The autoxidation of iron(II) in aqueous systems: the effects of iron chelation by physiological, non-physiological and therapeutic chelators on the generation of reactive oxygen species and the inducement of biomolecular damage

Abstract

The ability of various iron(II)-complexes of biological, clinical and chemical interest to reduce molecular oxygen to reactive oxy-radicals has been investigated using complementary oxygen-uptake studies and e.s.r. techniques. It is demonstrated that although the rate of oxygen reduction by a given iron complex is directly related to its redox potential [thus complexes with low values of E0 for the Fe(III)/Fe(II) couple are the most effective reductants of oxygen], the overall ability of an iron(II) complex to induce oxidative biomolecular damage is also determined by its ability to undergo redox-cycling reactions with reducing radicals formed following the reaction of hydroxyl radicals with organic substrates present in the system (e.g. metal-ion chelators and organic buffers). Evidence is presented to suggest that the "Good" buffer MOPS forms a reducing radical following attack by .OH, and hence encourages the autoxidation of iron with the generation of oxy-radicals (as also observed for some of the chelates studied); this may have important implications for the use of such buffers in free-radical studies.