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Conditional Copper‐Catalyzed Azide–Alkyne Cycloaddition by Catalyst Encapsulation
Author(s) -
Brevé Tobias G.,
Filius Mike,
Araman Can,
Helm Michelle P.,
Hagedoorn PeterLeon,
Joo Chirlmin,
Kasteren Sander I.,
Eelkema Rienk
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202001369
Subject(s) - catalysis , cycloaddition , chemistry , copper , alkyne , click chemistry , combinatorial chemistry , supramolecular chemistry , carbene , synergistic catalysis , molecule , organic chemistry
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.

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