Quantum chemical studies of methyl and fluoro analogs of chrysene: metabolic activation and correlation with carcinogenic activity.

Specific electronic properties related to metabolic transformation and adduct formation by DNA were calculated for a series of methyl, dimethyl and n-fluoro-5-methyl derivatives of chrysene with the aim of identifying molecular properties which could be used as reliable indicators of their relative carcinogenic behavior. Using the semiempirical all valence electron IEHT method, the bay region bonds of 5MC were found to have enhanced nucleophilic reactivity to epoxide formation relative to chrysene. In addition, in one of the nonequivalent bay regions, the 1, 2, 3, 4 region, the distal (1, 2) bond was found to be more reactive than the proximal (3, 4) bond. This reactivity pattern leads to an easily formed diol epoxide carbocation, the postulated ultimate carcinogen. By contrast, in the other (7, 8, 9, 10) bay region, the proximal (9, 10) bond is the more reactive, suggesting formation of the "wrong," i.e., less stable diol epoxide carbocation. Consistent with earlier studies of other PAH, calculations by the INDO method of the ease of carbon cation formation from a bay region diol epoxide yielded a set of values which gave a good correlation with carcinogenicity.