Quantum chemical studies of the metabolism of polycyclic aromatic amines and the stabilities and electrophilicities of their arylnitrenium ions in relation to their mutagenic/carcinogenic potencies.

Electronic parameters related to the cytochrome P450-catalyzed reactions of eight polycyclic aromatic amines have been calculated using all valence electron semiempirical molecular orbital methods. The reactions considered lead to the presumably carcinogenic arylnitrenium ions and to the competing hydroxylation and epoxidation products. The stabilities of the arylnitrenium ions relative to the N-hydroxylamines and their sulfate esters were also calculated, together with electrophilic reactivity parameters of the ions. The resulting parameters were used to predict major metabolites of the parent compounds and also to correlate with observed mutagenic activities of the four pairs of polycyclic aromatic amines studied. The major factor in determining mutagenic potencies of parent compounds appears to be the extent of N-hydroxylation and competing ring oxidations, as well as the electrophilic properties of the arylnitrenium ions.