Peroxovanadates

Vanadate (sodium orthovanadate or peroxovanadate) exhibits insulin-like effects in vitro (activation of insulin receptor tyrosine kinase, PI 3-kinase, Akt) and in vivo (diabetic rats, humans). These effects can be explained at least in part by the inhibition of phosphotyrosine phosphatases which deactivate the INSR tyrosine kinase. 

Design concepts are now being applied more effectively to mineral supplements. For example, by controlling the redox potential of iron, toxic effects associated with excess Fe(II) during parental supplementation can be avoided. Peroxovanadate complexes can inhibit insulin-receptor-associated phosphotyrosine phosphatase and activate insulin receptor kinase, and both V(IV) and V(V) offer promise as potential insulin mimics. 

Peroxovanadates are effective at much lower doses (ca. 100-fold) than vanadate itself, but readily decompose in aqueous solution and must be administered by injection. Posner et al. have shown that organic ligands can stabilize peroxo complexes and that peroxovanadate complexes such as 105 (with L-L = e.g., phenanthroline, picolinate,... 

It is not clear whether V(V) or V(IV) (or both) is the active insulin-mimetic redox state of vanadium. In the body, endogenous reducing agents such as glutathione and ascorbic acid may inhibit the oxidation of V(IV). The mechanism of action of insulin mimetics is unclear. Insulin receptors are membrane-spanning tyrosine-specific protein kinases activated by insulin on the extracellular side to catalyze intracellular protein tyrosine phosphorylation. Vanadates can act as phosphate analogs, and there is evidence for potent inhibition of phosphotyrosine phosphatases (526). Peroxovanadate complexes, for example, can induce autophosphorylation at tyrosine residues and inhibit the insulin-receptor-associated phosphotyrosine phosphatase, and these in turn activate insulin-receptor kinase. 

Peroxovanadates, O NMR spectroscopy, 186 PeroxyacetaUzation of carbonyl functions ji-hydroperoxyalcohols, 273-7, 278 strained endoperoxide systems, 277-85... 

Chromium compounds are covered above. Most tetraperoxomolybdates(2-) and tetra-peroxotungstates(2-) explode when heated or struck [1], An acetate bridged bis-diperoxomolybdate(VI) exploded when heated [3], Organoperoxoniobium compounds occasionally explode on exposure to air [2], A peroxovanadate complex is reported seriously explosive. 

Analogous to the preceding cw-dioxovanadium(V)-catalyzed system of bromide oxidation by dihydrogen peroxide, Secco carried out a detailed kinetic analysis of vanadate-catalyzed oxidation of iodide by dihydrogen peroxide [75], Peroxovanadate species (i.e., V0[02]+ and V0[02]2 ) or their hydronated forms oxidize iodide in acidic aqueous solution, forming V02+ and V0(02)+, respectively however, once V0(02)+ and V0(02)2 are consumed, iodide reduces... 

Andersson, I., S J. Angus-Dunne, O.W. Howarth, and L. Pettersson. 2000. Speciation in vanadium bioinorganic systems 6. Speciation study of aqueous peroxovanadates, including complexes with imidazole. J. Inorg. Biochem. 80 51-58. 

Harrison, A.T. and O.W. Howarth. 1985. High-field vanadium-51 and oxygen-17 nuclear magnetic resonance study of peroxovanadates. J. Chem. Soc., Dalton Trans. 1173-1177. 

The reactions of hydrogen peroxide with vanadate have been of interest for many years. Much of the early work was concerned with the function of peroxovanadates as oxygen transfer agents. Alkenes and similar compounds such as allyl alcohols can be hydroxylated or epoxidized. Even alkanes can be hydroxylated, whereas alcohols can be oxidized to aldehydes or ketones and thiols oxidized to sulphones or sulphoxides. Aromatic molecules, including benzene, can be hydroxylated. The rich chemistry associated with the peroxovanadates has, therefore, led to extensive studies of their reaction chemistry. To this end, x-ray diffraction studies have successfully provided details of a number of peroxovanadate structures. 

Many peroxovanadates have potent insulin-mimetic properties [1,2]. Apparently, this functionality derives from the ability of these compounds to rapidly oxidize the active site thiols found in the group of protein tyrosine phosphatases that are involved in regulating the insulin receptor function [3], The discovery of vanadium-dependent haloperoxidases in marine algae and terrestrial lichens provided an additional stimulus in research toward obtaining functional models of peroxidase activity, and there is great interest in duplicating the function of these enzymes (see Section 10.4.2). 

FIGURE 5.1 Distribution diagram showing the formation of vanadate and peroxovanadate species as a function of the concentration of hydrogen peroxide and of pH. Conditions for the simulation 2mmol/L total vanadate 0.1 tmol/L to 10 mmol/L total hydrogen peroxide 0.15 mol/L ionic strength with NaCl pH values, as indicated. The formation constants are from reference 11. 

The most-well-known-cationic peroxovanadate is the monoperoxide, V0(02)(H20)31+, which is a red vanadate derivative often utilized in a test for the presence of vanadium. Figure 5.2 shows the pH dependence of product distribution for the major peroxovanadates under a fixed overall concentration ratio of 2 mmol/L vanadate to 4 mmol/L hydrogen peroxide. It is evident from this diagram that any significant proportion of the cationic complex occurs only below pH 3. The bisper-oxide is the dominant product throughout the pH range to at least pH 10. 

Tracey, A.S. and J.S. Jaswal. 1993. Reactions of peroxovanadates with amino acids and related compounds in aqueous solution. Inorg. Chem. 32 4235 4243. 

Olefins undergo a two-step oxidative process, with the first step leading to an epoxide that, in the presence of excess oxidant, subsequently is cleaved to afford aldehydes or ketones, dependent on the position of the olefinic bond. Oxidative reactions by peroxovanadates tend to be retarded by protic solvents such as water or methanol. For instance, oxidation of norbomene by picolinatooxomonoperoxo-vanadate in acetonitrile affords 22% of the product epoxide in 9 min. After 120 min in methanol solvent, only 1.8% yield was obtained. In dichloromethane, even cyclohexane is oxidized faster than this, giving 4% cyclohexanol and 9% cyclohexanone in 120 min, whereas benzene in acetonitrile yields 56% of phenol [23],... 

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