Iron(III) and aluminum(III) complexes with hydroxypyrone ligands aimed to design kojic acid derivatives with new perspectives

With the aim to design new chelators for the clinical treatment of different diseases involving the trivalent metal ions Fe(III) and AI(III), we present the equilibria of kojic acid and its derivative 6-[5-hydroxy-2-hydroxymethyl-pyran-4-one]-5-hydroxy-2-hydroxymethyl-pyra n-4-one with these two metal ions. Potentiometric and spectrophotometric techniques for iron, and potentiometry and H-1 NMR for aluminum were used, supported by X-ray, electrospray ionization-mass spectrometry (ESI-MS), calorimetry and quantum chemical calculations. In this work, evidence is given on the formation of MeL, MeL2, and MeL3 complexes of both metal ions with kojic acid, confirmed by the X-ray structure of the FeL3 complex, and of variously protonated Me2L2 and MeL2 complexes of 6-[5-hydroxy-2-hydroxymethyl-pyran-4-one]-5-hydroxy-2-hydroxymethyl-pyra n-4-one. The extremely good pFe value for this second ligand gives confidence to, and opens perspectives for, the search of new kojic acid derivatives

Iron III and aluminium III complexes with substituted salicyl-aldehydes and salicylic acids

The chelating properties toward ironIII and aluminium III of variously substituted salicyl-aldehydes and salicylic acids have been evaluated, together with the effect of methoxy and nitro substituents in ortho and para position with respect to the phenolic group. The protonation and iron and aluminium complex formation equilibria have been studied by potentiometry, UV-visible spectrophotometry and 1H NMR spectroscopy. The overall results highlight that salicyl-aldehydes present good chelating properties toward ironIII, with pFe ranging from 14.2 with nitro to 15.7 with methoxy substituent, being ineffective toward aluminium; the pFe values for salicylic acids are generally lower than those for salicyl-aldehydes, and about 4 units higher than the corresponding pAl values. The effect of the two substituents on the chelating properties of the ligands can be rationalized in terms of the Swain-Lupton treatment which accounts for the field and resonance effects. The structural characterization of the 1:2 iron complex with p-nitro salicylic acid shows that ironIII ion exhibits an octahedral surrounding where two salicylate chelating ligands supply two O-phenolate and two O-carboxylate donor atoms in a roughly equatorial plane. The trans-apical sites are occupied by two aqua ligands

Searching for new aluminium chelating agents: a family of hydroxypyrone ligands

Attention is devoted to the role of chelating agents in the treatment of aluminium related diseases. In fact, in spite of the efforts that have drastically reduced the occurrence of aluminium dialysis diseases, they so far constitute a cause of great medical concern. The use of chelating agents for iron and aluminium in different clinical applications has found increasing attention in the last thirty years. With the aim of designing new chelators, we synthesized a series of kojic acid derivatives containing two kojic units joined by different linkers. A huge advantage of these molecules is that they are cheap and easy to produce. Previous works on complex formation equilibria of a first group of these ligands with iron and aluminium highlighted extremely good pMe values and gave evidence of the ability to scavenge iron from inside cells. On these bases a second set of bis-kojic ligands, whose linkers between the kojic chelating moieties are differentiated both in terms of type and size, has been designed, synthesized and characterized. The aluminiumIII complex formation equilibria studied by potentiometry, electrospray ionization mass spectroscopy (ESI-MS), quantum-mechanical calculations and 1H NMR spectroscopy are here described and discussed, and the structural characterization of one of these new ligands is presented. The in vivo studies show that these new bis-kojic derivatives induce faster clearance from main organs as compared with the monomeric analog