College of Environmental Science and Engineering, North China Electric Power University, Beijing, 102206, China.
MOE Key Laboratory of Resources and Environmental Systems Optimization, North China Electric Power University, Beijing, 102206, China.
Environ Sci Pollut Res Int. 2020 Jul;27(19):24103-24114. doi: 10.1007/s11356-020-08725-0. Epub 2020 Apr 17.
Phthalate acid esters (PAEs) are among the most widely used plasticizers in plastic products. They are easily diffused from plastic during use and seriously affect the environment and human health. Therefore, designing environmentally friendly PAE derivatives has important practical applications. In this paper, the environmentally friendly molecular modification of PAEs was carried out according to a comprehensive structural evaluation based on a three-dimensional quantitative structure-activity relationship (3D-QSAR) pharmacophore model of four activity modes. First, the efficacy coefficient method was used to process the mobility, toxicity, degradation and bioconcentration data of the PAEs to calculate comprehensive evaluation values. The PAE 3D-QSAR pharmacophore complex model was constructed based on the PAE four-activity comprehensive evaluation value (a comprehensive value representing the mobility, toxicity, degradation and bioconcentration of the PAEs), and a total of 4 PAE derivatives with reduced comprehensive evaluation values were obtained. Functional evaluation of the derivatives showed that the five PAEs with lower comprehensive evaluation values were stable in the environment, while the insulating properties of the derivative molecules were less affected. Following the four-activity pharmacophore model (Hypo 1) of the target molecules, dimethyl phthalate (DMP) and di-n-octyl phthalate (DNOP), comprehensive evaluation models and their mobility, toxicity, degradation and bioconcentration single-activity models, the substitution sites selected by the comprehensive evaluation model were demonstrated to be highly representative. By constructing a two-dimensional quantitative structure-activity relationship (2D-QSAR) model of the comprehensive evaluation values of the PAEs and the four single-effect 2D-QSAR models of their derivatives, the different effects of the five key parameters on the comprehensive evaluation values, toxicity, degradation, mobility and bioconcentration of molecules were analysed.
邻苯二甲酸酯（PAEs）是塑料产品中最广泛使用的增塑剂之一。它们在使用过程中很容易从塑料中扩散出来，严重影响环境和人类健康。因此，设计环保型 PAE 衍生物具有重要的实际应用价值。本文根据基于四种活性模式的三维定量构效关系（3D-QSAR）药效团模型的综合结构评价，对 PAEs 进行了环保型分子修饰。首先，采用功效系数法对 PAEs 的迁移性、毒性、降解性和生物浓缩数据进行处理，计算综合评价值。基于 PAE 四种活性综合评价值（代表 PAEs 迁移性、毒性、降解性和生物浓缩性的综合值）构建了 PAE 3D-QSAR 药效团复合模型，共得到 4 种综合评价值降低的 PAE 衍生物。对衍生物的功能评估表明，五种综合评价值较低的 PAEs 在环境中稳定，而衍生分子的绝缘性能受影响较小。根据目标分子的四种活性药效团模型（Hypo 1），对邻苯二甲酸二甲酯（DMP）和邻苯二甲酸二正辛酯（DNOP）进行了综合评价模型及其迁移性、毒性、降解性和生物浓缩性单活性模型的构建，证明了综合评价模型中选择的取代位点具有高度代表性。通过构建 PAEs 综合评价值与四种单效 2D-QSAR 模型及其衍生物的二维定量构效关系（2D-QSAR）模型，分析了五个关键参数对分子综合评价值、毒性、降解、迁移性和生物浓缩性的不同影响。
