Nitro group orientation, reduction potential, and direct-acting mutagenicity of nitro-polycyclic aromatic hydrocarbons.

Nitro-polycyclic aromatic hydrocarbons (nitro-PAHs) are widespread genotoxic environmental pollutants. We have been interested in determining the structural and electronic features that may be useful in predicting the direct-acting mutagenic activity of nitro-PAHs in Salmonella typhimurium. In this study, a series of structurally related nitro-PAHs were used to determine the relationships among direct-acting mutagenicity, orientation of the nitro group, and reduction potential of the nitro group. The compounds consisted of isomeric mononitrated and dinitrated benzo[e]pyrenes, their derivatives, and other nitro-PAHs ranging from two to five aromatic-ring molecules in size. A general finding is that nitro-PAHs with their nitro substituent oriented perpendicular to the aromatic system exhibit either very weak or no direct-acting mutagenicity in S. typhimurium strains TA98 and TA100. However, if a nitro-PAH of this type has a relatively low first half-wave reduction potential, it may be direct-acting. Furthermore, a positive correlation between the first half-wave reduction potential and direct-acting mutagenicity is found only when the compounds are structurally similar. Consequently, the correlation cannot be made using nitro-PAHs with different molecular size. Nitro-PAHs having a perpendicular nitro orientation always have a higher (absolute value) first half-wave reduction potential than the isomer(s) with a parallel orientation. Perhaps due to electron-withdrawing by the second nitro group, dinitro-PAHs always have a lower first half-wave reduction potential than their mononitro analogues. These findings provide a useful molecular basis for interpreting and predicting the direct-acting mutagenicity of nitro-PAHs.