Carbon dioxide catalysis of the reaction of peroxynitrite with ethyl acetoacetate: an example of aliphatic nitration by peroxynitrite.

The reaction of peroxynitrite anion (O=N-OO-) with CO2 results in the formation of an unstable nitrosoperoxycarbonate anion adduct, O=N-OOCO-2 (1). Adduct 1 can serve as a source for several reactive intermediates, including the nitrocarbonate anion (O2N-OCO-2), the carbonate radical ion/nitrogen dioxide radical pair, and the nitronium ion/carbonate ion pair. One or more of these reactive intermediates mediate(s) electrophilic nitrations, for example of tyrosine residues in proteins, which is often observed in peroxynitrite-producing systems. We here report, for the first time, the nitration of an aliphatic substrate, ethyl acetoacetate, by peroxynitrite. The yield of nitration is markedly enhanced in the presence of added carbonate. The major product of this reaction is ethyl 2-nitroacetoacetate. The importance of this reaction is discussed in relation to the possible aliphatic nitrations of amines, sugars, thiols, and thioethers in peroxynitrite-producing biological systems.