A kinetic analysis of oxidation of the antioxidant N-acetyl-l-cysteine (NAC) by Pt(IV) complexes
作者:Daofeng You、Yanli Ren、Shuying Huo、Jingran Dong、Shuguang Ren、Tiesheng Shi
DOI:10.1007/s11243-016-0021-z
日期:2016.4
measurements were carried out over a wide pH range, demonstrating that the oxidation followed overall second-order kinetics. The observed second-order rate constants k′ versus pH profiles were established. A reaction mechanism was deduced, involving three parallel rate-determining steps; conceivable transition states were also proposed for these steps. Rate constants of the rate-determining steps, obtained from
N-乙酰-l-半胱氨酸 (NAC) 是一种抗氧化剂和补充剂,已被证明对重金属的多种毒性作用具有保护作用。尽管以前的工作表明 NAC 可以改善顺铂的严重毒性作用,但对 NAC 和基于 Pt(IV) 的前药之间的相互作用缺乏了解。在这项工作中,NAC 被顺铂前药 (cis-[Pt(NH3)2Cl4])、Pt(IV) 抗癌药物 ormaplatin 的原型 ([Pt(dach)Cl4]) 和模型化合物 ( trans-[PtCl2(CN)4]2-) 被详细表征。NAC 被氧化成 NAC-二硫化物,如质谱分析所确定的。时间分辨光谱和停流动力学测量在很宽的 pH 范围内进行,表明氧化遵循整体二级动力学。建立了观察到的二阶速率常数 k' 与 pH 曲线的关系。推导了反应机理,涉及三个平行的测速步骤;还为这些步骤提出了可能的过渡状态。从速率方程模拟到 k'-pH 曲线获得的速率决定步骤的速率常数在很大程度上与