SOLID STATE STRUCTURE AND MICELLAR MODELS OF THE BILE ACIDS

Sofia Candeloro¹, Angelo D'Archivio², Luciano Galantini², Enrico Gavuzzo³, Edoardo Giglio⁴

¹Facolta' di Medicina, Dipartimento di Chimica, Universita' di Roma "La Sapienza", Piazzale A. Moro 5, 00185 Roma, Italy , candeloro@caspur.it
²Dipartimento di Chimica, Ingegneria Chimica e Materiali, Universita' di L'Aquila, 67010 L'Aquila, Italy
³Istituto di Strutturistica Chimica 'Giordano Giacomello' del CNR, CP n. 10, 00016 Monterotondo Stazione, Roma, Italy
⁴Dipartimento di Chimica, Universita' di Roma "La Sapienza", Piazzale A. Moro 5, 00185 Roma, Italy

In the bile and gastrointestinal region a class of steroid-like amphiphilic molecules, the bile acids, are responsible for the solubilization and transport of water insoluble molecules of apolar nature, like bilirubin-IXalpha and cholesterol, and are, therefore, also connected with the mechanism of the formation and dissolution of biliary stones. Some of them are currently used as drugs. They also appear to have a regulatory role on the action of the lipases. In solution these surfactant molecules act as molecular aggregates (micelles), sometimes of very large size.

In the physiological medium the sodium and, sometimes, the calcium salts are of relevance. A long term project in our laboratory has been to study the crystal structures of these salts. This allowed us to detect some preferred molecular conformation and aggregation models that we have used for the study of the structure of the micelles and of their interaction complexes with relevant apolar molecules, carried out with appropriate spectroscopic techniques.

It has been found that, below some critical values of pH, the aggregates include protonated species. For this reason we are now studying the crystal structure of the acids in order to identify structural models suitable to represent the protonated micellar aggregates in aqueous solutions.

We have recently determined the crystal structure of glycodeoxycholic (GDCA), taurodeoxycholic (TDCA) and tauroursodeoxycholic (TUDCA) acids.

The crystal packing of GDCA is strikingly resembling that of the sodium salt of TDCA that we had previously determined. The -COOH group and an acetone molecule fill in the space occupied by the -CH2-SO3Na group and a water molecule of the sodium taurodeoxycholate structure.

The molecules of TDCA and TUDCA, that differ for the position of one of the hydroxyl groups (12alpha and 7beta, respectively), have isomorphous arrangement. Their crystals contain two water molecules per bile acid molecule and one of them is protonated (H₃O⁺), and form O...O distances (2.43, 2.52, 2.60 A) corresponding to very strong hydrogen bonds.

Some structural units have been identified in the crystal packings. They will be used and verified in the study of the protonated micellar aggregates in aqueous solutions.