Herein we report a facile transformation of hydroxylated cucurbit[n]uril (CB[n], n = 6 and 7) to other functionality-conjugated CB[n]s by nucleophilic substitution of the hydroxyl group with a wide range of nitriles and alcohols. The reaction proceeds efficiently via generation of a superelectrophilic carbocation on the CB framework from hydroxylated CB[n]s under superacidic conditions. One of the resulting CB[n] derivatives with reactive functionality, monocarboxylated CB, is efficiently conjugated to an enzyme (horseradish peroxidase, HRP) by amide coupling. This provides a CB-conjugated functional biomaterial (CB-HRP) that selectively detects proteins labeled with a guest, adamantylammonium (AdA), based on bioorthogonal high-affinity host–guest interactions between CB and AdA. We demonstrated the potential of overcoming the limitations in preparing reactive functional CB[n] derivatives, enabling the exploration of novel bioapplications of CB[n]-based host–guest chemistry with new CB[n]-conjugated functional materials.
Title: Superacid-Mediated Functionalization of Hydroxylated Cucurbit[n]urils Journal: : J. Am. Chem. Soc. 2019, 141, 17503−17506 https://doi.org/10.1021/jacs.9b09639