Acyclic cucurbituril congener binds to local anaesthetics

Abstract

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 (Δδ 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 103–108 M− 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 protein√ligand 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.