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Binding of dinitrogen to an iron–sulfur–carbon site


Nitrogenases are the enzymes by which certain microorganisms convert atmospheric dinitrogen (N2) to ammonia, thereby providing essential nitrogen atoms for higher organisms. The most common nitrogenases reduce atmospheric N2 at the FeMo cofactor, a sulfur-rich iron–molybdenum cluster (FeMoco)1,2,3,4,5. The central iron sites that are coordinated to sulfur and carbon atoms in FeMoco have been proposed to be the substrate binding sites, on the basis of kinetic and spectroscopic studies5,6,7. In the resting state, the central iron sites each have bonds to three sulfur atoms and one carbon atom. Addition of electrons to the resting state causes the FeMoco to react with N2, but the geometry and bonding environment of N2-bound species remain unknown5. Here we describe a synthetic complex with a sulfur-rich coordination sphere that, upon reduction, breaks an Fe–S bond and binds N2. The product is the first synthetic Fe–N2 complex in which iron has bonds to sulfur and carbon atoms, providing a model for N2 coordination in the FeMoco. Our results demonstrate that breaking an Fe–S bond is a chemically reasonable route to N2 binding in the FeMoco, and show structural and spectroscopic details for weakened N2 on a sulfur-rich iron site.

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Figure 1: N2 binding to iron in sulfur-rich environments.
Figure 2: N2 binding at an iron–sulfur–carbon site through Fe–S bond cleavage.
Figure 3: Fe–N2 complex supported by sulfur and carbon ligands.


  1. 1

    Einsle, O. et al. Nitrogenase MoFe-protein at 1.16 Å resolution: a central ligand in the FeMo-cofactor. Science 297, 1696–1700 (2002)

    ADS  CAS  Article  Google Scholar 

  2. 2

    Spatzal, T. et al. Evidence for interstitial carbon in nitrogenase FeMo cofactor. Science 334, 940 (2011)

    ADS  CAS  Article  Google Scholar 

  3. 3

    Lancaster, K. M. et al. X-ray emission spectroscopy evidences a central carbon in the nitrogenase iron-molybdenum cofactor. Science 334, 974–977 (2011)

    ADS  CAS  Article  Google Scholar 

  4. 4

    Wiig, J. A., Hu, Y., Lee, C. C. & Ribbe, M. W. Radical SAM-dependent carbon insertion into the nitrogenase M-cluster. Science 337, 1672–1675 (2012)

    ADS  CAS  Article  Google Scholar 

  5. 5

    Hoffman, B. M., Lukoyanov, D., Yang, Z.-Y., Dean, D. R. & Seefeldt, L. C. Mechanism of nitrogen fixation by nitrogenase: the next stage. Chem. Rev. 114, 4041–4062 (2014)

    CAS  Article  Google Scholar 

  6. 6

    Seefeldt, L. C., Hoffman, B. M. & Dean, D. R. Mechanism of Mo-dependent nitrogenase. Annu. Rev. Biochem. 78, 701–722 (2009)

    CAS  Article  Google Scholar 

  7. 7

    Spatzal, T., Perez, K. A., Einsle, O., Howard, J. B. & Rees, D. C. Ligand binding to the FeMo-cofactor: structures of CO-bound and reactivated nitrogenase. Science 345, 1620–1623 (2014)

    ADS  CAS  Article  Google Scholar 

  8. 8

    Yandulov, D. V. & Schrock, R. R. Catalytic reduction of dinitrogen to ammonia at a single molybdenum center. Science 301, 76–78 (2003)

    ADS  CAS  Article  Google Scholar 

  9. 9

    Holland, P. L. Low-coordinate iron complexes as synthetic models of nitrogenase. Can. J. Chem. 83, 296–301 (2005)

    CAS  Article  Google Scholar 

  10. 10

    MacBeth, C. E., Harkins, S. B. & Peters, J. C. Synthesis and characterization of cationic iron complexes supported by the neutral ligands NPi-Pr3, NArPi-Pr3, and NSt-Bu3 . Can. J. Chem. 83, 332–340 (2005)

    CAS  Article  Google Scholar 

  11. 11

    Dance, I. Ramifications of C-centering rather than N-centering of the active site FeMo-co of the enzyme nitrogenase. Dalton Trans. 41, 4859–4865 (2012)

    CAS  Article  Google Scholar 

  12. 12

    Hinnemann, B. & Nørskov, J. K. Chemical activity of the nitrogenase FeMo cofactor with a central nitrogen ligand: density functional study. J. Am. Chem. Soc. 126, 3920–3927 (2004)

    CAS  Article  Google Scholar 

  13. 13

    George, S. J. et al. EXAFS and NRVS reveal a conformational distortion of the FeMo-cofactor in the MoFe nitrogenase propargyl alcohol complex. J. Inorg. Biochem. 112, 85–92 (2012)

    CAS  Article  Google Scholar 

  14. 14

    Creutz, S. E. & Peters, J. C. Catalytic reduction of N2 to NH3 by an Fe–N2 complex featuring a C-atom anchor. J. Am. Chem. Soc. 136, 1105–1115 (2014)

    CAS  Article  Google Scholar 

  15. 15

    Anderson, J. S., Rittle, J. & Peters, J. C. Catalytic conversion of nitrogen to ammonia by an iron model complex. Nature 501, 84–87 (2013)

    ADS  CAS  Article  Google Scholar 

  16. 16

    Kästner, J. & Blöchl, P. E. Ammonia production at the FeMo cofactor of nitrogenase: results from density functional theory. J. Am. Chem. Soc. 129, 2998–3006 (2007)

    Article  Google Scholar 

  17. 17

    Schimpl, J., Petrilli, H. M. & Blöchl, P. E. Nitrogen binding to the FeMo-cofactor of nitrogenase. J. Am. Chem. Soc. 125, 15772–15778 (2003)

    CAS  Article  Google Scholar 

  18. 18

    Alwaaly, A., Dance, I. & Henderson, R. A. Unexpected explanation for the enigmatic acid-catalysed reactivity of [Fe4S4X4]2− clusters. Chem. Commun. 50, 4799–4802 (2014)

    CAS  Article  Google Scholar 

  19. 19

    Saouma, C. T., Morris, W. D., Darcy, J. W. & Mayer, J. M. Protonation and proton-coupled electron transfer at S-ligated [4Fe-4S] clusters. Chem. Eur. J. 21, 9256–9260 (2015)

    CAS  Article  Google Scholar 

  20. 20

    Lee, S. C., Lo, W. & Holm, R. H. Developments in the biomimetic chemistry of cubane-type and higher nuclearity iron–sulfur clusters. Chem. Rev. 114, 3579–3600 (2014)

    CAS  Article  Google Scholar 

  21. 21

    Ung, G. & Peters, J. C. Low-temperature N2 binding to two-coordinate L2Fe0 enables reductive trapping of L2FeN2 and NH3 generation. Angew. Chem. Int. Ed. 54, 532–535 (2015)

    CAS  Google Scholar 

  22. 22

    Rodriguez, M. M., Bill, E., Brennessel, W. W. & Holland, P. L. N2 reduction and hydrogenation to ammonia by a molecular iron-potassium complex. Science 334, 780–783 (2011)

    ADS  CAS  Article  Google Scholar 

  23. 23

    Hazari, N. Homogeneous iron complexes for the conversion of dinitrogen into ammonia and hydrazine. Chem. Soc. Rev. 39, 4044–4056 (2010)

    CAS  Article  Google Scholar 

  24. 24

    Danopoulos, A. A., Wright, J. A. & Motherwell, W. B. Molecular N2 complexes of iron stabilised by N-heterocyclic ‘pincer’ dicarbene ligands. Chem. Commun. 784–786 (2005)

  25. 25

    Takaoka, A., Mankad, N. P. & Peters, J. C. Dinitrogen complexes of sulfur-ligated iron. J. Am. Chem. Soc. 133, 8440–8443 (2011)

    CAS  Article  Google Scholar 

  26. 26

    Bart, S. C., Lobkovsky, E., Bill, E., Wieghardt, K. & Chirik, P. J. Neutral-ligand complexes of bis(imino)pyridine iron: synthesis, structure, and spectroscopy. Inorg. Chem. 46, 7055–7063 (2007)

    CAS  Article  Google Scholar 

  27. 27

    Creutz, S. E. & Peters, J. C. Diiron bridged-thiolate complexes that bind N2 at the FeIIFeII, FeIIFeI, and FeIFeI redox states. J. Am. Chem. Soc. 137, 7310–7313 (2015)

    CAS  Article  Google Scholar 

  28. 28

    Ellison, J. J., Ruhlandt-Senge, K. & Power, P. P. Synthesis and characterization of thiolato complexes with two-coordinate iron(II). Angew. Chem. Int. Edn Engl. 33, 1178–1180 (1994)

    Article  Google Scholar 

  29. 29

    Suess, D. L. M. & Peters, J. C. H–H and Si–H bond addition to Fe≡NNR2 intermediates derived from N2 . J. Am. Chem. Soc. 135, 4938–4941 (2013)

    CAS  Article  Google Scholar 

  30. 30

    Moret, M.-E. & Peters, J. C. Terminal iron dinitrogen and iron imide complexes supported by a tris(phosphino)borane ligand. Angew. Chem. Int. Ed. 50, 2063–2067 (2011)

    CAS  Article  Google Scholar 

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This work was supported by the National Institutes of Health (GM065313 to P.L.H.) and the Max Planck Society (E.B.). We thank A. Göbels for measurement of SQUID data and G. Brudvig for the use of an EPR spectrometer. Elemental analysis data were from the CENTC Elemental Analysis Facility at the University of Rochester, funded by the NSF (CHE-0650456), and we thank W. Brennessel for collecting these data. This work was supported in part by the facilities and staff of the Yale High Performance Computing Center, which was partially funded by the NSF (CNS 08-21132). We thank J. Mayer, N. Hazari, S. Bonyhady, N. Arnet, and C. MacLeod for constructive criticism on the manuscript.

Author information




I.Č. designed the iron–sulfur–carbon system for N2 binding, performed the laboratory experiments, and analysed data. B.Q.M. collected and interpreted crystallographic data. E.B. interpreted solid-state (SQUID) magnetic data. D.J.V. collected and fitted EPR data. P.L.H. supervised the research, and I.Č. and P.L.H. wrote the manuscript.

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Correspondence to Patrick L. Holland.

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The authors declare no competing financial interests.

Additional information

X-ray crystallographic data have been deposited in the Cambridge Crystallographic Data Centre ( with deposition numbers CCDC1402555–CCDC1402559.

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This file contains Supplementary Methods, Supplementary References and Supplementary Data (see Contents for details). (PDF 10994 kb)

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Čorić, I., Mercado, B., Bill, E. et al. Binding of dinitrogen to an iron–sulfur–carbon site. Nature 526, 96–99 (2015).

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