Faculty Research Interests and Projects

Professor Bruce S. Ault, PI

NSF-REU students in my laboratory will work on aspects of the overall project “Matrix Isolation and Theoretical Studies of the Reactivity of High Valent Transition Metal Compounds” (CHE 0243731 – 7/1/03 – 6/30/06). This project involves experimental and theoretical studies to develop a better understanding of the mechanism by which high valent transition metal oxo compounds oxidize organic and inorganic substrates. To do so, my group will identify and characterize the sequence of reactive intermediates in the reaction. Since these are short-lived and highly reactive species, they will be trapped in cryogenic matrices and characterized by infrared spectroscopy. By varying the deposition conditions, the reaction time and thermal energy provided to the initial reactants will be varied in a systematic way. This allows us to “stop” the reaction at different times after initiation, and will permit the trapping of different intermediates. My group also explores the visible/UV spectroscopy, extending our understanding of the electronic states of these reactive species. In addition to experimental work to investigate these systems, theoretical methods will be employed to model the intermediates under investigation. Specific systems of interest include high valent transition metal oxo compounds, including Cl3NbO, MoCl2O2, MoCl4O, the tungsten analogues, and permanganyl chloride ClMnO4. Our interest extends to related transition metal halide compounds, including Cl5Nb, Cl4V, Cl4Zr and Cl5Ta, as well as to a number of cyclopentadienyl (Cp) derivatives (e.g., Cp2TiCl2). Each REU student will have his/her own specific, well-defined project, one that can be substantially addressed in one summer. They will use all of the available tools, including matrix isolation, infrared and visible/UV spectroscopy and theoretical calculations.

Professor Anna D. Gudmundsdottir, co-PI

Recent discoveries in chemistry have led to the synthesis of new materials with fascinating magnetic, electrical and optical properties, which have prompted many new technological advances, anywhere from faster computers to stealth bombers. The pursuit of organic magnetic materials has sparked renewed interest in triplet aryl nitrenes, which are ideal candidates for magnetic materials because of their high spin properties. Several research groups have focused on making the triplet aryl nitrenes long lived. The approach that has given the best results to date is to form these intermediates in inert crystal lattices. We reported the first detection and trapping of triplet alkyl nitrenes in fluid solution and in the solid state.? However, little is known about the reactivity of nitrene intermediates in the solid state. Lack of such knowledge is important, as it prevents us from designing stable triplet nitrenes and utilizing their special physical properties.

Solution photolysis of phosphorazidic acid diphenyl esters yields singlet nitrenes, which decay by reacting with the solvent and by intersystem crossing to form long-lived triplets (see Figure 1). We will study the solid state reactivity of crystalline phosporazidic acid derivatives and correlate their reactivity with solid state structure. We will then apply crystal engineering to design crystals that will yield stable nitrene intermediates. We anticipate that solid state photolysis of the phospharazidic azides yield singlet nitrenes that will intersystem cross to form triplets. An REU student will synthesize the azide precursors and obtain their X-ray structures. This will expose the student to synthetic and purification methods. The student will also gain insight into spectroscopy by characterizing the azides with NMR, IR, mass spectroscopies and X-ray crystallography.

Professor Michael J. Baldwin

Many biological oxidation reactions use metalloenzymes to activate O2 as the oxidant. This strategy of using a transition metal catalyst to activate O2 is desirable for industrial oxidation reactions as well. Our group is interested in further developing an understanding of the factors that determine the efficiency and selectivity of catalytic oxygen activation catalysts so that this “green” technology can be more widely applied. Our strategy is to study the O2 reactivity and substrate oxidations by a transition metal in an oxidation state that generally does not react with oxygen, since this will highlight the critical features required for O2 activation and will likely result in unique reactions. Thus, we have developed a new ligand system that supports the first Ni(II) complexes to react with O2 without the requirement of irreversible ligand oxidation. We are also working to discover related reactions of these Ni(II) complexes with other environmentally or biologically relevant oxidants. Using oxygen as the oxidant, the Ni(II) complexes promote oxidation of methanol to formaldehyde with multiple turnovers. We will use this same substrate oxidation to determine whether oxidants like NO2 or various quinones will oxidize methanol in the presence of the Ni(II) complex. Our preliminary studies demonstrate that quinones are reduced by the Ni(II) complex. Depending on the interests of the student, a project will be developed on some aspect of this research that will focus on inorganic synthesis of metal complexes of interest, organic synthesis of new ligands to expand our ligand library, physical methods such as various spectroscopic and electrochemical techniques to characterize the complexes, or analytical methods to evaluate the reactivity and mechanisms of the methanol oxidation reactions with the different oxidants. Some exposure to each of these areas will accompany the project, which will be guided by both Dr. Baldwin and a graduate student. The student will gain experience in a variety of spectroscopic, synthetic and analytical methods, as well as being actively involved in our research group meetings.

Professor Thomas L. Beck

My group’s research centers on theory and molecular modeling of complex chemical systems. These systems include liquid chromatographic interfaces, biological ion channels, and molecular electronic devices. Our group has developed several novel multiscale methods for electrostatics and electronic structure calculations for the modeling of transport in ion channels and electron motion through molecular electronic devices. Our research on the liquid chromatographic interface led to significant insights into the nature of hydrophobic surface interactions with water. An undergraduate working in our lab will gain expertise in several areas of computational chemistry and molecular modeling, skills that are vital in a wide range of chemical problems. The undergraduate researcher will likely partake in our wide-ranging study of selective ion conduction in chloride channels. We are addressing several issues related to these highly complex proteins, including the ion conduction pathways, calculations of pKa’s of ionizable groups, electrostatic modeling, and molecular dynamics simulations of channel gating. Two postdocs and two graduate students are currently working in the group on these problems, so the student would benefit greatly from active interactions with several experts in the research. Another major benefit is that the research would introduce the student to the rapidly growing area of computational biology. Research in the ion channel field is leading to both fundamental insights into channel function and to new drug design strategies based on channel structure and function. Our group is part of a six-investigator team, including two researchers in the medical school here at the University of Cincinnati, and these highly collaborative projects are beneficial to young scientists exploring interdisciplinary careers.

Professor William B. Connick

In keeping with the objectives of our NSF-sponsored research (CHE-0134975), we have prepared the first example of a two-electron platinum reagent that undergoes nearly reversible, cooperative outer-sphere two-electron transfer. The unique architecture of Pt(pip2NCN)(tpy)+, composed of two mer-coordinating ligands bonded to a Pt(II) center, is capable of stabilizing both square planar Pt(II) and octahedral Pt(IV), thereby allowing for mechanistic studies aimed at elucidating the underlying principles governing multi-electron catalysis.

The proposed research targets the synthesis of complexes with a series of photo-active mer-coordinating ligands, including 4'-pyrel-T. Because a pendant pyrenyl group is known to dramatically enhance the excited-state lifetime of Pt(II) terpyridyl complexes, we anticipate that the target complexes will be the first complexes to undergo photoinduced, reversible outer-sphere two-electron transfer. Students will prepare the ligands and new Pt(II) complexes, including Pt(pip2NCN)(4'-pyrel-T)+. To characterize their products, the students will use NMR spectroscopy, X-ray crystallography and GC mass spectrometry. Students also will examine the kinetics of electron transfer using electrochemical and stopped-flow methods. The photophysical and photochemical properties will be investigated using steady-state emission spectroscopy, as well as time-resolved emission and transient absorption spectroscopies.

Professor Ruxandra I. Dima

My group is developing and applying database mining approaches and other bioinformatics methods to the determination of binding motifs at interfaces between various biological molecules; the goal of this research is to build a repository of specific and non-specific interactions between macromolecules which can be used for targeted drug-design. An REU undergraduate researcher will gain ampleexperience with databases for protein and RNA structures, protein families and motifs and will learn to design software applications to extract statistical information from such large databases. The information obtained through this bioinformatics effort is coupled with computational modeling of biological macromolecules dynamics in order to gain insight into mechanisms of macromolecular assembly with specific applications to amyloid diseases (such as Alzhmeimer's and the Mad Cow Disease) and mechanosensitivity of the cell. An undergraduate researcher involved with this research will gain knowledge of realistic modeling of proteins and their cellular environment (water, ions) and of the computational packages that follow the dynamics of such systems.

Professor William R. Heineman

Professor Heineman's research interests are primarily in the areas of electroanalytical chemistry and bioanalytical chemistry. Many of the projects are interdisciplinary in nature and involve collaborations with scientists in physical chemistry, biochemistry, engineering, and the medical sciences. Currently, most of the research involves exploration of new concepts for development of chemical sensors and biosensors. For example, some projects come from the general area of developing sensors based on spectroelectrochemistry. This new type of sensor combines three levels of selectivity in one device: selective partitioning into a film, electrochemical excitation signal, and optical response signal. The improved selectivity is a breakthrough in sensing methodology. Students on this project gain experience in electrochemistry, absorption and fluorescence spectroscopy, preparation of thin selective coatings, instrumentation, theory to describe the spectroelectrochemical behavior, and applications to environmental and biomedical sensing problems. An REU student becomes part of a large research group of about 15 graduate students, postdocs, and visiting scholars. Although they work closely with more advanced graduate students, each REU student has an independent project of their own. The project has a carefully defined scope so that the student will learn new experimental techniques with which he/she can obtain positive results within a ten-week period. Results from their experiments are typically published in a journal such as Analytical Chemistry with the undergraduate student as a coauthor.

Professor Patrick A. Limbach

We currently have a collaborative NSF grant with Prof. Steven Soper at Louisiana State University aimed at developing new microfabricated (i.e., “lab-on-a-chip”) devices for single cell proteomics (NSF/DBI 0137924). The specific aims of that funded project include developing appropriate polymer-based microfabricated devices that allow for isolation of single cells, followed by cell lysis and proteomic analysis of the protein constituents of single cells. The front-end development work on single cell isolation, lysis and separation is done at LSU. At UC, our group is investigating the analytical performance and limitations of polymer-based microfabricated devices when interfaced to modern mass spectrometry. Our group is responsible for generating modules for on-chip enzymatic digestion, peptide separation and interfacing to the mass spectrometer.

In this project, we are focusing on developing technological improvements that reduce the number of cells needed for accurate protein analysis. Our current research efforts are to develop integrated sample preparation devices that includes immobilizing enzymes directly within the channels of the microchip such that sample losses are minimized between (e.g., tryptic) digestion and mass spectrometric analysis. We have already developed the necessary interface for coupling PMMA-based microchips to mass spectrometry for protein analysis, and we have optimized on-chip enzymatic digestions. The REU students will work side-by-side with group members on enzyme and antibody immobilization studies, will learn how to fabricate polymer-based microchips, and will learn modern proteomics using these devices.

Professor James Mack

Solvent has been considered a necessity in chemical reactions since the days of Aristotle’s proclamation “No Coopora nisi Fluida” (transl. “no reaction occurs without solvent.”) Aristotle based this claim on his observations that water-based foods spoil much faster than dry or powdered foods. Because of this, chemists have been trained to use solvent in organic synthesis to such an extent that solid-state chemistry is not considered. A ramification of solvent-based synthesis is the tremendous amount of solvent waste that is produced. In order to reduce the solvent waste in organic synthesis, our group focuses on solid state organic synthesis specifically through the use of high speed vibrational milling (HSVM). HSVM is a procedure in which solid reactants (crystals or powders) are placed inside a steel vessel along with a steel ball. The vessel is sealed and placed inside the milling apparatus whereby it is agitated. The high speed agitation (60 Hz) forces the steel ball to pulverize the reagents, causing them to react. Our purification procedure generally involves only a water wash, thus minimizing harmful solvent-use both in the reaction as well as at the purification stage. NSF-REU students in my laboratory will work on various reactions using the HSVM technique as well as learn of other environmentally friendly procedures. In order to create a new generation of chemists who think of the environmental ramifications alongside the potential solutions to scientific problems, aspects of green chemistry must be taught to them early in their careers.

Professor Theresa M. Reineke

The development of efficient and nontoxic nucleic acid delivery vehicles has become one of the most significant and fundamental problems facing modern biotechnology research. Due to the dangers associated with viral delivery systems, polymeric vectors now show great promise. However, problems with toxicity, low delivery efficiency, and a lack of insight into the polymer structure-biological property relationships have hampered their use for many research purposes. To this end, it is hypothesized that an understanding will be gained of how discrete chemical and structural functionalities within polymers affect the biological processes involved in gene delivery. The significant preliminary results generated by graduate and undergraduate students involved in this work reveal that very subtle chemical changes in polymers have a significant effect on the toxicity and delivery efficiency of plasmid DNA to living cells.

REU students involved in this interdisciplinary program will gain a uniquely broad and in-depth experience in several areas ranging from synthetic chemistry and polymer science to molecular biology. For example, an REU student in our group will be involved in the process of new monomer and polymer design, synthesis, and purification. Also, students will learn and perform several materials characterization techniques such as: NMR, FT-IR, mass spec., and gel permeation chromatography-light scattering-viscometry. Also, undergraduates will learn the how to perform gel electrophoretic and dynamic light scattering assays as well as experience in several molecular biology techniques such as culturing living cells and performing several biological assays. The students will discover if the new polymers they created have the ability to deliver plasmid DNA containing various reporter genes to cultured cells. If the new polymers have the ability to deliver DNA that contains the luciferase reporter gene, cell lysates will luminesce (the amount of light given off is proportional to the amount of gene expression). Also, the students will learn how to perform assays to determine the degree of toxicity that each polymer structure induces in vitro.

Professor David B. Smithrud

The REU student in the Smithrud Group will be involved in the investigation of unique cellular transport agents. This research program has been designed to provide the student hands-on experience in synthesis, instrumental analysis, molecular modeling, and cellular transport. To ensure that the student obtains a meaningful exposure to this wide range of experiments, a known transporter will be modified, and its ability to associate with and transport a variety of guests will be determined using well-established methods. The student will first perform a series of Monte Carlo and Molecular Dynamic simulations to model the transporter-guest complexes. The modified transporter will then be synthesized, which should require only two or three synthetic steps. Product authenticity will be determined through a combination of NMR and mass spectrometric analyses. Analysis of fluorescence quenching assays will provide association constants for the transporter-guest complexes. Additional information about complex structure will be found using 2D-NMR analysis (COSY, TOCSY, NOESY, and ROESY experiments). The REU student will also perform the cellular transport studies. The student will expose plated cells to the agents and use fluorescence microscopy to find fluorescent cells and capture their image on film. These experiments will be performed in the Dedman Research Group at UC’s Genome Research Insititute (GRI). Besides hands-on research experiences, the REU student will attend our weekly group meetings where we present cutting research ideas and they will have informal discussions with researchers at the GRI who are experts in a wide range of disciplines and have diverse research interests.

Professor Apryll M. Stalcup

Currently, the fastest growing areas of high performance liquid chromatographic separations are in the areas of biomolecule separations and liquid chromatography-mass spectrometry (LC-MS). While the last few decades have seen phenomenal progress in mass spectrometry, the shortfalls inherent in the separations coupled to the mass spectrometer still present considerable barriers to accessing the full information content in biological samples. Biomolecule separations are challenging because they present a variety of interaction modalities ranging from hydrophobic to polar to electrostatic. Our work addresses the urgent need for improved technologies for novel and more universal separation strategies for biopolymers (e.g., polypeptides, proteins, oligonucleotides). Our approach treats separation mechanisms as an interesting paradigm for scientific inquiry. We have integrated the emerging field of ionic liquids into novel separation strategies for biomolecular separations with the goal of providing multimodal retention for the separation of a wide variety of biomolecular analytes. Novel stationary phases are synthesized in-house. Retention data is obtained on the proposed HPLC sorbents beginning systematically with small molecules (e.g., aromatics, nucleotides, amino acids) and extended to larger molecules (e.g., peptides, polynucleotides) as the separation space encompassed by the new media is mapped out. Capillary electrophoretic and liquid chromatographic techniques are used synergistically to explore selector/selectand interactions. Thus, the project provides excellent educational opportunities for undergraduate students. The integration of synthesis, materials characterization and separations in this project engenders the multi-faceted skill set and critical thinking expertise that is required both in graduate school and in the workplace.

Professor George Stan

Chaperonins are biological nanomachines that employ a spectacular mechanism to assist protein folding. During the chaperonin cycle, concerted, large scale, rigid body conformational changes, ultimately driven by ATP hydrolysis, result in a dramatically expanded chaperonin cavity serving as folding chamber. Currently, very little is known about the annealing action of eukaryotic chaperonins. Questions that we are trying to address are what are the chaperonin binding sites for substrate proteins, how does protein folding assistance take place in the absence of a change in chemical environment and how does the sequential opening of the eukaryotic chaperonin promote protein folding. We develop and apply computational molecular modeling tools, such as the widely used program CHARMM, in combination with extensive data mining of protein databases. This is an opportunity to acquire a diverse set of computational skills and apply them to problems of biomedical interest. In addition, our soon-to-be-built supercomputer cluster provides a chance to learn about designing and maintaining high-performance computers for data intensive applications.

Professor Pearl Tsang

The focus of research in the Tsang laboratory involves study of the molecular basis underlying protein-protein and protein-RNA interactions. One project described herein involves investigation of tRNA binding to human lysyl tRNA synthetase (“hKRS”). We are particularly interested in the tRNA binding properties of the N-terminal extension of this particular enzyme. hKRS is one of the aminoacyl tRNA synthetases which are enzymes essential to all living organisms due to their critical role during protein translation. Despite the obvious importance of these enzymes, a full understanding of their in vivo function in eukaryotic AARS is still lacking. Non-specific tRNA binding has been proposed to be important for ‘tRNA channeling’ which has been hypothesized to occur in higher eukaryotic systems in order to explain their highly rapid and efficient rate of protein synthesis. Since very little structural data exists with respect to the extensions of eukaryotic synthetase molecules, it is difficult to verify this channeling hypothesis.

An important goal of our research is to investigate the role of these eukaryotic AARS extensions with respect to tRNA binding. The protein extensions of several human AARS proteins must be produced via cloning and protein expression techniques. The tRNA binding properties of these extensions will be monitored using fluorescence and solution NMR techniques. REU students will learn molecular biology techniques to help produce the vectors required to produce the protein extensions studied. They will also learn spectroscopic techniques (CD, fluorescence, NMR) which will be used to characterize the secondary structure of the extensions, tRNA binding and three-dimensional structures of the extensions and their tRNA complexes.