ISSN:0365-6217    

DOI:10.1039/AR94643FP001

出版商:RSC    

年代:1946

数据来源: RSC

摘要:

ERRATAVOL. 42, 1945Page 224, line 1 , for (X) read (IX).224 ,, 2, for (IX) read (X).224. In the formula, for Progesterone the double bond shown betweencarbon atoms 9 and 11 should be a single bondPRINTED AND BOUND IN GREAT BRITdW BY RICHARD CLAY AND COXPANY, LTD.,BUNQAY, SU'FK)LK

ISSN:0365-6217    

DOI:10.1039/AR9464300004

出版商:RSC    

年代:1946

数据来源: RSC

摘要:

ANNUAL REPORTSON THEPROGRESS OF CHEMISTRY.GENERAL AND PHYSICAL CHEMISTRY.1. PHYSICAL ASPECTS OF THE HYDROGEN BOND.THE term “hydrogen bond” was introduced by W. M. Latimer andW. H. Rodebush 1 to cover a species of molecular interaction the qualitativeeffects of which have been extensively observed. These effects are generallymost pronounced when one of the participants is an O-H or N-H groupand the other is an 0, N, F, or C1 atom. As the properties of many im-portant families of organic compounds are intimately related to the presenceof the former groupings, the hydrogen bond has come to play a large r61ein many topics of organic chemistry.2 Here an attempt will be made tosummarise some of the more significant physical studies of this particularmolecular interaction.The magnitude of the interaction can be given by its energy value,measured by the chemist as A H , in kcal.per g.-mol. per bond. Despitethe extensive discussion of hydrogen bonds, it appears that satisfactorydeterminations of this key factor are far less numerous than might bedesired. Table I summarises those determined from equilibrium studies.Estimates from heats of dilution,3 heats of vaporisation,4 and similar generalprocesses, whilst possibly indicating the order of magnitude, cannot berelied upon for accuracy, for the number of hydrogen bonds broken is oftenundetermined and the allowance to be made for many other factorsinvolved in the changes is uncertain. To take equilibrium constants foundin different solvents and combine them to provide a AH value is clearlynot justifiable.A number of the uncertainties in the spectroscopic deter-mination of AH in solution have been indicated.6It is doubtful whether the particular “ bond ” ascribed to these pro-cesses is the sole factor contributing to A H . Apart from the assumptionof simple equilibria which may not always be strictly correct, the valuessuch as that for the aniline association should be compared with the heatJ . Amer. Chem. SOC., 1920, 42, 1419.L. Hunter, this vol., p. 141.K. L. Wolf, inter alia, Trans. Paraday SOC., 1937, 33, 179.(a) M. L. Huggins, J . Org. Chem., 1937, 1, 407; ( b ) L. A. K. Staveley, J. H. E.Jeffes, and J. A. E. Moy, Trans. Faraday SOC., 1943, 39, 5.H. M. Glass and W. M. Madgin, J ., 1933, 193, 1431.M. M. Davies and G. B. B. M. Sutherland, J. Chem. Physics, 1938, 6, 767WELLS : CRYSTAL GROWTH. 79only along lines, or even at points. In any case, the picture of two crystalsfitting perfectly together over a plane surface of union is probably far fromthe truth, as will be evident from the remarks in the next section on theprobable structure of actual crystal faces.( 5 ) The Perfection of Internal Structure and Faces of CrystaEs.-Theconcept of the mosaic structure of crystals was introduced by Darwin in1914, since when it has been discussed in a large number of papers, particu-larly in the Zeitschrift fur Kristullographie (1934, 89). Although a detaileddiscussion of mosaic structure is not possible here, it is relevant to considerits origin in terms of the mechanism of crystal growth.A difference betweenthe lattice parameters in the surface layers of a crystal and in the interior(the Lennard-Jones effect) was postulated by F. Zwicky 73 and later calcul-ated by J. E. Lennard-Jones and B. M. Dent 74. As the size of a crystalis reduced the volume of the external layers increases in proportion to thevolume of the whole crystal, so that for very small crystals it becomesjustifiable to speak of the parameter of the crystal as it whole, this being amean value. It was shown 75 that the parameter of very small crystalsmust be greater than normal in the case of ionic crystals but less than normalfor homopolar crystals. This effect has been verified experimentally forcertain metals (nickel,76 copper and iron 77).As a crystal grows, theexternal layers become internal ones and in the process the interatomicdistances therefore require readjustment. This readjustment can only goto completion if the mean thermal energy of the atoms or ions of the latticeis sufficient to enable them to adopt their equilibrium positions. If thisdoes not happen, however, the deviation of the structure from the idealcannot continue indefinitely. At some time the formation of a new nucleuswill be more advantageous from the energy standpoint, and therefore morelikely, than the further growth of the existing crystal with the deformedlattice. Thus the growth of the first crystal ceases and the new unstrainedcrystal begins to grow, i.e., the crystal growth is intermittent and leads toa structure consisting of separate (mosaic) blocks.The intermittent natureof the crystallisation of metallic crystals has been confirmed in the case ofcrystals grown from the vapour 78 and deposited electrolytically. Photo-micrographs of electrolytically deposited nickel,79% 80 cobalt,81 copper,s2etc., show a layer structure, the individual layers having a thickness ofaround cm. According to R. Suhrmann and H. S~hnackenberg,~~ the73 Physikal. Z., 1923, 24, 131.75 J. E. Lennard-Jones, 2. Krist., 1930, 79, 215.7 7 N. A. Shishakov, J. Exptl. Theoret. Physics U.S.S.R., 1940, 10, 1450.79 A. W. Hothersall and G. E. Gardam, Metal Ind., London, 1939, 55, Nos. 21 and80 E. Raub and M. Wittum, 2.EEektrochem., 1940, 46, 71.*1 G . A. Moore, Trans. Electrochem. SOC., 1937, 71, 247.82 V. Mattacotti, Metal Ind., N.Y., 1939, 37, 259.1x3 2. Elektrochem., 1941, 47, 277.74 Proc. Roy. SOC., 1928, A , 121, 347.H. BOOCBS, Ann. Phyaik, 1939, 35, 333.M. Straumanis, 2. physikal. Chern., 1931, B, 13, 316; 1932, B, 19, 63.2280 GENERAL AND PHYSICAL CHEMISTRY.energy of activation U of the ordering process (the readjustment mentionedabove) ranges from 150 cals./g.-atom for bismuth to 800 cals./g.-atom fornickel, and is very much less than for processes involving change of placeof atoms in the crystal. The number of atoms n capable of passing fromstates of non-equilibrium to states of equilibrium, when their total numberis N , will be given by n = Ne-V’kT.If crystallisation takes place at atemperature v U / k (the temperature of rest) then deformation of thelattice should not occur. It is also necessary that the rate of crystallisationbe not greater than the rate of the ordering process. M. Renninger ** showedthat in crystals grown from the melt by the Kyropoulos method there isno pronounced mosaic structure, in contrast to natural crystals of rock-salt.Stressesof the third kind arise, and are counterbalanced, within a particular mosaicblock, owing to the difference between the parameters of the internal layersand the surface layers. Stresses of the second kind arise because contiguousexternal layers of neighbouring blocks have different parameters, for theplane a t which the growth of one crystal block finishes (hence that farthestremoved from the state of equilibrium) touches the plane a t which growth ofthe next block commences (hence the plane nearest to the state of equil-ibrium). Just as a singlemosaic block is built up of layers, so the whole crystal is built up of mosaicblocks, and Joff6 supposes that if a, is the parameter of the internal layersand a2 that of the free surface of the crystal, then the parameter al of theinternal surface of the crystal will have some value intermediate betweena, and a2.For an ionic crystal a,>a&a,, and for a homopolar or metalliccrystal ao<ar<az. By analogy with the stresses of the third kind thereshould arise stresses of the first kind, counterbalanced within the limits ofvolumes comparable with the volume of the whole crystal. These stresseswould be oriented and capable, on reaching a certain magnitude, of causingsplitting or disruption of the crystal.Hence, on reaching a certain size amosaic crystal should become mechanically unstable, and disruption oflarge crystals grown from solution has been observed.86 It would thereforebe of some interest, as has been pointed out elsewhere in another connec-t i ~ n , ~ ’ ~ 88t 89 to have information about the largest known crystals ofdifferent substances, particularly if the maximum size could be correlatedwith the mode of growth and degree of mosaic structure. It is interestingthat in a number of cases it has been shown that if an impurity is addedto the solution much larger crystals can be grown.Joff6 suggests thatmany of the abnormal types of crystal growth should be explicable in termsof his picture of “ real ” crystals. A detailed description of many types ofV. S. Joff6 85 distinguished three types of stress in real crystals.These stresses are also counterbalanced locally.84 2. Krist., 1934, 89, 344.86 A. V. Shubnikov, “ How Crystals Grow,” Moscow, 1935.8 5 Uspekhi Khimii, 1944, 13, 144.C. Palache, Amer. Min., 1932, 17, 362.C. FrondeI, ihid., 1935, 20, 469.8s J. W. Retgers, 2. physikal. Ghem., 1892, 9, 278.no W. E. Gibbs and W. Clayton, Nature, 1924, 113, 492WELLS : CRYSTAL GROWTH. 81abnormality has been given by D. B. Gogoberid~e.~~ According to F.Bernauer 92 the bifoliate type of spherulite arises by growth in the directionof the long axis of the crystal at a constant rate accompanied by splittingat a constant angular velocity.In the above picture a real crystal, grown at too low a temperature, isin a metastable condition and not in true thermodynamic equilibrium.In contrast to this, D.Balarew 93 has developed a theory of “ growth con-glomerates ”, based on two postulates : first, that a crystal with perfectsurfaces and possessing edges and corners can never be in thermodynamicequilibrium with its environment, and second, that a large perfect crystalmust pass over spontaneously into one with mosaic structure. He supposesthat definite conditions of crystallisation give rise to a particular crystallineconglomerate and that the intermittent growth of crystals leads to a growthconglomerate comprising separate layers which is in thermodynamic equi-librium.The theory appears to be founded on a misinterpretation of theThomson-Gibbs equation as applied to crystals. For a liquid, this equation,vix., p, = p,e2Va rRT, relates the vapour pressure of a droplet of radius rt o the surface free energy per unit area (o), molecular volume ( V ) , and thevapour pressure of a plane liquid surface. When this is applied to a crystal,r becomes the central distance of the plane face (distance from the (‘ Wulffpoint ”), but Balarew 94 assumes it to mean the radius of curvature andregards corners and edges as having very great curvature, ( ( of atomicdimensions ”. The theory that crystals grow or dissolve “block byblock ” seems to rest on very doubtful experimental evidence.For example,in one of his experiments Balarew claims to show that the solubility ofgypsum depends on the direction of the ~tirring.~5 As I. N. Stranskig6points out, in a critical review of Balarew’s work, it is difficult to imaginehow the forces between blocks of the size suggested (some lo-* cm. side)could be adequate to orient the blocks in the formation of a single crystal,and moreover the mode of formation of the blocks has not been explained.Further references are given to Balarew’s work.97The shape of a crystal may, for many purposes, be described as a convexpolyhedron, and it was the perfection of many crystal faces which madepossible the development of crystaIlography as a science.However, thereare many ways in which crystals depart from the above description. First,there are the cases in which the crystal is still essentially a convex polyhedronbut (a) the simple faces are replaced by vicinal faces, ( b ) the ‘( face ” isactually formed into ridges caused by the alternation of faces of two types,91 Usp. Fiz. Nauk., 1940, 2, 242. 92 “ Gedrillte Kristalle ”, Berlin, 1929.93 “ Der disperse Bau der festen Systeme ”, Dresden, 19.39.94 Kolloidchem. Beih., 1930, 30, 258; 1931, 32, 203; 1933, 37, 184; 2. Krist., 1934,95 D. Balarew and N. Kolarew, ibid., 1939, 101, 156.9 7 D. Balarew, ibid., 1938, 100, 167; Zentr. Min., 1941, 228; Kolloidchem. Beih.,1939, 50, 178; 1940, 51, 123; 1941, 52, 45; Kolloid-Z., 1939, 88, 161, 268; 1940, 92,82; 1942, 98, 43.89, 268; 1936, 93, 166.Ibid., 1943, 105, 9182 GENERAL AND PHYSICAL CHEMISTRY.(c) the crystal is tapered, (d) the whole face is curved, or ( e ) there are localisedimperfections on an otherwise plane face.The last three phenomena appear,at least in many cases, to be associated with the presence of impurities inthe solution, as, for example, in the case of the low conical hillocks on (011)faces of potassium perchlorate crystals grown in the presence of certaindyes.98 The same phenomenon may be observed on the tetrahedron facesof sodium chlorate crystals grown from solutions containing sodium thio-sulphate. In the second large group come the more radical departuresfrom normal growth as a single crystal, such as spherulitic, dendritic, andtwinned structures.If a solution of sodium carbonate is allowed to diffuseslowly into a gel containing barium chloride (prepared from commercialgelatin and allowed to set) the precipitation of the barium carbonate takesplace in layers, and a variety of crystal forms is observed. These rangefrom needles, through " sheaves " to spherical aggregates. The structuresand optical properties of these spherulites have been studied recently insome detail, particularly by H. W. Morse and his co-worker~.~~ The growthof the practically spherical aggregates and of the intermediate forms can beaccounted for if it is postulated that crystallisation radiates from a centralnucleus in a limited solid angle only.It is assumed that growth is fastestin one direction, that every point at the surface of the growing cone offibres can act as a new starting point for further radiating growth, and thatthe spatial extent of the latter is controlled by the possible angle of apertureof the cone and by the mechanical obstruction of the existing fibres. Asgrowth proceeds, new fibres radiate from points reached by those formedearlier. The sheaf then opens out' in fan-like manner until an approximatelyspherical shape is reached, when presumably the process stops owing toexhaustion of material in the environment. A somewhat similar explan-ation has been given 100 for the two-dimensional spherulites of substancessuch as malonamide and resorcinol grown between glass plates.Betweencrossed Nicols the three-dimensional spherulites show in parallel light aninterference figure similar to that of a uniaxial crystal cut perpendicularto the optic axis and viewed in convergent light.In considering the genesis of twin crystals, which he classifies into growthtwins, transformation twins and gliding twins, M. J. Buerger emphasisesthe close relation of twinning to polymorphism, and suggests that growthtwinning is more likely, other things being equal, the greater the degree ofsupersaturation. Thus the condition causing supersaturation twins is mostlikely to arise just once-as the crystal nucleus forms-and not again, SOthat nuclei supersaturation twins are often characteristically simple pairs.This simple treatment does not account for the extraordinarily regularstructure of some lamellar twins, such as those of potassium &lorate grownD* H.E. Buckloy, Z . Krist., 1934, 89, 221.DD Bull. Soc. franq. Min., 1931, 54, 19; A m r . J . Sci., 1932, 23, 421, 440; 1933, 25,494; Amer. Min., 1933, 18, 66; 1936, 21, 391.loo B. Popoff, Latv. Farm. Zurn., 1934, 1.Amer. Min., 1945, 30, 469WELLS : CRYSTAL GROWTH. 83from supersaturated solution. To quote R. W. Wood,2 " a plate whichstarts with twin planes 0.0002 mm. apart apparently builds up seven hundredlaminz of the same thickness, while another plate starting with a different' grating constant ' sticks to it to the end." In other words, after a distancecorresponding to some 300 unit cells, the orientation of the crystal changes,and this change takes place regularly at intervals of about 2000 A.In a paper on the surface motion of particles in crystals and the naturalroughness of crystal faces J.Frenkel3 begins by pointing out that vicinalfaces with very high indices are not to be regarded as planes of high specificsurface free energy (compare Miers's paradox,44 that the faces actuallypresent on a growing crystal of alum are those with very low densities ofatoms per unit area), as is often assumed to be the case, In fact they con-sist of steps, the flat portions of which are planes of low indices [e.g., (111)in the case of the vicinal faces on alum]. For the two-dimensional analogue,a staircase-like line with identical steps n units in length and 1 unit inheight, the additional free energy per unit length is simply Nw, where w isthe additional energy per step and N = l / a n = ( l / a ) tan+, a being thelattice constant and + the angle of inclination of the vicinal face to the basicface.Since the surface free energyof the vicinal face is only slightly greater than that of the basic face itfollows that the surface of a crystal in statistical equilibrium consists, notof a plane surface, but of a series of vicinal faces which arise spontaneouslyas the result of thermal fluctuations. This fluctuating roughness can becharacterised by the ratio hla where A is the mean length of the separatesteps. To account forthe variations in the areas of the terraces it is supposed that atoms canmove freely over the horizontal portion of each terrace without interactionone with another.With respect to the " plane gas phase " adsorbed on agiven terrace, the next terrace, lying at a higher level, plays the r81e of thecondensed phase, and there exists a continuous exchange of atoms betweenthe two plane phases, leading to fluctuations in the areas of the separateterraces. This concept is further extended to the edges of the terraces, theatoms linearly adsorbed on the rectilinear portion of each edge behaving asa kind of linear gas, so ensuring the possibility of a reshaping of the outlinesof the separate terraces without changing their areas. The growth ofa crystal is visualised as taking place by the random deposition of particleson the growing face, in general on the flat portions of the atomic terraces,thereby passing into the two-dimensional gas phase.Later, some of thembecome attached, still in a perfectly random way, to the vertical stepsbounding the terraces (passing thus into the one-dimensional gas phase),and they move along until they become firmly attached at an angle (corner),as in the Kossel picture. This generalisation of the Kossel-Stranski theoryis also applicable to vaporisation, dissolution or melting, when the aboveprocesses take place in the reverse order. A mechanism of this type hasThus o = oo + w N = o0 + (w/a) tan$.Assuming ~ > n , it is found that A/U = 4eW'kT.a Phil. Mag., 1909, 18, 535. J . Physics, U.S.S.R.,1945, 9, 39284 GENERAL AND PHYSICAL CHEMISTRY.been suggested by P.Lukirsky to account for the development of vestigialcrystal faces on the surface of a crystalline body ground initially in the formof a sphere, and subjected to more or less prolonged heating.It might a t first sight appear that certain observations on the move-ment of layers across the faces of growing crystals are in conflict with theabove picture of crystal growth. Observations of the interference coloursof thin crystals of m-toluidine 69 6 indicate layers only a few moleculesthick. The layers mentioned by C. W. Bunn and H. Emmett must havea thickness of the order of the wave-length of visible light (some 103 atomsthick). They are observed only towards the edges of faces and presumablyare the result of thin layers overtaking one another.Observations havealso been made on layers spreading across faces of growing crystals of alkalihalides,s and interpreted as supporting the Kossel-Stranski theory of thegrowth of ionic crystals. M. Volmer has commented on the interpretationof some of these experiments. It seems likely that the above effects areobserved only under conditions (e.q., of rapid growth from supersaturatedsolutions) such that external factors-concentration gradients and diffusioneffects-are important, and that they are not relevant to the case of acrystal growing slowly in a well-stirred solution. The former conditions,and also the presence of suitable impurities in certain cases, are known tolead t o the formation of vicina.1 or curved faces, or tapered crystals.In allthese cases the surface is not a normal face but the contour of the edges oflayers, and the different types of divergence from normal plane faces of lowindices represent different relations between the rate of spread of layers andthe frequency of init’iation of new layers.S. Tolansky lo has studied the topography of crystal faces by means of amultiple beam interferometric method. A highly reflecting film of silverabout 500 A. thick is deposited on the crystal face, which is placed near,and parallel to, an optical flat of quartz. Interference fringes are producedusing a parallel beam of monochromatic light at normal incidence, and theyshow many interesting features of the structure of the crystal face.Ex-amination of a (100) face of quartz, of high optical quality, showed the faceto consist-not of a simple plane surface-but of vicinal faces inclined a tangles varying from 0.50 to 9.00 minutes of arc and mostly curved, withradii of curvature from 20 to 60 metres. There were also sub-microscopictetrahedral projections about 450 A. high, which may represent nuclei fromwhich subsequent growth would have started. A study of cleavage surfacesof mica and selenite 1’9 12 showed steps on the surface of the former down to40 A., all the steps being niultiples of 20 A., the c spacing of mica as determinedby X-ray diffraction. These steps are presumably the same as those in-4 Compt. rend. Acad. Sci. U.R.S.S., 1945, 46, 300.5 R. Marcelin, Ann. Physique, 1918, 10, 185.L.Kowarski, J . Chim. physique, 1935, 32, 303, 395, 469.Nature, 1946, 158, 164.‘‘ Kinetik der Phasenbildung,” p. 55.11 S. Tolansky, ibid., p. 51.8 Z. Gyulai, 2. Krist., 1935, 91, 142.lo Proc. Roy. Soc., 1945, A , 184, 41.l2 Idem, ibid., 1946, A , 186, 261WELLS : CRYSTAL GROWTH. 85ferred to exist on some mica surfaces from experiments made by Friedel onthe orientation of ammonium iodide crystals on such surfaces.It is not possible to reviewhere all the work done in the last few years on supersaturation and nucleusformation. The early work of Miers and others appeared to supportOstwald’s view that a t a given temperature there is a definite concentrationbelow which crystals are not formed spontaneously (it being possible tomaintain the solution indefinitely in this metastable state), whereas athigher concentrations spontaneous crystallisation occurs.The experi-ments of Miers, from which the actual “ supersolubility ” curve, betweenthe metastable and labile regions, was plotted, only show that under theconditions of these experiments there was a fairly sharp boundary betweenthe concentrations at which nucleus formation took place rapidly or fairlyslowly. Later work showed that the area of the “ metastable ” region canbe reduced by increasingly vigorous stirring or by the presence of foreignsolid particles. Comparable results were obtained with melts, though insome cases if the rate of cooling is very great nuclei are not formed but aglass results. Although far less importance would now be attached to theprecise position of Miers’s supersolubility curve, since this has been shownto depend on the experimental conditions, it is generally agreed that justbelow the saturation point there is a region in which the probability of nucleusformation is small (“ metastable ” region), but that this probability in-creases rapidly beyond a certain degree of supersaturation.For a super-cooled liquid L. C. de Coppet l3 gave a simple kinetic explanation.In technical crystallisation processes it is important to avoid excessiveformation of nuclei on cooling surfaces. Rapid agitation does not over-come this difficulty as mechanical shocks cause nucleation in the body ofthe solution. One way in which this has been overcome is to carry out thesupersaturation in one part of the apparatus and to allow crystal growthto take place in another vessel containing seed crystals, as in the Oslocrystalliser.14* l5 The supersaturation of the solution travelling from theevaporator is insufficient for appreciable nucleus formation to take placebut, of course, sufficient to cause growth of the seed crystals in the crystal-lising compartment.A kinetic derivation of the rate of nucleus formationfrom the vapour state has been given by I. N. Stranski and R. Kaishev.16Nucleus formation in supersaturated solutions can apparently be verycapricious. For example, it was found in some experiments that by intro-ducing seed crystals a t the saturation temperature and then cooling, growthfirst occurred only on the seed crystals, then a t a lower temperature a fewnew nuclei appeared, but only a t a still lower temperature did nuclei formin large numbers throughout the solution.17 Such effects are, however,(6) Miscellaneous.-(a) Nucleus formation.l3 Ann.Chim. Phys., 1907, 10, 457.l4 F. Jeremiassen and H. Svanoe, Chem. Met. Eng., 1932, 39, 594.l6 H. Svanoe, I n d . Eng. Chem., 1940, 32, 636.l6 Z. physikal. Chem., 1934, B, 28, 317.H. H. Ting and W. L. McCabe, Id. Eng. Chem., 1934, 20, 10086 GENERAL AND PHYSICAL CHEMISTRY.very dependent on the size and total number of seed crystals, rate of cooling,speed of stirring, etc. Some recent papers on supersaturation and nucleusformation in solution are noted.l* Brief reference only can be made toother recent work on crystallisation or recrystallisation processes.Fromstudies of the kinetics of the crystallisation of sucrose solutions, A. vanHook l9 concludes that the rate of growth of the crystals is determinedprimarily by some interfacial reaction rather than an interboundary re-action, i.e., that processes occurring at the crystal face (orientation andincorporation of molecules into the crystal) are more important thandiffusion under the conditions of his experiments. The effect of addedimpurities was also studied.20 The rate of crystallisation from super-saturated solutions of sodium sulphate has been studied.21 According toW. Lotmar,22 thin films of antimony deposited in a vacuum are originallyamorphous, and crystallise spontaneously only if the film thickness exceedsa certain critical value.The growth of crystals during electrodepositionis considered in a theoretical paper by K. M. Gorbunova and P. D. D a n k ~ v , ~ ~and the growth of crystallites in supercooled liquid thymol by G. G .Laemmleh2* P. Laurent 25 has derived formulte for the number of nucleiformed at a given time and for the velocity of crystallisation in allotropictransformations. The crystallisation of salts from thin films of solutionsspread on mercury has been investigated by H. Devaux.26There has been a number ofpapers concerned with the technique of growing large single crystals, asopposed to studies of the way in which the crystals grow (Section 2 ) . Theydescribe modifications of well-known methods.In order to obtain largecrystals (up to 200 g.) of Rochelle salt with preferential development alongthe y and x axes, crystals may be grown between glass plates in a solutionwhich is cooled from 30" at the rate of &lo per day.27 Large crystals ofpotassium dihydrogen phosphate 28 and alkali halides 29 may also be grownfrom aqueous solution. Single crystals of lithium fluoride, potassiumbromide, and sodium chloride weighing up to 35 lbs. have been made 30 bymelting the salt in a conical platinum crucible which is removed very slowlyfrom the furnace into n lower cooler chamber, the crystal growing from the18 K. Neumann and A. Miess, Ann. Physilc, 1942, 41, 319; R. Gopal, J. IndianChem. SOC., 1944, 21, 103, 145; B.S. Srikantan, ibid., 1945, 22, 55; 0. M. "ode, ActsPhysicochim. U.R.S.S., 1940, 13, 617; J. Amsler and P. Schemer, Helv. Physica Acta,1941,14, 318; C. G. Dunn, Physical Rev., 1944, 66, 215.(b) Technique of growing single crystals.18 I d . Eng. Chem., 1944, 36, 1042, 1048; 1945, 37, 782.zO A. van Hook, ibid., 1946, 38, 50.21 E. L. Krichevskaya, J. Physical Chem. U.S.S.R., 1945, 19, 382.22 Helv. Physica Acta, 1945, 18, 232, 369.23 Compt. rend. Acad. Sci. U.R.S.S., 1945, 48, 15.26 Compt. rend., 1944, 219, 205; Rev. met., 1945, 42, 22.26 Compt. rend., 1944, 219, 565.27 L. C. Baker, New Zealand J . Sci. Tech., 1943, 25, B, 62.28 W. Bantle, Helv. Physica Acta, 1943, 16, 207.2s F. Henroteeu, Astronom. J., 1945, 51, 122.3O R. L. Taylor and H.C. Kremers, Chem. and Ind., 1944, 55, 906.z4 Ibid., p. 168WELLS : CRYSTAL GROWTH. 87end of the conical crucible. By allowing the crystallisation of the melt tostart at a surface of a mica sheet, C. D. West 31 has obtained oriented sectionsof single crystals of sodium nitrate. The method is also applicable tosodium, potassium, and rubidium iodides and potassium bromide, whenthe crystal grows with (111) parallel to (001) of the mica. A modificationof the original Verneuil furnace, in which the powdered material is pro-jected into an oxy-hydrogen flame, has been used to obtain syntheticsapphires (single crystals of a-alumina) .32 Fused silica may be convertedinto perfect small crystals of quartz when heated in a solution of sodiummeta~ilicate.~~ Mixed thallous bromoiodide single crystals have beenprepared for use in military infra-red optical instruments.Crystalscontaining 42 moles % of thallous bromide were grown from the melt byusing a, modified Bridgman furnace.35 The melt was held at 470" in afurnace divided into two parts by an insulating baffle, the temperatures inthe two sections being independently controlled, and the baffle serving toproduce a steep temperature gradient in the region where growth tookplace. The best results were obtained witha high temperature gradient and a slow rate of passage through the gradient.Methods of obtaining single crystals, particularly of metals, have beenreviewed by A. Duran 36 (references to 32 papers). The first general methodconsists in slow cooling of the molten material in a crucible, either by re-moving the crucible slowly from the furnace (a method used by P.W.Bridgman3' to obtain single crystals of W, Sb, Bi, Te, Cd, Zn and Sn, andrecently by D. C. Stockbarger for lithium fluoride35) or by slowly coolingthe whole furnace. Various devices are adopted to start the crystallisationfrom a nucleus with the desired orientation,3*9 39 and many designs of furnaceand crucible have been developed.40 The second method is to bring anucleus into contact with the surface of the molten material and to with-draw the crystal slowly,41 a method particularly useful for growing largesingle crystals of certain halides. A third method, recrystallisation in thesolid state, has long been used for preparing mono-crystal wires of metals.Heating combined with compression in a steel mould has also been used.42A conical crucible was used.A.P. W.31 J . Opt. Soc. Amer., 1945, 35, 26.32 K. W. Brown, R. C. Chirnside,tL. A.'_Dauncey, and H. P. Rooksby, Gen. Electric33 N. Wooster and W. A. Wooster, Nature, 1946, 157, 297.34 0. F. Tuttle and P. H. Egli, J . Chem. Physics, 1946, 14, 571.35 Rev. Sci. Instr., 1936, 7 , 133.36 Anal- Pis. Quim., 1941, 37, Supplement, p. 33.37 Proc. Amer. Acad., 1925, 80, 305.3B L. Schubnikow, P ~ o c . K . Akad. Wetensch. Amsterdam, 1930, 33, 327.40 H. Tazaki, J . Sci. Hiroshima Univ., 1940, A , 10, 37, 109; H. E. Farnsworth,Physical Rev., 1935,48,:972; M. F. Hasler, Rev. Sci. Instr., 1933, 4, 656; C.A. Cinnamon,ibid., 1934, 5, 187.(Q.E.C.) Journal, 1944, 13, 63.38 L. Graf, 2. Physilc, 1931, 67, 388.41 s. Kyropoulos, 2. anorg. Chem., 1926, 154, 308.42 H. S . MiiIler, 2. Physik, 1935, 96, 32188 GENERAL AND PHYSICAL CHEMISTRY.4. CRYSTALLOGRAPHY.X-Ray diffraction by crystals is being widely applied to a great variety ofproblems. While the general stereochemical arrangements in molecules ofsome complexity such as penicillin and sucrose are examined and the lesscompletely ordered structures of polymers or soap are studied, preciseinteratomic distances are determined in simpler substances such as methyl-ammonium chloride. Some crystal structures such as that of ice which mightbe considered simple continue to reveal more and more detail as fuller use ismade of all the observable X-ray effects. A mass attack has been made onthe crystal chemistry of the rare earths, thorium, plutonium, neptuniumand, it is presumed, other transuranic elements. As a result of the examin-ation of 150 compounds it was claimed (at the Institute of Physics Conferenceon X-ray analysis during the War) that the crystal chemistry of these ele-ments is now " known " better than that of most other elements.So farthis knowledge is not available in detail. The structures of some complexchlorides of molybdenum have been revealed, but that there are still diffi-culties in structure determination is shown by work on CSCUCI,~. Thisapparently simple structure seems to be based on close packing of czesiumand chlorine ions, but no detailed arrangement has yet been found in agree-ment with the observed diffraction effects.X-Ray examinations continue in use for identification, molecular-weightdetermination, and the testing of proposed molecular formula2 As anexample of identification, the structure determinations of the plutonium andneptunium compounds mentioned above are of some interest.The chemicalidentities of most of the compounds were in this case deduced from theirX-ray diffraction patterns given by very small quantities of materials pre-pared by known methods. The power of the X-ray method to reveal detailsthat are with difficulty determinable by analytical methods is shown in agroup of compounds that might have been supposed to be impure Bi203 butwhich are shown to be built up of approximately spherical units of com-position SiBi,,O,, 3 containing always an atom of silicon a t the centre of thegroup.In another instance 67 the completion of a Fourier electron-densityprojection made possible by the existence of several related structures led tothe revelation of a previously unsuspected molecule of methyl alcohol in thesubstance formerly known as p-quinol but thus shown and subsequentlyconfirmed by analysis to be a compound of composition 3C,H,(OH),,MeOH.Weissenberg photography has been used to show that a sample presumed tobe DDT had a deficiency of one chlorine atom per molecule and to identify itas DDD.*H. P. Klug and G. W. Sears, J. Amer. Chern. SOC., 1946, 98, 1133.E. P. Abraham, D.1\1. Crowfoot, A. E. Joseph, and E. M. Osborn, Nature, 1946,L. G . Sillen; reported at Institute of Physics Conference on War-time Progress inNature,158, 744.X-Ray Analysis, July, 1946 ; see also Arkiv Kemi, Min. GeoE., 1937, A , 12, 18.1945,155, 305.M. Schneider and I. Fankuchen, J. Amer. Chent. Soc., 1946, 98, 2669POWELL : CRYSTALLOGRAPHY. 89B. Strijk and C. H. MacGillavry have examined the structure of a high-temperature modification of sodium nitrite with a view to discover whetheran abrupt change in the temperature coefficients of the cell constants and asimultaneous loss of the original strong piezoelectric effect may be due to theoccurrence of two symmetrical sets of atomic positions in an average structureor to an oscillation of the atoms along one axis.A correction now givenshows that a decision between the two models is not possible from the availabledata.D. A. Hutchinson 6 has used density and X-ray data of calcite, diamond,lithium fluoride, sodium chloride, and potassium chloride to obtain atomicweights. This is done by comparing the molecular weights of two sub-stances calculated from unit cell dimensions and densities. If the atomicweights of some of the elements are assumed, those of others, here calciumand fluorine, may be calculated. The values derived are Ca = 40-0849 50.003, 3' = 18.9967 5 0.0013 and it is concluded that such a determinationis as reliable as other standard atomic weight procedures.Other uses of X-rays include a study of t,he thermal decomposition ofsilver oxalate by means of oscillation and Weissenberg photographs.' Thecrystals are shown to undergo fragmentation in which portions of the originalcrystals break away and assume orientations in which their a axes are notparallel to that of the parent crystal.On further heating, the powder linesof metallic silver appear with definite maxima. This is presumably due tothe orienting influence of the silver oxalate crystals. Many similar reactionscould be investigated in this way.Experimental Methods and Calculations.-A. Turner- Jones and C. W.Bunn have extended the " tilted crystal " method of indexing, and describea method of indexing the reflexions on rotation photographs of a singlecrystal set up in a random orientation.By this method it is possible to takean irregular fragment of a crystal of completely unknown crystallography,set it up on an ordinary X-ray rotation goniometer in any position, take twophotographs, and deduce the unit cell and space-group from these photo-graphs. M. Farquhar and H. Lipson have discussed the general principlesby which improved accuracy may be obtained in the determination of unit-cell dimensions from single-crystal photographs. The principles, based onthose used for powder photographs, applied to an orthorhombic crystalenabled an accuracy of the order of 0.005% to be attained. The integralbreadths of Debye-Scherrer lines for a divergent incident X-ray beam havebeen considered by A. J. C. Wilson.lo The broadening due to the appreciablephase differences between different parts of the crystal, even in the size rangefor which line broadening occurs, is calculated and is shown to be ordinarilynegligible.The accuracy of atomic co-ordinates derived from X-ray data has beenRec. Trau.chim., 1943, 62, 705; 1946, 65, 127.J. Chim. Physics, 1945,13, 383.R. L. GrifEth, ibid., 1946, 14, 408.Proc. Physical SOC., 1946, 58, 200.J . Sci. Imtr., 1946, 23, 177.lo Ibid., p . 40190 GENERAL AND PHYSICAL CHEMISTRY.the subject of theoretical consideration by A. D. Booth.ll By a comparisonof two independent sets of observed F values i t is found that the error inexperimenally observed F’s is independent of the magnitude of F. It isconcluded that this source of inaccuracy in derived atomic co-ordinates is asecondary one and for a particular case the error for a carbon atom isestimated as approximately *0.003 A.The larger error due to the non-infinite limits of Fourier summations is also considered and a possible wayof correcting for it is devised. In a special case the distortion produced isfound to have an upper limit between 0.02 and 0.005 A., experimentallyobserved errors being about 0.02. The effect of thermal agitation is to givea considerable decrease in accuracy, Another paper l1 deals with the problemof determining the maxima in a Fourier synthesis, and is based on examiningthe rapidly varying differential coefficient rather than the function itself.The problem of the steadily increasing magnitude of routine calculationnecessary for any structure determination has received further attention.Forcomputing Fourier series punched-card methods have been used with existingcalculating machines by I?. A. Schaffer, V. Schomaker, and L. Pauling,l2who point out that the method has applications in other fields of molecularstructure determination. Punched cards and a computing service wereemployed in the evaluation of electron densities for penicillin l3 a t intervalsof about 0.25 A. throughout the unit cell. At present this procedure seemscostly. Several machines for performing these calculations have beendesigned or constructed, One described by D. MacLachlan l4 depends on thespreading of layers of sand in sinusoidal waves over a scale plan of the unitcell so that the height of sand at any point is proportional to the electrondensity.An electrical Fourier summation machine has been developed byG. Hagg and T. Laurent.15A. R. Stokes l 6 has described a development of the “ fly’s eye ” whichobviates the calculation of structure amplitudes in the trial-and-error stagesof structure determinations. I n the device described, a regular repeatedpattern representing the structure is produced on a photographic plate by useof a fly’s eye composed of an array of small lenses embossed on the surface of apiece of “ Perspex ” which has been pressed a t its softening temperature intoa copper plate previously indented by means of a steel ballbearing. The dis-advantages of the pin-hole method previously used, ‘uiz., diffuseness of thepin-hole images and blocking of the pin-holes by dust, are overcome.Insteadof a movable lamp to represent the atoms, a uniformly illuminated screenwith a number of opaque discs may be used, so that no negative need be madeand only one exposure is necessary instead of one for each atom.As is well known, the determination of crystal structure by Fouriersynthesis requires the observation of as many X-ray reflections as possiblel1 Proc. Roy. SOC., 1946, A , 188, 77; Trans. Faraday SOC., 1946, 43, 444.l2 J . Chem. Physics, 1946, 14, 648.l3 D. M. Crowfoot and B. W. Rogers, to be published.l4 See Nature, 1946, 158, 260. l6 J . Sci. Imtr., 1946, 23, 155.Proc. Physical Soc., 1946, 58, 306POWELL : CRYSTALLOGRAPHY. 91and the summation of appropriate Fourier series in which the structurefactors, derived easily from these observations, appear as the coefficients.The obstacle to a simple and automatic application of the procedure to anydesired crystal rests in the fact that the structure factor is a complex quantity.The magnitude is derivable from observed quantities but the phase angleescapes observation.At present all the essential work of the determinationis that of discovering these phase angles by a process of trial greatly assistedby a variety of auxiliary means such as the use of physical properties,Patterson methods, introduction of heavy atoms, consideration of pre-viously known structures, and the study of isomorphous or related com-pounds. In the special case of centrosymmetric structures the problemreduces to that of giving the positive or negative sign to the observedstructure factor Phkl for each of the observed hkl reflexions, possibly severalhundred or more in number..If a given arrangement of atoms is considered, it is possible to computethe value of F for all points in reciprocal space, i.e., for a reflexion from aplane of any selected spacing and orientation. For centrosymmetricstructures we may imagine the group of atoms arranged around the originand repeated by simple translations of any desired lengths and directions toform a lattice. The resulting F plot in the reciprocal space is characteristicof the original arrangement and nature of the group of atoms. The value ofF is seen to vary in magnitude from point to point and to undergo changes ofsign. If a continuous variation of spacings could be made without otheralterations in the structure, or at least with only such alterations as could beallowed for, it would be possible to observe a continuous variation in themagnitude of F and to determine the points where it vanished.These wouldcorrespond to changes of sign and hence all the signs could be found. Anapproximation to this procedure was adopted by Perutz l7 in a structurewhere the reflexions from a particular direction in a protein crystal areobservable over a continuous range of spacings due to the taking up ofvariable amounts of liquid between layers. In ordinary practice the valuesof F observed from the Bragg reflexions are only those that correspond to theparticular planes that occur in the crystal under investigation, i.e., at certaincomparatively widely separated points in reciprocal space and without thepossibility of continuous variation.A. D. Booth,18 however, has suggesteda possible limited application of the method by the use of the diffusereflexions. Although it is difficult owing to background to establish theexistence of a point of zero intensity, it may be possible to show that there isno such point in a given region. Thus if a strong streak of diffuse X-rayscattering connects two regions in the reciprocal lattice of a centrosymmetriccrystal the F’s corresponding to those two regions must have the same sign.This, it is suggested, might sometimes help to determine a few signs but wouldnot go far towards solving the general problem.(Mrs.) K. Lonsdale l9l7 J. Boyes Watson and M. F. Perutz, Nature, 1946, 15l, 714.l8 Ibid., 1946, 158, 380. 19 IbicE., p. 68292 GENERAL AND PHYSICAL CHEMISTRY.points out that the argument is sound if the diffuse scattering is due to dis-placement or vibration of those atoms whose diffraction is mainly responsiblefor the reinforcing waves which give the Bragg reflexions, i.e., the scatteringin the streak and the two Bragg spots which it connects must be mainlydue to the same atoms. In ice, however, where the contribution of thecentrosymmetrically arranged oxygen atoms certainly decides the phases,strong diffuse streaks do connect regions where F's are not of the same sign.Moreover, the diffuse pattern is more symmetrical than could be the case ifBooth's rule were satisfied.Any such attempts even at this very limitedcircumvention of sign computation must therefore be made with extremecaution.Inorganic 8tructures.-Crystal chemistry of neptunium and plutonium.20I n the sexa-, quadri-, and ter-valent compounds the crystal radii decrease inthe order uranium, neptunium, plutonium. Tht crystal chemistry of thoriumand especially cerium is closely related to that of uranium, neptunium, andplutonium in the quadrivalent state. In the tervdent state the elementsLa-Sm show a marked similarlity to uranium, neptunium, and plutonium intheir crys t a1 chemistry .Oxides, hydroxides, and basic salts.The cell dimensions of a number ofdouble oxides belonging to the perovskite type of structure have beenaccurately measured by H. D. Megaw.21 This group of compounds includesstructures of very varied but different symmetry, all based on small modi-fications of the same cubic cell. The ideal perovskite type includes SrTiO,,SrSnO,, SrZrO,, BaSnO,, BaZrO,, BaThO,, and BaTiO, above 120". Some,including the usual form of BaTiO,, have a tetragonal cell derived from thecubic structure by simple compression or extension along one of the fourfoldsymmetry axes. Others, including CaTiO, (the mineral perovskite), arederived from the cubic structure by a shear in the 010 plane and a slightextension or compression along the b axis giving a monoclinic pseudo-cellwith the a and c axes equal, so that the lattice is to be described as ortho-rhombic.Changes in some of the atomic parameters cause a doubling of thecell edges. Thepseudo-cell is obtained by a slight compression of the cubic cell along the cubediagonal but the true cell is a multiple of this. The occurrence of the variousstructure modifications is interpreted in a genera1 way by steric considerationsbased on Goldschmidt's ionic radii.Quenselite,22 PbMnO,(OH), has a structure characterised by the super-position of sheets of ions perpendicular to the a axis in the sequence Mn, 0,Pb, OH, Pb, 0, Mn.The decomposition products of lead dioxide at 400" in air have beeninvestigated.23 It was found that lead dioxide samples contained a small2o W.H. Zachariasen reporting a t Institute of Physics Conference on War-timeProgress in X-Ray Analysis, Royal Institution, July 1946; see also ref. (14).21 Proc. Physical SOC., 1946, 58, 133.22 A. Bystrom, Arkiv Kemi, Min. Geol., 1945,19, A, 35.BaTiO, can also be prepared in a rhombohedra1 form.There is a good cleavage parallel to the sheets.A. Westgren and H. Hagg, ibid., 1945-1946, 20, A, 11POWELL : CRYSTALLOGRAPHY. 93amount of water which probably forms part of the anion lattice as hydroxylgroups. The oxygen content cannot be below that corresponding toPbOl.,,. A decomposition product a-PbO, may also be obtained by oxidationof certain preparations of PbO in oxygen at 300-350". This compound hasa range of homogeneity with limits close to the formulae Pb,O, and Pb,O,.The structure is very complicated and not determined with certainty.Thenext step in the decomposition is represented by p-PbO,. The composition isnear to Pb,O, and a structure is proposed in which the lead atoms occupypositions similar to those of the heavy atoms in cubic Bi,O, and cubicSb20,. It is concluded, contrary to the views of M. LeBlanc and E. E b e r i ~ s , ~ ~that the tetragonal and orthorhombic modifications of PbO have no range ofhomogeneity or very narrow ones. Some preliminary data are also givenwhich perhaps represent a third modification of PbO.W. Feitknecht and W. Marti 25 have examined the products of oxidationof manganese( 11) hydroxide and of ammoniacal manganese( 11) salt solutionsby oxygen and hydrogen peroxide, By powder photography the productsare found to be Mn(II),(III) double hydroxide, hausmannite, hydrohaus-mannite, a-, p-, and y-MnO(OH), Mn,O,.Excepting hausmannite andy-MnO(OH), the degree of oxidation of the manganese in all these compoundscan vary within certain limits, i.e., they are non-Daltonian compounds. Themanganites obtained from solutions of Mn(I1) and other metals have adouble layer structure with hexagonal layers of MnO, and disorderedhydroxide layers of the lower-valent metal such as Ca,Mg,Zn. The disorderis shown by varying sharpness of the inner rings or by their absence.W. Feitknecht26 gives some data on basic cadmium sulphate, and W. Lotmar2'has obtained single-crystal data from basic zinc chloride, ZnC12,4Zn( OH),.This has a rhombohedra1 double layer structure, but no detailed parameterdetermination is made.Precision measurements 28 on a sample of exceptionally purelead, 99.999% by spectrographic analysis, give a unit cell dimension,4-9408f.O.0001 kX, slightly higher, as was to be expected, than previousvalues derived from samples that may have contained other atoms which aresmaller than that of lead.Polonium29 is shown to have two crystallineforms, a low-temperature structure described as simple cubic with a = 3.34,and a high-temperature simple rhombohedral form with a 3-36 A., a = 98'13'.The simple structure of graphite with its ababab sequence oflayers was modified by Edwards and Lipson 30 on account of extra lines whichindicate the presence of certain layers in the abcubc order, and J.Gibson 31now reports the appearance of still further faint lines which are not accountedfor by this arrangement. They have been observed in ordinary graphite andElements.Graphite.24 2. physikal. Chem., 1932, A , 160, 69.26 Ibid., p. 1454.28 H. I?. Klug, J . Amer. Chem. SOC., 1946, 98, 1493.3O Nature, 1942, 149, 328; Ann. Reports, 1942, 39, 99.31 Nature, 1946, 158, 752.25 Helv. Chim. Acta, 1945, 28, 149.27 Ibid., 1946, 29, 14.137. H. Beamer and C. R. Maxwell, J . Chem. Physics, 1946, 14, 56994 QENERAL AND PHYSIOAL CHEMISTRY,in very pure artificial graphites. Some of the lines are double, with anangular separation of 0.20". No explanation has been given for these effectswhich might be due to other causes such as impure X-radiation.The term amorphous carbon has been used todescribe more or less impure forms of carbon devoid of any obvious crystallinecharacteristics, but such materials prepared in a variety of ways all giveessentially the same type of X-ray powder photograph with broadeneddiffraction maxima in the same positions.These have been interpreted asdue to graphite-like structure with very small particles and varying disorderof the layers. It is now 32 found that a carbon prepared by carbonisation ofhexaiodobenzene at 5"/min. up to 1000" in an atmosphere of nitrogen givespractically no coherent scattering of X-rays and thus seems to be almostcompletely without any ordered structure. Hexaiodobenzene was selectedsince the large iodine substituents might be expected t o prevent a linking oftwo aromatic residues with their rings coplanar and so favour the formation ofa hypothetical carbon structure in the form of a three-dimensional repetitionof o-tetraphenylene residues.The material obtained is thought to consist ofsuch a cross-linked structure, but highly disordered because of the presence ofoxygen and hydrogen atoms, and it is suggested that small disordered chunksof this type of structure play some part in the building up of chars and cokes.Further evidence is required before this can be regarded as established.The diffuse X-ray scattering obtained fromice crystals gives further information on this structure.33 The diffusepattern is of thermal origin but cannot in the main be due to acousticalvibrations because no combination of elastic constants can give the atar-shaped pattern found.Since the diffuse streaks cannot be due to oxygen(see above) there must be strong vibratory movement of the hydrogennuclei. J. D. Bernal and R. H. Fowler 34 show that the unit cell must be atleast three times as large as the apparent simple cell, while L. P a ~ l i n g , ~ ~from considerations of the residual entropy, has concluded that the watermolecules in ice cannot have definite orientations which would permit aunique crystalline configuration such as that of Bernal and Fowler. Thisnew work by Lonsdale confirms Pauling's suggestion that change from oneconfiguration to another is accomplished by group movements of hydrogennuclei each of which would move from the neighbourhood of an oxygen atomto the next oxygen, or by rotation of water molecules.The small unit cell istherefore a statistical one, and even a t low temperatures the apparent cellmay be small owing to freezing in of different molecular configurations indifferent parts of the crystal. A similar star-shaped diffuse pattern isobtained for ammonium fluoride, isomorphous with ordinary ice. Somehailstones have been shown 36 to contain moderate sized single crystals of theordinary ice form." Amorphous " carbon.Ice and ammonium Jluoride.32 J. Gibson, M. Holohan, and H. L. Riley, J., 1946, 456.33 K. Lonsdale, ref. (19).36 " Nature of the Chemical Bond ", New York, 1939, p. 281.36 K.Lonsdale and P. G. Owston, Nature, 1946, 157, 479.3 4 J . Chern. Physics, 1933, 1, 515POWELL : CRYSTALLOGRAPHY. 95Methylammonium chloride. The unit cell formerly ascribed t o methyl-ammonium chloride was based partly on powder-photograph measurementsand was incorrect. It istetragonal, and the whole structure may be regarded as a somewhat distortedcmium chloride arrangement, in which methylammonium ions are surroundedby the chlorine ions of the top and bottom faces of the cell. The lengths ofthe methylammonium ions which point alternately up and down are parallelto the c axis, and from the Fourier analysis results the distance C-N =1-465&0-01 A. The predicted value is 1-47 if no allowance is made for theformal charge, but with such an allowance it is 1.44, so the formal chargeappears not to have the expected effect although the differences here seem tobe fairly close to the possible errors.I n working out this structure it wasfound necessary to apply separate temperature factors for the methyl-ammonium and the chlorine ions and an anisotropic temperature factor wasused for chlorine with the maximum vibration along the c axis as is suggestedby the form of the corresponding electron-density peak.Halogen-containing complexes. Data concerning a structure deter-mination of aluminium bromide 38 have now become available. Separatemolecules of A]&, are arranged in a monoclinic cell to give a slightlydeformed hexagonal close packing. The molecules are of the type found byPalmer and Elliot in the gaseous state by electron diffraction, i.e., themolecules consist of two tetrahedra of bromine atoms around aluminiumatoms, the tetrahedra sharing an edge. There are some marked differencesin the intramolecular distances derived from the crystal structure and thosegiven by electron diffraction.I n particular the A1-A1 distance 3 . 1 4 ~ . isappreciably shorter than the 3-39 A. found in the gaseous state, and in generalthe values found are closer to those that would be expected for a model con-structed from two regular tetrahedra. The molecule is much less deformedthan in the gaseous state, and it seems that the structure yields less to therepulsive force between the central aluminium atoms. A suggested explan-ation is that it would be impossible to obtain such a good packing with themore deformed molecules and there would be a consequent loss of van derWaals attraction between the bromine atoms.The compound hitherto given the formula Mo3C14( OH),,8H20 has beenexamined.39 Analytical data suggest seven rather than eight water mole-cules, and although the unit-cell dimensions and density agree with sixmolecules of water, it is considered that seven is the more probable figuresince the density determined may be low.From the structure determinationthe formula is now rewritten as [Mo,CI,](OH)~,~~H,O. The [Mo,Cl,] groupis a slightly irregular cube with chlorine a t each corner and with molybdenumatoms at the centres of each cube face but raised slightly, about 0.05 A., abovethe faces.These groups are enclosed in a three-dimensional network ofThe cell now37 found contains two molecules.37 E. W. Hughes and W. N. Lipscombe, J . Amer. Chem. SOC., 1946, 68, 1970.a* P. A. Renes and C . H. MacGillavry, Rec. Trav. chim., 1945,64, 276.C . Brosset, Arkiv Kemi, Min. Geol., 1945-1946, 20 A 796 GENERAL AND PHYSICAL CHEMISTRY.oxygen atoms. Each molybdenum atom has four chlorine neighbours a t2.50, 2.57, or 2-62 A. and one oxygen at 2-29 A. In all, there are 18 oxygenatoms connected with one [Mo,c1,] group. Of these, 4 must be OH and 14must be water, although the 18 atoms are distributed in one group of 6 andone group of 12 equivalent point positions of the hexagonal cell. It issupposed that the 32 hydrogen atoms are distributed statistically among the18 oxygen atoms.The oxygen-oxygen distances, which are not known withgreat certainty, are about 2 . 7 ~ . The compound formerly described as[Mo,C1,,2H20]CI, ,2H20 has a tetragonal structure 39a which contains thesame Mo,CI, group and is now rewritten [MO6C1,](C1,,2H2O). I n the[Mo,Cl,] group the average Mo-Mo distance is 2.64 A.Precipitated potassium cryolite 40 has a variable composition dependingon the fluorine-ion concentration a t precipitation. The general formula isKzAlF3 + z(H20)3 - %, x being between 2.9 and 3. With x = 2-9 the compoundis isomorphous with ammonium cryolite and has a cubic cell a = 8.41, A.The unit cell of K3A1F6 is probably large and derived from a body-centredtetragonal cell a = 5-96, c = 8.46,.In precipitated potassium cryolitesome [All?,] groups may be replaced by [AlF5(H20)] when the fluoride-ionconcentration is not high enough. For every such grcrup replaced onepotassium ion is lost from the lattice.Phosgenite, Pb2C12C03, and the isomorphous bromine compound havebeen e~arnined.4~ A previous structure determination on phosgenitesuggested that there were no carbonate groups in the structure but thearguments used are invalid since the unit cell determined now has the cdimension of the unit cell doubled. The intermediate reflexions thatestablished this are exceptionally weak but are more pronounced in thecorresponding bromide. The positions of lead and bromine have beendetermined and the rest of the structure inferred from packing considerations.It consists of lead, halogen, and carbonate ions.There is no evidence oflinking to form Pb-C1 groups.Organic Crystals (General) .-The general constructional principles under-lying the formation of organic crystals have been examined by W. Nowacki 42who, in presenting the statistics for the compounds that have been suitablyexamined-a fraction of a per cent. only-points out that it remains to con-firm the conclusions on the rest. However, the total number of compoundsis considerable, about a thousand, and it seems unlikely that the high fre-quency of occurrence of certain space-groups which is familiar to workers inthis field is accidental. G . Hagg43 considered that the results might beinfluenced by the inclusion of a great number of space-group determinationswhich have been made on optically active substances, but Nowacki 44 replieswith a table showing the frequencies before and after the subtraction ofcrystals which contain optically active molecules.I n the first case in a totalArkiv KeTni, Min. Geol., 1946, 22, A, 11. 40 Ibid., 1946, 21, A , 9.*? Helv. Chint. Acta, 1943, 26, 459.4 4 Helv. Chirn. Acta, 1945, 28, 664.* l L. G. Sillen and R. Petterson, ibid., p. 13.43 Quoted by Nowacki, ref. (42)POWELL : URYBTBLLOGRAPHY. 97of 914 compounds the group P2, is found for 12%, P2& for 10.5%, andP2,2,2, for 22%. On elimination of 173 crystals with optically activemolecules the statistics are not fundamentally altered the percentages beingrespectively 12,7, and 22.Over 40% of the known organic structures there-fore have these space-groups. Seven other space-groups, viz., PI (2-4),C2 (2.4), C2/c (3.4), P2,2,2 (2*7), Pbcu (2.1), Pnma (3.4) and C4/amm,account each for between 2 and 3.5% and leave about one-third of all thecompounds for distribution among more than 200 remaining space-groups.In explanation of this, Nowacki says that the tendency to close packing,which is so frequently found in inorganic crystals, is certainly not a guidingprinciple, and quotes the 75% of all organic substances so far examined ashaving primitive lattices, with a further 16% having double primitivelattices, whereas a face-centred lattice, fourfold primitive, should lead to amaximum space filling.Although this is clearly so for the simplified case ofcubic close packing of spheres, this part of the argument does not appear tothe Reporter to be a strong one, since any structure may be referred, by asuitable choice of axes, to a primitive lattice, and in monoclinic crystals, forexample, the investigator makes a deliberate choice of axes to avoid theselection of a cell centred in any way except, in some crystals, on (001) faces.Further, when the packing of awkward-shaped molecules is considered, it isfound that by use of suitable symmetry operations the centres of moleculesmay be made to lie in positions closely approximating to those for a face-centred close packing although the structure as a whole is not formallycentred, e.g., in the structure of picryl iodidet5 space-group P4,2,.In this connection also A.Kitaigoro&kyt6 by assuming intermolecularradii for each atom, C 1-70, H 1.18 A,, has calculated the proper volumes of asmall number of aromatic hydrocarbons and compared them with the volumesper molecule in the crystal. Packing fractions between 0.68 and 0.72 areobtained and may be compared with the value 0.74 for closest packing.For molecules which are markedly different in their extensions in differentdirections, centring which involves parallel repetition does not seem soeffective for packing purposes as the use of symmetry operations whichinvolve head-to-tail or similar packing. Apart from this, experience showsthat molecules of the most diverse shapes tend to adopt arrangements inwhich the projecting portions of one fit into the indentations left by thesurrounding molecules in such a way as to achieve a good degree of spacefilling. New structures often appear very striking not only in the mannerwhereby they maintain the familiar van der Waals separations of unlinkedmolecules, but also in the avoidance of any large gaps that would give inter-group separations appreciably greater than the normal.When openstructures appear they are usually attributable to some special circumstancesuch as the directional requirements of hydrogen-bond linkages as in a-resorcinol*' or even more strikingly in quinol.** Nowacki further points out45 G. Huse and H. M. Powell, J., 1940, 1398. '* Acta Phyakochh. U.R.S.S., 1946, 21, 379.47 J.M. Robertson, Proc. Roy. SOC., 1936, A , 158, 79. 48 Ref. (67).REP.-VOL. XLIII. 98 GENERAL AND PHYSICAL CHEMISTRY.that, since the majority of organic molecules have little symmetry of theirown, any higher symmetry of the crystal must result from the arrangementof the molecules and thus selects the 92 asymmorphous space-groups as ofspecial significance for organic crystals. Of all the compounds, 72% arefound to belong to these space-groups. Since many of the molecules havean electric moment, the molecular arrangement will seek to bring about themost effective mutual saturation of dipoles. This is so when the moleculesare arranged in zigzag chains. Only three symmetry elements achieve this,the two-fold screw axis 2,, a network of symmetry centres I, and a glide planeof symmetry c , a, b, d, or n.On the assumptions that the favoured space-groups for organic structures obey the principles of (1) a primitive lattice,( 2 ) asymmorphism, ( 3 ) symmetry elements permissible, are only those statedabove either alone or in suitable combination, those to be expected areP2,, PZ,/c, Pca, Pna, P2,2,2, and Pbca. Some but not all of these occur inthe list of commonly found space-groups, and a further limiting principle isintroduced, that of efficient dipole saturation of one zigzag chain of mole-cules by the others. This requires that a two-fold screw axis may only be per-pendicular to a glide plane, and thus leaves only P2,, P2,/c, and P2,2,2, asthe specially preferred space-groups for organic crystals, i.e., the three firstmentioned as accounting for over 40% of the total.Among the other space-groups the number of examples is too small for any certain conclusions con-cerning their frequency, but some general tendencies can be understood ;e.g., in a comparable set of space-groups the frequency of occurrence increaseswith increase in the number of 2, screw axes as in P222 (0.002~0), P222,(0.003), P2,2,2 (2.7), and P2,2,2, (10.4).C. A. Beevers and W. Cochran49 give apreliminary account of the structure of the sucrose molecule from anexamination of the compound C,,H2,OlI,NaBr,2H,O and the isomorphouschloride. The heavy atoms simplify the phase-angle determinations. Theaccepted structural formula ofsucrose as 1 -a-glucopyranose-2-p-fructofuranose (I) is confirmed. I<:= I l(vo>l Parameters for all atoms are givenI30 \rl’-o- 3’1 1 CH,*OH with an estimated error 0.5 A.for interatomic distances and of(1.) 5” for bond angles.The oxygenatoms attached to carbon atoms 1 and 2 are in the cis-configuration, andsimilarly those of 2’ and 3’. The five atoms of the furanose ring arenot coplanar, atoms 3’, 4’, 5’ being displaced so as to bring the attachedgroups more nearly into the mean plane of the ring. Within the ring themean C-C distance is given as 1 . 4 4 ~ . and the mean angle as 104”. Thepyranose ring is of the Sachse trans-(chair-shaped) form. This result shouldbe compared with that obtained by E. G. Cox and G . A. Jeffrey 50 for glucos-amine hydrobromide where the same form occurs, and by Cox, T.H.Organic Xtructures.-Sucrose.CH,-OH CH,*OHH 6 1-0, H p, HH H HO Hre Nature, 1946, 167, 872. 6o Ibid., 1939,142, 894POWELL : CRYSTALLOQRAPHY. 99Goodwin,51 and A. I. Wagstaff who find the five carbon atoms in a plane withthe oxygen atom out of the plane in methylated aldopyranoses. In thepresent compound each sodium ion is surrounded in a nearly regular octa-hedral manner by one bromine, two water molecules, and three hydroxylgroups, but the surroundings of the bromine are irregular.An earlier attempted structure of m - dini tro benzeneled to a false conclusion through the deceptive character of the crystals whichwere assigned to a too high symmetry class. I n a further examination of thestructure 52 based on the space-group Pbn instead of Pbnm the molecule isfound to be nearly planar.The results of the Fourier analysis are expressedin two diagrams (Fig. 1) projected on the plane of the benzene ring and atm -Dinitrobenxene .1.411-41FIG. 1.(Reproduced by permission from Proceedings of the Royal Society, 1946, A, 188, 59.)right angles to it. This picture is, however, derived from one projection only,and the size and shape of the nitro-group were largely assumed from theresults on other compounds. Some part of the small distortions from thesymmetrical form of the molecule may be spurious. In the molecularcompounds mentioned below the nitro-groups of 4 : 4'-dinitrodiphenyl havea mirror plane passing through the terminal carbon and the nitrogen atomperpendicular to the plane of the benzene rings but the carbon-nitrogen linkis tilted slightly out of the plane of the ring.The determination of structuresof aromatic nitro-compounds has been particularly beset with difficulties andthere is scope for further accurate work.Molecular compounds. Compounds of aromatic polynitro-compounds with61 J., 1936, 1496. IM E. M. Archer, PTOC. Roy. SOC., 1946, A , 188, 61100 QENERAL AND PHYSICJAL CHEMISTRY.other aromatic substances frequently have a 1 : 1 ratio of the two moleculesand this has sometimes been regarded as evidence for an electronic rearrange-ment which provides a chemical link of some kind between the components.It has also been suggested that the association of the two components might beexplained in terms of various interactions (dipole induction effects, dispersioneffect) between one molecule and the other without the necessity for a bond, a i dthat these interactions are most effective if the planes of the aromatic rings areparallel.53 Such a parallelism is observed in many crystalline molecularcompounds of this type.W. S. Rapson, D. H. Saunder, and E. T. Stewart 54have investigated the compounds of 4 : 4'-dinitrodiphenyl with variousdiphenyl derivatives and their results have a bearing on both these supposi-tions. Molecular complexes are formed only with 4-substituted and 4 : 4'-o-00 &-A -0uo IApprox 20A. < bFIG. 2.disubstituted diphenyls. The crystal structures of several of these have beenexamined and are all of the same general type, indicated in Pig.2. In thisidealised structure the dinitrodiphenyl molecules are arranged in planes oneabove the otheq separated by 3.7 A. Running through the structure perpen-dicular to the planes of these molecules are channels in which the other com-ponent molecule, e.g., 4-hydroxydiphenyl, is seen end on with its lengthperpendicular to the plane of the paper. None of the intermoleculardistances is shorter than those normally found in crystals of aromatic nitro-compounds. These results therefore agree with those of H. M. Powell,G. Huse, and P. W. Cooke 55 on other compounds and reveal no localisedbonding between the molecules. Diffuse X-ray reflexions and diffractioneffects due to irregularities somewhat similar to those observed by G .Huseand R. M. Powell 56 in the compounds of hexamethylbenzene with picrylhalides are observed. The molecular ratios in this new set of compounds aredetermined by geometrical considerations. They depend on the number63 D. H. Saunder, Proc. Roy. SOC., 1946, A, 188, 21.'6 Ibid., 1943, 163.~5' J., 1946, 1110.Ibid., p. 436POWELL : CRYSTALLOGRAPHY. 101of dinitrodiphenyl layers that can be accommodated along the length ofthe other component molecule. Thus the length of the 4 : 4’-diacetoxy-diphenyl molecule, after allowance for approach of the next molecule in theend-on position, is 17-18a. This, divided by 3-7, the separation of thenitro-compound layers, gives n = 4-6-4-9 and the compound formed has a5 : 1 ratio of the dinitro-compound to the other molecule.Similar agree-ment is found for the other molecules, the values of n being close to 4,3&, or3 depending on the length of the molecule and in agreement with the com-positions determined by analysis. These structures therefore show thatneither the common 1 : 1 ratio of components nor parallelism of the aromaticrings is essential in these moleuclar compounds.A preliminary communication by D. E. Palin and H. M. Powell 57describes an entirely new type of relationship between the components of amolecular compound. Quinol forms a series of compounds of ideal formula3C,H,(OH),,%f, where M is a small molecule, e.g., sulphur dioxide. Thequinol molecules are linked through hydrogen bonds to form indefinitelyextended cage structures in three dimensions.This structure, of a formimposed by the dimensions of the quinol molecules and the directionalrequirements of the hydrogen bonds, is of such an open character that asecond identical framework structure can completely interpenetrate it.There is thus a mutual multiple enclosure of two giant molecules which haveno direct linkages but are inseparable without the breaking of their ownstructures. This complex of interpenetrating molecules is still not veryclosely packed and contains cavities which are large enough to contain thesmall molecules which form the second component of the molecular com-pound. The formula is determined by the ratio of available cavities to thecage material, and M is restricted to such small molecules as will fit into thespace.The enclosed material once trapped cannot escape despite thevolatile nature of the component in the free state. Whether a given moleculeM will form such a compound is determined, apart from size considerations,by the possibility of obtaining it in sufficient concentration in the samesolution with quinol but does not otherwise depend on the chemical characterof the second component.W. T. Astbury and C. J. Brown 68report that terylene (polyethylene terephthalate) gives a well-oriented fibrediagram with spots that could be indexed on a triclinic unit cell. The fibreaxis has the length of 10-8, A . , which is compared with the 10.9 A. calculatedfor the repeat structureFibres and other complex structures.Increasing disorientation is shown in the usual way by the drawing out ofspots, but terylene is peculiar in that poorly oriented preparations give67 Nature, 1945, 156, 335; see J ., 1947, 208. 68 Ibid., 1946, 158, 871102 GENERAL AND PHYSICAL CHEMISTRY.photographs like those of single crystals rotating about an axis inclined a t asmall angle to the principal axis. Spots are displaced to varying extentsout of the layer lines, and an intense 110 reflexion is seen as two overlappingspots one above and one below the equator. This means that in the drawingprocess it is more difficult to pull 1iO planes into parallelism. From thegreat intensity of this reflexion the chains must be approximately flat andparallel to 110.On drawing, chains or groups are first pulled straight byslipping parallel to this plane, and afterwards, with greater difficulty, theseplanes are themselves pulled into parallelism.A new micro-method for X-ray diffraction of biological objects has beenused by D. Kreger.59 By its means a fibre pattern was obtained from a singlestarch grain. There were a considerable number of spots but the detailedstructure has not been found. Diffraction patterns have previously beenobtained with fairly simple small objects, such as a tungsten thread, and thisextension seems to be of considerable importance.Diffraction patterns of isoprene a t 20'9. and 80" K. show many linesaccording to observations by C. J. B. Clews and A. Schal1amach.m Theseestablish the crystalline character of the material in these conditions butthere is some difficulty in selecting a unit cell. Fibre patterns have beenobtained with filaments of amylose and of amylose containing an uncertain,possibly variable amount of potassium hydroxide.61The diffraction of X-rays by aqueous solutions of hexanolamine oleate 62and of sodium oleate G3 has been studied, and a general structure for themonooleyl disaturated triglycerides has been proposed.64 The structure ofsoap micelles 65 has also been investigated.The X-ray diffraction effects innot too dilute aqueous solution indicate a structure of double layers of soapmicelles with " water" layers between them. In the double layers thehydrocarbon chains are oriented towards each other with the polar endstowards the water. Micelle layer spacings are observed varying from 30 to100 A., and in the plane of the layers there is a nearly constant spacing of 4.5 A.for normal paraffin-chain soaps at all concentrations from 4.5 to 30%.Addition of salts does not materially affect the short spacing, but potassiumor sodium chloride produces a marked effect on micelle layer spacing and onthe intensities of the X-ray pattern. The probable effect is that sodiumchloride makes them smaller.A preliminary report 66 concerning zinc p-toluene-sulphonate and isomorphous substances of type (CH,°C6H4*S03)2Zn,6H,0contains a Fourier electron-density projection which shows all atoms clearlywith the exception of one of the oxygen atoms of the sulphonate group whichoverlaps with the sulphur atom. There is a regular octahedral arrangementOther structures.59 Nature, 1946, 158, 199.6 1 F. R. Senti and L. P. Witnauer, J . Amer. Chem. SOC., 1946, 68, 2407.6a S. Ross and J. W. McBain, ibid., p. 296.6 4 L. J. Filer, S. S. Sidhur, B. F. Daubert, and H. E. Langenecker, ibid., p. 167.65 W. D. Harkins, R. W. Mattoon, and M. L. Corrin, ibid., p. 220.6 6 A. Hargreaves, Nature, 1946, 158, 620.6o Ibid., 1946, 157, 160.63 Ibid., p. 547POWELL : CRYSTALLOGRAPHY. 103of water molecules round each zinc atom. More precise details of the stereo-chemical relationships await a determination of the third atomic co-ordinate for each atom.Unit cell dimensions have been given from two sources 67 for a number ofdiphenyltrichloroethane derivatives. One compound, op’-dichlorodiphenyl-trichloroethane, has a triclinic cell with the unusual number of 20 moleculesper unit cell. There must therefore be at least 10 molecules in the asym-metric unit, a state of things that may perhaps be attributed to the generalawkwardness of the molecular shape for packing purposes. Wild andBrandenberger on the basis of Patterson analysis have suggested atomicpositions for the chlorine atoms in DDT. Schneider and Fankuchen, whohave also studied this substance, conclude that these suggested parametersrequire some modification, but details are not available. The highly sym-metrical form of the quinuclidine molecule might lead one to suppose that itwould form a hexagonal close packing, but this is not the case, since at roomtemperature it forms isotropic cubic crystals with a = 8.977&0.009 A. andfour molecules per unit cell. The translation lattice is face-centred, i.e.,the molecule centres form a cubic close packing. In order to bring thetrigonal symmetry of the molecule into agreement with the cubic symmetrythere must be either free rotation of the molecules about their centres or astatistical disordered structure with the molecular trigonal axes parallel tothe four sets of three fold axes of the cubic unit. On space considerations thelatter is the more probable. H. M. P.MANSEL DAVIES.P. JOHNSON.H. M. POWELL.A. F. WELLS.67 H. Wild and E. Brandenberger, Helv. C?~im. Acta, 1946, 29, 1024; M. Schneiderand I. Fankuchen, J . Amer. Chem. SOC., 1946,68, 2669

ISSN:0365-6217    

DOI:10.1039/AR9464300005

出版商:RSC    

年代:1946

数据来源: RSC

摘要:

INORGANIC CHEMISTRY.1. NON-STOICHEIOMETRIC COMPOUNDS.RECENT work in inorganic chemistry has raised the question of the validityof the law of constant proportions, as applied to solid compounds. Theexistence and classification of “ Berthollide ” compounds have been notedpreviously in these Reports,l and it appears opportune to review our presentstate of knowledge of the subject.It is generally recognised that the intermediate phases in metallic systemsmay exist over a range of composition, not necessarily including a rationalchemical formula, ; an idealised chemical formula can usually be assigned,however, based on the composition of the unit cell of the crystal.2 Betweenintermetallic and ionic compounds there is a transition, rather than anabrupt demar~ation,~ depending on the difference in electronegativity ofthe combining atoms, and whereas the elements of Groups VB, VIB, andVIIB form true salts with the most electropositive metals (Groups IA, IIA),their compounds with the transition and B-sub-group metals display acomplete transition from the ionic to the quasi-metallic type.Variabilityof composition runs broadly parallel t o sub-metallic properties, but is byno means limited to compounds of obviously sub-metallic character.The distinction between solid solutions, interstitial compounds and non-stoicheiometric compounds is, in the last analysis, rather arbitrary.N. S. Kurnakow first proposed the term “ Berthollide ” (as distinct from“ Daltonide ”) to describe homogeneous phases in systems where themaxima or minima of properties-melting point, conductivity, lattice order,etc.-do not coincide with a rational atomic ratio of the components. Forthe purpose of this report it is convenient to follow W.Schottky andC. Wagner in considering the familiar “ Daltonide ” type as a specialcase of the “ ordered mixed phase ”, a 2-component (or multicomponent)system with statistically regular lattice array.Our present knowledge of crystal structure confers precise meaning onthe term “solid solution” as applied to crystals of atomic lattice types.I n a crystal phase of ideal formula AB,, a stoicheiometric excess of elementB can be accommodated structurally in only three ways : (i) Substitutionalsolid solution : B atoms replace A atoms on lattice sites proper to A.(ii)Interstitial solid solution : additional B atoms are located in inter-latticepositions. (iii) Xubtractive solid solution : all B atoms occupy proper Blattice sites, but a number of A lattice sites is left untenanted.Since (ii) increases and (iii) decreases the average weight per unit cell,distinction between them is possible by combining density and X-ray cellAnn. Reports, 1933, 30, 381; 1935, 32, 211.A. Westgren, Angew. Chem., 1932, 45, 33.Cf. E. Zintl, ibid., 1939, 52, 1.2. physikal. Chem., 1930, B, 11, 163.a 2. anorg. Chem., 1914, 88, 109ANDERSON : NON-STOICHEIOMETRIC COMPOUNDS. 106dimension measurements. I n this way it was shown that in pyrrhotite,FeS-FeSl.l,,6 ferrous selenide, FeSe-FeSe,.,,' and wiistite, FeOl.m-FeO,.,, the stoicheiometric excess of non-metal represents a cationdeficiency, the anion lattice being substantially complete.Thus a pyr-rhotite Fe,S, is properly represented Fe,,.,,S; it cannot be regarded as asolid solution between two Daltonide compounds, and is a true non-stoicheio-metric compound. In the €-phase of the Fe-Sb system (ideally FeSb),increase in cell dimensions with increasing iron content above the idealformula indicates that the excess of iron is accommodated interstitially .gSubstitutional solid solution is likely only in intermetallic compounds,where ionic repulsions mould not be involved. Thus, in the @-phase of theNa-Pb system (27-35 atoms % Na; ideal composition, NaPb,), thestoicheiometric phase lies outside the iange of homogeneity ; the stablephase has 4-9% of the Pb atoms replaced by Na.lo According to M.J.Buerger,ll in the marcasite-type FeSb,, FeAs,, FeS,, the stoicheiometricexcess of iron usually present is substituted for a proportion of the non-metal. Such substitution in a metallic sulphide seems improbable, andthis series could profitably be reinvestigated.The conditions of equilibrium of lattice defects in a real crystal wereworked out by W. Schottky and C . Wagner?? l 2 I n a stoicheiometriccrystalline compound MX, displacement of atoms from their regular latticepositions would be an endothermic process ; the resulting interstitial atomsor vacant lattice sites could be distributed a t random amongst any of theavailable positions of the crystal lattice.The defects therefore contributesubstantially to the configurational entropy, as well as raising the totalenergy of the crystal, and it emerges that at all temperatures above 0" K.the free energy G (= H - TX) is a minimum for certain finite concentrationsof lattice defects of each kind (depending on the energy involved in creatingthe defects). If interstitial M atoms, interstitial X atoms, vacant M sites,and vacant X sites are all present in significant CQncentrations, the equi-librium conditions are rather complex. However, if-as is reasonable forkT <energy of defect formation-it can be assumed that all types ofdefect are not equally probable, two simple limiting cases arise : (i) Equalconcentrations of vacant cation sites and vacant anion sites (Schottkydefects); l3 believed valid, e.g., for NaC1.(ii) Interstitial atoms of one orG. Hagg and G. Siicksdorf, 2. physikal. Chem., 1933, B, 22, 444; Nature, 1933,131, 167.G. Htigg and A. L. Kindstrom, 2. physkal. Chem., 1933, B, 22, 453.* E. R. Jette and F. Foote, J . Chem. Physics, 1932, 1, 29.0 A. Oftedal, 2. physikal. Chem., 1927, 128, 135; G. HBgg, 2. Krist., 1928, 68,lo E. Zintl and A. Harder, 2. physikal. Chem., 1931, A , 154, 63.l1 Amer. Min., 1934, 19, 37.12 W. Schottky, 2. physikal. Chem., 1935, B, 29, 335; R. H. Fowler and E. A.13 W. Schottky, Naturwiss., 1935, 23, 656; 2. physikal. Chem., 1935, By 29,470.Guggenheim, " Statistical Thermodynamics ", Cambridge, 1939, paras. 1302, 1303.335106 INORGANIC CHEMISTRY.other kind, with a corresponding number of vacant lattice sites (Frenkeldefects) ; l4 example, AgBr.For thecrystal in contact with the vapour of one of its components (e.g., a diatomicnon-metal, such as O,, I,, etc.), we must consider the possible addition orremoval of X- ions a t the surface of the originally stoicheiometric crystal,by such processes as (I) or (11).(1) M++M++ + eAddition of supernumerary X- ions to the crystal involves ( a ) an increasein valency of a corresponding number of M+ ions and (b) the creation ofvacant cation sites which will ultimately distribute themselves by diffusionthroughout the lattice.(11) X- + Mf (on lattice site) + 4X2 (gas) + M+ (interstitial) + e (trappedRemoval of X- ions from the lattice involves ( a ) effective conversion of thesame number of M+ cations into M atoms and (b) creation of interstitialatoms or (for crystals with Schottky defects) vacant anion sites.Addition or removal of X ions will accordingly involve changes bothin total energy and in configurational entropy as compared with thestoicheiometric crystal.The minimum free energy for any temperatureand any given pressure px of the vapour X, corresponds (for a crystal withFrenkel defects) with concentrations of defects given * byThe stoicheiometric compound is, however, a limiting case.&X2 + e (at surface) ---+ X- (on lattice site) + cation holenear interstitial atom)Nh = Nl . px). exp. - Ex/kT . . . . . . . (1)Ni = Nl . p x - t . exp. - (Eh + Ei + E x ) / k T .. . (2)where Nh, Ni = number of M holes and interstitial M atoms in a crystalcontaining NZ cations ; Eh, Ei = energy expenditure to produce one vacantM site or interstitial M ?tom in the stoicheiometric crystal, Ex = expenditureof energy in adding one additional X atom to the crystal. The concen-trations of holes and interstitial atoms are not independent, being related by(3) defines in effect the equilibrium constant of a quasi-chemicaldissociation :Lattice site occupied by ion ---+ Interstitial ion + lattice holeFor the stoicheiometric crystal,6 is the intrinsic disorder of the stoicheiometric crystal, which is in equi-librium with one particular partial pressure of the component X only.l4 J. Frenkel, 2. Physik, 1926, 35, 652.* Approximately, the.contributions to the vibrational energy being neglected (cf.Nrt*lN1 = Ni*/NI = 6 = exp. -(Eh + Ei)/2kT . . (4)Mott and Gurney, " Electronic Processes in Ionic Crystals ", Oxford, 1940, p. 29)ANDERSON : NON-STOICHEIOMETRIC COMPOUNDS. 107For any other pressure of X the crystal will contain at equilibrium astoicheiometric excess (or deficiency) of X given by Nh - Ni, which dependsupon the intrinsic disorder of the stoicheiometric phase. Writing (Nh -Ni)/Nl = n, and the pressures of X in equilibrium with MX1.OOO, MX, + 12as p(O), p(n), respectively, we have. . . ( 5 )Variation of stoicheiometric defect for two values of 6 is illustrated in thefigure. If the stoicheiometric crystal is almost perfectly ordered, the40 1 6 = 0 - 0005I 6= U405equilibrium pressure must increase very steeply to produce even smallchanges in composition.The essential consequences of this thermodynamic theorem are asfollows.(i) It is perfectly general, suggesting potential variability of compositionfor all ionic, semimetallic, or intermetallic compounds.(ii) Unless the degree of lattice disorder in the stoicheiometric compoundis appreciable, variation of composition under experimentally accessibleequilibrium conditions may be imperceptibly small.The “ Daltonide ”compound thus appears as a special case.15(iii) The intrinsic disorder 6 will be small unless production of defectsis not too endothermic, as compared with the thermal energy. Eh, Ei aresmaller than the lattice energy of the crystal by a factor depending l6 onthe polarisation and distortion of the crystal lattice around each defect.Non-ionic interactions ( e . g ., van der Waals forces) between the atoms areparticularly important in stabilising defects and in favouring the locationof atoms or ions in interstitial positions. Compounds of the transition orl6 A. &mder, 2. physikal. Chern., 1933, A , 165, 65.l6 W. Jost, J . Chem. Physics, 1932, 1, 466; W. Jost and G. Nehlep, 2. physikal.Chem., 1936, B, 32, 1 ; N. F. Mott and M. J. Littleton, Trans. Faraday Soc., 1938,34,485; W. Jost, ibid., 1938, 34, 860108 INORGAXIU CHEWSTRY.B-sub-group metals are therefore likely to possess a higher degree of intrinsicdisorder than are structures bugt up from the inert-gas-like ions.Estimatesof 6 in typical compounds have been made by J. Addink l7 and by E. Kochand C. Wagner.l*(iv) Deviation from stoicheiometry involves a valence change. Excessmetal may be incorporated by converting some cations effectively intoneutral atoms, or into cations of lower valency. This decrease in valencyis possible for any cation, including the inert-gas-like cations. The alkalihalides, heated in the vapour of the corresponding metal, will take up afew atoms per thousand of excess metal.19 Excess non-metal involves thepresence either of cations of higher valency (energetically permissible onlyin compounds of the metals displaying variable valency), or of anions oflower valency. The low binding energy renders the latter source of stoicheio-metric variation less favoured, but potassium iodide (e.g.) will incorporatea stoicheiometric excess of iodine (up to a few atoms per million I- ions).lg* 2OIt seems likely that supernumerary S, molecules may be built into the pyritestructure on lattice sites proper to S2,- groups (vide infru, NiS,, CoS,).For a compound to be stable over an appreciable range of composition,certain conditions must evidently be fulfilled.,l The energy expenditure toproduce defects must not be too large; the energy difference between thetwo valency states involved must also be small; the difference in sizebetween the ions in the two valency states must be small, so that the latticemay not be distorted to the point of collapse.In all these respects thecompounds of the heavier metals occupy a special position, and it is amongstthese that marked variations from stoicheiometric simplicity have beenencountered.The Schottky-Wagner theory makes no reference to factors limiting therange of existence of a crystal phase, and is strictly valid only where theconcentration of lattice defects is very small.The tolerance of a crystallattice for excess of its components is actually limited. The positions ofall atoms adjacent to an interstitial atom, lattice hole or ion of highervalency must undergo adjustment, and if the concentration of such latticedisturbances exceeds some limiting value, the crystal lattice may breakup t o give a second phase and a structure " saturated " with defects.Anattempt to include this within the scope of the theory has been made22by considering not only the energy expenditure to produce lattice defects,but also an energy of interaction of defects when adjacent to each other.The effect of this is that the distribution of defects through the crystallattice is no longer completely random. Below a critical temperature1 7 Nature, 1946,157, 764.by, the effects of secondary structure, 6 being much smaller still.18 2. physikal. Chem., 1937, B, 38, 295.19 Cf. R. W. Pohl, Proc. Physical SOC., 1937, 39, Extra part, 1.20 E. Mollwo, Ann. Physik, 1937, 29, 304.2 1 W. I<Iemm, Atti X Cony. int. Chiin., Rome, 1938, 2, 696; Die Chemie, 1943,56, 6.22 J. S. Anderson, Proc. Roy. SOC., 1946, A, 185, 69.These estimates include, and are probably dominateANDERSON : NON-STOIUHEIOYETRIU UOMPOUNDS.109(dependent on the interaction energy) the lattice is stable only when theconcentration of defects is less than a limiting value; if this is exceeded,the non-stoicheiometric phase breaks up into a 2-phase system. As thesaturation concentration of (e.9.) vacant cation holes and interstitial cationswill in general be different, the range of accessible compositions on themetal-poor and the metal-rich side of the ideal formula can differ widely.I n particular, the maximum permitted concentration of interstitial atomscould be less than would correspond to the intrinsic disorder 6 of the latticeof the stoicheiometric compound. The ideal composition would then fallwithin the 2-phase region, and the stoicheiometric compound would beunstable : only the phase with a stoicheiometric excess of non-metal wouldexist.I n a number of well-established instances (see below) this is foundt o be the case. This model is over simplified but reproduces some typicalfeatures of equilibria involving non-stoicheiometric phases.Occurrence of Non-stoicheiometry in Binary Compounds.-Apart fromsome compounds of variable composition long known from their mineraloccurrence (e.g., pyrrhotite), evidence for the existence of non-stoicheio-metric compounds has come principally from studies of phase equilibriain binary systems, and needs critical examination. I n metallic and quasi-metallic systems, the standard methods of thermal analysis may revealthe range of stability of intermediate phases.Where one component isvolatile (e.g., in oxide and sulphide systems), study of the ( p , X ) , equilibriumis convenient, as used in the long series of memoirs from the attingen andHanover schools of W. Biltz.23 If a solid phase has a range of composition,the system is bivariant over the same range; the equilibrium pressurevaries with the composition of the solid phase instead of changing abruptlyfrom one univariant equilibrium to another at the composition of eachstoicheiometric solid compound. However, (p,X) isotherms or ( T , X )isobars of similar shape can result from a completely different cause:formation of the product of a reaction in a stoicheiometric but " active "state-e.g., imperfectly crystallised or having high surface energy owing toits state of subdivision24-whereby false equilibria are set up. This hastoo frequently been overlooked, and conclusions drawn from the shape ofdegradation curves have in several instances (cf.lead and antimony oxides,below) subsequently been found incorrect. Where, as in such systems asNiS-NiS, 25 and CoS-CoS, 26 the experimental measurements have beenmade at temperatures high enough for recrystallisation and true equili-bration (diffusion is appreciable above 0.5 x absolute melting the29 Key papers to the experimental method are : W. Biltz and H. Muller, Z. anorg.Chem., 1927, 163, 257; W. Biltz and R. Juza, ibid., 1930, 190, 162; F. Wiechmann,M. Heimburg, and W. Biltz, ibid., 1939, 240, 129.24 R.Fricke, Maturwws., 1943, 31, 469; Q. F. Huttig and F. Kolbl, 2. anorg. Chem.,1933, 214, 289.25 W. Biltz, A. Voigt, K. Meisel, F. Weibke, and P. Ehrlich, ibid., 1936, 228, 273.1 6 0. Hiilamann and W. Biltz, ibid., 1936, 224, 73.'7 G. Tammann, ibid., 1926, 149, 67110 INOWANIC CHEMISTRY.evidence of ( p , X ) isotherms is significant. Less weight attaches to evidenceobtained similarly for oxide systems. The melting points of oxides areusually so high that “active” states hamper the attainment of realequilibria.X-Ray studies have been widely used alone or in conjunction with( p , X ) p or ( T , X ) , measurements. Where the diffraction lines of the minimumdetectable amount of a new phase must be sought, the tendency is toexaggerate the range of existence of a phase.A narrow, but finite, rangeof existence may equally well be overlooked. Most conclusive, but usedhitherto in too few instances, is the precise measurement of cell dimensions.Occurrence of a non-stoicheiometric phase can generally be unequivocallydetected, and the mode of incorporation of the excess of one componentcan be d e d ~ c e d . ~ ~ 28, 2 9 ~ 30 With paramagnetic or ferromagnetic compoundsof the transition metals, magnetic measurements can be used to determinethe phase 32Minute departures from stoicheiometric balance, below any limit ofanalytical detection, may still be detected through the electronic semi-con-ducting properties they coder on otherwise non-conducting crystals.33 Eachatom of excess metal represents a supernumerary cation + trapped electronin the lattice, and constitutes a filled impurity level from which, by thefluctuations of thermal energy, the electron may be excited to the con-duction band of the crystal.A cation of higher valency, in a crystal withexcess non-metal, is a site of electron deficiency, an empty impurity levelt o which an electron may be excited from the originally filled valency bandof the crystaLN Electrons in the first case, or “positive holes’’ in thesecond case, are thereby rendered mobile, giving rise to electronic con-ductivity but differing in respect of the sign of certain consequential effects(Hall effect, thermoelectric effect) .35 The relation of semiconductingproperties to variability of composition is revealed, for metallic oxides,by the effect of the oxygen pressure.Diminution of oxygen pressureincreases the conductivity of oxides derived from the highest valency stateof a metal (stoicheiometric excess of metal increased), and decreases the(positive hole) conductivity of oxides derived from lower valency states(stoicheiometric excess of oxygen de~reased).~~ Even the most refractoryoxides, like Al,O, and CaO, become metal-excess conductors at high tem-peratures ; 37 colour changes such as those of ZnO, In,O,, CeO, are associatedwith the reversible loss of oxygen atoms from the crystal lattice. C. Wag-28 G. Hagg and G. Soderholm, 2. physikal. Chem., 1935, B, 29, 88.29 H. Haraldsen, 2. anorg. Chem., 1937, 234, 372.W.Klemm and N. Fratini, ibid., 1943, 251, 222.31 H. Haraldsen, ibid., 1937, 231, 78; 1941, 246, 169, 195.32 H. Haraldsen and F. Mehmed, ibid., 1938, 239, 369.33 C. Wagner, 2. physikal. Chem., 1933, B, 22, 181.34 For a general review, cf. F. Seitz, J. AppZ. Physics, 1945, 16, 553.35 For a general review, cf. R. J. Maurer, ibid., p. 563.86 E . Friederich, 2. Physik, 1925, 31, 813; W. Meyer, ibid., 1933, 85, 278.97 W. Hartmann, ibid., 1936, 102, 709ANDERSON : NON-STOIUHEIOMETRIO OOMPOUNDS. 111ner38 has sought to follow the ( p , X ) equilibria in the ZnO and the Cu,Osystems on the basis of plausible assumptions as to the relation betweenconductivity and stoicheiometric excess, but his assumptions are in doubtfulaccord with the whole range of experimental facts.39The following survey is not exhaustive, and includes only those com-pounds for which explicit evidence has been cited ; intermetallic compoundsare omitted.Non-stoicheiometric phases are indicated (cf. Klemm) 21 bya bar above the idealised formula.(I) Nydrides.-The interstitial semimetallic hydrides of Zr, Th, Ta andthe rare-earth metals approach stoicheiometric compositions only as anupper limit of hydrogen content .40 The essentially Berthollide Pd-Hequilibria were discussed from the statistical thermodynamic viewpoint byJ. R. Lacher,4l and it has recently been shown4, that the Zr-H system hassimilar characteristics when the complicating effect of oxygen, present ininterstitial solution in the metal-which vitiated much of Sieverts’s work-is avoided.The complete equilibria might be interpreted along the linesindicated in ref. (22).43(11) Su.lphides, Selenides, Tellurides.-The table collects data for MX andMX, compounds of the first transition series, but omits the (quasi-metallic)subsulphides, etc., some of which (e.g., pentlandite Ni,S,44 and the Co4S3phase45) undoubtedly have a range of existence. In every case, the MXcompounds with NiAs type structure exist over a wide range of composition(contrast MnS and the low-temperature forms of FeSe and NiS) throughthe omission of cations from the structure. In some cases at least (e.g.,C-) the stoicheiometric compound’is unstable. In the light of the theor-etical discussion (equation 5 ) it is important that the proportion 6 of vacantsites of both kinds in the stoicheiometric phase may apparently be as highas 5-’7%.49 The complete transition between VSe and VSe,, CoTe andCoTe,, NiTe and NiTe, is particularly noteworthy.The NiAs and theCd1,structures are so related that the former is transformed into the latterby the ordered omission of half the cations. Thus, in the V-Se system,38 H. H. von Baumbach and C. Wagner, 2. physikal. Chem., 1933, B, 22, 199;H. Diinwald and C. Wagner, ibid., p. 212; J. Gundermann, K. Hauffe, and C. Wagner,ibid., 1937, By 37, 148.39 Cf. B. Gudden, Ergebn. exakt. Naturwws., 1934, 13, 222; J. S. Anderson andM. C. Morton, Proc. Roy. SOC., 1945, A , 184, 83; Trans. Faraday SOC., in the press.4O A. Sieverts et al., 2. anorg.Chem., 1926, 153, 289; 1930, 187, 155; 1928, 172,1 ; 1931,199, 384.dl Proc. Roy. SOC., 1937, A , 161, 525.42 M. N. A. Hall, S. L. H. Martin, and A. L. G. Rees. Trans. Paraday SOC., 1945,43 Dr. A. L. G. Rees, private communication.44 Cf. J. E. Hawley, G. L. Colgrove, and H. F. Zurbrigg, Econ. Geol., 1943, 38, 335.46 0. Hulsmann and F. Weibke, 2. anorg. Chem., 1936, 227, 113.46 W. Biltz, P. Ehrlich, and K. Meisel, ibid., 1937, 234, 97.4 7 W. Klemm and E. Hoschek, 2. anorg. Chem., 1939, 242, 49.48 W. Biltz and A. Kocher, ibid., 1939, 241, 324.49 H. Haraldaen, ibid., 1937, 234, 372; H. Haraldsen and A. Neuber, ibid., p. 337.41. 306TiVCrMnFecoNiCorn- Struc-pound. ture.TiSTIS ,. 6TSa C6VS (a) BS m., (8)MnS (a) B1 $4 B3MnS2FTS B8S S , C2, C18G S B8CoSl.3a H11cos, c2 -NiS B13E S B8NiS, c2n.1.0-1*11.1-1.51.5-2.0 *1*0-1*161.17-1.531.0-1.1 71.22-1.481.002-001 SO-1 * 141.95-2'051.05-1.251.3331 * 9- > 2 -01 *oo1.0-1.22->3Ref.4647484951525354526564558Compounds MX, of Transition Metals.Corn- Struc-pound.ture. n.V S e (a)SS 0.98-1-2Vs.6 (p)M 1.2-1.6VSe, ( y ) C6 1.6-2.0C x e (a) B8 1.0-1.15CrSe,.,, (8) M 1.20-1.33CrSe,15 ( y ) H 1.44-1.50FeSe T 1 -00FeSe, C18 ?FTSG (a) B8 1.0-1.13(8) M 1.13-1.31case, c 2 ?NiSe, C2 ?Ref.473265757* At high temperatures; range of existence narrower a t231, NaCl type. B3, ZnS type. B8, NiAs type. B13, trigonal millerite type.C6,tme. H11, spinel type. M , H , T, monoclinic, hexagonal, and tetragonal phases of otheANDERSON : NON-STOICHEIOMETRIC COMPOUNDS. 113the a-phase is stable with up to 17% of the cation sites vacant, the " holes "being distributed at random. A corresponding proportion of V2+ ions isreplaced by V3+ or V4+. Further increase in the concentration of cationholes initiates an ordering process which lowers the crystal symmetry@-phase). Finally, with 38--50% of the original cation sites vacant, theholes are segregated largely into alternate cation sheets of the originalstructure. Another hexagonal, Cd1,-type structure results, ideally VSe,,but including up to 20% extra cations (partial replacement of V4+ by V2').Only in exceptionally favourable cases can the range of existence be as wideas this, and the gaps of miscibility as narrow, but a similar sequence ofchanges is met with in some oxide systems.The high-temperature modifications of these, witha random distribution of cations,60 are stable with a wide range of cationdeficiency ; certainly up to Cul.,S, Cul.,Se, Cu,.,Te.Certain properties-conductivity, self-diffusion, etc.-have a maximum value close to thecomposition Cu1.,X.61, 6, The C q phase is of considerable mineralogicalinterest; N. W. Buerger G3 considers that cubic chalcocite has the idealcomposition Cul.,S (i.e., 10% of cations missing) and is distinct from theCu,S phase proper. CuS does not appear t o have a measurable range ofexistence.64 As befits the instability of higher valency states of silver, Ag,Sis not stable over any wide range of composition, but does take up a measur-able excess of sulphur.65 Equilibrium compositions a t 300" areVapour pressure of S, mm................... 0 0-6 5.2 21Composition.. ..................................... . Ag2*000S Agl'BB92S Agl*BB7S Agl*9B6S-I____ Cu,S, Cu,Se, Cu,Te.(111) Arsenides, etc.-Transition metals form compounds MX, MX,,with NiAs and (mostly) marcasite structures respectively ; few systemshave been investigated thoroughly. Lollingite, FeAsz, usually contains an60 H. Haraldsen and A. Neuber, 2. anorp. Chem., 234, 353.61 W. Biltz and F. Wiechmann, ibid., 1936, 228, 268.62 R. Juza and W. Biltz, ibid., 1932, 205, 275; H. S. Roberts, J. Amr. Chem. Soc..1935, 57, 1034; H.Haraldsen, 2. anorg. Chem., 1937, 231, 78; 1941, 246, 169, 195;2. Elektrochem., 1939, 45, 370; E. Jensen, Amer. J. Sci., 1942, 240, 695; J. J. Lukes,C. F. Prutton, and D. Turnbull, J . Arner. Chem. Soc., 1945, 67, 697.63 Ref. (11).64 F. G. Smith, Amer. M i n . , 1942, 27, 1.65 A. Oftedal, 2. physikal. Chem., 1928, 132, 208.6 8 H. Haraldsen, 2. anorg. Chem., 1935, 224, 8 5 ; M. Heimbrecht, W. Biltz, and67 S. TengnBr, ibid., 1938, 239, 127. m Ref. (30).6o P. Rahlfs, 2,physikaZ. Chem., 1936, B, 31, 157.61 H. Reinhold and H. Mohring, ibid., 1937, B, 38, 221 ; H. Reinhold and H. Seidel,62 H. Reinhold and H. Brauninger, ibid., 1938, B, 41, 397.G3 J . Chem. Physics, 1939, 7 , 1067; Econ. Beol., 1941, 36, 19.64 A. M. Bateman, {bid., 1932, 27, 62; R.Juza and W. Biltz, 2. anorg. Chem.,6s H. Reinhold and K. Schmitt, 2. physikd. Chem., 1939, B, 44, 76.K. Meisel, ibid., 1939, 242, 229.68 Ref. (25).ibid., p . 245.1930, 190, 161114 INORQANIC CHEMISTRY.excess of iron.66 FeSb exists a t the ordinary temperature only over therange Fe,.,,Sb to Fel.,,Sb,67 and the maximum melting point correspondsroughly to Fel.,5Sb.68 The ideal formula, however, is established by theNiAs lattice type. NiSb 69 and NiBi 7O similarly have an existence rangewith excess of metal. Stoicheiometric FeSi, is non-existent; 7 1 the phaseof maximum melting point has a 20% deficiency of cations, due possiblyto substitutional solid solution.72,(IV) Oxides.-Non-stoicheiometric phases have been reported in thesystems listed below but, as will be evident, finality has not been reachedin a number of instances.Possible reasons for over-estimating ranges ofexistence have already been indicated.Titanium. 73 a-Phase, TiO,, TiO, .oo-TiO,.,, ; p-phase, lower symmetrythan rutile, TiOl.80-TiOl.70 ; y-phase, Ti203, corundum type, TiOl.56-TiO,.,, ; &phase, TYO, NaCl type, Tiol.35-TiOo.6 ; in addition, the metaltakes up about 42 atoms yo of oxygen in interstitial solid s0lution.~4 TheTX phase is of interest as showing how, in'a structure with a very highdegree of Schottky lattice disorder, stoicheiometric variation arises fromthe unbalance of anion and cation holes.--__Composition. Ti01.33. TiOl.12. TiOl.oo. TiOo.6s.Lattice sites occupied : Ti, yo ............74 81 85 960, Yo ............... 98 91 85 66Zirconium. Oxides have not yet been investigated, but the metaltakes up oxygen interstitially to a t least Zr0,.,.75Vanadium. V203, corundum type, extends from VO,.,, to VO,.,approx. ; vG NaCl type, from VO,., to VO,.,, though the range of existenceis much narrower a t low temperatures.',Oxides have very limited ranges of composition (cf. the lessready variability of valency of Nb as compared with V). Nb,O, has aprobable range NbO,.,-NbO,., ; NbO,, NbO (cf. T O and m) no detectableranges, though the NbO structure is of a unique defect lattice type.77Results for chromium oxides are conflicting, and need revision.A. Cameron, E. H. Harbard, and A. King 78 found bivariant equilibria in the6 6 L.H. Bauer and H. Bermann, Amer. Min., 1927, 12, 39; M. J. Buerger, ibid.,1934, 19, 37.8 7 Ref. (9).0 8 R. Vogel and W. Dannohl, Arch. Eisenhiittenw., 1934, 8, 39.69 E. 8. Makarov, Ann. Sect. d'Anal. Phys.-Chim., 1943, 16, No. 1 ; A . , 1943, I, 15.70 G. HZigg and G . Funke, 2. physikal. Chem., 1929, B, 6, 272.7 1 G. Phragmen, J . Iron SteeE Inst., 1926, 114, 397; M. Bamberger, 0. Einerl,72 J. L. Haughton and M. L. Becker, J . Iron Steel Inst., 1930, 121, 315.v 3 P. Ehrlich, 2. Elektrochem., 1939, 45, 362.74 Idem, 2. anorg. Chern., 1941, 247, 53.75 J. H. de Boer and J. Fast, Rec. Trav. chim., 1940, 59, 161.7 6 W. Klemm and L. Grimm, 2. anorg. Chem., 1942,250, 42.7 7 G. Brauer, ibid., 1941, 248, 1.Niobium.and J. Nussbaum, Stahl u.Eisen, 1925, 45, 141ANDERSON : NON-STOICHEIOMETRIC COMPOUNDS. 115ranges Cr01.7-Cr01.9, C~O,.,-CTO,.~, covering the range of complex oxidesreported by earlier workers.79 A. Michel and J. B6nard,so however, donot find these phases, but report that Cr203 has an upper limit of com-position about Cr01.56.Lower oxides of molybdenum have long been a matter of disagreement.According to G . Hagg and A. Magnhli,81 the system is similar to that of thetungsten oxides, with p- and p'-phases, roughly MoO~.,,-MOO~.,, ; y-phaseMoO,.,-MOO~.~, ; &phase MOO,.0. Glemser and H. Sauer 82 find : a-phase W0,-WO,.,,;p-phase W02.,2-W0,.88 ; y-phase W0,.,,-W0,.6, (W,O1,, with X-raydiagram identical with the W,O,, of F. Ebert and H. Flasch); 83 %phaseWO,.O,-WO,.,.Hagg and Magnhli substantially confirm these results.81Closely related are the interesting tungsten bronzes, Na,WO,, etc., of whichthe stoicheiometric compounds (x = 1) apparently do not exist; the cubicsodium bronzes (x = 0.95-0.30) are of defective perowskite type, givingplace (for x = 0.3-0.2) to structures of lower symmetry.84 The tungstenblues, and the hydrogen-containing compounds studied by Ebert andFlasch and by 0. Glemser and H. Sauer 82, 85 appear similar inconstitution.Uranium. It seems clearly established that a t elevated temperaturesstoicheiometric UO, is unstable, and the U,08 phase is of widely variablecomposition.86Manganese. Numerous oxides intermediate between Mn20, and MnO,have been reported, but their individuality is questionable : if they are notmixtures, a non-stoicheiometric phase seems likely.A. Simon and F. Feller 87inferred the existence of such a phase from tensimetric studies, but otherworkers 88 appear agreed that pyrolusite has, at the most, only a smallcomposition range, although it usually contains less oxygen than corre-sponds to MnO,.oo. However, at least three modifications of MnO, appearto e x i ~ t . 8 ~ ~ ~ 0 Wet methods of preparation [e.g., oxidation of Mn(OH), orMnO-OH] can produce hydrous oxides of variable composition (but fewstructural defects) through double substitution of Mn3+ for Mn4+ and OH-7 8 J., 1939, 55; S. S. Bhatnagar, A. Cameron, E. H. Harbard, P. D. Kapur,79 Cf. A. Simon and T. Schmidt, 2. anorg. Chem., 1926, 153, 191.Tungsten.A.King, and B. Prakash, J., 1939, 1433.Bull. Xoc. chim., 1943, 10, 315.Arkiv Kemi M i n . Geol., 1944, 19, A , No. 2; A., 1946, I, 144.82 2. anorg. Chem., 1943, 252, 144.83 Ibid., 1934, 217, 95; 1935, 226, 65.8 p G. Hiigg, Nature, 1935, 135, 874; 2. physikal. Chem., 1935, B, 29, 192.s5 2. anorg. Chem., 1943, 252, 160.8 7 2. Elektrochem., 1932, 38, 137.W. Biltz and €1. Muller, ibid., 1927, 163, 257.M. Le Blanc and G. Wehner, 2. physikal. Chem., 1934, A , 168, 59; C. Druckerand R. Huttner, ibid., 1928, 131, 237; P. Dubois, Ann. Ckirn., 1936, 5, 411.89 P. Dubois, loc. cit., ref. (88); 0. Glemser, Ber., 1939, 72, 1879.90 W. F. Cole, A. D. Wadsley, and A. Wslkley, private communication116 INORGANIC CHEMISTRY.for 02-.90, 91 It is reported that one modification of Mn203 takes up excessoxygen to MnO,.,, a t least.92Iron.Two ranges of non-stoicheiometric oxides are of importance inmetallurgy. (I) R. Schenck and T. DingmannS3 first reported that theFeO (wiistite) phase, stable only above 580", invariably contains a stoicheio-metric excess of oxygen which represents an excess of vacant cation sites.8At 1400" the range of composition extends from FeO,.,, to Fe0,.,9.94Although his interpretation cannot be accepted, the work of J. BBnardS5has shown that in the oxidation of iron a t high temperatures the primaryproduct is the K O phase, with a continuous composition gradient from theiron-rich limit to the oxygen-rich limit. A means is thereby provided fora continuous diffusion of iron through the oxide film to the FeO-02 inter-face, as envisaged by K.F i s ~ h b e c k . ~ ~ (11) G. Haggg7 showed that Fe30,and the y-Fe,03 defective spinel structure represented the limits of onephase of variable composition. At high temperatures, where y-Fe,03 isunstable, the phase relations are still uncertain. R. C. Sosman and J. C.Hostetter9* concluded that a-Fe203 and Fe304 had extended ranges ofexistence towards lower and higher oxygen contents respectively, andJ. C. White g9 appears to confirm this substantially. Later work by Sosmanet d 1 O 0 indicated that neither Fe203 nor Fe,O, was appreciably variable incomposition.Cobalt. M. Le Blanc and E. Mobius lol and M. Watanabe lo2 report thatCOO and Co304 can each take up a substantial stoicheiometric excess ofoxygen.Black NiO was found by M.Le Blanc and H. Sachse lo3 tocontain an excess of oxygen, although a homogeneous phase. Accordingto W. Klemm and E. Haw, stoicheiometric NiO is metastable, breaking upinto NiO,., + Ni.lo4CuO is apparently stoicheiometric, but the much studied semi-conducting properties of Cu,O depend on a small excess of oxygen, whichis present in true equilibrium with the gaseous phase a t high temperatures,as envisaged by theory. Measurements by C. Wagner and H. Hammen lo5give, in equilibrium with 0.7 mm. of 0, at lOOO", C~2Ol.000~2; with 33 mm.Nickel.Copper.of 02, C~201-rn114-91 W. Feitknecht and W. Marti, Helv. Chim. Acta, 1945, 28, 129, 149.92 ( a ) M.'Ulumenthal, Bull. SOC.chim., 1933, 53, 1418; ( b ) C. B. Holtermann, Ann.O3 2. anorg. Chem., 1927, 166, 113.94 L. S. Darken and R. W. Gurry, J . Amer. Chem. Soc., 1945,67, 1398.g5 Ann, Chim., 1939, 12, 5 ; Compt. rend., 1943, 217, 7 7 .9 7 2. pihysikal. Chem., 1935, B , 29, 95.89 Iron and Steel Inst., Carnegie Schol. Mem., 1938, 27, 1.100 Amer. J . Sci., 1935, 30, 239.102 Sci. Rep. Tdhoku, 1934, 23, 89; A., 1934, 699.Io3 2. Elektrochem., 1926, 32, 68, 204.m4 2. anorg. Chem., 1934, 219, 82.Chim., 1940, 14, 121.2. Metallk., 1932, 24, 313; Metallwirts., 1935, 14, 733.98 J . Amer. Chem. SOC., 1916, 38, 807.lol 2. physikal. Chern., 1929, A , 142, 151.lo6 2. phyeikaE, Chem., 1938, B, a, 197ANDERSON : NON-STOICHEIOMETRIC COMPOUNDS. 117Zinc. Although the composition of ZnO is not measurably variable,its semiconducting properties show that the colour change on heating isassociated with a loss of oxygen and the presence of a minute excess ofzinc.lo6 The red ZnO obtained by A.Kutzelnigg lo7 has been shown byA. Greenstone and W. Ehret lo8 to contain up to 0.02% excess of zinc, butmay well be thermodynamically highly unstable. Cadmium oxide probablyhas at least a similar range of composition,10s and the reversible colourchanges of other oxides (In,03, CeO,) can probably be interpreted similarly.Finality as to the oxides of lead has certainly not yet been reached. Pb304seems to be a closely stoicheiometric compound, but M. Le Blanc andE. Eberius concluded that PbO, PbO,, and another intermediate oxidewere all non-stoicheiometric.It now appears ll1 that PbO, has only anarrow range, perhaps from PbO,.,, to PbO,.,; it is probably not obtain-able without constitutional water and the limited stoicheiometric variabilitycould arise from replacement of 202- by 20H-, Pb4+ by Pb2+, in the idealstructure (.cf. MnO,). By degradation of PbO,, or by reaction of PbO withoxygen, two definitely non-stoicheiometric intermediate oxides may beformed, but there is no agreement as t o their nature. Bystrom’s a-PbO,with the range Pb01.,-Pb01.,7 may correspond with the non-stoicheio-metric 112 or stoicheiometric 113 Pb,O, or Pb701, 92b phases of other workers(although there is no agreement as to the symmetry of this phase). Bystrom’sP-PbO, (Pb01.4,-Pb01.,1) probably corresponds to G.L. Clark andR. Rowan’s PbO,. However, the discrepancies between different workersare not to be reconciled.The oxides provide an instructive instance of false conclu-sions drawn from tensimetric measurements, indicative of a phase of con-tinuous composition between Sb203 and Sb,O, 114 and apparently confirmedby X-ray measurernents.ll5 Later work 116 has put a completely differentAntimony.interpretation on the facts, and provides no evidence of stoicheiometricallyvariable antimony oxides.(V) Halides.-The electrical conductivity of cuprous iodide is stronglydependent on the pressure of iodine in equilibrium with the solid compound.This, as first shown by K. Badeker,l17 takes up a stoicheiometric excess of1013 Ref.(38).108 J . Amer. Chern. SOC., 1943, 65, 872.lo* R. Faivre, Ann. Chim., 1944, 19, 58; H. H. v. Baumbach and C. \Va,nner,ll1 A. Bystrom, Arkiv Kemi Min. Qeol., 1945, 20, A , No. 11;112 G. L. Clark and R. Rowan, J . Amer. Chem. SOC., 1941,63, 1305.113 F. Fischer and H. Ploetze, 2. anorg. Chem., 1912, 75, 1.114 A. Simon and E. ThaIer, ibid., 1927, 162, 253.116 U. Dehlinger, 2. physikal. Chem., 1929, B, 6, 127; U. Dehlinger and R. Glocker,116 K. Dihlatrom and A. Westgren, ibicl., 1937, 235, 153; K. Dihlstrom, ibicl., 1938,lL7 Ann. Physik, 1907, 22, 749; 1909, 29, 566; Physikal. Z . , 1908, 9, 431; 1912,1°7 2. anorg. Chem., 1932, 208, 23; 1934, 221, 116.2. physikal. Chem., 1933, B, 22, 199. 110 Ibid., 1932, A , 160, 60.2. anorg. Chem., 1927, 165, 41.239, 51.13, 1080; K. Nagel and C.Wagner, 2. physikal. Chem., 1933, B, 25, 71118 INORGANIC CHEMISTRY,iodine, up to the composition Cu11.M)45. The CUI system is one of the fewfor which ( p , T , X ) equilibrium data can be correlated properly with measure-ments of semiconducting properties.ll8(VI) Ternary Compounds.-Distinction between non-stoicheiometriccompounds and mixed-crystal phases is here more arbitrary, since in additionto subtractive and interstitial types of solid solution, there is the possibilityof " anomalous " solid solutions-also involving the creation of vacantlattice sites or interstitial atoms-f the kind exemplified by the y-A120,-MgA120, phase,28 and the defective fluorite-type solid solutions studied byZintl et al.l19 However, certain classes of ternary compound have beendescribed which are inherently non-stoicheiometric, e.g., the tungstenbronzes already mentioned.84 Sillkn and his co-workers have recentlydescribed a number of double oxides and oxy-halides of bismuth withbivalent metals in which, by variation in the M3' : M2+ cation ratio, either(i) the cation lattice remains complete, but a variable proportion of oxygensites is vacant, or (ii) the anion lattice is perfect, but the number of cationsin the structure is variable. Rational formulz cannot always be assigned to" idealised " compounds.cadmium and the alkaline earths.122 The oxyhalides of bismuth with cal-cium,lZ3 cadmium,124 and other bivalent metals are of type (ii), and exemplifysome very interesting structural principles ; the inherently non-stoicheio-metric phases M~~2-wBil+2z02X3, M112-3zBi3+2z04X5, MI12 -3zBi5+2z06X7(X = C1, Br) have been described.According to C. Brosset,125 potas-sium cryolite, ideally K3A1F5, may vary in composition through replace-ment of AIF,3- groups by CAW5( H20)l2- groups, with corresponding omissionof K+ cations (up to 3%) from the structure. A range of homogeneity hasalso been assigned to the alkali tantalates and niobates.126 It is likelya priori that the ternary sulphides, etc., will be variable in composition, butfew systems have been closely studied. Chalcopyrite appears definitelynon-stoicheiometric, with the limiting composition CuFeS,.,,. 127R6le of Non-stoicheiometric Phases in the Reactions of Solids.-Reactionsbetween solids, or between solid and fluid substances, take place a t theinterface between the reactants.Transport of reactant to this interfacemust take place, in general, by diffusion through the solid product of reac-tion, and this may be the rate-determining process in the reaction. TheOf type (i) are the double oxides iMI12zBi2 - 2z03 ---f2.g., Pb1.2Bi0.802.40 to Pbo.64Bil.3602.68,120 and analOgOUS compounds Of118 R. J. Maurer, J . Chem. Physics, 1945, 13, 321.119 2. anorg. Chem.; 1939, 240, 145, 150; 1939, 242, 79.120 L. G. Sillen and B. Aurivillois, Naturwiss., 1939, 27, 388; 2. Krist., 1939, 101,n1 L. G. Sillen and B. Sill&, 2. physikal. Chem., 1941, B, 49, 27.lZ2 B. Aurivillois, Arkiv Kemi Min.Cfeol., 1943, 16, A , No. 17.lZ3 L. G. Sillen and A. S. Gjorling-Husberg, 2. anorg. Chem., 1941, 248, 121, 135.lZ4 L. G . Sill&, ibid., 1941, 248, 331.125 A ~ k i v Kcini Min. Geol., 1946, 21, A , No. 9.lZ6 F. Halla, A. Neth, and F. Windmaisser, 2. Krist., 1942, 104, 161.127 H. E. Merwin and R. H. Lombard, Econ. Geol., 1937, 32. 203.483ANDERSON : NON-STOICHEIOMETRIC COMPOUNDS. 119mechanism of diffusion, and of ionic conduction, in polar solids can beinterpreted in terms of the presence and migration of lattice defects,33 anddeparture from stoicheiometry, by controlling the concentration of inter-stitial ions or vacant sites, affects the diffusion coefficient D. This appliesboth to ionic conductivity or diffusion along a concentration gradient andto self-diffusion, 128 as has recently been shown e~perimentally.~~~ Whereonly one ion (most frequently the cation) is mobile, D is a minimum for thestoicheiometric crystal, in the case of a crystal with Frenkel defects, orincreases monotonically with stoicheiometric excess of non-metal for thecase of Schottky defects.I n reactions, stoicheiometric variations enable acomposition gradient to be set up through the layer of reaction product.C. Wagner 130 has derived a quantitative theory for " tarnish " reactions,which proceed by continuous migration of cations t o the solid-gas interface[cf. ref. (96)], and has extended it to include reactions between solids-e.g.,double salt, spinel, and silicate f0rmati0n.l~~ The acceleration of suchprocesses by conditions producing small deviations from stoicheiometry hasbeen demonstrated for the formation of MgA1204.132 Both Al,O, and MgOare metal-excess conductors a t high temperatures, and their union proceedsmarkedly faster in vacuum or in hydrogen than in air.Such factors mayhave considerable significance in ceramic processes.133There is some evidence that non-stoicheiometric phases can be formedunder non-equilibrium conditions, as intermediate stages in the formationor dissociation of solid compounds. For instance, brucite formed by slowoxidation of magnesium in moist oxygen,lM or partially dissociated silveroxide 135 is stated to contain an excess of metal. Analogous cases are onrecord. lo7$ l36In a broad sense, the non-stoicheiometric character of a solid may beassociated with the mechanism of catalysis in heterogeneous reactions.Thus, C.Wagner and K. Hauffe 137 have deduced the rate-determining stepin the nickel-oxide-catalysed reactions 2CO + 0, = 2CO,, 2N,O = 2N2 + O,,from the composition of the oxide catalyst (as shown by its electronic con-ductivity) in the stationary state. Similar observations have been madefor the H, + S + H2S reaction catalysed by silver suiphide,138 andthe mechanism of the catalysed water-gas reaction 139 and the ammonia128 C. Wagner, 2. physikal. Chem., 1931, Bodenstein Festb., 177.12@ J. S. Anderson and J. R. Richards, J., 1946, 537.l30 Z.physika1. Chem., 1933, B, 21,25; 1936, B,32,447; Angew. Chem., 1936,49,735.131 C. Wagner, 2.physikal. Chem., 1936, B, 34, 309, 317.132 H. C. Castel, S. Dilnot and M. Warrington, Nature, 1944, 153, 653.133 Cf. J. A. Hedvall, Die Chemie, 1942, 55, 334; Trans. Chalmers Uniu. Technology,134 R. Faivre and A. Michel, Compt. rend., 1939, 208, 1008.135 R. Faivre, ibid., 1940, 210, 398.136 E. I. Mokeeva and N. I. Mokeeva, J . Physical Chem. RUSS., 1941, 15, 686.137 2. Electrochem., 1938, 44, 172.138 H. Reinhold, W. Appel, and P. Frisch, 2. physikal. Chem., 1939, A , 184, 273.13* E. Doehlmann, 2. Elektrochem., 1938, 44, 178.Goteborg, 1942, No. 15120 INORGANIC CHEMISTRY.synthesis have been discussed from a similar standpoint. A further influenceupon the surface properties of solids is shown by the dependence of adsorptiveproperties of metallic sulphides upon small variations of stoicheiometriccomposition.140J.S. A.2. COMPLEX COMPOUNDS OF THE PLATINUM METALS.it was observed that platinum metal complexes have recentlyreceived special attention particularly by Russian workers, but it wasfound necessary to defer discussion of their work to a later report, and itis this work which forms the bulk of the present review.In 1944Platinum.OZe$n Complexes.-The complexes formed by metallic salts and olefinswere discovered before 1830 but no satisfactory structure has yet beenassigned to them. Since the last review of this subject in 1936 a com-prehensive account of these compounds by R. N. Keller and a considerablevolume of work by Hel’man and his co-workers have been published.Platinum salts form the best-known and most stable complexes, so workhas been limited almost entirely to the platinum series.Palladium com-plexes are less stable and recent attempts to obtain cobalt and nickel com-plexes were unsucce~sful.~ Typical members of the series are K[Pt C2H4 GI3],[(Pt C,H4 Cl,),], [Pt C,H, py CI,] and the most recently added member[Pt C2H4 NH, py C1]N0,.5 The anionic complex is very much more stablethan the cationic complex, and attempts to obtain two mono-olefins attachedto one platinum atom have so far failed.6, l 6Unsaturated molecules behave similarly to ammonia and occupy onlyone co-ordination place round the platinum atom, but they differ fromammonia and pyridine in their directing influence on substituents enteringa complex which already contains an olefin.They labilise the group inthe trans-position so that, in preference to the cis-groups, it is replaced bythe entering substituent. This difference is illustrated by comparing thereactions (A) and (B) with the analogous reactions (C) and (D).’, *Whilst the products (I) and (11) are identical, but different from Jor-gensen’s [Pt(NH,) py Cl,], products (111) and (IV) are isomeric. (Ij, (11),and (111) are claimed to be cis-isomers, but (IV) is claimed to be the truns-l40 J. A. Hedvall and S . Nord, 2. Elektrochem., 1943, 49, 467.1 Ann. Reports, 1944, 41, 98. a W. C. Zeise, Mag. Pharm., 1830, 35, 105.Chern. Reviews, 1941, 28, 229.A. D. Hel’man and I. B. Litvak, Ann. Secteur phtine, Inst. chim. gin.(U.S.S.R.),ti A. D. Hel’man and E. A. Meilakh, Compt. rend. Acad. Sci. U.R.S.S., 1946,51, 207.’ I. I. Chernyaev and A. D. Hel’man, Ann. Secteurplatine, I n s t . chim. ge’n. (U.S.S.H.),1039, 16, 29.A. D. Hel’man, ibid., 1939, 23, 532.1935, 15, 5.A. D. Hel’man, Compt. rend. Acad. Sci. U.R.S.S., 1939, 22, 107.S. M. Jorgensen, J . pr. Chem., 1886, 33, 489CHATT: COMl’LEX COMPOUNDS OF THE PLATINUM METALS. 121isomer, and the analogously prepared pyridine complex [Pt(C,H,) py Cl,]reacts with pyridine to give trans-[Pt py2 C1,].lo(B) K[Pt py + NH3 = [Pt py (NH3) C121 + KCl(11.)(c) K[Pt(NH3)C&] + c2H4 = [Pt(NH3)(C,H&C&I KC1(111.)(N.)(D) qPt(C2H4)C13] -k NH3 = [Pt(C2H&(NH3)C1,] + KC1Reactions (C) and (D) have been shown to be general and have beenapplied to obtain similar isomers containing other olefins and carbon mon-further adaption isomers containing four different groups attached to theplatinum atom have been obtained, e.g., [Pt(C2H,)(P\TH3)C1Br].13It was shown by J.S. Anderson 14* 15 that the stability of the ethylenecomplexes of PtCl, was altered markedly by substitution of other univalentradicals in place of chlorine and also by substitution in the ethylene moleculeitself. This work has been repeated and extended by Russian workers,who have found that the amine substituent in [Pt(C,H,) am Cl,] causes adecrease of stability in the order : lo am = quinoline > pyridine > am-monia > thiourea. They confirm that the stability decreases as chlorineis replaced in the order : C1 > Br > I > NO, > CNS > CN, but differfrom Anderson in placing styrene higher than ethylene in the stability ofits complexes.They find the following order of stabilities : l 6 ~ l7 NO >CO > styrene > butadiene - C,H, > C3H6 - C,H,.This work is somewhat qualitative as no allowance is made for therelative volatilities and solubilities of the various olefins. The replacementsof unsaturated molecules were effected by reaction of the appropriateunsaturated substance Un with a dilute acid solution of the salt K[PtUn’C13],then trying the reverse replacement Un‘ into K[PtUnCl,]. Sometimes i twas found that both replacements occurred, e.g., with propylene andbutylene.Besides the above series of stabilities two interesting facts emerged ;when attempts were made to replace CO by NO in py H[Pt(CO)Cl,] in veryacid solution by passing NO through it for two months, the platinum wasoxidised and (py H),[PtC16] was isolated ; and also the reaction of ethylenewith the [PtCl,]“ ion in dilute acid solution is catalysed by propylene.1710 I.I. Chernyaev and A. D. Hel’man, Ann. Secfeur platine, Inst. chim. gdn. (U.S.S.H.),1937, 14, 77.11 A. D. Hel’man, Con@. rend. Acad. Sci. U.R.S.S., 1937, 16, 351.l2 A. D. Hel’man and M. Bauman, ibid., 1938, 18, 645.l3 A. D. Hel’man, ibid., 1943, 38, 310.l8 A. D. Hel’man, Compt. rend. Acad. Sci. U.R.S.X., 1041, 32, 347.17 A. D. Hel’man, ibid., 1938, 20, 307.oxide instead of ethylene as well as bromine instead of chlorine.l’, l2 BYl4 J., 1934, 971.15 J., 1936, 1042122 INORGANIC CHEMISTRY.By passage of a mixture of propylene and ethylene into an acid solution ofpotassium chloroplatinite for four days, a 52% yield of Zeise’s salt free fromthe propylene salt was obtained, whereas pure ethylene in the same timewould have given only a 15:L yield. It is suggested that the greatersolubility of propylene leads to a more rapid reaction with the [PtCl,]- ion,yielding [Pt (C,H,)Cl,]- as intermediate from which the propylene is rapidlyevicted by the ethylene.It is interesting that, although CO readily replaces all the olefins fromions of the type [Pt Un Cl,]-, the [Pt(CO)Cl,]- ion produced is comparativelyunstable, being decomposed by water except in strongly acid solution.Onthe other hand, the NO complexes are exceptionally stable, yet NO replacesthe olefins only very slowly.It appears that the diolefins, butadiene and diallyl, do not form chelatecomplexes but each double bond reacts with a different platinum atom.6316Attempts to obtain chelate compounds by using ethylenediamine ledto no greater success : l82K[Pt(C,H4 )C&I + C2H4(NH2 )2 [{ (C2H4 )PtC12 ,NHz*CHz*}2]The structure of these complex compounds remains unsolved.* Hel’man 19has suggested that the ethylene molecule undergoes an electromeric changein the presence of the platinum-containing ion, and the carbon atom with adeficiency of electrons accepts two electrons from the platinum atom, pre-sumably from a 5d orbital, thus raising the platinum to the platinic state.The other carbon atom now donates its electrons to the platinum atom,forming a four-electron bond between the ethylene molecule and the platinumatom.In support of this the electrometric titrations of K[Pt(NH,)Cl,],NH, [ Pt ( C2H4) Cl,] , K2 [ Pt C1, ( C4H6) Pt Cl,] , and NH,[Pt (NH,) C1 5] were com -pared in acid solution using 0-1x-permanganate to effect the oxidation.Oxidation occurred only when K[Pt(NH,)Cl,] was titrated ; 2o also theinitial potential of the solution of K[Pt(C,H,)Cl,] was 650 mv., and of theabove butadiene analogue 700 mv. as compared with 660 mv. forNH,[Pt(NH,)Cl,] and 520 mv. for NH,[Pt(NH,)Cl,]. These results supportthe suggestion that platinum in the olefin complexes is in the platinic state,but this point deserves further investigation for it would appear that we18 Doklady Akad.Nauk. S.S.S.R., 1943, 38, 272.19 A. D. Hel’man, Compt. rend. Acad. Sci. U.R.X.S., 1939, 24, 549.20 A. D. Hel’man and D. I. Ryabchikov, ibid., 1941, 33, 462.* Since this report was completed, A. D. Walsh (Nature, 1947, 159, 165; J . , 1947,89) has pointed out that the ionisation potential of the ?T electrons of ethylene is 10.45 v.as against 10.8 v. for the lone pair electrons of ammonia and suggested that the n elec-trons should be capable of donation to suitable atoms or groups thus binding togetherthree nuclei. This view is closely allied to that of Winstein and Lucas ( J . Amer. Chem.SOC., 1938, 80, 836) who proposed a resonance of the three structures:>c=c<Ag +after their study of the silver ion complexesCHATT : COMPLEX COMPOUNDS OF THE PLATINUM METALS.123have the unusual and somewhat loose combination of two reducing sub-stances to yield a product resistant to oxidation by permanganate.Bokii 21, 22, 23 has attempted to obtain the structure ofcis-[Pt (NH3)(CzH4)Cl2]by X-ray methods and claims that the substance is dimeric, with a Pt-Ptbond of length 1.4 A. Each platinum atom is surrounded in a distortedoctahedron by the other platinum atom, two carbon atoms, two chlorineatoms, and a nitrogen atom. Again i t would appear that the platinum isin the platinic state, but it must be remembered that the weight of previouschemical evidence has pointed to the platinum being in the bivalentstate.Acetylene compounds analogous to the ethylene complexes have notbeen obtained, and attempts lead only to brownish intractable substances.However, the substituted acetylene CMe,(OH)*CIC*CMe,( OH) ( = Un) hasyielded a compound [PtUn py Cl,] similar to the corresponding trans-ethylene complex.24Aminopyridine Complexes.-As might be expected from its stereo-chemistry, 2-aminopyridine (apy) does not form chelate compounds withplatinous chloride,25, 26 but the compounds formed [apy2PtCl,] and[apy4Pt]C1, are more stable than the corresponding pyridine or ammoniaderivatives.The former, obtained by direct action of 2-aminopyridine onpotassium chloroplatinate, has been asigned a cis-configuration, which isto be expected, and to account for its greater stability, A.M. Rubinshtein 27suggests that the co-ordination takes place through the tertiary nitrogenatom whilst the amino-hydrogen atoms take part in hydrogen-bond form-ation with the adjacent chlorine atoms. More highly substituted pyridines,e.g., 5-iodo-2-aminopyridineY react directly with potassium chloroplatinite toyield, in this case, truns-[iapy,PtCl,], probably because steric hindranceprevents formation of the cis-compound. The iodoaminopyridine is readilyreplaced by pyridine to yield trans-[py,PtCl,] .28, 29Thiosulphate Complexes.-Surprisingly little research into platinumthiosulphate complexes had been done until D. I. Ryabchikov 30 started avery thorough study of them in 1938 and found that the thiosulphate ionis co-ordinated very strongly to PtII.Previously, P. Shottlander 31 hadobtained Na6[Pt(S20,)4],10H,0 by action of excess of sodium thiosulphateZ1 G. B. Bokii and E. E. Baishteii, Doklady Akad. Nauk. S.S.S.R., 1943, 38, 323.22 G. B. Bokii and E. E. Vainshtein, Compt. rend. Acad. Sci. U.R.S.S., 1943,38, 307.zs G. B. Bokii, N. I. Usikov, and G. L. Trusevich, Bull. Acad. Sci. U.R.S.S., Classe24 A. D. Herman, S. Bukhovetz, and E. Meilakh, Compt. rend. Acad. Sci. U.R.S.S.,25 A. M. Rubinshtein, ibid., 1938, 20, 575.2 G A. M. Rubinshtein, Bull. Acad. Sci. U.R.S.S., Classe sci. chim., 1944, 42.27 Compt. rend. Acad. Sci. U.R.S.S., 1944, 43, 59.2 8 A. M. Rubinshtein, Bull. Acad. Sci. U.R.S.S., Classe sci. chim., 1944, 216.29 A. M. Rubinshtein, Compt.rend. Acad. Sci. U.R.S.S., 1944, 44, 277.30 Ibid., 1938, 18, 39.sci. chim., 1942, 413.1945, 46, 105.31 Annalen, 1866, 140, 200124 YXOBQANIU OHElKCSTRY.on potassium chloroplatinite, but the co-ordinating a M t y of the thio-sulphate radical is such that the halogen atoms of the [PtCI,]= ion can bereplaced two a t a time by action of sodium thiosulphate in theoreticalproportions,32 yielding the ions [Pt(S,O,)CI,]', [Pt(S,O,),]=, [Pt(S,03),]4-,and finally [Pt(S203)4]6-. These complexes are very stable; even hothydrochloric acid fails to produce elementary sulphur or other appreciablechange in them and the thiosulphate ion occupies either one or two co-ordination places.The extraordinary co-ordinating affinity of the thiosulphate ion isstrikingly illustrated by the action of sodium thiosulphate on [Pt (NH3),]C1,.33Normally, the replacement of the ammonia molecules by acid radicalsrequires an excess of reagent and does not proceed easily, but thiosulphatein theoretical quantity reacts in hot solution with evolution of ammonia toproduce [Pt(NH,),S,O,] or trans-Na,[Pt(NH,),(S,03),],6H20 according tothe proportions of the reagents, and excess of thiosulphate yieldsNa2[Pt(S203)4].Even thiourea is completely evicted from [Pt(CS(NH,),},]+fby excess of tliiosulphate.Particular interest attaches to the ion [Pt(S,O,),]= which has beenobtained in cis- and trans-form~,~~ an isomerism very common amongst thecationic and neutral platinous complexes but very rarely observed in anioniccomplexes.The two ions are produced together when the chloroplatiniteand thiosulphate (1-8 mols.) react in aqueous solution, and are readilyseparated by the great difference in solubility of their potassium salts.Ethylenediamine reacts differently with the two salts, and on the basisthat oxygen co-ordination places are attacked in preference to sulphur,the isomers have been orientated by the following reactions : 34Soluble isomer.,Sparingly soluble isomer.Hence the soluble isomer is cis-, and the less soluble is trans-.Ryabchikov also finds that the group trans- to the sulphur atom in thethiosulphate complexes is labilised in the same way as it is by thiourea.This fact strengthens his argument regarding the orientation of [Pt (S,03),]=and is well illustrated by comparison of the reaction between thiosulphateand cis- and trans-[Pt(NH,)2C12],35 which he has suggested as useful todistinguish cis- and truns-isomers of platinum diammines.36 Both isomers32 D.I. Ryabchikov, Conzpt. rend. Acad. S c i . U.R.S.S., 1940, 27, 349.33 Idem, ibid., p . 690. a4 Idem, ibid., 1943, 41, 208.36 Idern, ibid., 1940,28, 231. 36 Idem, ibid., 1941, 32, 344OHATT: UOMPLEX UOMPOUWDS 03 THE PLATINUM METALS. 125react with one molecule of thiosulphate to give sparingly soluble precipitatesbut these have different metal contents.cis-[(NH,),PtX,] + Na,S,O, 4 [(NH3)2 Pt S,O,] J.The labilising influence of the thiosulphate radical causes the X radicalin the trans-position in the unstable intermediate to be replaced by a watermolecule.Two molecules of sodium thiosulphate substitute both acid radicals inboth isomers, but the products (V) and (VI) differ markedly in their stabilitytowards excess thiosulphate, for, whilst (V), having both ammonia moleculeslabilised by trans-thiosulphate radicals, reacts with any slight excess of(V.) (VI.) (VII.)thiosulphate, yet (VI) is stable to 2 4 molecules excess of thiosulphate.Even the acid (VII), prepared from the barium salt by means of sulphuricacid, is stable in aqueous solution and is a strong acid.37 Larger excess ofthiosulphate replaces all the ammonia from both isomers.The converse eviction of thiosulphate ions by amines is p0ssible,~8 buteven thiourea in hot aqueous solution can replace only three thiosulphateradicals from K,[Pt(S,O,),] to give [Pt{CS(NH,),),S,O,]. Ammonia re-places only two to yield cis-K,[ (NH3),Pt(S203),], and ethylenediaminebehaves similarly, whereas pyridine, presumably through the intermediateformation of cis-K,[py,Pt(S,O,),], removes two thiosulphate ions, butbecause of the labilising effect of the trans-thiosulphate ions, the pyridine islost and the final product is K,[Pt(S,O,),] ; trans-K,[py,Pt(S,03),] is, ofcourse, quite stable.33Thiosulphate complexes of quadrivalent platinum could not be obtainedeither directly39 or by oxidation of the platinous c0mplexes.4~ In theformer case the platinum was reduced to the bivalent state by the thio-sulphate, and in the latter the oxidation occurred in three stages, the firstof which was oxidation of the thiosulphate with deposition of elementarysulphur.Palladium forms similar thiosulphate complexe~,*~ but as would be37 D.I. Ryabchikov, Compt. rend. Acad. Sci. U.R.S.S., 1940, 28, 236.Idem, ibid,, 1943, 40, 229.40 Idem, ibid., 1941, 33, 233.D. I. Ryabchikov end A. P. Imkova, Dokludg dead. Nauk. S.S.S.B., 1943, 41,The platinum salt was then oxidised and finally the sulphur.Idem, ibid., 1944,42, 178169126 INORGANIC OHEMISTRY.expected no isomerism was observed, and the equimolecular reaction ofthiosulphate and palladochloride produced PdS and PdS,O, but notNa,[Pd(S,O,)Cl,], which is in keeping with the lower stability of palladiumcomplexes usually observed.Hydroxylamine Complexes.-The lower stability of palladium complexesis well illustrated by the reaction of halogen acids with [Pt(NH,*OH)4](OH)2and its palladium analogue described by Goremykin and his co-workers intheir comparative study of these complexes.42~ 43Products from-Acid. [Pt(NHz'OH)4] (OH) 2.[P~(NH,*OH)~I(OH)Z.~ ~ ~ ~ ~ H " : : ~ ~ ~ ~ ~ ~ ~ ~ ~ HF [ P ~ ( N H z . O H ) ~ I ( ~ ~ Z ) ZHCl [Pt(NH,*OH)4]Cl,HBr [Pt(NH,-OH)4]Br, + [Pt(NH,*OH),Br,] [Pd(NH,*OH),Br,]HI [Pt(NH,*OH)4]12 + [Pt(NH,*OH),I,] PdI,Direct oxidation of the platinous hydroxylamine complexes by chlorineor bromine does not yield the platinic complexes, the hydroxylamine beingoxidised in preference to the platinum,44 but they have been prepared in avery interesting way.45¶ 46When a [Pt(NH,*OH),]++ salt is heated on a water-bath with 2 0 4 8 %hydrobromic acid the platinum is oxidised, presumably by the hydroxyl-amine liberated from the complex, and bright orange insoluble derivativesof PtIV can be isolated, e.g., [Pt(NH,*OH),Br,].Starting from mixed cis-tetramines, e.g., [Pt(NH,*OH),py,]++, mixed derivatives of type[Pt(NH2*OH) PY Br4Iare obtained.Unlike the platinous hydroxylamine complexes, the platinic complexesdecompose without explosion when they are heated, and also the hydroxyl-&mine can be replaced by pyridine. In the latter reaction the liberatedhydroxylamine reduces the platinum to the bivalent state again.Iridium.S'ulphito-compZexes.-Lebedinsky and Gurin have made a study ofchlorosulphitoiridites and aminosulphitoiridites in which iridium is tervalent.By heating sodium chloroiridite with an excess of sodium bisulphite threechlorosulphitoiridites are obtained according to the time of reaction.47 Ifthe heating is stopped when the olive-green solution has become light red,yellow Na,Ir(S0,),Cl2,7H,O crystallises out together with redNa,Ir(S0,),C14,7H,0.If the reaction is continued until the solution is dark red then only thered salt crystallises out and the yellow salt appears slowly from the42 v, I.Goremykin, Compt. rend. Acad. Sci. U.R.S.S., 1938, 18, 341.43 Idem, ibid., 1941, 32, 633.4 4 Idem, Bull. Acad. Sci. U.R.S.S., Classe sci. chim., 1944, 185.45 V. I. Goremykin and K. A. Gladyshevskaya, ibid., 1943, 108.4 6 Idem, ibid., p. 338.4 7 V. V. Lebedinsky and M.M. Gurin, Compt. rend. Acad. Sci. U.R.S.S., 1942,86, 22c u m : COMPLEX COMPOUNDS OF THE PLATINUM METALS. 127cold mother-liquor, whereas if the mother-liquor is evaporated by boiling,yellow Na,Ir( S03),C1,,5H,0 separates from the hot solution.48 This penta-hydrate retains one molecule of water up to 170°, whereas the heptahydrateloses all its water at loo", but both salts yield Na,Ir(S03)3(NH3)3,7H,0with ammonia.Conductivity measurements indicate that this ammine is only tri-ionicand it is considered that one of the sodium atoms is covalently linked inthe complex.49 By double decomposition with a zinc salt only two sodiumatoms are replaced by zinc.The parent salt Na,Ir(S03),C1,,5H,0 is also unusual in its reaction withdilute acid, which replaces two sodium atoms to yield a non-acidic crystallinesubstance Na5H,Ir(S0,),C1,,10H,0.This has a very poor conductivity 48and must have the hydrogen atoms and perhaps some sodium in the com-plex ion. The hydrogen atoms can be replaced by bases to produce againa neutral salt, and it seems probable that the above compounds are morecomplex than the simple formuh would indicate.One of thechlorine atoms is remarkably labile, conductivity measurements indicatedissociation into more than six ions at temperatures of over about 30°, andeven in the cold rubidium chloride reacts to yield NaRb3[Ir(S03)2C13],6H20.47The ammonium and potassium salts of the above chlorosulphitoiriditescould not be obtained,48 the tendency being to obtain salts of the ion[Ir(S0,),C13]4- which seems to be identical with that originally describedby C.Claus 50 in the salt K4[Ir(S03),C13],6H20.The prolonged action of large excess of ammonium bisulphite on am-monium chloroiridite did not replace all the chlorine atoms, but a new salt(NH4),[Ir(S0,),C1,], which could readily be converted into the sodium orpotassium salt by the alkali hydroxide, was formed.51Although suggestions have been made regarding the configurations ofmost of the compounds studied, it was not possible to assign a configurationto any of them with certainty.Organic Arsine CompZexes.-Continuing their investigation of the com-pounds formed by the platinum metals in their lower valency states,F. P. Dwyer and R. S. Nyholm have prepared a number of complexesof iridium dichloride and trichloride with aryldialkyl- and diarylalkyl-ar~ines.~,, 53 These are consistent with six-fold co-ordination of iridium inboth valency states.The simpler complexes [IrC1,,3AsPh2Me] (VIII),[IrC12,4AsPh,Me] (IX), and [IrC13,3AsPh2Me] (X) are all less stable thanthe corresponding rhodium compounds 54 and smell of the free arsine. Thehalogen, on the other hand, is strongly bound and not readily removedeven by silver nitrate. The compounds of type (IX) are not well defined48 V. V. Lebedinsky andM. M. Gurin, Compt. rend. Acad. Sci. U.R.S.S., 1943,38, 128.Qg Idem, ibid., 1941, 33, 241.61 M. M. Gurin, Compt. rend. Acad. Sci. U.R.S.S., 1944, 44, 100.62 J . Proc. Roy. SOC. N.S.W., 1944, 77, 116.64 Ann.Repork, 1944, 41, 101.NaSIr(S0,),C1,,7H,0 also shows unexpected properties.6o J . p r . Chem., 1817, 42, 348.63 Ibid., 1946, 79, 121128 IN0IK)BNIO (YHEMISTRY.and emit a strong odour of the fiee arsine; they are transformed into (VIII)by shaking with light petroleum. Compounds (VIII) and (IX) were theonly complexes obtainable from iridium dihalides and diphenylmethyl-arsine. They were prepared by reduction of the tervalent iridium com-plexes in presence of different quantities of the arsine with hypophosphorousacid in acid aqueous-alcoholic solu-( AsPh ,Me),XIr ‘IrX( AsPh,Me), tion. The complexes of type (VIII)were well defined and have beenassigned a bridged structure (XI), buteven in freezing benzene solution they are highly dissociated.The simple complex (X) is obtained by direct action of the arsine onthe halide IrX, in weakly acid aqueous-alcoholic solution.In boilingstrongly acid solution, however, a number of unexpected and interestingreactions occur.Iridium trichloride yields a yellow, slightly soluble compound isomericwith (X), probably [IrC1,,4AsPh,Me][IrC14,2AsPh,Me] (XII), and from themother-liquor from which this compound has separated an acidH[IrC14,2AsPh,Me] (XIII) can be isolated. It is acid to litmus and givespink ammonium and pyridinium salts but is insoluble in sodium hydroxidesolution.The analogous reaction in the bromine series yields the analogue of(XIII) but not of (XII); however, a complex containing bivalent iridiumis precipitated, viz., [IrBr2,2AsPh,Me].This reduction is unexpected and isprobably facilitated by the low solubility of the complex formed. A similarreduction does not occur in the iodine series except with aryldialkylarsines,but the iodides are quite soluble, and it appears that the instability of theiridium complexes is also important in helping this reduction which doesnot occur in the rhodium series although RhIII is generally easier to reducethan I+.X‘Xfl(XI.)Rhodium.Dimethylglyoxime Complexes .-In their search for square complexes ofhodium, F. P. Dwyer and R. S. Nyholm have prepared dimethylglyoximecomplexes of bi- and ter-valent s6 With dimethylglyoxime,rhodic chloride readily yields a sparingly soluble substance, all the propertiesof which are consistent with the structure (XIV).0- N N 4 Q ! IH I ‘ H Cl----Rh--Cl dl $/s b J .Proc. Roy. SOC. N.S.W., 1946,H,C-CH,I II H(XV.)78, 266. 66 Idem, aid., 1946, 79, 126WELCH : INORGANIC CHEMISTRY OF METALLURGICAL PROCESSES. 1%The complex is a strong acid of pronounced monobasic character. Itforms stable soluble salts and the halogen atoms cannot be removed evenby boiling silver nitrate or chelating acid groups. The silver salt is insolublein water but soluble in dilute nitric acid. The chlorine atoms are almostcertainly in the trans-position, particularly as the dimethylglyoxime canbe reversibly replaced by ethyleneiminebis-salicylaldehyde to yield a com-plex (XV) which must have the nitrogen and oxygen atoms in one plane.This latter complex also yields a violet sodium salt which would indicatebenzenoid-quinonoid resonance of the ion.The rhodic complex Rh(C,H,N,O,), was ultimately prepared in pooryield as an insoluble powder from rhodic sulphate.It dissolved in hydro-chloric acid to give a reddish solution, possibly of the cis-form of (XIV),which lightened in colour and finally deposited the stable trans-isomerPure rhodous complexes were not isolated, although evidence for theirformation by reduction of compound (XIV) with sodium formate wasfound.Continuing his study of the polarographic reduction of the platinummetal complexes, J. B. Willis 57 finds that, of the metals ruthenium, osmium,iridium, palladium, and platinum, only palladium complexes give a satis-factory polarographic step.This corresponds to the reduction of PdII toPd, and the half-wave potential of the ammino-complexes of palladiumbecomes more negative with increasing basic strength of the amine whilstthe reduction also becomes less reversible.Finally, attention should be directed to an excellent review of thestereochemistry of square complexes by D. P. M e l l ~ r . ~ ~(XIV).J. C.3. THE INORGANIC CHEMISTRY OF SOME METALLURGICAL PROCESSES.The enforced development of special metallurgical processes during waryears has necessarily involved new advances in, and applications of,fundamental inorganic chemistry, and several of these appear to merit reviewin these Reports. The topics selected for discussion are the extraction ofmagnesium (particularly from sea water) , the production of highly electro-positive metals by thermal reduction processes, the extraction of alumina andaluminium from clay, and the extraction chemistry of beryllium andzirconium.Magnesium from Sea Water.-The most successful of the commercialsea water processes is the Dow process, operated on a very large scale a tVelasco, Texas.l Here the filtered sea water (containing about 0.13% ofmagnesium) is treated with a controlled excess of calcium hydroxide (pre-pared by slaking lime obtained by calcining oyster shells), and magnesiumhydroxide is precipitated; by thickening the hydroxide is obtained as aW.P. Schambra, Trans. Amer. Inst. Chem. Eng., 1945, 41, 35; C. M. Shigley,57 J . Arner. Chem. Soc., 1945, 67, 547.5 8 Chene. Reviews, 1943, 33, 137.Amer. Inst. Min. Met. Eng., Tech. Publ. No. 1845 (1945).REP.-VOL. XLIII. 130 INORGANIC CHEMISTRY.slurry containing 12% of Mg(OH),. After filtration, the filter cake [25%Mg(OH),] is treated with hydrochloric acid solution containing a littlesulphuric acid (to aid precipitation of calcium as sulphate), and the resultingcrude 15 yo magnesium chloride solution is concentrated by submergedcombustion of natural gas, a controlled gas-air mixture being burned underthe liquid surface. This direct heating is necessary because calcium sulphatewould cause serious scaling of any ordinary form of evaporator. Afterevaporative cooling under vacuum, a 35% magnesium chloride solution isobtained ; a calculated quantity of magnesium sulphate, sufficient to pre-cipitate the unwanted calcium, is added, and the solution allowed to stand.Filtration from precipitated sodium chloride and calcium sulphate then givesa magnesium chloride solution of high purity, from which a solid salt of theapproximate composition MgC12,1-5H20 is obtained by a two-stage evapor-ation process.This salt is suitable for direct feed to the electrolytic mag-nesium cells, in which the electrolyte consists of molten magnesium, calcium,and sodium chlorides at 700-750°.2 The chlorine evolved at the cell anodesis converted into hydrochloric acid (for re-use in the process) by reaction withsteam and natural gas. The molten magnesium is ladled from the cells andcast into ingots of purity at least 99-9%.An interesting variant of the Dow process uses calcined and slaked dolo-mite (comprising a mixture of magnesium and calcium hydroxides) insteadof slaked lime in the initial treatment of the sea water; the magnesiumcontent of the dolomite is then retained with the hydroxide precipitatedfrom the sea water, and the process affords an economic means of utilisingboth sources of magne~ium.~The success of these processes is basically dependent on the very lowsolubility of magnesium hydroxide, which permits its precipitation fromextremely dilute solutions of magnesium salts.Although the engineeringproblems involved in the treatment of large volumes of sea water are con-siderable, and each stage of the process requires careful control, both methodshave been successfully applied.Magnesium from Dolomite and Silicate Minerals.-The abundance ofdolomite (MgCO,,CaCOJ in nature immediately suggests that its use as asource of magnesium should be economic, but the difficulty of separatingmagnesium from large amounts of calcium is considerable.The use ofdolomite in conjunction with sea water has been outlined above; anothertypical dolomite process has been described re~ently.~ The dolomite is firstcalcined and slaked with water to give a mixture of calcium and magnesiumhydroxides, which is boiled with ammonium chloride solution ; calcium thengoes into solution as the chloride, whereas magnesium hydroxide remainssubstantially unaffected : Mg(OH), + Ca(OH), + 2NH4C1 + Mg(OH), +CaC1, + ZNH, + 2H,O.The magnesium hydroxide may be separated by2 R. M. Hunter, Trans. Electrochem. SOC., 144, 86, Preprht 30, 343.4 J. M. Avery and R. I?. Evans, Amer. Inst. Min. Met. Eng., Tech. Publ. No. 1829See P. L. Teed, Bull. Inst. Min. Met., 1946, No. 479, 25.( 1945)WELCH : INORGANIC UHEWSTRY OF METALLURGICAL PROCESSES. 131thickening and filtration and converted into oxide by ignition,or the slurry fromthe previous stage may be treated directly with carbon dioxide to precipitatecalcium carbonate and leave magnesium chloride in solution : Mg(OH), +CaC1, + CO, + MgC1, + CaCO, + H,O. Purified magnesium chloridemay then be obtained from the solution by methods similar to those used inthe Dow process. Economic application of the process just described isensured by linking it with the ammonia-soda process, so that the reaction ofammonium chloride with slaked dolomite calcine provides the necessarymeans of recycling ammonia gas.Olivine, (Mg,Fe),SiO,, and other silicate minerals of magnesium are anattractive source of the metal in some localities.Such minerals are con-veniently attacked by hydrochloric acid, which extracts magnesium and ironas chlorides and leaves the silica substantially insoluble; the use of 20%acid at 90-110" ensures separation of silica in a form that settles well onstanding. Impurities in the acid extract (mainly iron) are precipitated ashydrated oxides by adding the requisite quantity of magnesia, either as suchor in the form of a sludge from electrolytic magnesium cells, containingmagnesium chloride and oxide.Magnesium chloride of sufficient purity forcell-feed is obtained from the solution by evaporation.Eledropositive Metuls by Thermal Reduction.-Until quite recently thedifficulty of reducing oxides or salts of metals such as magnesium, calcium,and potassium has necessitated the production of these metals by electro-lytic methods. Considerable use is now made of direct thermal reductionprocesses, particularly for magnesium, their industrial application havingbeen promoted by development of plant operating under high vacuum.The reduction of magnesium oxide by carbon a t temperaturesapproaching 2000" has for some time been known to be possible; the use ofthis reaction (MgO + C Mg + CO) is hindered by its rapid reversal atsomewhat lower temperatures, the magnesium vapour produced tending toreact with carbon monoxide before it can be condensed.The equilibriumpressures of magnesium vapour and carbon monoxide are calcqlated to reachone atmosphere at 1851", but they fall to less than 0-1 atmosphere at 1 6 0 0 O . 6Recent success with the carbon reduction process has depended on very rapid" quenching " of the hot product gases with hydrogen, natural gas, or a sprayof mineral oil.' This serves the double purpose of cooling the gases to atemperature at which the back-reaction occurs to a negligible extent, and ofslowing down this reaction by extensive dilution of the reactants with inertgas. The magnesium, contaminated with oxide and free carbon, is recoveredas a pyrophoric powder.In one typical application of this process8 themagnesium oxide (prepared from dolomite and sea water) is compressed intopellets with petroleum coke, and the pellets are fed continuously into anelectric-arc furnace lined with carbon blocks. As soon as the product gasesti E. C . Houston, Amer. Inst. Min. Met. Eng., Tech. Publ. No. 1828 (1945).6 K. K. Kelley, see ref. (8).7 See P. L. Teed, Bull. Inst. Min. Met., 1946, No. 479, 25.* T. A. Duncan, Amer. Inst. Min. Met. Eng., Teoh. Publ. No. 1671 (1944)132 INORGANIC CHEMISTRY.leave the reaction zone they meet a cold blast of natural gas issuing fromcooled jets mounted annularly round the exit pipe, and the average gastemperature quickly falls to about 250".The condensed magnesium dust iscollected in a large drum through which the gases pass and (mainly) inwoollen bag filters; it is then collected, without exposure to air, made into apaste with asphaltic material, or into briquettes, and transferred to sublim-ation retorts. I n these retorts, heated to 800°, the pressure is reduced to0.2 mm. or less, and magnesium of high purity sublimes on to a cylindricalsteel liner placed in the cooled head of each retort. After admission ofhydrogen and cooling, the liners are removed, and the magnesium is strippedOff.Reducing agents other than carbon have been widely used in the thermalreduction of magnesia, and successful use of ferrosilicon, calcium carbide, oraluminium is reported. The ferrosilicon process is notable for its simplicity,and for the fact that calcined dolomite may be used directly to supply part orall of the magnesium, the reaction being as follows : 2Mg0 + CaO + Si(from ferrosilicon) -+ 2Mg + ZCaO,SiO,.Use of this reaction a t readilyaccessible temperatures depends on the maintenance of a high vacuum;in practice, briquettes of calcined dolomite and ferrosilicon, containing a littlecalcium fluoride, are charged into steel retorts, which are heated to about1150" and pumped down to 0-05 mm. pressure. Magnesium condenses in thecooled head of each retort. Traces of alkali-metal salts in the charge givea small condensate of alkali metal, which may set fire to the magnesium whenthe retort is opened; this danger is minimised by condensing the morevolatile alkali metal in the retort cap, which is quickly removed when air isadmitted.Calcium carbide and aluminium are used as reducers in a very similarmanner,' the reactions involved being MgO + CaC, + Mg + CaO + 2C ;3Mg0 + 2A1+ 3Mg + A1,0,.The use of small additions of calciumfluoride to the charge appears to be general in most of the processes described,although the mechanism by which it promotes the reaction is admittedlyobscure.It has been found that calcium can be produced from lime convenientlyand economically in plant designed for the ferrosilicon reduction ofmagnesia,lO if aluminium is employed as the reducer a t about 1200". Thereaction is 6Ca0 + 2A1+ 3Ca + 3Ca0,Al,03. Since other alkaline-earthand alkali metals present in the charge distil with the calcium, the use ofhigh-purity lime is important.The regular production of potassium metal by thermal reduction isreported from Germany.11 Potassium fluoride is reduced a t 1000-1 150"with calcium carbide (2KF + CaC, + 2K + CaF, + 2C) or silicon, limebeing added in the latter case to combine with silica formed in the reactionQ L.M. Pidgeon, Canad. Mining and Met. Bull., 1944, No. 381.10 P. H. Staub, Chem. and Met. Eng., 1945, 52, No. 8, 94; C. c. Loomis, Trans.11 F.I.A.T. Final Report, No. 695.Electrochem. Xoc., 1946, 89, Preprint 9, 119WELCH : INORGABTO CHEMISTRY OF METALLURGICAL PROCIESSES. 133(4KF + Si + 4Ca0 + 4K + 2CaF2 + 2Ca0,Si02). The process is carriedout in steel retorts; the metal distils out of the reaction mixture, and iscondensed and collected under petroleum.Part of the potassium fluoridemay be substituted by potassium carbonate [2K2C0, + 3Si + 6Ca0 --+4K + 2C + 3(2CaO,SiO,)] or silicate [2K,SiO, + Si + 6Ca0 4 4K +3(2Ca0,Si02)] without appreciable loss of yield. All the reactants must bethoroughly dried; explosions are said to occur if moisture is present whenpotassium carbonate is used in the reaction.Aluminium from Clay and High-silica Bauxite.-The extraction ofalumina or aluminium metal from clay, its most abundant and accessiblenatural source, has been investigated over a long period, and a voluminousliterature of the subject exists.12 The objectionable impurities likely tooccur in alumina derived from clay are silica and iron, and each of the twomain types of process generally proposed deals effectively with dne only ofthese impurities; " acid " extraction methods applied to clay lead t o rapidseparation from silica, elimination of iron being difficult, whereas " alkali "processes, generally depending on an extraction of soluble sodium aluminateby water, cause difficulty with removal of silica.A recent careful study l3 of a sulphuric acid process for treatment of clayclearly indicates the difficulties associated with this method.The calcinedclay is leached with sulphuric acid, and iron is precipitated from the resultingaluminium sulphate solution by treatment with manganous sulphate andozone. After partial concentration, a clay residue is added to promoteprecipitation of silica.The purified solution is evaporated (by submergedcombustion), and the aluminium sulphate dehydrated and calcined toalumina; the sulphur oxides evolved in the calcination are recovered assulphuric acid for use in the first stage of the process.An alternative to the leaching of clay with sulphuric acid is roasting withammonium sulphate l4 (or in some similar processes, ammonium hydrogensulphate 15). Leaching of the product with water gives a solution from whichammonium alum may be crystallised; this is converted into hydratedalumina by treatment with ammonia evolved in the roasting stage.Ammonium sulphate can be recovered and re-cycled through the process.An interesting recent " acid " process l6 uses a combination of sulphuricand sulphurous acid leaching of clay, alumina being recovered by precipit-ation of a basic aluminium sulphate from the leach liquor.The basic saltis afterwards dissolved in sodium hydroxide solution (giving sodiumaluminate), and hydrated alumina is precipitated by controlled addition of12 See a recent bibliography by R. J. Woody, Washington Stale Coll., Electromet. Res.1s J. H. Walthall, P. Miller, and M. M. Striplin, jun., Trans. Amer. Inst. Chem. Eng.,14 H. W. St. Clair, S. F. Ravitz, A. T. Sweet, and C. E. Plummer, ibid., 1944,159,255.l5 Anon., Mining World, 1945, 7, No. 10, 22.16 0. Redlich, C. C. March, M. F. Adams, I?. H. Sharp, E. K. Holt, and J. E. Taylor,Lab., Bull. E-1 (1943).l345, 41, 55.Ind. Eng. Chem., 1946, 38, 1181134 INORUANIC CHEMISTRY.sulphuric acid.The sodium sulphate solution remaining is electrolysed togive sulphuric acid and sodium hydroxide solutions for use in earlier steps ofthe process.The most useful of the “ alkali processes ” for treatment of clay appears tobe the “ lime-soda sinter ” process, long known but largely investigated in theUnited States during the War.17 If clay is sintered a t a moderately hightemperature with controlled quantities of sodium carbonate and lime, itsaluminium content is converted into sodium aluminate (NaAIO,), and itssilica into an insoluble calcium silicate, probably ZCaO,SiO,. I n theory,extraction of the sinter with water should give a sodium aluminate solutionsubstantially free from silica, from which hydrated alumina could be pre-cipitated by “ seeding ” with the hydrate, or by treatment with carbondioxide; in practice, however, the extract is found to contain appreciableamounts of silica, a t least part of which is precipitated with the alumina, andthe product requires re-processing by the usual Bayer procedure before it canbe used for electrolytic production of aluminium.The lime-soda sinter process has been more usefully applied to low-gradebauxites containing much silica.18 I n the usual Bayer process bauxite istreated with hot sodium hydroxide solution under pressure, to give a silica-free sodium aluminate solution from which a pure alumina hydrate is pre-cipitated. If the bauxite contains much silica, uneconomic amounts of bothaluminium and sodium are retained in the Bayer treatment residue ((‘ redmud ”) as an insoluble sodium aluminium silicate.Recovery of the sodiumand aluminium may be effected by sintering the red mud from a high-silicabauxite with sodium carbonate and lime in suitable proportions, and leachingthe product with water. The extract contains sodium aluminate with a littlesilica, but if the solution is added to the alkali liquor used in a succeedingBayer treatment, this silica is precipitated during the pressure digestion.This ingenious addition to the well-established alumina process has extendedits useful application to poor-quality ores.“ Lime-sinter ” processes have also been investigated recently.19 Inthese, the clay is sintered a t a high temperature with lime, and the silica andalumina contents are converted into calcium silicates and aluminates.Ontreating the sinter with sodium carbonate solution, the silicates are unchanged,but the aluminates undergo double decomposition, calcium carbonateremaining in the residue and sodium aluminate being formed in solution.Alumina can be precipitated from the aluminate extract by the usual methods,the residual alkali being returned to the process as sodium carbonate.In a somewhat similar German process,20 clay has been sintered with cokel7 Univ. Kansas Publ., Kansas Xtate Geol. Survey Bull., 1943,47, 114.Chem. and Met. Eng., 1945, 52, No. 1, 106; J. D. Edwards, Amer. Inst. Min.Met. Eng., Tech. Publ., No. 1833 (1945).R. L. Copson, J. H. Walthall, and T.P. Hignett, Trans. Amer. Inst. Min. Met.Eng., 1944, 159, 241; F. R. Archibald and C. F. Jackson, Amer. Inst. Min. Eng.,Tech. Publ., No. 1700 (1944).2o C.I.O.S. Report, No. XXXII-21WELCH : INORGANIC CHEMISTRY OF METALLURGICAL PROOESSES. 135and anhydrite (CaSO,) to give a product apparently consisting of calciumaluminate and silicate ; on treatment with sodium carbonate solution thisaffords sodium aluminate solution and a residue (calcium carbonate, silicate,etc.) which can be recalcined to a cement of good quality.Some clay processes of a quite different type have also been investigatedin Germany.20 I n these the first step is a direct reduction of the alumina-silica ore with carbon in an electric-arc furnace, giving an alloy (" silumin ")containing about 60% of aluminium, with silicon and a little iron.Aluminium is then extracted from the finely divided alloy by treatment withmercury or molten magnesium. At about 600" and 22 atmospheres pressuremercury gives a solution containing nearly 40% of aluminium; on cooling,almost all the aluminium is precipitated and can be removed by a filtrationprocess, adhering mercury being removed subsequently by vacuum dis-tillation.If magnesium is used for the extraction it is recovered directlyfrom the alloy by vacuum distillation. The silicon-iron residue may ineither case be used for thermal reduction of magnesia, an economic advantageof the process. Other methods suggested for the processing of silumin areextraction with molten lead and volatilisation of aluminium subAuoride.21Beryllium.-The extraction of beryllium and its compounds is com-plicated by the difficulty of attacking beryl (3Be0,A1,0,,6Si02), the only oreavailable in large quantities, and by the somewhat difficult separation ofberyllium from the accompanying aluminium.The simplest method ofattack is to fuse the beryl in a carbon-lined electric arc furnace at not less than1500-1600" and quench the melt in cold water ; the resulting vitreous mass,after crushing, reacts readily with concentrated sulphuric acid, the berylliumand aluminium being converted into partly hydrated sulphates.22 The massof sulphates, containing insoluble silica, is leached with water, andammonium sulphate is added to the solution to precipitate the bulk of thealuminium as ammonium alum, (NH,),Al(S0,),,12H20, which has a very lowsolubility in beryllium sulphate solution containing ammonium sulphate.Crude hydrated beryllium sulphate is crystallised from the filtrate, andsubsequently purified by a recrystallisation procedure.High-grade beryl-lium oxide is obtained from the sulphate by ignition at 1350".A process used in Germany23 is similar in many respects. The beryl isfused with calcium oxide a t about 1500", and the quenched melt '' sulphated "by treatment with sulphuric acid; aluminium is removed as ammoniumalum, as before, and the crude solution of beryllium sulphate is freed fromiron (present initially as ferrous salt) by addition of hydrogen peroxide andcalcium carbonate, which precipitate hydrated ferric oxide. On passinggaseous ammonia into the resulting beryllium sulphate solution, thehydroxide, Be(OH),, is precipitated; this is finally ignited to the oxide atabout 1000".Attack of beryl by fusion or sintering with fluoride or complex fluoride,21 C.B. Willmore, U.S.P. 2,184,705.22 B. R. F . Kjellgren, Trans. Electrochem. Soc., 1946, 89, Preprint 6 , 83.z3 B.I.O.S. Final Report, No. 158; P.I.A.T. Final Report, No. 522, p. 46136 INORGANIC CHEMISTRY.originally a favourite method,24 still persists in recent processes ; the aim ofthe older fluoride methods of attack was usually to convert beryllium intosoluble sodium beryllium fluoride, Na2BeF4, and aluminium into insolublecryolite, Na,AlF,, so that a beryllium salt of moderate purity could beleached directly from the reaction product.Modern variants of the fluorideprocess are designed to extract the beryllium as a soluble fluoride and leavethe aluminium oxide and silica from the ore substantially unattacked. In anItalian process 25 the beryl is sintered at about 800" with sufficient sodiumhydrogen fluoride, NaHF,, to convert all the beryllium present into a sodiumberyllium fluoride, presumed (probably wrongly) to be 3NaF,2BeF2, whichcan be extracted with water from the residue of oxides. A more novelprocess 26 uses sodium ferric fluoride, Na3FeF6, as the attacking reagent ;this reacts preferentially with beryllium oxide (3Be0 + 2Na3FeF6 +3Na,BeF, + Fe203) and leaves alumina, silica, and iron oxide (impurity)unattacked.The sodium beryllium fluoride solution from either method ofattack is treated with alkali to precipitate beryllium hydroxide, preferablyby adding an excess of sodium hydroxide to redissolve the initial precipitate,and then pouring a further quantity of sodium beryllium fluoride solutioninto the hot liquid; this procedure gives a granular, crystalline hydroxidewhich is convenient to filter off.26 The filtrate contains sodium fluoride, andthe economic use of the process demands recovery of its fluoride content ;this is conveniently effected by adding ferric sulphate to precipitate sodiumferric fluoride [12NaF + Fe,(SO,), --+ 2Na,FeF6 + 3Na2S04], which maybe re-used in the attack of the ore.26 The sodium ferric fluoride mode of attackis stated to be applicable with advantage to a new low-grade beryllium orecomprising magnetite with small quantities of helvite, a beryllium ironaluminium silicate.Processes of this type, in which the desired ore con-stituent is selectively attacked without consumption of reagents by unwantedmaterial, are of special value in the utilisation of low-grade mineral deposits.The isolation of beryllium metal was formerly effected by electrolysis of afluoride melt, usually containing alkali or alkaline-earth fluoride withberyllium fluoride or oxyfluoride. This method required the use of relativelyhigh electrolyte temperatures, and highly toxic fluorine gases evolved a t theanodes were troublesome. Preference is now given to electrolysis of a meltof sodium and beryllium chlorides at about 350".23 Satis€actory applicationof this process depends on a supply of pure anhydrous beryllium chloride,now prepared by chlorinating briquettes of beryllium oxide and carbonat 700-800" (Be0 + C + C1, + BeC3, + CO) ; the beryllium chloridesublimes out of the furnace, and is subsequently purified by fractionalsublimation in it current of hydrogen.Beryllium powder has been satisfactorily prepared from the chloride byreduction by sodium vapour at reduced pressure.27 Beryllium fluoride may24 See, e.g., R. Rimbach and A. J. Michel, " Beryllium ", New York, 1932.26 P.I.A.T. Final Report, No. 522, p. 62.z 6 H. C. Kawecki, Trans. Electrochem. SOC., 1946, 89, Preprint 11, 133.27 J. M. Tien, ibid., Preprint 19, 223WELCH : INORGANIC CHEMISTRY OF METALLURGICAL PROCESSES, 137also be reduced with magnesium to give a pure Alloys of beryllium(particularly with copper or nickel) can be prepared by reducing berylliumoxide with carbon in presence of the free alloying meta1,22t28 but the berylliumcontent obtainable in the alloy is limited; beryllium fluoride may similarlybe reduced with magnesium in presence of base metal to give an alloy.28Zirconium-Considerable interest in zirconium, particularly in the metalin its ductile state,29 has been evident recently, and the publication of hreview 3o of much scattered information is timely.I n a typical recent process,31 zircon sand (mainly ZrSiO,) is heated withcarbon in an electric resistor furnace at about 2000", and arnixture of zirconiumand silicon carbides is formed; some of the silicon is said to be volatilisedfrom the charge as the monoxide, SiO. The mixture of carbides is heated inchlorine, and the tetrachlorides of zirconium and silicon are formed in astrongly exothermic reaction ; the zirconium tetrachloride can be fractionallycondensed from the mixture in a vessel held above 80", the condensatecontaining only 0.05--0.3:/, of silicon, with up to 0.5% of iron and otherimpurities. The chloride is purified by sublimation in hydrogen, whichreduces ferric chloride t o the relatively non-volatile ferrous chloride ; thesublimate contains only 0.05y0 of iron. The purified zirconium tetrachlorideis reduced with magnesium in a special furnace so designed that reactionoccurs between the tetrachloride vapour and molten magnesium, a heliumatmosphere in the furnace ensuring exclusion of air. The mixture of zir-conium metal, magnesium chloride, and excess of magnesium produced in thereaction is vacuum-distilled a t up to 900" in a second furnace ; the residue ofzirconium remaining may still contain up to 1% of magnesium chloride,magnesium, and hydrogen, which are removed by heating the metal in avacuum induction furnace a t 1500". Finally, the zirconium is melted downinto small ingots in an arc furnace in an atmosphere of helium at lowpressure. The product is ductile and can readily be rolled into sheet.Another method of reducing zirconium tetrachloride with magnesium hasbeen de~cribed.~2 A. J. E. W.J. S. ANDEBSON.J. CHATT.A. J. E. WELCH.28 W. J. Kroll. U.S. Bur. Mine.?, Inf. Circ. No. 7326 (1945).28 See, for example, D. B. AInutt and C. L. Scheer, Tians. Electrochem. SOC., 1945,30 W. J. Kroll and A. W. Schlechten, 77.8. Bur. Mines, Inf. Circ. No. 7341 (1 946).31 W. J. Kroll, A. W. Schlechten, and L. A. Yerkes, Trans. Electrochem. SOC., 1946,s2 R. von Zeppelin, Metal2 u. Em, 1943, 40, 252.88, Preprint 30, 357.89, Preprint 29, 365

ISSN:0365-6217    

DOI:10.1039/AR9464300104

出版商:RSC    

年代:1946

数据来源: RSC

摘要:

ORGANIC CHEMISTRY.1. INTRODUCTION.THE subjects selected for review in this section include the hydrogen bond,stereochemistry, carbohydrates, steroids, and a selection of heterocycliccompounds containing nitrogen.A review is given of those methods of detection of the hydrogen bondwhich have proved of greatest use in the elucidation of organic structures.Emphasis is laid on the physical conditions of the methods by which assess-ment of structure is made, and whether these conditions are likely to preservea hydrogen-bond structure. Methods based on the measurement of inter-atomic distances by means of both X-ray diffraction and electron diffractionare discussed, examples of the former being provided by phthalocyanine,melamine, and hyperol, and of the latter by hydrofluoric acid and carboxylicacids.Various indirect or comparative methods are also discussed, such asthose based on infra-red absorption, volatility, solubility and related pro-perties, and molecular weight determinations. Reference is made to thesolute-solvent interaction revealed by the work of C. S. Marvel and hiscollaborators, and to methods for the detection of molecular association andinternal hydrogen bonds (chelate rings). A review is included of the chemicaldifferences between compounds possessing a hydrogen bond structure andothers closely related to them, e.g., o-hydroxyazo-compounds, the benzilmonoximes ; of methods of alternative syntheses leading to a single individualcompound, e.g., p-diketones, methylnaphthazarin, quinhydrones, formazylcompounds; and of the effect of chelation in stabilising certain structuresand in favouring certain reactions.The chief examples (mainly organic) of compounds exhibiting hydrogenbmds of the following types are considered: F-H-F, F-H-N, F-H-0,0-H-0, N-H-0, N-H-N, N-H-S, 0-H-S.Some emphasis is laid on theimportant part played by the hydrogen bond in deciding crystal structureand other important physical properties, e.g., density of ice, layer cleavage ofanhydrous oxalic acid, configuration of proteins. The evidence for theengagement of the CH group in hydrogen-bond formation is considered insome detail fi.e., C-H-0, C-H-N), and a short account of hydrogen bondsinvolving other elements (S, C1, Br) is given. The close connection betweenhydrogen-bond association and tautomerism (" mesohydric tautomerism ")is given brief mention.An absolute asymmetric synthesis of ethyl d-tartrate from ethyl fumaratehas been reported.Mixtures of diastereoisomeric esters have been separatedby high-efficiency fractional distillation. The sulphur-oxygen bond insulphoxides, formerly supposed to be a co-ordinate bond, is shown t o be adouble bond, so that the figure corresponding with the sulphur valencies is atrigonal bipyramid and not a " tetrahedron ". Interesting stereochemicalstudies have been made of heterocyclic compounds of sulphur, selenium, anBAKER AND IIEY : INTRODUCTION. 139tellurium, and very complete investigations of the optical activity of hetero-cyclic and spirocyclic compounds of arsenic have been described.A base,which owes its molecular dissymmetry to the presence of two ring nitrogenatoms with stable " tetrahedral " configurations, has been resolved into d-and I-forms. A beginning has been made in the direction of discussingquantitatively steric effects in replacement reactions, and continued successfuluse has been made of optical activity for the study of molecularrearrangements.I n view of the growing biological importance of the inositols and theirderivatives, the opportunity has been taken t o review the developments inthis field, and an account has been given of the rarer methylpentose sugarsand their deoxy-derivatives, which are found combined in the cardiacglycosides. The use of chromatography to separate qualitatively andquantitatively mixtures of sugars and their derivatives is discussed ; themethod has been developed on the micro-scale for the separation of methyl-ated sugars and their glycosides.The section on the oxidation of a-glycolgroups (L. N. Owen, Ann. Reports, 1943,40, 115) with periodic acid and leadtetra-acetate has been continued. Sugar derivatives containing one ormore anhydro-rings of the septano-, pyrano-, furano-, and ethylene oxidetypes have been prepared and their structures elucidated. The Waldeninversion which occurs when an oxide ring is opened has been used t o provethe configuration of the amino-group in chondrosamine and to preparederivatives of the less accessible sugars.A summary is given of the more recent constitutional work on thestructure of the polysaccharides.A noteworthy advance has been made withthe enzymatic synthesis of amylopectin, and the degradative action of (3- andother amylases on this polysaccharide has received considerable attention.The polysaccharides from gum tragacanth, the c-galactan of the larch, anddamson tree gum have received a detailed examination. Gum tragacanth hasbeen shown to be a mixture ; the c-galactan is also considered t o be a mixtureby some authors ; damson tree gum appears to be homogeneous. All thesepolysaccharides are of the ramified type and odntain a variety of sugars.Stereochemical developments during the last eight years have confirmedthe general picture of the steroid nucleus given by Ruzicka in 1933, andevidence has been adduced to show that the various possible geometricalmodifications arising from chair-boat transformations of rings A and Bmake no contribution to the stereochemistry of the steroid nucleus.Methodsavailable for determination of the orientation of nuclear substituents aresummarised, and, in a review of the various nuclear positions, examples oftheir use are given. There is still no strict proof available to show that thehydroxyl group in cholesterol and cholestanol is (p)-orientated, but on thebasis of this assumption it has been possible to establish the configurationat C, of a whole series of derivatives of androstane, androst-5-ene, and theirhomologues. Attention is drawn to the fact that the configuration is knownat C7 in the bile-acid series but not in the sterol series; also that it seemsprobable that the previous arbitrary allocation of configuration at C7 in th140 ORGANIC CHEMISTRY.steroI series must be reversed.The proof given by Reichstein that theformerly accepted structure of deoxycholic acid is incorrect in regard toconfiguration at C,, and C17 has far-reaching repercussions; the sameconclusion, namely that the hydroxyl group at C,, and the side chain a tC17 are respectively ( a ) - and (@)-orientated, has been reached independentlyand on quite different grounds by groups of workers in America. It follows,inter alia, that, as originally suggested by Reichstein and Shoppee, the Cll-hydroxyl group characteristic of the natural adreno-cortical steroids has the(@)-configuration, and that the C,,-side chain in cholesterol, progesterone,corticosterone, the steroid sapogenins, and the cardiac aglycones is (@)-orientated.A further consequence is that the Digitalis heart poisons mustcontain a cis-C/D-ring union, a view now accepted by Ruzicka, Plattner,and their co-workers who, by the synthesis of steroids with hydroxyl groupsat C, and C,,, are preparing the way to the synthetic production of thesecompounds.In the field of reduced heterocyclic rings recent examples are discussedof the synthesis of piperidines and piperidones by (i) the reductive cyclisationof y-cyano-esters, (ii) the Eisleb double alkylation method (of a reactivemethylene group by di- p-chloroethylalkylamines), and (iii) the Dieckmann-like cyclisation of di-P-carbethoxyalkylamines. Attention is drawn to thepreparative advantages arising from the use of N-benzoylated and -nitros-ated derivatives as intermediates, and some new reactions of certain piperi-dines and piperidones are mentioned. Recent syiithetic work in the reducedbicyclic field (cycloalkano-pyrrolidines, -piperidines, and -thiazoles, andbicycloaza-alkanes) is briefly reviewed, and the stereocheinistry of @-biotinand its derivatives is summarised.A section on indoles deals with recentcritical studies of the Bischler synthesis from arylamines and a-halogeno-ketones, with improved prepsrative routes to trytophan and indole-3-aldehyde, with the synthesis of 7-azaindoles, and with the chemistry ofgliotoxin, the naturally-occurring antibiotic.Recent developments in thequinoline field are reviewed chiefly from the aspect of preparative improve-ments, particularly as applied to the synthesis of 4-hydroxyquinolines, alarge number of which have been prepared by condensation of arylamineswith ethyl ethoxymethylenemalonate followed by cyclisation or by variationsof this method. Brief mention is made of progress in the chemistry ofcinnoline derivatives. A comprehensive statement is given of the chemistryof the pterins, compounds which contribute to the pigmentation of the wingsof insects and which, until recently, were regarded as of academic interestonly. The chemistry of this group, which is related to the purines, haslately been greatly clarified and interesting and important biologicalproperties have been revealed.This section includes a description of thesynthesis and proof of structure of the antianzemic " Liver L. casei factor "(vitamin B,) and of its relationship to other active compounds, which arepterin derivatives, and with a general discussion of the vitamin B, problem.W. B.D. H. HHUNTER: THE HYDROGEN BOND. 1412. THE HYDROGEN BOND.The fact that hydrogen can sometimes link two other atoms together isnow beyond all question, but the mechanism of this virtual bivalency stillremains obscure.is by no means universally accepted, and an electrostatic union, largely theresult of the hydrogen atom being a bare proton with a minimum of envelop-ing electrons, has strong support.2 The latter view is in harmony withthe fact that the atoms linked by hydrogen bonds are confined almostentirely to the electronegative elements of small atomic radius (i.e., N, 0,B’), and that hydrogen bonds between atoms other than these are of theweakest kind.As between these two views there is good evidence forbelieving that resonance, if it contributes at all to the structure of thehydrogen bond, does so to a very inconsiderable e ~ t e n t . ~The resonance mechanism suggested by N. V. SidgwickMethods of Detecting the Hydrogen Bond.It is important in this connexion to distinguish between hydrogenbonds formed intramolecularly (by chelate rings) and those formed betweenmolecules. The former will usually lead to a unimolecular condition, thelatter to molecular association, and the resultant physical properties ofthe substance concerned will be largely influenced by these alternatives.It is evident, too, that the physical conditions under which assessment ofstructure is made will determine whether or not a substance will preserveits hydrogen-bond structure ; for example, a hydrogen-bond structure presentin the solid or liquid state may well be destroyed in dilute solution or inthe vapour state.Moreover, intermolecular hydrogen bonds are usualIymore sensitive than are intramolecular to the stresses imposed by vaporis-ation or dissolution.The following is a brief summary of the chief methods in general usefor the detection of hydrogen bonds.I. Interatomic Distance Methods.-These depend on the measurement ofthe distance between the atoms linked by the hydrogen bond, and arebased on the assumption that any approach of two such atoms to a distancesignificantly less than about 3.4 A.indicates a chemical link between them.The strengths of such bonds are in the inverse order of these interatomicdistances.Applied mainly to crystals, which are mostlikely to favour a maximum display of hydrogen bonds, this method hasyielded more information than any other about hydrogen-bond structures.It is, however, confined at present to relatively simple compounda (e.g.,inorganic salts), and becomes progressively more difficult to apply as1 Ann. Reports, 1933, 30, 112; 1934, 31, 40; “ Organic Chemistry of Nitrogen ”,Oxford University Press, 1937, xvii.2 L.Pauling, “ The Nature of the Chemical Bond ”, Cornell, 1940, p. 286.3 Manse1 Davies, this vol., p. 29.* The scope of diffraction methods as a guide to molecular structure is reviewed(a) X-Ray diffraction.*by J. M. Robertson, Tilden Lecture, J., 1945, 249142 ORGANIC CHEMISTRY.molecular complexity increases. It is not surprising, therefore, that itsapplication to organic hydrogen- bond structures has been limited to simpleexamples, although phthalocyanine,4 melamine,5 and hyper016 are notableexceptions. The method gives an accurate measure of the A-H-B distance,where A and B may be in the same or in different molecules, and, thoughit does not locate the hydrogen atom within this distance, it indicates withsome certainty the presence or absence of the hydrogen bond.For example,the presence of the O-H-0 bond in sodium hydrogen carbonate,7 potassiumdihydrogen phosphate and ar~enate,~ and ammonium periodate,(NH4)2H3106,10 and its absence in ammonium hypophosphite, NH,H2P02,11supports the chemical evidence that the former are true acid salts, whereasthe latter is not.Owing to the fact that this method is usuallyapplied to vapours a t low pressures, it is unlikely to reveal intermolecularhydrogen bonds. It is for this reason that the structures of hydrogenperoxide l2 and of hydrazoic acid l3 determined by this method give noindication of hydrogen bonding, although the physical properties of thepure substances clearly point to molecular association by hydrogen bonds.14On the other hand, the F-H-F bond in hydrogen fluoride is sufficientlypowerful to persist in the vapour, which is found l5 to consist of zigzagpolymers having a F-H-F distance of 2.55 A., the F-F-F angle being about140".This agrees well with the structure of solid hydrogen fluoride deter-mined l6 by the X-ray method, and seems incompatible with previouscyclic structures. The method has also been applied to the simpler carb-oxylic acids,11. Indirect (or Cmparative) Methods.-These depend very largely onthe fact that the engagement of a group in hydrogen-bond formationmodifies the physical, and to a lesser extent the chemical, properties of thegroup involved. They consist of a comparison of properties (many ofwhich may be capable of numerical expression) displayed by substanceswhich may possess a hydrogen-bond structure, with those of closely related(Miss) I.E. Knaggs and (Mrs.) K. Lonsdale, Proc. Roy. SOC., 1940, A, 177, 140;(b) EZectron di,ffruction.*the dimeric structure of which survives vaporisation.222 ORGANIC CHEMISTRY.and (LXXX), which were quantitatively reconverted into the parent acidsby hydrolysis with potassium carbonate. The C,,-hydroxyl group and theC1,-side chain must therefore lie on the same side of the general plane ofthe ring-system in these 12-epi-acids and on opposite sides in natural deoxy-cholic acid. This conclusion was supported by an examination 133 of thebehaviour of the methyl esters of the 12-epi-acids (LXXVII), (LXXIX),20-n- bisnordeoxycholic acid (LXXXI), and 20-isobisnordeoxycholic acid(LXXXIII) with phenylmagnesium bromide.Dehydration of the diphenyl-carbinols obtained from the esters of the 12-n-acids (LXXXI) and(LXXXIII), which results in disappearance of the centre of asymmetry atC,,,, gave the.same diphenylethylene (LXXXII) but no trace of a cyclicoxide. Similar dehydration of the diphenylcarbinols resulting from the12-epi-acids (LXXVII) and (LXXIX) gave the diphenylethylene (LXXXV)together, in the case of (LXXVII), with the cyclic oxide (LXXXIV).Me CPh, Me CO,HC. The @-Biotin Problem.-Work which has appeared since the lastreview in these reports42 has been mainly directed towards the elucidationof the steric configuration of p-biotin (LXII).Of the four racemates whichcan theoretically arise from the presence of three asymmetric centres (0)in (LXII), the three previously isolated by Harris and his co-workers43-dt-biotin, dl-allobiotin, and dl-epiallobiotin-have been studied from thisaspect in some detail.P4 It was shown that each of the alternative routes(LXIII) -+ (LXIV) ---+ (LXII) + (LXV) and (LXIII) --+ (LXVI) --+(LXVII) --+ (LXV) gave rise to the same dethiobiotin (LXV) when appliedto a given racemic bisacylamidothiophan derivative (LXIII) ; in this waydl-allo- (LXIII) and dl-epiallo- (LXIII) both gave dl-dethioalto- biotin (biologic-ally inactive), and dl-(LXIII) [the precursor of dl-biotin, of which natural(d-) p-biotin is one component] gave dl-dethiobiotin (biologically active),thus confirming that, in the three racemates (LXII), two have a trans-linkage a t C,-C, and one has a cis-, or vice versa.Now in the reaction(LXIV)-+ (LXII), the yield is almost theoretical in the case of dl-biotin,but this does not apply to the dl-alZo- and dl-epiallo-compounds. Thissuggests that dl-biotin has the cis-configuration at C,-C, (LXVIII), and thatthe dl-allo- and dl-epialbracemates are trans-compounds (LXIX) . This isstrikingly confirmed by the behaviour of the three racemates towards boiling(CXV.)The naturally-occurring pterins are mostly colourless or yellow com-pounds which show marked fluorescence in solution a t or near pH 7. Theyare found in the wings of various species of butterflies and ~ a ~ p ~ in the skin 134 and eyes 135 of fishes, and in the urine and liver of mam-m a l ~ .~ ~ ~ - ~ ~ ~ At an early stage of the researches on these compounds,which were carried out in the laboratories of H. Wieland and C. Schopf, i twas recognised 131 that a close relationship exists between the purines andleucopterin, one of the commonly-occurring pterins, and structure (CXV)was proposed 131 for this substance. Soon afterwards,132 it became necessaryto discard the formula C,,H,,O,N, in view of the isolation of guanidineas a hydrolytic product of a leucopterin derivative, and the loss of & of thetotal nitrogen of leucopterin on treatment with nitrous acid; to reconcilethese facts with the analytical data, a C19-N,, formulation was adopted,and this persisted, with minor variations, for some years.During thisperiod the chemistry of leucopterin and of its analogue, xanthopterin, waspainstakingly developed with small quantities of material ; and, althoughit was noticeable that many of the reactions (acetylation, chlorination withphosphorus pentachloride, action of nitrous acid, formation of glycol deriv-atives on oxidation with chlorine in various media) occurred in triplicate( L e . , implied the presence of three similarly-reacting groups in the pteririmolecules), simplified molecular formulz were not warranted in face of theanalytical data. The practical difficulties of the problem were unusuallyformidable. Apart from the labour of the isolation of pterins, whichinvolved the collection and manipulation of many thousands of butterfliesof a given species, these substances are insoluble in organic solvents, aredifficult to crystallise and purify, and decompose without melting ; theyoccur as hydrates which retain water very tenaciously and give spuriousanalytical data under ordinary conditions.128 R.Tschesche and H. J. Wolf, 2. physiol. Chem., 1937, 248, 34.129 M. Polonovski, R.-G. Busnel, and M. Pesson, Helv. Chim. Acta, 1946, 29, 1328.130 H. Wieland and C. Schopf, Ber., 1925, 58, 2178.131 C. Schopf and H. Wieland, ibid., 1926, 59, 2067.132 H. Wieland, H. Metzger, C. Schopf, and M. Biilow, Annalen, 1933, 507, 226.133 C. Schopf and E. Becker, ibid., p. 266; 1936, 524, 49; E. Becker and C. Schopf,134 R. Huttel and G. Sprengling, ibid., 1943, 554, 69; M.Polonovski, R.-G. Busnel,135 A. Pirie and D. M. Simpson, Biochem. J., 1946, 40, 14.136 W. Koschara, 2. physiol. Chem., 1936, 240, 127.13' Idem, ibid., 1943, 277, 159.ibid., p. 124.and M. Pesson, Compt. rend., 1913, 217, 163.138 Idem, ibid., p. 284; 279, 44252 ORGANIC CHEMISTRY.In 1940 the analytical difficulties were recognised and largely over-come,139 and the formula of leucopterin was disclosed as (C,H,O,N,),,where x = 1, 2, or 3. Synthesis of the pterin by fusion of 2 : 4 : 5-triamino-6-hydroxypyrimidine (CXVI; R = NH,) with oxalic acid l*O restrictedthe possible structures to (CXVII; R = NH,), (CXVIII), (CXIX), and(CXX). Of these (CXVIII) was excluded by the results of further applic-ations of the oxalic acid synthesis.Condensation of 4 : 5-diamino-2 : 6-OH OH OHN/\NH, N/\/%oH N'\NH,(CXVI.) (CXVII.) (CXVIII.) MeR!\N)'NH2 R\N/\N/ I 'I IOH ()AN/ I IINH,(CXXI.)(CXXII.)dihydroxypyrimidine (CXVI; R = OH) and of 4 : 5-diamino-6-hydroxy-3-methyl-2-pyrimidone (CXXI) with oxalic acid a t about 250" 141 gave,respectively, (" deaminoleucopterin ")(CXVII; R = OH) and the 3-methyl analogue (CXXII), which was notidentical with 3-methylxanthine-8-carboxylic acid (CXXIII),142 thusexcluding the alternative ring-closure of (CXXI). Structure (CXVIII) forleucopterin is thus eliminated if (as is very probable) the oxalic acid con-densations to give leucopterin, deaminoleucopterin, and (CXXII) all pro-2 : 6 : 8 : 9-tetrahydroxypteridineceed in the same sense; and this was proved for leucopterin and deamino-leucopterin by the conversion of the former into the latter by means ofnitrous acid.132 Further weight is given to this argument by the synthesisof 6-deoxyleucopterin (CXXIX ; see below), a transformation product ofleucopterin, by the oxalic acid method.Furthermore, purine-8-carboxylicacids are readily decarboxylated , whereas leucopterin does not decomposebelow 400".139 H. Wieland and R. Purrmann, Annalen, 1940, 544, 163.140 R. Purrmann, ibid., p. 182.142 W. Traube, ibid., 1923, 432, 266.141 Idem, ibid., 1941, 546, 98SIMPSON : HETEROCYCLIC COMPOUNDS. 253The choice between (CXVII; R = NH,), (CXIX), and (CXX) as thestructure of leucopterin was finally settled by the elucidation of the con-stitution of xanthopterin, another naturally-occurring pterin, and of itsrelationship to leucopterin.Fusion of (CXVI; R = NH,) with dichloro-acetic * acid gave the amide (CXXIV), which on cyclisation under mildconditions yielded xanthopterin ; 141 this is therefore 2-amino-6 : S-dihydroxy-pteridine (CXXV). Now xanthopterin takes up an atom of oxygen in con-tact with platinum in weakly acid solution, yielding leucopterin 139 (thesame result is obtained by treatment of xanthopterin with methylene-blueand an enzyme preparation,145 and by the prolonged action of hydrogenperoxide),lM and, as leucopterin is devoid of peroxidic properties,l43 thereaction can only be represented by hydroxylation of xanthopterin at C,.Leucopterin is therefore (CXVII; R = NH,).A third naturally-occurring pterin is 8-deoxyleucopterin or isoxantho-pterin (CXXVII), which was synthesised by hydrolysis, followed by decarb-oxylation, of the ester (CXXVI), obtained from (CXVI; R = NH,) anddiethyl ketoma1onate.l4 When this pterin was first isolated,l32 it wasgiven the name of anhydroleucopterin ; the above synthesis, however,discloses its relationship to leucopterin, and it has been obtained fromleucopterin by electrolytic reduction.145 The reverse reaction, vuiz., oxid-ation of isoxanthopterin to leucopterin, has not yet been achieved, butthe action on isoxanthopterin of nitrous acid and of chlorine water givesthe leucopterin derivatives (CXVII; R = OH) and (CXXXII; R = H)respectively. 146Several other ‘f natural pterins have been described.Uropterin, isolatedfrom urine,l36 has been proved to be ~anth0pterin.l~’ Another urinarypterin, u r ~ t h i o n , l ~ ~ is more complex. Its molecular formula is CllH,303N5S,.Both sulphur atoms are inert, and no thiol group is present. The pigment,unlike other pterins, is opticany active. Although there is as yet no rigid143 H. Wieland and R. Purrmann, Annalen, 1939, 539, 179.1 4 4 R. Purrmann, ibid., 1941, 548, 284.145 H. Wieland and R. Liebig, ibid., 1944, 555, 146.1 4 6 H. Wieland, A. Tartter, and R. Purrmann, ibid., 1940, 545, 209.* The use of the bisulphite compound of barium glyoxylate in sulphuric acid,instead of dichloroacetic acid, gives a greatly improved yield.137An interesting general account of the occurrence of pterins in wing-pigments isgiven by (Sir) F.G. Hopbs (Proc. ROY. soC.9 1942, B, 130, 359). It should be notedthat the purple pigment, rhodopterin, which is there discussed, is not a true pterh,but a condensation product of leucopterin and xanthopterin-9-carboxylic acid, andthat it has been re-named pterorhoh (R. Purnmnn and M. Maas, Annahm, 1944,660, 186)254 ORGANIC CHEMISTRY.proof that the molecule of urothion contains the pteridine skeleton, theexpression (CXXVIII) has been advanced on the basis of the foregoingdata and the following evidence. Urothion yields a tetra-acetyl derivative,which gives satisfactory cryoscopic molecular weight values and can behydrolysed to a monoacetyl derivative. The pigment is amphoteric, andamino-nitrogen estimations suggest the presence of a guanidine residue ;its ultra-violet absorption spectrum resembles those of xanthopterin, ribo-flavin, and other isoalloxazines ; and periodic acid oxidation yields form-aldehyde and a product, C,,H,O,N,S, (urothionaldehyde).The pigmentalso gives, with concentrated sulphuric acid, the red colour (thiophenolreaction) characteristic of compounds containing a thiol, or potential thiol,group attached to an aromatic ring.(also known as fluorescyanine),l29is likewise a pterin of unknown structure. It is reduced by fuming hydriodicacid with liberation of iodine, and on dilution the leuco-compound isreoxidised by the iodine. This extremely easy reversible oxidation-reductionis shown only by isoxanthopterin 146 and the acid 144 obtained by hydrolysisof (CXXVI). Xanthopterin is also reduced under the same conditions,l46but the dihydro-compound is not reoxidised by iodine, although it can beoxidised to the pterin by a variety of other reagents.14' Leucopterin, onthe other hand, is much more difficult to reduce,145* 146 but under appropriateconditions yields isoxanthopterin 145 or dihydr~xanthopterin.~~' * A con-trolling factor affecting the redox potential thus appears to be the pointof hydroxylation of the pyrazine ring; for this reason, and also becausethe absorption spectra of isoxanthopterin and ichthyopterin are very similar,it has been suggested 134 that this marine pterin is a derivative of 9-hydroxy-pteridine.It is to be noted, however, that the suggested molecular formula,C,H,O,N,, implies that it is a dihydro-derivative of this ring-system.Properties of Pterins.-Excluding differences in elementary composition,the criteria by which individual pterins can most readily be distinguishedare basicity (this may be very slight or considerable; acidic properties arewell-marked), fluorescence and the effect of pH thereon, absorption spectra,and the redox reaction already noted. The fluorescence of pterins has beenstudied in some detail ; lM, 1489 149, leucopterin exhibits its maximumfluorescence in strongly alkaline solution,149 but under these conditionsxanthopterin fluoresces only slightly, the intensity increasing rapidly withfall in pH.14, Various measurements of the ultra-violet absorption spectraof pterins have been recorded (frequently with similar data for purines andThe fish-skin pigment, ichthyopterin147 J.R. Totter, J . Biol. Chem., 1944, 154, 105.lPs P. Decker, 2. physiol. Chem., 1942, 274, 223.l50 M. Polonovski, S. Guinand, M. Pesson, and R. Vieillefosse, Bull. SOC. chim.,1945, 12, 924.* The reduction of leucopterin to dihydroxanthopterin, followed by oxidationof the latter with alkaline silver nitrate, enables a convenient synthesis of xantho-pferin to be effected from (CXVI ; R = NH,) and oxalic acid."'W. Jacobson and D. M. Simpson, Biochem. J . , 1946,40, 3 , 9SIMPSON : HETEROCYCLIC COMPOUNDS. 255flavins), but no systematic study has yet been made.l36, 138, 150-162, 162A useful, but not exhaustive, summary of the chemical and optical data isgiven by W.Jacobson and D. M. S i m p s ~ n . l ~ ~When leucopterin is treated with phosphorus pentachloride a mono-chloro-derivative is obtained. That the 6-position is involved in thisreaction was shown by reduction of the chloro-compound to the deoxy-derivative (CXXIX), which was synthesised from 2 : 4 : 5-triaminopyrimidineand oxalic acid.146 Application of the reaction to deaminoleucopterin(CXVII; R = OH) gave, similarly, the 2 : 6-dichloro-compound,153 butunder different conditions of isolation 2 : 6 : 8 : 9-tetrachloropteridine (CXXX)c1 c1(CXXIX. ) (CXXX.)was obtained, and it was found that the 2 : 6-dichloro-derivative had beenformed * by partial hydrolysis of (CXXX) under the conditions of isolation.In contrast, drastic alkaline hydrolysis was needed to convert the dichloro-derivative (2 : 6-dichloro-8 : 9-dihydroxypteridine) into (CXVII ; R = OH) ;the corresponding dichloropyrimidine (CXXXI) is also resistant .153 Inci-dentally it may be noted that the production of a tetrachloro-derivativefrom deaminoleucopterin is not possible on the basis of the purine-8-carb-oxylic acid structure (CXVIII) for leucopterin ; its formation thus constitutesan independent proof of the correctness of (CXVII; R = NH,).Before the constitution of leucopterin and xanthopterin had been settledby synthesis, a number of degradation products had been isolated duringattempts to unravel the complexities of the supposed C,, structures.Formul-ation of these reactions on the basis of (CXIV) illustrates clearly the closeparallel between them and well-known purine transformations.Oxidationof leucopterin with chlorine water or chlorine in methanol leads to the glycol(CXXXII; R = H) or its dimethyl ether (CXXXII; R = Me) respect-i ~ e 1 y . l ~ ~ Hydrolysis of (CXXXII; R = H) results, as with uric acid, inthe conversion of the pyrimidine into a hydantoin ring and in the isol-ation of derivatives of the latter, vix., (CXXXIII), (CXXXIV), and(CXXXV).139,154 The product formed by the action of chlorine in aceticacid on leucopterin is (CXXXVI),132, 139 corresponding to the formation oflS1 H. K. Mitchell, J . Amer. Chem. SOC., 1944, 66, 274.lS2 H. Fromherz and A. Kotzschmar, Annalen, 1938, 534, 283.lS3 C.Schopf and R. Reichert, ibid., 1941, 548, 82.154 H. Wieland and A. Kotzschmar, ibid., 1937, 530, 152.* It is of considerable interest that (CXXX) is apparently more readily hydrolysedin alkaline than in acid solution ; this is in direct contrast to recent evidence (see, forexample, C. K. Banks, J . Amer. Chem. Soc., 1944, 66, 1127, 1131 ; A. J. Tomisek andB. E. Christensen, ibid., 1945, 67, 2112; C. K. Banks and J. Controulis, ibid., 1946,88, 944) that hydrolysis of chloro-heterocyclic compounds is acid-catalysed, and suggest8that a different mechanism may be operative in the hydrolysis of (CXXX)256 ORGANIC CHEMISTRY.5-hydroxypseudouric acid from uric acid ; 155 analogously, oxidation ofdeaminoleucopterin (CXVII; R = OH) with chlorine in methanol givesOR&dkaliNH-=O(CXXXV.) HN//jN/JNH*CO*C02HH H (CXXXIV.)(CXXXVII).166 The glycol ether (CXXXII; R = Me) is extremelyunstable; in aqueous solution at 40" it yields the monoether (CXXXVIII),which readily decomposes further into (CXXXIX), guanidine, and carbondioxide by hydrolytic fission.132 Reference has already been made to theformation of leucopterin by hydrogen peroxide oxidation of xanthopterin ;OMethe reaction is not, however, quantitative, and under suitable conditionsimino-oxonic acid (CXL) is also formed.139 This reaction resembles theoxidation of uric to oxonic and, indeed, (CXL) is also formed fromH.Biltz and M. Heyn, Annalen, 1917, 413, 7.lS6 H. Wieland and A. Tartter, ibid., 1940, 543, 287.16' F.J. Moore and R. M. Thomas, J . Amer. Chem. SOC., 1918, 40, 1120; H. Biltzand R. Robl, Bw., 1920, 68, 1967SIMPSON : HETEROCYCLIC COMPOUNDS. 257the purine (CXLI) .l39 Oxidation of xanthopterin with hot sodium chlorateand acid, or with cold nitrosylsulphuric acid, brings about disruption ofthe pyrimidine as well as of the pyrazine ring, and oxalylguanidine (CXLII)is formed; this is also produced by similar treatment of (CXVI; R =NH,).15*Other Synthetic Pterins.-M. Polonovski, R. Vieillefosse, and M . Pesson 159have prepared, from (CXVI; R = SH) and 1 : 2-dicarbonyl compounds,three non-fluorescent 2-mercaptopterins (CXLIII; R = SH; R’ = H,CO,H, Ph; R” = H, OH, Ph), which were converted into 2-hydroxy-analogues l6O, by alkaline hydrogen peroxide ; these authors have alsoshown that the mercaptopterins undergo S-ethylation, and they conclude,from the fluorescence shown by the 8-alkyl- and the hydroxy- (in contrast tothe 2-thiol) derivatives, that the characteristic fluorescence of pterins dependson the preservation of an intact * aromatic structure in the pyrimidine ring,i.e., the 2-hydroxy-compounds exist as such whereas the 2-thiol derivativesexist in the tautomeric form.Condensations between (CXVI; R = NH,and OH) and a-diketones have been extended to include phenanthraquinoneand acenaphthenequinone.162 The original use 132 of the term “ isoleuco-pterin ” now appears unwarranted; 146 instead, the name is given to thesynthetic pterin (CXLIV) .145 This substance, unlike leucopterin, fails toreact with nitrous acid (isoguanine and guanine are similarly differenti-ated); 145 on the other hand, the xanthopterin molecule is disrupted by thisreagent and does not yield the deaminoxanthopterin (CXLIII; R = R’ =OH; R” = H) obtainable from (CXVI; R = OH) and the bisulphitecompound of glyoxylic 15*The Vitamin B, ProbZem..F-Casual observation of progress in this fieldhas hitherto been somewhat difficult owing to the apparent complexity ofthe problem.At an early stage in the purification of the one or moregrowth factors having antianaemic and/or microbiological (L. casei E,S. Zactis R, 8. fmcalis R) growth-stimulating properties it became clear thatthe biological characteristics of the product were dependent on the source(liver, yeast, spinach, and other vegetable sources).Thus Peterson and15* C. SchBpf and A. Kottler, Annalen, 1939, 539, 128.169 Bull. SOC. chim., 1945, 12, 78; see also ref. 150.l 6 0 R. Kuhn and A. H. Cook, Ber., 1937, 70, 761.161 K. Ganapati, J . Indian Chem. Soc., 1937, 14, 627.162 C. K. Kain, BI. F. Mallette, and E. C . Taylor, jun., J . Amer. Chem. SOC., 1946,68, 1996.* In the opinion of the Reporter, a direct correlat.ion of fluorescence with “ aromatic-ity ” produced via prototropy seems to be an over-simplification. Arguments whichmay have some bearing on this point, and which are certainlyrelevant to the wholequestion of the fine structure of pterins and other hydroxy-heterocyclic nitrogen com-pounds, have recently been advanced by F.Arndt (Rev. Pac. Sci. Univ. Istanbul, 1944,9, 19), who discusses the conception that the “ aromaticity ” of such compounds iscompatible with their existence in the keto-dihydro- (CO-NH) form by virtue of anelectromeric shift to ~--C&H-, and is thus potentially independent of tautomerism.REP.-VOL. XLIII. IThis problem is dealt with later in its biochemical aspect (p. 296)258 ORGANIC CHEMISTRY.his co-workers 163 obtained from liver and from yeast a " norite eluatefactor " essential for growth of L. casei (A. helveticus), which also appearedto be vital to the growth of chicks; 164 and the preparation from spinachof a factor, designated folic acid, having growth-stimulating properties forL. casei, 8. lactis R, and other bacteria, was reported almost simultaneouslyby H.K. Mitchell et Later, J. J. Pfiffner et ~ 1 . l ~ ~ described the isolationof a crystalline antianEmic factor from liver extracts, which, following anearlier suggestion,167 was named vitamin B, ; identity of this substancewith the norite eluate factor was claimed,166 and identity with folic acidwas suggested.166 It was then found by J. C . Keresztesy et aL168 that'' various types of extracts and liver preparations " yielded a substancewhich, although much more active than folic acid for 8. Zactis R, was inactivefor L. cusei, whereas folic acid is equally effective for each micro-organism.On the other hand, E. L. R. Stokstad, working with crystalline preparationsfrom liver and from found that the liver factor was equally activefor L.casei and for 8. lactis R, but that the yeast factor was only half asactive as the liver preparation for S. Zactis R, whereas both preparationswere equally effective for L. casei; and a new L. casei factor from an undis-closed source 170 (later described 171 as a fermentation residue; the factoris named the fermentation L. casei factor) 171, 174 was stated to be 85-90% as active as the norite eluate (liver) factor for L. casei, but only 6%as active for S . Zmtis R.It is clear from these results that several factors are involved, and thisconclusion is substantiated by the results of antianBmic studies. Followingthe original observation that monkey anmnia could be cured by yeastextracts (" vitamin M "),172 it was found that chicken anEmia could like-wise be cured by a crystalline yeast factor and also by vitamin B,, whichwas chemically distinct from the yeast f a ~ t 0 r .l ~ ~ Vitamin B, thus possesses163 E. E. Snell and W. H. Peterson, J . Bact., 1940, 39, 273; B. L. Hutchings,N. Bohonos, and W. H. Peterson, J. Biol. Chem., 1941, 141, 521.16* B. L. Hutchings, N. Bohonos, D. M. Hegsted, C. A. Elvehjem, and W. H.Peterson, J . Biol. Chem., 1941, 140, 68l-.165 H. K. Mitchell, E. E. Snell, and R. J. Williams, J . Amer. Chem. SOC., 1941, 63,2284; 1944, 66, 267. See also E. H. Frieden, H. K. Mitchell, and R. J. Williams,ibid., 1944, 66, 269; H. K. Mitchell and R. J. Williams, ibid., p. 271; H. K. Mitchell,ibid., p. 274.166 J. J. Pfiffner, S. B. Binkley, E. S. Bloom, R.A. Brown, 0. D. Bird, A. D. Emmett,A. G. Hogan, and B. L. O'Dell, Science, 1943,97, 404.167 A. G . Hogan and E. M. Parrott, J . Biol. Claem., 1940, 132, 507.I b 8 J. C. Keresztesy, E. L. Rickes, and J. L. Stokes, Science, 1943,97, 465.Isa E. L. R. Stokstad, J . Biol. Chem., 1943, 149, 573.l70 B. L. Hutchings, E. L. R. Stokstad, N. Bohonos, and N. H. Slobodkin, Science,1944, 99, 371; see also E. S. Bloom, J. M. Vandenbelt, S. B. Binkley, B. L. O'Dell,and J. J. Pfiffner, ibid., 100, 295.171 R. B. Angier et al. (for names see ref. 174), ibid., 1945, 102, 227.172 P. L. Day, W. C. Langston, and W. J. Darby, Proc. Soc. Exp. Biol. Med., 1938,J. J. Pfiffner, D. G . Calkins, B. L. O'Dell, E. S . Bloom, R. A. Brown, C. J. Camp-38, 860.bell, and 0.D. Bird, Science, 1945, 102, 228SIMPSON : HETEROCYCLIC COMPOUNDS. 259both antianaemic and microbiological (L. casei E) activity; the crystallineyeast factor (known as vitamin B, conjugate), on the other hand, has verylittle microbiological activity (L. casei, 8. fcecalis), but yields vitamin B,on enzymic digestion.173From this seemingly confused background the following clarificationshave emerged as a result of recent work : (a) proof of structure and synthesisof the liver L. casei factor (pteroylglutamic acid); (b) identification ofpteroylglutamic acid with vitamin B, ; (c) establishment of the chemicalrelationship between vitamin B,, vitamin B, conjugate, and the ferment-ation L. casei factor.Structure of L. casei Factor.-The constitution of this substance hasbeen proved to be (CXLV) by a group of sixteen workers in the followingFission with sulphurous acid of the fermentation L.caseifactor yielded an amine fraction (a) together with 2-amino-6-hydroxy-pteridine-&aldehyde (CXLVI ; R = CHO). The orientation of the aldehydewas determined (i) by its conversion under anaerobic alkaline conditionsinto the corresponding acid (CXLVI; R = C0,H) and (CXLVI; R = Me),followed by vigorous hydrolysis of the latter, by the method of J. Weijlardl74et u Z . , ~ ~ ~ to the known 175 2-amino-5-methylpyrazine (CXLVII) ; (ii) by theconversion of the known acid derived from (CXXVI) 144 into (CXLVI;R = C0,H) by means of phosphorus pentachloride and hydriodic acid;and (iii) by decarboxylation of (CXLVI; R = C0,H) and synthesis of theresultant 8-deoxyxanthopterin from (CXVI; R = NH,) and glyoxal.The$-methyl derivative (CXLVI; R = Me) was also obtained by decarboxyl-ation of (CXLVI ; R = CH,CO,H), itself prepared by condensation of(CXVI; R = NH,) and ethyl 2-keto-3 : 3-dimethoxy-n-butyrate. Acidhydrolysis of the amine fraction (a) gave p-aminobenzoic acid and glutamicacid (3 mols.).The fermentation L. casei factor was converted by anaerobic alkalinehydrolysis into the liver L. casei factor and an a-amino-acid (2 mols.) ; mobicalkaline hydrolysis, on the other hand, gave (CXLVI; R = C0,H) and anamhe fraction from which p-aminobenzoic acid was obtained by further17' R. B. Angier, J. H. Boothe, B. L. Hutchings, J. H. Mowat, J.Semb, E. L. R.Stokstad, Y. SubbaRow, C. W. Waller, D. B. Cosulich, M. J. Fahrenbach, M. E. Hult-quist, E. Kuh, E. H. Northey, D. R. Seeger, J. P. Sickels, and J. M. Smith, jun., ibid.,1946, 103, 667.17' J. Weijlard, M. Tishler, and A. E. Erickson, J . Amer. Chm. Soc., 1946, 07, 802260 OROANIU OHEMISTRY.hydrolysis. Consideration of these results, together with those obtainedby the sulphurous acid degradation, indicated that the liver L. casei factorhas the structure (CXLV), and that the introduction of two more glutamicacid residues into this molecule produces the fermentation L. casei factor.Synthesis of the liver L. casei factor was achieved by two methods as shownin the accompanying scheme, the yield in each case being ca. lSy,. Theintermediate (CXLIX) was derived from I(+)-glutamic acid. It will benoted that each synthesis proceeds through a dihydro-derivative andsubsequent in situ oxidation.(a) (CXVI ; R = NH,)yHBr*CH2Br + H2N<I>O*NH*CH*[CH2]2*C0,H (CXLIX.)+ 7 0 2 3 3CHO I acetate buffer(CXLVIII .) (UXLIX) + NaOMe + 4,(CXLV) fJ.J. Pfiffner et al. have shown 176 that vitamin B, conjugate consists ofthe vitamin combined with six glutamic acid residues in peptide form;comparison of the vitamin itself with pteroylglutamic acid showed that thetwo substances are identical. The biological specificity of vitamin B, con-jugate, of pteroylglutamic acid, and of the fermentation L. cusei factorthus depends on the nature of the acid side chain (or chains) attached toa common nucleus; and this conception is strengthened by the observationof Angier et al.174 that, if p-aminobenzoic acid is used instead of (CXLIX),syntheses (a) and (b) lead to a product which is active for 8.fceculis R butdevoid of activity for L. m e i and for chicks.It has also been shown that, for. antianmnic activity, the presence of aside chain is unnecessary. Thus nutritional anzmia of rats128 and offish 179 can be cured by administration of xanthopterin, and ichthyopterin(fluorescyanine) is curative in riboflavin-deficient rats and in aneurin-deficient rats and ~ i g e 0 n s . l ~ ~ A number of other synthetic pterins alsopossess this interesting dual biological activity for the rat and the pigeon;certain micro-organisms (Glaucoma, Polytomella C ~ c a ) , however, are moreexacting in their requirements, and are unable to utilise pterins in place ofa n e ~ r i n . l ~ ~In conclusion, two points of nomenclature should be mentioned. Inthe first place, recent comments on the synthesis of pteroylglutamic176 J. J. Pfiffner, D. G . Calkins, E. S. Bloom, and B. L. O’Dell, J . Amer. Chem. SOC.,17’ K. A. Jensen, Dansk Tidsskr. Farm., 1946, 20, 219; Lancet, 1946, i, 969;1946,68, 1392.1946, ii, 532, 680SIMPSON : HETEROCYCLIU COMPOUNDS. 261acid refer to this substance as folic acid, whereas the American workersconsistently l717 17*,l78 use the names pteroylglutamic acid or liver L. caseifactor when referring to their synthetic product. This distinction shouldclearly be retained for the present, because no announcement has beenmade of formal proof that the folic acid of H. K. Mitchell et is identicalwith pteroylglutamic acid; indeed, B. L. Hutchings et al. have pointedout 170 that absorption spectra measurements indicate that folic acid isnot identical with vitamin B,, vitamin B, conjugate, or the fermentationL. casei factor, and no modification of this view has appeared in literatureavailable t o the Reporter. Secondly, the American workers have departedfrom the established numbering of the pteridine nucleus (based on analogywith the purine ring-system), and have used a method 1627 174 based onlumazine 175 as the parent nucleus; this introduces an unnecessary com-plication, and the established nomenclature has been used throughout thisReport. J. C. E. S.W. BAKER.D. H. HEY.L. HUNTER.M. M. JAMISON.J. K. N. JONES.M. S. LESSLIE.C. m7. SHOPPEE.J. C. E. SIMPSON.E. E. TURNER.178 R. €3. Angier, Dansk Tidsskr. Farm., 1946, 20, 288.179 R. TVY. Simmons and E. R. Norris, J . Biol. Chem. 1941, 140, 679

ISSN:0365-6217    

DOI:10.1039/AR9464300138

出版商:RSC    

年代:1946

数据来源: RSC

摘要:

BIOCHEMISTRY.I. INTRODUCTION.THE continual development of biochemistry, reflected in its widening scopeand greatly increased specialisation, has for some years made inevitable agradual change in the nature of this section of the Reports. Whereas itwas earlier possible to survey in outline almost all the year’s principaladvances, fewer subjects can now be included each year in the space avail-able, unless their treatment is to be so superficial as to consist of littlemore than a catalogue.In the present Report, therefore, a selection of the important develop-ments is presented in the form of brief reviews, in some of which it hasbeen found possible to include more reference to the general backgroundthan was possible in the older form of annual annotation. Difficultiesdue to the still delayed publication of war-time researches remain a con-siderable handicap to the Reporters, and for this reason a contemplatedsurvey of the sulphydryl enzymes could not be completed for inclusion inthe present Report.I?.D.2. BIOLOGICAL METHYLATION.*About one hundred years ago several cases of poisoning occurred inGermany and were ascribed to the use of arsenical pigments on wall-papers.Summaries of the earlier literature on this subject have been published byR. Abel and P. Buttenberg,l H. HUSS,, and A. Maa~sen.~ L. Gmelin4noticed a garlic odour in rooms where the symptoms had developed. Thishe ascribed to a volatile arsenic compound liberated from the damp andmouldy wall-paper. F. Selmi suggested that the moulds producedhydrogen which, acting on the pigment, gave rise to arsine.A suggestionthat the gas was arsine had already been made by Martin in 1847but without reference to mould action. In 1846 Basedow suggested,but without experimental support, that the air of the rooms might containcacodyl oxide, Me,AsO*AsMe,.exposed a potato-mash containing arsenious oxideto the air. It quickly became infected with moulds and bacteria andevolved a garlic odour. Some of the moulds were intensely active,especially one which Gosio named Penicillium brevicaule-the modern nameIn 1891 B. Gosio2. Hyg., 1899, 32, 499.Arb. KaiS. Gesund., 1902, 18, 479. Karlsruher Zeitung, November 1839.Ber., 1874, 7, 1642. Gazette Mkdicale, 1847, Feb. 13, 130.7 Schmidt’s Jahrbuch, 1846, 52, 89.Arch.Itul. Biol., 1893, 18, 253, 298; ibid., 1901, 35, 201; Ber., 1897, 30, 1024.* Parts of this report are based on earlier articles by the author, particularly thata Ibid., 1914, 76, 361.published in Chem. Reviews, 1945, 38, 315CHALLENGER : BIOLOGICAL METHYLATION. 263is Scopulariopsis brevicaulis. Other organisms which exhibited this pheno-menon were Aspergillus glaucus, A . virens, and Mucor Mucedo. C. Thomand K. B. Raper extended this list to include A . Jischeri, A . sydowi, anda few soil organisms.B. Gosio 8 elaborated a biological method for the detection of traces ofarsenic in aqueous extracts of various materials. The evaporated extractwas added to a slice of sterile potato previously inoculated with 8.brevi-caulis. After a few hours at 25-30' inorganic arsenic could be detectedby the production of a garlic odour. H. R. Smith and E. J. CarneronlOstate that one-millionth of a gram of arsenious oxide in one gram ofmaterial can thus be recognised.By passing " Gosio-gas " from arsenical cultures of 8. brevicaulis througha hot tube, Gosio qoncluded that the gas contained an alkylarsine. P. Bigin-elli l1 aspirated the gas through mercuric chloride in dilute hydrochloricacid. The resulting precipitate was assigned the composition AsHEt2,2HgC1,,and Biginelli concluded that the gas was diethylarsine. P. Klason,lZ fromBiginelli's analyses and some further work, regarded it as diethylarsineoxide. N. Wigren l3 synthesised both these compounds and showed thattheir behaviour towards acid mercuric chloride (Biginelli's solution) wasdifferent from that of Gosio gas.Owing to the uncertainty regarding the nature of Gosio-gas work wascommenced by Challenger et al.in 1931. Four strains of 8. brevicaulis wereemployed.Sterile aqueous solutions of various arsenic compoundtJ were added tobread cultures of 8. brevicaulis arranged in series. Sterile air was passedthrough and volatile arsenic compounds absorbed in Biginelli's solution.Using arsenious oxide (0.2-0-25% in the bread) two different depositswere obtained according to the concentration of the mercuric chloride,consisting of the di- and the mono-mercurichloride of triniethylarsine,AsMe3,2HgC1, and AsMe,,HgCl,. Gosio-gas is therefore trimethylarsine.14Direct comparison with an authentic specimen confirmed this conclusion.With sodium methylarsonate, AsMeO(ONa), (1-1-5% in the bread), orsodium cacodylate, AsMe,O*ONa (0-1-0-3 yo in bread) (free from inorganicarsenic), the evolved gas gave the same mercurichloride.The identity of Gosio-gas was then confirmed by several observations.By absorption in nitric acid trimethylhydroxyarsonium nitrate,AsMe,(OH)*NO,, and the corresponding picrate were prepared, identicalwith those obtained from the synthetic arsine.Gosio-gas with alcoholicbenzyl chloride gave a quaternary salt and thence benzyltrimethylarsoniumpicrate.Evans et aE. l5 suggest a bimolecular structure for trimethylarsinedimercurichloride.lo Ind. Eng. Chem. (Anal.), 1933,5,400.l3 Annalen, 1924, 437, 285.Science, 1932, 76, 648.l1 Gazzetta, 1901, 31, 58.l4 P.Challenger, (Miss) C. Higginbottom, and L. Ellis, J., 1933, 95.l2 Ber., 1914, 47, 2634.R. C. Evans, F. G. Mann, H. S. Peiser, and D. Purdie, J., 1940, 1215264 BIOOHEMISTRY.Alkylarsonic Acids and S. brevicaulis.It seemed possible that the mould might cause fission of the arsenic-carbon link in sodium methylarsonate and cacodylate giving inorganicarsenic, or that the trimethylarsine might have arisen by reduction followedby dismutation, thus :AsMeO(OH), + AsMe(OH), ---+ AsMeO.3AsMeO = AsMe, + As,O,AsMe,O*OH -+ AsMe,-OHand3AsMe2*OH = ZAsMe, + As(OH),With sodium ethylarsonate in bread cultures of the mould dimethylethyl-arsine, AsMe,Et, was evolved and identified as the mercurichloride, thuseliminating both these possibilities.Absorption in benzyl chloride yielded benzyldimethylethylarsoniumchloride and in nitric acid dimethylethylhydroxyarsonium nitrate whichwere characterised as the picrates.This reaction was then studied further.16Addition of ( a ) diethylarsonic acid, AsEt,O*OH, (b) n-propylarsonic acid,and (c) allylarsonic acid, CH,:CH*CH,*AsO( OH),, to similar cultures of thesame strain of the mould in concentrations varying from 0.2 to 0.5% gavemixed methylated arsines.From ( a ) methyldiethylarsine was obtained and from ( b ) dimethyl-n-propylarsine. This arsine was also -obtained with methyl-n-propylarsonicacid and S. brevicaulis. It was identified as the dimercurichloride and asdimethyl-n-propylhydroxyarsonium picrate. Ethyl-n-propylarsonic acidgave methylethyl-n-propylarsine, and (c) gave dimethylallylarsine,CH,:CH*CH,*AsMe,, characterised as the dimercurichloride and as benzyl-dimethylallylarsonium picrate.Methylation of Inorganic Compounds of Xelenium and Tellurium.0.Rosenheim l7 showed that, when 8. brevicaulis was grown uponsterile bread containing inorganic compounds of selenium and tellurium,unpleasant odours were evolved. The substances responsible were notidentified. A. Maassen,18 judging entirely from odour, stated that thevolatile products were diethyl selenide and diethyl telluride. He alsoexamined the breath of animals injected with inorganic selenites andtellurites, and believed that here the odour was due to dimethyl selenideand dimethyl telluride (see also Japha 19).A similar conclusion on equallyunsatisfactory evidence had been reached as regards animals injectedwith tellurium compounds by F. Hofmeister.20 Maassen concluded there-fore that the animal body deals with compounds of selenium andtellurium differently from the organism of the mould.Methylation of Inorganic Compounds of Selenium.-The gas evolved fromRosenheim’s cultures containing selenium compounds was identified by113 F. Challenger and L. Ellis, J., 1935, 396; F. Challenger and A. A. Rawlings,J., 1936, 264.l7 Proc., 1902, 138.la Dissertation, Halle, 1842.l8 Arb. Kais. Gesund., 1902, 18, 479.20 Arch. exp. Path. Pharm., 1894, 33, 198CHALLENGER : BIOLOGICAL METHYLATION.265F. Challenger and H. E. North.21 The volatile products from severalcultures of two different strains of S. brevicaulis on bread containing sodiumselenate or selenite were aspirated through absorbents and characterised asdimethyl selenide mercurichloride and mercuribromide, SeMe2,HgX,,dimethylhydroxyselenonium nitrate, dimethyl selenide or-platinochloride,and benzyldimethylselenonium chloride, isolated as the picrate.Methylution of Inorganic Compounds of Tellurium-The odour exhaledby animals receiving inorganic derivatives of tellurium was first observedby C. Gmelin.22 A. H a n ~ e n , ~ ~ on administration of potassium telluriteto dogs or men, detected a garlic odour in the breath after a few minutes.This lasted for weeks, and the persons in question were obliged to forsakethe society of their fellows. See also W.B l ~ t h , ~ ~ who mentions the pheno-menon of " bismuth breath ", formerly well known to pharmacists and dueto the presence of traces of tellurium in medicinal preparations of bismuth.Further details are given by G. Brownen,Z5 E. A. Letts,26 and A. Rei~sert.~'In no case was the odorous substance satisfactorily identified.(Miss) M. L. Bird and F. Challenger 28 aspirated the product evolvedfrom test-tube cultures of S. brevicaulis on bread containing potassiumtellurite through about 5 C.C. of reagent. Oxidation was thus diminishedand dimethyl telluride mercurichloride was obtained and converted intodimethyl telluride dibromide. Absorption in alcoholic iodine gave dimethyltelluride di - iodide.The mould gas is therefore dimethyl telluride, and Maassen's statementthat it consists of the diethyl compound is incorrect.This conclusion wasalso confirmed with liquid cultures on 2 yo glucose-Czapek-Dox medium.Methyluting Capacities of certain Penicillia.A green mould which appeared as a spontaneous infection on breadcrumbs moistened with a tellurite solution was found by Dr. Thom of theU.S. Department of Agriculture, Washington, to be closely allied to Peni-cillium notatum, Westling. Cultures on bread and on 2% glucose-Czapek-Dox medium containing tellurite evolved dimethyl telluride which wasidentified as before and as benzyldimethyltelluronium picrate.P. chrysogenum Thom in tellurite-bread cultures gave dimethyl telluride,but only a faint odour was observed with P.notatum. Both organismsreadily gave dimethyl selenide in bread cultures containing selenite orselenate. This was also produced in bread-selenate cultures by the " greenmould ".I n bread cultures none of the three green Penicillia gives trimethylarsinewith arsenious acid, but all convert sodium methylarsonate into trimethyl-21 J . , 1934, 68.22 " Wirkungen . . . auf den tierischen Organismus", Tubingen, 1824, 43.23 Annalen, 1853, 86, 213.** " Poisons : their Effects and Detection ", 1884, 588.25 Pharm. J . , 1876, 6, 561.27 Arner. J . Pharm., 1884, 56, 177.26 Ibid., 1878, 9, 405, 407.28 J., 1939, 163266 BIOCHEMISTRY.arsine which is also produced in similar cultures of P.chrysogenum andP . notutum containing sodium cacodylate. Although methyl groups arepresent in the substrate, dismutation appears to be excluded because breadcultures of P . chrysogenum convert sodium allylarsonate into dimethyl-allylarsine, CH,:CH*CH,*AsMe,.Fission of the Disulphide Link in Dialkyl Disulphides by 8. brevicaulis andMethylation of the Alkyl S-Group.Attempts were made to obtain dimethyl sulphide by the use of twodifferent strains of 8. brevicaulis. Negative results 21 were obtained withsulphur, sodium sulphite, sodium thiosulphate, sodium tetrathionate,thiourea, thiodiglycollic acid and its sodium salt, and sodium formaldehyde-sulphoxylate ('< rongalite ',), and also with sodium ethanesulphonate andethanesulphinate, the last-named compound in liquid cultures.This was somewhat surprising in view of the experiments of 5.P ~ h l , , ~who noticed a leek-like odour in the breath of animals receiving injectionsof thiourea. The odorous product was non-reactive to sodium hydroxideor mercuric cyanide, and was therefore not an alkanethiol. It was, how-ever, absorbed by sulphuric acid and gave a precipitate with mercuricchloride. Pohl therefore concluded that the product was an alkyl sulphide.A similar odour is exhaled by patients suffering from hyperthyroidism andreceiving thiourea.30C. Neuberg and P. Grosser 31 stated that the precursor of the diethylsulphide which was shown by J. J. Abe13, to be evolved on warming theurine of dogs with alkali is methyldiethylsulphonium hydroxide ; also thatadministration of diethyl sulphide to dogs gives rise to this compound.Experimental details are lacking.The occurrence in nature of compounds such as cheirolin,CH3*S02*CH2*CH2*CH,-N:C:S ,erysolin, CH,*S0,*CH2*CH,*CH,*CH2*N:C:S 33 and methionine,demonstrates the possibility of a biological methylation of sulphur.Therelation of methionine to cysteine and to cystine suggested that compoundscontaining the -SH or -S-S- links might be more amenable to the methyl-ating action of the mould.Disulphides (R*S*S*R; R = Et or n-Pr) with excess of saturated aqueousmercuric chloride give insoluble compounds SR*HgC1,HgC1,,34 identicalwith those obtained from the alkanethiols. With dimethyl and diethyldisulphides the soluble products were shown to be the alkanesulphinicCH,-S*CH,*CH,*CH( NH,)-CO,H,29 Arch.exp. Path. Pham., 1904, 51, 341.30 References given by F. Challenger, Chem. Reviews, 1945, 36, 333.31 Centr. BE. PhysioE., 1905-1906, 19, 316.92 2. physiol. Chem., 1894, 20, 253.33 For references see E. F. Armstrong and K. F. Armstrong, " The Glycosides ",34 F. Challenger and A. A. Rawlings, J., 1937, 868.1931, 66CHALLENGER : BIOLOGICAL METHYLATION. 267acids, RSO,H, formed by dismutation of the sulphenic acid, SR-OH. Thesulphinic acids were characterised by Blackburn and Challenger 35 as thep-nitrobenzyl alkyl sulphones.S. brevicaulis and Dialkyl Disulphides.The behaviour of disulphides to mercuric chloride having been estab-lished, dialkyl disulphides (methyl to n-amyl) were added in dilute aqueoussuspension to bread cultures.The volatile products contained the alkane-thiol, SHR [absorbed in mercuric cyanide giving (SR),Hg], the unchangeddisulphide, R-SS-R, and the methyl alkyl sulphide, SRMe. The pre-cipitates obtained with mercuric chloride were mixtures of the mercuricchloride addition product of the methyl alkyl sulphide with varying amountsof RSHgCl,HgCl,, arising from fission of RS-SR. On treatment of thesemixtures with sodium hydroxide, pure methyl alkyl sulphide was evolved;this was converted into the mercurichloride, the benzylmethylalkylsulph-onium picrate, or the double compound with platinous chloride.The fission of the disulphide link by 8. brevicaulis appears, therefore,to be a general reaction of the simple aliphatic disulphides.as35Methylation of Inorganic Sulphate by Schizophyllum commune.Birkinshaw, Findlay, and Webb 36 have shown that the wood-destroyingfungus Schizophyllum commune, Fr., when grown on an aqueous mediumcontaining glucose, inorganic salts, and a trace of " marmite ", convertsinorganic sulphate into methanethiol.This was characterised as mercurythiomethoxide (SMe),Hg. Traces of hydrogen sulphide are also produced.This is the only recorded instance of the mycological methylation of in-organic sulphur. Although S. brevicaulis forms dimethyl selenide frominorganic selenium compounds no methylselenothiol is produced. F. Chal-lenger and P. T. Charlton37 find that dimethyl sulphide and disulphideaccompany the methanethiol evolved by S.wmrnune. The disulphideprobably arises by aerial oxidation of the thiol.Mycological Fission of the Carbon-Sulphur Link.The methanethiol evolved by cultures of 8. commune might possibly beformed by fission of the terminal SMe group of methionine,CH,*S*CH,*CH,*CH( NH,)*CO,H,synthesised by the fungus. Addition of dl-methionine to cultures of 8. com-mune, however, gave only traces of methanethiol. The question arosewhether a similar stability would be exhibited by methionine in breadcultures of 8. brevicaulis. Actually the amino-acid was readily convertedinto methanethiol and dimethyl sulphide. Under identical conditionsS-methyl-, -ethyl-, and -n-propylcysteine gave the corresponding alkanethioland methyl alkyl ~ulphide.~? This fission of the G S link appears to be a36 S.Blackburn and F. Challenger, J., 1938, 1872.36 J. H. Birkinshaw, W. P. K. Findlay, and R. A. Webb, Biochem. J., 1942, 36. 526.37 J . , 1947, 424268 BIOCHEMISTRY.new type of mycological action. The mechanism may be reductive givinghomoalanine as the other primary product, or hydrolytic when homoserine,CH,( OH)*CH,-CH(NH,)*CO,H, would be formed.The alkanethiols obtained in X. brevicaulis cultures from methionineand the S-alkylcysteines may be formed by the fission of the correspondingketo-acids rather than directly from the amino-acids. Methionine is con-verted by kidney or liver slices38 and also on feeding to rats39 into theketo-acid, CH3*S*CH2*CH2*CO*C02H. This keto-acid readily yields methane-thiol with dilute acids or alkalis.The fission of the C-SMe link in methionine and the X-alkylcysteines bymould cultures has only one other biological counterpart, namely the-probably reversible-fission of the unsymmetrical amino-acid cystathionine,CO,H*CH (NH,) *CH,*S*CH,*CH,*CH (NH,) *CO,H .40 In presence of rat liveror kidney slices or saline extracts of rat liver this gives cysteine and possiblyhomoserine or its phosphoric ester.41 Cystathionine appears to play animportant part in the biological conversion of methionine into cystine.42, 43Oxidative Demethylation of N-methyl Compounds.K.Hess et aLU showed that N-methylated keto-acids derived frompyrrolidine and piperidine on treatment with phenylhydrazine or semi-carbazide yield secondary alcohols, the >NMe group giving rise to >NHand the phenylhydrazone or semicarbazone of formaldehyde.Recent investigations using isotopic indicators show that certainmethylated amino-acids or amines undergo demethylation by animals oranimal tissues.Dimethylaniline yields the glycuronate of p-methylaminophenol inrabbits.45 Some methylaniline was detected in the urine.Demethylationof dimethylaniline to aminophenol is also effected by dogs. M. Lewisand R. A. Tager 46 state that N-methyl- and NN-dimethyl-sulphanilamidesare demethylated when administered to men or mice.E. S. Stevenson, K. Dobriner, and C. P. Rhoads4' found that in ratsdemethylation of p-dimethylaminoazobenzene occurs, accompanied byfission and reduction of the azo-linkage, and that the urine contains p-amino-phenol, N-acetyl-p-aminophenol, p-phenylenediamine, and NN'-diacetyl-p - phenylenediamine.Some earlier work may first be cited.38 E.Borek and H. Waelsch, J . Biol. Chem., 1941, 141, 99.39 H. Waelsch, ibid., 140, 313.40 G. B. Brown and V. du Vigneaud, ibid., 137, 61 1 ; V. du Vigneaud, G. B. Brown,and J. P. Chandler, ibid., 1942, 143, 59.41 F. Binkley and V. du Vigneaud, ibid., 144, 507; 3'. Binkley, W. P. Anslow, andV. du Vigneaud, ibid., 143, 659.42 D. Stetten, ibid., 144, 501.43 V. du Vigneaud, G. W. Kilmer, J. R. Rachele, and (Miss) M. Cohn, ibid., 1944,4 4 Ber., 1913, 46, 4104; 1915, 48, 1886; 1917, 50, 344, 351, 385.4 5 F. Horn, 2. Physiol. Chem., 1936, 242, 23; 1936, 238, 84.46 Yale J .Biol. Med., 1940, 13, 111.155, 645.4 7 Cancer Research, 1942, 2, 160CHALLENGER : BIOLOGICAL METHYLATION. 260K. Bloch and R. Schoenheimer 48 fed rats with (a) isotopic glycine and( b ) isotopic sarcosine (N-methylglycine). Glycine was. isolated from thetissue protein as the trioxalatochromate, the concentration of isotopicnitrogen being almost identical in each case. It is suggested that sarcosineis demethylated in the tissues without loss of nitrogen, and sarcosine canreplace glycine as a detoxicating agent when benzoic acid is fed to rabbits.N-ethylglycine causes no increase in the rate of excretion of hippuric acidwhen administered with benzoate to rabbits, suggesting that de-ethylationis at any rate a much slower process.49 The oxidative demethylation ofsarcosine to formaldehyde and glycine has been established with brokencell preparations of the liver of cats and Other N-methylamino-acids are not necessarily metabolised in the same way, N-methylalaninegiving pyruvic acid and methylamine with amino-acid o x y d a ~ e .~ ~du Vigneaud et ~ 1 . ~ ~ have shown that, unlike certain closely relatedcompounds (which do not eliminate a methyl group as formaldehyde),sarcosine exerts no methylating action in animal experiments (see p. 274).N1-methylnicotinamide (see p. 273) is stated 53 to undergo demethylationto nicotinic acid in rats when administered with glycocyamine. No increasein the urinary output of creatine and creatinine was observed.hasdiscussed the evidence available before 1945 for the demethylation ofpurines in animals or animal tissues and concludes that the question isstill controversial.Caffeine does not take part in transmethylation 55 (seep. 274).From a recent study of the metabolism of the mono-, di-, and tri-methyl-uric acids in the Dalmatian dog and albino rat, V. G. Myers and It. F.Hanzal 56 conclude that 3-methyluric acid appears to be completely demethyl-ated and converted into uric acid; the 1 : 3 : 7 derivative is partiallydemethylated in position 7, and the 1 : 3 compound is largely unchangedthough some demethylation may occur a t 3.In a comprehensive review on biological methylation, S. J. BachMechanism of Biological Methylation.Three mechanisms have been suggested to account for the phenomenaThe of biological methylation and the evidence has been fully disc~ssed.~’4a J .Biol. Chem., 1940, 135, 99.49 L. P. Abbot and H. B. Lewis, J . Biol. Chem., 1939, 131, 479; 1941, 137, 535.P. Handler, M. L. C. Bernheim, and J. R. Klein, J. Biol. Chem., 1941,138, 211;compare K. Hess, reference 44.61 D. Keilin and E. F. Hartree, Proc. Roy. SOC., 1936, B, 119, 114.52 V. du Vigneaud, J. P. Chandler, A. W. Moyer, and D. M. Keppel, J . Bid. Chem.,63 V. A. Najjar and (Miss) C. C. Deal, ibid., 1946, 162, 741.S4 Biol. Rev., 1945, 20, 158, 167.6 6 A. W. Moyer and V. du Vigneaud, J . Biol. Chem., 1942, 143, 373.6 6 Ibid., 1946, 162, 309.5 7 F. Challenger, Chem. and Ind., 1942, 61, 399, 413, 456; Chem. Reviews, 1945,1939, 131, 57.36, 315270 BIOCHEMISTRY.first of these involves the interaction of acetic acid with the compoundundergoing methylation and is based on the well-known " cacodyl re-action ".The second, the form-aldehyde hypothesis, merits further discussion on purely chemical grounds,and also in view of the production of formaldehyde by oxidative demethyl-ation under biological conditions. No direct evidence for this hypothesisis available on the biological side, however.For the third hypothesis-that of transmethylation-conclusive evidencehas been obtained from animals, though not yet from moulds. Themechanism by which the methyl group is transferred still remainsobscure.The Formaldehyde Hypothesis.-In moulds and animals any formaldehydeinvolved in methylation reactions is presumably of secondary origin andeven in plants some may arise by the demethylation of NMe groups, orby oxidation of purines to uric acid which, by way of allantoin, can giverise enzymically to glyoxylic acid, CHO*CO,H, and urea as shown by M.R.Fosse and A. Brunel and their colleague^.^*It was not possible to apply a crucial test to the formaldehyde hypothesisas regards moulds. In its application to the production of trimethylarsinefrom arsenious acid this postulates the formation of hydroxymethylarsonicacid, CH,(OH)*AsO(OH),, as the first stage, followed by reduction to methyl-arsonic acid, Me*AsO( OH),. After further reduction to Me.As(OH), theisomeric form Me*AsO(OH)H might be expected to react again with form-aldehyde, repetition of the process yielding cacodylic acid, Me,AsO*OH,and finally trimethylarsine.Hydroxymethylarsonic acid could not besynthesised, and its homologue CH,( OH)*CH,*AsO( OH), in bread culturesof the mould gave no volatile product. Had reduction of the p-hydroxylgroup occurred the formation of dimethylethylarsine would have beenexpected.5 *aIf selenious and tellurous acids can react as SeO,(OH)H and TeO,(OH)Hthe formaldehyde hypothesis can explain their conversion into dimethylselenide and dimethyl telluride in mould cultures. The work of W. Streckerand W. Daniel 59 raises doubt as to whether selenious acid can react inthis form. See, however, J. Loevenich, H. Fremdling, and M. Fohr 6o whofind that p-naphthylseleninic acid, CIoH,*SeO,H, gives a normal ester andalso a selenone.As applied to the fission of disulphides and methylation of the resultingthiol, the formaldehyde hypothesis demands the formation of RS*CH,*OH.Compounds of this type have been described 61 but are unstable and easilyIt need not be further considered here.Numerous references cited in Ohm.Reviews, 1945, 36, 338.F. Challenger, C. Higginbottom, and L. Ellis, J . , 1933, 95; F. Challenger andC. Higginbottom, Bwchem. J . , 1935, 29, 1757.5D Annalen, 1928, 462, 186.6o Ber., 1929, 62, 2856.T. G. Levi, Gaxzetta, 1932, 62, 775; F. Challenger and A. A. Rawlings, J.,1937, 868CHALLENGER : BIOLOGICAL METHYLATION. 27 1hydrolysed. The compound CH3*CH2*S*CH2*OH could not be freed fromtraces of ethanethiol and so its capability of reduction to SMeEt in mouldcultures could not be determined.6lThe Transfer of a Methyl Group-The transfer of a methyl group fromsome methylated compound such as choline or betaine was suggested by0.Riesser e2 to explain the production of creatine and of alkylated (pre-sumably methylated) derivatives of selenium and tellurium in animals.63F. Challenger and (Miss) C. Higginbottom 64 and F. Challenger, P. Taylor,and B. Taylor 65 found that sodium sulphite, organic disulphides, sodiumselenite, and sodium tellurite when heated with betaine (free from hydro-chloride, to avoid the formation of methyl chloride) and in absence ofsodium formate, yielded dimethyl sulphide, methyl alkyl or methyl arylsulphide, dimethyl selenide, and dimethyl telluride.All these praductswere characterised. The last three reactions exhibit a parallel with thebehaviour of these substances in cultures of S. brevicaulis (see pp. 265, 267).R. Willstatter 66 found that, on heating, betaine forms methyl dimethyl-aminoacetate , Me,N*CH,*CO,Me, a reaction clearly involving the migrationof a methyl It was suggested by F. Challenger 6s that these pyro-genic reactions might proceed as follows : (1) Me3d*CH,*CO0 + Na,SeO, =Me,N*CH,*CO,Na + MeSe0,Na. With selenites and tellurites a quaternarysalt is possibly first formed. The dimethyl selenide presumably arises bydecomposition of the sodium methaneselenonate. (2) Me36*CH,*CO0 +RS*SR = Me,N*CH,*CO,SR + RSMe. Under similar conditions primaryaromatic amines yielded N-monomethyl derivatives.I n the absence of any evidence as to the kinetics of these pyrogenicbetaine decompositions it is impossible to say whether a free methyl ionis concerned in the reactions.Experimental evidence is equally lacking as regards the kinetics of theproduction of methyl derivatives by living cells.Considering first aunimolecular mechanism of type X,1 it is noticed that almost all the com-pounds which undergo methylation by moulds or animals can give negativeions, which contain unshared electrons, so that co-ordination of a positivemethyl group would give a neutral molecule.69 This could then undergoreduction and ionisation followed by further co-ordination of a CH3+radical.Methylation of Arsenic, Selenium, and Tellurium Compounds.-The62 2.physiol. Chem., 1913, 86, 440.G3 See F. Hofmeister, Arch. exp. Path. Pharm., 1894, 33, 198.64 Biochem. J . , 1935, 29, 1757.e 5 J . , 1942, 48.66 Ber., 1902, 35, 584.67 Compare also H. T. Straw and H. T. Cranfield, J . SOC. Chem. Ind., 1936, 55,0 8 Chem. and Ind., 1942, 61, 413, 456.60 F. Challenger, Chem. Reviews, 1945,36, 341, 347; E. D. Hughes and C. K. Ingold,40 T..I.. 1933. 1571: J. L. Gleave. E. D. Hughes, and C. K. Ingold, J . , 1936, 236272 BIOCHEMISTRY.mechanism suggested by the b e d s school 69 may be illustrated in the caseof arsenious and selenious acids :+ 0‘OH(1) As(OH), ,+ H + (HO),AsO % CH3-AsfOH -+ .. ionMethylarsonic acidReduction OH c&H + CH,-AsfOH+ CH3-As( --+ ..‘0 ion 0Cacodylic acidH3C ReductionH3C:As+0 ----+ (CH,),As: .. H3C Trime thy larsineTrimethylarsine oxideThe suggested intermediate compounds have not been detected inmould cultures, but they all yield trimethylarsine when present in breadcultures of 8. brevicaulis.+ 0 Ionisation 0(2) H2Se03 --+ H + :Se/OH CH3*SefOH $ and reduction&Oion Methaneselenonic acid-/ O CHT f Reduction CH,*Se: -+ (CH3),Se4 -+ (CH3)2Bk:$0 0Ion of methane- Dimethylseleninic acid selenoneDimethylselenide.The postulated intermediate selenium compounds have not been detectedin the media, but (Miss) M. L. Bird and F. ChalIenger 70 showed that8. brevicaulis and certain Penicillia convert methane-, ethane-, and propane-1 -seleninic acids, RSeO,H, into dimethyl, methyl ethyl, and methyl n-propylselenides, RSeMe, as required by the suggested mechanism, thus :Reduction +RSeO, + CH, --+ R*SeO,*CH, + R-Se-CH,They point out, however, that direct reduction of the seleninic acid toselenothiol, R,*SeH, might occur followed by methylation to R*SeMe, thusavoiding the selenone stage.Potassium methane-, ethane-, and propane- l-~elenonates,~~ RSeO,*OK,in cultures of the same moulds gave only dimethyl selenide, owing to break-down of the selenonate giving R-OH and KHSeO,.This observation doesnot necessarily invalidate the suggested mechanism since the methane-70 J . , 1942, 574. 71 (Miss) M. L. Bird and F. ChaIlenger, J . , 1942, 570CHALLENGER : BIOLOGICAL METRYLATION. 273selenonic acid might be sufficiently stable, within the cell, to reach thenext stage without hydrolysis.Methylation of Sulphur Cmpounds.-The methyl alkyl sulphides obtainedfrom dialkyl disulphides in cultures of S.brevicuulis may arise by ionisationof alkanethiol first produced, followed by co-ordination of CH,, or thismay occur before fission.72Addition of sodium sulphite, methanesulphonate, or ethanesulphinate,Et*SO,Na, to liquid cultures of the mould gave no dimethyl or methylethyl sulphide. This might possibly be ascribed to the formation of methane-sulphonic acid or of dimethyl or methyl ethyl sulphone by reactions analogouswith those postulated for sodium selenite. Diethyl sulphone, unlike diethyls~lphoxide,~~ is not reduced to diethyl sulphide by S.brevicuulis, andsulphones, if formed, would probably accumulate, but the liquid culturemedia yielded no dimethyl or methyl ethyl sulphone. Methanesulphonicacid might also resist further reaction, when neither sulphone nor sulphidewould be formed. Attempts to detect this acid in liquid cultures con-taining sodium sulphite failed.Methylation of Nitrogen Compounds.-Co-ordination of a positive methylion would also explain the well-known conversion of neutral pyridine 74and quinoline 75 into methylpyridinium and methylquinolinium hydroxidesin the body of the dog.The formation of trigonelline 76 or N1-m ethylnicotinamide 77 (see below)on administrat,ion of nicotinic acid to various animals can be explained inthe same way.One alternative to methylation by elimination of a positive methyl ionis a bimolecular reaction of the Sx2 type.78Since, however, this also ultimately involves the attachment of methylto the unshared electrons of the metalloid the formulations on pp.271-272may be retained for convenience in representing the suggested intermediatestages in the methylation process. It is possible, however, that methylmay be transferred as a neutral radical. Attempts to obtain evidence ofthis by addition of sulphur, in powder or as a colloidal solution, or of finely72 F. Challenger, P. Taylor, and B. Taylor, J . , 1942, 48; F . Challenger, Chem.Reviews, 1945, 36, 344.73 F. Challenger and H. E. North, J., 1934, 68.74 W. His, Arch. exp. Path. Pharm., 1887, 22, 253.75 Y .Komori et al., J . Biochem. (Japan), 1926, 6, 21, 163;76 D. Ackerman, 2. Biol., 1912, 59, 17.7 7 J. W. HntTand W. A. Perlzweig, J . Biol. Chem., 1942, 142, 401; 1943, 150, 395.'13 J. L. Gleave, E. D. Hughes, end C. K. Ingold, J., 1935, 236; E. D, Hughes andS. Tamura, Chem.Abstracts, 1925, 19, 2705.C. I i . Ingold, J . , 1933, 1571274 BIOCHEMISTRY.divided mercury to cultures of 8. brevicaulis gave negative results, nomethyhted compounds being detected.As pointed out by Mr. J. H. Baxendale (private communication) thecapture of a neutral methyl group by a negative ion, e.g., arsenite, wouldgive nine electrons on the arsenic atom, an unstable system which wouldact as a strong reducing agent, readily forming neutral methylarsonic acid,MeAsO(OH),.This might possibly be concerned in the reducing actionswhich cultures of 8. brevicazllis obviously exert upon the higher valenciesof arsenic, selenium, and tellurium, inorganic arsenates, selenates, andtellurates yielding organic arsines, selenides, and tellurides.Transmethylation. Du Vigneaud's Experiments using Isotopic Indicators.Transmethylation from Methionine and Cho1ine.-The suggestion thatcertain biological methylations in animals might be conditioned by methylgroups detached from choline or betaine 62y 647 65 received support from thework of du Vigneaud and his colleagues. They have shown 79 that homo-cystine (I) can replace methionine (111) in the diet of the white rat onlyin presence of choline or betaine, which, however, produces the effect moreslowly than choline.It was suggested that a methyl group is transferredfrom the nitrogen of choline or betaine to the sulphur of homocysteine (11)(" transmethylation ") to give methionine and that the reaction might bereversible, methionine acting as a donor of methyl groups to a cholineprecursor.[CO,H*CH(NH),*CH,*CH,*S], CO,H*CH( NH,)*CH,*CH,*SH(1.1 (11.)CO,H*CH( NH,)*CH,*CH,*S*CH, CO,H*CH( NK,)*CH,*CH,*S*CD,(111.) (IV.)NH-CO FH3 / I N-fl*CH,*$IH*CO,HHN:C CH2 / CH TH HC \/ CO*CH,*CH,*NH, NH,*C( :NH)*NMe*CH,*CO,H \&H,N(V.) (VI-) (VII.)Choline prevents a pathological condition known as fatty infiltration ofthe liver in rats. It appeared possiblethat the growth observed in the dietary experiments might have been duesimply to this particular effect of choline, the liver thus being enabled toremain healthy and to carry out methylation by some other means than atransference of methyl from choline.This explanation was disproved when the choline was replaced by itsethyl analogue, NEt,( OH)*CH,*CH,-OH, which also prevents fatty infil-tration.This compound did not allow of the growth of rats on a choline-This is known as a lipotropic effect.7' J. P. Chandler and V. du Vigneaud, J. Biol. C h . , 1940, 135, 223; V. duVigneaud, J. P. Chandler, and A. W. Moyer, :bid., 1941, 139, 917CHALLENGER : BIOLWICBL METHYLATION. 275methionine-free diet containing homocystine.that, had an ethyl group been transferred, ethionine [S-ethylhomocysteine,SEt-CH,*CH,*CH( NH,)*CO,H] would have been formed, and this wasshown by H.M. Dyer g1 to be incapable of replacing methionine in the diet.Furthermore on feeding ethionine and oholine to rats on a methionine-freediet no growth resulted, indicating that homocysteine is not formed fromethionine in the body. This stability of the S-Et link in ethionine recallsthe difficulty experienced in the de-ethylation of ethylglycine in rabbits 49 orof certain N-ethylphenazine derivatives under purely chemical condifionsis2Du Vigneaud’s transmethylation hypothesis was tested by the use ofspecimens of deuteromethionine (IV) containing (a) 83-6 and (b) 87.5 atomper cent. of deuterium in the methyl group. These were fed to rats kepton a methionine-choline-free diet.8, Earlier work had shown that thedeuterium content of the urinary creatinine (VI) closely follows that of thecreatine (V) and choline of the tissues.The experiment with specimen (a)was, therefore, continued for 94 days until the methyl group of the creatininocontained 72.4 atom per cent. of deuterium. The animal was then killedand the choline isolated from the tissues as the chloroplatinate. The atompercentage of deuterium in the methyl groups of this choline was found tobe 74-2, the corresponding figure for the tissue creatine being 73. Thesefigures represent in all three cases approximately 85 per cent. of thetheoretically possible amount of deuterium, assuming that all the methylgroups had come from the deuteromethionine. This figure is the “deu-terium ratio ”, i.e., atom per cent.deuterium in methyl group of isolatedcompound/atom per cent. deuterium in methyl group of deuteromethionineadministered x 100. Oxidation of the choline to trimethylamine showedthat all the deuterium was contained in the methyl groups.It is concluded that these reactions are true transmethylations (themethyl group being transferred as a whole) and that they do not involvethe oxidative elimination of dideuteroformaldehyde, CD,0.44, On theformaldehyde theory of methylation dideuteroformaldehyde, if produced,would react with the amino-group of the choline precursor, presumably2-hydroxyethylamine,~ to give -NH*CD,*OH which, on reduction in theorganism, would give -NH*CD,H and not -NH*CD,. The deuterium con-tent of each methyl group of the choline could not then rise above two-thirds of that in the methyl group of the methionine administered, i.e.,the “ deuterium ratio ” would have a maximum at 66.6 per cent.Du Vigneaud et aLg5 then administered trideuterocholine,Du Vigneaud points outN(CD,),(OH)*CH,-CH,.OH,to rats, on a methionine-choline-free diet containing homocystine, for 23and 56 days, respectively.On isolation of the creatine (V) from the tissues8o V. du Vigneaud, Biol. Symposia, 1941, 5, 234.81 J. Biol. Chem., 1938, 124, 519.83 V. du Vigneaud, (Miss) M. Cohn, J. P. Chandler, J. R. Schenck, and (Miss) S.Simmonds, J . BWZ. Chem., 1941,140, 625.8‘ D, Stetten, ibid., 1941, 140, 143.82 H. McIlwain, J . , 1937, 1705.85 Ibid., 1943, 149, 519276 BIOCHEMISTRY.the deuterium content was 24 and 29 per cent.of the theoretical maximumand the deuteromethyl group was detected in tissue methionine. Themethyl groups of choline can therefore take part in transmethylation.This also occurs, to a lesser extent, when no homocystine is given or whenordinary methionine is given instead of homocystine.The authors consider that homocysteine is formed from methionine bythe animal, and that methionine is re-formed by means of the methyl groupsupplied by choline. Continuous synthesis of methionine therefore occursalthough more than enough is supplied in the diet. When deuteromethio-nine and an adequate supply of ordinary choline were fed together,formation of choline from methionine was found to proceed nevertheless.The occurrence of transmethylation has also been established in therabbit 86 by the use of deuteromethionine (79 atom per cent.D in themethyl group), and analysis of the creatinine of the urine, the choline ofthe tissues and the anserine (VII) of the muscle. Later S. Simmonds andV. du Vigneauda7 using the isotope technique, showed that the methylgroup of dietary methionine can be used by man in the synthesis of cholineand creatinine.Du Vigneaud et aL88 have investigated the relation of mono- and di-methylaminoethanol to choline and to transmethylation reactions. Whenthe dimethyl compound was fed to young rats on a methyl-free basal dietcontaining homocystine, growth was not so good as when choline wasfed-Le., methionine was less readily formed.However, deuterodimethyl-aminoethanol, ( CH,D),N*CH,*CH,~OH, under similar conditions was readilyconverted into a deuterocholine and thence into creatine by transmethyl-ation. The ratio D in body choline/D in body creatine was large, whereason feeding deuteromethionine to rats the ratio was almost unity.83These results suggest that dimethylaminoethanol does not take partdirectly in transmethylation but that it can accept methyl groups suppliedby methionine or some other methyl donor in the body, thus giving riseto choline and accounting for the limjted growth-producing power. If SO,it follows that choline, when engaging in transmethylation, releasesonly one methyl group giving dimethylaminoethanol. Experimentswith deuteromethylaminoethanol, CD,*NH*CH,CH,*OH, led to similarconclusions.The incapacity of the partly methylated aminoethanols totransfer their methyl groups is presumably due to the absence of thequaternary nitrogen atom which is present in choline and betaine.Further work on the relation between choline and the methylamino-ethanols has been carried out by Horowitz and his colleaguess9 using86 J. R. Schenck, (Miss) S. Simmonds, (Miss) M. Cohn, C. M. Stevens, andV. du Vigneaud, J . Bwl. Chem., 1943,149, 355.V. du Vigneaud, J. P. Chandler, (Miss) S. Simmonds, A. W. Moyer, and (Miss)M. Cohn, ibid., 1946, 164, 603.'* N. H. Horowitz and G. W. Beadle, J . Bid. Chem., 1943,150,325; N. H. Horowitz,D. Bonner, and (Miss) M. B. Houlahan, ibid., 1946, 159, 145; N.H. Horowitz, ibid.,1946, 162, 413.87 Ibid., 1942, 146, 685CHALLENGER : BIOLOGICAL METHYLATION. 277Neurospora crassa. Two mutant strains of this organism have lost theability to synthesise choline possessed by the wild type. One mutantstrain produces methylaminoethanol but is unable to convert it into cholineat the normal rate. It therefore accumulates and is to be regarded as anormal intermediate in choline synthesis. It was isolated as the picrolonate.The other mutant cannot synthesise methylaminoethanol but can methylateit to choline if an exogenous supply is available.Transmethylation from Betaine.Fina1 proof that betaine takes partin transmethylation has now been The experiments ofdu Vigneaud carried out with white rats on a methionine and choline-freediet containing homocystine 79 (see p.274) pointed clearly in this direction.Stetten 84 showed that on administration of betaine containing 15N to ratsthe concentration of this isotope in the glycine of the tissue-protein wasalmost as high as when isotopic glycine was fed, thus proving demethylationof the betaine. The fate of the methyl group was not rigidly established,but Stetten believed it to be captured by ethanolamine (arising from reduc-tion of the glycine) thus yielding choline, which was found to contain the15N. Furthermore betaine is a lipotropic agent9l (see p. 274) and alsoprevents the development of hEmorrhagic kidneys, activities which usually,though not invariably, indicate the presence of labile methyl.V.du Vigneaud et aLgO fed betaine labelled with deuteromethyl groupsand 15N to growing rats. Isotopic analJrses of the choline and creatineisolated from the rat tissues showed betaine to be a very effective methyldonor. Methyl groups from dietary betaine appear in tissue choline almostas rapidly as they appear from dietary deuterocholine. The disparity inthe amounts of 15N and of deuterium found in the tissues proves that thebetaine molecule is not converted as a whole into choline.Dimethylglycine containing deuterium in the methyl groups was fedto young rats. Transmethylation giving choline and creatine occurredonly to a very slight extent. Dimethylglycine was also unable to preventthe incidence of hzmorrhagic kidneys.The methyl group of dietary methionine appears more rapidly increatine 92 than do those of dietary betaine.H. Borsook and J. W. Dubnofffound that methionine can serve as a methyl donor in the enzymaticsynthesis in vitro of creatine from guanidoacetic acid (glycocyamine) bysurviving liver tissue, but that choline can function in this system only inpresence of homo~ystine.~~ The transfer of methyl groups from cholineand betaine to form creatine possibly involves transmethylation first tomethionine and then either directly or indirectly to creatine.O0 V. du Vigneaud, (Miss) S. Simmonds, J. P. Chandler, and (Miss) M. Cohn, J . BioE.Chem., 1946, 165, 639.References in Chem. Reviews, 1945, 36, 350.O2 V. du Vigneaud, J. P. Chandler, (Miss) M. Cohn, and G. B.Brown, J . Biol.Chena., 1940, 134, 787.93 Ibid., 132, 559; 134, 636; 1941, 138, 389, 406; 1945,160, 636278 BIOCHEMISTRY.u-Keto-acids from Derivatives of Cysteine and Nethionine.J. L. Wood and V. du Vigneaud94 find that the X-benzyl-N-methyl-derivatives of 1-cysteine and dl-homocysteine lose their methyl groups whenfed to rats and are excreted as the corresponding 8-benzyl-N-acetyl-Z-amino-acids. This is believed to occur through the N-free keto-acids,which are then re-aminated and a ~ e t y l a t e d , ~ ~ because d-amino-acid oxidaseand broken cell preparations of rat kidney and liver convert dl-N-methyl-methionine into the 1-keto-3-methylthiobutyricCH,*S*CH,*CH2*CO*C02H.P. Handler and (Miss) M. L. C. Bernheimg7 have shown that d(+)-meth-ionine is about half as active as the Z-isomer in promoting creatine synthesisby liver slices in vitro.Benzoic acid, which inhibits d-amino-acid oxidase,also prevents creatine synthesis (transmethylation) with d( +)-methionine,but not with the Z-isom&. It is assumed, therefore, that d(+)-methioninemust first be converted into the a-keto-acid, CH,*S*CH,*CH,*CO*CO,H.Whether this can undergo transmethylation as such, or only after reamin-ation to Z-methionine, has not been decided. It is, however, fully as activein creatine synthesis as methionine.Derivatives of Methionine.dZ-Methionine sulphoxide and methylsulphonium iodide can replacemethionine in the diet of the white rat, but &I-methionine sulphone cannot.This has a mycological parallel. Diethyl sulphoxide is readily reduced todiethyl sulphide in cultures of 8. brevicaulis, whereas the sulphone is not.73Neither the sulphoxide nor the sulphone appreciably increase the methyl-ation of glycocyamine by liver slices.97 The sulphoxide, however, exerts alipotropic action in rats.Assuming that this is due to a transfer of methylto a choline precursor (which has not been established), the inertness of thesulphoxide in Handler and Bernheim’s experiments in vitro is surprising.These authors state “ it appears probable that the intact animal possessessome mechanism whereby methionine sulphoxide may be reduced to theparent substance which may then be utilised for choline synthesis.”Synthesis of Labile Methyl in the Body.From work summarised in this report the hypothesis arose that theanimal organism is incapable of generating methyl groups for methylationsand that methyl groups in a particular form such as methionine and cholinemust be present in the diet.V.du Vigneaud, S. Simmonds, J. P. Chandler, and M. Cohn have recentlypresented evidence 98 for the synthesis of a small amount of labile methyl94 J . Biol. Chern., 1946, 165, 95.W. I. Patterson, H. M. Dyer, and V. du Vigneaud, ibid., 1936, 116, 277; M. WKies, H. M. Dyer, J. L. Wood, and V. du Vigneaud, ibid., 1939, 128, 207.P. H. Handler, F. Bernheim, and J. R. Klein, ibid., 1941,138, 20397 Ibid., 1943, 150, 335. Ibid., 1945, 159, 755CHALLENGER : BIOLOGICAL METHYLATION. 279groups in the rat maintained on a diet adequate in labile methyl.V. duVigneaud 99 occasionally found animals capable of showing some growth ona homocystine diet without added choline and the growth of rats on asimilar methyl-free diet was reported by Bennett et aZ.lOO The authorsraised the concentration of deuterium in the body water of two rats t oabout 3 atom per cent. by intraperitoneal injection of 99.5 per cent. D20and maintained this by giving drinking water containing 4 atom per cent.of D,O for three weeks. The deuterium content of the choline chloro-platinate then isolated from the tissues indicated that 7.7 and 8.5 per cent.respectively of the choline-methyl was derived from the body water. It isvery unlikely that a direct exchange reaction would cause the appearanceof deuterium in the methyl groups under these conditions.The authorsconsider that the synthesis of methyl groups by intestinal bacteria is themost logical interpretation of their results.Methylsulphonium Compounds in Natural Products.It was suggested lo1 in 1940 that sulphonium derivatives of methionine 97might play a part in biological processes. The fission of the alkyl S-C linkin methionine by S. brevicaulis observed by Challenger and Charlton 37 doesnot seem to be preceded by formation of a sulphonium derivative, sincemethionine methiodide gives dimethyl sulphide but no methanethiol incultures of S. brevicuulis. This decomposition appears to be analogous tothe evolution of dimethyl sulphide (but no methanethiol) from the marinealga Polysiphonia fastigiata observed by Haa,s,102 as F.Challenger and (Miss)M. I. Simpson (forthcoming publication) have shown that the precursor (ora fragment of the precursor) of the dimethyl sulphide in the alga is a salt ofdimethyl-2-carboxyethylsulphonium hydroxide, Me,$( OH)*CH2*CH2*C02Hor Me2~*CH2*CH,*CO0. This was isolated from P . fastigiata as the chloride(the bromide is already known lo3) and characterised as various derivatives,all of which readily evolved dimethyl sulphide a t ordinary temperature inpresence of sodium hydroxide. The sulphonium (thetine) salt may arisefrom methionine by deamination and oxidation, or from cysteine. Apartfrom the possible existence of a sulphonium compound in dogs’ urine,31 andthe isolation of an oxygenated derivative of diallyl disulphide from garlic lo4(which may be the monosulphoxide and therefore of “ sulphonium type ”),this is the first recorded instance of the occurrence of a sulphonium compoundin Nature.F. C.ss J . Biol. Chem., 1939, 128, cviii; 131, 57.loo M. A. Bennett, G. Medes, and G. Toennies, Growth, 1944,8, 59.lol G. Toennies, J . Biol. Chem., 1940, 132, 455 ; G. Toennies and J. Kolb, J . Arner.lo2 P. Haas, Biochem. J., 1935, 29, 1298.lo3 G. Carrara, Guzzettu, 1893, 23, i, 506; E. I. Biilmann and K. A. Jemen, Bull.SOC. chim., 1936,3, 2306; B. Holmberg, Arkiv Kemi, Min. Geol., 1946, 21 B, No. 7, 1.lo4 C. J. Cavallito and J. H. Bailey, J . Amer. Chem. SOC., 1944, 66, 1950; C. J.Cavallito, J. S. Buck, and C. M. Suter, ibid., p.1952.Chem. SOC., 1945, 67, 849280 BIOCHEMISTRY.3. STRUCTURAL PROTEINS OF MUSCLE.The proteins of muscle may be classified into two groups : (1) thosewith a structural function; and (2) the soluble proteins of the sarcoplasm.Strictly defined, Group 1 embraces the extracellular types (vascular tissue,collagen, the reticulin of the sarcolemma) and also components of intra-cellular origin (the proteins of the myofibril and of the nuclei). Of these,only those proteins which are assumed to compose the contractile elementswill be discussed. The proteins of Group 2 are largely enzymic, associatedfor the most part with the reactions of glycolysis, and will be discussed in asubsequent review. Some enzymes (succinic dehydrogenase, diaphorase,cytochrome oxidase) resist extraction with water and appear to be attachedto the structural components.Proteins of the Myofibril.In a previous review,l some emphasis was given to the view that thefibril, by virtue of its contractile function, must consist mainly if not whollyof proteins of the polymeric fibrous type.Of the classical protein fractions,as for example those of press-juice (myogen, globulin X, myoa1bumin)l.and the globulin obtained by salt extraction, only the last, containing themyosin complex, could be assigned to the fibril. The myosin chains wereconsidered to run in a regularly oriented manner through the anisotropic ( A )bands, and in a less oriented fashion through the isotropic ( I ) bands. Themore crystalline parts of the structure gave, both in living and in driedr n u ~ c 1 e , ~ ~ ~ and also in partially oriented films of isolated myosin+ a wide-angle X-ray pattern of the a-type, indicating that the same intramolecularfold, shown later to exist in fibrinogen, fibrin,6 and trop~myosin,~ had beenadapted for the elaboration of the ultimate contractile element.With thediscovery by N. M. Liubimova and V. A. Engelhardt 8 in 1939 that theadenosinetriphosphatase (ATPase) activity of muscle was always associatedwith myosin itself, and could not by any ordinary means be separated fromit, there appeared a direct link between the contractile mechanism and anenergy-yielding reaction. These various studies converged to give for thefirst time a clue to the nature of the contractile mechanism, and on themseveral tentative hypotheses for the more detailed mechanism werea d ~ a n c e d .~ ~ lo Recently, the problem has become more complicated by theK. Bailey, Advances in Protein Chemistry, 1944, 1, 289.Reviewed by M. Dubuisson, Bull. SOC. Roy. Sci. LiLge, 1945, 113.W. T. Astbury, Croonian Lecture, Proc. Roy. SOC., 1947, B, in press.W. T. Astbury and S. Dickinson, Nature, 1935, 135, 95, 765.Idem, Proc. Roy. SOC., 1940, B, 129, 307.K. Bailey, W. T. Astbury, and K. M. Rudall, Nature, 1943, 151, 716.K. Bailey, Biochem. J . , 1942, 36, 121.' K. Bailey, ibid., 1946, 157, 368. 8 Biochimia, 1939, 4, 716.lo M. Dainty, A. Kleinzeller, A. S. C. Lawrence, M. Miall, J. Needham, D. M.Needham, and S.-C. Shen, J . Gen. Physiol., 1944, 27, 355; J.Needham, A. Kleinzeller,M. Miall, M. Dainty, D. M. Needham, and A. S. C. Lawrence, Nature, 1942,150,46BAILEY : STRUCTURAL PROTEINS OF MUSCLE. 251discovery of two new proteins, both occurring in the fibril, and both ofasymmetric character, the actin of F. B. Straub l1 and trop~myosin.~Structure of the MyoJibriZ.-The level of molecular organisation observedin the electron microscope (EM) falls within the range of the larger period-icities revealed by X-rays, which in wide-angle diffraction are also used toelucidate the smaller repeating units. In an extensive examination ofmuscle: both living and dried, the predominant wide-angle pattern is thatof the a-keratin type, which does not change after a moderate contraction.The significance of this fact has been discussed a t length by Astbury, andleads, somewhat paradoxically a t first sight, to the conclusion that contrac-tion over the physiological range is not so much the transformation of thecrystalline parts of the fibril from which the diffraction pattern arises as themore regular folding in series of the less crystalline parts.By the capacityof these molecules to build up intromolecular combinations, the shorteningof muscle, as of myosin and keratin, involves changes of internal energyrather than of entropy.In muscle as in other structures, the EM and X-rays confirm the presenceof a large-scale pattern superimposed upon the smaller intramolecularpattern, and the comparison of patterns as between members of the keratin-myosin-fibrinogen group is of the highest importance.I. MacArthur l2has shown that a correspondence exists between these larger spacings inwool, porcupine quill tip, and dried frog sartorius muscle, but it cannot yetbe concluded that the full periods are identical, since their evaluation is notunambiguous. According to American workers l3 the master-period inmuscle is a t least 3 5 0 4 2 0 ~ . , whilst the probable width of the diffractingelements (27 A.) allows of only a few polypeptide chains.I n the adductor muscles of molluscs a new type of fibril occurs, differentboth in its resistance to disintegration by salt solutions, and in its large-scalemolecular pattern.14 After maceration in 0.3~1-potassium chloride anddifferential centrifugation, the muscle yields a fraction containing intact,needle-shaped fibrils (unfortunately designated “ paramyosin ”) which dis-integrate in 0.45~-potassium chloride.These vary from 200 to 1OOOa. inwidth and 1 to 40 p in length. With an “ electron stain ” they reveal aregular lattice of deeply staining spots, of separation 193 A. perpendicular tothe fibre axis, and 720 A. parallel. The separation of rows of spots along theaxis is, however, only one-fifth of this latter distance. X-Ray studies l5 hadearlier indicated a master-period of 725 A. There is no apparent change oflattice dimensions after contraction, and Schmitt et ~ 1 . ~ 3 suggest that thefibrils may serve a purely mechanical function in these rather specialisedmuscles.It should be noted here that the EM merely records densityl1 Stud. I n s t . Med. Chem. Univ. Szeged, 1942, 2, 3; idem, ibid., 1943, 3, 23.l2 Nature, 1943, 152, 38.lS R. S. Bear, J. Amer. Chem. Soc., 1945, 6’4, 1625; F. 0. Schmitt, R. S. Bear, C. E.Hall, and M. A. Jakus, N . Y . Acad. Sci., Conference on “Muscle contraction”, 1946.l4 C. E. Hall, M. A. Jakus, and F. 0. Schmitt, J. AWE. Physics, 1945,16,459.l6 R. S. Bear, J. Amer. Chem. Soc., 1944, 66, 2043282 BIOCHEMISTRY.(and/or thickness) gradients, and the repeating units of protein patterndeduced by X-rays should not be revealed by the EM except where theycoincide with stainable material assiciated with the protein. Such material,as in the above lattice, may be of mineral nature, or may form part of thenormal extractives (ATP, etc.) of muscle.With an electron stain, striated muscle shows all the details elicited byhistological techniques.16 It shows too that on contraction there is amigration of some substance in the A band towards the I .I n both A and Ibands, the myosin filaments pursue an uninterrupted course, being rather lessaligned in the latter, and, most strikingly, the picture remains much the sameafter contractions of 50%. The absence of gross change thus tends tosupport the intramolecular folding of chains as the mechanism of contraction,and disproves the hypothesis of A. Szent-Gyorgyi 1' based upon studies ofthe myosin-actin interaction, of a spiral, spring-like mechanism.Isolated Myosin.-General properties have recently been reviewed1* l8and will not be described again.EM Photographs of myosin dispersed insalt solutions reveal particles derived by a random fragmentation of thefibrillar substance, varying in width (50-250~.) and up to 15,000~. inlength; 16* l9 the average for rabbit myosin is 120 x 4100 A. Such poly-dispersity clearly invalidates attempts to assess particle weight by con-ventional methods.20 It has a bearing too on the nature of Szent-Gyorgyi'smyosin A.1732l Since this is the fraction which yields most readily to saltextraction, it may consist of those parts of the fibril most easily fragmentedand may thus comprise the shorter myosin micelles; its low viscosity tendsto support this inference. The crystallinity of myosin A in the acceptedsense cannot be admitted.The earlier electrophoretic studies 9* 20 of myosin sols have been extendedby M.Dubuisson.22 Three components, a, p, and y , in the proportions25, 70, 5% (rabbit myosin), have been distinguished. (These electrophoreticdesignations must not be confused with a- and p-configurations.) Thea-component carried the turbidity of the solution; the y was absent fromexhausted muscle and the a markedly decreased, The separation of thecomponents by fractional salting combined with a study of theirphysical properties, suggests that the a-fraction has a larger (average)particle weight than the p. The existence of electrophoretic componentsmight imply (a) that myosins of Mering composition and hence of differingnet charge occur, (b) that various complexes of myosin with other substances(actin, tropomyosin, ATPase) exist, or (c) that the net charge is dependentto some extent upon the degree of aggregation of the molecules, i.e., uponl6 C.E. Hall, M. A. Jakus, and F. 0. Schmitt, Biol. Bull. Woods Hole, 1946, 90, 32.l7 Acta Physiol. Scand., 1945, 9, suppl. 25.l8 V. A. Engelhardt, Advances in Enzymology, 1946, 6, 147.M. V. Ardenne and H. H. Weber, Kolloid-Z., 1941,97,322.2o M. Ziff and D. H. Moore, J . Biol. Chem., 1944, 153, 653.21 A. Sxent-Gyorgyi, Stud. I n s t . Med. Chem. Univ. Szeged, 1943, 3, 76.22 Experientia, 1946, 2, 258. 28 Idem (private communication)BAILEY : STRUCTURAL PROTEINS OF MUSCLE. 283the size of the micelle. In view of the known randomness of particle size,( c ) is the most likely, ( b ) a possible, and (a) an improbable explanation.Analytically, myosin is distinguished by its high content of free carboxyland basic groups, and in general amino-acid composition resembles fibrino-gen.1 The highly charged character is admirably suited to processesrequiring changes in the state of aggregation, and thus to the r6le whichboth proteins play in their respective biological environment.Improvedvalues for the hydroxyamino-acids 24 and the bases 25 have been obtained,but it is probable from the careful titration data of &I. Dubuisson 26 that thedicarboxylic acids 27 are underestimated. Analyses of myosin suffer fromthe lack of any criterion for the purity of the protein. Besides ATPase,which may or may not be identical with myosin, there are present tracesof nucleic acid,28 adventitious enzymes, and, for the type of preparationusually analysed, 1-2y0 of a ~ t i n .~ ~Adenosine Triphosphatase.-All available evidence suggests that ATPaseis either very firmly bound to, or part of, myosin itself. The salient pro-perties of the enzyme, already reviewed,l* l8 are : (1) its specific activationby the Ca ion9 and the remarkable effect of Mg++ in antagonizing thisaction; 30 (2) the inability to split more than one phosphate from ATP (ifmyosin is purified at a somewhat alkaline pH, it appears to retain myokinasewhich carries the degradation to adenylic acid31); (3) the alkaline pHoptimum of 9 ; ** (and carnosine)against heavy metal inhibition ; (5) the sulphydryl character of the enzyme.32SH oxidants (p~rphyrindin~~ hydrogen peroxide 33) , thiol reagents (p-chloro-mercuribenzoate 32) or alkylating reagents (chloroacetophenone, iodo-acetate 34) all reduce or destroy ATPase activity.However, oxidants aremore effective inhibitors than alkylating reagent~~~2.N and these must beadded in greater concentration than is necessary for most accredited SHenzymes. In considering the evidence for the identity of ATPase andmyosin, it is noteworthy that the extent of reaction of an oxidant such asiodosobenzoate with myosin SH groups46 is also greater than that of apowerful alkylating reagent such as ~hloroacetophenone.~4 In these respects,enzyme properties run parallel with those of myosin itself.(Anotherpeculiarity of the SH groups of myosin was observed by W. C. Hess andM. X. Sullivan.35 Hydrolysis of a myosin sol yields about 1 yo of the proteinweight as cysteine, but hydrolysis of myosin dried in a vacuum yieldsentirely cystine.)(4) the protective action of amino-acids24 M. W. Rees, Biochem. J . , 1946, 40, 632.26 Arch. Int. Physiol., 1941, 51, 133; idem, ibid., 1943, 53, 308.27 J. G. Sharp, Biochem. J., 1939, 33, 679.29 K. Bailey and S. V. Perry, unpublished.31 H. 0. Singher and A. Meister, J. Biol. Chem., 1945, 159, 491.32 T. P. Singer and E. S. G. Barron, Proc. SOC. Xxp. Biol. Med., 1944,56, 120.33 J. W. Mehl, Science, 1944, 99, 518; M. Ziff, J. Bio2. Chem., 1944,153, 25.s* K. Bailey, unpublished.2 5 H. T. Macpherson, ibid., p. 470.28 K.Bailey, unpublished.G. D. Greville and H. Lehmann, Nature, 1943, 152, 81.3b J . Biol. Chem., 1943, 151, 635284 BIOCHEMISTRY.D. B. Polis and 0. Meyerhof 36 have briefly described a method of obtain-ing a myosin fraction 2-3 times as active as the original. Somewhatearlier, W. H. Price and C. F. Cori 37 reported the separation of ATPase frommyosin, and found that the enzyme was no longer activated by Ca++, butwas so by creatine. The claim of separation has now been withdrawn,3*since further work shows that the myosin-free enzyme is creatine phospho-kinase, derived from impurities in the myosin preparation.Actin and Myosin A.-The many papers of Szent-Gyorgyi and hisschool 17*39 concerning the interaction of actin and myosin, and the hypothe-tical r6le of actomyosin in muscle contraction can be described only in outline.When minced muscle is left in contact with a salt solution adequate to extractmyosin, the resulting brei gradually thickens to a gel-like consistency. Thischange can be simulated with the isolated components of the reaction, firstby obtaining myosin A,40t41 which yields to salt solutions after a 20 minuteextraction period, and secondly by washing the muscle residue with analkaline buffer, drying the residue in acetone, and extracting with water toobtain " actin ".l1 The aqueous extract of actin is not viscous until salt isadded; it then changes to a limpid gel of " active actin " which is boththixotropic and flow-birefringent.I n salt solutions of ionic strength 0.5-1.5, the addition of actin to myosin A greatly increases the viscosity abovethat of either component a t the same dilution, and this increase is nullifiedby addition of ATP (1 mde/70,000 g.myosin).17 The action of ATP is notentirely specific, since inorganic pyrophosphate 42 (at 0" but not a t 20") and5% urea43 act similarly. In the EM, actomyosin appears to consist of anetwork of anastornosing filaments,U the type of structure which mightreadily be predicted from a consideration of its gel-like properties.Myosin prepared in the classical manner differs from myosin A in con-taining 1-2% of actin which enhances its viscosity. The addition of ATPtherefore effects a slight reduction in viscosity, an effect which was firstdiscovered by J.Needham and his collaborators lo before the discovery ofactin itself, By the ATP-viscosity test, myosin A contains no, or only atrace of, actin.In a sparse ionic atmosphere, the interaction of actin, myosin, ATP andsalt ions leads to interesting effects which have been woven rather pre-maturely into a theory of muscle ~0ntraction.l~ An aqueous gel of acto-myosin, within certain limits of salt (potassium chloride) concentration,precipitates, and the zone of precipitation is narrowed in presence of Mgions and/or ATP. In addition, ATP causes an enhanced shrinkage of the86 J . Biol. Chem., 1946, 163, 339.98 C. F. Cori, ibid., 165, 395.99 S. Karges, " Studies from the Institute of Medical Chemistry University Szeged ",40 I.Banga and A. Szent-Gyorgyi, ibid., 1941-1942, 1, 5.41 A. Szent-Gyorgyi, ibid., 1943, 3, 76.Is W. F. H. M. Mommaerts, Arkiv. Kemi, M i n . Qeol., 1945,198.44 W. T. Astbury, S. V. Perry, and R. Reed (private communication).37 Ibid., 162, 393.Basle and New York, 1941-1942, 1; 1942, 2; 1943, 3.42 F. B. Straub, ibid., 1943, 3, 38BAILEY : STRUCTURAL PROTEINS OF MUSCLE. 285particles, and this effect has been studied in some detail with threads ofactomyosin, prepared by dissolving the complex in 05~-potassium chlorideand squirting the solution into O-O5~-potassium chloride. If the environ-ment is now changed to one consisting of O.1M-potassium chloride-0.0lM-magnesium chloride-0.09 % sodium- ATP, an isodimensional contraction of60% is produced in 5 minutes.As Astbury has pointed out, this synaeresisof actomyosin in presence of small concentrations of ions cannot be con-sidered unique in chain-molecular systems. Its most important feature isthe enhancing action of ATP, and the explanation of this effect must besought in the same terms as that producing a reduction in viscosity whenATP is added to actomyosin in the stronger ( 0 . 5 ~ ) salt solutions.Though i t has not been emphasised by the Hungarian workers, the uniquefeature of the interaction of myosin and actin is that it occurs at ionicstrengths 17*45 (up to 2 ~ ) which would greatly reduce the purely electro-static interaction of one protein with another. It seems likely then that aspecial interaction is involved, perhaps a type of co-ordination, in which theactin and myosin interact a t some specific chemical grouping.This inferencewas fruitful, since it led to the finding46 that SH reagents (iodoacetate,iodoacetamide, p-chloromercuribenzoate, o-iodosobenzoate) prevented theinteraction. Only the SH groups of myosin are concerned : actin itself isrich in SH groups, but, of these, O.Syo (as cysteine/100 g. protein) may beoxidized by iodosobenzoate without influencing appreciably the reactionwith myosin. By contrast, the oxidation of the cysteine of myosin t o theextent of 0.5 yo (total 1 - 16 yo) prevents actomyosin formation. Moreover,the concentrations of the various poisons (as m-mol./mg. myosin) whichinhibit actomyosin formation are almost identical with those which Singerand Barron 32 found to inhibit ATPase.This quantitative correlationbetween myosin SH groups and its ATPase activity on the one hand, andwhat might be termed its gross colloidal behaviour on the other, arguesstrongly for the identity of myosin and ATPase; particularly so, when thesubstrate for the enzyme reaction (ATP) so profoundly influences thecolloidal reaction. These interrelationships are further strengthened by thefact that ATP, wherever it acts as substrate, does so with enzymes either ofproven or suggested SH character (creatine phosph~kinase,~~ yeast hexo-kina~e,*~ the choline acetylase system49), and may be deemed to have anaffinity for some type of SH grouping to be found in proteins.In the light of these facts, it is supposed that certain SH groupings inmyosin, probably identical with those of ATPase, can interact either withactin (through an unknown group) or with ATP, but that ATP competesmore successfully, and transforms the actomyosin gel into its freely-moving4 5 F.Guba, Stud. Inst. Med. Chem. Univ. Szeged, 1943, 3, 40.4 6 K. Bailey and S. V. Perry, Proc. Biochem. Xoc., 1947, 41, in press.4 7 H. Lehmann and L. Pollak, Biochem. J., 1942, 36, 672.4 8 R. van Heyningen, Report to Ministry of Supply, by M. Dixon, 1942, NO. 10;4' D. Nachmansohn and H. M. John, J. Biol. Chem., 1946,168, 157.K. Bailey and E. C. Webb, ibid., 1944, No. 30286 BIOUHEMISTRY.components. In concentrated salt solution the effect is revealed in viscosityreduction; in very dilute salt solutions, the loss of gel structure allows themyosin particles to precipitate in the way that actin-free, salt-free gels ofmyosin precipitate on addition of small amounts of salt.Schematically :I Myosin }SH : ATP + Actin ,-+ ADP + phosphate ATPaseThe view that the ATP-myosin-actin interaction is the keystone ofmuscle contraction is quite premature until more is known of the nature ofactin, the nature of the forces involved in its interaction, and the natureof the groups we have termed " sulphydryl " but which possess propertiesnot readily explained as simple reactions of the ordinary thiol g r o ~ p . ~ * ~The plausibility of a hypothesis must not be mistaken as its proof, and theinvocation of the lock and key mechanism, whereby actin is the lock andATP the key,l7 must obviously be explored; but the scope for hypothesisin the explanation of muscle contraction is so great, and the possibilities sonumerous, that it is more profitable to dissect the pieces than to constructthe whole.Any ultimate interpretation must show how ATP and actinaffect the intramolecular contractility of myosin chains; it would not seemto involve a consideration of synaeresis effects.Tropomyosin.-This newly discovered protein 7 of the fibril is of asym-metric character but of relatively low molecular weight (about 90,000). Inrabbit skeletal muscle it comprises 0.5% of the fresh muscle weight. Thoughwater-soluble after isolation, it cannot be extracted from minced muscle bywater and only slowly by salt solutions. Likewise, it is not extracted bywater from washed muscle residue dried in efhanol-ether, but is so byM-potassium chloride.These properties suggest a metathetic link withone or more constituents of the fibril.I n salt-free solutions, tropomyosin is extremely viscous and showspositive flow-birefringence ; addition of salt to 0 . 1 ~ effects a large reductionin viscosity (the reverse of the effect of salts on actin), and such solutionswhen subjected to isoelectric crystallisation procedures 51 deposit largebirefringent plates containing 90% of water. EM Studies 52 show that theenhanced viscosity in absence of salt is due to the perfectly regular aggregationof particles into fibres, built up presumably by electrostatic interaction ofone molecule with another.The phenomenon might suggest the mechanismwhereby the polymeric proteins (keratin, collagen, myosin) are initiallyelaborated from smaller units. The depolymerising action of guanidine andso Review by H. Neurath, J. P. Greenstein, F. W. Putnam, and J. 0. Erickaon,Chem. Reviews, 1944, 34, 157.61 K. Bailey, unpublished.W. T. Astbury and R. Reed, private communicationHARTREE : MAGNETIC PROPERTIES OF HBMATIN DERIVATIVES. 287urea gives some clue to the size of the submolecules which make up thenative protein, since it is unlikely that anything more than a splitting ofhydrogen bonds is inv0lved.5~ I n urea, myosin does in fact depolymerise tounits of the same average molecular weight 54 (100,000) as tropomyosin.The significance of tropomyosin rests entirely in the possibility that it is asub-unit of myosin.Not only is it an a-protein par excellence, but the amino-acid composition, now completed, is entirely of myosin type. The twoanalyses are not identical, since tropomyosin is rather more polar, and inany case we cannot consider that a pure myosin has yet been analysed or thatmyosin as we know it has been adequately analysed. The evidence for somefundamental relation between the two proteins, from structure, analysis,occurrence in the same histological site, is so impressive that the name tropo-myosin has been adopted to suggest it. Its existence as an a-keratin typewhich is both fibrous and crystalline is a logical outcome of all that is impliedin the systematic researches of the Leeds school.K.B.4. MAGNETIC PROPERTIES OF HBMATIN DERIVATIVES.Magnetic Susceptibility.-The volume susceptibility K of a substance is theratio of the intensity of magnetisation t o the strength of the magneticfield : K = I / H , and the mass susceptibility (i.e., per unit mass) x = ~ / p .Apart from the few ferromagnetics, all substances may be classified asdiamagnetic (x negative) or paramagnetic (x positive). In a non-uniformmagnetic field these two groups are subjected to forces directing themaway from or towards the region of maximum H respectively. Diamagnetismis a property of all matter arising from the effect of the field on the orbitalmotion of the electrons and has been recently reviewed.l Certain sub-stances (e.g., salts of transition elements, or oxygen) as well as organic freeradicals possess a permanent magnetic moment arising from unpairedelectron spins and therefore exhibit a pronounced paramagnetism whichswamps the numerically much smaller diamagnetism.Curie showed that paramagnetism usually obeyed the lawx m = CmIT .. . . . (1)where xm = xM and Cm = the Curie constant per g.-mol. The classicaltheory of Langevin for paramagnetic gases derives an expression Xm = a,2/3RTwhere u0 (g.-mol. magnetic moment) = p (molecular magnetic moment) x N .From the Bohr theory of atomic structure the natural quantum unit ofmagnetic moment = 9-174 x E.M.U. Hence unit per g,-mol. =9.174N X = 5564 E.M.U. This quantity is known as the Bohrmagneton (pB).Hence=o - dmzpB = 5564 -63 A. E. Mirsky and L. Pauling, Proc. Nut. Acad. Xci., 1936, 22, 439.54 H. H. Weber and R. Stover, Biochem. Z., 1933, 259. 269.W. R. Angus, Ann. Repo?ts, 1941, 38, 27. a D. H. Hey, ibid., 1940, 37, 263288 BIOCHEMISTRY.(el 0 0 0 0(f)/W 0 0 0 0Substitution from (1) givesFrom the quantum-mechanical development of Langevin's theory equationsare derived relating kB to the number of unpaired electron spins. Thesimplest type is in the formwhere g a n d j are functions of the orbital and spin moments of the electrons.This formula has successfully been applied to the paramagnetic rare earths:where the unpaired electrons are in an inner shell and consequently shieldedfrom the influence of neighbouring molecules.When considering salts ofiron and other transition elements it is necessary to postulate a consider-able diminution or even the disappearance of the orbital moment in orderto account for the experimental figures.. . . . . . ~ B z 2 . 8 4 - (2). . . . . . . pB = q4J-j (3)Equation (3) now reduces toP B = 2 2 / 5 ( 8 $ 1) . . . . (4)where s = resultant electron spin moment of the atom. The loss of orbitalcontribution is ascribed to the close proximity of other molecules in theliquid and solid states.*Electronic Structure and Magnetic Moment.-The Fe"' and Fe" ionscontain 24 and 25 orbital electrons respectively. Omitting the inner 18,which make up the stable argon configuration of 9 paired electrons, thearrangement of the remainder in the 3d shell can be expressed by ( a ) and(b) with 5 and 4 unpaired electrons (u.e.), respectively :3d 4s 4 P0 @ 0 0 0 dcjsp2Bonds0 0 0 0 0 HARTREE : MAGNETIC PROPERTIES OF HBMATIN DERIVATIVES.289In complex salts such as ferri- and ferro-cyanides two electrons from eachCN' (Sidgwick's lone pairs) fill the outer orbitals, leading to the stablekrypton configuration and to a decrease in paramagnetism following thepairing of 3d electrons, (c) and ( d ) . The structure of square 4-covalentcomplexes can be expressed by (e) and (f), but in such cases the maximumco-ordination number of 6 may be achieved by the formation of two ionicbonds when the probable structure is a resonance equilibrium of six equiv-alent bonds of intermediate type.6 No examples of type (f) are known,*and ( e ) is limited to a few hsematin derivatives.for each unpaired electron; hence,from (2) and (4) the relationships between the number of u.e.and the para-magnetism and valency of the iron may be calculated (Table I). AsL. Cambi and L. Szegoe have shown that hzemin obeys Curie's law, thesefigures can be applied to its derivatives.The value of s in equation (4) isUnpaired electrons ...... 0Valency of Fe ............ 2/.&B .............................. 0106xm ( 2 0 O ) .................. 0R' RTABLE I.1 2 3 4 51-73 2.83 3.87 4.90 5.921270 3390 6350 10,180 14,8203 2 3 2 3R = Me.R' = -CH:CH2.R" = -CH2*CH2*C02H.H e m (ferrous protoporphyrin) : the active group of hsmoglobin. Full lines repre-sent bonds which, on account of resonance, are intermediate between single and doublebonds.Structure and Nomenclature of Hcemin Derivatives.-The interrelationshipsof hzmatin derivatives have been formulated by D.Keilin but the intro-duction of a new system of nomenclature l o has led to some confusion.and by P. W. Selwood, " Magnetochemistry " (Intorscience Publishers, 1943). Experi-mental technique (Gouy method) is described by C. M. French and V. C. G. Trew,Trans. Paraday SOC., 1945,41, 439, and by L. Pauling and C. D. Coryell, Proc. Nat.Acad. Sci., 1936, 22, 159." Electronic Theory of Valency " (Oxford, 1937).L. Pauling, " The Nature of the Chemical Bond " (Cornell University Press,Rend. Ist. Lombard0 sci., 1934, 87, 275.Ergebn.Enzymforsch., 1933, 2, 239.1942).a M. L. Huggins, Ann. Rev. Biochem., 1942, 11, 652.lo L. Pauling and C. D. Coryell, Proc. Nut. Acad. Sci., 1936, 22, 210. * With the possible exception of ferrous phthalocyctnine ( J . p. Chem., 1939, 164,73).REP.-VOL. XLIII. 290 BIOOHEMISTRY ,The two systems are summarised in Table 11, where the basic structures ofthe more important derivatives are given. In this report the originalnomenclature will be used.TABLE 11.Original nomenclature.Haem * .....................Haemin .....................Haematin .....................Haemoglobin * (Hb) ......Oxyhsmoglobin ............Carbon monoxide Hb ...Acid methaemoglobin ...Alkaline metHb ............Haemochromogen * ......Parahaematin ...............Valency Groups attached to Feof Fe.other than porphyrin. New nomenclature.FerrohemeHeminFerriheme chlorideFerri heme hydroxide2 ‘ 2 % . 9) -t33 OH’ (H,O ?) t2 globin Ferrohemoglobin2 0, globin Oxyhemoglobin2 CO globin Carbonmonoxy Hb3 globin (H,O ?) Ferri hemoglo b in3 globin OH’ Ferri H b hydroxide2 denatured globin or 2 mols. Ferrohemochromogen3 1 organic base (e.g., pyridine) { Ferrihemochromogen* These combine reversibly with CO. t See structures postulated by T. H. Davies, J . BioE. Chem., 1940, 135, 697.Magnetic Measurements on Hcematin Derivatives.-Work in this field upto 1941 has been summarised by Selwood4 and by D. L. Drabkin.ll Themore recent publications have been devoted to catalase and peroxidase.The susceptibilities of the derivatives under review are collected in Table 111.The first precise magneticmeasurements on haemoglobin (Hb) and on HbO, and HbCO were made byPauling and Coryell.lo The iron of the oxygen and the carbon monoxidederivatives has zero magnetic moment, while the paramagnetism of Hbcorresponds to pB = 5.46, which is in excess of the theoretical 4.90 for4 u.e.The high value was attributed to hzm-hzm interactions whichtend “ to stabilise to some extent the parallel configuration of the momentsof the four hemes in the molecule.” The alternative explanation of anappreciable orbital contribution was rejected through consideration ofcertain ferrous complexes containing nitrogen.12 The combination of twoparamagnetics, Hb and oxygen, t o give a compound with zero momentmust result in a profound change in the oxygen molecule involving thedisappearance of two u.e.Electronic structures for HbO, and HbCO areput forward. Compounds of Hb with ethyl isocyanide l3 and with cyanideion and nitric oxide 1* have zero moment. Thus in Hb the iron bonding isionic, while in the derivatives the iron is covalently linked.By taking Hb (vB = 5.43) and HbCO (pB = 0) as standards at 24”,C. D. Coryell, F. Stitt, and L. Pauling l5 devised a simple method for deter-mining xnZ and pB for derivatives of Hb, using the Gouy technique. If AuHb isthe appafent change in weight on applying the magnetic field to a tube ofHbO, + reducing agent (Na,S,04) and A@.WCO the corresponding change after(A) Hcemoglobin and its (ferrous) derivatives.11 Ann.Rev. Biochem., 1942, 11, 652.l2 L. Pauling, J . Amer. Chem. Soc., 1931, 63, 1367.1‘ F. Stitt and C. D. Coryell, J . AWT. Chm. SOC., 1939,61, 1263.C. D. Russell and L. Pauling, Proc. Nut. A d . Sci., 1939, 25, 617.IbM., 1937, 69, 633HARTREE : MAGNETIC PROPERTIES OF HEMATIN DERIVATIVES. 291saturation with carbon monoxide, then A w ~ b - A w ~ c o is a measure of theparamagnetism of Hb (xm = 12,290 x 10-6) after correction for the dia-magnetism of the Na2S204. If Aw is the observed change in weight withan equimolecular solution of a Hb derivative, the molar susceptibility andmagnetic moment of the latter can be obtained from( Atu - AtuHbCO )* . 5.43FB = Xrn = - - ~ Aw - AcoHbCo . 12,290 xAwHb - AwHbCO AwHb - AwHbCOThe figures 12,290 xF.Stitt,16 are slightly lower than the original figures of Coryell et aZ.15several Hb’s :and 5.43, which are due to C. D. Coryell andD. S. Taylor and C. D. Coryell l7 found significant variations amongcow. Horse. Sheep. HUXIUUl.1 06xm .................. 12,290 12,260 12,390 11,910/LB ........................ 5.435 f 0.015 5-43 6.46 5.35The differences were ascribed to variations in hem-hem interaction whichare apparent also from variations in the oxygen affinity in the differentspecies. The identical susceptibilities of laked and unlaked red blood cellsare further evidence for the identity of intracorpuscular and free Hb.18Estimates of the susceptibility of the non-hemin Fe of blood were made.lgThe two theoretical bases of the Hb + 0, equilibrium proposed byG.S. Adair 20 and by L. Pauling 21 have been discussed by C. D. Coryell,L. Pauling, and R. W. Dodson 22 from the magnetic standpoint. They con-clude that the susceptibilities are more in accord with Pauling’s view of fouressentially independent hems in the Hb molecule where the oxygen affinityof one hEm is influenced by the oxygenation of a neighbouring hem. Adair’sconcept of a 4-fold hem structure combining progressively with 1-4 oxygenmolecules appears to require a much higher value for the magnetic moment.The theory of Hb structure due to J. Wyman23 postulates that the twodissociable acid groups of Hb detected by electrode-potential measurementswithin the range pH 5-9 are iminazole groups of histidine by which Fe islinked to the protein.,* C.D. Coryell and L. P a ~ l i n g , ~ ~ from a considerationof potentiometric and magnetic data, provide a theoretical basis of the Bohreffect (variation of oxygen affinity with pH) and also of the change onoxygenation from ionic to covalent bonding in terms of resonance equilibriaof the iminazole groups.Coryell, Stitt, and Pauling l5have measured the susceptibility of the acid and alkaline forms of MetHband of the F’, CN‘, and SH’ derivatives. Their results indicate 5 and 3 u.e.l6 J . Amer. Chem. SOC., 1940, 62, 2942.l* D. Keilin and E. F. Hartree, Nature, 1941, 148, 75.l8 G. Barkan and 0. Schales, 2. physiol. Chem., 1937, 248, 96.*O Proc. Roy. SOC., 1925, A, 109, 299.22 J .Physical Chem., 1939, 43, 825.(B) blethmmoglobin and its derivatives.l7 Ibid., 1938, 60, 1177.a1 Proc. Nat. Acad. Sci., 1935, 21, 186.23 J . Biol. Chem., 1939,.127, 581.The iminazole theory has been criticised by H. F. Holden, Ann. Rev. Biochem.,1946, 14, 599.Is J . Biol. Chem., 1940, 182, 769292 BIOCHEMISTRY.for acid and alkaline MetHb respectively, 5 me. for the F', and 1 me. forthe other derivatives. The considerable deviations from the theoreticalfigures are discussed from the points of view of hcem-hzm interactions andorbital contributions. These authors were obliged to postulate a hcem-hzem interaction as the cause of low values of magnetic moment in spiteof the fact that interaction had been considered responsible for the highvalues found for Hb.The whole position becomes less tenable followingthe magnetic measurements on myoglobin (see below). Magnetic studiesof the change from acid to alkaline MetHb indicated a pK of 8-12 for theequilibrium MetHbOH =+ MetKb' + OH', and the 1 : 1 ratio of Fe to CN'in MetHbCN was confirmed. The unstable irninazolel3 derivative as wellas compounds with azide ion and ammonia likewise appear to be essentiallycovalent (1 u.e.). A compound with EtOH has been reported with amoment of 5-39.16 A slight variation in pB, indicating three forms of acidMetHb, has been reported 26 corresponding to the dissociation of acidgroups. The possible structures of MetHb and derivatives are discussedbut without definite conclusions.Myoglobin contains only one hcem group per molecule,hence the difference between the moments of this pigment and of Hbshould be a measure of hcem-hzm interactions in the latter.D. S. Taylor 27found pB = 5-46 and 5.85 for myoglobin and acid metmyoglobin, respect-ively, which are virtually identical with the corresponding Hb figures.The excess over 4.90 in the case of Hb and myoglobin must therefore bedue to an exceptionally large orbital contribution. Among Fe" salts thiscontribution is small (0.2-0.3) and Taylor suggests that in Fe"-porphyrinsthe nitrogen atoms, being part of a rigid cyclic structure, are held a t agreater distance from the Fe atom than are the anions in simple Fe" salts.On this hypothesis a less effective quenching of the orbital contributioncan be expected.The view of Pauling et aLZ2 that haem-haem interactioncan markedly modify the magnetic moment cannot be generally accepted.A thorough studyof these simple derivatives is an essential prerequisite for a further inter-pretation of the susceptibilities of the natural hcem pigments. Cambi andSzegoe 7 found that the paramagnetism of a pyridine solution of haemindecreased with time. The recorded values of pB for crystalline hzemin are5 ~ 8 1 , ~ 5.83,28 5.69, 5*93,29 5*77,30 and 5.96-6.00. Leaving aside the lastfigures (calculated from the results of F. Haurowitz and B. Kitte131), theaverage of 5-81 indicates ionic bonds. According to Pauling and Coryell29the susceptibilities of hcematin, hzm, and hzmochromogens indicate 5, 4,and 0 u.e., respectively.W. A. Rawlinson32 investigated the same deriv-(C) Myoglobin.(D) Hcemin, hamatin, hcem, and hcemochromogens.26 R. v. Zeyneck, 2. physiol. Chem., 1901, 33, 426.27 J . Amer. Chem. Soc., 1939, 61, 2150.29 L. Pauling and C. D. Coryell, Proc. Nat. Acad. Sci., 1936, 22, 159.80 W. A. Rawlinson and P. B. Scutt, private communication.81 Ber., 1933, 00, 1040.m Auatr. J . Exp. Biol. Xed., 1940, 18, 186.28 Reporter's unpublished resultsHARTREE : MAGNETIC PROPERTIES OF HEMATIN DERIVATIVES. 293atives under different conditions. He confirmed the fall of susceptibilitywith time of haemin in pyridine and ascribed if to parahaematin formationin presence of traces of water; in absence of water pyridine does no6 co-ordinate with haemin.Pyridine parahzematin (hzemin in pyridine andsodium hydroxide) has the expected covalent bonding (pB = 1.97). Paulingand Coryell29 found pB = 5.56 for hzematin solution (hzemin in sodiumhydroxide solution) to which sucrose had been added to prevent aggregationand precipitation. In absence of sugar the lower values 3.52 32 and 3-23 28corresponding to 3 u.e. have been obtained. The high degree of aggregationof hzemin in aqueous alkalill may give rise to these lower values. Theaggregates can be broken down by addition of cyanide and consequentsaturation of the Fe ~ a l e n c i e s , ~ ~ and apparently also by sucrose. A measureof the influence of aqueous solvents can be obtained from the magneticmeasurements of Rawlinson and Scutt 30 on a series of compounds inthe solid state : chloro-, bromo-, acetoxy-, formoxy-, and aza-hsmins,haemin dimethyl ester, hzematin, and the anhydride and half anhydride ofhaematin. The experimental figures for pB range between 5.71 and 5-89except for one sample of haematin where the average value is 5.43.Thelow magnetic moment for hzmatin solutions therefore appears to be due tothe associating effect of the solvent.Of the components of cytochrome, only c can beextracted in a pure form. H. Theorel134 studied the absorption spectraand the magnetic properties of the oxidised (Fe"') pigment at varying pHand demonstrated the existence of 5 forms I-V in which 106xm rangesfrom 13,060 a t pH 0.8 to 1900 at pH 13.5. The results are interpreted inthe light of the iminazole linkage theory.23 Thus type I which exists invery acid solutions resembles spectroscopically the free hzmatin of cyto-chrome c and shows 5 u.e.Type V on the other hand is a typical para-hsmatin with covalent bonding. The intermediate forms represent stagesin the progressive titration of the iminazole groups which consequent changesin bond type. Type I11 exists over the pH range 4-10 and is thus theonly one of physiological significance (106xm = 3300). The strong covalentbonding precludes the formation of cyanide and fluoride derivatives whichcan be detected only at high or low pH when the Fe bonds may be loosened.A compound with nitric oxide in neutral solution has, however, beenreported.35 Ferrous cytochrome-c has the same absorption spectrum andzero magnetic moment a t all pH's.It is a typical hzemochromogen exceptthat it is not autoxidisable a t physiological pH. Some loosening of thebonds must occur a t extremes of pH in order to account for the observ-ations 35* 36 that the pigment is autoxidisable a t pH (4 and >10 andthat i t combines with carbon monoxide a t pH 13. Theorell concludes thatthe essential difference in structure between Hb and cytochrome-c is that(E) Cytochrome-c.33 K. Zeilo and F. Reuter, 2. physiol. Chein., 1933, 221, 101.34 J. Anzer. Chena. SOC., 1941, 63, 1804, 1812, 1818, 1820.35 D. Keilin and E. F. Hartreo, Proc. Roy. SOC., 1937, B, 122, 298.36 D. Keilin, ibid., 1930, B, 106, 418294 BIOCHEMISTRY.in the former only one of the two iminazoles is favourably orientated forstrong co-ordination with iron, but in the latter two strong bonds areformed. Thus, the bond available in Hb for reaction with oxygen or carbonmonoxide is only available to cytochrome-c at extremes of pH.(F) Cutulase and peroxidme. In order to deal with the very smallquantities of these enzymes which can be obtained in the pure state,H.Theorell 37 constructed an apparatus for micro-determination of suscept-ibility. A narrow glass tube divided by a central septum into two equallengths is suspended horizontally from two long fibres. Solvent and enzymesolution are placed in the two halves of the tube and a strong magneticfield is applied at the region of the septum. From the longitudinal dis-placement the paramagnetism of the iron may be calculated.Using crystalline horse-liver catalase, H.Theorell and K. Agner 38 cor-rected the earlier figure of pB = 4.64 39 and studied several derivatives ofcatalase. The magnetic study of this substance presents considerable diffi-culties. For instance, as the iron content is only 0-093y0, very concentratedsolutions must be used, involving large corrections for diamagnetism.Furthermore, in “ pure ” crystalline liver catalase only about 75% of the ironis present as haematin, the remainder being in the form of a bile-pigmentderivative. The necessity of assuming a value for the susceptibility of thelatter, and a t the same time assuming that it constitutes 25% of the iron,introduces uncertainties into the calculations of haematin-Fe susceptibility.The partition of iron between hzmatin and bile pigment in pure catalase isvariable,4O although Theorell finds evidence for about 25% of the latterin his samples by magnetic titration with hydrogen cyanide.By analogywith acid MetHb, the iron of catalase has 5 u.e. (pB = 5.89) and henceionic bonding. Similar bonding in azide catalase is in striking contrast tothe azide derivative of MetHb. D. Keilin and E. F. Hartree 41 showed thatazide catalase reacts with peroxides to give a derivative which combines withcarbon monoxide and is autoxidisable and therefore contains ferrous iron.It was proposed by analogy that free catalase would undergo a similarcyclic valency change during the decomposition of hydrogen peroxide.According to Theorell and Agner, however, the susceptibility of azide-catalase + peroxide in nitrogen or carbon monoxide indicates that noreduction takes place.These results are criticised by Keilin and Hartreeon the grounds that the peroxide derivatives are too unstable to remainunchanged during the magnetic masurements. Figures for the CN’, SH’,and F’ derivatives of catalase are given in Table 111.Crystalline horse-radish peroxidase and its derivatives have beenexamined by T h e ~ r e l l . ~ ~ * ~ ~ In this case the total iron (0.127y0) is present37 Arkiv Kemi, Min. Geol., 1942, 16, A, No. 1.38 Ibid., No. 7.39 L. Michaelis and S. Granick, J . am. Physiol., 1941, 25, 325.40 R. Lemberg and J. W. Legge, Riochem. J., 1943, 37, 117.4 1 Proc.Roy. Xoc., 1938, B, 124, 397; Biochem. J . , 1945, 39, 148.42 Enzymologia, 1942, 10, 250. 43 Arkiv Kemi, Min. Geol., 1942, 16, A, No. 3HARTREE : MAGNETIC PROPERTIES OF HEMATIN DERIVATIVES .TABLE I11 .Haemoglobin (ox blood) .................................0.. COY NO. CN. EtNC derivatives ..................&iethaemoglobin. acid .................................... .............................. .. alkalineY Y F’ .. CN’ .. S H‘9 9 iminazole .. NH.7 ) N. ..................................... .. EtOHMyoglobin ...................................................Metm yoglobin .............................................Haemin (cryst.) ..........................................Haematin (haemin in NaOH) ........................... ..+ sucrose ....................................Haem (haematin + Na.S.0. ) ...........................Parahaematin (hEmatin + pyridine) ...............Haemochromogens (pyridine. dicyanide. globin.nicotine) ............................................................................................................................................................... ................................................................................................Bromohaemin (solid) ....................................Acetoxyhaemin (solid) ....................................Formoxyhaemin (solid) .................................Azahaemin (solid) ..........................................Haematin (solid) ..........................................HEmatin anhydride (solid) ...........................Peroxidase (pH 4-9) ...................................... F’ ............................................. .. SH’ .......................................... .. CN’ .......................................... .. H.O. ..........................................Reduced peroxidase .................................... .. co .................................Catalase ................................................... .. CN’ ................................................ .. N. .................................................Haemin dimethyl ester (solid) ........................Haematin anhydride (solid) ........................17-I71 .. I‘ .................................................. SH’ ................................................ .. co ........................ h i d e catrtlme + H.O. in N. ........................ .. ..106xm . Temp .12. 290 24’14. 040 YY8. 340 Y Y 14. 610 .. 2. 610 Y Y2. 1402. 040 !%3. 700 ..3. 360 ..12. 25012. 400 ik14. 200 .. averageaverage13. 080 209. 310 191. 660 180014. 585 1414. 618 1214. 941 ..14. 320 1414. 376 1314. 569 .. 15. 053 ..14. 45612. 560 i b14. 840 .. 2. 440 .. 2. 970 Y711. 410 .. 0 ..14. 665 .. 6. 830 .. 14. 500 .. 14. 665 ..7. 290 .. 6. 600 Y )4. 920 9 )(4. 800 t YCLB .5.4305.804.475.922.502.262.662.932-845.395.465-855-823-535.564.691-9705-815.805.S65-765.756.795.895.77 ----- - -5.894.025.865.893-953.41-295u.0.405351111154563 ?54105555555555111 940536539?Pas haematin .The results (Table 111) are similar to those obtained withMetHb except that 106xm for free peroxidase in neutral solution is ratherlow for 5 u.e. (12. 650) and in alkaline solution it drops to 2800 . The figuresgiven for H,O, peroxidase are not significant. as a mixture of derivatives ispresent ; nevertheless. covalent bonding is probable . Theorell records avery labile green hydrogen peroxide derivative which changes rapidly tothe red hydrogen peroxide peroxidase I of D . Keilin and T . Mann.4 TheCN’. SH‘. and F‘ derivatives of peroxidase are strictly comparable withthose of MetHb .( G ) Covalent and ionic bonding .Although magnetic measurementsindicate ionic bonding in some hzmatin derivatives. the iron is held moresecurely than in iron salts . Hence. all tests for the ion are negative andit cannot be removed electrolytically . Furthermore. it has not been44 Proc . Roy . SOC., 1937. B. 122. 119 296 BIOCHEMISTRY.possible to introduce radioactive iron into Hb by ion exchange.45 Theenclosure of the iron atom within the cyclic porphyrin structure with itshigh resonance energy is no doubt responsible for its inaccessibility. Slightmodifications of the porphyrin such as removal of one iCH (bile pigment)or hydrogenation of some double bonds (porphyrinogen) render the ironmore labile.Analogies between Magnetic and Optical Properties of Hcematin Deriv-atives.-The relationships between absorption spectra and variation in ironbonding have already been outlined.43 Since the magnetic and spectro-scopic approaches to the study of hzmatin compounds must be regardedas complementary, inasmuch as the same processes may in general befollowed by both techniques, these relationships deserve special attention.The available data are collected in Table IV.TABLE IV.1‘0 F O Colour and spectrumGrouyi.valency. bonding. type. Examples.a 3 Ionic Green-brown. Abs. band Haemin in sucrose-NaOH.in red between 600 and Haemin in pyridine.640 mp. Strong band in MetHb and F’ cpd. Cata-blue, sometimes faint lase and F’ and N,’ cpds.bands in green.b 2 Ionic Carmine-red-purple.Dif- Haemoglobin. Myoglobin.fuse band in green. HEm.in green. MetHb.SH’, CN’ cpds. of peroxidase.Brown-red diffuse band in Parahaematins, e.g., cyto-green. chrome-c.d 2 Covalent Scarlet to pink; 2 very 0,, CO, NO cpds. of Hb.sharp bands in green. Haemochromogens (cyt.-c).Ezceptions .- (1) Alkaline MetHb is intermediate between ( a ) and (c) : 3 me., red-(2) MetHbCN falls into group ( c ) except that the spectrum resembles ( b ) .(3) Reduced peroxidase falls into group ( b ) but has two bands in the green.(4) CN’ and SH‘ compounds of catalase appear to have 3 u.e.Peroxidase and F’ cpd.C 3 Covalent Bright red; 2 diffuse bands S H , N3’, H,O, cpds. ofReduced peroxidase-CO.brown colour, two bands in the green plus a narrow band a t 600 mp.Otherwise they resemblethe corresponding MetHb compounds [group (c)].E.F. H.5. NUTRITION : ANTI-ANBMIA FACTORS.In the last three years a number of substances have been described withproperties which justify their inclusion in a single group. Among them arevitamin M, vitamin B,, the norite eluate factor, the L. casei factor, factor U,folic acid, and the 8. lactis R. factor. Properties common to most of themare stimulation of bacterial growth and of hzmatopoiesis in mammalsincluding man. It is the latter property which has given these substancesprominence in the treatment of human macrocytic aniernia. It is now certainmany of these substances share a common structure, varied by the attach-ment of different chemical groups.The precise relationship among them hasstill to be established. A certain confusion obvious in papers dealing with46 See Selwood, op. cit. (ref. 4), p. 171O’BRIEN : NUTRITION : ANTI-ANXMIA FACTORS. 297these factors lies in the indiscriminate use of names, in attempts to relate thoseactive towards micro-organisms with those active towards animals, and inneglect to state the source of the factors. The confusion is, however, beingrapidly dispelled by reports upon the chemical nature of the factors. Mean-while unambiguous use of names is essential.No discussion of the animal factors can be truly appreciated without asketch of those active towards L. m e i and 8. lactis R. The name “folicacid ” has been used most haphazardly in designating concentrates andsubstances active towards animals and micro-organisms.I n the firstinstance it was used by Williams to denote a substance isolated in a highlypurified form from spinach which stimulated the growth of S. Zactis R.This substance is also active towards L. casei. With these two micro-organisms as test objects, the existence of several active substances has beenestablished. Two factors have been isolated, one from liver and the otherfrom yeast, both equally active towards L. casei2 But towards 8. Zactis R.the liver factor is twice as active as the yeast one. A third L. cmei factorhas been obtained from a fermentation re~idue.39~ Compared with the liverL. cmei factor it is 85-90% as active towards L. casei and only 6% towardsS.Zactis R. Bydegradation and synthesis the structure of the liver L. casei factor has beenestablished by Angier and his colleagues 41These three factors have been obtained in crystalline form.(I).RN\ AC0,H “/ \(-yC0,H*[CH2],*~H*NH*CO-(>-NH*CH2-c HC: c N yNH2(1.) OHThe presence in the molecule of the p-aminobenzoyl group is of interestbecause of its antagonistic effects upon sulphonamides, and that of the2-amino-6-hydroxypteridine structure because of the many hints that the(11.1 OHpterins have a part in hzematopoiesis. Angier et aZ. recommend an acceptablenomenclature based upon pteroic acid (11), which, if adopted, would simplifyH. K. Mitchell, E. E. Snell, and R. J. Williams, J. Amer. Chem. SOC., 1941,63, 2284.E. L.R. Stokstad, J. Biol. Chem., 1943, 149, 573.B. L. Hutchings, E. L. R. Stokstad, N. Rohonos, and N. H. Stobodkin, Science,1044, 99, 371.R. B. Angier, J. H. Boothe, B. L. Hutchings, J. H. Mowat, J. Semb, E. L. R.Stokstad, Y. SubbaRow, C. W. Waller, D. B. Cosulich, M. J. Jahranbach, M. E.Hultquist, E. Kuh, E. H. Northey, D. R. Seeger, J. P. Sickels, and J. M. Smith, ibid.,1945, 102, 227.Ibid., 1946, 103, 667298 BIOCHEMISTRY.the existing terminology of these new anti-anaemic factors. The liver L. caseifactor would be named pteroylglutamic acid. The fermentation L. cuseifactor contains two extra glutamic acid residues; probably it is pteroyl-diglutamylglutamic acid. Another product was obtained by Angier et al.by the same method of synthesis used for the 1;.casei factor, by the condens-ation of p-aminobenzoic acid with N-(2-amino-6-hydroxy-8-pteridyl)rnethyl-pyridinium iodide. Unlike the other two substances, it is active towardsS. Zactis R. but not towards L. msei or the chick. It will be interesting if thisproduct turns out to be identical with pteroic acid and the S. lactis R. factorof Keresztesy and’ his co-workers.6It ishighly probable that other crystalline products active in the same respect areidentical with or closely related to pteroylglutamic acid. Pfiffner and hisco-workers 7* * s 9 have isolated two compounds in crystalline form; one, anorange coloured acid, named vitamin B,, and a second from yeast, whichhas been named vitamin B, conjugate. Both have anti-anaemic activity.Vitamin B, conjugate has a molecular weight of m.1400, roughly 2-3 timesthat of vitamin B,, and a spectral absorption very similar to vitamin B,.From hydrolysis experiments and electrophoretic behaviour, the conjugatehas been shown to contain 7 glutamic acid residuesYg a fact which relates itto the fermentation L. casei factor. It is, however, almost inactive micro-biologically, which differentiates it from the L. casei factor and vitamin B,.But on incubation with an enzyme, named vitamin B, conjugase, the con-j ugate yields vitamin B, which is microbiologically active. Following therecommendations of Angier et al. , Pfiffner and his co-workers have renamedthe conjugate pteroylhexaglutamylglutamic acid.The isolation of conjugates of vitamin B, and of the liver L.casei factorprovides an explanation of the different effects upon micro-organisms ofconcentrates of the factors and of partly purified substances. Illustrativeof this point is the difference in activity of the liver L. casei factor, thefermentation L. casei factor, and pteroylhexaglutamylglutamic acid towardsL. casei. The enhanced microbiological activity of concentrates of the factorafter enzymatic digestion obviously results from the conversion of conjugatesinto forms utilisable by micro-organisms. This conversion can be effectedby the enzyme vitamin B, conjugase,1° widely distributed in animal tissues.Some mention of what is known of this enzyme is worth while, since itmay play a part in the utilisation of conjugates by animals and micro-organisms.11 The method of testing conjugase activity consists in incubating6 B.C. Keresztesy, E. L. Rickes, and J. L. Stokes, Science, 1943, 97, 465.7 J. J. Pfiffner, S. B. Binkley, E. S. Bloom, R. A. Brown, 0. D. Bird, A. D. Emmett,8 Ibid., 1945, 102, 228.9 J. J. Pfiffner, D. G. Calkins, E. S. Bloom, and B. L. O’Dell, J . Amer. Chem. Soc.,10 0. D. Bird, S. B. Binkley, E. S. Bloom, A. D. Emmett, and J. J. Pfiffner, J . Biol.11 0. D. Bird and M. Robbins, ibid., 1946, 163, 661.Synthetic 1;. casei factor is active in preventing anaemia in chick^.^A. G . Hogan and B. L. O’Dell, ibid., p. 404.1946, 68, 1392.Chem., 1945, 157, 413O’BRIEN : NUTRITION : ANTI-ANBMIA FACTORS. 299extracts of tissues with concentrates or preparatiom of vitamin B, conjugate,and the estimation of the amount of 8.lactis R. factor in the digest.12 Con-jugase activity is shown by kidney, liver, pancreas, and intestine of animalsand birds, by almonds, by potatoes, and, to a slight extent, by moulds.1°*13Conjugase activity is not shown by phosphatase, nucleosidase, or p-glucos-idase.lO* l4 Chicken pancreas has a high conjugase content, whilst hog’skidneys are a good starting material for enzyme preparations.1° Fromkinetic studies and determinations of optimum pH values, the activity oftissues may be due to more than one c ~ n j u g a s e , l ~ * ~ ~ which may be foundto differ in their mode of action. But from comparative studies with crystal-line vitamin B, conjugate it would seem that the substrates attacked by theconjugases are structurally akin to the conjugates and do yield vitamin B,.More precise information upon these enzymes will be welcome, since theirabsence or inhibition in the gut may be a factor in human macrocytic anamiain which defects in intestinal absorption are a feature.Theyare the L.casei factor (from liver and the synthetic pteroylglutamic acid),the fermentafion A. casei factor 1‘ (pteroyldiglutamylglutamic acid), vitaminB,, and the vitamin B, conjugate (pteroylhexaglutamylglutamic acid). Inbiological and chemical properties vitamin B, is very similar to L. caseifactor. The fact that Pfiffner et al. designate vitamin B, conjugate aspteroylhexaglutamylglutamic acid, taken with their observation of thepresence of glutamic acid in vitamin B,, suggests that they believe vitamin B,to be pteroylglutamic acid.Tested microbiologically, vitamin B,, pteroyl-glutamic acid, and folic acid have the same activity towards L. casei l8and 8. Zuctis R., from which it has been concluded that they are one and thesame substance. It would seem that the active component is pteroyl-glutamic acid into which the conjugated forms are converted, possibly by theaction of the conjugases within the intestine.C. F. Campbell, M. M. McCabe, R. A. Brown, and A. D. Emmett l9have described in detail the hematological changes which occur in chicks asthe results of vitamin B, deficiency. After three weeks on the purified dietthe chicks showed very poor feathering.At about the same time there wasa definite anamia characterised by macrocytosis and normoblasts, pro-normoblasts and myeloblasts in the blood, a leukopenia, and a thrombopenia.These severe changes in the blood cells were prevented by diets containing100 pg. of crystalline vitamin B,/100 g. of diet. Not all workers agree thatvitamin B, alone can prevent anamia in the chick. M. L. Scott, L. C. Norris,Several factors are effective in preventing anamia in chicks.12 V. Mims, J. R. Totter, and P. L. Day, J . Bwl. Chern., 1944,155,401.l8 M. Laskowski, V. Mims, andP. L. Day, ibid., 1945,167, 731.l4 V. Mims and M. Laskowski, ibid., 159, 493.l6 J. G. Memon and J. R. Totter, ibid., p. 301.l* 0. D. Bird, M. Robbins, J. M. Vandenbelt, and J. J. Pfiffner, ibid., 1946,163,649.1 7 B.L. Hutchings, J. J. Oleson, and E. L. R. Stokstad, aid., p. 447.l8 B. C. Johnson, ibid., p. 255.19 Arner. J . Physwl., 1945, 144, 348300 BIOCHEMISTRY.G. F. Heuser, and W. F. Bruce 2o consider that either a- or p-pyracin is alsonecessary. The adjuvant effect of pyracin has not been observed by 0thers.1~The discrepancy is not resolved by the suggestion, based on the in vitroconversion of crystalline L. msei factor into S. lactis R. factor by liver, thatpyracin is conjugated with L. msei factor or part of enzyme responsible forthe conversion.21There are a number of problems of chick nutrition still to be solved.One at least appears to have been settled, and that is the nature of the factorconcerned with the feathering of chicks.Elvehjem and his co-workers 22reported the presence of two factors in the norite eluate concentrations;vitamin B,, responsible for good feathering and vitamin B,, essential forgrowth. Crystalline vitamin B, has been shown to prevent poor feathering.23Oleson and his co-workers have shown that pteroylglutamic acid added tosynthetic diet ensures good feathering and that other factors such as ascorbicacid and p-aminobenzoic acid are ~nnecessary.2~ It seems fair to concludethat vitamin B,, is very similar to pteroylglutamic acid. The relation of theantianaemic factors to feathering is not without interest when it is remem-bered that poor hair and nail growth is a feature of human macrocyticanaemia.It is impossible to discuss at length the extensive work upon the relationof the antianaemic factors to the good health of the rat.One or two phasesmay be selected to illustrate other properties of the pteridines. Our under-standing of agranulocytosis and of acute granulocytopenia associated with theadministration of drugs is poor. In rats a profound disturbance of growthand of blood formation characterized by agranulocytosis and hypocellularityof blood marrow develops from the inclusion in the diet of sulphaguanidineand sulpha~uxidine.~~*~~ These effects can be remedied by the feeding ofliver extracts rich in " folic acid " or by crystalline " folic acid ".26* 27*2t3In a small number of rats upon purified diets agranulocytosis develops withoutthe administration of sulph~namides.~~ This also responds to L.caseifactor. Daft and his co-workers 30 observed more severe blood disorders inrats fed a purified diet low in pantothenic acid. Pantothenic acid deficiencydid not manifest itself uniformly in a particular group of rats. In some ratszo Amer. J . Physiol., 158, 291.21 L. J. Daniel, M. L. Scott, L. C. Norris, and G. F. Heuser, ibid., 160, 265.22 G. M. Briggs, T. D. Luckey, C. A. Elvehjem, and E. B. Ward, ibid., 1943, 148,a3 C. J. CampbelI, R. A. Brown, and A. D. Emmett, ibid., 152, 483.24 J. J. Oleson, B. L. Hutchings, and N . A. Sloane, ibid., 1946, 165, 371.25 A. D. Welch, P. A. Wattis, and A. R. Latven, J . Pharm. Exp. Ther., 1942,75, 231.26 S. S. Spicer, F. S. Daft, W. H. Sebrell, and L. L. Ashburn, Publ. Health Reps.,27 A.Kornberg, F. S. Daft, and W. H. Sebrell, Science, 1943, 98, 20.28 F. S. Daft and W. H. Sebrell, Publ. Health Reps., Wash., 1943, 58, 1542.28 A. Kornberg, F. S. Daft, and W. H. Sebrell, Proc. SOC. Exp. Biol. Med., 1945,58,46.30 F. S. Daft, A. Kornberg, L. L. Ashburn, and W. H. Sebrell, Publ. HeaZth Reps.,163; 1944,153, 423.Wash., 1942, 57, 7559.Wash., 1945, 60, 1201O’BRIEN : NUTRITION : ANTI-ANZMIA FACTORS. 301granulocytopenia occurred together with anzemia ; in others, anaemia waB thepresenting symptom; in a few, granulocytopenia, and in some, no blooddyscrasia. The most $evere anaemia was seen in the granulocytopenic ratsand was accompanied by hypoplasia of the bone marrow. I n the anzmicanimals, hypoplasia of the marrow was less frequent and less severe.Noneof these blood disorders develops in the control animals which receive panto-thenic acid. Despite its prophylactic effectiveness, pantothenic acidproduced a slow cure of the anaemia and had a slight effect upon the granulo-cytopenia. On the view that pantothenic acid deficiency had produced adeficiency of another factor, the fermentation L. casei (or liver L. casei) factorwas administered together with pantothenic acid. This treatment provedfar more effective in curing the blood dyscrasias than that of either factoralone. Results similar to, although not identical with, those of Daft and hisco-workers were obtained by Carter and his co-worker~.~~ In their rats adeficiency of pantothenic acid led to a hypochromic anzmia and a reduction inpolymorphonuclear leucocytes.The bone marrow showed hyperplasia andevidence of failure of maturation of both erythropoietic and leucopoieticcells. Initiated a t an early stage of the disease, pantothenic acid therapyproduced a restoration of a normal blood picture. Furthermore, the controlrats receiving pantothenic acid developed an anzmia after a prolonged periodwhich might be attributed to the lack of anti-anzmic factor of the pteridinetype. It may be that adeficiency of pantothenic acid conditions a deficiency of “ folic acid.’’ It isto be noted that L. D. Wright and A. D. Welch 32 have considered that bothbiotin and “ folic acid ” may perhaps be essential for the storage or utilizationof pantothenic acid.For many years it has been recognised that inadequate diet produces aprofound and often fatal disorder of the blood in the m0nkey.~s*34*3~ Theblood picture of the animals is one of anaemia and leucopenia.The deficientanimals usually suffer from‘ ulcerated gums and from diarrhwa and theybecome easily susceptible to spontaneous infection. Untreated, the con-dition progresses to a fatal end. Yeast and yeast products and liver arecurative and often elicit a reticulocyte response. Since none of the well-known members of the vitamin B complex or other vitamins 36*37 affects thecondition, it has been attributed to lack of a factor known as vitamin M.Recently, preparations of “ folic acid ” have proved effective in treatment.38Some success had been obtained with xanthopterin, which produced a sub-31 C.W. Carter, R. G . Macfarlane, J. R. P. O’Brion, and A. H. T. Robb-Smith,Biochem. J . , 1945, 39, 339.32 J . Nutrition, 1944, 27, 55.33 L. Wills and H. S. Bilimoria, Indian J . Med. Res., 1932, 20, 291.34 L. Wills and A. Stewart, Brit. J . Exp. Path., 1935, 16, 444.s5 P. L. Day, W. C. Langston, and C. F. Shukere, J . Nutrition, 1935, 0, 637.86 W. C. Langston, W. J. Darby, C. F. Shukers, and P. L. Day, J. Exp. Med., 1938,1 7 S. Saslaw, H. F. Wilson, C. A. Doan, and J. L. Schwab, Science, 1943,97,614.88 H. A. Waiaman and C. A. Elvhjem, J . Nutrition, 1943, u, 381.The explanation of these findings is not easy.68, 923302 BIOCHEMISTRY.normal reticulocyte response and a ret& of blood cells to Theeffect of the pterin did not persist unless given together with liver powder.The most effective treatment has been with highly purified preparationsof L.casei factor or with crystalline L. w e i f a c t ~ r . N * ~ ~ Intramuscularinjections of crystalline L. casei factor produces a reticulocyte response ashigh as 47% within 4-7 days and restoration of the number of red and whitecells to normal and a definite clinical improvement. The remarkable successof L. casei factor in the treatment of nutritional anaemia of the monkey andsimilar conditions in other species indicates rather strongly that vitamin Mfalls in the class of the pteroylglutamic acids. This view is supported by thefact that, although the folk acid content (as measured by the growth of8.lcsctis R.) of substances with vitamin M activity-is low, it parallels thevitamin M potency of substances after they have been incubated with rat’sliver .42The therapeutic success of the L. casei factom in the treatment of anaemiaand leucopenia in animals justified their clinical trial in cases of macrocyticanaemia. There were also other reasons. In some respects vitamin de-ficiency in the monkey is analogous to sprue in man. Furthermore it haslong been auspected that an unknown factor of that group of miscellaneoussubstances, the vitamin B complex, has a r61e in those macrocytic anaemiasthe origin of which is nutritional deficiency. Among these anEmias may beincluded those called refractory because of their unresponsiveness to theusual therapeutic measures such as purified liver extracts and iron.Typicalexamples are refractory anzemias of pregnancy and malnutrition. Relatedto these on hamatological grounds are the anaemias of sprue and Addisonianpernicious anemia. The existence of anti-anaemic factor was indicated bythe curative action of crude yeast and liver preparations upon macrocyticanzmia of pregnancy and tropical macrocytic anzernia and by thebeneficial effect of dried yeast upon pernicious a n ~ m i a . ~ ~ In the last fiveyears the investigation of anzemia of pregnahcy has been pursued mostdiligently. But despite its similarity to pernicious anaemia, from which it ismost readily distinguished by free hydrochloric acid in the gastric juice,pregnancy anzemia responds only to the most vigorous therapeutic treat-ment,46 usually with liver in an unpurified It would seem thatJ.R. Totter, C. F. Shukers, J. Kolson, V. Mim, and P. L. Day, J . BioE. Chem.,40 P. L. Day, V. Mims, J. R. Totter, E. L. R. Stokstad, B. L. Hutchings, and N. H.4 1 P. L. Day, V. Mims and J. R. Totter, ibid., 161, 45.I2 J. R. Totter, V. Mims, and P. L. Day, Science, 1944, 100, 223.43 L. Wills, Brit. Ned. J., 1931, i, 1059.44 L. Wills and B. D. F. Evans, Lancet, 1938, ii, 416.46 M. Wintrobe, Amer. J. Med. Sci., 1939, 197, 286.46 L. S. P. Davidson, L. J. Davis, and J. Innes, Brit. Med. J . , 1942, ii, 31.47 H. W. Fullerton, ibid., 1943, i, 158.4a J. Wateon end W. B. Castle, Proc. SOC. Exp. Bid. Med., 1945, 58, 84; Amer.J .1944,152, 147.Sloane, ibid., 1945, 157, 423.Ned. Sci., 1946, all, 613O'BRIEN : NUTRITION : ANTI-ANIEMIA FACTORS. 303pregnancy anaemia and other macrocytic anaemias associated with mal-nutrition are the consequence of the lack of a substance which is not the anti-pernicious anazmia fact0r.~8 This factor may be related to pteroylglutamicacid or one of its several forms. For, in the last two years, a number ofreports have appeared upon the beneficial effect of the synthetic L. w e ifactor upon macrocytic anaemias of differing etiology. The claims made insome of the first reports would have been more convincing had they beenaccompanied by a statement of the criteria of diagnosis and data upon thechanges in the bone marrow. Moreover, no reports have been made offollow-ups of treated cases to allow a judgment of how lasting is the effect ofL.casei factor. Nevertheless i t would seem that, in pteroylglutamic acid inone form or another, we have a therapeutic agent of value.Evidence for the haemopoietic activity of synthetic L. msei factor isaccumulating. In 1945 Spies and his co-workers 49 reported a hematologicresponae in nine unspecified cases of macrocytic anaemia following theadministration of synthetic L. casei factor. During treatment the patientswere given a diet free from meat and meat products to reduce their intake ofthe extrinsic factor. Given intravenously or orally, the compound produceda reticulocytosis and a rise in haemoglobin and red cells. A second reportby Spies and his co-workers describes the effect of the synthetic materialupon fourteen cases of macrocytic anaemia ; nutritional macrocytic anaemia(6), Addisonian pernicious anaemia ( 5 ) , and indeterminate (3).In these and inothers 51 a full restoration of haemoglobin and red cells to normal values isnot always observed. Moore and his co-workers 52 also describe remissions intwo cases of pernicious anaemia and one case of anazmia of pregnancy followingthe administration of synthetic L. casei. In all three cases there was a reti-culocyte response of 40-50%, and a rise in haemoglobin and red cells withdoses of 20-100 mg. of synthetic L. casei factor given daily for 10-15 days.It is to be noted that a total dose of 1 g . of synthetic compound was in-sufficient to produce a complete remission in one of the cases of perniciousanaemia.On the other hand a dose of 2 mg. of " folic acid " given daily for20 days is stated to produce complete remission in a case of Addisonianpernicious anaemia.= There can be little doubt that in the macrocyticanaemia the synthetic L. casei factor has a hazmopoietic action and its use inthe treatment of macrocytic anemia of pregnancy and malnutrition may bevaluable. In pernicious anzemia it has not produced complete remission inthe amounts in which it occurs in therapeutic doses of liver extract," or ahaemopoietic response in amounts of 0.7 mg.-a dose in which highly purified49 T. A. Spies, C. F. Vilter, M. B. Koch, and M. H. Caldwell, South Med. J., 1945,38, 707.C.F. Vilter, T. D. Spies, and M. D. Koch, ibid., p. 781.C. V. Moore, 0. S. Bierbaum, A. D. Welch, and L.. D. Wright, J . Lab. CEin. Med.,b1 T . D. Spies, Lancet, 1946, i, 225.1946, 20, 1066.Sa C. A. Doan, H. E. Wilson, and C. 0, Wright, Ohw State Med. J., 1946,42,139.b4 Q. W. Clark, Amer. J , Med. Bci., 1946, aoS, 620304 BIOCHEMISTRY.liver extracts are active.55 Probably there are two or more factors, oneassociated with the defect in pernicious anaemia and the others with thedefects in the nutritional macrocytic anaemias. The similar biologicaleffects of the anti-pernicious factor and the L. casei factor may possibly bedue to their having in common a group such as that of the pterins.56In tropical and non-tropical sprue, synthetic L.cusei factor has a bene-ficial effect.57* 58e 59* 6oi 61 Most of the cases which have been treated fulfil thediagnostic criteria for sprue 62 in that they showed a macrocytic anaemia,leucopenia, glossitis, diarrhoea with increased fat in stools, loss of weight,pigmentation of the skin, etc. The presence of free hydrochloric acid in thegastric juice differentiated them from pernicious anaemia. The typicalresponse to pteroylglutamic acid is as follows. The intramuscular adminis-tration of 15 mg. of synthetic L. casei factor daily is followed within a fewdays by a reticulocyte response and rise in haemoglobin, red and white cells,and platelets. This haematologic response is accompanied by a definiteimprovement in the clinical condition. Glossitis disappears, diarrheasubsides, and appetite improves.Studies of the bone marrow 5 7 p 5 8 showthat the primitive red cells present before treatment disappear and the whitecell series return to normal. In most of the cases the response to treatment israpid and even dramatic, and, in some, most effective in that the patientsremain in excellent health.6l Most probably the beneficial effect of liverextract upon sprue can be ascribed to the presence of a substance allied to oridentical with pteroylglutamic acid. The close similarity of vitamin Mdeficiency in the monkey to sprue may permit this disease to be attackedmore vigorously from the experimental side.Pterins and the Macrocytic Ancemia Factors.The close link now established between the L. casei factors and thehematopoietic system gives a new significance to the pterins, the pigmentsof the wings of insects, for it is now certain that the L. casei factors containwithin their molecules the pteridine group. It may be said that withoutinformation of the biological effects of the pterins and of their chemicalstructure the elucidation of the nature of the L. casei factors would not havebeen so speedily achieved. Of these pigments, which, as early as 1889 6365 Y . SubbaRow, A. H. Hastings, M. Elkins, " Vitamins and Hormones ", Vol. 3,Academic Press Inc., New York, 1945, 237.W. Jacobson and D. M. Simpson, Biochem. J., 1946, 40, 3.6 7 W. J. Darby and E. Jones, Proc. SOC. Exp. Biol. Med., 1945,60, 259.68 W. J. Darby, E. Jones, and H. C. Johnson, Science, 1946,103, 108.69 T. D. Spies, F. Milanes, J. A. Menendm, and V. Mennich, J. Lab. Clin. Med.6o T. D. Spies, V. Minnich, M. Koch, G. G. Lopez, and J. H. Menendez, South Med. J.,61 G. G. Lopez, T. D. Spies, J. A. Menendez, and R. L. Toce, J . Amer. Med. Assoc.,61 F. M. Hams, Amer. J . Med. Sci., 1942, 204, 436.tm F. ct. Hopkins, Proc., 1889, 6, 117.1945, 30, 1056.1946, 39, 30.1946, 132, 906O’BRIEN : NUTRITION : ANTI-ANBMIA FACTORS. 305and as late as 1941,64 were investigated by Hopkins, two, xanthopterin andleucopterin, have been synthesised. From several lines of evidence they maybe involved in the processes of hzmatopoiesis. R. Tschesche and H. J.Wolf 65 claim that the injection of 10 pg. of xanthopterin cures the anzmiaof rats produced by feeding goat’s milk. The anaemia of trout fed on de-ficient diets also responds to natural and synthetic xanthopterin.66 Thesame pigment restores but does not maintain a normal picture in vitaminM-deficient monkeys 39 and is also beneficial to rats which, having ingestedsuccinylsulphathiazole, have developed le~copenia.~~ These effects may bemediated by xanthopterin per se. On the other hand, the trout, the rat, andthe monkey may be capable of synthesising the active hzematopoietic factorfrom the pterin.Xanthoptcrin is present in mammalian tissues, where it may exercise anenzymatic r61eyG8 perhaps similar to the flavins. It is present in liver 69and liver extracts 7O and is excreted in the urine of man.71 More interestingis the observation of Jacobson 72 that the argentaffin cells of the mucosa ofthe digestive tract contain pterins. These specially differentiated cells liein the cardiac and pyloric areas of the stomach and in the intestine, par-ticularly the duodenum. There is a similarity in the distribution of thesecells and those from which the anti-pernicious anaemia factor can be obtained.In autopsy specimens obtained from twelve cases of pernicious anzemia theargentaffin cells were absent or reduced in numbers.72 More recentlyW. Jacobson and D. M. Simpson 73 have compared the fluorescence spectraof the cytoplasmic granules of argentaffin cells with those of xanthopterinand leucopterin. They found that extracts of cells had a spectrum almostidentical with that of xanthopterin. On the other hand the fluorescencespectra of eighteen commercial and experimental liver extracts, all activeagainst pernicious anaemia, indicated the presence of leucopterin or a mixtureof leucopterin and some ~ a n t h o p t e r i n . ~ ~ Furthermore the hzemopoieticactivity of the extracts, assessed by their action upon cases of perniciousanzmia or upon splenectomised rabbits 75 and the intensity of their fluor-escence, run parallel. This would suggest that the haematopoietic activityand fluorescence arise from the same substance-the anti-pernicious anzmiafactor. Jacobson and Simpson 74 consider that this factor contains pterinbound to some other substance. Without further data it is premature tospeculate upon reconciliation of these findings with those upon factors64 F. G. Hopkins, Proc. Roy. SOC., 1942, B, 130, 359.155 2. physiol. Chem., 1937, 248, 34.66 R. W. Simmons and E. R. Norris, J . Biol. Chene., 1941, 140, 679.15’ J. R. Totter and P. L. Day, ibid., 1943, 147, 257.6 8 W. Koschara, 2. physiol. Chem., 1937, 250, 161.7o B. M. Jacobson and Y. SubbaRow, J . Clin. Invest., 1937,16,373.71 W. Koschara, 2. physiol. Chem., 1943, 277, 159.72 W. Jacobson, J . Path. Bact., 1939, 49, 1.73 Biochem. J . , 1946, 40, 3.76 Idem, J . Path. Bact., 1946, 57, 423.Ibid., 1936, 240, 127.74 Ibid., p., 9306 BIOCHEMISTRY,known to contain the pteridine group, especially as W. B. Emery and L. F. J.Parker 76 could find no specific ultra-violet absorption characteristics in ahighly purified preparation of the anti-pernicious anaemia factor made fromliver. J. R. P. O’B.K. BAILEY.F. CHALLENGER.F. DICKENS.E. F. HARTREE.J. R. P. O’BRIEN.76 Biochem. J., 1946, 40, Proc. iv

ISSN:0365-6217    

DOI:10.1039/AR9464300262

出版商:RSC    

年代:1946

数据来源: RSC

摘要:

ANALYTICAL CHEMISTRY.1. INTRODUCTION.THE various branches of analytical chemistry are seen to be inter-relatedwhen it is admitted that any property, physical or chemical, possessed by asubstance may be used to identify that substance, and to determine the pro-portion of that substance in a mixture. These topics are referred to in over2500 abstracts published in Section C of British Abstracts in 1946, and it ismanifestly impossible to report adequately in a few pages on the importantwork which many of these and other publications represent.A coherent impression of the progress made in a branch of analyticalchemistry may be presented either by considering means of identifyingand determining members of groups of substances (such as the constituentsof coal-tar distillates) or by describing analytical techniques and illustratingtheir applications by examples drawn from the various fields of chemistryin which they have been applied : such techniques are mass spectrometryand infra-red absorption spectrophotometry, which are referred to extensivelyfor the first time under Analytical Chemistry.Trends are indicated in theapplication of spectrography, colorimetry, turbidity measurements, polar-ography, and X-ray diffraction to the determination of small quantities, withemphasis on the importance of characterisation of physical state in additionto determinations of composition. J. R. N.2. CONSTITUENTS OF COAL-TAR DISTILLATES.Until comparatively recent years, the analysis of the various fractionsand products distilled from coal-tar has been, like the analysis of petroleumproducts, largely in terms of broad classes of constituents, for example, thetotal response to bromination or sulphonation as a conventional measureof the content of olefins or aromatics.Modern technological methods,however, leading to the isolation on a practical scale of a greatly extendednumber of individual compounds of actual or potential commercial use,',make it possible to think of the coal-tar distillates much more in terms of pureconstituents than was formerly the case. There is thus a corresponding callfor analytical methods for the determination of particular compounds, e . g . ,the individual cresols in mixed isomers, if these are to be used for condens-ation to plastic resins, or indene in distillation cuts intended for the same pur-pose ; indole, in the highly purified state required for perfumery ; or toluenefor nitration. In other cases analytical methods are required for the deter-mination of undesirable constituents in products of industrial use and im-portance, e.g., thiophen in benzene, aniline in dye intermediates, or o-hydroxy-1 0. Kruber, Angew.Chew., 1940, 53, 69; Ber., 1941,74, 1688.2 E. A. Coulson and J. I. Jones, Ind. Chent., 1946, 679308 ANALYTICAL CHEMISTRY.diphenyl in phenol (as a distinction of the synthetic from the natural material).In the present report an attempt has therefore been made to survey methodspublished over a space of about ten years, which appear applicable to thedetermination of individual compounds which occur in the coal-tar distillates.These compounds are, of course, frequently encountered in mixtures ofconsiderable complexity, often with homologues or other compounds of closelysimilar properties. It may therefore be understood as a general rule that suchspecific methods as are available will be applied only after the completestpracticable preliminary separation by solvent extraction, fractional dis-tillation, etc.Improved analytical techniques in fractionation have beendiscussed fairly recently by J. W. J. Fay,3 and a further contribution byW. J. Gooderham may also be noted. Much similar work has been done inthe nearly-related field of petroleum hydrocarbons. Adsorption also, usuallyon silica gel, has been applied to the separation of hydrocarbons.6>7-Filtration of light hydrocarbons through a column of silica gel retains thearomatic constituents but allows the passage of paraffins, olefins, andnaphthenes, which are preferably washed through with a light paraffin suchas pentane.The aromatics are desorbed by means of methyl alcohol, and,when this has been removed by washing with water, are recovered quantit-atively and can be further separated by fractionation. Active carbon, oxidesof magnesium and aluminium, and " Filtrol " have been used as alternativesto silica.A chromatographic concentration of anthracene in anthracene oils is advo-cated by F. R. Cropper and N. Straff~rd,~ adsorption being effected on activealumina, with a 1 : 4 mixture of chlorobenzene and light petroleum as solventand developing medium.Among the hydrocarbons, even after preliminary separation by suchmethods as the foregoing, few compounds exhibit sufficiently characteristicreactivity to allow of specific analysis by chemical means.Considerablework has, however, been directed to the elaboration of the colorimetric re-actions of nitrated aromatic hydrocarbons with a ketone in alkaline condi-tions.lo B. H. Dolin l1 reported that, when the nitrated hydrocarbons aretreated with butanone, colours are given by benzene, toluene, and thexylenes, but only that due to benzene persists on acidification with aceticacid. H. D. Baernstein l2 eliminates toluene from the nitrated mixture byoxidation to dinitrobenzoic acid, which does not react with butanone ; henceAnn.Reports, 1943, 40, 224.B. J. Mair and A. F. Forziati, J . Res. Nut. Bur. Stand., 1944, 32, 161, 165.N. C. Turner, Oil and Gas J . , 1943, 41, 48.J . SOC. Chem. Ind., 1944, 03, 6 5 ~ .5 E.g., H. J . Hepp and D. E. Smith, Ind. Eng. Chem. (Anal.), 1945, 17, 579.* P. Harteck and K. A. Suhr, Chemie, 1943, 56, 120. Certain hydrocarbons, e.y.,n-heptane and toluene, have also been separated on zeolites by the " molecular sieve "technique of R. M. Berrer ( J . SOC. Chem. Ind., 1946, 64, 131).@ Ibid., 1944, 68, 2 6 8 ~ .lo J. Peltzer, Chem.-Ztg., 1933, 57, 162.11 Ind. Eng. O h . (Anal.), 1943,16, 242; cf. Chm. Abs., 1946,40, 6023.I d . Eng. Chem. (Anal.), 1943, 16, 261KELLETT : CONSTITUENTS OF COAL-TAR DISTILLATES.309a combination of this procedure with that of Dolin makes it possible to estimatebenzene, toluene, and xylenes in the presence of each other. M. S. Bykhov-skaya l3 estimates benzene and toluene vapours when present together in air,by nitration in conditions leading to the formation of dinitrobenzene and tri-nitrotoluene. The latter is measured directly by its colour with alcoholicpotash. For the benzene estimation, the trinitrotoluene is eliminated byhydrolysis to phenolic compounds ; these are separated, by partition betweenaqueous alkali and an organic solvent , from the dinitrobenzene, which isthen estimated by the colour developed with potash and acetone. R. P.Marquardt and E. N. Luce l4 apply the reaction t o determine o-xylene inhydrocarbon liquors containing monoalkyl- and alkenyl-benzenes such asstyrene.The olefinic compounds are eliminated by steam-distillation follow-ing mercuration, which renders them non-volatile. The distilled alkyl-benzenes are nitrated and treated with potash and acetone, whereupon themonoalkylbenzenes give a blue colour fading to red, and the xylenes a stablegreen. The fading of the monoalkylbenzene colour is expedited by additionof ethanolamine, after which the intensity of the green element is measuredphoto - electrically.The standard gravimetric nitration method, due t o H. P. Reichel, fordetermination of m-xylene, has been extended l5 by the same author so as topermit of the determination of p-xylene also.Under the specified conditions(mixed nitric and sulphuric acids in glacial acetic acid) m-xylene is nitratedquantitatively to the trinitro-derivative, which is recovered by crystallisationfrom acetone, with an allowance for its small solubility in the cold solvent.p-Xylene is nitrated only in part to the trinitro-derivative, but the yield ofthis is a constant fraction (71.4%) of the theoretical. It may therefore beused as a measure of the p-xylene present, being recovered by evaporationfrom the acetone liquors, and recrystallised from alcohol, with allowance asbefore for its small solubility. The nitration products of o-xylene and ethyl-benzene, being soluble in alcohol, do not interfere. By an analogous pro-cedure, Reichel determines mesitylene, as its acetone-insoluble trinitro-derivative, in the coal-tar spirit fraction of boiling range 160-180".Chemical determinations of naphthalene are for practical purposes limitedto those based on formation of the picrate, after elimination of other picrate-forming substances.The earlier methods of handling the picrate are wellreviewed by A. P. Munch and R. T. Heukers l6 and W. L. Miller.17 A newprocedure has been proposed by A. Bolliger,l* who determines the picratesby extractive titration in chloroform with methylene- blue.For cyclopentadiene and its dimer, a colorimetric method has beendescribed by K. Uhrig, E. Lynch, and H. C. Becker,lg dependent on thel3 Zavodskaya Lab., 1945, 11, 537, through Chem. Abs., 1946, 40, 2419.l4 Ind. Eng.Chem. (Anal.), 1944, 16, 751l 5 Chem.-Ztg., 1941, 65, 446; 1943, 67, 121. l6 Chent. Weekblad, 1935, 32, 411.J . Assoc. 08. Agric. Ghem., 1934, 17, 308.Quart. J . Pharm., 1940, 13, 1 ; Analyst, 1939, 64, 416.I n d . Eng. Chem. (Anal.), 1946, 18, 550310 ANALYTICAL CHEMISTRY.formation of the highly coloured phenylfulvene by condensation of cyclo-pentadiene with benzaldehyde. Dicyclopentadiene does not react, but isdetermined as additional monomer after controlled depolymerisation in thepresence of decahydronaphthalene. It is stated that the materials normallyassociated with cyclopentadiene do not interfere; and though the method isdevised with reference primarily to petroleum oils, it would appear potentiallyapplicable to coal-tar spirits after a sufficient preliminary fractionation.R.Sefton 2o estimates cyclopentadiene in the lightest coal-tar distillates bymeasurement of its heat of condensation with maleic anhydride. The lackof specificity of the reaction is largely palliated by the much greater (almostinstantaneous) speed of reaction with cyclopentadiene, as compared with theother unsaturated hydrocarbons likely to be present.A second application of calorimetric technique is the estimation of smallamounts of benzene in solution by measurement of its heat of nitration.21This method, though obviously limited in its scope, is said to be rapid andconvenient for repeated estimates in special cases.The gravimetric method for indene proposed by M. Weger and A.Billman,22 based on precipitation of its benzylidene compound on treatmentwith benzaldehyde, can be effectively applied to determination of indene incoal-tar fractions such as heavy naphtha, if these are first subjected to steam-di~tillation.~~The Hochst gravimetric procedure for anthracene in anthracene oils(oxidation to anthraquinone) has been adversely criticised by Cropper andStrafford,S who prefer the measurement of anthracene by ultra-violet absorp-tion, after a chromatographic separation in which the anthracene zone on thechromatogram is located by its fluorescence in ultra-violet light.The ultra-violet fluorescence spectrum has been applied also to the evaluation of1 : 2-benzpyrene in anthracene the anthracene being first eliminatedby precipitating, from benzene solution, its complex with maleic anhydride.These procedures are representative of a general tendency to supplementthe limited number of chemical methods available for hydrocarbon analysisby physical, and especially by absorptiometric, techniques.Ultra-violetabsorption has been applied to the analysis of benzene, toluene, and xylenemixtures by A. Luszczak 25 and P. Laurin,26 who estimated the proportionsof these compounds by comparing the intensities of those bands which arecommon to their spectra and those which are not. Characteristic bands, theintensity of which could be used as a measure of concentration, were reportedby C. Weizmann, V. Henri, and E. Bergmann 27 for benzene, toluene, xylene,naphthalene, anthracene, and phenanthrene ; and R.Schnurmann and2o J . SOC. Chem. Ind., 1945, 64, 104; see also A. V. Kirsanov, I. M. Polyakova,and Z . I. Kuznetsova, J . Appl. Chem. U.S.S.R., 1940, 13, 1406 (through Chem. Abs.,1941, 35, 2445) for iodometric estimation of the excess of maleic acid.21 R. L. Bishop and E. L. Wallace, Ind. Eng. Chem. (Anal.), 1943,15, 563.22 Ber., 1903, 36, 640.24 A. Kling and M. Heros, Compt. rend., 1941, 212, 348.25 Wien. Med. Wochenschr., 1936, 86, 91, 150.26 J . Pharm. Chim., 1938, 27, 561.z3 R. D. Haworth, unpublished.27 Nature, 1940, 146, 230KELLETT : CONSTITUENTS OF COAL-TAR DISTILLATES. 31 1S. Whincup 2* have recorded the spectra of ethyl- and propyl-benzenes,styrene, and chrysene as well as the commoner aromatics. A. Berton29finds the bands narrower and more easily identified in the vapour state thanin liquids, and has thus determined as little as 0.01 mg.of benzene per litreof air; similarly 0.1 mg./litre of toluene or styrene, and 0.2 mg./litre ofxylene, anthracene, or phenanthrene.R. R. Gordon and H. Powell 3O measure the optical density and molecularextinction coefficient of hydrocarbon mixtures (benzene and toluene, ethyl-benzene and xylenes), obtaining readings at as many wave-lengths as themixture has components. The total optical density at any wave-length beingthe sum of those of the individual components, the group of readings can beformulated as simultaneous equations and solved for the concentration ofeach component. Ultra-violet spectrophotometry applied to anotherhydrocarbon (diphenyl) is further mentioned bel0w.3~Similar methods based on infra-red absorption have been applied t o mix-tures of benzene, toluene, and xylene with paraffins and naphthenes byB.Mani2~e,~l and although applications to benzenoid hydrocarbons have beenworked out in less detail than those of ultra-violet spectroscopy, the develop-ment of analogous methods for petroleum oils 32 suggests that the infra-redmay prove of similar use in the analysis of coal-tar spirits.Use has also been made of the Raman spectra of the benzene hydrocarbonsfor their estimation in admixture with one another. Although P. Traynard 33and D. H. Rank, R. W. Scott, and M. R. Fenske 34 were able to extend thistechnique only to binary mixtures (benzene and toluene), it has more re-cently 35 been applied to mixtures of from two to eight aromatic components,the proportions of which were determined with an accuracy of about 2%.Spectroscopic methods have been similarly adopted $0 some extent forthe analysis of the phenolic fractions from coal-tar.For instance, thequantitative and qualitative investigation, by infra-red absorption, of cresylicacids containing the three isomeric cresols has been described in papers byH. W. Thompson and D. H. Whiffen 36 and H. W. Thompson ; 37 in the latterpaper, the theoretical bases of the procedure are discussed in some detail.It is claimed that the bands of the infra-red spectra are in general sharperthan those of the ultra-violet. By utilising the sharper bands obtained in thevapour as compared with the liquid state, however, A.Berton 29 has employedultra-violet absorption for the determination of phenol and the three cresols.Mention may also be made of the estimation of o-hydroxydiphenyl, when usedas a fungicide, by means of its ultra-violet absorption in cyclohexane s0lution.~828 Petioleum, 1945, 8, 122.32 E.g., D. L. Fry, R. E. Nusbaum, and H. M. Randall, J . Appl. Physics, 1946, 17,33 Bull. SOC. chim., 1944, 11, 552. 34 Ind. Eng. Chem. (Anal.), 1942, 14, 816.35 D. H. Rank and R. V. Wiegand, J . Opt. SOC. Amer., 1946, 36, 325.36 Chem. and Ind., 1944, 343. 37 Analyst, 1945, 70, 443.3a H. E. Cox, ibid., p. 373. cycloHexane for spectroscopy may be freed fromaromatics by filtration through silica gel (S.A. Ashmore, unpublished).29 Ann. Chirn., 1944, 19, 394.31 Ann. Chim. anal., 1941, 23, 173. J . Inst. Petroleum, 1945, 31, 428.150312 ANALYTICAL CHEMISTRY.Diphenyl, which is generally present with its hydroxy-derivative, has also awell-defined maximum absorption, and can be similarly determined. In thecase of o-hydroxydiphenyl, the use of a spectrophotometer is not indispens-able, since the intensity of its fluorescence in ultra-violet light can be observeddirectly and compared with standards.The chromatography of the phenolic compounds has been studied byW. Bielenberg and L. F i ~ c h e r , ~ ~ who concluded that direct adsorption ofthese constituents gave no promising results. After a preliminary couplingwith diazotised p-nitroaniline, however, adsorption on alumina allowed ofgood separation ; this procedure was utilised for qualitative identificationof phenol, the three cresols, and p-xylenol in the presence of each other, andhas subsequently been extended to all the hydroxy- benzenes boiling below220".Although a number of methods for the chemical determination of phenolsin particular circumstances have been published during the period undersurvey, yet most of these cannot be said to introduce any new chemicalprinciple which might serve as a basis for a more general analytical reaction.Reference may be made to turbidity methods,m341>42 and to gravimetricmethods with iodine-applied also t o the naphthols and guaiaco143 and too-cresol and o-hydroxydiphenyl.a L.Bettelheim 45 separates phenol fromphenol-cresol mixtures and higher homologues by shaking it out with a 33%solution of sodium benzenesulphonate, while J.N. Miller and 0. M. Urbain 46effect its differential oxidation with chromic acid; the total phenols beingdetermined colorimetrically with diazotised sulphanilic acid both before andafter this treatment, phenol may be estimated by difference.The Chapin method for phenol, adopted by the Standardization of TarProducts Tests Committee, has been extended by T. S. Harrison,47 using theSpekker absorptiometer, to the simultaneous estimation of m-cresol ; the o-and p-isomers give no coloration with Millon's reagent, but m-cresol gives ayellow distinct from the red phenol colour, so that both can be determinedin the same alkaline extract.In conjunction with the S.T.P.T.C. methodfor o-cresol (observation of the melting point of its complex with cineole 48),C. E. Sage and H. R. Fleck 49 propose to utilise gravimetrically the resin-forming reaction given by o- and m-cresols, but not by p-cresol, with form-aldehyde in acid solution; from the two analyses, the m-cresol content of38 Biennstoff-Chem., 1940, 21, 236; 1941, 22, 278; 1942, 23, 283.40 W. Seaman, A. R. Norton, and R. T. Foley, Ind. Eng. Chem. (Anal.), 1943, 15,41 R. Paris and J. Vial, Compt. rend., 1946, 222, 324.42 J. Kay and P. J. C . Haywood, Ind. Eng. Chem. (Anal.), 1944, 16, 772.43 M. Franqois and M. Seguin, Bull. SOC. chim., 1933, 53-54, 711.44 W. 0. Emery and H. C . Fuller, Ind. Eng.Chem. (Anal.), 1935, 7 , 248.45 Svensk Kem. Tidslcr., 1942, 54, 194, 219, through Chem. Abs., 1944, 38, 3220,4 6 Ind. Eng. Chem. (Anal.), 1930, 2, 123.4 * F. M. Potter and €I. B. Williams, Analyst, 1932, 57, 267; 1939, 63, 621.4O Ibid., 1932, 57, 567, 773.159.3928.4 7 J . SOC. Chern. Ind., 1943, 62, 119KELLETT : CONSTITUENTS OF COAL-TAR DISTILLATES. 313mixed isomers can be estimated by difference. The resin-forming reactionwith formaldehyde has also been advocated by A. Castiglioni for the esti-mation of the naphthols ; the method is applicable to either a- or p-naphthol,but is not suitable for mixtures of the two. An alternative to the gravimetrictreatment is colorimetric estimation of the a-naphthol by means of the bluecolour given by the a-naphthol resin with sodium hydroxide.The well-known Koppeschaar deternlination of phenols , by brominationand final titration of the iodine liberated from potassium iodide by the excessbromine, has been further studied by W.Bielenberg and E. K ~ h n . ~ l Thecourse of the bromination was followed by a potentiometric method, andmodifications of the standard technique, especially as regards the use ofpotassium iodide, are proposed.Bor qualitative identification of many of the amino-compounds of thecoal-tar distillates, the formation of characteristic diliturates (&nitrobar-biturates) 52 may prove useful. The optical and crystallographic proper tiesof crystals of these derivatives are distinctive even when prepared frommixtures of isomers.Specific quantitative methods available in the amino-compound groupare not very numerous.The estimation of residual free aniline in anilinederivatives is, however, often of importance, and an interesting techniquefor aniline in aminoazobenzene has been described by I?. R. Cropper.53After diazotisation of the material and coupling with H-acid, the red dyeproduced from the aniline present is separated as a chromatogram on filter-paper, and the intensity of the band may be used as a quantitative measureof the aniline content. Aniline in methylanilines can be estimated by thepicryl chloride method in ethyl acetate solution.= The sodium chlorideresulting from neutralisation of the hydrochloric acid liberated is extractedwith water and titrated potentiometrically against silver nitrate.Analternative manipulation in the picryl chloride method is described byG . Spencer and J. E. B r i r n l e ~ . ~ ~A specific method for p-toluidine is based by C. H. Benbrook and R. H.Kienle 56 on the evolution of nitrogen on heating the diazotised material.The p-toluenediazonium derivative is relatively so stable, that o- and m-toluidines, aniline, etc., may be eliminated by three hours’ heating of thediazotised mixture, and any nitrogen subsequently evolved used as a measureof the p-toluidine content.For the polynuclear amino-compounds, no methods new in principle havebeen introduced for a considerable time. The methods available for di-phenylamine, with special reference to its estimation when used as a stabiliserin explosives, have been reviewed and compared by F.Ellingt~n.~’ A colori-50 Z. anal. Chem., 1938, 113, 428.52 13. T. Dewey and E. M. Plein, I n d . En,g. Chew,. (Anal.), 1946, 18, 516.53 Analyst, 1946, 71, 265.54 J. Haslam and F. Sweeney, ibid., 1945, 70, 413.6 5 J . SOC. Chem. Ind., 1945, 64, 53.6 6 I n d . Eng. Chern. (Anal.), 1942, 14, 427.5 1 Ibid., 1943, 126, 88.67 Analyst, 1946, 71, 305314 ANALYTICAL OHEMISTRY.metric method based on oxidation with potassium dichromate has beenproposed by H. Barnes.6*Among the heterocyclic constituents of the coal-tar distillates, preponder-ant importance attaches t o pyridine, and critical surveys of the methodsavailable for its determination have been published by A.Hamer, R. Pomfret,and W. V. S t ~ b b i n g s , ~ ~ R. P. Daroga and A. G. Pollard,60 and C. Belcot.61The method finally adopted by Daroga and Pollard, suitable for smallquantities, is a colorimetric measurement of the blue produced by the actionof reducing agents on the pyridine complex precipitated by silicomolybdicacid, while Hamer, Pomfret, and Stubbings prefer to utilise the clearing-temperature of solutions of pyridine perchlorate.Although a number of colorimetric estimations of indole have beendescribed, these mostly have reference to its production in bacterial cultures ;they are thus appropriate only to small amounts, and are frequently not veryspecific. Mention may, however, be made of the qualitative colour reactionwith xanthhydrol, which is not given by skatole or apparently by any otherindole-ring compound which is substituted in the P-position; 62 and of themost recent reviews of the determination with Ehrlich’s (p-dimethylamino-benzaldehyde) reagent .G3, f~For detection of acridine, J.C. Baro Graf 65 has recommended the pre-paration of highly characteristic crystals of the silicotungstate, easily dis-tinguishable under the microscope from those given by pyridine or quinolinebases, and obtainable a t a dilution of one part of acridine in 70,000. Theprocedure has, however, been criticised by G. Kohn and I. M. Kolthoff.66The technique of extractive titration of picrates and picrolonates againstmethylene-blue, already referred to,18 has been applied also to the determin-ation of the acridine bases.Colorimetric methods for thiophen, intended for its estimation in “ purebenzole ” and therefore adapted to very small quantities of thiophen, havebeen worked out by K.H. V. French.67 The colour reactions utilised arethose with isatin in the presence of ferric sulphate and sulphuric acid, andwith alloxan in the presence of sulphuric acid. The latter is somewhat theless sensitive, but the colour is more stable and gives on the whole betterprecision in working. F. S. Fawcett and H. E. Rasmussen68 have deter-mined the constants of a highly purified sample of thiophen, which may be ofuse in the preparation of standards for the colorimetric procedure.E. G. K.6 8 Analyst, 1944, 69, 344.6o J . Soc.Chern. Ind., 1941, 60, 2071..61 Ann. Chim. anal., 1938, 20, 173.6 2 W. R. Fearon, Analyst, 1944, 69, 122.63 L. H. Chernoff, I n d . Eng. Chena. (Anal.), 1940, 12. 273.O4 M. 73. Jacobs and S . Pinciis, Science, 1945, 102, 204.6 5 A n d Asoc. Qufm. Argentina, 1942, 30, 44, through Chem. A h . , 1942, 36, 5732.6 G J . Biol. Chem., 1943, 148, 711.6 7 J . SOC. Chem. Ind., 1946, 65, 15.60 Ibid., 1946, 71, 419.J . Amer. Chem. SOC., 1945, 67, 1705GRIFPTTRS : MASS SPECTRA. 3153. MASS SPECTRA.At very low pressures a suitable ribbon-shaped stream of positively chargedgaseous ions can be deflected in a carefully chosen electric or magnetic field,or both, so that ions of each value of mass/charge are brought to a separatefocus. If these operations are conducted in a mass spectrograph, the seriesof foci is arranged to fall on a photographic plate and produces a series oflines, each of which corresponds with a different mass provided each ioncarries only one electronic charge.An ion carrying a multiple electroniccharge suffers a larger deflection, and may be focused on the same spot as anion of lower mass carrying a single electronic charge. In a mass spectro-ineter arrangements are made to focus in turn ions of each value of mass/charge on a slit, behind which is a device for collecting and recording electriccharge or ion current.Early work in the field showed that positively charged gaseous ions travel-ling at right angles to an electric field are deflected along the direction of thefield, but in the case of a magnetic field deflection is at right angles to the fieldand to the line of motion.When a pencil of positive ions all of equal mass and electronic charge andtravelling with different velocities is subjected to parallel electric andmagnetic fields a t right angles to the line of motion, the ions fall on a paraboliccurve on a plane perpendicular to the original line of motion.This is theprinciple of the parabola method described by (Sir) J. J. Thomson for thestudy of positive ions. He pointed out that under these conditions ions ofeach different mass yield a different parabola, and therefore it would bepossible to identify ions in terms of their masses, and indicated the value ofthe method in chemical analysis, including the fact that only a very smallamount of material is required.It is important to remember that electricallyneutral atoms and molecules are not deflected in this way, and the preliminarybut essential process of ionisation which the volatile matter must undergousually causes some decomposition thereby altering the composition, and itis only within very recent years that it has been found possible to relate thocomposition of themixture of ions to the composition of the original electricallyneutral gas or vapour mixture, thus establishing a means of determining thecomposition of the latter by positive-ray analysis or mass spectra. Earlierwork was devoted almost entirely to the discovery and identification ofisotopes and the determination of their masses and relative abundance.In the course of this “ analysis of the elements ” various types of instrumentwere developed, based on several different methods devised for focusing thepositive ions.In Aston’s type of instrument the beam of ions is hetero-geneous with respect to velocity, and resolution and focusing are achievedby deflecting the ions electrically and then magnetically in the oppositedirection. But the beam of positive ions can be made homogeneous in“ Rays of Positive Electricity and their Applications to Chemical Analyses ”, 192 1 ,p. 179.2 F. W. Aston, “ Mass Spectra rand Isotopes ”, 1942316 ANALYTICAL CHEMISTRY.respect of one of the possible variables before passing through the focusingfields, thereby permitting the complexity of the latter to be diminished.In K.T. Bainbridge's systemy3 the ions are passed through a " velocityselector " and all ions emerging have the same velocity and are deflected alongsemicircuIar paths and focused in a uniform magnetic field. W. R. Smytheand J. Rlattauch removed all ions save those having certain velocities byapplying suitably spaced alternating electric fields a t right angles to thebeam of positive ions. The ions were then anaIysed by a radial electric fieldalone. Other developments including automatic recording are described byW. Bleakney and others.'A mass spectrograph is used in the accurate determination of atomicmasses since it is possible very accurately to determine the relative positionsof lines made by positive rays on a photographic plate, and relative abundancesof the different atoms may be determined by photometry of these lines.Amass spectrometer is used in the accurate determination of relative abund-ances of ions, and instruments of the form due to A. 0. Nier based on thatof A. J. Dempster are used in this type of analytical work. The rays areformed by the controlled ionisation of a stream of the vapour of the elementor compound or mixture under test, and the ions, of mass m and charge e, aredrawn out of the vapour stream by a small voltage and then acceleratedthrough two slits by a suitable applied potential E , focused magneticallyround the semicircular analyser, and collected on a plate behind the slit, andthe resulting ion current is measured by a valve-amplifying device.The equation of the circular path of radius r traversed by the ions focusedon the slit by the magnetic field H which is a t right angles to the plane of thesemicircle ismle = H2r2/2EIons of different mass may be focused successively on the slit by varyingthe accelerating potential E.The parts of the analyser are enclosed in a Pyrex container which permitseffective baking and out-gasing, a most important advance which permits theelimination of contamination by traces which by their presence would vitiatethe analyses of substances introduced into the apparatus.J.E. Taylor described a Nier type maw spectrometer suitable for routineisotope abundance measurements. He out-gased at 350" for 48 hours beforea determination, but there remained a small background of masses 18 (H20)and 28 (CO,).The abundance ratio 13C/12C was determined with a probableerror of 2% from abundance measurements a t mass 46 (12C1601a0), 45(13C160, and 12C160170)y and 44 (l2C160,).H. G. Thode, P. L. Graham, and J. A. Ziegler describe a mass spectro-meter for rapid determination of isotope abundance ratios with high accuracy,Physical Rev., 1932, 39, 847. Ibid., 1932, 40, 429.]bid., 1918, 11, 316.Canadian J . Res., 1945,533, B, 40.5 Ibid., 1937, 52, 933.7 Ibid., 1932,40, 496; 1934, 45, 761; 1938,53, 531.* Rev. Sci. Instr., 1944, 15, 1GRIFFITES : MASS SPEaTRA. 317I n a rapid recording instrument,lO the mass spectrum is scanned across theexit slit by varying the magnetic field, a procedure favoured by N.D.Coggeshall.ll Instruments are also the subject of patents.12Application.-There are two fields of analytical chemistry in which massspectrometry is an important, if not essential, technique. One is in thedetermination of isotope abundance ratios, and the other is in the analysis ofmixtures of gases or vapours, particularly hydrocarbons. The advantage ofspeed which the technique confers in petroleum refinery analysis and plantcontrol is frequently referred to.Isotope abundance ratios. A substance suitable for the direct determin-ation of the isotope abundance ratio of a constituent atom, by introduction intoa mass spectrometer, must be sufficiently volatile, should be well chosen as tothe masses of the ions which it will yield and must be pure and free fromsubstances which afford ions of masses which interfere.In measuring the rate of isotope exchange reactions between gases,l3ain testing theories of thermal diffusion of gases, and in following changes inabundance ratios consequent upon the operation of processes designed toseparate isotopes, the mass spectrometer has played an essential part.Signi-ficant features of technique already mentioned are illustrated by the work ofA. 0. Nier,13b who showed that a concentration gradient of 12CH, and 13CH4is set up in methane enclosed in a vessel in which a temperature gradientexists. Samples of the methane were burned to carbon dioxide in excess ofpure oxygen, and the carbon dioxide was purified by condensation in a Iiquid-air trap, any excess of oxygen or unburned methane being pumped off.Water vapour was later condensed out at about - 78".The carbon dioxidewas ionised by controlled electron impact and the ion currents due to 13C02(mass 45) and l2C0, (mass 44) were recorded. The relative heights of thepeaks for masses 45 and 44 were corrected for the 7% contribution to the 45peak due to 12C170160. Tests showed that the burning of the methane andthe subsequent manipulation had a slight but insignificant effect on the13C/12C ratio. It was necessary to burn the methane and operate with theresulting carbon dioxide rather than to analyse the methane itself owingto the identity of the masses of the ions 13CH4 and 160H; the latter isderived from the traces of water which could not be eliminated from theapparatus.H. G .Thode,l* in a review of the applications of stable isotopes, pointsout the advantages of using the mass spectrometer in place of density measure-ments on water when determining the abundance ratio of oxygen isotopesin tracer experiments. In order to avoid experimental difficulties which arisewhen l80 is introduced into a mass spectrometer in the form of water orlo J. A. Hipple, D. J. Grove, and W. H. Hickam, Rev. Sci. Instr., 1945, 16, 69.11 J . Chern. Physics., 1944, 12, 19.le H. Hoover, jun., U.S.P. 2,341,551, 15.2.44.13a J. D. Brandner and H. C. Urey, J . Chem. Physic4 1945,13, 351.lab Physical Rev., 1939, 66, 1009.14 Canad. Citem., 1943, 27, 647318 ANALYTICAL CHEMISTRY,oxygen gas, M.Cohn and H. C. Urey l6 converted l80 into C160180 by meansof the exchange reactionC1602 + Hz180 C160180 + H2l60and determined the 180/160 ratio in the carbon dioxide obtained.Such equilibria ashave been investigated extensively, and equilibrium constants can be cd-culated from the small differences in isotope abundance ratios found by massspectrometer measurements on the relevant molecules in equilibrium in thevapour and liquid phases.gThe determination of nickel isotopes after diffusion of the stable isotopesof nickel into copper involved an elaborate series of processes preliminary toconverting the nickel into nickel carbonyl which was analysed in a massspectrometer.16The versatility and fundamental importance of the technique is furtherillustrated by the accurate determination of differences in the abundance oflead isotopes 204, 206, 207, and 208, in common lead derived from mineralsof various geological ages and in radiogenic leads.The metal was convertedinto lead iodide, and the vapour at about 400" and 10-p-10-5 mm. Hg wasionised and analysed in a mass spectrometer.17 From a consideration ofthese results it is concluded that the most probable age of the earth is 3,350million years.In principle, any element or atom in amolecule, with an isotope abundance ratio different from normal, can befollowed through a sequence of processes or reactions by means of appropriateisotope abundance measurements. The analytical problems are very similarto those already indicated.Briefly, it may be necessary to synthesise thesubstance under investigation so that certain atoms have abnormal isotopeabundance ratios and these are determined by converting a few mg. of thesubstance into molecules suitable for examination in a mass spectrometer.After completion of the processes under investigation, the products are iso-lated, purified, and converted into substances for isotope abundance ratiodetermination. For example, methionine was synthesised l9 to have isotopeabundances above normal as indicated : CH3*34S*13CH2*13CH2*CH(NH2)*C02H,and when this was fed to rats, the cystine recovered from their hair had anabundance of 34S above normal, but the 13C/12C ratio was normal.20 TheNon-radioactive tracer elements.l6 J .Amer. Chem. SOC., 1938, 60, 679.16 W. A. Johnson, Amer. Inst. Min., Met. Eng., 1946, Tech. Publ. 2007, 13 pp. ;1 7 A. 0. Nier, J . Amer. Chem. SOC., 1938,60,1571; A. 0. Nier, R. W. Thompson, and18 A. Holmes, Nature, 1947, 159, 127.19 G. W. Kilmer and V. du Vigneaud, J . Bwl. Chem., 1944,154,247.Metals Tech., 13, No. 4.B. F. Murphy, PhysicaZ Rev., 1941,60, 112.V. du Vigneaud, a. W. Kilmer, J. R. Rschele, and M. Cohn, aid., 166,646GRIFFITI3S : MASS SPBUTRA. 319carbon was examined isotopically as carbon dioxide, but it was more con-venient to convert the sulphur into hydrogen sulphide than into mlphurdioxide 21 for examination.Many valuable tracer experiments have been described during recentyears 227 23 which illustrate the application of the above-mentioned principles.The interpretation of the isotope ratios found may be complex matters,24and the possible incidence of isotope exchange reactions during the course ofan investigation has t o be ~onsidered.~~T h e " isotope dilution method " of analysis depends for its success on theprovisos that a compound which has an abnormal isotope content of one ormore elements is inseparable from the compound of normal isotopic com-position by the ordinary laboratory procedures for isolating and purifyingthe compound,26 and that the relevant atoms are found not to undergoexchange reactions during the various processes.27 The method is particularlyvaluable in instances where it is difKcult, if not impossible, to separate fordetermination in a pure form all of a constituent from a mixture ; one maycite the difficulty of determining palmitic acid, for example, in a mixtureof higher fatty acids, and the amino-acids in protein hydrolysates.Theprinciple of the method is as follows.To a weight of a mixture containing an unknown weight y of a substanceY is added a weight x of substance Y containing a concentration Co abovenormal of, say, the heavy isotope of nitrogen, 15N, and after the mixture hasbeen made homogeneous, a proportion of Y (it does not matter how small) isisolated and purified, and the concentration, C, of 15N above normal isdetermined; then y = (Co/C - l)/x.The relative abundance of 15N in organic compounds has been deter-mined 28 by digesting a weight of sample, containing 0.5-2 mg.of nitrogen,in a micro-Kjeldahl, and, from the ammonia produced, the nitrogen isliberated by hypobromite and purified by passage through a trap immersedin liquid nitrogen. The ratio 15N : 14N is determined with a precision of0.003% in 15N in about 0.5 C.C. of the purified nitrogen which is introduced intoa mass spectrometer, in which the ion currents due t o 14N2 (mass 28) and15N14N (mass 29) are compared.The application of the method to the determination of a particular com-pound involves the synthesis of that compound from substances in which theproportion of the rarer isotope of one of the elements has been increased,e.g., 15N in ammonium salts, 13C in sodium cyanide, andW in sodium sulphate,21 A.0. Nier, Physical Rev., 1938, 53, 282.22 D. Rittenberg, J . Appl. Physics, 1942, 13, 561.23 Many authors, J . BioE. Chem., 1939,130, to 1946,166.2p E.g., D. Shernin and D. Rittenberg, ibid., 1946, 166, 621.z6 H. G. Wood, C. H. Werkman, A. Hemingway, and A. 0. Nier, ibid., 1941, 139,377.26 D. Rittenberg and G. L. Foster, ibid., 1940,133, 737.27 A. S. Keston, D. Rittenberg, and R. Schoenheimer ibid., 1939,127, 316.** D. Rittenberg, A. S. Keston, F. Rosebury, and R. Schoenheimer, ibid., 1039,127,201320 ANALYTICAL CHEMISTRY.Synthetic methods may have to be devised to avoid any loss of the valuablerare isotope ~oncentrate.~gComplications which are introduced by the use of synthetic isotope-richracemic compounds with optically active substances in the ordinary way areeliminated by either racemising the optically active substances or by resolvingthe isotope-rich racemic compounds and using the appropriate isomers orby adding the racemic mixture and isolating the natural isomer.A modifiedprocedure is used in attempting to detect d-glutamic acid in the presence ofI-glutarnic acid.30 The accuracy of the method depends upon (1) the purity ofthe isotope-rich compound added, (2) the purity of the compound isolated (apoint which can be checked by isotope ratio determination a t successivestages of the determination), and (3) the accuracy of the isotope determin-ation.The determination of the amino-acid composition of proteins is under-going substantial advances 31 as regards both decrease in quantity of proteinrequired and increased accuracy, and the isotope dilution method is playinga significant part.By the latter method, G. L. Foster 32 has determined theglutamic acid, aspartic acid, lysine, leucine, and glycine in only 7 g. ofx-lactoglobulin, the compounds isolated for purification being benzoylglycine,dibenzoyl-lysine, and the benzenesulphonyl derivative of leucine.AnaZysis of Miztures.-In principle it is possible to identify every elementin a mixture by means of determinations of the masses of the isotopes present,but on the experimental side there are difficulties presented by the necessityof volatilizing the elements and, in some instances, of distinguishing betweenisotopes and molecular ions of equal mass. Moreover, a particular method ofanalysis, however excellent, will only be used or gain acceptance if it hasadvantages over existing methods.The mass spectrometer has been applied to the analysis of traces of gases inmixtures of oxygen, nitrogen, and hydrogen, and of helium in nitrogen.Itis also employed where less than 1 C.C. of gas is available, and where continu-ous indication of composition is desired.33 The sensitivity of mass spectrumtechnique, used in conjunction with methods of concentrating material, intesting for the presence of traces may be illustrated by the demonstration thatstable 3H does not exist to anything like the extent of 1 in 1010 in ordinaryhydrogen.34The composition of a mixture may be deduced from the relative propor-tions of the different elements found by means of a mass spectrometer; e.g.,hydrogen, helium, oxygen, nitrogen, neon, and argon have been determinedin natural gas.50 Interference by other ions was allowed for by selectingsuitable mass peaks for observation.The error due to the last may amount to about 1.5%.29 R.Schoenheimer and S. Ratner, J. Bid. Chem., 1939,127, 301.30 s. Graff, D. Rittenberg, and G. L. Foster, ibid., 1940, 137, 745.31 Ann. Reports, 1945, 42, 247.83 J. A. Hipple, J . Appl. Physics, 1942, 13, 651.84 Lord Rutherford, Nature, 1937, 140, 303; F. W. Aeton, Proc. Roy. SOC., 1937, A,32 J. BioE. Chm., 1945, 159, 431.168, 391QRIPFITHS: MASS SPECTRA. 321Compounds. Apart from a few isolated instances, positive-ray or massspectrum technique has not been applied to the analysis of mixtures of com-pounds until recently.It was thought that the method had shown thepresence of methane, ethane, propane, and butane in the product obtainedby irradiating with ultra-violet light a mixture of ethylene and hydrogencontaining mercury v a p o ~ r , ~ ~ but subsequent experiments 36 with a massspectrometer showed that under electron impact butane yields positive ionscontaining C,, C,, C,, and C, and the propane previously reported might havebeen derived from butane disrupted by electron impact. It was found thatthe number and proportion of ionized fragments obtained by electron bom-bardment of various vapours depended on the nature of the molecule. Thus,approximately SCr-SO% of the positive ions derived from benzene containedc@ lO-20% contained C,, and small proportions only contained C,,C,, C, andC3' Somewhat similar results were obtained by E.Friedlander and H.Kallmann.38 These data were consistent with the proportions of individualions c6H6, C,H,, c6H,, etc., found later 39 by means of mass spectrometersimproved by developments in high-vacuum technique and the incorporationof arrangements for preventing contamination of the ion beam with productsfrom the decomposition of the vapour at the source of electrons. Undersimilar conditions, octane was more extensively disrupted than benzene.40Relative abundances of the positive ions produced by controlled electronbombardment of ammonia (N, NH, NH,, NH,, NH,, and N,), hydrazine(N2H, N2H2, N2H3, N2H4, and N ions),41 methane,42 ethane,43 ethyleneyU andmethyl and ethyl alcohols 45 have been determined under a variety of condi-tions.The proportion of C2H, ions produced in the ionisation of n-butaneis greater than in that of isobutane 46 and this is evidently related to differ-ences in the dissociation probabilities of the different linkings under electronimpact .47As a sequel to and consistent with these results, it is found that withmodern technique each hydrocarbon, methane, ethane, etc., gives its ownparticular abundance ratio of the various ions into which it is broken downby controlled ionisation. These characteristic abundance ratios are obtained36 A. R. OlsonandC. H. Meger, J . Amer. Chem. Soc., 1927, 49, 3131.36 H.R. Stewart and A. R. Olson, ibid., 1931, 53, 1236.37 E. G. Linder, Physical new., 1932, 41, 149.38 2. physikal. Chem., 1932, B, 17, 265.39 P. Kusch, J. T. Tate, and A. Hustrulid, PhysicaZ Rev., 1937, 51, 1007; 1938,40 E. G . Linder, J . Ghem. Physics, 1933, l , , 129.4 1 D. D. Taylor, Physical Rev., 1935, 47, 666.42 J. A. Hipple, jun., and W. Bleakney, ibid., p. 802.43 J. A. Hipple, jun., ibid., 1938, 53, 530.44 P. Kusch, A. Hustrulid, and J. T. Tate, ibid., 1937,452, 843.46 C. S. Cummings sand W. Bleakney, ibid., 1940, 58, 787.4 6 R. F. Baker and J. T. Tate, ibid., 1938, 53, 944.4 7 J. Delfosee and J. A. Hipple, jm., ibid., 54, 1060; M. W. Evans, N. Bauer, and1037.J. Y. Beach, J . Chem. PhpiM, 194% 1% 701.REP.-VOL. XLIII.322 ANALYTICAL CHEMISTRY.irrespective of whether the substance is pure or in a mixture. Further, ifeach of two or more constituents of a mixture yields a common ion, theproportion of this ion measured is the sum of the proportions derived fromeach of the constituents. Isomers, such as n- and iso-butane, yield differentabundance ratios, and as a consequence isomers can be determined inmixtures .47aH. W. Washburn, H. F. Wiley, and S. M. Rock 48 used a Nier type instru-ment ; ions of each mass were caused t o fall successively on the collector andthe resulting successive ion currents were so amplified that the magnitude ofeach ion current, or peak, was recorded at four different amplifications to 1 yoon an oscillograph. The quantitative analysis of such mixtures as propylene,propane, n- and iso-butane, isobutylene, butylene-1, butylene-2, n- and iso-pentane, and pentenes was carried out relatively rapidly.Less than 0.1 C.C.of liquid sample was required and a complete analysis, including the com-putations involved, usually took less than 4 hours compared with severaldays required by other methods. Routine analysis of such mixtures requiredsubstantially less than 4 hours. The error in determining components presentin large proportion was usually less than 1 mol. yo, and in the case of con-stituents present in very small proportions was usually less than 10% of themol. yo actually present. As many as 20 samples, containing as many as 15components, could be analysed in an 8-hour day.As an illustration of themethod of computation employed, in a mixture of n- and iso-butane, propane,ethane, and methane, only the first two contributed to peaks at masses 57and 58, and by means of coefficients derived from calibration experiments withthe pure hydrocarbons, the proportions were calculated, and their contribu-tions to the peak at mass 44 deducted from the observed value, the balancebeing due to propane. The ethane and methane contents were similarlydeduced from values at masses 30 and 16 respectively. The contribution ofeach hydrocarbon to other mass peaks was calculated, and the analysis wasregarded as satisfactory if the residuals were less than 1% of the peaks.Larger discrepancies were attributed to the presence of other substances andled, for example, to the detection and determination of acetone and napthenesin two hydrocarbon mixtures.The technique has been used for the analysisof mixtures of aromatic hydrocarbons and for the determination of smallamounts (0.036-8 yo) of diethylbenzene in ethylbenzene. Six isomericoctanes showed sufficient differences to permit the composition of mixturesto be determined with an error of less than h1.7 mol. %, but extension ofthe method to organic compounds containing oxygen has not met withuniform succe~s.4~The method of analysis has been examined by A. K. Brewer and V. H.Dibeler,% who have identified and determined 10 impurities in 1 : 3-buta-diene of 98% purity and analysed many mixtures of gases and vapours,47aD. P. Stevenson and J.A. Hipple, jun., J . Amer. Chem. SOL, 1942,64, 1688.48 Id. Eng. Chem. Awl., 1943,15, 641.49 H. W. Washburn, H. F. Wiley, S. M. Rock, and C. E. Berry, aid., 1945,17, 74.60 J . Res. Nat. Bur. Stand., 1945,35, 125; 1946,86, 338GRIFFITHS : INFRA-RED ABSORPTION SPECTRA. 323including natural gas and oil-flame fumes with as many as 14 components.Duplicate analyses agreed to O~1-4~O01~o. The vapour at about mm.Hg pressure is bombarded with electrons having not less than 50 volts ofenergy, and the ratios of the fragments into which the molecules are brokenare the same over a wide range of pressure for each molecular species but arenever the same for different species. Errors in the analysis may originate inthe instrument, in the sample, or in the computation.In precision work, themass spectra of the main ingredients of the mixtures should be checked daily.The proportion of ions with more than one electronic charge is small and canbe allowed for. The heights of certain peaks are corrected by deductingcontributions arising from the inclusion of ions containing 13C or D. Thus,the peak of mass 44 will include propyl ions containing either of these heavyisotopes, and corrections are calculated from adjacent lighter peaks by meansof coefficients. Accuracy in thepreparation from pure components of small quantities of mixtures of knowncomposition has been increased. R. C. Taylor and W. S. Young 51 describethe use of valves of sintered glass and mercury in mixing definite quantities ofvolatile liquids and in introducing the mixtures into mass spectrometers.The analysis, by mass spectrometer, of a standard mixture of six isomericoctanes prepared by this means was consistent with the proportions mixed.R, H.Busey, G. L. Barthauer, and A. V. Metler 52 blend low-boiling hydro-carbons by means of small bombs of the pure hydrocarbons connected to asystem of measuring vessels, a manometer, and a stock bomb into which thepure hydrocarbons are successively condensed. Composition is calculatedfrom individual pressure measurements or changes in the weight of thebombs. J. G. A. G.A table of these correction factors is given.4. INFRA-RED ABSORPTION SPECTRA.Until recent years, the analytical applications of infra-red absorption.spectroscopy have been limited mainly to the photographic and overtonevibration regions extending from 0.75 p to 2-5 p approximate1y.l Beyondthe photographic region (0.75-1-3 p) the mapping of spectra was tediousowing to the limitations of instruments, and relatively slow progress wasmade.The discovery of the unique characteristics of the infra-red absorp-tion spectra of molecules has stimulated the development of technique; andthe striking advances recently reported extend the range of application to15 p (the limit of transmission of rock-salt), and in principle to 25 p (thelimit of transmission of potassium bromide). It appears that the funda-mental vibration region, which covers the range 2-5-25 p approximately,is providing data of great utility in analytical chemistry, and the largenumber of publications during the past year justify a short report whichshould be read against the background of last year’s report on “RecentAdvances in Infra-red Spectroscopy ”.z61 Ind.Eng. Chem. And., 1945,17, 811. 62 Ibid., 1946, 18, 407.Ibid., 1945,42, 6. Ann. Reports, 1931, 28, 181 ; 1938, 35, 395324 ANALYTICAL CHEMISTRY.It is convenient to recall that there are two units employed in designatingportions of the infra-red spectrum : a wave-length unit, the micron, p(10,000 A. = 1 p = lo-* cm.), and a frequency unit, the wave-number orcm.-l, related to the wave-length unit by 1 cm.-l = l / l (cm.); for example,4000 cm.-l = 1/2.5 xInvestigations of infia-red absorption spectra depend upon the avail-ability of (1) a source emitting a continuous range of wave-lengths, (2) ameans of focusing and dispersing this radiation into very narrow bands ofdefinite wave-lengths, (3) a means of interposing a sample of suitable thick-ness in the path of the radiation, and (4) means of detecting, measuring,and recording the radiation transmitted.The source commonly employed is a Nernst filament or a silicon carbiderod (Globar) electrically heated, but nichrome and an alloy containing iron,chromium, and aluminium have also been used.Owing to the difficulty ofconstructing achromatic and transparent lenses for focusing infra-red radi-ation, surface-coated mirrors of gold or aluminium are employed. Prismstransparent to the limits indicated (glass 1.5 p, quartz 3 p, lithium fluoride5 p, fluorite 9 p, rock-salt 15 p, and potassium bromide 25 p) are generallyused to disperse the radiation.In a fresh comparison of relative merits,fluorite is preferred to lithium fluoride.6Calibration of a prism spectrometer may be effected by means of 6 or 8points ranging from the sodium D line to the carbon dioxide 14.97 p band.7Although atmospheric moisture causes deterioration of rock-salt surfaces, itis much used as a prism material and as the transparent portions of absorptioncells. Resistance to atmospheric corrosion may be increased by heating at600" for a few hours.* Other precautions, such as a small heating elementunder the prism tables, may be in~tituted.~ Absorption cells for substancesmolten at elevated temperatures may be made by cementing rock-salt platesto " Pyrex " glass with silver chloride, but the cell must be kept above 150"to prevent stresses from cleaving the rock-salt.lOAdvances in the detection, measurement, and recording of infra-redradiation are very striking.The present limit of photography (1-3 p) islikely to be extended to 1-53 p by placing infra-red sensitive phosphor screensin contact with photographic plates.ll A sensitive photo-conductive cell oflead sulphide with maximum sensitivity at 2.5 p and threshold at 3.6 pis mentioned,12 and filters of organic dyes and plastics, transmitting in theregion 1-3 p but passing little visible radiation, have been produced.13cm. = 1/26 p.3 N. Wright and W. Herscher, J .Opt. SOC. Amer., 1946, 36, 195.4 J. Savage, J . Sci. Instr., 1946, 23, 295.F, N. W. Scott, J . Opt. SOC. Amer., 1946, 36, 711.6 R. C. Gore, R. S. Macdonald, V. 2. Williams, and J. U. White, ibid., 1947, 37, 23.D. S. McKinney and R. A. Friedel, ibid., 1946,36, 715.A. Elliott, Nature, 1946, 157, 299. P. J. Kipp, J . Sci. Itaetr., 1946, 23, 246.12 R. J. Cashman, ibid., p. 356.10 G. L. Simmard and J. Steger, Rev. Sci. Instr., 1946, 17, 166,11 F. W. Paul, J . Opt. SOC. Amer., 1946, 36, 175.l3 E. R. Blout, W. F. Amon, jun., R. G. Shepherd, jun., A. Thomas, C. D. West, andE. H. Land, ibid., p. 460GRIFFITHS : TNFRA-RED ABSORPTION SPECTRA. 325The rapid scanning and recording of absorption spectra demands radiationdetectors of small time constant, and comparative studies of the performanceof infka-red receivers have been made.l*In respect of speed of response, thermopiles are somewhat wanting, butthe construction of thermopiles having time constants of only 0-01-4.03sec:15 suggests that the objection has been at least partly removed.Sensi-tive thermopiles of several designs, including vacuum types, have beendescribed.16 In one instrument, two halves may be connected in oppositiongiving a compensated thermopile which is free from drift or the two halvesmay be illuminated with different beams such as may be obtained with acompensated optical system. Another thermopile has four receivers in linefor use with a.double-beam infra-red spectrometer in which each of twodifferent beams fall on one of the two inner receivers, the two outer receiversproviding compensation.In some instruments the time constant has beendiminished to less than 0-05 sec.The construction of sensitive bolometers, instruments in which use is.made of the rapid change of resistance of a metal ribbon or film with temper-ature, has been described.17 The application of a fast superconductinginstrument operating at 14" K. is foreshadowed.ls Thermistor bolometersare made of semi-conductors of which the resistance varies rapidly withtemperature. An instrument with a time constant of 3 millisecs. is described l9,together with a detector system which scans 1 p in 1 minute.20G. F. Lothian 21 has given a survey of modern spectrometers, and, althoughthe relative merits of single- and double-beam instruments are debated,22reference may be made to a mirror double monochromator intended forwork in the infra-red, visible, and ultra-violet regions of the spectrum, andhaving two prisms each of quartz (0.2-2-7 p), flint (04-1-5 p), and rock-salt (0.2-16.0 v).The radiation receiver for infra-red is a compensatedthermopile and galvanometer, deflections of which may be magnified by arelay outfit and secondary gal~anometer.2~ J. U. White 24 described asimple infra-red spectrometer recording optical densities directly, and meansof presenting spectra extending over widths as great as 3 v on the screenof a cathode-ray tube have been reported.25Analysis.-Theory and experiment appear to be in agreement that unlesstwo molecules are identical, or are optical enantiomorphs, they will havel4 E.E. Boll, R. F. Bahl, A. H. Nielson, and H. H. Neilsen, J . Opt. SOC. Amer., 1946,l6 L. Harris, ibid., p. 597.17 F. G. Brockman, J . Opt. Soc. Amer., 1946, 36, 32; B. H. Billings, W. L. Hyde,and E. E. Barr, ibid., p. 354.18 D. H. Andrews, R. M. Milton, and W. DeSorbo, ibid., p. 518.19 W. H. Brattain and J. A. Becker, ibid., p. 354.20 J. A. Becker and H. R. Moore, ibid., p. 354.2l J. Sci. lmtr., 1946, 23, 293.Z3 P. J. Kipp, ibid., p. 246.Z6 E. F. Daly and G. B. B. M. Sutherland, Nature, 1946, 157, 547; J. King, R. € 336, 355.16 E. Schwarz, J . Sci. Instr., 1946, 23, 246.22 W. C. Price, ibid., p. 295.24 J . Opt. SOC. Amer., 1946,36, 362.Temple, and H. W. Thompson, ibid., 158, 196326 ANALYTICAL CHEMISTRY.different arrays of vibration frequencies and correspondingly different infra-red absorption spectra. It follows that each pure substance has its owncharacteristic infka-red absorption spectrum by which it can be identified.In order to operate a system of identification based on these spectra, a largenumber need to be recorded and suitably classified.Spectra of 363 organiccompounds have been indexed 29 and there are many distributed throughoutthe literature. As illustrative of the value of infra-red methods of identi-fication, and foreshadowing applications in the analysis of plastics, it isfound that natural rubber and synthetic rubbers afford different distinctiveabsorption spectra which can be used in the quantitative analysis of mix-tures.26 In an examination of 7 cycbpentanes and 5 cyclohexanes, thespectral differences between four dimethylcyclopentanes were found to bequite marked.27 neoPentane, not found hitherto in crude oil, was identifiedand determined along with the other consfituents of a fraction also containingpropane, n- and iso-butane, and isopentane.2*There are, however, spectral similarities between chemically relatedsubstances, and, as a result of correlation work, it has been found that certaingroups of atoms, and linkings, give rise to absorption bands in characteristicregions of the spectrum.29 These depend in some measure on the massesof the vibrating parts, and in this connection it may be recalled that theexistence of the heavy isotope of hydrogen was confirmed by the discoveryof bands due to 2H35Cl and 2H37Cl in the calculated position about 4.8 p ascompared with 3.46 p for lHC1.W In the high-frequency (3 p) region, thestretching vibrations between hydrogen and other atoms give rise to bandsbetween the limits indicated : 0-H 3700-3500 cm.-l (if hydrogen bondingoccurs, the frequency is lower), N-H 3500-3200 cm.-l, C-H 3200-2800cm.-1, S-H 2500 cm.-l approximately; CiC, CiN, and CiO are related to anabsorptian at close to 2000 cm.-l; C:O in esters, acids, aldehydes, and ketonesaffords absorption at 1750-1650 cm-l, and aliphatic C:C at 1660-1600cm.-l However, absorptions such as that due to C:C may be weak or non-existent if the linking occurs in a symmetrical position in a molecule, sinceinfra-red absorption only occurs if the associated vibration causes a changein dipole moment.Other correlations relating to more complex groupingshave been worked out, and they all play an essential part in analysis. Theunexpected appearance of such a band in the absorption spectrum of asubstance of known spectrum indicates the presence of an impurity.For example, isoborneol in camphor may be detected down to low limits bythe O-H band near 2 ~ 9 p . ~ ~ If the chemical history of the substance is(AnaE.), 1944, 18, 9.R. B. Barnes, V. Z . Williams, A. R. Davis, and P. Giesecke, I d . Eng. Chem.2 7 E. K. Plyler, R. Stair, and C. J. Humphreys, J. Opt. SOC. Amer., 1946,36, 716.L. C. Jones, jun., R. A. Friedel, and G.P. Hinds, jun., Id. Eng. Chem. (Anal.).2Q R. B. Barnes, R, C. Gore, U. Liddel, and V. Z. Williams, " Infra-red Spectro-30 J. D. Hardy, E. F. Barker, and D. M. Dennison, Physical Rev., 1932, 42, 279.31 G. B. B. M. Sutherland, Trans. Faraday SOC., 1945, 41, 206.1945, 17, 349.scopy ", 1944GRIFFITHS INFRA-RED ABSORPTION' SPECTRA. 327knpwn, the alien band may afford an important clue as to the identity ofthe impurity, particularly as the precise values of these frequencies arerelated to the structure of the rest of the molecule. When the identity ofthe impurity is established, then the characteristic band may also be used todetermine the proportion present.Some recent work on DDT [l : 1 : l-trichloro-2 : 2-&-(4-~hIorophenyl)-ethane] brings out the advantages of using infra-red absorption as comparedwith other analytical methods such as the determination of halogen orcolorimetric reactions.32 DDT has strong bands a t 9-1 p and 9-8 p which arecommon to isomers and impurities containing a p-C1-substituted phenylgrouping; isomers and other impurities have bands not possessed by DDTas indicated :1 : 1 : l-trichloro-2-(2-chlorophenyl)-2-(4-chlorophenyl)ethane, 9.6 p1 : 1 : l-trichloro-2-(3-chlorophenyl)-2-(4-chlorophenyl)ethane, 10.9 p ;1 : l-dichloro-2 : 2-di-(4-chlorophenyl)ethylene, 10.2 p ;di-4-chlorophenyl sulphone, 7.5, 8-6, and 7.8 p ;2 : 2 : 2-trichloro-l-(2-chlorophenyl)ethyl4-chlorobenzenesulphonate,The presence of these bands in commercial DDT was presumptive evid-ence of the presence of the corresponding impurities, and their concentrationscould be inferred from absorption measurements a t wave-lengths correspond-ing with these key bands. The fact that the absorption spectrum of pp'-DDD [l : l-dichloro-2 : 2-di-(4-chlorophenyl)ethane] in the range 7-15 IJ.shows only small differences from that of DDT adds a warning note thatinfra-red technique has limitations.The failure to observe certain bands characteristic of impurities does notnecessarily imply their absence.A certain minimum concentration, possiblyseveral units yo, may be necessary before bands from the impurity can bedistinguished from absorption due to the principal substance, or bands dueto the latter may mask those of the impurity. As instances, as little as0.5% of ethyl alcohol can be detected in acetaldehyde by the alcohol band ofwave-number 1052 cm.-l.The O-H band was not used because the aldehydcabsorbs a t 2.9 p.31 Concentrations of a-pinene as low as 2% could be de-tected in a mixture of terpenes by a band a t 787 cm.-l. Illustrative of theversatility of the technique, there have been detected organic phosphites inphosphonates, impurities in ethylidene chloride and tetrachloroethylene,trichlorobenzoic acid in the i&hl~ro-acid,~~ cyclohexane in toluene, and aslittle as 1 p.p.m. of hexane in carbon tetrachloride.34Quantitative Analysis.-Quantitative analysis may be performed by32 J. R. Downing, W. V. Freed, I. F. Walker, and G. D. Patterson, Ind. Eng. Chem.33 D.H. Wiffen, P. Torkington, and H. W. Thompson, Trans. Furuday Xoc., 1945,34 R. C. Gore and J. B. Patberg, Ind. Eng. Chem. (Anal.), 1941, 13, 768.(o-chlorophenyl group) and 13.3 p ;8.4 and 10.1 p.(AnuE.), 1946, 18, 461.41, 200.L 32s ANALYTICAL CHEXISTRY.empirical calibrations using mixtures of kiiowii composition, or by applicatioiiof Beer’s law, but i t must be borne in mind that this law would be expectedto be followed only if determinations of optical density are made with homo-geneous radiation. If a narrow band of wave-lengths is employed, as is usualin infra-red work by reason of the finite slit width which has to be employed,then departures from Beer’s law may be expected whenever the observationsare made at wave-lengths over which the extinction coefficient E changessharply with change of wave-length.I n practice, observations made a t thepeaks of bands usually follow the Lambert-Beer law.On the assumption that these laws are applicable to each of the n eom-ponents of a mixture, and that the optical density, dh a t any wave-length, isthe sum of the optical densities of the components, then, if I is the thicknessof the cell,dh = d1h + dd + - - * + &A= qc,s,x + + . * * + C?LE,IX)Consequently, it is necessary to determine the optical density at each ofn wave-lengths, a t which the values of E have been determined for the purccomponents, in order t o obtain n equations from which the concentrationsC,,C, . . . . C, can be calculated. The calculations inay be facilitated by specialnianipulation of the linear equations and tlie use of a calculating machinc,:35but the accuracy of the concentrations deduced depends upon several factors.For highest accuracy, tlie percentage absorptions should be in the neighbour-hood of 63% ; an error of 1 yo leads to larger errors in the value of C.36 Thethiclmcss of absor*i)tion cells may be made as small as 0.005 inin.in conse-quence of high values of E exhibited by many liquids, arid the accuracy withwhich values of C can be calculated depends on the accuracy with which I isdetermined. Interference methods with infra-red and visible light and theweight of contained liquid have been used.37 J. H. Lee38 has developedi n e t l d s of correcting for (1) scattered energy which reaches the receiver bycircuitous paths, (2) errors resulting from finite slit width and narrow absorp-tion bands, (3) pressure broadening and the effects of admixed molecules, andhas determined the composition of hydrocarbon vapour inixtures containingfive components with an error of less than 1-5 mol.o/,.He records datarelating to bands of 12 hydrocarbons. For instances of binary mixtures towhich Beer’s law does not apply, 1111. Fred. and F. W. Yorsche 39 describe agraphical method in which obscrved optical densities of the mixture detcr-mine tlie location of a point inside a co-ordinate network reading directlyin concentration.J. Lecomte 40 gives criteria for the use of infra-red spectra in determiningthe purity of hydrocarbons and makes the point that in the analysis of35 1,.J. Cornrio, J . S c i . Instr., 1944, 21, 129; J. L. Suuridcrson and H. H. Grossman,J. Opt. Xoc. Amer., 1946, 36, 243.3G A. It. Yhilpottx, I’rams. E’araclay SOC., 1945, 41, 197.37 G. B. B. 31. Sutherland and H. A. Willis, ibid., p. 181 ; A. E. Martin, ibid., p. 181.38 IrLd. Eng. Chent. (Anal.), 1946, 18, 650.3* Ibid., p. 603. Compt. rend., 1946, 222, 648CIASKIN : THE DETERMINATION OF SMALL QUANTITIES. 329hydrocarbon mixtures, such as motor spirits, the spectra are too complicatedunless carefully purified fractions are employed. Preliminary separationsare oft,en an essential feature, as, for example, in the analysis of mixtures ofxyle~iols.~~Infra-red absorption spectroscopy is playing a part in many branchcv ofnnalytical chemistry and recent applications include the accurate spctro-pholornetrjc determination of copper in hydrochloric acid solution by rii(misof measurements a t 0.97 p 41 and routine determination of CIZ'., Fe", Ni, and(lo" may be made by means of thallium sulphitle photo-clements. 12,42Minute amounts of hydrocarbons in soil gases may be tletcrmiiwtl bycombustion to carbon dioxide which is measured by infra-red absorption a t2.5-2-8 p,43 and the water vapour in a vertical column of the atmoqherehas been determined by using a transmission replica grating and an infra-redsensitive photo-cell to compare the radiant flux in the 0.94 p water vapourabsorption band with that at 1-01 p where no absorption O C C U ~ S .~ ~ Thedetermination of leucine and isoleucine in mixtures of the two derived fromthe hydrolysis of proteins is a matter of great difficulty analytically, andG . B.B. 31. Sutherland 45 has found sufficient differences between infra-rcyiabsorption spectra of these amino-acids, and also between their acetylderivatives, to permit determinations of the proportions with an accuracy ofabout 5%. The concentrations of oxyhzmoglo bin, methzmoglobin, aridcarboxyhzmoglobin in samples of blood have been determined from spectro-photometric observations made in the infra-red and the visible region of tliespectrum.46Among the advantages of infra-red absorption spectroscopy as a method ofanalysis, mention may be made of (1) the small quantities of material usuallyrequired for an analysis, (2) the absence of any decomposition and its conse-quences, by tlie radiation, except perhaps in very rare instances, and (3)the simplicity and speed with which an analysis can be performed afterthe preliminary calibrations have been made.Sufficient has been saidto indicate that the technique, in common with other physical methods ofchemical analysis, has its own particular fields of utility, in parts of which itis the method of choice, and in certain circumstances may be the only metliotlby which it is possible to carry out a particular analysis. J. G. A. G.5 . THE DETERMINATION OF SMALL QUANTITIES.It was the intention of the Reporter, under the above title, not only toreview the progress made in the determination of small quantities, but also touse such a review to indicate the present trends in analytical chemistry.l ' e c h ., 8, No. 5.4 1 Y. Giesecke, Amer. Inst. Min. Met. Eng., 1944, Tech. Publ. 1740, 15 pp. ; il.Zin.49 G. Berrae and E. T'irasoro, Anal. Inst. invest. cient. tecn., 1942-1943,12-13, 147.43 W. J. Sweeney, U.S.P. 2,170,435, 22.8.39.44 N. B. Foster and L. W. E'oskett, J . Opt. SOC. Amer., 1945, 35, 601.45 J . Inter. SOC. Leather Trades Chena., 1946, 30, 11.413 I3. L. Horecker and F. S. Brackett, J. Biol. C'hem., 1944, 152, 669330 ANALYTICAL CHEMISTRY.The term " small quantities " was to include, not only analyses made wherethe total material available was small, but also those where the quantitydetermined was small irrespective of the amount of material available. Thereview of work done was therefore to include largely microchemical methods,together with certain applications of quantitative spectrography, colorimetricand turbidity mFasurements, polarography, X-ray diffraction analysis,and some macro-analytical methods.A recent monograph 1 has, however,provided a very complete review of microchemical progress besides drawingattention to other reviews dealing with the same 33 In these cir-cumstances further detailed reference to such work here is unnecessary, and theReporter intends to proceed to the second half of his intended subject afterbriefly reviewing the other methods mentioned above. The references torecent literature in the following text are not necessarily comprehensive ;they have been selected became they indicate certain important trends inanalytical practice.Quantitative 8pectrography.-The large majority of workers in this fieldare broadly concerned with only two aspects of a spectrum, the position in itof a particular elemental line and the relative density of that line whenrecorded on a photographic plate.The accuracy with which the second ofthese measurements is being made is increasing steadily, and in recent workat the expense of the speed in making a determination. As regards the firstmeasurement the spectrograph is established as a powerful tool in qualitativeanalysis. Two recent publications, one dealing with the analysis of highpurity zinc and zinc alloys and the other with metallurgical analysis,6describe clearly the amount of care and research necessary to obtain resultsof maximum accuracy. Much attention must always be paid to generaltechnique, of which the photographic aspect is by no means the leastimportant.',Accurate assessment of the value of the quantitative spectrographicmethod involves three factors.As it is at present used, the spectrographernormally has some previous knowledge of the composition of the material heexamines, and the method has been largely applied to analyses where thisknowledge is largely implicit, e.g., metallurgical analysis. Such previousknowledge may, of course, have been obtained by the use of the spectrographbut more frequently by other examination. Thus it has been observed91 R. Belcher, " Microchemistry and its Applications ", Monograph published by the2 L.T. Hallett, Ind. Eng. Chem. Anal., 1942, 14, 956.G. H. Wyatt,Chem.and Ind., 1942,61,132.6 " Polarographic and Spectrographic Analysis of High Purity Zinc and Zinc Alloysfor Die Casting ", British Standards Institution Panel of the Non-Ferrous IndustryCommittee ; H.M. Stationery Office, 1945.6 " Collected Papers on Metallurgical Analysis by the Spectrograph ", edited byD. M. Smith; British Non-Ferrous Metals Research Association, 1945.7 E. H. Amstein, J . SOC. Chern. Ind., 1943,62, 61.* N. S. Brommelle and H. R. Clayton, ibid., 1944,63, 83.Royal Institute of Chemistry, 1946.H. Roth, Angew. Chem., 1940,53,441.W. Seith, Deut. Tech., 1941, 9, 264; Chem. Zentr., 1941,11, 928UASKIN : THE DETERMINATION OF SMALL QUANTITIES. 331that a combination of spectrographic and chemical methods is better andmore reliable for the determination of impurities in zinc than other methodssuch as the polarographic.Secondly, the spectrographer must be assured of a representative sample.Difficulties connected with this can to some extent be overcome by the facilitywith which many determinations can be made, but the Bureau of Mines inAmerica,lo for example, has found it necessary to develop methods for thepreparation of samples to be used for both spectrographic and X-ray examin-ation in the evaluation of dust hazards.Thirdly, the ability to make manydeterminations in a reasonable time allows a statistical survey of the resultsto be made.Such surveys, where an adequate number of results is available,are of recognised value.The above points have been mentioned to draw attention to the tendencyto use and regard the spectrograph as a testing rather than an analyticalinstrument. This is not surprising, for the natural advantages of themethod-low sample consumption, automatic permanent record of results,speed in making many determinations, etc.-are all of great value wheremuch routine testing has to be done. Nevertheless, the complexity of aspectrogram, the recognised interferences of elements present in the excitingsource, and the by no means negligible influence on a spectrogram of thephysical state of the material under examination all suggest that valuableinformation, additional to the amount of a particular element, might beobtained by further interpretation of a spectrogram.On these lines there islittle progress to report.Colorimetric and Turbidity Measurements.-It has been remarked that theabsorptiometer is primarily of use in the quantitative analysis of certainsolutions the composition of which is already qualitatively and possiblypartly quantitatively known.ll Such a statement applies equally well tomost instruments used for the mechanical measurement of colour and tur-bidities and indicates the value of these instruments in repetitive work. Forit is in this work that matching by means of a photoelectrical measuringdevice is more effectively done than matching by eye.12 It is not surprising,therefore, that, having an instrument which will give the same reading for thesame amount of a coloured substance, a great deal of attention has been paidto the development of measuring techniques13 and to the preparation ofselective organic reagents which produce -highly coloured compounds.14Methods involving turbidity measurements with some form of photo-electric cell have not made such strides.Certain satisfactory determinationshave been recorded, such as the determination of zinc by measurement of thelo J. W. Ballard, H. I. Oshry, and H. H. Shrenk, J . Opt. SOC. Arner., 1943, 33,l1 H. K. Whalley, Chem. and I n d . , 1942, 61, 495.l2 A. Ringbom, Chirn. et Ind., 1941, 45, No. 3 bis 304.l3 Abstract review of lectures delivered at symposium of the Analytical Group ofVerein deutscher Chemiker, Die Chemie, 1942,55, 361.l4 J.G. N. Gaskin, Ann. Reporb, 1945, 42, 256.667fluorescent turbidity of the oxine complex l5 and $he determination of s m damounts of bismuth by measurement of the turbidity produced by theaddition of bromate-bromide mixture.l6 Generally, howdver, acoura,temasurements of turbidities have inoreaaingly revealed the extent to whichsmall variatims in conditions affect the turbidity, e.g., barium alphate 1'and barium carbonate,ls In fact, basium sulphata figures are aften inaccurate.lg It becomes clear, then, that the introduction of the phoh-cellinto turbidity measurements czould provide much valuable knowledge of theformation of precipitates, paJcticularly up to the stage of coagulation.Pot?urugruphy.-The polarograph, as an instrument suitable for theacourate determination of amall amounts of particular elements and Cornrpounds, is becoming more widely appreciated.Reviews of its uses, rangingfrom its elementary applications zo to recent developments,21 hwe beenpublished. A panel of the British Standards Institution has produced recom-mended methods for the polarographic and spectrographic analysis of high-purity zinc and zinc alloys for die-casting, together with an aceount of theexperimental work leading to the recommendations made. More recently,accounts have been given of applications of the polarograph,22 its use in bio-chemical ahaJy~is,~3 in the analysis of aluminium, magnesium, and zincand of high-purity selenium, and compounds of nickel and cobalt.26The authors of these four papers emphasise that the polarograph must beregarded as complementary to, rather than replacing, existing analyticalmethods.They fhd it difl6cult to generalise about polarographic problem$ ;each problem has to be treated on its merits. Some polarographic methodsare considered t o be outstanding, e.g., the determination of cadmium as animpurity in zinc. The polamgraph is most easily adapted to routine testing,and it may be said that its potentialities in other directions have not beensufficiently examined because of this.X-Ray Diflrmtion.-Hitherto in this account the diffecent analytidmethods described can and often do provide the same information, that is;the amount of an element in a given material.It is frequently a matter ofpersonal choice whether mioro- or macro-methods, spectrograph, or polaro-graph are used. The X-ray diffraction camera on the othep hand providesinfbrmation which the other methods (except sometimes indiredly) cannot,and herein lies its importance. Thus the determinations of 0.1 % of calciumoxide in magnesium oxide, and of 0.2% of zinc oxide in zinc sulphide arequite feasible 26 and have been made. Similarly, X-ray diffraction studies ofl6 L. L. Merritt, jun., I d . Eng. Chem. Anal., 1944,16, 758.l7 W. Volmer and F. Frohlich, 2. anal. Chem., 1944,126,401.l* J. G. N. Gaskin, unpublished.l9 E. Canals and A. Charm, Bull. SOC. chim., 1945, 126, 89.2o J. G. N. Gaskin and H.K. Whahy, Chem. and Id., 1943,62,441.21 J. E. Page, Nature, 1944, 154, 199.23 J. E. Page, ibid., p. 52.p6 R. H. Jones, ibid., 1945, 70, 60.A. K. Majumdar, J . Indian CAaem. Soc., 1944,2l, 157.W. CuIe-Davies, Analyst, 1946, 71, 49.A. S. Nickelson, a%id., p. 58.*' H. P. Rooksby, ibid., p. 166GASKM : THE DETERMINATION OF SMALL QUANTITIES. 333psviog asphakj 2' reveal information unobtahmble by other means. and suchmaterids meeting the same specification have been found to differ greatly.A complete review of the applioation of monochromatic X-ram to the analysisof mixtures has been published by M. Patry ;28 S- T. Gross and D. E. Martin 2ghave also described the use of powdar-diffraction methods for the analysis ofcrystallhe mixtures. Attention has been drawn to the value of powder-diffraction analysis supplemented by and frequently preceded by spectro-graphic examinaticnM The preparation of suitable samples for X-ray workhas already been mentioned.Nqcro-methods.-For the purposes of this account two examples of the useof macro-methods in the determination of small amounts are of value.Theseare the published standard methods 31 for the chemical analvsis of high-purityzinc and zi4c alloys for die-casting whereby known standard metals can beprovided for spectrographic and other purposes, and the successful adajtationof the method of H. H. Willard and 0. B. Winter 32 to the determination ofsmall amounts of fluorine in f~ods,~S in coal and tactory dusts, and in aimMModern Outlook.-The great majority of the papers abstracted in theanalyticd sections of the various publications are concerned with eitherqualitative or quantitative examination for elements.Apart from organicmalysis only one of the recently developed methods attempts to make deter-minations of compounds as such in a submitted material. Few papers relatethe determined analytical @ures with the physical state of the materialexamined.Analysis for elements has been brough€ to a considerable state of per-fection, so much so that the successful repetition of quite difficult determin-ations is a commonplace. This achievement, and it is an achievement, hasundoubtedly been made possible by the introduction of the new physicalmethods, the spectrograph, the absorptiometer, and the polarograph.Nevertheless, it must be recognised that this ability to make numerouselemental determinations, as and when desired, and by the particular methodfavoured by the opergtor, does not constitute the full meamng of analysis orits complete purpose. Having made certain of his ability to determine theprimary constituents of his material, the analyst must surely now desire tostudy its structure.It has bees recognised that a combination of chemical and physicalm e t W can yield more information than either indi~idually.~~ The com-27 C. L. Wilfiford, Agric. and Mech. Coll. Texas, Eng. Exp. Stat. Bull., 73, 70 pp.;Road Ahs., 1945, 12, No. 4, 8.28 Chim. et Ind., 1941,45, No. 3, 259; Chem. Zentr., 1941,II, 3221.20 Ind. h'ng. Chern. Anal., 1944, 16, 95.30 L. K. Frevel, ibid., p. 209.31 British Standard Specification 1005, 1942 ; British Standards Institution.32 Ind. Eng. Chern. Anal., 1933, 5, 7.33 " Determination of Fluorine in Foods ", Report ofa Sub-committee of the Analyti-34 J. G. N. Gaskin, unpublished.*5 W. C . Crone, junr., The Proptier, 1945, 8, No. 4, 3/5 and 10/11.cal Methods Committees of the Society of Public Analysts, Analyst, 1944, 69, 243334 ANALYTICAL CHEMISTRY.plete realisation by the analyst that he must combine the information he getsfrom all of the main methods of examination (micro-, spectrograph, etc.)is a step in the right direction. Then, to render substantial assistance is thedevelopment of the X-ray diffraction camera which already yields informationbeyond the powers of existing analytical methods. Finally, certain possibledevelopments of the other physical methods may help. Harnessed to therigid necessity of performing its present qualitative and quantitative work,the spectrograph has to avoid different physical states in the exciting source,whereas such variation might be related to varying physical state. Similarlywith line interferences. How the absorptiometer might assist has alreadybeen indicated. The polarographer usually wishes to suppress unwantedmaxima in his diffusion currents and does so with " surface active " sub-stances. Attempts have already been made to use the suppression of thesemaxima to measure the quantity or indicate the presence of such compounds.Further, the polarograph can be used to prove the presence of and determinethe amounts of compounds where these are reducible a t the droppingelectrode.It must be recognised that this analysis for compounds and the determin-ation of physical state is of fundamental importance. A single example willshow this. Despite the tremendous amount of work which has been done inthe evaluation of dust hazards, the determination in a dust of the kind andamount of silica which causes silicosis is a problem which as yet is not com-pletely solved. The X-ray diffraction camera is providing new information,but for that to succeed preliminary and complementary work using manymethods will be necessary. Here then is the present and future position ofthe analyst. He will provideinformation as to compound constituents and their physical state.It would be wrong in this review not to draw attention to a matter whichhas been frequently discussed in recent times, viz., the necessity of improvinganalytical instruction in this country. It is hoped that the Reporter hasmade it clear what is to be expected of an analyst. Such an analyst wouldrequire a very wide scientific analytical knowledge. Where is he to get i t ?He can provide all elemental information.J. G . N. G.J. G. N. GASKIN.J. G. A. GRIFFITHS.E. G. KELLETT.J. R. NICHOLLS

ISSN:0365-6217    

DOI:10.1039/AR9464300307

出版商:RSC    

年代:1946

数据来源: RSC

摘要:

INDEX OF AUTHORS’ NAMES.Abbot, L. P., 269.Abel, J. J., 266.Abel, R., 262.Abraham, E. P., 88.Abramson, H. A., 45.Ackerman, D., 273.Ackerman, J., 155.Adair, G. S., 32, 52, 291.Adam, N. K., 231.Adams, H. E., 14.Adams, M. F., 133.Adams, R., 161, 163, 164.Addink, J., 108.Aeschbacher, R., 205.Affens, W. A., 50, 61.Agner, K., 294.Ahlborg, K., 190.Albert, A,, 148.Albertson, N. F., 243.Albisetti, C. J., jun., 249.Albrecht, G., 152.Alder, K., 203.Aldous, W. M., 144.Alexander, A. E., 28, 29.Alexander, E. -4., 6.Alfrey, T., 49, 61.Allison, J. B., 210.Alnutt, D. B., 137.Alther, H. B., 219.Amon, W. F., jun., 324.Arnsler, J., 86.Amstein, E. H., 330.Ananthakrishnan, R., 24.,4nderson, A. W., 163.Anderson, C. G., 167.Anderson, J.S., 108, 111hnderson, R. C., 156, 239Anderson, R. J., 168.Andrews, D. H., 325.Angier, R. B., 258,259, 260261, 297, 298.Angus, W. R., 28, 287.Anker, R.. M., 233.Anslow, W. P., 268.Anson, M. L., 39.Appel, W., 119.Archer, E. M., 99.Archer, S., 243, 244.Archibald, F. R., 134.Arcus, C. L., 167.Ardenne, M. V., 282.Armstrong, E. F., 266.Armstrong, K. F., 266.Arndt, F., 257.Arnold, R. T., 247.Arragon, G., 182.119, 121.240.Arth, G. E., 239.Arx, E. von, 222.Ashburn, L. L., 300.Ashford, W. R., 193, 244.Ashmore, S. A., 311.Assaf, A. G., 192.Astbury, W. T., 101, 280,281, 284, 285, 286.Astle, M. J., 29.Aston, F. W., 315, 320.Atkinson, C. M., 249, 250.Audrieth, L. F., 144.Auerbach, I., 180.Aumuller, W., 205.Aurivillois, B., 118.Auwers, K.von, 145, 152,Avery, J. M., 130.Bach, S. J., 269.Bachman, G. B., 249.Bachmann, W. E., 224,225.Badger, R. M., 7, 15, 16,17, 19, 154.Biideker, K., 11 7.Baernstein, H. D., 308.Bahl, R. F., 325.Bailey, K., 280, 283, 285,Bailey, M. E., 156.Bainbridge, K. T., 316.Baishteii, E. E., 123.Baker, H. A., 189.Baker, L. C., 86.Baker, R. F., 321.Baker, R. H., 248, 249.Baker, W., 144, 145, 148.Baker, W. O., 149.Balarew, D., 81.Baldwin, M. E., 193.Baldwin, R. R., 194.Balenovic, K., 238.Balfe, M. P., 165.Ballard, J. W., 331.Bamberger, M., 114.Banga, I., 284.Banks, C. K., 255.Bantle, W., 86.Barkan, G., 291.Barker, E. F., 20, 326.Barnes, H., 314.Barnes, R. B., 326.Barnes, R.P., 146.Baro Graf, J. C., 314.Barr, E. E., 325.Barr, T., 215.Barr, W., 232.153.286.3353arrer, R. M., 308.3arron, E. S. G., 283, 285.3arry, A. J., 197.3arry, V. C., 190, 196, 199.3arthauer, G. L., 323.3arton, D. H. R., 204.3artovics, A., 49, 61.3asedow, 262,3astiansen, O., 202.3ateman, A. M., 113.3ates, F. L., 193.3ates, L. F., 193.3ath, J., 143.3auer, E. H., 15.3auer, L. H., 114.3auer, N., 321.3auer, S. H., 9, 16, 19, 148.3auman, M., 121.3aumbach, H. H. von, 11 1,3awn, C. E. H., 15.3axendale, J. H., 274.3axter, R. A., 213.3ayley, J. H., 279.3each, J. Y., 9, 142, 321.Beadle, G. W., 276.Beamer, W. H., 93.Bear, R. S., 193, 194, 281.Becker, E., 251.Becker, H. C., 309.Becker, J. A., 325.Becker, M.L., 114.Beckmann, C. O., 39, 60.Beckmann, E., 145.Beevers, C. A., 12, 98.Belcher, R., 330.Belcot, C., 314.Bell, D. J., 180.Bell, E. E., 325.Bell, R. P., 154.Bknard, J., 115, 116.Benbrook, C. H., 313.Bennett, G. W., 72.Bennett, 3%. A., 279.Bentivoglio, M., 66, 72.Berg, C. J., 214.Berg, W. F., 73.Bergel, F., 232, 233.Berger, I<., 10.Bergmann, E., 201, 310.Bergmann, M., 53.Bergstrom, S., 215.Bermann, H., 114.Bernal, J. D., 13, 14, 94,150, 151, 155, 200, 206,217.Berner, E., 221.Bernfield, P., 193.117.L 2336 INDEX OF AUTHORS’ NAMES.Bernheim, F., 278.Bernheim, (Miss) M. L. C.Bernholz, E., 210.Bernstein, H. I., 166.Bernstein, S., 204.Berraz, G., 329.Berry, C. E., 322.Berthelot, M., 170.Rerton, A., 311.Bettelheim, I,., 31 2.Bhatnagar, S.S., 115, 288.Bhide, B. V., 155.Bielenberg, W., 312, 313.Bierbaum, 0. S., 303.Biginelli, P., 263.Biilmann, E. I., 279.Bilimoria, H. S., 301.Rillings, B. H., 325.Billman, A,, 310.Biltz, H., 256.Biltz, W., 109, 111, 113,Binkley, F., 268.Binkley, S. B., 258, 298.Binkley, W. W., 179.Bird, (Miss) M. L., 265, 272.Bird, 0. D., 258, 298, 299.Birkinshaw, J. H., 267.Bischoff, G., 238.Bishop, R. L., 310.Blackburn, S., 267.Blatterman, S. M., 210.Bleakney, W., 316, 321.Bloch, K., 269.Bloom, E. S., 258, 260, 298.Blout, E. R., 324.Blumenthal, M., 116.Blyth, W., 265.Robranski, B., 249.Boeder, P., 47.Boekelheide, V., 248.Bottinger, C., 170.Boezaardt, A. G.J., 168.Bohle, K., 217.Bohne, A., 214.Bohonos, N., 258, 297.Rois, E., 193.Bokii, G. B., 123.Bolam, T. P., 76.Bolland, J. L., 52.Bolliger, A., 309.Boltzmann, L., 40.Bonner, D., 276.Uonner, L. G., 24.Bonner, W. A., 189.Boochs, H., 79.Booth, A. D., 90, 91.Boothe, J. H., 259, 297.Boppel, H., 179, 192.Borek, E., 268.Borgstrom, E., 221.Born, M., 9.Borsche, W., 2.14, 249.Borsook, H., 277.Bosschieter, G., 20.269, 278.115.Bosshard, W., 213.Bouman, W. E., 173.Bourdillon, J., 32.Bourne, E. J., 196.Bourquin, J. P., 240, 242.Bouveault, A., 170.Bower, R. S., 179.Boyd, S. N., jun., 250.Boyes-Watson, J., 50, 91.Brackett, F. S., 329.Bragg, W. H., 11.Branch, G. E. K., 148.Brandenberger, E., 103.Brandner, J.D., 317.Brattain, W. H., 325.Brauer, G., 114.Braun, J. von, 237.Braune, H., 19.Brauninger, H., 113.Bray, H. G., 196.Breslow, D. S., 247.Bretans, W., 193.Brewer, A. K., 322.Bridgman, P. W., 87.Briegleb, G., 6, 7, 9, 10, 29.Briggs, G. M., 300.Brill, R., 11.Brimhall, B.. 195.Brimley, J. E., 313.Brockman, F. G., 325.Brockway, L. O., 18, 142,Brodski, A. E., 167.Brommelle, N. S., 330.Brosset, C., 95, 118.Brosteaux, J., 49.Brown, C. J., 101.Brown, F., 190, 195.Brown, F. S., 7.Brown, G. B., 268, 277.Brown, K. W., 87.Brown, R. A., 258,298,299,Brownen, G., 265.Bruce, W. F., 244, 245,246,Brunel, A., 270.Brungger, H., 206.Buck, J. S., 279.Buckles, R. E., 211, 212.Buckley, H. E., 74, 82.Bulow, M., 251.Buerger, M.J., 82.Bukhovetz, S., 123.Bull, H. B., 32, 53.Bullinger, H. R., 179.Bunina, V. J., 249.Bunn, C. W., 51, 78, 84, 89.Burgers, J. M., 48.Burness, D. M., 248.Burnharn, J., 24.Burrows, G. J., 158.Burstall, F. H., 149.Bury, C. R., 26.Busey, R. H., 323.Busnel, R. G., 251.161.300.300.Buswell, A. M., 16, 18, 19,Butenandt, A., 205, 207,Butler, G. C., 231.Buttenberg, P., 262.Bykhovskaya, M. S., 309.Bystrom, A., 92, 117.Bywater, R. A. S., 191.Caesar, G. V., 195.Caldwell, M. H., 303.Calkins, D. G., 258, 260,Callow, R. K., 144, 145,Cambi, L., 289, 292.Cameron, A., 114, 115.Cameron, E. J., 263.Campbell, A., 166.Campbell, C. F., 299, 300.Campbell, C. J., 258.Campbell, H., 58.Campbell, K. N., 248.Campbell, W.G., 197.Canals, E., 332.Cannan, R. K., 45.Carlisle, C. H., 200, 225.Cnrothers, W. H., 52.Carruthers, G. N., 145.Carsch, G., 249.Carson, J. F., jun., 183, 199.Carter, C. W., 301.Cartwright, C. H., 23.Cashman, R. J., 324.Castel, H. C., 119.Castle, W. B., 302.Cavallito, C. J., 279.Challenger, F., 263, 264,265, 266, 267, 269, 270,271, 272, 273, 279.Chandler, J. P., 268, 269,274, 275, 276, 277, 278.Chaplin, H. O., 145, 152.Chargaff, E., 182.Charlton, P. T., 267, 279.Charra, A., 332.Chbdin, J., 192.Chernoff, L. H., 314.Chernyaev, I. I., 120, 121.Chibnall, A. C., 54.Chirnside, R. C., 87.Christensen, B. E., 255.Cinnamon, C. A., 87.Claesson, S., 39.Clapp, M. A., 249.Clark, C. H. D., 17.Clark, G.L., 117.Clark, G. W., 303.Clayton, H. R., 330.Clayton, W., 80.Clbment, L., 192.Clemo, G. R., 147, 238, 244,Cleveland, F. F., 153.Clews, C. J. B., 102.22, 143.209, 210, 224, 226.298.200, 201, 204.249INDEX OF AUTHORS’ NAMES. 337Cochran, W., 98.Cochrane, C. C., 146.Cocker, W., 74.Coggeshall, N. D., 317.Cohn, E. J., 41, 51.Cohn, E. T., 66.Cohn, (Miss) M., 268, 275Cole, R. H., 26.Cole, W., 224, 242.Cole, W. F., 115.Coleman, G. H., 178, 189.Colgrove, G. L., 111.Comer, J. J., 76.Compton, J., 176.Comrie, L. J., 328.Conley, M., 184.Connell, W. V. &I., 29.Controulis, J., 256.Cook, A. H., 233, 234, 244Cook, D. J., 248.Cook, J. G., 238.Cook, J. W., 232.Cooke, P. W., 100.Coolidge, A. S., 6.Coop, I.E., 28.Cooper, D. E., 249.Copley, M. J., 144, 153.Copson, R. L., 134.Corey, R. B., 152.Cori, C. F., 284.Cornforth, J. W., 156.Cornforth, R. H., 156.Corrin, M. L., 102.Coryell, C. D., 289,290, 291Cosulich, D. B., 259, 297.Cottin, H., 239.Coulson, E. A., 307.Coulter, L. V., 14.Courtois, J., 182.Cowdrey, W. A., 207, 211.Cox, E. G., 98.Cox, H. E., 311.Cranfield, H. T., 271.Cremonini, A., 152.Cretcher, L. H., 183.Crone, W. C., jun., 333.Cropor, W. F., 29.Cropper, F. R., 308, 310.Cross, P. C., 24.Crowfoot, D., 50, 88, 90,200, 206, 209, 225.Crowther, A. F., 242.Cruickshank, J., 33.Cummings, C. S., 321.Curtiss, C. F., 8.Daft, F. S., 300.Daility, RI., 280.Dakin, H. D., 241.Daly, E. F., 325.Dane, E., 224.Dangschat, G., 169, 171.276, 277, 278, 318.257.292, 293.313.Daniel, L.J., 300.Daniel, W., 270.Danielli, J. F., 231.Dankov, P. D., 86.Dannenbaum, H., 209,210Dannohl, W., 114.Darby, H. H., 231.Darby, W. J., 258,301,304Darken, L. S., 116.Daroga, R. P., 314.Daubert, B. F., 102.Daughenbaugh, P. J., 210.Dauncey, L. A., 87.Davidson, G. F., 191.Davidson, L. S. P., 302.Davidson, N. R., 28.Davies, M. M., 5, 6, 7, 1016, 17, 19, 141.Davies, T. E., 145.Davies, T. H., 290.Davies, W. C., 158, 332.Davis, A. R., 326.Davis, L. J., 302.Davis, T. L., 155.Day, H. G., 195.Day, P. L., 258, 299, 301Deal, (Miss) C. C., 269.De Boer, J. H., 10, 114.Debye, P., 33, 48.Decker, P., 254.De Coppet, L. C., 85.Dehlinger, U., 117.Deinet, A.J., 249.Deitz, V., 18.Dejudicibus, I., 149.Delfosse, J., 321.Deming, L. S., 16.Dempster, A. J., 316.Denbigh, K. G., 7.Dennison, D. M., 20, 326.Dent, B. M., 79.Dervichian, D. G., 54.De Sorbo, W., 325.Deuel, H., 200.Devaux, H., 86.Dewar, E. T., 196.Dewar, J., 187.Dewar, M. J. S., 156.Dewey, B. T., 313.Dibeler, V. H., 322.Dickinson, R. G., 6.Dickinson, S., 280.Diels, O., 173, 210.Dienes, (Miss) M. T., 181.Dietz, 1’. C., 144.Dihlstrom, K., 117.Dillon, T., 190, 196, 199.Dilnot, S., 119.Dimler, R. J., 176, 182.Dimroth, K., 200, 224.Dingmann, T., 116.Dippy, J. I?. J., 154.Distelmair, A., 174.Dixon, M., 285.Djerassi, C., 205.302, 305.Doan, C. A., 301, 303.Dobriner, K., 268.Dobry, A., 57.Dodson, R.M., 249.Dodson, R. W., 291.Doehlmann, E., 119.Doeller, W., 249.Doering, W. E., 236.Dolan, L. A., 242.Dolin, B. H., 308.Donaldson, W. J., 76.Donnay, J. D. H., 69, 70.Dostrovsky, I., 161, 163,Doty, P., 33, 50, 61.Doudoroff, RI., 189.Doughty, M. A., 165.Downer, E. A. W., 165.Downing, J. R., 16, 19, 143,Drabkin, D. L., 290.Drake, B., 199.Drew, H. D. K., 146.Drucker, C., 115.Dubnoff, J. W., 277.Dubois, P., 116.Dubuisson, M., 280, 282,Dunwald, H., 111.Duff, R. B., 187.Dumazert, C., 193.Duncan, T. A., 131.Dunken, H., 26.Dunn, C. G., 86.Dunstan, S., 190.Duran, A., 82.Duschinsky, R., 242.Dutcher, J. D., 244, 245,Duveen, D. I., 166.Du Vigneaud, V., 241, 242,268, 269, 274, 275, 276,277, 278, 279, 318.Dwyer, F.P., 127, 128.Dyer, H. M., 278.Earlam, W. T., 147.Earp, D. P., 153.Easton, N. R., 239.Eberius, E., 93, 117.Ebert, 115.Eddy, C. R., 27.Edsall, J. T., 41, 45, 46, 54,Edwards, J. D., 134.Edwards, 0. S., 93.Edwards, R. T., 19.Egli, P. H., 87.Ehrenstein, M., 211, 214.Ehret, W., 117.Ehrhart, G., 205.Ehrlich, P., 109, 111, 114.Eichenberger, E., 206.Einerl, O., 114.Eirich, F., 49.Eisleb, O., 232.204.327.283.246.55, 56338 INDEX OF AUTHORS’ NAMES.Elderfield, R. C., 176, 247.Elkins, M., 146, 304.Elks, J., 243.Ellington, F., 313.Elliott, A., 324.Elliott, D. F., 243.Elliott, G. A., 163.Ellis, B., 211.Ellis, J. W., 15, 16, 143.Ellis, L., 263, 264, 270.Elvehjem, C. A., 258, 300,Emery, W.B., 306.Emery, W. O., 312.Emmett, A. D., 258, 298,299, 300.Emmett, H., 84.Engel, E., 239.Engelbrecht, G., 19.Engelhardt, V. A., 280, 282.Enqle, L. L., 201.Erickson, A. E., 259.Erickson, J. O., 286.Erlenmeyer, H., 238.Ernst, E., 71.Errera, J., 15, 23.Eubank, L. D., 27.Euw, J. von, 218, 226.Evans, A. A., 165.Evans, B. D. F., 302.ICvans, D. P., 154.Evans, G. E., 22.Evans, R I . W., 321.Evans, R. C., 263.Evans, R. F., 130.Evans, R. L.,.249.Evans, T. H., 193.Ewbank, E. K., 146.Faessler, C., 70.Fahraeus, R., 35.Fahrenbach, M. J . , 259.Faivre, R., 117, 119.Fankuchen, I., 88, 103, 200,Farnsworth, H. E., 87.Farquhar, M., 89.Fast, J., 114.Fawcett, F. S., 314.Fay, J. W. J., 308.Fearon, W.R., 314.Feher, F., 115.Feitknecht, W., 93, 116.Fenske, M. R., 311.Fenton, T. M., 6.Ferguson, R. B., 70.Fernelius, W. C., 149, 160.Fernholz, E., 210, 214.Ferraboschi, F., 187.Fieser, L., 201.Filer, L. J., 102.Fincke, H., 249.Findlay, W. P. K., 267.Fischheck, K., 116.Fischer, F., 117.Fischer, H. 0. L., 169, 171.301.206.Fischer, L., 312.Fischer, P., 149.Flasch, 115.Fleck, H. R., 312.Fleischer, G., 226.Fletcher, H. G., jun., 181,Fleury, P., 182.Flory, P. J., 45, 57.Flynn, E. H., 186.Fohr, M., 270.Foley, R. T., 312.Folkers, K., 156, 167, 186,239, 240.Foote, F., 105.Fordyce, R., 48.Fort, G., 187.Forziati, A. F., 308.Foskett, L. W., 329.Fosse, M. R., 270.Foster, G. L., 319, 320.Foster, J. F., 54, 55.Foster, N.B., 329.Fowler, R. H., 13, 94, 105,Fox, J. J., 15, 17, 20.Foz, 0. It., 148.France, W. G., 62, 71, 72.Franck, R., 214.Frangois, M., 312.Franz, E., 192.Fratini, N., 110.Fred, M., 328.Freed, W. V., 327.Fremdling, H., 270.French, C. M., 289.French, D., 193, 195.French, K. H. V., 314.Frenkel, J., 83, 106.Frerichs, F. H., 168.Freudenberg, K., 171, 179,Freudenberg, W., 183, 234.Frevel, L. K., 152, 333.Freymann, R., 15.Friclre, R., 109.Friedel, G., 69.Friedel, R. A., 324, 326.Frieden, E. H., 258.Friederich, E., 110.Friedlhnder, E., 321.Friedrich, W., 224.Frisch, I?., 119.Frohlich, F., 332.Fromherz, H., 255.Frondel, C., 75, 80.Frush, H. L., 187.Fry, D. la., 311.Fuchs, H. G., 216.Fuller, C.S., 149.Fuller, H. C., 312.Fullerton, H. W., 302.Funke, G., 114.FUOSS, R. M., 32, 57.Furter, M., 200, 202, 204,184.151.191, 192.230.Fuson, R. C., 234.Giitzi, K., 230.Gallagher, T. F., 204, 212,218, 219, 220, 221, 223.Ganapati, K., 257.Gardam, G. E., 79.Garner, W. E., 6.Garrara, G., 279.Garzuly-Janke, R., 199.Gaskin, J. G. N., 331, 332,Gaspart, R., 15.Gaubert, P., 78.Gaus, O., 249.Gee, G., 31, 57.Geiger, F., 192.Georges, L. W., 179.Geyer, U., 236, 237.Ghose, T. Y., 200.Giacomello, G., 200, 221.Gibbs, W. E., 66, 80.Gibson, C. S., 155.Gibson, J., 93, 94.Giesecke, P., 326, 329.Gigubre, P. A., 142.Gilbert, F. L., 160.Gilbert, V. E., 179.Gille, F., 71.Gillette, R., 10.Gilman, H., 249.Ginsberg, E., 144, 153.Girard, A., 169.Gjorling-Husberg, A.S.,Gladding, E. K., 187.Gladyshevskaya, K. A.,Glass, H. M., 5 .Glasstone, S., 153.Gleave, J. L., 271, 273.Glemser, O., 115.Glister, G. A., 244.Glocker, R., 117.Glockler, G., 22.Gmelin, L., 262, 265.Goepp, R. M., jun., 178,179, 183, 184.Gogoberidze, D. B., 81.Goldacre, R., 148.Goldberg, M. A., 249.Goldberg, M. W., 202, 204,Goldfinger, G., 191.Goldfrank, M., 195.Gooderham, W. J., 308.Goodwin, T. H., 99.Gopal, R., 86.Gorbunova, K. M., 86.Gordon, A. H., 180.Gordon, A. R., 39.Gordon, J. J., 154.Gordon, R. R., 311.Gordy, W., 16, 20, 143, 153.Gore, R. C., 324, 326, 327.Goremykin, V. I., 126.333.118.126.230INDEX OF AUTHORS’ NAMES. 339Gorin, M.H., 45.Gosio, B., 262, 263.Gossner, B., 150.Gottschalk, A., 189.Gould, R. G., jun., 247.Graalheer, H., 164.Graber, R. P., 167.Graf, L., 87.Graff, S., 320.Graham, P. L., 316.Gralen, N., 35, 57, 59, 60Granberg, W., 189.Grand, R., 216.Granick, S., 294.Graser, G., 244.Greenstein, J. P., 286.Greenstone, A., 117.Gregg, D. C., 236.Greville, G. D., 283.Griffith, R. L., 89.Grimm, L., 114.Grob, C. A., 176.Gross, H., 58, 60, 61.Gross, P. M., 27.Gross, S. T., 333.Gross, W. J., 164.Grosser, P., 266.Grossman, H. H., 328.Grove, D. J., 317.Griissner, A., 240, 242.Guba, F., 285.Gudden, B., 111.Giinther, P., 142.Gurtler, P., 199.Guggenheim, E. A., 34, lotGuinand, S., 254.Gundermann, J., 111.Gunther, P., 11.Gurin, M.M., 126, 127.Gurry, R. W., 116.Gyulai, Z., 84.Haas, P., 279.Hhgg, G., 90, 92, 96, 106Halcrow, B. E., 249.Hales, R. A., 178.Halford, J. O., 6, 15.Hall, C. E., 281, 282.Hall, D. M., 249.Hall, M. N. A., 111.Halla, F., 118.Hallett, L. T., 330.Hallock, L. L., 247.Halsall, T. G., 190.Hamamura, Y., 173.Hamer, A., 314.Hammen, H., 116.Hammer, H. F., 247.Handler, P., 269, 278.Hanes, F. M., 304.Hanisch, G., 210.Harm, R. M., 183,186,187.62.110, 114, 115, 116.Hems, B. A,, 243.Henbest, H. B., 217.Henderson, G. M., 158.Henderson, R. B., 249.Hendricks, S. B., 14, 16,Hendrixson, W. S., 6.Hendry, J. L., 51.Henri, V., 310.Henroteau, F., 86.Hentschel, H., 11.Hepp, H. J., 308.Herbrandson, H. F., 247.Herman, R.C., 6, 23.Hermann, C., 11.Hermanns, L., 176.Hermans, P. H., 192.Heros, M., 310.Herscher, W., 324.Herzberg, G., 12, 18.Heslop, (Miss) D., 187.Hem, H. V., 212.Hess, K., 189, 192, 194, 268,Hess, W. C., 283.Heubner, C. F., 182.Heukers, R. T., 309.Heuser, G. F., 300.Heusser, H., 204, 216, 226,Hewitt, J. T., 7.Hey, D. H., 287.Keyn, M., 256.Heyningen, R. van, 285.Hibben, J. H., 23.Hibbert, H., 48, 193.Hickam, W. H., 317.Hicks, E. M., jun., 214.Higginbottom, (Miss) C.,Hignett, T. P., 134.lilbert,G.E., 193,194,195.Xildebrand, J. H., 6.lill, W. K., 28.lills, H. W. J., 165.-Iinden, W., 237.Iindley, N. C., 232.Iinds, G. P., jun., 326.lipple, J. A., jun., 317,320,Iirschfelder, J. O., 8.Iirschmann, H., 231.Eirst, E.L., 190, 191, 194,197, 198.[is, W., 273.[ixon, R. M., 180, 193.Hobbs, M. E., 27.Hockett, R. C., 181, 184.Hoehn, W. M., 212, 222.Hoffhine, C. E., jun., 167.Hoffmann, E. G., 17.Hofmeister, F., 264, 271.Hofstadter, R., 6, 16, 23.Hogan, A. G., 258, 298.Holden, H. F., 291.Holland, A. J., 247.142, 143.269.227.263, 270, 271.321, 322.Hanzal, R. F., 269.Haraldsen, H., 110, 11Harbard, E. H., 114, 115.Harder, A., 105.Hardy, J. D., 326.Hareeaves, A., 102.Harkema, J., 144.Harker, D., 11, 69, 70, 15(Harkins, W. D., 102.Harms, H., 10, 26.Harris, G. P., 16, 144.Harris, L., 325.Harris, S. A., 156, 239, 24(Harrison, T. S., 312.Harteck, P., 308.Hartley, G. S., 39.Hartmann, A., 27.Hartmann, W., 110.Hartree, E.F., 269, 291Harvey, G. G., 13.Hasbrouck, R. B., 245.Haskins, W. T., 1133.Haslam, J., 313.Hasler, M. F., 87.Haslewood, G. A. D., 231.Hass, E., 116.Hass, H. B., 156.Hass, R. H., 192.Hassell, O., 202.Kasselt, W. van, 167.Kassid, W. Z., 189, 195Hastings, A. H., 304.Hattori, Z., 213.Hauffe, K., 111, 119.Haughton, J. L., 114.Kaurowitz, F., 292.Kawley, J. E., 111.3aworth, J. W., 233.3aworth, R. C., 244.Taworth, R. D., 310.3aworth, (Sir) W. N., 52:187, 191, 193, 199.Iayes, H. T., 144, 152.Iaywood, P. J. C., 312.Ieafield, T. G., 142, 152,h a r d , R. D. H., 207.Ieath, R. L., 199.Iedvall, J. A., 119, 120.Eegedus, B., 243.Fegsted, D. M., 258.[eilbron, (Sir) I. M., 209,Ceimbrecht, M., 113.Ceimburg, M., 109.[eisenberg, W., 9.[elferich, B., 187.[el’man.A. D.. 120. 121.113.152.293, 294.196, 199.153.215, 233.I , , 122, 123.dmholz, L., 11, 20, 142,149, 150..emingway, A., 319340 INDEX OF AUTHORS’ NAMES.Hollander, V. P., 220.Holley, C. E., 144.Holliman, F. G., 158, 159.Hollingshead, E. A., 39.Holly, F. W., 167, 186.Holm, K., 11, 142.Holmberg, B., 279.Holmes, A., 318.Kolmes, G. S., 200.Holohan, M., 94.Holt, E. K., 133.Holt, N. B., 199.Holtermann, C. B., 116.Holtermann, H., 227.Honeyman, J., 185.Hoogerheide, J. C., 244.Hook, A. van, 86.Hooloy, J. G., 13.Hooper, I. R., 186.Hoover, H., jun., 317.Hopkins, (Sir) F. G., 253,Hopkins, G., 152, 153.Horecker, B. L., 329.Horn, F., 268.Hornstein, F., 189.Horowitz, N.H., 276.Hoschek, E., 111.Hostetter, J. C., 116.Hothersall, A. W., 79.Houlahan, (Miss) M. B., 276.Houston, E. C., 131.Howe, E. E., 244.Howton, D. R., 234.Hromatka, O., 238, 239.Hudson, C. S., 182, 183,Huckel, W., 27, 28.Hulsmann, O., 109, 111.Huttel, R., 251.Huttner, R., 115.Huff, J. W., 273.Huffmann, M. N., 230,231.Huggins, M. L., 5, 12, 29,48, 289.Hughes, E. D., 161, 163,204, 207, 209, 211, 271,273.Hughes,E. W., 95,142,152.Hughes, W.. 12.Hultquist, M. E., 259, 297.Humphreys, C. J., 326.Hunter, J. S., 156.Hunter, L., 5, 142, 144, 145146, 147, 149, 152, 153164, 155.Hunter, R. M., 130.Hunziger, F., 225.Hurd, C. D., 189.Huse, G., 97, 100.Huseman, E., 199.HUBS, H., 262.Hustrulid, A., 321.Hutchings, B.L., 258, 259261, 297, 299, 300, 302Hutchinson, D. A., 89.304, 305.186, 187.Kyde, W. L., 325.[ddles, H. A., 236.[ngold, C. K., 161, 204, 207,209, 211, 271, 273.[nhoffen, H. H., 205.[nnes, J., 302.[rvine, (Sir) J. C., 179.[sakova, A. P., 125.[sbell, H. S., 187, 199.[selin, B., 176, 178.[sherwood, F. A., 194.[vanov, V. I., 191.[wasaki, T., 214.Jackman, M. E., 244.Jackson, C. F., 134.Jacobs, M. B., 314.Jacobs, T. L., 249.Jacobs, W. A., 247, 249.Jacobson, B. M., 305.Jacobson, W., 254, 255,Jahrenbach, M. J., 297.Jakus, M. A., 281, 282.James, S. P., 186, 198.James, W. A., 39.Janetsky, E. F. J., 242,244.Japha, 264.Jayme, G., 191.Jeanloz, R., 176, 178, 193.Jeffes, J. H.E., 5.Jeffrey, G. A., 98.Jenkins, G. I., 152.Jenkins, H. O., 36.Jensen, E., 113.Jensen, K. A., 233,260,279.Jeremiassen, F., 85.Jette, E. R., 105.Jochinke, H., 187.Jorgensen, S. Rf., 120.Joffe, V. S., 80.John, H. M., 285.Johnson, B. C., 299.Johnson, H. C., 304.Johnson, J. R., 244, 245,Johnson, P., 56, 58.Johnson, W. A., 318.Johnston, J. P., 53.Jones, E., 304.Jones, E. J., 16.Jones, E. R. H., 217.Jones, J. I., 307.Jones, J. K. N., 180, 190,Jones, L. C.. jun., 326.Jones, It. E., 247.Jones, R. H., 332.Jones, W. G. M., 187.Jonsson, H., 200, 224.Joseph, A. E., 88.Joslyn, M. A., 199.Jost, W., 107.Judenberg, K., 26.Julian, Y. L., 24%304, 305.246.197, 198.rullander, I., 33.ruza, R., 109, 113.Ggi, H., 244.Cahovec, L., 24.lain, C.K., 257.Caishev, R., 68, 85.Callmann, H., 321.Camm, O., 208, 210.Capiir, P. D., 115.larabinos, J. V., 177, 196.Carges, S., 284.Carle, I. L., 161.Carle, J., 18, 142.(arlson, P., 224.(arrer, P., 170, 172.Caslow, C. E., 248.(astner, J., 178.latz, A., 217.(aufman, H. S., 50.Cauzmann, W., 204.Cawai, S., 215.lawecki, H. C., 136.Cay, J., 312.(eilin, D., 269, 289, 291,293, 294, 295.Cekwick, R. A., 36.Celler, R. N., 120.{elley, K. K., 131.iempter, H., 17.<endall, E. C., 201, 205,Keneford, J. R., 250.Cenyon, J., 165, 166, 167.{eppel, D. M., 269.Keresztesy, J. C., 258, 298.Kermack, W. O., 196, 245,Kerr, R. W., 194.Keston, A. S., 319.Letelaar, J. A. A., 20.Khouvine, (Mme.) Y., 182.Kienle, R.H., 313.Kies, M. W., 278.Kiliani, H., 171, 174, 175,Kilmer, G. W., 268, 318.Kimura, S., 212.Kindstrom, A. L., 105.King, A., 114, 115.King, J.. 325.Kinsey, E. L., 15.Kipp, P. J., 324, 325.Kirby-Smith, J. S., 24.Kirkwood, J. G., 24, 25.Kirsanov, A. V., 310.Kitaigorodsky, A., 97.Kitchen, H., 194.Kittel, B., 292.Kjellgren, B. R. F., 135.Klason, P., 263.Kleber, W., 71.Klein, J. R., 269, 278.Kleinzeller, A., 280.Klemm, W., 108, 110, 111,218, 231.249.187.114, 116LNDEX OF AUTHORS’ NAMES. 311Kling, A, 310.Klug, H. P., 88, 93.Kluyver, A. J., 168.Knaggs, (Miss) I. E., 142.Kniss, E., 234.Koch, E., 108.Koch, M. B., 303, 304.Kocher, A., 111.Koechlin, B., 204, 223.Kogl, F., 167, 173.Koelsch, C.F., 232, 234Kohlrrtusch, K. W. F., 24.Kohn, G., 314.Kolarew, N., 81.Kolb, H. J., 76.Kolb, J., 279.Kolson, J., 302.Kolthoff, I. M., 314.Komori, Y., 273.Kon, G. A. R., 238.Konigsberg, M., 178.Kornberg, A., 300.Koschara, W., 251, 305.Kossel, W., 68.Koteswaram, P., 23.Kottler, A., 257.Kotzschmar, A., 255.Kowarski, L., 84.Kraemer, E. O., 44.Kranjc, B., 192.Kraus, O., 150.Krebs, I<. F., 143.Kreger, D., 102.Kremers, H. C., 86.Kretschmer, C., 27.Kreutzer, J., 6, 17.Krichevskaya, E. L., 86.Krishna, S., 200.Kroll, W. J., 137.Kronberg, M. L., 11, 150.Kruber, O., 307.Krueger, J. E., 211.Kubler, M., 171.Kudszus, H., 210.Kuehl, F. A., jun., 186.Kuh, E., 259, 297, 313.Kuhn, R., 257.Kumler, W.D., 200.Kuntner, J., 149.Kurnakow, N. S., 104.Kusch, P., 321.Kutzelnigg, A., 117.Kuznetsova, Z. I., 310.Kyropoulos, S., 87.Lacher, J. R., 111.Laemmlein, G. G., 86.Lambert, J. D., 6.Lamm, O., 39.Land, E. H., 324.Landquist, J. K., 146.Lane, J. T., 171.Lang, E. H., 236.Lang, W., 212.Langenecker, H, E., 102.235.Langston, W. C., 258, 301,Lappin, G. R., 248, 249.Lardon, A., 206, 213, 218.Lash, M. E., 72.Laskowski, M., 299.Lassettre, E. N., 6, 7, 145.Latimer, W. M., 5 .Latven, A. R., 300.Laue, M. von, 67.Lauer, W. M., 247.Lauffer, M. A., 58.Laurent, P., 86.Laurent, T., 90.Laurin, P., 310.Lawrence, A. S. C., 280.Lawson, E. J., 209, 221.Lebedinsky, V. V., 126,127Le Blanc, M., 93, 115, 116Lebret, M.C., 244.Lecomte, J., 328.Lee, E., 20.Lee, J., 234.Lee, J. H., 328.Legge, J . W., 294.Lehmann, H., 283, 285.Lehrman, L., 193.Leighton, P. A., 24.Leisener, E., 194.Lemberg, R., 294.Lemin, D. R., 74.Lemke, G., 237.Lemon, J. G., 219.Lennard-Jones, J. E., 79.Leonard,N. J., 247,249,250Leonhardt, J., 11.Le Roux, L. J., 163.Lett&, H., 203, 206, 215.Letts, E. A., 265.Levene, P. A,, 171,176,186Levi, T. G., 270.Levine, R., 142.Levy, H. A., 152.Lew, B. W., 175, 179.Lewis, G. N., 151.Lewis, H. B., 269.Lewis, M., 268.Lewis, R. H., 154.Aiddel, U., 16, 143, 326.iebig, R., 253.ieser, T., 192.Ander, E. G., 321.2ndstedt, G., 182, 199.indwall, H. G., 244, 248.i n k , K. P., 176, 182.inke, R., 27.insk, J., 212.insker, F., 249.ippman, E.von, 171.ipscombe, W. N., 95.ipson, H., 89, 93.ittleton, M. J., 107.itvak, I. B., 120.itvan, F., 231..iubimova, N. M., 280.,oflund, F., 173.117.Loevenich, J., 270.Lohman, H., 192.Lohmaa, R., 182.Lombard, R. H., 118.London, F., 7.Long, R. W., 6.Long, W. P., 204, 218, 219,220, 223.Longuet-Higgins, H. C., 53,154.Lonsdale, (Mrs.) K., 91,142.Loomis, C. C., 132.Lopez, G. G., 304.Lothian, G. F., 325.Lothian, (Miss) 0. M., 148.Lotmar, W., 86, 93.Lott, M. H., 230, 231.Low, W., 197.Lowry, T. M., 160.Lu, C. S., 142.Lucas, H. J., 122, 211.Luce, E. N., 309.Luckey, T. D., 300.Ludington, R. S., 164.Luders, H., 213.Luttringhaus, A., 164.Lukes, J. J., 113.Lukirsky, P., 84.Lundquist, F., 233.Luszczak, A,, 310.Lutz, R.E., 248, 249.Lynch, E., 309.Lyon, D. R., 159.Maas, M., 253.Maassen, A., 262, 264.MacArthur, I., 281.McArthur, N., 187.McBain, J. W., 102.Macbeth, A. K., 147.McCabe, M. M., 299.McCabe, W. L., 85.McClean, J., 196.McCloskey, C. H., 189.McClure, F. T., 8.McCready, R. M., 195, 196,McCreath, D., 186.McCrone, W. C., jun., 244.Macdonald, R. S., 324.MacDougall, F. H., 6, 26.McElvain, S. M., 234, 236.McFarlane, A. S., 36.Macfarlane, R. G., 301.McGeogh, S. N., 243.MacGillavry, C. H., 89,95.McGuckin, W. F., 201, 218.Machemer, H., 52.McIlroy, J., 200.McIlwain, H., 147, 275.McKay, A. F., 207.McKennis, H., 242.McKenzie, B. F., 201, 218,HlcKinney, D. S., 324.blackly, A.C., 177.199.231342 INDEX OF AUTHORS' NAMES.MacLachlan, D., 90.Maclay, W. D.. 183, 199."layer, W.. 174.McMGters, M..M., 194.McMeekin, T. L., 52.MacMillan, D. P., 13.McNrtlly, W. H., 196.Macpherson, H. T., 283.McReynolds, J. P., 160.Madgin, W. M., 5.Maeser, S., 151.Magat, M., 10.Magnani, A., 242.MagnBli, A., 115.Mair, B. J., 308.Majer, J. R., 244.Majumdar, A. K., 332.Makarov, E. S., 114.Mallette, M. F., 257.Mamoli, L., 226.Mangini, A., 149.Maniere, B., 311.Mann, F. G., 158, 159, 242244, 263.Mann, T., 295.Mannich, C., 234.Maquenne, L., 167.Marcelin, R., 84.March, C. C., 133.Marchi, L. E., 160.Margenau, H., 8.Marion, L., 244.Maris, S., 191.Mark, H., 8, 33, 49, 61, 152191.Marker, R.E., 205, 208209, 210, 211, 217, 221225.Marquardt, R. P., 309.Marrian, G. F., 231.Marriott, J. A., 152, 155.Marshall, C. W., 219.Marti, W., 93, 116.Martin, 262.Martin, A. E., 15, 17, 2CMartin, A. J. P., 180.Martin, D. E., 333.Martin, P. C., 143.Martin, S. L. H., 11 1.Marvel, C. S., 144, 153.Maryott, A. A., 27.Mason, H. L., 222.Mason, R. I., 184.Masson, C. R., 33.Masterman, S., 207.Mathur, K. N., 288.Mattacotti, V., 79.Mattauch, J., 316.Mattoon, R. W., 102.Mattox, V. R., 201.Mauger, (Miss) R. P., 200Maurer, K., 192.Maurer, R. J., 110, 118.Mauthner, J., 210.Maxwell, C. R., 93.Maycoclr, R. L., 19, 22.328.read, D. J., 32, 57.[ocke, R., 6, 17, 24.[econey, J. W., 164.[edes, G., 279.legaw, H. D., 14, 92, 150,[eger, C.H., 321.lehl, J. W., 283.fehmed, F., 110.leier, K., 226, 227.Ieilakh, E. A., 120, 123.Ieisel, K., 109, 111, 113.leisenheimer, J., 146, 171,leister, A., 283.leister, P., 207.lellor, D. P., 129, 160.iielville, H. W., 33.Ienendez, J. A., 304.dennich, V., 304.denzel, A. E. O., 244.denzies, R. F., 33.derkel, K., 26.derrish, R. C., 199.derritt, L. L., 332.derwin, H. E., 118detler, A. V., 323detzger, H., 251.deyer, A. S., 178.deyer, E. W., 242.deyer, J.. 206.rleyer, K., 194, 199, 226Heyer, K. H., 193, 194Ileyer, W., 110.Ileyerhof, O., 284.Heystre, C., 230.Miall, M., 280.Ilichaelis, L., 294.Micheel, F., 167, 173, 176.\lichel, A., 115, 119.Michel, A. J., 136.Miers, H. A., 73.Miess, A., 86.Mikluchin, G.P., 167.Mikus, F. F., 193.Milanes, F., 304.Miles, F. D., 71, 76.Milkonian, G. A., 188.Miller, J. N., 312.Miller, L. L., 245.Miller, M. W., 163.Miller, P., 133.Miller, W. L., 309.Miller, W. R., 231.Milton, R. M., 325.Mims, V., 299, 302.Mirsky, A. E., 287.Mitchell, A. D., 146.Mitchell, H. K., 255, 258Mitzler, O., 239.Mobius, E., 116.Miihring, H., 113.155.249.229.196.261, 297.Moelwyn-Hughes, E. A., 7,Moffatt, J. S., 212.aoffatt, R. B., 212.Mohr, F., 169.Mokeeva, E. I., 119.Mokeeva, N. I., 119.Mollet, P., 15.Mollwo, E., 108.Mommaerts, W. F. H. Rf.,Montgomery, E. M. M., 195.Montgomery, R., 184.Monti, P., 149.Moody, F. B., 178.Ilooney, R. C. L., 142.door, E., 236.doore, C.V., 303.doore, D. H., 282.doore, F. J., 256.doore, G. A., 79.doore, H. R., 325.rloore, M., 215, 221.kloore, S., 182.kloore, T. S., 152.kloore, W. J., 152.klorgan, (Sir) G. T., 149.Ilorgenstern, H., 71.Mori, T., 171.Ilorrell, W. E., 6.Morrison, A. L., 232, 233.Morse, H. W., 82.qorton, M. C., 111.Morton, R. A., 147.Mosimann, H., 62, 197.Mott, N. F., 107.Mowat, J. H., 259, 297.Moy, J. A. E., 5.Moyer, A. W., 269, 274,276.Rloyer, L. S., 45.Mozingo, R., 156, 167, 186,Muller, H., 109, 115, 168.Muller, H. S., 87.Muller, J., 173.Muller, J. W., 193.Muhr, A. C., 214.Munch, A. P., 309.Murphy, B. F., 318.Murray, M. J., 153.Murty, G. V. L. N., 23.Muskat, I. E., 191.Mustafa, A., 146.Myers, V. G., 269.Myrbiick, K., 179, 194, 196.Nachmansohn, D., 285.Nagel, K., 117.Naggatz, J., 215.Najjar, V.A., 269.Nanji, H. R., 238.Nargund, K. S., 155.Natsakoff, A. M., 189.Natta, F. J. van, 52.Needham, D. M., 280.Necdham, J., 167, 280, 284.10.284.239, 240INehlep, G., 107.Nernst, W., 73.New, A. T., 183.Neth, A., 118.Neuber, A., 111, 113.Neuberg, C., 266.Neuberger, A., 54.Neuhaus, A., 71, 78.Neumann, K., 86.Neumann, W., 177.Neumiiller, G., 188.Neurath, H., 39, 286.Nichols, J. B., 36.Nickelson, A. S., 332.Nielsen, A, H., 325.Nielsen, H. H., 325.Nielsen, J. R., 19.Niemann, C., 53.Nier, A. O., 316, 317, 318,Niggli, P., 72.Norberg, E. J., 180.Nord, S., 120.Norris, E. R., 261, 305.Norris, L. C., 299, 300.North, H.E., 265, 273.Northey, E. H., 259,297.Northrop, J. H., 39.Norton, A. R., 312.Nowacki, W., 96.Nuckel, H., 6.Nusbaum, R. E., 311.Nussbaum, J., 114.Nyholm, R. S., 127, 128.Oakley, H. B., 32.Oakwood, T. S., 210.O’Brien, J. R. P., 301.Oddo, G., 152.O’Dell, B. L., 258, 260, 298Olander, A., 107.Oftedal, A., 105, 113.O’Gorman, J. M., 156.Ogston, A. G., 53.Ohle, H., 188.Oleson, J. J., 299, 300.Olson, A. R., 321.Oncley, J. L., 41, 45.Onsager, L., 24.Ordas, E. P., 249.Order, R. B. van, 244.Osborn, E. M., 88.Oshry, H. I., 331.Oster, G., 24, 25.Ott, E., 48.Ott, G. H., 217.Owen, L. N., 183.Owston, P. G., 94.Ozerov, K. N., 77.Paal, C., 189.Pacsu, E., 193.Padoa, M., 193.Page, J. E., 332.Paige, M. F.C., 213.Pttine, P. A., 71.319.DEX OF AUTHORS’ NAMES. 343Palache, C., 80.Palaqios, J., 147, 148.Palin, D. E., 101.Palmer, W. G., 155.Papapetrou, A., 74.Paranjape, K. D., 155.Parham, W. E., 234.Paris, R., 312.Parker, L. F. J., 306.Parrott, E. M., 258.Parry, E. G., 215.Partridge, S. M., 180.Pataki, J., 226, 237.Patberg, J. B., 327.Patry, M., 333.Patterson, G. D., 327.Patterson, W. I., 278.Paul, F. W., 324.Paul, H., 226.Paul, R., 239.Pauling, L., 9, 11, 13, 16.18, 24, 28, 90, 94, 141,142, 143, 150, 153, 162,287, 289, 290, 291, 292,293.Peacock, M. A., 70.Pearlmann, W. H., 231.Peat, S., 186, 191, 193, 194,Peck, P. L., 167.Pedersen, K. O., 34, 36, 44,Peel, E. W., 167.Peiser, H. S., 263.Percival, E.G. V., 187, 196.Perkin, W. H., 245.Perlzweig, W. A., 273.Perrin, F., 41, 46.Perry, S. V., 283, 284, 285.Perutz, M. F., 50, 91.Pesson, M., 251, 254, 257.Peterlin, A., 47.Peters, C., 11.Peterson, F. C., 107.Peterson, W. H., 257, 258.Petrenko-Kritschenko,P. I.,Petrow, V. A., 211, 216,Petrzilka, T., 212.Petterson, R., 96.Pfeiffer, P., 149.Pfiffner, J. J., 258, 260,Phalnikar, N. L., 155.Phillips, G. M., 156.Phillips, H., 165.Philpotts, A. R., 328.Phragmen, G., 114.Pickard, R. H., 211.Pidgeon, L. M., 1’32.Pierce, W. S., 13.Pigman, W. W., 195.Pincus, G., 231.Pincus, S., 314.Pirie, A., 196, 251.196, 199.53.234.249.298, 299.Pitzer, K. S., 14.Plambeck, L., jun., 205.Plankenhorn, E., 171.Platt, B. C., 165.Plattner, P.A., 204, 205,212, 213, 216, 226, 227.Plein, E. M., 313.Ploetze, H., 117.Plummer, C. E., 133.Plyler, E. K., 326.Pohl, H. A., 27.Pohl, J., 266.Pohl, R. W., 108.Pohland, E., 8, 152.Polis, D. B., 284.Pollak, L., 285.Pollard, A. G., 314.Polonovski, M., 251, 254,Polson, A., 54.Polyakova, I. M., 310.Pomfret, R., 314.Poplett, R., 165.Popoff, B., 82.Porsche, F. W., 328.Poschmann, L., 224.Posternrtk, T., 167, 168,170, 171, 172.Potter, F. M., 312.Powell, H., 311.Powell, H. M., 97, 100, 101.Power, F. B., 170.Prakash, B., 115.Prelog, V., 157, 201, 207,211, 215, 217, 231, 236,237, 238, 239.Prentiss, A. M., 51.Press, H., 218.Preston, G. D., 51.Price, C. C., 247, 248.Price, J. R., 147.Price, W.C., 325.Price, W. H., 284.Priescher, K., 224.Prietzschk, A., 13.Prins, D. A., 176, 177, 178,179, 230.Prins, J., 193.Proehl, E. C., 195.Pros, Z., 149.Prutton, C. F., 113.Purdie, D., 242, 263.Purrmann, R., 252, 263.Purves, C. R., 187, 192.Puskas, T., 185.Putnam, F. W., 286.257.Putzeys, P., 49.Rachele, J. R., 268, 318.Raffauf, R. F., 232.Rahlfs, P., 113.Ramet, M., 182.Ramsden, H. E., 181.Randall, H. M., 311.Rank, D. H., 311.Rao, A. L. S., 23344 INDEX OB AUTHORS' NAMES.Rao, C. S. S., 24.Rao, P. S., 200.Rao, R., 24.Raper, K. B., 263.Raper, R., 238.Rapson, W. S., 100.Rasmussen, H. E., 314.Ratner, S., 320.Itaub, E., 79.Rautenfeld, F. von, 28.Ravitz, S. F., 133.Rawlings, A. A., 264, 266,Rawlinson, W.A., 292, 293.Reber, F., 175.Redlich, O., 133.Reed, K. J., 234.Reed, R., 284, 286.Rees, A. L. G., 111.Rees, H. A., 144, 152.Rees, M. W., 283.Reich, H., 213, 217, 218.Reich, W. S., 178.Reichel, H. P., 309.Reichert, R., 250, 255.Reichstein, T., 175, 176,177, 178, 185, 201, 204,205, 206, 216, 217, 218,219, 221, 222, 223, 225,226, 227, 230.270.Reiff, G., 192.Reindel, F., 209.Reinhardt, K., 221.Reinhold, H., 113, 119.Reissert, A., 265.Reitsema, R. H., 247.Renes, P. A., 95.Renfrew, A. G., 249.Renninger, M., 80.Retgers, J. W., 80.Reuter, F., 293.Rhoads, C. P., 268.Rice, F. A. H., 196.Richards, J. R., 119.Richtmeyer, N. K., 182.Rickes, E. L., 258, 298.Riegel, B., 247, 248, 249.Riesser, O., 271.Riley, H. L., 94.Rimbach, R., 136.Rinderknecht, H., 232, 233.Ringbom, A., 331.Rinne, F., 11.Riso, P., 172.Rittenberg, D., 319, 320.Rivihre, C., 192.Robb-Smith, A.H. T., 301.Robbins, M., 298, 299.Roberts, C. B., 147.Roberts, H. S., 113.Roberts, R. M., 247.Robertson, J. M., 11, 12,97, 141, 142, 151.Robinson, J. R., 46.Robinson, R., 231, 245.Robl, R., 256.Rock, S. M., 322.Rodebush, W. H., 5, 16, 18,19, 22, 27, 143.Rogers, B. W., 90.Rogers, M. T., 11, 20, 149,Rooksby, H. P., 87, 332.Rosebury, F., 319.Rosenberg, H. R., 230.Rosenberg, J. L., 39, 60.Rosenheim, O., 205, 211,Ross, S., 102.Roth, H., 330.Rouse, P. E., 6.Rowan, R., 117.Roy, M. F., 16, 143.Royer, L., 70, 77.Rubinshtein, A. M., 123.Rubtzov, M.V., 249.Rudall, K. M., 280.Ruhenstroth-Bauer, G.,205.Ruigh, W. L., 215.Rule, H. G., 158.Rundle, R. E., 193, 194,Runnicles, D. F., 39.Rushig, H., 205.Russell, C. D., 290.Rutherford, (Lord),. 320.Ruzicka, L., 200, 202, 204,205, 206, 207, 213, 214,215, 217, 226, 227, 229,230, 231.Ryabchikov, D. I., 122,123,124, 125.Sachse, H., 116.Sack, H., 15.Sadron, C., 61.Sage, C. E., 312.Sagrott, P. E., 193.St. Clair, H. W., 133.Salt, (Missj E., 187.Salvia, R., 147.Samant, K. M., 209.Samec, M., 193.Saslaw, S., 301.Satre, M., 191.Sauer, H., 115.Saunder, D. H., 100.Saunders, R. H., 153.Saunderson, J. L., 328.Savage, J., 324.Savare, B., 193.Schaffer, P. A,, 90.Schaffner, I. J., 248.Schales, O., 291.Schallamach, A,, 102.Schambra, W.P., 129.Scheer, C. L., 137.Scheibler, C., 171.Schenck, J. R., 275, 276.Schenck, R., 116.Schenk, F., 215.Scherer, D., 167, 170.150.264.195.Scherrer, P., 86.Schiebold, E., 192.Schlechten, A. W., 137.Schluchterer, (Miss) M., 200.Schmid, H., 240.Schmidt, 0. T., 174.Schmidt, T., 115.Schmidt-Thome, J., 220.Schmitt, F. O., 281, 282.Schmitt, K., 113.Schnackenberg, H., 79.Schneider, G., 199.Schneider, I., 27, 28.Schneider, M., 88, 103.Schnider, O., 240, 242.Schnorr, W., 71.Schnurmann, R., 310.Schoch, T. J., 193.Schonberg, A., 146.Schoenhauer, W., 238.Schoenheimer, R., 269, 319,Schopf, C., 250, 251, 255,Schofield, K., 247, 250.Schomaker, V., 90, 142.Schorigina, N. N., 191.Schottky, W., 104, 105.Schubnikow, L., 87.Schultz, J., 249.Schulze, H., 192.Schwab, G.M., 78.Schwab, J. L., 301.Schwarz, E., 325.Schwarzkopf, E., 214.Scott, A. D., 207.Scott, M. L., 299, 300.Scott, R. W., 311.Scutt, P. B., 292, 293.Seaman, W., 312.Searle, C. E., 165.Searles, A. L., 248.Sears, G. W., 88.Sebrell, W. H., 300.Seebeck, E., 205, 219.Seeger, D. R., 259,297.Sefton, R., 310.Seguin, M., 312.Seidel, H., 113.Seifert, H., 77.Seith, W., 330.Seitz, F., 110.Selmi, F., 262.Selwood, P. W., 289, 290,Semb, J., 259, 297.Sen, H. K., 238.Senequier, R., 193.Senti, I?. R., 102.Seshadri, T. R., 23.Shabica, A. C., 244.Sharp, F. H., 133.Sharp, J. G., 283.Sheffield, E. L., 184.Shemin, D., 319.Shen, S.-C., 280.320.257.296INDEX or AUTHORS’ NAMES.345Shepherd, R. G., jun,, 324.Sherman, A., 10, 28.Shigley, C. M., 129.Shishakov, N. A., 79.Shoppee, C. W., 177, 201,204, 217, 218, 223, 225,226.Shottliinder, P., 123.Shrenk, H. H., 331.Shubnikov, A, V., 80.Shukers, C. F., 301, 302.Sickels, J. P., 259, 297.Sidgwick, N. V., 141, 144,145, 146, 152.Sidhur, S. S., 102.Sieverts, A., 111.Siggia, S., 191.Signer, R., 68, 60, 61, 193.Sillen, B., 118.Sillen, L. G., 88, 96, 118.Simha, R., 49.Simmard, G. L., 324.Simmonds, (Miss) S., 275,Simmons, R. W., 261, 305.Simon, A., 115, 117.Simons, J. H., 9, 142.Simpson, D. M., 251, 254,Simpson, J. C. E., 209, 247,Simpson, (Miss) M. I., 279.Singer, T. P., 283.Singher, H.O., 283.Slater, J. C., 14.Sleator, W. W., 20.Sloane, N. H., 300, 302.Slobodkin, N. H., 258, 297.Smith, A. R., 145.Smith, C., 146.Smith, C. W., 243.Smith, D. E., 308.Smith, D. M., 330.Smith, F., 179, 186, 187,Smith, F. G., 113.Smith, H. R., 263.Smith, J. M., jun,, 259, 297.Smyth, C. P., 9.Smythe, W. R., 316.Snell, E. E., 258, 297.Snyder, H. R., 243, 244,Soderholm, G., 110.Sokova, K. M., 191.Soltzberg, S., 183, 184.Sommer, N. B., 248.Sorkin, E., 185, 221, 222,Sosman, R. C., 116.Spaeth, E. C., 249.Spangenberg, K., 7 1.Spatz, S. M., 249.Spencer, G., 313.Spicer, S. S., 300.Spielman, M. A., 157.276, 277, 278.255, 304, 305.249, 250.198.247.223, 227.Spies, T. A., 303, 304.Sprengling, G., 251.Spring, F.S., 213, 218.Sprinson, D. B., 182.Spurr, It., 142.Spurrell, W. J., 145.Srikantan, B. S., 86.Stacey, M., 179, 186, 187,Staedeler, G., 168.Stafford, J. E., 212.Stair, R., 326.Stanford, S. C., 16, 143,S tarkheeva-Kaverzneva, E.Starling, W. W., 211, 216.Staub, P. H., 132.Staveley, L. A. K., 5.Stavely, H., 212.Steck, E. A., 247.Steger, J., 324.Steiger, M., 218.Stein, G., 175, 203.Stein, P., 217.Stein, R. S., 33, 50.Steinman, R., 144.Stephen, J. M. L., 247.Stephenson, C. C., 13, 14.Stephenson, O., 249.Stephenson, S. P., 29.Stetten, D., 268, 275.Steurer, E., 194.Stevens, C. M., 276.Stevens, T. O., 214.Stevens, T. S., 243.Stevenson, D. P., 322.Stevenson, E. S., 268.Stewart, A., 301.Stewart, E. T., 100.Stewart, H.R., 321.Stewart, J. M., 243.Stewart, T. D., 151.Stiller, E. T., 179, 205.Stitt, F., 290, 291.Stockbarger, D. C., 87.Stockmayer, W. H., 8.Stodola, F. H., 231.Stoermer, R., 249.Stover, R., 287.Stokes, A. R., 90.Stokes, J. L., 258, 298.Stokstad, E. L. R., 258,259,297, 299, 302.Stoner, E. C., 288.Stork, G., 234, 236.Stoughton, R. W., 164.Strafford, N., 308, 310.Stranski, I. N., 68, 81, 85.Stratton, C. H., 234.Straub, F. B., 281, 284.Straumanis, M., 70.atraw, H. T., 271.Strecker, W., 270.Streurer, E., 28.Strijk, B., 89.196, 200.153.D., 191.Striplin, M. M., jun., 133.Strunz, H., 11, 142.Stryk, F. von, 187.Stuart, H. A., 47.Stubbings, W. V., 314.Subbarow, Y., 259, 297,Sucksdorf, G., 105.Sugden, S., 163.Suhr, K.A., 308.Suhrmann, R., 79.Sullivan, M. X., 283.Suranyi, L. A., 207.Surrey, A. F., 247.Suter, C. Rf., 243, 279.Sutherland, G. B. B. M., 5,16, 17, 20, 22, 143, 325,326, 328, 329.304, 305.Sutra, R., 189.Sutton, L. E., 28, 156.Suzuki, V., 167.Svanoe, H., 85.Svedberg, T., 34, 35, 36, 44,Swan, G. A., 244, 249.Sweeney, F., 313.Sweeney, W. J., 329.Sweet, A. T., 133.Synge, R. L. AT., 180.Szegoe, L., 289, 292.Szent-Gyorgyi, A., 282,284.Szpilfogel, S., 236, 237.Tager, R. A., 268.Tagmann, E., 201,211,215.Takaiski, M., 167.Tamm, C. O., 179.Tammann, G., 109.Tamura, S., 273.Tanret, C., 170, 193.Tarbell, D. S., 247.Tarnoky, A. L., 166.Tartter, A,, 253, 25G.Tate, J. T., 321.Taval, P.von, 193.Taylor, B., 271, 273.Taylor, D. D., 321.Taylor, D. S., 291, 292.Taylor, E. C., jun., 257.Taylor, E. D., 70.Taylor, J. E., 133, 316.Taylor, P., 271, 273.Taylor, R. C., 323.Taylor, R. L., 86.Taylor, T. W. J., 144, 146,Tazaki, H., 87.Teed, P. L., 130, 131.Temple, R. B., 325.Tengnkr, S., 113.Tennant, H. G., 58.Terrey, H., 288.Thaler, E., 117.Theobald, C. W., 163.Theorell, H., 293, 294.Thode, H. G., 316, 317.53, 197.152346 INDEX OF AUTHORS' NAMES.Thomann, G., 200.Thomas, A., 324.Thomas, R. M., 256.Thompson, A., 186.Thompson, H. W., 16, 311Thompson, R. W., 318.Thompson, W. C., 237.Thomson, (Sir) J. J., 315.Tien, J. M., 136.Tiffany, B., 247.TiImans, J. J., 77.Ting, H. H., 85.Tinker, J., 247.Tipson, R.S., 183, 249.Tishler, M., 244, 259.Toca, R. L., 304.Tode, 0. M., 86.Toennies, G., 279.Tolansky, S., 84.Tomisek, A. J., 255.Tonkin, I. M., 247,Torkington, P., 327.Totter, J. R., 254, 299, 30:Traube, W., 252.Traynard, P., 31 1.Treloar, L. R. G., 57.Tremblay, J. A., 70.Trew, V. C. G., 289.Trusevich, G. L., 123.Tschesche, R., 217, 251Tschinajewa, A. D., 212.Tschumatschenko, T. K.Tullar, B. F., 243.Turnbull, D., 113.Turner, D. L., 225.Turner, E. E., 158, 249.Turner, N. C., 308.Turner, R. B., 201.Turner-Jones, A., 89.Turton, L. M., 187.Tutin, F., 170.Tuttle, 0. F., 87.Tyrrell, H. J. V., 20.Ubbelohde, A. R., 11, 12Uenzelmann, M., 173.Uhle, F. C., 249.Uhlenbeck, G. E., 20.Uhrig, K., 309.Unkauf, H., 197.Urbain, 0.M., 312.Urey, H. C., 317, 318.'Jschakow, M. I., 212.Usikov, N. I., 123.Vainshtein, E. E., 123.Valentino, A., 182.Valeton, J. J. P., 71.Valtieres, G., 193.Vandenbelt, J. M., 258, 299.Van Vleck, J. H., 288.325, 327.305.305.234.151.Vargha, L., 185.Vaughan, W. R., 248.Venkataramiah, H. S., 28.Verkade, P. E., 242.Verwey, E. J. W., 10.Vial, J., 312.Vickerstaff, T., 74.Vieillefosse, R., 254, 257.Vierling, O., 24.Vilbrandt, C. F., 58.Vilter, C. F., 303.Virasoro, E., 329.Vischer, E., 177.Vogel, R., 114.Voigt, A., 109.Volmer, M., 68, 84.Volmer, W., 332.VotoEek, E., 178.Wadsley, A. D., 115.Waelsch, H., 268.Wagner, C., 104, 105, 108110, 111, 116, 117, 119.Wagner, J., 24.Wagner-Roemmich, M.Wagstaff, A.I., 99.Wahrhaftig, A. L., 19.Waisman, H. A., 301.Waksman, S. A., 244.Walker, I. F., 327.Walker, J., 247.Walker, 0. J., 288.Walkley, A., 115.Wall, F. T., 6.Wallace, E. L., 310.Waller, C. W., 259, 297,Wallis, E. S., 166, 204, 210,Walsh, A. D., 122.Walter, E., 209.Walthall, J. H., 133, 134.Walton, E., 156.Ward, E. B., 300.Ward, N. E., 19.Warner, R. C., 52.Warren, 13.Warren, F., 218.Warrington, M., 119.Washburn, H. W., 322.Watanabe, M., 116.Waters, A. H., 181.Watson, H. B., 154, 219.Watson, J., 302.Watt, G. W., 149.Wattis, P. A., 300.Webb, E. C., 285.Webb, R. A., 267.Weber, H. H., 282, 287.Weeks, I. F., 8.Weeks, M., 199.Weger, M., 310.Wehner, G., 115.Wehrli, H., 187.Weibke, F., 109, 111.Weidenkaff, E., 189.249.214.Weidinger, A., 192.Weijlard, J., 259.Weisblatt, D.I., 196.Weizmann, C., 310.Welch, A. D., 300, 301,Wells, A. F., 11, 66, 67, 70,Wenner, W., 221.Wenzke, U., 27.Werkman, C. H., 319.West, C. D., 87, 324.West, J., 142.West, R., 241.west, w., 19.Westgren, A., 92, 104, 117.Westphalen, T., 213.Whalley, H. K., 331, 332.Wheland, G. W., 7.Whiffen, D. H., 311.Whincup, S., 311.Whistler, R. L., 103.White, E. V., 197, 198.White, J. C., 116.White, J. U., 324, 325.Whitmore, F. C., 208, 210.Widmer, R., 172.Wiechmann, F., 109, 113.Wiegand, R. V., 311.Wieland, H., 172, 224, 251,252, 253, 255, 256.Wieland, P., 157, 207, 231.Wiffen, D. H., 327.Wiggins, L. F., 183, 184,185, 186, 187.Wigren, N., 263.Wild, H., 103.Wilds, A. L., 205, 224.Wiley, H. F., 322.Willard, H. H., 333.Willems, J., 77, 78.Williams, C. B., 193.Williams, H. B., 312.Williams, R. C., 51.Williams, R. J., 258, 297.Williams, T. I., 244.Williams, V., 23.Williams, V. Z., 324, 326.Williford, C. L., 333.Willis, H. A., 328.Willis, J. B., 129.Willmore, C. B., 135.Wills, L., 301, 302.flillstiitter, R., 271.Wilson, A. J. C., 89.Nilson, A. N., 239.Wilson, H. E., 303.Nilson, H. F., 301.Nilson, P. I., 187.Nindaus, A., 175, 176, 201211, 212, 213, 214, 215.Windmaisser, F., 118.Vinmill, T. F., 7, 152.Vinstein, S., 122, 211, 212Vinter, 0. B., 333.303.150.249INDEX OF AUTBORS’ NAMES. 347Wintersteiner, O., 215, 221,Wintrobe, M., 302.Winzor, F. L., 147.Wise, L. E., 197.Wishart, R. S., 172.Wissler, A., 61, 192.Witkop, B., 244.Witnauer, L. P., 102.Wittum, M., 79.Wolf, D. E., 156, 239, 240.Wolf, H. J., 261, 305.Wolf, K. L., 5, 26.Wolff, A., 224.Wolfrom, M. L., 177, 178,179, 186, 196.Wolmer, W., 332.Wood, H. G., 319.Wood, J. L., 241, 242, 278.Wood, R. W., 83.Woodruff, H. B., 244.Woodward, I., 11, 12.Woodward, L. A., 20.Woodward, R. B., 236.244.Woody, R. J., 133.Wooster, N., 87.Wooster, W. A., 87.Wright, C. S., 303.Wright, L. D., 301, 303.Wright, N., 324.Wu, C. K., 17, 20.Wulf, 0. R., 16, 18, 143.Wulff, G., 67.Wyatt, G. H., 330.Wyckoff, R. W. G., 51,152.Wyman, J., 48, 291.Xenoe, J. R., 212.Yabroff, D. L., 148.Yang, C. T., 17.Yates, J., 211.Yerkes, L. A., 137.Yoshimura, K., 167.Young, E. G., 196.Young, F. G., 204.Young, W. S . , 323.Yuan, H. C., 164.Yusem, M., 184.Zachariasen, W. H., 11, 13,92, 142, 150.Zambito, A. J., 244.Zechmeister, 179.Zeile, K., 293.Zeise, W. C., 120.Zeiser, H., 174.Zellhoefer, G. F., 144.Zeppelin, H. von, 137.Zettlemeyer, A. C., 14.Zeyneck, R. von, 292.Zief, M., 184.Ziegler, J. A., 316.Ziegler, J, B., 244.Ziervogel, M., 199.Ziff, M., 282.Zimm, B. H., 33, 50, 61.Zintl, E., 104, 105.Ziihlsdorff, G., 205.Zumwalt, L. R., 7, 16, 164.Zurbrigg, H. F., 111.Zwicky, F., 79

ISSN:0365-6217    

DOI:10.1039/AR9464300335

出版商:RSC    

年代:1946

数据来源: RSC

摘要:

INDEX OF SUBJECTS.Absorptiometer in quantitative analysis,Acanthias vulgaris, scyllitol from, 169.Acetaldehyde, defection in, of ethyl alco-hol, 327.Acetamide, hydrogen bond in, 152.Acetanilides, o-substituted, hydrogenbonds in, 145.Acetic acid, entropy and hydrogen bondforce constant for, 15.lead salt, fission of a-glycols by, 180.reactionof, with sugarderivatives, 181.Acetobacter suboxydans, action of, onmeaoinositol, 168.a-d-Acetochloroglucose, reaction of, withbenzene and aluminium chloride, 188.Acids, carboxylic, dielectric polarisationof, in relation to association, 26, 27.fatty, association of, in benzene, 26.Acridine, detection of, 314.Acridine- 1 -carboxylic acid, basic strengthActin, 281.reaction of, with myosin, 285.Actomyosin, 284.Adenosinetriphosphatase, 280, 283.Adsorption by metallic sulphides, 120.Ztio-5-aZZochola-14 : 16-dienic acid, 3(/3)-hydroxy-, acetyl derivative, methylester, 227.Btiocholane, structure of.200.331.of, 148.Btiocholanic acid, 3(a) : ll(a)-dzlydroxy-,* 219, 221.Btio-5-UZZocholanic acid, 3(p)-hydroxy-,17-iso&ti0-5-allocholanic acid, 227.14-aZZo-17-isorE;tiocholanic acid, methylAEtiodeoxycholic acids, lactone formation17 - isoBtio-5 : 14 - diaZZocholanic acid,Aglycones, Digitalis group, synthesis of,Agranulocytosis, 300.Air, detn. in, of fluorine, 333.Albumin, egg-, sedimentation equili-brium of, 36.Alcohols, association of, and X-H stretch-ing vibration, 15.dielectric polarisation of, in carbonin relation to association, 26.polyhydric, 183.secondary, optically-active, propertiesof, 165.Alizarin, overgrowths of, on crystallinesalts, 77, 78.N-Alkenylpiperidines, reactivity of, 234.acetyl derivative, methyl ester, 227.ester, 229.by, 223.methyl ester, 227.225.tetrachloride, 27.4-Alkylaminoquinolines, synthesis of, 248.Alkyl bromides, bimolecular substitutionof, activation energies of, 163.S-Alkylcysbines, fission of, by mouldcultures, 268.Alkyl-oxygen fission of alcohols and theiresters, 165, 166.Allitol from d-glucose, 178.4-O-Allylresacetophenone, Claisen re-arrangement of, 148.Aluminium, analysis of, 332.from bauxite and clays, 133.mirrors for infra-red spectroscopy, 324.reduction of magnesia with, 132.Aluminium bromide, crystal structure of,Amides, mol.wt. and structure of, 152.Amine oxides, properties and structureAmino-acids, detn. of, in proteins, 320.hydrogen bond in, 152.separation of, on moist filter paper, 180.Amino-compounds from coal-tar, detec-Aminosulphitoiridites, 126 .Ammonia, catalytic synthesis of, 119.hydrogen bond in, 152.ionisation of, 321.molecular interactions in, 8.Ammonium alum, crystals, growth velocityazide, hydrogen bond in, 152.bromide, crystals, effect of ions on habitchloride, crystals, effect of ions on habitfluoride, crystal structure of, 94.fluorides, structure of, 150.dihydrogen arsenate, entropy of, 14.trihydrogen paraperiodate, entropy of,dihydrogen phosphate, crystals, effectoxalate rnonohydrate, crystals, effect ofperiodate, hydrogen bond in, 142, 150.I-Amphetamine, optical resolution with,Amygdalin, oxidation of, 182.Amylopectin, end-group determination95.of, 151.tion and detn.of, 313.for, 72.of, 76.of, 76.14.of ions on habit of, 76.entropy of, 14.ions on habit of, 76.156.in, 190.heterogeneity of, with amylose, 194.synthesis of, 196.pectin, 193.hydrolysis of, by /3-amylase, 194.separation of, from starch, 193.structure of, 102.\mylose, differentiation of, from amylo-34INDEX OliAnemia, chicken, cure of, by vitamin-&&4narnia, cure of, by ichthyopterin andhuman, treatment of, factors for, 296.macrocytic, pregnancy, and refractory,monkey, cure of, by vitamin-M, 258.pernicious, treatment of, 302.prevention of, in chicks, factors for, 298,treatment of, with pterins, 305.Analcime, crystals, face development andspace group in, 70.Analgesics, search for, 232.Analysis, biochemical, polarographic, 332.metallurgical, spectrography in, 330.microchemical, 329.polarographic, 332.spectrographic, metallurgical, 330.spectroscopic, absorption infra-red, 323.and yeast factor, 258.xanthopterin, 260.treatment of, 302.299.quantitative, 330.of hydrocarbons, 310, 311.Analytical chemistry, 307.Androst,ane, derivatives, odour of, 207..4ndrostane, cis-3(/3) : 1G : 17-trihydroxy-,Androst-16-ene, 3-hydroxy-derivatives,3(p)-hydroxy-, hydroxylation of, 231.Androst- 5-en- 17 -one, 3( p) -chloro-, 2 10.Androsterone, a-chloro-, struoture of, 210.1 : 6-Anhydro-/3-d-galactose 1 : 6-anhydro-1 : 6-Anhydro-jI-d-idose, 3-amino-, 186.Anhydroleucopterin, 253.1 : 4-Anhydromannitol, 184.2 : 5-Anhydrosorbitol, 184.Anhydroxylitol, 183.Aniline, detn.of, in its derivatives, 313.Ansa-compounds, 165.Anthracene, chromatography of, in an-thracene oils, 308.detn. of, in anthracene oils, 310.heat of formation of trinitrobenzene and,intergrowths of, with chloranil, 78.spectrum of, absorption, ultra-violet,310.Anthracene oils, detn. in, of anthraceneand of 1 : 2-benzpyrene, 310.Anti-anaemia factors, 296.Antibiotics, gliotoxin, 244.Antimony films, crystallisation of, 86.d - Arabinose, preparation of, from d-man-nitol, 183.1-Arabinose, conversion of, into 1-xylose,185.Arginine, optical resolution with, 156.Arlitan, 183.Arsenic, detection of, 263.Arsenic compounds, methylation of, bytrihydride from action of moulds onstructure of, 200.231.musk odour of, 207./?-d-idose, %amino-, 186.in carbon tetrachloride, 7.moulds, 271.pigments, 262.SUBJECTS.349Arsenides, composition and structure of,Arsenious acid, methylation of, 272.Arsine. See Arsenic trihydride.Arsines, complex compounds of, with4-Arylarninoquinolines, synthesis of, 248.4-Arylcinnolines, preparation of, 249.Arylolefinic acids, restricted rotation of,163.4-AryIpiperidines, 4-cyano-, N-substituted,reactivity of cyano-groups in, 235.Aspartic acid, detn. of, in a-lactoglobulin,320.Aspergillus, production of arsenic com-pounds by, 263.Aspergillua fumigatus, gliotoxin from, 244.Asphalt, paving, X-ray diffraction by, 333.Atoms, groups of, absorption spectra of,7-Azaindole, preparation of, 244.bicyclo[2 : 3 : 11-l-Azaoctane, 238.Azobenzene, amino-, detn.in, of aniline,Axo -compounds, o-hydroxy -, structure113.iridium salts, 127.326.313.and properties of, 146.structure of, 152.192.groups by, 279.Bacillus xylinium, bacterial cellulose from,Bacteria, intestinal, synthesis of methylBarium titanate, crystal structure of, 92.Bauxite, aluminium from, 133.Beer's law, 328.Benzanilide, formation of, from benzo-phenone oxime hydrochloride, 167.Benzene, analysis of, mixed with tolueneand xylene, 310.detn. of, by heat of nitration, 310.in presence oftoluene and xylenes, 309.interaction energy in, 9.spectrumof, absorption, ultra-violet, 3 10.Benzene, hezaiodo-, carbon from, 94.nz-dinitro-, crystal structure of, 99.Benzil monoximes, structure and pro-Benzoic acid, structure of, isotope effectBenzoic acid, trichloro-, detection of, inp-fluoro-, dielectric polarisation of, 27.2 : 6-dihydroxy-, ionisation constant of,1 : 2-Benzpyrene, detn.of, in anthraceneBenzyl alcohol, absorption intensity andO-H absorption of, in various solvents,2 : 4-Benzylidene xylitol, structure of, 183.Berthollide compounds, 104.Beryl, attack of, for beryllium extraction,Beryllium, extraction of, and its separ-perties of, 146.on, 12.the dichloro-acid, 327.148.oils, 310.association in, 17.19.135.ation from aluminium, 135360 INDEX OEBeryllium, isolation of, 136.powder, 136.Betaine as lipotropic agent, 277.transfer of methyl group from, 27 1.transmethylation from, 277.Betitol, 171.Bile acids, structure of, 205, 224.Binary compounds, non-stoicheiometrysystems. See under Systems.in, 109.Biochemistry, 262.Biological objects, X-ray structure of, 102.dl-Biotin, configuration of, 239.resolution of, 156.synthesis of, 240.dl-alloBiotin, 239.dl-epidloBiotin, 239.@-Biotin, configuration of, 239.Ae-spiroBisisoarsindolinium bromide, 159.Bisdehydrodoisynolic acids, stereochem-Bisdehydromarrianolic acid, stereochem-Bismuth, crystals, structure of, 80.detn.of, by turbidity measurements, 332.Bismuth breath, 265.double oxides and oxyhalides, 118.medicinals, tellurium in, 265.istry of, 224.istry of, 224.20-n- and -iso-Bisnordeoxycholic acids,methyl esters, reaction of, withphenylmagnesium bromide, 222.12-epi-20-n- and 40-Bisnordeoxycholicacids, synthesis of, 221.As-spiro-Bis-1 : 2 : 3 : 4-tetrahydroiso-arsinolinium bromide, 159.Blood, detn.in, of carboxy-, met-, andoxy-hsmoglobin, 329.Blood disease in monkeys due to in-adequate diet, 3Q1.Bolometers, 325.Bonds, absorption spectra of, 326.Boric acid, crystalline, structure of, 151.isoBorneo1, detection of, in camphor, 326.Boron hydrides, hydrogen-bond structureof, 154.Bravais' law, 69.Bromal hydrate, interaction in, 16.Bromanil, overgrowths of, on silver andon sodium chloride, 78.Bromine, activation energies of exchangeof, and steric hindrance, 162.Brucite containing excess metal, 119.Bushy stunt virus protein, mol.wt. of, 36.1 : 3-Butadiene, detection and detn. ofn- and iso-Butanes, ionisation of, 321.Butterfly wings, pterins in, 251.d-sec.-Butyl alcohol, 156.tert.-Butyl alcohol, association of, incyclohexane, 26.Cadmium, detn. of, in zinc, 332.Cadmium oxide, composition of, 11 7.Calcite, crystals, etching of, 70.Calcium, at. wt. of, from X-ray data, 89.impurities in, 322.sulphate, basic, crystal structure of, 93.IUB JECTS .Calcium carbide, reduction of magnesiaoxide, detn. of, in magnesium oxide,titanate, crystal structure of, 92.with, 132.332.Camera, X-ray diffraction, 332.Camphor, detection in, of isoborneol, 326.2 -Carbethoxyacetamidobenzoic acid, 4-chloro-, methyl ester, low-temper-ature cyclisation of, 248.Carbohydrates, 167.chromatographic separation of, 178.polymeric, end-group analysis of, 51.Carbon, amorphous, structure of, 94.Carbon tetrachloride, detection in, ofmonoxide, oxidation of, nickel-oxide-Carboxyhzmoglobin, sedimentation equi-Carrageenin from Iceland moss, 196.Catalase, magnetic properties of, 294.Catalysis in heterogeneous reactions, 119.Catechol, 3-nitro-, b.p. of, 144." Celite," 179.Cells, photochemical, for infra-red absorp-photo-electric, for turbidity measure-physiological, living, formation by, ofCellulose, amorphous and crystalline, 192.bacterial, from Bacillus xylinium, 192.hydrogen bonds in, 143.membranes, 33.methylated, degradation of, by sodiumoxidation of, with dinitrogen tetroxide,polydispersity of, and its derivatives, 59.polymerisation and structure of, 52.acetates, effect of salts and solvents on,192.nitrate, sedimentation equilibrium of,in amyl acetate, 67.nitrates, mol.wt. and shape of, insedimentationconstants of, in acetone,Chalcocite, composition and structure of,Chalcopyrite, 11 8.Cheirolin in nature, 266.Chelate compounds, metallic, formation of,Chenodeoxycholic acid, rotation of, 216.Chicks, feathering of, factor for, 300.Chitin, deacetylated, reaction of, withChloral hydrate, interaction in, 16.Chloranil, intergrowths of, with anthra-hexane, 327.catalysed, 119.librium of, 35.tion, 324.thallium sulphide, 329.ments, 331.methyl derivatives, 271.in liquid ammonia, 191.with periodates, 191.192.Cellulose acetate, mol.wt. of, 33, 62.acetone, 60.59.113.and hydrogen bond structure, 148.structure of, 214.nitrous acid, 187.cene, 78INDES OPChlorosulphitoiridites, 126.Cholane, structure of, 200..‘i-aZloCholane, structure of, 200.Cholanic acid, 3 : 6-dihydroxy-derivatives,Cholestane, structure of, 200.Cholestane, 3-chloro-derivatives, 207.3-hydroxy-derivatiyes, 208.mono- and di-hydroxy-derivatives, 205.Cholestane-3(p) : 5 : 6(/3)-triol, 211.U- and fi-Cholestanyl chlorides, structureCholestene, 3 : 7-dihydroxy-derivatives,Cholest-2-ene, 208.Cholest- 5 -one, 3( fi) -chloro -, 209.Cholesterol, autoxidation of, 215.212.of, 207.215.3(8) : 7-dihydroxy-derivatives, 216.oxides, structure of, 212.structure of, 206.Cholesteryl chloride, structure of, 209.Cholic acid, structure of, 214.Choline, lipotropic effect of, 274.transme thy lation from, 2 7 4.Chondroitin, structure of, 196.Chondrosamine, structure of, 186.Chromatography of carbohydrates, 178.Chromium oxides, composition andstruct.ure of, 114.Chrysene, spectrum of, 31 1.dl-Cincholoiponic acid, ethyl ester, 236.Cinchona bark, quinic acid in, 172.Cinnolines, 249.Cinnolines, 4-hydroxy-, preparation of,249.Cinnoline- 3-carboxylic acid, 4-hydroxy-,reaction of, with acetic anhydrideand pyridine, 250.Civetone, odour of, 207.Clays, aluminium from, 133.for, 133.Coal-tar.See under Tar.Cobalt, crystals, structure of, 79.detn. of, 329.Cobalt compounds, analysis of, 332.oxides, composition of, 116.sulphides, phase equilibria in, 109.Cocosite, 168.Cocositol, 168.Coffee beans, quinic acid in, 172.Colour, measurement of, 33 1.Conduritol, 171.Convolvulin, d-fucose in, 178.Copper, crystals, structure of, 79.detn. of, in hamocyanin, 51.spectrophotometrically, 329.Coprostane, structure of, 200.Coprostane-3(/3) : 5 : 6(p)-triol,tion of, 21 1.Coprostanol, structure of, 206.Corticosterone, structure of, 225.synthesis of, 2 18.Corundum, crystals, habit of, 77.Creatino, synthesis of, by liver slices, 278.froni glycocyamine, 277.treatment of, acid and alkali processesconstitu-SUBJECTS. 351Creatine phosphokinase, 284.Cresols, detection of, in presence of phenoland p-xylenol, 312.detn.of, by ultra-violet absorption, 311.o-Cresol, detn. of, 312.w-Cresol, detn. of, 312.Cresylic acids, analysis of, by infra-redabsorption, 3 1 1.Crystals, equilibrium of lattice defects in,105.topography of, by multiple beamfaces, roughness of, 83.interferometric method, 84.form of, factors influencing, 66.growth of, 62.effect of solvents on, 65.habit of, effect of dyes on, 74.inorganic, 92.lattices, relation of, to face developmentand space group, 68.mosaic structure of, 79.non-conducting, semi-conduction by,110.nucleus formation in. and super-saturation, 85.organic, 96.oriented overgrowths of, 77.properties of, and hydrogen bonds, 150.X-ray diffraction by, 88.reflexions of, on rotation photographs,shape of, 81.single, growth of, 71, 86.stress in, 80.structure of, by Fourier synthesis, 90.indexing of, 89.effect of deuterium substitution 011,.“ fly’s eye ” device for calculation of,11.90.hydrogen bonding in, 10.Crystallisation, technical, 85.Crystalliser, Oslo, 85.Cuprous iodide, composition and con-ductivity of, 117.oxide, crystals, enantiomorphism of, 7 1.Cyanamides, hydrogen bond in, 144, 152.Cyclisation, high-temperature, 247.Cymarose, structure and synthesis of, 176.Cystathionine, fission of, by rat liver,Cytochrome-c, magnetic properties andpp‘-DDD, spectrum of, absorption, infra-surface motion of particles in, 83.twinning of, 82268.spectra of, 293.red, 327.327.DDT, analysis of, by infra-red absorption,Daltonide compounds, 104.Dambonite, 169.Damson gum, constituents of, 198.Deam inoleucopterin, 2 5 2 .Dehydroisoandrosterone oxides, 214.2-Deoxy-d-allose, synthesis of, 178.Deoxycholic acid, structure of, 221, 223352 INDEX OF SUBJECTS.17-isoDeoxycorticosterone, synthesis anc2-Deoxy-l-fucose, synthesis of, 178.3-Deoxy-d-glucose, 178.6-DeoxyIeucopterin, synthesis of, 252.8 - Deox yleucopterin, 2 53.17-Deoxylumimstrone, 224.3-Deoxy-d-mannose, 175.2-Dooxy-l-rhamnose, 178.2-Deoxysorbitol from d-glucose, 178.Desylaniline, conversion of, into 2 : 3.Dethiobiotin, synthesis of, 241.Dethiogliotoxin, 246.Deuterium, substitution by, effect of, onhydrogen-bonded structures, 11.Deuterodimethylethanol, transmethyl-ation of, 276.Deuteromethionine, metabolism of, fed t orats, 275.Deiiteromethylaminoethanol, metabolismof, 276.Dextrin, effect of, on crystallisation oflead salts, 76.Dextrins, formation of, from amylopectin,195.Dialkyl disulphides, fission of, by Sco-pulariopsis brevicaulis, 266, 267.Diamagnetic susceptibility, hydrogenbonding and, 28.1 : 2-5 : 6-Dianhydromannitol, derivativesof, 185.2 : 3- 1 : 6-Dianhydro-~-d-taIose, 186.Diastereoisomerides, separation of, bybicycIor2 : 2 : 21-1 : 4-Diaxaoctane, 238.Diazoamino-compounds, hydrogen bondsand metallic derivatives of, 149.Dicyanodiamide, hydrogen bond in, 152.Dielectric constant of liquids, equationslarge, due to hydrogen bonding, 24.polarisation.hydrogen bonding and, 24.A14:16-Dienes, hydrogenation of, 229.Diet, inadequate, blood disease in monkeysDiethyl selenido in selenium mouldtelluride in tellurium mould cultures,Diethylarsine from arsenical cultures ofDiethylbenzene, dotn. of, in ethylbenzene,cis- and trans-3 : 4-Diethylpiperidines, 234.Diffusion, rotational, 45.Diffusion coefficients, measurement of, 39.Digestive tract, pterins in argentnffin cellsDiginose, 177.Digitalis, heart poisons from, structure of,225.Digitalose, structure and synthesis of, 173.Digitoxal, 175.degradation of, 226.diphenylindole, 243.distillation, 156.for, 25.due to, 301.cultures, 264.264.moulds, 263.322.transitional, 38.rotational, 45.of, 305.Digitoxonic acid, 17.7.Digitoxose, structure and synthesis of, 175.Digoxigenin, structure of, 21 7.Dihydrocholesterol, 206.cis- and trans-Dihydrotestosterono 17-Dihydrosanthopterin, 254.Diketopiperazine, hydrogen hond in, 152.Dilsea ~ d ? i 1 i .~ , galactnn sulphntn from,196.1 : 3-Dimethylally1 hydrogen phthtilate,optically-active, 165.Dimethylaliylnrsinc in nrsenical mouldcultures, 264.p-Dimethyluminoazobenzene, demeth) 1-ation of, in rnts, 26s.Dimethylaniline, p-methylnminophenylglycuronate from, in rnhhits, 268.Dimethylbic?/cloaznhsptane, 3.3 9.Dimethyl-2-cwrboxyethylsulphoninm salts,279.1 : 3-2 : 4-Dimethylene ndonitol, struetiireof, 183.2 : 4-3 : 5-Dimethylene I-iditol, 183.1 : 3-2 : 5-Dimathylcnc Z-rhnmnitol.183.2 : 4-3 : 5-Dimcthylene xylitol, striic*trircof, 183.Dimethylethylnrsine in arsenical mouldcultures, 264.2 : 5-Dimethyl A4-glucosacchnro-3 : 6-lactone, 187.Dimethyl glucose, separation of, from2 : 3 : 6-trimethyl d-glucose, 1RO.Dimethylglyosime, complex comporindsof, with rhodium salts, 128.2 : 3-Dimethylindole, prcpttration of, 244.Dimethylcyclopcntnnes, spcctrti of, 926.1 : 3-Dimethyl-4-piperidonc, prCpfiri\t ionDimethyl -n-propylarsino in ttrscn ivtilDimethyl selenide in seloniurn moiiltlNS-I)imethylsiilphnnilami(l~s, tlcmct hy 1 -Dimethyl telluride in tellririilin nioiiltlDimethyluric wids, mctnholism of, in tlioDicyclopentndicnc, cletn. of, 310.Diphenyl, moloc.iilar struetiire of, 161.3pheny1, o-hydrosy-, dctn.of, 311, 312.on cttlrite or sodium nitrate, 77.phony1 dnrivativos, 100.acetates, hydrolysis of, 230.of, "4.mould riiltures, 264.cult nres, 264.ation of, in the bocly, 268.cultures, 204.body, 2G!),pp'-dihydroxy-, crystals, overgrowths of,4 : 4'-dinitro-, compounds of, with di-liphenylamine, detn. of, 313.liphenyltrichloroethane, op'-dichloro - ,crystal structure of, 103.! : 3-Diphenylethane, 1 : l-dichloro-2 : 2 -d i - 4 - ch loro - .SrvDDT.See p p '- 1) DD .1 : I : I-tricliloro-2 : 2-di-4-chloro-.: 1 -Diphenyl hexitolu. 189.' : 3-Diphenylindole, from dcsylnniljnt~,243INDEX 01Diisopropylidene aldehydo-d-arabinose,183.1 : 2-3 : 4-Diisopropylideno d-mannitol,183.2 : 3-4 : 5-Diisopropylidene xylitol,structure of, 183.Disaccharides, 189.Distillation of diastsrooisomerides, 156.Dolantin, synthesis of, 233.Dolomite, magnesium from, 130.Dow process for magnesium, 129.Dusts, detn.in, of fliiorine, 333.Dyes, effect of, on crystal habit, 74.Egg-albumin. See under A41bumin.Ehrlich's reagent, 314.Electric field, alternating, orientation in,Electrons, diffraction of, and hydrogendetection of hydrogen bonds by, 142.Electron microscope, molecular dimensionsdetermined with, 5 1.Electrophoresis, molecular shape from, 45.Elements, co-ordinntioq number 8, stereo-Equations, Clausius-Clapeyron, for47.bond, 142. 1chemistry of, 160.vapour pressure, 9.for dielectric constant of liquids, 26.for osmotic pressure, 31.Equilenin, stereochemistry of, 224.isoEquilenin, stereochemistry of, 224.Equilibria, phase, in binary systems, 109.Ergostane, S(a)-chloro-, 209.Ergostanyl chloride, structure of, 209.Erysolin in nature, 266.Ethane, ionisation of, 321.Ethane- 1 -seleninic acid, methylation of,Ethane- 1 -selenonic acid, potassium salt,Ethyl alcohol, association of, in cyclo-272.methylation of, 272.hexane, 26.detection of, in acetaldehyde, 327.interaction energy in, 9.ionisation of, 321.molecular distribution in, 13.2 -Ethyl- 7 -azaindole, 244.Ethylbenzene, detn.in, of diethylbenzene,o-Ethylbenzyl bromide, 0-2-bromo-, useEthylene, complex compounds of, withEthylene; tetmchloro-, detection in, ofEthylene chlorohydrin, hydrogen-bondEthyleneimine, hydrogen bond in, 114,Ethylglycine, cte-ethylation of, in rabbits,Ethylidene chloride, detection in, of322.spectrum of, 31 1 .of, in syntheses, 159.platinum salts, 120.ionisation of, 321.impurities, 327.strength of, 7.152.275.impurities, 327.SUBJECTS.3536-Ethylindolizidine, synthesis of, 239.1 -Ethyl-4-piperidono, preparation of, 234.Ferric yanides, electronic fitruc ture of, 2 S 9.Ferrocyanides, electronic striictiirc of, 889.Forrosilicon, reduction of magnesia with,Ferrous cytochrome-c, niagrict ic rnomcritFerrous seienide, strncture of, 105.Fibres, structure of, J 01.Fish, eyes and skin of, pterins in, 351.Flax, New Zealnnd, polyuronide from, 200.Fluorescyanine from fish skins, 254.Fluorine, at.wt. of, from X-ray data, 89.detn. of, in air, dusts, and foods, 333.Folic acid, 258, 207.nature of, 261.Foods, detn. in, of fluorine, 333.Formaldehyde, condensation of, with 11-132.and spectrum of, 203.toluidine, 157.in methylation reactions, 270.Formic acid, entropy and 11ydrogon I w n t l2-Formyl-2-methylc~~c~lolisxanone, optitatil4-For1nyl-2-phonylosntrinzolc, lS4.Fourier summation machins, 90.Fourier synthesis, crystal structuro detor-Frictional constant, molecular dimensionsFurnaces, for obtaining single crgstnls, S7.2-Furylmethylcarbinol, esters, hydrolysisforce constant for, 15.rotation of, 155.miriation by, 90.from, 37.of, 166.c-Galactan, frnctionotion of, 107.Galactiironic acid, synthesis of, 187.Garnet, crystals, face development i 1 1 1 t lGas, natural, analysis of, by mass spct-tra,space group in, 70.320.water, catitlytic syntliosis of, 119.Gas analysis, by means of niass spectra,3".Gelatin, mol.wt. of, by stronming bire-fringence, 61.Gentisic acid, 4-bromo-, dociimcth~ Icmoether, stereoisomerism of, 164.Gigartinn stellcrtn, galactan sulphute from,196.Gitoxigenin, dt~griLtlatiori of, 229.GZiocZnrEiui,L $t,tbriznltou, gliotoxiii froni,Gliotoxin, formation and striicturo of, 244.a-d-Glucopyranosido-a-Z-sorbofuranoside,d-Glucose, electrolytic reduction of, 178.Glucurone, structure of, 187.Glucuronic acid, synthesis of, 187.Glutamic acid, tictn. of, in a-ltictogIoInilin,d-Glutamic acid, detection of, in presc'nceisolactoiies from, 223.244.189.1 -phosphate, polysuccliaride from, 195.320.of I-glutamic acid, 320354 INDEX OF SUBJECTS.Glycine, detn.of, in a-lactoglobulin, 320.Glycocyamine, creatine synthesis fromGlycogen, end-group determination inGlycogens, 193.a-Glycols, fission of, by lead tetra-acetatea-Glycol groups, oxidation of, 180.Glycosides, cardiac, sugars in, 173.Goethite, crystals, face development andGold mirrors for infre-red spectroscopy," Gosio-gas," 263.Gramine methiodide, tryptophan synthesisfrom, 243.Granulocytopenia, 300.Graphite, crystal structure of, 93.Growth conglomerates, theory of, 81.Growth factors, L. casei, haemopoieticstructure of, 259.treatment of anaemia with, 302.norite eluate, 258.purification of, 257.Guaiacol, detn.of, 312.Z-Gulomethylitol from d-glucose, 178.Gum tragacanth, constituents of, 198.Guvacine hydrochloride, 236.Gymnemu sylvestra, 2-quercitol in leaves of,277.190.180.space-group in, 70.324.activity of, 303.170.Haem, magnetic properties of, 292.Haematin, derivatives, covalent and ionicstructure of, 289.bonding in, 295.296.electronic structure of, 289.magnetic and optical properties of,magnetic properties of, 287, 290.magnetic properties of, 292.Haematopoiesis, pterins in, 305.Haemin, derivatives, nomenclature andmagnetic properties of, 292.structure of, 289.292.Hzmochromogens, magnetic properties of,Haemocyanin, detn. in, of copper, 51.HeEix, molecular shape of, 56.Haemoglobin, and its ferrous derivatives.magnetic properties of, 290.detn.in, of sulphur, 51.mol. wt. of, 51.Heparin, structure of, 196.cycZoHeptano-2 : 3-pyrrolidine, 236.Heterocyclic compounds, 232.Mills-Nixon effect in, 238.4 : 6-Hexahydrobenzylidene 3-deoxy-a-methyl-d-glucoside, 179.Hexamethylbenzene, compounds of, withpicryl halides, crystal structure of,100.Hexane, detection of, in carbon tetra-chloride, 327.cycZoHexane, detection of, in toluene, 327.Hexofuranosides, oxidation of, withHexose diphosphoric acid, oxidation of,Homocystine, replacement of methionineHomomeroquinene, synthesis of, 236.( + )Hydratropamide, Hofmann reactionHydrazine, ionisation of, 321.Hydrazinium difluoride, hydrogen bondHydrazoic acid, hydrogen bond in, 142.Hydrides, composition and structure of,Hydrocarbons, aromatic, nitrated, colourperiodic acid, 181.182.by, in diet, 274.with, 167.in, 11.structure of, 150.structure of, 142.111.reactions of, with ketones, 308.benzenoid, spectra of, Raman, 31 1.detn.of, in soil gases, 329.low-boiling, blending of, 323.mixed, analysis of, 322.molecular extinction coefficient andpurity of, from infra-red spectra,separation of, by adsorption, 308.Hydrocyanic acid, dielectric constant of,Hydrofluoric acid, and its salts, hydrogenbonding energy and interaction in, 9.dielectric constant of, 24.gaseous, absorption of, 22.hydrogen bond in, 142.solid, hydrogen bond in, 11.angular deformation of, 23.detection of, 141.electrostatic effects and, 28.energy values and frequency changes of,force constant for, 23.frequency changes of, and of deuteriumoptical density of, 311.328.24.bonds in, 149.Hydrogen bonds, 5, 141.19.bonds, 19.Hydrogen bridge, 29, 155.Hydrogen-carbon bonds, 153.Hydrogen cyanide.See under Hydro-Hydrogen fluoride. See under Hydro-Hydrogen-fluorine bond, 149.Hydrogen-fluorine-nitrogen bond, 150.Hydrogen-nitrogen bond, 152.Sydrogen-Ntrogen-oxygen bond, 15 1.Hydrogen-nitrogen-sulphur bond, 162.Kydrogen peroxide, hydrogen bond in,3ydrogen-oxygen bond, 150.lydrogen-oxygen-sulphur bond, 163.3ydrogen sulphide, formation of, silver-Iydroxy-compounds, organic, molecularcyanic acid.fluoric acid.142.structure of, 142.sulphide-catalysed, 119.association in, 15 1INDEX OF SUBJECTS.355Hydroxylamine, complex compounds of,with palladium and platinum salts,126.Hydroxyl bond, 29, 150, 155.a- and 8-Hyodeoxycholic acids, constitu-Hyperol, hydrogen bond in, 142.Ice, crystal structure of, 92, 94.tion of, 212.entropy of, 13.structure of, and equilibrium withwater, 151.Ichthyopterin, antianaemic activity of,260.from fish skins, 254.d- and 1-isoIdides, 185.1-Idomethylose, synthesis of, 178.Illicium religiosum and verum, shikimicacid in, 171.Indene, detn. of, 310.Indole, detn. of, colorimetrically, 314.Indoles, 3-nitroso-, 1 : 2-disubstituted,cyanine dyes from, 244.ozonisation of, 244.substituted, dipole moment andstructure of, 244.synthesis of, 242.Indole-3-aldehyde, preparation and re-actions of, 244.Indole trimethincyanines, 244.Infra-red.See under Spectra and Spectro-scopy.Inorganic compounds,non-stoicheiometric,104.Inositols, 167.d - and Z-Inositols, 169.mesoInosito1, 167.synthesis of, 172.Inosose, 168.Intermetallic compounds, substitutionalIntermolecular forces, 7.Iodic acid, hydrogen bond in, 11.Ions, positive, parabola method for, 315.Iridium salts, complex compounds of,Iron, crystals, structure of, 79.Iron oxides, composition and structure of,Isomorphism and overgrowths of crystals,Isoprene, crystal structure of, 102.Isotope abundance ratios, 316, 317.Isotope dilution method in analysis, 319.Jalopin, d-fucose in, 178.Keto-acids, N-methylated, secondaryalcohols from, 268.a-Keto-acids from cysteine and methioninederivatives, 278.3-Ketoaetio-5-allocholanic acid, methylester, Wolff-Kishner reduction of,226.solid solution in, 105.126.ferrous, detn.of, 329.ions, electronic structure of, 288.116.77.2-Keto-d-gluconic acid from carrageenin,196.l-Keto-3-methylthiobutyric acid, form-ation of, from dZ-N-methylmethionine,278.Kidneys, haemorrhagic, prevention of, bybetaine, 277.Kojic acid from tetra-acetyl glucosonehydrate, 187.Lactobacillus casei, growth factors for,treatment of anaemia with, 303.treatment of sprue with, 304.320.258, 297.liver growth factor for, synthesis of, 250.a-Lactoglobulin, detn. in, of amino-acids,Larch, arabogalactan of, 197.Law of constant proportions, applied t oLead, isotope abundance ratio of, 318.Lead alloys with sodium, phase equilibriumLead tetraacetate, fission of a-glycols by,reaction of, with sugar derivatives,solids, 104.in, 105.180.181.bromide, crystals, hemihedrism of, 71.chloride, crystals, hemihedrism of, 7 1.dioxide, thermal decomposition of, 92.oxides, composition and structure of,salts, crystallisation of, effect of colloidsLepidines, preparation of, 248.Lepidocrocite, crystals, face developmentLeucine, detn.of, in a-lactoglobulin, 320.n- and iso-Leucines, detn. of, in mixtures,Leucopterin, chloro-derivatives, 255.Lichenin, 199.isolichenin, 199.Light, scattering of, mol. wt. from, 33, 49.Light filters for hfra-red rays, 324.Light sources for infra-red spectroscopy,Linkings.See Bonds.Lithium fluoride, crystals, effect of dyesLithocholic acid, rotation of, 216.Liver, fatty infiltration of, prevention of,117.and dyes on, 76.and space-group in, 70.329.structure of, 251.synthesis of, 305.324.on habit of, 75.growth of, 86.274.growth factor from, 297.for Lactobacillus casei, 259.mammalian, pterins in, 251.norite eluate factor from, 258.xanthopterin in, 305.spectra of, fluorescence, 305.Liver extracts, antianemic factor from,Lollingite, composition and structure of,258.113356 INDEX OF SUBJECTS.Lumiandrosterone, 224.Lumiczstrone, 224.Lysine, detn. of, in a-lactoglobulin, 320.Macromolecules, dimensions and mol.wt,of, in solution, 30.?rIagnesium, analysis of, 332.from dolomite and silicates, 130.from sea water, 129.Jlugnesium aluminate, forinntion of, 1 19.oxide. detn. in, of c~ulcium oxide, 332.reduction of, by carbon, 131.“ Jlagnesol,” 179.Magnetic moment, electronic strnctiireand, 268.apparatus for measurement of, 201.suscoptibility, 2 87.Magneton, Bohr, 287.Maize starch, hydrolysis of, 195.Mrtlonamide, spherulite crystals, growthMaltose, reaction of, with paraldohyde,isoMaltose from maize starch, 195.Manganese hydroxide and salts, oxidationoxides, composition mid structure of,of, 82.189.of, 93.isohlannide, 184.neoMannide, 184.Mannitol, dehydration of, 184.Mannitol, 1 : 6-diamino-, derivatives of,d-Mannitol, structure of, 181.Pllnnnosaccharodilactone, structure of, 187.Mannuronic acid, synthesis of, 187.Rlcdicinals, bismuth, tellurium in, 265.Rilelamine, hydrogen bond in, 142, 152.Melezitose, oxidation of, with periodate,Melting point, “wet,” as guide to hydrogon-Membranes, permeable, cellulose, 33.RLercuric bromide, crystals, hemihedrismhlesitylene, detn.of, 309.Mesquite gum, constituents of, 198.Metals, crystalline, crystallisation of,115.185.182.bond structure, 145.qf, 71.79.production of, 87.thermal reduction, 13 1.electropositive, production of, byMetal wires, single-crystal, 87.Metallic hydroxides, structure of, 150.oxides, semiconducting properties of,sulphides, adsorption by, 120.Metallurgical snalysk, spectrography in,processes, inorganic chemistry of, 129.Methzemoglobin, and its derivatives,detn.of, in blood, 329.Methane, ionisation of, 321.Methane- 1 -seleninic aoid, methylation of,110.330.magnetic propertie8 of, 291.272.Methane- 1 -selenonic acid, potassium salt,Methanesulphonyl chloride, reactioii of,Methanethiol from inorgtinic sulphntts,Mothionine, as methyl donor in cl.piltinc’1)cbliaviour of, in Sc.o),rrl~~,.ic,f,~ihcttArivatives in tlivt, 2 7 s .fission of, by S(.oi)1rItr,.i0)).4j.~; b r w i c c i / t l i s ,in naturc, 26G.tritiismotliylatioii from, 274.with abnorniiil isotope iihnnrl:~nc*e, 3 1 S.methylation of, 272.with sugar derivatil es, 187.267.synthesis, 27 7.brez’icartZis ciiltiiws. 267.279.~-RIetliosyhcn~hy~lr~l, and its wters,6-Jlethosycluinoline, 8-nitro-, rra~tion of,Methyl alcohol, dielectric constant of,hydrolysis of, 165.with srilphuryl chIorid~~, 249.24.internction energy in, 9.ionisation of, 32 1.molecular distribiition in, 13.Methylaminc, spectrum of, I<AIII:\II, 24.LV - 31 e t h y 1 coinpo iin d s , ox ic It1 t ive ( leme t h y 1 -RIetliyI dorivatives, formation of‘, 1)yMethyl groups, labile, synthesis of, iri t Iication, 268.living cells, 271.body, 278.transfer of, 57 1 .ture of, 95.Rfethylitmrnonium chloritlc, crystnl strrlc*-Rlethylanilinos, dctn.in, of anilino, 31 3.RIethy lation, biologic>ii 1, 2 6 2.mechanism of, 26!).2-hlethyl-7-azaindole, 244.~lethylcelluloso, mol. wt. of, by stremiiiigbirefringence, 6 1.4-bIethyleinnolines, preparation of, !!4!).Methyldiethylarsino in arsenical mollltlcultures, 264.2 : 4-Methylene adonitol, strnc.tiirc1 of,183.Metliylene-blue, spectra of, nbsoq)t i o n .174.2 : 5-Methylene Z-rhamnitol, 183.2 : 4-Mothylene sylitol, structuro of, 183.Rlethyletliylacetic acid, cl-2-niethyll)rlty1d- and Z-Methylethylacetic acids, 156.ethylet ethyl-n-propylarsiris in arsenicalN-Methyl-l-glucosfimine from hydrolysis1-Jiethyl-d-glucoside, oxidation of, 19 1.3-Methylindolo, preparation of, 244.bfethylnaphthazarin, synthesis of, 147.N1-Methylnicotine, demethylation of, i nrats, 269.l-Methyl-4-piperidone, 3-cyano-, prcpnr-‘ ation of, 234.N-R~ethylsulphanilamides, demethylationester, distillation of, 156.mould cultures, 204.of streptomycin, 186.of, in the body, 208INDEX OF SUBJECTS.3575-Methyltryptophan, 243.Methyluric acids, metabolism of, in theMica, cleavage surfaces of, 84.JIicrochemical analysis, 330.Micron, 324.Microscope, electron, molecular dimensionsMolecular association and hydrogen bond-equilibria of, from ctlsorption in-spoctroscopic changes due to, 15.in a velocity gradient, 46.body, 269.determined with, 51.ing, 145.tensity, 17.47.orientation in alternating electric fields,shape from frictional constant, 37.weight and hydrogen-bond structure,145.from light scattering, 33,49.from osmotic pressure 3 1.from X-ray diffraction, 50.from sedimentation equilibria, 34, 44.from viscosity, 48.of corpuscular proteins, 53.of macromolecules in solution, 30.Molecules, asymmetric, 56.corpuscular, 52.macro-.See Macromolecules.saturated, interaction between, 7.Molybdenum chlorohydroxide octahydrate,oxides, composition and structure of,MOSS, Iceland, carrageenin from, 196.Moulds, action of, on pigments, arsineMucor mucedo, production. of arsenicMuscle, adductor, of molluscs, fibrils of,atlenosinetriphosphatase activity of,mesoinositol from, 167.proteins, 280.crystal structure of, 95.115.from, 262.methylation by, 262, 279.compounds by, 263.281.280.Muscovite, crystals, face developmentMyoalbumin, 280.Myofibril, proteins of, 280.Myoglobin, magnetic propertios of, 292.Myosin, properties and structure of, 282.Myosin A, 282, 284.hfytilitols, 172.Naphthalene, detn.of, 309.and space-group in, 70.structure of, 281.reaction of, with actin, 285.sols, electrophoresis of, 282.yicrate, heat of formation of, in nitro-spectrum of, absorption, ultra-violet,Naphthols, detn. of, 312, 313.l-Naphthylmethylcarbinol, esters, hydro-benzene, 7.310.lysis of, 166.~-Naphthylseloninic wid, and its deriv-Neptunium compoi inds, rryst :I 1 st rncti iwXeriiinL oleander, olcnndriri from. 177.Neurospora crassu, c~hoiine synthesis l):’,Nickel, crystals, structuro of, 79.atives, 370.of, S8, 92.277.detn. of, 329.isotope abundtincc rixtio of, 318.Nicltel compounds, analysis of, 332.oxides, composition of, 116.sulphides, phime equilibria in, 109.Nicotinic acid, methylation of, iii tlio I)ocly,Niobium oxides, composition and stmrtiirc~poZyNitro-compounds, nromtitic, cryst nlNitrogen, isotope ti1)untltmc.c rtitio of, 3 19.Nitrogen compounds, mothylittion of‘.inNitro-starch, prepration of, l!).;.Nitrous osiclc, dwomposition of, Iiica1,c.I-ositle-ciLtttlysecl, 11‘3.Non-stoichoiometry, 104,Nucleic acid, scdimentation const ant of,68.Nutrition, 296.Octa-acetyl cellobiose, soparittion of, onsilica gel, 179.Octa-acetyl gentiobiose, separation of,on silica gel, 179.Octanes, isomeric analysis of, 333.Gstra-1 : 3 : 5-triene,hydrouy-, 23 1.mstriol, structure of, 330.mstriols, cpimeric, 230.iso<Estriol A, 231.Olenndrin from Neriztm olemder, 177.Olenndrose, structuro of, 177.Olefins, complex c*ompounds of, witliplatinum stilts, 120.Oleic acid, hexanoliimine ester, X-raydiffraction by, 102.sodium salt, X-ray diffriiction by, 102.273.of, 114.structure of, 99.the body, 273.c i s - 3 : 16 : 17-tri-Oleyl triglyceridcs, structure of, 102.Oligosaccharides, constitution of, 188.Olivine, magnesium from, 13 1.Optical density, determination of, 328.instruments, military, infrrt-red, crystalsfor, 87.Osmometers, 32.Osmotic balance, 33.pressure, measurement of, 32.mol.wt. from, 31.Oxalic acid, dihydrate, hydrogen bond in,structure of, isotope effect on, 12.silver salt., crystals, thermal decom-position of, 89.spectrum of, Raman, 24.structure of, 151.uranium salts, complex, stereochemistry11.of, 160358 INDEX 0 1Oxalylguanidine, 257.Oxides, composition and structure of, 114.double, perovskite type, crystal struc-5 : 6( u) -0xidocholestane- 3( p) -01, 2 1 2.5 : 6( ~)-Oxidocoprostane-3( fl) -01, 2 13.Oximes, mol.wt. and structure of, 162.Oxy-acids, structure of, 150.Oxygen, isotope abundance ratio of,Oxyhaemoglobin, detn. of, in blood, 329.Palladium, equilibrium of, with hydrogen,111.Palladium salts, complex compounds of,with hydroxylamine and with thio-sulphates, 125, 126.Pantothenic acid, deficiency of, 300, 301.Paramagnetism, law of, 287.Paramyosin, 281.Pea starch, arnylose in, 194.Pectins, 199.Penicillin, electron densities for, through-Penicillium, gliotoxin from, 244.Penicillium brevicaule, production ofcycEoPentadiene, and its dimer, detn.of,neoPentane, detection and detn. of, incycloPentano-2 : 3-pyrrolidine, 236.Pentlandite, composition and structure of,neoPenty1 bromide, structure of, 162.Perovskite, crystal structure of, 92.Peroxidase, horse -radish, magnetic pro -Pethidine, synthesis of, 233.Petroleum hydrocarbons, fractionationPetroleum oils, analysis of, by infra-red2-Phenracylthioisochromanium salts, 2-p-Phenanthrene, spectrum of, absorption,Phenazhydrins, synthesis of, 147.Phenol, association of, and X-H stretchingin carbon tetrachloride, 26.detection of, in presence of cresols andp-xylenol, 312.detn. of, 312.by ultra-violet absorption, 311.shifting of X-H frequency in, 18.vapour deformation frequencies in, 23.Phenol, o-chloro-, gaseous, dipole momenthydrogen bonds in, 7, 154.intramolecular interaction of, 16.ture of, 92.317.out unit cell, 90.methylation by, 265.arsenic compounds by, 262.309, 310.crude oil, 326.111.perties of, 294.of, 308.absorption, 3 1 1.chloro-, resolution of, 160.ultra-violet, 310.vibration, 15.of, 27.o-fluoro-, infra-red absorption anddetn.of, 312, 313.t3tl'UCtUI'0 Of, 150.Phenols, chromatography of, 312.SUBJECTS.Phenylacetic acid, o-nitro-, dissociationconstant of, 154.Phenyl-p- (carboxymethoxy)phenyl-n-butylphosphine sulphide, 158.2-Phenyl-2-p-chlorophenacyl-1 : 2 : 3 : 4-tetrahydroisoarsinolinium salts, reso-lution of, 158.Phenylmethylcarbinol, esters, hydrolysisof, 166.2-Phenylquinolines, 4-hydroxy-, synthesisof, 247.Phosgenite, crystal structure of, 96.Phosphates, acid, isotope effect in, 12.Phosphine oxides and sulphides, 156.Phosphites, organic, detection of, inphosphonates, 327.Phosphor screens, infra-red sensitive, 324.Phthalic acid, structure of isotope effecton, 12.Phthalocyanine, hydrogen bond in, 142,152.Phytin, 167.Pigments, arsenic, in wall -paper, poisoninga-Pinene, detection of, in terpenes, 327.Pinitol, 170.Piperidines, 232.3 : 4-disubstitute& synthesis of, 232.N-nitrosation of, 235.a-Piperidone, mol.wt. and structure of,P iperidones , 2 3 2.2-Piperidones, 4 : 5-substituted, stereo-4-Piperidones, N-substituted, synthesis of,4-Piperidylmethyl-@-propionic acid, 1 -Platinum compounds, complex, stereo-metals, complex compounds of, 120.salts, complex compounds of, withaction of phosphatase on, 168.from, 262.152,isomeric, 234.233.nitroso-, 235.chemistry of, 160.aminopyridines, 1 2 3.with olefins, 120.with thiosulphates, 123.Plutonium compounds, crystal structurePoisoning from arsenic in wall-paper, 262.Polarograph , 332.Polarography, 332.Polonium, crystal structure of, 93.Polyisobutylene, osmosis of, in benzeneand cyclohexane, 57.Polygalitol, 183.Poly-w-hydroxydecoic acid, polymeris.ation of, 52.Polymers, molecular dimensions andweights of, 30.Polymorphism, twinning and, 82.Polysaccharides, 189.oxidation of, 189.Polysiph,onia fastigiata, dimethyl sulphidePolystyrene, molecular dimensions of, 50.of, 88, 92.from, 279.sedimentation constant of, 58INDEX OF SUBJECTS.359Polystyrenes, mol. wt. of, from streamin1Polyvinyl chloride, mol. wt. of, 57.Potassium, production of, by thermaPotassium alum, crystals, growth velocit!aluminium and chromium alums, overbromide, crystals, effect of dyes 01chlorate, crystals, effect of dyes 01:birefringence, 6 1.reduction, 132.for, 71.growths of, 77.habit of, 75.growth of, 71, 86, 87.habit of, 74.twinning of, 82.chloride, crystals, dendrites, growth ofeffect of dyes on habit of, 75.cryolite, 11 8.deuterium fluoride, infra-red spectra ofdzhydrogon arsenate, entropy of, 14.hydrogen bond in, 142, 150.hydrogen fluoride, infra-red spectra ofdihydrogen phosphate, crystals, growtk74.crystal structure of, 96.20.20.of, 86.entropy of, 14.hydrogen bond in, 142, 150.growth of, 71, 87.iodide, crystals, effect of dyes on habitperchlorate, crystals, effect of dyes onsulphate, crystals, effect of dyes onof, 75.habit of, 74.habit of, 74.Potato starch, isomaltose in, 195.Pregnane, structure of, 200.5-aUoPregnane, structure of, 200.6-alloPregnane, 3(j3) : 17 '' a "-dihydroxy-,Pregn-5-ene-3(P) : 21-diol-20-one oxides,Pregn-5-en-3(8)-01-2O-one oxides, 214.Pregn-5-en-3(j3) : 20 : 21-trio1 oxides, 214.@-Primeverose, synthesis of, 189.Prisms for infra-red spectroscopy, 324.Progesterone, structure of, 225.17-isoProgesterone, synthesis of, 226.Propane- l-seleninic acid, methylation of,272.Propane-l-selenonic acid, potassium salt,methylation of, 272.d-a-Propionoxypropionic acid, dl-aec-butyl ester, distillation of, 156.Propylbenzene, spectrum of, 31 1.3 : 4-isoPropylidene rnannitol, 183.Proteins, axial ratio and mol.wt. of, 64.crystalline, mol. wt. and shape of, 50.degree of solvation of, 52.detn. in of amino-acids, 320.frictional ratios of, 42.hydrogen bonds in, 143.molecular shape of, 45.mol. wt. of, and light scattering, 49.230.214.Proteins, muscle, 280.structure of, 152.trace element analysis of, 51.Proton bond, 155.Pteridin, 2 : 6 : 8 : 9-tetrahydroxy-, 252.Pteridine, 2-amino-6 : 8-dzxydroxy-, 253.Pteridines, properties of, 300.Pterins, 250.biological effects and structure of, 304.properties of, 254.Pterins, 2-mercapto-, 257.Pteroic acid, 297.Pteroyldiglutamylglutamic acid, 298.Pteroylglutamic acid, 259, 260, 298.Pteroylhsxaglutamylglutamic acid, 298.Pustulin from Umbilicaria pustulata, 199.a- and p-Pyracins, 300.Pyrazoles, hydrogen bond in, 144, 162.Pyridine, detn.of, 314.Pyridine, amino-, complex compounds of,Pyridine parahematin, 293.Pyrindan, synthesis of, 237.Pyrites, crystals, face development andspace group in, 70.Pyrrhotite, structure of, 105.Q-enzyme from potato juice, 196.Quartz, crystals, faces of, 84.from fused silica, 87.Quebrachitol, 170.Quenselite, crystal structure of, 92.Quercin, 169.Quercinite, 169.i-Quercitol, 170.-Quercitol in leaves of Qymnerna sylvestra,Juinaldine, 4-chloro-, 4-hydroxy-, andJuinic acid, 171.Juinol, crystals, overgrowths of, on calcitemolecular compounds of, structure of,auinoline, methylation of, in dogs, 273.auinoline, 3-amino-, 3-cyano-, and 3-synthesis of, 260.methylation of, in dogs, 273.with platinum salts, 123.170.their nitro-derivatives, 249.or sodium nitrate, 77.101.nitro-, synthesis of, 249.&amino-, 249.2- and 4-chloro-, preparation of, 249.4-hydroxy-, preparation of, 247, 248.$uinolines, 246.iuinoline-3-carboxylic acids, Bz-nitro-4-hydroxy-, decarboxylation of, 249.$uinuclidine, crystal structure of, 103.lacemic acid, resolution of, 156.lays, infra-red, receivers for, 325.C-Rays, diffraction of, analysis by meansand hydrogen bonds, 141.by crystals, 88.detection of hydrogen bonds by, 141.mol.wt. from, 50.leactions, heterogeneous, catalysis in, 119.of, 332360 INDEX OF SUBJECTS.Receivers for infra-red rays, 325.Reducing agents, 132.Resorcinol, crystallisation of, from water,Resorcinol, %nitro-, b. p. of, 144.a-Resorcinol, structure of, 150.a- and p-Resorcinols, structure of, isotopeeffect on, 12.d-Rhamnitol from d-glucose, 178.Rhizobium radiciwlum, polysaccharide of,200.Rhodium salts, complex compounds of,with dimethylglyoxime, 128.Rochelle salt, crystals, growth of, 86.Rubber, natural and synthetic, spectra of,absorption, infra-red, 326.Rubidium iodide, crystals, growth of, 87.Saccharodilactone, structure of, 187.Salep-mannan, 199.Salicylaldehyde, shifting of X-H frequencySalicylic acid, esters, shifting of X-HSamples, preparation of, for spectrography,Santonin, optically-active, 155.Sapogenins, steroid, structure of, 225.Sapphires, synthetic, 87.Sarcosine, demethylation of, in the body,Sarmentogenin, structure of, 217.Samentose, 177.Scheelite, crystals, face development andspace-group in, 70.Schizophyllum commune, methylation ofsulphates by, 267.Swpulariopsis brevicnulia, cultures of,on selenium and tellurium compounds,on sulphur compounds, 266, 267, 268.65.spherulite crystals, growth of, 82.hydrogen bonds in, 12.in, 18.frequency in, 18.331.269.arsenical, 263, 264.265.Scyllitol, 168.Sea water.See under Water.Seaweeds, polysaccharide sulphates in,196.Sedimentation constant, mol.wt. from, 44.Sedoheptulose, d-allose in, 178.Selenides, composition and structure of,Selenious acid, methylation of, 272.Selenite, cleavage surfaces of, 84.Selenium, analysis of, 332.Selenium compounds, methylation of, bymoulds, 264, 271.in the body, 264, 265.Semi-conduction of otherwise non-conducting crystals, 110.Shikimic acid, 171.Silene E.F., 179.Silica, detn. of, in dusts causing silicosis,equilibria, 34.velocity, 42.111.334.Silicates, mineral, magnesium from, 130.Silicosis, detn. of silica in dust8 causing,334.Silmin, 135.Silver films, deposition of, on quart% 84Silver trihydrogen paraperiodate, entropyof, 14.JS-Silver iodide, crystals, overgrowths of,on silver bromide, 78./3-Sitosterol, 210.Soap, micelle structure of, 102.Sodium alloys with lead, phase equilibriumin, 105.Sodium bronzes, 115.Sodium carbonate, solution, diffusion of,into barium chloride gels, 82.chloride crystals, effect of dyes on habitfluoride, crystals, effect of dyes andimpurities on habit of, 75.hydrogen carbonate, hydrogen bond in,142, 150.iodide, crystals, growth of, 87.nitrate, crystals, growth of, 87.nitrite, crystal structure of, 89.sulphate, crystallisation of, from super-saturated solutions, 86.decahydrate, entropy of, 14.Soils, gases in, detn.in, of hydrocarbons,329.Solids, reactions between, non-stoicheio-metric phases in, 1 1 8.Solid solution applied to crystals withatomic lattice, 104.Solubility of hydrogen-bond structures,144.Solutions,. supersaturated, nucleus form-ation in, 85.Solvents in crystal growth, 65.isosorbide, 184.Sorbitol, dehydration of.183.d-Sorbitol, structure of, 181.dl-Sorbitol from d-glucose, 178.Spectra, absorption, infra-red, and hydro-of hydrocarbons, 3 1 1.of organic compounds, index of,valency vibration involved inuse of, in analysis, 323.mass, 315.Raman, and hydrogen bonds, 23.Spectrograph, mass, 315, 316.Spectrometers, 325.mags, 315, 316.prism, calibration of, 324.Spheruiite, crystals, growth of, 81.properties and structure of, 82.Spinach, growth factor from, 258, 297.Spinel, cryst.als, face development andof, 75.growth of, 64, 68, 71, 73, 86.overgrowths of, on calcite and mica,77.gen bond, 143.326.hydrogen bond, X-H, 15.ultra-violet, of hydrocarbons, 310.space group in, 70INDEX OF SUBJECTS. 361Sprue, anamia of, treatment of, 302.treatment of, with L.casei factor, 304.Starch, corn, amylopectin activity from,end-group determination in, 190.hydrolysis of, by enzymes, 194.maize, hydrolysis of, 195.pea, amylose in, 194.potato, isomaltose in, 195.separation of, from amylose, 193.Staudinger's law, 48.Steam, molecular interactions in, 8.Stephanite, crystals, face development andSteroids, 200.195.space-group in, 70.cortical, 217.14-hydroxy-, synthesis of, 227.17(a)-substituted, synthesis of, 226.Steroid oxides, hydrogenation of, 214.Sterols, structure of, 224.Stigmastane, 3-chloro-, and 3-hydroxy-,209.a-and /3-Stigmastanyl chlorides, structureof, 209.Stigmasterol, 2 10.Stigmasterol oxides, 214.Streptococcus lactis R, growth factors for,Streptomycin, hydrolysis of, 186.inositol derivatives in, 167.Styracitol, 184.structure of, 181.Styrene, spectrum of, 311.Succinic acid, structure of, isotope effectSucrose, crystal structure of, 98.oxidation of, with periodic acid, 182.reaction of, with paraldehyde, 189.solutions, crystallisation of, 86.synthesis of, 189.with lead tetra-acetate, 181.258, 297.on, 12.Sugars, and their derivatives, reaction of,from cardiac glycosides, 173.osazones, triazole derivatives of, 188.oxidation of, with periodic acid, 182.purification of, and their derivatives, bychromatography, 179.separation of, and their derivativeson Celite, Magnesol, and Silene E.F.,179.Sulphaguanidine in diet, 300.Sulphasuxidine in diet, 300.Sulphides, composition and structure of,Sulphonamides, mol. wt. and structure of,Sulphoxides, structure of, 156.Sulphur, crystals, face development anddetn. of, in haemoglobin, 51.Sulphur compounds, methylation of, bySupersaturation, nucleus formation and,Supersolubility curve, 85.Surface energy, minimum, concept of, 66.111.162.space group in, 70.moulds, 273.85.Swarm-formation in association, 27.Systems, binary, phase equilibria in, 109.Tamarind seed pectin, constituents of,200.Tar, coal-, analysis of phenols from, 31 1.distillates, constituents of, 307.spirits, analysis of, 311.synthesis of, 155.and, 154.&Tartaric acid, ethyl ester, asymmetricTautomerism, hydrogen-bond structuremesohydric, 154.Tellurides, composition and structure of,Tellurium in bismuth medicinals, 265.Tellurium compounds, methylation of,by moulds, 264, 271.in tho body, 264, 265.Terylene, structure of, 101.cis- and trans-Testosterone acetates, 230.Tetra-acetyl glucosone hydrate, con-version of, into kojic acid, 187.23,-Tetrahydroquinoline, synthesis of, 237.Tetramethyl d-glucose, separation of, from2 : 3 : 6-trimethyl d-glucose, 180.Tetrame thy1 methyl -d-glucosides, separ -ation of, 180.Thallium bromide, crystals, growth of,87.bromoiodide, crystals, for militaryoptical instruments, 87.Thermopiles for infra-red spectroscopy,325.Thiazoles, preparation of, 238.Thioacridone, hydrogen bond in, 153.Thioamides, molecular association andThiocarboxylic acids, molecular associationThiophen, constants of, 314.Thiophenol, heats of mixing of, withThiosulphates, complex compounds of,Thiourea, alkyl sulphides exhaled afterovergrowths of, on crystalline salts andThymol, liquid, supercooled, crystalliteTitanium oxides, composition and struc-Tobacco mosaic virus, protein, molecularsedimentation constant of, 58.Toluene, analysis of, mixed with benzenedetection in, of cyclohexane, 327.detn.of, in presence of benzene andspectrum of, absorption ultra-violet,111.structure of, 152.in, 153.detn. of, colorimetrically, 314.solvents, 153.with palladium salts, 125.with platinum salts, 123.receiving, 266.on mica, 78.growth in, 86.ture of, 114.dimensions of, 50.and xylene, 310.xylenes, 309.310.roluene, o-nitro-, volatility of, 154362 INDEX OF SUBJECTS.p-Toluenesulphonic acid, zinc salt, crystalstructure of, 102.2-p-Toluenesulphonyl methyl-d-galacto-side, conversion of, into d-idosederivatives, 185.o-Toluic acid, dissociation constant of,154.ethyl ester, hydrolysis of, 154.m-Toluidine, crystals, growth of, 84.p-Toluidine, condensation of, with form-Tracer elements, non-radioactive, experi-Transmethylation, 274.from betaine, 277.,3/3-Trehalose, synthesis of, 189.Trideuterocholine, metabolism of, fed toTrimethylarsine from arsenical cultures ofaldehyde, 157.ments with, 318.detn.of, 313.rats, 275.moulds, 263.dimercurichloride, 263.2 : 4 : 6-Trimethyl &galactose, 197.2 : 3 : 6-Trimethyl d-glucose, separationof, from di- and tetra-methyl d-glu-coses, 180.Trimethyl methyl-Z-arabofuranoside, separ-ation of, from 2 : 3 : 4-trimethylmethyl-d-xyloside, 180.Trimethyluric acids, metabolism of, inthe body, 269.Triisopropylidene d-mannitol, structureof, 183.Troeger’s base, constitution of, 157.Tropomyosin, 28 1, 286.Tryptophan, synthesis of, 243.Tungsten blues, 1 15.Tungsten bronzes, 1 15, 1 18.Tungsten oxides, composition and struc-ture of, 115.Turbidity, measurement of, 331.Ultracentrifuge, technique of, 30.Urnbilicaria pustulata, pustulin from, 199.Uranium oxides, composition of, 115.Urea, hydrogen bond in, 152.Urine, mammalian, pterins in, 251.overgrowths of, on mica, 78.methyldiethylsulphonium hydroxidepigments from, 253.uropterin in, 253.xanthopterin in, 305.Uropterin from urine, 253.Urothion from urine, 253.Urothionaldehyde, 254.Ursodeoxycholic acid, rotation of, 21 6.Valves, mercury and sintered glass, forVanadium oxides, composition and struc-Vapour pressure, equation for, 9.Velocity gradients, orientation in, 46.fl-vicianose, synthesis of, 189.from, 266.structure of, 215.mixing volatile liquids, 323.ture of, 114.2-( 3-Vinyl-4-piperidy1)propionic acid, 236.Viscosity, mol. wt. from, 48.Vitamin-B,, for chick feathering, 300.Vitamin-B,, for chick growth, 300.Vitamin-Bc, 257, 298.cure of anaemia by, 258.deficiency of, in chicks, 299.Vitamin-Bc conjugase, 298.Vitamin-Bc conjugate, 259, 298.Vitamin-M, cure of anaemia by, 258.Volatility, hydrogen bond and, 143.Volemitol, d-allose in, 178.Wall-paper, arsenical pigments in poison-Wasp wings, pterins in, 251.Water, dielectric constant of, 24.intermolecular forces in, 10.sea, magnesium from, 129.spectrum of, Raman, 23.deficiency of. 301.ing from, 262.Wave -number, 3 24.Wood, fungi destroying, methylation by,Wiistite, structure of, 105.Xanthhydrol, indole reaction with, 314.Xanthopterin, 251, 253.antianzmic activity of, 260.oxidation of, 257.synthesis of, 305.synthesis of, 253.267.isoxanthopterin, spectrum of, absorption,254.Xylan, oxidation of, with periodates, 190.Xylene, analysis of, mixed with benzenespectrum of, absorption, ultra-violet,Xylenes, detn. of, in presence of benzeneo-Xylene, detn. of, 309.m-Xylene, detn. of, 309.p-Xylem, detn. of, 309.Xylenols, analysis of, 329.p-Xylenol, detection of, in presence ofcresols and phenol, 312.Xylitol, dehydration of, 183.Z-Xylose, formation of, from Z-arabinose,185.d-Xylylketose, condensation of, withd-glucose potassium l-phosphate, 189.Yeast, growth factors from, 258, 259,norite eluate factor from, 258.Yeast glucan. structure of, 199.Yeast mannan, structure of, 199.Zein, molecular shape of, 55.Zinc, analysis of, 332.and toluene, 310.310.and toluene, 309.297.and its alloys, analysis of, 330, 332,detn. in, of cadmium, 332.detn. of, by turbidity measurements,333.332INDEX OF SUBJECTS. 36393.detn. of, in zinc sulphide, 332.137.oxide, composition of, 117.Zircon sand, extraction of zirconium from,111.extraction of, from zircon sand, 137.production of, 137.Zirconium tetrachloride, reduction of,with magnesium, 137

ISSN:0365-6217    

DOI:10.1039/AR9464300348

出版商:RSC    

年代:1946

数据来源: RSC