Vanadium pp 35-49 | Cite as

Amavadine, a Vanadium Compound in Amanita Fungi

  • José A. L. da SilvaEmail author
  • João J. R. Fraústo da Silva
  • Armando J. L. PombeiroEmail author


This chapter is concerned with amavadine (also spelled as amavadin), a natural vanadium complex without the V=O bond, present in the fungus Amanita muscaria (L.:Fr.) Hook, which concentrates high levels of that metal (a capacity that is also known for a few other close Amanita fungi). The isolation, chemical synthesis and characterization of amavadine are reviewed, but its biological function remains unknown. However, the high stability constant of the complex, its redox behavior and ability to mediate the oxidation of some biological substrates support the possibility of a particular role (eventually concerning an enzyme) in the fungi, usually performed by other biomolecules, and biological functions of amavadine are suggested. The application of amavadine as a catalyst in chemical synthesis has been tested for some substrates, although under no biological conditions, and carboxylic acids, alcohols, ketones and halogenated compounds are obtained from oxidations of hydrocarbons catalyzed by very close models or a racemic mixture containing amavadine.


Amavadine Amanita fungi Catalase activity Peroxidase activity Oxidation of alkanes Oxidation of thiols Redox behavior Catalysis Electrocatalysis Non-oxo vanadium(IV) complexes Vanadium accumulation 



The authors are indebted to all co-authors cited in joint references, as well as to the Fundação para a Ciência e a Tecnologia (FCT) for partial financial support (pluriannual project PEst-OE/QUI/UI0100/2011).


  1. 1.
    Henze M (1911) Testings on the blood of ascidians I announcement – the vanadium compound of the blood corpuscles. Z Physiol Chem 72:494–501Google Scholar
  2. 2.
    Geml J, Tulloss RE, Laursen GA, Sazanova NA, Taylor DL (2008) Evidence for strong inter- and intracontinental phylogeographic structure in Amanita muscaria, a wind-dispersed ectomycorrhizal basidiomycete. Mol Phylogenet Evol 48:694–701CrossRefGoogle Scholar
  3. 3.
    Fraústo da Silva JJR (1989) Vanadium in biology – the case of the Amanita toadstools. Chem Spec Bioavailab 1:139–150Google Scholar
  4. 4.
    Bayer E (1995) Amavadin, the vanadium compound of Amanitae. In: Sigel H, Sigel A (eds) Vanadium and its role for life, metal ions in biological systems, vol 31. Marcel Dekker, New York, pp 407–421Google Scholar
  5. 5.
    Pombeiro AJL, Fraústo da Silva JJR, Fujiwara Y, Silva JAL, Reis PM, Palavra AMF Catalyst system and process for direct one-pot conversion of methane into acetic acid under relatively mild conditions, comprises vanadium complex, peroxodisulfate salt and trifluoroacetic acid. WO 2004/037416 A2. May 6, 2004Google Scholar
  6. 6.
    Ter Meulen H (1931) Regarding the distribution of the molybdene in nature. Rec Trav Chim Pays-Bas 50:491–504CrossRefGoogle Scholar
  7. 7.
    Bertrand D (1943) Le vanadium chez les champignons et plus spécialement chez les amanite. Bull Soc Chim Biol 25:194–197Google Scholar
  8. 8.
    Meisch H-U, Reinle W, Schmitt JA (1979) High vanadium content in mushrooms is not restricted to the fly agaric (Amanita muscaria). Z Naturforsch 66:620–621Google Scholar
  9. 9.
    Matoso CMM, Pombeiro AJL, da Silva JJR Fraústo, da Silva MFCG, da Silva JAL, Baptista-Ferreira JL, Pinho-Almeida F (1998) A possible role for amavadine in some Amanita fungi. In: Tracey AS, Crans DC (eds) Vanadium compounds – chemistry, biochemistry and therapeutic applications, American chemical society symposium series no. 711. American Chemical Society, Washington, DC, pp 241–247, Chapter 18, and references thereinCrossRefGoogle Scholar
  10. 10.
    Koch E, Kneifel H, Bayer E (1987) Occurrence of amavadin in mushrooms of the genus Amanita. Z Naturforsch 42c:873–878Google Scholar
  11. 11.
    Vetter J (2005) Mineral composition of basidiomes of Amanita species. Mycol Res 109: 746–750CrossRefGoogle Scholar
  12. 12.
    Falandysz J, Kunito T, Kubota R, Lipka K, Mazur A, Falandysz JJ, Tanabe S (2007) Selected elements in fly agaric Amanita muscaria. J Environ Sci Health A 42:1615–1623, and references thereinCrossRefGoogle Scholar
  13. 13.
    Bayer E, Kneifel H (1972) Isolation of amavadin, a vanadium compound occurring in Amanita muscaria. Z Naturforsch 27b:207–207Google Scholar
  14. 14.
    Kneifel H, Bayer E (1973) Determination of the structure of the vanadium compound, amavadine, from fly agaric. Angew Chem Int Ed 12:508–508Google Scholar
  15. 15.
    Koch E, Kneifel H, Bayer E (1986) Synthesis of new complexons – N-hydroxy-alpha, alpha′-iminodipropionic-hydroxyiminodiacetic and N-hydroxyiminodiacetic acid. Z Naturforsch 41b:359–362Google Scholar
  16. 16.
    Kneifel H, Bayer E (1986) Stereochemistry and total synthesis of amavadin, the naturally-occurring vanadium compound of Amanita-muscaria. J Am Chem Soc 108:3075–3077CrossRefGoogle Scholar
  17. 17.
    Hubregtse T, Neeleman E, Maschmeyer T, Sheldon RA, Hanefeld U, Arends IWCE (2005) The first enantioselective synthesis of the amavadin ligand and its complexation to vanadium. J Inorg Biochem 99:1264–1267CrossRefGoogle Scholar
  18. 18.
    Anderegg G, Koch E, Bayer E (1987) N-hydroxy-α, α′-iminodipropionic and N-hydroxyiminodiacetic acid as complexing agents and an example for selective coordination of the vanadyl ion VO2+ in amavadine. Inorg Chem Acta 127:183–188CrossRefGoogle Scholar
  19. 19.
    Hubregtse T, Kooijman H, Spek AL, Maschmeyer T, Sheldon RA, Arends IWCE, Hanefeld U (2007) Study on the isomerism in meso-amavadin and an amavadin analogue. J Inorg Biochem 101:900–908CrossRefGoogle Scholar
  20. 20.
    Smith PD, Berry RE, Harben SM, Beddoes RL, Helliwell M, Collison D, Garner CD (1997) New vanadium-(IV) and -(V) analogues of amavadin. J Chem Soc Dalton Trans 1997: 4509–4516CrossRefGoogle Scholar
  21. 21.
    Hubregtse T, Hanefeld U, Arends IWCE (2007) Stabilizing factors for vanadium(IV) in amavadin. Eur J Org Chem 2007:2413–2422CrossRefGoogle Scholar
  22. 22.
    Gillard RD, Lancashire RJ (1984) Electron-spin resonance of vanadium in Amanita muscaria. Phytochemistry 23:179–180CrossRefGoogle Scholar
  23. 23.
    Felcman J, Fraústo da Silva JJR, Vaz MCTA (1984) Metal-complexes of N-hydroxy-imino-di-α-propionic acid and related ligands. Inorg Chim Acta 93:101–108CrossRefGoogle Scholar
  24. 24.
    Bemski G, Felcman J, Fraústo da Silva JJR, Moura I, Moura JJG, Vaz MCTA, Vilas-Boas LF (1986) Amavadine, an oxovanadium(IV) complex of N-hydroxy-imino-α, α′-dipropionic acid. In: Xavier AV (ed) Frontiers in bioinorganic chemistry. VCH Verlagsgesellaschaft, Weinheim, pp 97–105Google Scholar
  25. 25.
    Bayer E, Koch E, Anderegg G (1987) Amavadin, an example for selective binding of vanadium in nature – studies of its complexation chemistry and a new structural proposal. Angew Chem Int Engl 26:545–546CrossRefGoogle Scholar
  26. 26.
    Carrondo MAAFdeCT, Duarte MTLS, Costa Pessoa J, Silva JAL, Fraústo da Silva JJR, Vaz MCTA, Vilas-Boas LF (1988) Bis-(N-hydroxy-iminodiacetate)vanadate(IV), a synthetic model of “amavadin”. J Chem Soc Chem Commun 1988:1158–1159CrossRefGoogle Scholar
  27. 27.
    Armstrong EM, Beddoes RL, Calviou LJ, Charnock JM, Collison D, Ertok N, Naismith JH, Garner CD (1993) The chemical nature of amavadin. J Am Chem Soc 115:807–808CrossRefGoogle Scholar
  28. 28.
    Paine TK, Weyhermuller T, Slep LD, Neese F, Bill E, Bothe E, Wieghardt K, Chaudhuri P (2004) Nonoxovanadium(IV) and oxovanadium(V) complexes with mixed O, X, O-donor ligands (X = S, Se, P, or PO). Inorg Chem 43:7324–7338CrossRefGoogle Scholar
  29. 29.
    Yadav HS, Armstrong EM, Beddoes RL, Collison D, Garner CD (1994) The molybdenum analog of amavadin. J Chem Soc Chem Commun 1994:605–606CrossRefGoogle Scholar
  30. 30.
    Galvão AM, Levi E, Pombeiro AJL, Guedes da Silva MFC, Silva JAL, Fraústo da Silva JJR (1995) Modelos da amavadina – estudos com o complexo de crómio(III) com hida. In: 2nd conference on inorganic chemistry of the Portuguese Chemical Society, Monte Real-Portugal, CP22, pp 91–92Google Scholar
  31. 31.
    Harben SM, Smith PD, Beddoes RL, Collison D, Garner CD (1997) Eight-coordinate [bis(oxyiminodiacetate)titanium(IV)]2- and nine-coordinate [bis(oxyiminodiacetate) aquazirconium(IV)]2−; variation in coordination mode in amavadin-like complexes. Angew Chem Int Engl 36:1897–1898CrossRefGoogle Scholar
  32. 32.
    Harben SM, Smith PD, Helliwell M, Collison D, Garner CD (1997) The synthesis, structure and nuclear magnetic resonance properties of some titanium relatives of amavadin: [Δ-Ti(R, R-hidpa)2]2-, [Δ, Λ-Ti(R, R-hidpa)2]2- and [Δ, Λ-Ti(hida)2]2- [H3hidpa = 2,2′-(hydroxyimino)dipropionic acid, H3hida = N-hydroxyiminodiacetic acid]. J Chem Soc Dalton Trans 1997:4517–4523CrossRefGoogle Scholar
  33. 33.
    Smith PD, Harben SM, Beddoes RL, Helliwell M, Collison D, Garner CD (1997) Synthesis and structures of niobium(V) and tantalum(V) analogues of amavadin: [M(hida)2]- (M=Nb-V or Ta-V, H3hida equals hydroxyimino-diacetic acid) and [Nb(R, R-hidpa)2]- [H3hidpa=2,2′-(hydroxyimino)-dipropionic acid]. J Chem Soc Dalton Trans 1997:685–691CrossRefGoogle Scholar
  34. 34.
    Smith PD, Cooney JJA, McInnes EJL, Beddoes RL, Collison D, Harben SM, Helliwell M, Mabbs FE, Mandel A, Powell AK, Garner CD (2001) New molybdenum(V) analogues of amavadin and their redox properties. J Chem Soc Dalton Trans 2001:3108–3114CrossRefGoogle Scholar
  35. 35.
    Carrondo MAAFD, Duarte MTLS, Silva JAL, daSilva JJRF (1991) The crystal and molecular-structure of N, N′-bipyridyl, N-methoxy iminodiacetate oxovanadium(IV). Polyhedron 10:73–77CrossRefGoogle Scholar
  36. 36.
    Berry RE, Armstrong EM, Beddoes RL, Collison D, Ertok SN, Helliwell M, Garner CD (1999) The structural characterization of amavadin. Angew Chem Int Engl 38:795–797CrossRefGoogle Scholar
  37. 37.
    Armstrong EM, Collison D, Ertok N, Garner CD (1999) NMR studies on natural and synthetic amavadin. Conference Information: XXXIst Colloquium Spectroscopicum Internationale, 05–10 Sept 1999 Ankara, Turkey Talanta 53 (2000) Spl. Issue SI 75–87Google Scholar
  38. 38.
    Armstrong EM, Collison D, Deeth RJ, Garner CD (1995) Discrete variational Xα studies of the electronic-structure of amavadin. J Chem Soc Dalton Trans 1995:191–195CrossRefGoogle Scholar
  39. 39.
    Remenyi C, Munzarova ML, Kaupp M (2005) Comparative density-functional study of the electron paramagnetic resonance parameters of amavadin. J Phys Chem B 109:4227–4233CrossRefGoogle Scholar
  40. 40.
    Geethalakshmi KR, Waller MP, Buhl M (2007) The presumption of innocence? A DFT-directed verdict on oxidized amavadin and vanadium catecholate complexes. Inorg Chem 46: 11297–11307CrossRefGoogle Scholar
  41. 41.
    Ooms KJ, Bolte SE, Baruah B, Choudhary MA, Crans DC, Polenova T (2009) 51V solid-state NMR and density functional theory studies of eight-coordinate non-oxo vanadium complexes: oxidized amavadin. Dalton Trans 2009:3262–3269Google Scholar
  42. 42.
    Nawi MA, Riechel TL (1987) The electrochemistry of amavadine, a vanadium natural product. Inorg Chim Acta 136:33–39CrossRefGoogle Scholar
  43. 43.
    Thackrey RD, Riechel TL (1988) Mediators for the oxidation of glutathione and other biological thiols. J Electroanal Chem 245:131–143CrossRefGoogle Scholar
  44. 44.
    Fraústo da Silva JJR, Guedes da Silva MFC, Silva JAL, Pombeiro AJL (1993) Redox properties of the amavadine models [V(hida)2]2− and [V(hidpa)2]2− and their electroinduced reactivity toward activated-thiols and activated-phenols. In: Pombeiro AJL, McCleverty JA (eds) Molecular electrochemistry of inorganic, bioinorganic and organometallic compounds. Kluwer Academic, Dordrecht, pp 411–415Google Scholar
  45. 45.
    Guedes da Silva MFC, Silva JAL, Fraústo da Silva JJR, Pombeiro AJL, Amatore C, Verpeaux J-N (1996) Evidence for a Michaelis-Menten type mechanism in the electrocatalytic oxidation of mercaptopropionic acid by an amavadine model. J Am Chem Soc 118:7568–7573CrossRefGoogle Scholar
  46. 46.
    Lenhardt JM, Baruah B, Crans DC, Johnson MD (2006) Self-exchange electron transfer in high oxidation state non-oxo metal complexes: amavadin. Chem Commun 44:4641–4643CrossRefGoogle Scholar
  47. 47.
    Lenhardt JM, Baruah B, Crans DC, Johnson MD (2009) Electron transfer in non-oxovanadium(IV) and (V) complexes: kinetic studies of an amavadin model. Conference Information: 6th international symposium on chemistry and biological chemistry of vanadium, Lisbon, Portugal, 17–19 July 2009, Pure Appl Chem 81:1241–1249Google Scholar
  48. 48.
    Reis PM, Silva JAL, da Silva JJRF, Pombeiro AJL (2000) Amavadine as a catalyst for the peroxidative halogenation, hydroxylation and oxygenation of alkanes and benzene. Chem Commun 2000:1845–1856CrossRefGoogle Scholar
  49. 49.
    Reis PM, Silva JAL, da Silva JJRF, Pombeiro AJL (2004) Peroxidative oxidation of benzene and mesitylene by vanadium catalysts. J Mol Catal A Chem 224:189–195CrossRefGoogle Scholar
  50. 50.
    Reis PM, Silva JAL, Palavra AF, da Silva JJRF, Kitamura T, Fujiwara Y, Pombeiro AJL (2003) Single-pot conversion of methane into acetic acid in the absence of CO and with vanadium catalysts such as amavadine. Angew Chem Int Engl 42:821–823CrossRefGoogle Scholar
  51. 51.
    Kirillova MV, Kuznetsov ML, Reis PM, da Silva JAL, da Silva JJRF, Pombeiro AJL (2007) Direct and remarkably efficient conversion of methane into acetic acid catalyzed by amavadine and related vanadium complexes. A synthetic and a theoretical DFT mechanistic study. J Am Chem Soc 129:10531–10545CrossRefGoogle Scholar
  52. 52.
    Kirillova MV, Kuznetsov ML, da Silva JAL, da Silva MFC, da Silva JJRF, Pombeiro AJL (2008) Amavadin and other vanadium complexes as remarkably efficient catalysts for one-pot conversion of ethane to propionic and acetic acids. Chem Eur J 14:1828–1842CrossRefGoogle Scholar
  53. 53.
    Kirillova MV, da Silva JAL, da Silva JJRF, Palavra AF, Pombeiro AJL (2007) Highly efficient direct carboxylation of propane into butyric acids catalyzed by vanadium complexes. Adv Synth Catal 349:1765–1774CrossRefGoogle Scholar
  54. 54.
    Reis PM, Silva JAL, Palavra AF, da Silva JJRF, Pombeiro AJL (2005) Vanadium-catalyzed carboxylation of linear and cyclic C-5 and C-6 alkanes. J Catal 235:333–340CrossRefGoogle Scholar
  55. 55.
    Pombeiro AJL, Kirillova MV, Kirillov AM, Silva JAL, Fraústo da Silva JJR method for the conversion, under mild conditions and in aqueous medium, of gaseous and liquid alkanes into carboxylic acids. WO/2008/088234-A1. July 24, 2008Google Scholar
  56. 56.
    Kirillova MV, Kirillov AM, Kuznetsov ML, Silva JAL, da Silva JJRF, Pombeiro AJL (2009) Alkanes to carboxylic acids in aqueous medium: metal-free and metal-promoted highly efficient and mild conversions. Chem Commun 2009:2353–2355CrossRefGoogle Scholar
  57. 57.
    Kirillova MV, Kirillov AM, Pombeiro AJL (2009) Metal-free and copper-promoted single-pot hydrocarboxylation of cycloalkanes to carboxylic acids in aqueous medium. Adv Synth Catal 351:2936–2948CrossRefGoogle Scholar
  58. 58.
    Kirillova MV, Kirillov AM, Pombeiro AJL (2010) Mild, single-pot hydrocarboxylation of gaseous alkanes to carboxylic acids in metal-free and copper-promoted aqueous systems. Chem Eur J 16:9485–9493CrossRefGoogle Scholar
  59. 59.
    Hubregtse T (2007) Structural investigations of amavadin-based vanadium complexes. D Phil thesis, Technical University of Delft, The NetherlandsGoogle Scholar
  60. 60.
    Carrondo MAAFD, Duarte MTLS, Silva JAL, Fraústo daSilva JJRF (1992) An X-ray study of the complex anion bis(N-hydroxy-iminodiacetate) vanadate(IV) – a model for vanadium containing biological compound. Struct Chem 3:113–119CrossRefGoogle Scholar
  61. 61.
    Fraústo da Silva JJR, Williams RJP (2001) The biological chemistry of the elements – the inorganic chemistry of life, 2nd edn. Clarendon, OxfordGoogle Scholar
  62. 62.
    Crans DC, Smee JJ, Gaidamauskas E, Yang L (2004) The chemistry and biochemistry of vanadium and the biological activities exerted by vanadium compounds. Chem Rev 104: 8499–902CrossRefGoogle Scholar
  63. 63.
    Durner J, Klessig DF (1995) Inhibition of ascorbate peroxidase by salicylic-acid and 2,6-dichloroisonicotinic acid, 2 inducers of plant defense responses. Proc Natl Acad Sci USA 92:11312–11316CrossRefGoogle Scholar
  64. 64.
    Cotton FA, Wilkinson G (1966) Advanced inorganic chemistry – a comprehensive text, 2nd edn. Interscience, New YorkGoogle Scholar
  65. 65.
    Borovicka J, Randa Z (2007) Distribution of iron, cobalt, zinc and selenium in macrofungi. Mycol Prog 6:249–259CrossRefGoogle Scholar
  66. 66.
    Williams RJP, Fraústo da Silva JJR (1996) The natural selection of the chemical elements. Oxford University Press, OxfordGoogle Scholar
  67. 67.
    Almeida M, Humanes M, Melo R, Silva JA, da Silva JJRF, Vilter H, Wever R (1998) Saccorhiza polyschides (phaeophyceae; phyllariaceae) a new source for vanadium-dependent haloperoxidases. Phytochemistry 48:229–239CrossRefGoogle Scholar
  68. 68.
    Strack D, Vogt T, Schliemann W (2003) Recent advances in betalain research. Phytochemistry 62:247–269CrossRefGoogle Scholar
  69. 69.
    Molina R, Trappe JM (1982) Patterns of ectomycorrhizal host specificity and potential among pacific northwest conifers and fungi. For Sci 28:423–458Google Scholar
  70. 70.
    Bertrand D (1950) The biochemistry of vanadium. Am Mus Nat Hist Bull 94:403–456Google Scholar
  71. 71.
    Watkinson JH (1964) Selenium-accumulating plant of humid regions – Amanita muscaria. Nature 202:1239–1240CrossRefGoogle Scholar
  72. 72.
    Meisch H-U, Schmitt JA, Reinle W (1978) Heavy-metals in higher fungi. 3. vanadium and molybdenum. Z Naturforsch 33c:1–6Google Scholar
  73. 73.
    Stijve T (1977) Selenium content of mushrooms. Z Lebensm Unters Forsch 164:201–203CrossRefGoogle Scholar
  74. 74.
    Drehmel D, Moncalvo JM, Vilgalys R (1999) Molecular phylogeny of Amanita based on large-subunit ribosomal DNA sequences: implications for taxonomy and character evolution. Mycologia 91:610–618CrossRefGoogle Scholar

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© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  1. 1.Centro de Química Estrutural, Complexo I, Instituto Superior TécnicoTechnical University of LisbonLisbonPortugal

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