Adams S M, Kaminsky L S
Mol Pharmacol. 1982 Sep;22(2):459-64.
Semiempirical molecular orbital calculations (by modified neglect of diatomic overlap method) were performed on diol epoxide metabolites of five polycyclic aromatic hydrocarbons (PAHs)--benzene, naphthalene, phenanthrene, chrysene, and benzo[a]pyrene (BP)--to gain insight into the various carcinogenic potencies of these compounds. Opening of the epoxide rings of the diol epoxides was calculated to be exothermic for all of the PAHs investigated. The bay-region diol epoxides of BP were calculated to open spontaneously to the triol carbonium ion upon protonation. For the bay-region trans- and cis-diequatorial diol epoxides of 5-methylchrysene the methyl group destabilized the epoxide. These results suggest that the conformation of the saturated, angular benzo-ring is important in determining bay-region epoxide stability. Conformational flexibility of the aromatic ring system is offered as one reason for partial stabilizing of bay-region epoxides. These results also suggest that the existence and potentiation of PAH carcinogenicity is correlated with the lack of stability of the bay-region epoxide ring. Considerations of thermochemical stability have value in predictions of carcinogenic potency.
采用半经验分子轨道计算方法（通过改进的忽略双原子重叠法），对五种多环芳烃（PAHs）——苯、萘、菲、 Chrysene和苯并[a]芘（BP）的二醇环氧化物进行了计算，以深入了解这些化合物的各种致癌潜力。对于所有研究的PAHs，二醇环氧化物的环氧环开环计算结果为放热反应。计算表明，BP的湾区二醇环氧化物在质子化后会自发开环形成三醇碳正离子。对于5-甲基Chrysene的湾区反式和顺式双赤道二醇环氧化物，甲基会使环氧化物不稳定。这些结果表明，饱和角状苯环的构象在决定湾区环氧化物稳定性方面很重要。芳香环系统的构象灵活性被认为是湾区环氧化物部分稳定的一个原因。这些结果还表明，PAH致癌性的存在和增强与湾区环氧环的不稳定性相关。热化学稳定性的考虑对于预测致癌潜力具有重要价值。
