The Sulfo-NHS ester is a mainstay reagent for facilitating amide bond formation between carboxylic acids and amine functionalities in water. However, the preparation of Sulfo-NHS esters currently requires hydrophobic carboxylic acids, which are poorly water-soluble, to first be reacted with the N-hydroxysulfosuccinimide sodium salt, which is insoluble in organic solvents. The mutually incompatible solvation requirements thus complicate the synthesis of Sulfo-NHS esters. As a simple, rapid, and cost-effective solution to this problem, we report that the use of 15-crown-5 to complex the sodium cation of N-hydroxysulfosuccinimide sodium salt circumnavigates these solvation incompatibility issues by rendering the N-hydroxysulfosuccinimide salt soluble in organic solvents, resulting in a cleaner esterification reaction and thus improved yields of activated ester product. We also demonstrate that the resultant “crowned” Sulfo-NHS-ester remains water-soluble and is no less reactive than its classic “uncrowned” Sulfo-NHS counterpart when used in bioconjugation reactions between protein amine-functionalities and hydrophobic carboxylic acids.

中文翻译：

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跨越溶解度卢比孔河：15-Crown-5 有助于在有机溶剂中制备水溶性磺基-NHS 酯

Sulfo-NHS 酯是促进水中羧酸和胺官能团之间形成酰胺键的主要试剂。然而，目前制备Sulfo-NHS酯需要水溶性差的疏水性羧酸，首先与不溶于有机溶剂的N-羟基磺基琥珀酰亚胺钠盐反应。因此，相互不相容的溶剂化要求使磺基-NHS酯的合成变得复杂。作为解决该问题的一种简单、快速且经济高效的解决方案，我们报告使用 15-crown-5 来络合N-羟基磺基琥珀酰亚胺钠盐的钠阳离子，通过使N-羟基磺基琥珀酰亚胺盐可溶，从而避免了这些溶剂化不相容性问题在有机溶剂中，导致更清洁的酯化反应，从而提高活化酯产物的产率。我们还证明，当用于蛋白胺官能团和疏水性羧酸之间的生物共轭反应时，所得的“加冕”Sulfo-NHS-酯仍然是水溶性的，并且其反应性不低于其经典的“无冠”Sulfo-NHS对应物。