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

ABSTRACT

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.

KEYWORDS:

• 3D-QSAR
• biological enrichment
• K_ow
• molecule modification
• PCNs

Funding

The research was supported by the Fundamental Research Funds for the Central Universities in 2013 (JB2013146) and the Key Projects in the National Science and Technology Pillar Program in the Eleventh Five-Year Plan Period (2008BAC43B01).