Prediction of stability for polychlorinated biphenyls in transformer insulation oil through three-dimensional quantitative structure-activity relationship pharmacophore model and full factor experimental design

Abstract

Based on the obtained data of half-lives(t1/2) for 31 polychlorinated biphenyl congeners(PCBs), 3D quantitative structure-activity relationship(QSAR) pharmacophore was used to establish a 3D QSAR model to predict the t1/2 values of the remaining 178 PCBs, using the structural parameters as independent variables and lgt1/2 values as the dependent variable. Among this process, the whole data set(31 compounds) was divided into a training set(24 compounds) for model generation and a test set(7 compounds) for model validation. Then, the full factor experimental design was used to research the potential second-order interactional effect between different substituent positions, obtaining the final regulation scheme for PCB. At last, a 3D QSAR pharmacophore model was established to validate the reasonable regulation targeting typical PCB with respect to half-lives and thermostability. As a result, the cross-validation correlation coefficient(q2) obtained by the 3D QSAR model was 0.845(>0.5) and the coefficient of determination(r2) obtained was 0.936(>0.9), indicating that the models were robust and predictive. CoMSIA analyses upon steric, electrostatic and hydrophobic fields were 0.7%, 85.9%, and 13.4%, respectively. The electrostatic field was determined to be a primary factor governing the t1/2. From CoMSIA contour maps, t1/2 increased when substituents possessed electropositive groups at the 2′-, 3-, 3′-, 5- and 5′- positions and electronegative groups at the 3-, 3′-, 5-, 6- and 6′- positions, which could increase the PCB stability in transformer insulation oil. Modification of two typical PCB congeners(PCB-77 and PCB-81) showed that the lgt1/2for three selected modified compounds increased by 13%(average ratio) compared with that of each congener and the thermostability of them were higher, validating the reasonability of the regulatory scheme obtained from the 3D QSAR model. These results are expected to be beneficial in predicting t1/2 values of PCB homologues and derivatives and in providing a theoretical foundation for further elucidation of the stability of PCBs.