Kojic acid derivatives as powerful chelators for iron(III) and aluminium(III)

Two new ligands have been synthesized to investigate their possible use in chelation therapy for excess iron(III) and aluminium(III) pathologies. One ligand is derived from from two units of kojic acid and one of o-vanillin; the other is derived from two units of kojic acid and one of vanillin. For the ligands in solution, protonation constants have been determined by potentiometry, and standard reaction heats by calorimetry. Hydrogen bonding plays an important role in the protonation reactions. The crystal structures of both ligands have also been determined. Complexation constants for the iron complexes have been determined by combined potentiometry/spectrophotometry; those of aluminium by potentiometry alone. All complexes were found to contain two metal ions. The proposed reaction scheme was confirmed by NMR chemical shift measurements, NMR diffusion measurements, electrospray mass spectrometry and density functional theory calculations. Both ligands show considerable promise as therapeutic agents for the removal of excess iron and aluminium.