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

RUI：胆汁酸聚集和客体-主体溶剂化的分子表征

• 批准号: 1153052
• 负责人: David Rovnyak
• 金额: $ 15.92万
• 依托单位: Bucknell University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-15 至 2016-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1153052&HistoricalAwards=false
• 关键词: RUI; Molecular; Characterization; Aggregation; Guest

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.

在这个项目中，巴克内尔大学的David Rovnyak教授和Timothy Strein教授得到了化学学部化学结构、动力学和机制项目的资助，利用核磁共振（NMR）、荧光和电泳等多种技术对胆汁酸聚集进行了广泛的研究。胆汁酸是肝脏中胆固醇衍生的两亲分子，促进脂质和胆固醇的运输。这些重要分子的基本物理化学性质在水溶液中以其盐类（又称胆汁盐）的形式存在，目前还不清楚。事实上，除了Small于1968年提出的胆汁聚集模型之外，关于胆汁聚集，即产生临界胶束浓度(s)、聚集数(s)、凝胶形成和主客相互作用等特性的分子间相互作用和动力学，一直很难达成共识。此外，胆汁聚集体对某些手性化合物的对映异构体的差异溶解能力尚未在分子水平上表征。该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，初步的工作表明，核磁共振方法明确地描绘了早期和初级胶束化阶段，这在以前没有被清楚地观察到。此外，具有强溶剂化性的平面荧光探针被用于检测和表征胆胶束疏水区域的存在。胶束电动毛细管电泳将被用作聚集阶段和主客相互作用的敏感探针。通过这些互补技术的使用，我们将更好地了解胆汁盐复杂的分子间化学反应。胆汁酸是一种迷人的自然产生的分子，其复杂的特性几十年来一直困扰着科学家。胆汁酸可以与某些种类的油发生强烈的相互作用，形成具有理想特性的凝胶，例如促进局部药物输送的能力，并且最近发现在维持人类健康方面发挥的作用比以前所了解的要广泛得多。胆汁酸还可以帮助区分用其他方法难以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，并更好地了解它们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到项目的各个方面。他们将获得多方面实验设计的实践经验，使用复杂的光谱仪器，并分析和解释使用这些仪器收集的数据。这种经历为学生进一步学习或未来就业做好了准备。