Novel Hydrogen-bonded Supramolecular Assemblies from Resorcinarene-derived Macrocycles & Elucidation of the Prerequisites for Terpene Cyclizations inside the Resorcinarene Capsule

The acid-catalyzed tail-to-head terpene cyclization promoted by the resorcinarene hexamer is a prime example of enzyme mimetic catalysis utilizing supramolecular capsules. The exact mode of activation and the reasons for the catalytic inactivity of the closely related pyrogallolarene hexamer however, remained elusive for some time. In this work we utilized synthetic chemistry to modify the resorcinarene macrocycle with the goal of obtaining new building blocks capable of self-assembly, forming new supramolecular structures with unprecedented properties. Firstly, a synthetic route was developed to access several new macrocycles with varying ratios of resorcinol and pyrogallol units, in order to elucidate the specific requirements for acid-catalyzed terpene cyclizations within the resorcinarene capsule. The resulting assemblies were characterized with respect to their catalytic activity in the cyclization of monoterpenes as well as several properties including guest uptake, stabilization of ion pairs, response to externally added acid (HCl) and water incorporated into the hydrogen bond network. The results revealed a correlation between the structural incorporation of water and the catalytic activity. This indicates the crucial role of the water molecules in the hydrogen bond network of the supramolecular capsule, which act as a proton shuttle activating the encapsulated substrate and enable efficient catalysis. Molecular dynamics simulation conducted using a model system provided additional details concerning the exact protonation pathway, supporting the experimental evidence. Secondly, a similar synthetic approach was used to synthesize a resorcinarene-derived macrocycle featuring four additional amide moieties capable of hydrogen bonding. Detailed 1H- and DOSY-NMR studies revealed the concentration-dependent self-assembly of a large, hexameric cage based on intermolecular amide−amide dimerization. An internal cavity volume of 2800 Å3 and a diameter of 2.3 nm make it the largest self-assembled cage/capsule structure self-assembled exclusively via hydrogen bonding. Supported by DFT calculations the results indicate that an unusual cage-like structure with large openings, reminiscent of covalently linked structures, is formed rather than a ‘closed-shell’ structure observed more commonly for hydrogen bonded assemblies. Additionally, the cage was found to form host-guest complexes with fullerenes (C60 and C70).