Modeling the active site of the CO-Dehydrogenase with synthetic low-molecular weight analogues

• Applicant: Professor Dr. Christian Limberg
• Subject Area: Inorganic Molecular Chemistry - Synthesis and Characterisation
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 572423689

In our preliminary work, we successfully developed a formate deprotonation strategy to sequentially assemble metal complexes featuring nickel–carbonite–metal units, where the metals included alkali metals, alkaline earth metals (Mg, Ca), or transition metals (Zn, Co, Fe). This enabled us to elucidate the electronic structure of the nickel–carbonite unit and to investigate the influence of the counter metal ions—including their effects on reactivity. Of particular interest was the case where the second metal was iron, as the [Ni–CO₂–Fe] complex closely resembles the corresponding unit in the Cred–CO₂ intermediate of the CODH enzyme. This project aims to both deepen and expand the insights gained so far. One focus will be on investigating the role of the central nickel atom, which has not yet been addressed. This will be done by synthesizing carbonite complexes through formate deprotonation using other divalent metal atoms that favor square-planar or tetrahedral coordination geometries or lack d orbitals altogether, followed by reactivity studies of these complexes. In addition, hydrogen-bonding interactions that the carbonite unit forms with amino acid residues in the second coordination sphere in the enzymatic intermediate will be mimicked in the model system, in order to explore their effect on carbonite reactivity. Furthermore, the knowledge gained from the formate deprotonation pathway will be leveraged to improve understanding along the CO₂ activation pathway and make advances there. Previous studies have shown that Nacnac-supported nickel(I) or nickel(0) complexes are capable of activating CO₂ and forming carbonite complexes equivalent to those generated via the formate deprotonation route. Since preliminary results have highlighted the crucial role of Lewis-acidic counterions in stabilizing/activating the carbonite ligands, Lewis acids will now be used to stabilize a CO₂ radical anion at a nickel(II) center—an intermediate that is expected to initially form when nickel(I) complexes react with CO₂. Finally, building on prior results and recent advances in biochemistry, we aim to take the next step in the biomimetic modeling of CODH. [Ni–CO₂–Fe] motifs, like those mentioned above, will no longer be generated via formate deprotonation followed by salt metathesis, but rather through direct CO₂ activation at a heterobimetallic [Ni–SR–Fe] unit with a three-coordinate nickel(I) center. These efforts are intended to further support the current biochemical mechanistic proposal and contribute to our understanding of how CODH can mediate CO₂ reduction without overpotential. In our artificial systems, suitable electrophiles will be used to trigger CO release and regenerate the initial state.

• DFG Programme: Research Grants