Basak Subhash C, Balasubramanian Krishnan, Gute Brian D, Mills Denise, Gorczynska Anna, Roszak Szczepan
Natural Resources Research Institute, University of Minnesota-Duluth, 5013 Miller Trunk Highway, Duluth, Minnesota 55811, USA.
J Chem Inf Comput Sci. 2003 Jul-Aug;43(4):1103-9. doi: 10.1021/ci020054n.
A hierarchical quantitative structure-activity relationship (HiQSAR) approach was used to estimate toxicity and genetic toxicity for a set of 55 halocarbons using computed chemodescriptors. The descriptors consisted of topostructural (TS), topochemical (TC), geometrical, semiempirical (AM1) quantum chemical, and ab initio (STO-3G, 6-31G(d), 6-311G, 6-311G(d), and aug-cc-pVTZ) quantum chemical indices. For the two toxicity endpoints investigated, ARR and D(37), the TC indices gave the best cross-validated R(2) values. The 3-D indices also performed either as well as or slightly superior to the TC indices. For the four categories of quantum chemical indices used for the development of predictive models, the AM1 parameters gave the worst performance, and the most advanced ab initio (B3LYP/aug-CC-pVTZ) parameters gave the best results when used alone. This was also the case when the quantum chemical indices were used in the hierarchical QSAR approach for both of the toxicity endpoints, ARR and D(37). The models resulting from HiQSAR are of sufficiently good quality to estimate toxicity of halocarbons from structure.
采用分层定量构效关系（HiQSAR）方法，利用计算得到的化学描述符对一组55种卤代烃的毒性和遗传毒性进行估算。这些描述符包括拓扑结构（TS）、拓扑化学（TC）、几何、半经验（AM1）量子化学以及从头算（STO-3G、6-31G(d)、6-311G、6-311G(d)和aug-cc-pVTZ）量子化学指标。对于所研究的两个毒性终点ARR和D(37)，TC指标给出了最佳的交叉验证R(2)值。三维指标的表现与TC指标相当或略优于TC指标。在用于开发预测模型的四类量子化学指标中，AM1参数表现最差，而最先进的从头算（B3LYP/aug-CC-pVTZ）参数单独使用时给出了最佳结果。在将量子化学指标用于ARR和D(37)这两个毒性终点的分层QSAR方法时，情况也是如此。HiQSAR得到的模型质量足够好，能够从结构估算卤代烃的毒性。
