Borosky Gabriela L
Unidad de Matemática y Física, INFIQC, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Córdoba 5000, Argentina.
Curr Med Chem. 2008;15(28):2901-20. doi: 10.2174/092986708786848686.
Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants well known as mutagenic/carcinogenic agents. This review will discuss recent theoretical studies regarding the stability and reactivity of ultimate carcinogenic metabolites from PAHs, focusing on their diol epoxide and amine derivatives. Geometrical and electronic features will be analyzed in order to obtain structure-activity relationships. Charge delocalization modes (positive charge density distribution), substituent effects, and conformational aspects will be considered. Computed properties will be compared with the available biological activity data. Correlations between experimental mutagenic potencies reported in the literature and calculated reaction energies and electronic properties will be shown. Heteroaromatic compounds (aza-PAHs, thia-PAHs, and heteroaromatic amines) will also be examined. To model the important step of covalent adduct formation, calculation of the adducts resulting from bond formation between some of these electrophilic intermediates and nucleotide bases (guanine, cytosine) will be described.
多环芳烃（PAHs）是广泛存在的环境污染物，是众所周知的诱变/致癌剂。本综述将讨论最近关于PAHs最终致癌代谢物的稳定性和反应性的理论研究，重点关注其二醇环氧化物和胺衍生物。将分析几何和电子特征以获得构效关系。将考虑电荷离域模式（正电荷密度分布）、取代基效应和构象方面。计算得到的性质将与现有的生物活性数据进行比较。将展示文献中报道的实验诱变效力与计算得到的反应能量和电子性质之间的相关性。还将研究杂环芳烃（氮杂PAHs、硫杂PAHs和杂环芳胺）。为了模拟共价加合物形成的重要步骤，将描述由这些亲电中间体与核苷酸碱基（鸟嘌呤、胞嘧啶）之间形成键产生的加合物的计算。
