Study On The Interaction Between Polybrominated Diphenyl Ether Derivatives And Biological Molecules

Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants in consumer products, such as polyurethane foam, textiles, furniture, and electronics. Recent studies have shown that, PBDEs would generate hydroxyl metabolites (OH-PBDEs or diOH-PBDEs) with a higher toxicity than PBDEs via the cytochrome P450 enzyme-catalyzed hydroxylation. And diOH-PBDEs will be catalyticly oxidized by peroxidase to a quinone derivative, which leads to various potential toxicities in biological systems. Therefore, it is significant to clarify the morbigenous mechanism of PBDEs quinone metabolites in biological tissue and organ lesions. This experiment was prepared by synthetizing PBDE-Qs as analog metabolic of PBDEs, which reacted with DNA, glutathione (GSH) and cysteine (Cys). The liquid chromatography-mass spectrometry detection technology was used to analyze the type of product and the reaction mechanism. Paper is divided into four chapters.In the first chapter, the research status of PBDEs, OH-PBDEs and PBDE-Qs were briefly introduced, including the source, test methods and toxicity. At the same time, the purpose and contents of this research had been pointed out.In the second chapter, we synthesized the deoxynucleoside (dG, dA and dC) adducts of PBDE-Qs, and characterized the deoxynucleoside adducts by HPLC-QTOFMS method. The experimental results showed that PBDE-Qs could generate two kinds, three kinds, and two kinds of adducts with dG, dA, dC respectively. The UPLC-MS was utilized for quantifying PBDEs adducts of dG, dA and dC at different pH value. For dA and dC, the yield of relative adducts would decrease with the increase of buffer pH, presenting a negative correlation. The PBDE-dG adducts would be yielded by irregular parabola variation. Finally, PBDE-DNA adducts was studied under physiology conditions.In the third chapter, we synthesised GSH adducts of PBDE-Qs. The trap-MS/MS was used to characterize the GSH adducts and clarify the mechanism of GSH detoxification to quinone derivatives. Five kinds of PBDE-Qs reacted with GSH generates four adducts, respectively. Finally, the stability of GSH adducts was studied at room temperature in 48 h. The conclusion is adduct 1 and 4 were unstable, easily oxidized to adduct 2 and 3 in the air.In the forth chapter, we synthesised Cys adducts of PBDE-Qs. HPLC-QTOFMS was used to characterize the Cys adducts and explore the mechanism of products’formation. Each kinds of PBDE-Q generated two kinds of adducts which reacted with Cys as 1:1 and 1:2. Finally, the stability of Cys adducts were studied at room temperature within 60 h. The PBDE-Qs adducts of Cys were completely oxidized or degraded within 60 h.