DFT investigation of the CO2 activation at the active site of the Carbon Monoxide Dehydrogenases

The sustainable production of chemical fuels from non-petrochemical resources and reduction of greenhouse gas emissions are two of the biggest societal challenges. Clean reduction of CO2 to liquid fuels could potentially provide solutions to both. However, a key requirement for the development of large- scale and sustainable process is the design of efficient and selective catalysts. The Ni-containing carbon monoxide dehydrogenases (Ni-CODHs) are the biological catalysts for the reversible reduction of CO2 to CO. The high catalytic efficiency and the absence of expensive metals in their active site (known as C-cluster), composed by an unusual [Fe3NiS4] structure bounded to an additional Fe atom (Feu), make the Ni-CODHs a very promising target for reverse engineering studies aimed at the design of bioinspired catalysts. Structural and spectroscopic studies on Ni-CODH provided multiple insights into the complex catalytic mechanism of this enzyme. However, further investigations of the stereoelectronic and catalytic properties of the C-cluster are required to better understand the enzyme reactivity. In this context, quantum mechanics calculations have been carried out in the framework of the Density Functional Theory (DFT) on a very large model of the active site (290 atoms) and on a minimal model of the C-cluster (62 atoms). A comparative analysis of results obtained using these two different models has allowed to investigate crucial effects of the protein environment on the stereoelectronic properties of the C-cluster. In particular, CO2 binding to active site have been investigated. Three redox states of the C-cluster, differing by one electron (Cred1, Cint, and Cred2), have been considered. According our results, the substrate binding is most favored when the C-cluster is reduced to the Cred2 state. A subsequent transfer of two electrons from the C-cluster to the ligand is responsible for the CO2 activation. Two stable conformations have been identified as stable isomers for the CO2-adduct; one in which the CO2 bridges the Ni and the Feu atoms and one in which it is terminally coordinated to Ni. Since the Ni ion is positioned at the end of the substrate channel, the latter is proposed to play a key role in the initial interaction between the CO2 and the C-cluster.