Conditional Copper‐Catalyzed Azide–Alkyne Cycloaddition by Catalyst Encapsulation

Angewandte Chemie International Edition, vol. 59, pp. 9340–9344

Abstract

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.

Authors 8

1. Tobias G. Brevé

   Delft University of Technology

   Affiliation as printed

   Department of Chemical Engineering Delft University of Technology van der Maasweg 9 2629 HZ Delft The Netherlands

   Department of Chemical Engineering, Delft University of Technology, van der Maasweg 9, 2629 HZ Delft, The Netherlands

2. Mike Filius

   Delft University of Technology

   Affiliation as printed

   Department of BioNanoScience Delft University of Technology van der Maasweg 9 2629 HZ Delft The Netherlands

   Department of BioNanoScience, Delft University of Technology, van der Maasweg 9, 2629 HZ Delft, The Netherlands

3. Can Araman Aachen

   Leiden University

   Affiliation as printed

   Leiden Institute of Chemistry Leiden University Einsteinweg 55 2333 CC Leiden The Netherlands

   Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands

4. Michelle P. van der Helm

   Delft University of Technology

   Affiliation as printed

   Department of Chemical Engineering Delft University of Technology van der Maasweg 9 2629 HZ Delft The Netherlands

   Department of Chemical Engineering, Delft University of Technology, van der Maasweg 9, 2629 HZ Delft, The Netherlands

5. Peter‐Leon Hagedoorn

   Delft University of Technology

   Affiliation as printed

   Department of Biotechnology Delft University of Technology van der Maasweg 9 2629 HZ Delft The Netherlands

   Department of Biotechnology, Delft University of Technology, van der Maasweg 9, 2629 HZ Delft, The Netherlands

6. Chirlmin Joo

   Delft University of Technology

   Affiliation as printed

   Department of BioNanoScience Delft University of Technology van der Maasweg 9 2629 HZ Delft The Netherlands

   Department of BioNanoScience, Delft University of Technology, van der Maasweg 9, 2629 HZ Delft, The Netherlands

7. Sander I. van Kasteren Aachen

   Leiden University

   Affiliation as printed

   Leiden Institute of Chemistry Leiden University Einsteinweg 55 2333 CC Leiden The Netherlands

   Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands

8. Rienk Eelkema corresponding

   Delft University of Technology

   Affiliation as printed

   Department of Chemical Engineering Delft University of Technology van der Maasweg 9 2629 HZ Delft The Netherlands

   Department of Chemical Engineering, Delft University of Technology, van der Maasweg 9, 2629 HZ Delft, The Netherlands