Design of clinically useful iron(III)‐selective chelators

Iron overload is a serious clinical condition which can be largely prevented by the use of iron‐specific chelating agents. Desferrioxamine‐B, the most widely used iron chelator in haematology over the past 30 years, has a major disadvantage of being orally inactive. Consequently, the successful design of an orally active, nontoxic, selective iron chelator has become a much sought after goal. In order to identify an ideal iron chelator for clinical use, a range of specifications must be considered such as metal selectivity and affinity, kinetic stability of the complex, bioavailability and toxicity. A wide range of chelator types bind iron(III) and of these, hexa‐, tri‐, and bidentate are capable of providing iron(III) with the favoured octahedral environment. In this review, the comparative properties of such ligands are discussed, examples being selected from hydroxamates, aminocarboxylates, hydroxypyridinones, orthosubstituted phenols and triazoles. © 2001 John Wiley & Sons, Inc. Med Res Rev, 22, No. 1, 26–64, 2002