Synthesis of a Disulfonated Derivative of Cucurbit[7]uril and Investigations of its Ability to Solubilize Insoluble Drugs.

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.