BAY-REGION DISTORTIONS IN A METHANOL ADDUCT OF A BAY-REGION DIOL EPOXIDE OF THE CARCINOGEN 5-METHYLCHRYSENE

The three-dimensional structure of the product of the reaction of a di ol epoxide of the carcinogen 5-methylchrysene with methanol has been d etermined by an X-ray diffraction analysis, The diol epoxide used to o btain this compound contains a stereochemically hindered bay region be cause of the location of the 5-methyl group, and this might be expecte d to affect the type of chemical reaction that occurs, The crystal str ucture analysis of this adduct of a polycyclic aromatic hydrocarbon (P AH) showed that a methoxy group has been added at the carbon atom of t he epoxy group that is nearest to the aromatic system, The bond that i s formed is axial to the ring system so that the carbon and hydrogen a toms of the methoxy group are considerably displaced from the PAH ring plane, The bay-region methyl group at position 5 is displaced out of the ring plane in the opposite direction, The major steric distortion in this methanol adduct is shown, by a comparison with crystal structu res of related non-methylated compounds, to be in the area of the 5-me thyl group and not in the tetrol-bearing ring, The steric effects that caused the axial conformation of the newly formed bond would also be expected to pertain in the DNA adduct of a PAH with a bay-region methy l group, Since the presence of the bay-region methyl group in 9-methyl chrysene has been shown to enhance the carcinogenicity of this PAH ove r the parent compound or compounds with methyl groups in other positio ns of the molecule, it might be anticipated that this axial bond is fo und in carcinogenic lesions in DNA, and that any factor that ensures t his axial conformation may accentuate the carcinogenic potential of a PAH of the appropriate size.