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School of Chemistry, University of Bristol, Bristol BS8 1TS, UK - Tel + 44 (0)117 95 46 334 - Fax + 44 (0)117 92 51 295
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        Anion Recognition and Transport    
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    Cholic acid is a readily available natural product with a rigid, polycyclic steroidal structure and a well-spaced array of differentiable functional groups.  It makes an excellent starting material for functionalised molecular architectures with well-defined geometrical properties.  We have used it in many of our research programmes (see elsewhere on this site), but especially for the construction of anion receptors with preorganised arrays of H-bond donor groups.    Cholic Acid    
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    In this early example, two steroids were used to create a cavity surrounded by 4 x OH and 2 x NH groups.  The molecule bound chloride and fluoride with moderate affinities.

See: A. P. Davis, J. F. Gilmer, J. J. Perry, Angew. Chem. Int. Ed. Engl. 1996, 35, 1312.

      
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More recently, we have adopted the “cholapod” architecture, based on a single cholic acid unit with three “legs”.  The legs can contain various numbers of H-bond donors, and these can be designed to be very powerful.  This example binds chloride with Ka ~ 1011 m-1 in chloroform.

For more details see: J. P. Clare et al., J. Am. Chem. Soc. 2005, 127, 10739 and A. P. Davis, Coord. Chem. Rev. 2006, 250, 2939.

      
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    The cholapods' unusual binding strength enables them to transport certain anions (especially chloride) across cell membranes.  It seems that they can extract the anion from water into the non-polar membrane interior, without transferring a counter-cation.  The anion is then carried across and released on the other side of the membrane.  The net effect is the same as a natural chloride channel.  Certain diseases, notably cystic fibrosis, occur because sufferers possess defective chloride channels.  Could cholapods replace the missing function in these patients?

For more, see: A. V. Koulov et al., Angew. Chem. Int. Ed. 2003, 42, 4931 and A. P. Davis, D. N. Sheppard and B. D. Smith, Chem. Soc. Rev. 2007, 36, 348.