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Enzymes are supreme catalysts when it comes to high enantiopurities and their immobilization will pave the way for continuous operation.

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.

Dynamic regulation of chemical reactivity is important in many complex chemical reaction networks,s uch as cascade reactions and signal transduction processes.S ignal responsive catalysts could play acrucial role in regulating these reaction pathways.R ecently,s upramolecular encapsulation was reported to regulate the activities of artificial catalysts.W e present ahost-guest chemistry strategy to modulate the activity of commercially available synthetic organocatalysts.T he molecular container cucurbit[7]uril was successfully applied to change the activity of four different organocatalysts and one initiator,enabling up-or down-regulation of the reaction rates of four different classes of chemical reactions.I nm ost cases CB[7] encapsulation results in catalyst inhibition, however in one case catalyst activation by binding to CB[7] was observed. The mechanism behind this unexpected behavior was explored by NMR binding studies and pKa measurements.The catalytic activity can be instantaneously switched during operation, by addition of either supramolecular host or competitive binding molecules,and the reaction rate can be predicted with akinetic model. Overall, this signal responsive system proves apromising tool to control catalytic activity.