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首页> 外文期刊>International Journal of Quantum Chemistry >Use of the HSAB Principle in Quantitative Structure-Activity Relationships in Toxicological Research: Application to the Genotoxicity of Chlorinated Hydrocarbons
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Use of the HSAB Principle in Quantitative Structure-Activity Relationships in Toxicological Research: Application to the Genotoxicity of Chlorinated Hydrocarbons

机译：HSAB原理在毒理学研究中定量构效关系中的应用：在氯化烃的遗传毒性中的应用

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摘要

In the field of genotoxicology, quantitative structure-activity relationships(QSAR) are frequently used to study the relationship between the structure of a toxic chemical and its biological activity. Nowadays, quantum chemical methods are often used to obtain relevant descriptors for the compound properties which are used in their turn to set up the QSAR equations. However, studies usually are restricted to the chemicals themselves and do not consider the metabolites formed, which in most cases are the real toxic agents. The work proposed here is a sequel to a QSAR-study on the genotoxicity of some 10 chlorinated hydrocarbons performed by us earlier. It was seen that there existed a relationship between the genotoxicity of the chemicals and the energy of their LUMO orbital, confirming the reductive activation metabolism by glutathione S-transferase for these chemicals suggested in the literature. Here, the episulfonium metabolites formed through this reaction path were considered. Their interaction energy with the DNA-base guanine was calculated using a density functional theory based hard and soft acids and bases approach. it was found that this interaction energy could explain the genotoxicity sequence, which had been experimentally obtained.
机译：在遗传毒理学领域，定量构效关系（QSAR）经常被用来研究有毒化学物质的结构与其生物学活性之间的关系。如今，通常使用量子化学方法来获得化合物性质的相关描述子，这些描述子又被用于建立QSAR方程。但是，研究通常仅限于化学物质本身，并且不考虑所形成的代谢产物，在大多数情况下，这些代谢产物是真正的有毒物质。本文提议的工作是QSAR研究的续集，该研究是我们之前进行的有关大约10种氯化烃的遗传毒性的研究。可以看出，这些化学物质的遗传毒性与其LUMO轨道的能量之间存在关系，这证实了谷胱甘肽S-转移酶对这些化学物质的还原活化代谢。在此，考虑了通过该反应路径形成的epi硫代谢物。使用基于硬和软酸和碱方法的密度泛函理论计算它们与DNA鸟嘌呤的相互作用能。发现该相互作用能可以解释通过实验获得的遗传毒性序列。

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