Enantioselective Fluorescent Analysis of Amino Acids

氨基酸的对映选择性荧光分析

• 批准号: 2153466
• 负责人: Lin Pu
• 金额: $ 48.3万
• 依托单位: University of Virginia Main Campus
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-15 至 2025-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2153466&HistoricalAwards=false
• 关键词: Enantioselective; Fluorescent; Analysis; Amino; Acids

With the support of the Chemical Structure, Dynamics, and Mechanisms B (CSDM-B) Program in the Division of Chemistry, Professor Lin Pu of University of Virginia is studying fluorescent sensors that can distinguish the enantiomers of chiral amino acids. A chiral amino acid can exist in L- and D-enantiomeric forms whose molecular structures are mirror images of each other, but not superimposable. L-Amino acids are the essential molecular building blocks of proteins in living systems on earth. D-Amino acids are less common in nature but are still found to play important roles in biological systems. Both L- and D-amino acids are very useful in the synthesis of diverse organic compounds including those of pharmaceutical importance. Because of the significance of L- and D-amino acids in biology and synthesis, it is important to analyze their chiral configuration and enantiomeric composition. Among the methods that have been developed to analyze the enantiomers of amino acids, using enantioselective fluorescent sensors has advantages such as readily available instrumentation, high sensitivity, real-time measurement, multiple sensing modes, non-invasive imaging, continuous online monitoring, parallel analysis, etc. Professor Pu will develop new enantioselective fluorescent sensors for amino acids to facilitate the deployment of these sensors for the rapid screening of catalysts being investigated for the asymmetric synthesis of amino acids and related compounds. The researchers engaged in this project will also conduct outreach activities to provide science education for local K-12 students of diverse background. In this project, a 1,1’-binaphthyl-coumarin-based fluorescent probe will be further developed for application in the rapid analysis of chiral amino acids obtained from asymmetric reactions. The pseudo-enantiomer of this probe will be prepared and the resulting pseudo-enantiomeric sensor pair will be applied to simultaneously determine the concentration and enantiomeric composition of an amino acid sample by one fluorescence measurement. This strategy also allows the identification of the absolute configuration of the amino acid. A systematic structural modification of this probe will be conducted to improve its enantioselectivity and expand the accessible substrate scope of the method. In order to minimize the interference of other components in an amino acid sample on the fluorescence measurement, a perfluoro alkyl group or an amphiphilic polymer chain will be incorporated into the fluorescent probes. These fluorous phase-based or polymer-supported fluorescent probes will be able to transport the sensor-substrate interaction away from the original sample phase for more accurate fluorescence measurements. The proposed fluorescent sensors will be used in the screening of chiral catalysts for the asymmetric alkyne addition to imines and for asymmetric Akabori-like reactions. These studies should facilitate the search of efficient and environmentally friendly chiral catalysts for asymmetric syntheses. The enantioselective fluorescent probes developed in this project also have potential to be used much more broadly in asymmetric synthesis, including in automated systems for high throughput catalyst screening.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.

在化学系化学结构、动力学和机理B（CSDM-B）项目的支持下，弗吉尼亚大学林璞教授正在研究能够区分手性氨基酸对映体的荧光传感器。 手性氨基酸可以以L-和D-对映体形式存在，其分子结构彼此镜像，但不可重叠。 L-氨基酸是地球上生命系统中蛋白质的基本分子构建块。 D-氨基酸在自然界中不太常见，但仍然被发现在生物系统中发挥重要作用。 L-和D-氨基酸在合成各种有机化合物，包括具有药物重要性的有机化合物中非常有用。 由于L-和D-氨基酸在生物学和合成中的重要性，因此分析它们的手性构型和对映体组成是非常重要的。 在已经开发的用于分析氨基酸对映体的方法中，使用对映体选择性荧光传感器具有诸如容易获得的仪器、高灵敏度、实时测量、多种传感模式、非侵入性成像、连续在线监测、并行分析等优点，蒲教授将开发新的氨基酸对映体选择性荧光传感器，以促进这些传感器用于快速筛选催化剂被研究用于氨基酸和相关化合物的不对称合成。 参与该项目的研究人员还将开展外展活动，为本地不同背景的K-12学生提供科学教育。 本计画将进一步发展一种以1，1 '-联萘香豆素为基的萤光探针，应用于不对称反应中手性氨基酸的快速分析。 将制备该探针的假对映体，并将所得的假对映体传感器对应用于通过一次荧光测量同时测定氨基酸样品的浓度和对映体组成。 该策略还允许鉴定氨基酸的绝对构型。 我们将对该探针进行系统的结构修饰，以提高其对映体选择性，扩大该方法的底物范围。 为了最小化氨基酸样品中其他组分对荧光测量的干扰，将全氟烷基或两亲聚合物链掺入荧光探针中。 这些基于荧光相或聚合物支撑的荧光探针将能够将传感器-基底相互作用从原始样品相转移出去，以进行更准确的荧光测量。 所提出的荧光传感器将用于筛选手性催化剂的不对称炔加成亚胺和不对称Akabori样反应。 这些研究有助于寻找高效、环境友好的手性催化剂用于不对称合成。 在这个项目中开发的对映体选择性荧光探针也有可能被更广泛地用于不对称合成，包括在自动化系统中的高通量催化剂screening.This奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

项目成果

One Molecular Probe with Opposite Enantioselective Fluorescence Enhancement at Two Distinct Emissions

一种分子探针在两种不同的发射下具有相反的对映选择性荧光增强

• DOI: 10.1021/acs.orglett.3c00692
• 发表时间: 2023
• 期刊: Organic Letters
• 影响因子: 5.2
• 作者: Mao, Yifan;Thomae, Evan;Davis, Stephanie;Wang, Chengyang;Li, Yichen;Pu, Lin
• 通讯作者: Pu, Lin

Near‐IR Fluorescent Recognition of Arginine: High Chemoselectivity and Enantioselectivity Promoted by La 3+

精氨酸的近红外荧光识别：La 3 促进的高化学选择性和对映选择性

• DOI: 10.1002/cplu.202300138
• 发表时间: 2023
• 期刊: ChemPlusChem
• 影响因子: 3.4
• 作者: Guo, Hongyu;Yang, Jiaqiao;Zeng, Jian;Yu, Xiaoqi;Yu, Shanshan;Pu, Lin
• 通讯作者: Pu, Lin

Synthesis of a BINOL‐Based C 3 Symmetric Schiff Base and Its Fluorescence Response to Zn 2+

基于 BINOL 的 C 3 对称席夫碱的合成及其对 Zn 2 的荧光响应

• DOI: 10.1002/cplu.202300036
• 发表时间: 2023
• 期刊: ChemPlusChem
• 影响因子: 3.4
• 作者: Lu, Kai;Guo, Hongyu;Jiang, Yixuan;Yang, Jiaqiao;Yu, Shanshan;Yu, Xiaoqi;Pu, Lin
• 通讯作者: Pu, Lin