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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
3R01GM077437-03S1
Application #
7739371
Study Section
Synthetic and Biological Chemistry A Study Section (SBCA)
Program Officer
Fabian, Miles
Project Start
2006-04-01
Project End
2010-03-31
Budget Start
2008-04-01
Budget End
2009-03-31
Support Year
3
Fiscal Year
2009
Total Cost
$43,032
Indirect Cost
Name
University of Texas Austin
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
170230239
City
Austin
State
TX
Country
United States
Zip Code
78712
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Lin, Chung-Yon; Lim, Stephanie; Anslyn, Eric V (2016) Model Building Using Linear Free Energy Relationship Parameters-Eliminating Calibration Curves for Optical Analysis of Enantiomeric Excess. J Am Chem Soc 138:8045-7
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Dragna, Justin M; Gade, Alexandra M; Tran, Lee et al. (2015) Chiral amine enantiomeric excess determination using self-assembled octahedral Fe(II)-imine complexes. Chirality 27:294-8
Jo, Hyun Hwa; Edupuganti, Ramakrishna; You, Lei et al. (2015) Mechanistic Studies on Covalent Assemblies of Metal-Mediated Hemi-Aminal Ethers. Chem Sci 6:158-164
Zhao, Qingyang; Wen, Jialin; Tan, Renchang et al. (2014) Rhodium-catalyzed asymmetric hydrogenation of unprotected NH imines assisted by a thiourea. Angew Chem Int Ed Engl 53:8467-70

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