ELEVENTH MEDAL AWARD 313 tests in two other ones, the inhibitory level was found to be as low as 3.12 ug./ml. Proteus vulgaris and S. typhosa were inhibited at 6.25 ug./ml., Pseudomonas aeruginosa at 12.5 ug./ml. The question might be raised as to why compound 3, being definitely more active than hexachlorophene, at least in vitro, is not being studied in vivo and perhaps used commercially? The reason lies in the difficulty of economically making 3,4,5-trichloro- phenol which is obtained in a multistep operation from p-nitroaniline (14, 15) and which is needed for the preparation of compound 3. The following general statements may be made: 1. In general the antibacterial activity of the bis-phenols is rather specific, being stronger against gram-positive organisms than against gram-negative ones. However, compounds 1, 2, 3, 6, 30 and 31 are excep- tions and do show good activity against E. coli. The presence of soap always lowers the inhibitory level against S. aureus. The potency against Trichophyton mentagrophytes is not striking, only three compounds (Nos. 8, 32 and 33) which have a similar chemical structure are fungistatic at a level lower than 2 ug./ml. 2. Linkage in the 2,2'-positions is essential for maximum activity. Previous observations (4) that bis-phenols linked in the 4,4'-positions are weak are generally correct however, we observed that compounds obtained by the condensation of thymol with benzaldehyde and partic- ularly with o- and p-chlorobenzaldehyde are quite active against S. aureus. However, in the presence of soap, the decrease in potency is more pronounced than with the 2,2'-methylenebis-phenols. 3. The methylene-bridged phenols are superior to the ones with ethyli- dene, benzylidene and thio-linkages in regard to activity against S. aureus in the presence of soap. 4. No compound without halogen in the phenol rings is active, with the exception of bis-phenols derived from thymol (Nos. 25, 26, 27), and one halogen must be in the para position. Chlorine substitution is usually preferable to bromine which is contrary to Florestano's findings (12). 5. Oxygen-containing linkages, such as --CO---, --SO•, --SO,_--, are detrimental. 6. Activity is lost if the hydroxyl groups are etherified (Nos. 55, 57). Esters, such as the diacetates, have been reported by Pileget et al. (11) to be active. We found this to be true, and believe, in agreement with Pfleger, that the esters are hydrolyzed to a large degree to the free phenols during the tests. 7. Replacement of the phenols by naphthols (Nos. 39, 61, 62) leads to inactive compounds. The Ns-compound from dichloresorcinol (No. 54) was also inactive at a level of 50 •g./ml.

314 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS SUMMARY Bacteriostatic and fungistatic data on a number of bis-phenols have been presented and the relationship between chemical structure and anti- microbial activity has been discussed. The standard of reference was hexachlorophene which was not surpassed in bacteriostatic activity against S. aureus and E. co/i, except by one of its isomers, 2,2'-methylenebis (3,4,5- trichlorophenol). The latter compound is distinctly more potent, but its manufacture would be difficult and costly. REFERENCES (1) Gump, W. S., U.S. Patent No. 2,250,480, July 29, 1941. (2) Cade, A. R., Soap Sanit. Chemicals, 20, No. 2, 11 (1944). (3) Gump, W. S., Ibid., 21, No. 3, 36 and No. 4, 50 (1945). (4) Cade, A. R., and Gump, W. S., "The Bis-phenols," chapter 14 in "Antiseptics, Disinfect- ants, Fungicides, and Chemical and Physical Sterilization," edited by George F. Red- dish, 2nd edition, Philadelphia, Lea & Febiger (1957). (53 Marsh, P. B., and Butler, M. L., Ind. Eng. Chem., 38, 701 (1946). (6) Marsh, P. B., Butler, M. L., and Clark, B. S., Ibid., 41, 2176 (1949). (7) Gump, W. S., and Cade, A. R., Soap Sanit. Chemicals, 28, No. 12, 52 (1952). (8) See Finkelstein, J., and Linder, S. M., 5•. Am. Chem. Soc., 71, 1010 (1949) for the prepara- tion of closely related substances. (9) Bechhold, H., and Ehrlich, P., Z. physiol. Chem., 47, 173 (1906). (10) Corey, R. R., and Shirk, H. S., Arch. Biochem. Biophys., 56, 196 (1955). (11) Pfleger, R., Schraufst/itter, E., Gehringer, F., and Sciuk, J., Naturforsch., 4b, 344 (1949). (12) Florestano, H. J., and Bahler, M. E., )t. Am. Pharm. Assoc., Sci. Ed., 42, 576 (1953). (13) Wendel, K., Zentr. Bakteriol. Parasitenk., Abt. II, 110, 45 (1957). (14) Johary, N. S., Guha, S.S., and Guha, P. C., •7. Indian Int. Sci., 34, 287 (1952). (15) Tiessens, G. J., Rec. Tray. Chim., 50, 112 (1931). CHICAGO CHAPTER NEWS DR. MORRIS V. SHEL^NSKI spoke on April 12. The subject was a very timely one in the general category of toxicological testing of cosmetic products. Dr. Shelanski attended Harvard University, 1939-1943, and continued his education in the Faculty of Medicine, McGill University and received degree M.D., C.M., in 1947. His present position is director, Industrial Biology Research and Testing Laboratories, Inc., Philadelphia, Pa. All meetings of the Chicago Chapter are held in Henrici's Restaurant in the Merchandise Mart.