Study of the oxidation products of the VO(dmpp) 2 complex in aqueous solution under aerobic conditions: comparison with the vanadate–dmpp system

Abstract

The redox behavior of the potential oral insulin mimetic compound bis[3-hydroxy-1,2-dimethyl-4-pyridinonate]oxovanadium(IV), VO(dmpp) 2, was studied in aqueous solution, under aerobic conditions and at different pH values and metal-to-ligand ratios, as well as the speciation of its V(V) oxidation products. Dissolution of this compound in water originates a violet solution with pH 4.7, which is partially oxidized to two V(V) species, VO 2L and [VO 2L 2] −, detected through their 51V NMR signals at −485 and −504 ppm. However, the VO(dmpp) 2 compound still remains to some extent in solution, as confirmed by EPR Spectroscopy. High pH values favor the oxidation of the V(IV) complex in solution, whereas at low pH the V(IV) species are predominant. Aqueous solutions containing vanadate–Hdmpp mixtures spontaneously yield V(IV) species, reflecting the reducing capacity of the ligand. This reduction process is favored by ligand excess and low pH. For a ligand excess of fivefold or higher, the [VO 2L 2] − complex, the only species present in solution, produces, at pH<7, the paramagnetic species, [VO(dmpp) 2(H 2O)] and [VO(H 2O) 5] 2+, as detected by EPR. At higher vanadate–hdmpp ratios [VO(dmpp)(H 2O) 2] + is also produced. The V(V) species formed in solution were studied through a parallel 51V and 1H NMR study of the vanadate–Hdmpp system, as a function of metal/ligand ratio and pH. The p K a values of the two main mononuclear V(V) octahedral complexes, VO 2L and [VO 2L 2] − (L=dmpp), were determined from the pH dependence of their 51V and 1H NMR chemical shifts. For VO 2L, p K a values of 5.88±0.03 and 3.30±0.07 were assigned, respectively, to protonation of [VO 2(dmpp)(OH)(H 2O)] − at the coordinated hydroxo ligand and at the ligand nitrogen atom. For [VO 2L 2] −, the three p K a values obtained, 3.96±0.06, 5.62±0.03, and 2.9±0.4, were attributed, respectively, to protonation of [VO 2(dmpp) 2] − at the nitrogen atom of one of the ligands, at one oxygen of the VO 2 + core, and at its resulting VOH group, with formation of the VO 3+ core. The stability constants of these two complexes (log K 1=10.48±0.05; log K 2=5.25±0.04; log β 2=15.73±0.05) were obtained from 51V NMR data, at pH 8.2, ionic strength 0.1 M, by changing the metal/ligand ratio at constant metal concentration.