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: 1800401
• 负责人: David Rovnyak
• 金额: $ 21.16万
• 依托单位: Bucknell University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1800401&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.

在这个由化学结构，动力学和机制B计划资助的合作项目中，教授David Rovnyak，Timothy Strein，Michael Krout和Maria Panteva试图了解胆汁盐组件如何与胆汁（右或左手）分子相互作用。 自然发生的胆汁盐引起了人们的关注，因为它们具有重要的生理功能以及在手性功能材料的设计和分析中的潜在应用。该项目调查了胆汁聚集体复杂表面的特定区域如何控制与手性宾客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用于对分子级相互作用的详细了解。 本科研究人员在整个工作中都发挥了主导作用，包括参与实验设计和结果传播。 重点是与教职员工进行密切互动，教师在发展独立数据获取和分析所需的专业知识时指导学生。 这项研究为妇女和来自代表性不足的群体的学生提供了机会，这些群体计划在科学领域计划职业。玻璃盐依赖浓度依赖于逐步聚集，并伴随着其表面和散装化学的复杂变化。 尽管进行了大量研究，但对结构，表面可用的结合位点的精确描述以及胆汁聚集体的对映选择性的“热点”才刚刚开始出现。 随着扩展的多学科工具包，这项研究提供了对天然和不自然胆汁盐系统的分子层相互作用的详细理解。 具体来说，这项工作涉及几个互补的焦点：（1）开发胆汁胶束手性选择的更详细的模型，包括胆汁脂肪族链如何有助于客人的手性选择性溶解度。这项研究采用了一个和二维NMR实验的套件，以及胶束电动毛细管电泳（MEKC），以通过迁移率差异的测量来表征手性结合。 （2）调查温度如何变化调整焓和熵驱动因子，以供宾客选择。等温滴定量热法用于分离与胆汁聚集体结合不同对映异构体相关的热差。 （3）通过关键区域的功能化胆汁酸的类似物的战略合成。 这种提高了对手性选择机制的理解，并允许设计改进的胆汁盐类似物。 （4）使用自发胆汁盐组装的严格，公正的分子动力学（MD）模拟。在与实验的协同作用下，计算有助于理解和预测总体结构和稳定性。该奖项反映了NSF的法定任务，并且使用基金会的知识分子优点和更广泛的影响审查标准，被认为值得通过评估来获得支持。

项目成果

Determining sequential micellization steps of bile salts with multi-CMC modeling

使用多 CMC 建模确定胆汁盐的连续胶束化步骤

• DOI: 10.1016/j.jcis.2023.03.146
• 发表时间: 2023
• 期刊: Journal of Colloid and Interface Science
• 影响因子: 9.9
• 作者: Rovnyak, David;He, Jiayi;Kong, Sophie;Eckenroad, Kyle W.;Manley, Gregory A.;Geffert, Raeanne M.;Krout, Michael R.;Strein, Timothy G.
• 通讯作者: Strein, Timothy G.