The Cu-free 1,3-dipolar cycloaddition of cyclooctynes and azides is an up-and-coming method in bioorganic chemistry and other disciplines. However, broad application is still hampered by major drawbacks such as poor solubility of the reactants in aqueous media and low reaction rates. It is thus of high demand to devise a fast and user-friendly strategy for the optimization of reaction conditions and reagent design. We describe a capillary electrophoresis (CE) study of reaction kinetics in strain-promoted azide–alkyne cycloadditions (SPAAC) using substrates with acidic or basic functionalities. This study reveals that the pH value has a significant effect on reaction rates as a result of changes in the reactants’ charge state via protonation or deprotonation, and the concomitant changes of electronic properties. This novel experimental setup also enables the study of even more challenging conditions such as reactions in micelles and we did indeed observe much faster SPAAC reactions in the presence of surfactants. Careful combination of the above-mentioned parameters resulted in the identification of conditions enabling remarkable rate enhancement by a factor of 80. This electrophoretic method may thus serve as a versatile, fast and reliable tool for screening purposes in all research areas applying SPAAC reactions.

中文翻译：

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毛细管电泳研究水溶液中应变促进的叠氮化物-炔烃环加成反应

环辛炔和叠氮化物的无铜1,3偶极环加成反应是生物有机化学和其他学科中一个崭新的方法。然而，广泛的应用仍然受到主要缺点的阻碍，例如反应物在水性介质中的溶解性差和反应速率低。因此，迫切需要设计一种快速且用户友好的策略以优化反应条件和试剂设计。我们描述了使用酸性或碱性官能团的底物在应变促进的叠氮化物-炔烃环加成反应（SPAAC）中的反应动力学的毛细管电泳（CE）研究。这项研究表明，由于质子化或去质子化导致反应物电荷状态的变化，以及电子性能的变化，pH值对反应速率有重大影响。这种新颖的实验装置还可以研究更具挑战性的条件，例如在胶束中的反应，而且在表面活性剂存在下，我们确实观察到了更快的SPAAC反应。仔细组合上述参数可确定条件，从而可将速率显着提高80倍。因此，该电泳方法可作为通用，快速且可靠的工具，用于在所有应用SPAAC反应的研究领域进行筛选。