Prediction of octanol-air partition coefficients for polychlorinated biphenyls (PCBs) using 3D-QSAR models

Based on the experimental data of octanol-air partition coefficients (K-OA) for 19 polychlorinated biphenyl (PCB) congeners, two types of QSAR methods, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA), are used to establish 3D-QSAR models using the structural parameters as independent variables and using log K-OA values as the dependent variable with the Sybyl software to predict the K-OA values of the remaining 190 PCB congeners. The whole data set (19 compounds) was divided into a training set (15 compounds) for model generation and a test set (4 compounds) for model validation. As a result, the cross-validation correlation coefficient (q(2)) obtained by the CoMFA and CoMSIA models (shuffled 12 times) was in the range of 0.825-0.969 (> 0.5), the correlation coefficient (r(2)) obtained was in the range of 0.957-1.000 (> 0.9), and the SEP (standard error of prediction) of test set was within the range of 0.070-0.617, indicating that the models were robust and predictive. Randomly selected from a set of models, CoMFA analysis revealed that the corresponding percentages of the variance explained by steric and electrostatic fields were 23.9% and 76.1%, respectively, while CoMSIA analysis by steric, electrostatic and hydrophobic fields were 0.6%, 92.6%, and 6.8%, respectively. The electrostatic field was determined as a primary factor governing the log K-OA. The correlation analysis of the relationship between the number of Cl atoms and the average log K-OA values of PCBs indicated that log K-OA values gradually increased as the number of Cl atoms increased. Simultaneously, related studies on PCB detection in the Arctic and Antarctic areas revealed that higher log K-OA values indicate a stronger PCB migration ability. From CoMFA and CoMSIA contour maps, log K-OA decreased when substituents possessed electropositive groups at the 2-, 3-, 3'-, 5- and 6- positions, which could reduce the PCB migration ability. These results are expected to be beneficial in predicting log K-OA values of PCB homologues and derivatives and in providing a theoretical foundation for further elucidation of the global migration behaviour of PCBs. (C) 2015 Elsevier Inc. All rights reserved.