College of Environmental Science and Engineering, North China Electric Power University, Beijing 102206, China; The State Key Laboratory of Regional Optimisation of Energy System, North China Electric Power University, Beijing 102206, China.
College of Environmental Science and Engineering, North China Electric Power University, Beijing 102206, China; The State Key Laboratory of Regional Optimisation of Energy System, North China Electric Power University, Beijing 102206, China.
J Hazard Mater. 2019 Feb 5;363:316-327. doi: 10.1016/j.jhazmat.2018.09.060. Epub 2018 Sep 27.
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 (logEC) of 14 PCNs to carry out a modification to lower the logEC 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.
建立了一套完整的环保型多氯萘（PCN）衍生物的设计和筛选系统，该系统基于三维定量构效关系（3D-QSAR）、分子对接、密度泛函理论（DFT）方法和基于动态多介质逸度模型的健康风险评估。使用实验生物毒性（logEC）对 14 种 PCN 进行了两种类型的 3D-QSAR 模型的建立，目的是对 CN-70 进行改性以降低其 logEC。因此，设计了 67 种新的单取代和双取代衍生物，其生物毒性低于 CN-70。此外，通过 3D-QSAR、分子对接和 DFT 方法对其持久性有机污染物特性（生物毒性、生物浓缩、长距离传输潜力、生物降解性）和实用性（稳定性、绝缘性、阻燃性）进行评价，选择了 21 种新的 CN-70 衍生物。最后，通过基于健康风险评估的动态多介质逸度模型相关系统，降低了 19 种不同暴露途径下的新 CN-70 衍生物的非致癌和致癌风险，筛选出了 5 种生物毒性（降低幅度：12.73%-32.51%）和风险（降低幅度：32.18%-59.19%）均显著降低的衍生物，作为环保型 PCN 衍生物。该研究为环保型阻燃剂和绝缘材料的设计提供了理论依据。
