Chelation therapy: evaluation of the coordination ability of bis-kojic and hydroxypyridinone derivative ligands towards Cd(II) ions via NMR spectroscopy

The soft acid CdII is an accumulative toxic metal ion which is able to substitute for the essential borderline ZnII ion in many zinc enzymes. Nuclear magnetic resonance (NMR) spectroscopy was used to assess the coordination ability of two ligands, an amine-bearing bis-kojic acid: 6'-(2-(diethylamino)ethylazanediyl)bis(methylene)bis(5-hydroxy-2-hydroxymethyl-4H-pyran-4-one) [1,2] and a hydroxypiridinone derivative: 5-hydroxy-2-(hydroxymethyl)pyridin-4(1H)-one [3], for their use as potential chelating molecules towards CdII ions in detoxification treatments. A combination of 1D, 2D total correlation spectroscopy (TOCSY), heteronuclear single quantum coherence spectroscopy (HSQC) and rotating-frame Overhauser effect spectroscopy (ROESY) experiments was used to assign the signals of both free and metal-bound ligands, as previously reported for similar systems [4-6]. The metal-ligand system was studied at physiological pH and different temperature values. Competition experiments with essential ZnII ions were also performed.