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2.B.34.  The Transmembrane Anion Transporter Bambusuril (Bambusuril) Family 

Semithiobambus[6]uril is  an efficient transmembrane anion transporter. Although all bambusuril analogs (having either O, S or N atoms in their portals) are excellent anion binders, only the sulfur analog is also an effective anion transporter capable of polarizing lipid membranes through selective anion uniport. This notable divergence reflects significant differences in the lipophilic character of the bambusuril analogs (Lang et al. 2017). The order of transport efficiency is:  Cl- > Br- > I- > NO3- > HCO3- > ClO4 > SO42-. It may catalyzed anion:anion antiport (Lang et al. 2017). 

 Lisbjerg et al. 2015 have described the anion transport properties of a series of fluorinated bambus[6]urils. These macrocycles (see below) are structurally related to biotinuril macrocycles, which had previously been shown to facilitate the transport of less hydrophilic anions such as chloride and nitrate over more strongly hydrated anions such as bicarbonate and sulfate.29 Both classes of macrocycles employ CH hydrogen-bond donors on their interior cavities to bind anionic guests within the macrocycle (Davis et al. 2020). The new series of fluorinated bambus[6]urils 31b–d were compared with parent compound 31a (see figure below) in a series of anion transport assays. A chloride/nitrate exchange assay was used to initially assess the transport properties of the compounds. The chloride-sensitive fluorescent dye lucigenin was encapsulated within POPC/cholesterol 70 : 30 LUVs, and the bambusurils were pre-incorporated into the lipid bilayer in a transporter/lipid ratio of 1 : 200. The LUVs were dispersed in NaNO3 solution (225 mM intra- and extra-vesicular), and transport was initiated by a pulse of NaCl (25 mM) into the extra-vesicular solution. The fluorescence of lucigenin was quenched by the influx of chloride into the vesicles allowing the transport process to be monitored. Amongst the series of four compounds, compound 31d proved to be the most effective transporter, facilitating chloride transport via chloride/nitrate exchange. When this assay was repeated using an NaHCO3 solution instead of NaNO3, transport was significantly faster for all four bambusurils. Lisbjerg et al. 2015 attributed this to the high affinity of the macrocycles for chloride and bicarbonate and the ability of the bambusurils to simultaneously complex chloride and bicarbonate, which would facilitate exchange of the anions at the lipid–water interface. The compounds also have exceptionally high affinities for nitrate; e.g. compound 31d has a stability constant of (5 ± 1) × 1011 M−1 with nitrate (added as the tetrabutylammonium salt) in acetonitrile at 30 °C as measured by isothermal titration calorimetry, which may disfavour decomplexation of nitrate and consequently slow the chloride/nitrate exchange process.

Bambus[6]urils 31a–31d.

References associated with 2.B.34 family:

Davis, J.T., P.A. Gale, and R. Quesada. (2020). Advances in anion transport and supramolecular medicinal chemistry. Chem Soc Rev. [Epub: Ahead of Print] 32692794
Lang, C., A. Mohite, X. Deng, F. Yang, Z. Dong, J. Xu, J. Liu, E. Keinan, and O. Reany. (2017). Semithiobambus[6]uril is a transmembrane anion transporter. Chem Commun (Camb). [Epub: Ahead of Print] 28634604
Lisbjerg, M., H. Valkenier, B.M. Jessen, H. Al-Kerdi, A.P. Davis, and M. Pittelkow. (2015). Biotin[6]uril Esters: Chloride-Selective Transmembrane Anion Carriers Employing C-H···Anion Interactions. J. Am. Chem. Soc. 137: 4948-4951. 25851041