Cucurbit[7]uril (CB[7]) is currently being investigated as a solubilising agent for insoluble drugs. We recently found that acyclic CB[n]-type receptors that bear sulfonate solubilising groups are well suited for this application. Herein, we report CB[7] derivative (1) that bears two sulfonate groups on its convex face that we hypothesised would be a superior solubilising excipient for insoluble drugs. Before using 1 for drug solubilisation experiments, we showed that 1 does not self-associate and that it retained its ability to bind to diammonium compounds as common guests for CB[7]-sized cavities. X-ray crystallography shows that 1 maintains the key structural features of CB[7] with only minor ellipsoidal deformations at the equator and carbonyl portals of 1. Unfortunately, the aqueous solubility of 1 (20 mM) is slightly lower than CB[7] (20–30 mM) which limits its potential as a solubilising excipient for insoluble drugs. We created phase-solubility diagrams for the solubilisation of three drugs (camptothecin, albendazole and cinnarizine) with two different containers (1 and CB[7]). CB[7] and 1 exhibit comparable solubilisation abilities (e.g. Ka and maximum solubility) towards camptothecin and albendazole but 1 is an inferior solubilising agent for cinnarizine because of the low solubility exhibited by the 1√cinnarizine complex.

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葫芦[7]脲二磺化衍生物的合成及其溶解难溶性药物的能力研究

目前正在研究葫芦 [7] 脲 (CB[7]) 作为不溶性药物的增溶剂。我们最近发现带有磺酸盐溶解基团的无环 CB[n] 型受体非常适合这种应用。在此，我们报告了 CB[7] 衍生物 (1)，在其凸面上带有两个磺酸盐基团，我们假设它是不溶性药物的优良增溶剂赋形剂。在将 1 用于药物增溶实验之前，我们表明 1 不会自结合，并且它保留了与二铵化合物结合的能力，作为 CB [7] 大小的空腔的常见客体。X 射线晶体学显示 1 保持了 CB[7] 的关键结构特征，在赤道和羰基入口处只有微小的椭圆形变形 1。不幸的是，1 (20 mM) 的水溶性略低于 CB[7] (20-30 mM)，这限制了其作为不溶性药物增溶赋形剂的潜力。我们为三种药物（喜树碱、阿苯达唑和桂利嗪）在两种不同的容器（1 和 CB[7]）中的溶解创建了相溶解度图。CB[7] 和 1 对喜树碱和阿苯达唑表现出相当的增溶能力（例如 Ka 和最大溶解度），但 1 是一种较差的桂利嗪增溶剂，因为 1√桂利嗪复合物表现出低溶解度。