The University of Pittsburgh's Department of Chemistry will conduct a Research Experiences for Undergraduates (REU) program, in Summer, 2002, the second year of a three year program. The projects available each year will vary and will range in scope from traditional to instrument intensive, from one discipline to multi-discipline in flavor, from specific target oriented to more open ended projects. The projects that are currently available are described here, in reverse alphabetical order according to the Professor's Last Name. Additional projects will be posted in the near future.
Professor Peter Wipf |
Measuring Asymmetric Inductions in Novel Synthetic Applications of Chiral Ortho Esters |
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Ortho esters represent a class of masked acid derivatives that greatly modify the reactivity pattern of the parent carboxylates; however, they have found surprisingly little use in organic synthesis to date, and much of their chemistry remains to be explored. We are most interested in the use of ortho esters for new carbon-carbon bond formations, and we have developed a novel approach toward chiral ortho esters using a cationic zirconocene-catalyzed rearrangement reaction (Wipf, P.; Aslan, D. C., "Synthesis of bicyclic ortho esters by epoxy ester rearrangements and study of their ring opening reactions." J. Org. Chem. 2001, 66, 337-343). In the presence of zirconocene(II) complex, these chiral ortho esters can lead to the chiral g,g-dialkoxyallylic zirconium species 1 that is expected to provide asymmetric induction in the addition to aldehydes. The study of the scope of this reaction and the analysis of asymmetric induction by chiral HPLC is the topic of this project. [1/02] |
Professor Steve Weber |
Using Gas-Phase Mass Spectrometric Measurement Methods to Understand and Design Solution Equilibria |
| Are solution phase equilibria reflected in the gas phase? This important question has been raised by mass spectroscopists using electrospray who have observed peaks identified as adducts of the appropriate stoichiometry. We propose to build a remarkably simple apparatus in which the concentrations of adduct-forming species can be varied in a controlled, reproducible way. The device relies on Taylor-Aris dispersion in an open channel to dilute in a mathematically known way the concentrations of a pair of adduct-forming species. The student will modify (~1 week) the front end of the existing, custom-built mass spectrometer in order to simultaneously achieve conditions yielding Taylor-Aris behavior and efficient electrospray ionization. The student will then measure how concentrations of each of the relevant solutes changes in time following its injection into the flow stream both theoretically and using 'standard' (e.g. absorbance) detection. Finally, ESI-MS of the flow will be performed to determine how well correlated observations of adducts are with predictions based on known concentration profiles. [2/02] | |
Professor Steve Weber |
Screening Measurements for Selective Receptor Design |
| How selective can an extraction be? Product purification, environmental cleanup, hemo-dialysis, analytical sample separation all rely upon extraction to achieve a partial purification. It would be beneficial to have selective extraction media to carry out these tasks. The key is to bury a selective receptor for the target molecule(s) in a very poor solvent so that only the molecule of choice is extracted. The student will work with a library of receptors allowing the student to choose the target. Once a receptor has been chosen by a screening procedure it will be chemically modified to make it compatible with a fluorocarbon solvent. The solution of the suitably modified receptor in a fluorocarbon solvent will be examined by physical methods (e.g. 1H-NMR), and applied to selective extraction.3. Peptide-copper complexes: Structure and reactivity. Cu(II)-peptide complexes are important both as tools for analyses and as biological entities. How does the peptide structure influence the reaction rate, stability, and redox potential of the complex? Several physical methods will be used, including 1H, 13C-NMR (there is some broadening, but the spectra are useful), UV-vis, rotating ring disc electrode. The results can be applied to the important field of proteomics as a method for the quantitative determination of proteins and peptides. [2/02] | |
Professor Steve Weber |
Measurements to Characterize Peptide-Copper Complexes |
| Peptide-copper complexes: Structure and reactivity. Cu(II)-peptide complexes are important both as tools for analyses and as biological entities. How does the peptide structure influence the reaction rate, stability, and redox potential of the complex? Several physical methods will be used, including 1H, 13C-NMR (there is some broadening, but the spectra are useful), UV-vis, rotating ring disc electrode. The results can be applied to the important field of proteomics as a method for the quantitative determination of proteins and peptides. [2/02] | |
Professor Gilbert Walker |
Controlling and Measuring the Release of Nitric Oxide in Bloodstream Implants. |
| Nitric oxide is a principal signaling agent for neurotransmission, cell death, and thrombosis. How does NO get around so much? What are its protein targets and how do they change conformation to reflect NO binding? Can polymer substrates that release NO be prepared for biomedical implants, such as artificial capillaries? How do cells respond to this invasion? Work on these and related problems in a cross-disciplinary team that includes cell biologists, chemists and chemical engineers. Your job would be to measure the rate of nitric oxide release from specialized polymer surfaces into environments that mimic the bloodstream. [1/02] | |
Professor Gilbert Walker |
Single Molecule Measurements of Protein Conformations at Artificial Implant Surfaces. |
| Protein and polymer folding at surfaces is important for signaling between cells and for adhesion at surfaces. Identifying these folding states and relating them to specific functions is a holy grail of biomedical science. We have developed a variety of single molecule scanning probe techniques to identify surface folding states, including surface force and spectroscopic methods. This summer project involve identifying the different folding states of the adhesion protein fibronectin, which is being used to seed implant surfaces for endothelial cell adhesion. You would use single molecule force spectroscopic techniques, which allow you to unfold proteins, one domain at a time. This work is working towards minimization of thrombosis and related aspects of cardiovascular disease. [1/02] | |
Professor David Waldeck |
Measuring Electron Tunneling in Organic Molecules. |
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Electron transfer is a primary step in many important
chemical and biological transformations.
Electron transfer between molecular residues is likely to play a
central role in future molecular devices.
Our research program is studying the primary interactions between
molecular subunits that control electron transfer reactions. A particular example of one such system is illustrated by the
Donor-Bridge-Acceptor molecule in the diagram.
Recently we demonstrated that the electron tunnels from the
naphthalene donor moiety through the phenyl ring of the bridge to be
captured on the electron acceptor and that the phenyl ring should lie in
the ‘line-of-sight’ between the donor and acceptor (Ref 1).
Future studies will examine the role played by the electronic
structure of the phenyl moiety and its motion on the electron transfer
reaction. [1/02] |
Professor David Waldeck |
Measurements Aimed at Understanding Electron Transfer Between Electrodes and Biomolecules. |
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Electron transfer at electrode interfaces is of immense importance
to a variety of current and future technologies.
Interfacial electron transfer is central to processes that range
from the ancient (corrosion is an excellent example of an old unsolved
problem with large monetary implications) to the future (e.g., molecular
electronics and bioelectronics). Our
group is investigating the use of organic molecular films (SAMs) to
control the electron transfer between an electrode and a surface bound
biomolecule. The diagram illustrates the underlying architecture used in
this approach – a metal electrode is coated with a monolayer thick
organic film that can selectively bind a biomolecule.
This architectural control allows us to investigate the electron
transfer kinetics and how it depends on properties of the system, such as
chain length, composition, dipole moment and others. [1/02] |
Professor David Pratt |
Measuring Hydrogen Bond Lengths in the Gas Phase. |
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Hydrogen bonds (HB's) play a key role in many molecular recognition and assembly processes.
Most HB's are asymmetric, with the hydrogen atom closer to the base, rather than the acid. But symmetric HB's are known,
and believed to be important in enzyme catalysis (1). This project will employ the recently developed
technique of high resolution electronic spectroscopy in the gas phase (2) to measure the moments of inertia of
1-benzoylacetone (1BA) and its deuterated analogs (3). Analyses of these data will yield the center-of-mass
coordinates of the hydrogen atom to an accuracy of +/- 0.02 A, thereby showing whether or not the HB in 1BA is symmetric. Time permitting, applications to other systems might also be
proposed. [2/02] 1. W.W. Cleland and M.M. Kreevoy, Science 264, 1887 (1994). 2. W.A. Majewski, et al., Laser Techniques in Chemistry 23, 101 (1995). 3. B. Schiott, et al., J. Am. Chem. Soc. 120, 12117 (1998). |
Professor Kazunori Koide |
A Combinatorial Approach Towards The Development of a High-throughput Assay System to Measure RNA Levels In Vivo |
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To develop a sensitive method to quantify primary RNA transcripts in
vivo, a system will be developed in which RNA itself catalytically
generates fluorescent molecules so that the
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fluorescent
signal is amplified.
A combinatorial library of coumarin derivatives will be prepared on
solid support according to scheme 1.
After the library of DNA is transfected into yeast, each coumarin
derivative will be incubated in an individual well combined with the yeast
library.
If an RNA molecule catalyzes the cleavage of ArO-R3 bond
to generate fluorescence, the yeast cells will be isolated by means of a
fluorescence-activated cell sorter. Our approach is flexible in that we will be able to manipulate both fluorescent molecules and RNA by means of synthetic organic chemistry and molecular biology. This flexibility would increase the feasibility of the proposed project exponentially. This proposed method would be facile and allow for high-throughput screenings to identify novel small molecules that regulate gene expression at the transcription level. Since the readout does not involve other steps besides transcription in gene expression, one will be able to observe transcriptional activities without disrupting living cells. A REU student is expected to carry out synthetic studies for the preparation of combinatorial library compounds.[1/02] |
Professor Kenneth Jordan |
Computer "Measurements" of the Properties of Atomic and Molecular Clusters |
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Computer simulations permit "measurements" on complex chemical systems
that would be difficult or expensive to characterize experimentally. In this project the student will use Monte Carlo or molecular dynamics computer simulation methods to characterize the melting behavior of neutral and charged water clusters. [1/02] |
Professor Kenneth Jordan |
Computer measurements of Protein Folding |
| Computer simulations have proven very valuable in providing insight into the protein folding process. In this project the student will explore the use of new optimization methods for locating the global minimum structure of models for protein folding. The project is flexible in the sense that the student can either use computer codes already developed within our group or can become involved in extending the codes to be more flexible. [1/02] | |
Professor Joseph Grabowski |
Measuring Activation Volumes for Reactive Intermediates: Application to Mechanism Determination in C-H Bond Activation |
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The activation of C-H bonds remains a potentially useful target in the area of organometallic chemistry. The design of catalysts, such as those necessary for C-H bond activation can be approached in at least two different ways, either by empirically trying compounds or by elucidating the detailed mechanism and from it, selecting the appropriate catalytic molecule to prepare and use. A major limitation in mechanism elucidation are tools for the characterization of the key reactive intermediates along the reaction coordinate. |
Recently, a new tool,
Photoacoustic Calorimetry (PAC) has emerged as a reliable methodology
which allows for the characterization of intermediates in at least some
reactions.(Ref. 1) In this project, the student will use the custom-built
PACs in the Grabowski group to measure the volume changes associated with
photodissociation of CO from selected metal carbonyls (e.g., CpMn(CO)3,
Cr(CO)6, etc.) in order to create a data base of values that
can be used to interpret the meaning of a similar measured volume change
for a proposed intermediate in an actual C-H activation catalyst. The
student will conduct a series of PAC experiments in an homologous series
of solvents, will experimentally measure the absolute quantum yield in one
of those solvents and relative values in the remaining solvents, and then
will interpret their observations, using custom-designed data alogrithims,
in terms of proposed intermediates. Simultaneous to making a series of
much-needed measurements, the student will also have the opportunity to
contribute to the refinement of this newly emerging, general purpose
measurement technique, either through instrumental or data reduction
modifications brought about by an understanding of their problem and the
operation of the existing instruments and programs.(Ref. 2)
[1/02] 1. Listening to Reactive Intermediates: The Application of Photoacoustic Calorimetry to B12", R. R. Hung; J. J. Grabowski J. Am. Chem. Soc., 1999, 121, 1359-1364 2. "Photoacoustic Calorimetry: An Advanced Undergraduate Physical-Organic Chemistry Laboratory", B. Fletcher; J. J. Grabowski J. Chem. Ed., 2000, 77, 640-645. |
Professor Joseph Grabowski |
Measuring the Specificity and Rapidity of Ion-Molecule Reactions for Real-Time Complex Mixture Analysis. |
| Gas-phase ion chemistry has
contributed enormously to our basic understanding of fundamental organic
chemistry properties and reactions, especially since the landmark papers by Brauman on
the acidities of the alcohols and basicities of the amines.(Ref 1)
We are now well positioned to use the chemical understanding that has
accumulated, along with the unique instrumental capabilities of the
Flowing Afterglow to develop applied, analytical
applications for the real-time, quantitative analysis of complex mixtures
of volatile organic compounds. For example, patients diagnosed with
schizophrenia seem to have substantially higher amount of carbon disulfide
on their breath than others, suggesting that it is being synthesized
somehow. However, these early studies were carried with cumbersome
chemical procedures necessarily limiting the amount of data that was
collected.
Can we design specific chemical reactions, which combined with the unique capabilities
of the Flowing Afterglow, can be used to identify and quantitate carbon
disulfide, in real time, in a complex mixture, without requiring
chromatography and without requiring calibration curves? The student working on this project will use our
laboratory based instrument (the SIFT, Figure; Ref. 2) to measure the specificity and
rapidity of some novel ion-molecule reactions in order to evaluate their
potential usefulness in for carbon disulfide detection. Once ideal
reactions are identified and characterized, they will then be applied to
complex mixtures to establish reliability and detection limits for
authentic samples. [1/02]
1. Brauman,
J. I.; Blair, L. K. J. Am. Chem. Soc. 1969, 91,
2126-2127. Brauman,
J. I.; Riveros, J. M.; Blair, L. K. J. Am. Chem. Soc. 1971, 93,
3914-3916. |
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Professor Paul Floreancig |
Measuring Stereochemistry to Aid Mechanistic Studies of the Single Electron Oxidation Initiated Cyclization |
| In this project the student will make measurements designed to explore the mechanism of a new chemical reaction, the single electron oxidation initiated cyclization, by determining the extent to which stereogenicity can be retained when an enantiomerically enriched substrate undergoes cyclization. Two mechanistic extremes can be envisioned for this transformation (shown below). The student working on this project will be expected to prepare enantiomerically enriched substrates and then subject them to the cyclization conditions. The extent to which each mechanism contributes to the overall process can be determined by comparing the enantiomeric excesses of the products to those of the substrates versus that predicted for each mechanism. Among other things, this project will provide the student with experience in the use of spectroscopic and/or chromatographic techniques for the measurement of enantiomeric excesses, and in the design of simple experiments directed toward the development of a mechanistic model for an organic reaction. [10/00] | |
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Professor Dennis Curran |
Synthesis and Measurements of New Fluorous Reagents |
| Recently developed techniques for
"fluorous synthesis" unite the reaction and separation processes in organic reactions (Refs.
1,2). Molecules bearing fluorous (highly fluorinated) tags can be separated from organic (non-tagged) molecules by fluorous
liquid-liquid or solid liquid extraction. However, because the field is very young, there are relatively few fluorous reagents
available to pair with the new separation techniques. This project will involve the synthesis of a new fluorous reagent or
protecting group and the study of its use in representative organic
transformations. [1/02] 1. A. Studer; S. Hadida; R. Ferritto; S. Y. Kim; P. Jeger; P. Wipf; D. P.Curran, Science 1997, 275, 823-826. 2. Luo, Z. Y.; Zhang, Q. S.; Oderaotoshi, Y.; Curran, D. P. "Fluorous mixture synthesis: A fluorous-tagging strategy for the synthesis and separation of mixtures of organic compounds" Science 2001, 291, 1766-1769. |
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Professor Ted Cohen |
Using Spectroscopic Measurements to Determine the Products of Alkyl Lithium Induced Diene Polymerizations |
| In a recent study of the lithium ene-cyclization, the intramolecular addition of an allyllithium to an unactivated alkene, we have learned that the reaction is far more facile than the better known magnesium ene-reaction but, unlike the latter, it is thermodynamically unfavorable and will only be observed when it is followed by an irreversible consummating reaction such as a 1,5-transfer of an allylic proton. This new insight allows for the first rational explanation of the fact that polymerization of butadiene or isoprene, initiated by butyllithium in the presence of tetramethylethylenediamine (TMEDA) under conditions that lead mainly to 1,2-addition, produces polymer with a substantial percentage of ring structure provided that the butadiene is fed in slowly. A number of very unsatisfactory explanations have been put forth in papers and patents. We surmise that in the case of butadiene the process shown in the scheme is occurring to form 1. In the case of isoprene, the 1,5-proton transfer is from an allylic methyl and an important intermediate would be protonated in workup to produce 3. The undergraduate research project would consist of performing oligomerizations using 3 moles of diene per mole of butyllithium. In the absence of excess diene, 2 or 3 would be produced. Various measurement techniques would be used to prove their structures. These will include 1D and 2D NMR spectra, IR spectra, mass spectra, unsaturation determination, and x-ray crystal structural measurements of a derivative. [10/00] | |
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Professor Rob Coalson |
Computer-based Measurement of Electric Current through Nanostructures |
| The Coalson group performs calculations of charge transfer
through both biological and synthetic nanostructures. In paricular, we study the transport of ions like Na+ and Cl- through protein channels which are embedded in cell walls. We also study electron transport through organic molecular wires. Fundamental concepts from theoretical chemistry are converted into computer programs which are run on large-scale computer platforms such as Pitt's Center for Molecular and Materials Simulation. These calculations aim to increase understanding of the charge transfer processes involved, and ultimately to enable improved design of both biological and synthetic nanowires and nanopores. Undergraduates with a strong interest in computing and physics, as well as chemistry, may find this line of research appealing. |
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Professor Toby Chapman |
Measuring the Effects of Covalently Attached Growth Factors in New Tissue Engineering Templates |
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We are interested in making biodegradable polymer templates for tissue engineering that contain functional groups allowing for attachment of recognition peptides and growth factors. We propose to make initiator molecules containing protected amines from which can be grown polylactic-polyglycolic acid copolymers or polycaprolactone. The amines would be unmasked under mild conditions and some short peptides would be attached. We would then test these for their competence in growing osteoblast precursor cells. We would also test the effect of covalently attaching growth factors know to be important in cell growth. [3/02] |
Professor Toby Chapman |
Measuring Solution Property and Surfactant Ability Differences in Symmetric and Asymmetric Isomeric Dendrimers. |
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Dendrimers are highly branched, uniform polymers with a number of very interesting properties. We have been studying amphiphilic poly-L-lysine dendrimers for their surfactant and emulsifier properties with their possible use in controlled drug delivery. Most of the dendrimers currently studied are symmetrical molecules with symmetry at each branching point. Polylysine, with both a-, and e-amines is not symmetric. Symmetry is believed to be important in some of the special solution properties of dendrimers but this, in fact, remains unstudied. We wish to synthesize a symmetric, achiral isomer if lysined, 4-amino-2-(2-aminoethyl)butanoic acid and prepare the corresponding dendrimers. These would be tested for their solution properties and surfactant properties to the lysine dendrimers and in this way test the influence of dendrimer symmetry, if any, on these properties. We will compare the ability of these molecules to solubilize hydrophobic medications as well. [3/02] |
Professor Toby Chapman |
Measuring the Light Emission and Non-linear Optical Properties of a New Conjugated Dendritic Polymer. |
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Conjugated dendrimers are rare, only one reported in the literature. A conjugated poly(phenylene vinylene) dendrimer would be of interest to compare with the known linear polymer. The latter emits light under the influence of an electric field and is a conductor of electricity after “doping”. The comparision with the dendritic isomer would be of interest. Also, these compounds should show the property of harvesting light and concentrating the energy at the central core. We propose to use these properties to make a photoredox catalyst as well as to create an organic quantum dot with strong non-linear optical properties.. [3/02] |
Professor Eric Borguet |
Measuring and controlling charge transfer and trapping processes at semiconductor interfaces with nanotechnological applications |
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With the ultimate goal of integrating molecular electronics with semiconductor electronics for nanotechnological applications, undergraduate researchers, working with advanced graduate students, will construct chemically modified semiconductor interfaces and probe charge transfer and trapping process at these interfaces. Our strategy is to design organic monolayers decorated with chemical functional groups that can provide either electron donating or accepting capability. Nonlinear optical techniques, that provide surface sensitivity are used to probe the charge transfer processes that may be initiated by a variety of means including optical, chemical and electrochemical perturbation. Students will have the opportunity to explore synthesis as well as state-of-the-art ultrafast laser spectroscopy. A variety of other probes including Atomic Force Microscopy and Scanning Tunneling Microscopy are available to characterize the surfaces on the nanometer scale. [2/01] |
Professor Sanford Asher |
Direct Spectroscopic Measurements of the First Steps in Protein Folding |
| With the completion of the determination of the human genome we will know the primary structure of the ~100 K proteins we make in order to live. Most human disease results from errors in the synthesis of proteins. It is now possible to determine the primary structure differences between the diseased protein and the normal protein. Strategies for disease treatment could be developed if the structure and function of the diseased and normal proteins were known. Unfortunately, the structure and function of over 95,000 of these proteins are unknown. Although it should be possible to calculate the structure and function of proteins from their primary sequence, the laws of protein folding are as yet unknown. My group is determining the rules of protein folding using measurements made with powerful laser techniques. This research program offers you the opportunity to have a positive impact on the human condition while learning both spectroscopy and biology. [1/02] | |
Professor Sanford Asher |
Measurements to Optimize Intelligent Materials for Chemical Sensing and Optical Switching |
| My group has developed novel smart materials whose optical properties can be altered by chemical analytes and light. These materials are being developed for use as optical switching transistors for the next generation of optical computers. In addition, these materials are being developed for use as in vivo glucose sensors for diabetic patients. The idea is to implant this sensor under the skin and to monitor its color in order to detect the glucose concentration. This is a research program which will teach students how to make measurements on prototype materials and then use the results of these measurements in conjunction with aspects of polymer synthesis, materials science and optics to refine the sensor under development. [1/02] | |
Professor Shigeru Amemiya |
Measuring Surface pH by Electrochemical Nanosensors |
| pH is an important parameter that determines the extent and rate of many chemical and biological reactions. Glass electrodes, therefore, have been widely used for decades to measure pH in bulk solutions. However, when such reactions occur at a surface, pH changes only near the surface. Surface pH, for instance, can be changed by transport of H+ through ion channels across biomembranes and by corrosion at metal surfaces. In order to quantitatively study surface reactions of biological and industrial importance, we will fabricate and characterize electrochemical pH sensors in submicrometer and nanometer dimensions. The pH sensors will be fabricated by using different materials such as polymer membranes and metal oxides. The sensors will be used as a probe of scanning electrochemical microscopy to measure surface pH in situ. For more information, please visit my web page by clicking my name!. [2/02] | |
REU Web page maintained by Prof. Joseph J. Grabowski. Updated
