Conformational selection in artificial catalysts and molecular machines

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Enzymes exist as a spontaneously interconverting ensemble of conformational states which likely enables their extremely high catalytic activity. Conformational selection proposes that the fastest reaction pathway samples different conformational states along the reaction coordinate, providing access to lower energy pathways otherwise inaccessible to any one conformation in isolation. This mechanical rate dependence is synonymous with information ratchet mechanisms, a process that drives every biological molecular machine. Although the impressive catalytic activities of enzymes have provided inspiration to chemists, the majority of artificial catalysts are designed to be static, a feature that may limit their catalytic potential. The introduction of dynamics to a catalyst can facilitate a ratchet mechanism allowing optimisation for opposing elemental steps thereby surpassing the static Sabatier limit.In addition to using ratchet mechanisms to improve catalytic efficiency, biology utilises ratcheting to build complexity through anabolism.2 Anabolism transforms low energy building blocks into higher energy products, an endergonic process. This endergonic transformation is possible as it is coupled it to an orthogonal exergonic process, generally using ATP as the chemical fuel. In contrast, the majority of synthetic transformations are exergonic proceeding energetically downhill to either a local or global energy minimum. Light driven reactions provide an exception to this rule allowing a higher energy plane to be traversed by the reagents and proceeding explicitly through a ratchet type mechanism. However, such transformations are limited to those which can interact with light either directly or via a catalyst. Similarly, deracemizations have been achieved through chemical fuelling but this is limited exclusively to entropic work. Taking inspiration from biology, to expand these fuelled endergonic reactions to otherwise inaccessible bond forming reactions would greatly expand the chemists' toolbox. Biology makes extensive use of ratchet mechanisms which contribute significantly to its efficiency. The implementation of these principles to synthetic catalysis, and synthesis more generally, has the potential to decrease both the cost and energy requirements whilst simultaneously expanding the chemical transformations available to the chemist.