Egan T J, Barthakur S R, Aisen P
Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York 10461.
J Inorg Biochem. 1992 Dec;48(4):241-9. doi: 10.1016/0162-0134(92)84051-n.
To help settle controversy as to whether the chelating agent diethylenetriaminepentaacetate (DTPA) supports or prevents hydroxyl radical production by superoxide/hydrogen peroxide systems, we have reinvestigated the question by spectroscopic, kinetic, and thermodynamic analyses. Potassium superoxide in DMSO was found to reduce Fe(III)DTPA. The rate constant for autoxidation of Fe(II)DTPA was found (by electron paramagnetic resonance spectroscopy) to be 3.10 M-1 s-1, which leads to a predicted rate constant for reduction of Fe(III)DTPA by superoxide of 5.9 x 10(3) M-1 s-1 in aqueous solution. This reduction is a necessary requirement for catalytic production of hydroxyl radicals via the Fenton reaction and is confirmed by spin-trapping experiments using DMPO. In the presence of Fe(III)DTPA, the xanthine/xanthine oxidase system generates hydroxyl radicals. The reaction is inhibited by both superoxide dismutase and catalase (indicating that both superoxide and hydrogen peroxide are required for generation of HO.). The generation of hydroxyl radicals (rather than oxidation side-products of DMPO and DMPO adducts) is attested to by the trapping of alpha-hydroxethyl radicals in the presence of 9% ethanol. Generation of HO. upon reaction of H2O2 with Fe(II)DTPA (the Fenton reaction) can be inhibited by catalase, but not superoxide dismutase. The data strongly indicate that iron-DTPA can catalyze the Haber-Weiss reaction.
为了帮助解决关于螯合剂二乙烯三胺五乙酸（DTPA）是促进还是抑制超氧化物/过氧化氢体系产生羟基自由基的争议，我们通过光谱、动力学和热力学分析对该问题进行了重新研究。发现二甲基亚砜中的超氧化钾能还原Fe(III)DTPA。通过电子顺磁共振光谱法测得Fe(II)DTPA的自氧化速率常数为3.10 M-1 s-1，由此预测在水溶液中超氧化物还原Fe(III)DTPA的速率常数为5.9 x 10(3) M-1 s-1。这种还原是通过芬顿反应催化产生羟基自由基的必要条件，并通过使用DMPO的自旋捕获实验得到证实。在Fe(III)DTPA存在的情况下，黄嘌呤/黄嘌呤氧化酶体系会产生羟基自由基。该反应受到超氧化物歧化酶和过氧化氢酶的抑制（表明产生HO·需要超氧化物和过氧化氢两者）。在9%乙醇存在的情况下捕获α-羟乙基自由基证明了羟基自由基（而非DMPO的氧化副产物和DMPO加合物）的产生。过氧化氢与Fe(II)DTPA反应（芬顿反应）产生HO·可被过氧化氢酶抑制，但不能被超氧化物歧化酶抑制。这些数据有力地表明铁-DTPA可以催化哈伯-维伊斯反应。
