Reactions of nitric oxide, peroxynitrite, and carbonate radicals with nitroxides and their corresponding oxoammonium cations.

Cyclic nitroxides effectively protect biological systems against radical-induced damage. However, the mechanism of the reactions of nitroxides with nitrogen-derived reactive species and carbonate radicals is far from being elucidated. In the present study, the reactions of several representative piperidine- and pyrrolidine-based nitroxides with *NO, peroxynitrite, and CO3*- were investigated, and the results are as follows: (i) There is no evidence for any direct reaction between the nitroxides and the *NO. In the presence of oxygen, the nitroxides are readily oxidized by *NO2, which is formed as an intermediate during autoxidation of *NO. (ii) *NO reacts with the oxoammonium cations to form nitrite and the corresponding nitroxides with k1 = (9.8 +/- 0.2) x 10(3) and (3.7 +/- 0.1) x 10(5) M(-1) s(-1) for the oxoammonium cations derived from 2,2,6,6-tetramethylpiperidine-1-oxyl (TPO) and 3-carbamoyl-proxyl (3-CP), respectively. (iii) CO3*- oxidizes all nitroxides tested to their oxoammonium cations with similar rate constants of (4.0 +/- 0.5) x 10(8) M(-1) s(-1), which are about 3-4 times higher than those determined for H-abstraction from the corresponding hydroxylamines TPO-H and 4-OH-TPO-H. (iv) Peroxynitrite ion does not react directly with the nitroxides but rather with their oxoammonium cations with k(10) = (6.0 +/- 0.9) x 10(6) and (2.7 +/- 0.9) x 10(6) M(-1) s(-1) for TPO+ and 3-CP+, respectively. These results provide a better insight into the complex mechanism of the reaction of peroxynitrite with nitroxides, which has been a controversial subject. The small effect of relatively low concentrations of nitroxides on the decomposition rate of peroxynitrite is attributed to their ability to scavenge efficiently *NO2 radicals, which are formed during the decomposition of peroxynitrite in the absence and in the presence of CO2. The oxoammonium cations, thus formed, are readily reduced back to the nitroxides by ONOO-, while forming *NO and O2. Hence, nitroxides act as true catalysts in diverting peroxynitrite decomposition from forming nitrating species to producing nitrosating ones.