Variability of the Fenton reaction characteristics of the EDTA, DTPA, and citrate complexes of iron

The common metal chelation agents, DTPA and EDTA are often used as models for physiological low-molecular weight iron complexes in biochemical studies, or for common biochemical protocols. In the biochemical literature there are apparent conflicts as to whether EDTA and DTPA are pro-oxidant or antioxidant additives. This apparent conflict is puzzling since in chemical systems Fe^IIEDTA and Fe^IIDTPA are well known Fenton reaction reagents. In this investigation we examined the voltammetric characteristics of the iron complexes of EDTA, DTPA, and citrate and the effect of the ligand:metal ratio (L:M) on the electrocatalytic (EC') waves that result from reduction of H₂O₂ by this complex. At a ratio of 1:1, the cyclic voltammetric waves of the complexes indicate the presence of a reversible species corresponding to the Fe^II/IIIL couple, along with a second irreversible reduction peak. The second irreversible voltammetric peak decreases at higher L:M ratios for EDTA and citrate. The 1:1 iron complexes of EDTA, DTPA, and citrate clearly induce the catalytic reduction of H₂O₂. In the presence of a greater than 100 fold excess of H₂O₂ relative to iron, higher L:M ratios greatly reduced the catalytic EC' wave compared to the 1:1 ratios. At H₂O₂:Fe ratios less than 50, the L:M ratio has very little effect of the EC' current. These observations may explain the apparent discrepancies in the biochemical literature. Addition of EDTA or DTPA may enhance oxidative processes if the L:M is low (less than unity), whereas rates of on-going oxidative processes may decrease if that ratio, along with the relative amount of H₂O₂, are both high (excess ligand). The impact of this study is of particular importance given the widespread use of these ligands in biochemical studies.