Correlation of calculated electronic parameters of fifteen aniline derivatives with their mutagenic potencies.

Electronic parameters for a series of amino-, chloro-, and nitro-substituted anilines relative to their potential for activation to hydroxylamines, aryl-nitrenium ions, and ring epoxides, and to their potential deactivation to phenols were calculated using semi-empirical molecular orbital methods. The relative mutagenic activities of aminoanilines could be explained by parameters reflecting potential for N-hydroxylation and stability of the arylnitrenium ions. Both chloro and nitro groups deactivate the amine group to N-hydroxylation and the ring to epoxidation, and no active products from cytochrome P-450 would be predicted. This result is consistent with lack of mutagenic activity observed for chloro derivatives, but does not account for activity of the nitro derivatives, which is presumed to be due to transformation of the nitro group itself to an active mutagenic species by other enzyme systems.