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; Del Castillo, Trevor J; Matson, Benjamin D et al. (2017) Catalytic N2-to-NH3 Conversion by Fe at Lower Driving Force: A Proposed Role for Metallocene-Mediated PCET. ACS Cent Sci 3:217-223
Deegan, Meaghan M; Peters, Jonas C (2017) CO Reduction to CH3OSiMe3: Electrophile-Promoted Hydride Migration at a Single Fe Site. J Am Chem Soc 139:2561-2564
Creutz, Sidney E; Peters, Jonas C (2017) Exploring secondary-sphere interactions in Fe-N x H y complexes relevant to N2 fixation. Chem Sci 8:2321-2328
Buscagan, Trixia M; Oyala, Paul H; Peters, Jonas C (2017) N2 -to-NH3 Conversion by a triphos-Iron Catalyst and Enhanced Turnover under Photolysis. Angew Chem Int Ed Engl 56:6921-6926
Rittle, Jonathan; Peters, Jonas C (2017) N-H Bond Dissociation Enthalpies and Facile H Atom Transfers for Early Intermediates of Fe-N2 and Fe-CN Reductions. J Am Chem Soc 139:3161-3170
Fajardo Jr, Javier; Peters, Jonas C (2017) Catalytic Nitrogen-to-Ammonia Conversion by Osmium and Ruthenium Complexes. J Am Chem Soc 139:16105-16108
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
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-N? Complex That Generates Hydrazine and Ammonia via Fe?NNH?: Demonstrating a Hybrid Distal-to-Alternating Pathway for N? Reduction. J Am Chem Soc 138:4243-8
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

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