Molecular orbital studies of epoxide stability of carcinogenic polycyclic aromatic hydrocarbon diol epoxides

Semiempirical molecular orbital calculations (by modified neglect of diatomic overlap method) were performed on diol epoxide metabolites of five polycyclic aromatic hydrocarbons (PAHs)--benzene, naphthalene, phenanthrene, chrysene, and benzo[a]pyrene (BP)--to gain insight into the various carcinogenic potencies of these compounds. Opening of the epoxide rings of the diol epoxides was calculated to be exothermic for all of the PAHs investigated. The bay-region diol epoxides of BP were calculated to open spontaneously to the triol carbonium ion upon protonation. For the bay-region trans- and cis-diequatorial diol epoxides of 5-methylchrysene the methyl group destabilized the epoxide. These results suggest that the conformation of the saturated, angular benzo-ring is important in determining bay-region epoxide stability. Conformational flexibility of the aromatic ring system is offered as one reason for partial stabilizing of bay-region epoxides. These results also suggest that the existence and potentiation of PAH carcinogenicity is correlated with the lack of stability of the bay-region epoxide ring. Considerations of thermochemical stability have value in predictions of carcinogenic potency.