Li Puzhen, Malveau Cédric, Zhu X X, Wuest James D
Département de Chimie, Université de Montréal, Montréal, Québec H2V 0B3 Canada.
Langmuir. 2022 May 3;38(17):5111-5118. doi: 10.1021/acs.langmuir.1c02175. Epub 2021 Nov 3.
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.
胆汁酸及其盐类水凝胶是用于药物递送、细胞固定化及其他应用的有前景的材料。然而，这些水凝胶在分子水平上的了解还很少，需要进一步研究以便通过设计创造出性能更优的材料。我们利用核磁共振光谱法探究了由甲酸和脱氧胆酸钠（NaDC，一种常见的胆汁酸盐）混合物形成的水凝胶。通过测定作为水凝胶纤维网络一部分而固定的脱氧胆酸盐分子与可扩散的脱氧胆酸盐分子的比例，我们发现，在典型条件下65%的脱氧胆酸盐分子仍保持游离状态。该网络似乎由脱氧胆酸盐的酸形式和盐形式组成，这可能是因为一定程度的电荷抑制了纤维的过度聚集和沉淀。自旋 - 自旋弛豫时间提供了凝胶 - 溶胶转变温度（42°C）的分子水平估计值，这与通过分析宏观参数确定的值几乎相同。饱和转移差（STD）核磁共振光谱法表明，主要以甲酸盐形式存在的甲酸并未作为凝胶网络的一部分被固定。相比之下，重水（HDO）与该网络相互作用，推测该网络具有带有暴露的亲水基团的表面，这些亲水基团与水形成氢键。此外，STD核磁共振实验表明该网络是一个动态实体，脱氧胆酸盐分子可逆地缔合和解离。这种交换似乎优先通过游离的脱氧胆酸盐分子的疏水边缘或面与作为网络组分固定的分子的疏水边缘或面接触而发生。此外，扩散排序谱（DOSY）实验表明，凝胶化对游离的NaDC和HDO的扩散影响很小。
