Acyclic Cucurbit[n]uril‐Type Molecular Containers: Influence of Linker Length on Their Function as Solubilizing Agents

• DOI: 10.1002/cmdc.201600090
• Publication Date: 2016-03-19T01:14:38Z
• Authors: David Sigwalt; Damien Moncelet; Shane Falcinelli; Vijaybabu Mandadapu; Peter Y. Zavalij; Anthony Day; Volker Briken; Lyle Isaacs
• Keywords: Linker; Dilution; Proton NMR; Biocompatibility

Two acyclic cucurbit[n]uril (CB[n])-type molecular containers that differ in the length of (CH2 )n linker (M2C2: n=2, M2C4: n=4) between their aromatic sidewalls and sulfonate solubilizing groups were prepared studied. The inherent solubilities M2C2 (68 mm) M2C4 (196 are higher than analogue with a )3 (M2, 14 studied previously. (1) H NMR dilution experiments show do not self-associate water, which enables use as excipients. We used phase solubility diagrams (PSDs) to compare capacities M2, M2C2, M2C4, hydroxypropyl-β-cyclodextrin (HP-β-CD), sulfobutylether-β-cyclodextrin (SBE-β-CD) toward 15 insoluble drugs. found M2C4-as gauged by slope PSDs-are less potent agents M2. However, allows concentrations drug be formulated using M2 several cases. ability SBE-β-CD similar many cases, Krel values averaging 23 12, respectively, relative HP-β-CD. In vitro cytotoxicity vivo maximum tolerated dose studies document biocompatibility M2C2.