Synthesis of a disulfonated derivative of cucurbit[7]uril and investigations of its ability to solubilise insoluble drugs

Abstract

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.