Robinson Elizabeth L, Zavalij Peter Y, Isaacs Lyle
Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742, USA.
Supramol Chem. 2015 May 1;27(5-6):288-297. doi: 10.1080/10610278.2014.940952.
Cucurbit[7]uril (CB[7]) is currently being investigated as a solubilizing agent for insoluble drugs. We recently found that acyclic CB[n]-type receptors that bear sulfonate solubilizing groups are well suited for this application. Herein, we report cucurbit[7]uril derivative () that bears two sulfonate groups on its convex face that we hypothesized would be a superior solubilizing excipient for insoluble drugs. Before using for drug solubilization experiments we showed that 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 maintains the key structural features of CB[7] with only minor ellipsoidal deformations at the equator and carbonyl portals of . Unfortunately, the aqueous solubility of (20 mM) is slightly lower than CB[7] (20-30 mM) which limits its potential as a solubilizing excipient for insoluble drugs. We created phase solubility diagrams for the solubilization of three drugs (camptothecin, albendazole, cinnarizine) with two different containers ( and CB[7]). CB[7] and exhibit comparable solubilization abilities (e.g. K and maximum solubility) toward camptothecin and albendazole but is an inferior solubilizing agent for cinnarizine because of the low solubility exhibited by the •cinnarizine complex.
葫芦[7]脲（CB[7]）目前正在作为难溶性药物的增溶剂进行研究。我们最近发现，带有磺酸盐增溶基团的无环CB[n]型受体非常适合此应用。在此，我们报道了一种葫芦[7]脲衍生物（），其凸面上带有两个磺酸盐基团，我们推测它将是难溶性药物的一种更优的增溶辅料。在将用于药物增溶实验之前，我们表明不会自缔合，并且它保留了与二铵化合物结合的能力，二铵化合物是CB[7]尺寸空腔的常见客体。X射线晶体学表明，仅在的赤道和羰基入口处有轻微的椭球变形，仍保持CB[7]的关键结构特征。不幸的是，（20 mM）的水溶性略低于CB[7]（20 - 30 mM），这限制了其作为难溶性药物增溶辅料的潜力。我们用两种不同的容器（和CB[7]）创建了三种药物（喜树碱、阿苯达唑、桂利嗪）增溶的相溶解度图。CB[7]和对喜树碱和阿苯达唑表现出相当的增溶能力（例如K和最大溶解度），但由于•桂利嗪络合物表现出的低溶解度，是桂利嗪的较差增溶剂。
