The project focuses on the mechanisms of action of enzymes called hydrogenases, of which there are two, [NiFe]- and the [FeFe]-hydrogenases, reflecting the metals at the active sites. These enzymes, which underpin H2-dependent metabolism of many pathogens in the human gut, act on two substrates protons (H+) and H2. Several related families of enzymes are known. The results are further relevant to fundamental catalyst technology. The work aims to clarify the structure and reactivity of the Ni-C, Ni-SI, Ni-R and Ni-L states of the [NiFe]-hydrogenases and the Hred state of the [FeFe]-hydrogenases. Special attention is directed at the location and behavior H2-derived substrates that are usually invisible to protein spectroscopy and are undetectable by protein crystallography. The active sites of these enzymes are highly unusual, featuring several distinctive cofactors, such as CO, cyanide, and, in the [FeFe] case, an aminodithiolate. The work employs the tools of organometallic chemistry to produce models (replicas) of the active sites. Molecular-level insights into behavior of the hydrogenic ligands will be examined by NMR spectroscopy and X-ray crystallography with attention to stereochemistry, redox potentials, acid-base behavior, and kinetic properties. The first theme examines methods for stabilizing nickelIII, characteristic of N-C state, using organometallic ligands that emulate the donor properties of thiolate ligands. The second theme examines the role of the cyanide cofactors bound to Fe, with attention to developing tools to modify the behavior of these groups.
This aim builds on preliminary evidence that boron reagents enable biomimetic activation of hydrogen in iron cyanides. The third theme, with a primary focus on the [FeFe] enzymes, elucidates the factors that lead to bidirectionality, the ability of models to both produce and oxidized H2. The last theme, which also emphasizes [FeFe]-hydrogenase, examines hypotheses that seek to explain the unusual structure-function of the reduced state of the enzyme. This theme will lead to new ligand scaffolds that stabilize terminal hydride ligands.
Hydrogen is a metabolic substrate and product for both pathogenic and beneficial members of human gut flora. This metabolism is mediated by hydrogenase enzymes. Through the work proposed herein we will elucidate the function of these enzymes on a molecular level, with emphasis on interactions involving iron and hydrogen.
|Li, Qianli; Lalaoui, Noémie; Woods, Toby J et al. (2018) Electron-Rich, Diiron Bis(monothiolato) Carbonyls: C-S Bond Homolysis in a Mixed Valence Diiron Dithiolate. Inorg Chem 57:4409-4418|
|Sommer, Constanze; Richers, Casseday P; Lubitz, Wolfgang et al. (2018) A [RuRu] Analogue of an [FeFe]-Hydrogenase Traps the Key Hydride Intermediate of the Catalytic Cycle. Angew Chem Int Ed Engl 57:5429-5432|
|Carlson, Michaela R; Gray, Danielle L; Richers, Casseday P et al. (2018) Sterically Stabilized Terminal Hydride of a Diiron Dithiolate. Inorg Chem 57:1988-2001|
|Pelmenschikov, Vladimir; Birrell, James A; Pham, Cindy C et al. (2017) Reaction Coordinate Leading to H2 Production in [FeFe]-Hydrogenase Identified by Nuclear Resonance Vibrational Spectroscopy and Density Functional Theory. J Am Chem Soc 139:16894-16902|
|Lalaoui, Noémie; Woods, Toby; Rauchfuss, Thomas B et al. (2017) Characterization of a Borane ? Complex of a Diiron Dithiolate: Model for an Elusive Dihydrogen Adduct. Organometallics 36:2054-2057|
|Yu, Xin; Tung, Chen-Ho; Wang, Wenguang et al. (2017) Interplay between Terminal and Bridging Diiron Hydrides in Neutral and Oxidized States. Organometallics 36:2245-2253|
|Schilter, David; Gray, Danielle L; Fuller, Amy L et al. (2017) Synthetic Models for Nickel-Iron Hydrogenase Featuring Redox-Active Ligands. Aust J Chem 70:505-515|
|Reijerse, Edward J; Pham, Cindy C; Pelmenschikov, Vladimir et al. (2017) Direct Observation of an Iron-Bound Terminal Hydride in [FeFe]-Hydrogenase by Nuclear Resonance Vibrational Spectroscopy. J Am Chem Soc 139:4306-4309|
|Carlson, Michaela R; Gilbert-Wilson, Ryan; Gray, Danielle R et al. (2017) Diiron Dithiolate Hydrides Complemented with Proton-Responsive Phosphine-Amine Ligands. Eur J Inorg Chem 2017:3169-3173|
|Zhao, Peihua; Gray, Danielle L; Rauchfuss, Thomas B (2016) Rational Synthesis of the Carbonyl(perthiolato)diiron [Fe2(S3CPh2)(CO)6] and Related Complexes. Eur J Inorg Chem 2016:2681-2683|
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