Catalytic Principles from Natural Enzymes and Translational Design Strategies for Synthetic Catalysts

[Image: see text] As biocatalysts, enzymes are characterized by their high catalytic efficiency and strong specificity but are relatively fragile by requiring narrow and specific reactive conditions for activity. Synthetic catalysts offer an opportunity for more chemical versatility operating over a wider range of conditions but currently do not reach the remarkable performance of natural enzymes. Here we consider some new design strategies based on the contributions of nonlocal electric fields and thermodynamic fluctuations to both improve the catalytic step and turnover for rate acceleration in arbitrary synthetic catalysts through bioinspired studies of natural enzymes. With a focus on the enzyme as a whole catalytic construct, we illustrate the translational impact of natural enzyme principles to synthetic enzymes, supramolecular capsules, and electrocatalytic surfaces.