Evaluation of 3,4-Hydroxypyridinecarboxylic acids as possible bidentate chelating agents for aluminium(III): synthesis and metal-ligand solution chemistry

In view of a possible application to aluminium(III) chelation therapy, 3-hydroxy-4-pyridinecarboxylic acid (3H4P) and 4-hydroxy-3-pyridinecarboxylic acid (4H3P) were synthesised, and their chemical interactions with the metal were investigated in aqueous 0.6 m (Na)Cl at 25 °C by means of potentiometric titrations. Only mononuclear complexes of type AlLlHh (l = 1, 2 and 3; h = 0, 1, ..., l) were formed. The qualitative and quantitative results obtained were confirmed by UV-spectrophotometry and 1H NMR spectroscopy. The efficiencies of the ligands to chelate aluminium(III) were evaluated at physiological pH and ion strength “in vitro”, together with the n-octanol/water distribution coefficients of the free ligands and of the ligand-metal complexes. The results suggest 3H4P and 4H3P lack sufficient chelation efficacy to be proposed as chelation therapy agents for aluminium(III). However, the results do suggest a strategy for the synthesis of more promising compounds.