Efficacy coefficient method assisted quadruple-activities 3D-QSAR pharmacophore model for application in environmentally friendly PAE molecular modification.

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.