NEW SYNTHETIC, SELECTIVE, HIGH-AFFINITY LIGANDS FOR EFFECTIVE TRIVALENT METAL-ION BINDING AND TRANSPORT

A series of new ligands containing 3-hydroxy-2-pyridylmethyl donor groups has been synthesized which form complexes of iron(III) having thermodynamic stabilities comparable to and greater than those of natural catecholtype siderophores. When this functional group is substituted on the triazacyclononane framework the resulting hexadentate ligand has an affinity for iron(III) which exceeds that of the natural siderophore, enterobactin, at physiological pH. Ethylenediamine and diethylenetriamine derivatives containing hydroxypyridyl and acetate donors also show high affinity for Fe(III) and other trivalent metal ions. The stabilities of the iron(III) chelates of the new ligands, particularly the triazacyclononane derivatives, are compared with those of other highly effective iron chelators published in the literature, such as the trishydroxamates and triscatecholate ligands.