110981-89-0Relevant academic research and scientific papers
Complex formation of ICL670 and related ligands with FeIII and FeII
Steinhauser, Stefan,Heinz, Uwe,Bartholomae, Mark,Weyliermueller, Thomas,Nick, Hanspeter,Hegetschweiler, Kaspar
, p. 4177 - 4192 (2004)
Complex formation of 4-[3,5-bis(2-hydroxyphenyl)-1,2,4-triazol-1-yl]benzoic acid (ICL670, H3Lx), 4-[3,5-bis(2-hydroxyphenyl)-1,2,4- triazol-1-yl]benzosulfonic acid (H3Ly), and 3,5-bis(2-hydroxyphenyl)-1-phenyl-1,2,4-triazole (H2Lz) with Fe3+ and Fe2+ was investigated in H2O and in H2O/DMSO mixtures by potentiometry, spectrophotometry and cyclic voltammetry. ICL670 has previously been considered as a promising drug for an oral treatment of iron overload. In this paper, the stability and redox properties of the various FeII and FeIII complexes were elucidated with a particular focus on their potential involvement in the generation of oxidative stress. The overall stability constants of [Fe III(Lx)] and [FeIII(Lx) 2]3- (25 °C, 0.1 M KCl in H2O) are log β1 = 22.0 and log β2 = 36.9, respectively. The affinity of these ligands for Fe2+ is remarkably poor. In particular, the 1:2 complexes [FeIII(Lx)2]4- and [FeII(Ly)2]4- were found to be less stable. As a consequence, the redox chemistry of the [Fe III(Lx)]/[FeII(Lx)]- and the [FeIII(Lx)2]3-/[Fe II(Lx)2]4- couples differs significantly. [FeIII(Lx)2]3- is a very weak oxidizing agent (E1/2 is approximately -0.6 V versus NHE) and reduction of [FeIII(Lx)2]3- is not anticipated under physiological conditions. The reduction potential of the [FeIII(Lx)]/[FeII(Lx)]- couple is considerably less negative and was estimated to be +0.1 V (versus NHE). The possible roles of the various Fe complexes as catalysts for the Fenton reaction in biological media are discussed. The crystal structures of H 3LX, Na[Fe(Lz)2]·4EtOH, Na[Al(Lz)2]· 4EtOH, and [Cu(Lz) (pyridine)]2 were investigated by single-crystal X-ray diffraction, and the possible influence of the particular steric requirements of these ligands on the stability of the metal complexes has been analyzed. ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004).
