The relationship of the carcinogenic/mutagenic potential of arylamines to their singlet-triplet nitrenium ion energies.

Utilizing intermediate neglect of differential overlap (INDO) and ab initio methodology, trends in the energy differences between the singlet and triplet states for mono- and polycyclic aryl nitrenium ions have been estimated. Calculations reveal an empirical correlation between the energy separation of the singlet and triplet states of the nitrenium ion and the ability of the parent amine to behave as a carcinogen or mutagen. Non-carcinogenic/non-mutagenic arylamines were characterized by nitrenium ions whose singlet states were much less stable than the triplet. Carcinogenic/mutagenic amines were characterized by nitrenium ions whose singlet states were of similar or greater stability than the triplet. By examination of the charge density at key ring atoms of the singlet and triplet species, a rational approach to the stabilization of one species relative to the other has merged and forms the basis for prediction of genotoxicity in closely related structures. The application of this empirical correlation to the prediction of the carcinogenic/ mutagenic potential of arylamines is discussed.