Large-Scale Screening Reveals That Geometric Structure Matters More Than Electronic Structure in the Bioinspired Catalyst Design of Formate Dehydrogenase Mimics

The design of inorganic molecular
complexes for the reversible
conversion of formate into CO2 inspired by formate dehydrogenase
(FDH) enzymes is challenged by a lack of understanding of how to mimic
the enzyme action. Here, we carry out a large-scale, high-throughput
screening study on all mononuclear Mo/W complexes currently deposited
in Cambridge Structural Database (CSD) that resemble the coordination
environment of the molybdopterin cofactors in FDH. Using density functional
theory, we systematically investigate the individual effects of metal
identity, ligand identity, oxidation state, and coordination number
on structural, electronic, and catalytic (i.e., H atom binding) properties.
We compare our results on molecular complexes with large quantum mechanical
cluster calculations on a representative FDH enzyme to understand
the influence of the enzyme environment. These comparisons reveal
that the enzyme environment primarily influences the metal-local geometry,
and these structural variations can improve catalysis. Through a series
of computational substitutions on molecular complexes of terminal
chalcogen atoms and metal centers, we extend beyond CSD structures
to identify the limits of varied chalcogen and metal identity. Through
this analysis, we demonstrate that the enzyme primarily affects the
geometric properties of the metal center, and terminal chalcogen moieties
primarily influence local electronic properties.