Abstract
Perturbational molecular orbital calculations were applied to a series of polynuclear aromatic hydrocarbons (PAH) to assess the energetics involved in generating electrophilic carbonium ions of two types, triol and benzylic carbonium ions. ΔE β , an index of carbonium ion formation and stability, was nearly always higher for benzylic carbonium ions attached to mesoanthracenic positions of PAHs than for terminal ring triol carbonium ions. Furthermore, the reactivity index N t for substitution reactions leading to benzylic carbonium ions was lowest in each molecule at the site corresponding to the most favorable ΔE β value. No similar relationship existed for ortholocalization energies of bonds at which addition reactions generate triol carbonium ions. Statistical analysis revealed that Iball indices for carcinogenicity showed higher correlation with both benzylic-relevant ΔE β and N t values than with triol carbonium ion ΔE β or ortholocalization energies. Various authors claim correlation between the energetics of triol carbonium ion generation and carcinogenicity, yet our observations along similar lines of reasoning demonstrate even stronger correlation and more favorable energetics for benzylic carbonium ions that require initial methylation at an exceptionally reactive center. Based on our calculations, we predict that animal tests, such as repeated application to mouse skin or repeated subcutaneous injection in mice or rats, should reveal benzylic carbonium ions arising from hydroxymethyl sulfate ester metabolites to be endowed with more complete carcinogenic potency than triol carbonium ions arising from dihydrodiol epoxide metabolites.
Published Version
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