A New Nitrogenase Mechanism Using a CFe8S9 Model: Does H2 Elimination Activate the Complex to N2 Addition to the Central Carbon Atom?

Nitrogenase enzymes are used by microorganisms for converting atmospheric N2 to ammonia, which provides an essential source of N atoms for higher organisms. The active site of the molybdenum-dependent nitrogenase is the unique carbide-containing iron-sulfur cluster called the iron-molybdenum cofactor (FeMoco). On the FeMoco, N2 binding is suggested to occur at one or more iron atoms, but the structures of the catalytic intermediates are not clear. In order to establish the feasibility of different potential mechanistic steps during biological N2 reduction, chemists have prepared iron complexes that mimic various structural aspects of the iron sites in FeMoco. This reductionist approach gives mechanistic insight, and also uncovers fundamental principles that could be used more broadly for small molecule activation. Here, we review recent results and highlight directions for future research. In one direction, synthetic iron complexes have now been shown to bind N2, break the N-N triple bond, and produce ammonia catalytically. Carbon and sulfur based donors have been incorporated into the ligand spheres of Fe-N2 complexes to show how these atoms may influence the structure and reactivity of the FeMoco. Hydrides have been incorporated into synthetic systems, which can bind N2, reduce some nitrogenase substrates, and/or reductively eliminate H2 to generate reduced iron centers. Though some carbide-containing iron clusters are known, none yet have sulfide bridges or high-spin iron atoms like the FeMoco.

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“…Recent computational studies propose that the carbide could even engage in covalent bonding with the N atoms during the N 2 reduction. 126,127 …”

Section: Carbide Complexes and Fe-n2 Complexes With Carbon Ligandsmentioning

confidence: 99%

Insight into the Iron–Molybdenum Cofactor of Nitrogenase from Synthetic Iron Complexes with Sulfur, Carbon, and Hydride Ligands

2016

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“…3 The experimental studies have been supplemented by many density functional theory (DFT) studies, which can give an detailed atomistic and energetic picture of the reaction mechanism. 3,[13][14][15][16][17][18][19][20][21][22][23][24][25][26] Unfortunately, they have led to strongly diverging mechanistic suggestions. For example, some studies have proposed that N 2 is sequentially protonated first on one N atom, which dissociates into NH 3 before the second atom is protonated, 23,25 whereas other studies have suggested that it is alternatively protonated on the two N atoms, forming N 2 H 2 and N 2 H 4 intermediates.…”

Section: Introductionmentioning

confidence: 99%

“…side-on to one Fe ion, 22 with one N atom bridging two Fe ions, after the dissociation of one of the sulfide ions, 23 in the centre of the cluster, displacing a triply protonated carbide ion, 24 or forming a covalent bond to the carbide ion. 25,26 In fact, there is not even any consensus regarding the structure of the central intermediate E 4 . For example, Hoffman and coworkers have proposed models with two protonated sulfide ions and two bridging hydride ions, 27 in agreement with spectroscopic results, whereas Siegbahn has argued that it is energetically much more favourable to triply protonate the central carbide ion.…”

Section: Introductionmentioning

confidence: 99%

Extremely large differences in DFT energies for nitrogenase models

Cao

Ryde

2019

Phys. Chem. Chem. Phys.

157

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Nitrogenase is the only enzyme that can cleave the triple bond in N 2 , making nitrogen avaiable for other organisms. It contains a complicated MoFe 7 S 9 C(homocitrate) cluster in its active site. Many computational studies with density-functional theory (DFT) of the nitrogenase enzyme have been presented, but they do not show any consensus -they do not even agree where the first four protons should be added, forming the central intermediate E 4 . We show that the prime reason for this is that different DFT methods give relative energies that differ by almost 600 kJ mol À1 for different protonation states. This is 4-30 times more than what is observed for other systems. The reason for this is that in some structures, the hydrogens bind to sulfide or carbide ions as protons, whereas in other structures they bind to the metals as hydride ions, changing the oxidation state of the metals, as well as the Fe-C, Fe-S and Fe-Fe distances.The energies correlate with the amount of Hartree-Fock exchange in the method, indicating a variation in the amount of static correlation in the structures. It is currently unclear which DFT method gives the best results for nitrogenase. We show that non-hybrid DFT functionals and TPSSh give the most accurate structures of the resting active site, whereas B3LYP and PBE0 give the best H 2 dissociation energies.However, no DFT method indicates that a structure of E 4 with two bridging hydride ions is lowest in energy, as spectroscopic experiments indicate.

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“…Unfortunately, there is no consensus in the detailed mechanism of the enzyme. For example, during 2015 and 2016 one group has suggested that N 2 binds side‐on to one Fe ion and is then protonated alternatively on the two N atoms, another that N 2 binds after the dissociation of one of the sulfide ions with one N atom bridging two Fe ions, and the non‐coordinating N atom is fully protonated and dissociates before the other N atom is protonated, whereas three groups have suggested that the central carbide ion is involved in the mechanism, either by receiving the incoming protons, or by covalently binding the N 2 substrate in various ways . A recent study addressed the role of His‐195 in the reaction mechanism…”

Section: Introductionmentioning

confidence: 99%

“…bridging two Fe ions, and the non-coordinating N atom is fully protonated and dissociates before the other N atom is protonated, [15] whereas three groups have suggested that the central carbide ion is involved in the mechanism, either by receiving the incoming protons, [16] or by covalently binding the N 2 substrate in various ways. [17,18] A recent study addressed the role of His-195 in the reaction mechanism. [19] The QM studies of nitrogenase are obstructed by the complicated nature of the FeMo cluster.…”

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confidence: 99%

Influence of the protein and DFT method on the broken‐symmetry and spin states in nitrogenase

Cao

Ryde

2018

Int J of Quantum Chemistry

108

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The enzyme nitrogenase contains a complicated MoFe7CS9 cofactor with 35 possible broken‐symmetry (BS) states. We have studied how the energies of these states depend on the geometry, the surrounding protein, the DFT functional and the basis set, studying the resting state, a one‐electron reduced state and a protonated state. We find that the effect of the basis set is small, up to 11 kJ/mol. Likewise, the effect of the surrounding protein is restricted, up to 10 and 7 kJ/mol for the electrostatic and van der Waals energy terms. Single‐point energies calculated on a single geometry give a good correlation (R2 = 0.92‐0.98) to energies calculated after geometry optimization, but some BS states may be disfavored by up to 37 kJ/mol. A change from the pure TPSS functional to the hybrid B3LYP functional may change the relative energies by up to 58 kJ/mol and the correlation between the two results is only 0.57‐0.72. Both functionals agree that BS7 is the most stable BS state and that the ground spin state is the quartet for the resting state and the quintet for the reduced state. With the TPSS functional, the BS6 state is the second most stable state, always at least 21 kJ/mol less stable than the BS7 state. However, with the B3LYP functional, BS10 is the second most stable state and for the protonated state it comes close in energy. Based on these results, we suggest a procedure how to consider the 35 BS states in future investigations of the nitrogenase reaction mechanism.

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A New Nitrogenase Mechanism Using a CFe₈S₉ Model: Does H₂ Elimination Activate the Complex to N₂ Addition to the Central Carbon Atom?

Cited by 30 publications

References 68 publications

Insight into the Iron–Molybdenum Cofactor of Nitrogenase from Synthetic Iron Complexes with Sulfur, Carbon, and Hydride Ligands

Insight into the Iron–Molybdenum Cofactor of Nitrogenase from Synthetic Iron Complexes with Sulfur, Carbon, and Hydride Ligands

Extremely large differences in DFT energies for nitrogenase models

Influence of the protein and DFT method on the broken‐symmetry and spin states in nitrogenase

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