Department of Chemistry,
University of Rochester

Nitrogenase and Nitrogen Chemistry

One topic of great interest in inorganic chemistry is N₂ reduction to NH₃ ("nitrogen fixation"). This reaction is necessary for life as we know it, because nitrogen fixation is the major route through which nitrogen from the atmosphere becomes available for organisms (nitrogen is an integral component of DNA, RNA, and proteins, for example). Nitrogen reduction is catalyzed in nature by the "iron-molybdenum cofactor" of iron-molybdenum nitrogenase (illustration above; PDB; QuickTime movie). The iron-molybdenum cofactor has six iron atoms that have an unusual trigonal pyramidal geometry. We hypothesize that the low-coordinate iron is important to perform this difficult six-electron reduction.

We envision a mechanism for N₂ binding in which reduction of the cofactor weakens or breaks a bond between the central ion and a trigonal-pyramidal iron atom. The resulting three-coordinate iron may bind nitrogen, or may be protonated to form a hydride complex that subsequently reacts with nitrogenase substrates. In research that evaluates this idea, we have created soluble complexes containing low-coordinate iron atoms that reduce the N-N bond order of N₂ from three to two, while other known iron-N₂ complexes have N-N triple bonds. (Click here for animated GIF's of a neutral dinitrogen complex and a potassium-complexed dinitrogen complex.) Mössbauer and computational studies show that in neutral FeNNFe compounds, the N₂ unit is significantly reduced in the iron complexes. The amount of electron transfer is highly metal-dependent, with more N₂ reduction in iron complexes, and less in cobalt and nickel complexes. Our work has been crucial in establishing these periodic trends. Current work is aimed at utilizing these insights to achieve reactivity of alkynes and N₂, as well as characterizing the adducts of these compounds as synthetic analogues of nitrogenase.

In other work, we have created synthetic complexes in which two reactive iron atoms are bridged by a sulfide; the Fe-S-Fe unit is reminiscent of the diiron units of the FeMoco shown above. We have found that the two iron atoms cooperatively break the N-N bond of certain hydrazines (see illustration below). Therefore, we are continuing to create other ligand environments that encourage cooperative reactions of multiple iron atoms.

sulfides

We have also created the first low-coordinate iron and cobalt hydride complexes. The hydride ligand contains protons and electrons for reduction of multiple bonds. The hydrides reduce many compounds, and completely cleave the N=N bond of diazenes. In addition, they are capable of binding N₂ using the electrons from the hydrides (illustration below).

In our most recent discovery, we have found a system in which four iron and two potassium ions break the N-N bond in N₂. This is the first example of an iron complex that cleaves N₂ to give nitrides, and we believe that the cooperative interactions between the metal atoms are important in enabling the reactivity. The nitride product also reacts with H₂ to release ammonia, in a model of the two component steps of the Haber-Bosch process.

Funding: National Institutes of Health

Publications:

Jeremy M. Smith, Rene J. Lachicotte, Karl A. Pittard, Thomas R. Cundari, Gudrun Lukat-Rodgers, Kenton R. Rodgers, Patrick L. Holland, "Stepwise Reduction of N-N Bond Order by a Low-Coordinate Iron Complex," J. Am. Chem. Soc. 2001, 123, 9222-9223. (PDF)

Jeremy M. Smith, Rene J. Lachicotte, Patrick L. Holland, "N=N Bond Cleavage by a Low-Coordinate Iron(II) Hydride Complex," J. Am. Chem. Soc. 2003, 125, 15752-15753. (PDF)

Patrick L. Holland, "Nitrogen Fixation," In Comprehensive Coordination Chemistry 2 (McCleverty, J., Meyer, T. J., Eds.); Vol. 8; Elsevier: Oxford, 2004, pp. 569-599.

Javier Vela, Sebastian Stoian, Christine Flaschenriem, Eckard Münck, Patrick L. Holland, "A Sulfido-Bridged Diiron(II) Compound and Its Reactions with Nitrogenase-Relevant Substrates," J. Am. Chem. Soc. 2004, 126, 4522-4523. (DOI)

Patrick L. Holland, "Low-Coordinate Iron Complexes as Synthetic Models of Nitrogenase," Can. J. Chem. 2005, 83, 296-301. (online)

Jeremy M. Smith, Azwana R. Sadique, Thomas R. Cundari, Kenton R. Rodgers, Gudrun Lukat-Rodgers, Rene J. Lachicotte, Christine J. Flaschenriem, Javier Vela, and Patrick L. Holland, "Studies of Low-Coordinate Iron Dinitrogen Complexes," J. Am. Chem. Soc. 2006, 128, 756-769. (DOI)

Ying Yu, Jeremy M. Smith, Christine J. Flaschenriem, and Patrick L. Holland, "Binding Affinity of Alkynes and Alkenes to Low-Coordinate Iron," Inorg. Chem. 2006, 45, 5742-5751. (DOI) (cover of Inorg. Chem.)

Sebastian A. Stoian, Javier Vela, Jeremy M. Smith, Azwana R. Sadique, Patrick L. Holland, Eckard Münck, and Emile L. Bominaar, "Mössbauer and Computational Study of an N₂-Bridged Diiron Diketiminate Complex: Parallel Alignment of the Iron Spins by Direct Antiferromagnetic Exchange with Activated Dinitrogen," J. Am. Chem. Soc. 2006, 128, 10181-10192. (DOI)

Travis J. Hebden, William W. Brennessel, Christine J. Flaschenriem, and Patrick L. Holland, "A dinucleating ligand related to the β-diketiminates,"Dalton Trans. 2006, 3855-3857. (DOI)

Javier Vela, Jordi Cirera, Jeremy M. Smith, Rene J. Lachicotte, Christine J. Flaschenriem, Santiago Alvarez, and Patrick L. Holland, "Quantitative Geometric Descriptions of the Belt Iron Atoms of the Iron-Molybdenum Cofactor of Nitrogenase and Synthetic Iron(II) Model Complexes," Inorg. Chem. 2007, 46, 60-71. (DOI)

Azwana R. Sadique, Elizabeth A. Gregory, William W. Brennessel, and Patrick L. Holland, "Mechanistic Insight into N=N Cleavage by a Low-Coordinate Iron(II) Hydride Complex," J. Am. Chem. Soc. 2007, 129, 8112-8121. (DOI) (Editor's Choice in Science)

Nicholas S. Lees, Rebecca L. McNaughton, Wilda Vargas Gregory, Patrick L. Holland, and Brian M. Hoffman, "ENDOR Characterization of a Synthetic Diiron Hydrazido Complex as a Model for Nitrogenase Intermediates," J. Am. Chem. Soc. 2008, 130, 546-555. (DOI)

Azwana R. Sadique, William W. Brennessel, and Patrick L. Holland, "Reduction of CO₂ to CO Using Low-Coordinate Iron: Formation of a Four-Coordinate Iron Dicarbonyl Complex and a Bridging Carbonate Complex," Inorg. Chem. 2008, 47, 784-786. (DOI)

Ying Yu, Azwana R. Sadique, Jeremy M. Smith, Thomas R. Dugan, Ryan E. Cowley, William W. Brennessel, Christine J. Flaschenriem, Eckhard Bill, Thomas R. Cundari, Patrick L. Holland, "The Reactivity Patterns of Low-Coordinate Iron Hydride Complexes," J. Am. Chem. Soc. 2008, 130, 6624-6638. (DOI)

Keying Ding, Aaron W. Pierpont, William W. Brennessel, Gudrun Lukat-Rodgers, Kenton R. Rodgers, Thomas R. Cundari, Eckhard Bill and Patrick L. Holland, "Cobalt-Dinitrogen Complexes with Weakened N-N Bonds," J. Am. Chem. Soc. 2009, 131, 9471-9472. (DOI)

Keying Ding, William W. Brennessel, and Patrick L. Holland, "Three-Coordinate and Four-Coordinate Cobalt Hydride Complexes That React with Dinitrogen," J. Am. Chem. Soc. 2009, 131, 10804-10805. (DOI)

Patrick L. Holland, "Metal-Dioxygen and Metal-Dinitrogen Complexes: Where Are The Electrons?" Dalton Trans. 2010, 39, 5415-5425.(DOI)

Patrick L. Holland, "Techniques Used in Functional and Structural Modeling of Nitrogenase," in Methods in Molecular Biology - Nitrogen Fixation (M. Ribbe, ed.), Springer: New York, 2011. (link)

Meghan M. Rodriguez, Eckhard Bill, William W. Brennessel, Patrick L. Holland, "N₂ Reduction and Hydrogenation to Ammonia by a Molecular Iron-Potassium Complex," Science 2011, 334, 780-783. (DOI)