GHOSH-DISSERTATION-2022.pdf (4.57 MB)
Biomimetic Model Systems of Aerobic CODH and Computational Insights on Its CO Oxidation Mechanism
thesis
posted on 2022-05-01, 00:00 authored by Dibbendu GhoshThe carboxydotrophic bacteria plays a key role in the global carbon cycle by catalyzing two-electron/two-proton interconversions of CO and CO2 to provide energy and the carbon source during chemolithoautotrophic growth using carbon monoxide dehydrogenase (CODH) enzymes. One of two known CODH variants contains a catalytic Mo/Cu cofactor whose MoVI–(µ2-S)–CuI active site has no synthetic or biological precedent and whose chemical mechanism for CO oxidation is under debate. Constructing synthetic models for this unusual inorganic functional group is a long-standing challenge and could contribute valuable insights regarding structural and functional aspects of the cofactor. Here, I will discuss the synthesis and characterization of (bdt)(O)(X)WVI–(µ2-S)–CuI(NHC) complexes (bdt = benzenedithiolate, X = O or OSiiPr3, NHC = a N-heterocyclic carbene) that faithfully mimic the structure of the (MCD)(O)(X)MoVI–(µ2-S)–CuI(SCys) cofactor in CODH (MCD = molybdopterin cytosine dinucleotide, X = O or OH, SCys = cysteine). In our findings we disclose that, in the absence of a protein environment, the core takes on an unreactive “closed” form in which an acute µ2-S angle enforces a short metal-metal distance and a close contact between the CuI center and either the bdt or X ligand. By contrast, the native cofactor features an active “open” form in which an obtuse µ2-S angle keeps the metal centers apart and the CuI site unsaturated. We used DFT calculations to estimate the strain energy required to open the synthetic model’s µ2-S angle, thus estimating the contribution of the CODH secondary structure towards cofactor activity. These observations support a mechanistic hypothesis wherein the Mo/Cu cofactor activates CO by virtue of a frustrated Lewis pair contained within the active site and enforced by the protein scaffold. We anticipate that our study will enrich hypotheses about biochemical multi-electron/multi-proton reactions as well as synthetic design of multimetallic catalysts.
History
Advisor
Mankad, NealChair
Mankad, NealDepartment
ChemistryDegree Grantor
University of Illinois at ChicagoDegree Level
- Doctoral
Degree name
PhD, Doctor of PhilosophyCommittee Member
Wink, Donald Glusac, Ksenija Nguyen, Andy Groysman, StanislavSubmitted date
May 2022Thesis type
application/pdfLanguage
- en