Acyclic cucurbit[n]uril-type molecular containers: influence of glycoluril oligomer length on their function as solubilizing agents.
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 12–42. 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.
Department of Chemistry and RECETOX, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic.
Laura
L
Gilberg
Ben
B
Zhang
Peter Y
PY
Zavalij
Vladimir
V
Sindelar
Lyle
L
Isaacs
D000480:Alkynes / Q000737:chemistry*; D018360:Crystallography, X-Ray; D057927:Hydrophobic and Hydrophilic Interactions; D007093:Imidazoles / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D006574:Heterocyclic Compounds, 2-Ring; D048289:Imidazolidines
D000480:Alkynes; D007093:Imidazoles; D011108:Polymers; C092018:glycoluril; D006574:Heterocyclic Compounds, 2-Ring; D048289:Imidazolidines