DFT法研究取代芳烃结构与毒性的定量关系

Correlation of quantitative structure with toxicity for substituted aromatic compounds using DFT

应用密度泛函方法(DFT)在B3LYP/6-311G^(**)水平上全优化计算38个取代芳烃的量子化学参数,结合辛醇/水分配系数研究取代芳烃化合物对发光菌毒性的定量构效关系(QSAR)。对训练集样本经逐步多元回归分析(SMR)后,所建QSAR方程的复关系数R^2及去一法交互检验复相关系数Q_(LOO)~2分别为0.920和0.896,用预测集样本预测外部,所得外部预测样本复相关系数R_(ext)~2和外部预测集交互检验Q_(ext)~2分别为0.870和0.849。模型结果显示:辛醇/水分配系数愈大,即分子疏水性愈强,化合物对发光菌的毒性愈大;取代基的吸电子能力愈强,化合物毒性愈大;前沿轨道能级差愈小,化合物毒性愈大。

The DFT-B3LYP method, with the basis set 6-311 G^＊＊, was employed to calculate some quantum chemical descriptors of 38 substituted aromatic compounds. The toxicity of these compounds to Photobacterium Phosphoreum along with the above descriptors and the octanol-water partition coefficient was used to establish the quantitative structure-activity relationship （QSAR）. The variables were reduced using stepwise multiple regression （SMR） method for the training set, and the statistical results indicate that the correlation coefficient in the multiple linear regression and cross validation using leave-one-out （LOO） were 0. 959 and 0. 896, respectively. To validate the predictive power of the resulting model, external validation was performed with Rext^2 and Qext^2, values of 0. 870 and 0. 849, respectively. Results show that the toxicity increass with the increase of octanol-water partition coefficient and the decrease of the energy difference between the highest occupied orbit and the lowest unoccupied orbit. The substituted groups which have strong electron-accepting ability would enhance the toxicity.