Mechanistic studies of addition of nucleophiles to arene oxides and diol epoxides: Candidate ultimate carcinogens

Potential energy surfaces for the SS1 and SS2 attack of water on protonated benzene oxide and benzene diol epoxide have been calculated using the mindo/3 method. Calculated enthalpies of activation are consistent with the known experimental behavior of related arene oxides and epoxides. The potential surfaces calculated here, plus prior calculations of internal rearrangements, allow the conclusion that diol epoxides preferentially undergo intermolecular reactions with nucleophiles, most likely by an SN2 mechanism, while arene oxides preferentially undergo internal rearrangement via carbocation formation. This difference in behavior could help explain why diol epoxides, rather than arene oxides, are found to form adducts with nucleic acids. The large positive charge found on the pentacoordinated carbon atom in the SN2 transition state could account for the correlations observed between calculated diol epoxide carbocation stability and carcinogenic potency of parent polycyclic aromatic hydrocarbons.