Bis(picolinato) complexes of vanadium and zinc as potential antidiabetic agents: synthesis, structural elucidation and in vitro insulin-mimetic activity study

Vanadium(v) compounds with 3,5-difluoropicolinic acid (HpicFF) and 3-hydroxypicolinic acid (H(2)hypic) and zinc(ii) compounds with HpicFF, H(2)hypic and 4-methylhydroxypicolinic acid (HpicCH(2)OH) in the presence or absence of pyridine (py), 4-(dimethylamino)pyridine (DMAP), and 1,10-phenanthroline (phen) have been synthesized and characterized. The crystal structures of NH4[VO2(picFF)(2)]center dot 1.6H(2)O (3 center dot 1.6H(2)O), NH4[VO2(hypic)(2)]center dot H2O (4 center dot H2O), [Zn(picFF)(2)(H2O)(2)] (5), [Zn(picFF)(2)(py)(2)]center dot py (6 center dot py), [Zn(picFF)(2)(DMAP)(2)]center dot 2/3H(2)O (7 center dot 2/3H(2)O), [Zn(picFF)(2)(phen)]center dot 2CHCl(3) (8 center dot 2CHCl(3)), [Zn(Hhypic)(2)(MeOH)(2)] (10), [Zn(Hhypic)(2)(DMAP)(H2O)] (11) and [Zn(Hhypic)(2)(phen)] (12) were determined by X-ray crystallography. The spatial arrangement of the vanadium(v) complex 3 possesses carboxylate oxygen atoms in a mutual trans orientation while crystal structure 4 represents the first crystallographic evidence for the formation of an isomer with two picolinato nitrogen atoms in a mutual trans position. Two different spatial arrangements were found in the zinc(ii) complexes with trans (5, 10 and 11) and cis (6, 7, 8 and 12) octahedral geometry. Insulin-mimetic activity of the selected (VO)-O-IV, (VO2)-O-V and Zn-II complexes was studied by in vitro inhibition of the free fatty acid (FFA) release from isolated rat adipocytes treated with epinephrine. All the studied metal complexes showed insulin-mimetic activity. Vanadium complexes 1-4 exhibit activities similar to VOSO4 with the Hhypic complexes being more active than the picFF ones. The zinc complexes also exhibited some insulin-mimetic activity, with the Hhypic complex (9) being more active than the other two, however, the insulin-mimetic activity of these complexes did not show more potent activity than ZnSO4.