Details

Autor(en) / Beteiligte

• Koppenol, W.H.
• Hider, R.H.

Titel

Iron and redox cycling. Do's and don'ts

Ist Teil von

• Free radical biology & medicine, 2019-03, Vol.133, p.3-10

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• A major form of toxicity arises from the ability of iron to redox cycle, that is, to accept an electron from a reducing compound and to pass it on to H2O2 (the Fenton reaction). In order to do so, iron must be suitably complexed to avoid formation of Fe2O3. The ligands determine the electrode potential; this information should be known before experiments are carried out. Only one-electron transfer reactions are likely to be significant; thus two-electron potentials should not be used to determine whether an iron(III) complex can be reduced or oxidized. Ascorbate is the relevant reducing agent in blood serum, which means that iron toxicity in this compartment arises from the ascorbate-driven Fenton reaction. In the cytosol, an iron(II)-glutathione complex is likely to be the low-molecular weight iron complex involved in toxicity. When physiologically relevant concentrations are used the window of redox opportunity ranges from +0.1 V to +0.9 V. The electrode potential for non-transferrin-bound iron in the form of iron citrate is close to 0 V and the reduction of iron(III) citrate by ascorbate is slow. The clinically utilised chelators desferrioxamine, deferiprone and deferasirox in each case render iron complexes with large negative electrode potentials, thus being effective in preventing iron redox cycling and the associated toxicity resulting from such activity. There is still uncertainty about the product of the Fenton reaction, HO• or FeO2+. [Display omitted] •There is no free Fe3+.•The window of redox opportunity ranges from +0.1 V to +0.9 V.•The pKa of Fe(H2O)62+ is 6.8.•HO• may be the main, but not the only, product of the Fenton reaction.•Do not use 2-electron potentials when deciding what could reduce Fe3+.