Supramolecular handshakes: characterization of urea‐carboxylate interactions within calixarene frameworks

The research of molecular capsules offers high application potential and numerous benefits in various fields. With the aim of forming supramolecular capsules which can be reversibly assembled and dissociated by simple external stimuli, we studied interactions between calixarenes containing urea and carboxylate moieties. To this end two ureido-derivatives of p-tert-butylcalix[4]arene comprising phenylureido-moieties and diacetate-calix[4]arenes were prepared. The binding of acetate by ureido-derivatives of calixarene in acetonitrile was characterized, revealing high affinity of ureido-calixarenes for carboxylates. This suggested high potential for uniting the complementary calix[4]arenes via H-bonds between carboxylic groups and urea moieties. The assembly of calixarenes was examined in detail by means of UV, 1H NMR, ITC, DOSY, MS, and conductometry providing insight in the structure-stability relationship. The tetraureido calixarene derivative formed the most stable heterodimers with diacetate-calix[4]arenes featuring practically quantitative association upon mixing the two calixarene counterparts. The possibility of controlling the formation of the heterodimer by protonating the carboxylates, thereby hindering the interactions critical for capsule assembly, was investigated. Indeed, the reversibility of breaking and re-forming the heterodimer by addition of an acid and base to the solution containing urea- and carboxylate-derivative calix[4]arene was demonstrated using NMR spectroscopy.