Hutcheson Ryan M, Engelmann Mark D, Cheng I Francis
Department of Chemistry, University of Idaho Moscow, Idaho 83844-2343, USA.
Biometals. 2005 Feb;18(1):43-51. doi: 10.1007/s10534-004-5769-5.
The 'push' hypothesis for the antioxidant action of Zn2+ is based on its displacement of iron from a low molecular weight pro-oxidant complex. In this study, the chemical plausibility of that proposed function is investigated by cyclic voltammetry. As a model for a pro-oxidative low molecular weight iron complex the Fe(II/III)/EDTA couple was examined. This complex was selected for its well-defined electrochemical, iron stability constants, and similarity to other low molecular weight chelates in physiological fluids in terms of logical binding sites, i.e. amino, and carboxylate groups. Also investigated were iron complexes of nitrilotriacetic acid and DL-glutamic acid. Results demonstrate that approximately 90% of the cyclic voltammetric peak current for Fe(III)EDTA reduction and the EC' current for the mediated reduction of H2O2 by Fe(II/III)EDTA (Fenton Reaction) are lost when Zn2+ is introduced to a 1:1 molar ratio relative to iron. All experiments were conducted in HEPES buffered solutions at pH 7.4. Iron (II/III) complexes of nitrilotriacetic acid and DL-glutamic acid followed the same trends. Cyclic voltammetric experiments indicate that Zn2+ displaces Fe(III) from EDTA despite the much larger stability constant for the iron complex (10(25.1)) versus zinc (10(16.50)). The hydrolysis aided displacement of Fe(III) from EDTA by Zn2+ is considered by the equilibria modeling program, HySS. With Fe(III) hydrolysis products included, Zn2+ is able to achieve 90% displacement of iron from EDTA, a result consistent with cyclic voltammetric observations.
锌离子抗氧化作用的“推动”假说基于其从低分子量促氧化复合物中置换出铁。在本研究中，通过循环伏安法研究了该假定功能的化学合理性。作为促氧化低分子量铁复合物的模型，研究了Fe（II/III）/EDTA电对。选择该复合物是因为其具有明确的电化学性质、铁稳定性常数，并且在生理流体中，就逻辑结合位点（即氨基和羧基）而言，与其他低分子量螯合物相似。还研究了次氮基三乙酸和DL-谷氨酸的铁复合物。结果表明，当锌离子以相对于铁1:1的摩尔比引入时，Fe（III）EDTA还原的循环伏安峰电流以及Fe（II/III）EDTA介导的H2O2还原（芬顿反应）的EC'电流大约损失了90%。所有实验均在pH 7.4的HEPES缓冲溶液中进行。次氮基三乙酸和DL-谷氨酸的铁（II/III）复合物呈现相同趋势。循环伏安实验表明，尽管铁复合物（10（25.1））相对于锌复合物（10（16.50））的稳定性常数大得多，但锌离子仍能从EDTA中置换出Fe（III）。平衡建模程序HySS考虑了锌离子通过水解辅助从EDTA中置换Fe（III）的过程。包括Fe（III）水解产物在内，锌离子能够实现从EDTA中90%的铁置换，这一结果与循环伏安观察结果一致。
