The project focuses on molecular mechanisms by which enzymes oxdize hydrogen gas and reduce protons to make hydrogen. The processing of hydrogen is employed by many micro-organisms including pathogenic ones and involves extremely unusual cofactors and active sites. The work provides mechanistic insights into the newly realized biological function of iron, i.e. where the metal operates at lower oxidation states and is supported by unusual ligands such as CO and cyanide. Mechanistic characterization of these replicas of the active site of the Fe-only hydrogenase will provide insights unavailable by classical enzymological characterization. Preliminary studies show that oxidative decarbonylation of diiron dithiolato carbonyls affords species that bear a close structural resemblance to the enzyme's active sites, such as the previously unobserved bridging CO ligand. The project will build on these initial successeswith the goal of generating species with hydrogenic substrates bound as predicted by mechanistic enzymologists. We will probe for the first examples of mixed valency in reduced Fe-S systems. The new diferrous models will be employed to generate the first iron dihydrogen species, directly relevant to the catalytic mechanism. Redox auxiliaries will be attached to the diiron center to probe the kinetic and thermodynamic benefits of coupling the electron donor and the proton receptor. The mechanistic role of the associated cofactors - both the redox reservoir Fe-S protein and azadithiolate - will be probed. The newly developed methodologies will be applied to related mechanistic and preparative challenges related to the NiFe hydrogenases: the biosynthesis of the cyanide cofactor, metallocenethiolates to confer novel geometries, and second coordination sphere control of proton availabilit.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM061153-08
Application #
7570691
Study Section
Macromolecular Structure and Function A Study Section (MSFA)
Program Officer
Anderson, Vernon
Project Start
2000-07-01
Project End
2009-12-31
Budget Start
2009-01-01
Budget End
2009-12-31
Support Year
8
Fiscal Year
2009
Total Cost
$236,524
Indirect Cost
Name
University of Illinois Urbana-Champaign
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
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
Schilter, David; Camara, James M; Huynh, Mioy T et al. (2016) Hydrogenase Enzymes and Their Synthetic Models: The Role of Metal Hydrides. Chem Rev 116:8693-749

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