Quantitative structure-activity relationship models for prediction of the toxicity of polybrominated diphenyl ether congeners.
Levels of polybrominated diphenyl ethers (PBDEs) are increasing in the environment and may cause long-term health problems in humans. The similarity in the chemical structures of PBDEs and other halogenated aromatic pollutants hints on the possibility that they might share similar toxicological effects. In this work, three-dimensional quantitative structure activity relationships (3-D-QSAR) models, using comparative molecular field analysis (CoMFA) and comparative similarity indices analysis (CoMSIA), were built based on calculated structural indices and a reported experimental toxicology index (aryl hydrocarbon receptor relative binding affinities, RBA) of 18 PBDEs congeners, to determine the factors required for the RBA of these PBDEs. After performing leave-one-out cross-validation, satisfactory results were obtained with cross-validation O2 and R2 values of 0.580 and 0.995 by the CoMFA model and 0.680 and 0.982 by the CoMSIA model, respectively. The results showed clearly that the nonplanar conformations of PBDEs result in the lowest energy level and that the electrostatic index was the main factor reflecting the RBA of PBDEs. The two QSAR models were then used to predict the RBA value of 46 PBDEs for which experimental values are unavailable at present.
Wang
Yawei
Y
State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Graduate School of Chinese Academy of Sciences, Beijing, 100085, China.
Liu
Huanxiang
H
Zhao
Chunyan
C
Liu
Hanxia
H
Cai
Zongwei
Z
Jiang
Guibin
G
D004785:Environmental Pollutants / Q000633:toxicity*; D004987:Ethers / Q000737:chemistry / Q000633:toxicity; D008962:Models, Theoretical; D011075:Polybrominated Biphenyls / Q000633:toxicity*; D021281:Quantitative Structure-Activity Relationship; D055672:Static Electricity
D004785:Environmental Pollutants; D004987:Ethers; D011075:Polybrominated Biphenyls