Poulsen M T, Loew G H
Cancer Biochem Biophys. 1981;5(2):81-90.
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.
为了确定可作为其相对致癌行为可靠指标的分子特性，我们计算了一系列甲基、二甲基和正氟 - 5 - 甲基屈衍生物与DNA代谢转化和加合物形成相关的特定电子性质。使用半经验全价电子IEHT方法，发现5 - 甲基屈的湾区键相对于屈对环氧化物形成具有增强的亲核反应性。此外，在其中一个不等价的湾区，即1,2,3,4区域，远端（1,2）键比近端（3,4）键更具反应性。这种反应模式导致易于形成二醇环氧化物碳正离子，即假定的最终致癌物。相比之下，在另一个（7,8,9,10）湾区，近端（9,10）键更具反应性，这表明形成了“错误的”，即较不稳定的二醇环氧化物碳正离子。与早期对其他多环芳烃的研究一致，通过INDO方法计算从湾区二醇环氧化物形成碳阳离子的难易程度得到了一组与致癌性具有良好相关性的值。
