Conditional Copper-Catalyzed Azide Alkyne Cycloaddition by Catalyst Encapsulation

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.