OPTICAL SENSING AND CHEMOMETRIC ANALYSIS OF CHIRAL COMPOUNDS

手性化合物的光学传感和化学计量分析

• 批准号: 2246747
• 负责人: Christian Wolf
• 金额: $ 54.48万
• 依托单位: Georgetown University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2246747&HistoricalAwards=false
• 关键词: OPTICAL; SENSING; CHEMOMETRIC; ANALYSIS; CHIRAL

With support of the Chemical Structure, Dynamic & Mechanism B Program of the Chemistry Division, Professor Christian Wolf’s research group of the Department of Chemistry at Georgetown University is developing optical sensing methodology that accelerates and broadens chiral compound analysis by introducing widely applicable small-molecule probes, conceptually new molecular recognition strategies, artificial intelligence tools, and automated high-throughput experimentation technology. This research has the potential to push current research and development boundaries, transform cumbersome analysis protocols, and unfold new opportunities, for example, continuous asymmetric reaction development workflows that eliminate slow and work-intensive laboratory practice. The proposed work is highly collaborative involving industrial and academic partners and provides multiple training opportunities for graduate, undergraduate and high school students from groups underrepresented in science.Chiroptical sensing assays for primary and secondary amines, amino alcohols, amino acids, alcohols and hydroxy acids have been introduced to date. However, comprehensive sensing--determination of absolute configuration, selectivity, and concentration--remains a challenge for a number of systems. These include (a) compounds devoid of functionalities such as nitriles, esters, amides, tertiary amines or aromatic scaffolds, (b) substrates that possess more than one chirality center and (c) multicomponent mixtures. To overcome these limitations, new molecular probe designs that quickly capture currently elusive chiral target compounds in solution and report the molecular recognition event via spontaneous chirality amplification across stereodynamic receptor scaffolds into a distinct and quantifiable chiroptical (circular dichroism and UV/vis absorption) response will be introduced. In addition, organic reaction based multi-modal optical chirality sensing methodology and chemometrics capable of orthogonal data fusion and spectral deconvolution will be developed to achieve comprehensive sensing of complicated mixtures by eliminating the common need for physical separation prior to the analysis. Finally, machine learning will be integrated with chiroptical high-throughput screening technology to enable original asymmetric catalysis discoveries.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.

乔治城大学化学系Christian Wolf教授的研究小组在化学系化学结构、动力学机制B项目的支持下，正在开发光学传感方法，通过引入广泛适用的小分子探针、概念上新的分子识别策略、人工智能工具和自动化高通量实验技术，加速和拓宽手性化合物的分析。这项研究有可能推动当前的研究和开发边界，改变繁琐的分析协议，并开辟新的机会，例如，连续的不对称反应开发工作流程，消除缓慢和工作密集的实验室实践。拟议的工作是高度协作，涉及工业和学术合作伙伴，并提供了多种培训机会，研究生，本科生和高中学生的群体在science. chiropical代表性不足的伯胺和仲胺，氨基醇，氨基酸，醇和羟基酸的手性传感测定已被引入到日期。然而，全面的传感-绝对配置，选择性和浓度的确定-仍然是一个挑战的一些系统。 这些包括（a）不含官能团如腈、酯、酰胺、叔胺或芳族骨架的化合物，（B）具有多于一个手性中心的底物和（c）多组分混合物。为了克服这些限制，将引入新的分子探针设计，其快速捕获溶液中当前难以捉摸的手性目标化合物，并通过立体动力学受体支架上的自发手性扩增将分子识别事件报告为独特且可量化的手性（圆二色性和UV/维斯吸收）响应。此外，基于有机反应的多模态光学手性传感方法学和能够正交数据融合和光谱解卷积的化学计量学将被开发，以通过消除分析之前的物理分离的常见需要来实现复杂混合物的全面传感。最后，机器学习将与手性高通量筛选技术相结合，以实现原创的不对称催化发现。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。