Vol. 70
2832
COMMUNICATIONS T O THE EDITOR CHAIN ELECTROLYTES'
trated solution within the liquid, regardless of total dilution. The polycation configuration will, We are studying polyelectrolytes in which chain however, depend on dilution : with decreasing atoms carry ionic charges. Typical is the poly- total concentration, probability of escape of electrolyte (I) formed by the addition of methyl bromide ions from the field of the polycation will bromide to the polyester obtained from methyldi- increase, and intramolecular mutual repulsion between unpaired charges on chain nitrogens will ethanolamine and succinic anhydride then cause the chain to uncoil. (I) HOICO(CH~)~COO(CH&N+Me~(CH~)zO].H--nBr' STERLING CHEMISTRY LABORATORY Theoretical bromide for n infinite is 26.99%; YALE UNIVERSITY DAVIDEDELSON two different preparations gave 22.73 and 23.38Q/,, NEWHAVEN,CONNECTICUT RAYMOND M. Fuoss indicating incomplete addition of methyl bromide. RECEIVED JULY19, 1948 End-group titrations gave molecular weights of 3515 and 2720. The salt hydrolyzes in water but is stable in methanol. ULTRAVIOLET ABSORPTION BANDS OF IODINE IN At 1.2 g./lOO cc. in methanol, (I) has a reduced AROMATIC HYDROCARBONS viscosity of 0.091. For comparison, polyvipylpy- Sir: ridine with molecular weight 80,000 has an intnnIn the course of an investigation of the nature sic viscosity of only 0.15. High viscosities thus of the solvent-solute interaction in solutions of seem to be characteristic of polyelectrolytes2 iodine now in progress, new evidence has been regardless of the location of the charges. found for the presence of addition compounds of Conductance curves in methanol are shown in iodine and the solvent molecyle. We find that Fig. 1, where concentration is stoichiometric nor- the absorption spectrum of the violet-red solution mality of bromide. The marked curvature indi- of iodine in benzene shows in addition to the well known absorption maximum a t 5000 k. with a molar extinction coefficient of 1010, an absorption maximum in the ultraviolet region a t 2970 A. having a molar extinction coefficient (based on the iodine concentration) of 9600. This new absorption peak does not appear in solutions of iodine in hexane and carbon tetrachloride which are a pure violet with absorption peaks a t 5200 k. in the visible region. The evidence therefore points to the presence of an iodine-benzene complex. Preliminary measurements show that the height of the absorption peak at 2970 k.is directly proportional to both the iodine concentration and the benzene concentration, indicating that the addition compound consists of one molecule of 0.00 0.01 0.02 0.03 0.04 iodine bound to one molecule of benzene. dr. A possible explanation for the presence of such a Fig. 1.-Conductance of salts I and I1 in methanol. complex appears to lie in an acid-base interaction cates a high degree of association of counter ions in the electron donor-acceptor sense such as we to the polycations. Ordinary electrolytes, such see in the union of I-, the base, with 12, the acid, form IS-. Evidence of basic character in as the addition product (11) of methyl bromide to to benzene is its union with boron trifluoride, boron methyldiethanolamine, are only slightly associtrichloride and with concentrated sulfuric acid. ated in solvents with high dielectric constant, as Additional evidence support of this hypothesis shown by the approach to the Onsager limiting is to be found in the inrecent work of Fairbrother,' slope. In our polysalts, ten positive charges are constrained to remain near each other, regardless who reports that iodine has a.n abnormally high of dilution. A bromide ion has a potential energy dielectric polarization in such solvents as benzene, large compared to kT in the resulting field and p-xylene, dioxane and di-isobutylene. If this therefore a t finite concentrations, a certain frac- basic character of benzene is also responsible for tion of bromide ions accompany the polycations. its union with iodine, then the substitution of methyl groups should increase basic strength and The polycations thus act like droplets of concen- ability to interact with iodine. This is borne
Sir :
(1) Office of Naval Research ProjectNR054-002. (2) R.M.Fuoos and U. P. Strouss, J . Polymsr Sd.,8, ud (194s).
(1)
F. Fairbrother, NcJura, 160, 87 (1947).
COMMUNICATIONS TO THE EDITOR
Aug., 1948
out by the fact that a simple visual examination of iodine solutions of equal concentration in benzene, toluene, o-xylene, mesitylene and amethylnaphthalene shows that the color shifts stepwise in that order ending with a brown solution. Preliminary measurements of the absorption spectra of these iodine solutions show an absorption band in the ultraviolet region similar to that of benzene. This work is being continued and a complete report of the results will be given in a paper soon to be submitted for publication. I
2833
THE CRYSTALLINE TRIHYDROCHLORIDES OF STREPTOMYCIN AND MANNOSIDOSTREPTOMYCIN
Sir:
The preparation of the crystalline reineckate, sulfate,' helianthate,2 and the calcium chloride double salt2of streptomycin and the reineckate of mannosidostreptomycina has been reported. To date, there has been no published information on the crystallization of a simple mineral acid salt of either of these antibiotics. We now wish to report that, starting with relatively pure material, we have obtained the trihydrochlorides of streptoDEPARTMENT OF CHEMISTRY HANSA. BENESI mycin and mannosidostreptomycin in the crystalUNIVERSITY OF CALIFORNIA JOELH. HILDEBRAND line state from methanol solution. 4, CALIFORNIA BERKELEY The streptomycin trihydrachloride crystallizes RECEIVED JULY15, 1948 with two molecules of water of crystallization as monoclinic prisms showing birefringence. The crystalline material was shown to be a single sub8-PELTATIN, A NEW COMPONENT OF stance by ,a modification of the Craig counterPODOPHYLLIN current distribution technique' and thus to be free Sir : of mannosidostreptomycin. On heating on the The fractionation of the drug podophyllin by hot-stage, the dihydrate decomposes gradually chromatographic adsorption on alumina has without melting. When the trihydrochloride was yielded, beside podophyllotoxin and a-peltatin,l dried a t 55' in vacuo, it had the following analytia new crystalline substance in about 4% yield for cal composition: c , 34.86; H, 6.36; C1, 14.25 which the name P-peltatin is proposed. The new (Calcd. for CzlH39N7012.3HC1.2Ha0 : C, 34.54; compound possesses about the same high necro- H, 6.36; C1, 14.57). After drying a t 100' in tizing activity2 for mouse sarcoma 37 as a-pelta- vacuo, the anhydrous material showed [a tin. -236.1' (1.Oyoin water) and the following analyti&Peltatin crystallizes from alcohol in colorless, cal data were obtained: c, 36.27; H, 6.14; transparent prisms, m. p. 231.1-238.0' (shrinks a t N, 14.29; C1, 15.69 (Calcd. for G1H39N7012.3HC1; 225.5') cor.; [a]% -115' (c, 1.009, absolute al- C, 30.50; H, 6.13; N, 14.19; C1, 15.40). : 63.75; cohol). Anal.a Calcd. for C t ~ H ~ 0 8C, When assayed with K. pneumoniae in a brothH, 5.35. Found: C, 64.0; H, 5.0. Calcd. for dilution test,6the trihydrochloride dihydrate had a three methoxyl groups: 22.5; found, 22.2. Molec- potency of 820 units/mg. and on this basis the ular weight values (Rast) for derivatives of both anhydrous material would have an activity of 891 a- and @-peltatinagree with the formula CnZHnOs units/mg.6 and indicate that the peltatins are thus isomeric The trihydrochloride of mannosidostreptomycin with podophyll~toxin.~a-Peltatin has one less crystallizes in the form of hexagonal plates which methoxyl group than 8-peltatin and podophyllo- are isotropic. By means of the counter-current toxin. distribution m e t h ~ dthis , ~ material was also shown Beside the methoxyl content, a- and p-peltatin to be a single entity and t o be free of streptodiffer in their color reactions with sulfuric acid and mycin. in the properties of their derivatives. With conAfter drying a t 55' in vacuo, the trihydrochlocentrated sulfuric aad, both peltatins give an im- ride was found to have the following analysis: mediate yellow color, rapidly turning reddish C, 36.45; H, 6.26; C1, 12.14 (Calcd. for C27H49brown with a-peltatin and green with 8-peltatin; N701.1.3HC1.2HzO: C, 36.47; R,6.35; C1, 11.96). the final color with both peltatins is red. A series When dried a t 100' in vacuo, the anhydrous maof derivatives of the peltatins has been prepared terial showed [C~-]"*~D-54.1' (1.0% in water) and will be reported at a later date. (1) J. Fried and 0. Wintersteiner, Science, 104, 273 (1946). Structural and biological studies with @-peltatin (2) R. L. Peck, N . 0. Brink, F. A. Kuehi, Jr., E. H. Flynn, A. are in progress. Walti and K. Folkers, THIS JOURNAL, 67, 1866 (1945). J Z 6 s 6 ~
NATIONAL CANCER INSTITUTE NATIONAL INSTITUTE OF HEALTH U. S. PUBLIC HEALTH SERVICE JONATHAN L. HARTWELL BETHESDA, MARYLAND WENDELL E. DETTY RECEIVED JULY22, 1948 (1) J. L. Haftwell, TEIS JOURNAL, 69, 2918 (1947). (2) Unpublished results of Joseph Leiter and Faith Jouvenal.
(3) By Mrs. M. M. Ledyard and Mrs. Evelyn Peake National Institute of Health. (4) W. Bocsche and J . Niemann, Bcr., 61,1633 (1932); E.Spiith, F. Wessely and E. Nadler, ibid., 66, 125 (1933).
(3) J. Fried and E. Titus, J . B i d . Chem., 168, 391 (1947). (4) A modification of the counter-current distribution described by Titus and Fried ( J . B i d . Chem., 174, 57 (1948)) has been deveioped by our colleagues Drs. Flaut and McCormack which eliminates the appearance of the tautomers of the two streptomycins in the Craig diagram. (5) R. Donovick, D. Hamrc, F. Kavanagh and G.Rake,J . Boct., 10, 623 (1945). (6) Based 09 the F. D. A. working standard. Spectrophotochemical asgays based on a maltol method, similar to that published by G. F. hfueller (THIS JOWRNAL, SO, 195 (1947)), have confirmed these microbiological results.
