Department of Chemical Engineering, 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.
Angew Chem Int Ed Engl. 2020 Jun 8;59(24):9340-9344. doi: 10.1002/anie.202001369. Epub 2020 Apr 7.
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.
超分子包封被认为可以改变客体分子的化学性质。我们将这种分子包封的策略应用于时间控制稳定的铜（I）-卡宾催化剂的催化活性。超分子主体葫芦[7]脲（CB[7]）对铜（I）-卡宾催化剂的包封导致铜催化的炔烃-叠氮环加成（CuAAC）反应完全失活。通过添加化学信号，可以通过从抑制 CB[7]催化剂配合物中释放催化剂来实现催化剂的近乎瞬时激活。为了扩大我们按需 CuAAC 反应的范围，我们用铜（I）-卡宾催化剂对 vinculin 进行了蛋白质标记，通过与 CB[7]包封来抑制其活性，并通过添加特定的信号分子随时开始标记。最终，该策略允许对小分子和蛋白质靶标进行铜催化点击化学的时间控制。
