Formation of nitroxyl and hydroxyl radical in solutions of sodium trioxodinitrate: effects of pH and XXXX .

@entity1 @entity137 @entity520 @entity28928 @entity521
Despite its negative redox potential, nitroxyl (HNO) can trigger reactions of oxidation. Mechanistically, these reactions were suggested to occur with the intermediate formation of either hydroxyl radical (.OH) or peroxynitrite (ONOO-). In this work, we present further experimental evidence that HNO can generate.OH. Sodium trioxodinitrate (Na2N2O3), a commonly used donor of HNO, oxidized phenol and @entity28928 SO to benzene diols and.CH3, respectively. The oxidation of Me2SO was O2-independent, suggesting that this process reflected neither the intermediate formation of ONOO- nor a redox cycling of transition metal ions that could initiate Fenton-like reactions. In solutions of phenol, Na2N2O3 yielded benzene-1,2-diol and benzene-1,4-diol at a ratio of 2:1, which is consistent with the generation of free.OH. Ethanol and Me2SO, which are efficient scavengers of.OH, impeded the hydroxylation of phenol. A mechanism for the hydrolysis of Na2N2O3 is proposed that includes dimerization of HNO to cis-hyponitrous acid (HO-N=N-OH) with a concomitant azo-type homolytic fission of the latter to N2 and.OH. The HNO-dependent production of.OH was with 1 order of magnitude higher at pH 6.0 than at pH 7.4. Hence, we hypothesized that HNO can exert selective @entity137 to cells subjected to @entity520 . In support of this thesis, Na2N2O3 was markedly more toxic to @entity1 fibroblasts and SK-N-SH @entity521 cells at pH 6.2 than at pH 7.4. Scavengers of.OH impeded the @entity137 of Na2N2O3. These results suggest that the formation of HNO may be viewed as a toxicological event in tissues subjected to @entity520 .
