Choleic acid

The history of iaclusion compounds (1,2) dates back to 1823 when Michael Faraday reported the preparation of the clathrate hydrate of chlorine. Other early observations iaclude the preparation of graphite iatercalates ia 1841, the P-hydroquiaone H2S clathrate ia 1849, the choleic acids ia 1885, the cyclodexthn iaclusion compounds ia 1891, and the Hofmann s clathrate ia 1897. Later milestones of the development of iaclusion compounds refer to the tri-(9-thymotide benzene iaclusion compound ia 1914, pheaol clathrates ia 1935, and urea adducts ia 1940. 

Fig. 14. Choleic acid inclusion chemistry (a) crystal stmcture of DCA inclusion compound with phenanthrene (b) view along a DCA inclusion helix accommodating DMSO and water guest molecules (oxygen and sulfur atoms and methyl groups are represented by open circles and large and small black...

DCA forms canal inclusion compounds, known as choleic acids, which most frequently have the orthorhombic space group P212121, or less frequently Pl l. In such crystals the DCA molecules hydrogen bond to each other to form an extended bilayer structure, thereby creating a hydrophobic canal between adjacent bilayers. The guest molecules present in these canals therefore tend to be non-polar or moderately polar molecules such as aromatic compounds, alkenes, ketones and certain carboxylic acids 92). Since the bilayers are held together only by van der Waals forces the canals are able to adopt different dimensions to accommodate the variety of... 

The most extensive study in the field of host-guest reactions in clathrates has been that of Lahav, Leiserowitz, and co-workers (56,241,243) on the choleic acids. The results of these combined chemical and crystallographic investigations are of possible importance for stereoselective steroid functionalization. In these studies potentially reactive guests were activated thermally or photochemically to produce species that attacked the walls of the channel at specific sites determined by the proximity, orientation, and reactivity of the host molecules at the wall relative to the activated guest species. 

These compounds include Flofmann and Wcrner-typc inclusion compounds. inclusion compounds of urea, thiourea and sclenourea, inclusion compounds of gossypol. inclusion compounds of phenolic hosts, inclusion compounds of denxycholic acid (choleic acids), inclusion compounds of macrocyclic and oligocyciic lattice hosts and recently designed organic host lattices. 

Another type of inclusion compd is the channel or canal compound. Here the straight chain compds, such as hydrocarbons, acids,esters , alcohols, aldehydes, ketones, etc are enclosed in the channels formed by compds, such as urea, thiourea, choleic acids, cyclodextrins, etc. As examples of channel compds may be cited, the urea-decone compd, [CO(NH2)2] g.C, 2H26, and various zeolites. (See also Ref 10, pp431 ... 

Some molecules aggregate in crystals, generally by hydrogen bonding, to give crystal structures that contain channels and cavities that can accommodate foreign molecules. Examples are provided by the choleic acids, the gas hydrates, and the clathrates. 

Choleic acid A specific complex between deoxycholic acid, which crystallizes with channels throughout the structure, and various organic molecules, such as hydrocarbons or fatty acids, that can fit in these channels. 

Wieland, H., and Sorge, H. Untersuchungen iiber die Gallensauren. II. Mit-teilung. Zur Kenntnis der Choleinsaure. [Research on bile acids. On the identification of choleic acid.] Hoppe-Seyler s Z. Physiol. Chem. 96, 1-27 (1916). Giacomello, G. von, and Kratky, 0. Rontgenographische Studien an Cholan-saurenathylestern. [X-ray studies of choleic acid ethyl esters. ] Z. Krisi. A95, 459-464 (1936). 

Particularly efficient solubilizing agents of the bile acid family are the salts of deoxycholic acid 6". Their complexes with water-insoluble compounds are called choleic acids . The aggregation number of deoxycholic acid (DCA) in distilled water is approximately 10-12 ( primary micelles ) and rises to about 100 ( secondary micelles ) in more concentrated solutions and/or after addition of electrolytes to primary micelles. The cmc of primary micelles lies in the range of 1-5 x 10 mol/L. Less polar cholic acids are in general much better... 

Insight into the photochemical reactions between deoxycholic or apocholic acid ( choleic acids ) and guest molecules in crystalline inclusion complexes has been obtained by X-rzy studies. The choleic acids form channels with wall structures determined by the nature of the guest molecule. Guest ketones of various types react photochemically by addition to the choleic acid at a site determined by the orientation of the ketone molecule in relation to the host (e.g. deoxycholic acid reacts at C-5 or C-6 with linear aliphatic ketones, but at C-16 with cyclohexanone).12... 

Aspects of photosensitization in organic synthesis were reviewed128 and stereospecific and regiospecific photoreactions inside the channels of choleic acids were reported.129 Irradiation of saturated acids or esters was reported130 to lead to Norrish type II reaction or a 1,2-elimination and was exemplified by conversion of cholanic acid or its ethyl ester into the A20(22>-compound (156). Photolysis of the... 

In these cases m.p. values alone are not an adequate criterion for identification or purity of a specific bile acid, since when solvate molecules are present in a fixed stoichiometry, a sharp but lower m.p. value is usually obtained. Finally, certain bile acids, most notably deoxycholic acid [5,42], form stable mixed crystalline complexes, so-called choleic acids with a variety of macromolecular guest molecules in a fixed bile acid guest stoichiometry (see Section III.3). 

This hitherto neglected area is now receiving major attention and the crystalline structures of many common and uncommon bile acids [43,44,48,49], their alkaline and alkaline metal salts [7,51,53] have been defined. Choleic acids have been the subject of much activity in this field. A summary of the earlier work on choleic acids can be found in Sobotka [42] and Small [5]. 

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