Mekenyan O G, Veith G D
Department of Physical Chemistry, Burgas University of Technology, Bulgaria.
SAR QSAR Environ Res. 1993;1(4):335-44. doi: 10.1080/10629369308029895.
The toxicity of chemicals is orthogonal with individual molecular descriptors used to quantify hydrophobicity and soft electrophilicity when considering large data sets. Estimating the toxicity of reactive chemicals requires descriptors of both passive transport and the stereoelectronic interaction, which are largely independent processes. QSARs using either log P or an electronic parameter alone are only significant for sets of chemicals that represent special, albeit some important, cases in QSAR. Chemicals were clustered according to their reactivity as soft electrophiles by defining isoelectrophilic windows along the toxicity response surface. Within these narrow windows of reactivity, the variation of toxicity was explained by the variation of log P. We observed that the dependence of toxicity on log P in different isoelectrophilic windows decreased as reactivity increased. The data are consistent with toxicity models where competing nucleophilic interaction sites are distributed along the transport route of the chemicals.
在考虑大数据集时，化学品的毒性与用于量化疏水性和软亲电性的单个分子描述符是正交的。估计活性化学品的毒性需要被动转运和立体电子相互作用的描述符，这两个过程在很大程度上是相互独立的。仅使用log P或单独的电子参数的定量构效关系（QSAR）仅对代表QSAR中特殊（尽管是一些重要）情况的化学品集有意义。通过沿着毒性响应表面定义等亲电窗口，根据化学品作为软亲电试剂的反应性进行聚类。在这些狭窄的反应性窗口内，毒性的变化可以用log P的变化来解释。我们观察到，随着反应性增加，不同等亲电窗口中毒性对log P的依赖性降低。这些数据与毒性模型一致，在该模型中，竞争性亲核相互作用位点沿化学品的转运途径分布。
