Using Nuclear Magnetic Resonance Spectroscopy to Probe Hydrogels Formed by Sodium Deoxycholate

Abstract

Hydrogels of bile acids and their salts are promising materials for drug delivery, cellular immobilization, and other applications. However, these hydrogels are poorly understood at the molecular level, and further study is needed to allow improved materials to be created by design. We have used NMR spectroscopy to probe hydrogels formed from mixtures of formic acid and sodium deoxycholate (NaDC), a common bile acid salt. By assaying the ratio of deoxycholate molecules that are immobilized as part of the fibrillar network of the hydrogels and those that can diffuse, we have found that 65% remain free under typical conditions. The network appears to be composed of both the acid and salt forms of deoxycholate, possibly because a degree of charge inhibits excessive aggregation and precipitation of the fibrils. Spin–spin relaxation times provided a molecular-level estimate of the temperature of gel–sol transition (42 °C), which is virtually the same as the value determined by analyzing macroscopic parameters. Saturation transfer difference (STD) NMR spectroscopy established that formic acid, which is present mainly as formate, is not immobilized as part of the gelating network. In contrast, HDO interacts with the network, which presumably has a surface with exposed hydrophilic groups that form hydrogen bonds with water. Moreover, the STD NMR experiments revealed that the network is a dynamic entity, with molecules of deoxycholate associating and dissociating reversibly. This exchange appears to occur preferentially by contact of the hydrophobic edges or faces of free molecules of deoxycholate with those of molecules immobilized as components of the network. In addition, DOSY experiments revealed that gelation has little effect on the diffusion of free NaDC and HDO.

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

“…59−64 Our group has worked extensively with these materials, and we have examined hydrogels formed by derivatives of bile acids in conjunction with carboxylic acids, 65 the sequestration of CO 2 by hydrogels containing bile acid salts, 66 and related topics. 51,67,68 ■ RESULTS AND DISCUSSION LCA has low solubility in water at pH 7, but solutions of the corresponding NH 4 + salt with concentrations of about 50 mM (2 wt %) can be obtained by warming aqueous mixtures made by combining LCA and NH 3 in a 1:16 molar ratio. Cooling the solutions to 25 °C led reproducibly to the formation of hydrogels, which were characterized by standard methods, including optical microscopy, electron microscopy, and rheological measurements.…”

“…As illustrated by LCA and DCA, bile acids have amphiphilic structures in which an extended convex hydrophobic surface is combined with hydrophilic hydroxyl and carboxyl groups. This amphiphilicity allows bile acids, their salts, and other derivatives to form biocompatible hydrogels that are promising materials for use in drug delivery, cellular immobilization, and other applications. − Our group has worked extensively with these materials, and we have examined hydrogels formed by derivatives of bile acids in conjunction with carboxylic acids, the sequestration of CO 2 by hydrogels containing bile acid salts, and related topics. ,, …”

Probing the Relationship between Crystallization and Gelation by Using Ammonium Salts of Bile Acids

“…57−62 Our group has worked actively in these areas, 15,49,63−66 and we have studied hydrogels formed by mixing carboxylic acids with derivatives of bile acids, 63 ways to sequester CO 2 in hydrogels containing bile acid salts, 64 and other topics. 65,66 Experience with bile acids and their derivatives has shown that a properly adjusted level of solubility in water is a prerequisite for hydrogelation.…”

“…These compounds have a tetracyclic steroidal structure that includes an extended convex hydrophobic face and an opposing concave hydrophilic face with hydroxyl and carboxyl groups. The resulting amphiphilicity gives rise to the formation of biocompatible hydrogels that are promising for use in drug delivery, cellular immobilization, and other applications. − Our group has worked actively in these areas, ,,− and we have studied hydrogels formed by mixing carboxylic acids with derivatives of bile acids, ways to sequester CO 2 in hydrogels containing bile acid salts, and other topics. , Experience with bile acids and their derivatives has shown that a properly adjusted level of solubility in water is a prerequisite for hydrogelation.…”

Preface to the Françoise M. Winnik Special Issue

“…This special issue celebrates her career with contributions from colleagues across the world. The included papers represent many topical areas, including microgels, elastomers, microbubbles, microemulsions, supramolecular assemblies, and thin films, with critical physical properties enabling applications as broad-ranging as carbon capture, medicine, and electronics. − Nonetheless, many of the papers are fundamental in nature, reflecting Professor Winnik’s enduring commitment to and interest in basic colloid and interfacial science.…”