Molecular Stiffening by Macrocycle Clustering

Abstract Allosteric stiffening of a portion of a protein surface is a strategy used in nature to regulate protein oligomerization and provide crucial functions for cells. However, a similar strategy to selectively control part of a compound dynamics remains elusive. Here we show that cucurbit[ n ]uril (CB[ n ]) macrocycles can bind almost all portions of a tetratopic guest molecule, stiffening the different parts of the guest to different extents. “Host–guest” interactions were found to be instrumental in selectively “freezing” guest molecular motions. The combination of 1 H‐NMR (1D, 2D), DOSY, VT‐NMR, isothermal titration calorimetry (ITC), mass spectrometry and molecular modelling enabled to highlight the crucial role of cucurbit[8]uril (CB[8]) binding in the selective hardening of relevant portions of the guest molecule. Beyond implications for bioinspired systems mimicking control of a system dynamic to create a new function, this approach has relevance for improving room temperature phosphorescence, and could also be used to allosterically control organocatalysis in water.