The Role of the Pyranopterin Dithiolene Component of Moco in Molybdoenzyme Catalysis

  • Sharon J. Nieter BurgmayerEmail author
  • Martin L. KirkEmail author
Part of the Structure and Bonding book series (STRUCTURE, volume 179)


An overview of the pyranopterin dithiolene (MPT) component of the molybdenum cofactor (Moco) and how MPT may contribute to enzymatic catalysis is presented. The chapter begins with a brief review of MPT and Moco biosynthesis and continues to explore the nature of what is arguably the most electronically complex ligand in biology. To explore this complexity, we have dissected MPT into its relevant molecular components. These include the redox-active ene-1,2-dithiolate (dithiolene) and pterin moieties, which are bridged by a pyran that may be found in ring-opened or ring-closed configurations. The various redox possibilities of MPT bound to Mo are presented, along with the electronic structure of the redox components. MPTs are found to display a remarkable conformational variance in pyranopterin Mo enzymes. This is discussed in terms of a relationship to enzyme function and the potential for the observed non-planer distortions to reflect different MPT oxidation and tautomeric states. The chapter ends with a series of case studies featuring model compounds that highlight how biomimetic small molecule studies have contributed to furthering our understanding of the roles this remarkable ligand plays in the catalytic cycles of the enzymes.


Dithiolene Moco Molybdenum cofactor Molybdenum enzymes Molybdopterin Pyranopterin 


  1. 1.
    Pritsos CA (2000) Cellular distribution, metabolism and regulation of the xanthine oxidoreductase enzyme system. Chem Biol Interact 129(1–2):195PubMedGoogle Scholar
  2. 2.
    Rooseboom M, Commandeur JNM, Vermeulen NPE (2004) Enzyme-catalyzed activation of anticancer prodrugs. Pharmacol Rev 56(1):53CrossRefGoogle Scholar
  3. 3.
    Kotthaus J et al (2011) New prodrugs of the antiprotozoal drug pentamidine. ChemMedChem 6:2233–2242PubMedGoogle Scholar
  4. 4.
    Havemeyer A et al (2010) Reduction of N-hydroxy-sulfonamides, Including N-hydroxy-valdecoxib, by the molybdenum-containing enzyme mARC. Drug Metab Dispos 38:1917–1921PubMedGoogle Scholar
  5. 5.
    Mendel RR, Kruse T (2012) Cell biology of molybdenum in plants and humans. BBA-Mol Cell Res 1823(9):1568–1579Google Scholar
  6. 6.
    Mendel RR, Schwarz G (2011) Molybdenum cofactor biosynthesis in plants and humans. Coord Chem Rev 255(9-10):1145–1158Google Scholar
  7. 7.
    Kotthaus J et al (2011) Reduction of N(ω)-hydroxy-L-arginine by the mitochondrial amidoxime reducing component (mARC). Biochem J 433:383–391PubMedGoogle Scholar
  8. 8.
    Sparacino-Watkins CE et al (2014) Nitrite reductase and nitric-oxide synthase activity of the mitochondrial molybdopterin enzymes mARC1 and mARC2. J Biol Chem 289(15):10345–10358PubMedPubMedCentralGoogle Scholar
  9. 9.
    Hille R, Hall J, Basu P (2014) The mononuclear molybdenum enzymes. Chem Rev 114(7):3963–4038PubMedPubMedCentralGoogle Scholar
  10. 10.
    Hille R (2002) Molybdenum enzymes containing the pyranopterin cofactor: an overview. Marcel Dekker, Inc, New York, pp 187–226Google Scholar
  11. 11.
    Berry CE, Hare JM (2004) Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and pathophysiological implications. J Physiol 555(3):589–606PubMedGoogle Scholar
  12. 12.
    Reiss J (2000) Genetics of molybdenum cofactor deficiency. Hum Genet 106(2):157PubMedGoogle Scholar
  13. 13.
    Stein BW, Kirk ML (2015) Electronic structure contributions to reactivity in xanthine oxidase family enzymes. J Biol Inorg Chem 20(2):183–194PubMedGoogle Scholar
  14. 14.
    Kirk ML, Stein B (2013) The molybdenum enzymes. In: Jan R, Kenneth P (eds) Comprehensive inorganic chemistry II, 2nd edn. Elsevier, Amsterdam, pp 263–293Google Scholar
  15. 15.
    Jones RM, Inscore FE, Hille R, Kirk ML (1999) Freeze-quench magnetic circular dichroism spectroscopic study of the “very rapid” intermediate in xanthine oxidase. Inorg Chem 38(22):4963–4970PubMedGoogle Scholar
  16. 16.
    Hille R, Nishino T, Bittner F (2011) Molybdenum enzymes in higher organisms. Coord Chem Rev 255(9-10):1179–1205PubMedPubMedCentralGoogle Scholar
  17. 17.
    Hille R (2005) Molybdenum-containing hydroxylases. Arch Biochem Biophys 433(1):107–116PubMedGoogle Scholar
  18. 18.
    Hille R (1997) Mechanistic aspects of the mononuclear molybdenum enzymes. J Biol Inorg Chem 2(6):804–809Google Scholar
  19. 19.
    Mtei RP et al (2011) Spectroscopic and electronic structure studies of a dimethyl sulfoxide reductase catalytic intermediate: implications for electron- and atom-transfer reactivity. J Am Chem Soc 133(25):9762–9774PubMedPubMedCentralGoogle Scholar
  20. 20.
    Hemann C et al (2005) Spectroscopic and kinetic studies of Arabidopsis thaliana sulfite oxidase: nature of the redox-active orbital and electronic structure contributions to catalysis. J Am Chem Soc 127(47):16567PubMedGoogle Scholar
  21. 21.
    Yang J et al (2015) Oxyl and hydroxyl radical transfer in mitochondrial amidoxime reducing component-catalyzed nitrite reduction. J Am Chem Soc 137(16):5276–5279PubMedPubMedCentralGoogle Scholar
  22. 22.
    Maia L, Moura JG (2015) Nitrite reduction by molybdoenzymes: a new class of nitric oxide-forming nitrite reductases. J Biol Inorg Chem 20(2):403–433PubMedGoogle Scholar
  23. 23.
    Hille R, Retey J, Bartlewski Hof U, Reichenbecher W, Schink B (1998) Mechanistic aspects of molybdenum containing enzymes. FEMS Microbiol Rev 22(5):489–501PubMedGoogle Scholar
  24. 24.
    Hille R (1996) Structure and function of mononuclear molybdenum enzymes. J Biol Inorg Chem 1(5):397–404Google Scholar
  25. 25.
    Hille R (1996) The mononuclear molybdenum enzymes. Chem Rev 96(7):2757–2816PubMedGoogle Scholar
  26. 26.
    Rothery RA, Stein B, Solomonson M, Kirk ML, Weiner JH (2012) Pyranopterin conformation defines the function of molybdenum and tungsten enzymes. Proc Natl Acad Sci U S A 109(37):14773–14778PubMedPubMedCentralGoogle Scholar
  27. 27.
    Kirk ML (2016) Spectroscopic and electronic structure studies of Mo model compounds and enzymes. In: Russ Hille CS, Kirk ML (eds) Molybdenum and tungsten enzymes: spectroscopic and theoretical investigations, RSC metallobiology series no. 7, The Royal Society of Chemistry, Cambridge, pp 13–67Google Scholar
  28. 28.
    Pushie MJ, George GN (2011) Spectroscopic studies of molybdenum and tungsten enzymes. Coord Chem Rev 255(9–10):1055–1084Google Scholar
  29. 29.
    Schwarz G (2016) Molybdenum cofactor and human disease. Curr Opin Chem Biol 31:179–187PubMedGoogle Scholar
  30. 30.
    Mendel RR, Leimkuhler S (2015) The biosynthesis of the molybdenum cofactors. J Biol Inorg Chem 20(2):337–347PubMedGoogle Scholar
  31. 31.
    Maia LB, Moura JJG, Moura I (2015) Molybdenum and tungsten-dependent formate dehydrogenases. J Biol Inorg Chem 20(2):287–309PubMedGoogle Scholar
  32. 32.
    Metz S, Thiel W (2011) Theoretical studies on the reactivity of molybdenum enzymes. Coord Chem Rev 255(9–10):1085–1103Google Scholar
  33. 33.
    Sugimoto H, Tsukube H (2008) Chemical analogues relevant to molybdenum and tungsten enzyme reaction centres toward structural dynamics and reaction diversity. Chem Soc Rev 37(12):2609–2619PubMedGoogle Scholar
  34. 34.
    Niks D, Hille R (2018) Molybdenum- and tungsten-containing formate dehydrogenases and formylmethanofuran dehydrogenases: structure, mechanism and cofactor insertion. Protein Sci 28(1):111–122PubMedGoogle Scholar
  35. 35.
    Kaufholdt D, Baillie C-K, Meinen R, Mendel RR, Hänsch R (2017) The molybdenum cofactor biosynthesis network: in vivo protein-protein interactions of an actin associated multi-protein complex. Front Plant Sci 8:1946PubMedPubMedCentralGoogle Scholar
  36. 36.
    Johnson JL, Rajagopalan KV (1982) Structural and metabolic relationship between the molybdenum cofactor and urothione. Proc Natl Acad Sci U S A 79:6856–6860PubMedPubMedCentralGoogle Scholar
  37. 37.
    Groves JT (2006) High-valent iron in chemical and biological oxidations. J Inorg Biochem 100(4):434–447PubMedGoogle Scholar
  38. 38.
    Rittle J, Green MT (2010) Cytochrome P450 compound I: capture, characterization, and C-H bond activation kinetics. Science 330(6006):933–937PubMedGoogle Scholar
  39. 39.
    Holt BTO et al (2009) Reaction coordinate of a functional model of tyrosinase: spectroscopic and computational characterization. J Am Chem Soc 131(18):6421–6438Google Scholar
  40. 40.
    Mirica LM et al (2005) Tyrosinase reactivity in a model complex: an alternative hydroxylation mechanism. Science 308(5730):1890–1892PubMedGoogle Scholar
  41. 41.
    Schwarz G, Mendel RR, Ribbe MW (2009) Molybdenum cofactors, enzymes and pathways. Nature 460(7257):839–847Google Scholar
  42. 42.
    Weiss MC et al (2016) The physiology and habitat of the last universal common ancestor. Nat Microbiol 1(9):16116PubMedGoogle Scholar
  43. 43.
    Leimkuhler S & Mendel R (2016) Molybdenum cofactor biosynthesis. In: Hille R, Schulzke C, Kirk ML (eds) Molybdenum and tungsten enzymes, RSC metallobiochemistry, vol 1, RSC, Cambridge, pp 100–111Google Scholar
  44. 44.
    Schwarz G, Mendel RR (2006) Molybdenum cofactor biosynthesis and molybdoenzymes. Annu Rev Plant Biol 57(1):623–647PubMedGoogle Scholar
  45. 45.
    Llamas A, Otte T, Multhaup G, Mendel RR, Schwarz G (2006) The mechanism of nucleotide-assisted molybdenum insertion into molybdopterin – a novel route toward metal cofactor assembly. J Biol Chem 281(27):18343–18350PubMedGoogle Scholar
  46. 46.
    Krausze J et al (2018) The functional principle of eukaryotic molybdenum insertases. Biochem J 475:1739–1753PubMedPubMedCentralGoogle Scholar
  47. 47.
    Krausze J et al (2017) Dimerization of the plant molybdenum insertase Cnx1E is required for synthesis of the molybdenum cofactor. Biochem J 474(1):163PubMedGoogle Scholar
  48. 48.
    Sempombe J, Stein B, Kirk ML (2011) Spectroscopic and electronic structure studies probing covalency contributions to C-H bond activation and transition-state stabilization in xanthine oxidase. Inorg Chem 50(21):10919–10928PubMedPubMedCentralGoogle Scholar
  49. 49.
    Ilich P, Hille R (1999) Mechanism of formamide hydroxylation catalyzed by a molybdenum-dithiolene complex: a model for xanthine oxidase reactivity. J Phys Chem B 103(25):5406–5412Google Scholar
  50. 50.
    Fischer B, Enemark JH, Basu P (1998) A chemical approach to systematically designate the pyranopterin centers of molybdenum and tungsten enzymes and synthetic models. J Inorg Biochem 72:13–21PubMedGoogle Scholar
  51. 51.
    Schwarz, G, Mendel RR (2006) Molybdenum cofactor biosynthesis and molybdoenzymes. Annu Rev Plant Biol 57(1):623–647PubMedGoogle Scholar
  52. 52.
    Greatbanks SP, Hillier IH, Garner CD, Joule JA (1997) The relative stabilities of dihydropterins; a comment on the structure of Moco; the cofactor of the oxomolybdoenzymes. J Chem Soc Perkin Trans 2(8):1529–1534Google Scholar
  53. 53.
    Enemark JH, Garner CD (1997) The coordination chemistry and function of the molybdenum centres of the oxomolybdoenzymes. J Biol Inorg Chem 2(6):817–822Google Scholar
  54. 54.
    Burgmayer SJN, Pearsall DL, Blaney SM, Moore EM, Sauk-Schubert C (2004) Redox reactions of the pyranopterin system of the molybdenum cofactor. J Biol Inorg Chem 9(1):59–66Google Scholar
  55. 55.
    Basu P, Burgmayer SJN (2011) Pterin chemistry and its relationship to the molybdenum cofactor. Coord Chem Rev 255(9‚10):1016–1038PubMedPubMedCentralGoogle Scholar
  56. 56.
    Matz KG, Mtei RP, Rothstein R, Kirk ML, Burgmayer SJN (2011) Study of molybdenum(4+) quinoxalyldithiolenes as models for the noninnocent pyranopterin in the molybdenum cofactor. Inorg Chem 50(20):9804–9815PubMedPubMedCentralGoogle Scholar
  57. 57.
    Matz KG, Mtei RP, Leung B, Burgmayer SJN, Kirk ML (2010) Noninnocent dithiolene ligands: a new oxomolybdenum complex possessing a donor acceptor dithiolene ligand. J Am Chem Soc 132(23):7830–7831PubMedPubMedCentralGoogle Scholar
  58. 58.
    Burgmayer SJN et al (2007) Synthesis, characterization, and spectroscopy of model molybdopterin complexes. J Inorg Biochem 101(11-12):1601–1616PubMedPubMedCentralGoogle Scholar
  59. 59.
    Kirk ML (2016) Spectroscopic and electronic structure studies of Mo model compounds and enzymes. In: Molybdenum and tungsten enzymes: spectroscopic and theoretical investigations, vol 3, Molybdenum and tungsten enzymes, The Royal Society of Chemistry, London, pp 13–67Google Scholar
  60. 60.
    Adamson H et al (2015) Electrochemical evidence that pyranopterin redox chemistry controls the catalysis of YedY, a mononuclear Mo enzyme. Proc Natl Acad Sci U S A 112(47):14506–14511PubMedPubMedCentralGoogle Scholar
  61. 61.
    Hille R, Anderson RF (1991) Electron transfer in milk xanthine oxidase as studied by pulse radiolysis. J Biol Chem 266(9):5608–5615PubMedGoogle Scholar
  62. 62.
    Bertero MG et al (2003) Insights into the respiratory electron transfer pathway from the structure of nitrate reductase A. Nat Struct Biol 10(9):681–687PubMedGoogle Scholar
  63. 63.
    Kloer DP, Hagel C, Heider J, Schulz GE (2006) Crystal structure of ethylbenzene dehydrogenase from Aromatoleum aromaticum. Structure 14(9):1377–1388PubMedGoogle Scholar
  64. 64.
    Jormakka M, Richardson D, Byrne B, Iwata S (2004) Architecture of NarGH reveals a structural classification of Mo-bisMGD enzymes. Structure 12(1):95–104PubMedGoogle Scholar
  65. 65.
    Dietzel U et al (2009) Mechanism of substrate and inhibitor binding of rhodobacter capsulatus xanthine dehydrogenase. J Biol Chem 284(13):8759–8767Google Scholar
  66. 66.
    Enroth C et al (2000) Crystal structures of bovine milk xanthine dehydrogenase and xanthine oxidase: structure-based mechanism of conversion. Proc Natl Acad Sci U S A 97(20):10723–10728 PubMedPubMedCentralGoogle Scholar
  67. 67.
    Leimkuhler S, Hodson R, George GN, Rajagopalan KV (2003) Recombinant Rhodobacter capsulatus xanthine dehydrogenase, a useful model system for the characterization of protein variants leading to xanthinuria I in humans. J Biol Chem 278(23):20802–20811PubMedGoogle Scholar
  68. 68.
    Truglio J et al (2002) Crystal structures of the active and alloxanthine-inhibited forms of xanthine dehydrogenase from Rhodobacter capsulatus. Structure 10(1):115–125PubMedGoogle Scholar
  69. 69.
    Westcott BL, Gruhn NE, Enemark JH (1998) Evaluation of molybdenum-sulfur interactions in molybdoenzyme model complexes by gas-phase photoelectron spectroscopy. The “electronic buffer” effect. J Am Chem Soc 120(14):3382–3386Google Scholar
  70. 70.
    Inscore FE et al (2006) Understanding the origin of metal-sulfur vibrations in an oxo-molybdenum dithiolene complex: relevance to sulfite oxidase. Inorg Chem 45(3):967PubMedGoogle Scholar
  71. 71.
    Hille R (1991) Electron transfer within xanthine oxidase: a solvent kinetic isotope effect study. Biochemistry 30(35):8522–8529PubMedGoogle Scholar
  72. 72.
    Hille R, Massey V (1981) Studies on the oxidative half-reaction of xanthine oxidase. J Biol Chem 256(17):9090–9095PubMedGoogle Scholar
  73. 73.
    Dong C, Yang J, Leimkühler S, Kirk ML (2014) Pyranopterin dithiolene distortions relevant to electron transfer in xanthine oxidase/dehydrogenase. Inorg Chem 53(14):7077–7079PubMedPubMedCentralGoogle Scholar
  74. 74.
    Gray HB, Winkler JR (2005) Long-range electron transfer. Proc Natl Acad Sci U S A 102(10):3534PubMedPubMedCentralGoogle Scholar
  75. 75.
    Kirk ML et al (2013) Superexchange contributions to distance dependence of electron transfer/transport: exchange and electronic coupling in oligo(para-phenylene)- and oligo(2,5-thiophene)-bridged-donor-bridge acceptor biradical complexes. J Am Chem Soc 135(45):17144–17154PubMedGoogle Scholar
  76. 76.
    Mtei RP et al (2011) A valence bond description of dizwitterionic dithiolene character in an oxomolybdenum–bis(dithione) complex. Eur J Inorg Chem 2011(36):5467–5470 PubMedPubMedCentralGoogle Scholar
  77. 77.
    Stiefel EI, Eisenberg R, Rosenberg R, Gray H (1966) Characterization and electronic structures of six-coordinate trigonal-prismatic complexes. J Am Chem Soc 88(13):2956–2966Google Scholar
  78. 78.
    Fourmigué M, Domercq B (1998) A non-innocent ligand in coordination chemistry: the dithiolene complexes. Actualite Chim 11–12:9–13Google Scholar
  79. 79.
    Wang K, McConnachie JM, Stiefel EI (1999) Syntheses of metal dithiolene complexes from thiometalates by induced internal redox reactions. Inorg Chem 38(19):4334–4341Google Scholar
  80. 80.
    Helton ME, Gruhn NE, McNaughton R, Kirk ML (2000) Control of oxo-molybdenum reduction and ionization potentials by dithiolate donors. Inorg Chem 39(11):2273–2278PubMedGoogle Scholar
  81. 81.
    Harmer MA et al (1986) Ligand and induced internal redox processes in Mo-S and W-S systems. Polyhedron 5(1–2):341–347Google Scholar
  82. 82.
    Stiefel EI (1998) Transition metal sulfur chemistry and its relevance to molybdenum and tungsten enzymes. Pure Appl Chem 70(4):889–896Google Scholar
  83. 83.
    Helton ME, Gebhart NL, Davies S, Garner CD, Kirk ML (2000) Thermally driven intramolecular charge transfer in an oxo-molybdenum dithiolate complex. J Am Chem Soc. Manuscript in PreparationGoogle Scholar
  84. 84.
    Ray K, George SD, Solomon EI, Wieghardt K, Neese F (2007) Description of the ground-state covalencies of the bis(dithiolato) transition-metal complexes from X-ray absorption spectroscopy and time-dependent density-functional calculations. Chemistry 13(10):2783–2797PubMedGoogle Scholar
  85. 85.
    Kirk ML, Helton ME, RL MN (eds) (2004) The electronic structure and spectroscopy of metallo-dithiolene complexes, vol 52. John Wiley and Sons, Inc, Hoboken, pp 111–212Google Scholar
  86. 86.
    Yang J, Mogesa B, Basu P, Kirk ML (2016) Large ligand folding distortion in an oxomolybdenum donor acceptor complex. Inorg Chem 55(2):785–793PubMedGoogle Scholar
  87. 87.
    Sugimoto H et al (2010) Monooxomolybdenum(VI) complexes possessing olefinic dithiolene ligands: probing Mo-S covalency contributions to electron transfer in dimethyl sulfoxide reductase family molybdoenzymes. Inorg Chem 49(12):5368–5370PubMedPubMedCentralGoogle Scholar
  88. 88.
    McNaughton RL, Lim BS, Knottenbelt SZ, Holm RH, Kirk ML (2008) Spectroscopic and electronic structure studies of symmetrized models for reduced members of the dimethylsulfoxide reductase enzyme family. J Am Chem Soc 130(14):4628–4636PubMedGoogle Scholar
  89. 89.
    Kirk ML, McNaughton RL, Helton ME (2004) The electronic structure and spectroscopy of metallo-dithiolene complexes. In: Stiefel EI, Karlin KD (eds) Progress in inorganic chemistry: synthesis, properties, and applications, Progress in inorganic chemistry, vol 52, Wiley, Hoboken, pp 111–212Google Scholar
  90. 90.
    Inscore FE et al (1999) Spectroscopic evidence for a unique bonding interaction in oxo-molybdenum dithiolate complexes: implications for sigma electron transfer pathways in the pyranopterin dithiolate centers of enzymes. Inorg Chem 38(7):1401–1410Google Scholar
  91. 91.
    Yang J et al (2018) Ground state nuclear magnetic resonance chemical shifts predict charge-separated excited state lifetimes. Inorg Chem 57(21):13470–13476PubMedGoogle Scholar
  92. 92.
    Yang J et al (2014) Ligand control of donor-acceptor excited-state lifetimes. Inorg Chem 53(10):4791–4793PubMedGoogle Scholar
  93. 93.
    Chang C-SJ, Rai-Chaudhuri A, Lichtenberger DL, Enemark JH (1990) He I valence photoelectron spectra of oxomolybdenum (V) complexes containing diolato or alkoxide ligands. Polyhedron 9(15–16):1965–1973Google Scholar
  94. 94.
    Lalitha S, Manoharan PT (1989) X-ray photoelectron spectroscopic studies on some dithiolate complexes. J Electron Spectros Relat Phenom 49(1):61–75Google Scholar
  95. 95.
    Gleiter R, Spanget-Larsen J (1979). Top Curr Chem Spectrosc 86:139–195Google Scholar
  96. 96.
    Donahue JP, Holm RH (1998) 3,4-bis(l-adamantyl)-1,2-dithiete: the first structurally characterized dithiete unsupported by a ring or benzenoid frame. Acta Crystallogr C 54:1175–1178PubMedGoogle Scholar
  97. 97.
    Davison A, Holm RH (1967) Metal complexes derived from cis-1,2-cyano-1,2-ethylenedithiolate and bis(trifluoromethyl)-1,2-dithiete. Inorg Synth 10:8–26Google Scholar
  98. 98.
    Frei F et al (2014) Ultrafast electronic and vibrational relaxations in mixed-ligand dithione-dithiolato Ni, Pd, and Pt complexes. Dalton Trans 43(47):17666–17676PubMedGoogle Scholar
  99. 99.
    Espa D et al (2014) Role of the acceptor in tuning the properties of metal [M (II)= Ni, Pd, Pt] dithiolato/dithione (donor/acceptor) second-order nonlinear chromophores: combined experimental and theoretical studies. Inorg Chem 53(2):1170–1183PubMedGoogle Scholar
  100. 100.
    Deplano P, Pilia L, Espa D, Mercuri ML, Serpe A (2010) Square-planar d(8) metal mixed-ligand dithiolene complexes as second order nonlinear optical chromophores: structure/property relationship. Coord Chem Rev 254(13–14):1434–1447Google Scholar
  101. 101.
    Perera E, Basu P (2009) Synthesis, characterization and structure of a low coordinate desoxomolybdenum cluster stabilized by a dithione ligand. Dalton Trans (25):5023–5028Google Scholar
  102. 102.
    Sproules S et al (2009) Characterization and electronic structures of five members of the electron transfer series [Re(benzene-1,2-dithiolato)(3)](z) (z=1+,0,1-,2-,3-): a spectroscopic and density functional theoretical study. Inorg Chem 48(23):10926–10941PubMedGoogle Scholar
  103. 103.
    Stein BW et al (2018) Vibrational control of covalency effects related to the active sites of molybdenum enzymes. J Am Chem Soc. Accepted for PublicationGoogle Scholar
  104. 104.
    Pauff JM, Cao H, Hille R (2009) Substrate orientation and catalysis at the molybdenum site in xanthine oxidase crystal structures in complex with xanthine and lumazine. J Biol Chem 284(13):8751–8758Google Scholar
  105. 105.
    Hemann C, Ilich P, Stockert AL, Choi EY, Hille R (2005) Resonance Raman studies of xanthine oxidase: the reduced enzyme – product complex with violapterin. J Phys Chem B 109(7):3023–3031PubMedGoogle Scholar
  106. 106.
    Hemann C, Ilich P, Hille R (2003) Vibrational spectra of lumazine in water at pH 2-13: Ab initio calculation and FTIR/Raman spectra. J Phys Chem B 107(9):2139–2155Google Scholar
  107. 107.
    Davis M, Olson J, Palmer G (1984) The reaction of xanthine oxidase with lumazine: characterization of the reductive half-reaction. J Biol Chem 259(6):3526–3533PubMedGoogle Scholar
  108. 108.
    Dong C, Yang J, Reschke S, Leimkühler S, Kirk ML (2017) Vibrational probes of molybdenum cofactor–protein interactions in xanthine dehydrogenase. Inorg Chem 56(12):6830–6837PubMedGoogle Scholar
  109. 109.
    Qiu D, Kilpatrick LT, Kitajima N, Spiro TG (1994) Modeling blue copper protein resonance Raman spectra with thiolate-Cu(II) complexes of a sterically hindered tris(pyrazolyl)borate. J Am Chem Soc 116(6):2585–2590Google Scholar
  110. 110.
    Garton SD et al (2000) Resonance Raman characterization of biotin sulfoxide reductase: comparing oxomolybdenum enzymes in the Me2SO reductase family. J Biol Chem 275(10):6798–6805PubMedGoogle Scholar
  111. 111.
    Johnson MK, Garton SD, Oku H (1997) Resonance Raman as a direct probe for the catalytic mechanism of molybdenum oxotransferases. J Biol Inorg Chem 2(6):797–803Google Scholar
  112. 112.
    Garton SD et al (1997) Active site structures and catalytic mechanism of Rhodobacter sphaeroides dimethyl sulfoxide reductase as revealed by resonance Raman spectroscopy. J Am Chem Soc 119(52):12906–12916Google Scholar
  113. 113.
    Johnson MK (ed) (2004) Vibrational spectra of dithiolene complexes, vol 52, John Wiley and Sons, Inc., Hoboken, pp 213–266Google Scholar
  114. 114.
    Rajagopalan K (1991) Novel aspects of the biochemistry of the molybdenum cofactor. Adv Enzymol Relat Areas Mol Biol 64:215–290PubMedGoogle Scholar
  115. 115.
    Hille R, Massey V (1982) The presence of a reducible disulfide bond in milk xanthine oxidase. J Biol Chem 257(15):8898–8901PubMedGoogle Scholar
  116. 116.
    Youngblut MD et al (2016) Perchlorate reductase is distinguished by active site aromatic gate residues. J Biol Chem 291(17):9190–9202PubMedPubMedCentralGoogle Scholar
  117. 117.
    Jacques JGJ et al (2014) Reductive activation in periplasmic nitrate reductase involves chemical modifications of the Mo-cofactor beyond the first coordination sphere of the metal ion. BBA-Bioenergetics 1837(2):277–286PubMedGoogle Scholar
  118. 118.
    Ceccaldi P et al (2015) Reductive activation of E. coli respiratory nitrate reductase. BBA-Bioenergetics 1847(10):1055–1063PubMedGoogle Scholar
  119. 119.
    Gardlik S, Rajagopalan K (1991) Oxidation of molybdopterin in sulfite oxidase by ferricyanide-effect on electron transfer activities. J Biol Chem 266(8):4889–4895PubMedGoogle Scholar
  120. 120.
    Gardlik S, Rajagopalan KV (1990) The state of reduction of molybdopterin in xanthine-oxidase and sulfite oxidase. J Biol Chem 265(22):13047–13054PubMedGoogle Scholar
  121. 121.
    Karber LG, Dryhurst G (1984) Electrochemical oxidation of 5-methyl-5,6,7,8-tetrahydropterin. J Electroanal Chem 160(1–2):141–157Google Scholar
  122. 122.
    Karber LG, Dryhurst G (1982) Electrochemistry of 6-methyl-5,6,7,8-tetrahydropterin. J Electroanal Chem 136(2):271–289Google Scholar
  123. 123.
    Egeserpkenci D, Raghavan R, Dryhurst G (1983) Oxidation of methylated tetrahydropterins – structure of the initial quinonoid-dihydropterin intermediate. Bioelectrochem Bioenerg 10(4):357–376Google Scholar
  124. 124.
    Dryhurst G, Raghavan R, Egeserpkenci D, Karber LG (1982) Electrochemistry of reduced pterin cofactors. Adv Chem Ser (201):457–487Google Scholar
  125. 125.
    Raghavan R, Dryhurst G (1981) Redox chemistry of reduced pterin species. J Electroanal Chem 129(1–2):189–212Google Scholar
  126. 126.
    Bailey SW, Ayling JE (1983) 6,6-Dimethylpterins – stable quinoid dihydropterin substrate for dihydropteridine reductase and tetrahydropterin cofactor for phenylalanine hydroxylase. Biochemistry 22(8):1790–1798PubMedGoogle Scholar
  127. 127.
    Brown DJ (1988) Fused pyrimidines. Wiley, New YorkGoogle Scholar
  128. 128.
    Pfleiderer W, Zondler H (1966) Pteridine, 31. Synthese und Eigenschaften blockierter 7.8-Dihydro-pterine. Chemische Berichte-Recueil 99(9):3008Google Scholar
  129. 129.
    Randles D, Armarego WLF (1985) Reduced 6,6,8-trimethyllpterins – preparation, properties and enzymic reactivities with dihydropteridine reductase, phenylalanine hydroxylase, and tyrosine hydroxylase. Eur J Biochem 146(2):467–474PubMedGoogle Scholar
  130. 130.
    Kappock TJ, Caradonna JP (1996) Pterin-dependent amino acid hydroxylases. Chem Rev 96(7):2659–2756PubMedGoogle Scholar
  131. 131.
    Kemsley JN et al (2003) Spectroscopic and kinetic studies of PKU-inducing mutants of phenylalanine hydroxylase: Arg158Gln and Glu280Lys. J Am Chem Soc 125(19):5677–5686PubMedGoogle Scholar
  132. 132.
    Stoll S et al (2010) Nitric oxide synthase stabilizes the tetrahydrobiopterin cofactor radical by controlling its protonation state. J Am Chem Soc 132(33):11812–11823PubMedGoogle Scholar
  133. 133.
    Hurshman AR, Krebs C, Edmondson DE, Marletta MA (2003) Ability of tetrahydrobiopterin analogues to support catalysis by inducible nitric oxide synthase: formation of a pterin radical is required for enzyme activity. Biochemistry 42(45):13287–13303PubMedGoogle Scholar
  134. 134.
    Marletta MA (1993) Nitric oxide synthase structure and mechanism. J Biol Chem 268(17):12231–12234PubMedGoogle Scholar
  135. 135.
    Soyka R, Pfleiderer W, Prewo R (1990) Pteridines, 94. Synthesis and characteristics of 5,6-dihydro-6-(1,2,3-trihydroxypropyl)pteridines – covalent intramolecular adducts. Helv Chim Acta 73(4):808–826Google Scholar
  136. 136.
    Schircks B, Bieri JH, Viscontini M (1985) Pterinechemistry, 84. A new, regiospecific synthesis of L-biopterin. Helv Chim Acta 68(6):1639–1643Google Scholar
  137. 137.
    Dong C, Yang J, Leimkuhler S, Kirk ML (2014) Pyranopterin dithiolene distortions relevant to electron transfer in xanthine oxidase/dehydrogenase. Inorg Chem 53(14):7077–7079PubMedPubMedCentralGoogle Scholar
  138. 138.
    Kappler U, Bailey S (2005) Molecular basis of intramolecular electron transfer in sulfite-oxidizing enzymes is revealed by high resolution structure of a heterodimeric complex of the catalytic molybdopterin subunit and a c-type cytochrome subunit. J Biol Chem 280(26):24999–25007PubMedGoogle Scholar
  139. 139.
    Gisewhite DR et al (2018) Implications of pyran cyclization and pterin conformation on oxidized forms of the molybdenum cofactor. J Am Chem Soc 140(40):12808–12818PubMedPubMedCentralGoogle Scholar
  140. 140.
    Sugimoto H et al (2016) A model for the active-site formation process in DMSO reductase family molybdenum enzymes involving oxido alcoholato and oxido thiolato molybdenum(VI) core structures. Inorg Chem 55(4):1542–1550PubMedPubMedCentralGoogle Scholar
  141. 141.
    Spence J (1983) Modeling the molybdenum centers of the molybdenum hydroxylases. Coord Chem Rev 48(1):59–82Google Scholar
  142. 142.
    Pilato R, Stiefel E (1993) Bioinorganic catalysis. Marcel Dekker, New York, pp 131–188Google Scholar
  143. 143.
    Maia LB, Moura I, Moura JJG (2017) Molybdenum and tungsten-containing enzymes: an overview. The Royal Society of Chemistry, Cambridge, pp 1–80 Google Scholar
  144. 144.
    Enemark JH, Young CG (1993) Bioinorganic chemistry of pterin-containing molybdenum and tungsten enzymes. Adv Inorg Chem 40:1–88Google Scholar
  145. 145.
    Doonan CJ et al (2008) Electronic structure description of the cis-MoOS unit in models for molybdenum hydroxylases. J Am Chem Soc 130(1):55–65PubMedGoogle Scholar
  146. 146.
    Enemark JH, Cooney JJA (2004) Synthetic analogues and reaction systems relevant to the molybdenum and tungsten oxotransferases. Chem Rev 104(2):1175–1200PubMedGoogle Scholar
  147. 147.
    Holm RH (1987) Metal-centered oxygen atom transfer-reactions. Chem Rev 87(6):1401–1449Google Scholar
  148. 148.
    McNaughton RL, Helton ME, Rubie ND, Kirk ML (2000) The oxo-gate hypothesis and DMSO reductase: implications for a psuedo-sigma bonding interaction involved in enzymatic electron transfer. Inorg Chem 39(20):4386Google Scholar
  149. 149.
    McNaughton RL, Tipton AA, Rubie ND, Conry RR, Kirk ML (2000) Electronic structure studies of oxomolybdenum tetrathiolate complexes: origin of reduction potential differences and relationship to cysteine-molybdenum bonding in sulfite oxidase. Inorg Chem 39(25):5697–5706PubMedGoogle Scholar
  150. 150.
    Peariso K, Helton ME, Duesler EN, Shadle SE, Kirk ML (2007) Sulfur K-edge spectroscopic investigation of second coordination sphere effects in oxomolybdenum-thiolates: relationship to molybdenum-cysteine covalency and electron transfer in sulfite oxidase. Inorg Chem 46(4):1259–1267PubMedGoogle Scholar
  151. 151.
    Nemykin VN, Olsen JG, Perera E, Basu P (2006) Synthesis, molecular and electronic structure, and TDDFT and TDDFT-PCM study of the solvatochromic properties of (Me(2)Pipdt)Mo(CO)(4) complex (Me(2)Pipdt = N,N′-dimethylpiperazine-2,3-dithione). Inorg Chem 45(9):3557–3568Google Scholar
  152. 152.
    Boyde S, Garner CD (1991) Electrochemistry of tris(quinoxaline-2,3-dithiolato)molybdate(IV) in acidic solution: multi-electron ligand-based redox activity. J Chem Soc Dalton Trans 713–716Google Scholar
  153. 153.
    Armstrong EM et al (1993) Synthesis of cyclopentadienyl-ene-1,2-dithiolatocobalt complexes and coupled proton-electron transfer in a substituted quinoxalinyl derivative. Heterocycles 35(2):563–568Google Scholar
  154. 154.
    Dicks JP et al (2015) Synthesis, structure and redox properties of asymmetric (cyclopentadienyl)(ene-1,2-dithiolate)cobalt(III) complexes containing phenyl, pyridyl and pyrazinyl units. Eur J Inorg Chem 21:3550–3561Google Scholar
  155. 155.
    Hsu JK et al (1996) Direct conversion of alpha-substituted ketones to metallo-1,2-enedithiolates. Inorg Chem 35(16):4743–4751Google Scholar
  156. 156.
    Kaiwar SP, Vodacek A, Blough NV, Pilato RS (1997) Protonation-state-dependent luminescence and excited-state electron-transfer reactions of 2- and 4-pyridine (-ium)-substituted metallo-1,2-enedithiolates. J Am Chem Soc 119:9211–9214Google Scholar
  157. 157.
    VanHouten KA, Boggs CV, Pilato RS (1998) Synthesis and characterization of alpha-phosphorylated ketones: models for the molybdopterin precursor. Tetrahedron 54(37):10973–10986Google Scholar
  158. 158.
    Pilato RS et al (1993) Pterins, quinoxalines, and metallo-ene-dithiolates – synthetic approach to the molybdenum cofactor. ACS Symp Ser 535:83–97Google Scholar
  159. 159.
    Pilato RS et al (1991) Model complexes for molybdopterin-containing enzymes: preparation and crystallographic characterization of a molybdenum-ene-1-perthiolate-2-thiolate (trithiolate) complex. J Am Chem Soc 9372–9374Google Scholar
  160. 160.
    Fogeron T, Retailleau P, Chamoreau LM, Li Y, Fontecave M (2018) Pyranopterin related dithiolene molybdenum complexes as homogeneous catalysts for CO2 photoreduction. Angew Chem Int Ed 57(52):17033–17037Google Scholar
  161. 161.
    Porcher JP et al (2015) A bioinspired molybdenum complex as a catalyst for the photo- and electroreduction of protons. Angew Chem Int Ed 54(47):14090–14093Google Scholar
  162. 162.
    Gisewhite DR, Nagelski AL, Cummins DC, Yap GPA, Burgmayer SJN (2019). Modeling pyran formation in the molybdenum cofactor: protonation of quinoxalyl-dithiolene promoting pyran cyclization. Inorg Chem 58(8):5134–5144. PubMedPubMedCentralGoogle Scholar
  163. 163.
    Gisewhite D (2018) The molybdenum cofactor: modeling the Swiss army knife of metabolic diversity. PhD, Bryn Mawr CollegeGoogle Scholar
  164. 164.
    Williams BR, Fu YC, Yap GPA, Burgmayer SJN (2012) Structure and reversible pyran formation in molybdenum pyranopterin dithiolene models of the molybdenum cofactor. J Am Chem Soc 134(48):19584–19587PubMedPubMedCentralGoogle Scholar
  165. 165.
    Williams BR, Gisewhite D, Kalinsky A, Esmail A, Burgmayer SJN (2015) Solvent-dependent pyranopterin cyclization in molybdenum cofactor model complexes. Inorg Chem 54(17):8214–8222PubMedPubMedCentralGoogle Scholar
  166. 166.
    Bray R, Adams B, Smith A, Bennett B, Bailey S (2000) Reversible dissociation of thiolate ligands from molybdenum in an enzyme of the dimethyl sulfoxide reductase family. Biochemistry 39(37):11258–11269PubMedGoogle Scholar
  167. 167.
    Bell AF et al (2001) Active site heterogeneity in dimethyl sulfoxide reductase from Rhodobacter capsulatus revealed by Raman spectroscopy. Biochemistry 40(2):440–448PubMedGoogle Scholar
  168. 168.
    George GN, Hilton J, Temple C, Prince RC, Rajagopalan KV (1999) Structure of the molybdenum site of dimethyl sulfoxide reductase. J Am Chem Soc 121:1256–1266 Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of ChemistryBryn Mawr CollegeBryn MawrUSA
  2. 2.Department of Chemistry and Chemical BiologyThe University of New MexicoAlbuquerqueUSA

Personalised recommendations