Issue 13, 2015

Acyclic cucurbit[n]uril-type molecular containers: influence of glycoluril oligomer length on their function as solubilizing agents

Abstract

We present the synthesis of a series of six new glycoluril derived molecular clips and acyclic CB[n]-type molecular containers (1–3) that all feature SO3 solubilizing groups but differ in the number of glycoluril rings between the two terminal dialkoxyaromatic sidewalls. We report the X-ray crystal structure of 3b which shows that its dialkoxynaphthalene sidewalls actively define a hydrophobic cavity with high potential to engage in π–π interactions with insoluble aromatic guests. Compounds 1–3 possess very good solubility characteristics (≥38 mM) and undergo only very weak self-association (Ks < 92 M−1) in water. The weak self-association is attributed to unfavorable SO3⋯SO3 electrostatic interactions in the putative dimers 1242. Accordingly, we created phase solubility diagrams to study their ability to act as solubilizing agents for four water insoluble drugs (PBS-1086, camptothecin, β-estradiol, and ziprasidone). We find that the containers 3a and 3b which feature three glycoluril rings between the terminal dialkoxy-o-xylylene and dialkoxynaphthalene sidewalls are less efficient solubilizing agents than 4a and 4b because of their smaller hydrophobic cavities. Containers 1 and 2 behave as molecular clip type receptors and therefore possess the ability to bind to and thereby solubilize aromatic drugs like camptothecin, ziprasidone, and PBS-1086.

Graphical abstract: Acyclic cucurbit[n]uril-type molecular containers: influence of glycoluril oligomer length on their function as solubilizing agents

Supplementary files

Article information

Article type
Paper
Submitted
29 Jan 2015
Accepted
23 Feb 2015
First published
23 Feb 2015
This article is Open Access
Creative Commons BY license

Org. Biomol. Chem., 2015,13, 4041-4050

Author version available

Acyclic cucurbit[n]uril-type molecular containers: influence of glycoluril oligomer length on their function as solubilizing agents

L. Gilberg, B. Zhang, P. Y. Zavalij, V. Sindelar and L. Isaacs, Org. Biomol. Chem., 2015, 13, 4041 DOI: 10.1039/C5OB00184F

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