Iron-catalyzed hydroxyl radical formation. Stringent requirement for free iron coordination site.

TLDR

Iron catalyzes the formation of reactive oxygen species in biological systems, a process well documented in the literature. This study tests whether iron‑catalyzed hydroxyl radical production from superoxide and hydrogen peroxide requires an open or water‑bound coordination site on iron. The authors measured catalytic activity of 12 iron chelates using hypoxanthine/xanthine oxidase to generate superoxide and assessed coordinated water via UV‑visible spectroscopy and 1H NMR relaxation. Only chelates lacking coordinated water—Fe³⁺ with DTPA, EDTA‑di(o‑hydroxyphenylacetic acid), phytate, and Desferal—failed to generate hydroxyl radicals, demonstrating that an available coordination site is essential for the Fenton reaction and informing chelator design for oxidative damage control.

Abstract

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.