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Vanadium(III, IV, V)-chlorodipicolinate (dipic-Cl) complexes, including H[VIII(dipic-Cl)2] · 5H2O (V3dipic-Cl), VIVO(dipic-Cl)(H2O)2 (V4dipic-Cl) and K[VVO2(dipic-Cl)] (V5dipic-Cl), were prepared with the indicated oxidation states. Our aim was to evaluate the anti-diabetic effects of V3dipic-Cl, V4dipic-Cl and V5dipic-Cl in streptozotocin-induced diabetic rats. Vanadium complexes were orally administered to diabetic rats at concentrations of 0.1-0.3 mg/ml in the drinking water. We found that vanadium-chlorodipicolinate (V-dipic-Cl) complexes at the concentration of 0.1 mg/ml did not exhibit blood glucose-lowering effects when administered to diabetic rats for 20 days. However, the levels of fasting blood glucose in diabetic rats were decreased after treatment with 0.3 mg/ml of V4dipic-Cl and V5dipic-Cl complexes for the following 20 days. Although administration of both V4dipic-Cl and V5dipic-Cl significantly lowered diabetic hyperglycemia, the vanadium intake from administration of V4dipic-Cl is nearly 1.5-fold greater compared to that of V5dipic-Cl. Treatment with the H2dipic-Cl ligand and all three V-dipic-Cl complexes significantly lowered serum cholesterol, while administration of the V5dipic-Cl complex lowered serum cholesterol significantly more than administration of the ligand alone. Treatment with ligand alone did not have an effect on serum triglyceride, while administration of the V4dipic-Cl and V5dipic-Cl significantly lowered the elevated serum triglyceride associated with diabetes. Oral administration of the ligand and all V-dipic-Cl complexes did significantly lower diabetes elevated serum alkaline phosphatase. Treatment with H2dipic-Cl ligand and V4dipic-Cl and V5dipicCl significantly lowered diabetes elevated aspartate amino transferase. These results indicate that the health of the treated animals did not seem to be further compromised compared to that of diabetic animals. In addition, oral administration of H2dipic-Cl, V3dipic-Cl, V4dipic-Cl and V5dipic-Cl did not alter diabetic serum creatinine and blood urea nitrogen levels, suggesting no significant side effects of vanadium treatment on renal functions at the dose of 0.3 mg/ml in diabetic rats. The results presented here suggest that the anti-diabetic effects of treatment with V-dipic-Cl complexes were likely associated in part with the oxidation state of vanadium.

Vanadate has been recognized as a specific and potent phosphatase inhibitor since its structure is similar to that of phosphate. In this study, we measured the inhibition of glutathione S-transferase-tagged protein tyrosine phosphatase 1B (GST-PTP1B) and alkaline phosphatase (ALP) by the insulin enhancing compounds, bis(maltolato)oxovanadium(IV) (BMOV). The results showed that the activity of GST-PTP1B was reversibly inhibited by solutions of BMOV with an IC(50) value of 0.86+/-0.02 microM. Steady state kinetic studies showed that inhibition of GST-PTP1B by BMOV was of a mixed competitive and noncompetitive type. In addition, incubation of GST-PTP1B with BMOV showed a time-dependent biphasic inactivation of the protein. On the other hand, the inhibitory behavior of BMOV on ALP activity was reversible and competitive with an IC(50) value of 32.1+/-0.6 microM. Incubation with BMOV did not show biphasic inactivation of ALP. The reversible inhibition of GST-PTP1B by BMOV is more potent than that of ALP, but solutions of BMOV inhibited both enzymes. This data support the suggestion that mechanisms for the inhibitory effects of BMOV on GST-PTP1B and ALP are very different.

The anti-oxidant properties of L-ascorbic acid were investigated in the confined medium produced by a sodium bis(2-ethylhexyl)sulfosuccinate (aerosol-OT, AOT) self-assembled reverse micelle. Using 1H-1H NOESY (proton-proton 2D nuclear overhauser enhancement correlation spectroscopy) NMR spectroscopy, the location of ascorbic acid was investigated and found to be at the AOT-interface in contrast to earlier studies where the ascorbate was assumed to be in the water pool in these microemulsions. The reaction of ascorbic acid with oxygen was investigated using EPR spectroscopy. A delocalized monoanionic ascorbate radical was observed in microemulsions prepared from pH 5.6 stock solutions. This is in contrast to studies carried out in aqueous media where no radical formation was observed. The oxidation of ascorbic acid by aqueous V(V) was investigated in reverse micelles. Modest changes in the kinetic parameters were observed for this system compared to that in water. Details of these reactions were examined and can be summarized as the microemulsion solvating and stabilizing reactive intermediates via rate inhibition or enhancement. The inhibition of the oxidation is due to solvation stabilization of ascorbic acid in microemulsion media. Since ascorbate is a valuable marker of oxidative stress, our results suggest that compartmentization can modify the stabilization of the ascorbate radical and the changes in properties could be important in biological systems.

The study has been designed to investigate the anti-diabetic effects of cesium aqua (N,N'-ethylene (salicylideneiminato)-5-sulfonato) oxovanadium (IV) dihydrate (VO(salen-SO(3))), an organic vanadium compound, in streptozotocin-induced diabetic rats. VO(salen-SO(3)) was orally administrated to diabetic rats at the dose of 0.3 mg/ml through drinking water for 24 days. Blood glucose level was significantly declined, and oral glucose tolerance was improved after VO(salen-SO(3)) treatment. Moreover, liver and muscle glycogen concentrations were markedly increased in VO(salen-SO(3))-treated diabetic rats. On the other hand, aspartate amino transferase and blood urea nitrogen in serum were significantly decreased after treatment with VO(salen-SO(3)). Taken together, these results suggested that VO(salen-SO(3)) may be of potential value in the therapy of diabetic symptom and hyperglycemia-induced hepatic and renal dysfunction.

The interior water pool of aerosol OT (AOT) reverse micelles tends toward bulk water properties as the micelle size increases. Thus, deviations from bulk water behavior in large reverse micelles are less expected than in small reverse micelles. Probing the interior water pool of AOT reverse micelles with a highly charged decavanadate (V(10)) oligomer using (51)V NMR spectroscopy shows distinct changes in solute environment. For example, when an acidic stock solution of protonated V(10) is placed in a reverse micelle, the (51)V chemical shifts show that the V(10) is deprotonated consistent with a decreased proton concentration in the intramicellar water pool. Results indicate that a proton gradient exists inside the reverse micelles, leaving the interior neutral while the interfacial region is acidic.

How water, metabolites and proteins associate and traverse the lipid interface is generally investigated by using probes with spectroscopic handles. Cellular confinement limits the tools of investigation to indirect approaches. Studies of a variety of different probes become important to understand the effects of confinement on chemical reactions and biological function. Confinement of water affects the properties of water and this effect is important for cellular systems. A versatile model system for studying the effect of water confinement on biological processes uses reverse micelles (RMs). Molecular probes are also used to investigate environments that are not readily accessible to direct measurements. Most of the dyes in use contain large hydrophobic chromophores and do not have size and structural flexibility to probe a surface that is both hydrophobic and hydrophilic as common in biological systems. We present the use of vanadium-containing probes for exploration of the fundamental properties of restricted water and lipid interfaces in RMs. The presence of a vanadium atom in these probes provides multiple handles such as chemical shifts, signal linewidth and lifetime experiments in the quadrupolar 51V nuclei as well in 1H and 13C nuclei for investigations. The quadrupolar nuclei have a greater battery of useful spectroscopic parameters and combined with the conventional methods provide multiple handles in one probe. Furthermore, the vanadium-containing probe structure, charge and polarity can be modified for use in various biological settings. Here we introduce the concept and describe a few applications of this approach.

The location and interactions of solutes in microheterogeneous environments, such as reverse micelles, critically influence understanding of many phenomena that utilize probe molecules to characterize properties in chemical, biological, and physical systems. The information gained in such studies depends substantially on the location of the probe used. Often, intuition leads to the assumption that ionic probe molecules reside in the polar water pool of a system. In this work, the location of a charged polar transition metal coordination complex in a reverse micellar system is determined using NMR spectroscopy. Despite the expected Coulomb repulsion between the surfactant headgroups and the negatively charged complex, the complex spends significant time penetrating into the hydrophobic portion of the reverse micellar interface. These results challenge the assumption that ionic probe molecules reside solvated by water in microheterogeneous environments and suggest that probe molecule location be carefully considered before interpreting data from similar systems.