| Abstract: | 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. |
