Robert Wertz

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First Name: 
Robert
Last Name: 
Wertz
Official Title: 
Grants Administrative Coordinator
Additional Titles: 
Webmaster
Contact Information
Office Location: 
454 N
Office Hours: 
m-f 9-5
Email: 
rwertz@sas.upenn.edu
Phone: 
215-573-7887

Jeffrey D. Winkler

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First Name: 
Jeffrey D.
Last Name: 
Winkler
Official Title: 
Merriam Professor of Chemistry

Organic Chemistry 

Additional Titles: 
Undergraduate Chair
Contact Information
Office Location: 
449 Chemistry Bldg.
Email: 
winkler@sas.upenn.edu
Phone: 
(215) 898-0052
Fax: 
(215) 573- 6329
Admin Support: 
Education: 
  • A.B. Harvard College (1977)
  • M.A., M.Phil., Ph.D. Columbia University (1981-83)
Research Interests: 

New Synthetic Pathways Based on the Intramolecular Dioxenone and Vinylogous Amide Photocycloaddition Reactions

We have developed these methods and have applied them to the first total syntheses of several molecules of biological importance, including manzamine A, 1, saudin, 2 , and ingenol, 3.

 

Total Synthesis of Manzamine-Related Structures

Current efforts in our laboratory are focused toward the synthesis of nakadomarin, 4, a structurally complex hexacyclic alkaloid that displays a range of promising biological activities including cytotoxic activity against murine lymphoma L1210 cells, inhibitory activity against cyclin dependent kinase 4, and anti-microbial activity against a fungus and a Gram-positive bacterium. We have also demonstrated that manipulation of the structure of 1 via Grubbs metathesis leads to the formation of novel structures, i.e., 5, with antibacterial properties comparable to those of ciprofloxacin. Finally, we have embarked on a program directed toward the synthesis of neokauluamine, 6, a dimeric manzamine with highly potent immunosuppressive properties. 

 

Transformations Using Organic Photochemistry

We have recently discovered a novel approach to the synthesis of substituted thiophenes 8 from arylsulfide enone precursors 7. The study of the mechanism of this unusual transformation (9 is a byproduct) as well as its application to the synthesis of more complex structures is currently underway in our laboratory.

 

Development of Novel Inhibitors of Hedgehog Signaling Based on Cyclopamine

Aberrant activation of the Sonic Hedgehog (Hh) signaling pathway has been associated with numerous malignancies in the brain, breast, pancreas and other organs. In vivo evidence suggests the antagonism of excessive Hh signaling may provide a route to unique mechanism-based therapies for the treatment of cancer. The steroidal alkaloid cyclopamine 10 suppresses the Hh signaling pathway, and has recently been been shown to be effective in the treatment of cancer using a variety of mouse models. Human cells are also sensitive, supporting the promising use of this natural product. However, the metabolic instability of cyclopamine precludes its clinical use. A significant demand exists for more stable cyclopamine-like structures. This project is directed toward the synthesis of cyclopamine-like structures, i.e., 11, from readily available metabolically-stable steroidal precursors, i.e., estrone.

 

Total Synthesis of Cortistatin A

The development of specific anti-angiogenic agents that could serve as anticancer chemotherapeutic agents is an important goal. In 2006, Kobayashi isolated the cortistatins from the marine sponge Corticium simplex. Cortistatin A 12 is the most active member of this family. It exhibits antiproliferative activity against human umbilical vein endothelial cells at nM concentrations. The total synthesis of the cortistatins and designed materials with cortistatin-like properties is one of the goals of our laboratory.

Bradford B. Wayland

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First Name: 
Bradford B.
Last Name: 
Wayland
Official Title: 
Emeritus Professor of Chemistry

Inorganic Chemistry

Contact Information
Office Location: 
Senior Faculty Suite
Email: 
wayland@sas.upenn.edu
Research Interests: 

Metallo-radical and organo-metal substrate reactions are used in both obtaining living radical polymerization for application in block copoymer materials and energy relevant small molecule organometallic transformations.

Our NSF supported polymer program spans areas from transition metal catalyst development and block co-polymer synthesis to materials applications of nano-structured polymer arrays in membranes, sensors, and microelectronic devices. The reactivity of metal-centered radical species and organometallic derivatives are exploited in the control of radical polymerization by catalytic chain transfer and living radical polymerization. Organo-cobalt porphyrin complexes have recently been observed to mediate a highly precise living radical polymerization of acrylate monomers to form low polydispersity homopolymers and block co-polymers. This new approach to obtaining living radical polymerization occurs by a degenerative transfer pathway that involves rapid interchange of polymeric radicals in the polymer with polymeric units in the organo-cobalt porphyrin complexes. This pathway to obtain living radical polymerization is a transition metal form of degenerative transfer that we refer to as radical interchange polymerization (RIP). The expanding capabilities of living radical polymerization to provide new classes of materials required to advance issues that have significant technological relevance are exploited through an active collaboration with materials science and engineering .Two of the issues targeted as focal points for this collaboration are 1) membranes for water purification and 2) low dielectric thin films for advanced micro electric devices. New materials design strategies are determined for each of the central topics along with the requisite approaches for polymer synthesis, morphology, and property evaluation.

The DOE supported energy related research interests are centered on developing new strategies to accomplish thermodynamically and or kinetically challenging reactions such as methane activation and carbon monoxide reductive coupling and hydrogenation. Ligands are designed to achieve high selectivity through steric and electronic constraints on forming the transition states for substrate reactions .The primary focus is on group nine (Co, Rh, Ir) metal complexes where the importance of metallo-radicals is a recurring theme. Metallo-porphyrins, chlorophylls, and related macrocycles are prominent thermal and photocatalysts in biological systems and emerging as important catalyst materials for chemical manufacturing processes. The unique unique chemical and physical properties of metallo-porphyrins and macrocyclic complexes are used in producing thermal and photocatalytic cycles for small molecule reactions. Several important examples include hydrogenation of CO and CO2, activation of methane, oxidation of alkenes, photoreductions and alkene polymerization. Tethered diporphyrin ligands have been designed and synthesized that are used in forming bimetalloradical complexes of Rh(II). Bimetalloradicals provide preorganization of transition states that involve two metalloradicals and give rapid highly selective substrate reactions. Structural, kinetic-mechanistic, thermodynamic, and reactivity studies are used in characterizing intermediates, anticipating new types of reactions, and guiding strategies to produce selective catalyst materials.

Other Affiliations: 

Temple University, Department of Chemistry

Patrick J. Walsh

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First Name: 
Patrick J.
Last Name: 
Walsh
Official Title: 
Professor of Chemistry

Inorganic Chemistry, Organic Chemistry, Chemical Catalysis

Contact Information
Office Location: 
3001 IAST
Email: 
pwalsh@sas.upenn.edu
Phone: 
(215) 573-2875
Fax: 
(215) 573-6743
Admin Support: 
Education: 
  • Advisor Prof. K. Barry Sharpless
  • 1986 B.A. in Chemistry, University of California, San Diego
  • 1991 Ph.D in Chemistry, University of California, Berkeley
  • 1991-1994 NSF Postdoctoral Fellow Postdoctoral, The Scripps Research Institute
Research Interests: 

Research in the Walsh group merges the fields of catalysis and organic and inorganic synthesis with the goal of achieving new catalytic asymmetric transformations for the synthesis of chiral building blocks. The transformations we have chosen to study are asymmetric C-C and C-O bond forming reactions, because construction of these bonds lies at the very heart of organic synthesis. We are also interested in the development of tandem reactions that combine several steps in a single reaction vessel. By introducing tandem reactions, we can increase synthetic efficiency while reducing the number of purification steps necessary. 

 

Shown below are examples of tandem reactions developed in the Walsh group:

 

We are also interested in reaction mechanisms, which gives us the opportunity to synthesize some interesting catalysts. Shibasaki's M3(THF)n(BINOLate)3Ln (Ln = lanthanide, M = Li, Na, K) catalyst are among the most efficient known in asymmetric catalysis. We have studied the structure and reactivity of these amazing catalysts, one of which is shown below.4-6 

We are also interested in structural organozinc chemistry. The first example of zinc coordinated to C-C double bond was recently reported from our group.7 

In 2006 the Walsh group crystallographically characterized about 40 compounds, most of which contained metals.

Donald Voet

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First Name: 
Donald
Last Name: 
Voet
Official Title: 
Emeritus Associate Professor of Chemistry

Biological Chemistry

Contact Information
Office Location: 
349 N
Email: 
voet@sas.upenn.edu
Phone: 
(215) 898-6457
Education: 
  • B.S. California Institute of Technology (1960)
  • Ph.D. Harvard University (1967)
  • Post Doc at MIT, Cambridge, MA, 1966–1969 in the laboratory of Alexander Rich
  • Member ACS and AAAS
  • Visiting Scholar, Weizmann Institute of Science, Rehovot, Israel, 1993 and 1998
  • Editor-in-Chief, Biochemical and Molecular Biology Education.
Research Interests: 

We are studying the structures of biologically interesting molecules by X-ray crystallography in an effort to understand their structure-function relationships. Current projects include:

 

Yeast inorganic pyrophosphatase

Pyrophosphatases are essential enzymes that catalyze the hydrolysis of inorganic pyrophosphate to phosphate and, in doing so, drive the many biosynthetic reactions that yield pyrophosphate (e.g., polypeptide and polynucleotide synthesis) to completion. We have determined the refined 2.7-angstrom resolution structure of yeast inorganic pyrophosphatase, a dimeric enzyme of identical 286-residue subunits. We are presently determining the X-ray structures of selected mutant forms of this enzyme, both alone and in complex with inhibitors of this enzyme. The results of these studies, when correlated with the enzymological characteristics of the mutant enzymes, should lead to the formulation of a catalytic mechanism of inorganic pyrophosphatases as well as a greater understanding of biological phosphoryl transfer reactions in general.

 

Granulocyte -macrophage colony-stimulating factor (GM-CSF)

GM-CSF is a protein growth factor (cytokine) that stimulate the differentiation, proliferation, and activation of white blood cells known as granulocytes and macrophages. The therapeutic use of GM-CSF therefore holds considerable promise for the treatment of immunosuppressive conditions such as AIDS and the consequences of cancer chemotherapy. Indeed, GM-CSF is presently in clinical use to facilitate bone marrow transplantation. We have determined the refined X-ray structure of human GM-CSF to 3.0-angstrom resolution. We plan to determine the X-ray structures of selected mutant varieties of human GM-CSF in an effort to understand how GM-CSF interacts with its cell surface receptor. We also intend to determine the X-ray structure of the human GM-CSF receptor, both alone and in complex with GM-CSF. 

 

 

The x-ray structure of yeast inorganic pyrophosphatase. A 286-residue monomer unit of this homodimeric enzyme is shown with its polypeptide backbone represented in ribbon form embedded in its solvent accessible surface. The side chains of its active site residues are shown in ball-and-stick form.

Selected Publications: 

Voet , Voet; Biochemistry, 3rd Edition Student Companion Site

Michael R. Topp

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First Name: 
Michael R.
Last Name: 
Topp
Official Title: 
Professor of Chemistry

Physical Chemistry 

Contact Information
Office Location: 
249 N, Lab: 240 N
Email: 
mrt@sas.upenn.edu
Phone: 
(215) 898-4859
Admin Support: 
Education: 
  • B.Sc. Sheffield University (1966) - Haworth Medal winner
  • Ph.D. University College London and the Royal Institution of Great Britain (1969)
  • Member of Technical Staff, Bell Labs, (1969-71)
  • IBM Research Fellow, Pembroke College, Oxford (1971-73)
Research Interests: 

Conformational Relaxation in Isolated Molecular Clusters

When molecules become electronically excited, the rearrangement of electronic charge can precipitate many types of relaxation processes. To probe details of such events, one can employ isolated molecular clusters consisting of only a few hydrogen-bonded molecules. One particularly interesting case is the cluster involving a Coumarin 151 molecule bonded to a water dimer. Two different structures have been identified in the ground state, as shown below.

 

 

Recent experiments have shown that the species shown on the left here is unstable in the excited state, and relaxes to that shown on the right on a picosecond or nanosecond time scale depending on the available energy. This corresponds to movement of the water dimer by ~10Å from one side of the molecule to another, following and yet the activation energy is only 60 cm-1. Such conformational changes have been studied by a combination of fluorescence and infrared double resonance techniques in conjunction with ionization and mass resolution.

 

Hydrogen-Bonded Molecular Dimers

 

Hydrogen-bonded dimers present important opportunities to study short-range intermolecular interactions, including modification of the electronic structure, and corelated proton or hydrogen atom transfer. Molecules such as the dimer of 4-Amino-N-methylphthalimide, shown here, reveal dramatic changes in their infrared spectra between the ground and excited states. The simple ground-state ground-state infrared spectrum reflects the high symmetry of the ground state. On the other hand, the much more complex excited-state spectrum shows evidence for a loss of symmetry resulting from changes in the acid-base properties of NH2 and >C=O groups, which may result in proton transfer across the intermolecular hydrogen bonds. These types of strongly bonded dimers are different from many other dimer systems studied so far, because both their electronic and vibrational spectra are highly structured, despite the large increase in binding energy upon electronic excitation. Femtosecond-domain experiments are planned, to follow in real time the changes in vibrational spectra, which will provide further insights into the reasons for their complexity in the excited state.

 

 

Ultrafast Electronic Relaxation of Hydrogen-Bonded Molecules Studied by Femtosecond Pump-Probe Spectroscopy

 

Femtosecond pump-probe experiments allow us to observe the time evolution of the first events following pulsed laser excitation, including motions in the first coordination shell of a hydrogen-bonded molecule in fluid solution. New pump-probe experiments involving the detection of ultrashort-lived fluorescence have explored spectroscopic changes of aminophthalimide molecules in hydrogen-bonding solvents on a time scale more than 10 times faster than existing data for fluorescence Stokes shifts. Both fluorescence upconversion and pump-probe methods are being used to investigate ultrafast energy transfer processes in complex molecules, in collaboration with the Regional Laser and Biomedical Technology Laboratories at Penn.

Edward R. Thornton

Photo: 
First Name: 
Edward R.
Last Name: 
Thornton
Official Title: 
Emeritus Professor of Chemistry

Organic and Bioorganic Chemistry 

Contact Information
Office Location: 
Senior Faculty Suite
Email: 
ert@sas.upenn.edu
Phone: 
(215) 898-8309
Education: 
  • B.A. Syracuse University (1957)
  • Ph.D. Massachusetts Institute of Technology (1959)
  • N. I. H. Postdoctoral Fellow, M.I.T. (1959-1960)
  • N.I.H. Postdoctoral Fellow, Harvard University (1960-1961)
Research Interests: 

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.

Joseph Subotnik

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First Name: 
Joseph
Last Name: 
Subotnik
Official Title: 
Edmund J. and Louise W. Kahn Endowed Term Professor of Chemistry

Physical and Theoretical Chemistry

Contact Information
Office Location: 
268 Cret wing
Email: 
subotnik@sas.upenn.edu
Phone: 
215-746-7078
Admin Support: 
Education: 

B.A. Harvard University, 2000

Physics and Math (summa cum laude)


Ph.D.  UC Berkeley, 2006  Biophysics

 

NSF International Research Fellow (2007 -2009), Tel-Aviv

Postdoctoral Fellow, Northwestern University (2009-2010)

Research Interests: 

Research in the Subotnik group focuses on the intersection of static quantum chemistry methods (especially for excited states) with nonadiabatic dynamics methods (specifically surface hopping). The focus is quantifying electron transfer, energy transfer, and electronic relaxation. Applications are to almost all photo-induced processes!

Larry G. Sneddon

Photo: 
First Name: 
Larry G.
Last Name: 
Sneddon
Official Title: 
Emeritus Professor of Chemistry

Inorganic, Energy and Materials Chemistry

Contact Information
Office Location: 
452 Chem ’73
Email: 
lsneddon@sas.upenn.edu
Phone: 
(215) 898-8632
Admin Support: 
Education: 
  • B.S. Centenary College of Louisiana (1967)
  • Ph.D. Indiana University (1971)
  • Postdoctoral Fellow, University of Virginia (1971-73)
  • Postdoctoral Fellow, Massachusetts Institute of Technology (1973-74)
Research Interests: 

 

Our research in inorganic chemistry, energy-storage and materials science includes synthetic studies in main-group, transition metal and materials chemistry along with physical and structural investigations of molecular, polymeric, and solid-state materials. Brief overviews of ongoing projects are presented in the following sections.

 

Alternative Energy Carriers: New Chemical Methods for Hydrogen Storage

 

The development of efficient methods for hydrogen storage is a major hurdle that must be overcome to enable the use of hydrogen as an alternative energy carrier. We are exploring the use of chemical hydrides such as ammonia borane and ammonia triborane to store and deliver large amounts of hydrogen through dehydrogenation and/or hydrolysis reactions. As depicted in the example in Figure 1, we have shown that the rate and the extent of hydrogen release from these amineboranes can be significantly increased through the use of metal catalysts, ionic liquids and/or chemical additives. We are continuing to investigate both new methods for the controlled hydrogen release from amineboranes and the development of energy-efficient methods for their regeneration from spent-fuel products.

 

Figure 1. Rhodium catalyzed hydrolysis of ammonia triborane

 

Chemical Precursors to Ultra High Temperature Aerospace Materials

The production of complex structural and electronic materials in useable forms is one of the most challenging problems of modern solid-state chemistry and materials science. Our research in this area is focused on the design, syntheses and applications of new processible molecular and/or polymeric precursors to advanced carbide, nitride and boride ceramics that allow the formation of these technologically important materials in forms that cannot be produced with conventional methods. We are especially interested in ultra high temperature materials, such as HfB2 and ZrB2 based composites, that are potentially important in hypersonic (i.e. flying faster than 5 times the speed of sound) aerospace vehicles (Figure 2). A second part of the project is focused on the formation and properties of micro- and nanostructured ceramics, including fibers, tubes and porous materials.

 

Figure 2. New chemical precursor systems for ultra high temperature hafnium-ceramics that were developed at Penn

 

Transition Metal-Promoted Reactions of Inorganic Compounds

We are developing new general, metal-catalyzed methodologies that enable the systematic, high-yield syntheses of important polyborane compounds and materials. Our goals are both to discover new types of catalytic reactions and to develop an understanding of their fundamental reaction mechanisms and controlling factors.

 

Figure 3. (Left) Metal-catalyzed synthesis of the poly(norbornenyldecaborane) polymer; and (Right) The crystallographically determined structure of a new dendritic decaborane (you can manipulate this molecule online at

 

Ionic Liquid Promoted Reactions

 

Ionic liquids have properties that make them attractive solvents for synthesis, including: negligible vapor pressures, thermal stability to elevated temperatures; the ability to dissolve a range of compounds, salts and gases, immiscibility with many hydrocarbons and/or water thus enabling two-phase reaction systems, weakly-coordinating anions and cations that provide a polar, inert reaction medium, and the ability to stabilize polar intermediates and/or transition states. While ionic liquids have been widely employed for organic synthesis, our recent work showing that decaborane olefin-hydroboration and alkyne-insertion reactions proceed in biphasic ionic-liquid/hydrocarbon solvents without the need of the catalysts required in conventional solvents, was the first demonstration of the unique activating effects of ionic liquids for polyborane syntheses. We are continuing to explore the scope of ionic liquid mediated polyborane reactions along with experimental and computational studies of the mechanisms by which these reactions occur.

 

Inorganometallic Chemistry

Because of the unusual ranges of their accessible charges and coordination geometries, polyboranes can function as versatile ligands that can stabilize transition metals in a much wider array of environments than their organic counterparts, such as the cyclopentadienide anion. We are using integrated synthetic, structural (NMR and X-ray crystallography), electrochemical, and computational (DFT/GIAO) investigations to elucidate the nature of polyborane-metal bonding. The unique properties of metallapolyborane complexes are also being exploited to design new metallocene-like complexes with chemical, optical and/or bioactivity properties of importance to solid-state and/or anticancer applications. 

 

 

Figure 4. (Left) Comparisons of the bonding modes of the cyclopentadienyl and tricarbadecaboranyl ligands; (Right) The crystallographically determined structures of new maganatricarbadecaboranyl complexes illustrating a cage-slippage reaction analogous to a cyclopentadienyl ring-slippage process

Amos B. Smith III

Photo: 
First Name: 
Amos B.
Last Name: 
Smith III
Official Title: 
Rhodes-Thompson Professor of Chemistry

Organic Chemistry

Contact Information
Office Location: 
440N
Email: 
smithab@sas.upenn.edu
Phone: 
(215) 898-4860
Fax: 
(215) 898-5129
Education: 
  • B.S.- M.S. Bucknell University (1966)
  • Ph.D. Rockefeller University (1972)
  • Associate, Rockefeller University (1972-73)
Research Interests: 

Smith's research interests encompass three diverse areas: natural product synthesis, bioorganic chemistry and materials science. To date, more than 90 architecturally complex natural products having significant bioregulatory properties have been prepared in his Laboratory. In addition, Smith, in collaboration with Ralph Hirschmann, has achieved the design and synthesis of non-peptide peptidomimetics of neuropeptideic hormone/transmitters and protease enzyme inhibitors and, also with Stephen Benkovic (Penn State), haptens for the production of catalytic antibodies capable of peptide bond formation. At Monell, in collaboration with Peter Jurs (Penn State), he pioneered the use of computerized pattern recognition techniques for the analysis of primate chemical communication. Collaborative programs at the LRSM include the chemistry and physics of novel liquid crystals and the fullerenes. To date Smith research achievements have been reported in more than 500 peer reviewed publications.

Department of Chemistry

231 S. 34 Street, Philadelphia, PA 19104-6323

215.898.8317 voice | 215.573.2112 fax | web@chem.upenn.edu

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