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，巴克内尔大学的教授戴维·罗维尼亚克（David Rovnyak）和蒂莫西·斯特雷（Timothy Strein）由化学划分的化学结构，动力学和机制计划资助，以使用包括核磁共振（NMR），漏液和电泳的多种技术对胆汁酸聚集进行广泛的研究。 胆汁酸是肝脏中胆固醇的两亲分子，可促进脂质和胆固醇的转运。 在水溶液中占主导地位，因为它们的盐（又名胆汁盐），这些重要分子的基本物理化学特性尚不清楚。 实际上，很难就胆汁聚集达成共识，即，分子间相互作用和动力学产生诸如关键胶束浓度（S），聚集数，凝胶形成和来宾 - 宿主相互作用之类的特性，超越了Small of Bile of Bile聚集的模型。 1968年。此外，在分子水平上尚未表征胆汁聚集体差异化某些手性化合物的对映异构体的能力。 该项目将使用各种技术来检测和验证行为，这些行为有可能帮助解释文献中看似不同的报告。 例如，初步工作表明，NMR方法明确描绘了以前尚未清楚地观察到的早期和原发性胶束化阶段。 此外，使用表现出强溶性的平面荧光探针用于检测和表征胆汁胶束疏水区的存在。 胶束电动毛细管电泳将用作聚集阶段和客体宿主相互作用的敏感探针。 通过使用这些互补技术，我们将更好地理解胆汁盐的复杂分子间化学。 胆汁酸令人着迷的自然产生的分子，其复杂的特性数十年来挑战了科学家。 胆汁酸可以与某些类别的油相互作用，形成具有理想特性的凝胶，例如促进局部药物递送的能力，最近发现在维持人类健康中起着比以前所理解的更广泛的作用。 胆汁酸还可以帮助区分化合物的异构体，这些异构体难以通过其他方式分离。 然而，有必要在分子尺度上解释胆汁酸的特性和行为。 有了对胆汁酸的分子尺度行为的深入了解，有可能利用更大的胆汁酸应用潜力，并更好地理解它们在人类生物学中的广泛作用。 从事这些项目的本科生将参与该项目的各个方面。 他们将获得实践经验，用于设计多方面实验，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时。 这种经验为学生提供了进一步学习或将来就业的准备。