Research Programs

SynthesisAnalytical and Bioanalytical Chemistry
Biological and Medicinal Chemistry
Biophysical Chemistry
Inorganic/Organometallic Chemistry
Materials and Polymer Chemistry
Organic Chemistry
Physical Chemistry and Chemical Physics
Theoretical Chemistry

Analytical and Bioanalytical Chemistry
Analytical chemistry at the University of Virginia offers students a variety of analytical methodologies that are brought to bear on a range of fundamental and applied problems, such as surface and interface studies, trace element analysis, design and application of luminescence sensors and molecular probes, smart sensors in metal composites, polypeptide and DNA sequencing, plasma chemistry, polymer characterization, archaeological studies, and environmental monitoring. Students working in a given area will normally master and utilize several complementary analytical techniques in the course of their graduate research careers. Considerable effort is directed toward the development of new instrumentation and measurement techniques that advance the present state of the art. These studies encompass not only the enhancement and optimization of existing methods, but also the development of entirely new analytical techniques. These are often used in an interdisciplinary fashion to study problems involving biochemistry, clinical chemistry, geochemistry, environmental chemistry, forensic science, and archaeology.

The sizeable effort in bioanalytical chemistry plays off of the biological strength of the Chemistry department at Virginia. Bioanalytical research efforts involve the use, modification or building of state-of-the-art instrumentation for interrogating biological systems. A significant part of this research is targeted at (but not exclusive to) the understanding proteins and their roles in health and disease by gaining a general understanding of proteins through their conformational structure and their interaction with their environment. Major areas of interest being instrument-based including mass spectrometry, electron spin resonance, nuclear magnetic resonance and micro-electrophoresis separation systems. Students working in a given area will normally master and utilize several complementary analytical techniques in the course of their graduate research careers.

Efforts are underway to gain a general understanding of structure and function of proteins through their interaction with their environment. This includes understanding the significance of small molecule interaction with folded proteins through NMR studies, as well as probing the way proteins interact with biological membranes using EPR. EPR methodology is beginning to unravel the complicated mosaic of cellular membranes with respect to lipid domain composition and function, and it is providing information on protein structure and dynamics that can not be obtained using conventional structural methods. This approach is strengthened by improvements in current EPR instrumentation and in the design of novel spin labels. For example, the development of loop-gap resonators has dramatically improved the range and sensitivity of EPR experiments, and classes of sulfhydryl reactive probes have been developed to attach spin probes in a site specific manner through site-directed mutagenesis. NMR is a powerful tool for interrogating how small molecules or ions explore the surface and interior of folded protein structures in aqueous solutions. When this approach involves nuclear magnetic relaxation induced by oxygen, the results can provide a map of effective oxygen occupancy at each amino acid site in the folded proteins. NMR is also being exploited to understand the differences between normal protein structure and function, and that in dysfunctional states associated with certain diseases. NMR-defined structural differences between normal cellular proteins and their oncogenic counterparts are identifying novel avenues for the design of therapeutics agents for neoplasms in tissue associated with these proteins. Studies with NMR to decifer structural differences between normal and oncoproteins are complimented by efforts in proteomics using mass spectrometry. In this latter approach, proteins in healthy and diseased cells or tissues are digested proteolytically with the resultant mixture of more than 400,000 peptides analyzed by molecular weight with a newly constructed Fourier transform mass spectrometer. Subtraction of the data acquired on the two cell types identifies peptides unique to the diseased cell, and the sequence (defined by tandem mass spectrometry are searched against protein and genomic data bases to identify the parent protein. The same approach can be employed to define signal transduction pathways upregulated in the diseased cell or tissue. Application of this approach to the field of immunology has led to the discovery of potential vaccine candidates for lung and skin cancer as well as infectious disease. Finally, the development of new electrophoretic platforms for the analysis of proteins is also underway. Microchip-based electrophoretic separation systems, fabricated in a clean-room facility comparable to those used to generate electronic microchips (for computers), are capable of rapidly detecting trace levels of proteins and may facilitate the early detection of markers for the onset of diseases such as cancer. Moreover, these micro-electrophoretic systems, ideal for analysis of genetic sequences, have already impacted our ability to interrogate the genome. It is likely that micro-electrophoretic systems will play a role in understanding other aspects of the biochemistry of cells.

Biological and Medicinal Chemistry
PolymerResearch in biological and medicinal chemistry involves the discovery of large and small molecules for potential use as effective treatments in biological and medical-related problems. The Department has a rich history in biological and medicinal chemistry, which began with the late Dr. Alfred Burger. The tradition continues with our current faculty and the successful discovery of several modern day medicines is a hallmark of their present commitment to actively search for new drug molecules and targets.

Exciting areas of drug discovery are being investigated through the applications of fundamental principles of organic chemistry, natural product chemistry, biochemistry, molecular pharmacology, molecular modeling, 3D-QSAR, and combinatorial chemistry. Graduates of this program are expected to be thoroughly familiar with the chemistry of organic compounds, including their synthesis and biosynthesis, their reactivity, and their interactions with and alteration by living organisms. These are exciting times in medicinal and biological chemistry and our faculty have formed substantial collaborations with many elite pharmaceutical companies, medical schools and internationally and nationally known researchers in the quest to explore the chemistry of medicine.

Biophysical Chemistry
Graduate study in biophysical chemistry involves the merging of several areas including biology, cell biology, biochemistry, synthetic chemistry, spectroscopy, and biophysics. Formal programs of study are assembled individually and build on the core curriculum in chemistry, the foundation of all of these areas.

Current research programs are based strongly on spectroscopy as a tool to understand biomolecular structure and function. NMR spectroscopy is a primary tool for structure determinations and present work focuses on transcription regulatory proteins such as core binding factor and its various oncoprotein forms. Protein dynamics, thought to be critical to understanding function and control, are studied by a combination of high resolution NMR and magnetic relaxation methods that provide information over a time range of 15 orders of magnitude. Studies of membrane biophysics seek to understand how proteins attach to membranes, how structure of membrane-bound proteins and peptides is altered to provide function in cell signaling and growth, how sodium- potassium ATPase function, and how ion transport is controlled.

Inorganic/Organometallic Chemistry
Inorganic reactions and substances are pervasive in modern chemistry, playing a significant role in nearly all areas of chemical research. The scope of the field today is enormous, encompassing the transition and lanthanide metals and main-group elements as well as the interdisciplinary areas of organometallic, metal-containing polymers, solid-state, bioinorganic, and physical inorganic chemistry. At Virginia, established research programs are operative in all these fields.

Physical ChemistryOrganometallic chemistry directed toward the development of organic synthesis methods is emphasized by several groups in our department. Transition metals are being studied as dearomatization agents for arenes and heterocycles. The localization of p electrons of the organic substrate provides useful synthons to polycyclic natural products. Catalytic reactions, including asymmetric ones, are also being explored by several groups. Metal catalysts are also employed for the development of new ligands and chiral conjugated polymers via cross coupling strategies, and also for their ability to promote controlled polymerizations. Chiral molecules as well as macromolecules are investigated in the preparation of new metal catalysts for olefin polymerization. Introduction of reactive centers-both Lewis acids and transition metals-to rigid chiral conjugated polymers leads to site isolated catalysts for single or tandem asymmetric transformations. The polymer support simplifies product purification, and allows catalyst recycling in continuous production. Macroligands and monodispersed polymers with tailored binding sites, also present new ways to tailor the outer sphere of catalysts upon metal coordination.

The Department is also active in the area of metal-containing polymers. In addition to their value for catalysis, chiral conjugated metallopolymers also find application as non-linear optical materials, with enhanced thermal stability, NLO properties, and synthetic tunability of molecular building blocks. Similar versatility is exhibited by polymeric metal complexes, synthetic analogues of metalloproteins, prepared by living polymerizations and a modular metal template approach. These diverse multifunctional materials are being explored for sensors, drug delivery vectors, imaging agents, biocompatible coatings, and anti-oxidants in wound treatments. And in block copolymers, metals lend responsive features, making macromolecules and their nanoscale assemblies dynamic. Of particular interest are luminescent lanthanide and transition metal systems for sensors, and photonic and OLED materials.

Research at the interface of inorganic and biological chemistry ranges from the complexation of biologically important molecules by metal ions to NMR and EPR studies of metals and metalloenzymes in aqueous media.

In the physical inorganic area, currently active programs deal with such topics as the photochemistry of luminescent metal complexes, which are useful in solar energy conversion and as probes of biological structures, the detection and spectroscopic study of new species generated by matrix isolation techniques, and investigations of the electronic structure of molecules and metal ions via circular dichroism and theoretical calculations.

Materials and Polymer Chemistry
Research in materials chemistry at Virginia spans many fields of science. Active programs in synthetic, analytical, physical, and biological chemistry, combined with collaborative ventures with engineering departments, physics and the medical school, as well as links to other facilities and nationally recognized programs beyond the University, provide abundant opportunities to explore many facets of the highly interdisciplinary field of materials chemistry. Close ties between research groups in the Department and various industries aim to translate scientific advances into new technologies, and provide students with excellent training and networking opportunities for their future professional careers.

A number of research groups at Virginia are concerned with the synthesis and physical properties of light emitting materials that can be incorporated into sensors. The sensors are typically based on transition and lanthanide metals, as well as conjugated organic materials. Analyte detection ranges from small molecules (e.g. O2, CO2, and pH) to biomolecules and more complex chiral organic molecules. For example, luminescent Ru-containing polymers are employed in pressure sensitive paints and in the detection of oxygen levels in blood. Other metal-centered polymers prepared in the Department exhibit detectable color changes when exposed to heat and reagents of different kinds. In another program, properly designed chiral antenna molecules allow for the rapid and convenient determination of enantiomeric excesses in asymmetric reactions by fluorescence. Strengths in the spectroscopy of inorganic complexes and chiral molecules, world-class facilities, and expertise in microscopy at Virginia enhance the capabilities of departmental research efforts in these areas. For example, fluorescence microscopy is proving to be an invaluable tool for characterizing sensor molecule interactions with the critical polymer supports. In the biotechnology field, the development of high throughput screening methods makes it possible to separate and detect biomolecules in new "lab on a chip" technologies that substantially depend on novel materials processing and bio-passivation techniques. The ability to fabricate analytic microchips in a dedicated fabrication facility within the Department, as well as work out surface chemistry and separation optimization, allow for the development of devices that promise to deliver a paradigm shift to clinical diagnostics.

Research in photonic materials at Virginia involves the design and synthesis of novel polymers with various chromophores and luminophores. Chirality is introduced into conjugated polymers to improve the nonlinear optical properties and it may also lead to materials that can emit circularly polarized light. Also under investigation are metal-containing polymers that self organize or can be processed into regular arrays on small length scales. Collaborations to explore the practical applications of these materials have been established both nationally and internationally.

Research in catalyst development provides students with the chance to gain experience across traditional disciplinary lines of organic, inorganic and polymer chemistry. Topics under investigation include chiral conjugated polymers that give unprecedented enantiomeric excesses and can be recycled, exploration of living polymerizations with metal catalysts, as well as the preparation of well-defined "macroligands" that are useful for tailoring the outer sphere surrounding reactive metal centers. In addition to soft matter systems, projects exploring the reaction dynamics of heterogeneous catalysis on platinum and other metal surfaces using advanced scanning probe and laser techniques are also ongoing. The latter work on catalytic model systems interfaces with theoretical and experimental programs optimizing practical solid state catalysts and surface modification in Chemical Engineering, and metal surface corrosion and electrochemistry in Materials Science Departments at the University.

An NSF Integrative Graduate Education and Research Training (IGERT) fellowship program on the "Science and Engineering of Laser Interactions with Matter" supports multi-disciplinary research on materials creation, processing, and spectroscopy using the University's extensive laser resources. These resources include the University's shared Ultrafast Laser Facility located in Chemistry and a University of Virginia laboratory accessing the world's most powerful free electron laser at the Thomas Jefferson National Accelerator Facility in Newport News, Va. Non-linear optics of chiral polymers, intramolecular vibrational energy transfer in polymers, ultrafast laser induced surface photochemistry, 2-photon photoemission spectroscopy of surface electronic states, ultrafast MALDI, and ultrafast pump/probe photoelectron spectroscopy of size-selected cluster compounds, are just some of the research topics under current exploration. In a collaborative venture between polymer synthesis groups and materials science, a new matrix assisted laser evaporation (MAPLE) technique is being explored to address fundamental questions, and to coat particles and surfaces for drug delivery and photonic materials. Along with chemical and biomedical engineers, chemistry researchers are exploring new ways to decorate metal and other kinds of surfaces with polymers for selective detection and attachment of biomolecules and cells.

Many research groups in the Chemistry Department contribute to the exciting new target area of nanoscience. In the polymer field, new metal-containing block copolymers are easily accessed via a metal template approach. These systems self assemble to form nano-patterned films with discretely positioned metal functionalities that serve as responsive elements, akin to metalloprotein assemblies in biology. Low temperature scanning tunneling microscopy (STM) provides opportunities to manipulate, image, and perform spectroscopy on single atoms and molecules. Across campus, nanoscopic dynamic processes of self-assembly, lithography, diffusion, reaction, and corrosion on surfaces are being actively explored by STM, atomic force microscopy, a wide variety of electron microscopies, and focused ion beam scattering and spectroscopic techniques. Theoretical studies are also underway. Integral equation methods are employed to characterize the solvent mediated interactions between nanoparticles in liquids and in supercritical fluids, as well as their interactions with various substrates.

Recent advances in controlled biomolecule and polymer synthesis, combined with an ever-increasing molecular level understanding of the biological-synthetic materials interface, present numerous opportunities for the development of new materials for medicine and biotechnology. Biodegradable polymers for targeted and triggered release drug delivery, biocompatible surface coatings and wound healing formulations, and materials equipped for detection by various methods, as well as "lab on a chip" biomolecule separation strategies using capillary electrophoresis are all under investigation in the Chemistry department. Other initiatives in this area are concerned with bio-inspired materials design. Numerous joint projects with investigators in engineering and medical schools at Virginia, a special NIH sponsored Biotechnology Graduate Training Program, and interdisciplinary educational offerings are available for interested students.

Organic Chemistry
The application of chemical principles to the study of allied fields is an especially exciting facet of contemporary research. Organic chemistry is at the core of much of the ground-breaking research presently being pursued in such diverse areas as materials, biology, and medicine. Research in organic chemistry in the Department emphasizes these interdisciplinary opportunities, particularly at the biological-chemical interface. Some of the research topics currently being pursued in the Department include:

1) Synthesis of complex natural and unnatural compounds
2) Mechanistic studies on metal toxicity in biological systems
3) Synthetic and mechanistic aspects of organometallic chemistry
4) Isolation and characterization of biologically active natural products
5) Characterization and mechanistic studies on biological receptors
6) Development of new catalysts and chiroptical materials
7) Development of probe molecules for the study of the function of biological membranes
8) Synthesis of polymeric inorganic-organic hybrid materials for use as biosensors, drug delivery vectors, and other biotechnology applications.

Many of the above research opportunities involve the interaction of two or more research groups, thereby allowing interdisciplinary approaches to the study of important problems. The research experience is further expanded by the availability of a wide range of "state-of-the-art" instrumentation on a "hands on" basis, giving the researcher an in-depth understanding of both the operational and conceptual features of sophisticated spectroscopic and chromatographic tools. Students in organic chemistry benefit from a curriculum featuring courses in reaction mechanisms, synthesis, and spectroscopic techniques, as well as specialized offerings on selected topics in synthetic, bioorganic, and organometallic chemistry. Our students' experience is broadened by an active Departmental colloquium and seminar series that attracts eminent scientists from leading centers of research throughout the world.

Physical Chemistry and Chemical Physics
The quest for ever more detailed, microscopic level descriptions of molecular structure and processes dominates physical chemistry research at the University of Virginia. Improving our molecular understanding of physical phenomena provides the basic science that is enabling advances in many fields ranging from nanotechnology and catalysis, to molecular biology and medical imaging, and environmental monitoring through laser spectroscopy. In our research, we employ photon, electron, and scanning probe spectroscopies/microscopies to characterize the concentration and structure of molecules, and time-resolved spectroscopic techniques to explore the mechanism, kinetics, and dynamics of molecular processes that can occur on time scales as short as tens of femtoseconds.

Representative research includes: the study of reaction kinetics and dynamics in gases, liquids, matrices, or on catalytic surfaces; investigations of molecular vibrational energy flow and structural dynamics using the complementary techniques of high resolution infrared/microwave spectroscopy and ultrafast laser spectroscopy; the study of time and enantiomer resolved optical dichroism; the development of luminescence chemical sensors and molecular probes; the elucidation of the electronic structure of nano-cluster compounds; and biophysical investigations of ion transport through membranes and drug action. The development and testing of theoretical models of molecular reactivity, structure, and spectroscopy are vigorously pursued. Over the course of their training, students will learn to master a range of both theoretical and experimental techniques.

Theoretical Chemistry
Theoretical research in the Chemistry Department at the University of Virginia covers all major areas of Theoretical Chemistry, including ab initio quantum calculations, quantum and classical statistical mechanics, and molecular mechanics. Various quantum chemical methods, such as density functional theory, are employed in the electronic structure calculations. Statistical mechanical theories, including integral equation and mode-coupling theory, are used to investigate structural and dynamical properties of liquids and supercritical fluids. Methods of molecular mechanics are utilized to represent various aspects of chemical structure and reactivity.

Representative research topics include the calculation of structures and vibrational frequencies for the products of reactions of transition metal atoms and small molecules, the study of the effects of clustering on translational and rotational diffusion in supercritical fluids, and the microscopic statistical mechanical investigation of the nanoparticle self-assembly process in liquid solutions. The ultimate goal of theoretical research is to explain the currently available experimental data and to provide guidance for future experiments. Accordingly, the vast majority of theoretical projects are carried out in close interaction with the experimental groups.