Superacid-Mediated Functionalization of Hydroxylated Cucurbit[]urils.

Herein we report a facile transformation of hydroxylated cucurbit[]uril (CB[], = 6 and 7) to other functionality-conjugated CB[]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[]s under superacidic conditions. One of the resulting CB[] derivatives with reactive functionality, monocarboxylated CB[7], is efficiently conjugated to an enzyme (horseradish peroxidase, HRP) by amide coupling. This provides a CB[7]-conjugated functional biomaterial (CB[7]-HRP) that selectively detects proteins labeled with a guest, adamantylammonium (AdA), based on bioorthogonal high-affinity host-guest interactions between CB[7] and AdA. We demonstrated the potential of overcoming the limitations in preparing reactive functional CB[] derivatives, enabling the exploration of novel bioapplications of CB[]-based host-guest chemistry with new CB[]-conjugated functional materials.