Vanadium Complexes with Mixed O,S Anionic Ligands Derived from Maltol:  Synthesis, Characterization, and Biological Studies

Abstract

Four mixed O,S binding bidentate ligand precursors derived from maltol (3-hydroxy-2-methyl-4-pyrone) have been chelated to vanadium to yield new bis(ligand)oxovanadium(IV) and tris(ligand)vanadium(III) complexes. The four ligand precursors include two pyranthiones, 3-hydroxy-2-methyl-4-pyranthione, commonly known as thiomaltol (Htma), and 2-ethyl-3-hydroxy-4-pyranthione, commonly known as ethylthiomaltol (Hetma), as well as two pyridinethiones, 3-hydroxy-2-methyl-4(H)-pyridinethione (Hmppt) and 3-hydroxy-1,2-dimethyl-4-pyridinethione (Hdppt). Vanadium complex formation was confirmed by elemental analysis, mass spectrometry, and IR and EPR (where possible) spectroscopies. The X-ray structure of oxobis(thiomaltolato)vanadium(IV),VO(tma)(2), was also determined; both cis and trans isomers were isolated in the same asymmetric unit. In both isomers, the two thiomaltolato ligands are arranged around the base of the square pyramid with the V=O linkage perpendicular; the vanadium atom is slightly displaced from the basal plane [V(1) = 0.656(3) A, V(2) = 0.664(2) A]. All of the new complexes were screened for insulin-enhancing effectiveness in streptozotocin-induced diabetes in rats, and VO(tma)(2) was profiled metabolically for urinary vanadium and ligand clearance by GFAAS and ESIMS, respectively. The new vanadium complexes did not lower blood glucose levels acutely, possibly because of rapid dissociation and excretion.

Application of DFT methods to the study of the coordination environment of the VO2+ ion in V proteins

“…complexes with V-O, V-N, and V-S bonds: [VO(H 2 O) 5 ] 2? (1) [51], [VO(acac) 2 ] (2), where acac is acetylacetonato(-) [52], [VO(ma) 2 ] (3), where ma is maltolato(-) [53], [VO(salen)] (4), where salen is N, [56], [VO(tma) 2 ] (7), where tma is 2-methyl-3-oxy-4H-pyran-4-thionato(-) [57], [VO(mnt) 2 ] 2-(8), where mnt is 1,2-dicianoethylene-1,2-dithiolato(-) [58], and [VO(edt) 2 ] 2-(9), where edt is ethane-1,2-dithiolato(2-) [59]. The functionals B3LYP, B3PW91, and B3P86, coupled with the basis set 6-311g, were used; for the structures containing V-S bonds, diffuse and polarization functions were also added on the sulfur atom.…”

Vanadium in diabetes: 100 years from Phase 0 to Phase I

“…Clearly, compounds that do not dissociate readily tend to have no insulin-mimetic effect in vivo [10,163,164]. Among complexes with fairly similar short-term potencies, such as BMOV, BEOV, VO(pic) 2 , VO(6MPA) 2 , VO(acac) 2 , and VO(Etacac) 2 [152,165,166], the deciding factor may relate more to the ligand itself than to the complex.…”

Impact of Bidentate Chelators on Lipophilicity, Stability, and Biodistribution Characteristics of Cationic 99mTc-Nitrido Complexes

“…Thiomaltol (Htma) and ethylthiomaltol (Hetma) were prepared according to the literature methods (17)(18)(19)(20)(21). Synthesis of N-ethoxyethyl-N,Nbis[2-(bis(3-methoxypropyl)phosphino)ethyl]amine (PNP5), N-ethoxyethyl-N,N-bis[2-(bis (3-ethoxypropyl)phosphino)ethyl]amine (PNP6) and N-methoxyethyl-N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (L6) has been described in our previous report (1).…”