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Chemosphere. 2019 Jul;226:159-165. doi: 10.1016/j.chemosphere.2019.03.130. Epub 2019 Mar 23.

The critical factors affecting typical organophosphate flame retardants to mimetic biomembrane: An integrated in vitro and in silico study.

Author information

1
CAS Key Laboratory of Coastal Environmental Processes and Ecological Remediation, Yantai Institute of Coastal Zone Research (YIC), Chinese Academy of Sciences(CAS), Shandong Key Laboratory of Coastal Environmental Processes, YICCAS, Yantai, 264003, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China.
2
CAS Key Laboratory of Coastal Environmental Processes and Ecological Remediation, Yantai Institute of Coastal Zone Research (YIC), Chinese Academy of Sciences(CAS), Shandong Key Laboratory of Coastal Environmental Processes, YICCAS, Yantai, 264003, PR China. Electronic address: fli@yic.ac.cn.
3
CAS Key Laboratory of Coastal Environmental Processes and Ecological Remediation, Yantai Institute of Coastal Zone Research (YIC), Chinese Academy of Sciences(CAS), Shandong Key Laboratory of Coastal Environmental Processes, YICCAS, Yantai, 264003, PR China.
4
CAS Key Laboratory of Coastal Environmental Processes and Ecological Remediation, Yantai Institute of Coastal Zone Research (YIC), Chinese Academy of Sciences(CAS), Shandong Key Laboratory of Coastal Environmental Processes, YICCAS, Yantai, 264003, PR China; Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266237, PR China.

Abstract

Organophosphate flame retardants (OPFRs) have been reported to induce cytotoxicity in a structure-dependent manner. The toxic effects may be due to the damage of biomembrane integrity and/or the interference of membrane signal pathway. In this study, the damages of fifteen typical OPFRs (chlorinated phosphates, alkyl phosphates, aryl phosphates, and alkoxy phosphates) to mimetic biomembrane were determined by the electrochemical impedance spectroscopy (EIS). The molecular structure descriptors that characterized the action mechanisms were screened by stepwise regression. The six molecular descriptors (MATS7e, DLS_05, Mor19m, Mor22v, Mor12v and MATS8m) were screened to study the actions between OPFRs and mimetic biomembrane. A quantitative structure-activity relationship (QSAR) model was developed by the partial least squares (PLS) method. Statistical results indicated that the QSAR model had good robustness and mechanism interpretability. The distribution of atomic electronegativities (MATS7e) and atomic masses in three dimensional spaces (Mor19m) were the key factors influencing the actions between OPFRs and simulated biofilms. The compounds with strong electron-withdrawing property could invade the inner layer of membrane and destroy its integrity. High levels of steric hindrance could impair the damage capacity caused by electronegativity. Moreover, drug-like index (DLS_05), spatial structures of particle (Mor22v, Mor12v) and atomic masses (MATS8m) also affected the actions. The results revealed the mechanism of the actions of OPFRs with simulated biofilms and elucidated the key structural characteristics affecting the actions of OPFRs, which could provide theoretical basis for ecological risk assessment of OPFRs.

KEYWORDS:

Electrochemical impedance spectroscopy (EIS); Mimetic biomembrane; Organophosphate flame retardants (OPFRs); Partial least squares (PLS); Quantitative structure-activity relationship (QSAR)

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