MINDO-3 CALCULATIONS OF THE CONFORMATION AND CARCINOGENICITY OF EPOXY-METABOLITES OF AROMATIC-HYDROCARBONS - 7,8-DIHYDROXY-9,10-OXY-7,8,9,10-TETRAHYDROBENZO(A)PYRENE

Quantum mechanical calculations in the MINDO/3 approximation were performed on the four conformations of the alicyclic moiety of 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene. Total charge and frontier orbital densities show that attack by nucleophiles will occur predominantly at Position 10 of all configurations of the dihydroxyepoxybenzo(a)pyrene. The calculations show the cis diastereomer to be more stable than the trans, although no evidence for hydrogen bonding in the (ax, ax′) conformer was found. On the basis of the results obtained for the stability of the various conformers, a model is proposed to explain the higher carcinogenicity of the trans isomer as compared to the cis. Such a model implies the formation of an intercalation complex between the diol epoxide metabolite and nucleic acids. © 1979.