氯酚化合物对发光细菌毒性的构效关系研究  

A Quantitative Structure-Activity Relationship Study on the Toxicity of Chlorophenols to Microtox

作　　者：顾云兰[1] 费正皓[1] 张玉莹[1] 

机构地区：[1]盐城师范学院应用化学与环境工程研究所,江苏盐城224051

出　　处：《分析科学学报》2012年第3期333-337,共5页Journal of Analytical Science

基　　金：国家自然科学基金(No.21077087);江苏省高校自然科学基础研究项目(No.10KJD150006);江苏省滩涂生物资源与环境保护重点实验室开放基金(No.JLCBE09019)

摘　　要：本文对20种氯酚化合物进行DFT-B3LYP/6-311G**水平全优化计算,据所得量子化学参数构建其对发光细菌毒性的定量构效关系(QSAR)模型。经逐步多元回归分析后,所建立的QSAR模型的相关系数R及去一法(LOO)交互检验复相关系数R2cv分别为0.962和0.876;用预测集样本进行了外部预测,所得外部预测集交互检验Q2ext为0.961,表明所建立的QSAR模型具有较好的稳定性和较强的预测能力。结果表明:分子的体积愈大,化合物毒性愈强;最负非氢原子净电荷愈负,毒性愈强。对模型应用域(AD)进行了表征,所建立的模型可以应用于应用域内氯酚化合物对发光细菌毒性的预测,具有潜在应用价值。DFT-B3LYP method, with the basis set 6-311G^＊＊, was employed to calculate the molecular geometric and electronic structures of chlorophenols. μ,EHOMO ,ELUMO ,△E,qH^＋ ,q^- ,qc-ou ,a and V were selected as quantum chemical descriptors. The toxicity of chlorophenols to microtox along with the above descriptors was used to establish the quantitative structure-activity relationship（QSAR）. The variables were reduced using stepwise multiple regression method, and the statistical results indicated that the correlation coefficient in the multiple linear regression and cross validation using leave-one-out were 0. 962 and 0. 876, respectively. To validate the predictive power of resulting model, external validation was performed with Q^2ext value of 0. 961. These showed that the QSAR model had good stability and predictability. The study indicated that the toxicities were increased with the increase of the volume（V） and the decrease of the most negative atomic net charge of molecule（q- ）. Moreover, the applicability domain of the developed model was assessed and visualized by the Williams plot. The developed QSAR model can be used to predict the toxicities of chlorophenols within the application domain to microtox.

关 键 词：氯酚 发光细菌 密度泛函方法 定量构效关系 应用域 

分 类 号：O641[理学—物理化学]