Probing the Relationship between Gelation and Crystallization by Using Salts of Lithocholic Acid

Hydrogels derived from lithocholic acid (LCA), other bile acids, and their salts are promising materials for drug delivery, cellular immobilization, and other applications. We have found that ammonium salts of LCA are particularly useful for probing the mechanism of hydrogelation and for understanding the relationship between molecular organization in gels and crystals. The well-defined amphiphilic steroidal structure of the lithocholate anion favors a consistent pattern of association under different conditions. However, the nature of the resulting aggregates can be controlled by systematically varying the ammonium counterions, giving rise to hydrogels, mixtures of fibrils and crystals, or only crystals under essentially identical conditions of assembly. By using tools for studying gels in tandem with methods of crystal engineering, we have developed a detailed understanding of the association of ammonium lithocholates. In particular, our work suggests how molecules of lithocholate are arranged in networked fibrils that give rise to hydrogelation, provides evidence that gelation and crystallization are intimately related in this system, and helps explain in molecular detail why certain salts give rise to gels and others favor crystallization.