Todd A. Davis
Assistant Professor of Chemistry
Postdoctoral Studies, 2004-2007
Vanderbilt University, Advisor: Ned Porter
Ph.D. Organic Chemistry, 2004 Texas Tech University, Advisor: Bob Flowers
B.S. Chemistry
Grand Valley State University
| Research Area: | Organic, Medicinal, and Bio-analytical Chemistry |
| Student Experience required for research: | Chem. 301 and Chem. 302 |
| Student Experience gained from research: | Organic Synthesis, Mechanistic Investigation, and Instrumentation (NMR, GC, GC-MS, HPLC, and HPLC-MS-MS) |
| Ideal Preparation for: | Careers in the Pharmaceutical and Chemical Industries, Graduate and Professional School |
Research Description
1.)Synthetic Organic Chemistry: Designing Organocatalysts Based on Urea/Thiourea Derivatives:
The ability to synthesize molecules stereoselectively has become of utmost importance to the field of organic chemistry. There have been numerous examples in the pharmaceutical industry in which a particular chiral center can have a profound increase in biological activity in comparison to its stereoisomer. Although there have been a variety of methodologies developed to synthesize molecules stereoselectivity, there are still limitations.
We are investigating the design and application of urea and thiourea containing molecules as organocatalysts for diastereoselective and enantioselective synthesis. Urea (pKa=27) and thiourea (pKa=21) are acidic in nature and therefore have been shown to have a strong hydrogen bonding interaction with a variety of functional groups.(Scheme 1). We are currently investigating the thermodynamic parameters of bidentate interaction of urea/thiourea with a variety of 1,2 and 1,3 substituted ketones (scheme 1).
Based on these interactions the design of urea/thiourea organocatalysts for diastereoselective and enantioselective organic transformations will be investigated. A future goal of this research will be the design of catalysts to be used in an aqueous medium providing a “greener” approach to current synthetic methodologies.
2.) Development of LC-MS-MS Methods for Analyzing Oxidation Products of Cholesterol Esters
Lipid oxidation has been associated with a variety of disease states including neurodegenerative disease and atherosclerosis. Oxidation products derived from polyunsaturated fatty acids (PUFA’s) occur via free radical initiated reactions with molecular oxygen. The problem with analyzing PUFA’s oxidation products is 1.) There are numerous products that can form making the separation extremely difficult, and 2.) analysis usually involves a laborious work-up involving the hydrolysis of the intact cholesterol ester followed by derivitization. Our focus is to develop analytical techniques using HPLC-MS-MS to analyze classes of intact cholesterol esters from the oxidation of linoleate (18:2) and arachidonate (20:4). In particular, we are interested in analyzing the oxidation products derived from linoleate (hydroxyoctadienoates HODEs) and arachidonate cholesterol esters (hydroxyeicosatetraenes HETEs and isoprostane’s Isop’s) (Scheme 2). The development of these methodologies will progress toward the analysis of cholesterol oxidation products from in vivo sources such as urine, liver, and other tissue.
Scheme 2: Oxidation Products from Linoleate and Arachidonate Cholesterol Esters
Recent Publications:
“Simultaneous Analysis of Multiple Lipid Oxidation Products in vivo by Liquid Chromatographic-Mass Spectrometry (LC-MS)” Yin, H.; Davis, T.A.; Porter, N.A. Invited Book Chapter. In Press
“In vivo and in vitro Lipid Peroxidation of Arachidonate Esters: The Effect of Fish Oil ω-3 Lipids on Product Distribution” Davis, T.A.; Gao, L.; Yin, H.; Morrow, J. D.; Porter, N.A. J. Am. Chem .Soc. 2006, 128, 14897-14904.
“Chelation-Controlled Reductions of α-Fluoroketones” Mohanta, P. K.; Davis, T. A.; Gooch, J. R.; Flowers, R. A., II J. Am Chem. Soc. 2005, 127, 11896-11897.
“Reduction of β-Hydroxyketones by SmI2/Et3N/H2O” Davis, T. A.; Chopade, P.; Flowers, R. A., II. Org. Lett. 2005, 7, 119-122.
“Solvent Dependent Diastereoselectivities in Reductions of β-Hydroxyketones by SmI2” Chopade, P.; Davis, T.A.; Prasad, E.; Flowers, R.A., II Org. Lett. 2004, 6, 2685-2688.
“Molecular Recognition of Heavy Metals by Polymer Supported Carbohydrates.” Todd A. Davis and Robert Smart, 1999 McNair Scholars Summer Research Journal.