Anion Binding and Transport Activity of semithio-Bambus[6]uril

Ion transport across the cell membrane is essential for maintaining the cell ion homeostasis and regulating key processes of life. Generally, nature achieves these tasks using membrane proteins and large macromolecular assemblies. Otherwise, small synthetic molecules, which function as ion transporters, could be used as therapeutic agents for treating anion channelopathies.

As cyclic hexamer of dimethyl-glycoluril (i.e., 1; X=O) connected by methylene bridges, the bambus[6]uril, 2, strongly binds anions in its interior.^[1] Realizing that this property reflects the electrostatic landscape of the glycoluril molecular surface, we envisioned that the replacement of either one oxygen atom or both by another heteroatom, such as sulfur or nitrogen, i.e., 3 or 4, respectively, would significantly modify its anion binding properties and afford novel transporting opportunities.^[2]

Here we report the first example of bambusuril-based anion transporter. Semithio-bambus[6]uril, 3 can accommodate and transport chloride across lipid bilayer membranes in a leakage-free anion-selective manner. The present experimental results^[4] opens a plethora of transportation opportunities based on the synthetically accessible and modifiable bambusuril structure^[5] and design of synthetic unimolecular anion channels based on semiaza-bambusurils.^[6]

References:

1. Yawer, M. A.; Havel, V.; Sindelar, V. Angew. Chem. Int. Ed. 2015, 54, 276.
2. Solel, E.; Singh, M.; Reany, O.; Keinan, E. PCCP, 2016, 18, 13180.
3. Singh, M.; Solel, E.; Keinan, E.; Reany, O. Chem. Eur. J. 2015, 21, 536.
4. Lang, C.; Mohite, A.; Deng, X.; Dong, Z.; Xu, J.; Liu, J.; Keinan, E.; Reany, O. submitted
5. Singh, M.; Parvari, G.; Botoshansky, M.; Keinan, E.; Reany, O. Eur. J. Org. Chem. 2014, 933.
6. Singh, M.; Solel, E.; Keinan, E.; Reany, O. Chem. Eur. J. 2016, 22, 8848.