Synthesis of a Disulfonated Derivative of Cucurbit7uril and Investigations of its Ability to Solubilize Insoluble Drugs

摘要

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 (>1) that bears two sulfonate groups on its convex face that we hypothesized would be a superior solubilizing excipient for insoluble drugs. Before using >1 for drug solubilization 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 solubilizing excipient for insoluble drugs. We created phase solubility diagrams for the solubilization of three drugs (camptothecin, albendazole, cinnarizine) with two different containers (>1 and CB[7]). CB[7] and >1 exhibit comparable solubilization abilities (e.g. Ka and maximum solubility) toward camptothecin and albendazole but >1 is an inferior solubilizing agent for cinnarizine because of the low solubility exhibited by the >1•cinnarizine complex.