title: Formation and characterization of glutathione adducts derived from polybrominated diphenyl ethers.
abstract: The reactions of glutathione (GSH) with polybrominated diphenyl ethers (PBDEs) quinones with different degrees of bromination on the PBDEs ring were studied. Liquid chromatography coupled with mass spectrometric (LC-MS) analysis showed that four types of adducts were formed from the reaction of each PBDEs quinone (PBDE-Q) with GSH. The proposed reaction pathway was confirmed using ion trap-MS/MS technique. Our results demonstrate that adduct-1 was formed following the Michael Addition, a reaction of the sulfhydryl group from GSH with electron deficient carbon from PBDEs-Q ring. Compared with other carbons on the quinone ring, carbon in position 6 has a smaller steric hindrance, thus the addition reaction is likely to occur in that position. Hydrated quinone-GSH adduct-1 is easily oxidized to generate an adduct-2 in an aqueous solution. Substitution reaction from bromine atom on adduct-2 quinone ring with sulfhydryl group from GSH further generates adduct-3 that is unstable and can be readily hydrolyzed to adduct-4 in aqueous solution. Both adduct-1 and adduct-4 were unstable as well, immediately oxidized to adduct-2 and adduct-3 in the air, respectively. The results reveal that brominated quinones undergo a rapid non-enzymatic debromination upon reaction with GSH, and open a new view for our understanding on mechanism of metabolism and the toxicity of this class of compounds.
authors.affiliation: Ministry of Education Key Laboratory of Analysis and Detection Technology for Food Safety, Fuzhou University, Fuzhou 350002, China; State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong Special Administrative Region.
authors.forename: Lihua
authors.initials: L
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong Special Administrative Region.
authors.forename: Yongquan
authors.initials: Y
authors.lastname: Lai
authors.affiliation: California Department of Public Health, 850 Marina Bay Parkway, G365, Richmond, CA 94564, USA.
authors.forename: Charlie
authors.initials: C
authors.lastname: Li
authors.affiliation: Ministry of Education Key Laboratory of Analysis and Detection Technology for Food Safety, Fuzhou University, Fuzhou 350002, China; State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong Special Administrative Region.
authors.forename: Bin
authors.initials: B
authors.lastname: Qiu
authors.affiliation: State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong Special Administrative Region. Electronic address: zwcai@hkbu.edu.hk.
authors.forename: Zongwei
authors.initials: Z
authors.lastname: Cai
mesh_terms: D002853:Chromatography, Liquid; D005411:Flame Retardants / Q000032:analysis*; D005978:Glutathione / Q000737:chemistry*; D055768:Halogenated Diphenyl Ethers / Q000737:chemistry*; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D011809:Quinones / Q000737:chemistry
chemical_list: D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D011809:Quinones; D005978:Glutathione
keywords: GSH; LC–MS; PBDE-quinone; PBDEs