MODELLING MICELLAR AGGREGATION OF BILE SALTS. Sofia Candeloro De Sanctis, Facolta' di Medicina, Dipartimento di Chimica, Universita' di Roma "La Sapienza"

The bile salts anions are amphiphilic steroid-like molecules with a rigid backbone of four fused rings from which three methyl and a variable number of hydroxyl groups are protruding. The molecules have flexible side chains of variable length and chemical constitution. In the physiological medium they interact through micellar aggregation, with important molecules like cholesterol, bilirubin, phospholipids, fatty acids. In most of the crystals we have studied so far they aggregate into very stable helical structures.

The helices are stabilized by an extended network of hydrogen bonds, as well as ion-ion and ion-dipole interactions. Molecules with different side chains and counterions can give rise to very similar packing motifs with similar hydrogen bonding schemes, indicating the important role of the hydrogen bonds for such structures.

The outer surfaces of the helices in the crystals have large non polar regions. However, for some of the bile salts we have evidences indicating the stability of the helical structures in the aqueous solutions, suggesting their presence possibly in the physiological medium as well. We are, therefore, using the helical arrangements found in the crystals as models for the micellar aggregation of bile salts and for their possible selective interactions with the molecules of the biological medium.