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Ultimate Carcinogenic Metabolites from Aromatic and Heterocyclic Aromatic Amines: A Computational Study in Relation to Their Mutagenic Potency
journal contribution
posted on 2007-02-19, 00:00 authored by Gabriela L. BoroskyThe 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 17 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). The 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.