Electron transfer in transition metal-pteridine systems

  • Sharon J. Nieter Burgmayer
Part of the Structure and Bonding book series (STRUCTURE, volume 92)


The combination of a pterin and a transition metal in many enzymes is the motivation for exploring the chemistry of pteridine complexes in detail. Unlike other biological ligands for essential transition metals, pterin is unique in displaying multi-electron redox reactivity, an ability that resembles the redox capabilities of transition metals. It is perhaps because these two partners, metal and pterin, have this chemical similarity that their compounds defy traditional categorization by formal oxidation number. The result challenges the chemist to formulate fresh interpretations of these deceptively ordinary complexes. This review concerns reports of metal-pterin complexes that appeared from the early 1980s through 1996. In a few cases older literature is briefly mentioned to build a context for the newer work. The review comprises four sections. Section 1 introduces the pteridine family and its important contributions to biochemistry. Section 2 is devoted to studies of molybdenum (6+) complexes reacted with reduced pterins. Section 3 describes redox interactions between reduced pterins and the first row metals copper and iron. Finally, Section 4 turns to a discussion of the electronic interactions in flavin complexes of various metals. An Epilogue closes the review.


Metalloenzyme molybdenum pteridine tetrahydropterin 


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  1. 1.
    Brown DJ (1988) Fused pyrimidines, pt 3. pteridines. Wiley, New YorkGoogle Scholar
  2. 2.
    Hurst DT (1980) Chemistry and biochemistry of pyrimidines, purines and pteridines. Wiley, New York, p 64Google Scholar
  3. 3.
    Pfleiderer W (1992), J Heterocycl Chem 29: 583CrossRefGoogle Scholar
  4. 4.
    The name pyrimido[4,5-b]pyrazine was adopted by Chemical Abstracts for a period of time and sometimes appears in older literatureGoogle Scholar
  5. 5.
    Albert A (1976) Adv Heterocycl Chem 20: 117CrossRefGoogle Scholar
  6. 6.
    Bieri JH, Viscontini M (1977) Helv Chim Acta 60: 447CrossRefGoogle Scholar
  7. 7.
    Bieri JH, Viscontini M (1977) Helv Chim Acta 60: 1926CrossRefGoogle Scholar
  8. 8.
    Armarego WLF, Waring P (1980) J Chem Res 318Google Scholar
  9. 9.
    Armarego WLF, Schou H (1977) J Chem Soc Perkin Trans 1: 2529CrossRefGoogle Scholar
  10. 10.
    Ganguly AN, Sengupta PK, Bieri JH, Viscontini M (1980) Helv Chim Acta 63: 395CrossRefGoogle Scholar
  11. 11.
    Weber R, Viscontini M (1975) Helv Chim Acta 58: 1772CrossRefGoogle Scholar
  12. 12.
    Benkovic SJ (1980) Annu Rev Biochem 49: 227PubMedCrossRefGoogle Scholar
  13. 13.
    Williams TC, Storm CB (1985) Biochem 24: 458CrossRefGoogle Scholar
  14. 14.
    Dryhurst G (1982) Electrochemistry of reduced pterin cofactors. In: Kadish KM (ed) Electrochemical and spectrochemical studies of biological redox components. American Chemical Society, Washington p 457Google Scholar
  15. 15.
    Dryhurst G (1977) In: Electrochemistry of biological molecules. Academic Press, New York, p 320Google Scholar
  16. 16.
    Pfleiderer W, Gottlieb R (1985) Electrolysis of pteridines. In: Wachter H, Curtius H, Pfleiderer W (eds) Biochemical and clinical aspects of pteridines. DeGruyter, Berlin, p 3Google Scholar
  17. 17.
    Kaufman S (1961) J Biol Chem 236: 804PubMedGoogle Scholar
  18. 18.
    Lazarus RA, DeBrosse CW, Benkovic SJ (1982) J Am Chem Soc 104: 6871CrossRefGoogle Scholar
  19. 19.
    Benkovic SJ, Sammons D, Armarego WLF, Waring P, Inners R (1985) J Am Chem Soc 107: 3706CrossRefGoogle Scholar
  20. 20.
    Archer MC, Scrimgeour KG (1970) Can J Biochem 48: 278PubMedCrossRefGoogle Scholar
  21. 21.
    Bailey SW, Ayling JE (1983) Biochemistry 1790Google Scholar
  22. 22.
    Blair JA, Pearson AJ (1975) J Chem Soc Perkin Trans 2Google Scholar
  23. 23.
    Kappock TJ, Caradonna JP (1996) Chem Rev 96: 2659PubMedCrossRefGoogle Scholar
  24. 24.
    For example, common artificial cofactors are 6,7-dimethyl tetrahydropterin and 6-methyltetrahydropterinGoogle Scholar
  25. 25.
    Massey V, Palmer G, Ballou D (1971) On the reaction of flavins and flavoproteins with molecular oxygen. In: Kamin H (ed) Flavins and flavoproteins. University Park Press, Baltimore, p 349Google Scholar
  26. 26.
    Mager HIX, Addink R, Berends W (1967) Recueil 86: 833Google Scholar
  27. 27.
    Pember SO, Villafranca JJ, Benkovic SJ (1986) Biochemistry 25: 6611PubMedCrossRefGoogle Scholar
  28. 28.
    Pember SO, Benkovic SJ, Villafranca JJ, Pasenkiewicz-Gierula M, Antholine WE (1986) Biochemistry 26: 4477CrossRefGoogle Scholar
  29. 29.
    Blackburn N, Strange RW, Carr RT, Benkovic SJ (1992) Biochemistry 313: 5298CrossRefGoogle Scholar
  30. 30.
    McCracken J, Pember SO, Benkovic SJ, Villafranca JJ, Miller RJ, Peisach J, (1988) J Am Chem Soc 110: 1068CrossRefGoogle Scholar
  31. 31.
    Carr RT, Benkovic SJ (1993) Biochemistry 32: 14,132CrossRefGoogle Scholar
  32. 32.
    Johnson JL, Hainline BE, Rajagopalan KV (1980) J Biol Chem 255: 1783PubMedGoogle Scholar
  33. 33.
    Pilato RS, Stiefel EI (1993) Catalysis by molybdenum-cofactor enzymes. In: Reedjik J (ed) Bioinorganic catalysis. Dekker, New York, p 131Google Scholar
  34. 34.
    Enemark JH, Young CG (1993) Bioinorganic chemistry of pterin-containing molybdenum and tungsten enzymes. In: Advances in inorganic chemistry, vol 40, p 1Google Scholar
  35. 35.
    Hille R (1996) Chem Rev 96: 2757PubMedCrossRefGoogle Scholar
  36. 36.
    Rajagopalan KV (1991) Novel aspects of the biochemistry of the molybdenum cofactor. In: Meister A (ed) Advances in enzymology and related areas of molecular biology, vol 64. Wiley, New York, p 215Google Scholar
  37. 37.
    Johnson JL, Hainline BE, Rajagopalan KV, Arison BH (1984) J Biol Chem 259: 5414PubMedGoogle Scholar
  38. 38.
    Johnson JL, Rajagopalan KV (1982) Proc Natl Acad Sci USA 79: 6856PubMedCrossRefGoogle Scholar
  39. 39.
    Kramer SP, Johnson JL, Ribeiro AA, Millington DS, Rajagopalan KV (1987) J Biol Chem 262: 16,357Google Scholar
  40. 40.
    Wuebbens MW, Rajagopalan KV (1993) J Biol Chem 268: 13,493Google Scholar
  41. 41.
    Johnson JL, Wuebbens MW, Rajagopalan KV (1989) J Biol Chem 264: 13,440Google Scholar
  42. 42.
    Johnson ME, Rajagopalan KV (1987) J Bacteriol 169: 110PubMedGoogle Scholar
  43. 43.
    Boyington JC, Gladyshev VN, Khangulov SV, Stadtman TC, Sun PD (1997) E. coli formate dehydrogenase. Science 275: 1305PubMedCrossRefGoogle Scholar
  44. 44.
    Romao MJ, Archer M, Moura I, Moura JJG, LeGall J, Engh R, Schneider M, Hof P, Huber R (1995) Desulfovibrio gigas aldehyde oxidoreductase. Science 270: 1170PubMedCrossRefGoogle Scholar
  45. 45.
    Huber R, Hof P, Duarte RO, Moura JJG, Moura I, Liu M-Y, LeGall J, Hille R, Archer M, Romao MJ (1996) Proc Natl Acad Sci USA 93: 8846PubMedCrossRefGoogle Scholar
  46. 46.
    Schindelin H, Kisker C, Hilton J, Rajagopalan KV, Rees DC (1996) Rhodobacter sphaeroides DMSO reductase. Science 272: 1615PubMedCrossRefGoogle Scholar
  47. 47.
    Schindelin H, Kisker C, Rees DC Chicken liver sulfite oxidase (personal communication)Google Scholar
  48. 48.
    Schultz B, Hille R, Holm RH (1995) J Am Chem Soc 117: 827CrossRefGoogle Scholar
  49. 49.
    Hille R, Sprecher H (1987) J Biol Chem 262: 10,914Google Scholar
  50. 50.
    Hille R, Massey V (1982) J Biol Chem 257: 8898PubMedGoogle Scholar
  51. 51.
    Dolphin D (1980) Model studies and the biochemical function of coenzymes. In: Biomimetic chemistry. American Chemical Society, Washington, DC, p 65Google Scholar
  52. 52.
    Bruice TC (1980) Acc Chem Res 13: 256CrossRefGoogle Scholar
  53. 53.
    Blakely RL, Benkovic SJ (1984) Folates and pterins. Wiley, New YorkGoogle Scholar
  54. 54.
    Vonderschmitt DJ, Scrimgeour KG (1967) Biochem Biophys Res Comm 28: 302PubMedCrossRefGoogle Scholar
  55. 55.
    Burgmayer SJN, Baruch A, Kerr K, Yoon K (1989) J Am Chem Soc 111: 4982CrossRefGoogle Scholar
  56. 56.
    Burgmayer SJN, Stiefel EI (1986) J Am Chem Soc 108: 8310CrossRefGoogle Scholar
  57. 57.
    Perkinson J, Brodie S, Yoon K, Mosny K, Carroll PJ, Burgmayer SJN (1991) Inorg Chem 30: 719CrossRefGoogle Scholar
  58. 58.
    Bessenmacher C, Vogler C, Kaim W (1989) Inorg Chem 28: 4645CrossRefGoogle Scholar
  59. 59.
    Kohzuma T, Masuda H, Yamauchi O (1989) J Am Chem Soc 111: 3431CrossRefGoogle Scholar
  60. 60.
    Kohzuma T, Odani A, Morita Y, Takani M, Yamauchi O (1988) Inorg Chem 27: 3854CrossRefGoogle Scholar
  61. 61.
    Mitsumi M, Toyoda J, Nakasuji K (1995) Inorg Chem 34: 3367CrossRefGoogle Scholar
  62. 62.
    Hueso-Urena F, Jimenez-Pulido SB, Moreno Carretero MN, Quiros-Olozabal M, Salas-Peregrin JM (1997) Polyhedron 16: 607CrossRefGoogle Scholar
  63. 63.
    Burgmayer SJN, Arkin MR, Bostick L, Dempster S, Everett KM, Layton HL, Paul KE, Rogge C, Rheingold AL (1995) J Am Chem Soc 117: 5812CrossRefGoogle Scholar
  64. 64.
    Wieghardt K, Hahn M, Swiridoff W, Weiss J (1984) Inorg Chem 23: 94CrossRefGoogle Scholar
  65. 65.
    Fischer B, Strahle J, Viscontini M (1991) Helv Chim Acta 74: 1544CrossRefGoogle Scholar
  66. 66.
    Kaufmann HL (1977) PhD dissertation. Bryn Mawr College, Bryn Mawr, PAGoogle Scholar
  67. 67.
    Gardlik S, Rajagopalan KV (1990) J Biol Chem 265: 13,047Google Scholar
  68. 68.
    Gardlik S, Barber MJ, Rajagopalan KV (1987) Arch Biochem Biophys 259: 363PubMedCrossRefGoogle Scholar
  69. 69.
    Kaufman S (1961) J Biol Chem 236: 804PubMedGoogle Scholar
  70. 70.
    Fischer B, Schmalle H, Dubler E, Schafer A, Viscontini M (1995) Inorg Chem 34: 5726CrossRefGoogle Scholar
  71. 71.
    Kaufmann HL, Burgmayer SJN (submitted to Inorg Chem)Google Scholar
  72. 72.
    Holm RH (1990) Coord Chem Rev 100: 183CrossRefGoogle Scholar
  73. 73.
    Holm RH (1987) Chem Rev 87: 1401CrossRefGoogle Scholar
  74. 74.
    Stiefel EI (1977) The coordination and bioinorganic chemistry of molybdenum. In: Lippard SJ (ed) Progess in inorganic chemistry, vol 22. Wiley, New York, p 3Google Scholar
  75. 75.
    Liu W, Thorp HH (1993) Inorg Chem 32: 4102CrossRefGoogle Scholar
  76. 76.
    Thorp HH (1992) Inorg Chem 31: 1585CrossRefGoogle Scholar
  77. 77.
    Brown ID, Altermatt D (1985) Acta Crystallogr B41: 244CrossRefGoogle Scholar
  78. 78.
    Soricelli CL, Szalai VA, Burgmayer SJN (1991) J Am Chem Soc 113: 9877CrossRefGoogle Scholar
  79. 79.
    Pilato RS, Eriksen K, Greaney MA, Gea Y, Taylor EC, Goswami S, Kilpatrick TG, Spiro TG, Rheingold AL, Stiefel EI (1993) Pterins, quinoxalines, and metallo-ene-dithiolates: synthetic approach to the molybdenum cofactor. In: Stiefel EI, Coucouvanis D, Newton WE (eds) Molybdenum enzymes, cofactors, and model systems. American Chemical Society, Washington, DC, p 83Google Scholar
  80. 80.
    Pilato RS, Eriksen K, Greaney MA, Gea Y, Taylor EC, Goswami S, Kilpatrick TG, Spiro TG, Rheingold AL, Stiefel EI (1991) J Am Chem Soc 113: 9372CrossRefGoogle Scholar
  81. 81.
    Chan MK, Mukund S, Kletzin A, Adams MWW, Rees DC (1995) Science 1463Google Scholar
  82. 82.
    Burgmayer SJN (unpublished results)Google Scholar
  83. 83.
    Burgmayer SJN, Pearsall D, manuscript to be submitted to J Am Chem Soc.Google Scholar
  84. 84.
    Funhashi Y, Kohzuma T, Odani A, Yamauchi O (1994) Chem Lett 385Google Scholar
  85. 85.
    Yamauchi O (1995) Pure Appl Chem 67: 297Google Scholar
  86. 86.
    Burgmayer SJN, Everett KM, Arkin MA, Mosny K (1991) J Bioinorg Chem 43: 581Google Scholar
  87. 87.
    Burgmayer SJN, Bharwani L, Mosny K (unpublished results)Google Scholar
  88. 88.
    Nasir M, Karlin K, Chen Q, Zubieta J (1992) J Am Chem Soc 114: 2264CrossRefGoogle Scholar
  89. 89.
    Schafer A, Fischer B, Paul H, Bosshard R, Hesse M, Viscontini M (1992) Helv Chim Acta 75: 1955CrossRefGoogle Scholar
  90. 90.
    Fischer B, Schafer A, Paul H, Bosshard R, Hesse M, Viscontini M (1993) Pteridines 4: 206Google Scholar
  91. 91.
    Schafer A, Fischer B, Bosshard R, Hesse M, Viscontini M (1993) In: Ayling JE, Gopal Nair M, Baugh CM, Viscontini M (eds) Chemistry and biology of pteridines. Proceedings of the 10th International Symposium on Pteridines and Folates. Plenum Press, New York, p 29Google Scholar
  92. 92.
    Albert A (1950) Biochem J 47: xxviiPubMedGoogle Scholar
  93. 93.
    Albert A (1953) Biochem J 54: 646PubMedGoogle Scholar
  94. 94.
    Hemmerich P, Muller F, Ehrenberg A (1965) The chemistry of flavin-metal interactions. In: King TE, Mason HS, Morrison M (eds) Oxidases and related redox systems, vol 1. Wiley, New York, p 157Google Scholar
  95. 95.
    Hemmerich P, Lauterwein J The structure and reactivity of flavin-metal complexes. In: Eichhorn GL (ed) Bioinorganic chemistry, chap 32, p 1198Google Scholar
  96. 96.
    Wade TD, Fritchie CJ (1973) J Biol Chem 248: 2337PubMedGoogle Scholar
  97. 97.
    Yu MY, Fritchie CJ (1975) J Biol Chem 250: 946PubMedGoogle Scholar
  98. 98.
    Muller F, Hemmerich P, Ehrenberg A, Palmer G, Massey V (1970) Eur J Biochem 14: 185PubMedCrossRefGoogle Scholar
  99. 99.
    Clarke MJ, Dowling MG, Garafalo AR, Brennan TF (1980) J Biol Chem 255: 4372Google Scholar
  100. 100.
    Clarke MJ, Dowling MG (1981) Inorg Chem 20: 3506CrossRefGoogle Scholar
  101. 101.
    Abelleira A, Galang R, Clarke MJ (1990) Inorg Chem 29: 633CrossRefGoogle Scholar
  102. 102.
    Selbin J, Sherrill J, Bigger CH (1974) Inorg Chem 13: 2544CrossRefGoogle Scholar
  103. 103.
    Sawyer DT, Doub WH (1975) Inorg Chem 14: 1736CrossRefGoogle Scholar
  104. 104.
    Kaufmann HL, Burgmayer SJN (submitted to Inorg Chem)Google Scholar
  105. 105.
    Frausto da Silva JJR, Williams RJP (1991) The bioinorganic chemistry of the elements. Clarendon Press, OxfordGoogle Scholar
  106. 106.
    Pierpont C (1994) Prog Inorg Chem 41: 331Google Scholar

Copyright information

© Springer Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • Sharon J. Nieter Burgmayer
    • 1
  1. 1.Department of ChemistryBryn Mawr CollegeBryn MawrUSA

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