Just Add Water: Modulating the Structure-Derived Acidity of Catalytic Hexameric Resorcinarene Capsules

The hexameric undecyl-resorcin[4]­arene
capsule (C11R6) features eight discrete
structural water molecules located at the vertices of its cubic suprastructure.
Combining NMR spectroscopy with classical molecular dynamics (MD),
we identified and characterized two distinct species of this capsule, C11R6-A and C11R6-B, respectively featuring 8 and 15 water
molecules incorporated into their respective hydrogen-bonded networks.
Furthermore, we found that the ratio of the C11R6-A and C11R6-B found in solution can be modulated by controlling the water content
of the sample. The importance of this supramolecular modulation in C11R6 capsules
is highlighted by its ability to perform acid-catalyzed transformations,
which is an emergent property arising from the hydrogen bonding within
the suprastructure. We show that the conversion of C11R6-A to C11R6-B enhances the catalytic rate of a model Diels–Alder
cyclization by 10-fold, demonstrating the cofactor-derived control
of a supramolecular catalytic process that emulates natural enzymatic
systems.