Carcinogenicity of naphthylamines: A theoretical study of the stacking interaction of 1- and 2-naphthylnitrenium ions with guanine,adenine, and the dinucleoside monophosphate cytidyl-(3′-5′)-guanosine

Theoretical computations are performed with the stacking interactions of the 2-naphthylnitrenium ion, the ultimate metabolite of 2-naphthylamine and N-hydroxy-2-naphthylamine, with guanine and adenine. The most stable stacked complex of guanine with this compound is found to be distinctly more stable than that of adenine. The optimized stacking interaction of guanine with 1-naphthylnitrenium ion yields an energy close to that with 2-naphthylnitrenium. By contrast, the dinucleoside monophosphate cytidyl-(3′-5′)-guanosine held in two preselected intercalated conformations is seen to favor 2-naphthylnitrenium over 1-naphthylnitrenium by a significant amount of energy. The possible relevance of this finding to explain the difference in adduct formation with guanine in DNA by the isomeric naphthylnitrenium ions is discussed.