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)

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(IV)-DHP-ligand B (B
= oxalate, lactate, citrate or phosphate) was studied by pH-potentiometry.
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 high excess of ligand. The results in the ternary system
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).