Cucurbit[8]uril Controls the Folding of Cationic Diaryl Ureas in Water

Abstract

The ability of cucurbit[8]uril (CB[8]) to control the folding of diaryl ureas 1 and 2 in water was investigated. Compounds 1 and 2 contain two ureidyl C–N bonds which can each populate two conformational states resulting in a conformational ensemble comprising at least three states. We find that the presence of CB[8] results in the selective population of the (E,E)-2 conformer by the formation of CB[8]·(E,E)-2 complex at CB[8]:2 stoichiometries of 1: < 1; at higher stoichiometries, an unfolding process takes place during the formation of CB[8]·(Z,Z)-2 ₂. In contrast, compound 1 forms the 2:2 complex CB[8]₂·(Z,Z)-1 ₂ over a broad range of CB[8]:2 stoichiometries. The absolute stoichiometries of these complexes were established by diffusion ordered spectroscopic methods (DOSY). The folding of 2 into the (E,E)-2 conformer under the formation of CB[8]·(E,E)-2 is responsive to the presence of guests in its environment. For example, the addition of 8 results in the expulsion of (E,E)-2 from the cavity of CB[8] followed by its unfolding to the thermally preferred mixture of (Z,Z)- and (Z,E)-2 conformers. These results suggest that complexation within synthetic molecular containers—just like their natural counterparts the chaperones—may be an efficient route to control the folding behaviour of non-natural oligomers in aqueous solution.

Keywords:

• Cucurbit[n]urils
• Foldamers
• Molecular containers
• Biomimetic systems

Acknowledgements

We thank the National Science Foundation (CHE-0615049) and the National Institutes of Health (GM-61854) for financial support of this work.