Structures and biotransformations of potent insulinenhancing V-IV O complexes with picolinate derivatives.

The potential use in the therapy of type 2 diabetic patients is one of the most important applications of vanadium in medicine [1,2]. Promising insulin-like effects have also been found in the case of V(IV)O picolinato complex and its derivatives [3]. Three new VIVO compounds with the 5-cyanopyridine-2-carboxylic acid, 3,5-difluoropyridine-2-carboxylic acid and 3-hydroxypyridine-2-carboxylic acid have been synthesized and characterized by X-ray, EPR and DFT methods. Their interactions with the blood proteins apo-transferrin and albumin have also been studied by EPR spectroscopy. Studies in the solid state and in solution have revealed cis-octahedral structure of all three compounds with the solvent or monodentate ligand in equatorial position cis to the V(IV)O moiety, while the arrangement of the bidentate picolinate ligands is variable. In the solid state OC-6-23 and/or OC-6-24 arrangements of the complexes have been determined, but in the solution partial isomerization into OC-6-42 complexes has been observed. In the presence of protein apo-hTf at physiological pH complexes decompose and the majority of VIVO2? ions binds to the protein, while in the presence of HSA mixed species with ligands can also be formed.