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Cu(I)-catalyzed azide-alkyne cycloadditions (CuAAC) have gained increasing interest in the selective labeling of living cells and organisms with biomolecules. However, their application is constrained either by the high cytotoxicity of Cu(I) ions or the low activity of CuAAC in the internal space of living cells. This paper reports the design of a novel Cu-based nanocatalyst, water-soluble thiolated Cu30 nanoclusters (NCs), for living cell labeling via CuAAC. The Cu30 NCs offer good biocompatibility, excellent stability, and scalable synthesis (e.g., gram scale), which would facilitate potential commercial applications. By combining the highly localized Cu(I) active species on the NC surface and good structural stability, the Cu30 NCs exhibit superior catalytic activities for a series of Huisgen cycloaddition reactions with good recyclability. More importantly, the biocompatibility of the Cu30 NCs enables them to be a good catalyst for CuAAC, whereby the challenging labeling of living cells can be achieved via CuAAC on the cell membrane. This study sheds light on the facile synthesis of atomically precise Cu NCs, as well as the design of novel Cu NCs-based nanocatalysts for CuAAC in intracellular bioorthogonal applications.

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Publication history
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Acknowledgements

Publication history

Received: 08 May 2022
Revised: 03 July 2022
Accepted: 26 July 2022
Published: 10 August 2022
Issue date: January 2023

Copyright

© Tsinghua University Press 2022

Acknowledgements

Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 22071127), Taishan Scholar Foundation (No. tsqn201812074); the Natural Science Foundation of Shandong Province (No. ZR2019YQ07), and the NanoBio Lab (IMRE, A*STAR, Singapore).

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