A Multi-Technique Investigation of the Complex Formation Equilibria between Bis-Deferiprone Derivatives and Oxidovanadium (IV)

Abstract

The increasing biomedical interest in high-stability oxidovanadium(IV) complexes with hydroxypyridinone ligands leads us to investigate the complex formation equilibria of V^IVO²⁺ ion with a tetradentate ligand, named KC21, which contains two 3-hydroxy-1,2-dimethylpyridin-4(1H)-one (deferiprone) moieties, and with the simple bidentate ligand that constitutes the basic unit of KC21, for comparison, named L5. These equilibrium studies were conducted with joined potentiometric-spectrophotometric titrations, and the results were substantiated with EPR measurements at variable pH values. This multi-technique study gave evidence of the formation of an extremely stable 1:1 complex between KC21 and oxidovanadium(IV) at a physiological pH, which could find promising pharmacological applications.

Keywords: EPR spectroscopy; UV spectrophotometry; deferiprone; oxidovanadium (IV); potentiometry.

Figure 1

Chemical structures of the ligands KC21, L5 and DFP.

Figure 2

Speciation plot of L5 ligand calculated with HySS [22] according to the protonation constants in Table 1.

Figure 3

Calculated molar absorptivity spectra of the differently protonated forms of L5 (A) and KC21 (B) ligands.

Figure 4

Speciation plots of V^IVO²⁺-ligand systems calculated with HySS program [22]. Top: UV–spectrophotometric titration conditions, 1:2 V^IVO²⁺:ligand molar ratio and ligand concentration 3 × 10⁻⁴ M and 5 × 10⁻⁴ M, respectively, for L5 and KC21, (A) L5, (B) KC21. Bottom: EPR measurements conditions, 1:2 and 1:1 V^IVO²⁺:ligand molar ratio, respectively, for L5 and KC21 at V^IVO²⁺ concentration 2 × 10⁻³ M, (C) L5, (D) KC21. Charges are omitted for simplicity.

Figure 5

Calculated molar absorptivity spectra of differently protonated forms of V^IVO²⁺ complexes with L5 (A) and KC21 (B) ligands.

Figure 6

High field region of the anisotropic X-band EPR spectra, at increasing pH, of V^IVO²⁺-L5 system at 1:2 V^IVO²⁺:ligand molar ratio (A) and V^IVO²⁺-KC21 system at 1:1 V^IVO²⁺:ligand molar ratio (B). V^IVO²⁺ concentration is 2 × 10⁻³ M.

Figure 7

Molecular drawings of the V^IVO²⁺ species with the ligand KC21 based on the solution studies.