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The aqueous speciation, formation constants, and solution structure were determined for a new insulin-mimetic organic vanadium(V) compound (ammonium (dipicolinato)oxovanadate(V)). The solution properties of the system were characterized by using potentiometry, 1H, 13C, and 51V NMR 1D and 2D spectroscopy, and UV/visible spectroscopy. These studies were conducted using the crystalline compound as well as combinations of the free ligand and the metal salt. The major complex is most stable in the acidic pH range, although it does protonate at low pH. It protonates at pH ∼1 and decomposes below pH 0. The dipic ligand is coordinated in a tridentate manner throughout the pH range studied. Protonation at low pH takes place on one of the oxo groups. Dynamic processes were explored using 1H and 13C EXSY NMR spectroscopy. VO2dipic- was found to exchange between the complex and the ligand at high and at low pH values. In the intermediate-pH range, no evidence for exchange processes was obtained, documenting the inertness of the complex at pH 3−4. The high stability and inertness in the pH 3−4 region may be of biological significance since the combination of high stability and low lability suggests the complex will be more resistant to hydrolysis at the pH of the stomach.

The aqueous vanadium(III) (V(III)) speciation chemistry of two dipicolinate-type complexes and the insulin-enhancing effects of V-dipicolinate (V-dipic) complexes in three different oxidation states (V(III), V(IV), and V(V)) have been studied in a chronic animal model system. The characterization of the V(III) species was carried out at low ionic strength to reflect physiological conditions and required an evaluation of the hydrolysis of V(III) at 0.20 M KCl. The aqueous V(III)-dipic and V(III)-dipic-OH systems were characterized, and complexes were observed from pH 2 to 7 at 0.2 M KCl. The V(III)-dipic system forms stable 1:2 complexes, whereas the V(III)-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 for the V(III), presumably reflecting bidentate coordination of the second dipic(2)(-) to the V(III). The thermodynamic stability of the [V(III)(dipic)(2)](-) complex was compared to the stability of the corresponding V(IV) and V(V) complexes, and surprisingly, the V(III) complexes were found to be more stable than anticipated. Oral administration of three V-dipicolinate compounds in different oxidation states {H[V(III)(dipic)(2)H(2)O].3H(2)O, [V(IV)Odipic(H(2)O)(2)].2H(2)O, and NH(4)[V(V)O(2)dipic]} and the positive control, VOSO(4), significantly lowered diabetic hyperglycemia in rats with streptozotocin-induced diabetes. The diabetic animals treated with the V(III)- or V(IV)-dipic complexes had blood glucose levels that were statistically different from those of the diabetic group. The animals treated with the V(V)-dipic complex had the lowest blood glucose levels of the treated diabetic animals, which were statistically different from those of the diabetic group at all time points. Among the diabetic animals, complexation to dipic increased the serum levels of V after the administration of the V(V) and V(IV) complexes but not after the administration of the V(III) complex when data are normalized to the ingested dose of V. Because V compounds differing only in oxidation state have different biological properties, it is implied that redox processes must be important factors for the biological action of V compounds. We observe that the V(V)-dipic complex is the most effective insulin-enhancing agent, in contrast to previous studies in which the V(IV)-maltol complex is the most effective. We conclude that the effectiveness of complexed V is both ligand and oxidation state dependent.

Biochemistry Biochemistry Z 0250The Chemistry and Biochemistry of Vanadium and the Biological Activities Exerted by Vanadium Compounds -[801 refs.]. -(CRANS*, D. C.; SMEE, J. J.; GAIDAMAUSKAS, E.; YANG, L.; Chem. Rev. (Washington, D. C.) 104 (2004) 2, 849-902; Dep. Chem., Colo. State Univ., Fort Collins, CO 80523, USA; Eng.) -Lindner 20-288

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