标准差标准化方法修正的PBBs多效应3D-QSAR模型及其在环境友好性分子修饰中的应用

构建了标准差标准化方法修正的兼具多溴联苯(PBBs)分子红外振动强度、 生物富集性和毒性3种效应的CoMFA模型, 分析了PBBs分子力场对其综合值的影响, 确定取代位点, 并进行兼具易红外光谱检出、 低生物富集性和毒性特征的PBB分子修饰(以PBB-153为例). 研究结果表明, 构建的CoMFA模型对PBBs分子的红外振动强度、 生物富集性和毒性3种效应综合值具有较好的预测和拟合能力, 且具有较好的稳定性, 静电场和立体场的贡献率分别为59.9%和40.1%. 根据模型三维等势图选择正电性高于Br原子的5种取代基团对目标分子PBB-153进行单、 双取代, 筛选出6个3种效应综合值上升的PBB-153衍生物. PBBs衍生物分子单效应计算或预测结果验证表明所构建的兼具PBBs分子红外振动强度、 生物富集性和毒性3种效应综合值的CoMFA模型可以有效应用于PBBs分子的修饰. 设计的PBB-153衍生物分子具有较好的稳定性, 同时阻燃性与目标分子相当, 环境持久性及迁移性方面优于目标分子. 2D-QSAR模型表明, PBBs分子的偶极矩、 最负电荷及邻位Br原子数对其红外振动强度、 生物富集性和毒性单效应和综合值影响趋势一致.

3D-QSAR Model of Polybrominated Biphenyls Tri-effect Modified by Standard Deviation Standardization Method and Its Application in Environmental Friendly Molecular Modification ?

A CoMFA model of tri-effect comprehensive values of infrared vibration intensity, bioconcentration and toxicity of PBBs via standard deviation method was constructed. The influence of PBBs’ molecular force fields on comprehensive values were analyzed to determine substitution sites. And the modification for PBB-153 with easy infrared detection, low bioconcentration and toxicity was accomplished. The CoMFA model had a good fitting and predicting ability on PBBs comprehensive values of infrared vibration intensity, bioconcentration and toxicity and had a good stability, the influencing force fields were electrostatic fields(E, 59.9%) and steric fields(S, 40.1%), respectively. Five substituents with higher electropositivity than Br were selected for single and double substitution of the target molecule PBB-153 according to the contour maps of CoMFA model, and six PBB-153 derivatives with increased tri-effect comprehensive values were screened. Predicting or calculating results of single effect of PBB derivatives indicated that the constructed CoMFA model can be applied to the modification of PBBs molecules. In addition, the flame retardancy and environmental friendliness of designed derivatives was comparable to the target molecule and the stability of derivatives was well. The results of 2D-QSAR model showed that the influence trends of dipole moment, maximum negative charge and the number of ortho Br atomic on the three single effects and comprehensive values were consistent.