Núñez-Vergara L J, Díaz-Araya G, Olea-Azar C, Atria A M, Bollo-Dragnic S, Squella J A
Laboratory of Bioelectrochemistry, Faculty of Chemical & Pharmaceutical Sciences, University of Chile, Santiago.
Pharm Res. 1998 Nov;15(11):1690-5. doi: 10.1023/a:1011948410183.
To determine the formation of the one-electron reduction product from nisoldipine and its reactivity with relevant thiols in mixed medium.
Cyclic voltammetry (CV) and electron paramagnetic resonance (EPR) techniques were used to determine the one-electron reduction product corresponding to the nitro radical anion. CV was employed to assess both the rate constants corresponding to the decay of the radicals and its interaction with relevant thiols.
The nisoldipine radical anion follows second order kinetics, with an association rate constant of 283+/-16 l mol(-1) sec(-1). Nitro radical anion from nisoldipine significantly reacted with thiol compounds. This reactivity was significantly higher than the natural decay of the radical in mixed medium. EPR spectra recorded in situ using DMF/ 0.1 N NaOH (pH 13) confirmed the formation of the nitro radical anion, giving a well-resolved spectra in 35 lines using 0.1 G modulation.
Electrochemical and EPR data indicated that all the tested thiols scavenged the nitro radical anion from nisoldipine. The following tentative order of reactivity towards the thiols can be proposed: cysteamine approximately glutathione > N-acetylcysteine > captopril > penicillamine.
确定尼索地平单电子还原产物的形成及其在混合介质中与相关硫醇的反应活性。
采用循环伏安法（CV）和电子顺磁共振（EPR）技术来确定对应于硝基自由基阴离子的单电子还原产物。利用循环伏安法评估自由基衰减的速率常数及其与相关硫醇的相互作用。
尼索地平自由基阴离子遵循二级动力学，缔合速率常数为283±16 l·mol⁻¹·s⁻¹。尼索地平产生的硝基自由基阴离子与硫醇化合物发生显著反应。这种反应活性明显高于混合介质中自由基的自然衰减。使用DMF/0.1 N NaOH（pH 13）原位记录的电子顺磁共振光谱证实了硝基自由基阴离子的形成，在0.1 G调制下给出了35条谱线的清晰光谱。
电化学和电子顺磁共振数据表明，所有测试的硫醇都能清除尼索地平产生的硝基自由基阴离子。可以提出以下对硫醇反应活性的初步排序：半胱胺≈谷胱甘肽＞N-乙酰半胱氨酸＞卡托普利＞青霉胺。
