Ma Guangcai, Yuan Quan, Yu Haiying, Lin Hongjun, Chen Jianrong, Hong Huachang
College of Geography and Environmental Sciences, Zhejiang Normal University, Yingbin Avenue 688, 321004, Jinhua, PR China.
College of Geography and Environmental Sciences, Zhejiang Normal University, Yingbin Avenue 688, 321004, Jinhua, PR China.
Ecotoxicol Environ Saf. 2017 Apr;138:92-97. doi: 10.1016/j.ecoenv.2016.12.022. Epub 2016 Dec 23.
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) of neutral organic chemicals with large structural variance, logK 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, 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 values for chemicals in application domain, accordingly to provide basic data for the toxicity assessment of the chemicals.
有机化学品与血清白蛋白的结合可显著降低其在血液中的游离浓度，并影响其生物反应。在本研究中，我们针对结构差异较大的中性有机化学品，开发了一种新的定量构效关系（QSAR）模型，用于预测其与牛血清白蛋白（BSA）的水分配系数（K），logK值涵盖3.5个数量级（1.19 - 4.76）。所有化学结构均通过半经验PM6算法进行优化。选择了几个反映各种分子间相互作用以及疏水性的量子化学参数来建立QSAR模型。结果表明，由logK、原子上最正的净原子电荷、康诺利溶剂排除体积、极化率和亚伯拉罕酸度推导得到的回归模型，可以解释有机化学品在BSA和水之间的分配机制。模拟外部验证和交叉验证表明，所开发的模型具有良好的统计稳健性和预测能力，因此可用于估算应用领域中化学品的logK值，从而为化学品的毒性评估提供基础数据。
