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

Organic & Biomolecular Chemistry
Laura GilbergLyle Isaacs

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 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 re...Continue Reading

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Citations

Nov 26, 2015·Organic Letters·David SigwaltLyle Isaacs
Sep 26, 2015·Organic Letters·Brittany VinciguerraLyle Isaacs
May 4, 2016·Chemical Reviews·Frank Biedermann, Hans-Jörg Schneider
Aug 6, 2016·Chemistry : a European Journal·Nengfang SheLyle Isaacs
Aug 10, 2016·Journal of Computer-aided Molecular Design·Stefano BosisioJulien Michel
Sep 14, 2016·The Journal of Organic Chemistry·Tomas LizalVladimir Sindelar
Sep 30, 2016·Journal of Computer-aided Molecular Design·Juyong LeeBernard R Brooks
Jun 7, 2017·Chembiochem : a European Journal of Chemical Biology·Shweta GanapatiLyle Isaacs
Aug 30, 2018·Organic & Biomolecular Chemistry·Wenjin LiuLyle Isaacs
Apr 12, 2019·Dalton Transactions : an International Journal of Inorganic Chemistry·Yang WangYong Yao
May 22, 2019·Organic & Biomolecular Chemistry·Weijian XueLyle Isaacs
Jul 28, 2019·Chemistry : a European Journal·Michael Heilmann, Konrad Tiefenbacher
Jan 1, 2019·Supramolecular Chemistry·Weijian XueLyle Isaacs
Aug 21, 2019·Chemical Communications : Chem Comm·Wenjin LiuQiaoli Yan
Feb 20, 2021·Chemical Communications : Chem Comm·Martin DračínskýJiří Kaleta
Jan 1, 2020·New Journal of Chemistry = Nouveau Journal De Chimie·Sandra Zebaze NdendjioLyle Isaacs
Oct 7, 2021·Chemistry : a European Journal·Adam T BrockettLyle Isaacs

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