79371-66-7Relevant academic research and scientific papers
Characterization of new bisphenol A metabolites produced by CD1 mice liver microsomes and S9 fractions
Jaeg, Jean Philippe,Perdu, Elisabeth,Dolo, Laurence,Debrauwer, Laurent,Cravedi, Jean-Pierre,Zalko, Daniel
, p. 4935 - 4942 (2004)
Bisphenol A [2,2-bis(4-hydroxyphenyl)propane] (BPA) is a widely used industrial chemical resulting in occupational and consumer exposure. BPA possesses weak estrogenomimetic activity and can be cytotoxic, though the underlying mechanisms of its toxicity toward cells are not completely understood. The metabolism of BPA by CD1 mice liver microsomal and S9 fractions was investigated. Nine metabolites were isolated and characterized using HPLC and mass spectrometry. Many of these metabolites were characterized for the first time in mammals, namely isopropyl-hydroxyphenol (produced by the cleavage of BPA), a bisphenol A glutathione conjugate, glutathionyl-phenol, glutathionyl 4-isopropylphenol, and BPA dimers. Most of these metabolites apparently share a common metabolic pathway, for which considerable evidence supports the hypothesis of the production of a reactive intermediate, and also helps explain BPA cytotoxicity.
Structural Identification and Kinetic Analysis of the in Vitro Products Formed by Reaction of Bisphenol A-3,4-quinone with N-Acetylcysteine and Glutathione
Stack, Douglas E.,Conrad, John A.,Mahmud, Bejan
, p. 81 - 87 (2018)
Bisphenol A (BPA) has received considerable attention as an endocrine disrupting chemical and a possible substrate for genotoxic metabolites. BPA metabolism leads to formation of electrophilic o-quinones cable of binding to DNA and other endogenous nucleophiles. We have structurally identified the products resulting from the reaction of bisphenol A-3,4-quinone (BPAQ) with N-acetylcysteine (NAC) and glutathione (GSH). The major and minor isomers are both the result of 1,6-conjugate addition and are produced almost instantly in high yield. Reactions using 1.3 equiv of GSH showed the presence of a bis-glutathionyl adduct which was not observed using higher GSH concentration relative to BPAQ. NAC reactions with BPAQ showed no bis-N-acetylcysteinyl adducts. Stopped-flow kinetic analysis reveals the 1,6-conjugate additions to be reversible with a forward free energy of activation of 9.2 and 7.8 kcal/mol for the NAC and GSH reactions, respectively. The bimolecular forward rate constant at 19.4 °C was approximately three time faster for GSH compared to NAC, 1547 vs 496 M-1 s-1. The free energy of activation for the reverse reactions were similar, 11.7 and 11.2 kcal/mol for NAC and GSH, respectively. We plan to use this model system to further explore the mechanism of adduct formation between sulfur nucleophiles and o-quinones and the resulting chemical properties of both NAC and GSH adducts.
Photo-oxidation of bisphenol A in aqueous solutions at near neutral pH by a Fe(III)-carboxylate complex with oxalacetic acid as a benign molecule
Xu, Jing,Zhao, Chuxuan,Wang, Tianbei,Yang, Shaojie,Liu, Zizheng
, (2018/06/06)
The photo-oxidation of organic pollutants as induced by ferric-carboxylate complexes was known to be a photo-Fenton-like process. The use of a carboxylate ligand with higher efficiency and lower toxicity at near neutral pH is of high interest to researchers. In this work, photo-oxidation of bisphenol A (BPA) induced by a ferric-oxalacetic acid complex in aqueous solutions was investigated under 395 nm LED lamps. The results showed that the rate of BPA degradation increased in the order pH 10.0 8.0 6.5 4.0 within the first 10 min. More than 90% of BPA was successfully oxidized with Fe(III)/oxalacetic acid with a ratio of 1:5 at pH 6.5, which was primarily attributed to the generated hydroxyl radical. Iron in the Fe(III)-oxalacetic acid system was reused by simple addition of oxalacetic acid to the reaction mixture. Compared to common carboxylate ligands (pyruvic acid, oxalic acid, and citric acid), oxalacetic acid is more efficient and environmentally friendly for the Fe(III)-carboxylate complex-based photo-Fenton-like process at near neutral pH.
Efficient access to bisphenol A metabolites: Synthesis of monocatechol, mono-o-quinone, dicatechol, and di-o-quinone of bisphenol A
Stack, Douglas E.,Mahmud, Bejan
supporting information, p. 161 - 167 (2017/12/28)
2-Iodoxybenzoic acid (IBX) oxidation of bisphenol A (BPA) is described. The selective production of either the mono-o-quinone or the di-o-quinone can be controlled by IBX stoichiometry. Isolated yields of quinone were greater than 80%. Previous synthesis of BPA-di-o-quinone using a large excess of Fremy’s salt produced only trace amounts of product. In addition to o-quinone products, both mono- and dicatechols of BPA can synthesize in high yield and isolated without chromatography. The more stable catechols can be quantitatively converted back to o-quinones using silver oxide oxidation in either acetone or DMF. These one-pot reactions provide access to four different BPA metabolites in high yield and significant scale.
Preparation of nitrogen doped K2Nb4O11 with high photocatalytic activity for degradation of organic pollutants
Qiu, Yongfu,Wang, Lei,Leung, Chi-Fai,Liu, Guijian,Yang, Shihe,Lau, Tai-Chu
experimental part, p. 23 - 30 (2012/04/10)
Nitrogen doped K2Nb4O11 (K 2Nb4O11-N) has been prepared by solid state reaction between K2Nb4O11 and urea at 400 °C. K2Nb4O11-N has been characterized by XRD, SEM, XPS and UV/vis diffuse reflectance. The photodegradation of various organic pollutants in water by this material, including Orange G (OG), bisphenol A (BPA) and pentachlorophenol (PCP) have been studied at λ > 330 nm and >399 nm. The results show that the photocatalytic activity of K 2Nb4O11-N at >399 nm is higher than those of K2Nb4O11 and Degussa TiO2 P25, indicating the activating effect of nitrogen doping. A mechanism for the photodegradation of organic substrates by K2Nb4O 11-N is proposed.
Comparison of the modulatory effects of human and rat liver microsomal metabolism on the estrogenicity of bisphenol A: Implications for extrapolation to humans
Elsby,Maggs,Ashby,Park
, p. 103 - 113 (2007/10/03)
Bisphenol A [BPA, 2,2-bis(4-hydroxyphenyl)propane], a xenoestrogen, is a monomer for the synthesis of polycarbonate plastics, epoxy resins, and composites. Metabolism of BPA to the monoglucuronide will determine the extent of its estrogenicity in vivo. Investigation of the metabolism of BPA (500 μM) by isolated female rat hepatocytes confirmed the formation of BPA glucuronide as the major metabolite. There was a significant difference (p max (mean ± S.E.M., n = 4) of glucuronidation by pooled male or female human (four livers in each case) and immature female rat liver microsomes (5.9 ± 0.4, 5.2 ± 0.3, and 31.6 ± 8.1 nmol/min/mg of protein, respectively). Estrogenic activity of BPA, assessed in a coupled microsomal metabolism-yeast estrogenicity assay, was decreased 3- and 7-fold following glucuronidation by human female and immature female rat liver microsomes, respectively. Incubations of BPA with pooled human or rat liver microsomes, in the presence of NADPH, resulted in the formation of 5-hydroxybisphenol A [2-(4,5-dihydroxyphenyl)-2-(4-hydroxyphenyl)propane], which was 10-fold less potent than BPA in the yeast estrogenicity assay. However, there was insufficient turn-over to achieve a significant effect on the estrogenic activity of BPA. Because human liver microsomes did not glucuronidate BPA as extensively as the rat liver microsomes, estrogen target tissues in humans may be subject to greater exposure to BPA than the tissues of the immature female rats used for assessing estrogenicity of xenobiotics.
