Hydroxypyrones, an intriguing family of chelating agents for Fe(III) and Al(III)

With the aim to design new chelators for the clinical treatment of different diseases depending on overload of trivalent metal ions Fe(III) and Al(III), we presented the equilibria between these two metal ions and kojic acid, and three its derivatives. Potentiometric and spectrophotometric techniques for iron, and potentiometry and H-1 NMR for aluminium were used, supported by X-ray, electrospray ionization-mass spectrometry (ESI-MS), calorimetry and quantum chemical calculations. Evidence was given of the formation of ML, ML2, and ML3 complexes of both metal ions with kojic acid, confirmed by the X-ray structure of the FeL3 complex, and of variously protonated M2L2 and MeL2 complexes for all the three derivatives. The extremely good pFe value for these ligands gives confidence to, and opens perspectives for, the search of new kojic acid derivatives. In this paper we present the synthesis of four new derivatives characterized by a longer linker, and the study of their acid-base properties based on potentiometric, spectrophotometric and H-1 NMR measurements