The earliest history of capillary chemistry - Journal of Chemical

The earliest history of capillary chemistry. I. Traube. J. Chem. Educ. , 1940, 17 (7), p 324. DOI: 10.1021/ed017p324. Publication Date: July 1940. Cit...
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The EARLIEST HISTORY of CAPILLARY CHEMISTRY I. TRAUBE University of Edinburgh, Edinburgh, Scotland


H E branch of science called "capillary chemistry" was founded by the author of this paper and developed by Herbert Freundlich (see his excellent standard work on capillary chemistry (I)). Hence the saying, learned accidentally by the author, that H. Freundlicb was "the father" and I. Traube "the grandfather" of this domain of science. The earliest paper of Traube dates back to the year 1884 (2). At that time significant theories of capillarity were known. In the theories of La Place, Poisson, Gauss, and others, i t was assumed that with complete wetting the contact angle of the liquid in capillary tubes was equal to 0. Its cosine would be equal to 1, and hence the meniscus should be a hemisphere. Traube showed in his first papers that this assumption in general was not right (3), that the angle changed with the temperature and that even a t ordinary temperature the cosine was 1 only for water and certain aqueous solutions. The experimental work on capillarity a t that time was very limited. The works of Quinke, Volkmann, and others may be mentioned. These authors investigated solutions of inorganic salts, acids, and bases, employing generally the method of capillary tubes. In a few cases the dropping method was applied by Quinke and others, but very imperfectly. This method was developed by Traube. His simple instruments, the Stalagmometre and the Stagonometre, have found general application in science and industg. (4). If the area from which the drop fell was circular, and its diameter so big that the drop completely wetted this surface, but became detached only from it, very regular drops were obtained. The rate of dropping and the temperature, however, had to be considered. Either the number of drops in a given volume was determined by means of the stalagmometer or the number of calibrations, corresponding to one drop, were determined with the stagonometer, i . e., a calibrated capillary tube with dropping area. According to this principle a medical dropping glass found general application in all countries where dropping glasses are used. The theoretical papers of Th. Lohnstein (5), F. Kohlrausch (6), and Rayleigh (7), and the experimental paper of E. Duclaux (8). dealing with the dropping methods, should also be mentioned. As has been noted, the experimental papers by former investigators (Quinke, Volkmann, and others) related only to inorganic salts, acids, and bases, but as early as 1864 a dispensing chemist, C. Musculus (9), had investigated some aqueous solutions of pharmaceutically

important substances such as alcohol, acetic acid, soap, and bile. He found that such substances lowered the surface tension and had a much greater influence on the surface tension than salts and other inorganic substances, but polyhydroxy-compoundssuch as the sugars had the same effect as salts. The merits of Musculus concerning the foundation of capillary chemistry should not be forgotten. However, a systentatic examination of aqueous solutions of organic substances had not been made when the present author began his investigations (10). These investigations showed that many organic substances, dissolved in water, influenced the surface tension of the solution much more than inorganic salts. While such salts generally raise the surface tension of water slightly, many organic substances such as primary alcohols, fatty acids, ketones, esters, and so forth, lower the surface tension of water often to a considerable extent. Water-soluble substances were therefore divided into two groups: surface inactive and surface actiwe substances. This distinction proved later to be very useful and i t can be brought in parallel. t a - t h e distinction between electrolytes ahd non-electrolytes. Surface actiwe substances especially have to be important because numerous properties of substances are closely related to surface activity. The influenceof different solutes on the surface tension of water is shown in the accompanying table which was published in 1885 (11). The surface tensions, measured by the method of capillary tubes and calculated in mg. mm., are plotted along the ordinates whereas the abscissas show the percentage weights in equal volumes of solution. It is obvious that the salt curves are practically straight lines while those of the capillary-active alcohols are parabolas. It was also shown that the minutest quantities of the higher members of a homologous series decrease the surface tension of water. The action is much more pronounced in dilute solutions than a t higher concentrations. If the substance is only sparingly soluble the saturated solution shows a surface tension very nearly equal to that of the solute as such. This fact in itself points to a simple relationship between surface tension and solubility, e. g., for isomeric substances (12). Quantitatively i t was shown by the author's experiments on aqueous solutions that the surface tension of capillary-activecompoundsbelonging to onehomologous series decreased with each additional CHa group in a constant ratio which is approximately 3:l (13).

325 Thus the concentrations of isocapillary solutions i n the series oJaqueous solulions oJnlro/~ols, eslns, ketones, ethers, fullv acids. o d so forth. werein iherario 1:3:32:3'. . . . . "This rule, called "Traube's Rule" generally held true up

to high concentrations of the solutions. The validity of that rule was proved by the author and later on by Forch ( l a ) , Windisch and Dietrich (15),and Sternglanz and Weber (16) even for substances of a high molecular weight. Aqueous solutions of N/9000 uudecylic acid approximately showed the same surface tension as a N/3000 solution of caprynic acid and a N/1000 solution of nonylic acid. It is seen from these numbers that very small quantities of strongly surfaw active substances can be analytically determined. It could be shown that Traube's coehcient 1:3 decreased very gradually for substances of high molecular weight (17). In such aqueous solutions as carbon disulfide, carbon tetrachloride, and so forth, not the slightest effect on the surface tension of water could be demonstrated, though i t was shown by physiological and other experiments that such substances have a certain solubility in water (18). But there are two kinds of solubility. A substance can be dissolved not only as single particles, but also as complex particles. There can be colloidal distribution, and in many cases an equilibrium between dissolved single particles and dissolved colloidal particles results. In a concentrated solution of amyl alcohol a certain fraction is already in colloidal solution. This fraction is far greater in the solution of a higher alcohol, such as octyl alcohol, where under the ultramicroscope many submicrones are visible which concentrate gradually a t the interface between aqueous phase and immersion oils or air, and so forth (19x Alcohols and fatty acids of still higher molecular weight

dissolve only as colloidal particles which influence the surface tension of water very little or not a t all. To give only a few examples: It is possible by cataphoresis to prepare aqueous solutions of nonylic acid which show the same surface tension as that of water. The ultramicroscope reveals that such solutions contain a number of big particles only. These complex particles are broken down by the addition of a few drops of hydrochloric acid. The Brownian movement of a very great number of submicrones can be observed, and the surface tension of the solution which previously was practically equal to that of water falls to about half the value. The same phenomenon is observed when a few drops of an alkali solution are added to an aqueous solution of atropine (20),the dissolved particles of which have increased in size through prolonged standing of the solution. The solution which previously h a d the surface tension of water now shows vivid Brownian movement, and the breakdown of the compki aggregates results in a considerable decrease of the surface. tension. ,. , The following theoretical points must be added (ZI); Between the particles of the solute and the solvent van der Waals forces or electric forces areacting as the case may be. The possibilities of attraction are: a,@ and alal or m a . These attractive forces correspond to forces which this author called "Haftintensitat" in earlier works. If the attraction alaz is very great only single molecules will generally be dissolved particularly in dilute solutions. However, the smaller the attractive forces between solveut molecules and solute particles the greater will be the tendency of the solute particles to form complex particles. he greater the surface activity of a compound and the less soluble i t is the greater is its tendency to form complexes. The presence of submicrones in solutions of sparingly soluble substances is shown by the Tyndall beam and the ultramicroscope (22). The ~ i which e bears the author's name was first advanced from purely empirical reasons. But it was further shown that i t was of importance for a great many scientific, especially biological and technical problems (23). As long as these problems have a simple relation to the surface tension, the validity of the rule could also be shown in these other fields. A theoretical explanation of the rule was given thiefly by Irving Langmuir (24)in his classical researches. One objection, however, has to be raised. According to Langmuir the rule should not hold for higher concentrations of the solutions but only for dilute solutious. In this case we can assume with Langmuir that the dissolved particles spread horizontally a t the interface. However, according to my experimental findings, the rule still holds a t rather high concentrations (25). This fact in itself shows that a horizontal arrangement of the CHa chains is not necessary for the understanding of the rule. It is sufficient for our case to assume that the inteusities of adhesion (i. e., van der Waals numbers a l a ) of two successive members of homoloaous series of surface active substances are in the ratio l : 3 (26). The

amounts of work required to bring a dissolved molecule from the interior of the liquid to the surface would then be in the same ratio. It was found by the author that simple ratios resembling those in homologous series also hold in other respects for the surface tension of aqueous solutions (27). Thus we obtain the ratio 1:1 for isomerides of fatty acids and ethers, for norinal and iso-fatty acids as well as for alcohols, for the transition of numerous capillary-active amino-compounds into hydroxyl-compounds, and so forth; in other words, when a NH2 group is replaced by an OH group. The concentrations of iso-capillary solutions of allyl- and propyl-compounds are in the ratio 2:l. There exists a near relation between surface tension and adsorfition. According to Gibbs' principle the excess of substance accumulated per unit interface as compared to the inc du terior of the solution is p = -- where c, R, T and r RT dc have the usual meanings. Therefore the concentration of surface or interfacial active substances is increased in the surface or interface, and the concentration of surface inactive substances in.the surface or interface is decreased. The changes of concentration are corresponding to the surface tension. With increasing surface activity the "chance" of an adsorption in a second phase also increases, and therefore we can postulate a simple relation between surface tension and adsorption. It obviously follows that such a relationship exists if we compare the adsorption isotherms according to the theory of Boedicker-Frenndlich with the relative curves of surface tension. The curves are very similar, but we will not enter here into the particulars of that well-known theory, and we will merely state that this theory of adsorption is certainly important but empirical. We must also content ourselves by mentioning the brilliant works of adsorption, which were accomplished in a later period of the developmenSof capillary chemistry by the two famous American scientists, I. Langmuir (24) and Harkins. Langmuir found that the capillaryactive substances are adsorbed a t the interface in a regular manner, &., in layers which he called monomolecular layers. Harkins (28) also formulated a regular arrangement of the molecules a t the interface by calculating the work of adhesion which is exercised by the polar and non-polar groups of the molecules toward the solvent. The beautiful experiments carried out by Adam (29) and Rideal (30) in connection with Langmuir's theory should not be forgotten. As a result of Langmuir's investigations, i t was possible for the first time (31) to transfer the gas laws and the van der Waals theory to twodimensional systems. The first experiment in this, line was carried out by the author of this communication. Rona and other authors (32) have established that substances of great surface activity can displace snbstances of less surface activity or surface inactive substances from the surface of the adsorbent. Freundlich (33), this author (34) and his pupil, Skumburdis, (35)

have published tables, which show that indeed the relations between surface activity and adsorption are very near, but this is by no means always the case. Thus, for example, the adsorption of many aromatic substances by charcoal is considerably greater than corresponds to their surface activity. The author pointed out that such substances are dissolved partially or completely as colloids, and that these colloidal particles, though they increase the adsorption, do not generally influence the surface tension. This is one of the reasons of the cause for the divergence. While according to Langmuir the adsorption of capillary-active substances a t the interface of water-air takes place in monomolecular layers, for water-soluble as well as for water-insoluble surface active and polar substances, the adsorption of colloidal droplets of oleic acid. and so forth.- bv ~owderedminerals (36) > , . (lead. , felspar, and so forth) was found to take place in thousands of layers. The oil drops adhere much closer to ores such as lead than to minerals such as felspar. Related to this is the fact that adsorbents such as anthracene and naphthalene frequently adsorb only small quantities of solute from the aqueous solutions. Thousands of layers, however, are adsorbed as soon as substances such as octyl alcohol and caprylic acid are brought into contact with the adsorbent in form of an aqueous emulsion (37). On the addition of water i t is usually found impossible to separate the droplets from the adsorbent. Even if the adsorbed substance is water-soluble, only single molecules are separated from the adsorbent when it is shaken. The colloidal droplets adhere closely to the adsorbent. Special attention may be directed to the relations of surface tension and permeability and/or osmosis. When a liquid or dissolved substance is adsorbed by a solid, porous, or gel-like adsorbent, the former will either adhere to the surface of the adsorbent or i t will permeate partially or completely into the interior of the solid substance. If the solid, p~ssihiyin the form of a gellike substance, forms a membrane which is surrounded by a layer of liquid on both sides osmosis takes place, and i t is of importance to find out the character of the osmotic forces which are responsible for the osmotic process. According to the osmotic theory of van't Hoff-as applied to diluteiolutionsand the theory of electrolytical dissociation by Arrhenins which forms a useful supplement to the theory of van't Hoff, the numher of particles to be found in solution on either side of the membrane is responsible for the course and direction of the osmotic process. As driving force we have to consider the osmotic pressure, which is found to he equal to the gaseous pressure-the same cause being made responsible for both. Gradually, however, it became apparent that the purely physical theory of osmotic pressure camed with it considerable disadvantages. Whereas the gas molecules move about in a free space, the dissolved molecules in concentrated as well as in dilute solution are in continual contact with the molecules of the solvent. There is to a greater or smaller extent considerable attraction between the


molecules of the solute and those of the solvent. Whereas for dilute gases van der Waals magnitudes a, and az, need not to be taken into account these attractions a, and as cannot, as was the case in van't Hoff's theory, be neglected even in very dilute solutions. The theories of van't Hoff and Arrhenius did not take any notice of those intensity factors governing the attractions between solvent and solute, though these factors are responsible for the action of the solutions just as is the case for the number of particles in solutions. The direction of osmosis and the osmotic force as such depends not only on the number of particles but also to a considerable extent on the forces of attraction mentioned above, which correspond to the surface activities of the solute particles (38). The direction and velocity of the osmosis as well as the osmotic equilibrium are therefore determined above all by the surface tensions of the solutions, a fact which was neglected for a long time. Indeed, i t could be shown that in general the time of flow of aqueous solutions through a capillary tube is parallel to the surface tension. At a time when the entire scientific world was in favor of the theory of van't Hoff and that of Arrhenius, the author of this communication was the only one, especially among the German scientists, who pointed out the deficiencies of those theories, which were later indeed shown to exist also by physicists like Bjerrum, Miluer, and especially-Debye and Huckel and others. As long ago as 1904 and 1908 the author pointed out that when two aqueous solutions were separated by a membrane generally the solution with the lower surface tension permeates through the membrane (39). This assumption could be confirmed for numerous processes especially those of a biological nature. First of all may be mentioned the digestion and kidney secretion. The stomach and gastric juices normally have a considerably lower surface tension than the blood or blood serum, and the blood in turn has a lower surface tension than the. urine. The examination of numerous urines under normal and pathological circumstances led to the results that there is an intimate relation between the functioning of the kidney and the surface tension of the urines (40). If in certain diseases of the kidney the surface tension of the urine became too small a counter-action became effective which decreased the activity of the kidneys. The examination of exudates and transudates also confirmed this consideration. It was shown that for all sorts of osmotic processes, differing widely among themselves, in cells of plants and animals, the osmotic process depended largely on the surface tension of the solution in question. The plasmolytic experiments of Overton (41) led to the result that in aqueous solutions the permeation into the cells was hardly noticeable for substances such as salts, sugars, and glycol; that i t was slow for glycerol; a little quicker for glycine and acetamide; rapid, however, for monobasic alcohols, esters, and fatty acids. The series of the surface tensions and of the osmotic velocities were the same according to my investigations. Analogous observations were made for the osmosis of red blood

corpuscles, and so forth (42). These relationships were shown to hold true both qualitatively and quantitatively. Traube's rule was confirmed by the author and other observers for numerous biological processes, especially for processes which depend on adsorption and osmosis, such as plasmolysis and haemolysis, narcosis of tadpoles, the development of fertilized eggs of sea urchins (43),the transition of antiheliotropism of crustaceae into heliotropism, various fermentation processes, oxidation, wetting, and so forth (44). The interesting investigations of Czapek and his pupil Kisch (44) showed that cells of leaves died and yeast cells lost their power of budding, if they were introduced into iso-capillary solutions of alcohols, esters, ketones, and so forth, having a definite threshold value. Naturally, chemicals owe their poisonous properties to very different causes, but on comparing the poisonous action of a certain class of medicinals among themselves such as certain alkaloids of the morphine group or of the cocaines, i t is possible to say that the substance of higher surface activity shows a stronger toxic and pharmacological action (45). Among the most highly capillaryactive alkaloid substances are the hydrocupreines investigated by Morgenroth and his collaborators. They are hydroquinine derivatives, such as eucupine, wcine, and so forth. Their enormous bactericidal action is in conformity with their great surface activity (46). It has already been mentioned that an aqueous solution of an alkaloid such as atropine, which, when newly prepared, is strongly capillary-active can be made completely inactive on long standing on account of the aggregation of the single particles. Accordingly, the toxicity decreases considerably. Tadpoles only lived for fractions of a minute in the former solution, but for eighteen hours and longer in the inactive solution (47). This relation between toxicity or decrease in toxicity and complex formation of the particles dissolved in a medium is very remarkable from the serological point of view (48). Many problems in pharmacology and allied sciences are closely related to these considerations. A later series of experiments by myself and my pupils also showed that the rate of permeability of equivalent aqueous solutions of capillary-active substances depends first of all on the surface ac6vity of the solutions (49). The rate of permeability and the surface activity are parallel to each other. This finding is of considerable interest especially from the biological standpoint, as it shows how important a factor, the surface tension, or interface tension, respectively, constitutes for all determinations of permeability. Considering how this factor was neglected it is not surprising that van't Hoff's theory broke down especially when applied to biological processes. After the failure of van't Hoff's theory when applied to biology the so-called lip& theory (50) aroused much interest. E. Overton and H. H. Meyer assumed that the surface of all plant and animal cells contained lipoids, and pointed out that the entrance into the cells of substances present in an aqueous solution was dependent on their

solubility in lipoids or rather on their partition coefficient in lipoids and water. No doubt cell osmosis and lipoid solubility are often parallel but this is by no means invariably the case. Furthermore i t is doubtful if all cell walls contain lipoids. Indeed it was shown by the author of this communication that the lipoid solubility does play a considerable rBle in connection with cell osmosis, but the driving osmotic force is nothing else thanthe surface activityor the interface activity, respectively. According to the author's experiments this action is adequate to the rate of permeability in all cases, even where no lipoids can be detected. However, where lipoids are present their action cannot be neglected. As to the many relations which connect the chapter of surface tension with a very great number of problems of pharmacology and therapy, of toxicology, bacteriology, balneology, and also serology, the reader may he referred to earlier publications (see the foregoing literature). Finally one other point may be stressed. Pure chemists are accustomed to make constitution solely responsible for the properties and action of the substances. A Chemotherapeutical Science grew up which achieved tremendous success. The great achievements of Ehrlich's school might he recalled, but still more so the astonishing successes which have been obtained in recent times in the field of hormones and evilurnins. It was the ingenuity of the most eminent scientists which made i t possible to determine the structure of most complicated compounds and whichled to a new fruitful era of organic

chemistry. Thus i t seemed as if only the chemotherapeutical science was entitled to tackle diverse biological and other problems. However, in connection with these investigations, compounds which had nothing in common with respect to their constitution were frequently found to show the same physiological and other effects. Further, substances which exhibit a marked action only in animal physiology were found to be of plant origin and, on the other hand, important plant matters were found in products of animal metabolism. These facts which appear strange on first sight can only be interpreted in terms of physics. Let us remember that properties such as surface tension, electric potential, and so forth, though they depend on the constitution of the substances in question, can have thesame value for compounds that vary considerably in composition. If, furthermore, we consider that different biologically important processes such as adsorption, permeability, osmosis, and so forth, are closely related to surface tension, surface activity, and so forth, we can understand that compounds of different composition sometimes exhibit the same vitamin or hormone action. Thus the constitution of compounds is of importance only inasmuch as it is the cause for certain physical and chemical properties which can be responsible for their biological and other behavior. In this connection surface tension is of first importance. A physicotherapeutical science will have to supplement the chemotherapeutical one.


(1) FREUNDLICH, "Kapill~r~hemie."2te Aufl., Leipzig, 1930. (2) TRAUBE. Ber., 17, 2294 (1884). (3) TRAUBE, J . pmkt. Chem., N . F., 31, 177 (1885).. VOLRMANN. Ann. Chem. Pharm... 226.. 96:. ibzd., 31, 514 .~--(1885): Scnma. ibid.. 223, 49; ibid., 223, 58. WOLF,Compt. r e d . , 42, 968; Pogg Ann., 102, 571. J . prakt. Chem., N. F., 34, 292 (1886); Ber., 19, (4) TRAUBE. 1674 (1886): ibid.. 19.1679 (1886); ibid., 19,1871 (1886). TRAUBE, "ober das Stalagmometer and Stagonometer." Ber.. 20, 2644, 2824. 2831 (1887). T R A ~ EBiochem. , Z., 24, 341 (1910); ib& 42, 500 (1912); ibid., 120, 105 (1921). Ann. Physik. 20, 607 (1906); ibid.. 22, 767 (5) LOHNSTEIN,

(9) (10) (11) (12)



TRAUBE AND ONODBRA. Intern. Z . F. physik. chem. B i d . I , 35 (1914); Biochem. Z.. 42,470 (1912). TRAUBE, Kolloid Z., 32, 22 (1923). TRAUBE AND KWIN,ibid., 29, 236 (1921); TRAUBE, ibid., 32. 22 (1923). r. PflGers Arch. zes. Phvsiol.. 153. 293 (1913);



physik. Chem., A169, 246

. .

(1934). Ann. Chem. Pharm., 265,47-53. (27) TRAUBE. HARX~NS. J . A m . Chem. Sac.. 38, 2221 (1916); ibid., 39, (2% ~ 1848 (i917). KOHLRAUSCH, ibid., 20, 798 (1906). (29) ADAM.Chem. Rm'ews, 3,163 (1926). RAYLEIGH,Phil. Mag., 151 48, 321 (1899). (30) RIDEAL, "An introduction to surface chemistry," CamDUCLAUX, Ann. Cham. Phys. (1878); T R A ~ E Ber., , 17, bridee Universitv Press. Cambridge. England, 1926. 2316 (1884). ~ , ~ h & . Phnrm., 26: (31) T ~ A u BAnn. Muscu~us,Cham. Zentr., 1864,922. RIDEAL,Physika, N,23 (Nov., 1937). TRAUBE,Ber., 17, 2294 (1884); J. +kt. Chcm., N . F., (32) RONAAND VON TOTH,Biochem. Z., 64, 293 (1914). 31, 218 (1885). (33) FREUNDLIC~, "Kapillarchemie," 2nd ed., Akademie Verlag TRAUBE, I. prakt. Chem., N . F., 31,219 (1885). Gesellschaft. Leipzi~.Vol. I, p. 261 1930. TRAUBE, Bcr., 17, 2304 (1884); PfErigers Arch, ges. Physiol., .tn- fiszm - - - - ,. 115, 548 (1904). J&O,_ (35) SKUMBURDIS, Kolloid Z.. 44, 127 (1"""' TRAUBE, Ann. Chem. Pharm., 265, 29. AND BARISCH, Kolloidchem . Beihefte. 20.. 74 (1924). . (36) TRAUBE FORCE, Ann. Physik. 68, 810 (1899). Trans. Faraday Soc., 31, 1734 (1935). WIND~~C AND H Dlsrn~cn. Biochem. Z.. 97, 1% (1919); (37) TRAUBE, (38) TRAUBE,Pj'Ziigers Arch. ges. Phyriol., 105, 541 and 559 Kolloid Z., 26, 193 (1920). (1904); ibid., 123, 419 (1908); ihid., 132, 511 (1910); STERNGLANZ AND WEBER. Z . physik. Chem.. A169, 246 ibid.. 140, 109 (1911); ibid., 153, 276 (1913); ibid., 160, (1934). 501 (1915); ibid., 176, 70 (1919); ibid., 218, 750 (1925) MEYER, Biochem. Z., 279, 173 (1935); ibid., 282,445 (1935). ibid.. 105, 540 (10nAj TRAUBEAND KLEIN,Kollold z . , 29, 236 (1921); B~oCham. (39) TRAUBE. (40) TRAUBE AND BLUMENTHAL, Z . exptl. Path. Therap. (Berlin). Z . , 120, 111 (1926). 1905. TRAUBE AND KLEIN, . e l l o i d Z.. 29, 240 (1921) ; WUBE P%iigns Arch. ges. Physiol., 105, 555 (1904) (41) OVERTON, AND VON BEEREN. zbd., 47, 47 (1929). l10"7\ ,A"".,.

(6) (7) (8)




(13) (14) (15) (16) (17) (18) (19)


FUHNER AND N E U B A ~Biochem. R. Z.. 10, 374 (1908). Tnawe, ;bid., 16, 182 (1909). TnaueE, Pfliigcrs Alch. ger. Physid., 153, 275 (1913). TRAuBE, Biochem. Z., 98, 177 (1919); Ber. deul. pharm. Ges., 25, 379. 388 (1915). TRnwe, C h m . Zfg., 43, No. 32/33 (1919); Kolloidchen. Bcikcjfc. 3, 236 (1912). TRAUBE, B i o c h a . Z., 98, 197 (1919). TRAUBE. d i d . . 98, 188 (1919).

(48) "Die Resonanztheorie, eine Theorie der Immunit8tserscheinungen," Z . ImmunifZs.. 9, 246 (1911). AND SIAR-HONG WAANG,Biochem. Z., 203, 365 (49) %UBE (1928).

(50) TRAuBE, ibid., 54, 311 (1913); TnAwE, ibid., 153, 358 (1924); rbid., 157, 383 (1925). Tnnuse, PfEiigns Arch. ges. Phyrdol., 105, 541, and 559 (1904); ibid., 123, 419 (1908); ibid., 132, 511 (1910); ibid., 140, 109 (1912).