The fenton activity of iron(III) in the presence of deferiprone.
Hydroxyl radical production from a range of clinically relevant iron chelators in the presence of hydrogen peroxide was measured using the deoxyribose oxidation assay. Hydroxyl radical production from an iron complex is dependent on whether the ligand is able to completely surround the iron, thereby preventing access of reductants to the coordinated iron cation. The partially coordinated [(deferiprone)(2)Fe(III)](+) complex is able to generate hydroxyl radicals in the presence of oxidants, whereas the fully coordinated [(deferiprone)(3)Fe(III)](0) complex is not. Hydroxyl radical production from iron(III)deferiprone complexes is dependent on the molar ratio of iron to deferiprone, which, in turn, affects the speciation of the complex. Mass spectrometry data have confirmed the presence of the [(deferiprone)(2)Fe(III)](+) complex in aqueous solution. Hydroxyl radical production from the [(deferiprone)(2)Fe(III)](+) complex is maximal in the presence of equimolar ascorbate and hydrogen peroxide and is abolished in the absence of hydrogen peroxide. Under biological conditions, any [(deferiprone)(2)Fe(III)](+) complex formed intracellularly will be rapidly reduced by ascorbate. The resulting unstable iron(II) complex will dissociate to hexa-aquo iron(II), a major component of the endogenous intracellular labile iron pool.
Devanur
Lakshmi D
LD
Division of Pharmaceutical Sciences, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK. lakshmi.devanur@kcl.ac.uk
Neubert
Hendrik
H
Hider
Robert C
RC
D001205:Ascorbic Acid / Q000494:pharmacology; D000077543:Deferiprone; D004492:Edetic Acid / Q000737:chemistry; D006861:Hydrogen Peroxide / Q000737:chemistry* / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000737:chemistry; D007501:Iron / Q000737:chemistry*; D007502:Iron Chelating Agents / Q000737:chemistry*; D010084:Oxidation-Reduction; D011728:Pyridones / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization
C045076:Fenton's reagent; D007502:Iron Chelating Agents; D011728:Pyridones; D000077543:Deferiprone; D017665:Hydroxyl Radical; D004492:Edetic Acid; D006861:Hydrogen Peroxide; D007501:Iron; D001205:Ascorbic Acid