Evaluation of 1-methyl-3,4-hydroxypyridinecarboxylic acids as possible bidentate chelating agents for iron(III): Metal–ligand solution chemistry

The chemical interactions of 1-methyl-3-hydroxy-4-pyridinecarboxylic acid (1M3H4P) and 1-methyl-4-hydroxy-3-pyridinecarboxylic acid (1M4H3P) with Fe(III) were investigated in aqueous 0.6 m (Na)Cl at 25 °C by means of potentiometric titrations and UV–Vis spectrophotometry. A large number of complexes were formed in solution with stoichiometry FeLxHy, x = 1, 2, 3 and y = 0, −1, −2. In view of a possible application to Fe(III) chelation therapy, the efficiencies of the ligands to chelate the metal ion were evaluated in vitro at physiological pH. 1M3H4P and 1M4H3P show a lower complexation efficiency with Fe(III) than that of other available chelators, but higher than that of their non-methylated analogs 3H4P and 4H3P.

Graphical abstractThe aqueous solution chemistry of Fe(III)/1-methyl-3-hydroxy-4-pyridinecarboxylic acid and Fe(III)/1-methyl-4-hydroxy-3-pyridinecarboxylic acid was studied by potentiometry and UV–Vis. Thermodynamic results were supplemented by chelation efficiency measurements. The two ligands show a lower efficiency with Fe(III) than that of available chelators, but higher than that of their non-methylated analogs 3-hydroxy-4-pyridinecarboxylic acid and 4-hydroxy-3-pyridinecarboxylic acid.Figure optionsDownload full-size imageDownload as PowerPoint slide