Graf E, Mahoney J R, Bryant R G, Eaton J W
J Biol Chem. 1984 Mar 25;259(6):3620-4.
The catalysis by iron of the formation of reactive oxygen species in biological systems has been well documented. In this present study, we have investigated the hypothesis that iron-catalyzed formation of hydroxyl radical (.OH) from superoxide anion radical (O-.2) and H2O2 requires the availability of at least one iron coordination site that is open or occupied by a readily dissociable ligand such as water. This hypothesis was tested by measuring the catalytic activity of 12 different iron chelates using hypoxanthine and xanthine oxidase to generate O-.2. In these same chelates, we also determined the presence or absence of coordinated water by UV-visible spectroscopy and 1H NMR relaxation measurements. Of all chelates tested, only Fe3+ coordinated to diethylenetriamine pentaacetic acid; ethylenediamine di(o-hydroxyphenylacetic acid), phytate, and Desferal lacked coordination water; and only these four complexes failed to produce hydroxyl radical. Separate determinations of the two redox half-reactions involved (i.e. Fe3+ + O-.2----Fe2+ + O2 and Fe2+ + H2O2----Fe3+ + .OH + OH-) indicate that an available coordination site is necessary for the latter (Fenton) reaction. This principle governing iron reactivity may help advance our understanding of the mechanism of oxidative damage in biological systems and may also permit the design of more effective chelators for the control of iron in biological systems.
铁在生物系统中催化活性氧形成的现象已有充分记载。在本研究中，我们探讨了这样一个假说：铁催化超氧阴离子自由基（O₂⁻）和H₂O₂形成羟基自由基（·OH）需要至少有一个铁配位位点，该位点未被占据或被诸如水等易于解离的配体占据。通过使用次黄嘌呤和黄嘌呤氧化酶产生O₂⁻来测量12种不同铁螯合物的催化活性，对该假说进行了验证。在这些相同的螯合物中，我们还通过紫外可见光谱和¹H NMR弛豫测量确定了配位水的存在与否。在所有测试的螯合物中，只有与二乙三胺五乙酸配位的Fe³⁺；乙二胺二（邻羟基苯乙酸）、肌醇六磷酸和去铁胺缺乏配位水；并且只有这四种配合物未能产生羟基自由基。对所涉及的两个氧化还原半反应（即Fe³⁺ + O₂⁻→Fe²⁺ + O₂和Fe²⁺ + H₂O₂→Fe³⁺ + ·OH + OH⁻）的单独测定表明，一个可用的配位位点对于后者（芬顿）反应是必要的。这一控制铁反应性的原理可能有助于推进我们对生物系统中氧化损伤机制的理解，也可能有助于设计更有效的螯合剂来控制生物系统中的铁。
