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

Abstract

Vanadium(V) compounds with 3,5-difluoropicolinic acid (HpicFF) and 3-hydroxypicolinic acid (H₂hypic) and zinc(II) compounds with HpicFF, H₂hypic and 4-methylhydroxypicolinic acid (HpicCH₂OH) 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]·1.6H₂O (3·1.6H₂O), NH₄[VO₂(hypic)₂]·H₂O (4·H₂O), [Zn(picFF)₂(H₂O)₂] (5), [Zn(picFF)₂(py)₂]·py (6·py), [Zn(picFF)₂(DMAP)₂]·H₂O (7·H₂O), [Zn(picFF)₂(phen)]·2CHCl₃ (8·2CHCl₃), [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 V^IVO, V^VO₂ 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.