Conditional Copper-Catalyzed Azide Alkyne Cycloaddition by Catalyst Encapsulation

ChemRxiv

Abstract

Supramolecular encapsulation is known to alter chemical properties of guest molecules. Here we apply this strategy of molecular encapsulation to temporally control the catalytic activity of a stable Cu(I)-carbene catalyst. Encapsulation of the Cu(I)-carbene catalyst by 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 labelling of Vinculin using the Cu(I)-carbene catalyst, to inhibit its activity by encapsulation with CB[7], and to initiate labelling at any moment by adding a specific signal molecule.

Authors 8

1. Tobias G. Brevé

   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 Biotechnology, 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 Biotechnology, 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

3. Can Araman Aachen Leiden Institute of Chemistry

   Leiden University · 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 Biotechnology, 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

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

4. Michelle van der Helm

   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 Biotechnology, 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 BioNanoScience, 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

   Department of Chemical Engineering, 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 Biotechnology, 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

7. Sander I. van Kasteren Aachen Leiden Institute of Chemistry

   Leiden University · Delft University of Technology

   Affiliation as printed

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

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

8. Rienk Eelkema

   Delft University of Technology

   Affiliation as printed

   Delft University of Technology