Synthesis of a new tetradentate chelator with 1-Hydoroxy-2(1H)-pyridinone (HOPO) as chelating unit: Interaction with Fe (III), solution thermodynamics and DFT studies

Abstract

1,2-Hydroxypyridinone (1,2-HOPO) forms very stable transition metal complexes that may be useful in various ways, among these the iron complexes have been long used for the treatment of iron overload diseases like β-Thalassemia. A new tetradentate chelator, 1-hydroxy-N-[3-[2-[2-[3-[(1-hydroxy-6-oxo-pyridine-2carbonyl)amino]propoxy]ethoxy]ethoxy]propyl]-6-oxo-pyridine-2-carboxamide (L) having two 1,2-HOPO units with long chain amine backbone has been synthesized and characterized through various techniques like TLC, solubility, melting point, FT-IR, 1H NMR, 13C NMR, ESI-MS, UV–Vis and emission spectroscopy. The protonation constants of the ligand were determined by both potentiometrically as well as spectrophotometrically in aqueous medium at 25° ±1 °C. The solution thermodynamics of the ligand its Fe(III) complexes in aqueous solution were also studied. The pKa values for ligand are found to be 7.34 and 6.06 and the formation constant of metal complex (M2L3) is found to be logβ230 = 42.45. To support the experimental data, theoretical calculation at DFT level of theory was done using GGA (Gradient Generalized Approximation) with BLYP functional and DZP basis set. The results of calculated thermodynamic properties suggest that, ΔG follows the same trend of protonation as determined by potentiometry and spectrophotometry. Studies of the DFT optimized structures of LH2, LH− shows that, there is π stacking interaction between the hydroxypyridinone rings in the species and the intramolecular π-stacking interaction decreases as the distance between two pyridine ring increases upon deprotonation and was found to be 2.7, 3.2 and 14.6 Å for LH2, LH− and L−2 respectively.