Loew G H, Phillips J, Pack G
Cancer Biochem Biophys. 1979;3(3):101-10.
Electronic parameters related to the cytochrome P450-catalyzed reactions of eight polycyclic aromatic amines have been calculated using all valence electron semiempirical molecular orbital methods. The reactions considered lead to the presumably carcinogenic arylnitrenium ions and to the competing hydroxylation and epoxidation products. The stabilities of the arylnitrenium ions relative to the N-hydroxylamines and their sulfate esters were also calculated, together with electrophilic reactivity parameters of the ions. The resulting parameters were used to predict major metabolites of the parent compounds and also to correlate with observed mutagenic activities of the four pairs of polycyclic aromatic amines studied. The major factor in determining mutagenic potencies of parent compounds appears to be the extent of N-hydroxylation and competing ring oxidations, as well as the electrophilic properties of the arylnitrenium ions.
使用全价电子半经验分子轨道方法计算了与8种多环芳烃胺的细胞色素P450催化反应相关的电子参数。所考虑的反应会生成可能具有致癌性的芳基氮鎓离子以及竞争性的羟基化和环氧化产物。还计算了芳基氮鎓离子相对于N-羟基胺及其硫酸酯的稳定性，以及这些离子的亲电反应性参数。所得参数用于预测母体化合物的主要代谢产物，并与所研究的四对多环芳烃胺的观察到的诱变活性相关联。决定母体化合物诱变潜力的主要因素似乎是N-羟基化程度和竞争性的环氧化，以及芳基氮鎓离子的亲电性质。
