A New hydroxypyrone powerful chelator: from synthesis to Al^III, Fe^III, Cu^II and Zn^II complex formation equilibria, and structural characterization

In the frame of our research interest on kojic acid derivatives as powerful chelators for the trivalent iron and aluminium cations [1-4], we have designed, synthesized, and characterized the new ligand 6,6'-(((2-(diethylamino)ethyl)azanediyl)bis(methylene))bis(5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one), L9. In this communication will be present the study on protonation constants and on the complex formation equilibria with iron and aluminium and with the bivalent essential metal ions, zinc and copper. X-ray structures of the ligand and of some of its metal complexes will be also presented

A New bis-3-hydroxy-4-pyrone as a potential therapeutic iron chelating agent: effect of connecting and side chains on the complex structures and metal ion selectivity

This work reports the synthesis, characterization and study of complex formation equilibria of the new ligand 6,6′-(2-(diethylamino)ethylazanediyl)bis(methylene)bis(5-hydroxy-2-hydroxymethyl-4H-pyran-4-one) with FeIII, AlIII, CuII and ZnII. On the basis of previous encouraging results with tetradentate bis-kojic acid chelators, this ligand was designed to improve the pharmacokinetic properties: increase the solubility, neutral at physiological pH 7.4, and enhancement of membrane crossing ability. FeIII and AlIII complexation gave evidence of high metal-sequestering capacity of L9. Cellular assays showed that the ligand is capable of crossing cellular membranes and it does not present toxic effects. Complex formation equilibria with the essential metal ions CuII and ZnII have been furthermore studied to evaluate disturbances of this chelator on the homeostatic equilibria of these essential metal ions. A variety of techniques (potentiometry, UV–visible spectrophotometry, 1D and 2D NMR spectroscopy, ESI–MS (electrospray ionization–mass spectrometry), quantum mechanical calculations and X-ray diffraction) have facilitated the characterization of the ligand, and the corresponding iron and zinc complexes, together with an exhaustive analysis of the protonation and complex equilibria