Superacid-Mediated Functionalization of Hydroxylated Cucurbit[n]urils

Abstract

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[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[n] derivatives, enabling the exploration of novel bioapplications of CB[n]-based host−guest chemistry with new CB[n]-conjugated functional materials.

Cucurbituril‐Based Biomacromolecular Assemblies

“…their crystal structure [45] . e) Detection of ADA‐BSA using CB[7]‐HRP‐catalyzed oxidation of luminol by H 2 O 2 [48] . The crystal data in (a–d) are deposited in the Protein Data Bank (PDB).…”

“…For example, the chemical modification of hydroxylated CBs has been readily realized through nucleophilic substitution under acidic conditions (Figure 5 e). [48] To explore the practicability of protein labeling and detection, one of the transformation products, monocarboxylated CB[7], was conjugated with horseradish peroxidase (HRP) via amide condensation. Consequently, the adamantane‐grafted bovine serum albumin (ADA‐BSA) was visually detected with assistance of CB[7]‐grafted HRP (CB[7]‐HRP), which was jointly attributed to the tight host–guest association and the amplified chemiluminescent signal output triggered by H 2 O 2 .…”

Supramolecular chemistry of substituted cucurbit[n]urils

“…51 The Kim group recently demonstrated a superacid-mediated conversion of the hydroxyl group on Q[n]s (n = 6 and 7) to yield other important functional groups in high yields. 52 Additionally, they found that the resulting substituted Q[n] can be readily conjugated to an enzyme to afford a Q[n]-conjugated enzyme which is useful in protein blotting assays. 53 Other groups also have made significant progress towards functionalizing Q[n] homologues.…”

Cucurbituril‐Based Biomacromolecular Assemblies

“…[45] e) Detection of ADA-BSA using CB [7]-HRP-catalyzed oxidation of luminol by H 2 O 2 . [48] The crystal data in (a-d) are deposited in the Protein Data Bank (PDB).…”

“…[47] In turn, the photophysical performance of the included chromophoric guest molecules could be considerably enhanced by the mutual cooperation between CBs and proteins.M eanwhile, the emergence of chemically modified CBs has opened up great opportunities to widen the biological applications of multicomponent CB-protein assemblies.F or example,t he chemical modification of hydroxylated CBs has been readily realized through nucleophilic substitution under acidic conditions (Figure 5e). [48] To explore the practicability of protein labeling and detection, one of the transformation products, monocarboxylated CB [7],w as conjugated with horseradish peroxidase (HRP) via amide condensation. Consequently,the adamantane-grafted bovine serum albumin (ADA-BSA) was visually detected with assistance of CB [7]-grafted HRP (CB [7]-HRP), which was jointly attributed to the tight hostguest association and the amplified chemiluminescent signal output triggered by H 2 O 2 .T his practical synthetic methodology can remove the roadblocks in the site-selective functionalization of the CB skeleton, which may allow the creation of al ibrary of biosensing platforms based on the chemically active CB derivatives.…”