Allosteric initiation and regulation of catalysis with a molecular knot

Molecular knots occur in DNA, proteins, and other macromolecules. However, the benefits that can potentially arise from tying molecules in knots are, for the most part, unclear. Here, we report on a synthetic molecular pentafoil knot that allosterically initiates or regulates catalyzed chemical reactions by controlling the in situ generation of a carbocation formed through the knot-promoted cleavage of a carbon-halogen bond. The knot architecture is crucial to this function because it restricts the conformations that the molecular chain can adopt and prevents the formation of catalytically inactive species upon metal ion binding. Unknotted analogs are not catalytically active. Our results suggest that knotting molecules may be a useful strategy for reducing the degrees of freedom of flexible chains, enabling them to adopt what are otherwise thermodynamically inaccessible functional conformations.