Acyclic cucurbituril congener binds to local anaesthetics

The recognition properties of acyclic cucurbit[n]uril (CB[n]) congener 1 towards seven local anaesthetic drugs (2-8) are reported. Job plots constructed from ¹H NMR experiments confirm the 1:1 host:guest nature of these complexes, whereas the changes in chemical shift observed upon complex formation ( values) provide information about the geometry of the host-guest complexes. For complexes between host 1 and guests 2-5 and 8, a single geometry was preferred, whereas for guests 6 and 7 a mixture of two diastereomeric complexes was indicated. The K _a values for complexes between 1 and 2-8 fall in the range of 10 ³-10 ⁸M ¹ as determined by UV-vis and ¹H NMR competition experiments. The results further establish that acyclic CB[n]-type receptor 1 is preorganised into the C-shape required for binding and that its aromatic o-xylylene walls endow it with a potency towards aromatic ammonium ions. The K _a values reported in this paper constitute a blind data-set used in the SAMPL3 challenge aimed at testing computational methods relevant to proteinligand systems. The work thus highlights the great potential of CB[n] receptors as model systems to promote synergy between the supramolecular and computational chemistry communities.