Biological enrichment prediction of polychlorinated biphenyls and novel molecular design based on 3D-QSAR/HQSAR associated with molecule docking

Based on the experimental data of octanol-water partition coefficients (K(ow), represents bioaccumulation) for 13 polychlorinated biphenyl (PCB) congeners, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were used to establish 3D-QSAR models, combined with the hologram quantitative structure–activity relationship (HQSAR), the substitution sites (mono-substituted and bis-substituted) and substituent groups (electron-withdrawing hydrophobic groups) that significantly affect the octanol-water partition coefficients values of PCBs were identified, a total of 63 monosubstituted and bis-substituted were identified. Compared with using 3D-QSAR model alone, the coupling of 3D-QSAR and HQSAR models greatly increased the number of newly designed bis-substituted molecules, and the logK(ow) reduction in newly designed bis-substituted molecules was larger than that of monosubstituted molecules. This was established to predict the K(ow) values of 196 additional PCBs and carry out a modification of target molecular PCB-207 to lower its K(ow) (biological enrichment) significantly, simultaneously maintaining the flame retardancy and insulativity after calculation by using Gaussian09. Simultaneously, molecular docking could further screen out three more environmental friendly low biological enrichment newly designed PCB-207 molecules (5-methyl-PCB-207, 5-amino-PCB-207, and 4-amino-5-ethyl-PCB-207).