title: Glutathione Peroxidase-Like Activity of Amino-Substituted Water-Soluble Cyclic Selenides: A Shift of the Major Catalytic Cycle in Methanol.
abstract: We previously reported that water-soluble cyclic selenides can mimic the antioxidative function of glutathione peroxidase (GPx) in water through a simple catalytic cycle, in which the selenide (>Se) is oxidized by H₂O₂ to the selenoxide (>Se=O) and the selenoxide is reduced by a thiol back to the selenide. In methanol, however, the GPx-like activity could not be explained by this simple scenario. To look into the reasons for the unusual behaviors in methanol, monoamino-substituted cyclic selenides with a variable ring size were synthesized, and the intermediates of the catalytic cycle were characterized by means of77Se-NMR and LC-MS spectroscopies. In water, it was confirmed that the selenide and the selenoxide mainly contribute to the antioxidative function, though a slight contribution from the dihydroxy selenane (>Se(OH)₂) was also suggested. In methanol, on the other hand, other active species, such as hydroxyselenonium (>Se⁺-OH) and hydroxy perhydroxy selenane (>Se(OH)(OOH)), could be generated to build another catalytic cycle. This over-oxidation would be more feasible for amino-substituted cyclic selenides, probably because the ammonium (NH₃⁺) group would transfer a proton to the selenoxide moiety to produce a hydroxyselenonium species in the absence of an additional proton source. Thus, a shift of the major catalytic cycle in methanol would make the GPx-like antioxidative function of selenides perplexing.
authors.affiliation: Department of Chemistry, School of Science, Tokai University, Kitakaname, Hiratsuka-shi, Kanagawa 259-1292, Japan. k-arai4470@tokai-u.jp.
authors.forename: Kenta
authors.initials: K
authors.lastname: Arai
authors.affiliation: Department of Chemistry, School of Science, Tokai University, Kitakaname, Hiratsuka-shi, Kanagawa 259-1292, Japan. yokoyaman45@yahoo.co.jp.
authors.forename: Ayako
authors.initials: A
authors.lastname: Tashiro
authors.affiliation: Department of Chemistry, School of Science, Tokai University, Kitakaname, Hiratsuka-shi, Kanagawa 259-1292, Japan. fairy_yui44@yahoo.co.jp.
authors.forename: Yuui
authors.initials: Y
authors.lastname: Osaka
authors.affiliation: Department of Chemistry, School of Science, Tokai University, Kitakaname, Hiratsuka-shi, Kanagawa 259-1292, Japan. miwaoka@tokai.ac.jp.
authors.forename: Michio
authors.initials: M
authors.lastname: Iwaoka
mesh_terms: D002384:Catalysis; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000737:chemistry*; D000432:Methanol / Q000737:chemistry*; D015394:Molecular Structure; D016566:Organoselenium Compounds / Q000737:chemistry*; D010084:Oxidation-Reduction
chemical_list: D016566:Organoselenium Compounds; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D000432:Methanol
keywords: antioxidant; enzyme model; glutathione peroxidase; hydroxy perhydroxy selenane; selenide; selenoxide