title: In Silico Investigation of the Thyroid Hormone Activity of Hydroxylated Polybrominated Diphenyl Ethers.
abstract: Polybrominated diphenyl ethers (PBDEs) have been shown to have a disruptive effect on the thyroid hormone system, and one possible mechanism is the direct binding of their hydroxylated metabolites (HO-PBDEs) to thyroid hormone receptors (TRs). However, the experimental data on the thyroid hormone activity of HO-PBDEs are limited, and the molecular interaction mechanism remains unclear, impeding the ecological risk assessment for these widespread contaminants. In the present research, a quantum chemical approach was developed to predict the thyroid hormone activity of HO-PBDEs using the electronic structure parameters of neutral molecules. The ab initio HF/6-31G** algorithm was employed to optimize the molecular geometry and to calculate local molecular parameters regarding effective energy and electron transfer amount. The mechanistic analysis shows that the ability of the hydroxyl oxygen and hydrogen atom to donate or accept additional electron charges is an important property affecting the chemical activity of the thyroid hormone. The derived regression model was shown to have a good statistical performance and could be used to predict the thyroid hormone activity of other HO-PBDE congeners for which experimental measurements are not possible or are restricted. Therefore, the model has the potential to be a useful tool in the application of integrated testing strategies.
authors.affiliation: †College of Geography and Environmental Sciences, Zhejiang Normal University, Yingbin Avenue 688, 321004 Jinhua, P.R. China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Yu
authors.affiliation: ‡UFZ Department of Ecological Chemistry, Helmholtz Centre for Environmental Research, Permoserstrasse 15, 04318 Leipzig, Germany.|§Institution for Organic Chemistry, Technical University Bergakademie Freiberg, Leipzig Strasse 29, 09596 Freiberg, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Wondrousch
authors.affiliation: ∥Yantai Institute of Coastal Zone Research, Chinese Academy of Science, Chunhui Road 17, 264003 Yantai, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: †College of Geography and Environmental Sciences, Zhejiang Normal University, Yingbin Avenue 688, 321004 Jinhua, P.R. China.
authors.forename: Jianrong
authors.initials: J
authors.lastname: Chen
authors.affiliation: †College of Geography and Environmental Sciences, Zhejiang Normal University, Yingbin Avenue 688, 321004 Jinhua, P.R. China.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Lin
authors.affiliation: ⊥College of Environmental and Resource, Zhejiang University, Yuhangtang Road 866, 310058 Hangzhou, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Ji
mesh_terms: D003198:Computer Simulation; D055768:Halogenated Diphenyl Ethers / Q000737:chemistry* / Q000494:pharmacology; D006900:Hydroxylation; D015394:Molecular Structure; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism; D013963:Thyroid Hormones / Q000737:chemistry* / Q000378:metabolism
chemical_list: D055768:Halogenated Diphenyl Ethers; D013963:Thyroid Hormones