Redox Properties and Activity of Iron-Citrate Complexes: Evidence for Redox Cycling
Redox Properties and Activity of Iron-Citrate Complexes: Evidence for Redox Cycling
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DOI：
10.1021/tx500377b
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发表时间：
2015-04-01
影响因子：
4.1
通讯作者：
Koppenol, Willem H.
中科院分区：
文献类型：
--
作者：
Adam, Fatima I.;Bounds, Patricia L.;Koppenol, Willem H.
铁超载疾病中的铁以非转铁蛋白结合铁的形式存在，由铁、柠檬酸盐和白蛋白组成。我们研究了柠檬酸铁的氧化还原性能的电化学，其与抗坏血酸的反应动力学，ESR，并通过分析的抗坏血酸与柠檬酸铁配合物的反应产物在H2 O2的存在下与4-羟基苯甲酸作为报告分子羟基化。对于（Fe 3 +-cit/Fe 2 +-cit）电对，我们报告-0.03V < E度>+0.01V。柠檬酸铁与抗坏血酸盐反应的第一步是快速形成铁与柠檬酸盐和抗坏血酸盐的混合络合物，然后缓慢还原为Fe 2 +-柠檬酸盐，k = ca。3 M-1秒（-1）。抗坏血酸自由基由Hasc（-）的柠檬酸铁氧化形成，k = ca。0.02 M-1 s（-1）;形成的大部分抗坏血酸自由基通过与铁络合而被螯合，并保持EPR沉默。H_2O_2存在下抗坏血酸盐还原柠檬酸铁的芬顿催化对羟基苯甲酸羟基化反应分三个阶段进行：第一阶段不依赖于O-2的存在，表现为非零截距，反映了积累的Fe ~（2+）与H_2O_2的快速反应;中间的氧依赖相符合一级产物积累，在有氧条件下k = 5 M-1 s（-1），在厌氧条件下k = 13 M-1 s（-1）; k = 5 x 10（-2）M-1 s（-1），在有氧和厌氧条件下。在有氧条件下的产品收率大于从铁的初始浓度预测，但它们小于预测的连续氧化还原循环中存在过量的抗坏血酸。羟基化产物的持续形成支持柠檬酸铁的缓慢氧化还原循环。因此，当H2 O2可用时，铁-柠檬酸盐复合物可能有助于铁超负荷疾病的病理生理学表现。
Iron in iron overload disease is present as non-transferrin-bound iron, consisting of iron, citrate, and albumin. We investigated the redox properties of iron citrate by electrochemistry, by the kinetics of its reaction with ascorbate, by ESR, and by analyzing the products of reactions of ascorbate with iron citrate complexes in the presence of H2O2 with 4-hydroxybenzoic acid as a reporter molecule for hydroxylation. We report -0.03 V < E degrees' > +0.01 V for the (Fe3+-cit/Fe2+-cit) couple. The first step in the reaction of iron citrate with ascorbate is the rapid formation of mixed complexes of iron with citrate and ascorbate, followed by slow reduction to Fe2+-citrate with k = ca. 3 M-1 s(-1). The ascorbyl radical is formed by iron citrate oxidation of Hasc(-) with k = ca. 0.02 M-1 s(-1); the majority of the ascorbyl radical formed is sequestered by complexation with iron and remains EPR silent. The hydroxylation of 4-hydroxybenzoic acid driven by the Fenton reduction of iron citrate by ascorbate in the presence of H2O2 proceeds in three phases: the first phase, which is independent of the presence of O-2, is revealed as a nonzero intercept that reflects the rapid reaction of accumulated Fe2+ with H2O2; the intermediate oxygen-dependent phase fits a first-order accumulation of product with k = 5 M-1 s(-1) under aerobic and k = 13 M-1 s(-1) under anaerobic conditions; the slope of the final linear phase is ca. k = 5 x 10(-2) M-1 s(-1) under both aerobic and anaerobic conditions. Product yields under aerobic conditions are greater than predicted from the initial concentration of iron, but they are less than predicted for continuous redox cycling in the presence of excess ascorbate. The ongoing formation of hydroxylated product supports slow redox cycling by iron citrate. Thus, when H2O2 is available, iron-citrate complexes may contribute to pathophysiological manifestations of iron overload diseases.