The reaction rate of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186)) with hydroxyl radical
The reaction rate of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186)) with hydroxyl radical
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DOI：
10.1248/cpb.52.186
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发表时间：
2004-02-01
影响因子：
1.7
通讯作者：
Tamaki, T
中科院分区：
文献类型：
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作者：
Abe, S;Kirima, K;Tamaki, T
吡唑啉衍生物依达拉奉是一种有效的羟基自由基清除剂，已被批准用于减轻缺血-再灌注引起的脑损伤。在本工作中，我们首先确定了依达拉奉清除水溶液中芬顿反应产生的自由基的速率常数k（r，），在该速率常数下，存在与依达拉奉竞争的自旋捕获剂5，5-二甲基-1-吡咯啉-N-氧化物（DMPO）。我们检测了依达拉奉清除羟自由基过程中的自由基，发现依达拉奉与羟自由基的反应在扩散极限附近（k（r）=3.0 × 10（10）m（-1）s（-1））。通过辣根过氧化物酶-过氧化氢体系氧化，采用快速流动法观察依达拉奉自由基的EPR（电子顺磁共振）光谱。这种自由基物种是不稳定的，并随着时间的推移改变为另一种自由基物种。此外，还发现依达拉奉在辣根过氧化物酶（HRP）-H2 O2体系中氧化时消耗分子氧，并且依达拉奉能够向亲电试剂提供两个电子。根据这些发现，研究了依达拉奉氧化的可能机制。
The pyrazoline derivative edaravone is a potent hydroxyl radical scavenger that has been approved for attenuation of brain damage caused by ischemia-reperfusion. In the present work, we first determined the rate constant k(r,) at which edaravone scavenges radicals generated by a Fenton reaction in aqueous solution in the presence of the spin trap agent, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), which competed with edaravone. We detected the edaravone radicals in,the process of hydroxyl radical scavenging and found that edaravone reacts with hydroxyl radical around the diffusion limit (k(r)=3.0 x 10(10) m(-1)s(-1)). The EPR (electron paramagnetic resonance) spectrum of the edaravone radical was observed by oxidation with a horseradish peroxidase-hydrogen peroxide system using the fast-flow method. This radical species is unstable and changed to another radical species with time. In addition, it was found that edaravone consumed molecular oxygen when it was oxidized by horseradish peroxidase (HRP)-H2O2 system, and that edaravone was capable of providing two electrons to the electrophiles. The possible mechanisms for oxidation of edaravone were investigated from these findings.