Peroxovanadates complexation

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. 

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. 

Stimulation of insulin receptor kinase by peroxovanadates (complexes of vanadate and H2O2) presumably represents a mechanism of insulin mimesis different from that of vanadate or vanadyl. ° Low concentrations (5-20 M) of peroxovanadate, but not vanadate, potentiated insulin-stimulated glucose uptake in rat adipocytes, an effect that correlated with an increase in protein phosphotyrosine content. Peroxovanadate inhibited lipolysis, stimulated protein synthesis and lipogenesis, and promoted autophosphorylation and activation of the IR tyrosine kinase, similarly to insulin. Although peroxovanadate, unlike vanadate, increased tyrosine kinase activity in intact cells, neither compound, unlike insulin, had any effect on the kinase activity of partially purified adipocyte IR preparations. ... 

Scheme 5.8 Insulin-mimetic vanadium complexes. In the peroxovanadate complex, L = bipyridine (bipy), oxalate (ox), phenanthroline (phen) and picolinate (pic). BMOV represents bis(maltolato)oxovanadium(IV).

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. 

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. 

Studies of the oxidation of organic sulfides with amino acid-derived ligands in acetonitrile revealed very little difference between the mechanism of their oxidation and that of halides, except for one major exception. Despite the fact that acid conditions are still required for the catalytic cycle, hydroxide or an equivalent is not produced in the catalytic cycle, so no proton is consumed [48], As a consequence, there is no requirement for maintenance of acid levels during a catalyzed reaction. Peroxo complexes of vanadium are well known to be potent insulin-mimetic compounds [49,50], Their efficacy arises, at least in part, from an oxidative mechanism that enhances insulin receptor activity, and possibly the activity of other protein tyrosine kinases activity [51]. With peroxovanadates, this is an irreversible function. Apparently, there is no direct effect on the function of the kinase, but rather there is inhibition of protein tyrosine phosphatase activity. The phosphatase regulates kinase activity by dephosphorylating the kinase. Oxidation of an active site thiol in the phosphatase prevents this down-regulation of kinase activity. Presumably, this sulfide oxidation proceeds by the process outlined above. 

This book does not follow a chronological sequence but rather builds up in a hierarchy of complexity. Some basic principles of 51V NMR spectroscopy are discussed this is followed by a description of the self-condensation reactions of vanadate itself. The reactions with simple monodentate ligands are then described, and this proceeds to more complicated systems such as diols, -hydroxy acids, amino acids, peptides, and so on. Aspects of this sequence are later revisited but with interest now directed toward the influence of ligand electronic properties on coordination and reactivity. The influences of ligands, particularly those of hydrogen peroxide and hydroxyl amine, on heteroligand reactivity are compared and contrasted. There is a brief discussion of the vanadium-dependent haloperoxidases and model systems. There is also some discussion of vanadium in the environment and of some technological applications. Because vanadium pollution is inextricably linked to vanadium(V) chemistry, some discussion of vanadium as a pollutant is provided. This book provides only a very brief discussion of vanadium oxidation states other than V(V) and also does not discuss vanadium redox activity, except in a peripheral manner where required. It does, however, briefly cover the catalytic reactions of peroxovanadates and haloperoxidases model compounds. 

In contrast to the systems addressed above (i.e. those containing the ligands lactate, citrate or alanylserine), the coordination of alanylhistidine to vanadate is drastically enhanced by concomitant coordination of peroxide, a fact which also applies to the coordination of imidazole, which, in the absence of peroxide, forms only very weak complexes with vanadate. In the ternary system peroxide-vanadate-alanylhistidine, the predominant complex between pH 4 and 9 is V( 2)2(ala-his). In the peroxovanadates, alanylhistidine coordinates through Ne (Figure 2.15).P 1... 

Examples of peroxovanadates stabilised by ligands containing one A-function and a variable number of 0-donors. The selection of complexes shown here has been carried out so as to approach as closely as possible the active centre in the peroxo form of the Cur. officinalis chloroperoxidase, V0(0H)(02)N (Figure 4.16c). 

Inorganic (top row) and organic (bottom row) vanadium compounds which are of (historical) interest as insulin mimics (sodium) vanadate (3) vanadyl (sulfate) (4) peroxovanadate (mixtures of vanadate and H2O2) (5) a peroxo-picolinato complex (6) bis(maltolato) complexes 7 R = CH3 BMOV = [VO(ma)2] = C2H5 BEOV 7b R = iPr 7c and the allixinato complex 7d and... 

The addition of hydrogen peroxide to acidic Vv solutions gives a red color due to the formation of peroxo complexes, where oxygen atoms in V04 are replaced by one or more Of- groups several peroxovanadates have been isolated,12b e.g., K[V(02)3 bipy]-4H20. 

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