A hydrogen-bond stabilized cavitand receptor for coronene that has an unprecedented conformational flexibility and adapts to the guest's shape.

The conformational equilibria and guest exchange process of a resorcin[4]arene derived self‐folding cavitand receptor have been characterized in detail by molecular dynamics simulations (MD) and 1H EXSY NMR experiments. A multi‐timescale strategy for exploring the fluxional behaviour of this system has been constructed, exploiting conventional MD and accelerated MD (aMD) techniques. The use of aMD allows the reconstruction of the folding/unfolding process of the receptor by sampling high‐energy barrier processes unattainable by conventional MD simulations. We obtained MD trajectories sampling events occurring at different timescales from ns to s: 1) rearrangement of the directional hydrogen bond seam stabilizing the receptor, 2) folding/unfolding of the structure transiting partially open intermediates, and 3) guest departure from different folding stages. Most remarkably, reweighing of the biased aMD simulations provided kinetic barriers that are in very good agreement with those determined experimentally by 1H NMR. These results constitute the first comprehensive characterization of the complex dynamic features of cavitand receptors. Our approach emerges as a valuable rational design tool for synthetic host‐guest systems

We report a chiral deep cavitand receptor based on calix[5]arene stabilized by a cooperative network of hydrogen bonds and having a highly flexible structure. The cavitand displays enantioselective molecular recognition with a series of chiral quaternary ammonium salts, providing unprecedented stability ratios between the corresponding diastereomeric host–guest complexes. Molecular dynamics simulations corroborate the higher flexibility of the new host and the emergence of superior induced-fit behavior with regards to resorcin[4]arene derived self-folding cavitands.

We report a chiral deep cavitand receptor based on calix[5]arene stabilized by a cooperative network of hydrogen bonds and having a highly flexible structure. The dynamic features of the host have been studied by 1H NMR spectroscopy, revealing a bowl inversion motion that is slow in the NMR time scale. The cavitand displays enantioselective molecular recognition with a series of chiral quaternary ammonium salts, providing unprecedented stability ratios between the corresponding diasteromeric host-guest complexes. Molecular dynamics simulations corroborate the higher flexibility of the new host and the emergence of superior induced fit behavior with regards to resorcin[4]arene derived self-folding cavitands.

We report a chiral deep cavitand receptor based on calix[5]arene stabilized by a cooperative network of hydrogen bonds and having a highly flexible structure. The dynamic features of the host have been studied by 1H NMR spectroscopy, revealing a bowl inversion motion that is slow in the NMR time scale. The cavitand displays enantioselective molecular recognition with a series of chiral quaternary ammonium salts, providing unprecedented stability ratios between the corresponding diasteromeric host-guest complexes. Molecular dynamics simulations corroborate the higher flexibility of the new host and the emergence of superior induced fit behavior with regards to resorcin[4]arene derived self-folding cavitands.