-??FunctionalLnFe-??NxHyModelsofBiologicalN2Fixation Nitrogenase (N2ase) is a metalloenzyme that mediates biological nitrogen fixation and is essential to 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 low coordinate geometries that may accommodate dinitrogen and other NxHy functionalities. We posit these geometries as relevant to Fe-??NxHy intermediates of the FeMoco. By analogy to the modes of Fe-??mediated biocatalytic O2 reduction, two limiting single-??site mechanisms are emphasized. The first is an alternating mechanism, where successive H-??atom transfers (via H+/e-??steps)occuratthedistalandproximalN-??atomsoftheFe-??N?Nsubunitinanalternatingfashion(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 H-??atom transfer at the distal N-??atom to liberate an NH3 equivalent precedes transfers to the proximalN-??atom(e.g.,Fe-??N2+3e-??+3H+?Fe?N+NH3).Wealsoexploreanewhybridmechanismthatfirst invokes a distal intermediate (Fe=NNH2) that then crosses to an alternating intermediate (Fe-??N2H4) before releasingthefirstNH3equivalent.Wewillusesyntheticmodelcomplexestotesttheviabilityofeachofthese mechanistic pathways, and to understand how the nuclearity, local geometry, and electronic structure of Fe-?? NxHy species control their relative stabilities and reactivity patterns. This knowledge will be applied to the study, via spectroscopic, electrochemical, and theoretical methods, of the first examples of single-??site iron catalystsforN2-??to-??NH3conversionthatwediscoveredinthepreviousgrantperiod,andtowardsthedesignof newN2-??fixingcatalystswithenhancedefficiency.Regardlessoftheprecisemechanismfornitrogenreduction attheFeMoco,itsultimatesolutionwillrequirecomparisonofspectroscopicdatafromthecofactortorelated data obtained for well-??defined model complexes. We will therefore continue to collaborate with researchers thatspecializeinspectroscopicstudiesoftheFeMocotomakesuchcomparisons,andotherinvestigatorswith expertisecomplementarytoourown.Insum,thefunctionalFe-??NxHymodelchemistryproposedwillcontinue to play a critical role alongside current biochemical, spectroscopic, and theoretical model studies aimed at unravelingthechemicalmechanismofbiologicalnitrogenfixation.

Public Health Relevance

Nitrogenase (N2ase) is an iron-??rich metalloenzyme that mediates biological nitrogen fixation, a process by which inert N2 is converted into a bio-??available form (NH3), and is essential to life. Our research uses functional iron model complexes to test and constrain hypotheses concerning the mechanism of biological nitrogenreduction,anddevelopsnewironcatalysttechnologiesforN2-??to-??NH3conversion.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM070757-13
Application #
9357658
Study Section
Macromolecular Structure and Function A Study Section (MSFA)
Program Officer
Anderson, Vernon
Project Start
2005-02-01
Project End
2020-08-31
Budget Start
2017-09-01
Budget End
2018-08-31
Support Year
13
Fiscal Year
2017
Total Cost
Indirect Cost
Name
California Institute of Technology
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
009584210
City
Pasadena
State
CA
Country
United States
Zip Code
91125
Chalkley, Matthew J; Del Castillo, Trevor J; Matson, Benjamin D et al. (2018) Fe-Mediated Nitrogen Fixation with a Metallocene Mediator: Exploring p Ka Effects and Demonstrating Electrocatalysis. J Am Chem Soc 140:6122-6129
Drover, Marcus W; Nagata, Koichi; Peters, Jonas C (2018) Fusing triphenylphosphine with tetraphenylborate: introducing the 9-phosphatriptycene-10-phenylborate (PTB) anion. Chem Commun (Camb) 54:7916-7919
Drover, Marcus W; Peters, Jonas C (2018) Expanding the allyl analogy: accessing ?3-P,B,P diphosphinoborane complexes of group 10. Dalton Trans 47:3733-3738
Matson, Benjamin D; Peters, Jonas C (2018) Fe-mediated HER vs N2RR: Exploring Factors that Contribute to Selectivity in P3EFe(N2) (E = B, Si, C) Catalyst Model Systems. ACS Catal 8:1448-1455
Deegan, Meaghan M; Peters, Jonas C (2018) Electrophile-promoted Fe-to-N2 hydride migration in highly reduced Fe(N2)(H) complexes. Chem Sci 9:6264-6270
Thompson, Niklas B; Green, Michael T; Peters, Jonas C (2017) Nitrogen Fixation via a Terminal Fe(IV) Nitride. J Am Chem Soc 139:15312-15315
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; Del Castillo, Trevor J; Matson, Benjamin D et al. (2017) Catalytic N2-to-NH3Conversion by Fe at Lower Driving Force: A Proposed Role for Metallocene-Mediated PCET. ACS Cent Sci 3:217-223
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
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

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