Environmentally friendly polychlorinated naphthalenes (PCNs) derivatives designed using 3D-QSAR and screened using molecular docking, density functional theory and health-based risk assessment

Abstract

A complete design and screening system for environmental-friendly polychlorinated naphthalene (PCN) derivatives was established through three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking, density functional theory (DFT) methods and health-based risk assessment based on dynamic multimedia fugacity model. Two types of 3D-QSAR models were established for PCNs using the experimental biological toxicity (logEC₅₀) of 14 PCNs to carry out a modification to lower the logEC₅₀ of CN-70. Consequently, 67 new monosubstituted and disubstituted derivatives with a lower biological toxicity than CN-70 were designed. Furthermore, 21 new CN-70 derivatives were selected through the evaluation of their persistent organic pollutant properties (biological toxicity, bio-concentration, long-range transport potential, biodegradability) and practicability (stability, insulativity, flame retardancy) using 3D-QSAR, molecular docking and DFT methods. Finally, the non-carcinogenic and carcinogenic risks of 19 new CN-70 derivatives in different exposure pathways were reduced, and 5 derivatives with a significant decrease both in biological toxicity (amplitude reduction: 12.73%-32.51%) and risk (amplitude reduction: 32.18%-59.19%) were selected as environmental-friendly PCN derivatives, which had been screened using the health-based risk assessment system associated with dynamic multimedia fugacity model. This study provides a theoretical basis for the design of environmental-friendly flame retardants and insulating materials.

Keywords: 3D-QSAR models; Biological toxicity; Derivatives modification; Health-based risk assessment; Polychlorinated naphthalenes.