Bis- and tris(pyridyl)amine-oxidovanadium complexes: characteristics and insulin-mimetic potential

Two novel vanadium complexes, [V(IV)O(bp-O)(HSO(4))] (1) and [V(IV)O(bp-OH)Cl(2)]center dot CH(3)OH (2 center dot CH(3)OH), where bp-OH is 2-{[bis(pyrid-2-yl)methyl]amine}methylphenol, were prepared and structurally characterised. EPR spectra of methanol solutions of 2 suggest exchange of Cl-for CH(3)OH and partial conversion to [VO(bp-OH)(CH(3)OH)(3)](2+). Speciation studies on the VO(2+)-bpOH system in a water/dmso mixture (4:1 v/v) revealed [VO(bp-O)(H(2)O)(n)](+) as the dominating species in the pH range 2-7. The insulin-mimetic properties of 1 and 2, [V(IV)O(SO(4))tpa] (3), [V(IV)O(pic-trpMe)(2)] (5) and the new mixed-ligand complexes [V(V)O(pic-trpH) tpa]Cl(2) (4Cl(2)) and [V(V)O(pic-OEt)tpa]Cl(2) (6Cl(2)), tpa = tris(pyrid-2-yl) methylamine, picH-trpH = 2-carboxypyridine-5-(L-tryptophan) carboxamide (picH-trpMe is the respective tryptophanmethyl ester), pic-OEt = 5-carboethoxypyridine-2-carboxylic acid, were evaluated with rat adipocytes, employing two lipolysis assays (release of glycerol and free fatty acids (FFA)), respectively and a lipogenesis assay (incorporation of glucose into lipids). The IC(50) values for the inhibition of lipolysis in the FFA assay vary between 0.41 (+/- 0.03) (5) and 21.2 (+/- 0.6) mM (2), as compared to 0.81 (+/- 0.2) mM for VOSO(4).