The chemistry of peroxovanadium compounds relevant to insulin mimesis

  • Alan Shaver
  • Jesse B. Ng
  • David A. Hall
  • Barry I. Posner
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 16)


The inorganic coordination chemistry of peroxovanadium compounds relevant to insulin mimesis is reviewed. The structure and kinetic reactivity of solutions of vanadate anion, vanadyl complexes and peroxovanadate complexes are briefly compared. Peroxovanadium compounds contain an oxo group, one or two peroxo ligands (O 2 2− ) and an ancillary ligand which is usually bidentate. These compounds approximate a trigonal bipyramidal structure which can be divided conceptually into a polar ‘oxo’ half and a relatively non-polar organic half. This presents a number of interesting design variations which are discussed with respect to the development of a rudimentary structure-activity correlation of insulin mimetic ability.

Key words

peroxovanadium compounds structure-activity relation of vanadium insulin mimetic activity 













































ethylenediaminetetraacetic acid












nicotinic acid




Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Clark RJH: Vanadium. In: J.C. Bailar Jr, H.J. Emeléus, R. Nyholm (eds). A.F. Trotman-Dickenson (exec ed.). Comprehensive Inorganic Chemistry. Pergamon Press, Toronto, 1973, vol 3, pp 451–551.Google Scholar
  2. 2.
    Oltz EM, Bruening RC, Smith MJ, Kustin K, Nakanishi K: The tunichromes. A class of reducing blood pigments from sea squirts: Isolation, structures and vanadium chemistry. J Am Chem Soc 110: 6162–6172, 1988CrossRefGoogle Scholar
  3. 3.
    Smith MJ, Kim D, Horenstein B, Nakanishi K, Kustin K: Unraveling the chemistry of tunichrome. Acc Chem Res 24: 117–124, 1991CrossRefGoogle Scholar
  4. 4.
    Vilter H: Vanadium-an element involved in the biosynthesis of halogenated compounds and nitrogen fixation. Phytochemistry 23: 1387–1390, 1984CrossRefGoogle Scholar
  5. 5.
    Weber R, de Boer E, Plat H, Krenn BE: Peroxidases from phaeophyceae: a vanadium(V)-dependent peroxidase from Ascophyllum nodosum. FEBS Lett 216: 1–3, 1987CrossRefGoogle Scholar
  6. 6.
    Plat H, Krenn BE, Wever R: The bromoperoxidase from the lichen Xanthoma parietina is a novel vanadium enzyme. Biochem J 248: 277–279, 1987PubMedGoogle Scholar
  7. 7.
    Krenn BE, Plat H, Wever R: The bromoperoxidase from the red alga Ceranium rubrum also contains vanadium as a prosthetic group. Biochim Biophys Acta 912: 287–291, 1987CrossRefGoogle Scholar
  8. 8.
    Hales BJ, Case EE, Morningstar JE, Dzeda MF, Mauterer LA: Isolation of a new vanadium containing nitrogenase from Azotobacter vinelandii. Biochemistry 25: 7251–7255, 1986PubMedCrossRefGoogle Scholar
  9. 9.
    Robson RL, Eady RR, Richardson TH, Miller RW, Hawkins M, Postgate JR: The alternative nitrogenase of Azotobacter chroococcum is a vanadium enzyme. Nature 322: 388–390, 1986CrossRefGoogle Scholar
  10. 10.
    Nechay BR, Nanninga LB, Nechay PSE, Post RL, Grantham JJ, Macara IG, Kubena LF, Phillips TD, Nielsen FH: Role of vanadium in biology. Fed Proc 45: 123–132, 1986Google Scholar
  11. 11.
    Rehder D: The bioinorganic chemistry of vanadium. Angew Chem Int Ed Engl 30: 148–167, 1990CrossRefGoogle Scholar
  12. 12.
    Chasteen ND (ed.): Vanadium in biological systems. Kluwer Academic Publishers, Dordrecht, 1990Google Scholar
  13. 13.
    Tolman EL, Barris E, Burns M, Pansini A, Partridge R: Effects of vanadium on glucose metabolism in vitro. Life Sci 25: 1159–1164, 1979PubMedCrossRefGoogle Scholar
  14. 14.
    Dubyak GR, Kleinzeller AD: The insulin-mimetic effects of vanadate in isolated rat adipocytes. Dissociation from the effects of vanadate as a (Na+K+) ATPase inhibitor. J Biol Chem 255:5306–5312, 1980PubMedGoogle Scholar
  15. 15.
    Shechter Y, Karlish SJD: Insulin-like stimulation of glucose oxidation in rat adipocytes by vanadyl (IV) ions. Nature 284: 556–558, 1980PubMedCrossRefGoogle Scholar
  16. 16.
    Heyliger CE, Tahiliani AG, McNeill JH: Effect of vanadate on elevated blood glucose and depressed cardiac performance of diabetic rats. Science 227: 1474–1477, 1985PubMedCrossRefGoogle Scholar
  17. 17.
    Ramanadham S, Mongold JJ, Brownsey RW, Cros GH, McNeill JH: Oral vanadyl sulfate in treatment of diabetes mellitus in rats. Am J Physiol 257: H904–H911, 1989PubMedGoogle Scholar
  18. 18.
    McNeill JH, Yuen VG, Hoveyda HR, Orvig C: Bis(maltolato)-oxovanadium(IV) is a potent insulin mimic. J Med Chem 35: 1489–1491, 1992PubMedCrossRefGoogle Scholar
  19. 19.
    Shechter Y, Shisheva A, Lazar R, Libman J, Shanzer A: Hydrophobic carriers of vanadyl ions augment the insulinomimetic actions of vanadyl ions in rat adipocytes. Biochemistry 31: 2063–2068, 1992PubMedCrossRefGoogle Scholar
  20. 20.
    Sakurai H: A new orally active insulin-mimetic vanadyl complex: bis(pyrrolidine-N-carbodithiotato)oxovanadium(IV). J Med Chem 37: 876–877,1994PubMedCrossRefGoogle Scholar
  21. 21.
    Kadota S, Fantus IG, Deragon G, Guyda HJ, Hersh B, Posner BI: Peroxide(s) of vanadium: a novel and potent insulin mimetic-agent which activates the insulin receptor kinase. Biochem Biophys Res Commun 147: 259–266, 1987PubMedCrossRefGoogle Scholar
  22. 22.
    Posner BI, Burgess JW, Faure R, Bevan AP, Lachance D, Zhang-Sun G, Fantus IG, Ng JB, Hall DA, Soo Lum B, Shaver A: Peroxo-vanadium compounds: a new class of potent phosphotyrosine phosphatase inhibitors which are insulin mimetics. J Biol Chem 269: 4596–4604, 1994PubMedGoogle Scholar
  23. 23.
    Crans DC: Aqueous chemistry of labile oxovanadates: relevance to biological studies. Comments Inorg Chem 16: 1–33, 1994CrossRefGoogle Scholar
  24. 24.
    Crans DC: Enzyme interactions with labile oxovanadates and other polyoxometalates. Comments Inorg Chem 16: 35–76, 1994CrossRefGoogle Scholar
  25. 25.
    Butler A, Parsons SM, Yamagata SK, De la Rosa RI: Reactivation of vanadate-inhibited enzymes with desferrioxamine B, a vanadium(V) chelator. Inorg Chim Acta 163: 1–3, 1989CrossRefGoogle Scholar
  26. 26.
    Chasteen ND: Vanadyl(IV) EPR spin probes. Inorganic and biochemical aspects. Biol Magn Reson 3: 53–119, 1981Google Scholar
  27. 27.
    Butler A, Clague MJ, Meister GE: Vanadium peroxide complexes. Chem Rev 94: 625–638, 1994CrossRefGoogle Scholar
  28. 28.
    Campbell NJ, Dengel AC, Griffith WP: Studies on transition metal peroxo complexes-X. The nature of peroxovanadates in aqueous solution. Polyhedron 8: 1379–1386, 1989CrossRefGoogle Scholar
  29. 29.
    Sala-Pala J, Guerchais JE: Peroxo-complexes: triperoxovanadates(V) complexes. J Chem Soc (A) 1132–1136, 1971Google Scholar
  30. 30.
    Vuletic N, Djordjevic C: Oxodiperoxovanadate(V) complexes with bidentate ligands. J Chem Soc Dalton Trans 1137–1141, 1973Google Scholar
  31. 31.
    Bhattacharjee M, Chaudhuri MK, Islam NS, Paul PC: Synthesis, characterisation and physicochemical properties of peroxo-vanadium(V) complexes with glycine as the hetero-ligand. Inorg Chim Acta 169: 97–100, 1990CrossRefGoogle Scholar
  32. 32.
    Vuletic N, Djordjevic C: Oxodiperoxovanadate(V) complexes with bidentate ligands. J Chem Soc Dalton Trans: 1137–114, 1973Google Scholar
  33. 33.
    Szentivanyi H, Sternberg R: The crystal structure of ammonium (2,2′-bipyridine) oxodiperoxovanadate (V) tetrahydrate, NH4[VO (O2)2(C10H8N2)]·4H2O, at −100°C. Acta Chem Scand A37: 553–559, 1983CrossRefGoogle Scholar
  34. 34.
    Schwendt P, Petrovic P, Uskert D: Oxo-peroxokomplexe des vanadiums(V). Z Anorg Allg Chem 466: 232–236, 1980CrossRefGoogle Scholar
  35. 35.
    Begin D, Einstein FWB, Field J: An asymmetrically coordinated diperoxo compound. Crystal structure of K3[VO(O2)2(C2O4)]·H2O. Inorg Chem 14: 1785–1790, 1975CrossRefGoogle Scholar
  36. 36.
    Schwendt P, Pisárcik M: Vibrational spectra of ammonium amine-oxo-diperoxovanadate. Coll Czech Chem Commun 47: 1549–1555, 1982CrossRefGoogle Scholar
  37. 37.
    Drew RE, Einstein FWB: The crystal structure of ammonium oxodiperoxoamminevanadate (V). Inorg Chem 11: 1079–1083, 1972CrossRefGoogle Scholar
  38. 38.
    Hartkamp H: Darstellung von ammonium-[(pyridin-2,6-dicarboxylato)-oxo-peroxo-vanadat(V)]. Angew Chem 71: 553, 1959CrossRefGoogle Scholar
  39. 39.
    Drew RE, Einstein FWB: Crystal structure at −100°C of ammonium oxoperoxo(pyridine-2,6-dicarboxylato)vanadate (V) hydrate, NH4−[VO(O2)(H2O)(C5H3N(COO)2)]·xH2O (x=1.3). Inorg Chem 12: 829–835, 1973CrossRefGoogle Scholar
  40. 40.
    Mimoun H, Saussine L, Daire E, Postel M, Fischer J, Weiss R: Vanadium(V) peroxo complexes. New versatile biomimetic reagents for epoxidation of olefins and hydroxylation of alkanes and aromatic hydrocarbons. J Am Chem Soc 105: 3101–3110, 1983CrossRefGoogle Scholar
  41. 41.
    Quilitzsch U, Wieghardt K: Kinetics of the diperoxovanadate(V)-monoperoxovanadate(V) conversion in perchloric acid media. Inorg Chem 18: 869–871, 1979CrossRefGoogle Scholar
  42. 42.
    Shaver A, Ng JB, Hall DA, Soo Lum B, Posner BI: Insulin-mimetic peroxo vanadium complexes: preparation and structure of potassium oxodiperoxo(pyridine-2-carboxylato)vanadate(V), K2[VO(O2)2−(C5H4NCOO)]·2H2O, and potassium oxodiperoxo(3-hydroxypyridine-2-carboxylato)vanadate(V), K2[VO(O2)2(OHC5H3NCOO)]·3H2O, and their reactions with cysteine. Inorg Chem 32: 3109–3113, 1993CrossRefGoogle Scholar
  43. 43.
    Mimoun H, Chaumette P, Mignard M, Saussine L: First d° metal alkylperoxidic complexes. Synthesis, X-ray structure and hydroxylating properties of vanadium(V) dipicolinato alkylperoxides. Nouv J Chim 7: 467–475, 1983Google Scholar
  44. 44.
    Stomberg R: The crystal structures of potassium bis(oxalato)oxoperoxovanadate(V) hemihydrate, K3[VO(O2)(C2O4)2]•l/2H2O, and potassium bis(oxalato)dioxovanadate(V) trihydrate, K3[VO(O2)-(C2O4)2]·3H2O. Acta Chem Scand A40: 168–176, 1986CrossRefGoogle Scholar
  45. 45.
    Szentivanyi H, Stomberg R: The crystal structure of (2,2′-bipyridine)-oxoperoxo(pyridine-2-carboxylato)vanadium(V) hydrate, [VO-(O2)(C5H4NCOO)(C10H8N2)]·H2O at −100°C. Acta Chem Scand A37: 709–714, 1983CrossRefGoogle Scholar
  46. 46.
    Basumatary JK, Chaudhuri MK, Dutta Purkayastha RN, Hiese Z: First synthesis and structural assessment of alkali-metal carbonatodioxoperoxouranate(VI) monohydrates, A2[UO2(O2) CO3)]·H2O, and carbonatooxodiperoxovanadate(V) trihydrates, A3[VO(O2)2(CO3)]·3H2O. J Chem Soc Dalton Trans: 709–711, 1986Google Scholar
  47. 47.
    Stomberg R: The crystal structure of potassium carbonatooxodiperoxovanadate(V), K3[VO(O2)2(CO3)]. Acta Chem Scand A39: 725–731, 1985CrossRefGoogle Scholar
  48. 48.
    Shaver A, Hall DA, Ng JB, Lebuis AM, Hynes RC, Posner BI: Bisperoxovanadium compounds: Synthesis and reactivity of some insulin-mimetic complexes. Inorg Chim Acta 229: 253–260, 1995CrossRefGoogle Scholar
  49. 49.
    Shaver A, Ng JB, Hynes RC, Posner BI: Potassium (5-nitro-l,10-phenanthroline-N1,N10)oxodiperoxovanadate(V) dihydrate: an insulin mimetic peroxovanadate. Acta Cryst Sect C C50: 1044–1046, 1994CrossRefGoogle Scholar
  50. 50.
    Djordjevic C, Craig SA, Sinn E: A polymeric peroxo heteroligand vanadate(V). Synthesis, spectra, and structure of M1[VO(O2)(C4H54N). Inorg Chem 24: 1281–1283, 1985CrossRefGoogle Scholar
  51. 51.
    Djordjevic C, Lee M, Sinn E: Oxoperoxo(citrato)- and dioxo-(citrato)vanadates(V): synthesis, spectra and structure of a hydroxy1 oxygen bridged dimer K2[VO(O2)(C6H6O7)·]2–2H2O Inorg Chem 28: 719–723, 1989CrossRefGoogle Scholar
  52. 52.
    Chaudhuri MK, Ghosh SK: Synthesis of alkali oxydiperoxytluorovanadates(V). Polyhedron 1: 553–555, 1982CrossRefGoogle Scholar
  53. 53.
    Stomberg R: The crystal structure of potassium fluorooxodiperoxovanadate(V), K2[VFO(O2)2]. Acta Chem Scand A38: 223–228, 1984CrossRefGoogle Scholar
  54. 54.
    Stomberg R: The crystal structure of ammonium difluorooxodiperoxovanadate(V), (NH4)3[VF2O(O2)2]. Acta Chem Scand A38: 541–545, 1984CrossRefGoogle Scholar
  55. 55.
    Djordjevic C, Wampler GL: Antitumour activity and toxicity of peroxo heteroligand vanadates(V) in relation to biochemistry of vanadium. J Inorg Biochem 25: 51–55, 1985PubMedCrossRefGoogle Scholar
  56. 56.
    Wieghardt K: Preparation and characterization of dipicolinatovanadium(V) complexes. Kinetics and mechanism of their reaction with hydrogen peroxide in acidic media. Inorg Chem 17: 57–64, 1978CrossRefGoogle Scholar
  57. 57.
    Schwendt P, Sivak M, Lapshin AE, Smolin YI, Shepelev, YF, Gyepesova D: Ethylenediaminetetraacetato-monoperoxo complexes of vanadium(V). Trans Metal Chem 19: 34–36, 1994CrossRefGoogle Scholar
  58. 58.
    Vilter H, Rehder D: 51V NMR investigation of a vanadium(V)-dependant peroxidase from Ascophyllum nodosum (L) lejol. Inorg Chim Acta 136: L7–L10, 1987CrossRefGoogle Scholar
  59. 59.
    Campbell NJ, Capparelli MV, Griffith WP, Skapski AC: On the existence of triperoxo vanadium complexes. X-Ray crystal structures of K3[VO(O2)2(C2O4)]-H2O2 and of (NH4)[VO(O2)2(bipy)]·4H2O. Inorg Chim Acta 77: L215–L216, 1983CrossRefGoogle Scholar
  60. 60.
    Szentivanyi H, Stomberg R: The crystal structure of 2,2′-bipyridinium(l+)ì-hydrogen-bis[(2,2′-bipyridine)oxodiperoxovanadate](l-)-x-hydrogen peroxide-(6-x)-water, (Hbipy)[H{VO(O2)2bipy}2]-·xH2O2-(6-x)H2O, x ≈ 0.5, at –100°C. Acta Chem Scand A38: 101–107, 1984CrossRefGoogle Scholar
  61. 61.
    Stomberg R, Szentivanyi H: The crystal structure of 2,2′-bipyridinium(l+) (2,2′-bipyridine)oxodiperoxovanadate(1-)-(3+x)-hydrogen peroxide-(2-x)-water,(C10H9N2)[VO(O2)2(C10H9N2)]·(3+x)H2O2-(2-x)H2O, x ≈ 0.4, at –100°C. Acta Chem Scand A38: 121–128, 1984CrossRefGoogle Scholar
  62. 62.
    Bhattacharjee M, Chaudhuri MK, Paul PC: Synthesis and physicochemical studies of newer mono and diperoxo heteroligand complexes of vanadium. Can J Chem 70: 2245–2248, 1992CrossRefGoogle Scholar
  63. 63.
    Chaudhuri, M. K., Paul PC: Complex peroxovanadates(V) containing the chelated cysteinate as the co-ligand: synthesis and spectroscopic studies. Ind J Chem 31 A: 466–468, 1992Google Scholar
  64. 64.
    Chaudhuri MK, Ghosh SK:- Alkali-metal and ammonium triperoxyfluorovanadates(V), A2[V(O2)3F]. Inorg Chem 21: 4020-4022, 1982CrossRefGoogle Scholar
  65. 65.
    Chaudhuri MK, Ghosh SK, Islam NS: First synthesis and structural assessment of alkali-metal triperoxovanadates(V), A[V(O2)3]. Inorg Chem 24: 2706–2707, 1985CrossRefGoogle Scholar
  66. 66.
    Wu D, Lei X, Cao R, Hong M: Synthesis and structure of the peroxovanadium(V) complex containing the nitriloacetate Na2[VO- (O2)N(CH2COO)3]·5H2O. Jiegou Huaxue 11: 65–67, 1992Google Scholar
  67. 67.
    Wei YG, Zhang SW, Huang GQ, Shao MC: Synthesis, spectrum and single crystal structure of a peroxovanadium complex of nitrilotriacetate ligand without water of crystallization, K2[VO(O2)NTA]. Polyhedron 13: 1587–1591, 1994CrossRefGoogle Scholar
  68. 68.
    Kuchta L, Sivak M, Pavelcik F: Synthesis, characterization and crystal structure of barium (nitrilotriacetato)oxoperoxovanadate(V) trihydrate. J Chem Res S 393, 1993Google Scholar
  69. 69.
    Chaudhuri MK, Ghosh SK: The [VO(O2)2Cl]2−-[V(O2)3Cl]2− pair in peroxovanadium(V) chemistry: Synthesis of the first chloroperoxyvanadate(V) compounds and evidence for diperoxyvanadate(V)-triperoxyvanadate(V)interconversion. Inorg Chem 23:534–537, 1984CrossRefGoogle Scholar
  70. 70.
    Bhattacharjee M, Chaudhuri MK, Islam NS, Paul PC: Synthesis characterization and physicochemical properties of peroxo-vanadium(V) complexes with glycine as the heteroligand. Inorg Chim Acta 169: 97–100, 1990CrossRefGoogle Scholar
  71. 71.
    Bhattacharjee MN, Chaudhuri MK, Islam NS: Reactivity of coordinated peroxide at a highly peroxygenated vanadium(V) center in an aqueous medium. Inorg Chem 28: 2420–2423, 1989CrossRefGoogle Scholar
  72. 72.
    Jaswal JS, Tracey AS: Formation and decomposition of peroxovanadium complexes in aqueous solution. Inorg Chem 30: 3718–3722, 1991CrossRefGoogle Scholar
  73. 73.
    Stomberg R, Olson S, Svensson IB: The crystal structure of ammonium-μ-oxobis(oxodiperoxovanadate) (4-), (NH4)4[O{VO(O2)2}2]. A refinement. Acta Chem Scand. A38: 653–656, 1984CrossRefGoogle Scholar
  74. 74.
    Campbell NJ, Flanagan J, Griffith WP, Skapski, AC: X-ray structure of the peroxovanadate [HV2O11]3− ion in the ammonium peroxovanadate salt (NH4)3[HO{VO(O2)2}2]·H2O. Trans Met Chem 10: 353–354, 1985CrossRefGoogle Scholar
  75. 75.
    Djordjevic C, Puryear BC, Vuletic N, Abelt CJ, Sheffield SJ: Preparation, spectroscopic properties, and characterization of novel peroxo complexes of vanadium(V) and molybdenum(VI) with nicotinic acid and nicotinic acid N-oxide. Inorg Chem 27: 2926–2932, 1988CrossRefGoogle Scholar
  76. 76.
    Colpas GJ, Hamstra BJ, Kampf JW, Pecoraro VL: A functional model for vanadium haloperoxidase. J Am Chem Soc 116: 3627–3628, 1994CrossRefGoogle Scholar
  77. 77.
    Szentivanyi H, Stomberg R: The crystal structure of (2,2′-bipyridine)oxoperoxo(pyridine-2-carboxylato)vanadium(V) hydrate. Acta Chem Scand A37: 709–714, 1983CrossRefGoogle Scholar
  78. 78.
    Lever ABP, Gray HB: Electronic spectra of metal-dioxygen complexes. Acc Chem Res 11: 348–355, 1978CrossRefGoogle Scholar
  79. 79.
    Rehder D, Wieghardt K: The 51V NMR spectra of some oxo-, peroxo-, nitrosyl- and hydroxylamidovanadium complexes. Z Naturforsch 36B: 1251–1254, 1981Google Scholar
  80. 80.
    Rehder D, Weidemann C, Duch A, Priebsch W: 51V shielding in vanadium(V) complexes: A reference scale for vanadium binding sites in biomolecules. Inorg Chem 27: 586–587, 1988Google Scholar
  81. 81.
    Yale J-F, Lachance D, Bevan AP, Vigeant C, Shaver A, Posner, BI: Hypoglycemic effects of peroxovanadium compounds in Sprague-Dawley and diabetic BB rats. Diabetes in pressGoogle Scholar
  82. 82.
    Barford D, Flint AJ, Tonks NK: Crystal structure of human protein tyrosine phosphatase 1B. Science 263: 1397–1404, 1994PubMedCrossRefGoogle Scholar
  83. 83.
    Gresser MJ, Tracey AS: Vanadates as phosphate analogs in biochemistry. In: N.D. Chasteen (ed.). Vanadium in Biological systems. Kluwer Academic Publishers, Dordrecht, 1990, pp 63–79Google Scholar
  84. 84.
    Ballistreri FP, Tomaselli GA, Toscano RM, Conte V, DiFuria F: Application of the thianthrene 5-oxide mechanistic probe to peroxometal complexes. J Am Chem Soc 113: 6209–6212, 1991CrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1995

Authors and Affiliations

  • Alan Shaver
    • 1
  • Jesse B. Ng
    • 1
  • David A. Hall
    • 1
  • Barry I. Posner
    • 1
  1. 1.Departments of Chemistry and MedicineMcGill UniversityMontréalCanada

Personalised recommendations