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)：简单地说，我们的目标是创建真正实用的比色法测定对映体过量(Ee)和反应产率。这些检测方法既可用于高通量筛选，也可用于台式检测。所谓真正的实用，我们指的是用户友好，适合任何有机化学家实施，并对许多不同的官能团有用。化验方法的简单性和普遍适用性是这一建议的主要智力优点。 在我们的方法中，手性受体与指示剂相关联。当引入含有手性客体(GR和GS)的溶液时，形成了非对映异构体主客体络合物。这些络合物使指示剂发生不同程度的置换，因此，溶液的颜色取决于样品的ee。然而，人们还必须知道客体的总浓度，使用第二个使用手性受体的IDA来进行这一测定。数学分析将总浓度和ee与颜色联系起来。该技术在概念上简单，易于实现。 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，类似于酰肼-酰肼的相互转化是很好的可能性。我们从这一特殊的交换过程中得到了启发，提出了基于胺/肼到甲醇醇胺的相互转化和基于醇/胺到半缩醛/甲醇醇胺的相互转化的方法。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络合物的动态IDA方法。 我们的方法将对手性酮/醛和手性醇/胺进行研究。我们将创建需要数学分析的第一代协议。在第二代中，我们计划创造出不需要数学分析就能产生较大视觉色彩变化的方法。较大的颜色变化将在双电池技术中使用两个指示器。为了消除数学分析的要求，我们将实现人工神经网络(ANN)。指导原则是使这些技术在实施过程中变得越来越容易，并直接适用于实际分析。 为了测试它们的实用性，本文创建的分析将用于分析已知的不对称转换，并将通过涉及德克萨斯州农工大学金斯维尔的本科生将它们用于“现实生活”的情况。通过国立卫生研究院资助的A&M金斯维尔大学和德克萨斯大学奥斯汀分校化学系之间的协议，少数族裔学生将来到奥斯汀进行研究。NIH申请中提出的研究特别适合这个交流项目，这个NIH项目将被用来展示这两所大学之间的合作努力。