Ultimate carcinogenic metabolites from aromatic and heterocyclic aromatic amines: a computational study in relation to their mutagenic potency.

BOROSKY, GABRIELA L.

CHEMICAL RESEARCH IN TOXICOLOGY (WASHINGTON)

American Chemical Society

Año: 2007 vol. 20 p. 171 - 180

0893-228X

Formation of nitrenium ions from their precursors was examined by density functional theory (DFT) calculations in order to analyze the role of these electrophilic intermediates on the mutagenic activity of the parent amines. The relative reactivities for N-O bond dissociation from the N-hydroxy, N-acetoxy and N-sulfate derivatives of aniline were evaluated. Furthermore, the N-acetoxy esters from a set of seventeen aromatic and heteroaromatic amines of diverse structure were considered, and correlations were sought between the calculated properties and the reported mutagenic potencies. The mutagenic activity was found to increase when a more negative charge developed at the exocyclic nitrogen of the nitrenium ion (qN), and with nitrenium ion stability. Different functional correlations were observed for the amine derivatives grouped according to their classification as aromatic (Ar), imidazo-carbocyclic (Imi-C) and imidazo-heterocyclic (Imi-H). Formation of N-acetyl nitrenium ions from aromatic amides was also considered and found to be less favorable than nitrenium ion generation from the corresponding amines.