Release of iron from ferritin by aceto- and benzohydroxamic acids

Abstract

The release of iron from ferritin by aceto- and benzohydroxamic acids was studied at two different iron chelator concentrations (100 and 10 mM), at two pH values (7.4 and 5.2), and in the presence or absence of urea. Collectively, the results demonstrate that both aceto- and benzohydroxamic acids remove iron from ferritin. Aceto- and benzohydroxamic acids penetrate the ferritin shell and react directly with the iron core of the ferritin cavity probably forming mono(hydroxamate) iron(III) complexes which exit ferritin and react with the excess hydroxamate in the solution to produce bis(hydroxamate) iron(III) complexes. The sizes of both the benzohydroxamic acid and the mono(benzohydroxamate) iron(III) complex, 6 and 7 Å, respectively, are larger than that of the ferritin channels which indicates the flexibility of the channels to allow the entry and exit of these molecules. The size of the hydroxamic acid influenced the effectiveness of the iron release from ferritin following the expected trend with smaller iron chelators showing greater effectiveness. Likewise, the percentage of iron removed from ferritin was pH-dependent; the percentage of iron removed at pH 5.2 was greater than that at pH 7.4. Finally, the presence of urea, capable of opening the ferritin channels, dramatically increased the effectiveness of the iron chelator in removing iron from ferritin, especially at pH 7.4. © 2005 American Chemical Society.