Studies on the redox activity of iron N,O-complexes: Potential T1-contrast agents

Abstract

Objectives: The goal of this study was to determine the redox activity of iron (ethylenebis[2-(o-hydroxyphenyl)glycine]) (EHPG) and (ethylenebis[2-(o-hydroxybenzyl)glycine]) (EHBG) (N,N′-bis(2-hydroxybenzyl)ethylenediamine-N,N′-diacetic acid) derivative complexes and of some N,O–salan complexes of iron. The hexadentate chelate (EHPG and EHBG) ligands varied in their substituents (polar OMe, NHAc, or lipophilic Ph), while the latter had different charge and lipophilicity. The low redox activity of these complexes is important in their potential applications as magnetic resonance imaging contrast agents.Methods: Redox activity was assessed in the entire Haber–Weiss cycle and separately in the Fenton reaction. The spin-trapping method with 5,5-dimethyl-1-pyrroline-N-oxide monitored in electron paramagnetic resonance was used. The standard Mn marker was applied as a reference for quantitative analysis. Additionally, ascorbate oxidation was analyzed with UV–Vis spectrophotometry.Results: Both the Haber–Weiss cycle and in particular the Fenton reaction showed low redox activity of the studied complexes, which did not exceed 30% of [Fe(EDTA)]− or FeCl3 activity. The N,O–salan complexes expressed even lower activity, i.e. 10–20% activity of [Fe(EDTA)]−.Discussion: For the EHPG and EHBG complexes, it is likely that hydrophobicity and the possibility of H-bond formation play a major role in the resulting redox effects. For this reason, chelates equipped with phenyl groups in the majority belong to less redox-active complexes. For N,O–salan complexes, activity is not correlated with the charge of the coordination sphere, but again, the highly hydrophobic character of the groups and the non-pendant substituents capable of H-bonding that are present in these ligands limit the affinity of hydrophilic species.