Functional LnFe-NxHy Models of Biological N2 Fixation Nitrogenase (N2ase) is a metalloenzyme that mediates biological nitrogen fixation and is essential to sustain life. As such, the study of nitrogenase attracts intense scrutiny among the biology and chemistry communities. Nonetheless, the mechanism by which nitrogenase enzymes promote the biological reduction of nitrogen under ambient conditions remains a fascinating and unsolved problem. The broad goal of our research is to evaluate the mechanisms by which a single iron site is able to mediate catalytic N2 reduction in synthetic model systems and, by extension, in biology. The proposed program is to design and study biomimetic Fe-NxHy model complexes to address this goal. Our experimental approach stresses functionally, rather than structurally, faithful models of the iron-molybdenum cofactor (FeMoco). Low molecular weight Fe-NxHy complexes will be developed to explore iron sites in local 4- and 5-coordinate geometries that may accommodate dinitrogen and other NxHy functionalites. We posit these geometries as relevant to Fe-NxHy intermediates of the FeMoco. By analogy to the modes of biocatalytic O2 reduction, two limiting mechanisms will be evaluated. The first is an alternating mechanism, where successive protonations occur at the distal and proximal N-atoms of the Fe-N?N subunit in an alternating fashion (e.g., Fe-N=NH ? Fe-NH=NH ? Fe-NH-NH2 ? Fe-NH2-NH2 ? Fe-NH2 + NH3). The second is a distal mechanism, where complete protonation at the distal N-atom precedes protonation at the proximal N-atom (e.g., Fe-N2 + 3 e- + 3 H+? Fe?N + NH3). We will use synthetic model complexes to understand how the nuclearity, local geometry, and electronic structure of Fe- NxHy species control their relative stabilities and reactivity patterns. The intent is to apply this knowledge to design model systems that can facilitate catalytic N2ase activity. Regardless of the precise mechanism for nitrogen reduction at the FeMoco, its ultimate solution will require comparison of spectroscopic data from the cofactor to related data obtained for well-defined model complexes. We will collaborate with researchers that specialize in spectroscopic studies of the FeMoco to make such comparisons. In sum, the functional Fe-NxHy model chemistry proposed will continue to play a critical role alongside current biochemical, spectroscopic, and theoretical model studies aimed at unraveling the chemical mechanism of biological nitrogen fixation.

Public Health Relevance

Nitrogenase (N2ase) is an iron-rich metalloenzyme that mediates biological nitrogen fixation and is essential to life. Our goal is to use functional iron model complexes to test hypotheses concerning the mechanism of biological nitrogen reduction, and to discover model systems that facilitate catalytic nitrogen reduction. These model systems will provide data to help constrain a mechanistic interpretation of the nitrogenase cofactor.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM070757-10
Application #
8600286
Study Section
Macromolecular Structure and Function A Study Section (MSFA)
Program Officer
Anderson, Vernon
Project Start
2005-02-01
Project End
2015-12-31
Budget Start
2014-01-01
Budget End
2014-12-31
Support Year
10
Fiscal Year
2014
Total Cost
$246,308
Indirect Cost
$88,808
Name
California Institute of Technology
Department
Chemistry
Type
Schools of Engineering
DUNS #
009584210
City
Pasadena
State
CA
Country
United States
Zip Code
91125
Chalkley, Matthew J; Peters, Jonas C (2016) A Triad of Highly Reduced, Linear Iron Nitrosyl Complexes: {FeNO}(8-10). Angew Chem Int Ed Engl 55:11995-8
Rittle, Jonathan; Peters, Jonas C (2016) Proton-Coupled Reduction of an Iron Cyanide Complex to Methane and Ammonia. Angew Chem Int Ed Engl 55:12262-5
Del Castillo, Trevor J; Thompson, Niklas B; Peters, Jonas C (2016) A Synthetic Single-Site Fe Nitrogenase: High Turnover, Freeze-Quench (57)Fe Mössbauer Data, and a Hydride Resting State. J Am Chem Soc 138:5341-50
Rittle, Jonathan; Peters, Jonas C (2016) An Fe-N₂ Complex That Generates Hydrazine and Ammonia via Fe═NNH₂: Demonstrating a Hybrid Distal-to-Alternating Pathway for N₂ Reduction. J Am Chem Soc 138:4243-8
Ung, Gaël; Peters, Jonas C (2015) Low-temperature N2 binding to two-coordinate L2Fe(0) enables reductive trapping of L2FeN2(-) and NH3 generation. Angew Chem Int Ed Engl 54:532-5
Creutz, Sidney E; Peters, Jonas C (2015) Diiron bridged-thiolate complexes that bind N2 at the Fe(II)Fe(II), Fe(II)Fe(I), and Fe(I)Fe(I) redox states. J Am Chem Soc 137:7310-3
Del Castillo, Trevor J; Thompson, Niklas B; Suess, Daniel L M et al. (2015) Evaluating Molecular Cobalt Complexes for the Conversion of N2 to NH3. Inorg Chem 54:9256-62
Anderson, John S; Cutsail 3rd, George E; Rittle, Jonathan et al. (2015) Characterization of an Fe≡N-NH2 Intermediate Relevant to Catalytic N2 Reduction to NH3. J Am Chem Soc 137:7803-9
Rittle, Jonathan; McCrory, Charles C L; Peters, Jonas C (2014) A 10(6)-fold enhancement in N2-binding affinity of an Fe2(μ-H)2 core upon reduction to a mixed-valence Fe(II)Fe(I) state. J Am Chem Soc 136:13853-62
Creutz, Sidney E; Peters, Jonas C (2014) Catalytic reduction of N2 to NH3 by an Fe-N2 complex featuring a C-atom anchor. J Am Chem Soc 136:1105-15

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