Dynamically accelerated catalysis through conformational selection by a molecular motor

Conformational dynamics is increasingly recognized as an important contributor to enzyme catalysis, but is often overlooked in synthetic catalyst design. Here we experimentally demonstrate dynamically accelerated catalysis by conformational selection, caused by the stochastic interconversion of two well-defined conformations of a catenane-based organocatalyst. The dependencies of the reaction rates on the relative positioning of the catalyst components during different stages of the catalytic cycle enable the dynamic organocatalyst to achieve order-of-magnitude rate accelerations over static or predominantly single conformer analogues. Furthermore, the dynamical rate acceleration results in the emergent property of the organocatalyst acting as a directionally rotating motor, driven by an information ratchet mechanism, with the observed acceleration in catalysis corresponding to the kinetic asymmetry of the ratchet. In demonstrating that conformational dynamics can overcome linear scaling relationships for reaction kinetics these findings have implications for theories of enzyme catalysis and for artificial catalyst design. The link between faster catalysis and directionally biased conformational dynamics may also suggest that motor-molecules, essential components of cellular processes, could have first arisen in primitive form as a consequence of prebiotic evolutionary pressure to achieve faster catalysis.