Sulfonamide derivatives have been used in pharmaceutics for decades. Here we report a new approach to release sulfonamides efficiently using a bioorthogonal reaction of sulfonyl sydnonimines and dibenzoazacyclooctyne (DIBAC). The second-order rate constant of the cycloaddition reaction can be up to 0.62 M⁻¹ s⁻¹, and the reactants are highly stable under physiological conditions. Most significantly, we also discovered the mutual orthogonality between the sydnonimine–DIBAC and benzonorbornadiene–tetrazine cycloaddition pairs, which can be used for selective and simultaneous liberation of sulfonamide and primary amine drugs.

中文翻译：

---

磺酰胺的生物正交释放和两种药物的相互正交释放†

磺酰胺衍生物已经在药物中使用了数十年。在这里，我们报告了一种新的方法，该方法可使用磺酰基亚砜亚胺和二苯并氮杂环辛炔（DIBAC）的生物正交反应有效地释放磺酰胺。环加成反应的二级速率常数可以高达0.62 M ^-1 s ^-1，并且反应物在生理条件下是高度稳定的。最重要的是，我们还发现了亚砜亚胺-DIBAC与苯并降冰片二烯-四嗪环加成对之间的相互正交性，可用于选择性和同时释放磺酰胺和伯胺药物。