Model quantum-chemical studies on the reaction between the candidate proximate carcinogen benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide and guanine

Recent experimental evidence has pointed to “bay-region” diol epoxides as possible proximate metabolites for a range of polycyclic aromatic hydrocarbons that form adducts with the bases of cellular nucleic acids. The authors present a theoretical model study of a possible reaction mechanism to produce such adducts. This mechanism consists of an electrophilic substitution on the NH2 group of guanine by a carbonium ion derived from the opening of the epoxide. It involves the formation of a quaternary intermediate followed by an OH− assisted deprotonation. The easy deformability of the NH2 group of the base plays an important role in the evolution of the reaction.