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Published in

Taylor and Francis Group, Supramolecular Chemistry, 5-6(27), p. 288-297, 2014

DOI: 10.1080/10610278.2014.940952

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

Journal article published in 2014 by Elizabeth L. Robinson, Peter Y. Zavalij, Lyle Isaacs ORCID
This paper is available in a repository.
This paper is available in a repository.

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Abstract

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.