First-Principles Calculations on Ni,Fe-Containing Carbon Monoxide Dehydrogenases Reveal Key Stereoelectronic Features for Binding and Release of CO₂ to/from the C-Cluster

Abstract

In view of the depletion of fossil fuel reserves and climatic effects of greenhouse gas emissions, Ni,Fe-containing carbon monoxide dehydrogenase (Ni-CODH) enzymes have attracted increasing interest in recent years for their capability to selectively catalyze the reversible reduction of CO₂ to CO (CO₂ + 2H⁺ + 2e^- <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mo>⇌</mml:mo></mml:math> CO + H₂O). The possibility of converting the greenhouse gas CO₂ into useful materials that can be used as synthetic building blocks or, remarkably, as carbon fuels makes Ni-CODH a very promising target for reverse-engineering studies. In this context, in order to provide insights into the chemical principles underlying the biological catalysis of CO₂ activation and reduction, quantum mechanics calculations have been carried out in the framework of density functional theory (DFT) on different-sized models of the Ni-CODH active site. With the aim of uncovering which stereoelectronic properties of the active site (known as the C-cluster) are crucial for the efficient binding and release of CO₂, different coordination modes of CO₂ to different forms and redox states of the C-cluster have been investigated. The results obtained from this study highlight the key role of the protein environment in tuning the reactivity and the geometry of the C-cluster. In particular, the protonation state of His93 is found to be crucial for promoting the binding or the dissociation of CO₂. The oxidation state of the C-cluster is also shown to be critical. CO₂ binds to C_red2 according to a dissociative mechanism (i.e., CO₂ binds to the C-cluster after the release of possible ligands from Fe_u) when His93 is doubly protonated. CO₂ can also bind noncatalytically to C_red1 according to an associative mechanism (i.e., CO₂ binding is preceded by the binding of H₂O to Fe_u). Conversely, CO₂ dissociates when His93 is singly protonated and the C-cluster is oxidized at least to the C_int redox state.