bull. Chem..Soc. Japan, 11935, 10, 485, 490;I. Cornet, J . Chem. Physics, 1943, 11, 1; L. Hansen, W. Samuel, and P. Forni, Ind.Eng. Chern., 1940, 32, 116 ; L. Spitze and L. Hansen, iW., 1942, 34, 506.24 Kautsky and his collaborators have studied the sorptive properties of siloxene.A list of references is given by McBain, ref. (1). See also H. Kautsky and F. Grieff,2. anorg. Chem., 1938, 236, 124.25 G. Nagelschmidt, 2. Krist., 1936, 95, 481 ; see also S. B. Hendricks, J . PhysicalChem., 1941, 45, 65.z6 0. Weigel, Sitz. Gea. Naturwiss. Marburg, 1924, 73; G.Huttig, Fmtschr. Chem.,1924, 18, 5 ; Kolloid-Z., 1924, 35, 337; 0. Schmidt, 2. physikal. Chem., 1928, A , 133,263; E. Rabinowitsch, ibid., 1932, B, 16, 43.27 M. Hey, Min. Mag., 1935, 24, 99; E. Rabinowitsch and W. C. Wood, Trans.Faraday SOC., 1936, 32, 947; R. M. Barrer, ref. (21).la Bull. SOC. franp. Min., 1896, 19, 94.2o Bull. Soc.franc. Min., 1910, 33, 5. Min. Mag., 1932, 23, 103BARRER : ZEOLITES AS ABSORBENTS AND MOLECULAR SIEVES. 35where 8 denotes the fraction of all the available interstices occupied bysolute molecules, and p is the equilibrium pressure. Values for the constant in750135ti?Q‘h: * 4rooa 75 2B-a96 50G273°K.384°K. 25c 20 Pressure (cm.). 300FIG. 1.Isotherms of N, in chabazite.’?“I-0 I400 500 600 7000 Temperature (OK).FIG.2.Isobars of typical gases in ~?tabazite.~0Curve 1 : He (400 mm.).Curve 2 : H, (400 mm.).Curve 3 : N, (400 mm.).Cuwe 4 : CO, (200 mm.).Curve 5 : NH, (100 mm.).Curve 6 : H,O ( 7 mm.).(1) have recently been obtained21 corresponding to the progressive conversionof translational and rotational degrees of freedom of the solute moleculeinto vibrational ones when the solute is transferred from the gas phase t36 GENERAL AND PHYSICAL CHEMISTRY.the zeolitic interstice. The value of this constant is a sensitive measure ofthe mobility of the solute within the crystal lattice, and actual isothermsare best reproduced with values of the constant in (1) appropriate for three-dimensional oscillators within the zeolite, so that no large proportion ofoccluded molecules is mobile.An extension of equation (1) has been based 22 upon the discovery l6that, contrary to earlier observations,28 chain molecules such as n-paraffinsmay be copiously absorbed in certain zeolites. This sorption has beenfollowed for the n-paraffins as far as n-heptane, and it is certain that such160 200 25il 300 350 400 450 500Temp.(OK).FIG. 3.12.18 c.c./g. of mineral.I6a molecule must; have a stretched configuration in the interstitial channelof the zeolite, which sheaths it closely. Many configurations possible inthe gas phase are thus precluded when the molecule enters the crystal,and this in turn introduces an additional negative entropy of occlusion.The configurational entropy has been calculated under certain conditions,and also the total entropy of occlusion.The negative value of the con-figurational entropy of occlusion increases with increasing chain length, anddecreases the affinity of occlusion (AA = AU - TAX). For very long-chain solutes the configurational effect would outweigh all others, and makeAA positive, so that occlusion would become negligible in spite of the greatheat of occlusion.Xaturation Values for Sorption in Zeolites.-Attempts have been madeto measure the quantity of gas required to saturate a zeolite. 0. Weigel *9sammarised all analyses of the water content of zeolites and plotted theamount of water, in order of increasing value, against the number ofanalyses. The curves obtained had lengthy central portions either nearlyflat or of gentle slope, suggesting a fairly definite if not quite sharp satur-ation value towards water, because at room temperature water is very28 0. Schmidt, ref.(26); T. Baba, Bull. Chem. Xoc. Japan, 1930, 5, 190; J. Same-shima, ibid., 1929, 4, 96.2s Centr. Min., 1922, 164-178, $01-208.Isosteres for some hydrocarbons occluded in chabazite. The amount sorbed iBARRER: ZEOLITES AS ABSORBENTS AND MOLECULAR SIEVES. 37strongly absorbed? and occlusion isotherms are nearly rectangular. Thewater contents in Table I may thus be taken as substantially saturationvalues towards this species. Reported approximate saturation values forother vapour-chabazite systems, in C.C. (at N.T.P.)/g., are :He ...............400 30 NH, ............... 270,30 170 l7H, CO, .................. 170 ............... 350,30 280 l7A .................. 250 l7 CH,*OH ............ 166 s1N, ............... 175,30 170,30 164 l7 C2H,*OH ......... 110 91These data are not always concordant, and the lack of uniformity is prob-ably in large degree a measure of the uncertainty of the extrapolation ofexperimental data, which has often been considerable. Another piocedurehas therefore been suggested 16 in which a well-established experimentalfigure is taken, and saturation values for other solutes derived from it.Satisfactory figures are 170 C.C. (at N.T.P.)/g. for nitrogen-chabazite, or266 C.C. (at N.T.P.)/g. for water-chabazite, the latter figure being derivedfrom the formula of Table I.Long-chain solutes are stretched out withinthe narrow zeolitic channel (see previous section), so thatLength (or diameter) of N, (or H,O) - Saturation value for chain moleculeLength of chain molecule - Saturation value for N, (or H,O)In this way the saturation values given in Table I1 were obtained. Satur-ation values towards water may be obtained from Table I for other zeolites,TABLE 11.Saturation Values in Chabaxite and Active Analcite.Saturation value, C.C. (at N.T.P.)/g.Diameter or v AGas. length (A,). Chabazite. Active analcite.H20 ........................... 2.76 266 * 97 *NH, ........................... 3.60 193 72 .............................. 3.74 186 69 .............................. 3-84 181 670, .............................. 3-83 181 67N, ..............................4.08 170 f- 63CH4 ........................... 4-00 173 64C2HS ........................... 5.54 125 46.4t~n-C,H,o ........................ 7.78 89 33.1~z-CGH~, ........................ 9.04 77 28-5n-CeH14 ........................ 10.34 67 25-0C,H, ........................... 6-52 106 39.5n-C,H,, ........................ 11.56 59 22.2* Experimental value from Table I.f- Value used to calculate all others save that for water.but molecular sieve effects (p. 44) or lattice collapse on dehydration (seenext section) may effectively prevent other gases from replacing the water.Phase Formation and Zeolitic Solid Solution.-A recent investigation hascombined X-ray measurements with dehydration isobars,32 and suggests30 E.Rabinowitsch, ref. (26); E. Rabinowitsch and W. Wood, ref. (27).31 0. Weigel and E. Steinhoff, 2. Krist., 1926, 61, 126.32 W. Mi- and H. Weiser, ref. (6)38 GENERAL AND PHYSICAL CHEMISTRY.that, among fibrous zeolites, scolecite and natrolite give evidence of lowerhydrates but that thomsonite and mesolite dehydrate without discontinuity,as do stilbite and heulandite (laminar structures) and chabazite and analcite(robust three-dimensional networks). The less robust chain and sheetstructures show lattice changes during heating which may extend to com-plete breakdown of the parent structure; but the chabazite and analcitelattices show little change in X-ray pattern on heating. The existence ofan amrnoniate of natrolite has also been demonstrated ; l7 above a thresholdpressure, sorption of ammonia occurred autocatalytically to give an approx-imately univariant system.It has been suggested that zeolitic solidma. 4.Gibbs free energy (G) plotted against Tfor the system Zeolite, xNH, + (1 - x)NH,. Fig.4~ shows the condition for a continuous sorption isobar, and Fig. 4B the condition for adiscontinuous sorption isobar, x changing at a certain temperature from 0.9 to O-1.2'solution occurs normally when the zeolitic lattice suffers no marked changeduring sorption or desorption, and'that new phases tend to form if con-comitant lattice changes are ~onsiderab1e.l~ Another criterion has beensuggested which shows how the alternatives of zeolitic solid solutions(ammonia-chabazite) or phase changes (ammonia-natrolite) may arise.Ina system Zeolite, zNH, + (1 - x)NH,, for example, when the free energy-temperature curves lie for different values of x as in Fig. 4A, the sorption-desorption isobar is continuous, but with a small displacement as in Fig. 4B,one or more discontinuities may arise.21 This is because the lower envelope,representing the most stable state of minimum free energy, curves conBARRER: ZEOLITES AS ABSORBENTS AND MOLECULAR SIEVES. 39tinuously and touches each G-T curve at one point only in Fig. 4A; but inFig. 4B this envelope consists of two intersecting lines, coinciding with theG-T curves for x = 0.9 and x = 0.1.Heats and Free Energies of ZeoZitic Solid 8oZution.-Heats of occlusionin zeolites have been measured directly,% and by the use of the Clapeyronequation.34 Although it is not certain that the calorimetric and thermo-dynamic methods measure exactly the same heat, these heats do not differsignificantly where both methods have been used on the sameFor non-polar gases these heats are within experimental accuraoy inde-pendent of temperature, but are characteristic functions of the amount ofgas occluded 179 16, 21 (Fig.5). A rather similar form of curve is alsoobtained for van der Waals adsorption on glass,36 charcoal,37 gra~hite,~Band simple ionic crystals,39 and various causes of it have been discussed.38, 1 7 9 3 9Sorption heats in chabazite, even of small permanent gases such as nitrogen,are unusually large,l7 and it has been shown that this can be due to theinterstitial position of the solute molecule.For equal diameters of soluteand interstice the van der Waals energy of interaction may amount toabout 8 times the value observed when the occluded molecule is transferred33 A. Lamb and E. Ohl, J . Amer. Chem. SOC., 1936, 67, 2154; M. G. Evans, Proc.Roy. SOC., 1931, A , 134, 97; M. Hey and F. Bannister, Min. Mag., 1934, 28, 483.34 Idem, ref. (12); M. Hey, ref. (27); A. Tiselius, 2. phyaikal. Chem., 1935, A , 174,401 ; E. Rabinowitsch, ref. (26);. R. M. Barrer, refs. (5) and (7).36 E.g., M. Hey, ref. (27); see also S. Brunsuer, “ The Adsorption of Gases andVapours,” Vol. 1, Oxford Univ. Press, 1944, Chap. 8.as W. Keesom and J. Schweers, Physicu, 1941, 8, 1007, 1020, 1032.37 A. van Itterbeek and W.van Dingenen, ibid., 1937, 4, 389.38 R. M. Barrer, Proc. Roy. SOC., 1937, A , 161, 476.39 W. J. Orr, ibid., 1939, A , 178, 349.J. de Boer and J. Custers, 2. phyeikal. Chem., 1934, B, 26, 22640 GENERAL AND PHYS1tJA.L CHEMISTRY.to a plane surface of the same sorbent. The sorption heat of n-paraffinsin chabazite is nearly a linear function of the number of CH, groups in themo1ecule,l6 and rises by about 3000 cab. per CH,. For high molecularweight n-paraffins the sorption heat could become greater than for manychemical reactions, although it is due only to dispersion and polarisationforces .I6Entropies (p. 36) and free energies of occlusion have also been obtainedfor sorption in chabazite and active analcite, as functions of the charge ofgas and a t different temperatures.16 Free energy-0 curves have the sameform as the corresponding heat of sorption-0 curves, and the standard freeenergy series for a given zeolite and group of solutes parallels the corre-sponding series of sorption heats; i.e., entropies of occlusion are all of thesame order (AA = AU - TAS).I I I I00 20 40 so 80 Id0 % DehydrationFIG. 6.Sorption at 0" and 1600 mm..of CO,, O,, and H, by chabazite at various degreesof dehydration .41Curve ( 2 ) : 0,. Cutwe (1) : C02. Curve (3) : H,.Factors Injluencing Sorption Equilibrium in Zeolites.-The power of azeolite to occlude depends in large measure upon the severity and durationof the heating and degassing treatment to which it has been subjected.These determine the extent of both lattice collapse or alteration and ofdehydration. Fig.6 shows the equilibrium sorption of carbon dioxide bychabazite as a function of the water content of the mineraL41 A maximumoccurs a t about 95% dehydration; conditions severe enough to removemore water probably lead simultaneously to lattice collapse. Parallel withthis striking result, the heat of occlusion was measured as a function of thedegree of hydration 42 (Fig. 7).A recentstudy using mordenites revealed that base-exchange may alter both mole-4l A. Lamb and J. Woodhouse, J . Amer. Chem. SOC., 1936, 58, 2637.A. Lamb and E. OH, ref. (33).Sorption equilibrium may also be modified by base-exchangeBARRER: ZEOLITES AS ABSORBENTS AND MOLECULAR SIEVES.41cular sieve properties of zeolites (p. 4.4) and sorption equilibria and heats.’Affinities and heats of sorption of nitrogen and oxygen increased, for theexchanging ions Na+ < Ba++ < Ca++, in the order of the relative polarisingpower of the interstitial cation. Similar results were deduced 7 from thereIative escaping tendency of water vapour from base-exchange stilbites,chabazites, and he~landites.~~Yo Debydraflon of chabazite.FIG. 7 .Heats of sorption of CH,*OH i n chubazite (at a charge of 0.000178 mol.Ig.) a8 afunction of the yo dehydration of the chubazite.gaKinetic Behaviour of Solutes in Zeolites.-One must distinguish betweenthe usual simple zeolitic solution and the less usual sorption in whicha new phase appears, with discontinuity in the isobar or isotherm (p.38).In the latter case the sorption rate was “autoca6alytic” and the processwas regarded as a growth and diffusion of phase boundaries.17 Whensimple zeolitic solutions are formed, occlusion has been interpreted as a purediffusion process not complicated by slow rates of transfer of solute acromthe ingoing surface. As a diffusion process, sorption rates follow Fick’alaws, and the ‘‘ parabolic ” diffusion equation has been most successfully73 16 Potential solutes may be divided into three groups (seeTable V) : ( a ) molecules occluded extremely rapidly, (b) those occludedslowly at room temperature or above, ( c ) those excluded from the zeolitelattice. These groups grade continuously into one another.Group (a)comprises small molecules, or molecules of small cross section (e.g., inchabazite, gmelinite, and active analcite, helium, hydrogen, oxygen, nitro-gen, argon, methane, and ethane; and in natural mordenite, helium,hydrogen, oxygen, and nitrogen). For the first three minerals, Group ( b )included n-paraffins, and Group (c) included iso-paraffins and aromatichydrocarbons, but in mordenite Group ( b ) included methane and ethane,and Group ( c ) n-paraffins. Group ( b ) solutea enter the lattice by a diffusion43 E. Lowenstein, 2. anorg. Chem., 1909, 83, 69.4 4 P. Emmett and T. DeWitt, J . Amer. Chem. Soc., 1943, 66, 1263.B 42 GENERAL AND PHYSICAL CHEMISTRY.process of which each unit act requires an energy of activation.l6Y 7, 44 Thisenergy is needed to move the solute molecule from one position of maximumsorption potential to another within the crystal, and in an appropriatelattice was observed even for the inert gas argon. Table I11 records anumber of apparent energies of activation, which for the n-paraffin seriesincrease somewhat with increasing charge of gas and chain length.TABLE 111.Apparent Activation Energies for Diffusion of Some Solutes into Ze~lites.~sZeolite.Diffusing molecule. Ed (cals. /g.-mol. of solute).C3H 8 4500, 6700Chabazi te n-C&,, 8900, 8600n-C 6H 12 7100, 6800n-C,H,, 11,100, 11,400, 9600C,H,.CN 5900H.CO,Et 7300CH,*CO,Me 40,000Active analcite C3H 8 6800, 7300Mordenite C2H6 4300CH3*CN 830035004900 ACa-Mordenite N, 1040Several measurements have been made of diffusion constants, D, ofammonia and water in analcite and h e ~ l a n d i t e .~ ~ In heulandite, diffusionanisotropy occurs, and at 20" normal to the (201) and (001) planes (eachnormal to the unit lamellae of the heulandite layer lattice), Dool : D,, =1 : 11-6-20. In one sample the activation energies for the diffusion across(001) and (201) planes were 5400 and 9140 cals./g.-mol. A kinetic theoryof the diffusion constant has been successfully applied to Tiselius's measure-ments of D.47 The diffiision constant is a function of the charge of solutealready within the lattice. At first, inhomogeneity of the zeolite lattice,chemical or physical, causes solute molecules to be anchored at sites ofhighest sorption potential, so restricting their mobility.Again, when nearlyall sites are occupied the chance of an adjacent vacant site into which thesolute might move is small and so mobility is again reduced. In a homo-geneous zeolite, D is related to 8, the fraction of the interstices occupied,and Do, its value when 8 = 0, by D = Do (1 - 8).48 A considerable volumeof evidence has been obtained that D does behave in the mannerpredicted.16, 7,Rates of Occlusion of Solutes as a Function of Water Content, HeatTreatment, and Grain Size.-The treatment accorded to a zeolite may greatlymodify the sorption rates of solutes. One important variable is the extentof dehydration, the mineral occluding gases more rapidly the more com-pletely the water is removed, providing conditions do not simultaneously4 6 R.M. Barrer, J . Soc. Chem. Ind., in press.46 A. Tiselius and S. Brohult, 2. physikal. Chem., 1934, A , 168, 248; A. Tiselius,ibid., 1934, A, 189, 425; idem, ref. (34).4 7 M. Hey, ref. (26); see also idem, Phil. Mag., 1936, 22, 492.48 R. M. Barrer, ref, ( 1 ) ; Trans. Faraday SOC., 1941, 37, 690.Ba-Mordenite NBARRER : ZEOLITES AS ABSORBENTS AND MOLECULAR SIEVES. 43give lattice collapse. Conditions for producing very active chabazite insmall amount have been established,l6 and the influence of degree ofdehydration on some sorption rates and equilibria measured44 (cf. p. 44)).Molecular sieve properties of chabazite in relation to its water content aresummarised in Table IV.These results were extended by the observationTABLE IV.Effect of Degree of Dehydration upon Sorption Rates and Equilibria inChabaxite.Dehydr-&ion, yo. Gas. Behaviour.50 C02 Considerable sorption at -78".67N,H,N2O2A96 NO:} All three gases copiously and rapidly occluded at - 183".Athat nitrogen entered the chabazite when 67% dehydrated by a process ofactivated diffusion,44 whereas there is no measurable energy of activationAppreciable sorption at -78"; occlusion at negligible rate at -195".Considerable sorption at - 195".Still only small sorption in finite time at -183".Copiously occluded at - 183".Copiously occluded at - 183".700 200 300Time. in minutes.FIG. 8.Influence of state of subdivision of chabazite upon the rate of occlusion of propanein it.In all experiments, the 11u;~ss of chabazite = 3.336 g., the initial pressure ofC,H, = 9.6 f 0.1 cm. H g and T = 200" C.16Curve 1 : Particles $-J$ inch diameter, outgassed 14 hrs. at 470-480" C.Curve 2 : Particles 20-30 mesh, outgassed 14 hrs. at 470-480" C.Curve 3 : Particles 80-100 msh, outgassed 14 hrs. at 470-480" C.Curve 4 : Particles < 200 mesh, outgassed 14 hrs. at 470-480" C.Curve 6 : Particles 180-200 mesh, outgassed 7 hrs. at 470-480" C.when this gas enters a well outgassed chabazite.17 It seems likely thatwater molecules immobilised in the zeolitic channel a t - 1 8 3 O impede theflow of nitrogen within the crystal. Other examples in which one substanc44 GENERAL AND PHYSICAL CHEMISTRY.impedes the sorption of a second substance by a zeolite have been reported,and may in some cases be due to the same cause.45An investigation of the influence of degree of subdivision upon sorptionrates of n-paraffins revealed that, in qualitative accord with the theory ofdiffusion, the smaller the particle dimensions the more rapid was thesorption l6 (Fig.8).Molecular Xieve Properties.-The sorptive properties of several zeoliteshave now been extensively investigated, and in Table V are summarisedTABLE V.Molecules Occluded or Excluded by the Three Classes of Molecular Sieve.45Typicalmoleculesrapidlyoccluded atroom temp.or below.Section (i).Class 1 minerals HeNeAH 2N2 co(302 cos, cs,H2OHCl, HBrNOZZ:*OHCH,*NH,CH,*CNHCNC1aCH,Cl, CH3BrCH,FCH3-SHSection (ii).Class 2 minerals HeNeNH3Ha0Section (iii).Class 3 minerals HeNeTypical moleculesmoderately rapidlyor slowly occludedat room temp.orabove in the thermalstability range.C,H, and simpleC,H ,*OHC,H ,*NH,higher n-paraffisCZHSFCaH5BrI,, HICH,BraCH,IC,H ,*CNC,H,*SHHCO,Me, H*C02EtCOMe,CH,*CO,MeNHMe,, NHEt,CaHbC1CHj*NH,CI.I,.CNCH3Cl, CH,FHCNCS,c1,AHClm3Typical moleculesoccluded at negligiblerates, or totallyexcluded withinthe thermalstability range.Branched-chain hydro-carbons. cyclo-Paraf-fins. Aromatic hydro-carbons. Derivativesof all these hydro-carbons. Heterocyclicmolecules (e.g., thio-phen, pyridine, pyr-role).CHCl,, CCl,,CHCl:CCl,, CH,*CHCl,,CHCl,.CCl,, C,C16 andanalogous bromo- andiodo-compounds. Se-condary straight-chainalcohols, thiols, ni-triles, and halides.Primary amines withNH, attached to asecondary C atom.Tertiary ammes.Branched-chain ethers,thioethers, and second-ary amines.All classes of moleculesin cols. 3 and 4 above.All molecules referred toin col. 4, section (ii).Also : CH,, C,H;,CH,*OH, CH,*SH,C H a * C N , CHa*NH,,CHSCl, CHaFBARRER : ZEOLITES AS ABSORBENTS AND MOLECULAR SIEVES. 45the sorptive and molecular sieve characteristics of three distinct categoriesof sieve.45 Class 1 is represented by well-outgassed chabazite, gmelinite,active analcite, and a synthetic crystalline zeolitic mineral; class 2 bywell-outgassed natural mordenite ; and class 3 by well-outgassed calciumand barium mordenites produced hydrothermally a t high temperatures.Convenient dehitions of the three classes of molecular sieve were given asfollows : Class 1 exclude iso-paraffins, occlude n-paraffins slowly, and methane,ethane, and molecules of smaller cross-section rapidly, a t room temperature.Class 2 exclude n-paraffins (and molecules of similar and larger cross-section) ,occlude methane and ethane slowly, and nitrogen and molecules of similarand smaller cross-section rapidly, at room temperature.Class 3 shownegligible occlusion of methane and ethane, and molecules of larger cross-section, but occlude nitrogen, oxygen, and molecules of smaller cross-sectionrapidly.The three classes of crystal sieve have been used to resolve molecularmixtures, frequently with striking success.For example, by using chabaziteit has been shown that simpler n-paraffins may be separated quantitativelyfrom all iso-paraffins and aromatic hydrocarbons, and that C, and C, hydro-carbons may be removed from propane and higher hydrocarbon^.^^^ 49The molecular sieve method was extended to the separation of polarand polarisable molecules from admixture with other m0lecules.~5 One ormore constituents were removed from 52 different typical liquid mixturescontaining as many as five components, by using a class 1 zeolite; 17 suchseparations were effected by means of a class 2 zeolite; and 6 by class 3zeolites. In many cases these separations are single representatives onlyof whole groups of separations, so that the method is of some generalityand power.The separation depends primarily upon differences in molecularshape and size, and not upon differences in boiling point. In this way itmay supplement distillation technique, e.g., in resolution of azeotropicmixtures, many of which (some of industrial importance) can be separated.The rate of separation varies from extremely rapid to very slow, but pro-vided the components of the mixture do not decompose on heating, rise intemperature frequently accelerates the separation rate many times.Monosubstituted methanes in which the substituent groups are small,such as C1, CH,, OH, CN, NH, and the like, are very rapidly occluded bychabazite, and monosubstituted ethanes with similar substituent groupsenter the lattice considerably more slowly (Table V).Both classes of solutemay be quantitatively separated from molecules in col. 4, section (i), ofTable V, and the monosubstituted methanes can also be partly or com-pletely separated from similarly substituted ethanes. In a natural mordenitethe monosubstituted methanes were slowly occluded (CH,*OH, CH,*NH,,CH,*CN and the like), but monosubstituted ethanes were excluded (Table V).Separations were therefore obtained of one- from two-carbon molecules.On the other hand, the class 3 occlusives, calcium and barium mordenite,did not occlude even molecules with one carbon atom, so that the separations4 9 R.M. Barrer, B.P. No. 548,905; U.S.P. No. 2,306,61046 GENERAL AND PHYSICAL CHEMISTRY.obtained were of simple inorganic molecules (NH,, H20, HCl) from organicgases and vapours.R. M. B.4. CRYSTALLOGRAPHY.i. Introduction.SECTIONS iii and iv of this Report aim at giving a reasonably complete accountof the more important inorganic and organic structures which have beendetermined by X-ray or electron-diffraction methods during the year. Ina few cases, however, only a bare reference is given; and it is possible thatcertain other work may have been missed entirely, because many of thepublications are still rather inaccessible.On the other hand, no attempt is made to cover the wider aspects of thesubject in the form of a systematic Annual Report.Instead, the plan is tohave certain special articles at longer intervals which will review variousbranches of the subject. This year Section ii gives a brief account of ambi-guities which may occur in the analysis of diffraction patterns, a subjectwhich is clearly of importance in all structural work. The large and growingamount of X-ray work on natural and synthetic fibre structures demandssome special treatment, and this is given in Section v. Finally, we includea brief general article on the electron microscope in Section vi. The applica-tions of this instrument to problems of chemical interest are steadily increas-ing. Ultimately we may expect some overlap between electron microscopemethods and the more usual diffraction methods, in the analysis of complexmolecular structures.With this possibility in mind, the present sectionhas been included in this Report and is of an introductory nature.A number of important topics are of necessity entirely omitted from thisReport, but it is hoped that these may in turn be covered by further specialarticles in the future. A,mong these subjects are optical and magneticproperties, lattice vibrations and the physics of crystals in general, thestructure of metals, alloys, and minerals, the investigation of surface problemsby electron diffraction,l the structure of proteins and other complex sub-stances not of the fibre type, the diffraction of X-rays by liquids and amor-phous substances, and general improvements in experimental and interpre-tative technique.The recent extensive work on the structure of diamondsof different types may also merit a special review when the results becomeclearer.The new structure determinations now reported (Sections iii and iv)contain a fairly large number of reasonabIy accurate bond-length deter-minations, notably for halogen derivatives. The whole question of thederivation of bond lengths from the standard covalent radii is now under-0. P. Thomson, J . Inst. Metal8, 1943, 69, 191 (lecture).N. S. Gingrich, Rev. Mod. P h y s k , 1943,15, 90 (review).a (Sir) R. Robertson, J. J. Fox, and A. E. Martin, Phil. Trans., 1943, A , 232, 463;Proc. Roy. SOC., 1936, A, 157, 579; (Sir) C. V. Raman et al., Proc. Indian A d . Sci.,1944, 189; G. D. Preston, Nature, 1945, 156, 69; (Mrs.) K.Lonsdale, ibid., p. 144ROBERTSON : CRYSTALLOGRAPHY. 47going considerable revision. Following the new single- bond covalent radiifor oxygen, nitrogen, and fluorine,* contractions from predicted values arenow seen to be more numerous than was previously thought, and their causeis the subject of much discussion. In general, the effect on the distance ofthe polar character of the bond between unlike atoms is probably greaterthan was formerly realised. The new data now recorded should be of greatvalue in any general rediscussion of bond distances. Amongst new structuredeterminations that of ammonium pentachlorozincate, (NH,),ZnCl,, is ofinterest as it reveals only a four-fold type of co-ordination, the structureconsisting of a packing of NH,+, C1-, and ZnC1,- ions, a situation somewhatreminiscent of the structures of phosphorus penta-chloride and - br~rnide.~In the organic section, the structure of the carboxyl group has receivedconsiderable attention and the latest determinations make the two C-0distances almost as different as for pure single and pure double bonds.That is for non-associated acids ; on association, interesting changas aredetected and the distances become more nearly equal, although still mmain-ing quite distinct.Finally, in the ion, complete equality is to be expected.Other new results indicate that the conjugating power of phenyl groupsmay be less than has hitherto been supposed, and in compounds like diphenylthere appears to be very little contraction in the length of the connectinglink. The tendency for coplanarity of the rings is correspondingly small,and in the vapour the molecule of diphenyl is probably not coplanar.Thecrystal structure should be re-examined. The structure of the highlysymmetrical coronene molecule has now been examined by crystal analysisand the preliminary results are in good agreement with molecular orbitalcalculations of the interatomic distances.J. M. R.ii. Ambiguities in the Analysis of Diffraction Patterns.If a crystal structure is expressed as a continuous distribution of scatter-ing matter a knowledge of the absolute values of the structure amplitudes isnot sufficient to define the distribution. An infinite number of distinctdistributions can clearly be obtained by attaching arbitrary values to theunknown phase constants associated with the observed amplitudes, andevaluating the corresponding Fourier series.I n nearly all actual cases thefundamental assumption is therefore made that the structure is composed ofatoms, of a kind and number indicated by elementary chemical analysis.The problem can then be reduced to finding what co-ordinates must beattached to a limited number of scattering points in order fo explain theobserved diffraction pattern.In single-crystal analysis the number of observed and measurable X-rayreflections is always much greater than the number of atoms whose positiomhave to be discovered. In fact, it should generally be possible to make 60V. Schomaker and D.P. Stevenson, J . Amer. Chern. Soc., 1941, 65, 37; see Ann.Reports, 1943, 40, 86.ti Ibid., 1942, 39, 10148 GENERAL AND PHYSICAL CHEMISTRY.or more observations per atom without difficulty. It might then be thoughtthat atomic positions which yielded perfect agreements between the measuredand the calculated X-ray intensities throughout the whole range of observ-ations would constitute a unique solution of the structural problem involved.That this is not necessarily the case was proved originally by L. Panling andM. D. Shappell for a special point of the space-group Ti - Ia3, wherepositive and negative values of one parameter were found to yield the sameX-ray intensities. A similar property is shown by the correspondingspecial point for the space-group Oy - I ~ 3 d .~ In general, any distinctdistributions of points which possess the same vector distances will obviously@ . . *. . .@a ....... - ....(-J(f+-=. ' *. . . s a :@.* :. . .. . . * * .. .. * . ::L .......-......FIG. 1.Three set8 of homometric quadrupletsfor the cyclotomic set n = 16, r = 8(A. L. Patterson, Physical Rev., loc. cit.).give rise to the same X-ray diffraction pattern. Such sets of points arecalled " homometric."A. L. Patterson has now provided a very useful general discussion ofsuch ambiguities in X-ray crystal analysis. His treatmenf is confinedchiefly to one-dimensional cases. Such linear periodic distributions can beconvenienfly represented by plotting the points on the circumference of acircle, and the cases examined are those obtained by using Q of the n vkrticesof an inscribed regular polygon.Sets of points obtained in this way arecalled " cyclotomic " sets. Out of 2664 cyclotomic sets examined (up ton = 16) Patterson has found a total of 390 homometric pairs, 7 sets of homo-metric triplets, and 3 sets of quadruplets. The last distributions are shown2. Krist., 1930, 75, 128. A. L. Patterson, Nature, 1939, 145, 939.3 Physical Rev., 1944, 65, 195ROBERTSON : CRYSTALLOGRAPHY. 49by the black dots in Fig. 1. I n these sets each member obviously representsa distinct distribution of points, yet all four would give rise to exactly thesame X-ray diffraction pattern.There appears to be considerable difficulty in developing any generaltheory for the occurrence of homometric sets, but the treatment can beextended in various ways.For example, it is sometimes possible to intro-duce a variable parameter between certain points and so produce an infinityof homometric pairs. It is also possible to extend the treatment to two andthree dimensions, but these possibilities have not yet been fully explored.The results so far obtained, however, are very significant and they clearlyreveal the limitations of the X-ray method of crystal analysis. The sametype of ambiguity must also apply, in a more drastic manner, to the resultsof gas-diffraction experiments. There the molecules are widely separatedand scatter independently. The experimental data give in effect the super-position of all the interatomic distances in the molecule, and as these distancesarQ no longer vector quantities, the possibility of ambiguity must be greatlyincreased.For example, the cases illustrated (see Fig. 1) represent onlylinear periodic distributions for crystal analysis, but in gas-diffraction analysiscyclic molecules of these types would give rise to similar ambiguities.These findings emphasise the fact that the results of diffraction experi-mefits should in general be confirmed by other independent lines of physicaland chemical evidence. Optical and magnetic properties, for example,afford valuable auxiliary evidence, and the various experiments should allagree before a structure is finally accepted as being true. The essence of adiffraction experiment is rather to show that a given postulated structure isconsistent with the data, than to attempt to establish a truly unique solution.At the same time if alternative solutions should exist in any given case, itseems very unlikely that they would both be chemically reasonable.The above discussion, of course, assumes complete ignorance of the phaseconstants of the X-ray reflections.If these can be determined, a trulyunique solution to the problem immediately becomes possible. In a largeand growing number of cases this can be done, for example, by the com-parison of members of an isomorphous series, as in the phthalocyanines4or by successive approximations involving the use of a heavy atom in them~lecule.~ The ambiguities discussed above do not arise in such cases, andthe results do represent unique solutions.J.M. R.iii. Inorganic Strwtures.Halogen Derivatives of Tin, Arsenic, and iVitrogen.-A very extensiveinvestigation by electron diffraction of 14 of these derivatives has now beenreported by A. H. Skinner and L. E. Sutt0n.l From 6 to 9 plates were takenon the vapour of each substance, and these showed from 4 to 6 maxima for* J. M. Robertson, J., 1935, 615; 1936, 1195.Idem, Nature, 1939, 143, 75; J. M. Robertson and (Miss) I. Woodward, J., 1940,Trans. Faraday SOC., 1944, 40, 164.3650 GENERAL AND PHYSICAL CHEMISTRY.the various compounds. Both the radial distribution and the correlationmethod of analyses were used. The models employed for the tin compoundsassumed the four valencies to be directed to the corners of a tetrahedron(not necessarily regular).For the compounds of nitrogen and tervalentarsenic non-coplanar valencies were assumed. Free rotation of the methylgroup was assumed in all compounds, and tested with satisfactory resultsin the case of trimethyltin monochloride.The final results regarding interatomic distances and valency anglesare given in Table I, together with some previous results for the tetrahalidesof tin and the trihalides of arsenic.2 The table also gives the length of theb6nd to the halogen as calculated from the covalent radii of L. Pauling andM. L. Huggins; for nitrogen, however, the new radius of 0.74 A. is used.4The small but progressive contraction which occursin the bond lengthwhen more halogens are added to the central atom is very clearly broughtout by these results.(The percentage contraction from the calculatedvalue is given in the last column of the table.) This phenomenon is a verygeneral one and has already been investigated and discussed in other seriesof compounds, such as thesilanes . tiCompound.SnMe,Cl .........SnMe,CI, .........SnMeCl, .........SnCl, ............SnMe,Br .........SnMe,Br, ......SnMeBr, .........SnBr, ............SnMe,I .........SnMe,I, .........SnMeI, .........SnI, ...............AsMe,Cl .........AsCl, ............AsMe,Br .........AsBr, ............AsI, ...............NMeCl,. ...........AsMeJ .........NMe,Cl.. ..........AngleX-M-X.108°f40110 f 5108 f 4109.5109 f 3-109.5109.5 f 2109.5-109.5109.5 f 3109.5 f 2109.598 f 3103 &396 f 3100 f 298 A4100 &2-108 f lfluorinated- methanes and the chlorinatedTABLE I.C-M, A.2-1 9 f 0.032.19f0.052-17 f0-05-2.17-2.17-2.17-----1.47 -+0*02 -* Expansion.M-X, A.obs.2.37 f0.032-34 f 0-032.32 f 0.032.30 f0-032.49 f0.032.48 f0-022-45 k0.022.44 f0.022.72 f0.032.69 f0.032-68f 0.022.64 &O-022-1 8 f0.042.16f0.032*34&0*042.36 k0.042-52 f 0-032-58 IfI0.051-77 f0.021-74 f0.02M-X,calc.2-392-392.392.392.542.542.542.542.732-732.732-732-202.202.352-352.542-541-731.73Contrac-hion, yo.0.82-12.93.82.02.43.53.90-41.51.83.30.91.80.00.00.8-1.6 *-2.3 *-0.6 *As Skinner and Sutton point out, any straightforward explanation ofthis effect in terms of either bond multiplicity or ionic character of bonds isdifficult, but the latter effect appears to be the more important for these2 I,.0. Brockway and F. T. Wall, J. Amer. Chem. SOC., 1934,56,2373; M. W. Listerand L. E. Sutton, Trane. Farachy SOC., 1941, 37, 393, 406.2. KrGt., 1934, 87,205.4 V. Schomaker and D. P. Stevenson, J. Amer. Chem. SOC., 1941, 63, 37.6 L. 0. Brockway and H. 0. Jenkins, ibid., 1936,58,2036.6 L. 0. Brockway and I. E. Coop, Trans. Furuday Soc., 1938,34,1429ROBERTSON : CRYSTALLOGRAPHY. 51cases. Each successive halogen addition will tend to increase the positivechange on the central atom, with corresponding decrease of its normalradius.There will be a similar enlargement of the halogen atom withnegative charge, but this effect on any one of the halogens will tend todiminish as more halogens are added. The net attractive force will alsoincrease between the central atom and each halogen, and so from bothcauses we might expect a small progressive decrease in bond distance. Wemay expect a more quantitative development of this theory in the future.Phosphoryl and Thiophosphoryl Halides.-Further interesting deviationsfrom the predicted covalent bond radii for halogen-phosphorus, oxygen-phosphorus, and sulphur-phosphorus distances have been observed byJ. H. Secrist and L. 0. Brockway in an electron-diffraction investigationof the compounds POBr,, PSBr,, PSFBr,, and PSF,Br.For the first twomolecules trigonal symmetry is assumed and the structures are described interms of two parameters, the Br-P-Br angle and the P-0 or P-S : P-Brbond-length ratio. The calculations are therefore relatively straight-forward. The lower symmetry of the other molecules makes the calculationsmore difficult, but a large number of models have been tested and examined.The radial distribution method has also been employed in each case.The final results for the bond lengths (in A.) and valency angles in thesemolecules are given in Table 11. Allowance being made for all uncertaintiesit is clear that the phosphorus-halogen distances (especially the P-F dis-tance) are considerably shorter than the predicted values.The P-0 andP-S distances are also distinctly less than the sum of the respective double-bond radii. In general, the new results confirm and extend the findings ofprevious investigations on similar compounds.*TABLE 11.CovalentPOBr,. PSBr,. PSFBr,. PSF,Br. radius sum.P S ......... - 1*89&0*06 1-87 f0.05 1.87 f0.05 1.94 *P-F ......... - - 1.50f0-10 1.45f0-08 1.74P-Br ......... 2.06f0-03 2.13f0.03 2.18f0.03 2.14&0*04 2-24 - - 1.57 * P-0 ......... 1.41 k0.07 -A - - BrPBr ...... 108Of3" 106:f3" 100°f3"F@Br ...... - - - 106"f3" -* Calculated for double bond.Silicon Halides.-Further electron diffraction studies have been carriedout by R. L. Livingsfone and L. 0. Brockway8a on silicon dimethyldichloride, silicon methyl trichloride, and trifluorosilicon chloride.TheSi-Cl distances are similar to previous measurements and the Si-C distancesshow some contraction, but details must be deferred.' J . Amer. Chrn. SOC., 1944, 66, 94.L. 0. Brockway and J. Y . Beach, ibid., 1938, 60, 1836; D. P. Stevenson and H.Ruase11, $bid., 1939, 61, 3264; J. Y. Beach and D. P. Stevenson, J . Chem. P h y e b ,1938, 6, 75.8a J . Arner. Chern. XOC., 1944, 86, 9452 GENERAL AND PHYSICAL CHEMISTRY.Silver Salts and the Ag-0 Bond.-The crystal structure of potassium silvercarbonate has been determined by J. Donohue and L. Helmh~lz.~ Thecarbonate group is assumed to have the same configuration and dimensionsas in calcite,1° and the positions of the potassium and silver atoms can bedetermined with considerable accuracy from Fourier analyses of the visuallyestimated intensities.It is found that the silver atoms are surrounded byfour oxygen atoms a t 2.42 & 0.05 A. There is one potassium-oxygendistance of 2.65 & 0.08 A., and others varying from 2.9 to 3.0 A.of the structure of silver carbonate, wherethe silver atoms are surrounded by deformed tetrahedra of oxygen atomswhose distance is estimated at about 2.3 A.Silver oxalate has been examined by R. L. Gr%th.ll The monocliniccrystals appear to be rather similar to some other oxalates, with a short btranslation (3.46 A.), and two molecules in the unit cell (space-group C& -P2,/c). Intensities were estimated visually, and Fourier projections serveto define the positions of the silver atoms with some accuracy, but theoxygen and the carbon atoms can hardly be located at all.Conclusionsregarding the structure of the oxalate group are therefore unreliabk, butthese groups appear to be bound together to form chains by means of twoshort Ag-0 bonds of length 2.17 and 2.30 A. Four other Ag-0 distancesrange from 2.6 to 3.0 A.The average Ag-0 bond distance is found to vary considerably in differentcompounds,12 from 2.51 A. in silver chlorate to 2.06 A. in the oxide. Suchvariations in the Ag-0 distance are of interest in connection with the rulesuggested by K. S. Pitzer and J. H. Hildebrand l3 which relates the colourof a compound formed from colourless ions to the amount of covalentcharacter in the bond between these ions.For Ag-0 the ionic radius sumis 2-46 A. and the covalent radius sum 2.19 A., so that for comparable struc-ture types it should in some cases be possible to make estimates of thebond character. This matter is discussed in the paper by Donohue andLevine . l2Ammonium Pentachloroxincate.-A very full determination of the crystalstructure of this salt, (NH,),ZnC15, has now been made by H. P. mug andL. Alexander.14 The work is of interest in View of the rather infrequentoccurrence of the MX, group in inorganic chemistry. I n the exampleswhich have already been studied the actual co-ordination has usually provedto be some combination of four- or six-fold types. In phosphorus penta-chloride there is a combination of tetrahedral Pa+, and octahedral PC1;;groups,15 and in the pentabromide PBri and Br- ions.16 The crystalA brief report is also given9 J , Amer.Chem. SOC., 1944, 66, 295.N. Elliott, i b d . , 1937, 59, 1380. l1 J . Chem. Physics, 1943, 11, 499.l4 Ibid., 1944, 66, 1056.l2 L. Helmholz and R. Levine, J . Amer. Chem. SOC., 1942,64,354.18 Ibid., 1941, 65, 2472.16 H. M. Powell, D. Clark, and A. F. Wells, J . , 1942, 642; Ann. Reports, 1942, a,l6 H. M. Powell and D. Clark, Nature, 1940, 146, 971.101ROBERTSON : CRYSTALLOGRAPHY. 53structures of TlAlF, and K&lF,,H,O 1' show that infinite chains of AlF,octahedra extend through the crystal in such a way as to make the netcomposition AlF5.Ammonium pentachlorozincate .crystals are orthorhombic, space-groupDG - Pnma, and the unit cell contains four molecules of the composition(NH,),ZnCl,. The analysis was carried out bn about 600 reflections (Cu-Karadiation) obtained from small crystals.The intensities were estimatedvisually from oscillation photographs, the multiple film technique l8 beingemployed. Analysis of the structure by trial proved too difficult, but thepositions of the heavy atoms were finally obtained by evaluating the Patter-son functions. Two-dimensional Fourier projections then gave the positionsof all the atoms with considerable accuracy.The unit cell is found to contain four tetrahedral ZnC1, groups, theaverage Zn-C1 distance being 2.25 & 0.03 A,, a value very close to the sumof the tetrahedral covalent radii l9 (2.30 A,).The remaining chlorineatoms are separated from the zinc atoms by over 4.4 A., and each of thesechlorines is surrounded by a distorted octahedron of NH,+ ions, with anaverage Cl-NH, distance of 3.41 A,, which is rather greater than the sum ofthe ionic radii. Each ammonium ion is in turn surrounded by groups ofchlorine atoms.The structure is thus seen to represent a, packing of NH,+, C1-, andZnC1,- ions, which would be better expressed by writing the chemicalformula as (NH,) ,ZnCl,,NH,Cl. The Zn-C1 bonds are essentially covalent,but the other linkages are ionic (except N-H). Once again, therefore, thecrystal is found t o avoid the difficulty of five-fold co-ordination.Sulphur Compounds.-C. S. Lu and J. Donohue20 have examined anumber of sulphur compounds by the method of electron diffraction.Forsulphur itself they find that the S8 molecule has essentially the same con-figuration as in the crystal,el vix., a regular, puckered, eight-memberedring. It is interesting to note that several systematic distortions of thisring, such as the " tub," " chair," " cradle," and " butterfly '' forms, weretested and shown to be incompatible with the radial distribution curve.Hence, the fraction of sulphur molecules which have these configurationsin the vapour phase must be very small. However, the results do show thatthere must be a rather large thermal vibration associated with the puckeredring structure. The S-S distance of 2-07 & 0.02 A., and the angle S S S of105" -& Z0, are fairly close to previous determinations.Orpiment sublimes at high temperatures apparently to give Aspsgmolecules, for a model based on this structure 22 gives a satisfactory explan-ation of the pattern.In this model As-S = 2.25 & 0.02 A,, angleC. Brosset, 2. anorg. Chem., 1937, 236, 139.18 J. M. Robertson, J . Sci. Instr., 1943, 20, 175.19 L. Pauling and M. L. Huggins, 2. Krist., 1934,87,205.2O J . Arner. Chem. SOC., 1944, 66, 818.21 B. E. Warren md J. T. Burwell, J . Chm. P h y e k , 1936,8,6.2z R. M. Bozorth, J . Amer. Chem. BOG., 1923, 45, 162154 GENERAL AND PHYSICAL CHEMISTRY.ASS-As = 100' &- 2". These molecules also display rather large thermalvibrations.Two other structures, those of sulphur nitride, S4N4, and realgar, Asps4,have been included in this electron-diffraction study, but although usefulresults have been obtained, which should assist in the exact analyses of thecrystals, yet the structures cannot be established with certainty from thegas-diffraction data alone.However, several previously proposed structurescan be definitely eliminated, and it is shown that an alternating eight-membered ring, of " cradle " shaped configuration, can lead iN\/"B to a satisfactory explanation of the diffraction pattern inboth cases. The " cradle " model for sulphur nitride is S\N/'\N/ rather closely related to the formula (inset) proposed byM. H. M. Arnold, J. A. C. Hagill, and J. M. H u t s ~ n , ~ ~ which wouldinvolve resonance among several bond structures.Other Structures.-Finally, reference may be made to a number of in-organic structures which have either been briefly reported, or for which thefull papers are not available to the Reporter.These include magnesiumcarbide,24 zinc cyanide,25 cadmium iodide 26 (which has a random structureif crystallised quickly), and the compounds SrMg,, BaMg,, and CaLi,.27The hydrate SrCI2,6H,O appears to have been fully studied 28 and has achain type of structure with linkages through the water molecules. Ortho-rhombic lead mon0xide,2~ antimony trifiuoride 3O (with an Sb-F distanceof 2.0 A.), natrophilite, NaMnP04,31 colemanite, 2Ca0,3B,03,5H,0,32ammonium ~hloroiridate,~3, sodium and ammonium iodateF4 and the high-temperature modification of sodium nifriteF5 have all received attention.The lattice constants of an isomorphous series magnesium, manganese,ferrous, cobalt, nickel, and zinc metantimonites, MSb,O,, have beenmemured, and the structures are reported to be similar to that of pb,04.36In another isomorphous series, comprising chromium vanadate and nickel,cobalt, copper, zinc, and cadmium chromates, both the metal atoms aresurrounded by distorted octahedra or tetrahedra of oxygen atoms withcommon edges.37J.M. R.23 J., 1936, 1645.24 M. A. Bredig, J . Amer. Chem. Soc., 1343, 65, 1482.25 H. S. Shdanov, Compt. rend. A d . Sci. U.R.S.S., 1941, 31, 352.26 G. Hagg and E. Hermansson, Arkiv Kemi, Min., ffeol., 1943, 17, B, No. 10.27 E. Hellner and F. Laves, 2. Krist., 1943,105, 134.** A. T.Jensen, " 5 Nordische Kemikermode," 1939, 201.29 A. Bystrom, Arkiv Kemi, Min., Qeol., 1944, 17, B, No. 8.30 A. Bystrom and A. Westgren, ibid., 1943, 17, B, No. 2.a2 V. A. Nikolsli, Compt. rend. A d . Sci. U.R.S.S., 1940, 28, 59.33 G. B. Boki and P. I. Usikov, ibid., 1940,26, 782.34 C. H. MacGillavry and C. L. Panthaleon van Eck, Rec. Trav. chirn., 1943, 62,a5 B. Strijk and C. H. MacGillavry, ibid., p. 705.a6 S. Stahl, Arkiv Kemi, Min., Cfeol., 1943,17, B, No. 6.A Bystrom, ibid., No. 4.729.K. Brandt, ibid., 1943, 17, A, No. 6ROBERTSON : CRYSTALLOGRAPHY. 55iv. Organic Structures.Ethylene.-An early study of ethylene 1 provided some single-crystaldata, but the structure proposed is an improbable one because it fails to satisfymodern ideas regarding both interatomic and intermolecular distances.From the original data (which consist of only seven observed reflections)C.W. Bunn 2 has now calculated a reasonable structure, and has shown thata model with a C=C distance of 1.33 A. can give an even better account of theobserved X-ray intensities than the structure originally proposed. In thenew structure the closest approach between carbon atoms on neighbouringmolecules is now 3.8 A., a reasonable value.Xtructure of the Carboxyl Group.-The first detailed diffraction studies ofthe carboxyl group, carried out on the vapour of formic acid,3 indicated thatthe carbon-oxygen distances were equal, at about 1-29 A. A later quantit-ative X-ray investigation of oxalic acid dihydrate crystals gave slightlydifferent distances, of 1.30 and 1.24 A.From an examination of the struc-tures involved in the carboxyl group one would not expect equal distancesin the case of the acids themselves. Later spectroscopic studies on themonomers and dimers of formic and acetic acids 5 have confirmed this view.Equality of the C-0 distances might reasonably be expected, however, forthe free carboxylate ion.have now published a comprehensiveelectron-diffraction study of the monomers and dimers of formic, acetic, andtrifluoroacetic acids. The interesting question of what changes, if any,occur in the C-0 distances on association does not appear to have beenexamined in detail before, and it is almost certainly beyond the reach ofX-ray crystal analysis, where the crystal molecules would normally be asso-ciated in pairs, or in some larger groups, or with water molecules.In thegas-diffraction experiments the monomers were studied by photographingthe equilibrium vapour at approximately 150°, which represents over 90 yoJ. Karle and L. 0. BrockwayTABLE 111.Carboxylic acids (distances in A.).Formic acid.Monomer. Dimer. IA 1C-QH ......... 1-42&0-03 1*36&0*04'C%O ............ 1-24&0*03 1.25f0.03 c-c - -C-F - --OH. ... O=.. . - 2-73 f0.05........................Acetic acid. Trifluoroscetic acid.I ' -Monomer. Dimer. Monomer. Dimer.1.24 f0.03 1.25 f0-03) (average)1*54&0.04 1.54f0.04 - 1.48 f0.03 - - 1.36 f0.05 1.36 f0.03- 2.76&0*06 - 2.76 f0.06A1.43 f0.03 1.36 f0.04 - 1.30f0.03HO-&O ......117Of2" 121°f2" 122-138" 130°f3" - 130"f3"1 W. H. Keesom and K. W. Taconis, Physica, 1935, 2, 463.Trans. Faraday SOC., 1944, 40, 23.L. Pauling and L. 0. Brockway, Proc. Nut. Acad. Sci., 1934, 20, 336, 340.J. M. Robertson and (Miss) I. Woodward, J . , 1936, 1817.L. G. Bonner and R. Hofstadter, J . Chem. Physics, 1938, 6 , 531; M. M. Daviesand G. B. Sutherland, ibid., p. 755.a J . Arner. Chem. SOC., 3944, 60, 57456 QENBRAL AND PHYSICAL CHEMISTRY.monomer. For the experiments on the dimers, the vapour densities indi-cated a 9-15% dissociation, which could be allowed for in the calculations.The results of the diffraction experiments concerning distances andangles are set out in Table 111.For the monomers, i.e., for the unassociatedcarboxyl group, a surprisingly large difference of nearly 0-2 A. is foundbetween the two C-0 distances. In fact, the longer distance (1.42 A.) isabout the same as that observed in ether linkings, whereas the shortercorresponds to that found in ketones. The hydrogen must clearly beattached to one of the oxygens only, with the result that the carbon-oxygenbonds are more or less of the ordinary single- and double-bond types,respectively.In the analysis of the dimers the molecules are assumed to have theplanar centrospmetrical type of bridge (inset),and the agreements obtained on this basis of calcu-dimensions of the carboxyl group, it is significantthat attempts to explain the diffraction pattern with models based on themonomer were unsuccessful.The final results (Table 111) show a veryconsiderable equalising of the C-0 distances, brought about almost entirelyby a shortening of the " single"-bond C-OH distance. However, thereremains a considerable difference between the two C-0 distances, about0.1 A., which is in tolerable agreement with X-ray crystal results on otherstructures. Owing to this difference in C-0 distances, it seems clear thatthe hydrogen atom must remain attached more strongly to one of thepartners in the dimer than to the other. If it occupied an (average) centreposition in the O-H . . . 0 bridge we would expect correspondingsymmetry and equality in the C-0 distances. This is in general agreementwith spectroscopic and X-ray evidence for the type of hydrogen bridgeinvolved in these structures, which has a length (oxygen-oxygen distance)of about 2.7 A.In trifluoroacetic acid the relatively high scattering power of the CF,group prevented a full determinatiofi of structure.The C-0 distancescould not be determined individually, but the average is estimated at 1.30 A.The C-F distance of 1.36 A. and the reduced G-C distance of 1.48 A. are inagreement with other observations on such bonds. It is rather surprisingthat the tendency towards dimerisation and also the length of the hydrogenbridge are apparently but little affected by the increased strength of thisacid.Karle and Brockway also examined deuterium acetate dimer but nodifference could be observed between the qualitative appearance of thephotographs obtained and those of acetic acid.Although an isotope effect(increase in length of the hydrogen bridge on substitution of deuterium forhydrogen) as great as that observed in oxalic acid dihydrate 7 might bedetected by electron diffraction, yet it is unlikely that the acetic acid bridgewould display such a large effect. The effect, if any, would more likely beJ. M. Robertson and A. R. Ubbelohde, Proc. Roy. Soc., 1939, A , 170, 222.-C/O \OH * ' . ' , Ho . o>- lation justify the assumption. With regard to thROBERTSON : CRYSTALLOURAPHY. 57comparable to those observed in succinic and benzoic acids,' which are small.A hydrogen bridge of length 2.76 A . is not expected to give rise to a largeisotope effect.Organic SuZphonates.-A series of interesting single-crystal measure-ments have been made by L.M. Jensen and E. C. Lingafelter on thequarter-hydrates of sodium 1-octane-, l-decane-, l-dodecane-, l-tetra-decane-, 1-hexadecane-, and 1-octadecane-sulphonate. In each case thespace group is C: (Aa) or more probably C$ (A2/a), and the unit cell con-tains 32 molecules of the hydrate or 8 molecules of 4R*S03Na,H,0. Thecross-sectional area of the molecules is somewhat greater than that of sodiumstearate or stearic acid, and decreases uniformly from 20.99 A .z in the octanederivative to 20.08 A . ~ for the octadecane derivative; at the same time thep angle increases by about 6'. The c-axis increases in steps of 10.2 A. from55.39 to 106.46 A,, which corresponds to an increase of eight carbon atomsalong the c-axis for every additional two carbon atoms in the chain.Typicaldimensions are : a = 16.86, b = 10.17, c = 55.39 A., p = 101'39' forC8Hl,*S0,Na,&H20, and a = 16-73, b = 10.05, c = 106.46 A., p = 107" 13'for C,,H,,~SO,~a,~H,O. Such a good series of single crystals of long-chaincompounds has seldom been available for X-ray analysis.Four-membered Rings.-Methylenecydobutane (I) and l-methylcyclo-butene (11) have been studied by W. Shand, V. Schomaker, and J. R. Fi~cher,~by the gas-diffraction method. These two structures are so similar that aunique determination by means of electron diffraction alone would bedifficult or impossible. The diffraction evidence, however, is sufficient toestablish quite definitely that neither of the compounds can have the Gpiro-pentane structure which has recently been advocated by F.Rogowski.1°This is in agreement with the chemical evidence. The final results of thopresent investigation indicate coplanar ring structures. For (I) the distancesare C-C = 1-55 i= 0.02 A., C=C = 1.34 0.03 A., and angle C,ClC2 = 92.5"&- 2O, in very good agreement with values obtained earlier by S. H. Bauerand J. Y. Beach.ll For (11) G C = 1.54 -+ 0.03 A., C=C = 1.34 5 0.03 A.,angle C,C,C, = 125" 5 4 O , angle C,C,C, = 93" 40' & 3". Symmetricalring structures In (11)the bond distortion appears to be distributed equally between the externalC-G-C and C=C-C angles.3" distortion are thus indicated in both cases.4 4(1.) (11.)Polyphenyls and Pheny1enes.-The type of binding between aromaticgroups is a matter of considerable interest, but the evidence available has10 Ber., 1939, 72, 2021.J. Arner. Chem. SOC., 1944, 66, 1946. Ibid., p. 636.11 J . Amer. Chem. Soc., 1942, 64, 1142; see Ann. Reporh, 1942, 39, 10458 GENERAL AND PHYSICAL CHEMISTRY.hitherto been rather unsatisfactory. The crystal structures of diphenyl,l2p-diphenylbenzene,13 o-diphenylbenzene,14 1 : 3 : 5-triphenylbenzene,l5 and4 : 4'-diphenyldiphenyl l6 have all been examined, but not with the accuracyavailable in modern technique, and individual bond lengths remain uncertain.In these early studies the ring size is generally given as 1.41 or 1.42 A., andthe connecting bond lengths as about 1.48 A. In diphenylene more recentelectron-diffraction results l7 give a ring size of 1-41 + 0.02 A., and connect-ing links of 1.46 & 0.05 A.(Miss) I.L. Karle and L. 0. Brockway18 have now made a carefulstudy of diphenyl, o-diphenylbenzene, and tetraphenylene by the electron-diffraction method. Such structures are, of course, much too complex to yieldanything like unique solutions by the gas-diffraction method. The processrather consists of showing that a certain model, or sometimes several differentmodels, are compatible with the data, while other models are not. But themethod is very sensitive, and changes of bond length amounting to 0.02 or0.03 A. are frequently sufficient to destroy the agreement for a given model.In diphenyl three different models satisfy qualitatively the appearance ofthe photographs.The first is planar, with ring size 1.39 A. and inter-ringdistance 1.54 A. The second has a slightly distorted benzene ring and aninter-ring distance of 1-48 A., while the third is non-planar with free rotationof one ring with respect to the other. It is concluded that a non-planarstructure for diphenyl is the most probable, especially as it avoids sterichindrance between the o-hydrogen atoms. The most probable average ringdistances are 1-39 & 0.02 A., and inter-ring distance 1.52 & 0.04 A.In o-diphenylbenzene the molecule cannot possibly be planar, and theaverage position of the two attached rings is thought to be orthogonal to thecentral ring, with possible oscillation of 1 5 O from the normal position.Thesame bond distances apply.In tetraphenylene (111) all planar models provedunsatisfactory. A good solution was obtained from amodel with four regular (1.39 A.) benzene rings and a :u'v) non-planar cyclooctatetraene ring. In the latter the\/\ /\ bonds alternate in length around the ring, between1.39 A. and 1.52 A., the former of course being the sidesof the benzene rings. The benzene rings are directedalternately above and below the average plane of themolecule in such a way that 120" angles are maintained between every pairof bonds.The general conclusion from these studies, based both on inter-ring12 J. Dhar, Indian J . Physics, 1932, 7, 43.Is (Miss) L. W. Pickett, Proc. Roy.Xoc., 1933, A , 142, 333.1 4 C. J. B. Clews and (Mrs.) K. Lonsdale, ibid., 1937, A , 161, 493.l6 B. P. Orelkin and (Mrs.) K. Lonsdale, ibid., 1934, A , 144,630; (Mrs.) K. Lonsdale,1 6 (Miss) L. W. Pickett, J . Amer. Chem. SOC., 1936, 58, 2299.18 J . Amer. Chem. Soc., 1944, 66, 1974.'->/ \(111.)2. Krist., 1937, 97, 91.See Ann. Reports, 1943, 40, 92ROBERTSON : CRYSTALLOURAPHY. 69distances and on the non-coplanarity of the molecules, is that the conjugationeffects between adjacent aromatic rings are less than had hitherto beenthought, and considerably less than between double or treble bonds andaromatic rings.lg More definite conclusions must await really detailed X-rayinvestigations of the crystal structures.A preliminary X-ray examination of crystals of triphenylmethyl chlorideand bromide has been made.20 They belong to the hexagonal system, andthe space group is either C3+H5 or C31-H3, with six molecules in the hex-agonal unit cell.The structures are obviously fairly complex, and althoughthe halogen a!oms have been located approximately by evaluating thePatterson functions, yet nothing definite can so far be said about the con-figuration of the triphenylmethyl group in these crystals.Coronene.-A preliminary X-ray analysis of the crystal structure of thearomatic hydrocarbon coronene (IV) has succeeded indetermining the position oE the carbon atoms with con-siderable certainty by means of a two-dimensional Fourierprojection of the structure along the monoclinic b crystalaxis.21I I distances cannot be measured very accurately, but, a strictly b\/ planar structure being assumed, there is already evidence(IV. 1 that the average C-C distance is slightly greater than theaccepted value for benzene (1.39 A.), and may be rather nearer to the graphitevalue of 1.42 A.The arrangement of the molecules in the crystal is such thatit should ultimately be possible to make very accurate measurements of allthe C-C distances.These findings are of considerable interest in view of detailed calculationsrecently carried out by C. A. Coulson by the method of molecular orbitalson the coronene bond orders and lengths.22 He has computed the energiesof the mobile electrons in terms of the fundamental resonance integral p,23and from these results it is possible to obtain the bond orders and lengthsrelative to the standard values for C-C, C=C, and CGC in ethane, ethylene,and acetylene.The calculated bond lengths are as follows :\/\ At the present stage of the analysis the interatomicCoronene. Graphite. Benzene.Mean length of C-C bonds (A.) ............... 1.406 1.417 1.389Length of central bonds (A,) .................. 1.418 1.417 1.389For structures of high symmetry and links between atoms of the samekind such calculations are obviously capable of considerable refinement.At present the experimental measurements are not nearly good enough toprovide an adequate test of the theory, but we may perhaps hope for someimprovement in this direction.19 J. M. Robertson and (Miss) I.Woodward, Proc. Roy. SOC., 1937, A , 162, 568;20 S. N. Wang and C. S. Lu, J . Amer. Chem. SOC., 1944, 66, 1113.21 J. M. Robertson and J. G. White, Nature, 1944, 154, 605.22 Ibid., p. 797.1938, A , 164, 436.23 Proc. Roy. SOC., 1939, A , 169, 41360 GENERAL AND PHYSICAL CHEMISTRY.Other Structures.-Other investigations in the field of organic structureswhich may be briefly mentioned are unit cell and space-group determinationsfor phloroglucinol d i h ~ d r a t e , ~ ~ the low-temperature form of abieticcodeine and P-methylmorphimethine.26 Ferritin and apoferritin 27 are bothface-centred cubic and contain the same protein. Although the cell size isthe same, the X-ray intensities are different. The iron atoms in ferritinapparently occupy interstices between the protein molecules.The structure of copper NN-di-n-propyldithiocarbamate has been studied,and the copper shown to have planar co-ordination.28 Phytomonic acid,C20H4002,29 has been shown to have a relatively long chain structure and asingle side chain, probably a methyl group. J.M. R.v. Natural and Synthetic Fibre Structures.Introduction.-Fibre structures have not recently been reviewed as suchin these Reports. The present note covers especially the last two years,mainly from the X-ray standpoint. Metals, complex biological fibres, andapplied aspects are omitted. The unity of macromolecular studies has beenreflected in the co-ordination of all relevant physico-chemical techniques intheir problems, which are as basic to colloid science, medicine, and biologyas to the industries of textiles, soaps, plastics, and rubbers.Dominantfeatures are the increasing tendency to treat long-chain molecules fromfundamental first principle&; the extension to fibres of ideas and results(energetics and structure) from the simpler metal and n-aliphatic chainsys,tems; the growing emphasis on secondary structure, aided by newtechniques such as electron microscopy and small-angle X-ray scattering ;and the success in interpreting physical and especially mechanical fibreproperties on a molecular basis. Surveys, varying conditions and environ-ment, still yield more fundamental results with fibres than separate precisionstructure analyses.New 8ourw.-High-polymer studies have brought about the formationof sub-groups of physico-chemical societies,l increasingly participate inothers, and have reoriented a vast applied literature.New governmentaland research associations 2 and two complete abstracting digests dealexclusively with fibres, whose structural problems have been focused in four24 C. R. Bose and R. Sen, Indian J. Physics, 1943,17, 163.26 H. S. Shdanov, M. J. Lazarev, and N. G. Sevastianov, Compt. ~ n d . Amd. SCi.26 L. Castelliz and F. Halla, 2. K ~ i s t . , 1943, 105, 156.27 I. Fankuchen, J . Biol. Chem., 1943, 150, 57.D8 G. Peyronel, Qazzetta, 1943, 73, 89.29 S. F. Velic, J . Bwl. Chem., 1944, 165, 101.U.R.S.S., 1941, 31, 767.E.g., Division of High Polymer Physics, Amer. Physical Soc., June, 1944 ; BritishE.g., Southern Agric.Res. Stn., U.S.A.“Natural and Synthetic Fibres,” M. Harris and H. Mark, Intersci. Publ. Inc.,1944; “ Resins, Rubbers, and Plastics,” H. Mark and E. S. Proskauer, Intersci. Publ.Inc., 1942.Rheologists’ Club, 1940MACARTRDR : CRYSTALLOGRAPHY. 61recent symposia.* Annual reviews have been found necessary in the proteinfield alone.5 Among new journals should be noted J . makromol. Chem.; ofbooks and surveys, Vols. 4, 5 of the “ High Polymer’’ series are fibre-structural landmarks among many.6The Fibrous State.--Ii’ibres are imperfectly ordered solids, occurringusually as discrete filaments, though also in compact form. Genesis and growthare discussed by W. Ostwald.7 They are formed of long-chain molecules,usually high polymers, but comprise also sheet-like plates linked in columnarform,8 by stress-interlea~ing,~ or by mere van der Waals forces.1° Fibresof animal and plant origin have a histological and cytological structure : inwool the fibre structure and properties are those of the cortical cell.ll Chemi-cal composition may vary longitudinally in a single fibre, and markedly SOas between medulla, cortex, and scale.12 Various degrees of order areobtainable with chains whose packing is a function of shape, mobility, andlocal intermolecular forces.The fringed-micelle theory l3 is now preferredto the crystallite 14 and continuous structure 15 pictures. In this, a singlechain may thread its way through alternate crystalline and amorphousregions which really differ only in degree, and alter (though with more thancybotactic permanence) with temperature, stress, pressure, swelling, etc.The crystalline nuclei give a brittle strength, the amorphous tangle tenacityand resilience of orientation, with some plastic flow. Fibre structureanalysis has therefore to deal not only with the phase-ordered crystallites,but also with their shape, size, and relation to the matrix. Special orient-“ Mol.Wt. Distrn. in High Polymers,” Trans. Paraday SOC., 1944,40,217; “ FibreStructures,”X-Ray Anal. Gp., Inst. of Phys., Mtg. Oxford (1944) ; “Physics of Rubberand other H.P.’s,” Amer. Physical SOC., cf. J . Appl. Physics, 1944, 15; “ PhysicalChemistry of Proteins,” Chem. Rev., 1942.Cf. Annual “ Advances in Protein Chemistry,” M.L. Anson and J. T. Edsall,1944, I, Acad. Press Inc., N.Y. ; “ Advances in Colloid Science,” 1942, I; “ Advancesin Enzymology,” I, 11, Intersci. Publ. Inc., N.Y. ; “ Review of Biochemistry,” StanfordUniv. P.O., California.“ Natural and Synthetic H.P.’s,” 1942, 708 pp., K. H. Meyer, Intermi. Publ. ;“ Cellulose and Cellulose Derivatives,” 1943, 1196 pp., E. Ott, Intersci. Publ.; cf.also “ Physical Chemistry of H.P. Systems,” 1940, 353 pp., H. Mark, Intersci. Publ. ;“ Elastic and Creep Properties of Filamentous Materials and other H.P.’s,” 1943,H. Leaderman, Text. Fdn. Washington;) Rep. Prog. Physics, L. R. G. Treloar,2942-43, 9, 113 ; G. Gee, Ann. Reports, 1942, 39, 7 ; J. Needham et al., J . Qen. Physiol.,1944, 27, 201.Kolloid-Z., 1943, 102, 35.E.g., Sodium thymonucleate, W.T. Astbury, Sci. Progr., 1939,133, 1. ’ E.g., Chrysotile asbestos, E. Aruja, J. Sci. Inslr., 1944, 21, 115.lo E.g., Fibrous carbon, J. Gibson, H. L. Riley, and J. Taylor, Nature, 1944, 154,544.H. J. Woods, Proc. Roy. SOC., 1938, A , 166, 76.J. B. Speakman, J . Text. Inst., 1941, 32, 3.0. G8m@osa, I(. Herrmann, and W. Abitz, Biochem. Z., 1930,228,409; K. Herr-and 0. Gemgross, Kautschuk, 1932,8, 181.K. H. Meyer and H. Mark, “Der Aufbau der H.P. in org. Naturst.,” 1930;H. Mark, J. Physical Chem., 1940, 44, 764.l5 H. Staudinger, “ Die hochmol. org. Verbind. Kautschuk u. Cellulose,” 193262 GENERAL AND PHYSICAL CHEMISTRY.ations may occur in cell-wall structures ; l6 normally, the crystallites arelong rods or ribbons with random radial orientation, but approximatelyparallel to the fibre axis; biaxial orientation may be securable in rolledfilm.” X-Radiograms taken perpendicular to the fibre axis are thus inter-mediate to rotating-crystal and powder X-radiograms, the arcing of reflec-tions depending on the degree of tolerance between crystallite and fibre axes.For this reason, meridian reflections, barred in crystal rotation photographs,often appear.Technique.-Fibre cameras are best fitted with stretching frames andconditioning gadgets ; l8 screening foil and vacuum chamber minimisegeneral scattering from air and amorphous fibre regions ; monochromatisedradiation, as in the arrangements of A.Guinier l9 or I. Fankuchen,m is vitalfor small-angle scattering and ordinarily preferable.Moving cameras such asthose of 0. Kratky 21 simplify interpretations, the geometry of which has beensummarised by Y. Go.22 Of recent photometers, that of N. H. Chamberlain 23has many fibre applications. For speedy intensity recording of uniaxial fibrespectra, the G-M counter 24 has advantages. High resolution being requiredfor the fine detail of macromolecular structure and texture, fine slits per-mitting registration up to >600 A. are now frequent practice,25 especially inconjunction with high-power X-ray generators.2s In this connection, pre-cision beam foc~sing,~’ permitting the origin of X-rays to function as theinitial slit, enhances useful intensity. X-Ray power is expedient in allowingquick comparative study of homologues,28 or of fibres maintained at succes-sive small intervals of humidity, pH, swelling, temperature, pressure,extension, etc.; it extends the scope of X-ray methods in following suchtopochemical reactions as mercerisation 2~ or nitration of cellu1ose.m Theuse of glass-capillary slits (0.03 mm.in diameter) providing mirror reflectionhas been extended to the micro-analysis of single fibres and the drawingprocess.31 Of special fibre interest is the application of diffuse low-anglescattering to problems of grain size and texture ( q . ~ . ) , and of the analyticaltechnique for statistical arrangements such as mixed crystallisation, inter-calation, or turbostratic layering in swelling studies. The local chemicalRelative intensities need special settings or calculation.l6 R.D. Preston, Biol. Rev., 1939, 14, 281.l7 C. W. Bunn, Trans. Faraday Soc., 1939, 35, 482.lB W. T. Astbury, unpublished.lo Compt. rend., 1937, 204, 1115; Ann. Physique, 1939, 12, 161.Nature, 1937, 139, 193.0. Kratky, F. Schossberger, and A. Sekora, 2. Elektrochem., 1942,48,409.Bull. Chem. SOC. Japan, 1940, 15, 239. 23 J . Text. Inst., 1944, 35, T61.24 A. Eisenstein and N. S. Gingrich, Rev. Sci. Instr., 1941, 12, 582.25 E.g., R. Hosemann, 2. Elektrochem., 1940, 46, 535.26 I. MacArthur, Electron. Eng., 1944, 17, 272; 1945, 17, 317; W. T. Astbury and27 A. Guinier and J. Devaux, Rev. Sci., 1943, 341 ; Compt. rend., 1943, 217, 682.28 I. MacArthur, Mtg. X-Ray Anal. Gp., Inst. of Phys., Oxford (1944).30 M.Mathieu, Compt. rend., 1941, 212, 80.31 I. Fankuchen and H. Mark, J . Appl. Physim, 1944, 15, 364.I. MacArthur, Nature, 1945, 156, 108.E. Green, Ph.D. Thesis, Leeds University (1938)MACARTHUR : CRYSTALLOGRAPHY. 63composition and density of reflecting regions, required in structure analyses,are not necessarily easy determinations. Valuable analytical developmentsare new and improved methods for amino-acids 32 (protein fibres) ; theelectron probe with its transmitted velocity spectrum peaked by the excit-ation of X-ray K, L, or M levels33 will be of future interest. Porosity,preferential swelling, and adsorption of the immersion medium by the non-crystalline matrix are germane in density determinations ; comparativeresults of the usual immersion methods and the helium procedure of P.M.Heertzes 34 are described.35Inorganic.-Common alumina and silicate fibres are of membrane typewith liquid c0ntent.3~ Technical methods described for producing (e.g.,in glass) suitable strength and texture include high temperature centrifugalspinnerets, and surface and admixture treatrnent~.~~ Filamentous carbon,prepared by cracking of methane, has given a fibre X-radiogram,lo thelamellar hexagon layers, - parallel to the fibre axis, showing the usual3.5 A. graphitic spacing. A pioneer in the technique of diffuse scattering,A. Guinier extends the work on amorphous carbons and coa1F8 determiningmicelle dimensions and distribution ; as expected, activated carbons showa very fine state of division which varies with treatment.39 Similar studieson fibrils of chrysotile 40 reveal the hexagonal close-packing of parallel rods,earlier found in n-paraffins 41 and n-alcohols,42 in a discrete pair of longspacings of ratio fi : 1. Fibril diameters vary between 195 and 250 A.Further independent work on chrysotile asbe~tos,~~ 43 reveals novel features.The monoclinic cell has a 14.64, b 9.22, c (fibre axis) 5.33 A., p 93.2".TheSi4OI1 chains originally proposed yield place to a duplex sheet structure ofSi,05Mg3( OH), consisting of a branch-type sheet of O,( OH),Mg6( OH), linkedto O,Si,O,(OH), (hexagonal net of tetrahedral SiO, with OH in the planeof the tops of the tetrahedra) by the-common O,(OH),. Certain diffusereflections reveal irregularly stacked packing : their positions and asymmetricnature accord with two-dimensional net scattering and, together withthose of the congener antigorite, have been used by E.Aruja to interpretfine detail. Cell and space-group of giimbelite45 are determined. An32 A. J. P. Martin and R. L. M. Synge, Biochem. J . , 1941,35,91,1358; A. H. Gordon,A. J. P. Martin, and R. L. M. Synge, ibid., 1944,38,65 ; R. Consden, A. H. Gordon, andA. J. P. Martin, ibid., p. 224; J. R. McMahon and E. E. Snell, J . Biol. Chem., 1944,162, 83; A. C. Chibnall et al., Biochem. J . , 1943, 37, 354, 360, 372.33 J. Hillier and R. F. Baker, J . Appl. Physics, 1944, 15, 663.34 Rec. Trav. chim., 1933, 52, 305.35 Idem, ibid., 1941, 60, 91, 329; 1942, 61, 761; R. P.Rossman and W. R. Smith,38 W. Ostwald, Kolloid. Z., 1943, 102, 181.38 B.C.U.R.A. Conference, 1943, London; Proc., 1944.39 H. Brusset, J. Devaux, and A. Guinier, Compt. rend., 1943, 216, 152.40 I. Fankuchen and M. Schneider, J . Arner. Chem. SOC., 1944, 66, 500.41 A. Muller, Proc. Roy. SOC., 1932, A , 138, 514.42 I. MacArthur, unpublished.44 Idem, Phyeiccrl Rev., 1941, 59, 693.Ind. Eng. Chem., 1943, 35, 972.B.P. 563,678; U.S.P. 2,338,473, 2,331,944/5/6.43 B. E. Warren, Amer. Min., 1942, 27, 235.4 5 E. Aruja, Min. Mag., 1944, 27, 1164 GENERAL AND PHYSICAL CHEMISTRY.interesting discussion of gelatinising silicates in terms of lateral radical andnetwork structure is made by K. J. Murata.46n-AZipliatic Unbranched Chains.-(a) Soaps. Soaps fibre with the paraffinchains perpendicular, not parallel, to the fibre axis.47 Further X-rayevidence 48 confirms their existence in gel or solution as head-to-head bimole-cules of standard chain cross-section, giving “ long spacings ” (L) whichincrease on dilution, or on addition of benzene or dye solubilisation, byintercalation at heads and tails respectively.Micelle aggregates arelamell~e?~ with the dominant cohesion along the smallest axis. As withmontmorillonite, thixotropy is evidenced, e.g., by magnesium stearate inbenzene,50 the temperature of the sol-gel transformation increasing linearlywith soap concentration. The equilibrium has been studied spectro-phot~metrically.~~ The most direct evidence of gel structure and fibre sizeand texture is still the excellent electron micrographs (EM) for sodiumlaurate,62 statistical analysis of whose interlocked mesh of ribbon fibrilsshowed a multi-pile lamellar structure of parallel, slightly hydrated, bi-molecular chains.Fibering of metal soaps in mineral oil 53 is favoured byfree acid. Calcium and aluminium cations yield very small fibres, but, forsodium soaps, large fibres are favoured by low-viscosity polar oils, un-saturated soap chains, and shearing stress in combination with polaradditants such as glycerol. Growth mechanisms and energetics have been * Transparent soap is not amorphous, but is composed ofultra-fine random fibres (y-form, q.v.) with free glycerol.55Characterisation of the numerous phase structures and their stabilityranges and transitions, complicated as they are by water content, continuesby X-ray and thermal methods.For the sodium palmitate-water systemF. G. Chesley s6 finds six transitions. In addition to the liquid-crystallinestate, four crystalline modifications have been given X-ray criteria for thesodium stearate-water system. 5’ and many well-known features of longaliphatic chains with polar end-groups have been confkmed and extended byfibre X-radi~grams.~~ Transitions variously indicate change of water content,46 Amer. Min., 1943, 28, 545.47 S . Ross, J . Physical Chem., 1942, 46, 414 ; 0. E. A. Bolduan, J. W. McBain, and48 H. Kiessig, Kolloid-Z., 1941, 96, 252; J. W. McBain and K. E. Johnson, J .49 W. Philippoff, Kolloid. Z., 1941, 96, 255.6o B.S. Kandelaki, Izv. Gruz. Ind. Inst. Kirova, 1940, 13, 109.J. Stauff, 2. Elektrochem., 1941,47, 820.62 L. Marton, J. W. McBain, and R. D. Vold, J. Amer. Chem. SOC., 1941, 63, 1990.53 W. Gallay and I. E. Puddington, Canadian J. Res., 1944, B, 22, 66, 90, 103.64 J. Stauff, Kolloid-Z., 1941, 96, 244.6 5 J. W. McBain and S . Ross, Oil and Soap, 1944, 21, 97.56 J . Chem. Physics, 1940, 8, 642.6 7 R. H. Ferguson, F. B. Rosevear, and R. C. Stillman, Ind. Eng. Chem., 1943, 35,6 8 J. W. McBain, 0. E. A. Bolduan, and S. Ross, J. Amer. Chem. SOC., 1943, 65,S . Ross, J . Physical Chem., 1943, 47, 528.Amer. Chem. SOC., 1944, 66, 9.1005.1873; J. W. McBain, A. de Bretteville, and S. Ross, J. Chem. Physics, 1943, 11, 179MACARTHUR : CRYSTALLOGRAPHY.65change of inclination of paraffin chain axes to polar layer planes, genotypictransformations (1 -dimensional melting), confirmed by the sudden variationin thermal expansion and onset of effects on the surface tension and viscosityof surrounding polar and the inception at the waxy-superwaxy trans-ition of the hexagonal symmetry of " molecular rotation." 6* Temperature-spectra showing the latter effect together with some L variation have beenmade for sodium stearate.61 R. H. Ferguson believes the water is present onlyin solid solution ; M. J. Buerger,62 using de Jong and precision Weissenbergtechnique on sodium stearate crystals prepared by A. de Bretteville, has deter-mined the a, p, y forms as -$H,O, -hH,O, and anhydrous respectively.Sodium stearate, +H,O is monoclinic, a 9.16, b 8-00, c 1 0 3 .9 6 ~ . , p 93" 43',space-group A2/a. The variety of crystal forms and packing detail adoptedby n-aliphatic polar molecules is much wider than is commonly supposed.While broad essentials are obtainable from fibre and powder X-radiograms,particularly by use of the anisotropic thermal expansion in temperature-spectra,28 complete crystallographic analyses, such as those of A. Miiller 63and C. W. Bunn,l7 could well be extended to other forms in a field where somuch understanding of molecular structure and forces can be gained by theprecise use of X-ray, thermal, polarisation, and force-field methods.While higher paraffins fibre with some tenacity, lowermembers give moderately tough and rubbery fibres only on admixture, e.g.,with lithium stearate.64 Work continues on the lines of A.Miiller andA. R. Ubbelohde, crystalline forms, transitions, stability ranges, and pre-melting being discussed by C. G. Gray, A. van Hook, and H. FrOhli~h.~~Dielectric measurements extend previous experimental results ; molecularff exure, invoked to account for the entropy changes involved, is found such asto leave - half the chains untwisted at the second-order transition. Therecent infra-red conclusion that in polythene some branching occurs-inparticular -2% of methyl groups 66-may bear on certain systematicanomalies met l7 in its crystal structure determination.Branched-chain Hydrocarbons and Rubbers.-(a) General and Macro-structure. Rubber-like materials consist of long flexible chains weaklycross-linked.They are distinguished from ordinary liquids and solidsrespectively by these few links (chemical, vulcanised, sterically knotted) andby their weak control of form through entropy rather than energy. Localcrystallisation, impeded by plasticisers and temporary knots, is promoted by(b) n-Parafins.5D W. Gallsy and I. E. Puddington, Canadian J . Res., 1943, B, 21, 211, 225.6O L. Pauling, Physical Rev., 1930,36,430 ; T . E. Stern, Proc. Roy. SOC., 1931, A , 130,s1 A. de Bretteville and J. W. McBain, J . Chem. Physics, 1943, 11, 426.62 M. J. Buerger, A. de Bretteville, F. V. Ryer, and L. B. Smith, Proc. Nat. Awd.63 Proc. Roy. SOC., 1928, A , 120, 437.64 Foote Min. Co., Rev. Sci. Instr., 1944, 15, 157.6 5 H.Frohlich, Trans. Faraduy Soc., 1944, 40, 498; A. van Hook and L. Silver,6 6 H. W. Thompson, J . , 1944, 183.551.Sci., 1942, 28, 526; M. J. Buerger, ibid., p. 529.J . Chem. Physics, 1942, 10, 686; C. G. Gray, J . Inst. Petr., 1943, 29, 226.REP. VOL. XLI. 66 GENERAL AND PHYSICAL CHEMISTRY.addition of active fillers such as carbon or dry silica.67 Normally, crystallitesare absent or randomly oriented ; stretching favours fibering.Secondary structure in such systems, in particular its relation to elasticity,has been widely studied, mainly by statistical and thermodynamic methods.68I n such treatments, the properties of bulk polymer are usually referred tothose of individual Gaussian or free-link chains involving the chain length (asdetermined by osmotic pressure, viscosity, or light scattering 69 methods)or its mean end-to-end distance (A).A is unaffected by a symmetrichindrance potential; 70 for unsymmetric steric effects, the form of the Adistribution function remains unchanged, but its magnitude increases. 70C. Sadron’s treatment 71 replaces the free-link chain by its “ equivalentparticle,” a time-average of its mean geometric articulation ; this surface ofrevolution, whose shape reflects chain rigidity, is then treated by Brownianmovement methods. Fundamental constants of diffusion, orientation,translation, viscosity, and temperature effects are expressible. Actual casesrequire individual correction because of the special importance of steric andpolar factors.72 Model experiments on threaded beads to simulate the effectof varying chain length, concentration, solvent nature, e t ~ ., ~ ~ give generalconfirmation.An interesting treatment of the melting of high polymers 74 explains interms of degree of polymerisation (P), latent heat per link, crystalline-amorphous ratio, and structural co-ordination numbers-(a) convergence ofmelting points with increase in P, ( b ) melting ranges, (c) stable coexistence ofamorphous and crystalline regions in a composite phase; data by N. Bekke-dahl 75 corroborate for rubber, Recent determinations of crystallite size(rubber) have been made by means of line-broadening (A. Taylor’s analysis 76)and small-angle diffuse 77 The values (80, 52-81 A. perpendi-cular to, -300 A.parallel to, stretch) confirm older figures.78 EM deter-minations show & gel fibril structure of minimum width 100-400 A,, but, in67 P. Rebinder, G. A. Ab, and S. J. Veiler, Comp. rend. Acad. Sci., U.R.S.S., 1941,31, 444; C. E. Hall et al., I n d . Eng. Chem., 1944, 36, 634.6 8 H. M. James and E. Guth, J . Chem. Physics, 1943, 11, 455, 531: F. H . Miiller,Angew. Chem., 1940, 53, 425; Kolloid. Z., 1941, 96, 326; W. and H. Kuhn, Helu.Chim. Acta, 1943, 26, 1394; F. T. Wall, J . Chem. Physics, 1943, 11, 527; P. J. Floryand J. Rehner, J . Chem. Physics, 1943,11, 512; R. Simha, Ann. N.Y. Acad. Sci., 1943,44, 297; J. J. Hermans, Kolloid. Z., 1943, 103, 210; J. D. Ferry, Ann. N.Y. Acad. Sci.,1943, 44, 313; J. J. Press and H. Mark, Rayon Text.Monthly, June-Aug., 1943;R. Houwink, J . Physical Chem., 1943, 47, 436; L. R. G. Treloar, Trans. Faraday SOC.,1944, 40, 109; and especially ref. 6.*@ P. Debye, J . Appl. Physics, 1944, 15, 338; W. W. Lepeschkin, Kolloid. Z., 1943,105, 141.70 P. J. Flory and J. Rehner, Ann. N . Y . A m d . Sci., 1943, 44,419.71 C. Sadron, J . Phys. Radium, 1943, 14, 92.72 C. W. Bunn, Proc. Roy. SOC., 1942, A , 180, 67, 82.73 H. A. Stuart, Natumoiss., 1943, 31, 123.7 4 E. M. Frith and R. F. Tuckett, Trans. Paraday SOC., 1944, 40, 251.7 5 J . Res. N u t . Bur. Stand., 1936, 15, 503.77 s. D. Gehman and J. E. Field, J . Appl. Physics, 1944, 15, 371.78 J. Hengstenberg and H. Mark, 2. Krist., 1928/9, 69,271.7 6 Phil. Mag., 1941, 31, 330MACARTHUR : CRYSTALLOGRAPHY.87addition, amorphous nodules also appear, often of considerable size.79 Fora standard 600% stretch in rubber, crystalline fraction and tensile strengthincrease as crystallite size decreases. The increase in crystallisation ofrubber with stretch is determinable by the parallel increases of magneticanisotropy 8o and fibre X-radiogram intensity. Lattice size is very constantduring stretch and density increases > 1 %.81 Cell expansion with temper-ature is anisotropi~.~*Important results on the phenomena of second-order transitions withtheir time effects and structural implications are those of R. F. Boyer andR. S. Spencer 82 (rubbers, nylon, polythene, etc.) and of H. Mark et(polystyrene). The former authors, for polymers, copolymers, and mixtures,determine by dilatometry the rates of expansion (PI? p,) below and abovethe transition point (Tt); the relations found are applicable to the deter-mination of crystalline-amorphous ratios, nature of phases, and somethingof the variation in P.Mark finds that above the polystyrene Tt, the specificvolume V-T curve is fixed; below Tt, aV/aT is fixed (= pl) but V itselfdepends on the speed of cooling, Tt being higher the quicker the speed.On quick heating from the lower temperatures, any particular V-T curvais retraceable, but on maintaining T fixed in a wide range (40-80") V fallsto a minimum curve a t a rate increasing with T. The phenomena, whichrecall comparable cyclical results of R. Buckingham 84 and, in another field,of W.A. emphasise the effect of time of relaxation phenomena inlong-chain molecules. This is vital in analysing load-extension and hysteresisphenomena, especially in textile fibres,86 is instanced in mechanical depoly-nierisations by supersonic frequencie~,~~ and also in Tt variations, whichare closely related to viscosity.88 Tt increases with increasing difliculty ofmovement. Thus Tt is raised by bulky groups or rings as side chains(polystyrene), by primary valency cross-linking (polydivinyl benzene), or bydipole forces (polyacrylic acid); Tt is lowered by mobile non-polar sidechains (polybutadiene) or by screening of dipoles (polyacrylic esters).Tb x pz a=. const. for many series.82Structures for rubber, rubber hydrochloride, poly-chloroprene and p-guttapercha have been noted.89 By electron diffractionof thin (250 A.) films of guttapercha, K.H. Storks finds the macromoleculein concertina-like Structures based on fibre X-radiograms with(b) Fine structure.7D C. E. Hall, E. A. Hauser, D. S. LeBeau, F. 0. Schmitt, and P. Talalag, Ind. Eng.Cliem., 1944, 36, 634.E. Cotton-Feytis, Compt. rend., 1942, 214, 485; 215, 299.81 W. H. Smith and N. P. Hanna, J . Res. Nut. Bur. Stand., 1941, 27, 229.82 J. Appl. Physics, 1944, 15, 398.83 T. Alfrey, G. Goldfinger, and H. Mark, dbid., 1943, 14, 700.84 Trans. Paraday SOC., 1934, 30, 375.85 S. L. Smith and W. A. Wood, Proc. Roy. SOC., 1941, A , 178, 93.86 E.g., H. Leaderman, ref. 6.G. Schmid and E. Beuttenmuller, 2. Elektrochem., 1943, 49, 325.E.Jenckel, Kolloid. Z., 1942, 100, 163.Ann. Reports, 1942, 108; 1943, 96. Bo Bell Lab. Rec., 1943, 21, 39068 GENERAL AND PHYSICAL CHEMISTRY.limited and partly unresolved reflections cannot attain the precision of crystalanalyses : G. A. Jeffrey's p-guttapercha structure 91 differs from that ofC. W. Bunn in that a planar distribution of the C-C bonds about the doublebond is found, with no distortion of the methyl group out of the plane; andorientation of the CH,-CH, bond to the plane of the double bond is ratherlarger (80" v. 63"). The C-atom parameters listed yield the more normalbond lengths and angles of C-C 1-54, C-C 1.33 A., LC-C-C 122",LC-C-C 109".Stretched polyisobutylene yields possibly the finest fibre X-radiogram yetfound for high polymers.C. S. Fuller et aLg2 find a rhombic cell with a 6.94,b 11-95, c 18-03 A. From intensity analysis, two chains penetrate the cell,and the isobutyl residues are held to coil spirally, each CMe, group rotating45" about the fibre axis (c) with respect to its predecessor to remove methylgroup steric interference. It may be notedg3 that certain (001) absencesbasic to this structure appear on permitting meridian reflection, that mutualmethyl group interference is still considerable, and that some adjustment ofthe methyl groups brings the structure in closer agreement, on force-fieldtheory, with the remarkable anomalies found for the heat of formation.94Polpethers, -esters, -amidea.-In these polymers the chain itself is modi-fied by the insertion of oxygen or nitrogen atoms.The mutual adjustmentbetween alkyl chain and polar layer forces depends on average P, and type,mobility, size, shape, density and distribution of the groups inserted. Theforce fields being differently responsive to variations in physical conditions,all grades of elasticity and plasticity occur, crystalline forms and transitionsare numerous and individualistic, and amorphous, fibrous, mesornorphous,and crystalline regions occur.When polar groups are small and their distribution dense and regular,good fibre diagrams are obtainable. Thus polyoxymethylenes (-CH,-O-),are hexagonal, CS2, with a fibre period of 17.25 A. Chain orientation is non-planar tub form with helical progression along the fibre axis.95 Similarly,polyethylene oxide (-CH2-CH,-O-), (I) is monoclinic, a 9.5, b (fibre axis)19-5, c 12.0 A.*~ 101"; 4 chains per cell, 9 units per fibre period, involvingagain a folded chain.95, 96 Less order is shown in X-ray and electron diffrac-tion studies on methacrylate fibres.97 With a low density of dipoles, theparaffin chain packing becomes more dominant ; for the decamethyleneseries 98 (11) C. S.Fuller finds monoclinic types with normally-packed zigzagchains parallel and also inclined to the fibre axis. The cells of the tri-O1 Trans. Faraday SOC., 1944, 40, 517.92 C. S. Fuller, C. J. Frosch, and N. R. Pape, J. Amer. Chem. SOC., 1940, 62, 1905;93 W. T. Astbury and H. J. Woods, unpublished.94 M. Polanyi, unpublished.D5 E. huter, 2. physikal.Chem., 1933, B, 21, 161, 186.O 7 H. A. Robinson, R. Ruggy, and E. Slantz, J . Appl. Physics, 1914,15, 343 ; G. D.cf. also R. Brill and F. Halle, Nuturwiss., 1938, 26, 12.H. and M. Staudinger, ibid., 1937, B, 37, 403.Coumoulos, Proc. Roy. SOC., 1943, A , 182, 166.Chem. Rev., 1940, 26, 143MACARTHUR : CRYSTALLOQRAPHY. 69methylene poly-esters of dibasic acids usually consist of normally-packedparaffin chains lying parallel to the cell long asis (itself at -30' to the fibreaxis) with the planes of dipoles perpendicular to the fibre axis.99 A slightlydifferent end-group packing from those of (I), (11), is indicated by a lower L,but the same ZCH, increment. Odd and even members show finer distinc-tions. On stretching the fibre, cells aline nearer the fibre axis, and equatorialand meridian reflections resolve to non-axial pairs.On strain release, theprocess is reversible. In the 1.16 member, chains show only the parallelalinement of the mesomorphic state characterised by the 4-2 A. lateral spacing.Structural analyses have been made for several nylons,lOO especially thecondensate of NH,*[CH,],*NH, and C02H*[CH2]p*COZH, but no satisfactorystructure is yet released in detail. The strong equatorials at 4.4 and 3.8 A.conform with one type of paraffin chain packing; meridians indicate anaxial periodicity (16.8 A.) rather less than that demanded by a vertical zigzagchain. Hydrogen-bonding at the CO*NH links emphasises the parallel with proteins. C. s.Fuller's extensive studies 2 attempt to relate structure and physical properties.The same features appear as in poly-esters, e.g., the transition from extendedto balanced retracted chains with inclination of chains to fibre axis a functionof tension.Forms range over amorphous, mesomorphous, and fibrous, fromcoplanar dipoles with radially random chains to parallel chains with randomdipoles. Co-polymerisation and weakening of polar forces (e.g., by N -methylation) affect side-packing less than fibre-axial period. IncreasingN-methylation lowers melting point and elastic modulus, increases watersorption, and broadens the 3 . 8 ~ . spacing. The retracted chain form isfavoured by high temperature annealing, high N-methylation, low polargroup density along the chain, relaxed longitudinal strain, swelling, andpolar plasticisers. As with polythene, rolling (which induces the extendedchain form) gives biaxial orientation.The mobility of such chains has beenshown by many methods. For the condensate of adipic acid and (CH2)sN,,R. Brill finds the transition from monoclinic lattice to the hexagonal formcharacterising " rotating chains " to be lowered in temperature and speededby moisture. Similar polarisation studies 4 to those on ketones also confirmchain mobility, while spontaneous adjustments and coiling are seen in theelectron diffraction of films,90a in film deposition 6 and in other phenomena.2-Altering the balance of stresses in such systems may lead to macro-@O C. s. Fuller, J . Amer. Chem. SOC., 1942, 64, 154.loo I.Sakurada and I. Hizawa, J . SOC. Chem. Ind., Japan, 1940, 43, B, 348; L. E. R.R. Brill's unit cell 1 has a 9.66, b 8-32, c 17.2 A., y 65".Taylor, unpublished.Z . physikal. Chem., 1943, B, 53, 61.W. 0. Baker and C. S. Fuller, J . Amer. Chem. SOC., 1942, 64, 2399; 1943, 65J . pr. Chem., 1942, 161, 49.W. 0. Baker and W. A. Yager, J . Arner. Chem. SOC., 1942,64,2164, 2171.A. Muller, Proc. Roy. SOC., 1937, A , 158, 403; 1940, A , 174, 137.F. H. Muller, Kolloid. Z., 1943, 103, 144.W. B. Bridgman and J. W. Williams, J . Amer. Chem. SOC., 1937, 59, 1579.112070 GENDAAL AND PFIYSICAL CEEMISTRY.structures along the fibre axis sufficiently regular to give diffraotion pheno-mena. For nylons and ply-estera respectively, macrospacings by H. Mark 31aand by K.Hess and H. Kiessig,s which increase irreversibly on heating, andothers by E. Ott 8h for polyoxymethylenes have no relation to the well-defined fibre axis periods, but are of the order of crystallite size determinedfrom electron diffra~tion.~ Degraded nylon fibres do not yield the fine-diameter (50-100 A.) proto-fibrils so characteristic of natural celIuloses.10Curbohydrutes.--Cellulose, with its great proportion of active polar groupsand regular chain of cellobiose units, forms fibres with well-markedcrystallites. P vmies greatly, -2000 being usual for untreated cotton,ramie, etc.,ll compared with -250, >low, for starch amylose and amylo-pectin respectively.12 Very long L are not found, though weak links atregular 2600 A. intervals have been ~1airned.l~ EM determinations ofwidth l4 confirm the X-ray values (30-100 A.) for the finest fibrils.InEM'S, the branched polysaccharide dextran shows periodic swellings at800 A. intervals.15 Three crystalline structures, cellulose, hydrate-cellulose(mercerised), and water-cellulose are well differentiated. The first nativeplant cellulose found in the mercerised state is the halicyst membrane.l6Two types of cellulose cell are distinguished,l7 (a) ramie type : a 8-28,b 10.3, c 7-89 A., p 84"; (b) coltsfoot type : a 8.05, b 10.3, c 7.98 A., p 89.0".A further variation suggested 1* has been shown to be due to waxy contamin-ation.19 Fibre diagnosis by X-radiograms is now standard practice forcotton and jute.20Determination of micelle size by low-angle diffuse scattering 31a andelectron microscopy 14 confirm early results by X-ray line-broadening(ramie, -50 x >600 A.; viscose, -40 X 350 ~ . ) . ' * a In this field, intensivestudies by the former method have been made by A. Guinier,21 R. Hose-mann,22 0. Kratky et aZ.,23 and H. M;~rk.~la The theory of scattering asapplied to gases can be applied t o other particles; if these are loose-packedand amorphous, each particle scatters with a " particle form factor " akin tothat of an atom and its electrons; scattering for the whole is coherent andNaturwim., 1943, 31, 171.9 M. v. Ardenne, E. Schiebold, and G. Giinther, 2. Physik, 1943, 119, 362.10 E. Husemann and A. Carnap, J . makromol. Chem., 1943,1, 16.l1 E.g., 0. A. Battista, I d .Eng. Chern. Anal., 1944, 16, 361.le J. F. Foster, Iowa State Coll. J . Sci., 1943, 18, 36.l3 0. V. Schulz and E. Husemann (with H. J. Lohmann), 2. physikal. Chem., 1942,l4 E.g., D. Beischer, Discussion, 2. Elektrochem., 1940, 48, 650; A. Hamann, Kolloid.l 5 B. Ingleman and K. Siegbahn, Arkiv Kerni, Min., Qeol., 1944, B, 18, No. 1.l6 W. A. Sisson, Contr. Boyce-Thompson Inst., 1941, 12, 31.l7 K. H. Meyer and A. van der Wyk, 2. Elektrochem., 1941, 47, 353.N. Gralth, S. Berg, and T. Svedberg, Ber., 1942, 75, 1702.l9 K. Hess, H. Kiessig, and W. Wergin, Ber., 1943, 78, 449.2o Ann. Rep. Ind. Assoo. Cult. Sci., 1943.22 2. Elektrochern., 1940, 48, 535; 2. Physik, 1939, 113, 751.23 0. Kratky, Naturwiss., 1942, 30, 542.B, 52, 23, 50.Z., 1942, 100, 248.Ann.Physique, 1939, 12, 161MACARTKUR : UBYSTALLOQRAPHY. 71additive. For particles of micelle size, this scattering is intense only at verylow angles. By comparing the intensity distribution found with that calculablefrom geometrical systems (e.g., elongated ellipsoids for fibres), size, shape,and orientation of the macrostructures may be determinable. Treatmentsdiffer, Hosemann following Guinier with increased precision, Kratky, doubtfulof the interference of internal particle structure and close-packing, preferringa statistics of interdistances. Conditions can be improved by suitableswelling agents or inter-micellar deposition of heavy scattering material.25, 31aBy such means, n-paraffin lamelke have been-found 400 A. thick, and distri-butions for ramie and cellulose triacetate have maxima at 3000, 2 0 0 ~ .respectively (length) and <400 A.(width).22 In favourable cases (e.g.,colloid sols of spherical chymotrypsin) precision may reach 3 3 A,=The crystalline-amorphous ratio (C/A = +) is important in physicalproperties of cellulose fibres. Alternative methods of defining " crystalline "and '' amorphous '' are not necessarily identical, for fringe intermicellarmaterial, especially on stretching, has more than random order thoughwithout exact phase relationship. Broadly speaking, the crystalline regionshave lower swelling, energy, entropy, little accessibility to dyes and mildchemical reagents, greater compactness and density, and measurementsinvolving these are indicative.Where C + A (rubber), 4 is simply got byX-ray diffraction ; 26 where C *- A (cellulose), calibration may be made fromlike mixtures, e.g., sugar (C)-sugar glass (A) .27 Measurements of density(rubber), latent heat of fusion (polythene), vapour pressure isotherms(nylon, cellulose) have been employed ; swelling anisotropy, magneticanisotropy, birefringence are applicable. Chemical methods for celluloseinclude peroxidation 28 and thallation in akyl ethers.29 Indications are alsoderivable by use of the Tuckett equation,7& or in certain cases from volumechanges above a second-order transition point .82aStructural indications are given well by swelling phenomena in coii-junction with X-ray analysis. The transition cellulose + hydrate-cellulosehas been followed by X-rays.30 Swelling by n-alkyl primary amines takesplace exclusively between the (101) by the creation of 0 H N links, DlO1increasing regularly with length of alkyl ~hain.3~ By the use of nitrogenpentoxide, important results for the nitrocellulose systems have been ob-tained by something approaching X-ray cinematography ; 3a the nature of24 0.Kratky, B. Baule, A. Sekors, and R. Treer, Kolloid. Z., 1942, 98, 170 ; 0.25 0. Kratky and F. Schossberger, 2. physikul. Chem., 1938, B, 39,1451 ; 0. Kratky,2 6 J. E. Field, J. Appl. Physics, 1941, 12, 23.2 7 I. Fankuchen and H. Mark, Rec. Chem. Prop., 1943, July-Oct., 54.2s G. Gol&nger, H. Mark, and S. Siggia; I n d . Eng. Chem., 1943,85, 1083.29 A. G. Assaf, R. H. Haas, and C.B. Purves, J . Amer. Chem. SOC., 1944, 66, 59.3o T . Kubo, Kolloid. Z., 1940, 93, 338.31 W. E. Davis, A. J. Barry, F. C. Peterson, and A. J. King, J . Amer. Chem. SOC.,3a M. Mathieu, Compt. rend., 1941, 212, 80.Kratky and A. Sekora, Naturwiss., 1943, 31, 46.A. Sekora, and R. Treer, 2. Elektrochern., 1942, 48, 587.1943, 65, 129472 GENERAL AND PHYSICAL CHEMISTRY.chain slip and the growth of the di- and tri-nitro-derivatives is followed, whileon swelling with acetone gelatiniser, definite lattice structures exist at1 mol./glucose, 1 mol./O*NO,, 3 mols./glucose, beyond which the fibrestructure breaks down.33 Similar experiments with series of ketones, esters,and alcoholic nitrates show unidirectional swelling, only u of the monocliniccells varying appreciably.Water is of special structural importance. Forcellulose, adsorption isotherms have been determined, and heats of sorptionnoted.35 The heat of adsorptionfor hydrate-cellulose a t 3-5 kg.-cals./mole '=. twice that for native cellulose(1.60), giving, per mole of water, the heat of adsorption value for hydrationof p-sugars and dcohol-water mixtures. The energy difference betweennormal and superfinely ground sugars equals the heat of solvation, superfinegrinding also destroying the lattice.36 Thus heats of sorption are an indexof + in a fibre. For cellulose, water sorption falls into three categories 37-interpreted as a unimolecular layer on theThe adsorption curves are 3-stage sigmoid.(a) 1 H20 per primary OH(b) 1 H20 per secondary OH 1 accessible surface.( c ) Collection in capillaries : non-structural.At stage (a), compression of water takes place, presumably by attachmentthrough two hydrogen bonds.The hydrate-cellulose lattice is not distorted.A treatment using the Langmuir and Brunauer-Teller mono- and multi-layer adsorption isotherms is that of J. D, Babbitt.38 Bound water has alsobeen surveyed by K. C. Blan~hard.~~An interesting application of specific rotatory power locates the copperin the cuprammonium cellulose complex.40 By comparison with glucosides,sufficient conditions for similarly enhanced rotations are shown to be freehydroxyls at positions 2 and 3 and substitution at 4.For this seaweed fibre consisting ofa succession of P-d-mannuronic acid residues,41 the rhombic cell has a 8-60,b (fibre axis) 8-72, c 10.74 A,, space-group V3(P2,22,), almost V4(P21212,).42The cell contains, in addition to 4 residues, -4H,O which extend a only;for the dry cell, u = 7-75 A.Using standard bonds and angles and thechair form of glucose ring, two pairs of positions for glucosidic O-linkingpermit a linear chain extension parallel to the fibre axis. One pair gives aperiod of 4.35 A,, hence probably holds for alginic acid (cf. 2 x 4.36) andprobably for pectin also (because of the stereochemical relation of side groups33 M. Raison and M. Mathieu, Gompt. rend., 1941,212,157 ; G. V. Schulz, 2. phylsikal.B, 52, 253.34 T. Petitpas, These, 1943, Paris.35 K. Lauer, R. Doderlein, C. Jiickel, and 0.Wilde, J . makromol. Chem., 1943,36 J. Gundermann, KoZZoicE. Z., 1942, 99, 143.37 A. 0. Assaf, R. H. Haas, and C. B. Purves, J . Awr. Chem. SOC., 1944, 66,66.38 Canadian J . Res., 1942, A, 20, 143.39 Cold Spring Harbor Symp. Q. Bwl., 1940, 8, 1.O0 R. E. Reeves, Science, 1944, 99, 148.41 E. L. Hirst, J. K. N. Jones, and W. 0. Jones, J . , 1939, 1880.42 W. T. Aatbury (in press).Fine Structure.-(a) Alginic acid.1, 76MACARTHUR : CRYSTALLOQRAPHY. 73in a-galacturonic and @-mannuronic residues). A full spatial analysis willbe of interest.The second pair of positions gives an extension of 5.18 A.,suggesting a normally built structure for cellulose (and chitin). While G. L.Clark’s analysis 43 confirmed the Meyer-Misch stru~ture,4~ models show somediscrepancies.The Astbury-Davies skeletons for alginic acid and cellulosereveal the possibility of interchange with only slight bond strain,45 withobvious repercussions on carbohydrate stereochemistry. Other recentmodifications have been suggested. P. H. Hermans’s m0de1,~6 using standardbonds and angles, provides a similar bent cellobiose radical to fit the fibreperiod, and does not permit parallelism in successive glucose rings. Chainshave alternating polarities in successive layers along c ; along b chain layersare staggered by 3 4 A. F. T. Peirce4’ proposes three modifications ofthe Meyer-Misch model :(i) A pyranose ring with perpendicular ,0, valencies and more nearlycoplanar C’s, though precision analyses on simpler sugars strongly favour theunstrained chair model.(ii) With the principal plane of the rings in the ab plane, the primaryalcohol groups can form OH bonds with the pair of secondary alcohol groupsof the adjacent parallel chain; an alternative bond with 2 0 of the samechain is held to account for the slight departure from rhombic symmetry.(iii) The pyranose rings are turned out of the ab plane of similarlyoriented chains towards that containing fhose of alternate sense, with OHbonding between the two sets of chains instead of within one.This modelis claimed to explain better identity period,-symmetry, and the facts ofregenerated cellulose.Structures for lignin 48 and pectin 49 have been advanced; the fibreperiod of the latter is 8-7 A. as with alginic acid.Lignin is a polycapillary(30-20,000 A. diameter) lamellar disperse organophilic mixture.The two components of starch, amylose and amylopectin,are respectively linear and branched chains. P of amylose and of the inter-branch length of amylopectin are determinable by measurements of themolecular extinction coefficient and h of peak absorption.50 Starch chainsare more flexible than the cellulose type 51 and configurations vary withtreatment.52 In the fibrous “ B ” modification, chains are fully extendedin a rhombic cell with a 16.0, b (fibre axis) 10.6, c 9 . 2 ~ . , probable space-group V(1).52 Butanol-precipitated amylose and the starch-iodine complex,(b) Cellulose.(c) Starch.43 S. T. Gross and G. L. Clark, 2. Krist., 1938, 99, 357; Text.Res., 1938, 9, 7.4 4 K. H. Meyer and L. Misch, Helv. Chim. Acta, 1937, 20, 232.4 6 W. T. Astbury and M. M. Davies, Nature, 1944, 154, 84.4 6 P. I€. Hermans, J. de BOOYS, and C. J. Maan, Kolloid. Z . , 1943, 102, 169.4 7 Nature, 1944, 153, 586.4 8 R. Jodl, Brennstoff-Chem., 1942, 23, 163, 178; cf. Ann. Reports, 1942, 39, 142.49 F. A. Henglein, J . makromol. Chem., 1943, 1, 121.50 R. R. Baldwin, R. S. Bear, and R. E. Rundle, J . Amer. Chem. SOC., 1944, 66, 8461 R. E. Rundle and L. W. Daasch, ibid., 1943, 65, 2261.52 R. E. Rundle, L. Daasch, and D. French, ibid., 1944, 66, 130.c 74 GENERAL AND PHYSTUAL mMISTRY.however, reveal a helical starch chain of pitch and diameter 8 and 13.7 A.respectively, with six glucose residues per turn. The helices are approx-imately close-packed, alternate helices oppositely alined, both space-groupsprobably v4-P212121.53 Like the iodine, the butanol is enclosed lengthwaysinside the helix, absorption optics confirming this.54 With glycerolas plasticiser, another fibrous form of amylose (period 7.5 A.) is obtained.51Polarisation optics differentiate this from the ‘‘ V ” form, and a linear foldrather than a helical chain is indi~ated.~l Starch cannot absorb iodinevapour when in the “ A ’’ or ‘‘ B ” configuration, but on conversion intothe “ V ” configuration, by alcohol precipitation, iodine is taken up up to 1 I,per six glucose rings.S5Proteins.-( a) General. Despite difficulties in recording, resolving,indexing, and analysing fibre X-radiograms of large and protean chains liableto polyphase and cytological structure, mixed crystallisation, polymorphism,disorder of strain, layering, and swelling, giving possibly only local crystall-isation of many-parameter elements of uncertain chemical content, structuralprogress continues by the combined use of all relevant physico-chemicaltechniques. Structural unity in crystalline and fibrous proteins is nowrecognised as based on the packing of polypeptide and side-chain elements.D. Wrinch’s structural basis 56 is the polypeptide chain mesh itself, with itscyclisations and folding to cage fabrics ; its success in interpreting structuralprotein features and X-ray data, e.g., for insulin, has been variously estim-ated.57 W, T.Astbury’s basis 5* is the packing of side chains, the polypeptideskeleton adopting the configuration permitting close-packing and thepresentation of the specific patterns so characteristic of enzyme action.Forkeratin, a lamellar structure completely reoriented with reference to thefibre axis has been suggested.59 Recent general analyses are due toM. L. Huggins 6O and D. G . DervichianaG1 Using principles such as pseudo-hexagonal close-packing, standard bonds and angles, N = . H * * 0 bridging,Z-configuration of residues, and a fibre screw axis (to prevent any asymmetricbending tendenoy), the former derives conceivable skeleton structures for silkfibroin, p- and a-keratin, and collagen. The favoured a-structure resemblesAstbury’s and adheies to a 100% intramolecular extension in the tc + atransition.The collagen model consists of linked spirally-coiled polypeptidechains with a pseudo-rhombic cell having a 4.5, b 5-8, c 22 A. Dervichianpostulates for proteins a two-dimensional double layer of amino-acids, withpolar and non-polar groups on opposite sides of a layer. Polar groups nor-mally form the external surface. Internal structure is imposed by symmetrical53 R. E. Rundle and F. C. Edwards, J. Amer. Chem. Soc., 1943, 65, 2200.54 R. R. Baldwin, Iowa State Coll. J. Sci., 1943, 18, 10.5 5 R. E. Rundle and D. French, J. Amer. Chem. SOC., 1943, 65, 1707.5 6 Phil. Mag., 1940, 30, 64; Proc. Roy. SOC., 1937, A , 161, 505; A , 160, 59.5 7 I. Langmuir, Proc. Physical SOC., 1939, 91, 592; I. Langmuir and D. Wrinch,ihid., p.613; J. D. Bernel, ibid., p. 618; L. Pauling and C . Niemann, J . Amer. Chem.SOC., 1939, 61, 1860; D. Wrinch, ibid., 1941, 63, 330.5 8 J . , 1942, 337. 59 L. W. Janssen, Protoplasma, 1939, 33, 410.6o Chern. Rev., 1943, 32, 195. 61 J . Chem. Phy8k8, 1943, 11, 236MACARTHUR : URY STALLOGRAPHY. 76hexagonal packing of parallel rod-like side chains. One plate is thus theminimum unit, its component amino-acids necessarily in 2m3u proportions.The passage from globular to fibrous state is simply the smectic-nematictransition of liquid crystals.62 In denaturation, a plate is ruptured and thepolypeptide chain, presenting hydrophobic groups also, becomes the dominantelement.Examination of the 2m3n rule for the occurrence and distribution ofamino-acid protein components continues.The rule, established by ultrn-centrifuge measurements,63 follows structurally from the geometry ofWrinch’s cages and Dervichian’s symmetric packings ; support for itsspatial regularity is given by analysis of keratin fibre X-radi~grams.~~Prom a wealth of chemical analyses by methods of improved 65it is now dear 66 that the rule is followed mostly with high precision, butwith equally precise exceptions, which, however, do not necessarily invalidatethe rule for component lamella. A mathematical analysisG7 of the con-ditions that permit the periodic chain congruences upheld by M. Bergmann,6sshows that the numbers 2 and 3 have no special privilege in the general caseand, further, that for certain proteins, if constituted as a &ngk chain, such adistribution cannot occur.Specific evidence against the full rigidity of theBergmann-Niemann hypothesis is seen in the observed multiple functionof certain residues (serine in fibroin,6e cystine in keratin 70) and in the com-ponents of partial hydr~lysis.~~ Dipeptides so formed often corroboratethe polar-nonpolar sequence assumed in various 61 The possi-bility that protein amino-acids may not be exclusively of one optical con-figuration 72 does not lessen structure-analytical difficulties.Denaturation X-ray studies 73 continue for their structural interest andas an aid in the production of strong protein fibres with wool-like qualities.Protein complexes are formed with detergents such as alkyl benzenesulphon-ate 75 or sodium dodecyl ~ulphitte.~~ The detergent ( a ) unfolds globular62 Trans.Faraday SOC., 1933, 29, 881.64 I. MacArthur, Nature, 1943, 152, 38; Wool Reu., 1940, 9.6 5 D. Bolling and R. J. Block, Arch. Biochem., 1943, 2, 93; 3, 217; H. B Vickery,G6 A. C. Chibnall, Proc. Roy. SOC., 1942, B , 131, 136.6 7 A. G. Ogston, Trans. Faraday Xoc., 1943, 39, 151.6 8 M. Bergmann and C. Niemann, J. Biol. Chem., 1937, 118, 301; 1938, 122, 577;Chm. Rev., 1938, 22, 423.A. H. Gordon, A. J. P. Martin, and R. L. M. Synge, Biochern. J., 1943, 37, 538;S. Blackburn, W. R. Middlebrook, and H. Phillips, Nature, 1942, 150, 57.70 W. R. Middlebrook and H. Phillips, Biochem. J., 1942, 36, 294; W. C. Hoss andM. X. Sullivan, Arch. Biochem., 1943, 3, 53.71 A.H. Gordon, A. J. P. Martin, and R. L. M. Synge, Biochem. J., 1941,%, 1369;1943, 37, 92 ; R. L. M. Synge, Chem. Rev., 1943, 32, 135.7 2 R. L. M. Syngo, Biochem. J., 1944, 38, 285.M. Spiegel-Adolf and G. C. Hsnny, J . Physical Chem., 1941,45,931; 1942,4$, 581.74 F. R. Senti, C. R. Eddy, and T. G. Nutting, J . Amer. Chem. SOC., 1943, 85, 2473.7 5 H. P- Lundgren, D. W. Elam, and R. A. O ’ C o ~ e l l , J. BioE. Chem., 1943,149,183,7~3 F. W. Putnam and H. Neureth, ibid., 1943,160,263.T. Svedberg, Proc. Roy. SOC., 1939, 3, 127, 1.Ann. N.Y. Acad. Sci., 1941, 41, 8776 GENERAL AND PHYSICAL CHEMISTRY.proteins, ( b ) allows precipitation with a minimum of inorganic ion, and(c) prevents crystallisation in drawing the fibres. Conditions for effectivefibering are a function of protein, nature and concentration of detergent,temperature, and pH.77 Egg albumin, edestin, zein, casein, pepsin, lacto-globulin, feather keratin, soybean, and peanut proteins have been used; onremoval of salt and detergent the steam-extended fibres develop considerablestrength.74 K. J. Palmer’s X-ray results for egg albumin are important.78The complex shows L (30 A.) of detergent and 4.7 and 10 A. rings of protein;detergent removal leaves the disoriented P-form as in heat-denaturation ;500% extension in steam gives the p-form oriented with the definition anddegree of silk. Orientation being here a chain not a miceZle phenomenonexplains the difference in strength and orientation from Astbury’s films.79The facts of electrophoresis and the curious compositions and phase stabilityare quantitatively explained by structures in which denatured egg albuminforms a polar-apolar monolayer with a covering unimolecular layer of close-packed detergent chains held by their hydrophobic ends, and the Astbury-Pauling 4-plate structure of native egg albumin contains detergent as aparallel bimolecular tail-to-tail layer, held close-packed between the appro-priate hydrophobic albumin groups so that detergent chains are unidirec-tionally parallel to the plates and perpendicular to the stack.Detergent-gelatin complexes show a single detergent chain forest-layer polar- bonded tothe basic nitrogen of the protein, followed by a covering reverse layer beforepeptisation.81The prevalence of intercalation, mixed systems, and mutual stoicheio-metric accommodation in organic fibres is due to a similarity in C, N, and 0bonds and angles ; e.g., the aliphatic chain interdistance (4.6 A.near m. p.) .=the backbone of a polypeptide grid (4.65 A.), while the relations of the fibrerepeat of the common units of structure (Table) are equally striking :Component unit. Increment (I). n. nI. ....................................... Aliphatic (CH,), 2.548 A. 4 1 0 . 1 9 A .p-Keratin ................................................... 3-38 3 10-14Nucleotides ............................................. 3.34 3 10.02a-Keratin ................................................... 5.14 2 10.28Muscle (normal) ..........................................5-13 2 10.26Cellulose, chitin .......................................... 5-16 2 10-30Alginic acid, pectin .................................... 4.36 2 8-72Collagen ................................................... 2-88 3 8.64Muscle (L-P) ............................................. 2.83 3 8.48Viscose-casein, protein-polyamide , polyamide-ester, polyamide-cellulose,L. Pauling 82 has7 7 H. P. Lundgren, J. Amer. Chern. Xoc., 1941, 63, 2854.78 K. J. Palmer and J. A. Galvin, ibid., 1943, 65, 2187; K. J. Palmer, J. Physical?# W. T . Astbury, S. Dickinson, and K. Bailey, Biochem. J., 1935, 29, 2361.80 W. T. Astbury, Nature, 1936, 137, 803; L. Pauling, J. Amer. Chem. SOC., 1940,81 I(. G. A. Pankhurst and R. C. M. Smith, Trans. Pura&ay Xoc., 1944, 40, 565.8, L.Pauling and D. H. Campbell, Bcknce, 1942, 95, 440.and cellulose-protein systems have industrial importance.Chern., 1944, 48, 12.82, 2643MACARTHUR : CRYSTALLOGRAPHY. 77used the mutual effect of globulin and denaturant to synthesise in vitroantibodies specific to the phenylarsonic group. Chromosomes have not yetyielded to X-ray structural analy~is.~3 Structural results on lipids, nerve,and plasmosin fibres have been recently reviewed.84Water content and its nature are structurally important in protein fibres.J. R. Katz early showed 85 that water entered between the side chains of thegelatin lattice, the spacing increase being linear up to 35% content.A. Weidinger,s6 using Co(CoC1,) t 2[Co( H20)6]C12, as indicator for free andbound water, identifies these as intra- and inter-micellar by X-rays.In furtherstudies, S. E. Sheppard 87 and 0. L Sponsler et aLS8 find, in addition to theside-spacing increase, a new fixed spacing at 7.5 A., no change in the fibre-axial 2-8 A., but a fall in the backbone from 4.4 to 3-3 A. The latter authors,from consideration of the amino-acid content of gelatin and the normal water-co-ordination of the hydrophilic groups involved, locate the adsorbed waterfirst on the hydrophilic side chains and later on the peptide links, corrobor-ating this by infra-red spectroscopy. J. B. Speakman’s analysis 89 of the woolkeratin adsorption isotherm shows similar fractions : (i) a-H,O (up to 6%)combining exothermically with hydrophilic side-chains without effect on suchmechanical features as rigidity, (ii) P1-H20, which associates with the peptidegroups up to a 1 : 1 limit and affects mechanical properties, and (iii) p,-inter-stitial H20.A similar study of protein hydration in general, with a spatialmolecular interpretation of the energetics of adsorption layers, has importantstructural implications. I n a favourable instance, admirable use has beenmade of hydration for phase deterininations in Fourier synthesis .gl* Aswith soaps 92 and viruses,93 intermicellar water may reach great dimensionsin lipid-protein complexes without greatly disturbing regularity of array.94The interpretation, on a molecular structural basis, of elasticity andplasticity in protein fibres is difficult, mainly because of their compositecrystalline-amorphous nature and the time effect in mechanical tests.Despite its successes and improved or-form, Astbury’s or + p transition inwool, with its reversible 100% intramolecular extension, is not yet universallyaccepted.The histological objection has been negatived by H. J. Woods.95It has been variously suggested that the transformation is an ordinary gel-sol83 J. B. Buck and A. M. Melland, J . Hered., 1942, 33, 173.81 F. 0. Schmitt, “ Advances in Protein Chemistry,” 1944,1,25.8 s J. R. Katz and J. C. Derksen, Rec. Traw. chim., 1932, 51, 513.8 6 A. Weidinger and H. Pelser, ibid., 1940, 59, 64.8’ J . Physical Chenb., 1940, 44, 185.8fi Trans. Faraday SOC., 1944, 40, 6.fio H. B. Bull. J .Amer. Chem. SOC., 1944, 66, 1499.9 1 J. Boyes-Watson and M. F. Perutz, Nature, 1943,151, 714.O2 K. Hess, W. Philippoff, and H. Kiessig, Kolloid. Z., 1939, 88, 40.03 J. D. Bernal and I. Fankuchen, J . Gen. Physiol., 1941, 25, 111.94 K. J. Palmer, F. 0. Schmitt, and E. Chargaff, J . Cell. Comp. Physiol., 1941, 18,43 ; R. S. Bear, K. J. Palmer, and F. 0. Schmitt, ibid., 1941,17,355 ; K. J. Palmer andI?. 0. Schmitt, ibid., p. 385.0. L. Sponsler, J. D. Bath, and J. W. Ellis, ibid., p. 906.s5 Proc. Roy. SOC., 1938, A , 166, 7678 GENERAL AND PHYSICAL CZIEMISTRY.is interpretable statistically like that of vulcanised rubber,Q6 cannot give100% fibre extension unless cross-links are broken,96, 97 is really irreversible,g6and can be obtained without fibre extension a t all; 97 that proto-fibril andmacroscopic fibre (e.g., collagen) need not be elastically parallel; 84 that theintramolecular interpretation fails to account for the importance of water inthe transition,98 the correlation of poor elasticity and high c r y ~ t a l l i n i t y , ~ ~ ~ ~ 96and the absence of long spacings in the p-form; and that its biologicalgenerality and 3-residue a-fold are disproved by the Picken structure foraged muscle.99 Astbury’s point of view stresses the absence of loq-mngereversibb extension in straight chains such as fibroin, the specificity ofproteins as compared with rubber, the evidence of optical birefringence anddenaturation,79 the generality of the relation in the keratin-myosin groupindependent of chemical composition as such, 58 and its thread of biologicalsequence, as all referring it to a fundamental configurational chain feature,the 100% molecular extension best fitting all the evidence.Apart fromfurther recent X-ray w0rk,4~a the developing chemistry of keratin cross-links,100, 1 consideration of their relation to elasticity and setting in thoseregions available to acid dyes,2 and the remarkable properties of the cupr-ammonium-keratin compIex,3 promise valuable information on thesestructure-elasticity relations.(b) Specijc. Fibroin. M. Bergmann’s analytical figures supporting the2m3n distribution rule have undergone review,’lb and E. Abderhalden main-tains a diketopiperaeine structure. rejects tyrosine from thecryetalline region and favours there a regular alternation of alanine andglycine (with 1 serine replacing 1 alanine in 12) to fit the Kratky-Kuriyamawhich may, however, be a simple fractional relation of the real one.R.Brill holds that the cell structure is like that of the polyamides, with anextension of b to accommodate side chains, and lateral connection of thezigzag chains in the ac plane by N H 0. Preliminary results of a recentstudy suggest chains (I, 1300 A. ; N, 33,000) mainly of regular periodicity,but with two symmetrically-set regions containing the four proline residuesin a tyrosine-rich section. Specific structures based on chain folds a t6-co-ordinated copper atoms (2H20, 2 prol., 1 tyr., 1 other) are proposedfor the chains dissolved in cupriethylenediamine (1 Cu to 2 peptide N).I(.H. Meyer9 G H. B. Bull and M. Gutmsn, J . Amer. Chem. SOC., 1944, 66, 1253.97 W. Harrison, Chenz. and Ind., 1941, 558.s 8 H. J. Woods, €‘roc. Leeds Phil. Soc., 1940, 3, 577.OD W. Lotmar and L. E. R. Picken, Helv. Chim. Acta, 1942, 25, 538.loo T. Barr and J. B. Speakman, J . SOC. Dyers Col., 1944, 60, 335; J. L. Stoves,Trans. Faraday Soc., 1942, 38, 254, 501 ; 1043, 39, 294, 301 ; M. Harris et al., J. Res.Kat. Bur. Stand., 1941, 27, 89.M. Harris, L. R. Mizell, and L. Foort, ibid., 1942, 29, 73.G. H. Elliott and J. B. Speakman, J . SOC. Dyers and Col., 1943, 59, 124C. S. Whswell and H. J. Woods, Nature, 1944,154, 546.2. physiol. Chem., 1940, 265, 23.K. H. Meyer, M. Fuld, and 0. Klemm, Halv. Chim. Ada, 1940, 28, 1441.0. Kratky and S.Kuriyama, 2. physikal. Chem., 1931, B, 11, 363. ’ D. Coleman and I?. 0. Howitt, Nature, 1945, 155, 78MACARTHUR : CRYSTALLOGRAPHY. 79Pibin. This insoluble fibrous form of fibrinogen is now shown to be amember of the keratin-myosin group.8 Normally a-form, the p-form isproduced by stretching or lateral pressure. The mechanical properties havebeen considered on the basis of a mesh s t r ~ c t u r e . ~EM’S lo confirm the difference in disorder between scale andcortex, proto-fibrils of the former showing a minimum diameter of -1000 A.without evidence of fine structure. Mercury and water at 80” hydrolysepreferentially the extra-micellar regions of wool (to 48%), no changesshowing in the cc- or P-pattern, stretched or unstretched.11 Acidic reagents andhydrogen peroxide produce a degraded structure, held by E. Elod12 to be ad-keratin distinct from the p-form.I. MacArthur’s precision recording 626of the super-structure of porcupine quill yields a very complete spectrumwith a fibre period of either 658 or 198 A. (ratio 10/3). The first alternativehe shows t o contain, with its strong sub-orders, 2m3n numbers of amino-acidresidue lengths, and suggests a multi-ladder structure with spatial regularitiesaccording with much of the Bergmann-Niemann theory ; this interpretationis adopted by Astb~ry.~~bs l3 The smaller figure is preferred by R. S. Bear l4on the basis of similar X-ray measurements. Positions of constituentamino-acid residues have not yet been located in complete accordance withthe intensity distribution.R. S. Bear’s feather keratin period l4 (95 A.)scarcely includes the full spectrum. A less compact a-keratin structurecontaining 2 not 3 residues per 5.14 A. period has been suggested.60bP 96b, 99bThe nature of the muscle proteins, of which myosin is the chief,has been recently re~iewed.1~ By ultracentrifuge analysis, two long mono-disperse rod-shaped myosin proteins are found l6 and to these the diffractionsof muscle are attributed. EM’S show protofibrils clown to 50-100 A. thick.17These have a regular banded structure,18 especially on treatment with osmicacid,lQ and of mean period 360 A . ~ ~ Long X-ray spacings by Bear reveal aregular periodicity of 726 A. up to a t least the 40th order, with characteristicintensification a t 5 m intervals.20 Such complementary use of EM andX-ray methods is a promising one in protein fibre analysis.On the groundsof the relation of the 5.1 A. period of muscle to this 726 A. spacing, Mac-Arthur’s extension of possible 2”3“ periodicities to muscle 64b is rejected.Keratin.Myosin.K. Bailey, W. T. Astbury, and K. M. Rudall, Nature, 1943, 151, 716.U. Ebbecke, KoZZoid. Z., 1940, 91, 134.lo €1. Zahn, TextiZber., 1942, 23, 157; C. W. Hock and H. F. McMurdie, Amer.Dyes Bepr., 1943, 32, 433, 451.l1 E. Elad, H. Nowotny, and H. Zahn, TextiZber., 1940, 21, 385.l2 Idem, ibid., p. 617.l3 “ Advances in Enzymology,” 1943,.3, 63.l4 J. Arner. Chem. SOC., 1943, 65, 1784..l5 H. B. Bailey, “Advances in Protein Chemistry,” 1944, 1, 289; E.Wohlischl6 0. Schramm and H. H. Weber, ibid., 1942, 100, 242.l7 M. v. Ardenne and H. H. Weber, ibid., 1941, 97, 322.l 8 F. Sjostrand, Nature, 1943, 151, 725.l9 M. A. Jakus, C. E. Hall, and F. 0. Schmitt, J. Anter. Chem. SOC., 1944, 66.313.2o Ibid., p. 2043.Kolloid. Z., 1941, 96, 26180 GENERAL AND PHYSICAL CHEMISTRY.But, its exact origin apart, this 7 2 6 ~ . spacing is just the 128th multiple(2730 as for a-keratin) of the other muscle fibre period, R. 0. Herzog’s earlyresult 21 having now been confirmed with the precision of a ramie photographfor an aged preparati~n.~~b Recording conditions are critical, new preparationsgiving only the usual a-keratin structure. From 18 reflections, W. Lotmarand L.E. R. Picken derive the monoclinic cell a 11.70, b (fibre axis) 5 . 6 5 ,c 9.85 A., p 73” 30’, with four amino-acid residues per cell if density = 1.27.The probable space-group C22 affords the dyad screw axis along b desiredby M. L. Huggins.606 A statistical distribution of particular amino-acids ispostulated. A structure is found in which cis-type peptide residues aline witha fibre-axial extension of 2.83 A., and are laterally bonded by N H 0 links.That the maximum intramolecular extension of 25% is insufficient to explainthe elastic range observed is met by allocating residual extension to the amor-phous regions. The cis-formation and axial residue length recall Astbury’scollagen form; 22 the normal myosin structure (period 5.1 A.) is held torepresent 2 not 3 residues.The crystallite size in the L-P structure mustbe >> the diameter of the fibre bundles (estimated a t -100 A. from the peak oflow-angle scattering by 0. Kratky), and weak equatorial spacings observedat 33,42, and 66 A. are attributed 23 to regular side-spacings, though similarvalues found in nerve fibres have been referred to persistent tissuelipids.-Collagen. Gelatin. The diketopiperazines found in gelatin hydrolysatesmay be attributable to artefacts from dipeptide~.~* The macrostructure haabeen examined by X-rays by 0. Kratky and A. Sekora 25 and by R. S. Bear.26Both find in collagen many orders of a fibre-axial period of 642 A., absent ingelatin. The period varies from 680 to 615 A. according as swelling or tanningprocedures are applied, without any corresponding variation in the dominant2-86 A.period. Thus the lattice and superlattice may have no close commonorigin. The large period is not removed by swelling in acid or alkali andredrying, but disappears on thermal or chemical shortening of the fibre. Thealternation of intensities in odd and even orders when wet, disappears ondrying. That the macrostructure seems more a function of protofibril thanlattice is confirmed by EM. The 6 4 4 ~ . period so found2’ with possible160 A. sub-peaks, can be greatly extended by tension, which also alters theratio of the lengths of dark and light bands. Further elucidation of thenature of this banded superstructure will be of the greatest interest.Viruses. EM’S 28 have confirmed X-ray findings.No further analysishas been presented of the wide-angle pattern of tobacco mosaic virus, whichseems based on rhombohedra1 units, though further X-ray data indicate a lowerZ1 R. 0. Herzog and W. Jancke, Naturyiss., 1926,14, 1223.22 J . Int. SOC. Leather Trades Chemists, 1940, 24, 69.23 0. Kratky, A. Sekora, and H. H. Weber, Naturwiss., 1943, 31, 91.24 A. H. Gordon, A. J. P. Martin, and R. L. M. Synge, Biochem. J., 1943, 37, 92.25 J . makromol. Chem., 1943, 1, 113.26 J . Amer. Chem. SOC., 1944, 66, 1297.27 F. 0. Schmitt, C. E. Hall, and M. A. Jakus, J . CeZZ. Comp. Physiol., 1942, 20, 3 1 .W. M. Stanley, J . Biol. Chem., 1942, 146, 25PRESTON : CRYSTALLOGRAPHY. 81molecular weight than R. B. C o r e y ’ ~ .~ ~ Optical analysis of solutions underpressure 30 suggests that the ribonucleic acid and protein frameworks combineso that the planes of the purine and pyrimidine rings are mainly parallel toeach other and to the plane of the indole ring of tryptophan, and probablyperpendicular to the long molecular axis. I. MAcA.vi. Electron Microscopy.The electron microscope is one of the new tools available for the studyof the fine structure of matter. Although the fundamental identity ofgeometrical optics and the dynamics of a particle was known to Hamiltona century ago, the idea of using electrons instead of light in a microscope isa very recent development. Looking back, it now seems curious thatthe discovery of the electron in 1896 was not very quickly followed by theinvention of electron-optics.The knowledge of Maxwell’s electromagneticequations and of Hamilton’s optical and dynamical theories, together withthe existence of the charged particle, provided all the essential features forthe inception of the idea of electron-optics. Nearly 30 years passed beforede Broglie, Thomson, Davisson, and Germer showed that electrons, like X-rays, are diffracted by crystals just as light is diffracted by a ruled grating.Even the discovery that the motion of an electron is governed by a wavedid not lead immediately to the idea of using electrons in a microscope. Thefirst step towards the practical realisation of the electron microscope mayprobably be recognised in a paper by A. Busch in 1926, in which he showedthat electrons could be focused by electrostatic and magnetic fields, just aslight is focused by a lens.It is an interesting fact that, although the scienceof light developed from the ray treatment to the wave theory with all itsconsequences-interference, diffraction, polarisation-yet with electronsthe historical sequence is reversed. Following the period in which theywere treated as massive particles, which is analogous to the idea of thephoton, the diffraction of electrons, i.e., that aspect of their behaviourwhich is attributable to a wave, received attention whereas their treatmentas rays has only been fully studied in the last ten years or so.The arrival of the electron microscope probably owes something todevelopments in many branches of scientific investigation which created ademand for such an instrument.The study of the fine structure of matterreceived an enormous impetus from the application of the technique of X-raycrystal analysis, but the step from magnitudes that were optically visibleto the knowledge of atomic spacings and arrangements was so large that agap was left. The limit of resolution of the optical microscope may be set,in round numbers, at about em. as a lower limit. Particles smallerthan this may be seen as diffraction discs when suitably illuminated but theirC. G. Vinson, D. K. McReynolds, and N. S. Gingrich, Missouri Agr. Exp. Stn.Res. Bull., 1939, No. 297, 11 pp.30 A. Butenandt, H. Friedrich-Freksa, S. Hartwig, and G. Scheibe, 2. physw2.Chem.,1942, 274, 276.1 Ann. Physik, 1926, 81, 97482 GENERAL AND PHYSIUAL UHEMISTRY.size and shape will not be determinable. X-Ray diffraction carries us a tone step down to orders of magnitude of about cm., but the method isnot very suitable for telling us much about structural detail in the region of10-6 cm. It is here that we may hope the electron microscope will step inand show us a world not accessible at all to light waves and difficult of accessby X-ray methods.It is perhaps worth while briefly considering the fields open to in spectionby the three methods-light, electrons, and X-rays. The following tableem.Limit of unaided vision 10-8Bacteria ..................................................................... 10-4 = 1 IL.red ............................................ 8 x 10-6Wave-length of light violet ......................................... 4 x 10-6ultra-violet ................................2 x10-6Inter-atomic distances in solids ...................................... 3 x 10-8Wave-length of X-rays ..................................................Wave-length of 60-EV. electrons ..........................................................................................Viruses, protein molecu { es, smoke part cles, oxide films .........lo-’ = 1 A.5 x 10-10shows a few of the magnitudes of small objects together with the wave-lengths of light, X-rays, and electrons. There are, of course, X-rays ofwave-lengths other than cm., but for crystal analysis the wave-lengthsused are commonly about 1.5-24 x cm.The K characteristicradiations of copper, iron, chromium, and cobalt fall in this range.The range of magnitudes open to inspection by light is limited a t thelower end by the wave-length of light itself. The figure quoted above,10-6 cm., is one-mh of the wave-length and is probably optimistic. Itwill be seen that there is a wealth of material, organic and inorganic, belowthis limit the structure of which cannot be ascertained by optical means.Other things being equal, the limit to the resolving power of X-ray or electronmicroscopes would be the same, Le., one-fifth of the wave-length. Lookingat the table, we see that the X-rays used in crystal analysis have a sufficientlyshort wave-length t o enable us to see atoms-always, of course, subjectto the above specified condition The difficultywith X-rays is that we have no lenses to bend and focus them in the waythat light is focused by the objective and eye lenses of a microscope.Allwe can do is to record a diffraction pattern and then send out for a mathe-matician who, given sufficient data, can see with his mind’s eye and willproduce an electron map of the crystal for us. The resolving power is, infact, just about the same fraction of a wave-length as in the case of light.The synthesis carried out by the mathematician can be effected by anoptical device due to Sir W. Lawrence Bragg,2 which he has called an X-raymicroscope.The wave-length isextremely short ; it is less than that of light by a factor of but wecannot yet make use of this enormous potential increase of resolving power.Unlike X-rays, but like light, electrons can be deflected from their straightother things being equal.”With electrom the case is somewhat different.Nature, 1939, 143, 678; 1942, 149,5470PRESTON : CRYSTALLOGRAPHY.83paths-not by material lenses, which would stop an electron beam com-pletely, but by magnetic or electrostatic fields. These electron lenses sufferin an exaggerated degree from the defect known in optics as sphericalaberration. There are other defects of the image but this seems to be themost important one. Up to the present, electron lenses free from this defecthave not been produced and to minimise its consequences recourse hasbeen had to the device of narrowing the aperture of the lens and using anextremely fine pencil of electrons to illuminate the specimen. The netresult is that the resolving power obtained in practice is about 50 A., thoughin favourable circumstances it seems that a figure of 20 A.may be attained.This means that the resolving power is about 100 times greater than that ofan optical microscope.The growth of electron microscopes from small experimental laboratorymodels t o the type of commercial product which is now available (or would bebut for the war) has been fairly rapid and has gone on simultaneously andindependently in this country, America, and Germany. Here, L. C. Martin,3in collaboration with Metropolitan Vickers, produced an experimentalmodel.B ~ r t o n , ~ and his collaborators,6 were a t work in Toronto anddemonstrated clearly the practical possibilities of high-resolution electronmicroscopy. In Germany, both Siemens and the A.E.G. had investigatorsa t work and just before the war the former firm had a model for sale, but sofar as the Reporter is aware none wits imported into this country. TheA.E.G. instrument was of the electrostatic type, i.e., the electron lenseswere electrostatic fields. This type is stated to be rather simpler in designand construction than the magnetic type, in which the lenses are magneticfields produced by oircular coils carrying a current. Published photographsby H. Mahl and others at magnifications up to 10,000 are certainly of goodquality. The magnetia instruments appear to be capable of rather highermagnifying power but the stabilisation of the electric supplia presents adifficult problem.The Toronto instrument has been developed commercially by the RadioCorporation of America, and several of these instruments are now in servicein this country.The lenses are magnetic and their functions are closelyanalogous to the lenses of the optical microscope. An image of the electron~ource, a hot tungsten filament, is focused on the specimen by a condenserlens; an objective lens produces a magnified image of the specimen and thisimage is subjected to a further stage of magnification by a projector lens.The final image at from 2000 to 30,000 diameters is viewed on a fluorescentscreen and can be recorded photographically.Usually for high magnifi-cation work an electron magnification of about 10,000 is used, followed by8 L. C. Martin, R. V. Whelpton, and D. H. Parnum, J . Sci. Instr., 1937, 14, 14.4 E. F. Burton and W. H. Kohl, “The Electron Microscope,” Reinhold Carp.,6 E. F. Burton, J. Hillier, and A. Prebus, Physical Rev., 1939, 56, 1171; A. Prebus6 f;. tech. Physik, 1939, 20, 316.New York, 1942.and J. Hillier, Canadian J . Res., 1939, A , 17, 4984 GENERAL AND PHYSICAL CHEMISTRY.optical enlargement up to 10 times. These R.C.A. instruments are arrangedso that specimen and photographic plate can be introduced into the vacuumthrough air locks; these operations can be carried out quickly withoutdestroying the vacuum in the body of the microscope column.Recently the R.C.A.' have described a simpler and smaller model, alsoof the magnetic type. The G.E.C. of America 8 have produced a simplifiedelectrostatic model. Both firms have realised that there will probably bea demand for a cheaper and smaller instrument in industry, hospitals, anduniversities, with not quite the same high resolving power, but still capableof giving results much in advance of anything obtainable optically. TheG.E.C. model is particularly simple. The electron magnification is about500, and the image on the fluorescent screen is photographed outside thevacuum, a further stage of optical magnification up to a total of about 5000being possible. These smaller instruments would certainly appear to havesome points in their favour for routine work where the highest resolvingpower is not required.The instruments mentioned above are all of the '' optical " type in thesense that there is a very close analogy between the function of the electronlenses and the lenses of the optical microscope. There are several otherdevices, which may be called microscopes since they are intended to revealfine structure, two of which deserve mention, M. Benjamin and R. 0.Jenkins have described a method of investigating the auto-electronicemission from fine metallic points which produces a very high magnification.In principle, the apparatus consisted of a very small spherical tip of metal atthe centre of a large evacuated spherical vessel coated internally with a thinlayer of fluorescent material. A difference of potential was maintainedbetween the metal point and the sphere sufficient to drag electrons from themetal. The electrons starting with negligible velocity follow the straightlines of electrostatic force, and an image of the point is projected on to thesurface of the containing vessel. The magnification is the ratio of the radiiof the containing vessel and the metal tip. V. K. Zworykin,lo J. Hillier, andR. L. Snyder lo have described an electron microscope of a novel kind suitablefor the examination of opaque, massive specimens, such as metals. Theidea is to use the electron lenses to produce a very fine beam or pencil ofelectrons. This is moved over the area to be examined, and the secondaryelectrons, released from the bombarded surface, are accelerated on to afluorescent screen where they produce light, the intensity of which dependson the number of secondaries and therefore on the nature of the very smallarea subject to bombardment. The light fluctuations from the fluorescentscreen are converted into electrical impulses by a photo-electric cell, and theseimpulses after amplification are recorded on a drum where a magnifiedpicture of the surface is built up. The instrument will produce magnifiedimages up to some 5000 diameters.7 V. K. Zworykin and J. Hillier, J . Appl. Physics, 1943, 14, 658.8 C. H. Bachman and S. Ramo, ibicl., p. 155. @ Proc. Roy. Soc., 1940, A , 176, 262.10 Amer. SOC. Testing Mat., Aug., 1944; C. J. Overbeck, J . Sci. Imtr., 1944, 21, 1PRESTON : CRYSTALLOURAPHY. 85Applications.-(a) Biological. One of the most interesting fields towhich electron microscopy is being applied is in microbiology. There areobviously serious drawbacks to be overcome ; the necessity of placing thespecimen in a vacuum and bombarding it with high-speed electrons is to betaken into account, and due care must be exercised in ensuring that theresults are not affected by changes induced by drying of the material. Not-withstanding the perishable nature of the material and the manifest ill-treatment to which it is subjected, there seem to be grounds for believingthat these drawbacks are not in fact so serious as might at first sight appear.Bacteria, viruses, and tissue seem to withstand a reasonable amount ofbombardment in a vacuum without undergoing any progressive change inappearance. I. M. Abraham and J. W. McBain l1 have described a methodof enclosing the specimen in a cell which is thin enough to allow the electronsto pass without much scattering and yet strong enough to enclose the speci-men in a film of water. Applications of the electron microscope to biologicalproblems have been recently reviewed by G. E. Donovan,12 who gives a listof recent papers on this aspect of the matter. There seems to be a widefield for investigation, and it is being quickly explored.Under this heading there appear to be a t present twomain uses for the electron microscope. The first is the determination ofgrain size and shape in smokes, powders, clays, etc. The great opacity ofsmall grains to electrons makes their use particularly apt; particles ofcolloidal dimensions, 100 A. in diameter, can be detected, and the thicknessof material which crystallises in flakes, can be estimated. As examples ofthis type of investigation attention may be directed to a paper by T. Marxand G. Wehner l3 on the shape and size of particles of Mg( OH) ,, which appearto be flakes about 100 A. thick. Carbon soot from different sources has beenexamined by various workers,14~ l5 and at a recent conference called by theBritish Coal Utilization Research Association a short account of the applica-tion of the electron microscope to the study of coal was given.16 The changesin shape and size of particles in the transformation of y-FeO*OH into y-Fe ,O,and or-Fe203 have been studied by R. Fricke, T. Schoon, and W. Schroder.17Mention must be made of the work of C. E. Hall and A. L. Schoen 18 at theEastman Research Laboratories on the structure of silver bromide grains inphotographic emulsions. The change in the bromide crystals during exposureto the electron beam is recorded and the production of filaments of silverin the development of the exposed bromide is shown.The second type of problem in the inorganic world is metallurgical.l1 J . Appl. Physics, 1944,15, 607.l2 Nature, 1944, 154, 356.l3 Kolloid-Z., 1943, 105, 226.l4 U. Hofman, A. Ragoss, and F. Sinkel, ibid., 1941, 96, 231.l5 M. von Ardenne and U. Hofman, Z. physikal. Chem., 1941, By 50, 1.l7 G. D. Preston and F. W. Cuckow, 1943 Conference on the Ultra-fine Structure ofla J . Opt. SOC. Amer., 1941, 31, 281.(b) Inorganic.Ibid., p. 13.Coal and Cokes, B.C.U.R.A86 GENERAL AND PHYSICAL CHEMISTRY.The examination of an etched metal surface requires a special technique l9which appears likely to yield valuable results. To examine the surface, it isreproduced in the form of a thin cast or replica in a film of some suitablematerial such as nitrocellulose or '' formvar '' (polyvinyl formal). A dilutesolution of one of these materials is allowed to dry on the surface of the metaland is then detached and used in the electron tnicroscope as a specimen.Surface irregularities developed on the metal by etching are reproducedin the film as variations of thickness which muse differences in the intensityof the transmitted electron beam. A highly magnified image of the surfacecan thus be obtained. In certain cases a thin oxide film may be detachedfrom the metal and used as the specimen in the same way; this techniquehas been used successfully with aluminium alloys. The variation of surfaceelevation and the thickness of small particles have also been investigated byR. D. Heidenreich and L. A. Matheson,20 using a stereoscopic method.Changes in elevation and thicknesses of 150 A. can be measured.The intensive development of synthetic polymers in recentyears has focused attention on the large molecular aggregates in these sub-stances. Some attempts have been made to examine these structures bymeans of the electron microscope. Photomicrographs of polyoxymebhylene 21crystals degraded by acids and alkalis have been published. The same papercontains some observations on chemical and bacterial degradation of cellulosefibrils.The above very brief summary of the uses to which the electron micro-scope has been put shows that up to the present the work carried out hasbeen of an exploratory nature. Both the type of problem suitable forinvestigation and the technique of obtaining specimens in a form suitablefor examination must inevitably first be found. At the same time theobservations have t o be correlated with existing knowledge obtained byoptical methods on the one hand and by X-ray and electron diffraction onthe other. Progress is undoubtedly being made quickly and it may be hopedthat with the advent of simpler instruments electron microscopes will be ascommonly found in hospital, industrial, and university laboratories as aretheir optical prototypes. A very valuable bibliography of this rapidlygrowing subject has been compiled by C. Marton and S. Samza(c) Organic.G . D. P.A. E. ALEXANDER.R. M. BARRER.C. N. HINSHELWOOD.I. MACARTHUR.G. D. PRESTON.J. M. ROBERTSON.19 V. J. Schaefer, Physical Rev., 1942, 68, 496; 3. A w l . Physics, 1942, 13, 427;2O l b i d . , 1944, 15, 423.21 M. Staudinger, Chem. Ztg., 1943, 67, 316.R. D. Heidenreich and V. G. Peck, ibid., 1943, 14, 23.J . Appl. Physics, 1943, 14, 522; 1944, 16, 575

ISSN:0365-6217    

DOI:10.1039/AR9444100005

出版商:RSC    

年代:1944

数据来源: RSC

摘要:

INORGANIC CHEMISTRY.THE task of reviewing progress in Inorganic Chemistry during the past yearhas been made very difficult by war conditions, which have no doubt pre-vented publication of the more outstanding reoent advances. The limitedavailability of numerous continental publications has also restricted thefield under review.Section 1 of the present Report comprises a general survey in which anattempt has been made t o correlate the salient developments of the pastyear. I n Sections 2 and 3 the chemistry of gallium and germanium has beenreviewed; these elements seem to have been studied along parallel linesever since both were predicted in the classical work of Mendelhf, andnumerous additions to their chemistry appear in the literature of the pastfew years.There is at present an evident lack of modern British reference books anInorganic Chemistry, and of a journal in the English language primarilydevoted to inorganic topics.It is to be hoped that attention will be givento these matters when more favourable conditions return.1. GENERAL.Separation and Use of Isotopes.-Continued interest in the preparationand use of separated isotopes is evident, and the varied nature of the workrecently reported augurs well for further rapid development of this funda-mental and widely-useful field of chemistry. The chemical exchangemethod largely developed by H. C. Urey 1 and the thermal diffusion methodof K. Clusius and G . Dicke12 still provide the most successful means ofseparating isotopes in reasonably high yield.Nitrogen preparations con-taining 6.0% of 15N have been obtained by chemical exchange: the reactionemployed being 15NH4 (liquid) + 14NH, (gas) =$ 14NH ( 1; quid) + 15NH,(gas). I n this case exchange occurs between 60% ammonium nitratesolution and ammonia gas at 90 mm. pressure in packed towers, throughwhich gas and solution pass in the same direction. The sepamtion of oxygenand carbon isotopes by means of the reactions CO, (dissolved) + HZOT-H2C0, and CO, (dissolved) + OH’ =+ HCO,’ has also been examined, andit strong catalytic effect of solid surfaces on the exchange process dete~ted.~I n a brief theoretical study of the type of exchange reaction favouredby Urey, a basis has been secured for predicting the manner in which heavyand light isotopes of the same species may be distributed between the gaseousand the liquid phase.Cf.Ann. Reports, 1941,38, 83.A. F. Reid and H. C . Urey, J. Chem. Physics, 1943,11, 403.L. Waldmann, Naturwiss., 1943, 31, 205.Cf. &id., 1940, 37, 153.3 K. Clusius and E. Becker, 8. p h y s i h l . Chem., 1943, A , 193, 6488 INORUANIC CHEMISTRY.The outstanding recent success of the CIusius-Dickel method is theseparation of substantially pure samples of 1802 and 15N14N.6 This wasaccomplished with six separation tube units with an aggregate length of82 m. In the case of oxygen the equilibrium 2l6O1*O + lSO, + lSO2 isset up in the vicinity of the hot wire, and lS0, can be concentrated a t the" heavy " end of the system without difficulty.With nitrogen, however,rearrangement of 15N14N molecules to 15N, and 14N, does not occur in thetube under normal conditions, and the " heavy " product is 15N14N; if asuitable catalyst is incorporated in the tube, separation of 15N, becomespossible.Calculations have recently been made of the energy required to separatethe uranium isotope 235U by thermal diffusion of the volatile uraniumhexafluoride.7 The interesting conclusion is reached that the total energyneeded for the separation would be 40--80% of the energy yielded by sub-sequent fission of the 235U nuclei. If this estimate is verified, and if no moreefficient method of separating the light isotope can be formed, the use ofuranium as a source of nuclear energy does not offer the possibilities oftensupposed previously.The separation of oxygen isotopes by distillation of water in a series ofthree 25-foot fractionating columns has recently been studied.* Distillationfor 120 days afforded products containing in all 23 g.of l80 in excess ofnormal; these included 150 ml. of water enriched 6-5-fold in l80, and 2.7-fold in 1 7 0 .Non-metallic Halides and Related Compounds.-Attention has recentlybeen given to a wide range of volatile mixed halides and related derivativesof the non-metals. of the preparation of allthree chloroisocyanates of silicon, SiCl,NCO, SiCl,(NCO) 2, and SiCI(NCO),,by interaction of silicon tetrachloride and silicon tetraisocyanate a t temper-atures ranging from 135' to 600', and by reaction of silver isocyanate withexcess of silicon tetrachloride in solution in organic solvents.The latterreaction apparently affords no SiCI(NCO),; the former gives all threecompounds, any mixture or pure compound in the range SiCI,-Si(NGO),undergoing " random rearrangement " a t elevated temperatures, in theabsence of a catalyst. Even at room temperature, SiCl,(NCO) rearrangest o the extent of several units yo in four months, a fact which indicates thatrearrangement reactions must be taken into account wherever the purityof a compound of this general type is in question after storage.The ease with which these " mixed " compounds undergo rearrangementreactions has also hampered physicochemical measurements intended toshow the effects of progressive substitution; it is on record lo that thecompounds PCIl,NCO, POCl,SCN, and SiC1,SCN have been obtained, butDetails have now been given13 K.CIusius, G. Dickel, and E. Becker, Natumiss., 1943, 31, 210.* H. G. Thode, S. R. Smith, and F. 0. Walkling, Canadian J . Res., 1944, 22, 127.A. E. Brodski, Acta Physicochim. U.R.S.S., 1942, 17, 224.H. H. Anderson, J. Arner. Chem. Xoc., 1944, 66, 934.lo H. H. Anderson, unpublished data; cf. ref. ( 1 1 ) WELCH : GENERAL. 89rearrangements have apparently prevented isolation of the other membersof these replacement series by fractional distillation. The stability of thesilicon-oxygen bond suggests that mixed derivatives containing oxygendirectly bound to silicon might rearrange less readily, and this has beenconfirmed in the case of the silicon methoxyisocyanates. All three of thesecompounds, vix., Si(OMe)(NCO),, Si(0Me) 2(NCO) 8, and Si(OMe),NCO, havebeen isolated 11 by fractional distillation of the products of the reactionbetween silicon isocyanate and methyl alcohol a t room temperature.Thesecompounds evidently rearrange very slowly, the reaction of the dimethoxydi-isocyanate in a tube at 600' being too slow for convenient study.Reactions of silicochloroform and hexachlorodisilane with silver cyanate,investigated in attempts to prepare corresponding silicon isocyanates, gavesilicon isocyanates and cyanate together with free silicon. Use of leadcyanate with hexachlorodisilane gave a colourless product which could notbe distilled without decomposition, and this may contain Si 2(NC0),.12Rearrangement reactions have also been examined in several otherinstances covering the halides of carbon, silicon, germanium, and stannictin; l3 in all these cases the chlorobromides appear to coexist in randomdistribution, the rearrangements occurring with increasing facility on passingfrom carbon to tin.In the CC1,-CBr, system appreciable rearrangementrequires the presence of moist aluminium chloride as a catalyst, the change torandom distribution then being complete after 7 hours at 170'. Siliconchlorobromides (and chloroiodides) rearrange on passage through a tube a t600', and the products are separable by fractional distillation. The german-ium and stannic compounds appear to rearrange so readily that separationof the components by distillation is not possible and the existenceof randomly-distributed mixed halides can be inferred only from the character of their" distillation curves," obtained by plotting boiling point against totalvolume of distillate collected.Evidence for the existence of a new germaniumchlorobromide, GeCl,Br, b. p. 112O (approx.), was obtained.Introduction of fluorine into non-metal halides by conventional methodshas been further studied. The partly fluorinated silanes, SiHF,, SiH,F,,and SiH,F, the last two of which are new, have been prepared by the actionof antimony trifluoride, in presence of antimony pentachloride, on thecorresponding chlorides.14 The products have anomalously high boilingpoints, silylene fluoride (b.p. - 77.8') being less volatile than silicon tetra-fluoride ; the Trouton constants are high, indicating considerable associationin the liquid phase. All three compounds undergo slow disproportionation,even at room temperature, to monosilane and silicon tetrafluoride, thistendency being most marked with silicofluoroform and silyl fluoride.The action of zinc fluoride on mono- and di-ethyl- and -phenyl-siliconchlorides has also been shown to yield the corresponding fl~0rides.l~ Thesel1 G. S. Forbes and H. H. Anderson, J . Amer. Chem. SOC., 1944,66, 1703.l2 Idem, aid., p. 1706.l4 H. J. Emelbus and A. G. Maddock, J., 1944, 293.l5 H. J. Emelbus and C. J. Wilkins, J., 1944, 464.l3 Idem, ibid., p. 93190 INORGANIC CHEMISTRY.are also obtained by the action of hydrogen fluoride on the appropriatesiliconic acids, (R*SiO 2H)z, and silicones, (SiR,O),, (affording the mono- anddi-alkyl compounds, respectively).The reactivity of these alkylsiliconfluorides falls sharply as alklyl substitution proceeds ; monoethylsiliconfluoride is immediately (although incompletely) hydrolysed by water a t roomtemperature, whereas the triethyl compound resists hydrolysis strongly. l6Attempts to prepare phenylsilicon 3uorochlorides by treatment of' thetrichloride with a deficit of zinc fluoride were unsuccessful.Reaction of thiophosphoryl bromide, PSBr,, with antimony trifluoride,in the absence of a catalyst, afforde the corresponding fluoride, PSF,, and thetwo bromofluorides, PSF,Br and PSFBr,.17 The latter are liquids, b.p.35.5" and 125.3'; PSFBr, is stated to be less reactive than PSF,Br, and toshow unusual resistance to hydrolysisj by alkalis.In spite of the frequent occurrence of " mixed " halides among othernon-metals, attempts to prepare boron chlorofluorides by conventionalreactions have been entirely unsuccessful.l* Reaction of boron trichloridewith antimony trifluoride (in presence of 'antimony pentachloride) a t differenttemperatures, and of boron trifluoride with calcium fluoride a t 200°, bothresult in formation of boron trifluoride containing none of the " mixed "analogues. Rearrangement does not occur when mixtures of boron tri-chloride and trifluoride are heated or passed through an electric discharge.The formation of stable additive compounds between boron halides(particularly the fluoride) and electron-donating molecules is well known,and further attention has been given to such compounds.Methylboron&fluoride and dimethylboron fluoride both react with trimethylamine,forming the compounds BMeF 2,NMe3 and BMe ,F,NMe,, respectively. l9The boron-nitrogen bond in the former compound is markedly less stablethan that in BF,,NMe,, but the mono- and the di-methyl derivative do notdiffer appreciably in this respect. Free energies of dissociation have beenestimated for these compounds in order to provide a quantitative measure ofthe effect of substitution on the strength of the boron-nitrogen bond.Hexamethylenetetramine, (CH 2)6N4, would be expected to form anadditive compound with four molecular proportions of boron trifluoride ;such a compound has now been prepared by adding the trifluoride to asolution of the tetramine in liquid sulphur dioxide.20 As the temperaturerises, this compound evolves boron trifluoride until the composition of theresidue approximates to (CH 2)6N4,BF3, but no discontinuities in gas evolu.tion occur that would indicate the existence of stable compounds inter.mediate in composition between this and the original (CH2)6N4,4BF3.Thionyl and sulphuryl chlorides do not react with boron trifluoride orJ.A. Gierut, F. J. Sowa, and J. A. Nieuwland, J. Amer. Chem. SOC., 1930, 58,897.l7 H. S. Booth and C. A. Seabright, ibid., 1943,65, 1831.l 8 H. S. Booth and S. G. Frary, ibid., p.1836.lo A. B. Burg and (Miss) A. A. Green, ibid., p. 1838.2a A. B. Burg and LaV. L. Martin, ;bid., p. 1636WELUli: GENERAL. 91trichloride ; phosphoryl chloride does not react with boron trifluoride, butwith the trichloride the compound POCl,,BCl, is formed.2lA modification of H. Meerwein and W. Pannwitz’s procedure for thepreparation of the dihydrate of boron trifluoride 22 has recently been de-~cribed.2~ A product melting sharply a t 5:9-6-1° is prepared by passing1 mol. of boron trifluoride into 2 mols. of water cooled in ice, or by absorbingan excess of the trifluoride in water and adding the requisite quantity ofwater to give the composition BF,,2H20. Distillation of the dihydrate,even at pressures down to 1 mm., causes some decomposition, successivefractions showing a small variation in density.Distillation under 25 mm.yields a fraction of b. p. 8 5 O , identified as dihydroxyfluoboric acid, H3B02F2,which can be redistilled without decomposition even at atmospheric pressure.A higher-boiling fraction from the dihydrate appears to be a mixture ofseveral molecular species. In dioxan solution boron triflumide dihydrateis considerably dissociated, as cryoscopic measurements show, and it isprobable that the liquid material contains an equilibrium mixture of hydroxy-fluoboric acids.Since organosilicon compounds are almost exclusively prepared fromsilicon halides as starting materials, it is appropriate to consider them at thispoint. Recent work on the simpler derivatives includes the preparation oftrimethylsilane from trichlorsilane and methylmagnesium bromide, and thedirect conversion of the trimethylsilane into trimethylchlorosilane bytreatment with chlorine at - Trimethylchlorosilane has also beenprepared by reaction of methylmagnesium chloride with a mixture ofmethylchlorosiIanes in ethereal solution.25 The reawakening of interest inorganosilicon compounds, due to their potential industrial value in the fieldof synthetic resins, lends importance to the chemistry of the simpler membersof the group.Other recent developments in organosilicon chemistry include theisolation of trimethylsilanol,26 SiMe,*OH, a colourless liquid prepared byhydrolysis of the reaction product of methylmagnesium iodide and dimethyl-silicone :(SiMe20), + sMgMeI --+ xSiMe,*OMgI(cf. ref.27). A second method is the ammonolysis of trimethylchlorosilaneto hexamethyldisilamine, SiMe,*NH*SiMe,, and treatment of this productwith dilute hydrochloric acid :SiMe,*NH*SiMe, + 2H20 + HC1~+ ZSiMe,*OH + NH,C1SiMe,*OMgI + H20 --+ SiMe,*OH + MgIOH21 A. B. Burg and M. K. Ross, J . Amer. Chem. SOC, 1943,65, 1637.22 J . pr. Chem., 1934, 141, 123.23 J. S. McGrath, G. G. Stack, and P. A. McCusker, J . Arner. Chem. SOC., 1944, 66,24 A. G. Taylor and €3. V. de G. Walden, ibid., p. 842.25 W. F. Gilliam and R. 0. Sauer, ibid., p. 1793.26 R. 0. Sauer, a i d . , p. 1707.27 F. S. Kipping and J. E. Hackford, J . , 1911, 99, 138.126392 INORGANIU CHEMISTRY.Trimethylsilanol is more readily dehydrated than higher silanols, prolongedrefluxing at room temperature resulting in loss of water.Desiccants alsopromote dehydration. Hexamethyldisiloxane, Si 20Me6, has also beenprepared by hydrolysis of trimethylchlorosilane. Methoxy- and ethoxy-trimethylsilane have been prepared by the action of the correspondingalcohols on trimethylchlorosilane in toluene and xylene solution, respectively,in presence of pyridine. The n-butoxytrimethyl compound is obtained bydirect interaction of trimethylchlorosilane and n-butanol. These trimethyl-silyl ethers form azeotropic mixtures with the corresponding alcohols.The action of phosphoric oxide on hexamethyldisiloxane gives tris( trimethyl-silyl) phosphate, (SiMe,),PO,.Metallic Oxides.-In the past, incomplete understanding of the nature ofmetal-oxide systems has frequently led to the formulation of " lower oxides "of apparently anomalous composition.A comprehensive study of theoxides of tungsten28 has now clarified a particularly difficult case of thiskind. Mixtures of tungsten and its trioxide were prepared, covering in 19steps the whole range of net compositions between and WOzs8;these mixtures were heated in argon at 800°, and the products examined byDebye-Scherrer X-radiograms and density and electrical conductivitymeasurements. The results show clearly the existence of four distinctphases in the composition range given; the a-phase, WO,, is replaced a tslightly lower oxygen contents (WOP9, to W0,.88) by a closely-related butsupposedly distinct P-phase of lower symmetry ; the y-phase, representingthe intermediate oxide variously formulated by previous workers as W,O, orW4OI1, has a stability range between W02.,6 and W02.65, the formulaW4011 appearing to be correct; the WO, phase (6) is stable in the rangeW02.03-W02 oo.I n the intermediate ranges (W0,.8,-Wo2. 56 andW02.65-W02,03) two-phase systems occur. Similar systems are obtainedby reduction of tungsten trioxide .with hydrogen under suitably controlledconditions. Products apparently containing combined water, obtainedby reduction of tungstic acid instead of the trioxide, ?re regarded asanalogues of the tungsten bronzes, and formulated as W0,,nH2 (n < 1) (cf.tungsten bronzes, WO,,nNa) .29 Supposed hydroxides, W,O,( OH) andW1203,( OH) 2,30 are probably of this tungsten-bronze type.The formation of " tungsten-blue " has also been the subject of recents t ~ d y .~ 1 Reduction of suspensions of tungsten trioxide by acid stannouschloride solution or by zinc and hydrochloric acid yields a blue productwhich is readily reoxidised to the trioxide by atmospheric oxygen; it givessubstantially the same X-radiogram as tungsten trioxide, and correspondswith the a-phase referred toeabove. It is, in fact, tungsten trioxide with asmall proportion of the oxygen atoms removed from the lattice. Reductionof M-ammonium tungstatc solution with acid stannous chloride gave a very28 0. Glemser and H. Sauer, 2. ano.rg. Chem., 1943, 252, 144.29 G. Hagg, 2. physikal. Chem., 1935, B, 29, 192.30 F.Ebert and H. Flasch, 2. anorg. Chem., 1934, 217, 95; 1936, 226, 65.31 0. Glemser and H. Sauer, ibid., 1943, 252, 160WELCH : GENERAL. 93similar product, again readily reoxidised, giving an X-radiogram identicalwith that of tungstic acid. However, if the ammonium tungstate is reducedby zinc and hydrochloric acid, a tungsten-blue stable to atmospheric oxygenis obtained ; this is found to correspond with the hydrogen analogue of tung-sten bronzes, referred to above. This substance is also obtained, in admix-ture with some free metal, by the action of sulphuric acid on tungsten undervarious conditions.The existence and stability of rhodium oxides have recently been studiedby methods involving " degradation isotherms," or curves showing the vari-ation of equilibrium oxygen pressure during isothermal removal of oxygenfrom the oxide phase.32 Previous work 33 had indicated the existence of theoxides Rh ,O,, Rho, and Rh ,O, together with a hydrated dioxide, Rho ,,nH20 ;the existence of Rh,O and Rho was inferred from the fact that phasescorresponding in composition with these oxides gave oxygen dissociationpressures ( p ) such that log p varied linearly with 1/T, the log p-l/T curvesfor each supposed oxide being distinct.The degradation isotherm of rho-dium trioxide, Rh,03, at 1050°, shows, however, that only one lower oxide,Rho, is formed as oxygen is removed from Rh,O,, the oxygen pressure ofRh-Rho at this temperature being 219 mm. Re-examination of the pre-vious oxygen-pressure data a t different temperatures shows that the supposedcurves for Rho and Rh,O cannot be sharply distinguished.The oxygen dissociation pressure of rhodium trioxide is considerablyreduced by admixture of magnesium, beryllium, calcium, or zinc oxide,owing to the formation of compounds (of the type Mg0,Rh ,03) correspondingwith the well-known group of spinels; the existence of these compounds assolid phases is shown by well-marked horizontal sections on the degradationisotherms obtained a t 1100O.The magnesium and the zinc compound arecapable of taking appreciable proportions of the oxides of these metals intosolid solution. With oxides of other bivalent metals (cobalt, nickel, andcopper) the systems become more complex owing to formation of compounds(such as Cu,Rh,O,) other than those of the simple spinel type.Systemscontaining a high proportion of cupric oxide in admixture with rhodiumtrioxide give an oxygen pressure greater than that of cupric oxide alone, thereaction 2CuO + 2Cu0,Rh,03 + 2(Cu,O,Rh,O,) + 0, occurring insteadof 4CuO --+ 2Cu,O $- 0,. Formation of mixed crystals by rhodiumtrioxide and aluminium, chromium, or manganese trioxide or ferric oxidecauses interesting variations of oxygen pressure ; cerium dioxide and silicahave the apparently anomalous effect of increasing this pressure. Thispaper illustrates very well the large amount of useful information which canbe derived from accurately executed studies based on phase-rule principles.Phase-rule methods have also been applied to a study of the behaviour offerric oxide towards added oxides of other elements at temperatures in the3a R.Schenck and F. Finkener, Ber., 1942, 75, 1962.33 L. Wohler and W. Muller, 8. unorg. Chem., 1925,149,125 ; L. Wohler and K. F. A.Ewald, ibid., 1931, 201, 145; L. Wohler and N. Jochum, 2. physikal. Chem., 1933, 167,16994 INORGANIO CHEMISTRY.neighbourhood of 1300°.34 The effect of adding the foreign oxide is inferredfrom the resulting change of the oxygen dissociation pressure due to thereaction 6Fe,03 --+ 4Fe30, + 0,. Silica and aluminium and berylliumoxides have little effect; chromic oxide and titanium dioxide are shown toyield solid solutions of high stability, ferric titanate being formed in thelatter case.With manganese trioxide a spinel, Mn0,Fe e03, is obtained,ferric oxide behaving as a " foreign oxide " which promotes reduction of themanganese to the bivalent state.The formation of so-called " ortho-salts " by addition of sodium oxideto a variety of supposedly " neutral " salts has already been de~cribed.3~Some novel new compounds of similar type have recently been disc~ssed.~6.The oxides of bivalent zinc, copper, nickel, and cobalt all give additivecompounds with sodium oxide on sintering the components a t 350-450".The products of highest sodium oxide content are Na,ZnO,, Na,CuO,,Na,Ni02, and Na,CoO,, respectively. Evidence was obtained for theexistence of other similar compounds containing smaller proportions ofsodium oxide. The chemical individuality of the compounds formulatedabove has been fully established by X-ray powder diagrams.Structurallythe compounds appear to tend towards a class of which the spinels arecharacteristic, in which closely-bound structural units do not occur in thelattice. They may possibly, however, show some transition towardsstructures with distinct anion groupings ; their compositions, and the factthat no corresponding magnesium compound can be prepared, in spite ofsimilar ionic dimensions of magnesium and the four metals concerned,suggest that bonds of other than polar type exist in the solid structures.Clearly the increasing range of compounds of this charaoter provides scopefor the application of crystal chemistry.Binary Compounds of Metals (other than' Oxides) .-A nitride of nickel,Ni,N, has been described; 37 it is prepared by heating nickel or its fluorideor bromide in ammonia a t 445".Although soluble in mineral acids, thisnitride is not decomposed by sodium hydroxide solution ; it appears to be aninterstitial compound, the nickel atoms forming a hexagonal close-packedlattice into which the nitrogen atoms are packed.The chemistry of metallic phosphides is now reoeiving increased attention.An electrolytic method which has been successful in other cases has beenapplied to the preparation of phosphides of copper ; 38 two compounds,Cu,P and Cu,P, are distinguished, both being obtained (together withmetallic copper) at the cathode on electrolysis of fused sodium metaphosphatecontaining dissolved cuprous chloride or cupric oxide. Both phosphides areoxidised in warm air, and Cu,P readily evolves phosphorus on heating.I n the literature no less than five different phosphides of aluminium have34 N.G. Schmahl, 2. Elektrochem., 1941, 47, 835.35 E. Zintl and W. Morawietz, 2. anmg. Chern., 1938, 236, 372.36 G. Woltersdorf, ibid., 1943, 253, 126.37 R. Juza and W. Sachsze, *id., 1943,251,301.38 M. Chbne, Compt. rend., 1942, 214, 977; 215, 81WELCH : GENERAL. 95been reported, and a careful study of the preparation and composition ofaluminium phosphide 39 is therefore welcome. A phosphide wm obtainedmost satisfactorily by placing an intimate mixture of aluminium powderand excess of red phosphorus in a Pyrex-glass reaction tube, displacing airin the tube.by hydrogen, heating some phosphorus in the hydrogen streamto provide some phosphorus in the vapour phase, and igniting the mixture bystrong local heating of part of the tube in contact with it. A vigorousreaction proceeded through the mixture. Unreacted phosphorus wasafterwards removed from the product by sublimation. A special method ofanalysis was developed to permit determination of phosphorus combined a8phosphide, free aluminium, total aluminium, and phosphoric oxide in a singlesample of the substance. From the analytical results, and from the factthat only a single DebyeScherrer X-radiogram could be obtained frompreparations containing aluminium and phosphorus in different ratios, it isconcluded that only one phosphide of aluminium, All?, is obtained by themethod of preparation described ; this method yields a product containingabout 94% of Alp. Various other methods of preparation tested failed togive phosphides of different composition.The phosphide A1P is a grey oryellowish-grey crystalline solid which in the absence of moisture or otherreactcants does not melt, sublime, or decompose at temperatures up to 1000°.It reacts readily with water, and still more readily with acids or alkalis, togive phosphine which is not spontaneously inflammable in air at ordinarytemperatures. This investigation provides an interesting example of theapplication of a specially devised method of analysis in the solution of adifficult problem.Metallic phosphides, together with the more numerous and better knownsulphides, have also been considered in relation to systematic affinitytheory,4O and interesting generalisations relating to the number and type ofsulphides and phosphides formed by different elements have resulted.These should provide a useful guide in further research in this field.Basic Xults, &c.-Considerable research into the composition and natureof basic salts has been carried out recently, the wider availability of X-raydiffraction methods having provided the necessary means of establishing theindividuality of solid phases.W. Feitknecht and his collaborators havecontinued their series of studies on basic salts of bivalent metals with fourpapers on zinc and cadmium hydroxyhalides, in which a careful systematicstudy is made of the conditions of preparation and the structures of basicsalts falling into several classes.41In work on the precipitation of phosphates, many of them basic, thetechnique of " acidimetric precipitation " has been introduced ; 42 potassium39 W.E. White and A. H. Bu~hey, J . A m r . Chem. Soc., 1944, 66, 1666.40 W. Biltz, 2. physikal. Chem., 1941, A , 189, 10.41 W. Feitknecht and H. Weidmann, Helv. Chirn. Acta, 1943, 26, 1560, 1604; w.42 W. Rathje, Ber., 1941, 74, 342; F. Giesecke and W. Rathje, ibid., p. 349; w.Feitknecht and H. Bucher, ibid., pp. 2177, 2190.Rathje, ibid., pp. 357, 64696 INORGANIC CHEMISTRY.or sodium dihydrogen phosphate solution is added slowly to a boiling dilutesolution of the nitrate or chloride of the metal, neutrality of the solutionbeing maintained by simultaneous, controlled addition of sodium hydroxidesolution.Although a number of metals give normal orthophosphates,M,II(PO,), (MI1 = Mg, Ba, Cd, Mn, FeII, Co, Ni, Cu) or MIIIPO, (MI11 = Al,La, Ce, Bi), by this procedure, yet basic salts of the general formula3M3K1(P0,)2,MII(OH)2 (MI1 = Ca, Sr, Zn, Pb) are formed in other cases ; theformal relation of these salts to apatite [3Ca3(P0,) ,,CaF,] is evident, and it isnoteworthy that when 3Ca3(P0,) ,,Ca(OH) is treated with dilute sodiumfluoride solution, partial exchange of hydroxyl and fluoride ions takes place.A single basic magnesium nitrate, Mg(N03),,4Mg(OH),, is stated to beproduced by addition of alkali carbonate or hydroxide solutions to 4-5M-solutions of magnesium nitrate ; more dilute solutions of the magnesium saltafford the hydroxide, Mg(OH),, as the stable solid phase.43An interesting anomaly is observed when phosphoric acid solution istitrated with calcium hydroxide; after rather more than one equivalent ofthe alkali has been added, further additions lower the pH of the solution.During prolonged shaking subsequently the pH rises slowly.44 It hasrecently been pointed out 45 that when one equivalent of base has been addedto the phosphoric acid, the solution contains Ca**, HPO,", and H,PO,' ionstogether with undissociated CaHPO,.This may act as an acid duringfurther addition of calcium hydroxide and give a precipitate (possiblyCaOH,CaPO,) containing calcium and phosphorus in a ratio of at least 2 : 1.Removal of CaHPO, by this precipitation lowers the value of HPO," andconsequently reduces the pH.If a suitable seed-crystal is present, the initialprecipitate may decompose on keeping into Ca,( PO,) or a related compound,the base again being liberated into the solution and causing the pH torise.A new ammine of basic cupric chromate, 2Cu0,4NH3,Cr03,H,0, hasrecently been described.,6 Deposition of a crystalline tetramminocupricchromate, Cu(NH,),CrO,, from ammoniacal cupric chromate solution hasbeen observed previously; the new compound is obtained in small yieldfrom solutions deficient in chromium and containing a considerable excessof ammonia, and separates as deep blue-green crystals when the solution iskept at room temperature.The nature of the pigment known as " zinc yellow" has long been asubject of controversy, some investigators regarding it as a basic zincchromate of definite composition, and others as an adsorption complex.The recent preparation 47 of crystalline potassium, sodium, and ammoniumsalts of the type M2I0,4Zn0,4CrO3,3H2O is therefore of interest ; thesesalts are obtained by reaction of an aqueous suspension of zinc oxide withsolutions of alkali (or ammonium) tetrachromate, M ZICr40 Well-43 (Mme.) L.Walter-LBvy, Gompt. rend., 1943, 216, 846.4 4 G. A. Wendt and A. H. Clarke, J . Amer. Chem. Soc., 1923, 45, 881.46 I. Greenwaid, ibid., 1944, 66, 1305. 46 W. H. Hartford, ibid., p. 312.0. F. Tarr.M. Darrin, and L. G. Tubbs, ibid., p. 929WELCH : GENERAL. 97crystallised specimens of the basic salts were obtained in each case by slowneutralisation of a hot acid solution of the original product cohtaining anexcess of dichromate.The existehce of a normal chromate of indium appears doubtful in thelight of recent work.,8 The yellow precipitate obtained by addition ofpotassium chromate to a solution of an indium salt, after filtration andthorough washing, contains only about one-tenth of the amount of chromiumrequired by the formula 1n2(CrOJ3. It appears likely that the precipitateformed is a basic salt; if the normal chromate exists at any stage of theprecipitation, it is rapidly hydrolysed.A basic nitrite of lanthanum containing La20, and N20, in the ratio ofapproximately 1 : 1 is obtained by making a faintly acid solution of lanthanumchloride 0.5-2w, with respect t o sodium nitrite, and subsequently boilingit .*9Reference may be made here to the isolation of an interesting new seriesof hydroxy-salts, the cadmutes, which can be crystallised from solution ofcadmium hydroxide in concentrated aqueous alkalis.5O Typical members ofthis series are Na,[Cd(OH,] and Sr,[Cd(OH)6] ; a compound formulated asNa2[Cd(OH),.,5Bro. ,J affords evidence that at least part of the hydroxylmay be replaced by a halogen. Attempts to prepare correspondingmercurates were unsuccessful.Silicates, Ahminutes, etc.4everal recent contributions to the study ofsilicates and compounds of similar type, which provide a wide and usefulfield of research, deserve brief mention.I n a further paper of a seriesdealing with silicate chemistry, a detailed study of the synthesis of topaz,Al,SiO,(F,OH,O) 2, is described.51 Topaz is obtained by heating a mixtureof anhydrous aluminium fluoride and silica ; the reaction proceeds rapidlybetween1 750" and 950", these temperature limits being sharply defined.Below 750' and above 950" a different solid product, resembling mullite instructure but containing 5-6% of fluorine, results. Formation of topaz issaid t o occur through intermediate formation of silicon tetrafluoride, thesequence of reactions being as follows : 4A1F3 + 6H20 + ZA1203 + 12HF ;12HF + 3$io2 4 383, + 6H20; 2A1203 + SiF, + SiO, --+2A12Si0,F,.Water adsorbed on the solid reactants is regarded as sufficientt o permit this mechanism. Formation of the solid phase of mullite typeapparently occurs by direct reaction between solids. I n the course of thiswork a new oxyfluoride of aluminium, formulated as Al,O,,F, was charac-terised; this is formed by the action of steam on anhydrous ahminiurnfluoride at temperatures less than 600".In a further study of the same series 52 some reactions of anhydrouspyrophyllite, A1,(Si,O,o)O, have been examined and compared with corres-4 8 M. F. Stubbs, J . Amer. Chein. SOC., 1023, 45, 498.49 G. R. Sherwood, ibid., p. 1228.5o R. Scholder and E. Staufenbiel, 2. anorg. Chem., 1941, 247, 259.51 R. Schober and E. Thilo, Ber., 1940, 73, 1219.52 E. Thilo and U.Schwarz, ibid., 1941, 74, 196.REP. VOL. XLI. 98 INORGANIC CHEMISTRY.ponding reactions of talc, the magnesium analogue. Pyrophyllite itselfdoes not decompose below 1150°, but in presence of magnesium oxidedecomposition occurs at 900°, magnesium spinel (MgAl,O.,) and silica (ormagnesium silicates) being produced; it is to be noted that 900" is also thetemperature at which decomposition of talc begins. A similar reaction(affording a copper spinel, CuA1,0,, and silica) occurs readily with cupricoxide at 950". With magnesium chloride pyrophyllite reacts on heating togive cordierite (2Mg0,ZAI ,03,5Si0 ,), but cobaltous chloride gives cobaltspinel (CoAI,O,), silica, and hydrogen chloride, with an unidentified bluesolid. Thermal decomposition of pyrophyllite is concluded to occur bydisruption of the layers of silicon-oxygen tetrahedra into simple fragments.Phase-rule methods have been used in a study of relatively complexsystems involving potassium and calcium carbonates, silica, and variousdcrived ~ilicates.~3Continued interest in hydrothermal reactions is shown by recent workon the decomposition of tricalcium aluminate (3Ca0,Al,03) by steam at350"; the products are 4Ca0,3A1,03,3H,0 and calcium hydroxide, theformer being dehydrated to 12Ca0,7A1,03 and alumina i'n air at 650-750".The formation of alkali metasilicates from silica and sodium oxide,sodium or potassium carbonate, or sodium bicarbonate has been studiedrecently.55 The reaction of anhydrous sodium carbonate and amorphoussilica in equimolecular proportion is substantially complete in 80 minutes at875". At lower temperatures reaction proceeds readily to a point such thatabout half the carbon dioxide is expelled from the reaction mixture, butfurther reaction is slow ; X-radiograms give no evidence of formation of anintermediate product at this stage.Complex Compounds.-Although the field is wide and difficult to review,interesting advances in the chemistry of complex compounds have beenrecorded recently, complexes of the platinum metals having received par-ticular attention; discussion of the considerable bulk of Russian work onthis subject has been deferred to a later Report.Special interest attaches to a wide range of complexes derived fromcupric azide, Cu(N3) , ; the preparation and properties of the crystallineazide itself, and of two basic azides, Cu(OH)N, and Cu(N3),,2Cu(OH) ,,,have been described in considerable detai1.56~ 57 The first group of com-plexes 58 comprises compounds closely analogous to the halide; of complexcupric cations containing co-ordinated ammonia or amines ; [Cu(NH3),](N3) ,and [ Cu (CH,AH2) ](N3), are typical of this group.Another group 63 CH,*NH, ,includes numerous compounds formulated a,s non-electrolytes, such as53 C. Kroger, K. W. Illner, and W. Graeser, 2. anorg. Ghem., 1943, 251, 270,5 * H. Johnson and T. Thorvaldson, Canadian J. Res. 1943, 21, B, 236.5 5 G. F. Hiittig and K. Dimoff, Bet.., 1922, 75, 1573.5 6 M. Straumanis and A. CTrulis, 2. anorg. Ghevn., 1943, 251, 315..5' A.Cirulis and M. Stmumanis, ibid., p. 332.ti8 M. Straummin Bnd A. Cirulis, ibid., p. 335.69 A. Cipulia and M. Straumanid, ibid., p. 341WELCH : GENERAL. 99[Cu(NH,) 2(N3) ,] and [Cu(C5H5N) 2(N3) ,I. Other non-electrolytes Go derivedfrom a wide variety of simple and complex organic amines include com-pounds of the general types [Cu(amine) ,(N3),], [Cu(amine)(N,) ,I, and[Cu(N,) ,(amine)Cu(N,) ,] ; the apparent tercovalency of the copper atomin many of these compounds merits further study. A totally differentclaw of complex is furnished by the " azidocuprates" in which copperoccurs in the anion; 61 these are of the type M,T[CU(N,)~], M21[Cu(N3),],MI[Cu(N,),], and M1[(N3),CuN,Cu(N,),], the cations in the compoundsdescribed being alkali or alkaline-earth metals or organic bases.Tercovalentcopper appears t o occur in many of these complexes also. I n the laterpapers of the series the range of azidocuprates with organic cations is ex-tended,62 and more detailed attention is given to the azidocuprates ofpotassium, rubidium, and s t r ~ n t i u r n . ~ ~ Although the potassium compound,K[Cu(N,),],H,O, and the strontium compound, Sr[Cu(N,),],3H20, appear topossess mononuclear anions, the rubidium and the caesium salt are of thetype MI[Cu 2(N3)5], evidently involving a binuclear complex. Attempts toprepare beryllium and magnesium compounds were unsuccessful, andalthough evidence for the existence of a calcium compound was obtained,this was not isolated. The B sub-group metals of Groups I and I1 do notgive azidocuprates.It is noteworthy that in lithium azidocuprate, sixazide groups are co-ordinated per copper atom, and three molecules of waterof hydration may occur ; in the rubidium and the caesium salt the co-ordin-ation has fallen t o five azide groups per pair of copper atoms, and hydratesare not obtained. The effect of cation size on co-ordination in the anion isthus well illustrated, and structural studies of these compounds by X-raymethods will be awaited with interest. Interesting transitions also occur inthe stability and solubility relations in this range of compounds, and in thefacility with which they crystallise from solutions. As expected, many ofthe complexes of cupric azide detonate on percussion.Other interesting examples of copper complexes include a group ofcomplex cuprous thiosulphates 64 of which the simpler types areMICu ,S ,03,nH ,O and M,Wu ,S ,O,,nH ,O.Copper also gives an interestingstable complex ion with ethylenebi~diguanide,~~ affording a number ofsalts of the type [RH,]X,,nH20, where the group R has the structure(I) and X is a univalent anion. .CH ,*NH*C(NH)*NH*C*NH,6o A. Cirulis and M. Straumanis, J. pr. Chem., 1943, 162, 307.6 1 M. Straumanis and A. Cirulis, 2. anorg. Chem., 1943, 252, 9.62 A. Cirulis and M. Straumanis, Ber., 1943, 76, 825.64 G. Spacu and J. G. Murgulescu, Kolloid-Z., 1940, 91, 294.6 5 P. Riiy and S. P. Ghosh. J . Indian Chem. Soc., 1943,20,291.M. Straumanis and A. Cirulis, 2. anorg. Chem., 1943, 252, 121100 INORGANIC CHEMISTRY.Related nickel and cobalt compounds also exist.bisdiguanide with tervalent silver are known.66Although a compound with thiourea, Pb(N0,) ,,6CS(NH,) ,, has beenprepared, indicating a possible co-ordination number of six, this compoundis extensively dissociated in boiling solution and may be an additive molecularcompound.Continuing a series of studies on the chromammines, C.L. Rollinson andJ. C. Bailar, jun., have investigated the preparation of diacidobisethylenedi-amine salts by thermal decomposition of related trisethylenediamine (luteo)complexes.68 The salt [Cr en,](SCN),,H ,O loses its water of crystallisationand one-third of its ethylenediamine on heating a t 130°,being formed. The corresponding chloride, [Cr en,]C1,,3-5H20, decom-poses in a similar manner at 160' giving cis-[Cren,Cl,]CI.In bothcases the decomposition is catalysed to a marked extent by traces of theammonium salt corresponding with the luteo-salt cation, the action ofwhich appears t o be specific; this peculiar catalytic effect, which meritsfurther investigation, suggests that the reaction mechanism involves entryof negative ions from the catalyst molecules into the complex nucleus.The reactions described provide convenient and efficient methods for thepreparation of the diacidobisethylenediamine salts.The reactions of sexavalent chromium compounds with liquid ammoniahave recently been studied systematically.6g Addition of chromic anhydrideor potassium chlorochromate to liquid ammonia a t - 33" results in formationof a yellow-tan solid material of evidently complex composition ; analysisshows that in this material about one in four of the originally sexavalentchromium atoms has been reduced to the tervalent state.The gaseousnitrogen recovered from the reaction represents about half that equivalentt o the chromium reduced; the " missing " nitrogen can be recovered byheating the solid residu'e, and appears to be held chemically in some chromiumcomplex. Treatment of ammonium dichromate with liquid ammoniacauses reduction of about one-eighth of the chromium ; ammonium chromatedoes not react. Ammonium nitrate, dissolved in the liquid ammonia, in-creases the extent to which the sexavalent chromium is reduced, but waterhas the opposite effect.Although these facts permit certain conclusions tobe drawn concerning the equilibria in liquid anlmonia solutions of chromiumcompounds, the precise nature of the reactions involved remains to be found.The yellow-tan solid may be a highly ammoniated chromic ammoniumchromate or an ammoniated chromic amminochromate.The chemistry of some new complex compounds of rhenium has beene~amined.7~ K2Rea6 or K,ReCl, in aqueous solution gives no complexesComplexes of ethylene-The co-ordination number of bivalent lead has been discussedtrans-[Cr en,(SCN) ,]SCN6 6 P. Riiy and K. Chakravarty, J . Indian Chem. SOC., 1944, 21, 47.6 7 R. C. Haworth and F. G. Mann, J . , 1943, 661.68 J . Amer. Chem. Soc., 1944, 66,641.io V.V. Lebedinski and B. N. Ivanov-Emin, J. Gen. Chem. RUSS., 1943, 13, 253.6s H. H. Sisler and F. E. Jirik, ibid., p. 1344WELCH : QENERAL. 101with ammonia, pyridine, or thiourea, but with a large excess of ethylenedi-amine the yellow crystalline compound [Re0 en ,]C1 is obtained ; othersalts of the same complex cation can be obtained from this by double decom-position. An aqueous solution of [Re0 , en,lCl undergoes marked changes ofcolour on addition of hydrochloric acid; a t pH 2.8-3.2 the solution is red,and precipitates [ReO(OH) en,]Cl, when alcohol is added; at still higheracid concentrations the colour changes through violet to deep blue ( 8 ~ -acid), [Re(OH), en,]Cl, being obtained from the blue solution.Attempts have been made to prepare cyanato-complexes of tervalentcobalt.'l It is found, however, that the action of potassium or silver cyanateon aquocobaltammine salts affords carbamato-complexes by a rapid exo-thermic reaction in which OCN' ions add directly to the co-ordinated watermolecules.The carbamato-cobaltic complex ions of which salts are describedare [Co(NH,),CO,~NH,]" and [Co(NH,),(H,O)CO,~NH,]".Although potassium nickelocyanide, K ,Ni( CN),, is familiar and otherrelated salts are known, a number of nickelocyanides of metals and complexcations, described recently,72 are new.Further work on the chemistry of bivalent rhodium complexes forms auseful recent contribution to the study of the simpler types of complexcompound. A number of compounds containing dialkylarsines as co-ordinated addenda have been prepared ;73 they are of the types 1 c1[RhX ,(AsMe ,R)J, k(AsMe ,R) ,Rh' ' Rh( AsMe ,R)@ ,\c1/[ Rh ( AsMe ,R),] [ R h1,AsMe ,R] , and [ Rh ( AsMe ,R),] [ RhI,( AsMe ,R) 4], whereX is a halogen and R an aryl group.These compounds are obtained,generally, by reduction of related complexes of tervalent rhodium withhypophosphorous acid in presence of the free alkylarsine. A range of bivalentrhodium halide complexes with pyridine has also been described.'* Treat-ment of the compound [Rh py6]Br3 in solution a t 100" with hypophosphorousacid affords [Rh py6]Br2, isolated as yellow crystals. This compound, byappropriate reactions, gives [Rh py,Br]Br, [Rh py4Br2],BrBrBrSimilar compounds containing halogens other than bromine have beenprepared in some cases.The existence of bivalent rhodium in both cationicM. Linhard and H. Flygare, 2. anorg. Chem., 1943, 251, 25.72 F. Feigl, V. Demant, and 0. E. de Oliveira, Anal. Asoc. Quim. B r a d , 1944, 3,73 F. P. Dwyer and R. S. Nyholm, J . Proc. Roy. SOC. N.S.W., 1943, 76, 133.74 Idem, ibid., p. 275.72102 INORGANIC CHEMISTRY.and anionic complexes is confirmed by a polarographic study of solutions oftervalent rhodium salts.'5In view of the known existence of a compound, K,Ni(CN),, in whichnickel appears to show zero valency, the isolation of an analogous compoundof palladium, K,Pd(CN),,76 is of interest. This is obtained by the action ofmetallic potassium on a solution of K,Pd(CN), in liquid ammonia; a com-pound K2Pd(CN),, corresponding with a known complex cyanide of univalentnickel, apparently does not occur ,as an intermediate product.A.J. E. W.2. GALLIUM.Although many minerals have been investigated, particularly in Russia,no important new sources of gallium have been discovered during the pastfew years. Small quantities have been found in topazes and beryls, in themineral deposits of Kazakstan, and in a number of coals.1 Other sourcesinclude the waste materials of the zinc industry, zinc blendes, in Switzerlandas well as Russia, and the waste products of the non-ferrous metallurgy inthe Urals., Outside Russia, small amounts of gallium have been dis-covered in ores in America, in the rocks of Virginia,, in Greenland, in rocksof the Skaergaard i n t r ~ s i o n , ~ and in Japan in certain hot springs.5Much work has been carried out recently on the compounds of gallium.The element has a uniform valency of three and gives no series of compoundsof any other valency, although a suboxide GaO has been described, as wellas a dichloride GaCl,, formed by heFting the trichloride with the metal.The system gallium oxide-water resembles the alumina-water systemclosely.At 300-1400" the stable form is p-Ga,O,, which is insoluble inwater and mineral acids. At 100-300° GaO(0H) is formed by heatingGa203 with water; it is soluble in mineral acids. In an atmosphere con-taining water vapour under pressure, the metastable gallium trihydroxideis sometimes formed a t 167-170". Once formed, both these hydroxidesare fairly stable, but a t high temperatures they are both converted into p-oxide. The cr-oxide is difficult to separate, but can be obtained by precipitat-ing a dilute boiling solution of gallium trichloride with sodium carbonate,and drying the precipitate a t 425".The dehydration curves of galliumhydroxide give some indication of the formation of yet another hydroxy-7 5 J. B. Willis, J . Amer. Chem. Soc., 1944, 66, 1067.7 6 J. J. Burbage and W. C. Fernelius, ibid., 1943, 65, 1484.1 S. A. Borovik, Compt. rend. Acad. Sci. U.R.S.S., 1941, 31, 24; S. K. Kalinin,Bull. Acad. Sci. U.R.S.S., SBr. phys., 1941, 253; V. M. Kostrikin and B. N. Ivanov-Emin, J . Appl. Chem. U.S.S.R., 1940, 13, 1498.2 V. I. Babikova and Z . A. Gornova, Tsvet.Met., 1940, No. 5-6,121; F. I. Abramovand A. K. Rusanov, Soviet Qeol., 1938, 8, No. 5, 64; G. Beck, Mitt. Naturforsch. Ges.Berne .Sitxber., 1937, 5-6 (1938); V. S. Syrokomskii and A. K. Sharova, Tsvet. Met.,1938, No. 11, 23.A. Matthews and H. Ussery, Proc. Virginia Acad. Sci., 1940-41.L. R. Wagner and R. L. Mitchell, Min. Mag., 1943, 26, 283.Kazuo Kuroda, Bull. Chem. Soc., Japan, 1940, 15, 234ROBINSON : GALLIUM. 103compound, Ga ,O( OH),., The gelatinous precipitate obtained by addingalkali t o a solution of a gallium salt is hydrous gallium oxide, which on stand-ing in contact with ammonium hydroxide becomes the monohydrateGa,O,,H,O.'The normal chloride of gallium, GaCl,, closely resembles aluminiumchloride, as would be expected from the positions of gallium and aluminiumin the Periodic Table.It is readily prepared in quantitative yield byheating gallium metal at 200" in an atmosphere of hydrogen chloride. Theproduct may be sublimed and kept in an anhydrous state in sealed tubes ifthe air is replaced by nitrogem8 Up to 200' it cxists in the dimeric formThe dichloride, GaCl,, was prepared 9 by heating the trichloride in a tubeat 175' with excess of gallium, and purified by sublimation in a vacuum.It forms colourless crystals, m. p. 170-5', which deliquesce to a thick, colour-less solution when exposed t o air. I n water, it forms a chocolate-colouredprecipitate which reacts with water slowly, evolving hydrogen. Heated toabove 200°, it disproportionates into gallium and the trichloride.Vapour-density determinations in the range 400-470' indicate that the vapourcontains some GaCl, molecules, in which gallium must show the anomalousvalency of 2 . In the experiments no indication of a monochloride of galliumwas obtained.Gallium trichloride dissolves in many organic solvents to give yellowishsolutions unless the solvents are especially purified, the solution then beingcolourless. From such solutions the additive compounds GaCl,,PhCN, m. p.125", GaCl,,p-C,H,Me*NO,, m. p. 95", and GaC13,BzC1, m. p. 46O, have beenseparated.1° It also reacts with dimethylzinc t o give an 85% yield oftrimethylgalliurn.ll 2GaC1, + SZnMe, --+ 2GaMe, + 3ZnC!,. A bettermethod, however, is to heat gallium metal with dimethylmercury, whereby anearly quantitative yield of the dimethyl compound is obtained : l2 2Ga +SHgMe, --+ 2GaMe, + 3Hg.With ether, trimethylgallium forms the compound GaMe,,Et ,O, which inturn dissolves in ammonia to give the ammoniate GaMe,,NH, on evaporation.The latter, a white solid, m.p. 31°, reacts with potassium hydroxide accord-ing to the equation GaMe,,NH, + KOH + GaMe,OK + CH, + NH,.Trimethylgallium ammoniate reacts with sodium in liquid ammonia accord-ing to the equations : 13Ga &I,.2[GaMe,,NH,] + Na --+ (GaMe,),NH,Na + 4H2 + NH,2[GaMe,,NH,] + 2Na -+ (GaMe,),Na, + 2NH,A. W. Laubengayer and H. R. Engle, J . Amer. Chem. SOC., 1939,61, 1210. ' H. B. Weiser and W. 0. Milligan, Chem. Reviews, 1939, 25, 1.* W. C. Johnson and C. A. Haskew, " Inorganic Syntheses," New York, McGraw-Hill Book Co., 1939, p. 26.A.Laubengayer and F. Schirmer, J . Amer. Chem. SOC., 1940, 62, 1578.lo H. Ulich and G. Heipe, 2. physikal. Chem., 1941, B, 49,284.l1 C. Kraus and F. Toonder, Proc. Nut. Amd. Sci., 1933, 19, 292.l2 E. Wiberg, Th. Johannsen, and 0. Stecker, 2. ahorg. Chem., 1943, 251, 114.l3 C. Kraus and F. Toonder, J . Amer. Chem. Soc., 1933, 65, 3547104 INORUANIC CHEMISTRY.Similarly with lithium in liquid ethylamine GaMe,,NH,Et + Li --+GaMe,,NHEtLi + 4H2. If dimethylgallium chloride is reduced withsodium in liquid ammonia, dimethylgallium is obtained. This also forms asolid ammine GaMe 2,NH3, which decomposes slowly, according to theequation GaMe,,NH, ---+ GaMe2*NH2 + 4H2. With sodium the probablereaction is GaMe,,NH, + Na --+ GaMe,,NaNH, + &H2.Trimethylgallium is also decomposed by iodine or hydrogen iodide a troom temperature :GaMe, + 31, --+ GaI, + 3MeIGaMe, + 3HI + Gar, + 3MeHThe reaction with tertiary amines produces crystalline, difficultly volatile,white addition compounds of the composition GaM,,NR,.The trimethyl-amine derivative is a white solid, m. p. 96~2"~ which dissociates partly intoits components on vapourising; GaMe,,NEt, melts at 97" and boils withdecomposition at 167".Both triethyl- and triphenyl-gallium have been prepared by the method,already stated fdr trimethylgallium, of heating the metal with the appropriatealkyl- or aryl-mercury, triethylgallium by A. Laubengayer and W. Gilliam,14and triphenylgallium by H.Gilman and R. G. Jones.1, The phenyl compoundis recrystallised from chloroform ; short exposure to dry air has little effect,but it is decomposed by moisture.The bromides and iodides of gallium are formed by direct union of theelements. Fluorides are also known. The trihydrate GaF,,3H20 isobtained by dissolving thc metal or the oxide in hydrofluoric acid, and theanhydrous salt may be obtained by thermal decomposition of ammoniumgallium fluoride (NH,),GaF, in fluorine. If solutions of metal fluorides inhydrofluoric acid are mixed with gallium fluorides, the following mixedfluorides result : Li3GaF6, Na,GaF,, K,(GaF,,H,O), Rb(GaF,,BH,O),Cs(GaF ,,2H ,O), (NH,),GaF,, 3SrF6,GaF,,3H ,0, Ba,( GaF,) ,,H ,0,A&( GaF,), 10H ,O, T1( GaF,,H ,O), and six of the composition[M(H,0),][GaF5,H20] where M = Cu, Zn, Cd, Mn, Coy or Ni.Gallium fluoride has alow activity towards ammonia, and hence it is necessary first to prepare thehydrate GaF3,3H,0 by dissolving the nitrate or oxide in 40% hydrofluoricacid and crystallising the salt obtained.The hydrate is extracted 8-10times with liquid ammonia, and is then treated with gaseous ammonia atroom temperature. Finely powdered GaF3,3NH, is obtained. On beingheated, it shows a marked dissociation pressure at looo and a pressure ofone atmosphere a t 163". The occurrence of a diammoniate GaF,,2NH3is indicated, but because of thermal decomposition it is not definitelyestablished.TheThe fluorides of gallium also form ammoniates.17The gallium salts of many of the oxyhalogen acids are known.l4 J .Amer. Chem. SOC., 1941, 63, 477.l6 E. Einicke, Die Ch*mie, 1942, 55, 40.l5 Ibid., 1940, 62, 980.W. Klemm and H. man, 2. an..org. Chem., 1939, 241,93ROBINSON : GALLIUM. 105chlorate monohydrate, Ga(C10,),,H20, and the bromate may be obtainedfrom a solution of gallium sulphate by addition of a solution of bariumchlorate or bromate, and the iodate monohydrate is formed equally simplyby addition of hydriodic acid to a solution of gallium in nitric acid.Of the gallium salts of oxyhalogen acids, the perchlorate has been studiedin greater detail than the others. Gallium dissolves readily in concentratedperchloric acid, to give a clear solution from which gallium perchloratehexahydrate may be separated.ls A second hydrate Ga(C104),,9~H20 wasalso described, but D.Lloyd and W. Pugh state that. this is the nona-hydrate, which they prepared from gallium nitrate and a slight excess ofperchloric acid. If this is dehydrated with phosphoric oxide or sulphuricacid, the hexahydrate ia again obtained. It d,ecomposes on heating accord-ing t o the equation 4[Ga(C10,),,9H20] --+ 2Ga,03 + 36H,O + 6C12 + 210,.Evidence has also been obtained by Lloyd and Pugh for the formation of abasic perchlorate. 3Ga ,O,,Ga( (30 ,) 3.Gallium perchlorate readily forms a complex with urea when alco-holic solutions of the nonahydrate and urea are mixed. The complex,[Ga(CON2H4)6](C104)3, m. p. 1 7 9 O , is readily soluble in water, but decom-poses to give gallium hydroxide.The crystals decompose with violence onheating. Attempts to prepare a complex with pyridine and with thioureawere unsuccessful.Until recently, i t was thought that all elements up to four places beforea rare gas in the Periodic Table, together with boron, formed volatile hydrides.It now seems that this rule can be extended to five places before a rare gasto include hydrogen compounds of the third group of the Periodic System.So far, two hydrogen compounds of gallium have been prepared.20 Tri-methylgallium reacts with hydrogen-& a, glow discharge to give a colourlessviscous liquid of formula Ga2H2Me4, which decomposes above 130" accord-ing to the equation 3Ga2H2Me4 --+- 4GaMe, + 2Ga + 3H2. At roomtemperature the compound reacts with triethylamine to give a volatilegallium hydride Ga 2H6 and a triethylamine compound of trimethylgallium :3Ga2H2Me, + 4NEt3 --+ 4GaMe,,NEt, + Ga2H6.The boro-hydrides known until then were LiBH,, CH,*BeBH,, Be(BH,) and Al(BH,),.When, however, trimethylgallium is treated with an excess of diborane atroom temperature, a small decrease in pressure occurs; a metallic filmsuddenly appears, accompanied by an increase in pressure and the formationof hydrogen.The film was identified as gallium, and for each mol. oftrimethylgallium taken, approximately 3 mols. of methylated diborane,1.5 mols. of hydrogen, and 1 mol. of gallium were obtained. The reactiontherefore appears to be GaMe, + 3B,H, -+ Ga + 3CH,*B,H, + GH,.Recently, a borohydride of gallium has been described.21l8 L.Foster, J. Amer. Chem. SOC., 1939, 61, 3122.18 J., 1943, 76.20 E. Wiberg and Th. Johannsen, Die Chemie, 1942, 55, 38.21 H. Schlesinger, H. Brown, and G. Schaeffer, J. Amer. Chem. SOC., 1943, 85,D 21786106 INORGANIC CHEMISTRY.It seems probable that gallium borohydride is first formed, but this thenundergoes rapid autocatalytic decomposition :2GaMes + 9B2H6 --+ 2Ga(BH,), + 6B2H5Me2Ga(BH4), --+ 2Ga + 3B,H6 + 3H,Reaction between diborane and trimethylgallium at -45' results in form-ation of pure dimethylgallium borohydride, a volatile crystalline solid, m. p.1-5", which undergoes slow decomposition a t room temperature : 2GaMe3 +3B ,H, --+ 2GaMe ,BH4 + 2B ,H5Me.It dissolves readily in nitricacid, for example, to give a solution from which the octahydrate may becrystallised.A basic nitrate, Ga(0H) ,N03,Ga(OH),,2H ,O, is also known.16Other compounds containing nitrogen and gallium have also been pre-pared. These are the nitrides Ga,N, and GaN, which have been preparedby H. Hahn and R. Juga; 22 both are formed by heating the metal in astream of nitrogen, and GaN may also be prepared by heating ammoniumgallium fluoride (NH,),GaF, to 600" in ammonia. The former is a brightgrey solid which does not burn readily or completely to the oxide, and thelatter is a bright grey or yellow solid which burns in oxygen according to theequation 4GaN + 30,+ 2Ga20; + 2N, - 415-2 kg.-cals.With sulphuric acid, gallium forms a normal sulphate which is notdeliquescent, and from which many alums have been prepared; e.g.,R2H,SO,,Ga2(S0,),,24H2O, where R = NH,*OH, iso-C,Hll*NH2, or iso-C,H,ONH,.~~ Pseudo-alums, (NR'R,) zH,S0,,Ga,(S0,),,18H,0, have beenprepared by the same workers, (NR'R,) representing either diethyl- or tri-methyl- amine.A double sulphate, Ga,(SO,),,C,K,fNH,) ,SO4,l2H,O, has been obtainedby mixing saturated solutions of ethylenediamine sulphate and galliumsulphate; it is precipitated by addition of alcohol and ether.The cor-responding compound has also been prepared from propylenediaminesulphate .24A basic ammonium gallium sulphate, (NH,) ,S0,,Ga2(S0,),,2Ga20,,8H ,O,is also known. It is obtained as a precipitate by keeping a solution ofammonium gallium sulphate a t room temperature.16Gallium phosphate is obtained anhydrous by heating an alkylgalliumsalt solution with phosphoric acid in a sealed tube a t 200°, or as trihydrate,by dissolving freshly prepared gallium hydroxide in phosphoric acid.Twohypophosphites are known : GaH,(PO,) ,, obtained from gallium hydroxideand hypophosphorous acid, and GaPO ,,H ,O, obtained by treating a solutionof gallium nitrate with a solution of sodium hypophosphite.Gallium arsenate is prepared as the dihydrate by precipitation or byheating a gallium salt with arsenic acid in a Carius tube to 200'.The gallium salts of a number of organic acids have been prepared.Gallium forms salts with all strong acids.22 2. anorg. Chem., 1940, 244, 111.23 P. Neogi and K. Mondal, J . Indian Chem,.Soc., 1942, 19, 67.24 Idem, ibid., p. 501ROBINSON : GALLIUM. 107A basic formate Ga(C0 ,H),,Ga,O,,SH ,O is obtained by dissolving galliumhydroxide in formic acid, and a basic acetate Ga(OAc),,3Ga203,6H20,tartrate Ga2(C4H406)3,4H20, and oxalate Ga,(C204)3,3Ga203,7H20 arealso known. Gallium " alizarate," prepared by the interaction of aqueoussolutions of the potassium salt and gallium nitrate,24 has the composition~ 6 H , < ~ ~ > C 6 H 2 < ~ ~ . It is insoluble in water, but soluble inalcohol and ammonia. If dissolved in ammonia,it forms a violet solution from which a dull red precipitate of calcium galliumalizarate Ca3Ga,(C14H604)6 may be obtained by addition of a solution ofcalcium chloride. Other salts described by the same workers include themaleate, obtained by dissolving gallium hydroxide in maleic acid solution,and the salts of d- and Z-camphorsulphonic acid, obtained similarly.Quite recently, attempts have been described to prepare a carbonyl ofgallium.25 A compound of the type [CO(CO),]~G~ may have been prepared,but so far only qualitative evidence for its formation has been obtained.A number of solid systems involving gallium have been studied, andseveral intermetallic compounds described.The system Ag-Ga-Zn,studied by X-ray methods and by microscopic analysis,26 shows that a t hightemperatures it compound Ag3Ga is formed. With gold, gallium forms twocompounds,27 AuGa, which separates from melts of equiatomic compositiona t a maximum temperature of 468", and AuGa,, which crystallises above amaximum m.p. of 492'. Titanium and gallium form the compoundTiGa3,2s and magnesium forms the compounds Mg5Ga, and Mg2Ga. X-Raydiagrams indicate that in the Ga-Mg system other phases exist with greatergallium content.It is claimed toimprove the strength of magnesium-manganese alloys,2s and to increasemarkedly the ductility and strength of magnesium.30 Gallium was triedas a substitute for silver in dental fillings,31 but incorporation of the metalin the solid Ag-Sn alloy gave alloys which were too soft for dental work.Gallium trichlorideis effective as a catalyst for the reaction between ethylene and benzene; 32the optimum temperature is 50-60" and good yields of ethylbenzene areobtained. Gallium dichloride, too, has been found to be more active thanaluminium chloride in the synthesis of ketones and hydrocarbons.33It is a fast dye for cotton.Hitherto, metallic gallium has found but limited use.The chlorides of gallium may be used as catalysts.S .R. R.25 W. Hieber, H. Behrens, and U. Teller, 2. anorg. Chem., 1942, 249, 43.2 6 K. Moeller, 2. Metallk., 1939, 31, 19.27 I!. Weibke and E. Hesse, 2. anorg. Che& 1939, 240, 289.28 F, Laves and H. Wallbaum, Nuturwiss., 1939, 27, 674.29 U.S.P. 2,270,193.30 J..McDonald, Trans. Amer. Inst. Min. Met. E'ng., Inst. Metals Div., Tech. Pub.31 F. Weibke and E. Hesse, 2. Elektrochem., 1940, 48, 219.32 H. Ulich, A. Keutmann, and A. Geierhms, &id., 1943, 49, 292.83 H. Ulich, Die Chemie, 1942,55,377.No.1247 (1940)108 MORGBNIU CHEMISTRY.3. GERMANIUM.Besides the main sources already well known, a number of new sourcesof germanium have been discovered in the past few years, although in nocase was the percentage of germanium in an ore large. Most of the newsources were in Russia, where a large number of ores have been investigated.Germanium was found in small quantities in topazes and beryls,l in themineral deposits 0,' Kazakstan,2 and in various other Russian rocks,3 but byfar the most abundant supply is in coals,* coal and in various flue dustsfrom either coals or cement.6 Outside Russia, new deposits have beenfound in hot springs in Japan,' and in the flue dusts from Australian coals.8A new extraction of germanium from germanite has been described,gwhich depends on the following facts : (i) Its dioxide is very slightly solublein nitric acid.(ii) It is very soluble in ammonium oxalate, forming acomplex. (iii) The ammonium germano-oxalate is not decomposed byhydrogen sulphide, a fact which allows a rapid and excellent separationof metals forming insoluble sulphides, but (iv) is decomposed to germanic oxideon heating with concentrated sulphuric acid. The finely ground mineral isattacked by concentrated nitric acid. The solid residue is treated with waterto dissolve out any salts formed and leave germanic oxide, sulphur, leadsulphate, and part of the arsenic, molybdenum, tungsten, and iron.The insoluble part is boiled for 24 hours with its own weight of a mixtureof equal quantities of oxalic acid and ammonium oxalate, dissolved in theminimum quantity of water.The solution of germanic oxide is practicallycomplete, forming ammonium germano-oxalate.The oxalic acid liquor is treated with hydrogen sulphide, and afterseparation of the precipitated sulphides, is treated with ammonium sulphide.The remaining metals are precipitated in this way as the sulphides, exceptgermanium which remains in solution as the complex, together with a littlemolybdenum and tungsten, the precipitation of which is never complete.The mixture is then heated to fuming with sulphuric acid and a little nitricacid. The precipitation of germanic oxide is practically complete. Thesulphuric acid which contains the last impurities is decanted, and the pre-cipitate is washed with water made ammoniacal, dried, and calcined.Theammonia removes the last traces of molybdenum and tungsten. The ger-manic oxide thus obtained is spectroscopically pure.The determination of germanium has also received attention during the1 S. A. Borovik, Compt. rend. Acad. Sci. U.R.S.S., 1941, 31, 24.2 s. W. Icalinin, Bull. Acad. Sci. U.R.S.S., S6r. phys., 1941, 253.3 S. A. Borovik, N. M. Prokopenka, and I. L. Pokrovskaya, Compt. rend. Acad. S C ~ .4 A. I. Egorov and S. W. Kslinin, ibid., 1940, 26, 925; V. A. Zilbermints, A. K.5 V. M. Kostrikin, J . Appl. Chem. (U.S.S.R.), 1939, 12, 1449.6 W. Guertler, Metall. Em., 1940, 37,30, 46.7 Hazuo Kuroda, Bull. Chem. SOC. Japan, 1939,14, 303.8 W. T. Cooke, Trans.Roy. SOC. S. Australia, 1938, 62, 318.9 A. Tchakirian, Ann. Chim., 1939,12,415.U.R.S.S., 1930, 25, 618.Rusanov, and V. M. Kostrikin, Chem. Zentr., 1938, I, 1709ROBINSON : GERMANIUM. 109past five years.1° In two of the methods described, it is precipitated asgermanomolybdic acid by ammonium molybdate and a solution of 8-hydroxy-quinoline in acetic acid. The precipitate may be filtered off, and the ger-manium determined gravimetrically, or the complex broken down by boiling,and the germanium determined volumetrically. In the third method, thegermanium is determined colorimetrically by means of ammonium molyb-date-ferrous sulphate reagent. In all these determinations the initialgermanium-containing material must first be broken down, usually bytreatment with hydrogen fluoride and sulphuric acid, or, if chlorides arepresent, by fusion with sodium peroxide.Another method for the quantitative determination of germaniummakes use of a modified Marsh apparatus.1l The germanium is extractedfrom the mineral by treatment with nitric, hydrofluoric, and sulphuric acids,and determined either by precipitation and gravimetric determination asgermanic oxide, or by conversion into monogermane which is decomposed byheating to 360' in a tube, a ring of germanium being formed.The methodis particularly recommended by its originators for small quantities (less than1 mg.) of germanium. L. M. Dennis and R. P. Anderson,12 too, claimed that itis possible to obtain a ring with 6 x g. of germanic oxide by this method.Germanium forms two oxides, germanous and germanic, each of whichgives rise to a series of compounds..The sulphides, chlorides, and bromidesare readily hydrolysable, but the iodides are less so. Germanium also formspenta- (Ge50,,M,),13 ortho- (Ge04M4),14 meta- (Ge03M2),15 and per-ger-manates (Ge 20,M and Ge05M 2). l6Germanium gives complex ions in which it has a valency of 4, and a co-ordination number of 6, e.g., M,(GeF,) l7 and H8Ge(W20,)6.18 Thioger-manates of the types 2GeS2,3K2S,9H,0 and 2GeS2,3Na2S,9Hz0 areknown, and germanic sulphide with piperazine gives the compoundGeS 2,C4Hl@2,SH,.19Several nitrogen compounds have been prepared : Ge3N4,20 Ge(NH) 2,2110 I. P. Alimarin and 0. A. Aleksewa, J . AppEied Cheni. ( U.S.S.R.), 1939, 12, 1900 ;W.Geilmann and E. Steuer, Glastech. Ber., 1940, 18, 89; A. G. Hybbinette and E. R.Sandell, Ind. Eng. Chem. Anal., 1942, 14, 715.11 W. C. Aitkenhead and A. R. Middleton, ibid., 1938,10, 633.12 J . Amer. Chem. SOC., 1914, 36, 882.13 R. Schwarz, Ber., 1929, 62, 2477 ; R. Behwarz and E. Huf, 2. anorg. Chem., 1931,1 4 W. Pugh, J., 1926, 2828; J. H. Miiller, J . Amer. Chem. SOC., 1922, 44,2493.1 5 C. A. Winkler, J . p r . Chem., 1886, 34, 213; W. A. Roth and 0. Schwarz, Ber.,1926, 59, 338; W. Pugh, J . , 1929, 1992; J. H. Muller and C. E. Gulezian, J . Amer.Chem. SOC., 1939, 51, 2029.203, 188.16 R. Schwarz and H. Gieso, Ber., 1930, 63, 7 7 8 .17 J. H. Miiller, Proc. Amer. Phil. SOC., 1926, 65, Suppl. 5, 44.18 R. Schwarz and H.Giese, Ber., 1930,63,2430; A. Bruckl, Monatsh., 1930,56,179.1s L. Debucquet and L. Velluz, Bull. SOC. chim., 1932, 51, 1565.20 R. Schwarz and P. W. Schenk, Ber., 1930, 63, 296; W. C . Johnson, J . Amer.2 1 R. Schwarz and P. W. Schenk, Zoc. cit. ; W. Pugh and J. S. Thomas, J., 1926, 2051.Chern. SOC., 1930, 52, 5160110 INORGANIC CHEMLSTRY.Ge2N3H,,, and GeNH.23 Hydrides of the type GenHzn+, are known up toGe3Hs, as well as a solid hydride (GeH),. Known halogen derivatives areGeHCl,, GeHBr,, GeH ,C1 ,, GeH3C1, GeH ,Br 2, and GeH,Br,,* and themixed halides GeFCI,, GeF,CI,, and GeF,C1 25 have recently been prepared.Also, Dwo oxyhalides, Ge20CI, and GeOC12, are known.26In spite of the relatively large amount of work on germanium, it was notuntil quite recently that germanous oxide and a number of the correspondingsalts were prepared in a state of purity : Winkler and others could obtainonly mixtures of germanous and.germanic oxide by the action of sodiumhydroxide on a mixture of germanium tetrachloride (30%) and germano-chloroform (70%).The two methods described recently for the preparationof germanous oxide both involve the reduction of germanic salts, in one caseby zinc and sulphuric acid and'in the other by hypophosphorous acid.9In the first reduction, the solution must contain more than 25% of acid;the precipitate formed is dark brown, and after filtration and quick drying,is perfectly stable a t room temperature. In the second preparation, ger-manic oxide is dissolved in sodium hydroxide, hydrochloric acid added untilthe solution is 3 ~ , and after addition of hypophosphorous acid the solution isheated ; reduction is considered complete when a sample added to sulphuricacid does not give a precipitate of germanic sulphate (about 2 hours).By altering the conditions of the latter reduction it is possible to causedeposition of most of the germanium as a black precipitate, a small quantitybeing deposited on the walls of the flask as a reddish-grey mirror.Chemicalanalysis and X-ray study of the black precipitate and the mirror have notbeen able to prove whether they are lower oxides or mixtures of germanousoxide and metal. That lower oxides may be formed, is indicated by thefact that if the solution in which germanium has been reduced is treatedwith ammonia, hydrogen is evolved.Also, oxidation experiments withdilute nitric acid on the black powder and the mirror indicate the formulsGe,O and Ge30.Germanous hydroxide is orange-red ; when heated in a current of carbondioxide, or treated with concentrated sulphuric acid, it forms the darkbrown oxide. It is soluble in hydrochloric and hydrobromic acids, buthydriodic acid converts it into the insoluble iodide. All salts, in slightlyacid solution, give a bright orange precipitate of germanous sulphide withhydrogen sulphide. The sulphide is soluble in concentrated hydrochloricacid, and in ammonium sulphide to form the thiogermanate. All oxidisingagents convert it into germanic oxide.The hydroxide Ge(OH), may be considered as being germanoformic acid22 R.Schwarz and P. W. Schenk, loc. cit.23 W. C. Johnson, G. Morey, and A. Knott, J . Amer. Chem. SOC., 1932, 54, 4278.24 C. A. Winkler, J . p r . Chem., 1886, 34, 222; F. M. Brewer and L. M. Dennis, J .Physical Chem., 1927, 31, 1527; L. M. Dennis and P. R. Judy, J . Amer. Chem. XOC.,1929, 51, 2321.Z 5 H. Booth and W. Morris, ibid., 1936, 58, 90.26 R. Schwarz, P. W. Schenk, and H. Giese, Ber., 1931, 64, 362; R. Schwarz andF. Heinrich, 2. anorg. Chem., 1932, 209, 273ROBINSON : GERMANIUM. 111(H*GeO 2H) ; its solubility is 0.18~0. Conductometric measurements 27show that it is a weak acid ; with sodium hydroxide it forms a red solution ofsodium germanoformate, which is oxidised atmospherically to sodiumgermanate.The selenides of germanium, GeSe and GeSe2, have been used as a methodof detectihg germanium. Hydrogen selenide reacts with germanium in acidsolution t o give a characteristic yellow precipitate.2s A better method ofdetection, however, is t o introduce hydrogen selenide into an aqueoussolution of formaldehyde, in which it dissolves to form afairly stable derivative, probably as inset, which reacts withvH2 7H2 germanium to give a yellow precipitate.The sensitivity ofSe Se the test is 1 in 5,000,000. The presence of silicic, hydro-cyanic, hydrofluosilicic, and other acids does not affect thetest. If arsenic, tin, selenium, or other elements are present,however, it is necessary to add two drops of potassium fluoride solutionbefore adding the hydrogen selenide-formaldehyde reagent.In the presenceof fluoride ion, the germanium is precipitated very slowly with this reagent ;the other elements present, e.g., arsenic and tin, are precipitated and arefiltered off, and a little aluminium sulphate added. The aluminium ionremoves all the fluoride ion as AlF6---, and the germanium is thenprecipitated as usual.A better method for the preparation of germanous and germanic selenideis t o fuse together the correct amount of germanium and selenium.29 Bothselenides are somewhat soluble in acids and babes, and are oxidised by nitricacid to germanic oxide and selenious acid.The phosphide of germanium, GeP, is formed in a similar way by fusingfinely powdered germanium with excess of phosphorus to 400" in an evacuatedtube.30 The reaction is incomplete.X-Ray analysis shows that the pro-ducts contain germanium and phosphorus in the ratio of 1 : 1, and have astructure distinct from both free germanium and free phosphorus. Thisconclusion is confirmed by tension experiments on mixtures heated todefinite temperatures.A number of systems between germanium and other metals have recentlybeen studied. I n only four cases, however, v'L'x., those of amenic, iron,nickel and magnesium, are there maxima in the melting-point curves,showing the formation of intermediate compounds. Thermal analysis of thegermanium-arsenic system gives two weak maxima at 7 3 2 O and 737", cormsponding to the formation of GeAs2 and GeAs re~pectively.~l There aretwo maxima also in the system germanium-iron, at 1 MOO, correspondingto Fe2Ge, and at 866", corresponding t o FeGe,, and in the nickel-germaniumsystem, there is a maximum melting point at 1200", corresponding probablyPe\\ /CH22 7 A.Hantzsch, Z . anorg. Chem., 1902, 30, 289.28 v. I. Kuznetsov, J . Gen. Chem. (U.S.S.R.), 1939, 9, 1049.20 B. N. Ivanov-Emin, ibid., 1940, 10, 1813.30 M. Zumbusch, M. Heimbrecht, and W. Biltz, Z . anorg. Chem., 1939, 242, 237.31 .H. Stohr and W. Klsmm, ibid., 1940, 244, 205112 INORGANIC CHEMISTRY.to Ni,Ge.32 Magnesium and germanium form a compound Mg,Ge, m. p.11 15" &5°.33Germanous hydroxide does not dissolve in tartaric acid, but a solution ofthe tartrate may be obtained by treating a solution of germanous, chloride indilute hydrochloric acid with sodium tartrate ; from the resulting clearsolution it is impossible to precipitate germanium with ammonia or withhydrogen sulphide except on long standing. These facts are taken to indicatethe presence in the solution of a complex germanotartrate, in which 1 atomof bivalent germanium corresponds to 2 molecules of tartaric acid.Germanic oxide is somewhat soluble in hot oxalic acid solution.Itforms a complex in which the ratio of germanium atoms to oxalic acidmolecules is 1 : 3, and to which the formula [Ge(C,O,),]H, and the name ger-manioxalic acid were given.9 The acid could not be isolated in the freestate, but that there is combination between the oxalic acid and germaniumis shown by the fact that, if the solution is titrated with sodium hydroxide,neutralisation occurs when approximately three-quarters of the oxalic acidis accounted for.Similarly, if a mixture of potassium iodide and iodate isadded, the quantity of the iodine liberated is always less than that whichwould be expected for the oxalic acid : even after 24 hours, the reaction isnot complete.Germanic oxide is much more soluble in ammonium oxalate than inoxalic acid. The complex is quite stable, for it is not decomposed byhydrogen sulphide, and sulphuric acid decomposes it to germanic oxideonly on heating (this has been used in the separation of germanium fromores).If a solution of germanioxalic acid is mixed with a concentrated solutionof quinine oxalate, a salt ([Ge(C,O,),]C,,H,,O,N, H ,) is precipitated imme-diately.The strychnine salt { [Ge(C,0,),]2C,,H,,0,N2 H,} is formed inhot solution and precipitated on cooling. Both these salts are white powdersand are very hygroscopic. Their analyses confirm the formula [Ge(C,O,),]H,for germanioxalic acid.If, however, theoxide is boiled with a solution of mannitol, a stable solution containing 10 g./l.is quickly obtained. This has been utilised in the determination of ger-manium by acidimetric and .iodometric methods.The end-point to phenolphthalein when a, solution of germanic oxide istitrated with sodium hydroxide shows that 5 molecules of oxide are equivalentto 2 of the alkali. This coincides with the formula (Ge5011)H,, which isanalogous to metastannic acid (Sn,O,,)H,.The existence of this acid isshown to be very probable by the work of A. HantzschYu who described thesodium salt, and by R. S ~ h w a r z , ~ ~ who isolated the ac'id, obtained bydehydrating the hydrolysis product of germanium tetrachloride with sul-phuric acid.The solubility of germanic oxide in water is 6-8 g./l.K. Ruttewit and G. Masing, 2. Metallk., 1940, 32, 52.33 W. Klemm and W. Westlinning, 2. anorg. Chem., 1941, 245, 365.34 Ibid., 1902, 30, 316. 36 Ber., 1929, 62, 2477ROBTNGON : GERMANIUM. 113If mannitol, glycerol, glucose, or any other polyhydric organic compoundis added to the above, it acts as a strong acid. A complex organogermaniccompound is formed, so that on titration one atom of germanium corres-ponds t o one molecule of sodium hydroxide.Addition of mannitol topentagermanic acid causes a lowering of its association so that again amolecule of sodium hydroxide corresponds t o an atom of germanium. Hencea formula such as [Ge205(M)n]H2 is possible, where M is mannitol and n anumber at least equal t o two.If a mixture of potassium iodide and iodate is added to a solution of themannitogermanic acid, an atom of iodine is liberated per atom of germaniumpresent.36 The reaction is probably3[Ge205(M)n]H2 + KIO, + 5KI --+ 3[Ge@&M)JK, + 3H2O + 312This fact allows germanic acid to be determined in the presence of strongacids. Excess of a mixture of potassium iodide and iodate is added t o thesolution, and the liberated iodine titrated to the end-point ; the germanicacid is so weak as to have little effect on the titration, but on subsequentaddition of mannitol and titration of the iodine further liberated, the latteris equivalent to the quantity of germanic acid present.Its solution has pH 4.0 andliberates carbon dioxide from carbonates on boiling. It is a complex, for itgives no precipitate of germanic hydroxide with ammonia. If magnesiumchloride is added to a solution of germanic oxide, a quantitative precipitationof magnesium germanate occurs, but in the presence of mannitol, the pre-cipitation is not complete.Besides mannitol, germanic acid forms complex salts with strong electro-lytes, such as alkali sulphstes, chlorides, or nitrates ; the resulting solutionis a strong acid.With concentrated solutions of calcium chloride or magne-sium chloride, two molecules of the salt are combined per atom of germanium,indicating the existence of complex orthochlorogermanates, (I) and (11),r,Mannitodigermanic acid is a strong acid.where n is undetermined.In the case of the nitrates and chlorides of calcium and magnesium, theamount of sodium hydroxide required to neutralise the complex acid corres-ponds approximately to the complex (111), where A is the anion and C thecation of the strong electrolyte added. The temperature affects the form-ation of these complexes, since the amount of sodium hydroxide required onheating is greater than that in the cold. This leads us t o suppose that these36 A. Tchakirian, Compt. rend., 1928, 187, 229; Bull.SOC. chim., 1932, 51, 846114 INORGANIC CHEMISTRY,complexes are not formed instantaneously, and the molecule may undergohydration t o give salts different from the original, e.g.Germanous chloride, dissolved in hydrochloric acid with casium chloride,gives a white microcrystalline precipitate, GeCsC1,. A similar compoundis obtained with rubidium chloride, but not with the chlorides of lithium,sodium, potassium, calcium, strontium, and barium. T. Karantassis andL. Capatos have also prepared the corresponding bromides and iodide^.^'The compound between germanous chloride and caesium chloride may beeither GeC12,CsC1 or CsGeC1,. The latter is regarded as the more likely, forthe compound is not decomposed by a current of hydrogen chloride passedover it at the temperature of fusion, a fact which can hardly be reconciledwith the formula GeCl,,CsCl.If a solution of germanous chloride in 7~-hydrochloric acid is electro-lysed in a U-tube, at the end of 15 minutes a reddish precipitate of ger-manous hydroxide has been formed in the anode compartment, but there isno germanium in the cathode compartment. The explanation is that theion [Ge++Cl,]- proceeds t o the anode where it is neutralised and then hydro-lysed to germanous hydroxide. Thus it may well be that in the caesiumcompound, the formula is CsGeC1,.Several attempts were made to prepare alkyl- and aryl-substitutedderivatives of germanium tetrachloride but in no case was the yield good.G. T. Morgan and H. D. K. Drew 38 treated germanium tetrachloride withphenylmagnesium bromide, R. Schwarz and M. Lewinsohn 39 tetraphenyl-germanium with germanium tetrachloride, and E. A. Flood 40 germanousiodide with ethyl iodide; and W. R. Orndorff, D. L. Tabern, and L. M.Dennis 4 1 attempted the preparation of phenylgermanium trichloride byheating diphenylmercury with germanium tetrachloride in a sealed tube.The latest method, which gives very good yields, is to heat czsium ger-manium trichloride with an alkyl or aryl halide (preferably the iodide) in asealed tube.42 The reaction RX + CsGeC1, --+ RGeC1, + CsX takesplace. Hydrolysis of the resulting compounds gives rise to substitutedgermanoformic acid ; e.q., with methylgermanium trichloride, germano-acetic acid is formed : CH,*GeCl, + 2H20 --+ CH,*GeO,H + 3HC1. Thisreaction is reversible, for if the acid is treated with sufficiently concentratedhydrochloric acid, methylgermanium trichloride is regenerated.Ethyl- and phenyl-germanium trichlorides have been prepared by thismethod, as well as the digermanium compound from methylene iodide,37 C m p t . rend. 1934, 199, 64; 1935, 201, 74.38 J . , 1925, 127, 1760. Ber., 1931, 64, 2352.40 J . Amer. Chem. SOC., 1933, 55, 4935.4 ' Ibid., 1927, 49, 2512.42 A. Tchakirian, Compt. rend., 1931, 192, 233ROBINSON : GERMANIUM. 115CH,(GeCl,),.analogue of malonic acid is obtained as a white powder :If this compound is then hydrolysed by water, the germaniumTetra-substituted organo-germanium compounds of the type GeR, areknown. The tetraphenyl derivative has been prepared by D. E. W0rra11,4~from phenylmagnesium bromide and germanium tetrachloride in toluenefrom which all the ether used to prepare the Grignard compound has beendistilled, and also by refluxing germanium tetrachloride in toluene withsodium and bromobenzene. Schwarz and Lewinsohn prepared the compoundphenylethylisopropylgermanium bromide which is optically active.,fJ Thereexist also organo-germanium compounds where the germanium appears tohave valencies of three, two, and one.It is claimed 44that germanium forms alloys with magnesium which are suitable for castings,and that reflectors of high efficiency may be made by evaporating germaniumelectrically in a highly evacuated chamber, and causing it to deposit on glass.The germanium is then backed by aluminium.45The effect of the addition of germanic oxide to glass has been studied.46A partial or total replacement of silica in glass by germanic oxide causes anincrease in the refractive index and in the dispersion. At the same time,however, it causes a lowering of the chemical stability of the glass.Germanium appears as yet to have 1ittle.commercial use.S. R. R.S. R. ROBINSON.A. J. E. WELCH.4s J . Amer. Chem. SOC., 1940, 62, 3267.44 U.S.P. 2,278,726.46 K. Krakau, Optiko-Mekhan. Prom., 1939, 9, No. 4, 16.46 B.P. 508,205

ISSN:0365-6217    

DOI:10.1039/AR9444100087

出版商:RSC    

年代:1944

数据来源: RSC

摘要:

ORGANIC CHEMISTRY.1. INTRODUCTION.THIS section contains for the first time a report on recent research on amino-acids, the account being limited almost entirely to natural a-amino-carboxylicacids and their near derivatives. In addition to improved preparations bywell-established methods, attention is drawn to novel applications of themalonic ester synthesis to methionine, tryptophan, etc., to Hofmann andCurtius degradations of appropriate derivatives of cyanoacetic and malonicacid, and to the facile reduction of many arylhydrazones obtained by couplingdiazotates with substituted malonic and similar esters. Recent analyticalreactions of organic chemical interest are summarised and a brief account isgiven of the various applications of chromatography to amino-acids.Thereaction between amino-acids and formaldehyde, the transamination reactionand the formation and behaviour of dehydration products of amino-acidsand their near derivatives have been discussed as subjects of current interest.A notable feature of the material summarised under the last topic is theunexpected variety of the products, which include simple and poly-peptides,diketopiperazines, azlactones, and representatives of other heterocyclic series ;still more versatile are the dehydropeptides and derivatives thereof obtainedby extensions of the classical Ploechl-Erlenmeyer condensation of aldehydeswith glycine derivatives.Keten acetals are now readily available as a result of the investigationsof S. M. McElvain and his collaborators, who have introduced two generalmethods of preparation : (i) by the elimination, with potassium tert.-butoxide,of hydrogen bromide from an a-bromo-acetal, and (ii) by the removal of theelements of alkyl hypobromite from an a- bromo ortho-ester by treatmentwith sodium.The ethylenic linkage is highly reactive in the majarity ofketen acetals, and enters into addition reactions either in the normal manner(reaction I) or by a type of 1 : 4-addition, in which two moles of the acetalare involved (reaction 11).I. CH,:C(OEt), + AB ---+ A*CH,*CB(OEt),11. 2CH,:C( OEt), + AB _t A*CH,*C(OEt),*CH,*CB(OEt),The adduct formed in either type of reaction is frequently unstable, andmay decompose to give a variety of products, some of which may then reactwith a further quantity of keten acetal; in this way it is possible to accountfor the numerous by-products which are sometimes obtained.Reagentswhich readily form such adducts include alcohols, amines, phenols, acids,ap-unsaturated carbonyl compounds, and diazonium salts. Keten diethyl-acetal is particularly sensitive towards traces of acids, which lead to theformation of chain polymers.Considerable progress has recently been made in the elucidation oINTRODUCTION. 117problems concerning the structure of aldols and their dimeric forms. Thebalance of evidence appears to indicate that monomeric aldols are capableof existing in both the open-chain and the cyclic form, and it is now estab-lished that the dimers possess cyclic structures of the hydroxy-1 : 3-dioxantype, as exemplified by formula (I), now allocated to paraldol.Further-more, it has been shown that monomeric aldols react with simple aldehydesO-CHMe O-CHMe<()-&?ti 0- H*OHCHMe< ?€I2 (11.) (I.) CHMe(OH)*CH,*CHto give compounds of the same type. It follows that in the preparation ofaldols the formation of an aldol-aldehyde adduct, such as (11), is unavoidable,and it is now known that crude aldols are largely composed of such material,which accounts for some of the divergent properties of " aldols " recordedin the literature. It has also been shown that in the presence of complexalkoxides, an aldol may react with an aldehyde in a different manner, by acrossed Cannizzaro reaction, to give a glycol ester. Following the successfuloutEome of the investigations on the dimers, it has been possible to makefurther progress in the allocation of structures to the higher condensationproducts of acetaldol, such as dialdan and tetra-aldan.This section of theReport contains also a brief account of some recent work on crotonaldehydeand its cyclic polymers.In a summary of recent progress in the chemistry of acetylenic compoundsa number of new and improved preparative methods for the hydrocarbons,including the vinylacetylenes, the carbinols (I), and the glycols (11), are(1.) >C(OH)*CiC- >C(OH)*CiC*C(OH) < (11.)discussed. Distinct advantages accrue by operating in liquid ammonia,since sodamide, which is both readily formed and appreciably soluble in thismedium, can be employed either for the dehydrohalogenation of halogeno-olefins to acetylenes, or for the production of sodio-derivatives by replace-ment of the active hydrogen atom of acetylenic hydrocarbons.The sodio-compounds undergo smooth substitution reactions in liquid ammonia withalkyl halides and sulphates, yielding mono- or di-substituted acetylenes, andcarbinols (I) are formed by addition to most types of carbonyl compounds.The Grignard reagents derived from monosubstituted acetylenes, whichreact with alkyl sulphates or reactive alkyl halides, giving various types ofhydrocarbon, can be employed advantageously to obtain carbinols, and thedimagnesium bromide formed from acetylene itself still provides the mostconvenient laboratory route to the acetylenic glycols.Other processesemploying potassium hydroxide and either acetylene or calcium carbidehave been devised for the large-scale production of both carbinols andglycols. The isomerisation of acetylenes into allenes and conjugated dienes,and the catalytic conversion of cycbhexylacetylenes into alkylbenzenes arediscussed. Other topics which have received attention include the chlorin-ation of the hydrocarbons, carbinols, and glycols in reactive solvents such aI18 ORGANIC CHEMISTRY.methyl alcohol, the polymerisation of acetylenes with sulphur dioxide topolysulphones, and the formation of or-naphthol derivatives by condensationof arylacetylenes with diphenylketen. With amines in the presence ofmetallic salts, acetylene gives rise either to aminoacetylenes [e.g.,CH,*CH(NHPh)*CiCH] or to quinaldines.A variety of methods is availablefor the substitutive halogenation of acetylenic hydrogen atoms and thereactions of the 1 -halogeno-alkynes, especially the highly reactive dichloro-acetylene, for which a safe method of preparation has now been developed,present many interesting features. The carbinols and glycols (I and 11)undergo fission on heating with alkalis, the nature of the products havingbeen shown to be considerably dependent on the particular substituentgroups present and on the particular reagent employed. Initial substitution,followed by rearrangements to halogeno-allenes and -dienes, results fromtreatment of the carbinols with halogen acids together with cuprous salts.The complex changes which occur, leading amongst other products to dioxanand tetrahydrofuran derivatives, when the carbinols and glycols are causedto react with either methyl alcohol or acetic acid by means of the mercuricoxide-boron trifluoride catalyst, have been largely elucidated.The carbinolsand glycols derived from ap-unsaturated carbonyl compounds readilyisomerise in the presence of acids to conjugated vinylacetylenic alcohols.The general character of this novel type of anionotropic rearrangement hasbeen demonstrated and the facile transformation of the glycol from octa-trienal into a product containing a conjugated system of six ethenoid linkagesand one triple bond may be cited as an example of outstanding interest.Asa result of these investigations an examination of the light absorptionproperties of polyene systems containing an acetylenic linkage has been.possible, and the development of high intensify absorption due to theproduction of the vinylacetylene chromophore on isomerisation has beenutilised in kinetic studies. Interaction of vinylacetylene with aldehydes andketones gives carbinols (e.g., 111), the reactions of which have received muchattention. All hydration processes apparently involve initial isomerisationto the diethenoid ketones (e.g., IV), which can then undergo various addition(111.1 CH,:CH*CiC*C( OH)Me, --+ CH2:CH*CO*CH:CMe2 (IV.)reactions, giving tetrahydro-y-pyrones by addition of water and cyclisation,and (3-alkoxy-ketones by reaction with alcohols.Within recent years the significance of reactions between atoms or freeradicals and molecules has become more widely recognised. Such reactions,which involve the symmetrical fission of an electron pair, are discussed underthe heading Homolytic Reactions.Reactions of diazo and related com-pounds, which involve free-radical mechanisms, have been further utilisedfor synthetic purposes. The production of free radicals by the electrolysisof Grignard reagents has also been investigated, and Kharasch and his colla-borators have developed a new method for the generation of free radicals insolution by means of the catalytic action of certain metallic halides onGrignard reagents. The capacity of acyl peroxides to yield free radicals oINTRODUCTION.119thermal decomposition has led to the extensive use of such peroxides for theinitiation of chain reactions in solution involving free radicals and atoms,Reactions of acyl peroxides have also been used in a number of investigationsfor the purpose of obtaining a clearer understanding of the chemical propertiesof free radicals of various types. Considerable advances have been made inour knowledgk of addition polymerisation, which confirm the free-radicaltheory, since it has now been established that fragments of the catalyst andof the solvent are incorporated in the polymer and compounds other thanperoxides, which can give rise to free radicals, are also capable of initiatingpolymerisation.Growing recognition of the biological importance of nucleic acids hasstimulated chemical investigation of these substances ; the main outlines ofthe structures of the component nucleotides and nucleosides are now clear.The latter appear to be N,-ribo- or -2-deoxyribo-furanosidopyrimidines andjV,-ribo- or -2-deoxyribo-furanosidopurines ; in the nucleotides the phosphorylgroup probably esterifies the hydroxyl group a t C,’ of the carbohydrateresidue.Synthetic studies have not yet resulted in complete synthesis ofany natural nucleoside or nucleotide, but the close nucleoside analogues3-d-ribopyranosidouracil and 9-&-ribopyranosidoadenine have been obtainedby methods which should be capable of extension to the production of thenaturally occurring furanosides, and several partial syntheses of naturalnucleotides have been effected by phosphorylation of the correspondingnucleosides.The chemistry of the heterocyclic compounds is represented in theReport by a discussion of the most recent work on the biotin substances, andby a review of progress made in the structural investigation of several groupsof alkaloids.Inability to reconcile with his own observations the resultsobtained by V. du Vigneaud and his school in their study of biotin, led F. Koglto conclude that the materials handled by the two groups of workers were notidentical. This conclusion was confirmed by a direct comparison of theactive substances isolated from egg-yolk and from liver. A stepwise degrad-ation of a-biotin from egg-yolk afforded finally a sulphohexoic acid, theconstitution of which was determined, and on the basis of this and earlierwork, a structure has been advanced for a-biotin.The structure of p-biotin,obtained from liver or milk, has been confirmed by a complete synthesis ofthe substance. Two outstanding achievements in the chemistry of thecinchona alkaloids are reported : the first a total synthesis of quinine, andthe second a complete elucidation of the stereochemical orientation of thesealkaloids. Alstonine and a new RauwoZJia alkaloid, rauwolscine, have beenshown to contain the p-carboline nucleus, and gelsemine also is shown tobelong to the indole group. Hygroline, a new pyrrolidine base from coca,is closely related to hygrine. The structure previously assigned to retro-necine has been fully confirmed.Some progress has been recorded in thedifficult investigation of the aconite and veratrine groups. The closestructural relationship between the aconite and Delphinium alkaloids hasbeen conclusively demonstrated by the isolation of identical alkamines fro120 ORGANIC CHEMISTRY.alkaloids of the two genera, and evidence has been obtained that the alkaloidsof this group are related to the diterpenes. Further confirmation of thesteroidal nature of solanidine is afforded by its transformation into fourstereoisomeric solanidanols, closely analogous to the cholestanols ; theveratrine bases rubijervine and isorubijervine also appear to possess a regularsteroid skeleton similar to that proposed for the-Solanurn group, but it isdifficult to assign a like structure to the more highly oxygenated veratrinealkaloids on account of their different behaviour on degradation.A.H. COOK.D. H. HEY.E. R. H. JONES.B. LYTHGOE.H. T. OPENSHAW.L. N. OWEN.F. S. SPRING.2. AMINO-ACIDS.Introduction.This Report, necessarily arbitrary in extent as it is the first on its topicin this Section, is confined to advances in the organic chemistry of thoseamino-acids which are constituents of proteins and a few nearly relatedacids, and of simple derivatives thereof. No attempt has been made toreview aspects of biochemical or physicochemical interest or to summarisethe growing literature on p-aminobenzoic and similar acids.l The Reportcovers the past 2 yeah with some earlier work to afford cohesion.It is stated 2 that there are 18 amino-acids of general occurrence ; glycine,leucine, tyrosine, serine, glutamic acid, aspartic acid, phenylalanine, alanine,lysine, arginine, histidine, valine, proline, tryptophan, hydroxyproline,isoleucine, methionine, threonine.To these must be added 7 acids ofnarrow distribution (thyroxine, di-iodotyrosine, dibromotyrosine, norleucine,cystine, cysteine, and hydroxyglutamic acid) and 5 of very limited occurrencebut which may be present in proteins (thiolhistidine, dihydroxyphenyl-alanine, citrulline, canavanine and djenkolic acid), to which must probablybe added lanthionine. There are finally about 20 acids which have notbeen completely substantiated, with rather vaguely defined amino-acidssuch as that believed to be present in liver antianzemia f a ~ t o r .~1 Reviews, etc. : C. Schmidt, “Chemistry of the Amino-acids and Proteins,”1938, with Addendum, 1943; M. Sahyun, “ Outline of the Amino-acids and Proteins,”1944; E. J. Cohn and J. T. Edsall, “ Proteins, Amino-acids and Peptides as Ions andDipolar Ions,” 1943; R. J. Block and D. Bolling, “ Determination of Amino-acids,”1941 ; “ Amino-acid Composition of Proteins and Natural Foods,” 1944; “ Amino-acid Chemistry,” H. E. and L. E. G~YM, Pharm. J., 1944,153,22. See also volumesof Ann. Rev. Biochern. “ Imidazole amino-acids,” S. W. Fox, Chem. Rev., 1943, 32, 47.H. B. Vickery, Annals N.Y. Acud. Sci., 1941, 41, 87.Several examples of this mode of addition are given in Table I.Re-action (h) which results in C-alkylation, is of particular interest, but the yieldis poor owing to thermal decomposition of the keten diethylacetal a t the hightemperature required. Ally1 bromide reacts much more r e a d i l ~ , ~ but theproduct then contains diallylacetic ester (XIX ; A = allyl). A similarresult is obtained with benzyl br~rnide.~ Ethyl acetoacetate is probablya secondary product from ( i ) , but in the presence of the acetyl chloride it isconverted into the 0-acetyl derivative actually isolated as the main con-stituent ; the hydrogen chloride thereby evolved attacks a further mole ofketen diethylacetal, both by 1 : 4-addition (see later) and according to re-action ( c ) (X = Cl), to form ethyl acetate and ethyl chloride.Benzoylchloride reacts in the same way.g In reaction (j), the highly enolic dibenzoyl-methane adds almost quantitatively a t 25O, but in (k) and ( I ) the yields arepoor unless sodium ethoxide is present to increase the enolisation. Methyl-malonic ester fails to react even under the most vigorous enolising con-ditions.' The secondary products from (k) and ( I ) contain ethyl orthoacetate,formed by reaction of the liberated alcohol with a further mole of ketendiethylacetal.In many instances the addition takes a different course, convenientlyclassified as a 1 : 4-type. This occurs when one mole of AB reacts with twomoles of keten diethylacetal to give (XX) ; this adduct is frequently unstableand may decompose to give a number of different products.(XX.) A*CH,*C(OEt),*CH,*CB(OEt), CH,.C(OEt):CH*CO,Et (XXI.1Acids of sufficient strength will bring about 1 : 4-addition, so that re-action ( c ) is frequently accompanied by the formation of ethyl P-ethoxy-crotonate (XXI) derived from the primary 1 : 4-adduct by loss of EtOHand EtX.g The addition of bromine to bromoketen diethylacetal alsofollows both the 1 : 2- and the 1 : 4 - r o ~ t e .~ Maleic anhydride adds to ketendiethylacetal exclusively in the 1 : 4-manner, and 3 : 5-diethoxyrl : 6-di138 ORQANIC CHEMISTRY.hydrophthalic anhydride (XXII) rapidly separates from an ethereal solutionof the reactants.1° Further reaction of maleic anhydride with the con-jugated system in (XXII) may be accomplished by the use of benzeneas solvent to yield (XXIII).Dimethylmaleic anhydride does not give anadduct.CH%C( OEt),\o f--OEtp-Benzoquinone reach only by 1 : 2-addition to give a product whichon hydrolysis furnishes homogentisic acid (XXIV ; R = H). The adductwas at first lo thought to be-(XXV), but subsequently l6 this formula wasrejected in favour of the 5-hydroxy-2-ethoxycoumarone structure (XXVI ;R = H), which accounts equally well for the production of (XXIV ; R = H)on hydrolysis, but explains also the formation of 5-ethoxycoumaran-%one(XXVII) and the corresponding acid (XXIV; R = Et) by hydrolysis of theethyl ether of theideneacetone, andOH/%H,*CO,H II I\/OR(XXIV.)adduct (XXVI; R = Et). Other quinones, dibenzyl-benzylideneacetophenone also give 1 : 2-adducts with(XXV.) (XXVI.) (XXVII.)keten diethylacetal, though the yields are generally poor.1° With p-ethoxy-benzenediazonium chloride, 1 : 2-addition gives the unstable intermediate(XXVIII), which decomposes and reacts with a further mole of the diazoniumP-E~O*C,H,.N:N*CH,*CC~( OEt), 4 p-EtOC,H4*NH*N:CH*CO,EtI/ (XXVIII . )(XXIX.) p-E tO*C,H,*NH*N:C( C0,E t)*N:N*C,H4*OE t-pmlt to give ethyl di-p-anisylformazylformate (XXIX) . Simultaneous1 : 4.addition, wia the intermediate (XXX), leads to the formation of thOWEN : ALDOLS AND RELATED PRODUCTS. I39phenylhydrazone (XXXI) and thence 4-ethoxy-1 -p-anisylpyridaz-6-one(XXXII). The occurrence of both types of addition appears to be general(XXX.) p-EtO*C,H,*N:N*CH,C( OEt),*CH,*CCl( OEt), --+(XXXI.) p-EtOC H *NH*N:CH*C(OEt):CH*CO,Et i4 (XXxII.) p-Et~°C,H,*~<CO-CH~C'OEt N=CHfor substituted benzenediazonium chlorides, but benzenediazonium chlorideitself gives only the pyridazone, with no evidence of 1 : 2-addition.L.N. 0.4. ALDOLS AND RELATED PRODUCTS.Although it is more than seventy years since aldols were first prepared,it is only now that a clear understanding has begun to emerge of the manyproblems which these comparatively simple substances offer to the physicaland the organic chemist. Many different opinions have been held, evenwithin the last decade, on such aspects as the mechanism of the condens-ation,l the structure of monomeric aldols, and the changes which occur whenaldols polymerise, but recent investigations have done much to clarify theposition.Qenerd-Observations have been made on the catalysis of the aldolcondensation by amino-acids and by phosphorus o~ychloride.~ From apreparative point of view, these catalysts are inefficient, and with either typeof reagent the aldol is usually accompanied by a considerable quantity of thecorresponding @-unsaturated aldehyde.F. G . Fischer has recorded theproperties of p-methylacetaldol, which is conveniently prepared by theozonisation of dimethylallylcarbinol, according to the method first describedin 1939 by G. N. Burkhardt, I. M. Heilbron, and J. B. Aldersley.sThe formation of symmetrical dialkyl ketones, by the pyrolysis overchromia of normal primary alcohols, is believed to involve the intermediateformation of an aldol, according to the following scheme :R*CH,*CH,=OH 3 R*CH,*CHO 4 R*CH,*CH(OH)*CHR*CHO 3R*CH,-CH( OH)*CH,R 3 R*CH,*CO*CH,Rthat a higher yield ofketone is obtained when the appropriate aIdol is used in place of the alcohol ;n- butyraldol, for example, is readily converted into di-n-propyl ketone.In the condensation of an aldehyde with an unsymmetrical methyla W.Langenbeck and G. Borth, Ber., 1942,76,951; E. V. Budnitskeya, Biokhimiya,This mechanism is supported by the observationH. B. Watson, Trans. Faraday SOC., 1941, 37, 707.1941, 6, 146.M. BrtckBs, Bull. SOC. chim., 1942, 9, 60.Ber., 1943, 76, 734.Idem, ibid., p. 3269.B.P. 512,465.IJ V. I. Komarewsky and J. R. Coley, J . Amer. Chem. SOC., 1941, 63, 700140 ORGANIC CHEMISTRY.ketone Me*COCH,R, the ketol may be formed either by reaction with themethyl group or with the a-methylene group, depending partly upon thebranched or unbranched nature of the aldehyde.In an extension of someearlier work, S. G. Powell and F. Hagemann have shown that isobutyr-aldehyde condenses almost exclusively with the methyl group. Thestructures of the ketols are established by ozonisation of the @-unsaturatedketones obtained on dehydration. During the course of this work, aninteresting isomerisation was observed in the reduction by sodium and alcoholof 2-methyldec-3-en-5-one (I), obtained from isobutyraldehyde and methyln-amyl ketone. The product proved to be the &-unsaturated alcohol (11).(1.) CHMe2*CH:CH*CO*[CH,I4*Me __p CMe,:CH*CH,*CH(OH)*[CH,],*Me (11.)Structures of Monomeric Aldob.-Monomeric aldols may be formulatedeither as p-hydroxy-aldehydes (111) or as cyclic hemiacetals (IV), and thepossibility of an equilibrium involving both forms has long been envi~aged.~The open-chain structure is supported by the preparation of characteristic(111.) R*CH( OH)*CH,*CHO R*CH*CH,*CH*OH (IV.1L - 0 - Jderivatives, by reactions involving either the carbonyl or the hydroxylfunction.It has not always been realised that reactions of the formertype must be performed under mild conditions, and some derivatives originallyascribed to acetaldol have now been recognised as derived from croton-aldehyde.lOP11 Reactions involving the hydroxyl group are usually re-stricted by the ease with which the aldols polymerise, but E. Spath and T.Meinhard 12 have succeeded in preparing pure esters of monomeric acetaldolby slow distillation of the dimeric esters under reduced pressure. As willbe seen from the structure of the dimeric form (p.142), the yield by thisprocess cannot exceed 50% of the theoretical, but the method is neverthelessof some value.By the aldolisation of methoxyacetaldehyde, C. D. Hurd and J. L.Abernethy l3 have prepared tt 2 : 4-dimethyl aldotetrose, to which theopen-chain structure (V) is assigned. The presence of the free aldehydegroup is supported by a positive reaction with Schiff’s reagent. They alsofavour an open-chain structure for acetaldol on the grounds that methyl-ation of its dimethylacetal gives p-methoxybutyraldehyde dimethylacetal(V.) MeO-CH2*CH( OH)*CH( OMe)*CHO CH,*CH( OMe)*CH,*CH( OMe), WI.1(VI), but this result is inevitable, since the dimethylacetal itself can beformulated only as an open-chain derivative.The problem of structure isin fact analogous to that of the aldoses,14 and if, as appears very probable,O Inter alia, M. Backas, Compt. rend., 1935,200, 1669; M. Bergmann and E. Krann,l o I. Kasuya, J . A m r . Chem. SOC., 1937, 59,2742.l1 E. Spath, R. Lorenz, and E. Freud, Ber., 1942, 75, 1029.14 L. N. Owen, Ann. Reports, 1943, 40, 109.J . Amer. Chem. SOC., 1944, 86, 372.Annalen, 1924, 438, 278.Ber., 1943, 76, 504. l3 J . Amr. Chem. SOC., 1941, 83, 1966OWEN : ALDOLS AND RELATED PRODUCTS. 141an aldol in solution is present as an equilibrium mixture of open-chain andring forms, the isolation of derivatives of either form cannot be taken asconclusive evidence for the structure of the parent compound.The ultra-violet absorption spectrum of acetaldol, as determined byM, indicates that the presence or absence of a free carbonyl groupis dependent upon the solvent used.More recently, the Raman spectraof aldols have been investigated, but it is difficult to assess the value ofphysical evidence in this field, particularly in view of the different inter-pretations assigned to such evidence by the workers concerned. Forexample, R. H. Saunders, M. J. Murray, F. F. Cleveland, and V. I.Komarewsky l5 found no Raman line corresponding to the frequencyexpected for a carbonyl group, and correctly concluded that such a groupwas absent.* M.Back&s,16 on the contrary, explains the unusual Ramanspectrum by the postulation of a " rectified " carbonyl function, the abnormalcharacter of which is assumed to be due to the presence of a hydroxyl groupin the molecule.The independent investigations of several schools 1 7 0 l8, l 9 P *O have pro-vided an explanation for some, a t least, of the conflicting results recordedin earlier publications. It has been shown that aldols, as usually preparedin the crude state, are largely composed of an addition product with thecorresponding aldehyde (see p. 144). This material may either be distilledunchanged, or may break down into one mole of aldol and one mole of alde-hyde, according to the precise conditions employed.Much of the publisheddata on aldols is therefore erroneous, and should more correctly refer toaddition products of this type. Unfortunately, it is not always possibleto deduce the true nature of the material examined by some.workers, owingto insufficient experimental details of the method of purification.The Polymerisation of AldoZs.-Pure acetaldol, when freshly distilledunder reduced pressure, is obtained as a mobile liquid which on standingbecomes viscous and eventually crystallises as paraldol. On heating underreduced pressure, this substance, which has long been recognised as a dimer,is reconverted into monomeric acetaldol. Other aldols behave in a similarway. The changes which occur in this cycle have given rise to muchspeculation, and the earlier postulations of physical association and dis-sociation have more recently been discarded in favour of chemical interpret-ations, based on more profound variations in molecular structure.E.Spath and H. Schmid21 have suggested that an intermolecularcondensation of the secondary hydroxyl group of one acetaldol moleculewith the aldehyde group of another, to form the hemi-acetal (VII), is followed16 J . A m r . Cihem. Soc., 1943, 65, 1309.l7 R. H. Saunders, M. J. Murray, and F. F. Cleveland, J . A m r . Chem. SOC., 1943,18 Ibid., 1944, 66, 206.l o E. Splith, R. Lorenz, and E. Freund, Ber., 1943,76,67.*" E. Hanschke, ibid., p. 180.* It was shown subsequently (refs. 17, 18) that the material under investigation wasl6 Bull.SOC. chim., 1942, 0, 274.85, 1714.21 Ber., 1941, 74, 869.not a true aldol, but this does not invalidate the present argument142 ORGANIC CHEMISTRY.by a similar intramolecular reaction to give paraldol, which is thus formulatedas 6-hydroxy-4-methyl-2-(2'-hydroxy-n-propyl)-1 : 3-dioxan (VIII). ThisO--CHMe via acetateCH,*;H( OH) *CH,*CH< >CH, (VIII.) ------+ O-~H(OH)Y J H 2HO-CHM CH,*CH(OH)*CH,*CHO + HO CH,structure is supported by the properties of paraldol dittcetate, in whichone acetyl residue is very readily removed by dilute mineral acid, whereasthe other behaves normally; on formula (VIII), an acetyl group at position6 would be of the hemi-acetal type, and would be expected to show greatlability, in contrast with the one at position 2'.Furthermore, withhydrogen and palladium, the diacetate undergoes partial hydrogenolysis,and .saponification of the product yields 4-methyl-2-( 2'-hydroxy-n-propyl)-1 : 3-dioxan (IX), the structure of which is established by synthesis fromacetaldol and 1 : 3-butanediol. The hydrogenolysis had previously beenaccomplished by M. Bergmann, A. Miekeley, and E. von Lippmann,22 whocorrectly assigned formula (IX) to the saponified product, but suggested 23that it was formed, by a somewhat unorthodox mechanism, from a paraldolof structure (X) * This view has been adopted, though without the pro-duction of convincing evidence, by M. H ~ r i , , ~ but it is evident that theunsymmetrical formula (VIII) accounts more readily for the difference inreactivity of the two acetyl groups, and it is also supported by the isolationof the aldol-aldehyde products described in a later section of this Report.It is probable that 1 : 3-dioxan structures may also be allocated to thedimeric forms of other aldols.4~25~a6~27 There has been no recent in-vestigation of dimeric hydracraldehyde, which was formulated by theBergmann school 2 2 p 2 3 as a simple analogue of the eight-membered ringstructure (X).It would appear very probable that it is, in fact, 6-hydroxy-2- (2'- h ydroxyethyl) - 1 : 3-dioxan (XI).22 Ber., 1929, 62, 1467.2p J . Agric. Chem. SOC. Japun, 1941, 17, 1.25 E. Spath, R. Lorenz, and E. Altmann, Ber., 1943,76, 513.26 E. Spath and I. von SeilAgyi, ibid., p.949.2 7 E. Sfith, R. Lorenz, and E. Fmund, ibid., p. 1196.* (X) may theoretically be derived from (VII) by an alternative type of ring closure.z3 M. Bergmann and A. Miekeley, ibid., p. 2297OWEN: ALDOLS AND RELATED PRODUCTS. 143The dimerisation of acetaldol in the free state is usually complete in a fewhours. This has been shown 28 by eryoscopic determinations of molecularweight, on samples of different ages after distillation, solvents such as wateror dioxan being used in which the substance is relatively stable. In thepresence of acetic acid the dimerisation is greatly accelerated, and themolecular weight attains a constant value, corresponding to approximately80% of paraldol, within a few minutes.28 On prolonged standing in aqueoussolution, both acetaldol and paraldol give the same equilibrium mixture, thecomposition depending upon the concentration ; in dilute solution there is apreponderance of monomer.l1 Substantially similar results have beenobtained by M. who contends, however,29 that dimeric aldols willnot yield derivatives of the monomers. This view is criticised by E. Spath,R. Lorenz, and E. Freund,ll who have prepared several derivatives- ofacetaldol directly from paraldol ; furthermore, as already mentioned, estersof acetaldol may be obtained by depolymerisation of the corresponding estersof paraldol.12Aldol-Aldehyde Addition Products.-Assuming the validity of themechanism outlined above for the conversion of acetaldol into paraldol,it would be anticipated that similar compounds, also with a 1 : 3-dioxanstructure, would be formed by the reaction of an aldol with a simple aldehyde.This has been confirmed by E.Hanschke,20 and by E. Spath, R. Lorenz,and E. Freund,19 who have prepared 6-hydroxy-2 : 4-dimethyl-1 : 3-dioxan (XII), the addition product from acetaldol and acetaldehyde. Agradual scission of the product into these components is observed in aqueoussolution; this may be brought about also by slow distillation under 10-15 mm., preferably in the presence of acid or alkaline catalysts, but at lowpressures the substance distils without decomposition. The acetyl deriv-ative readily undergoes hydrogenolysis to 2 : 4-dimethyl-1 : 3-dioxan(XIII), the structure of which is confirmed by synthesis from acetaldehydeand 1 : 3-butanediol.These properties, which are strikingly similar tothose of paraldol, afford strong support for the formula (VIII) assigned tothe latter compound. The acetate had already been prepared by C. S.Marvel, J. Harmon, and E. H. Riddle,30 who condensed acetaldehyde withvinyl acetate in the presence of sodium, in the hope of obtaining the acetate(XIV) of the cyclic form of acetaldol, according to the following scheme :CH3*CH0 + CH2:CH*OAc -+ CH3*CH*CH2*CH*OAc (XIV.)The properties of their product led them to suggest for it the structureassigned later to the acetate of (XII). Comparison of the physical propertiesof the two substances leaves no doubt that they are identical. The crystal-line benzoate of (XII) 19s 2o is identical with a substance, of hitherto unknown‘0’8 8 L.N. Owen, J . , 1943, 445. 20 Bull. Soc. chim., 1942, 0, 69.J . Org. Chem., 1939, 4, 252144 ORGANIC CHEMISTRY.constitution, prepared in 1896 by P. C. Freer 31 from acetaldehyde, benzoylchloride, and sodium.The probability that crude acetaldol contains a product of structure(XII) was tentatively suggested by E. A. S h i l ~ v , ~ ~ but its presence as a mainconstituent has only recently been proved by the observation that acetylationof such material gives a high proportion of the acetate of (XII). Thisexplains a puzzling feature of many aldol condensations, in which the yieldof aldol never exceeds two-thirds of the theoretical, Previously, thishad been attributed to the establishment of an equilibrium between aldehydeand aldol.For example, in the aldolisation of isobutyraldehyde it wasconcluded,% by distillation of the product, that it contained 33% by weightof free aldehyde. This is precisely the yield which is obtained by the thermaldecomposition of the aldol-aldehyde additionCHPrS<O-CH(OH)>CMe, 0-CHPrB compound, 6-hydroxy-5 : 5-dimethyl-2 : 4-di-isopropyl- 1 : 3-dioxan (XV), a substance whichhas been the subject of independent examin-ations by R. H. Saunders, M. J. Murray, and F. F. Cleveland 1 7 and E.Spath, R. Lorenz, and E. F r e ~ n d . ~ ~ Analogous compounds have beenisolated from other crude aldols, and have also been prepared by the reactionof aldehydes with pure aldols.l8* 27 The disappearance of carbonyl groupsduring the progress of the reaction may be followed spectrographically.17It is clear that this hitherto unsuspected complication in the aldol con-densation should be borne in mind when interpreting the physical data onthe condensation mechanism, for which the end product has always beenassumed to be the free aldol.In the condensation of two or more different aldehydes, the possibilitiesare more numerous, and a wide range of substituted 1 : 3-dioxans is therebymade available.The crystalline Stritar product 34 prepared by the reactionof one mole of benzaldehydc and two moles of isobutyraldehyde is nowshown 25 to be 6-hydroxy-4-phenyl-5 : 5-dimethyl-2-isopropyl-1 : 3-dioxan(XVI), since it may be degraded to isobutyraldehyde and p-hydroxy-p-phenyl-aa-dimethylpropaldehyde (XVII) :OPENSHAW : HETEROCYCLIC COMPOUNDS.227The hydrocarbon, Cl&@ obtained from the dehydrogenation of a t i ~ i n e , ~ ~afforded a mixture of acids on oxidation; although these products have notbeen unequivocally identified, their nature suggests that the C,, hydrocarbonmay be a methylethylphenanthrene possessing one of the two structures(IV; R, R = Me, Et).Although the alkamines aconine (C,,H,,O,N) and delphonine (C,,H,,O,N),obtained by hydrolysis of aconitine and delphinine respectively, show nounsaturation by the usual tests, the strong ultra-violet absorption of theirsolutions indicates that they contain two conjugated double linkages,probably in proximity to the nitrogen atom ; tetrahydroatisine and hetera-tisine show a similar ab~orption.~5 The unusually high basic dissociationconstant of delphonine may also be ascribed to the presence of the structureC = C -N: 39, 65 ; the lower ultra-violet absorption shown by the saltsof these bases would then be due to the existence of an equilibrium of thetype :I I .t )~=&-b=b-$i~( += )c=c-~H-c=N(The presence of these double bonds makes possible a tetracyclic structurefor the alkaloids, which is more closely in harmony with their apparentrelationship to the diterpenoids.The structure (V) has been put forward asan example of a possible type of fundamental nucleus for the alkaloids ofthis group.65\ /M~N-cH,Veratrum and Solanum AZkabids. 66-Selenium dehydrogenation ofsolanidine affords, in addition to Diels's hydrocarbon,6' 5-methyl-Z-ethyl-pyridine,G8 suggesting the presence of a six-membered nitrogenous ring, andthe structure (I) has been advanced.By employing methods familiar in thesteroid-field, V. Prelog and S. Szpilfogel69 have converted solanidine into allfour possible solanidanols (dihydrosolanidines), differing in their stereo-chemical orientation a t C, and C,, and also into allosolanidane (rings A/B64 W. A. Jacobs and L. C. Cmig, J . Biol. Chem., 1942, 143, 589; A. Lawson andJ. E. C. Topps, J . , 1937, 1640.6 5 L. C. Craig, L. Michaelis, S. Granick, and W. A. Jacobs, J . Biol. Chenb., 1944, 154,293.6 6 Ann. Reports, 1940, 37, 378; 1942, 39, 207.H. Soltyz and K. Wallenfels, Ber., 1936, 69, 811 ; H.Rochelmeyer, Arch. Pharm.,68 V. Prelog and S. Szpilfogel, Helv. Chim. Acta, 1942, 25, 1306; W. A. Jacobs and6s Helv. Claim. Acta, 1944, 27, 390.1936, 274, 543.1 4 C. Craig, Science, 1943, 97, 122; J . Biol. Chem., 1943, 149, 271228 ORUANIC CHEMISTRY.cis).products and t h s e of the corresponding cholesterol derivatives.There is a very close parallelism between the optical rotations of theseThe formulae of several alkaloids of the veratrine group have been revised,and all the alkamines are now found to be C,, compounds, thus strengtheningthe formal relationship with the Solanurn group.70, 71Protoverine C2,H4,0,N Rubi j ervine C27H4302NGermine C27H4308N Solasodine C27H4302NCevine C27H4308N isoRubijervine C2,H4,02NJervine C27H3903N Solanidine C27H43ONW. A.Jacobs and L. C. Craig 7 1 have discussed the constitution of thesealkaloids in the light of recent experimental results. With the exceptionof jervine, all these substances are tertiary bases containing one ethyleniclinkage, and in each case all the oxygen atoms are accounted for as hydroxylgroups. They are therefore hexacyclic compounds, and have the nitrogenatom common to two rings. Jervine differs in being a secondary base, andin containing two conjugated double bonds, which can be hydrogenated.Since it is probably pentacyclic, it must contain two further, resistant doublebonds, which have not so far been detected.On dehydrogenation, the veratrine bases resemble solanidine in giving5-methyl-2-ethylpyridine, but differ in that they do not yield Diels’s hydro-carbon.Instead, the more highly oxygenated bases afford cevanthridine,and a mixture of hydrocarbons which appear to be tetracyclic or pentacyclicfluorene derivatives ; rubijervine, on the other hand, affords a hydrocarbon,Cl8HI6, similar to, but not identical with, 3’-methylcycbpentenophen-anthrene; its properties are in fairly close agreement with those of the1’-methyl isomer. Moreover, isorubijervine readily forms a digitonide, andrubijervine does so rather more slowly. The failure of the other veratrinebases to give precipitates with digitonin may be due either to their higherhydroxyl content or to the absence of the necessary steroidal structure.Rubijervine has been converted,y2 through the related ketone rubijervone,into an isomer, probably a mixture of albrubijervine and epialbrubijervine ;this product reacted only very slowly with digitonin, and differed from theoriginal material in giving a strong Rosenheim reaction. It is concluded70 W. A. Jacobs and L. C. Craig, J. Biol. Chem., 1943,148.41, 51, 67; 149, 271.71 Idem, ibid., 1943, 149, 451. 72 Idem, ibid., 1944, 152, 641OPENSHAW : HETEROCYCLIC COIPIPOUNDS. 229that the allomerisation proceeded in a manner analogous to the correspondingconversion of c holes ter ol into allocholes t erol :Rubijervine accordingly cannot possess an angular methyl group a t C,, andtherefore cannot contain the skeleton (11) previously proposed for theveratrine alkaloids, but is probably a hydroxy-derivative of (I). Attemptsto achieve a similar allomerisation of cevine were unsuccessful.The authors consider the possibility that the fluorene hydrocarbonsobtained by dehydrogenation of cevine, germine, and protoveratrine mayarise by a rearrangement, or by a recyclisation of the side chain (formed fromrings E and F) on to C16. If such were the case, a steroid structure similarto (I) could be assigned to all the veratrine alkaloids ; however, it is difficultto explain, on such a basis, the production, in high yield, of the acid (111), byoxidation of cevine and germine (but not rubijervine), unless this also involvesa rearrangement. The nature of ring B in these alkaloids thus requiresfurther investigation. Surface film studies 73 indicate the presence of anextended, hexacyclic system and are consistent with structures of the types(I) and (11). H. T. 0.73 A. Rothen and 1,. C. Craig, J . Amer. Chem. SOC., 1943, 65, 1102

ISSN:0365-6217    

DOI:10.1039/AR9444100116

出版商:RSC    

年代:1944

数据来源: RSC

摘要:

BIOCHEMISTRY.IT has again been found necessary to make a, somewhat arbitrary selectionfrom the many progressive branches of Biochemistry, and in this the aimhas been to choose topics which have arrived at a fairly clear-cut stage ofdevelopment since they were last considered here. They include aspects ofmetabolism, hormones, nutrition, and chemotherapy.I. PHOSPHORYLATION MECHANISMS.Phosphate Bond Energy.The inter-relationships of phosphorylations in the transport and storageof metabolic energy l have been further clarified and their range and inter-pretation have been extended.2* 3* It is doubtful if under physiologicalconditions appreciable synthesis of phosphoric esters could occur by reversalof their hydrolytic (esterase) cleavage, and the primary introduction ofphosphoric groups falls into two main classes, though doubtless otherroutes 59 6 also exist.Phosphorolysis of the glucosidic type of linkage in poly- or di-saccharidesoccurs reversibly, as is described below, and thus provides for the introductionof phosphate into organic metabolites without the need for external energysources.The second type of phosphorylation is associated with a markedincrease of free energy, which is commonly derived from enzymic dehydro-genation accompanying the addition of phosphate to a double bond.The differences in energy level in these two types of compound arenaturally reflected in their widely different properties. The esters ofphosphoric acid with alcohols such as hexoses (including the " glucosidic ''type represented by glucose 1 -phosphate), pentoses, trioses, glycerol, choline,serine, or the 2- or 3-position in glyceric acid, are stable compounds; theirhydrolysis whether by acids or enzymes is reversible, and is accompaniedby relatively small energy change ( AF about -3000 cals.) .But the cleavageof the second type of phosphoric compound is strongly exothermic (AF about-11,000 cals.). Lipmann has therefore introduced for the latter thesymbol - P, denoting the " high energy phosphate bond " by means of whichthe high potential energy of the phosphorus linkage may be indicated:the phosphate group he writes - ph. From the biochemical standpoint thisis justified by the emphasis which it places on the ability of such highpotential groups to promote synthetic reactions.Examples of this type ofcompound include anhydrides formed from phosphoric acid, with an organicSee Ann. Reports, 1941, 38, 241 ; 1940, 37, 386, 417.H. M. Kalckar, Chem. Rev., 1941, 28, 71 ; Biol. Rev., 1941, 17, 28.I?. Lipmann, " Advances in Enzymology," Interscience Press, N.Y., 1941, 1, 99.H. M. Kalckar, Bwchem. J . , 1939, 33, 631.S. P. Colowick, M. S. Welch, and C. F. Cori, J . B i d Chem., 1940, 133, 359; 1941,* A. A. Green and S. P. Colowick, Ann. Rev. Biochem., 1944, 13, 155.137, 343DICKENS : PHOSPHORYLATION MECHANISMS. 231phosphate as in the two terminal groups of adenosine'triphosphate, or with acarboxyl as in 1 : 3-diphosphoglyceric acid or acetyl phosphate, or with anacidic enol group as in phosphoenolpyruvic acid.The amidophosphate bondis another type of high energy linkage, present in creatine phosphate andarginine phosphate, the energy reservoirs of muscle and nerve.Following the primary introduction of inorganic phosphate into meta-bolites, other enzymic reactions are known to transport these groups, eitherinter- or intra-molecularly, thus forming the wide variety of phosphorylatedintermediates. According to the energy changes involved, such reactionsmay be reversible or irreversible. Thus reversible interchange of phosphateoccurs, on the higher energy level, between the adenosine triphosphate-adenylic acid system and the creatine-creatine phosphate or phospho-glycerate-diphosphoglycerate systems. On the lower potential level it maybe between glucose 1-phosphate and glucose 6-phosphate (enzyme, phospho-glucomutase), or between 3- and 2-phosphoglyceric acids (phosphoglycero-mutase) .The phosphorylation of glucose to glucose 6-phosphate by adeno-sine triphosphate (hexokinase), i.e., a change from the high to low level, isirreversible. The concept of phosphate bond energy, and in a wider sense ofgroup potential, has many applications to biological syntheses, includingacetylations, methylations, and aminations (cf. 3). It plays an importantpart in animal phosphorylations, as will be briefly considered here.Primary Introduction of Phosphate Groups : Phosphorylase.The preparation from skeletal muscle of this enzyme, which esterifies aglucose unit of a polysaccharide, or conversely synthesises polysaccharidefrom glucose 1-phosphate, is fully described by Cori and co-worker~.~. 8i loIt has been obtained in a crystalline (a) and an amorphous (b) form. Theformer is a euglobulin of M.W.340,000400,000 and has 60-70% of itsmaximum activity without addition of adenylic acid. The more solubleb form is inactive without addition of adenylic acid, but both a and b areequally active in its presence. The optimum rate of conversion is 4 x lo4mols. of glucose l-phosphate to glycogen/mol. enzyme/min. a t 30". Glucosecompetitively inhibits the activity, while cysteine increases both activity andsolubility. Extracts of muscle and spleen contain an enzyme (" PR ") which,like trypsin, removes the prosthetic group from a, converting it into theamorphous b form. Simultaneously, pentose (0.3 pg./mg.of protein) is lost,but the substance split off is not adenylic acid. Added adenylic acid doesnot render the b form crystallisable, nor is it firmly bound as is that presentin a. Possibly this non-dissociable union of the prosthetic group is aprotection in vivo.As with vegetable phosphorylase 11 the equilibrium position varies with' A. A. Green and G. T. Cori, J . Bid. Chem., 1943,151,21.G. T. Cori and A. A. Green, ibid., p. 31.C. F. Cori, G. T. Cori, and A. A. Green, ibid., p. 39.lo G. T. Cori and C. F. Cori, ibid., p. 57.l1 C. S. Hanes and E. J. Marshall, Biochem. J . , 1942, 36, 76232 BIOCEEMISTRY .pH; polysaccharide is formed from Cori ester only when a little “ priming ”polysaccharide is added.The reaction is considered to be9 : glucose1-phosphate + terminal glucose unit maltosidic chain unit + inorganicphosphate. The terminal glucose units are supplied by the end groups ofthe highly branched glycogen or amylopectin molecule (starch amylose doesnot activate animal phosphorylase lo), polysaccharide synthesis consisting of alengthening of the side chains by addition of glucose units in 1 : 4-glucosidiclinkages g* 12* l3 to form long unbranched chains of glucopyranose units.When a supplementary enzyme from heart or liver, obtained free fromphosphorylase, accompanies crystalline phosphorylase, a branched-chaintype of polysaccharide resembling glycogen results. Presumably branchcd-chain polysaccharides such as glycogen and amylopectin arise from the jointaction of phosphorylase and another enzyme lo or factor.12 It is uncertainwhether the supplementary enzyme in Cori’s experiments is another type ofphosphorylase, able to establish 1 : 6-glucosidic linkages, or else some kindof diastase not identical with that of blood serum.1OThe yield of phosphorylase from rabbit skeletal muscle (40-80 mg./100 g.)is not altered by previous stimulation of the muscle, but the proportioncrystallisable is diminished.** l4 Phosphorylase occurs in a variety of tissues,and in embryonic tissues is related t o the activity of their glycogen meta-b01ism.l~.l5 It is contained in adipose tissue,15 which utilises glycogen,15and in cartilage the enzyme may produce phosphoric esters, yielding phos-phate needed for calcification.lGAdenylic acid is not a component of potato phosphorylase l7 or ofdisaccharide phosphorylases,18 which require no coenzyme.It is noteworthythat in muscle phosphorylase adenylic acid acts as coenzyme without anyevidence of its phoaphorylation. l9 Adenosine di- or tri-phosphates have no,and inosic acid only feeble, coenzyme a c t i ~ i t y . ~ ~ 2oAdenosine Triphosphatase.The energy liberated by hydrolysis of the final2‘ phosphoric group ofadenosine triphosphate (ATP) is believed to be directly utilised for muscularcontraction.2a Engelhardt’s important discovery in 1939 22 that myosinl2 W. N. Haworth, S . Peat, and E. J. Bourne, Nature, 1944, 154, 236.l3 W. N. Haworth, R. L. Heath, and S.Peat, J., 1942, 55; W. Z. Hassid, G. T. Cori,K. H. Meyer, ‘‘ Advances in fand R. M . MoCready, J. Biol. Chem., 1943, 148, 89;Enzymology,” 1943, 3, 109; W. Z. Hassid, Ann. Rev. Biochem., 1944,13, 59.l4 A. Mkki and E. Wertheimer, Biochem. J., 1942, 36, 221.l6 B. Shapiro and E. Wertheimer, Biochem. J., 1943, 37, 397; A. Mirski, ibid., 1942,A. B. Gutman and E. B. Gutman, Proc. SOC. Ezp, Biol. Med., 1941,48,687; A. B.36, 232 ; E. Wertheimer, Nature, 1943, 152, 565.Gutman, F. B. Warrick, and E. B. Gutman, Science, 1942, 95,461.l7 D. E. Green and P. K. Stumpf, J . Biol. Chem., 1942,142, 355.l8 M. Doudoroff, ibid., 1943,151, 351; P. H. Hidy and H . G. Day, ibid., 1944,152,l* Cf. ref. (3), p. 124.2o C. F. Cori, Cold Spring Harbor Symposia on Quantitative Biology, 1939, 7, 260.21 Cf.refs. (32), (33)) and (28).477.8’ See Ann. Reports, 1941, 38, 241DICEENS : PHOSPHORYLATION MECHANISMS. 283“ which is the contractile constituent of muscle is at the same time thecatalytic agent which promotes the chemical reaction which provides thedirect source of energy of muscular activity ” 23 has been widely accepted asprobable after several careful studies,22* 249 251 26 and so far no more activefraction has been isolated from this globulin. Nevertheless, cataphoresis 25and sedimentation 26 analyses suggest that myosin may not be quite homo-geneous, though nearly s ~ . ~ ~ The most serious challenge to the view thatmyosin itself is the enzyme is the recent demonstration by KalckeLr 28 thatan adenosine polyphosphatase, present in the soluble albumin fraction frompotato and 50-100 times more active than myosin, is strongly and apparentlysomewhat specifically adsorbed by myosin.But even if the activity ofmyosin should eventually prove to be due to adsorbed adenosine triphos-phatase, the latter might still be linked to contraction of myosin. Thispotato enzyme, like that from liver, hydrolyses ATP directly to adenylicacid without intervention of myokinase. It thus differs from the muscleenzyme, which is considered specific for the triphosphate inasmuch as it doesnot act upon adenosine diphosphttte (ADP) except through myokinase ;28but it attacks inosine triphosphate even faster than ATP.29Although iodoacetic acid does not inactivate adenosine triphosphatase,3Ooxidation does so, and SH compounds reverse the inactivati~n.~I Appar-ently the establishment of the single thioether linkages by the former reagentis to be distinguished from the cross-linked S-S bonds believed to be hereproduced by oxidants.Radioactive phosphorus has been used t o show in muscle the coupling ofoxidation with the phosphorylation of adenylic acid and creatine 32 and therapidity of resynthesis of ATP after its breakdown.33* 34Phosphokinases (Phospherases) .Myohuse.-Although Lipmann’s terminology does not differentiate them,the terminal phosphate group of ATP is more reactive than that of thediphosphate (ADP), the latter being unable to transfer phosphate directly(e.g., to glucose in presence of hexokinase), but requiring the presence of awater-soluble enzyme, myokinase, obtained from muscle and other tissues.35* 36This enzyme, which is stable to heat and to acid, catalyses the reversible23 W.A. Engelhardt, Yale J. Bid. Me&., 1942, 15, 21 (Engl. trans. from Russianorig.).24 D. M. Needham, Biochem. J . , 19-12, 36, 113.25 K. Bailey, ibid., p. 129.26 G. Schrarnm and H. H. Weber, Kolloid-Z., 1942, 100, 242 ; Brit. Chem. Physiol.27 M. Ziff and D. H. Morre, J . Biol. Chem., 1944, 153, 663.p * H. M. Kalckar, ibid., p. 355.30 D. M. Needham, ibid., p. 113.38 R. F. Furchgott and E. Bhorr, ibicl., 1943,151, 65.33 E. V. Flock and J. L. Bollman, ibid., 1944, 152, 371.34 H. M. Kalckar, J. Dehlinger, and A. Mehler, ibid., 1944, 154, 275.35 S.P. Colowick and H. M. Kalckar, ibid., 1943, 148, 117.36 H. M. Kalckar, ibid., p. 127.Abs., 1943, 111, 348.2D A. Kleinzeller, Biochem. J., 1942, 36, 729.31 M:Ziff, J. Biol. Chem., 19-14, 153, 25234 BIOCHEMISTRY.reaction : 2ADP =+= ATP + adenylic acid. Inosin diphosphate is notaffected.29 The enzyme is inactivated by oxidants and activated by SHcompounds, and it is capable of transferring 4 times its own weight ofphosphorus per min. a t 30’.Hexokinase.-The occurrence of the hexokinase reaction : hexose +ATP --+ hexose 6-phosphate + ADP, is probable in various cells whichmetabolise glucose, and from several of these this water-soluble enzyme hasbeen extracted.35* 37* 38 With yeast hexokinase direct phosphorylation ofthe 6-position of the hexose occurs with glucose or fructose,39 but it is possiblethat in aerobic liver suspensions fructose may be directly phosphorylated inposition 1, or alternatively, as has been suggested for galactose l-pho~phate,~~there may be an equilibrium between these 1-phosphates and Cori ester.39Hexokinase is of special importance in the synthesis of glycogen fromglucose, the glucose 6-phosphate being reversibly converted via the 1 -phos-phate into glycogen, by means of the enzymes phosphoglucomutase andphosphorylase (cf.37).Phosphorylation of Fructose 6- Phosphate.-This reaction proceeds by wayof an enzyme not yet isolated, sometimes called Neuberg ester phospherase.It catalyses the reaction : fructose 6-phosphate + ATP --+ fructose 1 : 6-di-phosphate + ADP.It is stated to be inhibited by oxidising agents and evenby O/R indicators of B,>0.05 v., and this sensitivity has been held to be themechanism of the Pasteur effect, by which the fermentation is checkedaerobically 41 ; but this is perhaps an over-~implification.~~Other Enzymes concerned in Reactions of Phosphoryluted Intermediates.Recent outstanding advances include the purification of phosphogluco-m~tase,~’ the isolation of aldolase (or zymohexase) of muscle,43 now crystal-lised and its distribution studied,44 and of enolase (crystalline mercury salt,) ,45It is stated that the addition of phosphate to 3-phosphoglyceraldehyde is non-enzymic, and that the unknown intermediate in the dehydrogenation of thistriose phosphate (previously considered to be 1 : 3-diphosphoglyceraldehyde 22)has the nature of a “ loose physical addition product,” analogies for whichare sugge~ted.~~Oxidative Phsphrylations.The reaction just mentioned wasthe first in which the oxidative formation of high energy phosphate bondsPreceding the formation of pyruvate.37 S .P. Colowick and E. W. Sutherland, J. Biol. Chem., 1942, 144, 423.38 I. HuzAk, Biochem. Z., 1942, 312, 315.39 C. F. Cori, Biological Symposh, 1941, 5, 131.4 0 H. W. Kosterlitz, Biochem. J., 1943, 37, 318, 321, 322.4 1 W. A. Engelhardt and N. E. Sakov, Biochirnia, 1943, 8, 9.42 Cf. E. S. G. Barron, ‘‘ Advances in Enzymology,” 1943, 3, 149 (p. 183).43 D. Herbert, H. Gordon, V. Subrahmanyan, and D. E. Green, Biochem. J ., 1940,4 4 0. Warburg and W. Christian, Biochem. Z . , 1943, 314, 149, 399.4 5 Idem, ibid., 1941-2, 310, 384.46 0. Meyerhof and R. Junowicz-Kocholaty, J. Biol. Chern., 1943, 149, 71.34, 1108DICKENS : PHOSPHORYLATION MECHANISMS. 235was clearly demonstrated, inorganic phosphate being incorporated into thecarboxyl of the final product, 1 : 3-diphosphoglyceric acid. This is the morecommon mechanism by which such bonds arise. An alternative is seen inthe action of enolase, which merely by the removal of a molecule of waterfrom 2-phosphoglyceric acid reversibly produces the high energy enolic bondin the resulting phosphoenolpyruvic acid : in this remarkable reactionthe considerable energy of dehydration is conserved within the moleculeThus in the passage from a glucose unit of glycogen to pyruvate, throughthe well-known series of phosphorylated intermediates, one externallyintroduced - ph (from ATP) is required in the formation of fructose 1 : 6-di-phosphate, and, since two mols.of pyruvate are formed, 2 - ph arise at eachof the stages resulting in 1 : 3-diphosphoglyceric and phosphoenolpyruvicacids. Thus the removal of 4 hydrogen atoms should yield a balance of3 - ph per mol. of hexose metabolised. Starting from glucose, instead ofglycogen, the primary phosphorylation by ATP and hexokinase consumes afurther - ph, and at the pyruvate stage only 2 - ph remain on balance.Possibly in intact cells, as distinct from extracts, economies are effected byunknown mechanisms (e.g., the formation of fructose 1 : 6-diphosphate couldtheoretically occur by intermolecular transfer of the 1 -phosphate from Coriester to fructose 6-phosphate).3 The synthesis in intact cells of ATP frominorganic phosphate during glucose fermentation has beel'i dem~nstrated.~'During pyruvate metabolism. The simpler conditions prevailing inbacterial extracts enabled Lipmann 4** 49p 50 to demonstrate the productionof high energy phosphate bonds during the bacterial oxidation of pyruvateto acetate and carbon dioxide, and the formation of acetyl phosphate, nowisolated as the pure silver sa1t.w The latter has been synthesised frommonosilver phosphate and acetyl chloride and the properties and determin-ation of monoacetyl phosphate are de~cribed.~~ It is assumed 3* 52 that inthe enzymatic synthesis 50 the addition of phosphoric acid to the carbonylgroup of pyruvic acid is followed by the dehydrogenation of the resulting(unknown) compound ; the analogy with bisulphite and cyanohydrin com-pounds is suggested.This mechanism finds some support in purely chemicalstudies of E. Baer.53* 54 The reaction is represented as a dehydrogenative de-carboxylation : CH3*CO*C0,H + HO*ph CH,*C(O€€)(O*ph)*CO,H -"H,CH,*CO*O - ph + CO,. The closely similar reaction occurring in cell-freeextracts of Esch. coli : pyruvic acid + H3P0, += acetyl phosphate + formic(cf. 3).4 7 D. J. O'Kane and W. W. Umbreit, J. Biol. Chem., 1942, 142, 25.4 8 Cf. Ann. Reports, 1940, 37, 417.4p F. Lipmann, J. Biol. Chem., 1940,134,463 ; Symposium on Respiratory Enzymes,50 F.Lipmann, J. Biol. Chem., 1944, 155, 55.51 F. Lipmann and L. C. Tuttle, &id., 1944, 153, 571.52 F. Lipmann, Ann. Rev. Biochem., 1943, 12, 1.53 J . Amer. Chem. SOC., 1940, 62, 1597.54 J . Biol. Chem., 1942, 146, 391.Univ. of Wisconsin Press, 1941, 145; Federation Proc., 1942, 1, 122236 BIOCELEMISTRY.acid,55 has now been shown to be reversible,56* 57 13C of radioactive formicacid appearing in the carboxyl group of the keto-acid. Since in the bacteria,though not in these cell-free extracts, carbon dioxide is normally in equi-librium with formic acid, the mechanism of a new method of carbon dioxidefixation into the carboxyl of pyruvic acid is revealed by these experiments.The synthetic reaction resulting in carbon dioxide fixation is able to proceedonly because the dehydrogenation product is acetyl phosphate, and not thefree acid : the formation of acetic acid from pyruvate would result in anenergy loss of some 15,000 ~ a l s .~ ’As yet the evidence of the formation of acetyl phosphate or homologouscompounds in animal tissues is indirect, based on reactions such as acetyl-ations in viv0,68 in isolated tissues 59 or in tissue extracts.60 However, theoxidative formation of energy-rich phosphate bonds in such material hasbeen repeatedly proved by the phosphorylation of adenylic acid, creatine, orglucose 6-phosphate7 for example.5* 32* 33* 61The oxidation by acytochrome system of a-ketoglutarate to succinate 62 causes esterificationof 3 atoms of phosphorus for each oxygen atom consumed: in this 4-Cdicarboxylic acids did not function as hydrogen carriers.Obviously anoxidative decarboxylation as formulated above could give only a 1 : 1 ratio.Even the highly speculative assumption of a diphosphate formation leaves adeficiency of one phosphorus atom esterified. Perhaps even more remark-able is the observation 63 that the whole pyruvic molecule is oxidised in heartextract with precisely the same efficiency; P/O ratio = 3. This indicatesthat no less than 15 high-energy phosphate bonds are established by theoxidation of 1 mol. of pyruvate, which at the level of 11,000 cals./bond showsthe efficiency of conversion of oxidation into phosphate bond energy to benearly 60%. If the course of pyruvate oxidation through the “ tricarboxylicacid cycle ” 64 be accepted, those of the five dehydrogenation reactionsinvolved which have been shown to be accompanied by phosphorylation areas follows : a-Keto-acid oxidation (occurring twice) could generate 2 x 3 - ph 62 ; succinate --+ fumarate not more than 1 - ph 63 ; malate to oxalo-55 M.Silverman and C. H. Werkman, Proc. Soc. Exp. Biol. Med., 1940, 43, 777;M. F. Utter and C . H. Werkman, Arch. Biochem., 1943, 2, 491.56 M. F. Utter, C. H. Werkman, and F. Lipmann, J . Biol. Chem., 1944, 154, 723.157 F. Lipmann and L. C. Tuttle, ibid., p. 725.5 8 E. A. Doisy, jun., and W. W. Westerfield, ibid., 1943, 149,229; G. J. Martin andE. H. Rennenbaum, ibid., 1943,151, 417; K. Block and D. Rittenberg, ibid., 1944,155,243.59 P. J.0. M m , M. Tennenbeum, and J. IT. Quastel, Biochem. J . , 1939, 33, 1506.60 D. Nachmansohn and A. L. Machado, J . Neurophysiol., 1943, 6, 397; D. Nach-maJlsohn, H. M. John, and H. Waelsch, J. Biol. Chem., 1943,150,485.61 V. A. Belitzer and E. I?. Tsibakowa, Biochimiu, 1939, 4, 616 (cf. footnote, p. 493,ref. 63); S. Ochoa, J. Biol. Chem., 1941, 138, 751; S. P. Colowick, H. M. Kalckar, andC. F. Cori, ibid., 1941, 137, 343.The efficiency of this process is unexpectedly high.62 S. Ochoa, ibid., 1943, 149, 577; 1944,155, S7.63 Idem, ibid., 1943, 151, 493.64 A. H. Krebs, “Advances in Enzymology,” 1943, 3, 191NEUBERGER : THE INTERMEDIARY METABOLISM OF TRYPTOPHAN. 237acefate oxidation generates phosphate bonds (phosphopyruvic acid) to anunknown extent .G5 The remaining dehydrogenation, of isocitrate toa-ketoglutarahe, has not been studied in this respect.Hence, as yet onlyabout half of the 15 ester bonds established in the oxidation of 1 mol. ofpyruvate can be accounted for experimentally, and 5 such bonds are aa manyas could be reasonably expected on the basis of known mechanisms. Itfollows that there must be yet unexplored mechanisms.which enable theenzyme equipment of the cell to tap the large energy range (up to 1.2 v.)between the potential levels of oxygen and of the metabolites, and turn asmuch as 60% of it into phosphate bond energy. F. D.2. THE INTERMEDIARY METABOLISM OF TRYPTOPHAN.The metabolic importance of tryptophan (I) was realised soon afterits discovery by F.G. Hopkins and S. W. Cole in 1901. It cannot besynthesised in the mammal and has to be supplied in the diet. The ratcan utilise d( +)-tryptophan instead of the natural I( -)-isomer for growth ; 2tthis, however, is not the case in the chick.4 The intermediary metabolismof the two isomerides in many species, including the rat, appears to bedifferent and it can be deduced that an optical inversion does not take placeto a great extent under normal dietary conditions. In man ingestion ofd(+), but not of Z(-), -tryptophan leads to the excretion of a substance,possibly indole-3-acetic acid, which can be oxidised to a red pigment.6Deficiency of (I) in the diet of the rat leads to a decrease of serum proteinsand a slight hypochromic anemia.6 Apart from these unspecific changes,which are probably common to all deficiencies of essential amino-acids,cataract of the eye and corneal lesions have been 0bserved.7.~The intermediary metabolism of (I) has yielded a number of interestingcompounds.Kynurenic acid (VI), which was discovered in 1853 byLiebig,g has been isolated from the urine of dogs (as the name implies),rabbits lo and many other species.ll. l2 It is formed from Z( -)-tryptophan,and from indolepyruvic acid, but not from d( +)-tryptophan.l3Another substance was isolated from the urine of rabbits fed on polishedg6 H. M. Kalcker, J. Bwl. Chem., 1943, 148, 127.1 J . Phy~wl., 1901,27, 418.C. P. Berg, J. Bid. Chem., 1934, 104, 373.V. du Vigneaud, R. R. Sedock, and L.van Btten, &id., 1932, 98, 565.A. A. Albanese and J. E. Frankston, J . Biol. Chem., 1944, 166, 101.4 G. I?,. Grau and H. J. Almquist, 3. Nutrit., 1944, 28, 263.6 Idem, ibid., 1943, 148, 299.7 J. R. Totter and P. L. Day, J . Nutrit., 1942, 24, 159.8 A. A. Albanese and W. H. Buechke, Science, 1942,96, 684.Annalen, 88, 125.10 A. Ellinger, 2. physiol. Chem., 1904, 43, 325.l1 \IT. G. Gordon, R. E. Kaufmann, and R. W. Yackson, J . Biol. Chem., 1936, 118,12 R. W. Jackson, ibid., 1939, 131, 469.13 R. Borchers, C. P. Berg, and N. E. Whitman, ibid., 1942, 146, 657.125238 BIOCHEMISTRY.rice and supplied with excess of (I).14 It was assigned by its Japanesediscoverers the name kynurenine and the structure (11). It was shownrecently that structure (11) is incorrect and that kynurenine is representedby (IV).15 (IV) was synthesised, though in poor yield, by condensation ofo-nitrophenacyl bromide with ethyl sodiophthalimidomalonate, followed byacid hydrolysis and reduction.The synthetic material had chemical andoptical properties identical with those of the natural product ; identificationis, however, not quite complete, since the synthetic material has not yet beenresolved. The chain of reactions leading from tryptophan (I) to kynurenicacid (VI) now becomes clear. (I) is presumably oxidised to a-hydroxy-tryptophan (111), a substance so far only found in phalloidin, a toxic peptide,obtained from Aminata phalloides; l6 (111) is then further oxidised to (IV)with loss of carbon dioxide.Under normal dietary conditions this amino-acid is further broken down, probably through the ay-diketo-acid (V), whichrearranges itself to the quinoline derivative (VI).”-- --CH2-CH(NH,)*C0,H - I 11 lloH +2 i,!INH2@\-CO-CH,*CH(NH,)*CO,H + CO,(111.) \/\/NH JStill another substance derived from (I) has been isolated from the urineof rats fed on fibrin.17 The new substance, which was called xanthurenicacid because of’ its yellow colour, was shown to be 4 : 8-dihydroxyquinoline-Z-carboxylic acid (IX). Being an 8-hydroxyquinoline derivative, it formscomplexes with metals and the intense green colour given with ferrous saltsis used for its estimation. (IX) is excreted by rats,17 rabbits,17 and swine,18l4 Y. Kotake and J. Iwao, 2. physwl. Chem., 1931,195, 139.l5 A.Hutenandt, W. Weidel, and W. von Derjugin, Naturwiss., 1942, 30, 51; 2.16 H. Wieland and B. Witkop, Annulen, 1940, 543, 171.l 7 L. Musajo, Atti R. Accad. Lincei, 1935, 21, 368; Gazzetta, 1937, 67, 165, 171, 182.l8 G. E. Cartwright, M. M. Wintrobe, P. Jones, M. Lauritsen, and S . Humphreys,physiol. Chem., 1943, 279, 27.Bull. Johns Hopkins Hosp., 1944, 75, 35NEUBERGER : THE INTERMEDIARY METABOLISM OF TRYPTOPHAN. 239but not by d ~ g s . l ~ ~ l9 d( +)-Tryptophan, indolepyruvic acid and kynurenicacid do not give rise to excretion of (IX). L. Musajo and M. Minchilli 2oclaim that kynurenine does not form (IX), but Reid et state that it does.The immediate precursor of (IX) may therefore be either a dihydroxy-tryptophan (VII) or the hydroxykynurenine (VIII).A--- CH,*CH( NH,)*CO,H /\ CO*CH,*CH(NH,)*CO,HI 11 lloH !+)kH2(VII.) OH (VIII.)\/\/OH !\)kH26 H NHOH Xanthurenic acid and kynurenine are not excreted by animals rearedon normal diets, but the exact dietary deficiency necessary to produceexcretion of these substances was not known until Lep-OH kovsky et aZ.19 showed that the green pigment found in/\/\ the urines of pyridoxine deficient rats was the iron com- ' " 'CO& plex of (IX).Later work 18# l9 established the followingfacts : Xanthurenic acid is only found in pyridoxine- OH Ndeficient animals fed on diets containing I( -)-tryptophanand the amount excreted is proportional to the trypto-phan intake. Addition of pyridoxine to or omission of tryptophan fromthe diet leads to the disappearance of (IX) from the urine.Similarly,kynurenine excretion both in rats and in swine 18,19 depends on pyridoxinedeficiency. It seems fairly certain that kynurenine a t least is a normalintermediary product of tryptophan metabolism and it appears that inpyridoxine deficiency its further breakdown is impossible. It is likely thatpyridoxine is the prosthetic group of an enzyme responsible for the furtheroxidation of kynurenine and (IV) is excreted unchanged in its absence.(IX) may possibly be a pathological product. The fact, however, thatanimals on normal diets can metabolise (IX) may indicate that the formationof this 8-hydroxyquinoline derivative is an additional normal pathway oftryptophan metabolism, at least in certain species.Kynurenine has recently acquired considerable interest in anotherdirection. E.L. Tatum 21 had found that a hormone which stimulates theformation of a brown pigment in the eyes of Drosophda and other insects wasrelated to tryptophan. The formation of this hormone is controlled by aspecific gene and can be replaced by a substance formed by bacteria fromtryptophan. This hormone was isolated by Butenandt and co-workers l5and identified as kynurenine. E. L. Tatum and A. J. Haagen-Smit 22showed in 1941 that their crystalline product was a complex of sucrose andkynurenine. The gene is apparently responsible for the ability of theorganism to convert tryptophan into kynurenine.\/\/(IX.)10 S. Lepkovsky, E. Roboz, and A.J. Haagen-Smit, J . Biol. Chem., 1943, 149, 195;*O Qazzetta, 1940, 70, 307.21 Proc. Nut. Acad. Sci., 1939, 25, 486; E. L. Tatum and G. JV. Beadle, Science,22 J . Riol. Chern., 1911, 140, 575.D. F. Reid, S. Lepkovsky, D. Bonner, and E. L. Tatum, ibid., 1944, 155,299.19.10, 91, 458240 BIOCHEMISTRY.Another interesting observation has recently been reported by E. I,.Trttum and D. Banner.% These authors found that by X-ray treatment amutant of Neurospora can be produced which requires tryptophan for growth.This amino-acid can be replaced by a combination of indole and 2( -)-serino,but not by any other possible intermediates. The growth of this deficientstrain in the presence of indole is proportional to the serine added. Theformation of tryptophan was actually demonstrated by isolation.It isassumed that a direct combination of these two compounds takes place.It is also suggested that the decomposition of tryptophan brought aboutby E . coli 24 which leads directly to indole may be a reversal of the reactionfound in Neurospora. A. N.3. HORMONES.The Thyroid Gland.Thyroid G l a d and Iodine Metabolism.-The application of radioactiveiaotopes of iodine to the study of the production of thyroxine by the thyroidgland has been very fruitful.The investigations may be divided into two main classes : (a) thoseinvolving the administration of radio-iodine to the intact animal, followedby removal of the thyroid gland and other tissues for examination somehours or days later; and ( b ) those in which the uptake of radio-iodine byrespiring slices of isolated thyroid tissue is examined.That iodine is preferentially retained bythyroid tissue has been amply confirmed in experiments in which radio-iodine, administered orally or parenterally, has been found in greater con-centration in the thyroid gland than in any other tissue of the body withina few hours of administration.l.2a 3* I. Perlman, I. L. Chaikoff, and M. E.Morton 3 distinguish between “ tracer ” doses of radio-iodine, which containtoo little iodine for detection by ordinary chemical means, and what may betermed ‘‘ physiological ” doses of radio-iodine, measured in mg., in which aminute amount of radio-active material is mixed with ordinary potassiumiodide a8 a carrier, When a relatively large dose (e.g., 2.6 mg./kg.of bodyweight) of potassium iodide containing some radio-iodine is administered toa rat, 50-60% may be excreted in the urine and faeces within the next 24hours, and only about 1% may be found in the thyroid gland. Neverthelessthe thyroid gland collects, per g. of tissue, over a hundred times as muchiodine as other tissues in the body and retains it longer, one-half still beingpresent a t the end of 24 hours.3 When such large doses are administered,the thyroid tissue may become satorated with iodine and then lose its capacityto fix this element selectively, though this power may be regained within a*‘ D. D. Woods, Biochem. J., 1935,29,640.1 S. Hertz, A. Roberts, and R. D. Evans, Proc. SOC.Exp. Biol. Med., 1938, 38, 610.2 (a) J. G. Hamilton and H. M. Soley, Amer. J. Physiol., 1939, 137, 557; ( b ) idem,(a) Studies on the intact animal,*3 Proc. Nut. Acad. Sci., 1944, 30, 30.n’hid., 1940, 181, 135.J . Biol. Ghem., 1911, 139, 433.4 C. P. Leblond and P. Sue, Amer. J. Physiol., 1941, 184, 64YOUNG : HORMONES. 241few days.4 Radio-iodine in a non-ionic form (iodate or di-iodotyrosine) isnot fixed by the thyroid t i ~ s u e . ~The administration of a tracer dose of iodine to an animal labels itscirculating iodine without significantly increasing the total amount in theblood and tissues. Such tracer doses are rapidly taken up by rat thyroidtissue, 16-20~0 being retained therein within 2 hours, and a maximum of65% 3040 hours after administration.3 Thereafter the amount in thethyroid slowly dim in is he^.^ The fact that a tissue constituting only about0.01% of the body weight and containing approximately 20% of all theiodine in the body takes up as much as 65% of the tracer dose of this elementin a relatively short time suggests that the turnover of iodine by the thyroidgland is rapid, and that circulating iodine can be removed by thyroid tissuemore rapidly than it oan come into equilibrium with tissues other than thatof the thyroid.3 The specific activity of the thyroid gland in this respect isstrikingly emphasised.When tracer doses of iodine are given to a sheep, 2-13y0 is found inthe thyroid gland 4 hours later.Of this about 9% is in the inorganic form,85% as 3 : 5-di-iodotyrosine, and 6% as thyroxine.Forty-eight hours afteradministration 3 0 4 0 ~ 0 of the tracer dose is found in the gland, about 13%of this being in the inorganic form, 78% as di-iodotyrosine and 9% asthyroxine. Thus at the end of 48 hours 3 4 % of the dose of administerediodine is found to be in the form of thyroxine.6 These fhdings, which havebeen adequately confirmed, are compatible with a rapid formation of di-iodo-tyrosine, followed by a slower conversion of the latter into thyroxine.60 7Hypophpectomy depresses the thyroid’s ability to collect radio-iodine and toform di-iodotyrosine and thyroxine, but the administration of pituitary thyro-tropin or exposure to cold both enhance these effect^.^*^ In children witha myxmdema not associated with goitre the thyroid collects less administeredradio-iodine than does the normal gland, whereas the thyroid of a child witha goitrous myxcedema collects more than norma1.O In Graves’ disease thehyperactive thyroid gland fixes as much as 80% of a relatively large (2 mg.)dose of administered radio-iodine,1° and, according to C.P. Leblond,ll thehyperplastic thyroid of iodine deficiency is also able to collect administeredradio-iodine more rapidly than octn the normal gland. It seems probablethat increased efficiency in the collection of iodine is associated with pituitaryW. T. Salter, Physiol. Rev., 1940, 20, 345.I. Perlman, M. E. Morton, and I. L. Chaikoff, J. Biol. Chem., 1941,139, 449.7 (u) W. Msnn, C. P. Leblond, and S. L. Warren, ibid., 1942, la, 905; ( b ) A.Lein,Endocrinology, 1943, 32, 429.* (a) M. E. Morton, I. Perlman, E. Anderson, and I. L. Chaikoff, ibid., 1942, 30,495; ( b ) M. E. Morton, I. Perlman, and I. L. Chaikoff, J . Biol. Citem., 1941, 140, 603;(c) C. P. Leblond, Amat. Rec., 1944, 88, 285; ( d ) C. P. Leblond, J. Gross, W. Peacockand R. D. Evans, Arner. J. PhyeioE., 1944, 140, 671.9 J. G. Hamilton, M. H. Soley, and K. B. Eichorn, Arner. J. Dis. ChiU., 1943, 66,495.10 S. Hertt, A. Roberts, and W. T. Salter, J . Clin. Inuetlt., 1942, 81, 25.l1 Rev. Canadian Bwl., 1942, 1, 402242 BIOCHEMISTRY.stimulation of thyroid activity, a phenomenon not observed in myxcedemaresulting from pituitary deficiency.The therapeutic value of radio-iodine retained by the thyroid in Graves'disease l2 and by metastases of thyroid carcinoma 13 is apparently dis-appointing, but radio-iodine is of proven value for the assessment of thecompleteness of thyroidectomy l4 and in examination of the functionalactivity of the developing thyroid gland.15 In experiments of this typefunctional thyroid tissue can be detected radioautographcially, i.e., by itspower to record its presence on a suitable photographic plate some hoursafter the administration to the animal of a tracer dose of radio-iodine.When small amounts of radio-iodine in the form of potassium iodide are added to bicarbonate-Ringer solu-tion in which are suspended surviving slices of thyroid gland, 70% of the addedradio-iodine is present as di-iodotyrosine 3 hours later, and 12 yo as thyroxine,16though the addition of excess of inorganic iodide (non-radioactive) to themedium inhibits the formation of both di-iodotyrosine and thyroxine fromadded radio-i0dine.l' Thyroid gland which has been minced is much lesseffective, and a smooth suspension of finely divided tissue is almost completelyinactive.16 These results show clearly that the process of conversion of theadded radio-iodine into the organic form in which it is found depends on theintegrity of cell function, and is not merely the result of a chemical inter-change of radio-iodine.The process is inhibited by the exclusion of air, andby addition to the medium of small amounts of cyanide, sulphide, azide andcarbon monoxide, all of which inhibit the cytochrome-cytochrome oxidasesystem.18 But 10-3~-azide completely inhibits the formation of di-iodo-tyrosine and thyroxine by the slice while permitting the collection andretention in the inorganic form of 60% of the radio-iodine of the medium.18This and other similar evidence suggests that the thyroid mechanism for thecollection of inorganic iodine can be differentiated from that responsible forthe conversion of inorganic iodine into the organic form.Non-thyroidal Production of Thyroid-active Substances.-The belief thatthyroxine-like substances may be formed from administered iodine in thetissue of an animal lacking a thyroid gland l9 has been confirmed by thedemonstration that both di-iodotyrosine and thyroxine are produced from12 (a) S.Hertz and A.Roberts, J. CEin. Invest., 1942, 21, 624; (b) J. G. Hamilton13 A. S. Keston, R. P. Ball, V. K. Franz, and W. W. Palmer, Science, 1942, 95, 362.14 W. 0. Reinhardt, Proc. SOC. Exp. BioE. Med., 1942, 50, 81.1 5 (a) A. Garbman and H. M. Evans, a i d . , 1941, 47, 103; ( 6 ) idem, Endocrinology,18 (a) M. E. Morton and I. L. Chaikoff, J. Biol. Chem., 1942, 144, 565; ( b ) idem,1 7 M. E. Morton, I. L. Chaikoff, and S. Rosenfeld, ibid., 1944, 154, 381.18 (a) H. Schachner, A. L. Franklin, and I. L. Chaikoff, ibid., 1943, 151, 191; ( b )idem, Endocrinology, 1944, 34, 159.19 (a) A. Chapman, ibid., 1941, 29, 686; (b) A. Chapman, G. M. Higgins, and F. C.Mam, J. EndocrinoE., 1944, 3, 392; ( c ) I. Perlman, M. E. Morton, and I. L. Chaikoff,Endocrinology, 3942, 30, 487.(b) Studies on slices of thyroid tissue.and J.H. Lawrence, ibid., p. 624.1943, 32, 113.ibid., 1943, 147, 1YOUNG : HORMONES. 243radio-iodine by the fully thyroidectomised rat.20 The minute amounts ofthese substances containing radio-active iodine were identified by theirconsistent behaviour when relatively large amounts of non-radioactiveauthentic substances were added as carriers during the processes of fraction-ation.2O These results are of particular interest in view of the discovery,by W. Ludwig and P. von Mutzenbecher (1939),21 that preparations ofiodinated casein containing 6-43 yo of organically bound iodine, togetherwith certain other iodinated proteins, possess the physiological activity ofthyroid protein and yield, on alkaline hydrolysis, mono-iodotyrosine (cf.22),di-iodotyrosine, and pure thyroxine (100-200 mg./100 g. of iodocasein) .21The correctness of these findings has been completely confirmed.23 Thephysiologically active iodinated proteins were prepared by the addition of alimited amount of iodine to a solution of the protein in dilute sodium bicar-bonate, followed by incubation a t 37" for some hours. For maximal thyroidactivity two atoms of iodine should be taken up for each molecule of tyrosinein the protein (Turner et P. von Mutzenbecher (1939) also showedthat incubation at 37' of 3 : 5-di-iodotyrosine in alkaline solution (pH 8-9)for 1-2 weeks resulted in the formation of thyroxine in gross yield of about0.2570,24 and this finding, too, was amply 26* 27* 28 Von Mutzen-becher also observed that casein which had been iodinated in the cold inammoniacal solution exhibited little or no biological activity, but that thedevelopment of biological activity resulted from incubation of this iodinatedprotein in alkaline solution for some days.24 Finding that the formationof thyroxine from di-iodotyrosine by alkaline incubation was accompaniedby a fall of pH (e.g., from 8-8 to 8.4) and the formation of iodide, and furtherthat the addition of sodium sulphite inhibited the formation of thyroxinewhereas the addition of sodium thiosulphate did not, von Mutzenbechersuggested that the oxidation of the di-iodotyrosine to thyroxine might beassociated with- the splitting of iodine from di-iodotyrosine in the form ofhyp~iodite,~~ a suggestion that received some independent support .26 Onthe other hand, the reaction, which is inhibited by the presence of potassiumferricyanide and of 3 : 5-di-iodo-4-hydroxybenzoic acid, requires the presenceof air,27 and C.R. Harington and R. V. Pitt Rivers 2a find that it is inhibited2o M. E. Morton, I. L. Chaikoff, W. 0. Reinhardt, and E. Anderson, J . Biol. Chem.,1943, 147, 757.21 2. physwl. Chem., 1939, 258, 195.22 C. R. Harington and R. V. Pitt Rivers, Biochem. J., 1944, 38, 320.23 ( a ) Idem, Nature, 1939,144, 205 ; (b) E. P. Reineke, J. Dairy Sci., 1942, 25, 702 ;(c) $1. P. Reineke and C. W. Turner, Univ. Missouri Agric. Exp. Stat., 1942, Res. Bull.355, 88 pp.; ( d ) E. P. Reineke, M.B. Williamson, and C. W. Turner, J . BioE. C'hem.,1943, 143, 285 ; (e) E. P. Reineke and C. W. Turner, J. Clin. Endocrinol., 1943, 3, 1 ;(f) E. P. Reineke, M. B. Williamson, and C. W. Turner, J: Biol. Chem., 1943, 147, 115.24 2. physiol. Chem., 1939, 261, 253.26 P. Block, jun., J. Biol. Chem., 1940, 135, 51.26 T. B. Johnson and L. B. Tewkesbury, jun., Proc. Nut. Acad. Sci., 1942, 28, 73.27 A. E. Barkdoll and W. F. Ross, J. Amer. Chem. SOC., 1944, 66, 898.28 ( a ) C. R. Harington, J., 1944, 193; (b) C. R. Harington and R. V. Pitt Rivers,Biochem. J., 1944, 38, PPOC. xxxiv24.4 BIOUHBIMISTRY .in conditions under which the formation of hypoiodite would occur mostreadily. The simplest explanation might be that free iodine, which convertstyrosine into di-iodotyrosine, a h brings about the oxidation of the latterto thyroxine, but von Mutzenbecher's observation that the oxidation occursin the presence of thiosulphate is not in easy agreement with this hypothesis.C. R.Harington 2k has recently obtained a net yield of 3.4% of thyroxineby directly oxidising di-iodotyrosine in alkaline solution (pH 9-10} a t 100'with hydrogen peroxide, the thyroxine formed being continually shaken outwith butyl alcohol (a solvent into which di-iodotyrosine pasees to only a,slight extent from alkaline solution) in order to protect it against decom-position under the somewhat drastic conditions employed. These experi-ments unequivocally demonstrate that thyroxine can be formed fromdi-iodotyrosine by direct oxidation.The fact that disiodotyrosine can be so easily converted into thyroxinein vitro suggests the possibility that such a conversion may also easily takeplace in the body, but pure di-iodotyrosine possesses little or no thyroxine-like activity when administered to animals.On the other hand, J. Lermanand W. T. Salter 29 claim that the physiological activity of dried thyroidgland, which contains di-iodotyrosine, is proportional to its total iodinecontent and not to its variable proportion of thyroxine iodine. It seemspossible, therefore, that administered peptide-linked di-iodotyrosine may beconvertible into thyroxine in the body.Mecha,nisrn of Production of Thyroxine in vitro and in vivo.-Haringtonand Barger (1927) pointed out that thyroxine might be formed in vivo bythe coupling of two molecules of di-iodotyrosine, and this idea has recentlybeen developed by Johnson and Tewkesbury (1942) 26 to explain the form-ation of thyroxine by the prolonged incubation of di-iodotyrosine in alkalinemedium.These investigators recall that Pummerer eb aL30 oxidised p-cresol/ Y o x&(IIIa.) (IIIb.)PV.129 J. Pharm. Exp. Thsr., 1934, 1, 298.30 (a) R. Purnmerer, D. Melamed, and H. Puttfarehen, Ber., 1922, 55, 3116; ( b )R. Pummerer, H. Puttfarchen, and P. Schopflocher, W., 1925, 58, 1808YOUNG : HORMONES. 245with potassium ferricyanide in alkaline solution and obtained two mainproducts : a ketotetrahydrodibenzofuran derivative (IIIa ; R = MeX = H) and 2 : 2tdihydroxy-5 : 5’-dimethyldiphenyl (IV; R = Me, X = H).Yummerer explained the formation of (IIIa) as resulting from the rearrange-ment of the unstable quinonoid compound (11; R = Me, X = H), which,he suggested, was formed intermediately.Johnson and Tewkesbury pointedout that, if an analogous reaction is assumed for di-iodotyrosine, rearrange-ment of the intermediate quinonoid compound [I1 ; R = CH2*CH(NH2)*C02H(alanyl), X = I] to a stable tetrahydrodibenzofuran derivative cannot takeplace, being prevented by the presence of iodine atoms ortho to the phenolichydroxyl group. They suggest that the molecule may therefore stabiliseitself by splitting off the alanyl side chain attached to the carbon carryingthe ether oxygen, with the formation of thyroxine (IIIb; R = alanyl,X = I), and claimed to be able to identify pyruvic acid and ammonia amongthe products of the alkaline incubation of di-iodotyrosine, these presumablyhaving been formed by the decomposition of the discarded alanyl side chain.Subsequently W.W. Westerfeld and C. Lowe31 showed that the two com-pounds found by Pummerer et al. to be formed by the oxidation of p-cresolwith ferricyanide were also obtained by oxidation of this substance withhorseradish peroxidase and hydrogen peroxide.I n an interesting theoretical discussion of the mechanism of the reactionspostulated by Pummerer et al., Johnson and Tewkesbury, and Westerfeldand Lowe, Harington 2h considers the implications of the assumption thatp-cresol and di-iodotyrosine are oxidised in the form of the phenoxide ionand that the oxidation consists in the removal of an electron from the ion,followed by reaction of the free radial so formed.Harington points outthat the phenoxide ion would be expected to resonate among at least threestructures (V), (VI), and (VII), and that the oxidation of a p-substitutedphenoxide ion might be assumed to consist in the removal of one electronfrom the oxygen atom of form (V), giving (VIII), and from the carbon atomspara and ortho, respectively, to the carbon carrying the oxygen atom offorms (VI) and (VII), giving the corresponding free radicals (IX) and (X).With p-cresol the interaction of (VII) and (IX) would give (11; R = Me,R R R R R R\* I/\ /\\ : - I/\ A x /\I/\ 1x XI1 llx xll I/x x(Jx XI1 v Ilx x ( y - X(/ \/ \/.II(V.1 (VI.) (VII.) (VIII.) (IX.) (X., : OII: OI : o * II: OII.. .b.- .. .. : OX = H), which would rearrange to give (IIIa). Interaction of two moleculesof (X) would give (IV). With di-iodotyrosine (R = alanyl, X = I ) , com-pound (11), formed by the interaction of (VIII) and (IX), could not stabiliseas ( I I a ) owing to the presence of the iodine atoms ortho to the phenolic31 J . BioE. Chem., 1942, 185, 463246 BIOCHEMISTRY,hydroxyl group, and would therefore give (IIIb) (thyroxine). For similarreasons (IV), formed from p-cresol, would probably not arise fromdi-iodotyrosine.Chaikoff la suggests that the formation of both di-iodotyrosine andthyroxine by the thyroid gland is linked with aerobic oxidations in whichthe cytochrome-cytochrome oxidase system is involved, but E.W. Dempsey 32believes that peroxidase is present in the thyroid follicular cells and that thisenzyme may catalyse the conversion of di-iodotyrosine into thyroxine. It ispossible that hydrogen peroxide is formed in living cells by the action offlavoprotein systems, and any peroxidase present might catalyse the oxid-ation of iodide ions to free iodine and then assist the oxidation of the di-iodotyrosine, thus formed, to thyroxine. With milk, which contains theflavoprotein system xanthine oxidase, peroxidase, and the readily iodisableprotein casein, A. S. Keston 33 finds that the addition of xanthine as substratefor the xanthine oxidase system, together with a small amount of radio-iodine in the form of iodide ion, results in the rapid formation of organicallybound radio-iodine.This may provide a model for further investigationof the mechanism for the organic incorporation of iodine in animal cells.C. R. Harington 34 supports the simplest view, namely, that " the essentialbiochemical reaction leading to the synthesis of thyroxine may be the liber-ation of iodine from iodide by an oxidising enzyme system; if this were tooccur conditions would be set up, namely, the presence of iodine in a faintlyalkaline medium, which would not only be suitable for the iodination oftyrosine but would be analogous with those which . . . will effect the formationof thyroxine from di-iodotyrosine in vitro." 34 Certainly the ease withwhich thyroxine can be formed from tyrosine in witro in the absence of enzymesbut under physiological conditions not only emphasises the possibility thatthe formation of thyroxine from tyrosine and iodine, in the thyroid glandand elsewhere, may be a non-enzymic process but also allows considerationof the simplest hypothesis concerning the r61e of the thyroid, namely, thatthe primary function of this gland is the collection of circulating iodine.Goitrogenic Substances.-For many years the existence has been realisedof substances, both naturally occurring and artificial, which are capableof inducing enlargement of the thyroid gland on experimental administrationto animals, and until recently it has been accepted that the goitrogenicaction of such substances is neutralised by the addition of iodine to the diet.In 1941 J.B. MacKenzie, C. G. MacKenzie, and E. V. McCollum 35 reportedthat sulphaguanidine, employed to combat intestinal infection, produced aremarkable enlargement of the thyroid gland in the rat, and in the followingyear J. B. MacKenzie and C. G. MacKenzie showed that this goitrogenicactivity was shared by a series of sulphonamides and t h i ~ u r e a s . ~ ~ Thethyroid hypertrophy, which was accompanied by a fall in basal metabolic32 Endocrinology, 1944, 34, 27. 33 J . Biol. Chern., 1944, 153, 335.34 Proc. Roy. SOC., 1944, B, 132, 223. 35 Science, 1941, 94, 518.36 (a) Federation. Proc., 1942, 1, 122; ( b ) Endocrinology, 1943, 32, 185; ( c ) JohnsHopkins Hosp. Bull., 1944, 74, 86YOUNG : HORMONES.247rate, was not prevented by the administration of iodine but was inhibitedby the injection of thyroxine.36 These findings were quickly c0nfirmed,~7and analogous results with substituted thioureas 3 7 v 3 8 p 39 and natural goitro-gens reported. The thyroid hyperplasia induced by these goitrogens wasaccompanied by signs of increased activity of the anterior pituitary gland,and was lacking in hypophysectomised 3 7 1 The suggestionwas then made that these substances depressed thyroid hormone production,and that the thyroid hyperplasia was secondary to increased pituitaryactivity evoked by the About the same time it was observedthat the prolonged administration of potassium thiocyanate to humanbeings could induce the appearance of thyroid goitres, associated with a fallin basal metabolic rate,41 though the development of this type of goitre couldbe prevented by the administration of dietary iodine.Acting on the assumption that thiourea interferes with the productionof thyroid hormone E.B. Astwood 42 successfully treated clinical hyper-thyroidism by the daily administration of thiourea and showed that 2-thio-uracil also was effective. The therapeutic efficacy of this new treatment ofhyperthyroidism quickly received widespread confirmati~n,~~ and it wasshown also that the administration’ of thiourea or thiouracil to experimentalanimals duplicated the effects of thyroidectomy with respect to growth,44metabolism of isolated organ morphol~gy,~~ thyrotropin-induced373 7 ( a ) E.B. Astwood, J. Sullivan, A. Bissell, and R. Tyslowitz, Endocrinology.( c ) E. W, 1943, 32, 210;Dempsey and E. B. Astwood, Endocrinology, 1944, 32, 509.( b ) E. B. Astwood, J . Pharm. Exp. Ther., 1943, 78, 79;38 C. P. Richter and K. H. Clisby, Arch. Path., 1942, 33, 46.39 T. H. Kennedy, Nature, 1942, 150, 233.40 ( a ) W. E. Greisbach and H. D. Purves, Brit. J . Exp. Path., 1943, 24, 171 ; (b)V. I. E. Whitehead, ibid., p. 192.41 ( a ) It. W. Rawson, S. Hertz, and J. H. Means, J . Clin. Invest., 1942, 21, 624;(b) J. L. Kobacker, Ohio Sta. Med. J . , 1942, 38, 541 ; (c) M. P. H. Foulger and E. Rose,J . Arner. Med. ASSOC., 1943, 122, 1072; ( d ) R. W. Rawson, S. Hertz, and J. H. Means,Ann. Int. Med., 1943, 19, 829.4 2 J .Amer. Med. ASSOC., 1943, 122, 78.4 3 ( a ) R. H. Williams and G. W. Bissell, New England J. Med., 1943, 229, 97; (b)H. P. Himsworth, Lancet, 1943, ii, 465; ( c ) R. W. Rawson, R. D. Evans, J. H. Means,W. C. Peacock, J. Lerman, and R. E. Cortell, J . Clin. Endocrinol., 1944, 4, 1 ; ( d ) P. B.Newcombe and E. W. Deane, Lancet, 1944, i, 179; (e) J. L. Gabrilove and M. J. Kert,J . Arner. Med. ASSOC., 1944, 124, 504; (f) E. C. Bartels, ibid., 1944, 125, 24; (9) K. E.Paschkis, A. Cantarow, A. E. Rakoff, A. A. Walking, and W. J. Tourish, J . Clin.Endocrinol., 1944, 4, 179; (h) R. H. Williams and H. M. Chute, New England J . Med.,1944,230,657 ; (i) E. B. Astwood, J. Clin. Endocrinol., 1944,4,229 ; (j) T. H. McOavick,A. J. Gerl, M. Vogel, and D.Schwimmer, ibid., p. 249; ( k ) F. L. Ritchie and B. L.Geddes, Med. J. Aust., 1944, 1, 381 ; ( 1 ) M. H. Sloan and E. Shorr, Endocrinology, 1944,35, 200; (m) E. B. Astwood, ibid., p. 200; ( n ) H. P. Himsworth, C. A. Joll, H. Evans,G. Melton, and S. L. Simpson, Proc. Roy. SOC. Med., 1944, 37, 693; (0) E. M. Martin,Canadian Med. Assoc. J . , 1944, 51, 39; ( p ) J. K. McGregor, ibid., p. 37; ( q ) E. M.Watson and L. D. Wilcox, ibid., p. 29.4 4 ( a ) A. M. Hughes, Endocrinology, 1944, 34, 69; ( b ) R. H. Williams, A. R. Wein-glass, G. W. Bissell, and J. B. Peters, ibid., p. 317.4 5 B. J. Jandorf and R. E. Williams, Arner. J . Physiol., 1944, 141, 91.4 6 C. P. Leblond and H. E. Hoff, Endocrinology, 1944, 35, 229248 BIOCJHEMISTRY.metamorphosis of tadpoles,47 development of fish,48 pigmentation of birdand insulin ~ensitivity.~~ Thiouracil has also been successfullyemployed in an evaluation of the amount of thyroxine secreted by the thyroidgland under different condition^.^^ These results all support the view thatthioureas and thiouracil inhibit the formation of its hormones by the thyroidgland, but do not interfere with the action of the hormone once it has beenliberated into the blood stream.Mechanism of the Action of Thiouracil and of Other Qoitrogens on theProduction of Thyroid Hormone.-The daily administration of thiouracil toyoung rats for 8 days reduces the iodine content of the thyroid gland almostto zero, though the weight of the gland may be increased nearly threef~ld.~lIf the daily administration of thyroxine is now begun, with continuation ofthiouracil treatment, the iodine content of the gland remains low but thefollicles fill with densely staining colloid 51 Similar results followthe removal of the pituitary gland during thiouracil administration.51 Itseems that under these conditions the secreted colloid material containslittle or no t h y r ~ x i n e , ~ ~ .~ ~ and that the incorporation of iodine into thismaterial has been inhibited by the thiouracil.When radio-iodine is injected into rats previously made goitrous by theadministration of thiouracil, the power of the thyroid gland to collect theadministered iodine may be only 10-20y0 of 53e 54 and the form-ation of di-iodotyrosine and of thyroxine is also inhibited.53 The capacityof thiocyanate-induced goitres to collect administered radio-iodine may besupernormal, however,52 a finding which is significant in view of the factthat thiocyanate is an iodine-inhibited goitrogen.A.L. Franklin, I. L. Chaikoff, and S. R. Lerner 55 found that the addition,to the medium in which surviving. slices of thyroid tissue were maintained,of 10-3~-thiouracil, or of a like concentration of thiourea or of potassiumthiocyanate, depressed the ability of the tissue to convert added radio-iodineinto di-iodotyrosine and thyroxine. This concentration of thiourea and ofthiouracil had little effect on the capacity of the slices to collect iodine fromthe medium, although potassium thiocyanate in a similar amount signifi-cantly diminished the collection of added radio-iodine. The latter resultsare a t variance with the data from intact animals cited above.Sulphanil-amide also depresses the formation of di-iodotyrosine and thyroxine in slices4 1 A. M. Hughes and E. B. Astwood, Endocrinology, 1944, 34, 138.48 E. D. Chldsmith, R. F. Nigrell, A. S. Gordon, H. A. Charipper, and M. Gordon,49 RI. Juhn, ibid., p. 278.60 G. J. Martin, Arch. Biochern., 1943, 3, 61.61 E. B. Astwood and A. Bissell, Endocrinology, 1944, 34, 282.52 (a) R. W. Rawson, J. F. Tannheimer, and W. Peacock, ibid., p. 245; ( 6 ) R.Larson, F. R. Keating, jun., R. W. Rawson, and W. Peacock, ibid., 1944, 35, 200; (c)R. TY. Rawson, R. E. Cortell, W. Peacock, and J. H. Means, ibid., p. 301.ibid., 1944, 55, 132.53 A.L. Franklin, S. R. Lerner, and I. L. Chaikoff, ibid., 1944, 34, 265.54 (a) E. J. Baumann, N. Metzger, and I). Marine, ibid., p. 44; (b) A. S. Keston,5 5 I b i d . , 1944, 153, 151.E. D. Goldsmith, A. S. Gordon, and H. A. Charipper, J. Biol. Chem., 1944,153, 241YOUNG : HORMONES. 249of thyroid tissue, without depressing the capacity of the slices to collectiodide from the medium.laI 66As was suggested above (p. 241), the simplest hypothesis regarding thespecific function of the thyroid is that this gland possesses special ability tocollect iodine from the circulation. Since free iodine is presumably theiodinating agent in the formation of di-iodotyrosine from tyrosine, and sinceiodide ions constitute the form in which this element is collected from theblood stream, it seems probable that the first process which the collectediodide ions undergo is enzymic oxidation to free iodine.Inhibition of thisprocess might not only inhibit the formation of di-iodotyrosine and thereforethat of thyroxine but also depress the power of the gland to collect moreiodide. D. Campbell, F. W. Landgrebe, and T. N. Morgan 67 recall E. A.Werner's observation 58 that free iodine can oxidise thiourea to formamidinedisulphide, NH:C(NH,)*S*S*C(NH,):NH, being itself reduced to iodide ionsin the process, and suggest that this may be a mechanism whereby thioureamight interfere with the synthesis of the thyroid hormone. Another possi-bility is that thiourea and other similar goitrogens inhibit the adtion of anenzyme which catalyses the formation of iodine from iodide in the thyroidgland.Thiouracil does not poison cytochrome o ~ i d a s e , ~ ~ though cytochromeoxidase inhibitors do prevent the formation of thyroxine from inorganiciodide in surviving slices of thyroid tissue.18 Thiouracil poisons per-oxidase 32e 59 and polyphenol oxidases 60 and protects p-cresol against enzymicoxidation when present molecule for molecule of substrate.60 Dempseybelieves that, although peroxidase may be concerned in the formation ofiodine &om iodide in the thyroid gland, this enzyme also catalyses the con-version of di-iodotyrosine into thyroxine.32 This belief is based on theobservation by Dempsey and Astwood 37 that di-iodotyrosine, unlikethyroxine, does not prevent the goitrogenic action of thiouracil, the assump-tion being made that thiouracil must therefore inhibit the conversion ofdi-iodotyrosine into thyroxine.Since, however, the thyroid gland appearsto be unable t o utilise administered di-iodotyrosine, for the formation ofthyroxine, in the absence of goitrogenic agents,4* 43 the assumption wouldappear on the available evidence to be of doubtful validity.It may be concluded that thiourea and thiouracil interfere with the form-ation of iodine from iodide ions, either by reducing any iodine formed baokto iodide ions, or by poisoning the enzyme system catalysing the oxidationof iodide ions t o iodine. Whether or not these goitrogens interfere in anyother way with the formation of thyroxine in the body is as yet uncertain.Nature of the Thyroid Hormone.4anzanelli et aZ.61 found that the addi-tion of thyroglobulin, but not of thyroxine, to tissues respiring in vitro'' A.L. Franklin and I. L. Chaikoff, J . Biol. Ch~m., 1943, 148, 719; 1944, 152, 295.5 7 Lancet, 1944, i, 630.J. B. Sumner and G. F. Somers, " Chemistry and Methods of Enzymes," Academics* J., 1912, 101, 2166.Press lnc., New York, 1943.6o F. Chodat and G. Duparc, Helv. Chim. Acta, 1944, 27, 334.(a) A. Canzanelli and D. Rapport, Endocrinology, 1937,2l, 779; (b) A. Canzanelli,R. Guild, and D. Rapport, &id, 1939,25, 707250 BIOCHEM.1STRY.increases the rate at which oxygen is taken up, and a stimulating action ontissue respiration in vitro has also been observed with plasma from patientswith hyperthyroidism.62 These observations suggest that thyroglobulinmight be the circulating thyroid hormone, but immunological tests fail toreveal the presence of this protein in the blood stream under a variety ofOnly under such anabnormal condition as thyroid trauma was thyroglobulin detected in theblood stream 63 and it seems probable that thyroglobulin as such does notnormally leave the thyroid follicles.Proteolytic enzymes are present inthe thyroid gland, and their activity varies under physiological conditions 65and the hydrolysis of thyroglobulin to a less complicated thyroxine-contain-ing molecule is probably a preliminary step in the secretion of the thyroidhormone. Harington, whose earlier results suggested that the secretion ofthe thyroid gland might be a thyroxine-containing peptide rather thanthyroxine itself, has recently reviewed the evidence on this point34 andconcludes that there is no satisfactory reason to abandon the simplesthypothesfs, namely, that thyroxine itself is the circulating hormone.AsHarington and his colleagues had earlier shown,66 the administration to ratsof antisera raised against thyroxyl derivatives of horse-serum aIbumin andglobulin confers resistance against the usual metabolism-increasing activityof administered thyroxine or thyroglobulin. That the administration ofthese antisera was without effect on the metabolic rate of the treated rats,though such treatment prevented the normal action of administered thyroxineand thyroglobulin, was explicable on the basis of the great power of thenormal thyroid gland to respond to a call for increased secretory activity.66Harington34 suggests that the simplest explanation of the facts is that thecirculating antibodies of the passivity immunised animal, possessing sero-logical combining sites adapted to thyroxine, interfere with the access of thelatter to its normal sites of action in the tissues, so that it is most probablefhat the injected thyroxine is present as such in the circulation.He pointsout that this simple interpretation can be avoided only by the assumptionthat injected thyroxine follows the devious route of synthesis into thyro-globulin, followed by release as such (which seems on other grounds to beunlikely) or as a peptide, which is the real hormone, and such a complicatedprocess is a t least unnecessary to account for the immunological phenomenaobserved.34 Harington concludes that thyroxine is " the true thyroidhormone as it circulates in the body." 34 J.H. Means 6' in another recentreview concludes that " the thyroid hormone travels from the thyroid to itsend-organs in a form lower than the protein level, and that it acts upon itsend-organ in a form of higher level than that of the amino-acids. It may64 including that of hyperthyroidi~m.~~W. T. Salter and F. W. Craige, J . Clin. Invest., 1938, 27, 502.J. Lerman, ibid., 1940, 19, 555.64 L. I. Stellar and H. G. Olken, Endocrinology, 19.10, 27, 614.65 A. J. Dziemian, J . Cell.Comp. Physwl., 1943, 21, 339.G6 R. F. Clutton, C. R. Harington, and M. E. Yuill, Biochem. J . , 1938,32, 11196 7 Ann. Int. Med., 1943, 19, 567YOUNG : HORMONES. 251both travel and act in the form of a polypeptide or peptone,” 67 a conclusionalso compatible with the immunological evidence provided by Harington.If one accepts as significant the observation that thyroxine fails to stimulatetissue respiration in vitro whereas thyroglobulin and plasma from patientswith hyperthyroidism are effective under these 62 the simplestexplanation of all the available evidence, including the results of the immuno-logical investigations, appears to be that thyroxine stimulates tissue respir-ation only when it is combined in peptide form, and that it is transportedfrom the thyroid tissues to the gland in this form.In the sea, the liberation of iodine from iodine ions might occur on aminute scale wherever the oxidative catalysts of respiring cells of unicellularorganisms were active.Thus the tissue proteins of a primitive protozoonmight, as the result of the oxidative capacity of its enzyme systems, come tocontain organically bound iodine, in the form of thyroxine, with the aid ofthe mechanisms reviewed above. With Means 67 we may conclude that theelaboration of the thyroid hormone preceded that of the thyroid gland inthe process of evolution, and that the gland developed as an organ specialisedfor the production and subsequent distribution of a substance which originallywas produced in the tissues in general, and which, even in higher animals,can still be made in tissues other than that of the thyroid.Thyroxine, in acombined form, may therefore be a general constituent of living protoplasm,essential for the maintenance of respiration a t the high level which is char-acteristic of the cells of the highly developed metazoon. That being so, wemight regard thyroxine not as a specific internal secretion of one ductlessgland, but as an essential amino-acid.In some respects the position with respect to choline also is analogous.Choline is an essential constituent of the normal body and the body isapparently able to manufacture all but one portion of the molecule of thisimportant substance, namely, the methyl groups. Provided that a sourceof exogenous methyl groups is available to the body, e.g., from methionine,choline can be manufactured in sufficient amount for its particular require-ments, though otherwise this substance becomes an essential food factor andqualifies for the description of vitamin.Similarly, the only portion of thethyroxine molecule that the body cannot provide from its own resources-tyrosine is not an essential amino-acid-is iodine, and once free iodine isavailable the manufacture of thyroxine can proceed. In higher animals thepresence of the specialised thyroid gland is essential if the rate of collectionof iodine and thyroxine production are to keep pace with the demand forthis amino-acid, but in lower animals the tissues in general can probablyproduce in situ all they need, provided that the essential constituent is tohand.As Means points 0 ~ t , ~ 7 man could live happily without a thyroidgland if his food proteins were properly iodinated, and it is true to say thatto the higher animals from which the thyroid gland has been removedthyroxine, or ,z thyroxine-containing iodinated protein, has become anessential constituent of the diet, and might therefore be regarded as a vitaminfor such an animal252 BIOUHEMISTRT .Thyroxine, or a compound containing it in peptide linkage, can beregarded as a hormone. But such a description does not preclude thepossibility of regarding it, from Some points of view, as an essential amino-acid, or as a vitamin or coenzyme. Once more the overriding of boundarieswhich were once thought to divide different departments of scientific activitymay be regarded as the natural concomitant of progress and development.F.G. Y.4. NUTRITION.The excretion of methylated derivatives of nicotinic acid, the relationof pyridoxine to haematopoiesis and iron metabolism, and the nutritionalvalue of “ folio acid ” and vitamin B,, are reviewed in this section.The Excretion of Nicotinic Acid.described the presence in urineof a substance with a characteristic blue fluorescence, which they called F,.Its excretion was related to the availability of nicotinic acid and increased inproportion to the nicotinic acid intake. In view of the uncertainty of theform taken by the substance in urine, the symbol F, is a convenient means ofdenoting it.F, is absent from the urine of pellagrins2 and it slowly dis-appears from the urine of dogs fed upon a nicotinic acid-deficient diet,3whereas the administration of nicotinic acid or its derivatives increases itse ~ c r e t i o n . ~ . ~ The chemical nature of F, has been elucidated and the sub-stance has been isolated as waxy, hygroscopic, needle-shaped crystals, whichin neutral or weakly alkaline conditions have a greenish-blue fluorescence,and in acidic solution a blue.6e7e A substance identical in physical andchemical properties can be obtained by the treatment of nicotinamidemethiodide with baryta. It is .well known that alkalinisation of such acompound (I) will lead to the formation of a quaternary base (11), whichsubsequently may suffer transformation into a carbinol (111) by attachmentof the hydroxyl group to one of the a-positions of the pyridine ring :/NCO*NH, jf\)CO*NH, ./\ CO *NH, /\CO*NH,In 194-0 V. A. Najjar and R. W. WoodA LN)OH A It )O*C,H, \Nf’ Y - ‘NI1 I \Nf/ I’ ,/ OH’ / /c*3 CH3 CH3 CH,w.1 (111.) (11.1 (1.1* 1 PTOC. SOC. Exp. Biol. Med., 1940, 44, 386.2 V. A. Najjar and L. E. Holt, Science, 1941, 93, 20.3 V. A. Najjar, H. J. Stein, L. E. Holt, and C. V. Kabler, J. Clin. Invest., 1942,21,263.6 P. Ellinger and R. A. Coulson, Bwchem. J., 1944, 88, 266.6 J. W. Huffand W. A. Perlzweig, Science, 1943, 97, 538; J . Biol. Chem., 1943,150,7 P. Ellinger and R. A. Coulson, Nature, 1943, 152, 583; Biochem. J., 1943, 37,* V. A. Najjar, V. White, and D.B. N. Soott, Bull. Johns Hopkins H08p., 1944, 74,V. A. Najjar and L. E. Holt, PTOC. SOC. Exp. Bwt. M d . , 1941, 48, 413.395.Proc. xvii.378O'BRIEN : NUTRITION. 253It would appear that the subetance actually isolated from urine is the car-binol. But it is uncertain 697, * whether the fluorogenic substance in urineis the quaternary base, the #-base, a pyridinium salt, or a mixture of thesedependent upon the conditions. The fluorescence observed in vitro is con-sidered' to be due to a mixture of 6-hydroxy-l-methyl-1 : 6-dihydro-pyridine-S-carboxyamide and another carbinol with an o-quinonoid structure.Atmospheric oxygen and ferricyanide oxidise an alkaline solution of F2.8This treatment, which leads to a deep violet fluorescence, might be expectedto cause the formation of a pyridone from the base.An alternative possi-bility is that the fluorescence is due to the formation of a carbinol ether (IV)from the #-base and the isobutanol used to extract F,. Either suggestionwould explain the slow increase in fluorescent intensity of isobutanol extractof F, from alkaline solutions.Upon the fluorescence of the derivative of the pyridinium salt have beenbased methods for its estimation in urine.gDIO,ll The essential feature ofsome of them is a base exchange between the substance and permutit. Theuse of these methods has shown that there is a distinct individual variationand a fluctuation throughout the day in the excretion of F,.5 The pro-portionality between the amount eliminated and the intake of nicotinamidehas led naturally to the development of load tests for gauging nutritionalstatus as regards nicotinamide.Investigation of this kind of test hasdiminished the value of trigonelline excretion as a nutritional index, sinceits determination may include the pyridinium salt, which on acid or alkalinehydrolysis is converted into trigonelline.6s 12 Nevertheless as a nutritionalindex the excretion of F, will need to be used with careful discrimination.Its dependence on the body reserves of methyl donators whose level dependsupon the diet, has been indlcated.12 This view is well attested by experi-ments upon rats, guinea-pigs, and rabbits.13n 14- l5 The feeding of unusualamounts of nicotinamide to rats adversely affected their growth and theirlivers-effects which could be remedied by choline or methionine.Inguinea-pigs and rabbits no ill effects arise from the ingestion of large amountsof nicotinamide. There is a clear difference in the response of these animalsto nicotinamide. The rat excretes the N-methylnicotinamide in the urine ;the rabbit and the guinea-pig do not. Methylation of nicotinamide has beendemonstrated in vitro with rat liver slices.16 A consequence of a high levelof nicotinamide in the diet of the rat is a depletion of its store of methyldonators, the sequels of which are retarded growth and fatty livers. Thereverse of this, diminished stores of methionine and choline from faulty dietcreating low excretion of F,, is thus conceivable.* V.A. Najjar, Bull. Johns Hopkins Hosp., 1924, 74, 392.lo R. A. Coulson, P. Ellinger, and M. Holden, Biochem. J., 1944, 38, 150.l1 J. W. Huff and W. A. Perlzweig, J . Biol. Chem., 1943, 150, 483.l2 H. P. Sarett, ibid., p. 395.l3 P. Handler and W. J. Dann, ibid., 1942,146, 357.l4 P. Handler and F. Bernheimer, J . Biol. Chem., 1943,148, 849.l6 P. Handler, ibid., 1944, 154, 203.W. A. Perlzweig, M. L. C. Bernheim, and F. Bernheim, ibid., 1943,150 401254 BIOCHEMISTRY.The Relation of Pyridoxine to Ancemia.In the last decade accumulative evidence has indicated that deficiencyof the B vitamins, particularly pyridoxine and nicotinic acid, may interruptnormal erythropoiesis. Mention in this review is confined to work of recenttimes, which attempts to define clearly the type of anzmia from blood andbone marrow investigations.The most careful work upon the effect ofpyridoxine deficiency has been done on the pig and the dog.I n dogs a hypochromic anaemia would seem to be a feature of deprivationof vitamin B6.17~18119~20 The anaemia does not respond to iron or copper;yet prompt improvement follows oral or intravenous administration ofcrystalline pyridoxine. The fact that the initial improvement is not alwaysmaintained has led to the suggestion that other factors may beWith progressing severity of the anaemia the plasma iron rises, and rapidlyfalls with the administration of pyridoxine and with the initial bloodregeneration.22I n 1938 Chick and her collaborators 23 showed that omission of the eluatefraction of a liver concentrate, a source of pyridoxine, from a synthetic dietled to a microcytic anaemia and epileptic fits in young pigs.I n pigs lackingthe filtrate fraction a normocytic anaemia developed. Wintrobe and hisco-workers 24v 2 5 9 26 found that pigs fed on a diet supplemented with vitamins Aand D and all the known crystalline B vitamins except pyridoxine developa severe microcytic anaemia which is most clearly hypochromic at its height.As the anaemia progresses, anisocytosis becomes more marked ; large poly-chromatophilic corpuscles and cells containing blue-staining granules makean appearance. An irregular reticulocytosis may also occur. The anzmiais associated with hyperplasia of the bone marrow and an irregular reticulo-cytosis.The ansmia is not haemolytic in type ; no significant changes occurin the serum bilirubin or in the excretion of urobilinogen or urinary porphyrin.Fatty infiltration of the central portion of the hepatic lobules also occurs.Epileptiform convulsions are seen in the majority of B6-deficient pigs. Anoutstanding feature was haemosiderosis of the spleen, liver, and bone marrowand an increase in the serum iron, which is apparently chiefly in the ferric197.l7 P. J. Fouts, 0. M. Helmer, S. Lepkovsky, and J. H. Jukes, J . Nutrition, 1938,16,l8 Idem, Amer. J . Med. Sci., 1943, 199, 163.l9 H. J. Borson and S. R. Mettier, Proc. SOC. Exp. Biol. Med., 1940, 43, 429.2o H. R. Street, G. R. Cowgill, and H. M. Zimmerman, J . Nutrition, 1941, 51, 275.21 Idem, ibid., p.275.J. M. McKibbin, A. E. Schaeffer, D. V. Frost, and C. A. Elvehjem, J . Biol. Chem.,23 H. Chick, J. F. Macrae, A. J. P. Martin, and C. P. Martin, Biochenb. J., 1938, 32,24 M. M. Wintrobe, M. Samter, and H. Lisco, Bull. Johns Hopkins Hosp., 1939, 64,25 M. M. Wintrobe, R. H. Pollis, M. H. Miller, H. J. Stein, R. Alcayago,26 G. E. Cartwright, M. M. Wintrobe, and S. Hymphreys, J . Biol. Chem., 1944,1942, 142, 77.2207.399.S. Hymphreys, A. Suksta, and G. E. Cartwright, ibid., 1943, 72, 1.153, 171O’BRIEN : NUTRITION. 255state. Administration of pyridoxine produced a rapid regeneration of bloodwith a return of the red cells to normal size. This response was accompaniedby a niobilisation of iron, which was indicated by the disappeafance of thehaemosiderosis and a fall in the serum iron.These interesting results clearlyimply a r81e for pyridoxine in iron metabolism. From the fact that in com-bined pyridoxine and iron deficiency no hsmosiderosis or elevated serumiron occurs despite the development of anaemia, it would appear that thedisturbances in iron metabolism are due to increased absorption or decreasedexcretion. This is an interesting possibility, since it is contrary to the ideathat the animal absorption of iron is dependent upon its needs. In manyrespects-the ferrsmia, haemosiderosis, hyperplastic bone marrow andneurological disturbances-the pyridoxine anaemia is similar to perniciousansmia, although it differs in being characterised by a microcytosis and lackof response to liver extract.IYevertheless the study of the mechanism ofBs ansmia may provide some help towards the solution of perniciousanBmia.The possible relationship of the ansmia and kindred symptoms ofvitamin B,-deficiency with tryptophan metabolism has been referred to inDr. Ncuberger’s Report (p. 237).Folk Acid and Vitamin B,.During the last four years it has become evident that certain micro-organisms need for their growth one or more factors distinct from any of theknown vitamins. It has also become apparent that these factors have a r6lein animal nutrition which consists, in the main, in promoting growth, counter-ing the effect of sulphonamides, and in stimulating the formation of the cellsof the blood.I n 1940 E. E.Snell and W. H. Peterson 27 described a factor of acidicnature needed by Lactobacihs msei E ; to it they gave the name norit eluatefactor. From spinach concentrates another acidic factor, named folic acid,was prepared,2* defined as the material necessary for the growth of Xtrepto-COCCUS Zuctis R on a given medium. This nutrilite is abundant in green leavesand occurs in animal tissues and yeast.Williams and his co-workers 29,30131 have now obtained folic acid inamorphous form from spinach. It’is a substance of M.W. about 400, noteasily soluble in organic compounds and extremely labile. Esterification,acylation and methylation destroy its biological activity. It is also sensitiveto oxidation and reduction, and is none too stable in acid or alkaline solution.From analysis it has an approximate empirical formula of Cl,Hl,08N5 andabsorption spectra indicate that it may contain a structural unit similar toxant hop terin .322 7 J .Bact., 1940, 39, 273.29 Idem, ibid., 1944, 66, 267.30 E. H. Frieden, H. K. Mitchell, and R. J. Williams, ibid., p. 269.3 1 H. K. Mitchell, and R. J. Williams, ibid., p. 271.32 H. K. Mitchell: ibid., p. 275.H. K. Mitchell, E. E. SneII, and R. J. WilIiams,J. Amer. Chem. SOC., 1941,63,2288.1256 BIOUHEMISTRY.From most of the work on concentrates it would appear that the noriteluate factor and folic acid are either the same substance or closely similarcompounds: Concentrates of folic acid are active in stimulating the growthof yeast and other organisms, including Lactobacillus casei, and B, L.Hutch-ings, N. Bohonos, and W. H. Peterson have concluded33 that the eluatefactor was similarly of general nutritional significance for the lactic acidbacteria and the growth of Streptococcus Zuctis, From descriptions 31n34 ofconcentrates of folic acid it would appear that, together with folio acid, othersubstances of biological importance are present ; these include p-amino-benzoic acid and xanthopterin, which are capable of counteracting theinhibitory effect of sulphonamides upon the growth of bacteria and rats.The fact that concentrates prepared from different sources stimulate thegrowth of Lactobacillus casei and Streptococcus Zuctis probably led to theinterchangeable use of the terms folic acid and eluate factor.The term" folic acid " may therefore be used to indicate this group of growthstimulants .On animals, concentrates of the eluate factor and folic acid exert effectswhich may be attributable to similar groups of substances. In the chick,SSeluate factor has been found to promote growth; in the rat, folic acid.Z8Concentrates of both factors share with p-aminobenzoic acid the property ofantagonising the noxious effects of sulphonamides, sulphaguanidine andsulphathiazole, which are poorly absorbed from the intestine. Besides pro-ducing a reduction in growth ,86 sulphonamides may cause agranulocytopenia,leucopenia, and often ana?mia and other pathological conditions when theyare incorporated in synthetic diets adequately supplied with ~itamins.~'Their action may be partly due to an interference with enzyme sptems ofthe body or to suppression within the intestine of bacterial synthesis ofessential factors ; folic acid 38 and biotin are synthesised by intestinalbacteria.Both biotin and concentrates of the eluate factor and folk acidcounteract the growth inhibition which is produced by sulph~namides.~~Biotin and folic acid also appear to influence the utilisation of pantothenicacid by the rat. On diets abundantly supplemented with pantothenate andcontaining succinyl sulphathiazole, rats developed the characteristicsymptoms associated with deficiency of this vitamin.40 This change wascorrected by the administration of folic acid and crystalline biotin. Althoughagranulocytopenia and leucopenia, produced in rats by feeding sulphon-amides, respond to crystalline folic acid from different sources,41 the effectof concentrates upon growth and blood formation may not be due solely to33 J .Bid. Chem., 1941,141, 521.35 B. L. Hutchings, N. Bohonos, D. M. Hegsted, C. A. Elvehjem, and W. H. Peterson,36 S. Black, R. S. Overman. C. A. Elvehjem, and K. P. Link, ibid., 1942, 146, 137.37 F. S. Daft, S. S. Ashburn, and H. H. Sebrell, Science, 1942, 96, 322.38 H. K. Mitchell and E. R. Isbell, Univ. Texas Pub. No. 4327, 1942, 125.39 E. Nielsen and C. A. Elvehjem, J. Bid. Chem., 1942, 145;. 713.40 L. D. Wright and A. D. Welch, Science, 1943, 97, 423.4 1 F. S. Daft and W. H. Sebrell, Pub. Health Reps. U.S.A., 1943, 68, 1542.3d H.K. Mitchell, Science, 1943, 97, 442.J . Biol. Chem., 1940, 140, 647O’BRIEN : NUTRITION. 267their folic acid content. I n concentrates obtained from liver, Elvehjem andhis co-workers 42 claimed to have identified a growth factor, vitamin Bll,and a faotor necessary for good feathering in chicks, vitamin Blo, in additionto folic acid. In several respects the properties of vitamins KO and Bllare akin to those of folic acid.In 1940 A. G. Hogan and E. M. Parrott 43 observed that on simplifiedrations chicks developed a macrocytic hypochromic ansmia whioh wasattributed to the lack of a dietary factor, vitamin B,, present in aqueousextracts of liver. A greater incidence of anzemia in chicks is produced byfeeding sulphaguanidine.u Vitamin B, is insoluble in organic solvents,more stable in alkali than in acids, adsorbable on fuller's earth and super-filtrol, and precipitable with metallic salts and phosphotungstic acid 44-properties, in fact, similar to those of folic acid and the eluate fwtor.Itsantianzmic action could not be reproduced by xanthopterin or by the anti-pernicious anaemia factor. Vitamin Bc has now been obtained in the crystal-line form both as the free acid and as the methyl ester.45 Incorporated in asynthetic diet amply supplemented with all the known vitamins, the crystal-line substance prevented retardation in growth (both body weight andfeathering) and the development of anzmia and leucopeniaj6 Givenparenterally, it produced the same effects.46 This observation has beentaken to indicate that vitamin B, produces those effects which have beenclaimed for folic acid and vitamins B,, and Bll.Furthermore vitamin B,was highly active as a growth stimulant for Lactobacillus casei E. This ledto the suggestion that vitamin B,, the norit eluate factor and folic acid arethe same substance.The isolation of other crystalline substances has complicated rather thanclarified the relationship among the microbial and the animal factors. Twocrystalline compounds have been obtained; one from yeast and the otherfrom liver.47 Both are acids with similar absorption spectra and highlyactive towards Lactobacillus casei. There is a striking difference in theiractivities ; towards Lactobacillus casei they are equally active, towardsStreptococcus lactus R the yeast product is half as active as the liver one.Contrary to the behaviour of these crystalline acids, certain concentratesshow activities greater towards Streptococcus than Lactobacilhs. Thesefacts can be harmonised by assuming the existence either of two or moresubstances or of different forms of oneSubstance.In milk and in yeast folicacid may be present in a combined form, inactive to the two micro-organism%.Whole milk is more effective in inhibiting the harmful action of sulphon-4a G. M. Briggs, T. D. Luckey, C. A. Elvehjem, and E. B. Hart, J. BWZ. Ohm., 1943,148, 163; 1944,153, 423.43 Ibid., 1940, 132, 507.I4 B. L. O’Dell and A. G. Hogan, ibid., 1943, 149, 323.J. J. Pfiffner, S. B. Binkley, E. S. Bloom, R.A. Brown, 0. D. Bird, A. D. Emmett,46 C. J. Campbell, R. A. Brown, and A. D. Emmett, J . BWZ. Chem., 1944, 152, 483;47 E. L. R. Stokstad, ibid., 1943, 149, 573.A. G. Hogan, and B. L. O’Dell, Science, 1940, 97, 404.164, 721.REP. VOL. XLI. 258 BIOCHEMISTRY.amides upon rats than would be expected from its low folic acid content.48Yeast extracts have a high vitamin B, activity and low microbiologicalactivity. When submitted to enzymatic hydrolysis, they stimulate thegrowth of the micro-organisms. From such extracts by the same method asthat used in the isolation of the antianzcmic factor, a crystalline compoundhas been obtained which contains the same percentage amount of carbon,hydrogen, and nitrogen as vitamin B,.4g The individualisation of combinedforms of this vitamin and the bacterial growth factors will be an importantstep towards an explanation of the discrepancies which have been observedin the microbial activities of different materials.It may also elucidate therelation of folic acid and vitamin R, to vitamins B,, and Bll.It is too early to say how important the pterins may be in animal nutritionand lack of space prohibits their inclusion here. J. R. P. O’B.5. THE ASSAY OF VITAMINS B, WITH SPECIAL REFERENCE TOMICROBIOLOGICAL METHODS.The necessity of establishing nutritional requirements and levels forvitamins of group B has stimulated investigations of assay methods, and greatstrides have been made in recent years. These methods are of three maintypes : biological, microbiological, and chemical ; and each has its difficultiesand objections.Ideally, the three methods should be so developed thateach furnishes an accurate check on the others. The development of assaymethods provides an interesting example of modern collaborative work ;a number of teams in this country and the United States are engaged in thismanner, and some examples are quoted later.Aneurin.-The stimulatory effect of aneurin on fermentation by livingyeast has been shown to be highly .specific and formed the basis of one ofthe first microbiological methods for the assay of the vitamin as describedby A. S. Schultz, L. Atkin, and C. N. Frey.1 have foundthat by sulphite treatment the fermentation activity of aneurin is completely(99%) destroyed, whilst interfering substances are unaffected.The authorsdescribe a differential method, employing a new fermentometer, in which themeasurement of fermentation activity is determined before and after sulphitetreatment.H. H. Bunzel13 employs the same principle, but a different type ofapparatus. Results are obtained more rapidly and are accurate for amountsof the vitamin as small as 0.01 pg. A modified Warburg technique isdescribed by E. S. Josephson and R. S. Harris.*There is in general good agreement between results by the microbiologicaland the chemical methods, but sometimes differences are observed whenbiological assays are compared. reported48 A. D. Welch and L. D. Wright, Science, 1944, 100, 153.‘ 9 S. B. Binkley, 0. D. Bird, E.S. Bloom, R. A. Brown, D. G. Calkins, C. J. Campbell,a Ind. Eng. Chem. Anal., 1942,14,35.These authorsJ. C. Moyer and D. K. TresslerA. D. Emmett, and J. J. Pfiffner, ibid., p. 36.J . Amer. Chem. SOC., 1937,59,948,3547.Ibid., p. 279. Ibid., p. 755. Ibid., p. 788NORRIS : THE ASSAY OF VITAMINS B. 259assays on a number of frozen vegetables in which they used fermentationand thiochrome methods successfully. in astudy of aneurin in the materials and process of brewing found good agree-ment between results by the fermentation method and the thiochromemethod as described by R. G. Booth.7 Similar satisfactory comparisonswere made in a collaborative study by the Accessory Food Factors Com-mittee of the Medical Research Council8 in which flours and bread wereassayed by several biological methods, the fermentation method, the thio-chrome method and an azo method elaborated by B.S. Platt and G . E.A number of workers have reported assays using other organisms,including Phycomyces,lOI l1 Phycomyces bhkesleeanus,l2- l4 and Staphylococcusa u ~ e u s . ~ ~ These methods, however, have been criticised by C. F. Niven andK. L. Smiley l6 on various grounds. The authors claim that Streptococcussalivarius (Strain S20B) is more suitable. The growth response is deter-mined turbidimetrically, and owing to the extreme sensitivity of the organismno difficulty is experienced due to incidental turbidity of added food extracts.Co-carboxylase is some 40% more active than aneurin, a fact which has notyet found explanation, and which renders enzymatic hydrolysis necessaryfor precise determinations in some foods.The stability of aneurin to heat has been studied by B.W. Beadle, D. A.Greenwood, and H. R. Kraybill.17 Stability is a function not only of thehydrogen-ion concentration of the solution, but also of the particularelectrolyte system employed. Results were obtained by chemical andspectrographic examination and indicated that for a heating period of onehour at pH 5.4, there was 100% destruction a t the boiling temperature inthe presence of borates, as compared with 57% in unbuffered solution, 10%in the presence of acetates, and 3% where phosphates were used. R. G .Booth l8 confirms many of these findings and has extended his observationsto co-carboxylase, which he finds very much less stable than aneurin a t thesame pH.Destruction of aneurin is not primarily an oxidation effect,although, as copper can catalyse destruction, oxidation may be involved.An everyday application of work of this type concerns the losses of thevitamin which occur in cooking. Booth found that his estimate of lossagreed reasonably well with published figures.Ribo$avin.-Although both the microbiological and the fluorimetricmethods for assay of riboflavin have yielded results in reasonable accordR. H. Hopkins and S. Wiener~10cls.gJ . Inst. Brew., 1944, 41, 124.Biochem. J . , 1943, 37, 433.7 J . SOC. Chein. Ind., 1940, 59, 181.Ibid., p. 439.lo M. Malm and H. Lundeen, Svensk Kem. Tid., 1941, 55, 246.l 1 J.Lehmann and H. E. Nielsen, Acta Med. Skand., Suppl., 1941, 123, 374.l2 W. H. Schopfer and A. Jung, Compt. rend., 1937, 204, 1500.l3 J. Bonner and J. Erickson, Amer. J . Bot., 1938, 25, 685.l5 P. M. West and P. W. Wilson, Science, 1938, 88, 334.l o J . Biol. Chem., 1913, 150, 1.l 7 Ibid., 1943, 149, 339, 349.J. Meiklejohn, Biochem. J., 1943, 37, 349.Biochein. J . , 1943, 37, 518280 BIOCHEMISTRY.with those obtained by biological methods, much evidence has accumulatedthat interfering substances may be present in natural producfs. It isnecessary that each type of product should be treated in relation to its ownpecubrities and the problems arising therefrom. I n the fluorimetric method,originally developed by A. Z. Hodson and L.C. Norris,lg later modified byV. A. Naj jar,2o pigments and non-flavin fluorescent aubstances must eitherbe removed or allowed for.The original microbiological assay method of E. E. Snell and F. M.Strong 21 used Lactobacillus cusei-c as test organism. Henceforth this organismwill be denoted by its more convenient synonym, Lactobacillus helveticus.In a study of assay methods for cereals, J. S. Andrem, H. M. Boyd, andD. E. Terry 22 found that the method of extraction is of great importance ifaatisfactory results are to be obtained. Extraction with taka-diastase wasnecessary in order to eliminate the effects of undesirable impurities. I n thismmner agreement was obtained between results by the microbiologicalmethod and the fluorimetric method in the case of patent and whole wheatfloura, but there were discrepancies in the case of other cereal products.Onthe other hand, M. I. Wegner, A. R. Kcmmerer, and G . S. Fraps23 foundtaka-diastase (and also papain) treatment unsatisfactory in microbiologicalwork on similar products, nor could the difficulty be obviated by addingphotolysed extracts to the basal medium.J. C. Bauernfeind, A. L. Sotier, and C. S. Boruff 24 found that the effectof additional growth substances in some foodstuffs was observable in assaysusing L. helveticus, especially when the amounts of riboflavin were below theoptimum. The authors described methods for countering these effects, andsuggested that the interfering substances were of the nature of fatty acids.This suggestion was followed up in an important paper by F.M. Strong andL. E. Car~enter,~5 who examined the effects of added fatty acids, to whichthe organism was sensitive, and showed that the difficulty did in fact arisefrom their presence. If they are removed by suitable preliminary treatment,reliable values for riboflavin may be obtained.Satisfactory concordance in results by the microbiological method, whichwas modified by E. C. Barton-Wright and R. G. Booth,26 and the fluori-metric method, as adapted by V. A. Najjar,*O has been achieved by theseauthors in the assay of many cereals and cereal products. D. W. Kent-Jones and M. Meiklejohn 27 also have obtained satisfactory results by thesemerthods,give figures for riboflavin in brewingmaterials by the microbiological method, but indicate that additionalinvestigation of the fluorimetric method is necessary owing to disturbingfactors in such materials as hops.R.H. Hopkins and S. Wiener19 J . Bwl. Ciaem., 1939, 131, 621.21 Ind. Eng. Chem. Anal., 1939, 11, 346.23 J . Biol. Chem., 1942, 144, 731.26 Ibid., p. 909.27 Analyd, 1944, 69, 330.20 Ibid., 1941, 141, 366.24 Ind. Eng. Chem. Awl., 1942, 14, 666.2 6 Biochem. J.,1943, 37, 26.Ibid., 1942, 14, 271NORRIS: THE ASSAY OF VITAMINS B. 261Pinally, a collaborative study of the riboflavin content of meals servedin R.A.F. messes may be mentioned. In this instance good agreement wasobtained between the biological and the microbiological methods and it isconcluded by T. F. Macrae, E. C.Barton-Wright, and A. M. Copping 28 thatthe adult riboflavin requirement does not exceed 2 mg. per day.Nicotinic Acid.-An excellent review on nicotinic acid is contributed byC. A. Elvehjem and L. J. T e p l e ~ . ~ ~There are a large number of chemical methods and their modificationsfor the estimation of nicotinic acid. All depend on the reaction withcyanogen bromide, followed by colour production with an amine.30 Probablythe most extensive study has been made by E. K0dicek,~1 who later modifiedthe procedure in collaboration with Y. L. Wang.32 The colour-producingbase employed in both methods is paminoacetophenone ; other baaesproposed include orthoform (orthocaine) ,33 p-phenylenediamine dihydro -and procaine.35 The last gave good results with animal productssuch as meat extract and meat juice ; but in general it may be said that thechemical methods are unreliable for plant products.The method of E.X. Snell and L. D. Wright 36 was modified by W. A.Krehl, F. M. Strong, and C. A. El~ehjem,~' who employed LactobuciEZusarabinosus 17/6 and a synthetic medium.In a study of methods of extraction V. H. Cheldelin and R. R. Williams 38find that many materials yield their nicotinic acid completely under digestionwith taka-diastase and papain, and that similar values in the case of meatsand milk are obtained whether hydrolysis is enzymatic or by acid or alkali.On the other hand, acid or alkaline extracts of cereals give higher valuesthan those prepared by enzyme action.Comparison of results by microbiological and chemical methods of assayhas shown that higker results by microbiological assays are obtained whenplant products, particularly cereals, are treated in the preliminary stage withacid.R. D. Greene, A. Black, and F. 0. Howland39 employed a methodsimilar to that of Snell and Wright 36 for microbiological assays, and amodified cyanogen bromide method due to W. S. Jones.40 With someproducts, good agreement was found between the two types of method,although the authors prefer the microbiological method where small quanti-ties of nicotinic acid are present. J. A. Andrews, H. &I. Boyd, and W. A.Gortner 41 have studied the nicotinic acid content of cereals and cereal28 Biochenz. J . , 1944, 38, 132.30 W. Kbnig, J .pr. Chem., 1904, 69, 105.3 1 Riochem. J . , 1940, 34, 724.33 R. G. Martinek, E. R. Kirch, and G. L. Webster, J . Biol. Chern., 1943, 149, 245.3 4 A. E. Teeri and S. R. Shimer, ibid., 1944, 153, 307.36 E. C. Barton-Wright and R. G. Booth, Lancet, 1944, 565.36 J . Biol. Chem., 1941, 139, 675.37 Ind. Eng. Chem. Anal., 1943, 15, 471.3 8 Ibid., 1942, 14, 671.40 J . Amer. Pham. ASSOC., Sci. Ed., 1941, 30, 272.4 1 Ind. Eng. Chem. Anal., 1942, 14, 663.29 Chem. Reviews, 1943, 33, 185.32 Ibid., 1943, 37, 630.39 Ibid., 1943, 15, 77262 BIOCHEMISTRY.products, and also conclude that the microbiological assay is influenced bythe type of hydrolysis procedure employed.Nevertheless, the method of Krehl, Strong, and Elvehjem 37 is provingmost valuable, and has recently reached a high level of accuracy as modifiedby E.C. Bart~n-Wright,~~ who has applied it to a wide range of materials,which are extracted under pressure with N-hydrochloric acid. Fats andfatty acids do not appear to have any effect on the organism. D. W. Kent,-Jones and M. Meiklejohn 27 have applied the method with success.Pyridoxine.-Colorimetric methods for assay of pyridoxine have beenproposed by M. Swaninathan 43 and by J. V. S ~ u d i . ~ ~ Modifications of thelatter method have been suggested by 0. D. Bird, J. M. Vanderbelt, and A. D.Emmett,45 and by A. F. Bina, J. M. Thomas, and E. B. Br0wn.~6 The mostrecent reference to such methods is probably that by A. C. B ~ t t o m l e y . ~ ~A yeast growth method originally presented by L.Atkin, A S. Schultz,and C. N. Prey** has been modified by these authors together with W. L.Williams.49 The organism used is a yeast strain (No. 4228) which is char-acterised by a specific response to pyridoxine. Extracts of the materialsfor assay are prepared by acid treatment, and yeast growth is estimatedturbidimetrically. Satisfactory assays on a large number of substances arereported. Bound pyridoxine is liberated also by acid treatment underpressure by L. Siegel, D. Melnick, and B. L. O~ler.~O Their results for anumber of natural materials agreed well with those obtained by biologicalmethods.It was shown by E. E. Snell, B. M. Guirard, and R. J. Williams 51 thatStreptococcus Zuctis R would grow on a medium if in addition to the usualconstituents pyridoxine were present.Growth on such a medium, however,was many times as great as could be accounted for on the basis of actualcontent of pyridoxine. The indications were that pyridoxine is convertedinto a more highly active metabolite, called +pyridoxine for the present,prior to utilisation by the organism, and that +pyridoxine exists in naturalproducts. The original presence or derivation of pyridoxine renders micro-biological assays for pyridoxine invalid, and the case is complicated by thefact that the effect varies with different organisms ; e.g., very high values areobtained as indicated with Streptococcus Zactis R, but low values are obtainedwith Sacchuromyces cerevisice as test organism.In a later communication, E.E. Snell 52 advances suggestions as to thenature of +pyridoxine, and shows that mixtures having enhanced growth-promoting properties for Lactobacilli may be formed from pyridoxine byprocesses involving (a) possible amination and (b) partial oxidation. Thelatter change had also been noted by L. E. Carpenter and F. M. Strong.534 2 Biochem. J., 1944, 38, 314.44 J . Biol. Chem., 1941,139, 707.4 6 Ibid., 1943, 148, 111.4 8 ,J. Amer. Chem. Soc., 1939, 61, 193150 J . Biol. Chem., 1943, 149, 361.62 Ibid., 1944, 154, 313.4 3 Indian J . Med. Res., 1941, 29, 561.4 5 Ibid., 1942, 142, 317.4 7 Biochem. J . , 1945 (in the-press).49 Ind. Eng. Chem. Anal., 1943, 15, 141.5 1 Ibid., 1942, 143, 519.63 Arch. Biochem., 1944, 3, 375NORRIS : THE ASSAY OF VITAMINS B.263An amine (IV) and an aldehyde (11), “ pyridoxamine ” and “ pyridoxal ”respectively, have been synthesised,54 and there is much evidence that thesecompounds or their higher combinations are responsible for the +pyridoxineactivity of natural materials.N J NThe use of-biochemical mutants in the mould Neurospora induced by meansof ultra-violet and X-rays is an interesting development in microbiologicalmethods of assay of vitamins of the B group. The production of thesemutants has been described by G. W. Beadle and E. L. T a t ~ m , ~ ~ and theyare characterised by an inability to carry out specific syntheses which canbe effected by the normal unmutated strain.Ari X-ray-induced mutant of Neurospora sitqhila, produced by Beadleand Tatum is utilised as test organism by J.L. Stokes, A. Larsen, C. R.Woodward, and J. W. Foster 56 in a microbiological method for pyridoxine.Growth response is determined by actual dry weight of the mould, and themethod is thus free from some objections which arise in turbidimetric assays.Under the conditions employed, the organism exhibits a specific response topyridoxine, but none to +pyridoxine. The results obtained are in goodagreement with those obtained by biological assay.Biotin.-The elucidation of the structure of biotin has been discussedin detai1.57 The importance of this needs no stressing, since, apart fromscientific interest in the substance itself, it is a valuable tool in much modernmicrobiological work.It may be some time before a chemical test for biotin of the requireddelicacy and specificity is forthcoming.In the meantime, the micro-biological methods are being intensively studied, one of the more importantproblems centring on the question of free and bound biotin. Earlier methodsof extraction included treatment merely with hot water,58 but it was laterfound that much larger amounts of biotin were yielded by autolysis oftissues such as liver.59 Later still,60B61 a combination of autolysis and acidhydrolysis was resorted to, and in 1941, after a series of tests of all types oftreatment, R. C. Thompson, R. E. Eakin, and R. J. Williams 62 came to theconclusion that the best method for many types of material consists in drastic64 S. A. Harris, D. Heyl, K.Folkers, and E. E. Snell, J. Biol. Chem., 1944, 154, 315.5 5 Proc. Nut. Acaca. Sci., 1941, 27, 499; 1942, 28, 234.5 6 J . Biol. Chem., 1943, 150, 17.5 8 F. Kogl and W. van Hrtsselt, 2. physwl. Chem., 1936, 243, 189.5s E. E. Snell, R. E. Eakin, and R. J. Williams, J. Arner. Chem. SOC., 1940, 62, 175.6o R. E. Eakin, W. A. McKinley, and R. J. Williams, Science, 1940, 92, 224.61 Univ. Texas Publication, 1941, No. 4137.62 Science, 1941, 94, 589.6 7 Ann. Reports, 1943, 40, l i 2 264 BIOCHEMISTRY.aoid treatment. Some destruction of the biotin occurs, but it is remarkablystrtble in acid solution. The problem is complicated by the fact that biotinappears to exist in different combinations which are broken down with vary-ing degrees of ease, each type of product requiring individual treatment.I n earlier methods for the assay of biotin, the growth of yeast was usuallymeasured turbidimetri~ally,~~$ 64 a procedure which involved serious difficultywith solutions which were already cloudy or highly coloured.Similarly,P. M. West and P. W. Wilson 65 used Rhixobium trifolii as test organism.I n order to overcome inherent difficulties in these methods, G. M. Shull,B. L. Hutchings, and W. H. Peterson 66 proposed the use of Lactobacillushelveticus as test organism, and measured the effect of added biotin by theincrease in titratable acidity. An added advantage of this method lies inthe fact that the same organism may be used for assay of pantothenic acidand riboflavin, thus obviating additional cultures. G.M. Shull and W. H.Peterson 67 later suggested two modifications in the assay. The eluatefactor level in the yeast supplement in the basal medium is increased so thatoptimal growth of the organism is obtained. A procedure whereby theinoculum is independent of drop size is described.The chemistry and biochemistry of biotin is reviewed by K. Hofmann.68A detailed account of methods and results of microbiological assay of allvitamins in the B group is provided by R. J. Williams and his collaborators.69Pantothenic Acid.-No satisfactory chemical method of assay of panto-thenic acid has as yet been devised. The earlier microbiological methodsbased on stimulation of yeast growth have largely given place to methodsin which L.helveticus is used as test organism.70-75The method of Pennington et aE. employed autoclaving with or withoutprevious autolysis under benzene in order to free pantothenic acid from testmaterials. Various enzymatic methods have been ernpl~yed.~~I 76- ’*In more recent studies on the microbiological assay, A. L. Neal and F. M.Strong v9 have endeavoured to overcome some of the difficulties previously63 F. K6gl and B. Tonnis, 2. physiol. Chem., 1936, 242, 43.64 E. E. Snell, R. E. Eakin, and R. J. Williams, J . Amer. Chem. Soc., 1940, 62, 176.6 6 Enzymologia, 1940, 8, 152.6 7 Ibid., 1943, 151, 201.6* “ Advances in EnzymoIogy,” 1943, 3, 289.e9 Uniu. Texas Publications, 1941, No. 4137; 1942, No. 4237.70 E. E. Snell, F. M. Strong, and W. H. Peterson, Biochem.J., 1937, 31, 1789.71 Idem, J . Amer. Chern. SOC., 1938, 60, 2825.72 Idem, J . Bact., 1939, 38, 293.73 D. Pennington, E. E. Snell, and R. J. Williams, J. Biol. Chem., 1940, 135, 213.74 F. M. Strong, R. E. Feeney, and A. Earle, I n d . Eng. Chem. Anal., 1941,13,666.75 D. Ppnnington, E. E. Snell, H. K. Mitchell, 5. R. McMahan, and R. J. Williams,76 H. A. Waisman, L. M. Henderson, J. M. McIntire, and C. A. Elvehjem, J .7 7 A. H. Buskirk and R. A. Delor, J . Biol. Chern., 1942,145, 707. ’* E. Willerton and W. H. Cromwell, Ind. Eng. Chem. Anal., 1942,14, 603.6 6 J . Biol. Chem., 1942, 142, 913.Interscience Publishers, New York.Univ. Texm Publication, 1941, No. 4137, 14.Nutrition, 1942, 23, 239.Ibid., 1943, 15, 654NORRIS: THE ASSAY OF VITAMINS B.265encountered by modifying the medium employed and improving the methodof growing the inoculum. Enzymatic methods of liberating “bound ”pantothenic acid were studied until satisfactory results were obtained andsteps were taken to eliminate interfering fat-soluble substance^.^^^ 25 Theeffect of water-soluble substances, present particularly in brans, was mini-mised by modifications in the basal medium. The authors claim that themodified method gives concordant results at increasing levels of dosage, andthat very small amounts of the vitamin may be estimated with accuracy.There appears to be an additional growth factor or factors for L. helveticusin the concentrate of rice polishings according to M. F. Clarke, M. Lechycka,and A.E. Light.8O Notable increases in acid production were observed overand above those normally experienced with pure calcium pantothenete.The high values obtained by these workers may not, however, necessarilybe due to a supplementary growth stimulator. J. L. Stokes and B. B.Martin81 report that high acid production may be obtained merely byincreasing the amounts of glucose and sodium acetate in the medium. Witha view to increasing acid production and hence the titration range, A. E.Light and M. F. Clarke 82 propose a modification in the medium.Other test organisms have been employed, among which Streptococcuslac ti^,^^ Streptobacterium plantarum,84 Proteus rnorg~nii,~~a and L. arabin-osus may’be mentioned.A useful review of pantothenic acid is contributed by R.J. Williams.85p- Aminobenzoic Acid.-Chemical methods are not greatly in evideiira asyet, but are being developed. Colorimetric methods are described by E. R.Kirch and 0. Bergeim 86 and by H. W. E ~ k e r t . ~ ’Acetobacter suboxydans is recommended as test organism for p-amino-benzoic acid by M. Landy and D. M. Dicken,*8 who describe a suitable basalmedium. Related or derived compounds of p-aminobenzoic acid havelittle or no biological activity, and the method has high specificity.A mutant strain of Neurospora crassa of G. W. Beadle and E. L. Tatum 55is used by R. C. Thompson, E. R. Isbell, and H. K. Mitchell.89 Additionsof graded amounts of p-aminobenzoic acid to a synthetic medium stimulatea specific growth response in the mould which is determined by measurementof the growth produced..The extraction of p-aminobenzoic acid by waterand by acid hydrolysis is compared. The latter treatment involves a certainloss of the vitamin, but this loss is not significant in comparison with theenhanced yield of “ bound ” p-aminobenzoic acid. The same authorshave later shown that complete extraction is effected only by acid hydrolysis83 H. K. Mitchell, H. H. Weinstock, E. 33. Snell, S. R. Stanbury, and R. J. Williams,8 4 R. Kuhn and T. Wioland, Ber., 1940, 73, 962.84a M. J. Pelczar and J. R. Porter, J . Biol. Chem., 1941, 139, 075.84b H. R. Skeggs and L. D. Wright, ibid., 1944,156, 21.J . Biol. Chern., 1942, 142, 957.J . Amer. Chem. SOC., 1940, 62, 1776.Ibid., 1943, 147, 483.82 Ibid., p . 739.“ Advances in Enzymology,” 1943, 3, 253.J . Biol. Chem., 1943, 148, 445.Ibid., 1948, 146, 109.Interscience Publishers, New York.*O Ibid., 1943, 147, 485.Ibid., p . 197.88 Ibid., 1943, 148, 281266 BIOCHEMISTRYunder pressure. They suggest that the method of Landy and Dicken 88responds to only a fraction of the total yielded by acid hydrolysis.Quantitative response to p-aminobenzoic acid is evinced by ClostridiumacetobutyZicum Strain S9, which attains maximal growth in 24 hours on asuitable medium proposed by J. 0. Lampen and W. H. Peterson.g1 Theseauthors claim that the vitamin is rapidly destroyed by acid hydrolysis, andprefer to hydrolyse with alkali under pressure. This method of extractionis also favoured by J.C. who uses L. urubinosw as test organism.Reference should not be omitted to the synthetic medium of M. Landyand D. M. Dicken 93 for use with L. heEveticus and applicable to assay of eachmember of the group. Whilst this ideal has not perhaps been realised, themedium or modifications of it have proved useful to many workers.The family of B vitamins is ever-increasing and it is too early to discussassay methods for new members. It may be mentioned, however, thatmethods for “ folic acid ” are a ~ a i l a b l e . ~ ~ F. W. N.6. ACTIONS OF CHEMOTHERAPEUTIC AGENTS AND RELATED COMPOUNDS.Chemotherapy concerns interactions of drug, parasite and host, but themajority of investigations of chemotherapeutic agents during the periodreviewed have been of their effects upon bacteria.The present account ismainly limited to such effects and is arranged according to their type.Factors involved in the comparison of in vivo and in vitro actions of drugshave been examined,l and their relations to other interactions in thecomplete chemotherapeutic system have been reviewed elsewhere.2I. Biological Eflects.(a) Mor23hologicaZ.-Abnormal size or shape in bacterial cells is inducedby many agents ; 3* by sulphanilamide, andfrequently by compounds without known chemotherapeutic a ~ t i o n . ~ Theiroccurrence in response to changes in media has been ascribed to independenteffects of the change upon chemical factors conditioning cell elongation anddivision.5*(b) Upon Growth.--Sulphonamides increase the mean generation timeduring the logarithmic phase, and the length of the lag phase, of Bact.lactiscerogenes ; 7 pantoyltaurine, in concentrations active in vivo against Strepto-sometimes but not alwaysS1 J . Biol. Ghem., 1944, 153, 193.S3 J. Lab. Glin. Med., 1942, 27, 1086.B2 Ibid., 1942, 148, 441.1 Symposia, Trans. Paraday Soc., 1943, 39, 319; Ann. N . Y . Acad. Sci., 1943, 44,445.H. McIlwain, Riol. Rev., 1944, 19, 135.E.g., J. W. Foster and H. B. Woodruff, Arch. Biochem., 1943, 3, 241.G. H. Spray and R. M. Lodge, Trans. Paraday Soc., 1943, 39, 424.C. N. Hinshelwood and R. M. Lodge, Proc. Roy. SOC., 19-14, B, 132, 47.6 R. M. Lodge and C. N. Hinshelwood, Trans. FaracEay A’oc., 1943, 39, 420.D. S. Davies and C. N. Hinshelwood, ibid., p.431MCILWAIN : ACTIONS OF CHEMOTHERAPEUTIC AGENTS. 267coccus hcemolyticus, has effects upon that organism which are similar andwhich, like the in vivo activity, are annulled by pantothenate.8 The effectsof many other metabolite-analogues upon overall growth have been reported.Pyrithiamine, in which a pyridine ring replaces the thiazole ring of aneurin,inhibits several bacteria 9 ~ 1 0 and has greatest effects on those most exactingin their requirements for aneurin,g which antagonises its action. Inhibitionby benziminazole is counteracted by some aminopurines.11 Dethiobiotin,12biotin sulphone,13 and an analogous imidazolidone derivative l4 competitivelyinhibit certain organisms but to others may be indifferent or in some casesact as source of biotin ; or they may make available to bacteria, biotin whichis inactivated by avidin. 6 : 7-Dichloro-9-ribitylisoalloxazine l5 and phen-azine analogues of riboflavine l6 inhibit bacterial growth and this may berestored by riboflavine.New analogues of p-aminobenzoate l7 and panto-thenate, l8 some of which are antibacterial, have been reported. Inhibitorysubstances designed in this way can act upon strains of organisms resistantto the agent used as model,lg though cross-resistance can be developed toagents apparently different in type.20 Orthanilamide does not inhibit anorganism to which anthranilic acid is a growth-factor.2lConsidering existing chemotherapeuticals, the inhibition of growth ofEscherichia wli caused by atebrin 22 and of a lactobacillus and streptococcuscaused by diamidines 23 are antagonised by spermidine and polyamines.The interaction of p-aminobenzoate and sulphonamides has been investigatedunder various conditions of aeration 24 and temperat~re.~~ The latterfactor influences also the mutual interaction of p-aminobenzoate, sulphon-amides and urea ; 26 joint action of the last two can be additive, as urea issometimes bacteri~static.~~ Effects of sulphonamides on certain micro-H.McIlwain, Biochem. J . , 1944, 38, 97.9 D. W. Woolley and A. G. C. White, J . Exp. Med., 1943, 78, 489.10 0. U'yss, J . Bact., 1943, 46, 483.11 D. W. Woolley, J . Biol. Chem., 1944, 152, 225.12 K. Dittmer, D. B. Melville, and V. du Vigneaud, Science, 1944, 99, 203; V. G.13 K.Dittrner, V. du Vigneaud, P. Gyorgi, and C. S . Rose, Arch. Biochem., 1944, 4,l4 K. Dittmer and V. du Vigneaud, Science, 1944,100, 129.l5 R. Kuhn, F. Weygand, and E. F. Moller, Ber., 1943, 76, 1044.16 D. W. Woolley, J . Biol. Chem., 1944, 154, 31.1' 0. H. Johnson, D. E. Green, and R. Pauli, ibid., 1944, 153, 37.la J. Barnett, J., 1944, 5; J. Barnett, D. J. Dupr6, B. J. Holloway, and F. A.Lilly and L. H. Leonian, ibid., p. 205.229.Robinson, ibid., p. 94.H. McIlwain, Brit. J . Exp. Path., 1943, 24, 203.2O J. McIntosh and F. R. Selbie, ibid., p. 246.21 E. E. Snell, Arch. Biochem., 1943, 2, 389.22 JI. Silverman and E. A. Evans, jun., J . Biol. Chem.., 1943,150,265; 1944,154,521.23 E. E. Snell, ibid., 1943, 152, 475.24 J. W. McLeod, A. 'Mayr-Harting, and N.Walker, J . Path. Bact., 1944, 56, 377.2 5 S. W. Lee and E. J. Foley, Proc. SOC. Exp. Biol. Med., 1943, 53, 243.26 S. W. Lee, J. A. Epstein, and E. J. Foley, ibid., p. 245.27 W. M. M. Kirby, ibid., p. 109268 BIOCHEMISTRY.organisms differ from the compounds' normal antibacterial effects in notbeing antagonised by p-aminobenzoate.28 Lack of such antagonism is avaluable feature in the homosulphonamides, of which new members areactive in v ~ u o . ~ ~(c) Upon ViabiZity.-An outstanding finding of the period under reviewis of the unusual action of penicillin. At concentrations approximating tothose attained during therapy, penicillin has little effect upon the viabilityof staphyloco~ci,~~ hmmolytic streptococci 31 and meningococci 32 underconditions which do not permit growth of the organisms; e.g., in salt solu-tions or in very dilute broth, in rich media in the cold or in rich media whengrowth is inhibited by sulphonamides 33 or by boric acid.30 Under conditionsotherwise permitting growth, an extremely small concentration of peni-cillin is bacteriostatic, 0.0009 unit/ml. (c.0.0005 vg./ml.) having aneffect comparable with that of 100 pg./rnl. of sulphadiazine ; concentrationscomparable with those used therapeutically (e.g., of 1 /24 unit/ml.) are,however, bactericidal. Factors which normally increase the rate of growthof streptococci, in the presence of penicillin increase their rate of death.A proportion of organisms in staphylococcal cultures is not susceptible tobeing killed by penicillin ; such " persistent " organisms are considered to bein a particular cultural phase.The proportions of organisms of a culturewhich are persistent can be altered by manipulation of the culture; 30 theyincrease on chilling. Recommendations in the clinical use of penicillin havebeen made on the basis of the new findings.30 Varying susceptibility ofbacteria at different phases of the culture-cycle has frequently been observed 34and a further example has appeared recently in the greater sensitivity toacriflavine of B. salmonicida while it is in its logarithmic pha~e.3~Of agents already known to be bactericidal, the relations between con-centration and action 36 and time of exposure and action 37 of phenol havebeen further studied.The significance of rates of death has been discussed.3sSurface-active cations such as benzylalkylammonium chlorides are bacteri-cidal, but their toxic action upon bacteria can be prevented, and when inprogress halted, by anions of large molecular weight such as sodium dodecyl~ulphate.~g This shows two phases in the action of the cation : a pre-2 8 J. T. Tamura, J . Bact., 1944. 47, 529; F. Hawking, Brit. J. Exp. Path., 1944, 25,63.29 D. M. Hamre, H. A. Walker, W. B. Dunham, H. B. van Dyke, and G. Rake,Proc. SOC. Ezp. BioZ., N. Y., 1944, 55, 170; D. G. Evans, A. T. Fuller, and J. U'alker,Lancet, 1944, 247, 523.30 J. W. Bigger, ibid., p. 497.31 G. L. Hobby and M. H. Dawson, PTOC. SOC. Exp. BioZ. N.Y., 1944, 56, 178.32 C. P.Miller and A. Z. Foster, ibid., p. 205.33 G. L. Hobby and M. H. Dawson, ibid., p. 181.34 C.-E. A. Winslow and H. H. Walker, Bact. Rev., 1938, 3, 147.35 W. W. Smith. Proc. SOC. Exp. BioZ. N.Y., 1944, 56, 238.36 D. P. Evans and A. G. Fishburn, Quart. J . Pharm., 1943,16, 201.37 R. C. Jordan and S. E. Jacobs, J. Hygiene, 1944, 43, 275.38 0. Rahn, Bwdynamica, 1943, 4, 81.30 E. I. Valko and A. S. DuBois, J . Bact., 1944, 47, 16MCILWAIN : ACTIONS OF CHEMOTEERAPEUTIC AGENTS. 269liminary reversible one and later irreversible changes assooiated with death.The reversible one is considered to be the attachment of the agent to the oelland was shown to have some of the characters of ionic exchange; the actionwas reduced by the additional presence of less toxic cations.Suah anfagon-ism was effeutive against only limited concentrations of toxie cation. Gimilctrphases in the action of other bactericides have been proposed; 36 here alsothe second phase was considered to be fundamentally diffefent and to uonshtin denaturation or precipitation of the bacterial protein. The aotivitiea ofantiseptics a t different pH have been related to the conoentratima of ionisedand undissociated molecules ; undissociated and not ionised benzoic, salioylic,and sulphurous auids were found antisepti~.~~ CEstrogens and related com-pounds are bectericidalY41 42 but optimal antibacterial activity is not shownby members of greatest oestrogenic a~tivity.~3 Propamidine is bactericiddas well as bacteriostatic to staphylococci 44 and to Escherichia wli 45 and botheffects are antagonised by lecithin.46II. Biochemical Efsects.(a) Upon Energy- yieldijzg Processes.-Evidence has been collected 46suggesting a correlation of the inhibitions of bacterial respiration or anaerobiccarbon dioxide production, with inhibition of growth, by sulphonamides.The respiratory inhibition is only partial (and by some investigators has beenreported absent) at concentrations of aulphonamides which are compleklybaoteriostatic.To affect glycolysis or respiration of streptococci in thepresence of glucose and a few other substrates, pantoyltaurine is required inmuch greater preponderance over pantothenate than is required for if toinhibit growth ; these metabolic inhibitions also are relatively small ormay be absent. Oxidation of amino-acids by Escherichia coli is inhibitedby low concentrations of propamidine and is more sensitive to the compoundthan is oxidation of glucose.47 The inhibitions are markedIy increased byadding the inhibitor before the substrate, and by inorease in PH.~* Theaotivity of antimalarials in inhibiting oxygen uptake of malarial parasitesis correlated with their therapeutic efficacy.49(b) Upon Metabolism of Vitamin-like Compounds.-The system a t whiahsulpbonamides and p-aminobepzoate are believed to interaot has pot y0$been specified biochemioally, but further interpretations of actions ofaulpbonamides in terms of their competing with p-aminobenzoate for enzymes4 0 0. Rahn and J. E. Conn, I n d . Eng. Chem., 1944, 86, 185.4 1 G. H. Faulkner, Lancet, 1943, 245, 38.4 2 B. Heinemm, J . Lab. Clin. Med., 1944, 29, 254.*3 0. Brownlee, F. C. Copp, W. M. Duffi, and I. M. Tonkin, Biochem. J., 1943, 37,4 4 W. R. Thrower and F. C. 0. Valentine, Lancet, 1943, 244, 133.4 5 W. 0. Elson, J. Biol. Chem., 1944, 154, 717.4 6 R. J. Henry, Bact. Rev., 1943, 7 , 175.47 F. Bernheim, Science, 1943, 98, 223.4 8 F. Bernheim, J . Pharm. Exp. Ther., 1944, 80, 199.49 S. R. Christophers, Trans. Paraday Xoc., 1943, 39, 333.572270 BIOCHEMISTRY.have been 51 Increased synthesis of p-aminobenzoate haq beenfound to be associated with development of sulphonamide-resistance instaphyloc~cci.~~ By training certain strains of Corynebacterium diphtherimto synthesise pantothenate, strains resistant to pantoyltaurine were pro-duced in the absence of that compound and of any other inhibitor ; 53 butnot all drug resistance is by synthesis of specific- antag0nists.1~ The systemthrough which pantoyltaurine inhibits streptococcal growth has to someextent been characterised 54 and its functioning is associated with panto-thenate-inactivation. In the preparations studied, the pantothenatemetabolism required a concurrent energy- yielding process such as glycolysis.The pantothenate metabolism, but not glycolysis, was inhibited by con-centrations of pantoyltaurine even lower than those affecting growth andthe activities of a series of pantothenate analogues in inhibiting growth werecorrelated with their activities in inhibiting pantothenate-inactivation. Abacterial degradation of riboflavine is inhibited by structurally related com-pounds but occurs independently of a process such as glycolysis and itsinhibition does not affect growth.55111. Chemical or Physical Effects.Analyses of sulphonamide action, the effect of pH upon it, and itsantagonism, base these processes upon reversible combination of the drug,antagonist, or their ions with enzymes in accordance with the law of massaction.a* 519 56 The bulk of the p-aminobenzoate of preformed organisms isnot, however, displaced by bacteriostatic concentrations of sulphanilamide ;67the equilibria may obtain during or before paminobenzoate assimilation.Similar lack of displacement of pantothenate by pantoyltaurine has beenobserved.57 Correlation of the action of drugs with properties which theyexhibit apart from biological systems has been reported 36* 58 andrevie~ed,~ge 60IV. Chemotherapeutic Mechanism.The year’s findings have shown the multiplicity of types of antibacteria1action exhibited by chemotherapeuticals. The connection of these withchemotherapeutic activity in vivo is established only in certain cases and inothers would not be expected to be very close. Discussion of such con-nections (chemotherapeutic “ mechanisms ”) is beyond the scope of thepresent account, but it will be seen that evidence for such connections is,50 W. D. Kumler and T. C. Daniells, J . Amer. Chem. SOC., 1943, 65, 2190.5 1 I. M. Klotz, ibid., 1944, 66, 459.62 M. Lrsndy, N. W. Larkum, E. J. Oswald, and F. Streightoff, Science, 1943, 97,295.63 H. McIlwain, Brit. J . Exp. Path., 1943, 24, 212.54 H. McIlwain and D. E. Hughes, Biochem. J . , 1944, 38, 187.55 J. W. Foster, J . Bact., 1944, 48, 97.56 F. H. Johnson, H. Eyring, and W. Kearns, Arch. Biochem., 1943, 3, 1.57 H. McIlwain, Proc. Biochem. SOC., 1924, 38, viii.5* A. Albert and R. Goldacre, J . , 1943, 454.59 A. Albert, Australian J . Sci., 1944, 6, 137.60 W. S. Gledhill, ibid., p. 170MCILWAIN : ACTIONS OF CHEMOTHERAPEUTIC AGENTS. 27 1most fully provided in the cases of pantoyltaurine and the sulphonamides, byobservations in vivo and of categories I ( b ) , I1 (a), I1 ( b ) , and 111. Othercompounds are of radically different mode of action and one compound mayact in more than one way.g1 As the normal life of organisms involves a,working together of processes which include all the above categories, manyother means can be envisaged for their disturbance. H. McI.F. DICKENS.H. MCILWAIN.A. NEUBERQER.F. W. NORRIS.J. R. P. O'BRIEN.F. G. YOUNG.61 C. E. Hoffmann and 0. Rahn, J . Bact., 1944, 47, 177

ISSN:0365-6217    

DOI:10.1039/AR9444100230

出版商:RSC    

年代:1944

数据来源: RSC

摘要:

ANALYTICAL CHEMISTRY.ALTHOUGH this Report deals with only four topics, the first three sectionsillustrate a large variety of current analytical trends.I . Zinc.No spectacular advances in the analytical chemistry of zinc have beenrecorded, but there has been fairly steady development, stimulated ho someextent by recognition of the biological importance of the element.(1) Separations and Qualitative Tests.-A procedure is given 1 fordetermination of zinc and other metals in foodstuffs, by precipitationwith hydrogen sulphide a t pH 8 after a wet ashing process. The pre-cipitate is dissolved, and iron, etc., precipitated with ammonia. Afteracidification, copper is separated with hydrogen sulphide and zinc determinedwith 8-hydroxyquinoline.McLellanpoints out that in 1 : 19 hydrochloric acid there is appreciable coprecipitationof zinc with Group 2 metals.Laws uses a formic acid buffer for separationof zinc from many other metals in light and in nickel alloys, but S. A. Colemanand G. B. L. Smith prefer to use citric acid as a buffer. E. A. Ostroumov 5says that post-precipitation of cobalt on zinc sulphide can be prevented bythe use of acraldehyde in the solution and that filter-paper pulp, unlesspreviously treated with buffer solution, materially increases the contamin-ation. C. Zollner stated that in absence of hydrochloric acid, cadmium isquantitatively precipitated by hydrogen sulphide from a solution containing15 ml. of concentrated sulphuric acid per 100 ml. ; the solution is boiled, andallowed to cool while the gas is passing.There are also several references 7**, 9to separation of cadmium from zinc by means of aluminium foil or powder,which precipitates cadmium from a somewhat acid hydrochloric acid solution.It would appear best to separate most of the cadmium in this way, andrecover the remainder from the filtrate by means of hydrogen sulphide.If to a solutioncontaining cadmium and zinc, thiourea and Reinecke's salt are added in thecold, cadmium is quantitatively precipitated asleaving all the zinc in the filtrate. Complex thiocyanates have been studied ;e.g., W. C. Vosburgh, G. Cooper, W. J. Clayton, and H. P. Pfann l1 state thatOther authors 2 * 3 write on the use of hydrogen sulphide.A novel method is put forward by C.Mahr and H. OhleeloCd( CS=N,H,),, [Cr(CNS),"H,) 212,J. H. Hamence, Analyst, 1937, 62, 18.E. Q. Laws, Analyst, 1941,66, 54.Ann. Chim. anal., 1937, 19, 145.7 J. J. Lurie and V. F . Neklyntina, Zavod. Lab., 1936, 5, 87.8 E. I. Nikitins, ibid., 1939,8, 1172.Q F. E, Townsend and G. N . Cade, Ind. Ewg. Ghem. Anal., 1940,12, 163.lo 2. anal. Chew., 1937, 109, 1.* G. McLellan, J . Assoc. Off. Agric. Chem., 1941, 24, 728.Ind. Eng. Chem. Anal., 1941, 13, 377.2. anal. Chem., 1938, 114, 8.l1 Ind. Eng. Chem. Anal., 1938,10, 393WILSON: ZlNU. 273for precipitation of ZnHg(CNS),, 100 ml. of solution may contain not morethan 2.5 g. of nitric or 5 g. of sulphuric acid. The precipitate can be weighedafter drying at 105', but W. Hoffman and G. B. Thackray l2 prefer to titrateit by R.Lang's procedure,l3 or to use potassium iodate. In analysis of brassor bronze they precipitate copper as Cu,(CNS), as usual, and to the filtrateadd (NH,),Hg(CNS), to precipitate the zinc salt. Similarly, a micro-methodfor zinc in ores l4 precipitates ZnHg(CNS), and titrates it with potassiumiodate. Iron may be masked with potassium fluoride,.citric acid, or (best)phosphoric acid, but large amounts of iron or aluminium prevent theprecipitation -It is stated l5 that p-naphthaquinoline in 0-1N-sulphuric acid and potass-ium thiocyanate give a very sensitive qualitative reaction for zinc. Char-acteristic crystals appear from a 2~-acid solution containing more than 1part of zinc per 200,000 parts. Less than 0.5% of cadmium does notinterfere, but numerous other metals do.Forty-five proposed qualitative reagents are tabulated by P.Wenger andR. Duckert.16 They recommend pyridine and potassium bromide in neutralsolution (nickel also reacts), potassium ferrocyanide in acid solution (cad-mium also reacts), K,Hg(CNS), and cobalt chloride (iron and manganeseinterfere). As " spot " tests they recommend metanil-yellow with potassiumferricyanide, and also dithizone. Benzoin in presence of alkali and mag-nesium ions is a highly specific reagent for zinc,17 giving a compound with avivid green fluorescence in U.V. light. Only bismuth, boron, and antimonyinterfere and the test will detect 1 pg. of zinc in 1 ml. of solution.(2) Use of Organic Reagents.-Anthranilic acid, first proposed by H.Funkand M. Ditt,ls was thoroughly investigated by R. J. Sherman, J. H. F. Smith,and A. M. Ward,lg who dealt with the solubility of the Zn, Cd, Cr, Ni, andCu salts : the solubility of the zinc salt is increased by sodium acetate, buteven in absence of salts, results are somewhat low. Bromination of theprecipitate with standard bromide-bromate solution to the tribromo-compound is preferred, but C. W. Anderson 2o weighs the precipit'ate, whichis formed in acetic acid solution, salts being absent. Preliminary separationof the zinc is essential, and P. Wenger 21 points out that the temperature ofprecipitation is unimportant.R. R. Ray and M. K.Bose 22 claim very good results by a micro-precipitation with sodium quin-aldinate from a hot solution faintly acid with acetic acid.The precipitate isdried at 125". A thorough investigation was made by R. J. Shennan,*3who showed that the reagent completely precipitates copper between pHQuinaldinic acid has also received attention.l2 Analyst, 1941, 66, 321.l* J. J. Lurie and L. A. Philippovs, Zavod. Lab,. 1939, 8, 1047.l 5 E. B. Sandell, D. B. Wishnick, and E. L. Wishnick, Microchim. Acta, 1938,3, 204.l6 Helv. Chim. Acta, 1942, 25, 400.17 C. E. White and M. H. Neustadt, Ind. Eng. Chem. Anal., 1943,15,599.2O In&. Eng. Chem. Anal., 1943, 15, 367.22 Mikrochem., 1935, 17, 11.l3 2. anal. Chem., 1929, 79, 161.18 2. anal. Chem., 1933, 91, 332. lo Amlyst, 1936, 61,. 395.21 Helv. Chim. Acta, 1942, 25, 1499.23 Analyst, 1939, 64, 14274 ANALYTICAL CHEMISTRY.2.5 and 6.9, cadmium from pH 3.9 to 7.2, and zinc a t pH 2-3-66, NOseparations are possible, and acetates have a marked effect on the solubility,but P. R.Riiy and T. C. Sarkar24 showed that if the copper is reducedto cuprous in the presence of thiourea, it is masked and does not interfere;A similar process can be used in presence of mercury.5-Nitroquinaldinic acid precipitates zinc from feebly acid solutions, andhas been made the basis of a colorimetric method.25 Most other metalsinterfere. Another reagent with which most common anions and cationsinterfere, and which would therefore appear to be of very limited use, istetraphenylarsonium chloride.26 Salicylaldoxime also precipitates zinc.L. P.Biefield and W. B. Ligett 27 give the pH at which it precipitates zinc,copper, and lead. T. G. Pearson28 says i t is not a suitable reagent, andJ. H. Flagg and N. H. Furman 29 describe conditions under which it couldbe used. A really useful (but not selective) reagent, however, is 8-hydroxy-quinoline, probably the only one of these reagents which is often used. In amost important paper,30 the authors examined a number of “ oxinates ” byX-ray diffraction, and showed that the dihydrated oxinates of zinc andmagnesium (as of copper and iron) are amorphous, a fact of very greatimportance in explaining the difficulty of many separations which wouldappear to be possible with this reagent. They also showed that fromsolutions containing both ions, the precipitates are solid solutions.Thisdid not confirm other work31 which explained the same phenomenon byadsorption. An earlier paper 32 on separations states that zinc can beseparated from manganese in two precipitations a t pH 5-6, from iron andbismuth in presence of tartrates at pH 8, from arsenic and antimony, but notfrom cobalt or nickel, by this reagent.( 3 ) Colorimetric and Micro-procedures.-Although diphenylthiocarb-azone (“ dithizone ”) is one of the least specific of reagents, it has been usefulin the determination of really small amounts of zinc. It was a t first appliedrather tentatively, but the investigations of many recent authors, in particularthe members of the American “ Association of Official Agricultural Chemists,”have rendered it most serviceable in an enormous number of ways.Thefirst qualitative use of the reagent appears to have been by H. Fischer,=and later with G . L e ~ p o l d i , ~ ~ he showed how, in a barely acid solution, mostmetals could be masked with thiosulphate, rendering the reagent practicallyspecific for zinc, potassium cyanide being added if cobalt or palladium waspresent. I n fhe first application of the reagent to foods,35 a chloroformMikrochem., 1939, 27, 64.3 5 W. L. Lott, Ind. Eng. Chem. Anal., 1938,10, 331.* 6 H. H. Willard and G . M. Smith, ibid., 1939, 11, 269.37 Ibid., 1942, 14, 359.3O R. C. Chirnside, C. F. Pritchard, and M. P. Rooksby, Analyst, 1941, 66, 339.3l H. V. Mayer and W. J. Remington, Ind. Eng. Chem. Anal., 1938,10,212.33 C.Cimerman and P. Wenger, Mikrochem., 1939, 27, 76.33 Ibid., 1930, 8, 319.36 N. D. Sylvester and E. B. Hughes, Analyst, 1936, 61, 734.26 2. anal. Chem., 1938, 112, 179.Ind. Eng. Chem. Anal., 1940, 12, 663.34 2. and. Chem., 1936, 107, 241WILSON: ZINC. 275solution was used to extract a solution of the ash buffered a t pH 4.5 withammonium acetate. Zinc (with bismuth and cadmium if present) wasextracted from the chloroform solution with diluted hydrochloric acid andfinally titrated either with potassium ferrocyanide or, after addition ofpotassium ferricyanide and iodide, with N /500-thiosulphate solution.E. A. Coakhill 36 improved upon P. L. Hibbard’s colorimetric process.37In the analysis of commercial lead, the bulk of the lead (from a 2-5 g.sample) is removed as sulphate, and most of what remains by hydrogensulphide in a solution acid enough to prevent precipitation of zinc sulphide.Thioglycollic acid prevents reaction of lead with dithizone, so a just ammoni-acal solution is extracted with a chloroform solution of both reagents until nofurther change of colour takes place.A “ blank ” solution is now similarlytreated, and standard zinc solution run in until the colours match. A veryimportant colorimetric application is described by F. H. Vogelenzang 38in the determination of zinc in blood, etc. All reagents contain zinc andshould be extracted by the dithizone reagent before use ; glass often containszinc and such glass must not be used. Zinc and copper are extractedtogether from a weakly ammoniacal solution, zinc stripped out with 2 ~ -hydrochloric acid, and finally collected in a carbon tetrachloride solution ofthe reagent; after filtration, the solution is diluted to known volume, andthe red colour measured in a Pulfrich photometer.It has a maximumextinction at 5250 A., and obeys Beer’s law.Several investigators used dithizone to isolate the zinc, and bhen deter-mined it in some other way,39 but generally, progress has been in purecolorimetry, although E. B. Sandell 40 proceeds by “ extraction titration ”a t pH 4.1, sodium thiosulphate masking other elements in soils, and P. L.Hibbard,41 having isolated the zinc compound, titrates it with bromine.H. J. Wichman 42 points out that sodium diethyldithiocarbamate masksalmost all elements except zinc, and that photometry at the proper wave-length enables zinc to be determined without removing excess of reagents.This important modification is being extended by R.A. Caughley, G. B.Holland, and W. S. R i t ~ h i e , ~ ~ and the last two authors44 emphasise thepresence of zinc in most reagents and in glass, and include a valuable tablegiving the reaction of many metals in 0*02~-ammonia or O.O2~-hydro-chloric acid to dithizone, “ carbamate,” and both together ; in 0 . 0 2 ~ -ammonia, this combination is specific. The analytical procedure is typicalof this kind of technique. The extract of the plant ash or the like, containingammonia and ammonium citrate, is treated with a carbon tetrachloridesolution of dithizone, until all reacting metals are extracted.The tetra-chloride layer is then shaken with O*02~-hydrochloric acid, which removes36 Analyst, 1938, 63, 800.38 Phurm. Weekblad, 1939, 76, 89.39 E.g., J. H. Peekman and J. E. Menshing, J . Assoc. Off. Agric. Chem., 1937,20, 627.40 Id. Eng. Chem. Anal., 1937, 9, 464.42 J . Assoc. Off. Agric. Chem., 1938,21, 197.O3 Ibid., p. 204.37 Ind. Eng. Chem. Anal., 1937, 9, 127.4 1 Ibid., 1938, 10, 615.44 Ibid., 1939, 23, 333276 ANALYTICAL CHEMISTRY.lead, zinc, cobalt, silver, and cadmium, leaving copper and mercury in thesolvent layer. The aqueous layer ie made 0 . 0 2 ~ with ammonia, bufferedwith ammonia citrate, and extracted with carbon tetraehloride-dithizoneafter addifion, of “ carbamate,” which brings zinc into the solvent layer.Unfortunately, in presence of “ carbamate ” extraction of zinc is not quitecomplete,45 and the partition ratio between the tetrachloride dithizone phaseand the aqueous phase is influenced by pH and concentration of the reagentsin the two phases.By keeping these factors constant, accurate results canbe obtained, preferably by finally measuring extinction a t 5400 A., a moreconvenient process than extracting excess dithizone with O.OIN-ammoniayleaving zinc dithizone in the carbon tetrachloride phase. For zino in soils(and also copper) G. D. Sherman and J. S. McHargue4‘j proceed somewhatsimilarly to Holland and Ritchie, but before the final extraction of zinc,they mask other metals (e.g., lead) with sodium fhiosulphate.Finally, di- p-naphthylthiocarbazone is proposed as a superior reagentwith many features similar to d i t h i z ~ n e .~ ~ Transmission diagrams are given,and the reagent quantitatively extracts zinc from solutions of pH >76,even when “ carbamate ” is present. Full instructions are given for theelimination of interferences. If less than 0~05 mg. is present, and no cadmium,photometry of the carbon tetrachloride aolution is recommended, but if morezinc or zinc and cadmium are present, the tetrachloride solution is ‘‘ stripped ”with O.S~-hydrochloric acid and polarographed from - 0.3 to 1.3 v., thezinc step taking place a t - 1.1 v. The addition of cadmium (0.6 mg.) as an“ infernal standard ” is a useful device, or after polarography, aknown amountof zinc is added, and from the heights of the zino steps in the two polarograms,the zinc content of the sample is calculated.(4) MisceUaneous Devehpme?ets.-Poiarography aa a micro-method maybe far simpler than colorimetric methods.J. F. Reed and R. W. Cummings 48describe the polarogrephic determination in soda and plant ash. None ofthe constituents of plant ash interferes when the pH of the solution is 4.6,and the solution is 0.025~ with respecf t o thiocyanate ions. On a l-g.sample, zinc may be determined with an error of 5 5 yo when present between0.5% and 5 parts per million. The determination of zinc polamgraphicallyin paints 49 and in brass plate 50 is also described, the latter determinationbeing made in 20 minutes.A publication by the British Aluminium Com-pany, Lfd., discusses analysis of aluminium (and magnesium) alloys by meansof the polarograph and the spectrograph.61R. T. O’Connor b2 describes a spectrographic method for traces of zincin fertdisers, beryllium being added to act as an internal standard, and the45 H. Cowling and E. J. Miller, Ind. Eng. Chem. Anal., 1941,13, 145.46 J . Assoc. 08. A&. Chem., 1942, 25, 510.47 J. Cholak, D. M. Hubbard, and R. E. Burkey, I n d . Eng. Chern. Anal., 1943, 15,48 Ibid., 1940,12, 489.60 W. P. Tyler and W. B. Brown, ibid., 194&18, 520.61 Publication Ml, 1943.754.49 B. M. Abraham and R. S. Huff?nan, dbid., p. 656.52 I n d . Eng. Chem. Anal., 194i, 13, 697WILSON: ZINC. 277Be line 2348 A.being used. Zinc can be determined between 0.0008~0 andabout 1%. E. J. Magaziner and N, A. Zventitzki 53 suggest striking the arcbetween a copper electrode and the sample, using for comparkon the linesCu 2824 and Zn 2756, but if lead is also present Cu 2883 is used.In deposition fromneutral citrate solution, very many metals interfere,= but excellent resultsare obtained by electrolysis at 2 amps. from a slightly alkaline solution onto a copper-plated platinum electrode, after a preliminary separation ; 55the method, for alloys, is very rapid. A. Cohen 56 recommends electrolysisfrom alkaline tartrate solution in analysis of aluminium alloys, and alsodiscusses the mercury thiocyanate precipitation. He emphasises that bythe usual procedure of dissolving the alloy in sodium hydroxide, some zincalways remains insoluble.One or two papers discuss the use of complexcyanides in alloy analysis. C. C. Casto and A. J. B ~ y l e , ~ ' in analysis ofmagnesium alloys, remove manganese and copper, add citrate and dilutesulphuric acid, and proceed by Lang's method.l3 If less than 0.5% of zincis present, a larger sample must be used. In the ferricyanide titration,p-ethoxychrysoidine 58 and o-anisidine 59 are recommended as indicators.In brass analysis, by heating to 800-850" in a vacuum mm.), zinc(and also lead) are distilled off, and the efficiency is greater the higher theproportion of zinc.60 Finally, three papers on commercial analysis for zincare noteworthy. Zinc oxalate is found to be insoluble in 70% acetic acid ifammonium chloride is absent ; 61 the precipitate is washed twice in a centri-fuge tube with 10% acetic acid, and the oxalate finally titrated with per-manganate (nickel, lead, and copper interfere). L.G. Miller, A. W. Boyle,and R. B. Neill 62 dissolve magnesium alloys in dilute hydrochloric acid,adding lead if necessary to prevent solution of copper, then add a littleferricyanide to mask any iron usually present, make the solution ~ / 1 inrespect to hydrochloric acid, add excess of ferrocyanide solution, and afterfiltration, back-titrate excess with ceric sulphate. The method is very rapidand accurate to 1-6%. Zinc in magnesium alloys is also dealt with byS. Weinberg and T. F. Boyd.63 The sample is dissolved in diluted sulphuricacid, a large excess of ammonium chloride and tartaric acid added, thenexcess of ammonia, and the solution electrolysed for 20 minutes at 2 amps.If significant quantities of Group 2 metals are present, they must be removedby means of hydrogen sulphide.Apart from this case, the determinationis complete in 25 minutes.There are a few references to electrodeposition.H. N. W.b3 Zuvod. Lab., 1940, 9, 992. ". R. Winchester and L. F. Yntemrt, Ind. E i q . Chem. Anal., 1937,8,254.5 5 G. H. Osbourne, AnuEyst, 1941, 66, 412.5 6 Helv. Chim. Acta, 1943, 26, 75.5 7 I n d . Eng. Chem. Anal., 1943, 15, 624.G 8 W. I?. Tyler, ibid., 1942, 14, 114.50 H. F. Frost, AimZyst, 19-13, 68, 51.s1 P. J. Ewhg and J. C. Lamkin, Ind. Eng. Chem. Anal., 1944,16, 194.W.P. Treadwell and G. Frey, Helv. C'him. Ada, 1044, 27, 42.62 Ibid., p. 256. Ibid., p. 460278 ANALYTICAL CHEMISTRY.11. Arsenic.The following report is divided into sections, each dealing with the applica-tion of a particular reaction or technique.The Gutzeit Method.-A thorough investigation discusses various errorsto which the process is subject. Since zinc varies in activity, if densemassive zinc be used, the temperature of evolution of arsine should behigher (40-60"); even in the presence of stannous chloride, all thearsine is not evolved from quinquevalent compounds, and reduction bysulphurous acid on a water-bath is recommended, followed by brief boiling,before evolution of arsine, but addition of a little potassium iodide (as acatalyst) and then stannous chloride, following the A.O.A.C.method, isequally effective.A very important paper describes the determination of minute amounts,as little as 0.1 pg., with a probable error of less than 5% and sensitive to0.01 pg. The author uses thin cotton threads impregnated with mercuricchloride as absorbents ; they are enclosed in capillary tubes, into which theyjust fit. All conditions must be rigidly standardised, including temperatureof evolution and of the absorption tubes. Quinquevalent arsenic is reducedby potassium bisulphite, stated to be preferable to the iodide, and a littleferrous salt as catalyst. The stains are developed by ammoniacal silvernitrate solution and measured with a Vernier caliper. This technique hasbeen further ~tudied.~L.Truffert * returns to the reaction of arsine on a silver salt in determiningarsenic in wines. Platinised zinc and sulphuric acid are used to generatehydrogen, and the gases are passed first through potassium hydroxidesolution. The paper, used in strips, is coated with silver citrate, and is stablein the dark; 1-30 pg. can be estimated.The Sub-committee of the Institute of Brewing considers two methods ofestimating the evolved arsine-those of Marsh and Gutzeit. In the latter,discs are preferred to strips, and mercuric bromide is about twice as sensitiveas the chloride, but preparation of the paper, which will not keep, needsgreater care. The lowest limits are stated as 0.001 mg. for the Marsh-Berzelius method, and 0.0004 mg.for the Gutzeit process. Despite theimpermanent nature of the stains, the latter is preferred. For hops, malt,beer, sugar, and finings, methods of preparing the solutions which do notrequire destruction of organic matter are described. Coal is ashed with equalweights of magnesia and potassium permanganate, and in all cases potassiumiodide and sodium sulphite are used to reduce AsV. Alternatively,G coal orcoke is ashed with a mixture of magnesia, sodium carbonate, and potassiumnitrate ; after solution of the residue AsV is reduced by sulphite and deter-mined by the mercuric bromide modification of Gutzeit's method. A con-W. A. Davis and J. G. Maltby, AmaZyst, 1936, 81, 96.A. E. How, Id. Eng. Chem. Anal., 1938,10, 226.E. Cahill and L.Walters, ibid., 1942,14, 90.Ahn. Falsif., 1938, 31, 73.D.S.I.R. Fuel Research Paper No. 44, Oct. 28th, 1940.J . Inst. Brewing, 1938, 44, 359WILSON : ARSENIC. 279tinuous apparatus is described 7 in which hydrogen is evolved from a longcadmium cathode, from an electrolyte containing sulphuric acid and hydroxyl-amine ; from time to time a sample is introduced below the cathode, flows uppast it to the platinum anode, and so to waste. The evolved hydrogen ispassed through. a heated glass tube. As most samples examined are practicallyfree from arsenic, they can very rapidly be dealt with in this apparatus :a contaminated sample is immediately recognised and the mirror can becompared with standards.Less than 0.1 mg. of selenium is stated to have no effect on arsinemethods. *The estimation of arsenic in foodstuffs, etc., contaminated with wargases 9s lo cannot be suitably summarised.G. Taylor and J. H. Hamence l1state that if zinc alloyed with 0.3% of copper is used, the whole of the arsenicis liberated without the use of sulphites in the presence of “ stannated”hydrochloric acid in the Gutzeit method.Reduction by Means of Hypop7tosphite.-This method continues to receiveattention. White metals are dissolved in hydrochloric acid in presence ofbromine, arsenic precipitated with hypophosphite, redissolved, reduced withsodium sulphite after addition of sulphuric acid, and finally titrated withbromate solution. Antimony does not interfere.12 As internal indicatorsfor the bromate titration, Bordeaux, naphthol blue-black, and brilliantPonceau-SR are re~ommended.1~ If reduction is carried out in the solutionat 90°, it is so rapid that there is no loss of ar~enic.1~ The precipitated metalis dissolved in N/5o-CeriC sulphate solution, excess being titrated with ~ / 2 0 0 -arsenious oxide solution, with osmic acid as catalyst. Antimony and tin donot interfere, and the method is valid for 0.1-2 mg.of arsenic. W. J.Agnew l5 proceeds similarly, but uses N/lOO-potassium dichromate to dissolvethe metal, and back-titrates excess with N/lOO-ferrous sulphate. The effectof selenium and tellurium is discussed; H. J. G. Challis l6 points out thatthese elements are also precipitated by hypophosphite but below 50” areprecipitated free from arsenic.After filtration, arsenic can be precipitatedby more hypophosphite on boiling, but B. S. Evans l7 says that this is onlytrue of “traces” of arsenic. He precipitates the three elements (say, inanalysis of copper) together by hypophosphite, redissolves them, andprecipitates selenium with potassium iodide and tellurium with sulphurdioxide, leaving arsenic in solution to be precipitated later with hypophosphiteas usual. The process is applied la to organic arsenicals, after wet oxidation8 Fuel Research Board : Report for year ending March 31st, 1939.Q H. A. Williams, Analyst, 1941, 66, 228.lo A. McM. Taylor and W. J. Stainsby, ibid., p. 233.l2 C. W. Anderson, I n d . Eng. C‘hem. Anal., 1937, 9, 569.13 G. F. Smith and R. L. May, ibid., 1941, 13.460.l4 J. M. Iiolthoff and E. Andrew, ibi&., 1940,12, 177.l5 Analyst, 1943, 68, 111.H. C. Lockwood, Analyst, 1939, 64, 657.l1 Ibid., 1942, 67, 12.l6 Ibid., 1941, 66, 58. l7 Ibid., 1942, 67, 346.H. A. Sloviter, W. M. McNabb, and E. C. Wagner, Ind. Eng. Chem. Anal., 1942,14, 516280 ANALYTICAL CHEMISTRY,with sulphuric and nitric acids, but is not applicable 1Q to cacodyl derivatives,which should be decomposed with potassium birjulphate and sulphuric acid ;after solution is complete a version of the hypophosphite process 2o is used.There are two mentions of a curious process in which the reduced metalis kept in a colloidal suspension. J. V. Harispe*l applies this to the semi-rnicro-analysis of urine : after destruction of organic matter, hydrochloricacid, hypophosphite, and a dilute solution of potassium silicate (protectivecolloid) are added, and after the mixture has been heated on a water-bath,the colour is compared with standards. J.Thuret 22 says that the arsenicslowly flocculates even in presence of stabilisers, and recommends a standardsolution containing borax and colophony, which has the same appearance andremains stable for one month.Distillation Methods.-For other than traces, distillation of arsenictrichloride and titration of the distillate continues to be largely used. Thedetermination in wood of arsenic added as preservative is described : 23after wet oxidation with sulphuric and nitric acids, the latter acid is removedby repeated evaporation, and the trichloride distilled as usual.The distillateis oxidised with nitric acid, excess of this removed, AsV reduced in acid solu-tion with potassium iodide, and finally titrated with iodine in presence ofexcess of sodium bicarbonate. For smaller amounts, a modification ofGutzeit's process is used on aliquots of the distillate. An important paper 24describes the quantitative separation of arsenic, antimony, and tin by frac-tional distillation of the aqueous solution of the chlorides. For arsenic inpyrite~,~5 the mineral is fused with sodium carbonate and peroxide, the massacidified with hydrochloric acid, and the trichloride distilled, hydrazine andpotassium bromide being used aB reducing agents ; the distillate is titratedwith bromate. In the analysis of soils which have been treated with leadarsenate, L.Koblitsky 26 oxidises interfering organic matter if necessary with30% hydrogen peroxide, and distils after reduction with hydrazine andpotassium bromide. H. N. Wilson2' determines total arsenic in glass byfusion with sodium hydroxide, acidification of the melt with hydrochloricacid, in such a way that silica is not precipitated, distillation with this acid,hydrazine and br.omide being the reducing agents, and titration of thearsenious chloride in the distillate (which is of the correct acidity) by ~ / 2 0 0 -potassium iodate. The method, applicable to 0.02 yo arsenious oxide andupwards, is rapid and accurate. V. Dimbleby 28 discusses the same process.Colorimetric Processes.-The most interesting development in arsenicdeterminations is the growth in popularity-of these processes, in all of which19 V.Levine and W. M. McNabb, ibid., 1943,15, 76.20 Ref. 18.2 1 J. P h m . Chim., 1939, 30, 58.22 Ann. Falsif., 1939, 32, 328.23 Commonwealth of Australia.24 J. A. Schemer, Bur. Stand. J. Res., 1938, 21, 95.25 T. A. Fedorkin, Zavod. Lab., 1940, 9, 1324.26 J . Assm. Off. Agric. Chem., 1939, 22, 680.27 Analyst, 1943, 68, 361.Division of Forest Products, Reprint No. 29, 1936.28 Glass Review, 1943, 19, 120WILSON : ARSENIC. 281arsenomolybdate is formed and reduced, the blue colour being a function ofthe arsenic concentration. The arsenic is first isolated from interferingsubstances by distillation as chloride or hydride.Organic matter in must orwine 29 is destroyed with nitric and sulphuric acids and hydrogen peroxide,arsenic distilled as chloride, and the distillate evaporated to dryness withnitric acid. The arsenic, now quinquevalent, is colorimetrically determinedby 0. Zinzadze’s reagent,30 preferably with a Zeiss photometer. Theextinction is proportional to the arsine content from 0.01 to 0.8 mg. J. A.Schemer 31 describes a superior form of Zinzadze’s reagent. D. M. Hubbard 32distils the chloride in a current of carbon dioxide, oxidises the distillate asabove, and obtains molybdenurn-blue by a molybdate-hydrazine sulphatereagent, reacting at 70-75’ for 30 minutes. The colour is stable for 24hours. The maximum absorption is in the near infra-red a t 8400 A., whichgives twice the optical density of that a t 7400 A .~ ~ An elegant, oxidation ofthe chloride is effected 34 by distilling it in a special apparatus, so that thevapours pass through a few ml. of potassium iodate solution, whereby itis oxidised, steam and hydrogen chloride passing on to be condensed andreturned to the flask.Two methods avoid distillation by extracting the acid arsenious solutionwith a carbon tetrachloride solution of sodium ethylxanthate. A. Kleinand F. A. Vorhes 36 evaporate the extract to dryness and oxidise the residuewith bromine water, then applying Zinzadze’s reagent. T. B. B. Crawfordand I. D. E. Storey36 extract inorganic arsenite from blood, urine, etc., bymeans of the xanthate (three extractions) and then proceed as in the foregoingor by means of G .A. Levvy’s method.37Several papers deal with the evolution, oxidation, and colorimetricdetermination of arsine, the arsenomolybdate being used. E. B. Sandell 38passes the arsine and hydrogen (from 20-30 mesh zinc) through mercuricchloride and potassium permanganate, evolution of arsine being completein 30 minutes; the solution is filtered and treated by Hubbard’s method.*2The procedure is suitable for 1-10 pg. of arsenic. M. B. Jacobs andJ. Nagler 39 oxidise the arsine by hypobromite, and R. Milton and W. B.Driffield 40 by iodine and sodium hydrogen carbonate solution. In all casescareful adherence to standard quantities of reagents is necessary, and alsoto exact control of acidity, as is always the case for quantitative formationand reduction of molybdenum complex ions.In controlled conditions, theblue colour obeys Beer’s law from 0.001 to 0.1 mg. of arsenious oxide per10 ml.Arsenic can be colorimetrically determined in lead without distillation29 J. Burkard and B. Wallhorst, 2. Unters. Lebensm., 1935, 70, 308.30 I d . Eng. Chem. Anal., 1935, 7, 227.32 Ind. Eng. Chem. Anal., 1941, 13, 915.33 J. A. Stultzaberger, ibid., 1943, 15, 408.34 A. L. Chaney and H. J. Magnuson, ibid., 1940,12, 691.36 J. Assoc. 08. Agric. Chern., 1939, 22, 121.37 Ibid., 1943, 37, 598.3B Ibid., p. 442.The process is very rapid.31 Bur. Stand. J . Res., 1938, 21, 96.313 Biochem. J., 1944, 38, 195.a6 Ind. Eng. Chem. Anal., 1942, 14, 82.40 Analyst, 1942, 67, 279282 ANALYTICAL CHEMISTRY.the latter being nearly all removed from the nitric acid solution by sulphuricacid, and the molybdenum-blue reagent applied to the filt~ate.~lC.C. Cassil 42 recommends passing arsine into mercuric chloride solution,titrating this by adding excess of an iodine solution containing enoughiodide to hold excess of mercury in solution, and back titrating with thio-sulphate.Vuriow Methods.-Polarography is said43 to be possible only in acidsolution; the shape of the polarogram is influenced by the supportingelectrolyte, and sometimes four waves are visible. K. Bambach 44 collectsarsine in mercuric chloride solution, heats this to convert arsenides intoarsenites, and at pH 6 precipitates mercury with hydroxylamine.The clearsolution is polarographed after addition of hydrochloric acid. In 1*5~-acidthe half-wave is at - 0.35 v., in O-S~-acid at - 0.5 V. The process is moreaccurate than that of Gutzeit and quicker than colorimetry. J. J. Lingane 45says that AsVis not reduced at the dropping-mercury cathode, but As111 isreduced in two steps; in N-hydrochloric acid the wave height a t -0.8 V. isproportional to concentration. An ill-defined wave at - 0.9 v. may corre-spond to reduction to arsine. Tartrate or alkali suppresses the wave, and0-1 yo of gelatin should be present.S. Torrance 46 states that if a solution of copper containing less than one-fifth of its weight of arsenic in hydrochloric acid is electrolysed, all the arsenicis deposited with the copper.If the deposit is redissolved and electrolysedin sulphuric solution, only copper is deposited, leaving all the arsenic insolution.Among noteworthy miscellaneous methods are the distillation of arseniouschloride from solutions containing tungsten,47 the determination of arsenatesand selenates in presence of one another,48 a microtechnique for determinationas magnesium ammonium a r ~ e n a t e , ~ ~ the mechanism of Bettendorf's test,50and a method for quantitatively separating arsenic from copper by co-precipitation with hydrated manganese oxide.51 In determining arsenic insulphur, S. J. Fainberg and G. A. Taratorin 52 dissolve the latter in boilingsulphite solution, and add copper sulphate and acetic acid, whereupon allthe arsenic is carried down as trisulphide by the copper sulphido; or thesulphur is dissolved in alkaline hydrogen peroxide, and the arsenic determinedcolorime trically .41 E.A. Coakill, Analyst, 1938, 63, 801.42 J . Assoc. Off. Agric. Chem., 1938, 21, 198; (with H. J. Wichmann) 1939, 22,436;1941, 24, 196.T. A. Krinkova, Zavod. Lab., 1940, 9, 950.44 I d . Eng. Chem. Anal., 1942, 14, 265.4 6 Analyst, 1938, 63, 104; 1939, 64, 263.4 7 T. Millner and F. Kiinos, 2. anal. Chem., 1936,107, 96.4g F. Hecht and M. von Mack, Mikrochem. Acb, 1937, 2, 218.Eo W. B. King and F. E. Brown, J. Amr. Chem. Xoc., 1939, 61, 968.0 1 C. L. Luke, I d . Eng. Chem. Anal., 1943, 15, 626.52 Zavod. Lab., 1940, 9, 1223.46 Ibid., 1943,15,583.J. Milbauer, ibid., 1937, 109, 171-SON : FLUORINE.283Finally, an important paper is devoted to analysis of large numbersof samples of foodstuffs or the like : after wet oxidation and removal ofnitric acid, a few mg. of cadmium sulphate are added to the diluted solutionand precipitated as sulphide, carrying down all the arsenic. The cadmiumlater serves as an internal standard. The sulphide is collected on a smallsuction filter dressed with powdered graphite, and after being dried is arcedin a low-tension D.C. arc between graphite electrodes using a Hilger mediumspectrograph to record the spectrum. Normally, visual comparison betweenthe spectrogram and that of a standard sample suffices to show whether ornot the specified limits for arsenic, etc., have been exceeded. The method isvery expeditious and suitable for mass production methods of working, butas only 1 g.of sample is used, scrupulous care must be taken over " blanks "and absolute cleanliness of working.H. N. W.111. Fhmrine.Probably the determination of fluorine has changed more than that of anyother element in recent years. H. H. Willard and 0. B. Winter's procedure,lin which the fluorine was distilled as hydrosilicofluoric acid from an aqueousacid solution in which quartz powder was suspended, hydrolysed again tofluoride in the distillate, and titrated with N/lOO-thoriurn nitrate solutionwith alizarin43 as an indicator, wag a remarkable advance in analyticaltechnique. Much subsequent work has simply been refinement and ampli-fication of this method.Ashing.-The possibility of losing fluorine during ashing or calciningoperations cannot be too greatly stressed.J. M. Sanchis2 adds sodiumhydroxide solution before ashing in platinum, and distilling at 135-140'with sulphuric acid ; chlorine interferes, especially in presence of manganese,and should be removed by means of sodium nitrite. Finally, thedegree of fading caused by various aliquots of the distillate is comparedagainst standards, using zirconyl alizarin-S lake as is now usual. In themicro-determination of fluorine in bl00d,3 loss of fluorine is reduced byfirst charring in a porcelain crucible, then transferring to a gold one ! Theash must not be sintered. is recom-mended (i.e., zirconyl chloride and purpurin solution). Wine can be ashedwithout loss of f l u ~ r i n e , ~ and one distillation at 135" with perchloric acidremoves all the fluorine.For determining fluorine in impregnated wood,B. Ikert adds chromium acetate and calcium acetate solutions beforeashing, as this is stated to lead to a better recovery. In analysis of woolmoth-proofed with fluorine compounds, F. F. Elsworth and J. Barritt 'moisten the wool with sodium carbonate solution, and ignite below aJ. M. Kolthoff's colorimetric reagent53 D. A. Harper and N. A. Strafford, J . SOC. Chem. Ind., 1942, 61, 74.Ind. Eng. Chem. Anal., 1933, 5, 7.H. Wulle, Z. physiol. Chem., 1939, 260, 169.Ind. Eng. Chem. Anal., 1934, 6 , 118.Chem.-Ztg., 1939, 63, 754.a Ibid., 1934, 6 , 134.5 €I. G. Rempel, ibid., 1939, 11, 378.7 Analyst, 1943, 68, 298284 ANALYTIOAL UHEMISTRY.red heat.For fluorine in coal (26-150 parts per million), H. E. Crossley 8burns it with sodium carbonate at a low temperature, or ignites i t in acalorimetric bomb. I n the first case he follows combustion by a fusion,separates silica as usual, and distils. In the second case interference bynitrates is overcome by reduction with a zinc-copper couple before distill-ation. The distillates are compared visually with standards, the authorcorrectly observing that the zirconium lake colours are not suitablc forabsolute colorimetry. Calcium or magnesium peroxide is suggested' 9 asan adjunct in the ashing of soils. In the presence of much silica, magnesiumperoxide leads to low recoveries, but in presence of much organic matter andlow silica content, it is preferred to calcium peroxide, and leads t o a lessviolent reaction.Magnesium acetate may be used as an ashing agent ;loit is free from fluorine and gives very concordant results after ashing a t570'.DistiZEation.-This has been very thoroughly studied. Recovery offluorine decreases with increasing volume in the distilling flask, and thepresence of non-volatile acids hinders the distillation; the effect of volumeis less marked with sulphuric acid, volatilisatio? is slowest with phosphoricacid, and recovery is more rapid at higher temperatures.11 D. S. Reynoldsand his co-workers l2 describe a steam-distillation in which the temperatureis regulated by blowing in steam rather than by dropping in water, and itsapplication to phosphate rock.The process is typical; 0.5 g. is distilledwith 15 ml. of 2 : 1 perchloric acid, the temperature being maintained a t125-150". Ifpyrites or organic matter is present, distillation is preceded by oxidation withpermanganate. I n the presence of colloidal silica or alumina, which obstin-ately retain fluorine, it is necessary 13 to make a preliminary distillation withsulphuric acid at 165".Titration.-The use of thorium salts for this purpose has been thoroughlystudied. The amount of indicator in Willard and Winter's titrationwith N/lOO-thorium nitrate must be kept constant,14 and changes in pHcause errors proportional to the change and to the fluorine content. Thebest pH is 2-5-3.0, and a back titration is preferred.By using a buffer ofhalf-neutralised N-chloroacetic acid, pH 3, R. J. Rowley and H. V. Churchill l5avoided the use of alcohol, and titrated with N/lO-Th(NO,),, extending therange considerably. R. A. Clifford l6 measured the colour during the titra-tion, using a photometer, and showed that for very small quantities there is9 W. H. MacIntyre and J. W. Hammond, J . Assoc. Off. Agric. Chem,, 1939,22, 231.10 W. E. Crutchfield, jr., Ind. Eng. Chem. Anal., 1942, 14, 57.11 D. Dahlc and H. J. Wichmann, J . Assoc. 08. Agric. Chem., 2936,19, 303; 1937l2 Jbid., 1936, 19, 156; I d . Eng. Chern. Anal., 1939, 11, 21.l 3 D. Dahle and H. J. Wichmann, J. Assoc. Off. Agric. Chm., 1936 .19, 320.14 D. DaNe, R. W. Bonar, and H.J. Wichmann, ibid., 1938,21,469.l6 Id. Eng. Chem. Anal., 1937, 9, 551.lA R. A. Clifford, J . Assoc. Ofl. Agric. Chem., 1940, 23, 303.Recovery is complete when 150 ml. have been distilled.J . Soc. Chem. Ind., 1944, 63, 280.20, 297WILSON : FLUORINE. 286no “end-point,” but a gradual change. He recommends titration to anintermediate colow, adding the same amount of 0.0004~-Th(NO,), solutionto a “ blank ” containing the same quantity of indicator, and back-titratingwith a standard (1 ml. = 0-01 mg. F) solution until the colours match.The difficulties of titrating very small amounts are reviewed. l7 Fluorineconcentrations of 2-50 pg. and 0.2-5 mg. per 10 ml. were studied a t pH 3 inpresence and in absence of chloroacetic acid, and the thorium nitrate was0.0175~.In alcoholic solution in the lower range, fair agreement wasobtained, but the buffered solution gave high results; in aqueous solutionsall results were too high, the buffered solutions again being the higher. I nthe 0.2-5 mg. range all the systems gave good results. Micro-quantitiesof fluorine in aqueous solution must thus be titrated by empirically standard-ised solutions, but for alcoholic solutions the stoicheiometric factor can beused.Colorimetric Methods.-Numerous methods exist for colorimetric esti-mation of small amounts of fluorine, apart from the “ titralion-colori-metry.” 16# 260 27 Except in waters, it is almost always necessary to isolatethe fluorine by distillation. The development of the zirconium-alizarinlake method is shown by three papers.In waters,1* the usual amounts ofmanganese, aluminium, iron, silicate, sodium chloride and sulphate have verysmall effect, but ferric iron and phosphate completely vitiate the procedure.The sample is made acid with sulphuric and hydrochloric acids, a solution ofzirconyl nitrate + alizarin-S added, and the whole heated to boiling andallowed to stand overnight. It is compared in Nessler cylinders with standardssimilarly treated. W. L. Lamar and C. G. Seegmiller l9 describe a procedurein which only sulphuric acid is added to the water, which is not boiled, butallowed to stand overnight with the reagent, before comparison with stahd-ards containing 0-02-0-24 mg. of fluorine. What is perhaps the bestmethod for fluorine in small amounts in waters, etc., is given by A.P. Blacket aL20 and by R. D. Scott.21 The reagent contains alizarin43 and zirconiumoxychloride, made 1 . 5 ~ with regard to both hydrochloric and sulphuric acid,thus reducing to a minimum interference from chlorides and sulphates. Thecolour is bleached by fluoride ions, and the best range of standards is 0.01-0.1 mg. of fluorine per 100 ml., but it can be extended to 0.18 mg. Iron andaluminium both interfere if present to more than 0.5 parts per million. Thereaction is complete in 2 hours, and the reagent keeps very well. N. A.Talvitie 22 suggests a thorium nitrate reagent buffered at 3.5, and containing0.008% of alizarin-S. The sample is neutralised with dilute nitric acidbefore applying the reagent.The method is simple and rapid, and woulddetect 0.1 part per million on a 100-ml. sample.Two papers utilise the bleaching of the iron complex with 7-iodo-17 J. W. Hammond and W. H. MacIntire, J . Assoc. Off. Agric. Chem., 1940,23, 398.l9 Ind. Eng. Chem, Anal., 1941, 13, 901.*O J . Amer. Water Works ASSOC., 1941, 33, 1965.22 Ind. Eng. Chem Anal., 1943, 15, 620.0. J. Walker and G. R. Finlay, Canadian J . Res., 1940,18, 151.21 l b i d . , 1941, 33, 2018286 ANALYTICAL CHEMISTRY.8-hydroxyquinoline-4-sulphonic acid (" ferron ") by fluoride ions. Forfluorine in rocks,23 the sample is fused with alkali, and silica is separated bya modified Berzelius-Rose method, finally with zinc oxide and ammoniumcarbonate. An aliquot of the filtrate is taken, and a standard preparedcontaining the same concentration of salts. Each is treated with 2 ml.ofthe ferric " ferron " reagent, and the standard titrated with a ~/50-sodiumfluoride solution until the colours match; a difference of 0.05 mg. of fluorineis readily perceptible, and the range is 0-1-1-5 mg. Alternati~ely,~~ thefluoDine may be isolated by a preliminary distillation at 165" with sulphuricacid, the distillate being neutralised, concentrated, and redistilled at 135"with perchloric acid. An aliquot containing < 5 mg. of fluorine is treatedwith the reagent, and its extinction measured with a photometer, using a redfilter. In the peroxytitanicsulphate method 25 aluminium ions largely counteract the bleaching effectof fluorine on the colour ; if the same amount of pertitanate solution is addedto each of two aliquots, and aluminium to one of them, provided the pH benot changed, the difference in colour will be proportional to the fluorinecontent, irrespective of the colour of the original solution.The twomethods are similar; in the English method on a I-g.sample, 1 part permillion can be determined with an accuracy of 0.15 part; in the American,the best amount of fluorine to have present is 30-70 pg. The originalsmust be consulted for details, but reagents must be prepared especially tobe free from fluorine, and a little (< 1.5 pg.) always comes from the glass.Thorium nitrate solution (0-025%) is added to the final distillate to a faintpink colour, the same volume added to the " blank," and then standardsodium fluoride solution (1 ml.= 0.01 mg. F) to the blank until the coloursmatch. Further applications are recorded in various papers.28Miscellaneous.-The lead chlorofluoride method is applied to insecti-c i d e ~ . ~ ~ For the determination of fluoride in organic compounds two pro-cedures are given. A new technique is described by P. J. Elving and w. B.LigetL30 The compound is heated in a closed tube, like a Carius tube, withmetallic potassium cut into small pieces, air having been displaced by addinga few ml. of ether, which is sucked off as vapour, removing also water.After exhaustion, the tube is sealed, and heated to 400". After cooling,excess of potassium is destroyed by ethanol, the residue dissolved, thesolution filtered, and fluorine determined, e.g., as lead chlorofluoride.M.L. Nichols and J. S. Olsen 31 commence by fusion with sodium peroxide,potassium carbonate, and sugar in a Parr bomb; after extraction andneutralisation, fluorine is titrated potentiometrically with cerous nitrate.23 J. J. Fahey, Ind. Eng. Chem. Anal., 1939, 11, 362.24 P. Urech, Helv. Chim. Acta, 1942, 25, 1115.25 D. Dahle, J . Assoc. Off. Agric. Chem., 1937, 20, 505.2 G Society of Public Analysts Sub-committee, Analyst, 1944, 69, 243.2 7 Anon., J . Assoc. Off. Agric. Chem., 1944, 27, 90.2 * P. A. Clifford, ibid., p. 246; Anon,, ibid., p. 98.30 Ind. Eng. Chem. A n d . 1942, 14, 449.The fluorine content is read from a graph.There are two important papers on fluorine in foods.26#27Anon., ibid., p.75.3 l Ibid., 1943, 15, 342HERON AND WILSON : ORGANIC MICROCHEMICAL ANALYSIS. 287The concentration of fluorine in air is determined automatically byaspirating i t through a solution containing ferric chloride, potassium thio-cyanate, and persulphate. Fluorine bleaches the red colour, and the changeis measured photoelectrically.32 Full details of apparatus and procedure forsampling anhydrous hydrogen fluoride are given.33.34 It is then dilutedby addition to ice in a special weighing vessel, after which the solution isanafysed for hydrofluoric, hydrosilicofluoric, sulphurous and sulphuric acids.Qualitative Tests.-J. Fischer 35 adds to the neutral fluoride solutioneosin, lanthanium acetate, and sodium acetate ; on boiling, cooling, andcentrifuging, a red precipitate indicates fluorine ; 2 pg.can be detected.E. R. Caley and J. M. Perrer 36 describe apparatus for a micro-etching test,and suggest the preparation of a series of standard etched microscope cover-glasses, the amounts dealt with ranging down to 0.05 mg. of calcium fluoride.IV. Organic Microchemical Analysis.H. N. W.In 1942 an excellent review of the recent literature was published,land the following is a brief note on progress since then. The determinationof specific compounds is not reported, but only analysis for elements orradicals, with notes on new apparatus.The American Chemical Society recommendations for apparatus for thedetermination of sulphur and the halogens (Pregl’s methods) have beenpublished,2 and G.H. Wyatt 3 reviews all kinds of micro-volumetric appara-tus. The error of a single weighing on a microbalance is 3 pg., most ofwhich is due to the placing of the rider, but results are stated to be describedas surprisingly the standard deviation being 3.4 pg., and the largestemor to be expected from a single weighing being 7 pg. isdevoted to the errors of a Kuhlmann balance ; the tracing of errors is described,and every possible error due to environment, construction, wear, design, etc.,is considered. Random errors amount to about 5 pg., and suggestions aremade to reduce this to 1 pg. Simple apparatus are described for micro-ammonia distillation 7 and for semimicro-alkoxyl determinations,* preferablyby F.Viebock and C. Brechner’s m e t h ~ d . ~ The latter apparatus can alsobe used for wet methods of halogen determination. A V-shaped micro-pyknometer made of capillary tubing, and with a capacity of 0.01-0.02a2 L. S. Tschemodanova, Zavod. Lab., 1939, 8, 1248.33 U.S.A. Manufacturing Chemists’ Association, Ind. r i g . Chem. Anal., 1944, 16,84 C. F. Swinehart and H. F. Flisik, ibid., p. 419.35 Z . anal. Chem., 1936, 104, 344.A long article483.a8 Microchim. Acta, 1937, 1, 160.L. T. Hallett, Ind. Eng. Chem. Anal., 1942, 14, 956.G. L. Royer, H. K. Alber, L. T. Hallett, and J. A. Kuck, ibid., 1943, 15, 230.Analyst, 1944, 69, 81.M. Corner and H. Hunter, ibid., 1941, 66, 149.Committee on Micro-balances, American Chem. SOC., Ind.Eng. Chem. Anal., 1943,A. H. Corwin, ibid., 1944, 16, 258. R. Markham, Bwchem. J . , 1942, 36, 790T. White, Analyst, 1943, 68, 366.15, 415.@ Ber., 1930, 63, 3207288 ANALYTICAL CHEMISTRY.ml., is described; lo it can be mounted on a board carrying 2 scales, andcalibrated with the liquid a t various levels, read on the scales, and a graphplotted to show volumes a t various levels in the arms. Results are quotedcorrect to 3 or 4 digits. Methoxyl and ethoxyl groups may be determinedin the same molecules ; l1 the two alkyl iodides are collected in a 10% solu-tion of frimethylamine in alcohol, three receivers in series being used. After50 minutes the receivers are washed out with alcohol and water, thesolution evaporated to dryness, and trimethylethylammonium iodide ex-tracted with a saturated solution of tetramethylammonium iodide inabsolute alcohol.The tetramethylammonium iodide thus remaining isoxidised to iodic acid, and determined as usual. Results quoted forsamples of 10-15 mg. are good. An improved semimicro-method foralkoxy-groups in cellulose ethers, etc., is given.12 A. A. Houghton la describesa modified apparatus for simple and rapid working of Viebock’s method ; theapparatus requires very little attention and is suitable for repetition work.An analysis is completed in less than an hour, and errors on 10-mg. samplesare insignificant.Hydroxyl groups are determined 1* by weighing 2-10 mg. into a melting-point tube sealed a t one end, followed by a weighed amount (20-25 mg.) ofacetic anhydride, and excess (not weighed) of pure pyridine.The tube issealed, centrifuged to mix the reagents, and allowed to stand for 24 hours.It is broken under water, and excess of acetic anhydride titrated with 0.04.~-sodium hydroxide.E. W. Peel, R. H. Clark, and E. C.Wagner l5 fuse 15-20 mg. of substance in a Parr micro-bomb, with sodiumperoxide ; they prefer gravimetrio procedures, and weigh liquids in gelatincapsules rather than capillary tubes. A. F. Colson16 describes a modifiedapparatus for volatile compounds, for which the Parr bomb is unsuitable.In it modified Pregl’s apparatus, the compound is volatilised in a stream of airor oxygen, the stream passing through a heated platinum cylinder to act asa catalyst. In the cylinder is a glass rod, which forces the gas stream throughthe small annulus between the rod and the cylinder, thus ensuring efficientcontact.The chlorine is absorbed in solid sodium carbonate and granularlimo, the mixture dissolved in dilute nitric acid, reduced with hydrazine,and the chloride finally weighed as silver salt. Excellent results are quoted.P. J. Hardwick l7 determines bromine in biological fluids by heating in asealed tube with sodium ethoxide solution, evaporating the product, andafter gentle calcination, dissolving the residue, neutralising it, and oxidisingit either (i) to bromate with hypochlorite or (ii) to bromine with chloramine-TA blank is run simultaneously.Several papers treat of halogens.lo A. A. Houghton, Analyst, 1944, 69, 346.l1 L.M. Cooke and H. Hibbert, Id. Eng. Chem. Anal., 1943,15, 24.l2 E. Y. Sarnsel and J. A. McHard, ibid., 1942,14, 750.l4 J. W. Peterson, K. W. Hedberg, and B. E. Christensen, Ind. Eng. Chem. Anal.,l5 Ibid., 1943, 15, 149. 16 Analyst, 1942, 87, 47.Analyst, 1944, 69, 363.1943, 15, 225.1 7 Ibid., p. 223HERON AND WILSON : ORGANIC MICROCHEMICAL ANALYSIS. 289in presence of fluorescein, the red colour (eosin) produced being a measureof bromine present.G. Ingram18 deals with the uses of mercuric oxycyanide in micro-volumetric analysis. In neutral solution, this reagent reacts with halogensalts to liberate an equivalent quantity of hydroxyl, to be titrated with ~/100-sulphuric acid. He describes applications to the determination of halogens,a special apparatus for the combustion being described.By using oxygensaturated with water, the formation of sulphur trioxide mist from sulphurcompounds is avoided. If both sulphur and halogens are present, total acidformed may be titrated as usual, then halogen by means of the oxycyanide.The reagent may also be applied to the determination of alkoxyl groups.W. B. Price and L. Woods l9 describe a technique for the analysis ofminute bubbles of gases, e.g., from the bubbles in glass. The bubble ismeasured under a slide in glycerol by means of a microscope, and aftertreatment with reagents, measured again. The smallest bubble can be 0-2mm. in diameter or 0.004 mm. in volume, and hydrogen, oxygen, hydrogensulphide, carbon monoxide and dioxide can be determined.A semimicro-apparatus is described 20 for determining Reichert, Polenske,and Kirschner values in fats.The formyl group may be determined 21 similarlyto acetyl, except that the formic acid produced may be either titrated withalkali or oxidised by bromine in N/loO-solution, thus making the determinationspecific. The semimicro-determination of esters, which are heated to SO" inclosed 25-ml. flasks with 2~-sodium hydroxide in 90% methanol, is discussedwith reference to steric hindrance.22R. Belcher and C. E. Spooner 23 deal with attempts to hasten the usualLiebig or Prcgl form of analysis by using rapid air rates, and to simplify theapparatus by use of empty tubes. Originally put forward as a macro-method for the ultimate analysis of coal, the method embodies novel features.The coal sample is gradually introduced into a tube heated to 1350", and nopacking is used except a silver spiral at the cool exit end to absorb halogensand sulphur. The oxygen rate is 300 ml./minute, and a complete combustionoccupies ten minutes. Carbon, hydrogen, sulphur, and chlorine can bedetermined simultaneously. Micro- and semimicro-procedures are alsogiven. Combustion is conducted in an empty silica tube, a roll of silvergauze serving to trap halogens and sulphur ; oxides of nitrogen are trappedby ~/5O-potassium permanganate or dichromate in sulphuric acid. Theoxygen rate is 50 ml./minute. Carbon, hydrogen, and sulphur can bedetermined simultaneously, the last being dissolved off the silver spiral assilver sulphate, after which the spiral is again weighed. It is claimed thesemethods are more rapid and simpler than the standard procedure. The lastAnalyet., 1944, 69, 265. 19 Ibid., p. 117.2o B. Dyer, G. Taylor, and J. H. Hamence, ibid., 194.1, 66, 355.21 J. F. Alicano, Ind. Eng. Chem. Anal., 1943, 15, 704.22 J . Mitchell, D. M. Smith, and F. S. Money, ibid., 1944,16, 410.23 Fuel, 1941, 20, 130; Ind. Chem., 1943, 19, 653; J . , 1913, 313; R. Belcher, J .Inst. Fuel, 1944, 17, 160.REP. VOL. XLI. 290 ANALYTICAL CHEMISTRY.paper was followed by an interesting discu~sion,~~ the opinion being thatgood results were obtained by the macro- and the semimicro-procedure,but that on the micro-scale, trouble was caused by formation of oxides ofnitrogen.G. Ingram 25 describes a new method for determining carbon and hydro-gen. In a silica combustion tube the packing is placed in boats. Thecatalyst is a special mixture of ceria, litharge, silver dichromate, and silveroxide, and also a roll of copper gauze filled with a mixture of ceric andvanadic oxides. The combustion is conducted a t 500°, and is complete in50 minutes. Silver vanadate on pumice as the main oxidation filling issuperior to copper oxide and lead chromate, or to platinum contacts.A. E. H.H. N. W.A. E. HERON.H. N. WILSON.24 J . Inst. Fuel, 1944, 18, Suppl. p. 51.26 J . Soc. Chm. Id., 1942, 61, 112; 1943, 62, 175

ISSN:0365-6217    

DOI:10.1039/AR9444100272

出版商:RSC    

年代:1944

数据来源: RSC

摘要:

INDEX OE’ AUTHORS’ NAMES.Ab, G. A., 66.Abderhalden, E., 78.Abernethy, J. L., 140.Abitz, W., 61.Aborg, C. G., 11.Abraham, B. M., 276.Abraham, I. M., 85.Abramov, F. I., 102.Abrams, J. R., 184.Ach, L., 211.Adam, N. K., 5, 12.Adams, R., 165, 221, 225.Adamson, D. W., 130.Adickes, F., 126, 134.Agnew, W. J., 279.-4itkenhead, W. C., 109.Albanese, A. A., 237.Alber, H. K., 287.Albert, A., 270.Alhertson, N. F., 123.Alcayago, R., 254.Alder, K., 147, 148.Aldersley, J. B., 139.Aleksewa, 0. A., 109.Alexander, A. E., 6, 8, 9,Alexander, L., 52.Alfrey, T., 67.Alicano, J. F., 289.Alimarin, I. P., 109.Allechina, A. P., 151.Allsebrook, W. E., 211.Almquist, H. J., 237.Alquier, R., 156.Altmann, E., 142.Alyea, H. N., 193.American Chemical Society,Anderson, C.W., 273, 279.Anderson, E., 241, 243.Anderson, H. H., 88, 89.Anderson, R. P., 109.Andrew, E., 279.Andrews, J. S., 260, 261.Anson, M. L., 61.Anthes, H. I., 134.Anzilotti, W. F., 152.Archer, S., 123, 198.Ardenne, M. von, 70, 85.Arnold, M. H. M., 54.Aruja, E., 61, 63.Ashburn, S. S., 256.Askew, F. A., 11.Assaf, A. G., 71, 72.Astbury, W. T., 14, 61, 62,68, 72, 73, 74, 76, 79, 80.Astwood, E. B., 247, 248,249.10, 11, 12, 13, 14, 15.287.htkin, L., 258, 268.Australia, Commonwealth-4ustrian, R., 28.Baba, T., 36.Babajan, A. T., 152, 167,Babbitt, J. D., 72.Babikova, V. I., 102.Bachman, C. H., 84.Bachman, G. B., 168.Bachmann, W. E., 182.Back&, M., 139, 140, 141,Baddiley, J., 211, 212, 213,Badoche, M., 148.Baer, E., 235.Bailar, J.C., jun., 100.Bailey, H. B., 79.Bailey, K., 76, 79, 233.Baker, R. F., 63.Baker, W. O., 69.Baldwin, R. R., 73, 74.Ball, R. P., 242.Bambach, K., 282.Banks, W. H., 9.Bannister, F., 33, 39.Baranaev, M. K., 8.Baranov, V. I., 175.Barkdoll, A. E., 125, 243.Barker, G. R., 207.Barnos, H. M., 134.Barnett, J., 267.Barr, T., 78.Barrer, R. M., 32, 33, 34,39, 42, 45.Barritt, J., 283.Barron, E. S. G., 234.Barry, A. J., 71.Bartels, E. C., 247.Bartlett, P. D., 193.Barton-Wright, E. C., 260,261, 262.B as c hen ova - K o s 1 o v s k a j a ,L. I., 173.Bass, W., 200.Bastron, H., 162.Bath, J. D., 77.Battista, 0. A., 70.Bauer, S. H., 57.Bauernfeind, J. C., 260.Baule, B., 71.Baum, A.A., 166, 164.Baumann, E. J., 248.Bayer & Co., 152, 166.Beach, J. Y., 51, 67.of, 280.170.143.214.291Beadle, G. W., 239, 259,263, 265.Bear, R. S., 73, 77, 79, 80.Beard, P., 22.Beck, G., 102.Becker, B., 220.Becker, E., 87, 88.Behrens, H., 107.Beischer, D., 70.Bekkedahl, N., 66.Belcher, R., 289.Belitzer, V. A., 236.Bell, E. P., 150.Bellet, E., 160.Benedict, S. R., 207.Benjamin, M., 84.Berchet, G. J., 161, 165.Berg, C. P., 237.Berg, S., 70.Bergeim, O., 265.Berger, E., 204, 205, 211.Bergmann, M., 27, 75, 78,132, 133, 140, 142.Bernal, J. D., 74, 77.Bernhard, K., 207.Bernhoim, F., 253, 269.Bernheim, M. L. C., 253.Beuchelt, H., 203.Beuttenmiiller, E., 67.Beyerstedt, F., 134.Bezel-Sitscheva, V.A.,Biefeld, L. P., 274.Bigger, J. W., 268.Bijl, H. C., 145.Bilham, P., 12, 13.Billman, J. H., 124.Biltz, H., 211.Biltz, W., 95, 111.Bina, A. F., 262.Binkley, S. B., 267, 258.Bird, 0. D., 257, 258, 262.Birkofer, L., 212.Bissell, A., 247.Bissell, G. W., 247.Black, A., 261.Black, A. P., 285.Black, S., 256.Blackburn, S., 75.Blanchard, K. C., 72.Blicke, F. F., 158.Block, K., 236.Block, P., jun., 125, 243.Block, R. o., 75, 120.Blodgett, K. B., 7.Blomquist, A. T., 195.Bloom, E. S., 257, 258.Bloomfield, G. F., 191.162292 INDEX OF AUTHORS’ NAMES.Bodroux, D., 149.Bwseken, J., 154, 205.Boekelheide, V., 183.Boekenoogen, H. A., 154.Bohonos, N., 256.Boki, G. B., 54.Bolduan, 0.E. A., 64.Bolling, D., 75, 120.Bollman, J. L., 233.Bonar, R. W., 284.Bonner, D., 239, 240.Bonner, J., 259.Bonner, L. G., 55.Bonsdorff, K., 28.Boord, C. E., 151,Booth, H., 110.Booth, H. S., 90.Booth, R. G., 259, 260,261.Borchers, R., 237.Borg, W. A. J., 216.Borovik, S. A., 102, 108.Borson, H. J., 254.Borth, G., 139.Boruff, C. S., 260.Bose, C. R., 60.Bose, M. K., 273.Bottomley, A. C., 262.Bourguel, M., 152.Bourne, E. J., 232.Bovarnick, J. R., 130.Boyd, G. E., 6, 7.Boyd, H. M., 260, 261.Boyd, T. F., 277.Boyer,R. F., 67.Boyes-Watson, J., 77.Boyle, A. J., 277.Bozorth, R. M., 53.Bradbrook, E. F., 183.Brady, T. G., 202.Bragg, (Sir) W. H., 32, 34.Bragg, (Sir) W. L., 82.Braithwaite, D., 185.Brandt, K., 54.Braude, E.A., 176.Brechner, C., 287.Bredereck, H., 200, 202,203, 204, 205, 206, 211.Bredig, M. A., 54.Breitenbach, J. W., 193,Bremer, G., 193.Bresler, A. E., 7.Bresler, S. E., 7, 9.Brewer, F. M., 110.Bridgman, W. B., 69.Briggs, G. M., 257.Brill, R., 68, 69, 78.Briscoe, H. V. A., 8.British Aluminium Co . ,Brockway, L. O., 50, 51,Brodski, A. E., 88.Brohult, S., 42.Brosset, C., 53.Brown, B. B., 262.194.Ltd., 276.55, 58.Brown, E. V., 211.Brown, F. E., 282.Brown, H., 105.Brown, H. C., 186, 187,Brown, R. A., 257, 258.Brown, W. B., 276.Brownlee, G., 269.Bruckl, A., 109.Brunauer, S., 39.Bruson, H. A., 167.Brusset, H., 63.Bucca, M. A., 28.Bucher, H., 95.Buchman, E. R., 218.Buck, J. B., 77.Buckingham, R., 67.Budnitskaya, E. V., 139.Buchner, E., 183.Buell, M.V., 202.Buerger, M. J., 65.Buizov, B. V., 194.Bull, H. k., 77, 78.Bunn, C. W., 55, 62, 65, 66,Bunting, M. I., 28.Bunzell, H. H., 258.Burbage, J. J., 102.Burg, A. B., 90, 91.Burkard, J., 281.Burkey, R. E., 276.Burkhardt, G. N., 139.Burr, J. G., 152.Burton, E. F., 83.Burwell, J. T., 53.Busch, A., 81.Buschke, W. H., 237.Bushey, A. H., 95.Buskirk, A. H., 264.Butenandt, A., 81, 238,Butz, L. W., 162.Buurman, C. H., 132.Bystri)m, A., 54.Cade, G. N., 272.Cahill, E., 278.Calcott, W. S., 151.Caley, E. R., 287.Calkins, D. G., 258.Campbell, B. K., 155, 167.Campbell, C. J., 257, 258.Campbell, D., 249.Campbell, D. H., 76.Campbell, K. N., 150, 155,Cannan, R.K., 128.Cannon, G. W., 123.Cantarow, A., 247.Canzanelli, A., 249.Capatos, L., 114.Carnap, A., 70.Carothers, W. H., 150, 161,163, 164, 165, 171, 179.Carpenter, D. C., 10.Carpenter, F. H., 203.188, 189.68.239.167.Carpenter, L. E., 260, 262.Carter, A. S., 151.Carter, H. E., 122, 131.Cartwright, G. E., 238, 254Cary, A., 7.Cassidy, H. G., 127.Cassil, C. C., 282.Castelliz, L., 60.Casto, C. C., 277.Caughley, R. A., 275.Chadwick, A. F., 122.Chaikoff, I. L., 240, 241,242, 243, 246, 248, 249.Chakravarty, K., 100.Challis, H. J. G., 279.Chamberlain, N. H., 62.Chaney, A. L., 281.Chang, F. C., 191.Chang, F. T., 158.Chao, T. H., 186, 188.Chapman, A., 242.Chargaff, E., 77.Charipper, H.A., 248.Chatelain, P., 33.Cheldelin, V. H., 128, 261.Chihe, M., 94.Cheney, L. C., 218.Cherbuliez, E., 207.Cheronis, N. D., 122.Chesley, F. G., 64.Chibnall, A. C., 63, 75.Chick, H., 254.Chirnside, R. C., 274.Chodat, F., 249.Cholak, J., 276.Chou, C. Y., 127.Chou, T. Q., 219.Christ, R. E., 153, 154,Christensen, B. E., 288.Christian, W., 234.Christophers, S. R., 269.Chu, T. T., 219.Churchill, H. V., 284.Chute, H. M., 247.Cimerman, C., 274.Cirulis, A., 98, 99.Clapp, R. C., 190.Clark, A. J., 24.Clark, D., 52.Clark, G. L., 73.Clark, R. H., 288.Clarke, A. H., 96.Clarke, M. F., 265.Clarke, R. L., 134.Clayton, W. J., 272.Cleveland, F. F., 141, 144,Clews, C. J. B., 58.Clifford, P. A., 284, 286.Clisby, K.H., 247.Clusius, K., 87, 88.Clutton, R. F., 250.Coakill, E. A., 275, 282.Coates, H., 183.Cocker, A., 125.173.145, 154INDEX OF AUTHORS’ NAMES. 293Coffmann, D. D., 158, 162,Cohen, A., 277.Cohen, H., 134, 218.Cohen, S. G., 193.Cohn, E. J., 120.Cole, S. W., 237.Coleman, D., 78.Coleman, G. H., 149.Coleman, S. A., 272.Coley, J. R., 139.Colowick, S. P., 230, 233,Colson, A. F., 288.Compagnon, P., 147.Compton, J., 210.Conn, J. E., 269.Connolly, E. E., 146.Consden, R., 63.Cook, A. H., 183.Cooke, L. M., 288.Cooke, W. T., 108.Coop, I. E., 50.Cooper, G., 272.Copeland, L. E., 7.Copp, F. C., 269.Copping, A. M., 261.Corey, R. B., 81.Cori, C. F., 230, 231, 232,Cori, G. T., 231, 232.Corner, M., 287.Cornet, I., 34.Cornillot, A., 156.Cortell, R.E., 247, 248.Cortese, F., 210.Corwin, A. H., 134, 287.Coryell, C. D., 128.Cotton-Feytis, E., 67.Coulson, C. A., 24, 59.Coulson, R. A., 252, 253.Coumoulos, G. D., 68.Courtot, C., 160.Cowgill, G. R., 254.Cowling, H., 276.Craig, L. C., 221, 226, 227,Craige, F. W., 250.Crawford, T. B. B., 281.Criegee, R., 216.Crisp, D., 14,Cromwell, W. H., 264.Cross, E., 22.Crossley, H. E., 284.Crowther, J. A., 24.Crutchfield, W. E., 284.Cuckow, F. W., 85.Cummings, R. W., 276.Cupery, M. E., 164.Custers, J., 39.Cymerman, J., 162, 165,166, 176.Daasch, L. W., 73.Daft, F. S., 256.Dagley, S., 19, 23, 27.166, 171.234, 236.234, 236.228, 229.Dahle, D., 284, 286.Dakin, H. D., 130.Damerel, C.I., 134.Dana, C., 32.Danehy, J. P., 150, 168.Danielli, J. F., 10, 11.Daniells, T. C., 270.Dann, W. J., 253.Daudt, W. H., 190.Davies, D. S., 22, 26, 29,Davies, M. M., 55, 73.Davis, A. R., 207.Davis, R. E., 162.Davis, W. A., 278.Davis, W. E., 71.Dawson, M. H., 268.Day, H. G., 232.Day, P. L., 237.Deane, E. W., 247.De Boer, J., 39.De BOOYS, J., 73.De Bretteville, A., 64, 65.Debucquet, L., 109.Debye, P., 66.Dehlinger, J., 233.DelBpine, M., 146, 147.Delor, R. A., 264.De Man, T. J., 215.Demant, F., 101.Dempsey, E. W., 246, 247,Dennis, L. M., 109, 110,De Oliveira, 0. E., 101.Department of Scientificand Industrial Research,278.Derjugin, W. von, 238.Derksen, J. C., 77.Dervichian, D. G., 6, 74.Deskowitz, M.W., 28.Deux, Y., 178.Devaux, J., 62, 63.De Witt, T., 41.Dhar, J., 58.Dickel, G., 87, 88.Dicken, D. M., 265, 266.Dickinson, S., 76.Dillon, R. T., 127.Dimbleby, V., 280.Dimoff, K., 98.Dingenen, W. van, 39.Ditt, M., 273.Dittmer, K., 267.Dmochowski, A., 206.Dobromilskaja, I. M., 151.Doderlein, R., 72.Doering, W. E., 221.Doherty, D. G., 132, 133.Doisy, E. A., jun., 236.Dolgopolski, I. M., 151,Domnin, N. A., 154.Donohue, J., 52, 53.Donovan, G. E., 85.30, 266.249.114.163, 164.DOSS, K. S. G., 13.Doudoroff, M., 232.Downing, F. B., 151.Drake, N. L., 12, 207.Dranitzina, U. A., 151.Drew, H. D. K., 114.Driffield, W. B., 281.Du Bois, A. S., 268.Dubos, R., 31.Duckert, R., 273.Duffin, W.M., 269.Dunham, W. B., 268.Dunn, M. S., 126, 128.Duparc, G., 249.Du Pont, G., 151, 165, 171,Dupr6, D. J., 267.Durham, D. A., 194.Du Vigneaud, V., 122, 217,237, 267.Dwyer, F. P., 101.Dyer, B., 289.Dykstra, H. B., 151, 162,Dziemian, A. J., 250.Eakin, R. E., 263, 264.Earle, A., 264.Eastman, R. H., 218.Ebbecke, U., 79.Ebert, F., 92.Eby, L. T., 150, 167.Eck, C. L. P. van, 54.Eckert, H. W., 265.Eddy, C. R., 75.Edsall, J. T., 61, 120.Edwards, F. C., 74.Egorov, A. I., 108.Ehrenberg, J., 205.Eichorn, K. B., 241.Einicke, E., 104.Eisenstein, A., 62.Elam, D. W., 75.Elderfield, R. C., 219, 220.Elizarova, A. N., 174, 178.Elks, J., 183.Ellinger, A., 237.Ellinger, P., 252, 253.Elliott, G. H., 78.Elliott, N., 52.Ellis, J.W., 77.Elod, E., 79.Elson, W. O., 269.Elsworth, F. F., 283.Elvehjem, C. A., 254, 256,257, 261, 262, 264.Elving, P. J., 286.Emelbus, H. J., 89.Emmett, A. D., 257, 258Emmett, P., 41.Emster, K. van, 183.Engelhardt, E. J., 134.Engelmann, F., 189, 197.Engelmann, H., 181.Engle, H. R., 103.172, 174.163.262294 MDEX OF AUTHORS' NAMES.Englehardt, W. A., 232,233, 234.Epstein, J. A., 267.Erdos, J., 120.Erickson, J., 259.Erxleben, H., 215, 216.Etten, L. van, 237.Evans, B. S., 279.Evans, D. G., 268.Evans, D. P., 268.Evans, E. A., jun,, 267.Evans, H., 247.Evans, H. M., 242.Evans, M. G., 39.Evans, R. D., 240, 241.Evans, W. V., 184, 185.Ewald, K. F. A., 93.Ewing, P. J., 277.Eyring, H., 6, 270.Fahey, J.J., 2%.Fainberg, S. J., 282.Falconer, R., 207.Fankuchen, I., 60, 62, 63,Farag6, F. 28.Fargher, R. G., 147.Farmer, E . H., 161, 191,Faucett, P. H., 9.Faulkner, G. H., 269.Favorskaja, M. A., 163.Favorskaja, T. A., 170, 171.Favorski, A. E., 154, 162,Fedorkin, T. A., 280.Feeney, R. E., 264.Feigl, F., 101.Feitknecht, W., 95.Feofilaktov, V. V., 124.Ferguson, J., 27.Ferguson, R. H., 64, 65.Fernelius, W. C., 102.Ferrer, J. M., 287.Ferry, J. D., 66.Fiala, S., 128.Field, E., 184, 185.Field, 3. E., 66, 71.Fields, E. K., 196, 198.Fieser, L. F., 190, 191.Fildes, P., 18, 19, 25, 28.Finkener, F., 93.Finlay, G. R., 285.Fischer, A., 172.Fischer, E., 208, 209, 210,Fischer, F. G., 139, 173,Fischer, H., 274.Fischer, J., 287.Fischer, J.R., 57.Fishburn, A. G., 268.Flagg, J. H., 274.Flasch, H., 92.Flisik, H. F., 287.Flock, E. V., 233.71, 77.194.177.211, 225.174.Flood, E. A., 114.Flory, P. J., 66.Flygare, H., 101.Flynn, C. S., 28.Fogg, A. H., 27.Foley, E. J., 267.Folkera, K., 217, 218, 263.Follis, R. H., 254.Foort, L., 78.Foote Mineral Co., 65.Forbes, G. S., 89.Ford, F., 8.Forni, P., 34.Fosbinder, R. J., 9.Foster, A. Z., 268.Foster, J. F., 70.Foster, J. W., 263,266, 270.Foster, L., 105.Foulger, M. P. H., 247.Fourt, L., 7.Fouts, P. J., 254.Fox, J. J., 46.Fox, s. w., 120.Frankel, M., 128, 130.Franklin, A. L., 242, 248,Frankston, J. E., 237.Franz, V. K., 2.12.Fraps, 0. S., 260.Frary, S.G., 90.Frazer, A. C., 15.Freer, P. C., 144.French, D., 73, 74.Freudenberg, K., 223.Freund, E., 140, 141, 142,143, 144, 145, 146.Frey, C. N., 258, 262.Frey, F. E., 156.Frey, G., 277.Fricke, R., 85.Friedel, G., 33.Frieden, E. H., 128, 255.Friedliinder, 166.Friedrich-Freksa, H., 81.Frith, E. M., 66.Frahlich, H., 65.Froning, J. F., 167.Frosch, C. J., 68.Frost, D. V., 264.Frost, H. F., 277.Fruton, J. S., 133.Fuel Research Board, 279.Fuld, M., 78.Fuller, A. T., 268.Fuller, C. S., 68, 69.Funk, H., 273.Furchgott, R. F., 233.Furman, N. H., 274.Gabrilove, J. L., 247.Gagnon, P. E., 124.Gale, E. F., 20.Gallay, W., 64, 66.Galvin, J. A., 76.Ganz, E., 216.Gardner, A. D., 25.249.Cartland, 5. J., 193.Gatzi.K., 174.Gaudry, R., 124, 125.Geddes, B. L., 247.Gee, G., 9, 61.Gehman, S. D., 66.Geierhaas, A., 107.Geilmann, W., 109.Gerl, A. J., 247.Gerngross, O., 61.Gerschtein, N. A., 177.Ghersa, P., 9.Ghosh, R., 182.Ghosh, S. P., 99.Gibson, J., 61.Gierut, J. A., 90.Giese, A. C., 29.Giese, H., 109, 110.Giesecke, F., 95.Gillespie, H. B., 28, 168.Gilliam, W. F., 91, 104.Gilman, H., 104.Gingrich, N. S., 46, 62, 81.Gladstone, G. P., 18, 19, 25.Gladstone, M. T., 190.Glavis, F. T., 156.Glazov, N. I., 8.Gledhill, W. S., 270.Glemser, O., 92.Glock, G. E., 259.Glynn, H. E., 120.Glynn, L. E., 120.Go, Y., 62.Goldacre, R., 270.Goldfinger, G., 67, 71.Goldsmith, E. D., 248.Golovtschanskaja, A. P.,Goodson, J. A., 226.Gorbman, A., 242.Gordon, A.H., 63, 75, 80,Gordon, A. S., 248.Gordon, H., 234.Gordon, J., 22.Gordon, M., 248.Gordon, W. G., 237.Gornova, 2. A., 102.Gortner, W. A., 261.Gould, R. G., 221.Graenacher, C., 133.Grmser, W., 98.Graham, H. R., 193.GralBn, N., 70.Grandjean, M., 33.Granick, S., 227.Grau, G. R., 237.Gray, C. G., 65.Green, A. A., 90, 230, 231.Green, D. E., 232, 234, 267.Green, E., 62.Green, R. D., 261.Greenwald, I., 96.Greenwood, D. A., 259.Greisbach, W. E., 247.Grieff, F., 34.167.127INDEX OF AUTHORS’ NAMES. 295Grieve, W. 8. M., 182, 184.Griffith, R. L., 52.Grignard, V., 151, 160.Gros6, J., 241.Gross, S. T., 73.Grosse, A. V., 155.Giinther, G., 70.Guertler, W., 108.Guest, H. H., 152.Guild, R., 249.Guinier, A., 62, 63, 70, 71.Guirard, B.M., 262.Gulezian, C. E., 109.Gulland, J. M., 200, 203,207, 208, 210, 211, 214.Gundermann, J., 72.Guth, E., 66.Gutman, A. B., 232.Gutman, E. B., 232.Gutman, M., 78.Guttenberg, W. von, 8.Gyorgi, P., 267.Haagen-Smit, A. J., 239.Haas, R. H., 71, 72.Hackford, J. E., 91.Haddock, N. H., 183.Haddow, A., 31.Hadley, P., 28.Hadorn, H., 128.Hiigg, G., 54, 92.Hagemann, F., 140.Hagill, J. A. C., 54.Hahn, H., 106.Haines, R. B., 24.Hall, C. E., 66, 67, 79, 80:Halla, F., 60, 68.Hallett, L. T., 287.Ham, E. J. ten, 215.Hamann, A., 70.Hrtmence, J. H., 272, 279,Hamilton, J. G., 240, 241,Hamiin, K. E., 124.Hammond, J. W., 284, 285.Hamre, D. M., 268.Handler, P., 131, 253.Hanes, C.S., 231.Ham, R. M., 206.Hanna, N. P., 67.Hanschke, E., 141, 143.Hansen, L., 34.Hantzsch, A., 111, 112.Hardwick, P. J., 288.Harington, C. R., 125, 243,244, 245, 246, 250, 251.Harispe, J. V., 280.Harkins, W. D,, 6, 7.Harmon, J., 143.Harper, D. A., 283.Harris, M., 60, 78.Harris, R. S., 258.Harris, S. A., 206, 217, 218,85.289;242.263.Harrison, W., 78.Hrsrt, E. B., 257.Hartford, W. H., 96.Hartley, G. S., 10, 13.Hartung, W. H., 124.Hartwig, S., 81.Harvey, D. G., 220.Harvill, E. K., 130.Haskew, C. A., 103.Hrtsselt, W. van, 263.Hassid, W. Z., 232.Hauptmann, H., 168.Hauser, E. A., 67.Havinga, E., 9.Hawking, F., 268.Hawkins, W. L., 219.Haworth, J. W., 183.Haworth, R. C., 100.Haworth, R.D., 168.Haworth, W. N., 232.Heath, R. L., 232.Hecht, F., 282.Hedberg, K. W., 288.Heertzes, P. M., 63.Hegsted, D. M., 122, 256.Heidenreich, R. D., 86.Heilbron, I. M., 139, 162,165, 166, 171, 175, 176,177, 179, 183.Heimbrecht, M., 111.Heinemann, 3., 269.Heinrich, F., 110.Heipe, G., 103.Helferich, B., 209, 210.Hellner, E., 54.Helmer, 0. M., 254.Helmholz, L., 52.Henderson, L. M., 264.Hendricks, S. B., 34.Henglein, F. A., 73.Hengstenberg, J., 66.Henkel, K., 207.Henne, A. L., 155.Hennion, G. F., 149, 160,155, 156, 164, 166, 167,172, 173, 174.Henry, 0. C., 75.Henrici, A. T., 21. 7, R. J., 269.enry, T. A., 223.erbert, D., 234.Herbst, R. M., 129, 130.Hemans, J. J., 66.Hermans, P. H., 73.Hermansson, E., 54.Herrmann, K., 61.Hertz, S., 240, 241, 242,Herzog, R.O., 80.Hess, K., 70, 77, 219.Hess, W. C., 76.Heme, E., 107.Hesse, O., 219.Hey, D. H., 181, 182, 183,Key, M., 33, 34, 39, 42.247.184, 185, 198.Heyl, D., 263.Heymann, E., 7, 11.Hibbard, P. L., 275.Hibbert, H., 288.Hidy, P, H., 232.Hieber, W., 107.Higgins, 0. M., 242.Hilbert, G. E., 209, 211.Hildebrand, J. H., 62.Hiller, A., 127.Hillier, J., 63, 83, 84.Himsworth, H. P., 247.Hinshelwood, C. N., 16, 19,21, 22, 23, 25, 26, 27, 29,30, 266.Hirst, E. L., 72.Hizawa, I., 69.Hoar, T. P., 13.Hobby, G. L., 268.Hock, C. W., 79.Hockett, R. C., 204.Hodson, A. Z., 260.Hoehn, H. H., 157.Hoff, H. E., 247.Hoffman, W., 273.Hoffmann, C. E., 271.Hoffmann, R.A., 182.Hofman, U., 85.Hofmann, A., 220.Hofmann, K., 106,218,264.Hofstadter, R., 65.Hogan, A. G., 267.Holden, M., 253.Holiday, E. R., 203.Holland, G. B., 275, 276.Holloway, B. J., 267.Holst, W. H., 149.Holt, L. E., 252.Hopkins, F. G., 237.Hopkins, R. H., 259, 260.Horeau, A., 147.Hori, M., 142.Hosemann, R., 62, 70, 71.Houghton, A. A., 288.Houwink, R., 66.How, A. E., 278.Howard, G. A., 213.Howe, E. E., 123.Howitt, F. O., 78.Howland, F. O., 261.Huang, Y. T., 123.Hubbard, D. M., 276, 281.Hudson, C. S., 204, 206.Huttig, G. F., 98.Huf, E., 109.Huff, J. W., 252, 253.Huffman, R. S., 276.Huggins, M. L., 50, 53, 74,Hughes, A. M., 247, 248.Hughes, D. E., 270.Hughes, E. B., 274.Humphreys, S., 238, 254.Hunter, H., 287.Hunter, M.V., 226.Huntingdon, E., 19.80296 INDEX OF AUTHORS' NAMES.Hurbin, M., 154.Hurd, C. D., 140, 153, 154,Husemann, E., 70.Hutchings, B. L., 256, 264.Hutson, J. M., 54.Huttig, G., 34.Huziik, I., 234.Hybbinette, A. G., 109.I. G. Farbenindustrie, 158.Ibbitson, D. A., 34.Ikert, B., 283.Illner, K. W., 98.Imperial Chemical Indus-Ingerson, C., 32.Ingleman, B., 70.Ingold, C. K., 181.Ingram, G., 289, 290.Institute of Brewing, 278.Iositch, G. I., 168.Isbell, E. R., 256, 265.Itterbeek, A. van, 39.Ivanov-Emin, B. N., 100,102, 111.Iwao, J., 238.Jackson, E. L., 206.Jackson, R. W., 237.Jackson, W., 33.Jacobs, M. B., 281.Jacobs, S, E., 24, 268.Jacobs, T. L., 149, 154.Jacobs, W.A., 206, 221,Jacobsen, R. A,, 150.Jacobson, R. A., 163, 179.Jlickel, C., 72.Jakus, M. A., 79, 80.James, H. M., 66.Jancke, W., 80.Jandorf, B. J., 247.Jansen, E. F., 209.Janssen, L. W., 74.Jeffrey, G. A., 68.Jelinsk, A., 134.Jenckel, E., 67.Jenkins, H. O., 50.Jenkins, R. O., 84.Jensen, A. T., 54.Jensen, L. M., 57.Jirik, F. E., 100.Jochum, N., 93.Jodl, R., 73.Johannsen, Th., 103, 105.John, H. M., 236.Johnson, A., 219.Johnson, A. W., 162, 165,166, 169, 175.Johnson, F. H., 270.Johnson, H., 98.Johnson, J. K., 195.Johnson, J. R., 149, 171.Johnson, K. E., 64.Johnson, 0. H., 267.171, 173.tries, Ltd., 182, 183.226, 227, 228.Johnson, P. R., 134.Johnson, T. B., 209, 243,Johnson, W. C., 103, 109,Joll, C.A,, 247.Jones, E. R. H., 12, 147,162, 164, 165, 166, 171,175, 176, 177, 179.Jones, J. K. N., 72.Jones, P., 238.Jones, R. G., 104.Jones, R. N., 171.Jones, W. O., 72.Jones, W. S., 261.Jordan, R. C., 24, 268.Jorpes, E., 206.Josephson, E. S., 258.Journaud, 150.Judy, P. R., 110.Juhn, M., 248.Jukes, J. H., 254.Jung, A., 259.Junowicz-Kocholaty, R.,Juza, R., 94, 106.Kabler, C. V., 252.Kiimmerer, H., 193.Kalckar, H. M., 230, 233,Kalinin, S. K., 102.Kalinin, S. W., 108.Kamenskaya, S . , 194.Kandelaki, B. S., 64.Kane, S. S., 189.Kann, E., 140.Karabinos, J. V., 130.Karantassis, T., 114.Karle, (Miss) I. L., 58.Karle, J., 55.Karrer, P., 127, 131, 218.Kasuya, I., 140.Katchalski, E., 128, 130.Kathol, J., 165.Katz, J.R., 77.Kaufmann, R. E., 237.Kauppi, K., 28.Kautsky, H., 34.Kaye, M. A. G., 128.Kazarjan, L., 167.Kearns, W., 270.Keating, F. R., jun., 248.Keesom, W. H., 39, 55.Kehrer, F., 218.Kelbovskaja, M. K., 154.Kell, R. W., 192, 193.Keller, A., 218.Keller, O., 226.Keller, R., 127, 131.Kelly, G. D., 25.Kemmerer, A. R., 260.Kempner, W., 19.Kennedy, T. H., 247.Kenner, G. W., 213, 214.KeMer, J., 222.244, 245.110.234.236, 237. ..Kent-Jones, D. W., 260,262.Kern, W., 193.Kert, M. J., 247.Keston, A. S., 242, 246.Keutmann, A., 107.Kharasch, M. S., 181, 186,187, 188, 189, 190, 195,196, 197, 198, 200.Kheinman, A. S., 8.Kibrick, A. C., 128.Kiessig, H., 64, 70, 77.Kilian, H., 104.Killian, D. B., 150.Kilmer, 0.W., 122.King, A. J., 71.King, F. E., 124.King, W. B., 282.Kipping, F. S., 91.Kirby, W. M. M., 267.Kirch, E. R., 261, 265.Kittel, F., 218.Klebanski, A. L., 151, 163,Kleiman, M., 197.Klein, A., 281.Klein, W., 202.Kleinfeller, H., 165.Kleinzeller, A., 233.Klemm, O., 78.Klemm, W., 104, 111, 112.Klotz, I. M., 270.Klug, H. P., 52.Knaysi, G., 15.Knight, B. C. J. G., 18.Knott, A., 110.Kobacker, J. L., 247.Koblitsky, L., 280.Kodicek, E., 261.Kiigl, F., 9, 215, 216, 263,Koelsch, C. F., 183.Kanig, W., 261.Kothnig, M., 211.Kohl, W. H., 83.Kollek, L., 159, 168.Kolthoff, J. M., 279, 283.Komarewsky, V. I., 139,Kon, G. A. R., 13, 134, 168.Konovalova, R. A,, 226.Koser, S. A., 22.Kosterlitz, H.W., 234.Kostrikin, V. M., 102, 108.Kotake, Y., 238.Kozlov, N. S., 159.Krakau, K., 115.Kranzfelder, A. L., 149.Kratky, O., 62, 70, 71, 78,Kraus, C., 103.Kraybill, H. R., 259.Krebs, A. H., 236.Krebs, E., 192, 193.Krehl, W. A., 261, 262.Krestinski, V. N., 164, 171,164.264.141.80.172, 173INDEX OF AUTHORS' NAMES. 297Kriukova, T. A., 282.Kr6ger, C., 98.Kroeger, J. W., 150, 156,167, 168.Kruglov, A. A., 172.Kubo, T., 71.Kuchar, F., 128.Kuck, J. A., 287.Kuhlewein, M. von, 210.Kiinos, F., 282.Kuhn, H., 66.Kuhn, R., 168, 207, 212,265, 267.Kuhn, W., 66.Kulpinski, M. S., 145.Kumler, W. D., 270.Kundiger, D., 134.Kunitz, M., 203.Kuriyama, S., 78.Kuroda, K., 102, 108.Kurtz, P., 162.Kuznetsov, V. I.,.11 1.Labuzov, S. M., 165.Lacey, R. N., 162, 171.La Forge, F. B., 204.Lai, T. Y., 150.Lamar, W. L., 285.Lamb, A., 39, 40.Lambert, A., 183.Lamkin, J. C., 277.Lampen, J. O., 266.Landgrebe, F. W., 249.Landy, M., 30, 265, 266,Lang, K., 126.Lang, R., 273.Langenbeck, W., 139, 146.Langmuir, I., 5, 7, 8, 74.Langston, J. W., 134.Larkum, N. W., 30, 270.Larsen, A., 263.Larson, R., 248.Laubengayer, A. W., 103,Lauer, K., 72.Lauritsen, M., 238.Laves, F., 54, 107.Lavine, T. F., 127.Lawrence, J. H., 242.Laws, E. Q., 272.Lawson, A., 227.Lazarev, M. J., 60.Lazennec, I., 161.Lea, D. E., 24.Leaderman, H., 61, 67.Le Beau, D. S., 67.Lebedinski, V. V., 100.Leblond, C. P., 240, 241,Lechycka, M., 265.Lee, S. W., 267.Lehmann, J., 259.Lein, A., 241.Leonard, N.J., 219, 225.Leonian, L. H., 267.270.104.247.Leopoldi, G., 274.Lepeschkin, W. W., 66.Lepkovsky, S., 239, 254.Lerman, J., 244, 247, 250.Lerner, S. R., 248.Lespieau, R., 150, 152, 178.Levene, P. A., 200, 202,204, 205, 206, 207, 208,210, 223.Levina, R. J., 153, 165.Levine, R., 52.Levine, V., 280.Levvy, G. A., 281.Lewinsohn, M., 114, 115.Lewis, D. W., 196.Lewis, F. B., 183.Lewis, I. M., 28.Lewis, J. C., 266.Lewis, J. F., 151.Liang, C. K., 168.Lianghi, 123.Lichtenstein, N., 131.Lieb, D. J., 166.Liebermann, C., 219.Liebig, 237.Ligett, W. B., 274, 286.Light, A. E., 265.Lilly, V. G., 267.Lindgren, 32.Lingafelter, E. C., 57.Lingane, J. J., 282.Linhard, M., 101.Link, K.P., 256.Linn, C. B., 155.Linstead, R. P., 152.Lipmann, F., 208, 230, 235,Lippmann, E. von, 142.Lisco, H., 254.Lister, M. W., 50.Livingstone, R. L., 51.Lloyd, D., 105.Lobry de Bruyn, C. G., 145.Lockwood, H. C., 279.Lodge, R. M., 19, 21,22, 23,Lohmann, H. J., 70.Lowenburg, K., 173.Logemann, W., 165.Lohmann, H., 165.Long, R. S., 225.Lonsdale, (Mrs.) K., 46, 58.Lorenz, R., 140, 141, 142,143, 144, 145, 146.Loring, H. S., 203, 207.Lotmar, W., 78, 80.Lott, W. L., 274.Lowe, C., 245.Lowenstein, E., 41.Lucas, H. J., 146.Luckey, T. D., 257.Ludwig, W., 243.Luke, C. L., 282.Lundeen, H., 259.Lundgren, H. P., 75, 76.236.25, 27, 266.Lu, c. s., 53, 59.Lurk, J. J., 272, 273.Lythgoe, B., 205, 211, 212,213, 214.Maan, C.J., 73.MacArthur, I., 62, 63,McBain, 5. W., 8, 14,McCasland, G. E., 125.McCollum, E. V., 246.McCombie, J. T., 162,171, 175, 176, 177.McCready, R. M., 232.McCusker, P. A., 91,McDonald, J., 107.McElvain. S. M.. 134.79.64, 65, 85.159.75,32,50,'acFadyen, D. A., 126.iGavick, T. H., 247.:scGillavry, C. H,, 54.:cGrath, J. S., 91.:cGregor, J. K., 247.:cGrew, F. C., 165.:achado, A. L., 236.:cHard, J. A., 288.:cHarg;ue, J. S.. 276.McIlwt&,.H., 18, 25, 266,McIntire, J. M.. 264.267, 270.MMMMMMMMMMMMMMMMacIntire, W. H., 284, 285.cIntosh, J., 267.ack, M. von, 282.acKenzie, C. G., 246.acKenzie, J. B., 246.cKibbin, J. M., 254.cKinley, W. A., 263.cKinney, R.A., 30.aclay, W. D., 206.cLellan, G., 272.cLeod, J. W., 22, 267.cMahan, J. R., 63, 264.cMurdie, H. F., 79.cNabb, W. M., 279,280.cNeill, D., 211.acrae, J. F., 254.Macrae, T. F., 203, 211,McReynolds, D. K., 81.Meddock, A. G., 89.Magaziner, E. J., 277.Magnani, A., 134.Magnuson, H. J., 281.Mahan, J. E., 221, 225.Mahl, H., 83.Mahler, M., 133.Mahr, C., 272.Makino, K., 205.Malenok, N. M., 164.Malm, M., 259.Maltby, J. G., 278.Mann, F. C., 242.Mann, F. G., 100.Mann, P. J. G., 236.Mann, W., 241.Mannich, C., 158, 216, 219.261298 INDEX OB AUTHORS’ NAMES.Margnetti, C., 152.Marhenkel, E., 134.Marine, D., 248.Marion, L., 219.Mark, H., 60, 61, 62, 66,67, 70, 71, 193.Marker, R. E., 223.Markham, R., 287.Marsden, J., 5.Marshall, E, J., 231.Martin, A.E., 46.Martin, A. J. P., 63, 75,80, 127, 254.Martin, B. B., 265.Martin, C. P., 254.Martin, E. M., 247.Martin, G. J., 236, 248.Martin, L. C., 83.Martin, La V. L., 90,Martinek, R. Q., 261.Martini, A., 203.Marton, C., 86.Marton, L., 64.Marvel, C. S., 122, 143, 152,Marx, T., 85.Maschin, A,, 194.Masing, G., 112.Matheson, L. A., 86.Mathieu, M., 62, 71, 72.Mattei, G., 6, 9, 10.Matthews, A., 102.Maxwell, R. D., 149.May, R. L., 279.Mayer, H. V., 274.Mayo, F. R., 155, 181, 182,Mayr-Harting, A., 267.Meakins, R. J., 12.Means, J. H., 247, 248, 250,Medical Research Council,Medvedev, S., 194.Meek, C., 33.Meerwein, H., 91, 183.Mehler, A., 233.Meier, G., 146.Meiklejohn, J., 269.Meiklejohn, M., 260, 262.Meinhard, T., 140.Meister, M., 134.Melamed, D., 244.Melland, A.M., 77.Mellon, R. R., 29, 30.Melnick, D., 262.Melton, G., 247.Melville, D. B., 267.Melville, H. W., 192.Menshing, J. E., 275.Mercer, E. H., 8.Merling, G., 152.Mettier, S. R., 264.Metzger, N., 248.Meyer, A., 188.Meyer, H., 173.156, 165, 166, 168.194.251.259.Meyer, K. H., 27, 61, 70,73, 78, 169, 232.Meyerhof, O., 234.Mezhueva, K. I., 8.Michael, S. E., 194.Michaelis, L., 227.Middlebrook, W. R., 75.Middleton, A. R., 109.Miekeley, A., 142.M i h , N. A,, 166.Milbauer, J., 282.Miller, C. P., 268.Miller, E. J., 220, 276.Miller, L. G., 277.Miller, M. H., 254.Milligan, W. O., 32, 37, 103.Millner, T., 282.Milton, R., 281.Minchilli, M., 239.Mirick, G.S., 31.Mirski, A., 232.Mirsky, A. E., 201.Misch, L., 33.Mitchell, D. T., 162.Mitchell, H. K., 255, 266,Mitchell, J., 289.Mitchell, J. S., 10.Mitchell, R. L., 102.Mittelmann, R., 9.Mizell, L. R., 78.Moller, E. F., 267.Moeller, K., 107.Moise, I., 132.Mondel, K., 106.Money, F. S., 289.Mookerjee, (Miss) A., 220.Mooney, G., 19.Moore, C. W., 219.Moore, D. H., 233.Moore, S., 127.Moore, W. J., 6.Morawietz, W., 94.Morey, G., 32, 110.Morgan, G. T., 114.Morgan, T. N., 249.Mori, T., 207.Morita, N., 34.Morris, W., 110.Morrison, R., 198.Morton, M. E., 240, 241,Mouquin, H., 7.Moureu, C., 161.Moyer, J. C., 258.Mozingo, R., 217, 218.Mudd, S., 16.Miiller, A., 63, 65, 69.Miillei, 3’.H., 66, 69.Miiller, G., 204.Muller, J. H., 109.Miiller, W., 93.Murata, K. J., 64.Murgulescu, J. G., 99.Murray, M. J., 141, 144,264, 265.242, 243.146, 164.Murray, W., 25.Murray, W. S., 174.Musajo, L., 238, 239.Mutzenbecher, P. von, 243.Nachmansohn, D., 236.NageIschmidt, G., 34.Nagibina, T. D., 170, 174.Nagler, J., 281.Najjar, V. A., 252, 253, 260..Nasini, A. G., 6, 9, 10.Nazarov, I. N., 152, 167,174, 178, 179, 180, 181.Neal, A. L., 264.Needham, D. M., 233.Needham, J., 6 1.Nef, J. U., 165.Neill, R. B., 277.Neklyntina, V. F., 272.Nelson, A. B., 130.Neogi, P., 106.Neri, F., 28.Neuberger, A., 128.Neurath, H., 75.Neustadt, M. H., 273.Newcornbe, P. B., 247.Newton, E.B., 207.Nichols, M. L., 286.Nielsen, E., 256.Nielsen, H. E., 259.Niemann, C., 74, 75, 126.Nieuwland, J. A., 90, 149,150, 151, 154, 155, 166,159, 168, 173.Nigrell, R. F., 248.Nikitina, E. I., 272.Nikolic, R., 134.Nikolski, V. A., 54.Nitschmann, H., 128.Niven, C. F., 259.Nord, F. F., 145.Norris, D., 23.Norris, L. C., 260.Norris, R. O., 156.Norton, F., 32.Nowotny, H., 79.Nudenberg, W., 198.Nutting, (3. C., 7.Nutting, T. G., 75.Nyberg, C., 28.Nyholm, R. S., 101.Nyman, M. A., 123.Ochoa, S., 236.Ockrent, C., 9.O’Connell, R. A., 76.O’Connor, R. T., 276.Odake, S., 207.O’Dell, B. L., 257.Offermanns, H., 147.Ogston, A. G., 75.Ohl, E., 39, 40.Ohle, H., 272.O’Kane, D. J., 235.Olcott, H.S., 127.Oldham, J. W. H., 205INDEX OF AUTHORS’ NAMES. 289Olken, H. G., 250.Olsen, J. S., 286.Onishchenko, A. S., 124.Orelkin, B. P., 58.Orndorff, W. R., 114.Orr, W. J., 39.Osbourne, 0. H., 277.Osler, B. L., 262.Ostman, P., 210.Ostroumov, E. A., 272.OstwaId, W., 61, 63.Oswald, E. J., 30, 270.Ott, E., 61, 70, 160.Overbeck, C. J., 84.Overman, R. S., 256.Owen, L. N., 140, 143, 147.Oxford, A. E., 191.Pacsu, E., 122.Paillard, H., 164.Palmer, K. J., 76, 77.Palmer, R. C., 9.Palmer, W. W., 242.Pankhurst, K. G. A,, 76.Pannwitz, W., 91.Panov, E. M., 153.Pape, N. R., 68.Parker, E. E., 124.Parnum, D. H., 83.Pam, L. W., 28.Parrott, E. M., 257.Pascall, D. S. C., 182.Paschkis, K. E., 247.Pasternack, R., 211.Patterson, A.L., 48.Patterson, L. A., 166.Pauli, R., 267.Pauling, L., 48, 50, 53, 55,65, 74, 76.Peacock, W. C., 241, 247,248.Pearson, D. E., 166.Pearsori, R., 185.Pearson, T. G., 274.Peat, S., 232.Peck, V. G., 86.Peekman, J. H., 275.Peel, E. W., 288.Peirce, F. T., 73,Pelczar, M. J., 265.Pelser, H., 77.Penfold, W. J., 23.Pennington, D., 264.Perkin, W. H., jun., 147.Perlmm, I., 240, 241, 242.Perlzweig, W. A., 252, 253.Perrichon, H., 151.Perry, L. H., 14.Perutz, M. F., 77.Peters, J. B., 247.Peterson, F. C., 71.Peterson, J. W., 288.Peterson, W. H., 255, 266,Petitpas, T., 72.Petrov, A. A., 172.264, 266.Peyronel, G., 60.Pfann, H. F., 193, 272.Pfiffner, J. J., 267, 258.Phelps, F. P., 211.Philippoff, W., 64, 77.Philippova, L.A., 273.Phillips, H., 75.Pichon, M., 149.Picken, L. E. R., 78, 80.Pickett, (Miss) L. W., 68.Piekarski, G., 15.Piening, J. R., 218.Pitt-Rivers, R. V., 125, 243.Pitzer, K. S., 52.Plant, M. M. T., 146.Platt, B. S., 259.Platzer, G., 168.Pletz, V., 168.Plueddeman, E. P., 155.Pokhil, P. F., 12.PoEovsbaja, I. L., 108.Polanyi, M., 68.Polgar, N., 13.Poole, E. A., 23.Porter, J. R., 265.Powell, G., 125.Powell, H. M., 52.Powell, S. G., 140.Pray, H. A. H., 184.Prebus, A., 83.Prelog, V., 222, 225, 227.Press, J. J., 66.Preston, G. D., 46, 85.Preston, R. D., 62.Price, C. C., 192, 193, 194.Price, W. B., 259.Primosigh, J., 128.Pritchard, C. F., 274.Prokopenko, N. M., 108.Proskauer, E.S., 60.Progtenik, M., 222.Pryce, J. M. G., 26, 29, 30.Pryde, J., 220.Puddington, I. E., 64, 65.Pugh, W., 105, 109.Pummerer, R., 244, 245.Purves, C. B., 71, 72.Purves, H. D., 247.Putnam, F. W., 75.Puttfarchen, H., 244.Quastel, J. H., 236.Rabe, P., 221, 222.Rabinovitch, M. S., 226.Rabinowitsch, E., 34, 37,Ragoss, A., 86.Rahn, O., 24, 25, 288, 269,Raiford, L. C., 132.Raison, M., 72.Rake, G., 268.Rakoff, A. E., 247.Raman, (Sir) C. V., 46.Ramo, S., 84.39.271.Raphael, R. A., 162, 165,Rappen, L., 146.Rapport, D., 249.Rathje, W., 95.Rathsam, G., 135.Rawson, R. W., 247, 248.Ray, P., 99, 100.Ray, P. R., 274.Ray, R . R., 273.Rebinder, P., 7, 56.Reed, G. R., 31.Reed, J. F., 276.Reeves, R. E., 72.Rehner, J., 66.Reichstein, T., 174.Reid, A.F., 87.Reid, (Miss) A. T., 187.Reid, D. F., 239.Reineke, E. P., 243.Reinhardt, W. O., 242, 243.Remington, W. J., 274.Rempel, H. G., 283.Rennebaum, E. H., 30,236.Reppe, W., 158.Rettger, L. F., 22, 28.Reynolds, D. S., 284.Reynolds, W. B., 196.Richardson, G. L., 24.Richardson, G. M., 18, 19.Richardson, (Miss) M. F.,Itichter, C. P., 247.Richter, F., 203.Richter, G., 202, 203.Richter, M., 128.Richtmyer, N. K., 206.Riddle, E. H., 143.Rideal, E. K., 5, 7, 8, 9, 10,Riley, H. L., 61.Rist, C. E., 209.Ritchie, F. L., 247.Ritchie, W. S., 275, 276.Rittenberg, D., 236.Robbins, M. L., 28.Roberts, A., 240, 241, 242.Robertson, J. M., 49, 53,Robertson, (Sir) R., 46.Robinow, C. F., 15.Robinson, F.A., 267.Robinson, H. A., 68.Robinson, (Sir) R., 13.Roboz, E., 239.Robson, W., 220.Rochelmsyer, H., 227.Rockland, L. B., 126.Rodionov, V. M., 126.Roe, J. W., 10, 13.Rogowski, F., 57.Rollinson, C. L., 100.Rooksby, M. P., 274.Rose, C. S., 267.Rose, E., 247.Rosenfeld, S., 242.166, 171, 175, 176.225.14, 15.55, 56, 69300 INDEX OF AUTHORS’ NAMES.Rosevear, F. B., 64.Ross, M. K., 91.Ross, S., 64.Ross, W. C. J., 13.Ross, W. F., 125, 243.Rossander, S. S., 168.Rossman, R. P., 63.Rotenberg, I. A., 163.Roth, W. A., 109.Rothe, G., 203.Rothen, A., 229.Rothstein, E., 135.Rovno, I., 166.Rowley, R. J., 284.Royer, G. L., 287.Rudall, K. M., 79.Ruden, E., 147j 148.Ruggy, R., 68.Rundle, R.E., 73, 74.Rusanov, A. K., 102, 108.Russell, H., 61.Rutherford, J. K., 205.Ruttewit, K., 112.Ruzicka, L., 154, 165, 174.Ryden, L. L., 156.Ryer, F. V., 65.Sachsze, W., 94.Sadron, C., 66.Sahyun, M., 22, 120.Sakami, W., 125.Sakov, N. E., 234.Sakurada, I., 69.Salkind, J. S., 151, 152,165, 168, 171, 175.Salley, D. J., 193.Salter, W. T., 241, 244, 250.Sameshima, J., 34, 36.Samsel, E. P., 288.Samter, M., 254.Samuel, W., 34.Sanchis, J. M., 283.Sandell, E. B., 109,. 273,Sarasin, J., 211.Sarett, H. P., 253.Sarkar, T. C., 274.Sass, S., 86.Sauer, R. O., 91, 92.Sauerbier, R., 146.Saunders, R. H., 141, 144,Sauter, E., 68.Sayles, D. C., 198.Schachner, H., 242.Schaefer, V. J., 8, 86.Schaeffer, A. E., 254.Scheeffer, G., 105.Schaffer, J.M., 27.Scheibe, G., 81.Scheibler, H., 134, 172, 174.Schenck, R., 93.Schenk, P. W., 109, 110.Scherrer, J. A., 280, 281.Schiebold, E., 70.Schirmer, F., 103.275, 281.145.Schlayer, C., 19.Schlesinger, H., 105.Schmahl, N. G., 94.Schmid, G., 67.Schmid, H., 141, 218,Schmidt, C., 120.Schmidt, O., 34, 36.Schmitt, F. O., 67, 77, 79Schmitz, H., 151.Schneider, M., 63.Sch6ber1, A., 127.Schoen, A. L., 85.Scholder, R., 97.Schomaker, V., 47, 50, 57.Schoon, T., 85.Schopfer, W. H., 259.Schopflocher, P., 244.Schossberger, F., 62, 71.Schott, H. F., 126.Schramm, G., 79, 128, 233.Schroder, W., 85.Schroedinger, E., 31.Schutte, E., 125, 129.Schulman, J. H., 5, 9, 13,Schultz, A. S., 258, 262.Schultz, E.W., 22.Schulz, G. V., 70, 72, 194.Schumacher, H. J., 151.Schuster, K., 169.Schwartz, A. M., 149.Schwartz, H., 162.Schwarz, O., 109.Schwarz, R., 109, 110, 112,Schwarz, U., 97.Schweers, J., 39.Schwimmer, D., 247.Scott, D. B. N., 252.Scott, R. D., 285.Scudi, J. V., 262.Seabright, C. A., 90.Sealock, R. R., 237.Sebba, F., 8.Sebrell, H. H., 256.Secrist, J. H., 51.Seegmillek, C. G., 285.Sekawina, J., 33.Sekora, A., 62, 71, 80.Selbie, F. R., 267.Sen, R., 60.Senti, F. R., 75.Serini, A., 165.Sevastianov, N. G., 60.Shand, W., 57.Shapiro, B., 232.Shappell, M. D., 48.Sharova, A. K., 102.sharp, T. M., 219.Shaw, E. N., 152.Shaworonkow, P. W., 151.Shdanov, H. S., 54, 60.Shedlovsky, T., 221.Shemin, D., 129.Sheppard, S. E., 77.80.15.114, 115.Sherman, G.D., 276.Sherman, R. J., 273.Sherwood, G. R., 97.Shilov, E. A., 144.Shimer, S. R., 261.Shorr, E., 233, 247.Shull, G. M., 264.Siegbahn, K., 70.Siegel, L., 262.Sievers, O., 28.Siggia, S., 71.Silver, L., 65.Silverman, M., 236, 267.Simha, R., 66.Simpson, S. L., 247.Sinkel, F., 85.Sisler, H. H., 100.Sisson, W. A., 70.Sjbstrand, F., 79.Skeggs, H. R., 265.Skinner, A. H., 49.Sklyarenko, S. I., 8.Slantz, E., 68.Sloan, M. H., 247.Slobodin, J. M., 153.Sloof, G., 154.Sloviter, H..A., 279.Smagina, S. W., 152.Smiley, K. L., 259.Smith, C. W., 123.Smith, D. M., 289.Smith, G. B. L., 272.Smith, G. F., 279.Smith, G. M., 274.Smith, J. H. F., 273.Smith, L.B., 65.Smith, L. I., 157.Smith, R. C. M., 76.Smith, S. L., 67.Smith, S. R., 88.Smith, W. H., 67.Smith, W. R., 63.Smith, W. W., 268.Snell, E. E., 63, 255, 260,261, 262, 263, 264, 265,267.hell, J. M., 134.snow, J., 22.Snow, R. D., 156.Snyder, H. R., 123, 124.Snyder, R. L., 84.sobotka, H., 208.Society of Chemical In-Society of Public Analysts,Sokis, S. A., 165.Soley, H. M., 240, 241.Sologub, I. M., 164.Soltyz, H., 227.Somers, G. F., 249.sotier, A. L., 260.lowa, F. J., 90, 149, 156.Ipacu, G., 99.Spath, E., 140, 141, 142,143, 144, 145, 146, 218.dustry in Basle, 191.286INDEX OF AUTHORS’ NAMES. $01Speakman, J. B., 61, 77, 78.Spencer, R. S., 67.Spencer, W. V., 8.Spiegel-Adolf, M., 75.Spies, J.R., 207.Spinks, A., 183.Spitze, L., 34.Sponsler, 0. L., 77.Spooner, C. E., 289.Spray, G. H., .25, 266.Spring, F. S., 155, 169, 191.Stack, G. G., 91.Stiillberg, S., 13.Stahl, S., 54.Stainsby, W. J., 279.Stamm, G., 127.Stanbury, S. R., 265.Stanley, W. M., 80.Staudinger, H., 61, 68, 135,Staudinger, M., 68, 86.Staufenbiel, E., 97.Stauff, J., 64.Stecker, O., 103.Steiger, M., 211.Steiger, R. E., 122, 126,Stein, H. J., 252, 254.Stein, W. H., 127.Steinhoff, E., 37.Stellar, L. I., 250.Stenhagen, E., 13.Stephenson, M., 20.Ster, R. J., 151.Stern, T. E., 65.Steuer, E., 109.Stevens, C. M., 131.Stevenson, D. P., 47,50, 51.Stewart, H. C., 15.Stiles, W. S., 27.Stiller, E. T., 206.Stillman, R. C., 64.Stohr, H., 11 1.Stokes, J.L., 263, 265.Stokstad, E. L. R., 257.Stoll, A., 220.Storey, I. D. E., 281.Storks, K. H., 67.Story, L. F., 203, 207, 210,Stoves, J. L., 78.Strafford, N. A., 283.Straumanis, M., 98, 99.Strauss, I!’., 159, 168.Street, H. R., 254.Streightoff, F., 30, 270.Strijk, B., 54.Stritar, M. J., 144.Strobele, R., 212.Strong, F. M., 260, 261,Strufe, K., 211.Stuart, H. A., 66.Stubbs, M. F., 97.Stultzaberger, J. A., 281.Stumpf, P. K., 232.192.130, 131.211.262, 264.Subrahmanyan, V., 234.Sue, P., 240.Suksta, A., 254.Sullivan, J., 247.Sullivan, M. X., 75.Summ, N. I., 172, 173.Sumner, J. B., 249.Surgenov, D. M., 163.Suter, C. M., 123.Sutherland, E. W., 234.Sutherland, G. B., 55.Sutton, L.E., 49, 50.Suzuki, U., 207.Svedberg, T., 70, 75.Swain, G., 182.Swaminathan, M., 262.Swinehart, C. F., 287.Sykes, H. J., 195.Sylvester, N. D., 274.Synge, R. L. M., 63, 75,Syrokomskii, V. S., 102.Szabo, J. L., 130.Szilkgyi, I. von, 142.SziSnyi, G., 127.Szpilfogel, S., 227.Tabern, D. L., 114.Taconis, K. W., 55.Talalag, P., 67.Talmud, D. L., 9.Talvitie, N. A., 285.Tamura, J. T., 268.Tannheimer, J. F., 248.Taratorin, G. A., 282.Tarr, 0. F., 96.Tate, B. E., 193.Tatum, E. L., 239, 240,263, 265.Tauber, H., 126.Taylor, A., 66.Taylor, A. G., 91.Taylor, A. McM., 279.Taylor, G., 279, 289.Taylor, J., 61.Taylor, L. E. R., 69.-Taylor, W. H., 33.Tchakirian, A., 108, 113,Teeri, A. E., 261.Teller, U., 107.Tennenbaum, M., 236.Teorell, T., 8, 11.Tepley, L.J., 261.Terry, D. E., 260.Tewkesbury, L. B., jun.,243, 244, 245.Thackray, G. B., 273.Thannhauser, S. J., 202.Thilo, E., 97.Thode, H. G., 88.Thomas, J. M., 262.Thomas, J. S., 109.80, 127.114.Thompson, A. F., 152, 163,Thompson, H. W., 65.166.Thompson, It. C., 263, 265.Thomson, G. P., 46.Thorn, S. D., 149.Thorvaldson, T., 98.Thrower, W. R., 269.Thuret, J., 280.Tichomolov, P. A., 177.Tietzmann, J. E., 132, 133.Tiffenesu, M., 178.Tilley, F. W., 27.Tipson, R. S., 204,205, 207.Tiselius, A., 39, 42, 127.Todd, A. R., 182, 205, 211,212, 213, 214.Todd, E. W., 29.Toennies, G., 121.Tonnis, B., 264.Tonkin, I. M., 269.Toonder, F., 103.Topham, A., 213.Topps, J.E. C., 227.Tordai, N., 14.Torrance, S., 282.Totter, J. R., 237.Tourish, W. J., 247.Townsend, F. E., 272.Trapeznikov, A. A., 7.Traube, W., 211.Treadwell, W. D., 277.Treer, R., 71.Treloar, L. R. G., 61, 66.Tressler, D. K., 258.Trim, A. R., 15, 20.Truchet, R., 149, 154, 159.Truffert, L., 278.Tschemodanova, L. S., 287.Tscheoufaki, 151.Tsibakowa, E. F., 236.Tubbs, L. G., 96.Tuckett, R. F., 66.Tunnicliff, R., 25.Turba, F., 128.Turner, C. W., 243.Tuttle, L. C., 235, 236.Tyler, W. P., 276, 277.Tyslowitz, R., 247.Ubbelohde, A. R., 56, 65.Ulich, H., 103, 107.Umbreit, W. W., 235.United States Manufactur-ing Chemists’ Associa-tion, 287.Urech, P., 286.Urey, H. C., 87.Urry, W. H., 189, 197, 198,Usherwood, E.H., 144.Usikov, P. I., 54.Ussery, H., 102.Usteri, E., 218.Utter, M. F., 236.Valentine, F. C. O., 269.Valko, E. I., 268.Vanderbelt, J. M., 262.200302 INDEX OF AUTHORS’ NAMES.Van Dyke, H. B., 268.Vanghelovici, M., 132.Van Hook, A., 65.Van Slyke, D. D., 126, 127.Vaughn, T. H., 149, 153,Veiler, S. J., 66.Vek, S. F., 60.Velluz, L., 109.Verbanc, J. J., 155.Verbeek, J. H., 215, 216.Vickery, H. B., 75,120, 127.Viebock, F., 287.Viguier, P. L., 168.Vilallonga, F., 127.Vinogradova, J., 165.Vinson, C. G., 81.Virtanen, A. I., 28.Vogel, M., 247.Vogelenzang, F. H., 275.Vogt, R. R., 149, 152, 154,155, 156, 159, 164, 168.Vold, R. D., 64.Volker, O., 2%.Vorhes, F. A,, 281.Vosburgb, W. C., 272.Wachtel, J. L., 127.Waelsch, H., 236.Wagner, E.C., 279, 288.Wagner, L. R., 102.Waisman, H. A., 264.Walden, B. V. de G., 91.Waldniann. L., 87.Walker, E. W. A., 25.Walker, H. A., 268.Walker, H. H., 19, 268.Walker, J., 268.Walker, N., 267.Walker, 0. J., 285.Walkling, A. A., 247.Walkling, F. O., 88.Wall, F. T., 50, 66.Wallbaum, H., 107.Wallenfels, K., 168, 227.Wallhorst, B., 281.Walling, C., 155, 182, 195.Walpob, A. L., 152.Walter-LBvy, (Mme.) L., 96.Walters, L., 278.Walters, P. M., 134.Weng, S . N., 59.Wang, Y. I,., 261.Warburg, O., 234.Ward, A. F. H., 14.Ward, A. M., 273.Wardwell, E. D., 122.Waring, C. E., 184.Warren, B. E., 53, 63.Warren, F. L., 225.Warren, S. L., 241.Warrick, F. B., 232.Waters, W. A., 181, 182,Watson, E.M., 247.Watson, H. B., 139.159.185, 191, 198.Watters, A. J., 204.Weber, H. H., 79, 80, 233.Webster, G. L., 261.Weedon, B. C. L., 162, 166,Wegmann, E., 21 1.Wegner, M. I., 260.Wehner, G., 85.Weibke, F., 107.Weidel, W., 238.Weidinger, A., 77.Weidmann, H., 95.Weigel, O., 34, 36, 37.Weinberg, S., 277.Weinglass, A. R., 247.Weinstock, H. H., 265.Weiser, H. B., 32, 37, 103.Welch, A. D., 256, 258.Welch, M. S., 230.Wells, A. F., 52.Welsh, C. E., 155.Wendt, G., 207.Wendt, G. A., 96.Wenger, P., 273, 274.Wergin, W., 70.Werkman, C. H., 30, 236.Werner, E. A., 249.Werntz, J. H., 161.Wertheimer, E., 232.West, H. D., 122.West, P. M., 259, 264.Westerfield, W. W., 236,Westgren, A., 54.Westlinning, W., 112.Weygand, F., 126, 267.Wheland, G.W., 182.Whelpton, R. V., 83.Whewell, C. S., 78.White, A. G. C., 267.White, C. E., 273.White, J. G., 59.White, T., 287.White, V., 252.White, W. E., 95.Whitehead, V. I. E., 247.Whitman, N. E., 237.Wiberg, E., 103, 105.Wichmann, H. J., 275, 282,Wieland, C., 154.Wieland, H., 188, 238.Wieland, T., 128, 129, 265.Wiener, S., 259, 260.Wiggert, W. P., 30.Wilcox, L. D., 247.Wilde, O., 72.Wilkins, C. J., 89.Wilkinson, J. M., 225.Wilkinson, R., 183.Willard, H. H., 274, 283,Willemart, A., 147.Willerton, E., 264.Williams, G., 195.Williams, H. A., 279.175, 176, 177, 179.245.284.284.Williams, J. W., 69.Williams, R. E., 247.Williams, R. H., 247.Williams, R. J., 128, 255,262, 263, 264, 265.Williams, R. R., 261.Williams, R. T., 210.Williams, W. L., 262.Williams, W. W., 156.Williamson, M. B., 243.Willis, J. B., 102.Wilson, D. A., 8.Wilson, D. \Y., 125.Wilson, H. N., 280.Wilson, P. W., 259, 264.Winchell, A., 33.Winchester, R., 277.Winkler, C. A., 109, 110.Winslow, C. E. A., 19, 268.Winstein, S., 146.Winter, 0. B., 283, 284.Winternitz, J. K., 127.Wintrobe, M. M., 238, 254.Wirth, L., 128.Wishnick, D. B., 273.Wishnick, E. L., 273.Witkop, B., 238.Wittig, G., 194.Wohler, L., 93.Wohlisch, E., 79.Wohl, A., 219.Wolf, D. E., 217, 218.Wolf, G. M., 172.Wolfe, J. K., 12.Woltersdorf, G., 94.Womack, E. B., 130.Wood, R. W., 252.Wood, W. A., 67.Wood, W. B., 28.Wood, W. C., 34, 37.Woodhouse, J., 40.Woodruff, H. B., 266.Woods, D. D., 20, 25, 240.Woods, H. J., 61, 68, 77, 78.Woods, L., 289.Woodward, C. R., 263.Woodward, (Miss) I., 49,Woodward, R. B., 218, 221.Woolley, D. W., 267.Wormall, R. L., 128.Worrall, D. E., 115.Wright, L. D., 256, 258,Wrinch, D., 74.Wulle, H., 283.Wurtz, A., 146.Wyart, J., 33.Wyatt, G. H., 287.Wyk, A. van der, 70.Wyss, O., 267.Yager, W. A., 69.Yntema, L. F., 277.Yoffe, A., 7, 11.Young, C. A., 154, 155.65, 59.261, 266Young, T. F., 7.Yudin, M. F., 9.Yudkin, J., 20, 31.Yuill, M. E., 250.Zacharova, A. I., 152, 162,167, 170.Zahn, H., 79.Zalbn, E., 222, 225.INDEX OF AUTHORS’ NAMES.Zechmeister, L., 200.Zeile, K., 173.ZemplBn, G., 225.Ziegler, K., 191.Ziegner, H., 134.Ziff, M., 233.Zilbermints, V. A., 108.Zimmerman, H. M., 254.Zintl, E., 94.303Zinzadze, O., 281.Zisman, W. A., 7.Zollner, C., 272.Zuffanti, S., 216.Zumbusch, M., 11 1.Zurich, L. G., 151,163, 164.Zventitzki, N. A., 277.Zvorykina, V. A., 126.Zworykin, V. K., 84

ISSN:0365-6217    

DOI:10.1039/AR9444100291

出版商:RSC    

年代:1944

数据来源: RSC

摘要:

INDEX177.compounds, 148.OFcinchona, 221.Delphinium, 226.SUBJECTS.s-Acetylenic glycols, 167.as-Acetylenic glycols, preparation of, 168.Acetylenylcarbinols, 165.conversion of, into hydroxy-ketones,Meyer-Schuster rearrangement with,reactions of, 168.tert.-Acetylenylcarbinols, dehydration of,Acids, a-halogenated, amination of, 122.cis- and trans-unsaturated, oxidation of,Aconine, structure of, 227.Aconite alkaloids, 226.172.169.152.by permanganate, 9.Abietic acid, crystal structure of, 60.Absorbents, zeolites as, 3 1.Acetaldol, dehydration of, to croton-polymerisation of, 141, 143.spectrum of, absorption, ultra-violet,gallium salt, 107.glacial, reaction of, with acetyl per-magnesium salt, as ashing agent, 284.Acetic acid, trifluoro-, diffraction study of,65.Acetobacter suboxydans as test organismfor p-aminobenzoic acid, 265.'Acetyl peroxide, reaction of, with glacialacetic acid, 190.phosphate, detn.and properties of, 235.Acet yldehydrophenylalanyldehydro -phenylalanine, azlactone, heating of,with pyridine, 133.Acetyldehydrophenylalanylglycine, ethylester, heating of, in vacuo, 133.Acetylene, addition of hydrogen fluorideto, 155.addition reactions of, 155.catalytic condensation of, with alde-hydes and ketones, 168.catalytic polymerisation of, 151.Friedel-Crafts reaction with, 156.sulphur dioxide polymers of, 157.aldehyde, 146.141.Acetic acid, diffraction study of, 55.oxide, 190.Acetylene, dichloro-, 160.Acetylenes, halogenation of, substitution,159.oxidation of, 154.preparation of, 148.reactions of, 152.Acetylenes, amino-, 158.bromo-, chloro-, and iodo-, 159.Acetylenic chlorohydrins, reactions of,ergot, 220.indole, 219.Senecio, 224.Solanum, 227.Veratrum, 227.Alkoxyl groups, detn.of, 287.Allylacetylenes, 150.Alstonia constricta, alkaloids from, 21 9.Alstoniline, 2 19.Alstonine, 21 9.Alstyrine, 219.Aluminates, 97.Aluminium alloys, analysis of, 276.A1umini.b.m oxyfluoride, 97.phosphides, 94.Aconitum talasskum, alkaloid from, 226.Acyl peroxides, 188.decomposition of, 181.Adenine, synthesis of, 2 1 1.thiome thy1 pen toside, 20 7.Adeninedeoxyriboside, 202.Adeninedeoxyribosidephosphoric acid,Adenine-9-d-glucoside, 2 10.Adenosine, 201.201.regeneration of, from its picrate, 203.spectrum of, absorption, ultra-violet,structure of, 204.Adenosine triphosphatase, 232.Adenylic acid, coenzyme activity of, 232.phosphorylation of, 236.Adonitol, synthesis of, 178.Adsorption, equilibrium of, in zeolites, 40.Agglutination in monolayers, 15.Air, detn.in, of fluorine, 287.reactions a t water interfaces with, 8.Ajacine, 226.fi-Alanine, 126.Alanylalanine, preparation of, 129.Albumin, egg-, structure of, 76.serum-, surface pressure of, 11.Aldehydes, aliphatic, condensation of,catalysed by alkoxidss, 145.condensation of, with acetylene, 168.Aldols, 139.aldehyde addition products with, 143.monomeric, structure of, 140.polymerisation of, 141.spectra of, Raman, 141.Aldol condensation, catalysis of, 139.Aldolase, muscle, 234.AIginic acid, structure of, 72.Alkali metasilicates, formation of, 98.Alkaloids, 2 18.aconite.226.203INDEX OF SUBJECTS. 305Amination of a-halogeno-acids, 122.Amino-acids, 120.acylation of, anhydride formation in,analytical chemistry of, 126.chromatography of, 127.dehydration products of, 130.reaction of, with formaldehyde, 128.structure of, 63.synthesis of, 121.a-Amino-acids, Waser test for, 131.fl-Amino-acids, 126.Amino-compounds from acetylenes, 158.Ammonia, distillation of, microchemical,Ammonium chloroiridate, crystal structureiodate, crystal structure of, 54.pentachlorozincate, crystal structure of,Amy1 chloride, chlorination of, 188.Amylopectin, structure of, 73.Amylose, structure of, 73.Anaemia, hypochromic, from deprivationof vitamin-B,, 254.macrocytic, from vitamin-B, de-ficiency, 257.pyridoxine in relation to, 254.Analcite, active, 33.131.summary of, 121.287.of, 54.52.energy of occlusion and entropy forsorption in, 40.diffusion of ammonia and water in, 42.saturation of, by gases, 37.Analysis, combustion, 289, 290.organic microchemical, 287.apparatus for, 287.polarographic, 276, 282.Analytical chemistry, 272.Anethole hydrobromide, formation from,of hexoestrol dimethyl ether, 198.Aneurin, w a y of, 258.Anionotropic rearrangements, 175.o-Anisidine as indicator for zinc, 277.Anthranilic acid as reagent for zinc, 273.Antimalarials, inhibition by, of oxygenuptake by parasites, 269.Antimony trifluoride, crystal structure of,54.dl-Arabitol, synthesis of, 178.Arecaidaldehyde, 219.Arecoline, synthesis of, 219.Arsenates, detn. of, in presence of selenates,Arsenic, analytical chemistry of, 278.heat stability of, 259.282.detn.of, by distillation, 280.by Gutzeit method, 278.by hypophosphite reduction, 279.colorimetrically, 280.in brewing materials, 278.in foods, 279, 283.in glass, 280.in lead, 281.in soils, 280.in sulphur, 282,Arsenic, detn. of, in urine, as colloidalsuspension, 280.in wines, 278, 281.polarographically, 282.separation of, from copper, 282.Arsenic halides, crystal structure of, 49.Arsenicals, organic, analysis of, 279.Ashing in fluorine detn., 283.Atebrin, growth inhibition by, 267.Atisine, dehydrogenation of, 227.Azidocuprates, 99.Azlactones, formation of, 131.Bacteria, adaptation of, 18, 28.effect of chemotherapeuticals on, 266.growth cycle of, 16, 18.growth of, effect of drugs on, 25.physical chemistry of, 15.viability of, effect of chemothera-peuticals on, 268.Bactericides, 268, 269.effect of drug concentration on, 26.Bacterium lactis cerogenes, growth of, 19,growth of, effect of sulphonamides on,surface, 11.21, 25.266.Balances, errors of, 287.Base-exchange, effect of, on sorptionequilibrium, 40.Bettendorf’s test, 282.Benzaldehyde, addition product of iso-butyraldehyde and, 144.Benzeneazotriphenylmethane, effect of, onstyrene polymerisation, 194.Benzenediazonium chloride, thermal de-composition of, 184.hydroxide, p-bromo-, as catalyst instyrene polymerisation, 195.Benzoic acid, p.-amino-, assay of, 265.Benzoyl peroxide, reaction of, with tri-use of, to initiate reactions involvingcondensation of, with glycine, 132.phenylmethyl, 188.free radicals, 186.Biaryls, formation of, 196.Bile acids, degradation of, by means ofmeso-ww’-Bimethionine, 122.Biotin, structure of, and its assay, 263.synthesis of, by intestinal bacteria,a-Biotin, degradation and structure of,/3-Biotin, structure and synthesis of, 217.dl-alloBiotin, 218.dl-epialloBiotin, 218.Biotin sulphone, effect of, on bacteria,Biuret base, 130.Blood, detn.in, of fluorine, 283.of zinc, 275.Bomb, Parr micro-, 288.Boron trichloride, phosphoryl chloridecompound of, 91.preparation of, 183.N-bromosuccinimide, 191.256.215.267306 INDEX OF SUBJEUTS.Boron trifluoride, hexamethylenetetraminecompound of, 91.dihydrate, 91.Brass, analysis of, 277.Brass plate, detn.in, of zinc, 276.Brassidic acid, oxidation of, 9.Bread, detn. in, of aneurin, 259.Brewing materials, detn. in, of aneurin,259.of arsenic, 278.of riboflavin, 260.Bromination, 186.Bromine, detn. of, in biological fluids,Butadienes, 2-amino-, 158.l-Butyne, conversion of, into butadiene,153.isoButyraldehyde, addition product ofbenzaldehyde and, 144.n- and iso-Butyryl peroxides, decom-position of, in carbon tetrachloride,189.288.aldolisation of, 144.Cadmstes, 97.Cadmium, separation of, from zinc, 272.Cadmium hydroxyhalides, 95.Calcium aluminate, decomposition of, bysteam, 98.Cameras, fibre, 62.apocamphyl radical, 189.apocamphane- 1-carboxylic acid, peroxide,reaction of, with carbon tetrachloride,189.Cannabinol, constitution and synthesis of,182.Carbohydrates, structure of, 70.Carbon, detn.of, in organic compounds,fibrous, structure of, 61, 63.isotopes, separation of, 87.Carbon tetrachloride, action of peroxidesdioxide, equilibrium sorption of, iniodide, crystal structure of, 54.290.on, 189.chabazite, 40.Carbon soot, electron microscopy of, 85.Carbonyl chloride, photolysis of, in cyclo-Carboxyl group, structure of, 55.Carboxylation, 186.Z-B-Carboxy- y-rnethylbutanesulphonicacid, 216.Casein, iodinated, thyroxine formationfrom, 243.Catalysts, boron trifluoridsmercuricoxide, 173, 174, 175.for polymerisation, 192.Cells, division and morphology of, 24.Cellulose, cuprammonium complex of, 72.ethers, detn.in, of alkoxyl groups, 288.fibres, crystalline-amorphous ratio of,fibrils, bacterial and chemical degrad-structure of, 70, 73.hexane, 188.71.ation of, 86.Cereals, detn. in, of nicotinic acid, 261.of riboflavin, 260.Cerin, structure of, 12.Cevine, structure of, 228.Chabazite, 33.adsorption by, effect of dehydration on,energy of occlusion and entropy forequilibrium sorption of carbon dioxideisobars, isosteres, and isotherms in, 35.saturation of, by gases, 37.Charcoal, van der Wads adsorption on,Chemotherapeuticals, action of, 266.Chlorination, 186.a-Chloro-ethers, addition of, to vinyl.acetylenes, 163.Choline, formation of, in the body, 251.Chromammines, 100.Chrysotile, structure of, 63.Chrysotile asbestos, fibre structure of, 61,Cinchona alkaloids, 221.Cinchonidine, structure of, 224.Cinchonine, structure of, 224.Clostridium acetobutylicum, as test organ-ism for p-aminobenzoic acid, 266.Coal, analysis of, 289.detn.in, of fluorine, 284.electron microscopy of, 85.structure of, 63.43.sorption in, 40.in, 40.39.63.Cobalt, tervalent, cyanato-complexes of,101.Cobaltous chloride, effect of, in Grignardreactions, 196, 197, 198, 199, 200.Cocaine, production of, Z-hygroline fromliquors in, 218.Cocarboxylase, heat stability of, 250.Codeine, crystal structure of, 60.Colemanite, crystal structure of, 64.Collagen, structure of, 74, 80.Compounds, complex, 98.Condelphine, 226.Copper, separation of, from arssnic, 282.Copper phosphides, 94.Coronene, crystal structure of, 59.Cwrynebacterium diplitherice, training of,for pantothenate synthesis, 270.Cotton, X-ray fibre diagnosis of, 70.Counters, G-M, 62.Creatine, phosphorylation of, 236.p-Cresol, oxidation of, by potassium ferri.cyanide, 244.Croton tQZium, crotonoside from, 207.Crotonaldehyde, and its derivatives, 146.dimeric, 146, 147.trimeric, 148.Crotonoside, 207.Crystals, ionic, van der Wads adsorptionon, 39.Crystallography, 46.Culture media for Lactobacillus cusei-e,X-ray analysis of, 47.266MDEX OF SUBJECTS.307Cupric ctzide, complexes from, 98.chromate, basic, ammine of, 96.Cuprous thiosulphates, complex, 99.Cyclotomic points, 48.Cytidine, 201.structure of, 204.Cytidylic acid, 201, 202.Cytosinedeoxyribosidephosphoric acid,l-Decanesulphonic acid, sodium salt,Dehydrating agents, 152.Dehydrohalogenation by sodamide, 149.Dehydropeptides, formation of, 133.Delatine, 226.Delphamine, 226.Delpheline, 226.Delphinine, structure of, 226.Delphinium, alkaloids of, 226.Delphinium ajacis, alkaloid from, 226.Delphinium confmm, alkaloids from,Delphinium elatum, alkaloids from, 226.Delphinium staphisagria, alkaloids from,Delphonine, structure of, 227.Deoxyretronecine, 224.Deoxyribonucleic acids, 201.Dethiobiotin, effect of, on bacteria; 267.Dethioallobiotin, 218.Dextran, structure of, 70.Diacetylenes, 150.Diacetylenic carbinols, preparation of,168.Diacetylenic glycols, preparation of, 168.Dialdan, 146.D i -p - anisylformaz ylformic acid, ethylDiazo-compounds, 182.1 : 2 : 5 : 6-Dibenzfluorenone, synthesis of,182.3 : 5-Diethoxy-1 : 6.dihydrophthalic an-hydride, 138.Diethylacetic acid, a-amino-, 122.Diethyldithiocarbamic acid, sodium salt,as reagent for zinc, 275.Dihydroxyfluoboric acid, 9 1.a-Diketones from acetylenes, 154.2 : 4-Dimethyl aldotetrose, 140.Dimethylboron fluoride, reaction of, withtrimethylamine, 90.2 : 4-Dimethyl-1 : 3-diouan, 6-hydroxy-,143.5 : 5-Dimethyl-2 : 4-diisopropyl-1 : 3-di-oxan, 6-hydroxy-, 144.Dimethylethynylcarbinol, chlorination of,172.reaction of, using boron trifluoride-mer-curic oxide catalyst, 173, 174.Dimethylgallium, 104.Dimethylvinylethynylcarbinol, condens-ation of, with phenols, 179.Di-B-naphthylthiocarbazone, as reagentfor zinc, 276.201.crystal structure of, 57.226.226.ester, 138.as vulcanising agents, 194.Diphenyl, 196.Diphenylbenzenes, crystal structure of,Diphenylene, crystal structure of, 68.Diphenylketen, reaction of, with aryl-Diphenylthiocarbamide.See Dithizone.NN-Di-n-propyldithiocarbamic acid,Distillation, fluorine detn. by, 284.Dithizone, as reagept for zinc, 274.Divinylacetylene, polymerisation of, 164.s- and as-Divinylacetylenes, 151.l-Dodecanesulphonic acid, sodium salt,crystal structure of, 67.l-Dodecyne, 153.Drosophila, eyes, hormone forming brownpigment of, 239.Drugs, bactericidal action of, in relationto structure, 27.dl-Dulcitol, synthesis of, 178.alloDulcito1, synthesis of, 178.Electrodeposition in zinc analysis, 277.Electrolysis, 184.Electron microscope, 81.Electron microscopy, 81.Emulsions, 13.Enolase, 234.Ergocornine, 220.Ergocristine, 220.Ergocryptine, 220.Ergot alkaloids, 220.Ergotoxine, constituents of, 220.Erucic acid, oxidation of, 9.Escherichia coli, effect of chemothera-Esters, detn.of, 289.hydrolysis of, 9.4-Ethoxy- 1 -p - anisylpyridaz- 6- one, 1 3 9,2-E thoxybutadiene, 163.p-Ethoxychrysoidine as indicator forEthoxyl groups, detn.of, 288.Ethoxytrimethylsilane, 92.Ethyl bromide, reaction of, with ethyl-magnesium bromide, 195.Ethylene, crystal structure of, 56.Ethylenebisdiguanide, copper and silvercomplexes of, 99, 100.Ethylgermanium trichloride, 114.Ethylmagnesium bromide, reaction of,with ethyl bromide, 195.Ethyloctadecylmalonic acid, /3-hydroxy-,lactonisation of, 10.Ethynylbutadiene, polymerisation of, 164.Ethynylcarbinols, 166.Ethynylcyclohexane, isomerisation of,l-Ethynylcyclohexanol, 17 1.Ethynyl-A'-cyclohexene, isomerisation of,i-EthynylcycZohexene, 171 -crystal structure of, 58.58.acetylenes, 157.copper salt, crystal structure of, 60.effect of, on bacterial growth, 25.peuticals on, 267.zinc, 277.reaction of, with halogen acids, 170.153.153308 INDEX OF SUBJECTS.F2, detn.of, in urine, 253.Fats, detn. in, of Kirschner, Polenske, andReichert values, 289.y-Ferric hydroxide, electron microscopy.of, 85.Ferric oxides, effect of added oxides on, 93.Ferritin, crystal structure of, 60.apoFerritin, crystal structure of, 60." Ferron " reagent, 286.Fibres, natural and synthetic, structure of,Fibrin, structure of, 79.Fibroin, structure of, 78.Fibrous state, 61.Films, insoluble, at oil-water interfaces,interfacial, mechanical properties of, 11.monolayer, condensed, expanded, andin urine, 252.60.10.gaseous, 5 .evaporation through, 8.reactions in, 8.spreading and phase changes of, 7.structure of, 5.Flour, detn. in, of aneurin, 259.Fluorine, detection of, tests for, 287.detn.of, 283.by distillation, 284.by titration, 284.in air, 287.in blood, 283.in coal, 284.in foods, 286.in insecticides, 286.in organic compounds, 286.in rocks, 286.in water, colorimetrically, 285.in'wood, 283.in wool, 283.from spinach, 255.synthesis of, by intestinal bacteria, 256.of fluorine, 286.of zinc, 272.Folic acid, assay of, 266.Foods, detn. in, of arsenic, 279, 283.with dithizone, 274.Formaldehyde, reaction of, with amino-Formic acid, diffraction study of, 55.Forrnyl groups, detn. of, 289.Friedelin, structure of, 12.Fructose 6-phosphate, phosphorylation of,234.Gallium, 102.Gallium alloys, 107.Gallium alizarate, 107.arsenate, 106.borohydride, 105,bromate, 105.bromides, 104.chlorate hydrate, 105.chlorides, 103.as catalysts, 107.compounds, 102.acids, 128.gallium salt, 107.Gallium fluorides, 104.hydrides, 105.iodate hydrate, 105.iodides, 104.nitrides, 106.perchlorate, 105.phosphate, 106.sulphates, 106.Gases, analysis of bubbles of, 289.Gelatin, structure of, 80.water in, 77.Gelsemine, 2 19.isoGelsemine, 2 19.Qelsemium sempervirens, alkaloids from,Germanates, 109.Germanic acid, 112.Germaniosalic acid, 11 2.Germanite, extraction of germanium from,Germanium, 108.detection of, 111.detn.of, 108, 112.Germanium alloys, 1 1 1.for castings, 115.Germanium chlorobromide, 89.hydroxide, 110.organic compounds, 114, 11 5.monoxide, preparation of, 110.oxides, 109.phosphide, 1 11.salts, complex, 113.selenides, 1 1 1.Germanoacetic acid, 114.Germanoformic acid, 110.Germanotartrates, 112.Germine, structure of, 228.Gismondite, 33.Glass, addition of germanic oxide to, 115.219.108.analysis of gas bubbles in, 289.detn.in, of arsenic, 280.van der Waals adsorption on, 39.Gliadin, surface pressure of, 11.Glucose, phosphorylation of, 23 1.Glucose 6-phosphatq phosphorylation of,3-Glucosidocytosine, 209.3-Glucosidouracil, 209.Glycine, condensation of, with benz.aldehyde, 132.ethyl ester, self-condensation of, 130.Glycogen, synthesis of, from glucose, 234.Glycol esters, from aldehyde condens-4-Glycosidaminopyrimidine derivatives,Gmelinite, 33.Goitrogens, 246.Gomberg reaction, 182.Gramicidin, analysis of hydrolysates of,Gramine methiodide, 123.Graphite, van der Waals adsorption on,Graves' disease, iodine collection by236.ations, 145.preparation of, 2 1 2.127.39.thyroid in, 241INDEX OB SUBJECTS. 309Grignard reactions, free radicals in, 195.Grignard reagents, acetylenic, 165, 166.Growth cycle, 16, 18.alkylation with, 149.aromatic, electrolysis of, 185.inhibitors, effect of, on bacterial growth,substances, for bacteria, 18.Guaninedeoxyribosidephosphoric acid,Guanine glucoside, 210.Guanosine, 201.23.201.spectrum of, absorption, ultra - violet,structure of, 204.Guanylic acid, 201.Gumbelite, structure of, 63./3-Guttapercha, structure of, 67.Gutzeit method, 278.Haemolysis in monolayers, 15.Halides, non-metallic, 88.Halogens, detn.of, in organic compounds,287, 288.Halogen acids, addition of, to acetylenes,155.Halogenation, 186.Harman, 220,Harmotome, 33.dl-Heliotridan, synthesis of, 225.isoHeliotridene, 224.Heptyne, cyano-, addition of methylalcohol to, 161.Heptynyl radical, migratory ability of,178.Heteratisine, and its benzoyl derivative,226.Heterocyclic compounds, 215.Heterolysis, 18 1.Heulandite, diffusion of ammonia andwater in, 42.l-Hexadecanesulphonic acid, sodium salt,crystal structure of, 57.p-Hexadecylphenol, halogenation of, inmonolayers, 10.Hexaenyne glycol, 177.1 : 1 : 3 : 3 : 5 : 5-Hexaethoxycyclohexane,136.Hexamethyldisilsmine, 91.He xameth yldisiloxane , 9 2.Hexamethylenetetramine, boron tri-fluoride compound of, 90.CycZoHexene, chlorination of, 191.A2-cycEoHexeny1 chloride, 191.Hexokinase, 234.4-cycloHexy1- 1 -pentyne, isomerisation of,l-Hexyne, halogenation of, 155.Homolysis, 18 1.Homolytic reactions, 181.dl -Homomeroquinene, 22 2.Homometric points, 48.Hormones, 240.Kydracraldehyde, dimeric, structure of,203.153.oxidation of, to valeric acid, 154.142.Hydrocarbons, acetylenic, 148.occlusion of, in zeolites, 36.n-paraffi, sorption heat of, in chab-azite, 40.separation of, by molecular sievemethod, 45.Hydrogen, detn.of, in organic com-pounds, 290.Hydrogen fluoride, anhydrous, samplingof, 287.Hydroxy-acids, lactonisation of, 9.Hydroxyl groups, detn. of, 288.dl-Hygrine, 219.1-Hygroline, 218.Hyperthyroidism, treatment of, 247.Hypoxanthinedeoxyriboside, 202.Indene, polymerisation of, 193.Indium chromate, 97.Indole alkaloids, 2 19.Inorganic chemistry, 87.Inosine, 201.203.Inosinephosphoric acid, 201.Insecticides, detn.in, of fluorine, 286.Intestines, fat absorption in, 15.Iodine, isotopes, radioactive, use of, inIsomerisation of acetylenes, 162.Isotopes, separation and use of, 87.Jervine, structure of, 228.Jute, X-ray fibre diagnosis of, 70.Kephalin, surface pressure of, 11.Keratin, structure of, 79.a- and /%Keratins, structure of, 74.Keten acetals, 134.spectrum of, absorption, ultra-violet,thyroid study, 240.wool, water in, 77.reactivity of, 136.diisoamylacetal, 135.diisobutyl acetal, 134.diethylacetal, 1 : 2-addition products of,polymerisation of, 136.preparation of, and its bromo- and137.chloro-derivatives, 134.dimethylacetal, heat stability of, 135.di-n-propylacetal, 134.Ketones, ap-acetylenic, 154.condensation of, with acetylene, 168.Kynurenic acid, 237.Kynurenine, 238.Lactobacillus arabinosus, for nicotinic acidassay, 261.test organism for pantothenic acid, 265.Lactobacillus casei-c as test organism forbiotin and pantothenic acid, 264.as test organism in riboflavin assay, 260.eluate factor needed by, 265.Lactobacillw he16eticuu.See Lactobacillu8Lactones, hydrolysis of, 9.with vinylacetylene, 167.casei-e310 INDEX OF SUBJECTS.Lanthanum nitrite, basic, 97.Lauric acid, sodium salt, structure of,Lead, bivalent, co-ordination number of,64.100.commercial, analysis of, 275.detn.in, of arsenic, 281.Lead monoxide, orthorhombic, crystalstructure of, 54.Lecithin, surface pressure of, 11.Levynite, 33.Lignin, structure of, 73.Lithium azidocuprate, 99.Liver, autolysis of, biotin from, 263.Lupane derivatives, structure of, 12.d-Lysergic acid, conversion of, into 6 : 8-isoLysergic acid,’structure of, 221.d- and E-n- and -iso-Lysergic azides, 220.Lysolecithin, surface pressure of, 11.E-Lyxobenziminazole, 207.Magnesium alloys, a.nalysis of, 276, 277.detn. in, of zinc, 277.Magnesium carbide, crystal structure of,hydroxide, particle shape and size in, 85.nitrate, basic, 96.Magnitudes of small objects comparedwith wave-lengths of electrons, light,and X-rays, 82.Malaria, use of oil films in measuresagainst, 7.Mannitodigermanic acid, 113.Mannitogemanic acid, 1 13.Matter, structure of, by electron micro-Meals, R.A.F., riboflavin content of, 261.Mercuric oxycyanide, use of, in micro-salts, reaction of, with vinylacetylenyl-Metals, electron microscopy of, 86.Metallic halides, effect of, on GrignardMetantimonites, crystal struoture of, 54.Methacrylic acid, methyl ester, polymeris-ation of, benzoyl peroxides as cata-lysts for, 193.Methionine, synthesis of, 122.Methoxyacctaldehyde, aldolktion of, 140.p-Methoxycinnamylideneglyaine, deriv-atives, preparation of, 132.Methoxyl groups, detn.of, 288.Methoxytrimethylsilre, 92.Methyl alcohol, heat of adsorption of, inp-Methylacetaldol, preparation and pro-Methylboron diffuoride, reaction of, withl-Methylcyclobutehe, structure of, 67.2-Methyldec-3-en-5-oneY reduction of, bycrystalline growth factor from, 257.dimethylergoline, 221.54.scopy, 81.volumetric analysis, 289.carbinols, 179.reactions, 196.oxides, 92.chabazite, 41.perties of, 139.trimethylamine, 90.alcoholic sodium, 140.Methylenecyclobutane, structure of, 67.Methylgermanium trichloride, I 14.Methylketen diethylacetal, 136.Methylmagnesium bromide, reaction of,with cyclohexyl chloride and cobalt-iodide, electrolysis of, in n-butyl ether,reactions of, with acid halides, 199./3-Methylmorphimethine, crystal structureof, 60.Microbiology, electron microscopy appliedto, 85.Microscopes, electron, 81.X-ray, 82.Microscopy, electron, 81.Monocrotalic acid, structure of, 225.Monocrotaline, 225.Monolayers.See Films, monolayer.Mordenite, 33.Muscle, contraction of, energy for, fromhydrolysis of adenosine triphosphate,232.Musole-adenylic acid, 205.Myokinase, 233.Myosin, nature and activity of, 233.Myxedema, iodine collection by thyroidwith acid halides, 199.ous chloride, 197.184.structure of, 79.in, 241.Natrolite, ammoniate of, 38.Natrophilite, crystal structure of, 54.Neophyl radical, reaction of, with phenyl-magnesium bromide, 200.Neurospora, mutants, requiring trypto-use of, in vitamin-j? group assays,Neuro&pora crassa aa test organism forp-aminobenzoic acid, 265.Nickel nitride, 94.Nickelocyanides, 101.Nicotinamide, effecta of, in diet, 253.Nicotinic acid, assay of, 261.Nitro-compounds, aromatic, meth’ylationof, with lead tetra-acetate, 190.Nitro-groups, inhibition of polperisationby, 193.Nitrogen isotopes, separation of, 87.Nitrogen halides, crystal structure of, 49.Nitrosoacylarylamine reaction, 182.N-Nitrosoacylarylamines, as catalysts forNucleic acids, chemistry of, 200.Nucleosides, 200.phan, 240.263.from aaparagine, 130.excretion of, 252.polymerisation, 195.preparation of, 202.structure of, 203.synthesis of, 208.phosphoryl residue in, 206.preparation of, 202.eyntheeis of, 208.Nucleotides, 200.Nutrition, 252INDEX OF SUBJEUTS.31 1Nylon, structure of, 69.l-Octadecanesulphonic acid, sodium salt,crystal structure of, 57.l-Octanesulphonic acid, sodium salt,crystal structure of, 57.Octatrienal, isomerisation of acetylenicglycol from, 176.Octopin, synthesis of, 129.(Estrogens, bactericidal action of, 268.Oils, dcying, polymerisation of, in mono-Oleanolic acid, structure of, 12.Oleic acid, films, spreading of, 8.Organic analysis, microchemical, 287.Organic compounds, complex, molecularOrpiment, crystal structure of, 53.Ortho-salts, formation of, 94.Oxalic acid, gallium salt, 107.layers, 9.structure of, 12.dihydrate, diffraction study of, 56.silver salt, crystal structure of, 52.Oxalyl chloride, photolysis of, in C@O-Oxygen isotopes, separation of, 87.Ozonolysis, 154.Paints, detn.in, of zinc, 276.Palmitic acid, sodium salt, equilibrium of,with water, 64.Pantothenates, metabolism of, inhibitedby pantoyltaurine, 276.Pantothenic acid, assay of, 264.Pantoyltaurine, effect of, on growth ofStreptococcus hcenzolyticirs, 266.hexane, 188.respiratory inhibition by, 269.n-Para&s, fibre structure of, 65.Paraldol, condensation of, in presence ofPectin, structure of, 73.Penicillin, effect of, on viability ofbacteria, 268.Peptides, 133.hydrogen cyanide, 145.structure of, 142.chromatography of, 125.dehydration products of, 130.formation of, from azlactones, 133.synthesis of, from a-keto-acids, 129.action of, mixed with soap, 15.bacterial action of, 268.Phenols, antibacterial action of, 27.halogenation of, in monolayers, 10.dl-Phenylacetic acid, a-amino-, 122.Phenylalanine, synthesis of, 124.1 -Phenyl- 1 -butyne, 153.4-Phenyl-5 : 5-dimethyl-2-isopropyl-1 : 3-dioxan, 6-hydroxy-, 144.8-Phenylethyl radical in ethereal solution,199.Phenylethylisopropylgermanium bromide,115.Phenylethynyl radical, migratory abilityof, 178.Phenylgermanium trichloride, 1 14.Phalloidin, a-hydroxytryptophan in, 238.Phenol, anthelmintic and antibacterialPhenylmagnesium bromide, reaction of,with alkyl halides, with and withoutcobaltous chloride, 196.a-Phenylpropionic acid, a-amino-, 122.8-Phenylpropionic wid, B-amino-, prepar-ation of, 126.Phloroglucinol dihydrate, crystal struc-ture of, 60.Phosphates, precipitation of, 95.Phosphate bond energy, 230.Phosphate rock, detn.in, of fluorine, 281.Phospherase, Neuberg ester, 234.Phospherases, 233.Phosphides, metallic, 94.Phosphoglucomutase, purification of, 234.3-Phosphoglyceraldehyde, phosphate addi-tion to, 234.Phosphokinases, 233.Phosphoric acid, titration of, with calciumPhosphoryl chloride, boron trichloridehydroxide, 96.compound of, 91.halides, crystal structure of, 51.Phosphorylase, preparation of, 231.Phosphorylation, mechanism of, 230.oxidative, 234.Photometers, fibre applications of, 62.Phthaloc yanines, 1 83.X-ray structure of, 49.Phthioic acid, structure of, 13.Phytomonic acid, crystal structure of, 60.Pimanthrene, 226.Pimelic acid, a-amino-, 124.Plant ash, detn. in, of zinc, 276.Polarography in arsenic detn., 282.Polyamides, structure of, 68.Polyisobutylene, structure of, 68.Polychloroprene, structure of, 67.Polyesters, structure of, 68.Polyethers, structure of, 68.Polyethylene oxide, structure of, 68.Polymerides, catalysts in, 192.election microscopy of, 86.high, melting of, 66.linear, structure of films of, 14.rate of expansion of, 67.Polymerisation, addition, 192.inhibition of, by nitro-compounds, 193.in monolayers, 9.Polyoxymethylene, electron microscopyPolyoxymethylenes, structure of, 68.Polysulphones from acetylenes, 156.Porcupine quill, structure of, 79.Potassium azidocuprate, 99.in zinc detn., 276.of, 86.palladocyanides, 102.silver carbonate, crystal structure of,Potential, surface, 5.Powders, grain shape and size detn. in, 85.Pregneninolone, 168.Pressure, surface, 5.Proflavine, bacteriostatic effect of, 26.Propamidine, bactericidal action of, 269.Propargyl alcohol, alkali fission of, 169.5231 2 MDEX OF SUBJECTS.Propenylethynylcarbinol, isomerisationPropiophenones, amino-, 158.n- and iso-Propylketen diethylacetals, 135.n- and iso-Propylmagnesium bromides,Proteins, distribution and occurrence ofeffect of ultrs-violet light on monolayersof, 175, 176.electrolysis of, 185.amino-acids in, 75.of, 10.StNCtUre Of, 74.and their monolayers, 14.water in, 77.wool-like fibres of, 75.Proteus morganii, test organism forpantothenic acid, 265.Protoverine, structure of, 228.Purine nucleosides, 209, 2 11.Pyknometer, micro-, 287.Pyridine, rhodium halide complexes with,Pyridoxal, 263.Pyridoxamine, 263.Pyridoxine, assay of, 262.#-Pyridoxine, 262.Pyridylquinolines, 183.Pyrimidine, 5-amino-, preparation ofderivatives of, 213.4 : 5-diamino-, cyclisation of deriv-atives of, 212.4 : 6-diamino-, preparation of, 213.Pyrithiamine, effect of, on bacteria, 267.Pyrophyllite, reactions of, 97.Pyruvates, formation of, phosphorylationmetabolism of, phosphorylation during,101.relation of, to anaemia, 254.before, 234.235.Quaterphenyl, 196.Quillaic acid, structure of, 12.Quinaldines, formation of, from aoetylene,Quinaldinic acid, as reagent for zinc, 273.Quinaldinic acid, &nitro-, as reagent forQuinidine, structure of, 224.Quinine, structure of, 224.Quinoline, 8-hydroxy-, as reagent for zinc,Quinones, alkylation of, with acyl per-d-Quinotoxine, synthesis of, 221.Radicals, free, dimerisation of, 197.158.zinc, 274.synthesis of, 222.274.oxides, 191.formation of, in electrolysis, 184.from decomposition of acyl peroxides,181.Rauwolfia canascens, alkaloid from, 220.Rauwolscine, 220.Reactions, electrolytic, 184.homolytic, 18 1.Realgar, crystal structure of, 54.Reflectors, use of germanium in, 115.Retronecanone, synthesis of, 225.Retronecine, structure of, 224.Resins, synthetic, organo-silicon com-pounds in relation to, 91.Rhenium compounds, complex, 100.Rhizobium trifolii as test organism forbiotin, 264.Rhodium, bivalent, complexes of, 101.Rhodium oxides, 93.9-Ribitylisoalloxazine, 6 : 7-dichloro-,effect of, on bacteria, 267.Riboflavin, assay of, 259.bacterial degradation of, 270.Ribonucleic acids, hydrolysis of, 201.9-d-Ribopyranosidoadenine, 21 1.structure of, 214.Rice, polished, concentrates, growthRocks, detn.in, of fluorine, 286.Rosmarinecine, structure of, 225.Rosmarinine, 225.Rubber, action of benzoyl peroxide on,factor from, 265.194.hydrochloride, structure of, 67.structure of, 66, 67.vulcanising agents for, 194.Rubber-like materials, structure of, 65.Rubidium azidocuprate, 99.n- and iao-Rubijervines, structure of, 228.aZloRubijervine, 228.epialloRubijervine, 228.Rubijervone, 228.Rubrenes, formation and structure of, 168.Salicylaldehyde, azlactone, hydrolysis of,Salicylaldoxime as reagent for zinc, 274.Salts, basic, 95.Senecio, alkaloids from, 224.Selenates, detn.of, in presence of arsen-ates, 282.Silicates, 97.Silicofluoroform, 89.Silicon chloroisocyanates, 88.isocyanates, 89.halides, crystal structure of, 51.hydrides, fluorinated, 89.methoxyisocyanates, 89.organic compounds, 91.Silk fibroin, structure of, 74.Siloxene, 34.Silver bromide grains in photographicSilyl fluoride, 89.Silylene fluoride, 89.Smokes, grain shape and size detn. in, 85.Soaps, anthelmintic and antibacterialaction of, mixed with phenol, 15.132.emulsions, 85.carbonate, crystal structure of, 52.structure of, 64.Sodamide, preparation of, 149.Sodium cetyl sulphate, surface pressureof, 11.iodate, crystal structure of, 54.nitrite, crystal structure of, 54.oxide, compounds of, with cobalt, cop-per, nickel, and zinc oxides, 94INDEX OF SUBJECTS.313Soils, ashing of, 284.of zinc, 276.alloSolanidane , 2 2 7.Solanidanols, 227.Solanidine, structure of, 227, 228.Solanum, alkaloids of, 227.Solasodine, structure of, 228.Solutes, kinetics of, in zeolites, 41.Solutions, surface ageing of, 13.Sorbaldehyde, isomerisation of acetylenicSpinach, folic acid from, 255.Spreading of monolayers, 7.Spreading pressure of films, 11.Staphisine, structure of, 226.Starch, structure of, 73.Stearic acid, sodium salt, equilibrium of,with water, 64.Stearic acid, y-hydroxy-, lactonisation of,10.Sterols, molecular structure of, 12.Stilbene derivatives, estrogenic, adsorp-tion of, in monolayers, 15.Streptobacterium plantarum ps test organ-ism for pantothenic acid, 265.Streptococcus hamolyticus, growth of,effect of pantoyltaurine on, 266.Streptococcus lactis as test organism forpantothenic acid, 265.Streptococcus lactis R, folic acid for growthof, 255.Streptococcus salivariua for aneurin assay,259.Strontium azidocuprate, 99.chloride hemhydrate, crystal structureof, 54.Styrene, polymerisation of, 192.by heat without catalysts, 195.Succinimide, N-bromo-, use of, for substi-tution in olefins, 191.Sulphaguanidine, goitrogenic action of,246.Sulphanilamide, effect of, on cell morph-ology, 266.Sulphonamides, goitrogenic action of, 246.Sulphonates, organic, crystal structure of,Sulphonation, 186.Sulphur, and its compounds, crystaldetn.in, of arsenic, 280.carbinol and glycol from, 176.pyridoxine in growth of, 262.respiratory inhibition by, 269.57.structure of, 53.in organic compounds, 287.and sulphonation, 186.detn. in, of arsenic, 282.Sulphur nitride, crystal structure of, 54.Sulphuryl chloride, use of, in chlorinationSurface ageing of solutions, 13.Surface chemistry, 5.Surface potential, 5.Surface pressure, 5.isol'alatisidine, 226.Tartaric acid, gallium salt, 107.Terphenyl, 196.Tetra-aldan, 145.1 .Tetradecanesulphonic acid, sodium salt,2 : 3 : 4 : 5-Tetradehydrobiotiq 218.Tetrahydroacetophenones from vinyl-Tetrahydroalstonine, 2 19.Tetrahydroalstoninic acid, 219.6-Tetrahydro-2-furyl-n-valeric acids, 6-3 : 4-Tetramminocupric chromate, 96.Tetraphenylene, crystal structure of, 58.Tetraphenylsuccinonitrile, effect of, onstyrene polymerisation, 194.Tetrapyridylphthalocyanine, 183.Thapsic acid, 177.Theobromine-&-glucoside, 209.Theophylline glycosides, 210.Thiophan-3-ones, 2-substituted, synthesisThiophosphoryl bromide, bromofluorides,halides, crystal structure of, 51.Thiouracil, goitrogenic action of, 247.Thiourea, oxidation of, to iodine, 249.Thioureas, goitrogenic action of, 246, 247.Thorium salts, use of, in fluorine detn.,Thyminedeoxyribosidephosphoric acid,201.Thymonucleic acid, sodium salt, fibrestructure of, 61.Thymus-nucleic acid, enzymic fission of,202.Thyroglobulin, hydrolysis of, to thyroxine,250.Thyroid, 240.crystal structure of, 57.acetylene, 164.diamino-, 218.of, 218.and fluoride, 90.284.collection of iodine by, 241, 249.hormone of, goitrogenic effect on form-hyperplasia of, induced by goitrogens,ation of, 248.nature of, 249.246, 247.dl-Thyronine, 3 : 5-diiodo-, 125.Thyroxine as thyroid hormone, 250.formation of, from iodinated casein, 243.from iodine in thyroidectomy, 242.in vitro and in vivo, 244.synthesis of, 125.Tin halides, crystal structure of, 49.Tobacco mosaic virus, structure of, 80.Topaz, synthesis of, 97.Tosylthymidine, 205.Transamination, 129.Triethylgallium, 104.Trimethylohlorosilans, 91.Trimethylgallium, and its ammoniate, 103.Trimethylsilane, 9 1.Trimethylsilanol, 9 1.Triolein, oxidation of, by permanganate, 9.1 : 3 : 5-Triphenylbenzene, crystal struc-ture of, 58.Triphenylgallium, 104,Triphenylmethyl, addition of, to vinyl-acetylene, 163.reaction of, with benzoyl peroxide, 188314 INDEX OF SUBJECTS.Triphenylmethyl bromide and chloride,crystal struature of, 69.2 : 3 : 4-Triphenyl-a-naphthol, formationof, from diphenylacetylene, 157.Tris(trimethylsily1) phosphate, 92.Triterpene acids, structure of, 13.N6 : 2’ : 3’-Tritosyladenosine, 205.N6 : 2’ : 3’-Tritosyltrityldenosine, 205.Tr ityladenosine, 20 5.Tritylcytidine, 205.Tritylguanoeine, 205.Tritylthymidine, 206.Trityluridine, 205.Tryptophan, deficiency of, effects of, 237.intermediary metabolism of, 237.synthesis of, 123.Tungsten-blue, 92.Tungsten oxides, 92.Tyrocidin, analysis of hydrolysates of,Tyrosine, synthesis of, 124.Tyrosine, 3-iodo-, 125.t h yroidec tomy, 24 2.oxidation of, 245.127.diiodo-, formation of, from iodine inUnsaturated compounds, reaction of, withUracil- 3- Z-arabinoside, 209.Uracil- 3-d-galactoside, 209.Uracil-3-d-riboside, 209.Uracil-3-d-xyloside, 209.Uranium isotope, separation of, 88.Uric acid riboside, 207.Uridine, 201.structure of, 204.Uridylic acid, 201, 202.Urine, blue fluorescent substance in, 252.detn. in, of arsenic in colloidal suspen-intermediary products from tryptophandiazonium compounds, 183.sion, 280.in, 237, 238.Valine, synthesis of, 124.Vegetables, frozen, detn.in, of aneurin,Veratrum, alkaloids of, 227.Vinylacetylene, formation and poly-merisation of, 151.polymerisation of, 162.Vhylacetylenes, 151.alkylation of, 150.reactions of, 16 1,spectra of, absorption, ultra-violet, 161.Vinylacetylenic carbinols, reactions of,178.Vinylisupropenylacetylene, condensationof, with phenols, 179.Vhses, structure of, 80.Vitamin B group, assay of, 258.Vitamin-B,,, 257.259.Vitamin-B,,, 257.Vitamin-B,, 257.Water, detn. b, of fluorine, 285.evaporation of, prevention of, 7, 8.reactions at air interfaces with, 8,Wilhelmy plate, 11.Wines, ashing of, for fluorine detn., 283.detn. in, of arsenic, 278, 281.Wood, detn. in, of fluorine, 283.Wool, detn. in, of fluorine, 283.a-&transition in, 77.Xanthine, synthesis of, 2 1 1.Xanthosine, 20 1.Xanthurenic acid, 238.Xanthylic acid, 201.9-d-Xylopyranosidoadenine, 21 1.synthesis of, 214.9-d-Xylopyranosido.2-methyladenine, 21 1,spectrum of, absorption, ultra-violet,203.213.Yeast, crystalline growth factor from,Yeast-adenylic acid, 201.preparation of, 202.Zeolites as absorbents, 31.diffusion of solutes into, 42.heat of occlusion of, 39.isobars, isoteres, and isotherms in, 31.kinetics of solutes in, 41.molecular sieve properties of, 44.occlusion of solutes by, effect of de-saturation of, by gases, 36.structure of, 33.table of, 32.Zinc, analytical chemistry of, 272.commercial, analysis of, 277.detection of, reagents for, 273.detn. of, 272.257.hydration on, .42.in blood, 275.in brass plate, paints, and plant ash,in fertilisers, 276.in foods, 274.in magnesium alloys, 27 7.in soils, 276.electrolytic analysis of, 277.in glass and reagents, 275.separation of, from antimony, arsenic,bismuth, iron, and manganese, 274.276.from cadmium, 272.Zinc cyanide, crystal structure of, 34.hydroxyhalides, 95.Zinc yellow, 96.Zinzadze’s reagent, 28 1.Zirconyl alizarin3 lake, 283

ISSN:0365-6217    

DOI:10.1039/AR9444100304

出版商:RSC    

年代:1944

数据来源: RSC