The Reaction of Peroxynitrite with Organic Molecules Bearing a Biologically Important Functionality. The Multiplicity of Reaction Modes as Exemplified by Hydroxylation, Nitration, Nitrosation, Dealkylation, Oxygenation, and Oxidative Dimerization and Cleavage

The reactions of peroxynitrite with a variety of organic molecules which include a biologically important functionality have been examined to construct a simple model for the peroxynitrite-induced in vivo transformations as well as a chemical probe for the active species involved therein. Phenols were found to undergo hydroxylation, nitration, oxidative dimerization, and oxidation to cyclohexadienones and quinones. The ring nitration of catechol was confirmed for the first time in the in vitro reaction of peroxynitrite. Dealkylation and N-oxide formation were the major reaction modes observed for N,N-dimethyl-p-toluidine. 1,2-Phenylenediamine gave benzotriazole in high yield. The electron-deficient C–C double bond in 1,4-naphthoquinone underwent epoxidation, while the electron-rich C–C double bond in α-methylstyrene suffered oxidative cleavage to acetophenone. The activated double bond in trans-stilbene underwent oxidative cleavage and epoxidation in parallel to give benzaldehyde and trans-stilbene oxide as the major products. The triple bond in diphenylacetylene was simply oxygenated to form benzil, together with trace amounts of ring nitration products. 1-Phenylethanol, imidazole, 2′-deoxyadenosine, and 2′-deoxyguanosine were all quite slow to react, while uracil and cytosine were almost inert to peroxynitrite. The reaction modes exhibited by peroxynitrite are too widespread and complicated to explain the whole mechanistic pathway in terms of a single active species. All reaction modes observed for the peroxynitrite to date could be classified into five categories according to their types: i) electron transfer type, ii) O-electrophilic type, iii) N-electrophilic type, iv) O-nucleophilic type, and v) radical type. Some of these may compete under certain conditions. The active species involved in each of these types of reactions are as follows: i) NO+, NO2, and OH, ii) ONOOH, iii) ONOOH and NO+, iv) OOH− and ONOO−, and v) NO2 and OH•.