Proton-Assisted Air Oxidation Mechanisms of Iron(II) bis-Thiosemicarbazone Complexes at Physiological pH: a Kinetico-Mechanistic Study

Abstract

The kinetics of oxidation for different biologically-active FeII bis-thiosemicarbazone complexes in water at varying dioxygen concentration, temperature, pressure, and pH has been monitored. The oxidation reactions observed can be resolved as a single-step process, producing the expected ferric complex, with rates increasing with decreasing pH. From the pH-dependence of the observed rate constants, a rate law with two terms can be derived, one of them being independent of the acid concentration and the other one showing a saturation behaviour with respect to [H+]. Those results indicate the existence of two parallel pathways for oxidation; the acid-independent pathway is only operative for the complexes with ligands bearing terminal, non-coordinated, unsubstituted amines, whereas the term with a [H+]-limiting kinetic behaviour is observed for all the complexes and indicates that the reacting species has to be protonated prior to the oxidation step. From the data collected, the rate law and the thermal and pressure activation parameters have been used to interpret the operating reaction mechanisms. DFT calculations have been also carried out in order to explain the empirical trends, and the results suggest the possibility of formation under steady-state conditions of FeIII superoxo and hydroperoxo intermediates. The kinetics of reaction with hydrogen peroxide has been also studied and it was found to show a complex behaviour, involving a variety of processes, which include ligand oxidation to semicarbazones and photochemical reactions (both on the ferrous and ferric complexes). When the illumination of the sample is limited to wavelengths within the 500-800 nm range, a simpler reactivity pattern is observed. It is clear that a rather complex combination of different mechanisms are actuating for the oxidation reaction with hydrogen peroxide.