724 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS TABLE V--ANTIMICROBIAL SPECTRA OF 2,2•-METHYLENE (DICHLOROPHENOL) ISOMERS (Minimal Inhibitory Concentration, ug./ml.) Compound (by Number) Microbrganism I II 11I IV V VI S. aureus 6538* 0.48 0.50 0.50 0.78 0.48 0.48 S. epidermidis 155 0.63 0.31 0.06 1.56 0.78 0.10 B. subtilis 9372 0.25 0.20 0.05 0.98 0.63 0.08 B. ammoniagenes 6871 0.62 0.15 0.04 0.98 1.56 0.05 E. coli 11229 X t 9.80 7.80 100.00 X 7.80 S. choleraesuis 10708 X 12.50 9.80 100.00 62.00 7.80 S. typhosa 6539 X 20.00 12.50 X X 7.80 P. vulgaris 9920 3.12 3.12 1.28 5.20 0.78 1.95 Ps. aeruginosa X 25.00 20.00 X X 16.00 C. albicans 10231 X 6.25 6.25 31.50 16.00 6.25 S. cerevisiae X 6.25 6.25 7.80 5.00 4.00 P. funiculosum 11797 X 12.50 4.00 31.20 6.25 6.25 P. piscarium 12109 X 3.12 1.95 62.50 25.00 2.46 At. niger 9692 X 4.90 1.95 16.00 9.80 6.25 At./qavus 96•3 X 9.80 7.80 62.50 16.00 16.00 T. mentagrophytes 9129 0.96 0.96 0.39 0.78 0.62 0.78 T. rubrum 10218 0.50 1.00 0.78 0.62 0.30 1.00 C. vulgaris 9765 1.56 0.39 0.48 3.12 1.95 0.39 * American Type Culture Collection. t X denotes growth at 100 ug./ml. TABLE VI--BAcTERIOSTATIC LEVELS OF 2,2'-METHYLENEBIS (DICHI,OROPHENOL) ISOMERS IN THE PRESENCE OF SOAP* -Compounds (by Number) Organism I II III IV V VI S. aureus 0.98 S. epidermidis 1.25 B. ammoniagenes 1.55 E. coli • S. typhosa }-growth at 20/•g./ml. P. vulgaris• 1.25 0.63 1.25 0.98 0.98 0.63 0.16 1.95 1.25 0.20 0.31 0.16 1.55 1.95 0.16 * Soap/compound ratio: 100/1 for gram-positive bacteria. 50/1 for gram-negative bacteria. negative bacteria, with the exception of Proteus vulgaris, yeasts and molds grew at a level of 100 ug./ml. of this chemical. The most potent com- pound appears to be the 3,5-dichloro isomer (III), followed by the asym- metrical (VI) and 3,4-dichloro (II) isomers. These three compounds show superior activity against gram negative bacteria, yeasts and molds. All isomers are alike in their behavior against S. aureus, the dermatophytes and Chlorella vulgaris. In the presence of soap, no difference between the isomers could be ob- served all are active against gram positive bacteria and inactive at a level of 20 ug./ml. against gram-negative ones.

CHEMICAL STRUCTURE AND ANTIMICROBIAl. ACTIVITY OF BIS-PHENOLS 725 SUMMARY The broad spectrum antimicrobial activity of five isomeric 2,2'-methyl- enebis (dichlorophenols) and of the asymmetrical 3,4,4',5'-tetrachloro-2,2'- methylenediphenol was investigated. Greater over-all activity was shown by the three compounds in which the hydrogens adjacent to the hydroxyl groups are not substituted by chlorines, the most potent bis-phenol being the 3,5-dichloro isomer. On the other hand, less active was 2,2'-methyl- enebis (4,6-dichlorophenol), also referred to in the literature as G-5 ©. Against S. aureus, C. vulgaris and the dermatophytes, the activity of all isomers was found to be of the same magnitude. At a concentration of 20 ug./ml., no activity against gram-negative bacteria was observed in pres- ence of soap. (Received July 2, 1964) REFERENCES (1) Gump, W. S., and Walter, G. R., y. Soc. Cosmetic Chemists, 14, 269 (1963). (2) Gump, W. S. and Walter, G. R., Ibid., 11, 307 (1960). (3) Weiler, M., Wenk, B., and St6tter, H., U.S. Patent #1,707,181, March 26, 1929. Zinke, A. and Ziegler, E., Bet., 74, 1729 (1941). Ziegler, E. and Simmler, I., Ibid., 74, 1871 (1941). (4) J.R. Geigy, A. G., British Patent 3772,590, January 26,1955. Schetty, G., Stammbach, W., and Model, E., U.S. Patent 32,730,554, January 10, 1956. (5) Walter, G. R. and Gump, W. S., y. Soc. Cosmetic Chemists, 13, 477 (1962). (6) Tiessens, G.J., Rec. Tray. Chim., 50, 112 (1931). (7) Hurtley, W. H., y. Chem. Soc., 79, 1303 (1901). (8) Fox, D. L. and Turner, E. E., Ibid., 1853 (1930). Van Loon, A., Verkade, P. E., and Wepster, B. M., Rec. Tray. Chim., 79, 993 (1960). (9) Sloane, H. J., •tnal. Chem., 33, 691 (1961). (10) Kohn, M. and Fink, S., Monatsh. Chem., 56, 407 (1930). (11) Imperial Chemical Industries l,td., British Patent 3760,341, October 31, 1956. (12) Imperial Chemical Industries Ltd., British Patent 3760,342, October 31, 1956.