Gallium (III), Indium (III) and Iron (III) complexes of phenolic analogs of ethylenediaminetetraacetic acid

Abstract

Equilibrium studies of four new sexadentate ligands, N,N'-bis-(2-hydroxy-5-sulfobenzyl)disodium ethylenediamine-N,N'-diacetic acid (SHBED), N,N'-bis(2-hydroxybenzyl)ethylenediamine-N,N'-bis(methylenephosphonic acid monomethyl ester) (HBEDPOMe), N,N'-bis(2-hydroxybenzyl)ethylenediamine-N,N'-bis(methylenephosphonic acid monoethyl ester) (HBEDPOEt), and N,N'-bispyridoxylethylenediamine-N,N'-diacetic acid (PLED), are described. These ligands have two phenolate donor groups which impart specificity for trivalent metal ions such as those of Ga(III), In(III) and Fe(III). Potentiometric and spectrophotometric studies of the protonation constants of the ligands and stability constants of their Cu(II), Ni(II), Co(II), Zn(II) , Ga(III), In(III) and Fe(III) chelates are compared with those of analogous ligands, such as N,N'-ethylenebis-{2-(o-hydroxyphenyl)}-glycine (EHPG), N,N'-bis(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid (HBED) and N,N'-bis(2-hydroxybenzyl)ethylenediamine-N,N'-bis(methylenephosphonic) acid (HBEDPO). Comparisons of the affinities of all the ligands described above with those of human serum protein transferrin for Ga(III), In(III) and Fe(III) show that these ligands may compete successfully in vivo with transferrin for these metal ions.The binding of the ligand donor groups to the metal ions, as the pH is increased, occurs in several cases in a stepwise fashion, with the more basic phenolate groups requiring higher pH for activation. The order in which each phenolate group becomes coordinated to metal ions, and the coordinate bonding modes of the intermediate complexes, are deduced by correlating the potentiometric data with the electronic absorption spectra and nuclear magnetic resonance spectra.