We previously described a pH-sensitive phosphoramidate linker scaffold that can be tuned to release amine-containing drugs at various pH values. In these previous studies it was determined that the tunability of this linker was dependent upon the proximity of an acidic group (e.g., carboxylic acid or pyridinium). In this study, we confirmed that the tunability of pH-triggered amine-release was also dependent upon the pKa of the proximal acidic group. A series of 2-carboxybenzyl phosphoramidates was prepared in which the pKa of the proximal benzoic acid was predictably attenuated by substituents on the benzoate ring consistent with their σ-values.

中文翻译：

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可调节pH值的2-羧苄基氨基磷酸酯可裂解连接子。

我们之前描述了一种pH敏感的氨基磷酸酯连接基支架，可以对其进行调节以在各种pH值下释放含胺的药物。在这些先前的研究中，已确定该接头的可调性取决于酸性基团（例如，羧酸或吡啶鎓）的接近性。在这项研究中，我们证实了pH触发的胺释放的可调性还取决于近端酸性基团的pKa。制备了一系列的2-羧基苄基氨基磷酸酯，其中近端苯甲酸的pKa被与它们的σ值一致的苯甲酸酯环上的取代基可预测地减弱了。