Thermodynamic Properties of the Arene Epoxides and the Relative Carcinogenicities of Benzo[a]pyrene and Benzo[e]pyrene

The thermodynamic stabilities of all possible arene oxides of benzo[a]pyrene and benzo[e]pyrene, and of the two parent compounds, have been obtained using semiempirical AMI and molecular mechanics calculations. The calculations predict that all K-region epoxides are highly stabilized compared to other epoxides for both PAHs. The terminal ring epoxides include proximal and distal types, either close to or remote from the bay-region, respectively. The distal epoxides correspond to the necessary first intermediates in the enzymatic activation process leading to the ultimate bay-region dihydrodiol epoxide carcinogens. There are marked differences in the calculated heats of formation of the distal benzo[a]pyrene-7,8-epoxide and benzo[e]pyrene-9,10-epoxide (compared to either the respective parent PAHs or the K-region epoxides) favoring the epoxide from benzo[a]pyrene. One can propose that these thermodynamic differences may be a principal factor responsible for facile initiation of the activating metabolic pathway mediating the carcinogenicity of benzo[a]pyrene, and the blocking of the corresponding mechanism in benzo(e]pyrene.