| Abstract
| - The aqueous VIII speciation chemistry of two dipicolinate-type complexes and the insulin-enhancing effects of V−dipicolinate complexes in three different oxidation states (VIII, VIV, and VV) in a chronic animal model system have been studied. The thermodynamic stability of the [VIII(dipic)2]- complex was found to be higher than anticipated. The VV−dipic complex is most effective in lowering blood glucose and suggests that both ligand and metal oxidation state are important for how the compound acts.
- The aqueous vanadium(III) (VIII) speciation chemistry of two dipicolinate-type complexes and the insulin-enhancingeffects of V−dipicolinate (V-dipic) complexes in three different oxidation states (VIII, VIV, and VV) have been studiedin a chronic animal model system. The characterization of the VIII species was carried out at low ionic strength toreflect physiological conditions and required an evaluation of the hydrolysis of VIII at 0.20 M KCl. The aqueousVIII−dipic and VIII−dipic-OH systems were characterized, and complexes were observed from pH 2 to 7 at 0.2 MKCl. The VIII−dipic system forms stable 1:2 complexes, whereas the VIII−dipic-OH system forms stable 1:1 complexes.A comparison of these complexes with the V−pic system demonstrates that a second ligand has lower affinity forthe VIII, presumably reflecting bidentate coordination of the second dipic2- to the VIII. The thermodynamic stabilityof the [VIII(dipic)2]- complex was compared to the stability of the corresponding VIV and VV complexes, and surprisingly,the VIII complexes were found to be more stable than anticipated. Oral administration of three V−dipicolinatecompounds in different oxidation states {H[VIII(dipic)2H2O]·3H2O, [VIVOdipic(H2O)2]·2H2O, and NH4[VVO2dipic]} andthe positive control, VOSO4, significantly lowered diabetic hyperglycemia in rats with streptozotocin-induced diabetes.The diabetic animals treated with the VIII− or VIV−dipic complexes had blood glucose levels that were statisticallydifferent from those of the diabetic group. The animals treated with the VV−dipic complex had the lowest bloodglucose levels of the treated diabetic animals, which were statistically different from those of the diabetic group atall time points. Among the diabetic animals, complexation to dipic increased the serum levels of V after theadministration of the VV and VIV complexes but not after the administration of the VIII complex when data arenormalized to the ingested dose of V. Because V compounds differing only in oxidation state have different biologicalproperties, it is implied that redox processes must be important factors for the biological action of V compounds.We observe that the VV−dipic complex is the most effective insulin-enhancing agent, in contrast to previous studiesin which the VIV−maltol complex is the most effective. We conclude that the effectiveness of complexed V is bothligand and oxidation state dependent.
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