Development and evaluation of predictive model for bovine serum albumin water partition coefficients of neutral organic chemicals

作者：Ma, Guangcai; Yuan, Quan; Yu, Haiying^*; Lin, Hongjun; Chen, Jianrong; Hong, Huachang

来源：Ecotoxicology and Environmental Safety, 2017, 138: 92-97.

DOI：10.1016/j.ecoenv.2016.12.022

• Bovine serum albumin - water partition
• coefficients
• Quantitative structure - property relationship
• QSAR
• PM6
• Quantum chemical descriptors

The binding of organic chemicals to serum albumin can significantly reduce their unbound concentration in blood and affect their biological reactions. In this study, we developed a new QSAR model for bovine serum albumin (BSA) - water partition coefficients (K-BSA/W) of neutral organic chemicals with large structural variance, logK(BSA/W) values covering 3.5 orders of magnitude (1.19-4.76). All chemical geometries were optimized by semi-empirical PM6 algorithm. Several quantum chemical parameters that reflect various intermolecular interactions as well as hydrophobicity were selected to develop QSAR model. The result indicates the regression model derived from logK(ow), the most positive net atomic charges on an atom, Connolly solvent excluded volume, polarizability, and Abraham acidity could explain the partitioning mechanism of organic chemicals between BSA and water. The simulated external validation and cross validation verifies the developed model has good statistical robustness and predictive ability, thus can be used to estimate the logK(BSA/W) values for chemicals in application domain, accordingly to provide basic data for the toxicity assessment of the chemicals.

• 出版日期2017-4
• 单位浙江师范大学