Natural enzymes preorganize multiple catalytic residues to achieve exquisite reactivity. Using non-protein scaffolds for enzyme-mimicking catalysis remains an outstanding challenge. DNA as a scaffold for enzyme-mimicking catalysis has many advantages: programmable 3D architectures, precise control over the positioning of multiple abiotic groups, structural switchability (mimicking allostery), and DNA barcoding to enable high-throughput libraries (mimicking natural evolution). We report the use of DNA as an advantageous scaffolding architecture for accelerating a synergistic catalytic reaction involving two abiotic catalysts through increase in effective co-catalyst concentration. Using the Cu/TEMPO-catalyzed oxidation of benzylic alcohols as a model reaction, we observed a 110-fold increase in rate, and measured a corresponding increase in effective co-catalyst concentration. Capitalizing on programmable DNA assembly and the principles of DNA molecular rulers, we systematically modulated the DNA architecture to affect catalysis by varying inter-catalyst distance. By introducing a strand-displacement motif, we also demonstrated switchable catalysis using mean inter-catalyst distance as the controlling parameter. These switchable synergistic catalysts open up future opportunities in catalytic sensing and responsive materials. We also report the extension of DNA-scaffolded synergistic catalysis to DNA architectures that incorporate three or more abiotic groups. We describe using these architectures for combinatorial library synthesis and a high-throughput selection based on DNA barcoding for rapid discovery of enzyme-mimicking catalysts, thus combining the benefits of synthetic synergistic catalysis with DNA-mediated high-throughput discovery.

DNA architectures to accelerate and optimize synergistic catalysis

ACS Spring 2022

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