In recent years, bioorthogonal reactions have emerged as a powerful toolbox for specific labeling and visualization of biomolecules, even within the highly complex and fragile living systems. Among them, copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction is one of the most widely studied and used biocompatible reactions. The cytotoxicity of Cu(I) ions has been greatly reduced due to the use of Cu(I) ligands, which enabled the CuAAC reaction to proceed on the cell surface, as well as within an intracellular environment. Meanwhile, other transition metals such as ruthenium, rhodium and silver are now under development as alternative sources for catalyzing bioorthogonal cycloadditions. In this review, we summarize the development of CuAAC reaction as a prominent bioorthogonal reaction, discuss various ligands used in reducing Cu(I) toxicity while promoting the reaction rate, and illustrate some of its important biological applications. The development of additional transition metals in catalyzing cycloaddition reactions will also be briefly introduced.

中文翻译：

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过渡金属催化的生物正交环加成反应。

近年来，即使在高度复杂和脆弱的生物系统中，生物正交反应也已成为一种强大的工具箱，可用于对生物分子进行特异性标记和可视化。其中，铜（I）催化的叠氮化物-炔烃环加成（CuAAC）反应是研究最广泛且使用最广泛的生物相容性反应之一。由于使用了Cu（I）配体，Cu（I）离子的细胞毒性已大大降低，这使CuAAC反应能够在细胞表面以及细胞内环境中进行。同时，其他过渡金属如钌，铑和银也正在开发中，作为催化生物正交环加成的替代来源。在这篇综述中，我们总结了CuAAC反应的发展是一种重要的生物正交反应，讨论了用于降低Cu（I）毒性同时提高反应速率的各种配体，并阐明了其重要的生物学应用。还将简要介绍在催化环加成反应中其他过渡金属的开发。