Collaborative Research: RUI: Mechanism of High Enantiomeric Resolution with Bile Micelles

合作研究：RUI：胆汁胶束的高对映体分辨率机制

• 批准号: 1764352
• 负责人: Maria Panteva
• 金额: $ 4.34万
• 依托单位: University of Illinois at Springfield
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1764352&HistoricalAwards=false
• 关键词: Collaborative; Research; RUI; Mechanism; Enantiomeric

In this collaborative project funded by the Chemical Structure, Dynamics and Mechanisms B Program of the Chemistry Division, Professors David Rovnyak, Timothy Strein, Michael Krout, and Maria Panteva seek to understand how bile salt assemblies interact with chiral (right or left handed) molecules. Naturally occurring bile salts are of interest because of their significant physiological functions and for potential applications in the design and analysis of chiral functional materials. This project investigates how specific regions on the complex surfaces of bile aggregates control selective interactions with chiral guest molecules. Advanced tools in magnetic resonance, separation science, chemical synthesis, thermodynamics and computation are applied to achieve a detailed understanding of molecular-level interactions. Undergraduate researchers take leading roles throughout this work, including participating in experiment design and dissemination of results. Emphasis is on close interactions with faculty, who mentor students while they develop the expertise needed to perform independent data acquisition and analysis. This research provides opportunities for women and for students from under-represented groups who plan careers in science.Bile salts undergo concentration-dependent stepwise aggregation, accompanied by intricate changes in their surface and bulk chemistries. Despite considerable study, a precise description of the structure, the surface-available binding sites, and the enantioselective "hot spots" of bile aggregates is only beginning to emerge. With an expanded, multi-disciplinary toolkit, this research provides detailed understanding of the molecular-level interactions characteristic of both natural and unnatural bile salt systems. Specifically, this work involves several complementary foci: (1) Development of more detailed models for chiral selection by bile micelles, including how bile aliphatic chains contribute to chirally selective solubilization of guests. This research employs a suite of one and two-dimensional NMR experiments, as well as micellar electrokinetic capillary electrophoresis (MEKC), to characterize chiral binding by measurements of mobility difference. (2) Investigation of how temperature changes tune the enthalpic and entropic driving factors for chiral selection of guests. Isothermal titration calorimetry is used to isolate the heat difference associated with binding different enantiomers by bile aggregates. (3) Strategic synthesis of analogues of bile acids through functionalization of key regions. This advances understanding of the mechanisms of chiral selection and permits the design of improved bile salt analogues. (4) Employment of rigorous, unbiased molecular dynamics (MD) simulations of spontaneous bile salt assembly. In synergy with experiments, computations help to understand and predict aggregate structure and stability.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在这个由化学系化学结构，动力学和机制B计划资助的合作项目中，大卫罗夫尼亚克教授，蒂莫西·斯特雷因，迈克尔·克鲁特和玛丽亚·潘特瓦试图了解胆盐组装体如何与手性（右手或左手）分子相互作用。 天然存在的胆汁盐由于其重要的生理功能和在手性功能材料的设计和分析中的潜在应用而引起人们的兴趣。本项目研究胆汁聚集体复杂表面上的特定区域如何控制与手性客体分子的选择性相互作用。磁共振，分离科学，化学合成，热力学和计算的先进工具被应用于实现分子水平的相互作用的详细理解。 本科研究人员在整个工作中发挥主导作用，包括参与实验设计和结果传播。 重点是与教师的密切互动，他们指导学生，而他们发展所需的专业知识来执行独立的数据采集和分析。 这项研究为妇女和计划从事科学事业的代表性不足的群体的学生提供了机会。胆盐经历浓度依赖性的逐步聚集，伴随着其表面和本体化学性质的复杂变化。 尽管有大量的研究，胆汁聚集体的结构，表面可利用的结合位点和对映选择性的“热点”的精确描述才刚刚开始出现。 通过扩展的多学科工具包，这项研究提供了对天然和非天然胆盐系统分子水平相互作用特征的详细了解。 具体来说，这项工作涉及几个互补的焦点：（1）发展更详细的模型，胆汁胶束的手性选择，包括胆汁脂肪链如何有助于手性选择性增溶客人。本研究采用了一套一维和二维核磁共振实验，以及胶束电动毛细管电泳（MEKC），表征手性结合的迁移率差的测量。 (2)温度变化如何调节客体手性选择的热力学和熵驱动因子的研究。等温滴定量热法用于分离与胆汁聚集体结合不同对映体相关的热差。 (3)通过关键区域的功能化策略性合成胆汁酸类似物。 这推进了对手性选择机制的理解，并允许设计改进的胆盐类似物。(4)采用严格、无偏的分子动力学（MD）模拟自发胆盐组装。通过与实验的协同作用，计算有助于理解和预测骨料结构和稳定性。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。