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(IV) 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(IV)–DHP and in the ternary systems VO–DHP–ligand B (B = oxalate, lactate, citrate or phosphate) was studied by pH-potentiometry at 25.0 °C and at an ionic strength I = 0.2 mol dm⁻³ (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(IV), 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(IV).