The role of oxoammonium cation in the SOD-Mimic activity of cyclic nitroxides
The role of oxoammonium cation in the SOD-Mimic activity of cyclic nitroxides
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DOI：
10.1021/ja028190w
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发表时间：
2003-01-22
影响因子：
15
通讯作者：
Samuni, A
中科院分区：
文献类型：
--
作者：
Goldstein, S;Merenyi, G;Samuni, A
环状氮氧自由基（RNO.）模拟超氧化物歧化酶（SOD）的活性，并在许多体外和体内模型中显示抗氧化特性。其广泛的抗氧化活性可能涉及其还原和氧化形式的参与，即羟胺（RNO-H）和氧代铵阳离子（RNO+）。为了检验这种可能性，我们研究了RNO+和RNO+与HO 2的反应。O-2（.-）并与几种还原剂通过脉冲辐解和快速混合停流技术。2，2，6，6-四甲基哌啶氧基（TPO）和3-氨基甲酰基-2，2，5，5-四甲基吡咯烷氧基（3-CP）通过电化学和辐解氧化生成氧代铵阳离子。RNO反应的速率常数。在HO 2。TPO和3-CP形成RNO+的速率分别为（1.2 +/- 0.1）x 10（8）和（1.3 +/- 0.1）x 10（6）M-1 s（-1）。动力学结果表明，RNO.在HO 2。通过内层电子转移机制进行。RNO反应的速率常数。O-2（.-）小于1 × 10（3）M-1 s（-1）。RNO+与O-2（.-）反应的速率常数TPO+和3-CP+分别为（3.4 +/- 0.2）x 10（9）和（5.0 +/- 0.2）x 10（9）M-1 s（-1）。因此，两种氮氧自由基都通过RNO催化超氧化物歧化。RNO+氧化还原电对，和催化速率常数，k（猫），对pH值的依赖性，显示了一个钟形曲线具有最大值约pH 4。氧代铵阳离子氧化亚铁氰化物和HO 2-通过一个电子转移，而甲醇，甲酸盐和NADH的氧化进行通过两个电子转移反应。RNO./计算出3-CP和TPO的RNO+电对分别为0.75和0.89 V。阐明的机制提供了一个更清晰的洞察到环状氮氧化物的生物抗氧化性能，应该允许设计更有效的抗氧化剂。
Cyclic nitroxides (RNO.) mimic the activity of superoxide dismutase (SOD) and demonstrate antioxidant properties in numerous in vitro and in vivo models. Their broad antioxidant activity may involve the participation of their reduced and oxidized forms, that is, hydroxylamine (RNO-H) and oxoammonium cation (RNO+). To examine this possibility we studied the reactions of RNO+ and RNO+ with HO2./O-2(.-) and with several reductants by pulse radiolysis and rapid-mixing stopped-flow techniques. The oxoammonium cations were generated by electrochemical and radiolytic oxidation of 2,2,6,6-tetramethylpiperidinoxyl (TPO) and 3-carbamoyl-2,2,5,5-tetramethylpyrrolidinoxyl (3-CP). The rate constant for the reaction of RNO. with HO2. to form RNO+ was determined to be (1.2 +/- 0.1) x 10(8) for TPO and (1.3 +/- 0.1) x 10(6) M-1 s(-1) for 3-CP. The kinetics results demonstrate that the reaction of RNO. with HO2. proceeds via an inner-sphere electron-transfer mechanism. The rate constant for the reaction of RNO. with O-2(.-) is lower than 1 x 10(3) M-1 s(-1). The rate constant for the reaction of RNO+ with O-2(.-) was determined to be (3.4 +/- 0.2) x 10(9) for TPO+ and (5.0 +/- 0.2) x 10(9) M-1 s(-1) for 3-CP+. Hence, both nitroxides catalyze the dismutation of superoxide through the RNO./RNO+ redox couple, and the dependence of the catalytic rate constant, k(cat), on pH displayed a bell-shaped curve having a maximum around pH 4. The oxoammonium cation oxidized ferrocyanide and HO2- by a one-electron transfer, whereas the oxidation of methanol, formate, and NADH proceeded through a two-electron-transfer reaction. The redox potential of RNO./RNO+ couple was calculated to be 0.75 and 0.89 V for 3-CP and TPO, respectively. The elucidated mechanism provides a clearer insight into the biological antioxidant properties of cyclic nitroxides that should permit design of even more effective antioxidants.