Colorimetric Assays for Enantiomeric Excess

点击翻译按钮获取中文摘要

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.