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

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 CO 2 to CO (CO 2 + 2H + + 2e – CO + H 2 O). The possibility of converting the greenhouse gas CO 2 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 CO 2 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 CO 2 , different coordination modes of CO 2 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 CO 2 . The oxidation state of the C-cluster is also shown to be critical. CO 2 binds to C red2 according to a dissociative mechanism (i.e., CO 2 binds to the C-cluster after the release of possible ligands from Fe u ) when His93 is doubly protonated. CO 2 can also bind noncatalytically to C red1 according to an associative mechanism (i.e., CO 2 binding is preceded by the binding of H 2 O to Fe u ). Conversely, CO 2 dissociates when His93 is singly protonated and the C-cluster is oxidized at least to the C int redox state. Density functional theory was used to investigate Ni,Fe-containing carbon monoxide dehydrogenase enzymes. Different coordination modes of the substrate CO 2 to several forms and redox states of the C-cluster—the enzyme active site—were considered. The obtained results highlight the key role of the protein environment in tuning the reactivity and the geometry of the C-cluster. This helps to uncover which stereoelectronic properties of the active site are crucial for the efficient binding and release of CO 2 .