Reactions of peroxynitrite with phenolic and carbonyl compounds: Flavonoids are not scavengers of peroxynitrite

Peroxynitrite (ONOO-, oxoperoxonitrate(1-)), an isomer of nitrate that oxid izes and nitrates biomolecules, is likely to be formed in vivo from the rea ction of superoxide with nitrogen monoxide. To determine whether flavonoids scavenge peroxynitrite as postulated in the Literature, we studied the rea ctions of peroxynitrite with phenol, hydroquinone, catechol, and the flavon oid monoHER. These reactions are first-order with respect to peroxynitrous acid and zero-order with respect to the organic compounds, and proceed as f ast as the isomerization of peroxynitrous acid to nitrate Ln vivo, a large fraction of all peroxynitrite is likely to react with carbon dioxide to for m an unstable adduct, the 1-carboxylato-2-nitrosodioxidane anion (ONOOCO2-) . The presence of phenolic compounds did not influence the rate of disappea rance of this adduct, which was ca. 4 x 10(2) s(-1). On the basis of these kinetic studies, it can be concluded that flavonoids are not scavengers of peroxynitrite. The products from the reaction of peroxynitrite with hydroqu inone (benzene-1,4-diol) and catechol (benzene-1,2-diol) are para-benzoquin one and ortho-benzoquinone. respectively: no nitrated products were found. In a subsequent reaction, ortho-quinone reacted with nitrite, a common cont aminant of peroxynitrite preparations to form 1,2-dihydroxy-4-nitrobenzene. We also investigated whether carbonyl compounds could redirect the reactiv ity of peroxynitrite toward nitration, as carbon dioxide does. The reaction with acetone is first-order with respect to peroxynitrite and first-order with respect to the carbonyl compound. The rate constant is 1.8 m(-1)s(-1) at neutral pH and 20 degrees; peroxynitrite does not react with the carbony l compounds dimethyl acetamide, L-alanylalanine. or methyl acetate. It is n ot likely that the carbonyl compounds or the mono-, di-, or polyphenolic co mpounds can scavenge peroxynitrite in vivo.