GHOSH-DISSERTATION-2022.pdf (4.57 MB)
Biomimetic Model Systems of Aerobic CODH and Computational Insights on Its CO Oxidation Mechanism
thesisposted on 2022-05-01, 00:00 authored by Dibbendu Ghosh
The 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.
Degree GrantorUniversity of Illinois at Chicago
Degree namePhD, Doctor of Philosophy
Committee MemberWink, Donald Glusac, Ksenija Nguyen, Andy Groysman, Stanislav
Submitted dateMay 2022