The iron complex of Dp44mT is redox-active and induces hydroxyl radical formation - an EPR study

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Patric J Jansson, Clare L Hawkins, David B Lovejoy, Des R Richardson

Iron chelation therapy was initially designed to alleviate the toxic effects of excess iron evident in iron-overload diseases. However, some iron chelator-metal complexes have also gained interest due to their high redox activity and toxicological properties that have potential for cancer chemotherapy. This communication addresses the conflicting results published recently on the ability of the iron chelator, Dp44mT, to induce hydroxyl radical formation upon complexation with iron (B.B. Hasinoff and D. Patel, J Inorg. Biochem.103 (2009), 1093-1101). This previous study used EPR spin-trapping to show that Dp44mT-iron complexes were not able to generate hydroxyl radicals. Here, we demonstrate the opposite by using the same technique under very similar conditions to show the Dp44mT-iron complex is indeed redox-active and induces hydroxyl radical formation. This was studied directly in an iron(II)/H(2)O(2) reaction system or using a reducing iron(III)/ascorbate system implementing several different buffers at pH 7.4. The demonstration by EPR that the Dp44mT-iron complex is redox-active confirms our previous studies using cyclic voltammetry, ascorbate oxidation, benzoate hydroxylation and a plasmid DNA strand-break assay. We discuss the relevance of the redox activity to the biological effects of Dp44mT.

Original languageEnglish
JournalJournal of Inorganic Biochemistry
Volume104
Issue number11
Pages (from-to)1224-8
Number of pages5
ISSN0162-0134
DOIs
Publication statusPublished - Nov 2010
Externally publishedYes

    Research areas

  • Ascorbic Acid, Buffers, DNA Damage, Electron Spin Resonance Spectroscopy, Hydrogen-Ion Concentration, Hydroxyl Radical, Iron, Iron Chelating Agents, Iron Overload, Iron, Dietary, Oxidation-Reduction, Thiosemicarbazones, Journal Article, Research Support, Non-U.S. Gov't

ID: 174497472