Molecular Structure Basis for the Mutagenicity of Lignin- and Humic-DerivedChlorofuranones

摘要

The disinfection and industrial chlorination of humic-and lignin-containing waterproduces nonvolatile genotoxins, the most potent among them being the direct acting mutagen MX(3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone, compound (1). Finding the essential features of MX structure that make the component such a potent genotoxin was the goal of the project. Accordingly, the structure of MX was varied through the systematic replacement of the Cl atoms and the OH group by H. Thereafter, each compound was assayed in the Ames mutagenicity assay using Salmonella typhimurium (TA100). A total of ten 4-methyl-2(5H)-furanones and two 2(5H)-furanones were prepared and assayed. New methods were developed for preparing MX and members of the MX series that had not been prepared previously. The findings revealed that the minimum substitution required for potent mutagenicity is already incorporated in compound 2. The findings of the research will aid mutagenicity predictions for newly isolated, chlorine-substituted 4-methyl-2(5H)-furanones, and, thereby, assist risk assessment of water remediation procedures involving chlorination. Taking a broader view, the findings suggest that for a series of closely related compounds, genotoxic potency does not abruptly change to nontoxicity. Instead genotoxity diminishes gradually.