Chemical speciation of insulinomimetic VO(IV) complexes of pyridine-N-oxide derivatives: binary and ternary systems

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 compound VO(HPO)(2) (HPO, 2-hydroxypyridine-N-oxide): and VO(MPO)(2) (MPO, 2-mercaptopyridine-N-oxide), the speciation in the binary system VO(IV)-HPO and VO(IV)-MPO and in the ternary systems VO(IV)-HPO(MPO)-ligand B (B=oxalate, lactate, citrate or phosphate) was studied by pH-potentiometry. The stability constants of the complexes formed were determined in aqueous solution at I=0.2 M (KCl) and T=25 degrees C. The most probable binding modes of the complexes were determined by EPR method. The pyridine-N-oxides were found to form very stable bis complexes, which are predominant in the pH range 2-7. The results in the ternary systems demonstrate that only the citrate is a strong enough VO(IV) binder to compete with the carrier ligands. The binding ability of the high-molecular-mass (h.m.m.) serum proteins albumin and transferrin were also assessed and transferrin was found to be an efficient binder molecule. The actual solution state of these compounds in blood serum is compared with that of other insulin-mimic VO(IV) complexes.