Conditional Copper-Catalyzed Azide–Alkyne Cycloaddition by Catalyst Encapsulation

Tobias G. Brevé, Mike Filius, Can Araman, Michelle P. van der Helm, Peter Leon Hagedoorn, Chirlmin Joo, Sander I. van Kasteren, Rienk Eelkema

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Supramolecular encapsulation is known to alter chemical properties of guest molecules. We have applied this strategy of molecular encapsulation to temporally control the catalytic activity of a stable copper(I)–carbene catalyst. Encapsulation of the copper(I)–carbene catalyst by the supramolecular host cucurbit[7]uril (CB[7]) resulted in the complete inactivation of a copper-catalyzed alkyne–azide cycloaddition (CuAAC) reaction. The addition of a chemical signal achieved the near instantaneous activation of the catalyst, by releasing the catalyst from the inhibited CB[7] catalyst complex. To broaden the scope of our on-demand CuAAC reaction, we demonstrated the protein labeling of vinculin with the copper(I)–carbene catalyst, to inhibit its activity by encapsulation with CB[7] and to initiate labeling at any moment by adding a specific signal molecule. Ultimately, this strategy allows for temporal control over copper-catalyzed click chemistry, on small molecules as well as protein targets.

Original languageEnglish
Pages (from-to)9340-9344
Number of pages5
JournalAngewandte Chemie - International Edition
Issue number24
StatePublished - 8 Jun 2020

Bibliographical note

Publisher Copyright:
© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.


  • catalysis
  • click chemistry
  • cucurbit[n]uril
  • host–guest systems
  • protein labeling


Dive into the research topics of 'Conditional Copper-Catalyzed Azide–Alkyne Cycloaddition by Catalyst Encapsulation'. Together they form a unique fingerprint.

Cite this