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Proposed Research Projects
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Use of Persistent Radical Catalysts in Living Polymerization Reactions
Dr. Alexandru Asandei (Polymer Chemistry)
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Our group is interested in complex unconventional organic and polymer syntheses, new concepts, reactions and mechanisms. This includes radical polymerizations, polycondensations, liquid crystals, auxetic materials, self assembly and nanostructures. Molecular weight and polydispersity control in living radical polymerization (LRP) is based on the persistent radical effect (PRE). Persistent radicals are not involved in homodimerization reactions or addition to the double bond, and maintain radical concentration at low levels via their reversible end-capping with the growing chain. Various carbon or oxygen centered radicals (nitroxides, addition fragmentation derivatives) and metaloradicals (Cu, Ni, Fe, Ru complexes) are usually employed in LRP. Novel organic and inorganic systems capable of accomplishing LRP are currently being explored. One goal is the design, synthesis and characterization of catalysts capable of dual or multiple mechanism-polymerizations. The REU student will be involved in the synthesis of monomers, catalysts and polymers and in their characterization. He will acquire experience in organic, inorganic and polymer chemistry and will become familiar with instruments such as NMR, GPC, and DSC.
Asandei Group Web Site
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Novel Chemistry of Oxoammonium Salt: Environmentally Benign Oxidations
Dr. William Bailey (Organic Chemistry) |
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One of the primary research interests of our group involves development of novel synthetic methodologies. Much of our effort is devoted to the use of reactive main-group organometallics, particularly unsaturated organolithium compounds, for the generation of carbon-carbon bonds.
Recently, in collaboration with Prof. James Bobbitt of our department, we have begun to explore the use of oxoammonium salts for the oxidation of a variety of functional groups [Org. Letters 2006, 8, 5485; J. Org. Chem. 2007, 72, 4504]. Our efforts in this area have focused on investigation of the utility of 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (1), an inexpensive, readily prepared, and thermally stable oxidant that offers an environmentally benign alternative to more commonly used Cr(IV) reagents. |
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A particularly intriguing oxidation of benzyl ethers, displayed below, was discovered in the course of our investigations. The scope, limitations, and mechanism of this unprecedented reaction remain to be explored. This project is designed to allow a talented undergraduate to complete a project of some significance in a relatively short period of time. The study will expose the student to classical synthetic methodology as well as more modern techniques required for investigation of reaction mechanism. In addition, the project will acquaint the student with the use of chromatographic (GC, HPLC, TLC) and spectroscopic techniques (NMR, HPLC, GC/MS) used for the purification and identification of intermediates and products. |
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Synthesis and Study of DNA Damages
Ashis K. Basu (Bioorganic Chemistry) |
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We study chemicals and drugs that exert their biological effects through DNA damage. Some of the chemicals are environmental pollutants such as 1–nitropyrene. We also study ionizing radiation-induced DNA damages. The REU student will synthesize a specific DNA damage such as a DNA adduct of a nitroaromatic compound or induce an ionizing radiation damage into a designed oligo¬deoxy¬nucleotide. These DNA lesions can induce mutations which may represent the first step converting a normal cell into a cancer cell. Our goal is to correlate the type of mutation with three dimensional architectural effects induced in DNA. The modified DNA fragments will be used to study mutagenesis and DNA repair.
The project will introduce the REU student to a variety of organic synthesis and nucleic acid chemistry tools, chromatography, and structural characterization (NMR, UV-Vis, MS), and introduce the student to molecular biology and recombinant DNA techniques.
Basu Web Site
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Protein-Based Photovoltaic Devices
Dr. Robert R. Birge (Physical, Biophysical Chemistry) |
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One of the key challenges of the 21st century is to harness solar energy to provide clean and efficient power. Much work has been done using semiconductor technology, but despite considerable effort and significant expenditures, solar cells still operate with net efficiencies of only ~20%. In contrast, nature converts light to energy with 40% - 75% net efficiency. This project explores proteins as high efficiency photovoltaic converters. The proteins to be studied include bacteriorhodopsin and variants optimized via genetic engineering for photovoltaic applications. The cell that we are investigating not only generates electricity but also converts water into hydrogen and oxygen. The system has the potential of operating at a net efficiency of 55% or more. This research involves electro-chemistry, organic chemistry and biochemistry, and the interested student will decide which aspect of the project is of personal interest and contribute in that area. The student will be exposed to a more applied area of biochemistry and biophysics than is encountered in an undergraduate course or laboratory. Previous REU students have found this experience to be both unusual and intellectually exciting.
Birge Web Site
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The Conformation and Rotational Spectrum of N-Methylaniline
Dr. Robert K. Bohn (Physical Chemistry) |
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One research program of our group explores structures of substituted benzene compounds. In ethyl benzene, Ph-Et, the ethyl C-C bond lies in a plane orthogonal to the benzene ring while in the isoelectronic compound, anisole, Ph-O-Me, the O-C bond lies co-planar with the benzene ring. N–Methylaniline, Ph-NH-Me, is isoelectronic to ethyl benzene and anisole. There are two basic questions concerning its structure. What is the conformation of the methylamino N-C bond with respect to the benzene ring; orthogonal as in ethyl benzene, co-planar as in anisole, or adopting an intermediate conformation? Is the bonding around the N atom of the amino group coplanar as in an amide or pyramidal as in an amine?
The REU student will determine the structure of N-methyl aniline experimentally using microwave spectroscopy and computationally using quantum chemical calculations. As previous years have shown, the study is well-suited as a summer project for a bright, energetic REU student.
Bohn Web Site
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Synthesis of Pyrrole-Modified Porphyrins
Dr. Christian Brueckner (Organic Chemistry) |
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Photodynamic therapy (PDT) employs the combination of a photosensitizer, such as a porphyrin, and light to destroy diseased cells. For PDT to be most effective, the light that activates the drug must penetrate deep into tissue. However, while tissue is only transparent for red and infrared light, porphyrins cannot be activated using red light. Thus, our group has set out a program to modify synthetic porphyrins in a way that they can become photosensitizers which can be activated with red light. Although porphyrins are ubiquitous naturally occurring macrocycles, the regio-selective modification of them can be difficult. Hence, synthetic compounds are needed. We modify a class sof symmetric meso-aryl-substituted porphyrins by formally replacing one pyrrole by a different heterocycle. One reaction sequence involves the cleavage of the ß,ß’-bond (1 to 2), followed by ring-closure to, in this example, form morpholine-derived porphyrin 3. |
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The REU student will do multi-step syntheses (1-4 steps), purification (column and preparative thin layer chromatography) and characterization (UV-vis, IR, fluorescence spectroscopy, NMR) of porphyrins and metalloporphyrins (NiII, ZnII, AgII). The student will learn many analytic and synthetic techniques employed in modern organic and coordination chemistry.
Brückner Group Web Site
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Development of Caged-Complexes for Zn2+
Dr. Shawn Burdette (Inorganic Chemistry) |
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Zn2+ has many well-understood structural and catalytic functions of in biology; in addition, current research suggests that free Zn2+ may function as a neurotransmitter and have a role in the pathology of several neurological diseases. Studying these physiological functions remains challenging because Zn2+ is silent to most common spectroscopic techniques. Fluorescent sensors have been utilized to study biological questions, however, there are limitations to the information these chemical tools can provide. While fluorescent sensors can image endogenous metal ions, directly correlating fluorescence signals to specific biological events can be difficult. In order to elicit a physiological response, Zn2+ can be released from synaptic vesicles by electrical stimulation, or applied exogenously. Although observations made using these techniques may suggest certain functions, the concentration of Zn2+ used to initiate the activity may not be physiologically relevant. Caged compound can circumvent this problem by allowing controlled release of the analyte. Caged compounds release analytes of interest upon exposure to light of a specific wavelength. We are interested in developing several classes of caged-complexes for Zn2+. |
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The REU student will be involved in the synthesis of caged complexes, studying the metal coordination chemistry and photochemistry. Through this research, a student will learn techniques related to organic and inorganic synthesis, compound characterization, coordination chemistry and spectroscopic techniques.
Burdette Group Web Site
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Carotenoids in Biological Systems
Dr. Harry A. Frank (Biological and Physical Chemistry) |
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Carotenoids are ubiquitous brightly colored natural pigments that occur in a number of biological organisms (e.g. see the figure)*. All carotenoids come from photosynthesis where they play several important roles: Light-harvesting, photoprotection, singlet oxygen scavenging, excess energy dissipation, energy flow regulation, structure stabilization, and electron transfer. The most famous carotenoid is ß-carotene, the structure of which is shown. |
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A major goal of our research to understand how these molecules are able to carry out such diverse functions. The structures of carotenoids are being deduced in solution and in isolated photosynthetic pigment-protein complexes using X-ray diffraction, nuclear magnetic resonance (NMR) and resonance Raman spectroscopic techniques. In addition, information from steady state (absorption and fluorescence) and kinetic (nanosecond and femtosecond time-resolved) molecular spectroscopy is being used to help pinpoint specific molecular features that control the photochemical and photophysical processes they undergo in conjunction with chlorophyll after photoexcitation. This research will expose the participating REU student to topics in biochemistry, microbiology, bioanalytical chemistry, molecular spectroscopy, kinetics, and quantum chemistry. No prior knowledge of these areas is required, however – only a willingness to learn. For a podcast describing our research on carotenoids please visit our group’s web site.
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* The photograph was provided through the kind generosity of Mr. Jay Kimball, Wood's Seafood Market and Restaurant on the town pier, Plymouth, Massachusetts. |
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Synthesis of Novel Nucleosides
Amy R. Howell (Organic Chemistry) |
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Strained oxygen heterocycles, such as epoxides, play a role as biologically significant entities, as well as being versatile intermediates in the syntheses of a variety of molecules. Recently, our group has developed the first general synthesis of 1,5-dioxaspiro[3.2]¬hexanes 1, an unusual and little explored class of compounds. We discovered that dioxaspirohexanes display a fascinating dichotomy of reactivity, providing either highly functionalized ketones 2 or substituted oxetanes 3. We have recognized that with the proper nucleophile we can access novel nucleoside analogs 4. Nucleosides continue to be key therapeutic agents for the treatment of viral diseases, such as HIV and hepatitis B, and of certain types of cancer. |
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The REU student will prepare appropriately substituted dioxaspiro¬hexanes by well-established protocols and explore conditions for the efficient conversion of these compounds to novel nucleoside analogs. The student will routinely use chromatographic (GC, TLC, column chromatography) and spectros¬copic (NMR, IR, GC/MS) techniques for the purification and identification of intermediates and products.
Howell Group Web Site
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Photochemical Footprinting of Proteins
C. Vijaya Kumar (Biophysical) |
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Reagents that cleave proteins with high specificity under photochemical conditions (photochemical proteases) are useful for structure-activity studies of proteins, investigation of protein structural domains, and in converting large proteins into smaller fragments for mass spectrometry analysis.
Our research team discovered the first approaches to photochemically cleave proteins at specific sites. In the REU project, selected Co(III) and Cr(III) complexes will be prepared, and they will be used to replace bound metal ions on selected proteins (Steps 1&2). The protein-probe complexes will be photo-activated to cleave the protein backbone (Step 3). Competitive inhibition of the photo¬cleavage by the initial metal ion (Step 4) will test if the photocleavage is occurring at the anticipated metal binding site. |
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The REU student will analyze the peptide fragments by HPLC and sequence them using Edman degradation. Molecular modeling (RasMol) will be used to rationalize the observed protein cleavage sites. The student will gain experience in organic and inorganic synthesis as well as in spectroscopic methods. Advanced molecular modeling studies will particularly enhance the REU student's experience with integrated research methods that are not normally encountered in the standard undergraduate curriculum.
Kumar Group Web Site
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From the Kitchen to the Lab
Dr. Nicholas Leadbeater (Inorganic Chemistry) |
We all know that microwave ovens can be used for heating food fast. An exciting area of study in the synthetic chemistry community is the use of microwaves for making molecules rapidly, easily and cleanly. Using microwave heating, it is possible to enhance the rate of chemical reactions significantly and to do chemistry that was otherwise not possible. Unlike the microwave at home, we use state-of-the-art scientific microwave systems that allow precise control of reaction conditions. One limitation at the moment is the scale-up of reactions to make multi-gram or kilo quantities of compounds. However, we are about to receive a microwave apparatus that is designed to overcome this hurdle. As an REU student, you would play an important role in using this apparatus over the summer and would have your own mini-project focused around the use of microwave heating for scaling-up reactions. You will be mentored by a graduate student in the group. The reactions will be performed in water as a solvent rather than organic solvents thus making the chemistry more environmentally friendly. As well as being exciting, the project will introduce you to a range of modern synthetic chemistry techniques as well as analysis methods.
Leadbeater Group Web Site |
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Determination of the Metal Speciation in Biological Samples by Laser Ablation-ICPMS
Dr. Robert G. Michel (Analytical Chemistry) |
Research is based on the use of lasers, and chromatography, in novel analytical instrumentation to achieve extraordinarily high sensitivity, high accuracy selectivity, and
microsampling capabilities. Present research projects include work on the speciation of organometallic compounds, such as metalloproteins in biological samples, and mercury in fish, by use of chromatography to separate the compounds followed by detection of the metals with such techniques as laser excited atomic fluorescence in a flame or graphite furnace, or inductively coupled plasma mass spectrometry. Also, we are studying various topics in laser ablation of samples for ultra-trace metals determinations; and several projects that apply the techniques of atomic spectroscopy to the determination of the elements in environmental, biological, metallurgical, forensic samples, and samples of other materials such as polymers. The REU student will gain skills involved with the use of modern tunable laser technology, inductively coupled plasma mass spectrometry, atomic absorption and various chromatographic techniques, and will learn how the types of techniques encountered at the undergraduate level are used in research on analytical chemistry for the solution of important physical and biological problems. |
Michel Group Web Site |
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Nanoscale Controlled Light Emitting Devices by Self-Assembly Techniques
Dr. Fotios Papadimitrakopoulos (Polymer Chemistry |
Implantable biosensors could be a plausible way to continuously monitor blood glucose levels, provided they exhibit long-term stability and means to establish telemetry. However, their potential applications remain largely unexploited due to the negative tissue responses such as biofouling, inflammation, tissue fibrosis, and calcification generated by the implantation of such devices. Other problems such as electrical short, signal drifts and need for continuous calibration can lead to device malfunctioning and eventually failure. Also, one of the chief concerns is the possibility of sensor breakdown because of oxidative degradation of enzyme and other electrode coatings due to excess of hydrogen peroxide present in the immediate vicinity of the sensing electrode. This is a direct result of over-sampling of the glucose in the blood stream. Coating the device by a biocompatible, semipermeable membrane can rectify this situation. Apart from acting as a barrier to permeation of glucose, the membrane would protect the sensor from foreign molecules that cause fouling.
Our group investigated the simplistic, yet versatile approach of layer-by-layer (LBL) self-assembly of assembly of Humic Acids (Has), a naturally occurring biopolymer and Fe3+ cations. Not only did these coatings provide the required degree of glucose permeability, but in vivo results indicated their biocompatibility with reduced tissue fibrosis upon implantation. Furthermore, the conformation and growth characteristics of the HAs/Fe3+ membrane could be tailored by carefully adjusting the pH of the aqueous medium. Apart from the HAs/Fe3+ bilayers, we self-assembled films of HAs/poly (diallyldimethylammonium chloride) (PDDA) and also films of poly (styrene sulfonate) (PSS)/PDDA onto the sensory device. Moreover the diffusion coefficients of glucose through these membrane systems were investigated in order to explain the individual sensor response as it pertains to the microstructure of these outer semipermeable membranes. The hysterisis behavior of these sensors was studied as a function of permeability of the outer membrane. It was concluded that the microstructure of these coatings govern the permeability of glucose and correspondingly, the sensitivity, longevity and hysterisis of the sensors.
We plan to extend this outer membrane research to a more biocompatible polyelectrolytes like poly saccharides and proteins, which we aniticipate to finish within one summer. The incoming REU student will be exposed to a variety of techniques including electrochemical sensor fabrication, electro-analytical techniques, ellipsometry, enzyme immobilization, electropolymerization of conducting polymers, layer by layer assembly, in vitro and in vivo testing of electrochemical sensors as well diffusional based theoretical modeling of electrochemical sensors.
Papadim. Group Web Site |
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Synthesis as a Tool in Glycoscience
Dr. Mark W. Peczuh (Organic Chemistry) |
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Carbohydrates are indispensable to biological processes such as metabolism, protein folding, and cell-cell interactions. Our group is interested in the design, synthesis, and characterization (conformation, binding) of ring expanded carbohydrates that can interact with natural proteins such as lectins and glycosidases. The preparation of novel ligands of these two broad groups of carbohydrate binding proteins may provide new tools for glycobiology or even future drug leads.
The REU student will synthesize septanose carbohydrate glycosides and glycoconjugates designed for their ability to bind natural lectins and glycosidases. The routes for their synthesis will rely on established procedures, or will be developed by the student. They will be multistep sequences (4-6 steps), where compound purification (chromatography, crystallization) and spectroscopic characterization (NMR, IR, CD, MS) are critical aspects of the research. |
Peczuh Group Web Site |
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Electrochemical Enzymology with Thin Enzyme Films
Dr. James F. Rusling (Analytical, Physical Chemistry) |
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A goal in our research is to design stable thin films in which enzyme reactions are driven by direct electrochemistry. One enzyme process we are interested in is the cytochrome P450 catalyzed toxin activation of organic pollutants, a process occurring in the human liver. This process can result in the damage of DNA by the activated pollutants, a process which may be involved in carcinogenesis.
In the REU project, the student will utilize newly developed thin-film electrode coating techniques for in vitro studies of DNA damage by activated pollutants. Heme-, myoglobin-, and cytochrome P450-based systems will be designed to mimic natural toxic activation of pollutants and DNA damage. The devices will employ electron injection from electrodes to drive the enzyme-catalyzed pollutant activation and subsequent damage of DNA. Electrochemical and chromatographic analyses will be used to monitor these events. The student will learn state-of-the-art film preparation technology, thin-film cyclic voltammetry, and LC and GC.
Rusling Group Web Site
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Surface Initiated Polymerization on Inorganic Oxides
Dr. Thomas A.P. Seery (Polymer Chemistry) |
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Nanostructured materials have generated intense interest in recent years. The ability to control molecular structure on a scale intermediate between organic molecules and bulk matter has become increasingly important in technologies relying on thin organic films. Our research has advanced the concept of surface initiated polymerization (SIP) as a means to prepare conformal polymer monolayers on hard substrates. Gold and silicon oxide surfaces have been used as model systems to demonstrate this concept. Idealization of SIP consists of the following steps: (1.) Surface coverage of initiator is formed. (2.) Active catalyst is generated. (3.) Polymerization via chain growth mechanism provides polymer with catalyst on the living ends. (4.) Endcapping gives control over ultimate surface properties.
The REU student working on this project would lead the effort to extend this concept to titanium oxide surfaces. This is a fairly challenging task, but the student would be working alongside an interdisciplinary team of experienced graduate students and postdoctorals. The first task would involve functionalizing the titanium surface with monochlorosilane coupling agents that have terminal vinyl groups. The next step is detection of these species at the surface using ellipsometry and contact angle measurements. The vinyl species will be reacted with ruthenium alkylidene complexes to form catalytic species on the surface. Polymerization then occurs after addition of strained cyclic olefins. This project is modular, and the interdisciplinary nature will allow a student the freedom to focus on either synthetic or physical chemistry.
Seery Web Site
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New AIDS Drugs, Polymer Reagents, Anti-Cancer Drugs, and Natural Product Isolation
Dr. Michael B. Smith (Organic Chemistry) |
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My laboratory uses synthetic methodology and total synthesis techniques to solve problems in areas ranging from biomedical applications, to environmentally friendly chemical processes. We are developing the total synthesis of the anti-cancer compound pancratistatin based on an intramolecular are-oxazolone-driven Diels-Alder strategy. We are also using a chiral lactam as a template, combined with ring-closing metathesis techniques to prepare several classes of biologically active alkaloids.
We have synthesized 5-hydroxymethyl-2-pyrrolidinones with nucleobases at C3, as a new class of anti-viral drugs, with the goal of treating HIV. We are collaborating with the department of periodontology at the UConn Health Center to synthesize and verify the structure of a series on lipids, isolated from Pseudomonas gingivalis, that are powerful inflammatory agents and lead to serious disease. There is also some evidence that these compounds are present in atherosclerosis plaques, suggesting a link to heart disease. The goal is to verify the structure of the compounds and prepare the inflammatory agents for further biological testing.
We have also discovered, in collaboration with Professor Gregory Sotzing, that conducting polymers oxidize alcohols, without the need to attach other reagents to the polymers. This constitutes a new paradigm in polymer chemistry and will be an important contribution to environmental chemistry. The polymer oxidant can be recycled and does not involve toxic heavy metals. This work has significant implication to sensor research, and we have also embarked on new methods for the synthesis of small-ring heterocycles, that can be used to prepare important monomers, that lead to new conducting polymers. we are also looking at the possibility of preparing hydrogel polymers that are conducting, for use as nerve regenerating agents.
Smith Group Web Site
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Microwave Synthesis of Nanostructured Solids
Steven L. Suib (Inorganic Chemistry) |
Our NSF funded collaborative project with researchers at the U. of Massachusetts focuses on using microwaves for the synthesis and catalytic studies of porous octahedral molecular sieves and layered materials. These systems include Mn oxides and oxides of V, W, Ta, Fe, and Cr. We developed a novel in situ mixing nozzle microwave process, which involves mixing of precursors, formation of mixed droplets in an ultrasonic nozzle, followed by rapid microwave heating in a vertical reactor. This process has allowed formation of nano-size particles of various single and mixed metal oxide materials of a variety of structures.
This project is ideal for an REU student, particularly in synthesis, where much of the apparatus and techniques have already been developed and the REU student can learn about microwave cavity and reactor design. Kinetic and catalysis experiments can also be investigated, which involve use of various chromatographic and mass spectrometry methods for product analysis.
Suib Group Web Site |
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Mass Spectrometry to Investigate Micro-Scale Preparation of Peptide Samples
Dr. Xudong Yao (Analytical Chemistry and Biological Chemistry) |
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Mass spectrometry is used as a fast and sensitive tool to study peptides. Mass spectrometry analyzes charge-to-mass ratios of peptide ions in gas phase. A mass spectrum plots the intensities of ions against their charge-to-mass ratios. These ratios can be used to determine chemical structures of peptides, while the intensities give relative quantitation of the ions. Sample preparation of peptides is a key step for successful mass spectrometric analysis, and it is often done at a micro-scale. In REU summer projects, students will work on different sample manipulations of peptides such as chemical modification of peptide mixtures and use mass spectrometry to study the efficiency of various micro-scale procedures for peptide sample preparation.
The REU project will specifically investigate analytical challenges in mass spectrometric analysis of phosphopeptides. Phosphopeptides are fragments of phosphoproteins that are important regulators for cellular signaling. Analysis of protein phosphorylation is important to understand and treat various human diseases and to manipulate the fate of stem cells for therapeutic and regenerative applications. The REU researcher will study ß-elimination and Michael addition reactions of phosphopeptides. Objectives of the project are to minimize side reactions and maximize the efficiency of the sample preparation workflow that will be examined by high performance liquid chromatography and tandem mass spectrometry.
Yao Group Web Site |
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