INTERACTIVE CHLORINE-BY-BROMINE AND HYDROGEN-BY-HYDROXYL GROUP REPLACEMENT EFFECTS IN 2(5H)-FURANONE MUTAGENICITY

Both bromine- and chlorine-substituted 2(5H)-furanones are produced by the chlorination of ligno-humic waters containing bromide ion. The mo lar mutagenicities of four bromine-and chlorine-substituted a(5H)-fura nones were determined by the Salmonella typhimurium (TA100) assay to e xplore Cl-by-Br and H-by-OH replacement effects on mutagenicity. Each of these two replacements was expected to enhance mutagenicity based o n earlier work showing that lower LUMO energy levels and greater radic al anion stability correlated with elevated TA100 mutagenicity. The fo ur compounds investigated were the following: 2,3-dibromo-5-hydroxy-2( 5H)-furanone (mucobromic acid, MBA); 2,3-dibromo-2(5H)-furanone (reduc ed mucobromic acid, RMBA); 2,3-dichloro-5-hydroxy-2(5H)-furanone (muco chloric acid, MCA); and 2,3-dichloro-2(5H)-furanone (reduced mucochlor ic acid, RMCA). Mean molar mutagenicities were found to be 5.54, 1.18, 2.92, and 0.105 revertants/nmol for the four compounds in the order n amed. Mutagenicity enhancements resulting from Cl-by-Br and H-by-OH re placements were analyzed by simple ratios of mean molar mutagenicity a nd by multiple regression analysis. The effect of the Cl-by-Br replace ment on mutagenicity amounted to a 1.9-fold enhancement in the presenc e of C-5 OH, but an 11-fold enhancement in the presence of C-5 H. This demonstrated that the two replacement effects were interactive. Highe r mutagenicity values corresponded to lower AM1 computed LUMO energy l evels and greater radical anion stabilities.