title: Competition between ascorbate and glutathione for the oxidized form of methylated quercetin metabolites and analogues: tamarixetin, 4'O-methylquercetin, has the lowest thiol reactivity.
abstract: Quercetin (Q) is a bioactive compound with excellent antioxidant activity. However, the thiol reactivity of its oxidation product (oxQ) forms a disadvantage. The aim of the present study was to decrease this thiol toxicity. We found that methylated Q metabolites displayed lower thiol reactivity than Q. The most effective was tamarixetin, 4'O-methylquercetin (4'MQ), that has a corresponding oxidation product (ox4'MQ) with thiol reactivity 350 times lower than oxQ. The endogenous metabolism of Q to 4'MQ might be a physiological way to safely benefit from the antioxidant potential of Q in vivo. Our results were explained with Pearson's HSAB concept and corroborated by quantum molecular calculations that revealed a strong correlation between the relative thiol reactivity and the lowest unoccupied molecular orbital (LUMO). The polarity of the molecule and the π-π interaction between the AC- and the B-ring appeared to determine the LUMO and the thiol reactivity of the oxidation product.
authors.affiliation: Department of Toxicology, Maastricht University, 6200 MD Maastricht, The Netherlands. moalin@maastrichtuniversity.nl
authors.forename: Mohamed
authors.initials: M
authors.lastname: Moalin
authors.forename: Gino P F
authors.initials: GP
authors.lastname: van Strijdonck
authors.forename: Aalt
authors.initials: A
authors.lastname: Bast
authors.forename: Guido R M M
authors.initials: GR
authors.lastname: Haenen
mesh_terms: D000975:Antioxidants / Q000737:chemistry* / Q000378:metabolism; D001205:Ascorbic Acid / Q000737:chemistry*; D004187:Disaccharides / Q000737:chemistry* / Q000378:metabolism; D005978:Glutathione / Q000737:chemistry*; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D004187:Disaccharides; D013438:Sulfhydryl Compounds; C508967:tamarixetin; D011794:Quercetin; D005978:Glutathione; D001205:Ascorbic Acid