Quantitative Chiral Analysis by Chiral Tag Rotational Spectroscopy

通过手性标签旋转光谱进行定量手性分析

基本信息

批准号：
1904686
负责人：
Brooks Pate
金额：
$ 42万
依托单位：
University of Virginia Main Campus
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-15 至 2022-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1904686&HistoricalAwards=false
关键词：
Quantitative Chiral Analysis Tag Rotational

项目摘要

With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, Professor Brooks Pate and his research group at the University of Virginia are addressing challenges associated with the quantitative analysis of samples containing molecules not superimposable on their mirror image: i.e. "chiral" molecules, analogous to a person's right and left hand. The chemistry and interactions of chiral molecules - including many pharmaceuticals and most natural biomolecules - can depend sensitively on their chirality or "handedness." For example, the different chiral forms of a drug can have radically different efficacy and side reactions, despite their otherwise similar structure and properties. As a result, analysis of chirality is critically important, although it is generally a difficult, time-consuming, and often costly part of drug development and manufacture. The Pate group is pioneering new methods for rapid chiral analysis. The work exposes undergraduate and graduate students to state-of-the-art analysis methods.A specific focus of this work is to develop a chemical measurement technique that can perform quantitative analysis of the stereoisomers of a molecule with multiple chiral centers. The problem is challenging because it entails both diastereomers (isomers with distinct molecular geometries) and the non-superimposable mirror images of each diastereomer (enantiomers). Conventionally, different spectroscopic and/or chromatographic techniques are needed to perform both diastereomer and enantiomer analysis. The Pate group is developing a much simpler approach based on rotational spectroscopy using chiral tags - small molecules with chiral centers attached non-covalently to the target analyte(s). Accurate quantum chemistry calculations make it possible to determine the base enantiomer responsible for each spectrum recorded in the measurement. The ratio of enantiomers is determined by changes in spectral intensity observed when the measurement is performed using racemic and enantiopure samples of the chiral tag. In addition to proof-of-principle measurements to validate the concept, the team is exploring chemical ideas for designing chiral tag molecules that can improve analysis speed, reliability, and scope of application.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.

在化学系化学测量和成像项目的支持下，布鲁克斯·佩特教授和他在弗吉尼亚大学的研究小组正在解决与定量分析含有不叠加在其镜像上的分子的样品相关的挑战：即“手性”分子，类似于人的右手和左手。手性分子（包括许多药物和大多数天然生物分子）的化学和相互作用可能敏感地取决于它们的手性或“手性”。例如，药物的不同手性形式可能具有完全不同的功效和副作用，尽管它们在其他方面相似的结构和性质。因此，手性分析至关重要，尽管它通常是药物开发和制造中困难、耗时且成本高昂的部分。佩特小组正在开创快速手性分析的新方法。这项工作让本科生和研究生接触到最先进的分析方法。这项工作的一个具体重点是开发一种化学测量技术，可以对具有多个手性中心的分子的立体异构体进行定量分析。这个问题具有挑战性，因为它涉及非对映体（具有不同分子几何形状的异构体）和每个非对映体（对映体）的不可重叠的镜像。传统上，需要不同的光谱和/或色谱技术来进行非对映体和对映体分析。佩特小组正在开发一种更简单的方法，该方法基于使用手性标签的旋转光谱——手性中心的小分子以非共价键方式连接到目标分析物上。准确的量子化学计算可以确定测量中记录的每个光谱的基本对映体。对映体的比例由使用手性标签的外消旋和对映体纯样品进行测量时观察到的光谱强度的变化来确定。除了原理验证测量来验证这一概念之外，该团队还在探索设计手性标签分子的化学想法，以提高分析速度、可靠性和应用范围。该奖项反映了 NSF 的法定使命，并被认为是值得的通过使用基金会的智力优势和更广泛的影响审查标准进行评估来提供支持。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Accuracy of Quantum Chemistry Structures of Chiral Tag Complexes and the Assignment of Absolute Configuration

手性标签复合物量子化学结构的准确性和绝对构型的分配

DOI：
10.1039/d2cp04060c
发表时间：
2022-01
期刊：
Physical Chemistry Chemical Physics
影响因子：
3.3
作者：
Mayer, Kevin;West, Channing;Marshall, Frank;Sedo, G;Grubbs II, Smitty;Evangelisti, Luca;Pate, Brooks
通讯作者：
Pate, Brooks

Competition between In-Plane vs Above-Plane Configurations of Water with Aromatic Molecules: Non-Covalent Interactions in 1,4-Naphthoquinone-(H 2 O) 1–3 Complexes

水与芳香分子的面内构型与面外构型之间的竞争：1,4-萘醌-(H 2 O) 1â3 配合物中的非共价相互作用

DOI：
10.1021/acs.jpclett.2c02618
发表时间：
2022-10-13
期刊：
The Journal of Physical Chemistry Letters
影响因子：
5.7
作者：
Baweja, Shefali;Panchagnula, Sanjana;Sanz, M. Eugenia;Evangelisti, Luca;Perez, Cristobal;West, Channing;Pate, Brooks H.
通讯作者：
Pate, Brooks H.

Chiral analysis of pantolactone with molecular rotational resonance spectroscopy

分子旋转共振光谱法对泛内酯进行手性分析

DOI：
10.1002/chir.23379
发表时间：
2022-01
期刊：
Chirality
影响因子：
2
作者：
Sonstrom, Reilly E.;Neill, Justin L.;Mikhonin, Alexander V.;Doetzer, Reinhard;Pate, Brooks H.
通讯作者：
Pate, Brooks H.

Copper-Catalyzed Transfer Hydrodeuteration of Aryl Alkenes with Quantitative Isotopomer Purity Analysis by Molecular Rotational Resonance Spectroscopy

铜催化芳基烯烃转移加氢氘化，通过分子旋转共振光谱定量同位素异构体纯度分析

DOI：
10.1021/jacs.1c00884
发表时间：
2021-05
期刊：
Journal of the American Chemical Society
影响因子：
15
作者：
Vang, Zoua Pa;Reyes, Albert;Sonstrom, Reilly E.;Holdren, Martin S.;Sloane, Samantha E.;Alansari, Isabella Y.;Neill, Justin L.;Pate, Brooks H.;Clark, Joseph R.
通讯作者：
Clark, Joseph R.

Enantioselective Synthesis of Enantioisotopomers with Quantitative Chiral Analysis by Chiral Tag Rotational Spectroscopy

通过手性标签旋转光谱定量手性分析对映异构体的对映选择性合成

DOI：
10.1002/anie.202207275
发表时间：
2022-08-15
期刊：
Angewandte Chemie International Edition
影响因子：
0
作者：
Mills, Mitchell D.;Sonstrom, Reilly E.;Vang, Zoua Pa;Neill, Justin L.;Scolati, Haley N.;West, Channing T.;Pate, Brooks H.;Clark, Joseph R.
通讯作者：
Clark, Joseph R.