Voltammetric studies of Zn and Fe complexes of EDTA: evidence for the push mechanism.

The 'push' hypothesis for the antioxidant action of Zn2+ is based on its displacement of iron from a low molecular weight pro-oxidant complex. In this study, the chemical plausibility of that proposed function is investigated by cyclic voltammetry. As a model for a pro-oxidative low molecular weight iron complex the Fe(II/III)/EDTA couple was examined. This complex was selected for its well-defined electrochemical, iron stability constants, and similarity to other low molecular weight chelates in physiological fluids in terms of logical binding sites, i.e. amino, and carboxylate groups. Also investigated were iron complexes of nitrilotriacetic acid and DL-glutamic acid. Results demonstrate that approximately 90% of the cyclic voltammetric peak current for Fe(III)EDTA reduction and the EC' current for the mediated reduction of H2O2 by Fe(II/III)EDTA (Fenton Reaction) are lost when Zn2+ is introduced to a 1:1 molar ratio relative to iron. All experiments were conducted in HEPES buffered solutions at pH 7.4. Iron (II/III) complexes of nitrilotriacetic acid and DL-glutamic acid followed the same trends. Cyclic voltammetric experiments indicate that Zn2+ displaces Fe(III) from EDTA despite the much larger stability constant for the iron complex (10(25.1)) versus zinc (10(16.50)). The hydrolysis aided displacement of Fe(III) from EDTA by Zn2+ is considered by the equilibria modeling program, HySS. With Fe(III) hydrolysis products included, Zn2+ is able to achieve 90% displacement of iron from EDTA, a result consistent with cyclic voltammetric observations.