Chiroptical Sensing with Stereodynamic Probes

使用立体动力探针进行手性光学传感

• 批准号: 1764135
• 负责人: Christian Wolf
• 金额: $ 48万
• 依托单位: Georgetown University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1764135&HistoricalAwards=false
• 关键词: Chiroptical; Sensing; Stereodynamic; Probes

In this project, funded by the Chemical Structure, Dynamic & Mechanism B Program of the Chemistry Division, Professor Christian Wolf of the Department of Chemistry at Georgetown University is developing molecular probes for quantitative analysis of the amount, absolute configuration and enantiomeric composition of chiral compounds in complex samples. Many pharmaceuticals are chiral compounds and their effective analysis is clearly important in developing new medicines. This project could lead to new analysis methods that are compatible with modern workflow platforms, that can minimize waste production and operational costs, and that are applicable to automated parallel analysis of small scale reactions or biomarker sensing. The project is highly collaborative, involving industrial and academic partners. It provides multiple training opportunities for graduate, undergraduate and high school students, including those from underrepresented groups.The specific goals are to introduce and test several molecular probes that are designed to capture a chiral target either by covalent bond formation or noncovalent interactions and to then translate the molecular recognition event via spontaneous substrate-controlled chirality amplification across the stereodynamic receptor scaffold into a distinct chiroptical response. The prospects of this research are multifaceted and include important applications such as direct asymmetric reaction analysis or quantification of medicinally relevant biomarkers. Comprehensive optical sensing (determination of absolute configuration, enantiomeric purity and concentration of chiral substrates) is to be achieved using conceptually new molecular recognition and chiral amplification strategies. These strategies utilize stereodynamic cup-shaped architectures, foldamers, axially chiral reporter units, molecular propellers, multicomponent assemblies, dynamic covalent chemistry, organocatalysis, frustrated Lewis pairs, and tropos ligand derived metal complexes.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.

在该项目中，由化学系化学结构、动力学机制B计划资助，乔治城大学化学系Christian Wolf教授正在开发用于定量分析复杂样品中手性化合物的数量、绝对构型和对映体组成的分子探针。 许多药物是手性化合物，它们的有效分析在新药开发中显然是重要的。 该项目可能导致与现代工作流程平台兼容的新分析方法，可以最大限度地减少废物产生和运营成本，并适用于小规模反应或生物标志物传感的自动并行分析。 该项目是高度合作的，涉及工业和学术合作伙伴。它为研究生、本科生和高中生提供多种培训机会，具体目标是引入和测试几种分子探针，这些分子探针被设计成通过共价键形成或非共价相互作用捕获手性靶标，然后通过自发底物翻译分子识别事件-通过立体动力学受体支架将受控的手性扩增转化为独特的手性光响应。这项研究的前景是多方面的，包括重要的应用，如直接不对称反应分析或定量的医学相关的生物标志物。全面的光学传感（确定绝对构型，对映体纯度和浓度的手性底物）是实现使用概念上新的分子识别和手性放大策略。 这些策略利用立体动力学杯形架构、折叠体、轴向手性报告单元、分子推进器、多组分组装、动态共价化学、有机催化、受抑刘易斯对和tropos配体衍生的金属络合物。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而被认为值得支持。

项目成果

Enantioseparation and racemization of α-aryl-α-fluoroacetonitriles.

• DOI: 10.1002/chir.23367
• 发表时间: 2021-12
• 期刊: Chirality
• 影响因子: 2
• 作者: Steber SE;Pham ANDL;Nelson E;Wolf C
• 通讯作者: Wolf C

Tandem Use of Optical Sensing and Machine Learning for the Determination of Absolute Configuration, Enantiomeric and Diastereomeric Ratios, and Concentration of Chiral Samples

• DOI: 10.1002/anie.201912904
• 发表时间: 2019-12-19
• 期刊: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
• 影响因子: 16.6
• 作者: De los Santos, Zeus A.;MacAvaney, Sean;Wolf, Christian
• 通讯作者: Wolf, Christian

Click chemistry enables quantitative chiroptical sensing of chiral compounds in protic media and complex mixtures

• DOI: 10.1038/s41467-018-07695-9
• 发表时间: 2018-12
• 期刊: Nature Communications
• 影响因子: 16.6
• 作者: F. Y. Thanzeel;Kaluvu Balaraman;C. Wolf

Unified sensing of the concentration and enantiomeric composition of chiral compounds with an achiral probe

• DOI: 10.1016/j.chempr.2022.03.008
• 发表时间: 2022-06-09
• 期刊: CHEM
• 影响因子: 23.5
• 作者: Sripada, Archita;Thanzeel, Yushra;Wolf, Christian
• 通讯作者: Wolf, Christian

Dynamic Covalent Optical Chirality Sensing with a Sterically Encumbered Aminoborane

利用空间位阻氨基硼烷进行动态共价光学手性传感

• DOI: 10.1002/chem.202202028
• 发表时间: 2022
• 期刊: Chemistry – A European Journal
• 作者: De los Santos, Zeus A.;Lynch, Ciarán C.;Wolf, Christian
• 通讯作者: Wolf, Christian