Colorimetric Assays for Enantiomeric Excess

对映体过量的比色测定

基本信息

批准号：
7390853
负责人：
Eric V. Anslyn
金额：
$ 19.85万
依托单位：
UNIVERSITY OF TEXAS AT AUSTIN
依托单位国家：
美国
项目类别：
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

项目摘要

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）：简单地说，我们的目标是创建真正实用的方案，用于比色测定对映体过量 (ee) 和反应产率。这些测定适用于台式使用以及高通量筛选。真正实用是指用户友好，适合任何有机化学家实施，并且对许多不同的功能组有用。测定的简单性及其普遍适用性是该提案的主要智力优点。在我们的方法中，手性受体与指示剂结合。引入具有手性客体（GR 和 GS）的溶液后，形成非对映体主体：客体复合物。这些复合物不同程度地取代指示剂，因此，溶液的颜色取决于样品的 ee。然而，我们还必须知道客体的总浓度，并且使用使用非手性受体的第二个 IDA 来进行此测定。数学分析将总浓度和 ee 与颜色联系起来。该技术概念简单且易于实施。通过研究已知达到平衡的反应来扩展我们的 IDA 技术是合乎逻辑的。例如，酰肼-酰腙互变的类似物是很好的可能性。我们从这种特殊的互换中汲取经验，提出了基于胺/肼与甲醇胺相互转化以及醇/胺与半缩醛/甲醇胺相互转化的方法。然而，我们进一步提出了使用手性三氰乙烯衍生物和手性金属配合物的动态 IDA 方法。我们的方法将针对手性酮/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，我们计划创建能够提供大的视觉颜色变化并且不需要数学分析的方法。大的颜色变化将采用双电池技术中的两个指示剂。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容易实施并直接应用于实际分析。为了测试它们的实用性，本文创建的测定将用于分析已知的不对称变换，并且将通过来自德克萨斯农工大学金斯维尔的本科生的参与，将它们用于“现实生活”情况。通过 A&M Kingsville 化学系和 U.T. 之间的 NIH 资助协议奥斯汀，少数族裔学生将来到奥斯汀进行研究。该 NIH 申请中提出的研究特别适合该交流计划，该 NIH 项目将用于展示这两所大学之间的合作努力。