Issue 30, 2025

Insights from designing an artificial cascade catalysis system using principles from substrate channeling in enzymes

Abstract

Generalizing the key requirements of highly-selective, multi-step chemical conversions involving spatially separated reaction centers remains one of the grand challenges of chemistry. Much work towards this effort has focused on decomposing multi-step conversions into their constituent reactions, whose intermediates are successively upgraded in a chemical cascade via diffusion from center to center. This approach for synthesizing more complex molecules takes its cues from biochemical networks, where near-unit conversion of even complex carbohydrates is achieved by upgrading chemical precursors via enzymatic cascades. In this computational study we examine a simple cascade involving coupled Ag and Cu catalysts that sequentially converts CO2 to CO and then CO2 and CO to reduced products, generically named CO2Product and COProduct. The system architecture is inspired by the phenomenon of biological substrate channeling, and components are examined to evaluate their effects on conversion efficiency in the cascade. Aside from a substrate channel linking two reaction centers, we find efficient cascades must also incorporate directional substrate diffusion, compartmentalization of the reaction centers, and proper timing of substrate arrival at the active center. We make explicit linkages between these requirements and chemical conversion in known biological systems, revealing additional control elements that could be incorporated.

Graphical abstract: Insights from designing an artificial cascade catalysis system using principles from substrate channeling in enzymes

Supplementary files

Article information

Article type
Edge Article
Submitted
15 Apr 2025
Accepted
28 Jun 2025
First published
30 Jun 2025
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2025,16, 13667-13677

Insights from designing an artificial cascade catalysis system using principles from substrate channeling in enzymes

F. A. Houle, P. Agbo and J. Yano, Chem. Sci., 2025, 16, 13667 DOI: 10.1039/D5SC02781K

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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