The reaction of 2-(methylseleno)benzanilide with peroxynitrite.
2-(Methylseleno)benzanilide (MeSe), a main metabolite of ebselen in vivo, rapidly reacts with peroxynitrite, yielding 2-(methylseleninyl)benzanilide (MeSe = O) as the sole selenium-containing product. The reaction proceeds efficiently at acidic pH where peroxynitrous acid (ONOOH) is predominant, suggesting that MeSe reacts faster with ONOOH than with the peroxynitrite anion (ONOO-). MeSe is much less reactive with hydrogen peroxide. The second-order rate constant for the reaction at 22 degrees C was estimated from the relationship between substrate consumption and peroxynitrite concentration as 2.2 x 10(4) M-1 s-1 and 2.7 x 10(3) M-1 s-1 at pH 3.9 and 7.0, respectively, and from intermolecular competition with ascorbic acid as 3.4 x 10(3) M-1 s-1 at pH 7.1. The rate constant is about 2 orders of magnitude lower than that for the reaction of ebselen with peroxynitrite, but about 1-2 orders of magnitude higher than that reported in the literature for methionine or ascorbate. The selenoxide can be reduced back to MeSe by thiols. MeSe has previously been considered to be an inert metabolite of ebselen, but may show antioxidant activity against peroxynitrite.
Masumoto
H
H
Institut für Physiologische Chemie I, Heinrich-Heine-Universität Düsseldorf, Germany.
Sies
H
H
D000813:Anilides / Q000138:chemical synthesis / Q000737:chemistry*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry; D001205:Ascorbic Acid / Q000737:chemistry; D001393:Azoles / Q000737:chemistry; D001667:Binding, Competitive; D002851:Chromatography, High Pressure Liquid; D005609:Free Radicals; D054833:Isoindoles; D007700:Kinetics; D009566:Nitrates / Q000737:chemistry*; D016566:Organoselenium Compounds / Q000138:chemical synthesis / Q000737:chemistry*
D000813:Anilides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001393:Azoles; D005609:Free Radicals; D054833:Isoindoles; D009566:Nitrates; D016566:Organoselenium Compounds; C071762:2-(methylseleninyl)benzanilide; C039642:peroxynitric acid; C042986:ebselen; C068988:2-methylselenobenzanilide; D001205:Ascorbic Acid