Interaction between the low molecular mass components of blood serum and the VO(iv)–DHP system (DHP = 1,2-dimethyl-3-hydroxy-4(1H)-pyridinone)

Abstract

In order to estimate the impact of the low molecular mass (l.m.m.) VO() binders of blood serum on the potentially insulin-enhancing drug [VO(DHP) 2 ] [DHP = 1,2-dimethyl-3-hydroxy-4(1H )-pyridinone], the speciation in the binary system VO()-DHP and in the ternary systems VO-DHP-ligand B (B = oxalate, lactate, citrate or phosphate) was studied by pH-potentiometry at 25.0 ЊC and at an ionic strength I = 0.2 mol dm Ϫ3 (KCl). The binding modes of the complexes formed were determined by spectroscopic (electronic absorption and EPR) techniques. DHP was found to form stable mono and bis complexes via the coordination of (O,O) chelate(s). Through displacement of the oxo group of VO(), the tris complex is also formed, especially at a high excess of ligand. The results in the ternary systems demonstrate that, at physiological pH, none of the B ligands can compete with DHP; [VO(DHP) 2 ] therefore seems to remain almost completely intact, even in the presence of citrate, the strongest competitor among these B ligands. These findings indicate that, for DHP, unlike maltol or picolinic acid, ternary complex formation and thus transformation reactions with the l.m.m. binders of biofluids, is almost negligible. From among the three carrier molecules, only DHP can efficiently compete with serum transferrin for binding of VO().

Vanadium in diabetes: 100 years from Phase 0 to Phase I

“…The complex biochemistry of vanadium ions, with extensive binding to systemic and intracellular ligands, both large (transferrin, albumin) [156][157][158] and small (glutathione, citrate, ascorbate, lactate) [159][160][161], has also tended to confound efforts to pin down its preferred biological function [162] (vide infra).…”

Solution equilibria of anticancer ruthenium(II)-(η6-p-cymene)-hydroxy(thio)pyr(id)one complexes: Impact of sulfur vs. oxygen donor systems on the speciation and bioactivity

“…The proton dissociation constants of hydroxy(thio)pyr(id)ones can be attributed to the deprotonation of the hydroxyl functional group, whereas, in contrast to dhp, thiodhp (pK a = 9.46 at I = 0.2 M KCl, pK a = 9.47 at I = 0.1 M KCl [37]) is not protonated in the pH range 2-11.5. This is most probably attributable to the unfavorable catechol-type tautomeric form [38] in the case of thiodhp [39].…”

Biospeciation of Potential Vanadium Drugs of Acetylacetonate in the Presence of Proteins

“…In the literature, the thermodynamic stability constants on the system V V /acac are lacking. The data for maltol, a (O,O) ligand with similar basicity [pK a is 8.44 for maltol (Buglyo et al, 2002) and 8.76 for acetylacetone (Crans et al, 2001)], indicate that at these experimental conditions, the percentage of V in solution as…”