Supramolecular hydrogels based on bile acids and their derivatives

Molecular hydrogels are soft materials formed by the self-assembly of small molecules in aqueous solutions via supramolecular interactions. Although much effort has been made in the past several decades in the study of these hydrogels, the mechanism of their formation remains to be understood and the prediction of their formation is a challenge. The main purpose of this thesis is to develop novel molecular hydrogels derived from bile acids, which are naturally occurring biocompounds, and to find the relationship between the gelator structure and the gelation ability. Two new molecular gelation systems based on bile acids and their derivatives have been developed, which may be useful in biomedical applications. The marginal solubility of the solute in water has been found to be a prerequisite for the formation of such molecular hydrogels. The alignment of the nanofibers in the gels leads to the formation of nematic hydrogels. The first gelation system is based on a cholic acid dimer as a gelator, which has two cholic acid molecules covalently linked by a diethylenetriamine spacer. This dimer is insoluble in water, but it forms hydrogels with 3-D fibrous networks in the presence of selected carboxylic acids. The carboxylic acids protonate the dimer, making it marginally soluble in water to yield hydrogels. Only weak and hydrophilic carboxylic acids were capable of inducing the gelation of the dimer and the mechanical strength of the hydrogels could be varied by judicious choice of the acids. Hydrophobic interactions and hydrogen bonding between the side chains of carboxylic acids improve the mechanical properties of hydrogels. The marginal solubility of the acid-dimer complex is regarded to be the critical factor for the formation of hydrogels. Another hydrogelation system was developed by purging to the aqueous solutions of a series of bile salts with carbon dioxide (CO2), yielding hydrogels made of entire natural biological molecules and providing a convenient storage reservoir of CO2 in water. Bile salts are well dissolved in water, while the solubility of bile acids is limited. The carboxylate group of bile salts may be partially protonated in aqueous solutions by bubbling CO2, making them only marginally soluble in water. This forms fibrous structures. Both the appearance and mechanical properties of the hydrogels depend on the amount of CO2 purged. Bubbling CO2 initially induced the formation of transparent hydrogels with nanofibers. Continued purging with CO2 strengthened the hydrogel mechanically, while further addition of CO2 reduced the transparency and mechanical strength of the hydrogel. Both the transparent and opaque hydrogels reverted to transparent solutions when heated and bubbling N2. The sol-gel transition process was reversible and repeatable. The mechanical strength and transparency of the hydrogels could be improved by adding inorganic salts such as NaCl via a salting-out effect. All the hydrogel components are naturally biological compounds, making such hydrogels biocompatible and potentially useful in biomedical applications. The cholic acid dimer linked with a diethylenetriamine spacer was able to assemble in water and form isolated nanofibers in the presence of certain carboxylic acids at a much lower concentration than the CMC of sodium cholate. These nanofibers entangle with each other to yield well-dispersed and randomly-directed 3-D fibrous networks at higher concentrations. When the concentration of dimer salt is above the minimum gelation concentration, the fibrous network is strong enough to immobilize the solution, leading to the formation of an isotropic hydrogel. Further increase of the dimer salt concentration may transit the hydrogels to be anisotropic, thus the formation of nematic hydrogels. The formation of ordered domains of the aligned nanofibers led to anisotropic optical properties of the hydrogels. Stirring the aqueous systems of dimer salt also promoted the alignment of the nanofibers. These molecular hydrogels with ordered aggregates may be useful in applications such as cell culture and mechano-optical sensing.

Keyphrases: Molecular hydrogels, Bile acids, Supramolecular interactions, Self-assembled fibrous network, Biocompatible, CO2-induced hydrogel, Nematic hydrogel