Prediction of octanol-water partition coefficient for polychlorinated naphthalenes through three-dimensional QSAR models

Based on experimental data for the octanol-water partition coefficient (K-ow) of 21 polychlorinated naphthalenes (PCNs) congeners, two types of three-dimensional QSAR (3D-QSAR) models comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were established with Sybyl software. This was established to predict the K-ow values of 54 additional PCN congeners and carry out a modification of CN-73 to lower its K-ow significantly, simultaneously maintaining the stability and insulativity of CN-73. The contour maps of two models showed that the electrostatic field plays a dominating role in the logK(ow) values of PCNs, and the bioconcentration of PCN decreased when -Cl atoms on the 1-, 3-, 4-, 6-, and 7-positions of PCNs were replaced with electropositive groups. Moreover, there was a positive correlation between the number of -Cl atoms on PCNs and the average logK(ow) values of PCNs. After modification of CN-73 through the electrostatic contour maps, six types of new modified CN-73 compounds were obtained with logK(ow) values two orders of magnitude lower than that of CN-73. Meanwhile, there was not a significant difference observed between the calculated total energy (representing stability) and energy gap (representing insulativity) of the new modified compounds when compared with those of CN-73.