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 (1) that bears two sulfonate groups on its convex face that we hypothesized would be a superior solubilizing excipient for insoluble drugs. Before using1for drug solubilization experiments we showed that1does 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 that1maintains the key structural features of CB[7] with only minor ellipsoidal deformations at the equator and carbonyl portals of1. Unfortunately, the aqueous solubility of1(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 (1and CB[7]). CB[7] and1exhibit comparable solubilization abilities (e.g. Kaand maximum solubility) toward camptothecin and albendazole but1is an inferior solubilizing agent for cinnarizine because of the low solubility exhibited by the1•cinnarizine complex.
Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742, USA.
Elizabeth L
EL
Robinson
Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742, USA.
Peter Y
PY
Zavalij
Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742, USA.
Lyle
L
Isaacs