Cholapods

Anion binding and transport by steroid-based receptors , Coord. Ghent. Rev. 2006, 250, 2939-2951. 

The high chloride affinity and selectivity afforded by cholapods such as 4.97 suggests that they may be of use in the treatment of cystic fibrosis (Section 4.1) by acting as artificial chloride transporters. Chloride transport has been measured in an artificial vesicle system in which the fluorescent dye lucigenin is incorporated into the inner aqueous pore of the vesicle in the presence of a background 

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Figure 4.40 Chloride transport by a lipid vesicle membrane-incorporated cholapod. Chloride flux from outside to inside the vesicle quenches the fluorescence of the lucigenin dye in the interior of the system.

Careful control of preorganisation and hydrogen bond acidity can result in very high binding constants as in the cholapods. 

Cholapods (Scheme 9.5) are receptors based on a steroid core that feature both electron-withdrawing substituents (to enhance anion-binding) and a C2o side chain (to increase solubility in organic solvents). As might be expected, the rigid backbone present in cholapods makes them potentially ideal scaffolds in that they possess a fixed inner cavity as well as conformational rigidity [16,56,57]. However, only a few... 

Artificial analogues of the chloride transporter prodigiosin are effective symport HC1 carriers as exemplified in the model systems developed by the groups of Gale [39] and Davis [40], Biological inspiration is also behind another Cl- carrier. Cholic acid is a naturally occurring bile acid that functions as a surfactant in the intestine. Derivatives with three binding sites known as cholapods are able to transport isolated anions across lipid bilayers [41],... 

McNally BA et al (2008) Structure-activity relationships in cholapod anion carriers enhanced transmembrane chloride transport through substituent tuning. Chem Eur J 14 9599-9606... 

Extending their work on cholapods , A.P. Davis and co-workers have appended urea and thiourea groups from the 7 and 12 positions of the steroid scaffold and evaluated the ability of these receptors to bind chloride and bromide (added as their tetraethylammonium salts) [40]. 

Ayling, A.J. Perez-Payan, M.N. Davis, A.P. New cholapod anionophores High-affinity halide receptors derived Irom cholie acid. J. Am. Chem. Soc. 2001. 123 (50), 12716-12717. 

It is also possible to produce charged cholapods, typically using guanidinium or ammonium groups but also imidazolium and triazolium moieties. These charged systems have been employed as anion receptors, smart transfer agents, and membrane transport anionophores. 

Fang and coworkers have developed cholapods functionalized at the C-24 position, which provides both additional hydrogen-bonding functionality and an anthra-cenyl reporter group, compounds 60 and 61. 

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