The isocyano group is the structurally most compact bioorthogonal group known. It reacts with tetrazines under physiological conditions and has great potential for widespread use in the biosciences. In this account, we highlight the unique properties of the isocyano group as a bioorthogonal functionality. Protecting group chemistry based on the reaction of isonitriles and tetrazines that allows releasing payloads is a particular focus of the article. We further discuss the atypical steric attractions that take place in the transition state of the reaction between isonitriles and tetrazines, which result in an increase in the rate of the reaction with steric bulk of the tetrazine substituents. These findings will open up new possibilities in bioorthogonal chemistry where reactivity and stability are simultaneously desired. 1 Introduction 2 The Isocyano Group: A Structurally Compact Group for Bioorthogonal Chemistry 3 Bioorthogonal Protecting Group Chemistry 4 Steric Attractions in the Transition State Accelerate the Cycloaddition of Isonitriles and Tetrazines 5 Reactions of Tetrazines and Isonitriles are Compatible with Biomolecules and Living Organisms 6 Conclusions

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异腈的独特生物正交化学

异氰基是已知结构最紧凑的生物正交基团。它在生理条件下与四嗪反应，在生物科学中具有广泛应用的巨大潜力。在这个帐户中，我们强调了异氰基作为生物正交功能的独特性质。基于允许释放有效载荷的异腈和四嗪反应的保护基化学是本文的一个重点。我们进一步讨论了在异腈和四嗪之间反应的过渡态中发生的非典型空间吸引力，这导致与四嗪取代基的空间体积的反应速率增加。这些发现将为同时需要反应性和稳定性的生物正交化学开辟新的可能性。