RUI: Molecular Characterization of Aggregation and Guest-Host Solvation by Bile Acids

在这个项目中，巴克内尔大学的大卫罗夫尼亚克教授和蒂莫西·斯特雷因教授得到了化学系化学结构、动力学和机制项目的资助，利用核磁共振、荧光和电泳等多种技术对胆汁酸聚集进行了广泛的研究。 胆汁酸是肝脏中的胆固醇衍生的两亲分子，其促进脂质和胆固醇转运。 在水溶液中主要以其盐（a.k.a.胆汁盐），但这些重要分子的基本物理化学性质尚未得到很好的理解。 事实上，人们很难就胆汁聚集达成共识，即分子间相互作用和动力学，这些相互作用和动力学产生了诸如临界胶束浓度、聚集数、凝胶形成和宾主相互作用等性质，超出了Small提出的胆汁聚集模型。1968. 此外，胆汁聚集体差异溶解某些手性化合物的对映体的能力尚未在分子水平上表征。 这个项目将使用各种技术来检测和验证有可能帮助解释文献中看似不同的报告的行为。 例如，初步工作表明，NMR方法明确地描绘了以前没有清楚观察到的单独的早期和初级胶束化阶段。 此外，平面荧光探针，表现出强烈的溶剂化显色性用于检测和表征的胆汁胶束的疏水区域的存在。 胶束电动毛细管电泳将被用作聚集阶段和宾主相互作用的灵敏探针。 通过使用这些互补的技术，我们将更好地了解胆汁盐的复杂的分子间化学。 胆汁酸是迷人的自然产生的分子，其复杂的性质已经挑战了科学家几十年。 胆汁酸可以与某些种类的油强烈相互作用，形成具有期望性质的凝胶，例如促进局部药物递送的能力，并且最近发现在维持人类健康方面发挥比以前所理解的更广泛的作用。 胆汁酸还可以帮助区分难以通过其他方法分离的化合物的异构体。 然而，有必要在分子尺度上解释胆汁酸的性质和行为。 随着对胆汁酸分子尺度行为的深入了解，有可能挖掘胆汁酸新应用的更大潜力，并更好地了解其在人类生物学中的更广泛作用。 从事这些项目的本科生将参与该项目的各个方面。 他们将获得多方面实验设计，使用复杂的光谱仪器以及分析和解释使用这些仪器收集的数据的实践经验。 这种经验为学生进一步学习或未来就业做好准备。

In this project, Professors David Rovnyak and Timothy Strein of Bucknell University are funded by the Chemical Structure, Dynamics and Mechanisms Program of the Division of Chemistry, to conduct a wide ranging study of bile acid aggregation using multiple techniques including nuclear magnetic resonance (NMR), fluorescence and electrophoresis. Bile acids are cholesterol-derived amphiphilic molecules in the liver which facilitate lipid and cholesterol transport. Predominant in aqueous solution as their salts (a.k.a. bile salts), fundamental physico-chemical properties of these important molecules are not well understood. Indeed it has been difficult to achieve consensus on bile aggregation, namely, the intermolecular interactions and dynamics that give rise to properties such as critical micelle concentration(s), aggregation number(s), gel formation, and guest-host interactions, beyond Small's model of bile aggregation proposed ca. 1968. Also, the capacity of bile aggregates to differentially solubilize the enantiomers of certain chiral compounds has not been characterized at a molecular level. This project will use the various techniques to detect and validate behaviors that have the potential to help explain seemingly disparate reports in the literature. For example, preliminary work has shown that NMR methods unambiguously delineate separate early and primary micellization stages that have not been clearly observed before. Further, planar fluorescent probes that exhibit strong solvatochromism are used to detect and characterize the presence of hydrophobic regions of the bile micelles. Micellar electrokinetic capillary electrophoresis will be used as a sensitive probe of aggregation stages and of guest-host interactions. Through the use of these complementary techniques, we a better understanding of the complicated intermolecular chemistry of bile salts will emerge. Bile acids are fascinating naturally produced molecules whose complex properties have challenged scientists for decades. Bile acids can interact strongly with certain classes of oils, form gels with desirable properties such as the capacity to promote topical drug delivery, and most recently are being found to play much wider roles in the maintenance of human health than previously understood. Bile acids can also help distinguish among isomers of compounds that would be difficult to separate by other means. Yet there is a need to explain bile acid properties and behaviors on the molecular scale. With deeper insights into the molecular scale behaviors of bile acids, there is the possibility to tap into greater potential for new applications of bile acids, and for better understanding of their broader roles in human biology. The undergraduate students working on these projects will be involved in all aspects of this project. They will acquire hands-on experience in the design of multifaceted experiments, the use of sophisticated spectroscopic instrumentation, and in analyzing and interpreting data collected using those instruments. This experience provides students preparation for further study or future employment.