Edward R. Thornton

Professor of Chemistry
Organic and Bioorganic Chemistry

Office: 446 N
Lab: 434, 436 N
Phone: (215) 898-8309
Email: ertsasupennedu
Research Group Website: http://www.sas.upenn.edu/~ert/thornton.html

Jump to: Research Statement | Education and Academic History | Selected Publications

Research Statement
Research has recently focused on computational studies involving molecular interactions and selectivity, molecular architecture, and molecular recognition. Some of our most recent research has involved collaborations with Professors Ralph Hirschmann and Amos B. Smith, III (University of Pennsylvania) on electrostatic potentials as a means of understanding somatostatin receptor interactions, and with Professor Nobuo Tanaka (Kyoto Institute of Technology) on isotope effects in HPLC as a means of studying hydrophobic effects and interactions.

We have found substantial differences in electrostatic potential surfaces (shown in 1 and 2) between different aromatic systems such as benzene (1) vs. pyridine (2). These differences correlate nicely with binding properties of glucose-based peptidomimetics containing different aromatic substituents, and they appear to explain observed differences in binding to the somatostatin receptor.

We have studied the separation of hydrogen/deuterium isotopologue pairs by means of reversed-phase chromatographic separation in order to examine deuterium isotope effects on hydrophobic binding. The results (see Figure, where tr is the HPLC retention time) demonstrate that dispersion interactions in the hydrophobic phase are an important component of hydrophobic interactions.

We are also interested in design of extended three-dimensional structures with specific architectures and novel properties. Large molecules with architecturally complex structures and shapes, having properties designed for specific purposes, are of increasing importance in all areas of organic and bioorganic chemistry.

A major area of interest in our lab has been study of interactions, transition structures, and mechanisms, for example, mechanistic studies on deuterium and sulfur isotope effects, solvolysis reactions, E2 eliminations, mass spectra, electrical discharge reactions, acid-base catalysis, the Diels-Alder reaction, theory of transition state structural effects, and reactions of carbenes.

Previous bioorganic studies in our lab involved structures and interactions of saccharides and glycolipids utilizing 13C NMR relaxation times, hydrophobic interactions, carbene photochemical labeling of model membranes, and proteins of synaptic vesicles.

Education and Academic History

Selected Publications
Neelamkavil, S.; Arison, B.; Birzin, E.; Feng, J.-J.; Chen, K.-H.; Lin, A.; Cheng, F.-C.; Taylor, L.; Thornton, E. R.; Smith, A. B., III; Hirschmann, R. J. Med. Chem. 2005, 48, 4025-4030. "Replacement of Phe6, Phe7, and Phe11 of D-Trp8-Somatostatin-14 with L-Pyrazinylalanine. Predicted and Observed Effects on Binding Affinities at hSST2 and hSST4. An Unexpected Effect of the Chirality of Trp8 on NMR Spectra in Methanol."

Angeles, A. R.; Neagu, I.; Birzin, E. T.; Thornton, E. R.; Smith, A. B., III; Hirschmann, R. Org. Lett. 2005, 7, 1121-1124. "Synthesis and Binding Affinities of Novel SRIF-Mimicking beta-D-Glucosides Satisfying the Requirement for a pi-Cloud at C1."

Neelamkavil, S.; Mowery, B.P.; Thornton, E. R.; Smith, A. B., III; Hirschmann, R. J. Pept. Res. 2005, 65, 139-142. "A Practical Synthesis of Nalpha-Fmoc-L-pyrazinylalanine via Schöllkopf’s Chiral Auxiliary."

Turowski, M.; Yamakawa, N.; Meller, J.; Kimata, K.; Ikegami, T.; Hosoya, K.; Tanaka, N.; Thornton, E. R. J. Am. Chem. Soc. 2003, 125, 13836-13849. "Deuterium Isotope Effects on Hydrophobic Interactions: The Importance of Dispersion Interactions in the Hydrophobic Phase."

Prasad, V.; Birzin, E. T.; McVaugh, C. T.; van Rijn, R. D.; Rohrer, S. P.; Chicchi, G.; Underwood, D. J.; Thornton, E. R.; Smith, A. B., III; Hirschmann, R. J. Med. Chem. 2003, 46, 1858-1869. "Effects of Heterocyclic Aromatic Substituents on Binding Affinities at Two Distinct Sites of Somatostatin Receptors. Correlation with the Electrostatic Potential of Substituents."

Choudhury, A.; Thornton, E. R. Tetrahedron Lett. 1993, 34, 2221-2224, "alpha´-Benzoyloxy and alpha´-Methoxymethoxy Lithium Enolates Giving Opposite Diastereofacial Selectivities in Aldol Reactions. Use of (Probable) Extended Chelation for Reversal of Stereoselectivities."

Das, G.; Thornton, E. R. J. Am. Chem. Soc. 1993, 115, 1302-1312, "Aldol Additions of Pinacolone Lithium Enolate with Ketones: Reactivities Governed Predominantly by Field Effects."

Reddy, D. R.; Thornton, E. R., J. Chem. Soc., Chem. Commun. 1992, 172-173, "A Very Mild, Catalytic and Versatile Procedure for alpha-Oxidation of Ketone Silyl Enol Ethers Using (salen)Manganese(III) Complexes; A New, Chiral Complex Giving Asymmetric Induction. A Possible Model for Selective Biochemical Oxidative Reactions Through Enol Formation."

Bonner, M. P.; Thornton, E. R., J. Am. Chem. Soc. 1991, 113, 1299-1308, "Asymmetric Aldol Reactions. A New Camphor-Derived Chiral Auxiliary Giving Highly Stereoselective Aldol Reactions of Both Lithium and Titanium(IV) Enolates."

Tripathy, R.; Carroll, P. J.; Thornton, E. R., J. Am. Chem. Soc. 1991, 113, 7630-7640, "Diene-Dienophile Hydrogen-Bonding Control of Diels-Alder Reactions with Dienes Bearing a Remote Stereogenic Center. Amplification of the Receptor Nature of Dienes by Conformational Tuning Leading to High Diastereofacial Discrimination."

Siegel, C.; Thornton, E. R., Tetrahedron: Asymmetry 1991, 2, 1413-1428, "Diels-Alder Reactions with Dienes Bearing a Remote Stereogenic Center. Conformational Model for Diastereofacial Selectivity." [invited paper]

Prapansiri, V.; Thornton, E. R., Tetrahedron Lett. 1991, 32, 3147-3150, "Asymmetric Diels -Alder Reactions. Inverse Electron Demand Reactions of Esters of 3-Hydroxypyran-2-one with Vinyl Ethers: Use of High Pressure to Avoid Decarboxylation of Adducts."

Panyachotipun, C.; Thornton, E. R., Tetrahedron Lett. 1990, 31, 6001-6004, "Steric Influence of Silyl Groups in Titanium- and Lithium-Mediated Aldol Condensations."

Nerz-Stormes, M.; Thornton, E. R. J. Am. Chem. Soc. 1984, 106, 5240-5246, "Carbon-13 Spin-Lattice Relaxation Studies of GD1a Micelles. Limited Segmental Motion of Head Group Saccharide Units."

Keilbaugh, S. A.; Thornton, E. R. Biochemistry 1983, 22, 5063-5068, "Photolysis of Cholesteryl Diazoacetate in Small Unilamellar Vesicles."

Thornton, E. R. J. Am. Chem. Soc. 1967, 89, 2915-2927, "A Simple Theory for Predicting the Effects of Substituent Changes on Transition-State Geometry."