Colorimetric Assays for Enantiomeric Excess

对映体过量的比色测定

• 批准号: 7076448
• 负责人: Eric V. Anslyn
• 金额: $ 21.6万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7076448
• 关键词: chemical reaction; colorimetry; high throughput technology; mathematical model; stereoisomer; technology /technique development

DESCRIPTION (provided by applicant): Simply stated, our goal is to create truly practical protocols for the colorimetric determination of enantiomeric excess (ee) and reaction yield. These assays are intended for bench top use as well as high throughput screening. By truly practical, we mean user friendly, appropriate for any organic chemist to implement, and useful for many different functional groups. The simplicity of the assays and their general applicability is the primary intellectual merit of this proposal. In our method, a chiral receptor associates with an indicator. Upon introduction of solutions possessing chiral guests (GR and GS), diastereomeric host:guest complexes are formed. These complexes displace the indicator to differing extents, and therefore, the color of the solution is dependent upon the ee of the sample. However, one must also know the total concentration of the guest, and a second IDA using an achiral receptor is used for this determination. A mathematical analysis relates total concentration and ee to color. The technique is conceptually simple and facile to implement. It is logical to extend our IDA technique by studying reactions that are known to achieve equilibria. For example, analogs to acylhydrazine-acylhydrazone interconversion are good possibilities. We take our lead from this particular interchange, and propose methods based upon amine/hydrazine to carbinolamine interconversion, and alcohol/amine to hemi-acetal/carbinolamine interconversion. However, we further propose dynamic IDA methods using chiral tricyanoethylene derivatives and chiral metal complexes. Our methods will target chiral ketones/aldehydes and chiral alcohols/amines. We will create first generation protocols that require the mathematical analysis. In a second generation, we plan to create methods that give large visual color changes and do not require a mathematical analysis. The large color changes will employ two indicators in a dual cell technique. To remove the requirement of a mathematical analysis, we will implement artificial neural networks (ANNs). The guiding principle is to make the techniques increasingly facile in their implementation and directly applicable to practical analyses. To test their practicality, the assays created herein will be used to analyze known asymmetric transformations, and they will be used in "real-life" situations by involving undergraduates from Texas A&M Kingsville. Through a NIH funded agreement between the Departments of Chemistry at A&M Kingsville and U.T. Austin, minority students will come to Austin to perform research. The studies proposed in this NIH application are particularly well suited to this exchange program, and this NIH project will be used to showcase the collaborative efforts between these two Universities.

描述（由申请人提供）：简而言之，我们的目标是创建真正实用的协议，以确定对映体过量（EE）和反应产量的比色确定。这些测定旨在用于台式最高用途以及高通量筛选。通过真正的实用，我们的意思是用户友好，适合任何有机化学家实施，对许多不同的官能团有用。测定法的简单性及其一般适用性是该提议的主要知识分子。 在我们的方法中，手性受体与指标相关。在引入具有手性客人（GR和GS）的解决方案后，映射宿主形成了来宾综合体。这些复合物将指示器置换为不同的范围，因此，溶液的颜色取决于样品的EE。但是，还必须知道来宾的总浓度，并使用第二种使用Achiral受体的IDA进行确定。数学分析将总浓度和EE与颜色有关。该技术在概念上很简单，可以轻松实施。 通过研究已知可以达到平衡的反应来扩展我们的IDA技术是合乎逻辑的。例如，类似于酰基氢嗪 - 酰基羟基羟基互转换是很好的可能性。我们从这种特殊的交换中占据主导地位，并提出基于胺/氢氮的方法到卡比诺明互转换，酒精/胺降至半乙乙乙醇/碳纤维胺的互连。但是，我们进一步提出了使用手性三轮乙烯衍生物和手性金属配合物的动态IDA方法。 我们的方法将靶向手性酮/醛和手性醇/胺。我们将创建需要数学分析的第一代协议。在第二代中，我们计划创建可以进行大型视觉色彩变化并且不需要数学分析的方法。大颜色变化将在双电池技术中采用两个指标。为了消除数学分析的要求，我们将实施人工神经网络（ANN）。指导原则是使这些技术越来越轻松地实施，直接适用于实际分析。 为了测试其实用性，本文创建的测定将用于分析已知的不对称转换，并通过涉及来自德克萨斯州A＆M金斯维尔的本科生，将它们用于“现实生活”情况。通过A＆M金斯维尔和U.T.化学部门之间的NIH资助协议奥斯汀，少数民族学生将来奥斯汀进行研究。该NIH应用程序中提出的研究特别适合该交换计划，该NIH项目将用于展示这两所大学之间的协作工作。