Goldstein Sara, Samuni Amram, Merenyi Gabor
Department of Physical Chemistry, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Chem Res Toxicol. 2004 Feb;17(2):250-7. doi: 10.1021/tx0342363.
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.
环状氮氧化物能有效保护生物系统免受自由基诱导的损伤。然而，氮氧化物与氮衍生的活性物种及碳酸根自由基的反应机制仍远未阐明。在本研究中，研究了几种具有代表性的基于哌啶和吡咯烷的氮氧化物与NO、过氧亚硝酸盐和CO3-的反应，结果如下：(i) 没有证据表明氮氧化物与NO之间存在任何直接反应。在有氧气存在的情况下，氮氧化物很容易被NO2氧化，NO2是NO自氧化过程中形成的中间体。(ii) NO与氧鎓铵阳离子反应形成亚硝酸盐和相应的氮氧化物，对于源自2,2,6,6-四甲基哌啶-1-氧基（TPO）和3-氨基甲酰基-脯氨酰氧基（3-CP）的氧鎓铵阳离子，反应速率常数k1分别为(9.8±0.2)×10(3)和(3.7±0.1)×10(5) M(-1) s(-1)。(iii) CO3-将所有测试的氮氧化物氧化为其氧鎓铵阳离子，速率常数相似，为(4.0±0.5)×10(8) M(-1) s(-1)，比从相应的羟胺TPO-H和4-OH-TPO-H中夺取氢的速率常数高约3-4倍。(iv) 过氧亚硝酸盐离子不直接与氮氧化物反应，而是与它们的氧鎓铵阳离子反应，对于TPO+和3-CP+，反应速率常数k(10)分别为(6.0±0.9)×10(6)和(2.7±0.9)×10(6) M(-1) s(-1)。这些结果为过氧亚硝酸盐与氮氧化物反应的复杂机制提供了更好的见解，这一直是一个有争议的话题。相对低浓度的氮氧化物对过氧亚硝酸盐分解速率的影响较小，这归因于它们有效清除*NO2自由基的能力，NO2自由基是过氧亚硝酸盐在不存在和存在CO2的情况下分解过程中形成的。由此形成的氧鎓铵阳离子很容易被ONOO-还原回氮氧化物，同时形成NO和O2。因此，氮氧化物在将过氧亚硝酸盐分解从形成硝化物种转向产生亚硝化物种方面起到了真正的催化剂作用。
