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

Abstract

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.

Can electric fields drive chemistry for an aqueous microdroplet?

“…The significance of ~16 MV/cm increase in field strengths when projected onto bonds at the air-water surface would correspond to lowering an energy barrier, and the impact on chemical transformations would depend on the type of bond being broken and whether they are close to ions if they are present. The transition state lowering can be estimated in a number of ways 30 , but here we consider a simple bond dipole-field model 57 , 58 for breaking a water bond. We estimate the bond dipole in the transition state to be 2.75 D (~25% larger than the 2.2 D in the ground state) yielding a free energy lowering of ~2.1 kcal/mol, which in the exponential would increase the equilibrium constant of water or the rate of reaction by 1–2 orders of magnitude.…”

Globally Optimized Molecular Embeddings for Dynamic Reaction Solvate Shell Optimization and Active Site Design

“…Consequentially, the question is: How to bridge the gap between catalytic embedding and enzymatic design? As has been shown in the past [17], the in silico design of new enzymes has made huge steps forward, and certainly warrants the search for ever new ways of fueling its success [18,19]. An intuitive way of extracting enzymatic design improvement from a GOCAT result would be to start from a known catalytically active basis and then improve upon it by finding point mutations resulting in a more favourable electrostatic field.…”

Local thermodynamics of alcohols from THz-calorimetry: Spectroscopic fingerprints of entropic loss and enthalpic gain

“…Hydrophobic hydration is important to understand and predict fundamental biological processes, such as protein folding and aggregation [1][2][3] , molecular recognition [4][5][6] and liquid-liquid phase separation, [7][8][9] as well as in many other fields, e.g. water-mediated catalysis [10][11][12] and electro-catalysis [13][14][15] . Going from small solutes all the way up to large biomolecules, a subtle balance between hydrophilic and hydrophobic interactions is what dictates hydration free energies.…”