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 molar mutagenicities of four bromine- and chlorine-substituted 2(5H)-furanones were determined by the Salmonella typhimurium (TA100) assay to explore Cl-by-Br and H-by-OH replacement effects on mutagenicity. Each of these two replacements was expected to enhance mutagenicity based on earlier work showing that lower LUMO energy levels and greater radical anion stability correlated with elevated TA100 mutagenicity. The four compounds investigated were the following: 2,3-dibromo-5-hydroxy-2(5H)-furanone (mucobromic acid, MBA); 2,3-dibromo-2(5H)-furanone (reduced mucobraomic acid, RMBA); 2,3-dichloro-5-hydroxy-2(5H)-furanone (mucochloric acid, MCA); and 2,3-dichloro-2(5H)-furanone (reduced mucochloric 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 named. Mutagenicity enhancements resulting from Cl-by-Br and H-by-OH replacements were analyzed by simple ratios of mean molar mutagenicity and by multiple regression analysis. The effect of the Cl-by-Br replacement on mutagenicity amounted to a 1.9-fold enhancement in the presence 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. Higher mutagenicity values corresponded to lower AM1 computed LUMO energy levels and greater radical anion stabilities.