David S. Cafiso
Membrane Proteins and Cell Signaling
Membranes and membrane proteins participate in some of the most important and interesting cellular processes. Energy transduction, cell signaling, membrane excitability, secretion and immune recognition are examples of a few of the processes mediated by membrane proteins. However, the molecular mechanisms by which lipids and membrane proteins accomplish these tasks are largely unknown. We primarily use EPR spectroscopy and high-resolution NMR to investigate the structure and function of membrane proteins.
Protein – membrane surface interactions
Attachment is critical for cell-signaling because it controls protein-protein interactions and the access of enzymes to lipid substrates. We are currently determining the structure and electrostatic interactions made by highly positively charged protein motifs, such as those from MARCKS (the myristoylated alanine rich C-kinase substrate) with negatively charged lipid surfaces. In addition to regulating membrane attachment, these positively charged motifs function to sequester phosphatidylinositol 4,5, bisphosphate (PIP2), and regulate the activity of this phosphorylated inositol lipid within the cytoplasmic membrane. We are also determining the membrane interactions made by protein domains such as C2 domains. C2 domains perform critical roles in membrane trafficking, membrane fusion and membrane repair, and defects in these domains result in forms of muscular dystrophy and deafness.
Active transport across membranes
We are determining the molecular mechanisms by which BtuB transports vitamin B12 across the outer membrane of Escherichia coli. This protein is homologous to FecA, FepA and FhuA, outer membrane iron transport proteins that presumably function by similar mechanisms. These proteins belong to a class of transport proteins for which high-resolution structural models have been obtained, and they are extremely important for the survival of some bacterial pathogens.
Allosteric control of syntaxin 1a by Munc18-1: characterization of the open and closed conformations of syntaxin. Dawidowski D, Cafiso DS. Biophys J. 104:1585-94 (2013).
Monomeric TonB and the Ton box are required for the formation of a high-affinity transporter-TonB complex. Freed DM, Lukasik SM, Sikora A, Mokdad A, Cafiso DS. Biochemistry. 52:2638-48 (2013).
Taking the pulse of protein interactions by EPR spectroscopy. Cafiso DS. Biophys J. 103:2047-8 (2012).
Ligand-induced structural changes in the Escherichia coli ferric citrate transporter reveal modes for regulating protein-protein interactions. Mokdad A, Herrick DZ, Kahn AK, Andrews E, Kim M, Cafiso DS. J Mol Biol. 423:818-30 (2012).
Solution structure of the ESCRT-I and -II supercomplex: implications for membrane budding and scission. Boura E, Różycki B, Chung HS, Herrick DZ, Canagarajah B, Cafiso DS, Eaton WA, Hummer G, Hurley JH. Structure. 20:874-86 (2012).
John H. Bushweller
Our lab is fundamentally interested in understanding, from a structural and biophysical perspective, the functioning of proteins involved in regulating transcription, particularly those involved in the dysregulation associated with the development of cancer. Structural and functional characterization of the native forms of these proteins and their relevant complexes via NMR spectroscopy, X-ray crystallography, and a variety of other techniques provides a baseline of understanding. Subsequent characterization of the oncoprotein forms then provides a detailed understanding of the molecular mechanism of oncogenesis associated with altered forms of these proteins. Such knowledge leads to novel avenues for the design of therapeutic agents to treat the cancers associated with these particular oncoproteins.
One current focus is structural studies of a novel transcription factor referred to as the core-binding factor (CBF). This heterodimeric protein is essential for hematopoietic development. Gene translocations associated with the genes coding for the two subunits of CBF produce novel fusion proteins which have been implicated as playing a role in more than 30% of acute leukemias. We have carried out structural (NMR spectroscopy and X-ray crystallography) and functional studies of the oncoprotein forms of the two subunits of CBF that are associated with leukemia to gain an understanding of their roles in the development of leukemia. Another focus area is on fusion proteins involving the transcription factor MLL, which are implicated in a high percentage of pediatric leukemias. We also have an effort focused on the transcription factor ERG which has a critical role in leukemia as well as prostate cancer.
Our chemical biology efforts focus on the development of highly targeted small molecule inhibitors of the oncoprotein forms of CBF and MLL. Using structural information on the proteins, various screening approaches, NMR and fluorescence-based assays, and medicinal chemistry, we have developed the first small molecule inhibitors of these proteins. This is a collaborative effort with outside investigators at the University of Pennsylvania, University of Massachusetts, Cornell, and Loyola University. As these are transcription factor targets which have been viewed as “undruggable," our successful development of inhibitors targeting them is opening up new avenues for drug development.
A third focus for the lab has been the application of solution NMR methods to the structure determination of membrane proteins. The vast majority of drug targets are membrane-embedded proteins. This class of proteins has presented significant challenges for structure determination by any method. We completed the structure determination of the largest helical membrane protein to be solved by NMR spectroscopy at the time. This structure established a paradigm for determining structures of this class of proteins by solution NMR. We are currently examining additional technical improvements in this area as well as targeting new systems for structure determination.
- Small Molecule Inhibitor of CBFβ-RUNX Binding for RUNX Transcription Factor Driven Cancers. Illendula A., Gilmour J., Grembecka J., Tirumala VSS, Boulton A, Kuntimaddi A., Schmidt C, Wang L, Pulikkan JA, Zong H, Parlak M, Kuscu C, Pickin A, Zhou Y, Gao Y, Mishra L, Adli M, Castilla LH, Rajewski RA, Janes KA, Guzman ML, Bonifer C, and Bushweller JH. EBioMedicine. 8: 117-131 (2016). Pubmed PMID: 27428424; PubMed Central PMCID: PMC4919611
- Chemical biology. A small-molecule inhibitor of the aberrant transcription factor CBFβ-SMMHC delays leukemia in mice. Illendula A, Pulikkan JA, Zong H, Grembecka J, Xue L, Sen S, Zhou Y, Boulton A, Kuntimaddi A, Gao Y, Rajewski RA, Guzman ML, Castilla LH, Bushweller JH. Science. 347(6223):779-84 (2015). PubMed PMID: 25678665; PubMed Central PMCID: PMC4423805
- Degree of recruitment of DOT1L to MLL-AF9 defines level of H3K79 Di- and tri-methylation on target genes and transformation potential. Kuntimaddi A, Achille NJ, Thorpe J, Lokken AA, Singh R, Hemenway CS, Adli M, Zeleznik-Le NJ, Bushweller JH. Cell Reports. 11(5):808-20 (2015). PubMed PMID: 25921540; PubMed Central PMCID: PMC4426023.
- Structural and dynamic studies of the transcription factor ERG reveal DNA binding is allosterically autoinhibited. Regan MC, Horanyi PS, Pryor EE Jr, Sarver JL, Cafiso DS, Bushweller JH. Proc Natl Acad Sci U S A. 110:13374-9 (2013)
- MLL fusion partner AF9 is an intrinsically disordered transcriptional regulator which recruits multiple partners via coupled folding and binding. Leach BI, Kuntimaddi A, Schmidt CR, Cierpicki T, Johnson SA, and Bushweller JH. Structure, 21:176-83 (2013). PubMed PMID: 23260655. PubMed PMCID: PMC3545106.
Timothy L. Macdonald
Bioorganic and Synthetic Organic Chemistry
The unifying theme of my research program is the application of organic chemical theory and technique to the investigation of problems in biology. Our longstanding interest has been in elucidating the molecular interactions and mechanisms of small molecule-protein interactions. Such interactions are fundamental to physiology, pharmacology, and toxicology and understanding these processes in molecular terms is essential for predicting modes of metabolism and developing new drugs. Our efforts are currently directed at several rather broad areas: elucidation of the molecular pharmacology of ligand-receptor interactions; identification of the molecular processes underlying idiosyncratic drug reactions; determination of the chemical mechanisms of the oxidative transformation of foreign and endogenous compounds by monooxygenase and dioxygenase enzymes; and characterization of the molecular mechanisms underlying the neurotoxicity of small molecules, metal ions, and reactive oxygen species.
Current studies of ligand-receptor interactions include the lysophospholipid signaling system, the colchicinoid site on tubulin, and the ternary drug-DNA-topoisomerase II complex responsible for the cytotoxicity of this class of anticancer agents. Lipid phosphoric acid mediators, such as lysophosphatidic acid and sphingosine-1-phosphate, have a range of biological properties mediated through at least eight G-protein coupled receptors of the EDG family. The cellular biology of these receptors and the physiological mechanisms controlling the processing of the lysophospholipids is beginning to emerge. We are undertaking a set of investigations directed at elucidating the molecular pharmacology of this receptor family and at utilizing this knowledge to target the modulation of lysophospholipid signaling to treat human disease. Specifically, our studies of the lysophospholipid autocoids have been directed at identifying the molecular determinants of the lipid mediator and the receptor that have been proposed to be critical to activity and at developing receptor selective agents for the EDG receptors.
We also have a long-standing interest in understanding ligand-receptor interactions which form ternary DNA-drug complexes with a DNA processing enzyme, and a small molecular ligand. Such complexes are a common theme for a diverse variety of “effectors” of cellular function, including hormone regulators of cellular transcription and translation, and of many antineoplastic agents. We have been examining the interaction of the representative antitumor agent, etoposide, which forms a ternary DNA-drug complexes with DNA topoisomerase I. Another area of research involves elucidation of the molecular mechanism through which colchicine interacts with its target, tubulin. These programs have fully integrated synthetic studies of rationally designed molecules and mechanistic studies of the processes through which these agents interact with their targets. Our studies will advance the knowledge of antitumor drug development for these classes of agents and culminate in the design and synthesis of fundamentally new structural classes of inhibitors of these critical anticancer targets.
An additional area of research is the molecular and cellular mechanisms by which idiosyncratic drug reactions occur. These reactions are the source of a range of toxic reactions to therapeutic agents and are thought to be mediated through the confluence of risk factors associated with drug bioactivation to reactive species, the formation of specific protein antigens and subsequent immune response. A knowledge of the chemical and immunological basis for idiosyncratic reactions would enable a protocol for prospectively identifying individual patient risk or susceptibility to particular agents or drug classes. We have previously investigated the mechanism of blepharoconjunctivitis and dermatitis associated with the use of the antiglaucoma drug, apraclonidine. Our current focus is on the mechanism underlying the aplastic anemia associated with the use of the anti-epileptic agent, felbamate.
Our research is additionally exploring the mechanistic and etiologic relationships between neurotoxicity and aberrant CNS processing of foreign and endogenous agents. The brain is the site of multiple, chronically progressive and clinically devastating diseases in which specific neuronal populations undergo neurodegeneration. An environmental contribution has been implicated in the etiology of many of these diseases, including Parkinson’s disease, motoneuron disease, and Alzheimer’s disease. In one avenue of study, we are examining the potential for the formation of endogenous or exogenous toxins by oxidative enzymes that have been localized to particular neuronal populations, such as the cytochromes P450 and their associated reductases. Through these studies, we hope to ascertain whether this enzyme class represents a primary basis for the etiology or treatment of these neurodegenerative diseases.
A model for the regulation of T-type Ca(2+) channels in proliferation: roles in stem cells and cancer. Gray LS, Schiff D, Macdonald TL. Expert Rev Anticancer Ther. 13:589-95 (2013).
Cost-effective and Large-scale synthesis of 16:0 Lysophosphatidic Acid. East JE, Macdonald TL. Synth Commun. 42:3614-3618 (2012).
Amixicile, a novel inhibitor of pyruvate: ferredoxin oxidoreductase, shows efficacy against Clostridium difficile in a mouse infection model. Warren CA, van Opstal E, Ballard TE, Kennedy A, Wang X, Riggins M, Olekhnovich I, Warthan M, Kolling GL, Guerrant RL, Macdonald TL, Hoffman PS. Antimicrob Agents Chemother. 56:4103-11 (2012).
Development of a phosphatase-resistant, L-tyrosine derived LPA1/LPA3 dual antagonist. East JE, Carter KM, Kennedy PC, Schulte NA, Toews ML, Lynch KR, Macdonald TL. Medchemcomm. 2:325-330 (2011).
Sphingosine kinase type 1 inhibition reveals rapid turnover of circulating sphingosine 1-phosphate. Kharel Y, Mathews TP, Gellett AM, Tomsig JL, Kennedy PC, Moyer ML, Macdonald TL, Lynch KR. Biochem J. 440:345-53 (2011).
Sergei A. Egorov
Structure and Dynamics in Supercritical Fluids
Supercritical fluids (SCFs) are currently receiving much industrial and scientific interest as a result of their unique physical properties. The most characteristic features of SCFs are liquid-like densities, gas-like viscosities, and diffusivities that are intermediate between typical gas and liquid values. The resulting combination of high dissolving power and enhanced mass-transfer rates makes SCFs attractive alternatives to liquid solvents for a variety of industrial applications, such as extraction, separation and reaction processes. In addition, the high compressibility of SCFs in the near-critical region allows one to tune their properties to desired values by applying small changes in pressure, which in turn makes it possible to tailor the rates and selectivities of chemical processes. Since the aforementioned applications of SCFs generally involve dilute solutions, it is essential to develop a microscopic understanding of the structure and dynamics of a supercritical solvent in the vicinity of a solute.
We use the methods of classical statistical mechanics, such as integral equation theory and mode coupling theory, to study structural and dynamical properties of supercritical solutions. Some of the problems we address are as follows. How does the solvent-solute and solute-solute clustering affect the rates and equilibrium constants of chemical reactions in SCFs? How does the proximity to the critical point affect the transport properties and what are the ramifications for diffusion controlled chemical reactions? How is preferential solvation manifested in local composition effects in dilute supercritical solutions? The answers to these questions should help us shed further light on fundamental properties of SCFs and their practical applications.
Quantum and Semiclassical Many-Body Dynamics
Numerous problems in chemical physics involve calculations of quantum time correlation functions (TCFs) in many-body systems. Particular examples include: medium-induced electron transfer, dissipative tunneling, radiationless processes, and electronic spectroscopy of chromophores in crystals and in liquids. While certain systems require a fully quantum mechanical treatment, there exists a large class of systems of chemical interest for which classical mechanics provides a reasonably good approximation. An appealing approach to the calculation of TCFs for such systems involves using semiclassical methods, which are generally based on the assumption that quantum effects can be taken into account by introducing relatively small corrections to the classical results. However, the shorter the time scale on which the behavior is analyzed, the more important quantum corrections may become, even for systems which are classical as far as their static and low-frequency dynamical properties are concerned. One of the research projects in our group involves developing a systematic procedure for including quantum effects into the results for TCFs obtained from classical simulations.
An alternative approach to study quantum dynamics in condensed phases involves calculating imaginary-time correlation functions using path integral Monte Carlo (PIMC) method and performing analytic continuation to the real-time axis. Unfortunately, analytic continuation is numerically unstable, and therefore leads to uncontrollable amplification of statistical noise unavoidable in PIMC simulations. In our group we employ the information theory and the methodology from the field of inverse problems in order to develop various techniques, such as Maximum Entropy and Singular Value Decomposition, for stabilizing the procedure of analytic continuation of quantum imaginary-time TCFs.
Stiffness-Guided Motion of a Droplet on a Solid Substrate. Theodorakis PE, Egorov SA, Milchev A. J Chem Phys. Jun 28; 146(24):244705 (2017).
Milchev A, Egorov SA, Nikoubashman A, Binder K. J Chem Phys. May 21;146(19):194907 (2017).
Semiflexible Polymers Confined in a Slit Pore with Attractive Walls: Two-Dimensional Liquid Crystalline Order Versus Capillary Nematization. Milchev A, Egorov SA, Binder K. Soft Matter. Mar 1; 13(9):1888-1903 (2017).
Theoretical and Experimental Investigation of Microphase Separation in Mixed Thiol Monolayers on Silver Nanoparticles. Merz SN, Farrell ZJ, Dunn CJ, Swanson RJ, Egorov SA, Green DL. ACS Nano. Nov 22; 10(11):9871-9878 (2016).
Concentration-Induced Planar-to-Homeotropic Anchoring Transition of Stiff Ring Polymers on Hard Walls. Poier P, Egorov SA, Likos CN, Blaak R. Soft Matter. Sep 28; 12(38):7983-7994 (2016).
Elasticity of polymeric nanocolloidal particles. Riest J, Athanasopoulou L, Egorov SA, Likos CN, Ziherl P. Sci Rep. Nov 2; 5:15854 (2015).
Semiflexible Polymer Brushes and the Brush-Mushroom Crossover. Egorov SA, Hsu HP, Milchev A, Binder K. Soft Matter. Apr 7; 11(13):2604-16 (2015).
Membrane proteins facilitate the transfer of information across lipid bilayers, comprise approximately 25% of a typical proteome, and represent over half of all drug targets. The membrane proteins that mediate interactions between bacterial pathogens and hosts are of particular interest to our laboratory. Invasive bacterial pathogens are responsible for many lethal diseases and epidemics, including plague and meningitis. Although these bacteria have diverse mechanisms of cellular invasion, all of the pathways rely upon interactions between host and bacterial membrane proteins.
Our lab seeks to determine the structure and conformational changes of membrane proteins involved in bacterial infection using a combination of site-directed spin labeling (SDSL), nuclear magnetic resonance (NMR) spectroscopy, and X-ray crystallography, and also to develop tools to accelerate membrane protein structure determination by these methods.
Conformation transitions of the polypeptide-binding pocket support an active substrate release from Hsp70s. Yang J, Zong Y, Su J, Li H, Zhu H, Columbus L, Zhou L, Liu Q. Conformation transitions of the polypeptide-binding pocket support an active substrate release from Hsp70s. Nat Commun. 2017 Oct 31;8(1):1201. doi: 10.1038/s41467-017-01310-z. PubMed PMID: 29084938; PubMed Central PMCID: PMC5662698.
Modulating Vascular Hemodynamics With an Alpha Globin Mimetic Peptide (HbαX).Keller TC 4th, Butcher JT, Broseghini-Filho GB, Marziano C, DeLalio LJ, Rogers S, Ning B, Martin JN, Chechova S, Cabot M, Shu X, Best AK, Good ME, Simão Padilha A, Purdy M, Yeager M, Peirce SM, Hu S, Doctor A, Barrett E, Le TH, Columbus L, Isakson BE. Hypertension. 2016 Dec;68(6):1494-1503. Epub 2016 Oct 31.
Opa+ Neisseria gonorrhoeae has reduced survival in human neutrophils via Src family kinase-mediated bacterial trafficking into mature phagolysosomes. Johnson MB, Ball LM, Daily KP, Martin JN, Columbus L, and Criss AK. Cellular Microbiology. 17:648 – 665 (2015).
Tuning micelle dimensions and properties with binary surfactant mixtures. OliverRC, Lipfert, Fox DA, LoRH, KimJJ, DoniachS, Columbus L. Langmuir. 30:13353 – 13361 (2014).
Mapping membrane protein dynamics: a comparison of site-directed spin labeling to NMR 15N-relaxation measurements. Lo RH, Kroncke BM, Solomon T, Columbus L. Biophysical Journal.107:1697 – 1702 (2014).
Structure of the Neisserial Outer Membrane Protein Opa60: Loop Flexibility Essential to Receptor Recognition and Bacterial Engulfment. Fox DA, Larsson P, Lo RH, Kroncke BM, Kasson PM, Columbus L. J Am Chem Soc. 136:9938-9946 (2014).
James N. Demas
Photochemistry and Photophysics of Transition Metal Complexes
Professor Demas is not currently accepting graduate students.
Molecules excited by light lose energy by emission of light, transfer of energy or an electron to other molecules, photochemistry, and non-destructive radiationless processes. Solar energy conversion, chemical analysis, and light intensity measurements require information from the study of these processes. The processes can be highly sensitive to environmental factors such as solvent and interactions with organized media such as micelles, cyclodextrins, membranes, proteins, and DNAs. In addition, luminescence properties are very sensitive to the environment in polymer-supported sensors. We are elucidating the nature of these processes, correlating properties with molecular structure and environment, and developing new chemical, instrumental, and mathematical tools for studying these processes.
Our work includes:
- Design, synthesis and characterization of highly luminescent Os, Ir, Re, and Ru complexes.
- Evaluating photochemical properties, excited state ordering, and paths of energy loss.
- Fundamental and applied studies of interactions of photosensitizers with polymers, micelles, membranes and other organized media.
- Developing new luminescence-based sensors (e.g., oxygen, pH, metal ion).
- Design and utilization of metal complexes as probes of the structure and dynamics of organized media such as DNAs and membranes.
- Instrumental and theoretical developments in ultrasensitive, multicomponent fluorometric analyses.
The photoluminescence of a tris(4,7-diphenyl-1,10-phenanthroline)ruthenium (II) complex in a polymer film is shown while the film is being breathed over. The luminescence is quite sensitive to deactivation by oxygen, and the luminescence intensity is a direct measure of the oxygen in the subject’s breath. Less oxygen yields more luminescence. The region immediately after the subject held his breath is revealing.
Aromatic difluoroboron β-diketonate complexes: effects of π-conjugation and media on optical properties. Xu S, Evans RE, Liu T, Zhang G, Demas JN, Trindle CO, Fraser CL. Inorg Chem. 52:3597-610 (2013).
Viscosity and temperature effects on the rate of oxygen quenching of tris-(2,2′-bipyridine)ruthenium(II). Reynolds EW, Demas JN, DeGraff BA. J Fluoresc. 23:237-41 (2013).
Environmental sensitivity of Ru(II) complexes: the role of the accessory ligands. Dixon EN, Snow MZ, Bon JL, Whitehurst AM, DeGraff BA, Trindle C, Demas JN. Inorg Chem. 51:3355-65 (2012).
Photophysical and analyte sensing properties of cyclometalated Ir(III) complexes. Leavens BB, Trindle CO, Sabat M, Altun Z, Demas JN, DeGraff BA. J Fluoresc. 22:163-74 (2012).
Laser phosphoroscope and applications to room-temperature phosphorescence. Payne SJ, Zhang G, Demas JN, Fraser CL, Degraff BA. Appl Spectrosc. 65:1321-4 (2011).
Kateri H. DuBay
The design of self-assembling nanomaterials stands as one of the great challenges in modern molecular science. The DuBay group employs theoretical and computational tools to address this challenge through investigations that lie at the intersection of soft condensed matter physics, polymer chemistry, biophysics, and nanomaterials.
At these very small length scales, the effects of thermal fluctuations, entropy, energy, and kinetics are often comparable in magnitude, rendering materials highly sensitive to perturbations such as chemical doping and environmental changes. While a wide variety of useful structures can be made via self-assembly within a static environment by precisely tuning the interactions between assembling components, environmental controls give us the means to advance beyond the limitations of such endeavors. Biological systems provide a host of examples, demonstrating the remarkable complexity and high responsivity of materials formed via environmentally-directed assembly. Specifically our group looks at assembly within environments that vary either in space, such as in the presence of a chemical gradient, or in time, such as in response to biological signaling.
Given the physical length-scales of the systems we study and the time-scale over which they evolve, we design theoretical models to capture the essential physics of the studied phenomenon. Such schematic models leave out unnecessary details in order to isolate the factors of interest and enable us to probe more directly the fundamental questions surrounding the emergence of order and responsivity within the studied nanoassemblies.
An improved understanding of the rules governing assembly in these environments will yield novel insights into the formation of functional biomaterials as well as information useful for improving light harvesting, drug-delivery, environmental-sensing, and material fabrication; countless technological innovations await the ability to rationally design artificially-ordered and environmentally-responsive nanomaterials.
Construction of Donor-Acceptor Polymers via Cyclopentannulation of Poly (arylene ethynylene)s. X Zhu, S.R. Bheemireddy, S.V. Sambasivarao, P.W. Rose, R. Torres Guzman, A.G. Waltner, K.H. DuBay, and K.N. Plunkett. Macromolecules, 49 (1), 127-133 (2016).
Fluctuations within Folded Proteins: Implications for Thermodynamic and Allosteric Regulation. K.H. DuBay, G.R. Bowman, P.L. Geissler, Accounts of Chemical Research, 48 (4), pp 1098–1105 (2015).
A First-Principles Polarized Raman Method for Determining Whether a Uniform Region of a Sample is Crystalline or Isotropic. A.L. Weisman, K.H. DuBay, K.A. Willets, R.A. Friesner, The Journal of Chemical Physics 141(22), 224702 (2014).
Impact of Molecular Symmetry on Single-Molecule Conductance. E. J. Dell, B. Capozzi, K. H. DuBay, T. C. Berkelbach, J. R. Moreno, D. R. Reichman, L. Venkataraman, and L. M. Campos. J. Am. Chem. Soc. 135:32, 11724-27 (2013).
Chromophore-Controlled Self-Assembly of Highly Ordered Polymer Nanostructures. M. C. Traub, K. H. DuBay, S. E. Ingle, X. Zhu, K. N. Plunkett, D. R. Reichman, and D. A. Vanden Bout. J. Phys. Chem. Lett. 4:15, 2520-4 (2013).
Accurate Force Field Development for Modeling Conjugated Polymers. K. H. DuBay, M. L. Hall, T. F. Hughes, C. Wu, D. R. Reichman, and R. A. Friesner. J. Chem. Theory. Comput. 8, 4556-69 (2012).
Polarized Raman Spectroscopy of Oligothiophene Crystals to Determine Unit Cell Orientation. J. C. Heckel, A. L. Weisman, S. T. Schneebeli, M. L. Hall, L. J. Sherry, S. M. Stranahan, K. H. DuBay, R. A. Friesner, and K. A. Willets. J. Phys. Chem. A 116, 6804-16 (2012).
Long-Range Intra-Protein Communication Can Be Transmitted by Correlated Side-Chain Fluctuations Alone. K. H. DuBay, J. P. Bothma, and P. L. Geissler. PLoS Comput. Biol. 7:9, e1002168 (2011).
Cassandra L. Fraser
Oxygen Sensing Boron Biomaterials
Difluoroboron dibenzoylmethane-poly(lactic acid) analogues exhibit both intense fluorescence and long-lived room temperature phosphorescence. When fabricated as nanoparticles, these simple, dual-emissive biomaterials serve as optical oxygen probes for biology and medicine, with impressive combined spatial and temporal resolution. Along with fundamental studies, the materials have been optimized with respect to fluorescence and phosphorescence emission colors, relative intensities, luminescence lifetimes, oxygen sensitivities, and fabrication. With collaborators, we developed a portable, cost-effective, laptop camera imaging system that, in conjunction with boron nanosensors, allows for dynamic, real-time, single or dual mode (ratiometric and/or lifetime) tissue oxygen imaging. We have demonstrated the utility of these materials for in vitro and in vivo optical oxygen imaging in cell, tumor, wound, vascular, brain, immunological, tissue engineering, and other contexts.
Mechanochromic Luminescence and Other Stimuli Responsive and Environment Sensitive Properties
Difluoroboron b-diketonate dyes also show surprising properties as molecular solids. For example, we showed that the difluoroboron complex of avobenzone, a simple sunscreen ingredient, has narrow bandwidth green, cyan, or blue emission depending on the solid form. Furthermore, the emission color changes when crystals are crushed or films are scratched or rubbed. Surprisingly, for thin films, the mechanochromic luminescence is reversible. For the avobenzone complex, regions where force is applied turn yellow but return to the original green-blue background color within minutes at room temperature or seconds with heating. The writing-fading process may be repeated many times. Emission colors, force responsiveness, and self-healing times may be tuned through molecular design, and self-erasing properties may be monitored with video camera imaging. These simple Scratch the Surface InksTM show promise as mechanical sensors and renewable inks for rewritable surfaces. They have even inspired creative works in music, art, and design. Other interesting properties of boron dyes, and in some cases even b-diketones absent difluoroboron, include solvatochromism, viscochromism, halochromism, aggregation induced emission, dye thickness and loading effects, and energy transfer in dye mixtures. Interestingly, some dyes are also thermally responsive and form supercooled liquids. Synthesizing new dyes, exploring their many fascinating properties, and tailoring materials for imaging and sensing in biology, medicine, and other contexts serves as the focus of our research.
Integrative Interdisciplinary Projects
Professor Fraser also has a great passion for envisioning and leading innovative interdisciplinary programs that integrate teaching, research, community engagement and creative pursuits. These projects are often inspired by materials, and environmental health and sustainability themes. They build bridges across STEM and non-STEM disciplines and engage students, faculty, and the community with thought leaders from across UVA and the globe. Examples include the UVA Page Barbour supported Transduction and Plastic/ity projects, the Carnegie Corporation funded Designing Matter Common Course, the NIH Global Health funded Metals in Medicine and the Environment, the Biomaterials Workshop, the Echols seminar Color: Across the Spectrum, and the Science, Careers and Society Forum. Professor Fraser often collaborates with artists and designers on exhibitions and performances (e.g. Chromogenic Materials, Agents of Architecture, UVA Music Technosonics Festival, UVA Art Bestiary Exchange Portfolio, Environmental Art Activism, and Time books). She also engages in design projects to establish new kinds of venues for conducting and displaying interdisciplinary work (e.g. WallSpace, Real World Chemistry Lab). New research is concerned with Anthrochemistry—chemistry of the Anthropocene, investigating the human impacts of chemistry through element, molecule, and material case studies via an interdisciplinary global systems chemistry approach. Of particular interest are ways that materials, their pathways, and processes, are mapped onto and into our bodies and intersect with our everyday lives, affecting health and wellbeing. Laws, policies, social and environmental justice, and ethics and responsibility are also considered. Creative interdisciplinary ways of communicating findings to both university and broader audiences are also of interest.
Luminescent Difluoroboron β-Diketonate PLA-PEG Nanoparticles. Kerr, C.; DeRosa, C. A.; Daly, M. L.; Zhang, H.; Palmer, G. M.; Fraser, C. L. Biomacromolecules 2017, 18, 551-561.
Oxygen Sensing Difluoroboron β-Diketonate Polylactide Materials with Tunable Dynamic Ranges for Wound Imaging. DeRosa, C. A.; Seaman, S. A.; Mathew, A. S.; Gorick, C. M.; Fan, Z.; Demas, J. N.; Peirce, S. M.; Fraser, C. L. ACS Sensors 2016, 1, 1366-1373.
Mechanochromic Luminescence and Aggregation Induced Emission of Dinaphthoylmethane β-Diketones and their Boronated Counterparts. Butler, T.; Morris, W. A.; Samonina-Kosicka, J.; Fraser, C. L. ACS Appl. Mater. Interfaces 2016, 8, 1242-1251.
Polymorphism and Reversible Mechanochromic Luminescence for Solid-State Difluoroboron Avobenzone. Zhang, G.; Lu, J.; Sabat, M.; Fraser, C. L. J. Am. Chem. Soc. 2010, 132, 2160-2010.
A Dual-Emissive Materials Design Concept Enables Tumour Hypoxia Imaging. Zhang, G.; Palmer, G. M.; Dewhirst, M. W.; Fraser, C. L. Nat. Mater. 2009, 8, 747-751.
Multi-Emissive Difluoroboron Dibenzoylmethane Polylactide Exhibiting Intense Fluorescence and Oxygen-Sensitive Room-Temperature Phosphorescence. Zhang, G.; Chen, J.; Payne, S. J.; Kooi, S. E.; Demas, J. N.; Fraser, C. L. J. Am. Chem. Soc. 2007, 129, 8942-8943.
See more at Google Scholar: https://scholar.google.com/citations?user=gUlmJ6UAAAAJ&hl=en
One key area in understanding bacterial cell biology is spatiotemporal phenomena: Where, when, and how do individual biomolecules act and interact to govern the overall physiology of the cell? To answer this question, we develop new high-resolution imaging methods for 3D single-molecule localization in intact bacterial cells. In particular, we combine the resolving power of the electron microscope with the single-molecule sensitivity and specificity of fluorescence-based methods. With these tools, we can localize single biomolecules in 3D space with a precision of a few nanometers, track their motion over time, and then zoom in further to visualize how specific biomolecules combine with others to produce functioning assemblies in their native environment.
Bacteria are highly relevant to important challenges of our time. For example, the looming inability to effectively combat pathogenic bacteria with current antibiotics presents a major health concern. Finding new avenues to selectively target and alter key molecular pathways can provide us with further options for effective antibiotic drug development. Because bacteria are the smallest and arguably the simplest living organisms on the planet, they are also fundamentally interesting to study the molecular-level biology of the cell. Bacteria are able to precisely regulate protein activity throughout the intracellular space through finely tuned molecular interactions. Of particular importance are scaffolding proteins that partition the cytoplasm and provide specialized subcellular compartments for specific biochemical reactions to occur. On a smaller scale, scaffolding proteins are hypothesized to spatially organize multiple enzymes into biomolecular assemblies. Parts of these assemblies can be highly dynamic and therefore the precise architectures and the resulting functional consequences remain elusive.
Rapid progress of evolution has made the bacteria an extremely diverse and widely abundant group of single-celled organisms that affects almost every aspect of life on earth. The resulting bacterial physiological traits present a biological treasure trove that remains to be investigated with molecular resolution and, where possible, exploited to our benefit. With this in mind, we continue to push the limits of cellular imaging, as well as in situ structural characterization of biomolecular assemblies.
Bacterial Scaffold Directs Pole-Specific Centromere Segregation. J.L. Ptacin, A. Gahlmann, G.R. Bowman , A.M. Perez, A.R.S. von Diezmann, M.R. Eckart, W.E. Moerner, and L. Shapiro. Proc. Natl. Acad. Sci. USA, 2014, 111, E2046
Exploring Bacterial Cell Biology with Single-Molecule Tracking and Super-Resolution Imaging. A. Gahlmann and W.E. Moerner. Nat. Rev. Microbiol., 2013, 12, 9 (Cover Article)
Quantitative Multicolor Subdiffraction Imaging of Bacterial Protein Ultrastructures in Three Dimensions. A. Gahlmann, J.L. Ptacin, G. Grover, S. Quirin, A.R.S. von Diezmann, M.K. Lee, M.P. Backlund, L. Shapiro, R. Piestun, and W.E. Moerner. Nano Lett., 2013, 13, 987
Direct Structural Determination of Conformations of Photoswitchable Molecules by Laser Desorption-Electron Diffraction. A. Gahlmann, I-R. Lee, and A.H. Zewail. Angew. Chem. Int. Ed., 2010, 49, 6524
Structure of Isolated Biomolecules by Electron Diffraction-Laser Desorption: Uracil and Guanine. A. Gahlmann, S.T. Park, and A.H. Zewail. J. Amer. Chem. Soc., 2009, 131, 2806 (Cover Article)
Ultrashort Electron Pulses for Diffraction, Crystallography and Microscopy: Theoretical and Experimental Resolutions. A. Gahlmann, S.T. Park, and A.H. Zewail. Phys. Chem. Chem. Phys., 2008, 10, 2894
Astrochemistry concerns the behavior of atoms and molecules in astrophysical environments, which can include star-forming clouds and cores, and circumstellar and interstellar regions. The varied gas-phase chemical compositions of these environments are revealed by radio-telescope observations of molecular spectral-line emission and absorption, primarily in the mm and sub-mm bands. Infrared observations also indicate significant solid-phase abundances of simple hydrides, in the form of ices, which coat the sub-micron sized dust grains that permeate interstellar space. The process of star formation – which involves the heating and UV radiative processing of gas and solid-phase material alike – further encourages the production of complex organic molecules that may contribute to the store of pre-biotic material ultimately available on the surfaces of new planetary bodies.
The Garrod group develops and applies new computational techniques to the study of chemical kinetics in interstellar and star-forming environments. A particular focus of the group is the formation and processing of simple and complex organic molecules on dust-grain surfaces and within astrophysical molecular ices.
New techniques recently developed by the group include a unique, fully three-dimensional, off-lattice kinetic Monte Carlo code that can simulate surface chemistry on dust grains of arbitrary size and shape, over interstellar timescales. The method uses local surface interaction potentials to guide the chemical kinetics and the resultant structure of the ice that forms on the dust-grain surface. The simulated cross-sectional images of interstellar dust-grain ice mantles (below) demonstrate the dependence of ice porosity on physical conditions such as gas density.
Another major focus is the production of complex organic molecules during the star-formation process. The group has developed coupled gas-grain kinetics models to explain recent new detections of organic molecules and to predict interstellar abundances of biologically-significant species, including the amino acid, glycine. The group has also developed dedicated spectral-simulation codes to translate the model results into spectral emission maps, for comparison with observed star-forming cores. The simulated spectra below show predictions for the spectral emission of glycine in a nearby star-forming core.
“Detection of a branched alkyl molecule in the interstellar medium: iso-propyl cyanide.” Belloche, A., Garrod, R. T., Müller, H. S. P. & Menten, K. M., 2014, Science, 345, 1584.
“Three-dimensional off-lattice Monte Carlo kinetics simulations of interstellar grain chemistry and ice structure.”
Garrod, R. T., 2013, ApJ, 778, 158.
“Simulations of hot-core chemistry.” Garrod, R. T. & Widicus Weaver, S. L., 2013, Chemical Reviews, vol. 113, pp. 8939 – 8960.
“A three-phase model of hot cores: the formation of glycine.” Garrod, R. T., 2013, ApJ, 765, 60.
“On the formation of CO2 and other interstellar ices.” Garrod, R. T. & Pauly, T. A., 2011, ApJ, 735, 15.
Charles M. Grisham
Biophysical Chemistry; Magnetic Resonance Spectroscopy of Complex Biological Structures
There are currently two fundamental directions to our research. In one of these, biological membranes and complex biomolecules are being studied using nuclear magnetic resonance (NMR) and electron spin resonance (ESR) techniques. Current areas of interest include two ion transporting enzymes (kidney Na,K-ATPase and muscle Ca-ATPase), and two membrane-associated signalling enzymes (protein kinase C and phospholipase C). The ATPases use the free energy of hydrolysis of ATP to transport sodium, potassium or calcium across cell membranes against large concentration gradients. Protein kinase C is an intracellular mediator of hormonal and neurotransmitter stimuli and is also the receptor for phorbol ester tumor promoters. The geometry and active site structures of these complex systems are being examined by several methods. In one, we employ paramagnetic probes, such as Mn and Gd ions, Cr-nucleotide complexes and spin label analogues of enzyme substrates and inhibitors. Such probes perturb the nuclei in their vicinity and alter the nuclear relaxation rates. Quantitation of such effects can provide distances between the probes and nuclei on the enzyme surface. Another method, transferred nuclear Overhauser enhancement, permits additional studies of the conformation of substrates and activators at the active sites of these enzymes.
One of the most interesting of these membrane-associated enzymes is the adenylyl cyclase toxin from Bordetella pertussis. Attack of host cells by this toxin results in transport of the catalytic domain of this toxin across the plasma membrane. The mechanism of this transport is not understood, but it appears to depend on a family of b-sheet helix domains in the C-terminal portion of the toxin. We are characterizing the structure and function of the b-sheet helices of this toxin by a variety of magnetic resonance techniques.
We are also examining a series of metal complexes with organic bisphosphonates as potential therapeutic agents for osteoporosis and other bone diseases. Strength and integrity of bones depend upon a balance between bone formation by osteoblasts and bone resorption by osteoclasts. Osteoclasts depend for their activity on GTP-binding proteins Rho, Rab, and cdc42, which must be prenylated to be active. Prenyl groups are synthesized in the farnesyl pyrophosphate synthase (FPS) reaction. Bisphosphonates inhibit the FPS reaction and thus inactivate osteoclasts, which then undergo apoptosis, resulting in reduced bone resorption, lower bone turnover, and a positive bone balance. Stable complexes of bisphosphonates with Cr(III), Co(III), and Rh(III) are being examined as therapeutic alternatives to the metal-free bisphosphonates.
Structural Consequences of Divalent Metal Binding by the Adenylyl Cyclase Toxin of Bordetella Pertussis. Rhodes CR, Gray MC, Watson JM, Muratore TL, Kim SB, Hewlett EL, Grisham CM. Arch Biochem Biophys. 395, 169-76 (2001).
Influence of lipid on the structure and phosphorylation of protein kinase C alpha substrate peptides. Vinton BB, Wertz SL, Jacob J, Steere J, Grisham CM, Cafiso DS, Sando JJ. Biochem J. 330, 1433-42 (1998).
Intermolecular chiral recognition probed by enantiodifferential excited-state quenching kinetics. Stockman TG, Klevickis CA, Grisham CM, Richardson FS. J Mol Recognit. 9, 595-606 (1996).
31P NMR investigation of energy metabolism in perifused MMQ cells. Goger MJ, Login IS, Fernandez EJ, Grisham CM. Magn Reson Med. 3, 584-91 (1994).
T. Brent Gunnoe
Organometallic chemistry, inorganic chemistry, homogeneous catalysis, small molecule activation
The development of more efficient synthetic methods represents a major economic and environmental challenge for the chemical industry. With research interests that span the fields of inorganic and organic chemistry, we focus on the preparation and characterization of new transition metal complexes that are capable of activating organic molecules toward novel reactivity. By concentrating on fundamental aspects of inorganic and organometallic chemistry, our efforts are ultimately directed toward the rational design of single-site catalysts that form the foundation of new homogeneous synthetic methodologies.
Petroleum distillates make up a considerable fraction of the synthetic building blocks available to the chemical industry. With the steep rise in demand for oil, the efficient use of fossil resources is becoming increasingly important. Carbon and hydrogen are the major elemental constituents of fossil-derived products. Thus, one area of focus for our group is the design of complexes that selectively break C-H bonds and transform them into useful products. For example, we are exploring the use of late transition metal systems for catalytic C-C bond formation reactions that proceed through metal-mediated C-H activation. Systems based on Ru(II), Pt(II), Rh(III) and Pt(IV) developed in our labs catalyze the addition of aromatic (including arenes and heteroaromatic substrates) C-H bonds across the C=C bonds of olefins. By understanding how the metal identity, metal oxidation state, and ancillary ligand identities impact this reaction step, we can design improved catalysts.
Another area of interest is the reactivity of transition metal complexes with high d-electron counts that possess amido, nitrene, oxo, hydroxide and alkoxide ligands, which we are seeking to apply toward hydrocarbon functionalization reactions. By accessing systems with highly electrophilic metal centers yet basic/nucleophilic non-dative ligands, we can take advantage of tandem activation of organic substrates. We are exploring the application of such systems toward the activation of both non-polar (e.g., dihydrogen and C-H) bonds as well as polar bonds. For example, we have recently developed Cu catalysts for the addition of O-H, N-H and S-H bonds across the multiple bonds of olefins and alkynes. Both intramolecular and intermolecular variants have been demonstrated. In addition, we are using C-H activation reactions by transition metal alkoxide systems as a foundation to develop catalysts for the partial oxidation of hydrocarbons.
In addition to projects focused on organometallic chemistry and homogeneous catalysis, the Gunnoe group collaborates with a molecular biology group to design chemical delivery systems for novel insecticides and pesticides. This project, which has been funded by the United States Department of Agriculture, seeks to exploit complementary expertise in the two research groups to design new biotechnologies.
Catalytic Synthesis of "Super" Linear Alkenyl Arenes Using an Easily Prepared Rh(I) Catalyst, Webster-Gardiner, M. S., Chen, J., Vaughan, B. A., McKeown, B. A., Schinski, W., Gunnoe, T. B.* J. Am. Chem. Soc. 2017, 139, 5474-5480. DOI: 10.1021/jacs.7b01165. This manuscript was highlighted in Chemical and Engineering News 2017, 95(17), 8.
Mechanistic Studies of Single-Step Styrene Production Using a Rhodium(I) Catalyst,Vaughan, B. A., Khani, S. K., Gary, J. B., Kammert, J. D., Webster-Gardiner, M. S., McKeown, B. A., Davis. R. J., Cundari, T. R.*, Gunnoe, T. B.* J. Am. Chem. Soc. 2017, 139, 1485-1498. DOI: 10.1021/jacs.6b10658
Aerobic Epoxidation of Olefin by Platinum Catalysts Supported on Mesoporous Silica Nanoparticles, Munz, D., Wang, D., Moyer, M. M., Webster-Gardiner, M. S., Kunal, P., Watts, D., Trewyn, B. G.*, Vedernikov, A. N.*, Gunnoe, T. B.* ACS Catalysis 2016, 6, 4584–4593. DOI: 10.1021/acscatal.6b01532
Organometallic Complexes Anchored to Conductive Carbon for Electrocatalytic Oxidation of Methane at Low Temperature, Joglekar, M., Nguyen, V., Pylypenko, S., Ngo, C., Li, Q., O’Reilly, M.E., Gray, T.S., Hubbard, W.A., Gunnoe, T. B.*, Herring, A. M.*, Trewyn, B.G.*. J. Am. Chem. Soc. 2016, 138, 116-125. This manuscript was highlighted in C&E News, featured on cover of J. Am. Chem. Soc., and selected for JACS Spotlights.
A Rhodium Catalyst for Single-Step Styrene Production, Vaughan, B. A., Webster-Gardiner, M. S., Cundari, T. R.*, Gunnoe, T. B.* Science 2015, 348, 421-424. DOI: 10.1126/science.aaa2260. This manuscript was highlighted in Chemical and Engineering News 2015, 93 (17), 26.
W. Dean Harman
For decades, the dearomatization of arenes has been recognized as a chemical transformation of fundamental importance. It provides the connection between this robust and abundant source of hydrocarbons and the alicyclic frameworks common to many biologically active products. Thus, dearomatization methods have become powerful tools for organic synthesis.
The chemical properties of arenes are influenced by their coordination to a transition metal. For example, complexes such as (η6-arene)Cr(CO)3+ and its cationic analogs (e.g., FeCp+, RuCp+, Mn(CO)3+) are susceptible to nucleophilic substitution or addition, ultimately leading to the formation of substituted arenes or cyclohexadienes, respectively. During the past three decades, the application of η6-arene complexes to organic synthesis has been widely explored.
In the Harman Research Group, an alternative approach to the dearomatization of arenes has been developed in which the aromatic system may be activated toward organic transformations by η2-coordination. Here, the metal-arene bond is stabilized primarily by the interaction of filled metal dπorbitals with the π* system of the arene, an interaction having two important consequences for the activation of the aromatic ring. Through πbackbonding, the aromatic π system becomes more electron-rich, similar to what is observed for organic arenes bearing electron-donating groups. Additionally, structural data for complexes containing η2-coordinated aromatic rings show significant distortions in the bond lengths of the ring consistent with a localization of πelectron density. Together, these effects activate η2-bound aromatic systems toward electrophilic rather than nucleophilic addition. When the π base binds an aromatic heterocycle such as a pyridine, furan or pyrrole, novel tandem addition reactions and cycloaddition reactions become possible.
Of the handful of transition metal systems that are known to form stable η2 complexes with aromatic molecules, only d6 octahedral metal complexes have been shown to enhance the reactivity of the aromatic ligand toward electrophiles to date. For nearly a decade, despite our best efforts, this mode of arene activation was known only for the pentaammineosmium(II) system. However, in the past few years a new generation of dearomatization agents have been developed in our group based on a careful matching of the d5/d6 reduction potential of rhenium(I), tungsten(0), and molybdenum(0) complexes with that of pentaammineosmium(II).
Molybdenum(0) Dihapto-Coordination of Benzene and Trifluorotoluene: The Stabilizing and Chemo-Directing Influence of a CF3 Group, Myers, J. T.; Smith, J. A.; Dakermanji, S. J.; Wilde, J. H.; Wilson, K. B.; Shivokevich, P. J.; Harman, W. D., J. Am. Chem. Soc. 2017, 139, 11392-11400.
Sequential Tandem Addition Reactions to a Tungsten-Trifluorotoluene Complex: A Versatile Method for the Preparation of Highly Functionalized Trifluoromethylated Cyclohexenes, Wilson, K. B.; Myers, J. T.; Nedzbala, H. S.; Combee, L. A.; Sabat, M.; Harman, W. D., J. Am. Chem. Soc., 2017, 139, 11401-11412. *Article highlighted in C&EN.
Synthesis of Novel Hexahydroindoles from the Dearomatization of Indoline, Macleod, B. L.; Pienkos, J. A.; Wilson, K. B.; Sabat, M.; Myers, W. H.; Harman, W. D., Organometallics, 2016, 35, 370–387. *Article chosen as ACS Editors' Choice.
Enantioenrichment of a Tungsten Dearomatization Agent Utilizing Chiral Acids, Lankenau, A. W.; Iovan, D. A.; Pienkos, J. A.; Salomon, R. J.; Wang, S.; Harrison, D. P.; Myers, W. H.; Harman, W. D., J. Am. Chem. Soc., 2015, 137, 3649-3655. *Article highlighted in C&EN.
Surface Chemistry: Catalysis, Photochemistry, Reaction Kinetics and Dynamics
Catalysis is an essential technology supporting our way of life and contributes towards roughly one third of the material GDP of the US economy. At the beginning of the twentieth century, the catalytic transformation of nitrogen on nanoscale, potassium promoted, iron catalysts to ammonia, and ultimately fertilizer, profoundly changed the human condition and currently supports an additional 2.4 billion people beyond what the Earth could otherwise sustain. In the twenty-first century, the catalytic challenge will be to facilitate a rapid transition from a petroleum-based energy and chemical economy to a more generalized one based on natural gas, hydrogen, coal, biomass, and solar energy (photochemistry). Energy efficient chemical transformations, environmental protection, and green chemistry will continue to rely heavily on catalysis. Most industrially viable catalysis takes place on the surfaces of transition metal nanocrystallites dispersed on oxide supports. Our research focuses on understanding gas-surface reactions on simplified scientific model surfaces, namely, on single crystal surfaces. Recent progress includes the development of quantitative models for (i) the C-H bond activation of CH4 on metal surfaces that relates to the industrial production of H2 via natural gas reforming on metal nanocatalysts, and (ii) the chemical vapor deposition of Si on Si (100) by SiH4 that is central to Si homoepitaxy in microelectronics manufacturing. Current activities focus on exploring the thermal and photochemical reaction dynamics of catalytically important and energy-related small molecules, such as H2, CO2, CH4, alkanes, and alcohols, on transition metal surfaces. Our research typically employs ultrahigh vacuum surface analytical techniques (e.g., TPD, AES, XPS, RAIRS, STM, LEED) as well as some more specialized laser techniques (SFG, TOF) and/or microcanonical unimolecular rate theory. Our goal is to characterize the transition states of important catalytic reactions and to develop an improved understanding of how to design efficient and selective thermal and photochemically driven catalysts.
Rice−Ramsperger−Kassel−Marcus Simulation of Hydrogen Dissociation on Cu(111): Addressing Dynamical Biases, Surface Temperature, and Tunneling. Donald SB and. Harrison I. J. Phys. Chem. C, 118, 320-337 (2014).
Methane dissociative chemisorption and detailed balance on Pt(111): Dynamical constraints and the modest influence of tunneling. Donald SB, Navin JK and Harrison I. J. Chem. Phys. 139, 214707 (2013).
Communication: angle-resolved thermal dissociative sticking of CH4 on Pt(111): further indication that rotation is a spectator to the gas-surface reaction dynamics. Navin JK, Donald SB, Tinney DG, Cushing GW, Harrison I. J Chem Phys. 136:061101 (2012).
Dynamically biased RRKM model of activated gas-surface reactivity: vibrational efficacy and rotation as a spectator in the dissociative chemisorption of CH4 on Pt(111). Donald SB, Harrison I. Phys Chem Chem Phys. 214:1784-95 (2012).
An effusive molecular beam technique for studies of polyatomic gas-surface reactivity and energy transfer. Cushing GW, Navin JK, Valadez L, Johánek V, Harrison I. Rev Sci Instrum. 82(4):044102 (2011).
Professor Herbst’s major research field lies in the interdisciplinary area of molecular astronomy, which is the study of molecules throughout the universe, especially in regions in between stars known as interstellar clouds. These objects eventually collapse to form new generations of stars and planetary systems, so the molecules found in interstellar clouds are related to the molecules found in planets such as our own. Herbst is specifically interested in the chemical processes by which molecules grow, in using these chemical processes to predict the actual concentrations of molecules, and in the role of molecules in the understanding of their physical environments. His research was featured in Chemical and Engineering News, the popular journal of the American Chemical Society. A fellow of the American Physical Society and the Royal Society of Chemistry (U. K.), Herbst has won a number of international prizes including the Centenary Award of the Royal Society of Chemistry.
|Below are pictures of two astronomical objects where molecules are found.|
|On the right is a nebula of gas and dust surrounding an old star. It is known as the “red rectangle.”|
|Below is an interstellar cloud so dense that no light can pass through it.|
A New Model on the Chemistry of Ionizing Radiation in Solids: CIRIS,.Shingledecker, C. N., & Herbst, E., Phys. Chem. Chem. Phys., 19, 11043-11056 (2017)
Unified Microscopic-Macroscopic Monte Carlo Calculations of Complex Organic Molecule Chemistry in Cold Cores,. Chang Q., & Herbst, E., ApJ, 819:145(1-13) (2016)
Chemical and Physical Characterization of Collapsing Low-Mass Prestellar Dense Clouds, Hincelin, U., Commercon, B., Wakelam, BV., Hersant, F., Guilloteau, S., & Herbst, E., ApJ, 822:12(1-31) (2016)
Complex organic molecules in protoplanetary disks, Walsh, C., Millar, T. J., Nomura, H., Herbst, E., Widicus Weaver, S., Aikawa, Y., Laas, J. C., & Vasyunin, A. I., A&A, 563, A33(1-35) (2014)
Reactive Desorption and Radiative Association as Possible Drivers of Complex Molecule Formation in the Cold Interstellar Medium, Vasyunin, A. I., & Herbst, E., ApJ, 769, id. 34(1-9) (2013)
The science of organic synthesis is central to both the discovery and manufacturing of pharmaceuticals and other fine chemicals and the emergence of subdisciplines of biology that are becoming increasingly focused on phenomena at the molecular level (e.g., synthetic biology and chemical biology). Over the last half-century revolutionary advances in synthetic organic chemistry have made it possible to synthesize virtually any molecule given enough time, money, and manpower. However, this is frequently not enough since a lack of practical and cost-effective synthetic access can and does prevent promising drug leads from ever helping patients. The grand challenge for synthetic organic chemistry is therefore to advance the field of synthesis to the point where any molecule can be not only synthesized, but also synthesized in a way that minimizes the cost, time, and manpower required as well as environmental impact. Our group’s research is focused on eliminating synthetic considerations as a barrier to the discovery of new therapeutics.
Organocatalytic, Dioxirane-Mediated C-H Hydroxylation under Mild Conditions Using Oxone. W. G. Shuler, S. L. Johnson, M. K. Hilinski, Org. Lett. 2017, 19, 4790–4793. An Iminium Salt Organocatalyst for Selective Aliphatic C–H Hydroxylation. D. Wang, W. G. Shuler, C. J. Pierce, M. K. Hilinski, Org. Lett. 2016, 18, 3826–3829. Intermolecular Electrophilic Addition of Epoxides to Alenes: [3+2] Cycloadditions Catalyzed by Lewis Acids. W. G. Shuler, L. A. Combee, I. D. Falk, M. K. Hilinski, Eur. J. Org. Chem. 2016, 3335–3338. Chemoselective Hydroxylation of Aliphatic sp3 C–H Bonds Using a Ketone Catalyst and Aqueous H2O2. C. J. Pierce, M. K. Hilinski, Org. Lett. 2014, 16, 6504–6507.
Ku-Lung (Ken) Hsu
My laboratory aims to integrate state-of-the-art chemical biology and mass spectrometry to address fundamental challenges associated with studying the regulation of lipid metabolism and signaling in vivo. Our goal is to develop new chemical and bioanalytical methods to understand pathways of metabolic regulation and translate these findings into new therapeutic strategies for human disease. To achieve our goals, we synthesize and apply small molecule probes and inhibitors to detect and inactivate metabolic enzymes and pathways in living systems. By integrating innovative solutions from chemistry, genetics, biochemistry, and pharmacology, our interdisciplinary approach enables testing of mechanistic hypotheses for basic and therapeutic discovery. A major focus of my laboratory is to expand the number and type of molecular targets suitable for applications in immuno-oncology and chronic inflammation. Members of my group receive cross-disciplinary training in chemical biology, mass spectrometry, medicinal chemistry, and in vivo pharmacology.
The ligand binding landscape of diacylglycerol kinases. Franks CE, Campbell ST, Purow BW, Harris TE, and Hsu KL. Cell Chemical Biology 24, 870-880 (2017).
Liposomal delivery of diacylglycerol lipase-beta inhibitors to macrophages dramatically enhances selectivity and efficacy in vivo. Shin M, Snyder HW, Donvito G, Schurman LD, Fox TE, Lichtman AH, Kester M, and Hsu KL. Molecular Pharmaceutics (DOI: 10.1021/acs.molpharmaceut.7b00657).
Deconstructing lipid kinase inhibitors by chemical proteomics. McCloud RL*, Franks CE*, Campbell ST*, Purow BW, Harris TE, and Hsu KL (2017). Biochemistry (10.1021/acs.biochem.7b00962).
Donald F. Hunt
The goal of our research is to develop new methods and instrumentation for the structural characterization of proteins and their post-translational modifications at the low femtomole/attomole level and to apply these new methods to important structural problems in cell biology and immunology. Towards this end, we have pioneered the use of nanoflow HPLC in conjunction with microelectrospray ionization on ion trap and Fourier transform mass spectrometers. Briefly stated, the approach involves the use of proteolytic enzymes to convert the protein or group of proteins into a complex mixture of peptides, which are then fractionated by nanoflow-HPLC and eluted directly into the mass spectrometer. Mixtures containing thousands of different peptides can be analyzed in this manner. Protonated peptides of a particular mass are selected under computer control of the instrument, fragmented on collision with helium atoms and the resulting fragments are then separated and mass analyzed. Dissociation of the peptide ions occurs more or less randomly at each of the amide bonds in the molecules to produce a collection of fragments. The mass difference between two fragments differing by a single amino acid defines the mass and thus the identity of the extra residue in the longer fragment. Peptide sequence analysis is performed routinely at the femtomole and low attomole levels on the ion trap and Fourier transform instruments, respectively. Mass spectra acquired in the above manner can also be used to search databases and to identify known proteins. Currently, this approach is the most sensitive method in the world for protein characterization.
Our research focuses on two major applications of the above technology. The first involves identifying peptides that trigger the immune system to kill diseased cells. Cytotoxic T lymphocytes (CTL) or killer cells are an arm of the immune system concerned with recognition of cells that express new antigens, proteins, as a result of viral infection or cellular transformation (cancer). Cells convey their health status to the immune system by generating fragments from each of the approximately 10,000 proteins being synthesized, loading them onto a protein carrier (MHC molecule), and transporting them to the cell surface for screening by the killer cells. CTL lyse those cells that display new fragments, antigens that are associated with a particular disease state. Identification of these antigens is the first step in the preparation of vaccines that promote immunity against the above diseases. Peptides that cause the immune system to kill melanoma and lung cancer cells, to reject bone marrow transplants to leukemia patients, and to lyse tuberculosis infected cells have been identified in the laboratory recently. Efforts are in progress to characterize the peptide antigens that (a) cause rejection of tissue transplants, (b) trigger organ or tissue destruction in such autoimmune disorders as diabetes, arthritis, and multiple sclerosis, and (c) initiate an immunological response to breast, ovarian, colorectal, lung, and prostate cancers.
The second application involves research in the field of proteomics. DNA sequence information on the human genome and that of selected organisms is now becoming available at an ever-increasing rate and will provide the starting point for the development of novel therapeutic interventions against many of the world’s diseases. The next challenge is at the level of proteomics, understanding the functions of proteins encoded by a particular genome. Presently under development are mass spectrometry methods that will facilitate differential display and quantitation of most, if not all proteins expressed by healthy vs diseased cells or cells grown in the presence or absence of drugs or other agonists. Mass spectrometry is also being used to analyze all proteins secreted by a particular cell type, to identify components of functionally active protein complexes, to probe protein-protein and protein-DNA interactions, and to locate post-translational modifications and covalently attached ligands. Recently, we have developed methods that facilitate analysis of all phosphoproteins expressed in a particular cell population.
Peptide Binding Motifs of Two Common Equine Class I MHC Molecules in Thoroughbred Horses, Bergman T, Lindvall M, Moore E, Sidney J, Miller D, Talmadge R, Myers P, Shabanowitz J, Osterreider N, Peters B, Hunt DF, Antczak DF, Sette A, Immunogenetics, 2017 May; 69(5):351-358. PMCID:PMC 5555743.
Canonical and Cross–reactive Binding of NK Cell Inhibitory Receptors to HLA-C Allotypes is Dictated by Peptides Bound to HLA-C. Sim MJ, Malaker SA, Khan A, Stowell JM, Shabanowitz J, Peterson ME, Rajagopalan S, Hunt DF, Altmann DM, Long EO, Boyton RJ, Front Immunol 2017 Mar 14(8);193. Doi:10.3389/fimmu.2017.00193.eCollection 2017 PMCID:PMC 5348643.
The Antigenic Identify of Human Class I MHC Phosphopeptides is Critically Dependent Upon Phosphorylation Status, Mohammed F, Stones DH, Zarling AL, Willcox CR, Shabanowitz J, Cummings KL, Hunt DF, Cobbold M, Engelhard VH, Willcox BE, Oncotarget J, 2017; April 8 (33):54160-54172. PMID: 28903331.
Front-End Electron Transfer Dissociation Coupled to a 21 Tesla FT-ICR Mass Spectrometer for Intact Protein MS/MS Analysis, Weisbrod DR, Kaiser NK, Early L, Mullen C, Syka JEP, Dunyach JJ, Anderson LC, English AM, Blakney GT, Shabanowitz J, Hendrickson CL, Marshall AG, Hunt DF, J Amer Soc Mass Spectrom, 2017;Jul 18: PMID 28721671.
Shared Peptide Binding Specificities of HLA Class I and Class II Alleles Associate with Cutaneous Nevirapine Hypersensitivity and Identify Novel Risk Alleles, Pavlos R, McKinnon EJ, Ostrov DA, Peters B, Buus S, Koelle D, Chopra A, Rive C, Redwood A, Restrepo S, Bracey A, Kaever T, Myers, P, Speers E, Malaker SA, Shabanowitz J, Jing Y, Gaudieri S, Hunt DF, Carrington M, Haas DW, Mallal S, Phillips EJ, Sci Rep, 2017; 7(1):8653.doi:10.1038/s41598-017-08876-0. PMID: 28819312.
James P. Landers
Polyethylene Terephthalate Microdevices
Our research group has developed a technique for fabricating microfluidic devices with complex multilayer architectures using a laser printer, a CO2 laser cutter, an office laminator, and common overhead transparencies as a printable substrate via a laser print/cut and laminate (PCL) methodology. The printer toner serves three functions; (1) it defines the microfluidic architecture, (2) acts as the bonding agent, and (3) provides printable, hydrophobic "valves" for fluidic flow control. Using common graphics software, the protocol produces microfluidic devices with a design-to-device time of ~40 min. Devices of any shape can be generated for an array of multistep assays with colorimetric detection of molecular species ranging from small molecules to proteins. The simplicity of the protocol, availability of the equipment and substrate and cost-effective nature of the process make microfluidic devices available to those who might benefit most from expedited, microscale chemistry.
Figure 1. A microfluidic chip designed to dispense sample and mix reagents by rotating at varying speeds. This specific device is used to measure albumin concentration, white blood cell count, and hematocrit in whole blood.
Biological, Bioanalytical and Clinical Chemistry
Almost every aspect of the biochemical, biomedical and clinical sciences involves separation of species in complex matrices. Electrophoresis has been a benchmark technique for separation and characterization of biologically-active species. Instead of using conventional slab gel electrophoretic approaches, electrophoresis in micron-scale capillaries using applied fields as high as 30,000 volts, results in unprecedented resolution with unique selectivities and short analysis times. As a result of the microscalar nature of the capillary, only microliters of reagent are consumed by analysis with only a few nanoliters of samples injected for analysis. These characteristics, as well as the ability for on-line detection with laser-induced fluorescence sensitivities in the attomole (10-18 moles) range, made capillary electrophoresis (CE) appealing as a replacement for electrophoretic gels in the biomedical and clinical arenas. We have demonstrated the potential impact of CE on clinical diagnostics through the development of new CE-based assays for measuring kidney function, detecting multiple sclerosis and viral infections, screening for lymphoma, as well as for diagnosing drug abuse and alcoholism.
While the diagnostic impact of standard CE technology is clear, an alternative platform for electrophoresis in microscalar structures has evolved in the form of microchip electrophoresis. The use of microfabricated glass devices containing etched capillary-like channels provides an electrophoretic platform akin to CE but with more flexibility. “Microchip electrophoresis” allows for analysis times to be decreased by an order of magnitude over times achievable by CE (as fast as 10-200 seconds) and two orders of magnitude faster than gel electrophoresis. This provides obvious value to clinical diagnostic laboratories in terms of more rapid turn around time and capability for high throughput screening. We have demonstrated this with the detection T-cell and B-cell lymphoma in a separation remarkably faster than with conventional means.
Figure 2. Demonstration of microchip electrophoresis as a technique for rapid diagnosis of T-Cell lymphoma. Sample T1 shows a negative sample, which is represented by the smear after 100 seconds of separation. T4 is a positive sample with a sharp peak.
With a program focused on the application of miniaturized electrophoretic technology to the clinical and forensic sciences, our current efforts involve broadening the scope of applications for microchip technology. This involves addressing issues associated with integrating functions other than "separation" onto microchips. For example, we are focused on defining approaches for integrating DNA sample preparation into microchips. PCR amplification of DNA carried out using infrared-mediated thermocycling for rapid on-chip amplification and rapid DNA extraction using microchamber-bound solid phases are two examples of our integration efforts.
The successful integration of DNA extraction and amplification will lead to the development of an “Integrated Diagnostic” or ID-chip, which we ultimately hope will improve laboratory medicine. Efforts are also underway to 1) define better detection systems using acoustic-optic technology, 2) develop multichannel devices for high-throughput analysis using this optical technology, 3) explore proteomic aspects of disease using multi-dimensional microchips for protein separations, and 4) apply the relevant methods to forensic applications.
Simultaneous metering and dispensing of multiple reagents on passivelycontrolled microdevice solely by finger pressing. Xu K, Begley M, Landers JP. Lab on a Chip. 15: 867-876 (2015).
Integrated sample-in-answer-out microfluidic chip for Rapid HumanIdentification by STR analysis. Le Roux D, Root B, Reedy C, Hickey J, Scott O, Bienvenue J, Landers JP, Chassagne L, Mazancourt P. Lab on a Chip. 14:4415-4425 (2014).
DNA Analysis Using an Integrated Microchip for Multiplex PCRAmplification and Electrophoresis for Reference Samples. Le Roux D, Root B, Reedy C, Hickey J, Scott O, Bienvenue J, Landers JP, Chassagne L, Mazancourt P. Analytical Chemistry. 86:8192-8199 (2014).
Rapid, cost-effective DNA quantification via a visually-detectableaggregation of superparamagnetic silica-magnetite nanoparticles. Liu Q, Li J, Liu H, Tora I, Ide M, Lu J, Davis R, Green D, Landers JP. Nano Research. 7:755-764 (2014).
Dual-force aggregation of magnetic particles enhances label-freequantification of DNA at the sub-single cell level. Nelson D, Strachan B, Sloane H, Li J, Landers JP. Analytica Chimica Acta. 819:34-41 (2014).
Enhanced recovery of spermatozoa and comprehensive lysis of epithelialcells from sexual assault samples having a low cell counts or aged up to one year. Loundsbury J, Nambia S, Karlsson A, Cunniffe H, Norris J, Ferrance J, Landers JP. Forensic Science International: Genetics. 8:84-89 (2014).
John S. Lazo
The pharmacological mechanism of action of small molecules and on the fundamental biological role of protein tyrosine phosphatases in disease.
Our laboratory is currently focused on two major topics: (1) discovering and characterizing novel small molecules that could lead to treatments of cancer, Alzheimer’s disease, ionizing radiation exposure and neglected diseases, and (2) validating the fundamental biological role of protein tyrosine phosphatases in cancer.
We use a variety of platforms to seek new small molecules for human disease. These include computational modeling, high throughput target-based in vitro screening and phenotypic screening of small molecule and small interfering RNA libraries. We maintain several automated liquid handling devices and small molecule libraries for the purpose of exploring various areas of chemical space for bioactive compounds. We have been using human pluripotent cells as a model for radiation injury and mitigation.
A second major research project focuses on investigating how the dual specificity, protein tyrosine phosphatases, such as Cdc25B and phosphatase of regenerating liver PTP4A3, control cell proliferation, migration, invasion, and survival using both molecular biological and pharmacological approaches and on applying chemical biological methodologies to the discovery of new chemical probes and potential therapeutics. We currently have developed the first well-characterized, conditional PTP4A3 knockout mouse model to investigate the role of this unique protein in colorectal tumorigenesis and tumor angiogenesis. We are seeking to identify the endogenous substrates for PTP4A3 in tumor and endothelial cells using proteomic and informatics approaches. We have discovered several potent and specific small molecule inhibitors of these protein phosphatases and are investigating their pharmacological properties.
Targeted deletion of the metastasis-associated phosphatase Ptp4a3 (PRL-3) suppresses murine colon cancer. Zimmerman, M.W., Homanics, G.E. and Lazo, J.S. PLoS One, 8:e58300 (2013).
Effector kinase coupling enables high-throughput screens for direct HIV-1 Nef antagonists with antiretroviral activity. Emert-Sedlak, L.A., Narute, P., Shu, S.T., Poe, J.A., Shi, H., Yanamala, N., Alvarado, J.J., Lazo, J.S., Yeh, J.I., Johnston, P.A., and Smithgall, T.E. Chem Biol. 20:82-91 (2013).
Phenotypic screening reveals topoisomerase I as a breast cancer stem cell therapeutic target. Zhang,F., Rothermund, K, Gangadharan, S.B., Pommier, Y., Prochownik, E.V., and Lazo, J.S. Oncotarget. 3:998-1010 (2012).
Alkylation sensitivity screens reveal a conserved cross-species functionome. Svilar, D., Dyavaiah, M., Brown, A.R., Tang, J., McDonald, P.R., Shun, T. Y., Wang, X-H., Lazo, J.S., Pollack, I.F., Begley, T.J. and Sobol, R. W. Mol Cancer Res., 11:1683-1692 (2012).
Discovery of diverse small molecule chemotypes with cell-based PKD1 inhibitory activity. Sharlow, E.R., Mustata Wilson, G., Close, D., Leimgruber, S., Tandon, M., Reed, R.B., Shun, T.Y., Wang, Q.J., Wipf, P., and Lazo, J.S. PLoS One 6:e25134 (2011).
Compound acquisition and prioritization algorithm for constructing structurally diverse compound libraries. Ma, C., Lazo, J.S, and Xie, X.Q. ACS Comb Sci. 13:223-231 (2011).
Kevin K. Lehmann
There are many problems of both fundamental and of practical importance that requires measurement of extremely low concentrations of certain impurities. Molecular spectroscopy provides one approach that excels in the high specificity provided by the detailed structure in the spectrum, particularly for molecules in the gas phase. Lehmann’s group has been working on the development of new trace sensors, largely based upon the method of cavity ring-down spectroscopy (CRDS). In CRDS, one forms a stable optical cavity using mirrors with reflectivity > 99.99 percent and observes absorption of a sample contained inside the cavity by an increase in the rate of decay of light that is trapped between the mirrors. Sample absorption as low as 1 part in 109 per pass of the cell can be measured in this way. The Lehmann group pioneered the use of low cost and rugged diode lasers developed for the telecom industry in CRDS and has demonstrated detection of a number of small molecules, such as H2O, NH3, and CH4 at levels below one part per billion in a sample gas. Tiger Optics, Inc. is now selling instruments based upon this work to several industries. We have developed a new, fiber optic version of CRDS and have demonstrated that this could be used to detect a single cell that sticks to the surface of an optical fiber. We are developing a new broad bandwidth version of CRDS that will allow multiple chemical species to be monitored simultaneously, such as with an FTIR, but with much higher sensitivity. This instrument uses an optical cavity formed from a pair of Brewster Angle Prism Retroreflectors that are low loss over a wide spectral range, unlike the dielectric mirrors usually used which are only low loss for a band of ~5% in wavelength. The light source is a supercontinuum, covering 500 nm – 1.8 μm which is generated using a photonic crystal nonlinear fiber. Breath analysis for medical diagnosis is an important potential application of CRDS that we would like to explore. We are presently working on detection of NO using a mid-IR CRDS instrument that uses an external quantum cascade laser as a radiation source. It is anticipated that a detection limit of ~10 parts per trillion will be realized. Rapid detection of NO can be used as a marker for infection and asthma. We are also developing a near-IR instrument to detect the 13C/12C and D/H ratios in atmospheric methane. Such a ratio is affected by kinetic isotope effects and thus give information on the chemical reactions and form and destroy methane in the environment.
Spectroscopy in Superfluid Helium
Research in the Lehmann group has long used laser spectroscopy and theoretical modeling to study molecular dynamics – studying chemical reactions at their most fundamental level. In recent years, this line of work has focused on the spectroscopy of atoms and molecules dissolved in nanodroplets of superfluid helium. Helium Nanodroplet Isolation (HENDI) combines many of the most attractive features of both high resolution, molecular beam spectroscopy and more traditional rare gas matrix spectroscopy. The droplets cool any solvated molecule down to a temperature of only 0.38 K but remain liquid, which allows molecules to move and rotate nearly freely with relaxation times three to four orders of magnitude longer than in traditional liquids. This allows for the study of the interaction of molecules with a unique solvent, where quantum effects dominate. Fundamental questions are yet unresolved, such as how the molecules come into equilibrium with the superfluid and why quantized vortices (which are common in build liquid helium) have not been observed in the droplets. The droplets allow the production of new chemical species and new isomers of known compounds.
We are working on the spectroscopy of free radicals in helium. Traditional wisdom is that the reaction of two free radicals can occur without a barrier, but high-level ab initio calculations suggest that in many such reactions (such as O2+ O -> O3), small entrance channel barriers exist and these are believed to play an important role in the rates of three body recombination; a process that produces O3 in the atmosphere. It should be possible to quench entrance channel complexes and study their properties using HENDI. We have an atomic hydrogen source and plan to use it to study reactions such as H + CO -> HCO in the helium droplets. Such hydrogen addition reactions are believed to be important in the chemistry of interstellar space. We are finishing construction of a molecular beam machine to study helium droplets doped with atomic and molecular ions. We will mass select the droplets using a hemispherical energy analyzer. We will study the translational motion of ions in nanodroplets and attempt to create vortices by driving the ions with circularly polarized microwave radiation. Among other experiments, we plan to determine the binding energies of atomic and molecular cluster ions by the measurement of the number of helium atoms evaporated from the droplet by the cluster formation.
. Sung K, Brown LR, Huang X, Schwenke DW, Lee TJ, Coy SL, Lehmann KK. J. Quantitative Spectroscopy & Radiative Transfer. 113:1066-108 (2012).
A rigid, monolithic but still scannable cavity ring-down spectroscopy cell. Tang Y, Yang SL, Lehmann KK. Review of Scientific Instruments. 83:043115 (2012).
Sensitivity limit of rapidly swept continuous wave cavity ring-down spectroscopy. Huang H, Lehmann KK. J Phys Chem A. 115:9411-21 (2011).
(HCN)(m)-M-n (M = K, Ca, Sr): Vibrational Excitation Induced Solvation and Desolvation of Dopants in and on Helium Nanodroplets. Douberly GE, Stiles PL, Miller RE, Schmeid R, Lehmann KK. J. Phys. Chem A. 114, 3391-3402 (2010).
Long-term stability in continuous wave cavity ringdown spectroscopy experiments. Huang HF, Lehmann KK. Applied Optics. 49, 1378-1387 (2010).
The Machan group is interested in energy-relevant catalysis, particularly at the interface of molecular electrochemistry and materials. The development of efficient and selective transformations to produce commodity chemical precursors and fuels using CO2, O2, H2, and H2O as reagents remains an ongoing challenge for the storage of electrical energy within chemical bonds. Our approach is inspired by the numerous metalloproteins capable of catalyzing kinetically challenging reactions with significant energy barriers in an efficient manner under ambient conditions. This type of reactivity is achieved through the convergent evolution of active sites with tailored coordination environments and macromolecular structures which can, among other things, transport substrates and products to and from the active site. Our research focuses on developing new inorganic complexes and materials which incorporate co-catalytic moieties, non-covalent secondary sphere interactions, and substrate relays as catalysts.
In order to characterize and optimize these systems, research in the Machan group uses synthetic inorganic chemistry, electrochemistry, and advanced characterization techniques (spectroelectrochemistry, stopped-flow IR and UV-vis spectroscopies). This enables us to develop an understanding of electronic structure and mechanism in transformations of interest. A brief summary of current projects is listed below.
Dioxygen as Chemical Oxidant for C–H Bond Activation
The development of catalytic aerobic C–H activations is of general interest for petrochemical and biomass functionalization. First-row transition metals which use O2 as a substrate generally require high catalyst loadings, sacrificial reducing agents, and have limited selectivity. Transition metal oxo species, which are known to activate C–H bonds, have not been isolated to the right of Fe on the periodic table, which is a point of mechanistic divergence when comparing the reactivity of Fe and Co compounds with O2. To exploit the implications of this electronic constraint between Fe and Co, rigid and redox non-innocent ligand platforms are employed to generate tetragonal complexes with reactive metal-oxygen species, obviating the need for high oxidation states at the metal center.
Molecular Electrocatalysts for Converting Bicarbonate to Formate in Water
The efficient and cost-effective catalytic reduction of CO2 using renewable energy remains a significant challenge for molecular species. The capture and purification of gas for such transformations also requires a significant energy input. One of the simplest methods for CO2 capture is the formation of HCO3–using hydroxide, a reaction which is facile in water. The direct reduction of HCO3– would consequently circumvent the need to isolate pure CO2. In nature, small molecule transformations in aqueous systems pay lower energy penalties by using peptides to facilitate the transfer of electrons and substrates to an active site. Using biology as inspiration, we address these challenges by employing water-soluble molecular Fe compounds containing amino acids or short peptides in the secondary coordination sphere as active and selective catalysts for the reduction of HCO3– to HCO2–.
Porous Electrocatalyst Materials
Metal-organic frameworks (MOFs) and covalently linked organic frameworks (COFs) continue to attract significant interest in materials chemistry. MOFs and COFs offer many advantages in terms of porosity and stability over more amorphous materials or zeolites. Indeed, the translation of molecular properties to bulk materials in this manner has implications for the development of electrochemically responsive films and membranes. We are focused on developing new methods for synthesizing and processing conducting and semi-conducting 2D MOF and COF materials sensitive to the chemical environment. This is primarily focused on applications in molecular detection, separation, and catalysis. A fundamental understanding of how molecular properties are translated in these systems will enable future studies focusing on other applications in energy storage and optoelectronic devices.
Publications can be accessed at "see more"
Glenn J. McGarvey
Complex Glycoconjugate Synthesis
Carbohydrate-Based Molecular Recognition
Cell surface carbohydrates, typically conjugated to proteins and lipids, are key elements in the cellular communication that is essential to cellular organization and function in all organisms. Not only do these cell surface constituents mediate normal behavior in cells, but they may also participate in molecular recognition events that are associated with many serious human diseases, including rheumatoid arthritis, viral and bacterial infections, and cancer metastasis. This provides an extremely attractive opportunity for selective chemical intervention of cell function through the targeting of specific cell surface carbohydrate structures.
A central theme of our research is the application of synthetic organic chemistry to the preparation of appropriate carbohydrate structures in order to carry out detailed structural studies addressing their recognition properties. The highly complex structures of carbohydrates, particularly in the form of their corresponding glycoconjugates, often challenge the limits of existing synthetic technology and dictate the development of new methodology. As such, studies addressing biological carbohydrates offer opportunities for discoveries in the both the chemical and biological domains.
One for the focuses of our efforts is the development of synthetic cancer vaccines directed toward cell surface carbohydrate antigen structures. In this context, the synthesis of complex oligosaccharides is currently under investigation, as well as the development of new strategies for the assembly of unnatural glycopeptide structures that may prove useful in the assembly of effective vaccines.
In other studies, we are endeavoring to exploit the dense stereochemical and functional content of carbohydrates to generate new classes of molecules for highly selective biorecognition. In particular, C-glycoside oligosaccharide/peptide hybrids are being examined for specific cell surface and DNA recognition and binding toward the goal of making available new methods for the treatment of diseases and for the rational modification of biological function.
Studies on the stereoselective synthesis of C-allyl glycosides. McGarvey GJ, LeClair CA, Schmidtmann BA. Org Lett. 10, 4727-30 (2008).
The preparation of C-glycosyl amino acids – an examination of olefin cross-metathesis. Schmidtmann FW, Benedum TE, McGarvey GJ. Tetrahedron letters. 46, 4677-4681 (2005).
Synthesis of alpha- and beta-C-glycosides of N-acetylglucosamine. McGarvey GJ, Schmidtmann FW, Benedum TE, Keizer DE. Tetrahedron letters. 44, 3775-3779 (2003).
Development of co- and post-translational synthetic strategies to C-neoglycopeptides. McGarvey GJ, Benedum TE, Schmidtmann FW. Org Lett. 4, 3591-4 (2002).
David H. Metcalf
Chem 1410/1420 (general chemistry)
Chem 2821 (honors chemistry 4th semester lab)
Professor Metcalf, a native of Charleston, South Carolina, received his B.S in chemistry from the College of Charleston in 1979, and his Ph. D. in physical/inorganic chemistry from Duke University in 1985 under Prof. Richard A. Palmer. He came to the University of Virginia in the spring of 1985 as a post-doctorial research fellow, working with Prof. Fred Richardson. In the Richardson lab, he developed the new technique of time-resolved chiroptical luminescence spectroscopy, and studied the racemization kinetics of labile chiral compounds, and chiral recognition in the enantioselective quenching of racemic luminophores by resolved transition metal complexes.
Soon after arriving at U. Va., he began teaching the advanced physical chemistry (ICE) lab. After a two-year leave at Oak Ridge National Labs, he expanded his teaching responsibilities at U. Va., with the fourth-semester honors chemistry lab and physical chemistry. He began teaching general chemistry in 1998. He is currently teaching general chemistry, the ICE lab, and physical chemistry. All told, he has been teaching for more than twenty years in the Chemistry Department. Dave and his wife Gail South live in downtown Charlottesville. Dave’s outside interests include woodworking and photography.
Lisa Morkowchuk is an instructor for Introductory College Chemistry lecture (1410/1610) and laboratories (1411/1611). She received a B.S. in Chemistry from Moravian College in Bethlehem, Pennsylvania and a Ph.D. in Chemistry from Rensselaer Polytechnic Institute in Troy, New York. Much of her undergraduate education was presented in a guided-inquiry format, and she quickly realized the value of peer interaction in education and the depth of understanding that comes from inquiry-based learning. Implementation of these approaches can be a challenge in courses with large enrollments, but it is one way that physical institutions can provide value above that offered by online courses. Lisa strives to continually increase the proportion of “lecture” time spent utilizing non-lecture, evidence-based pedagogical techniques.
Before coming to the University of Virginia, she taught chemistry and mathematics courses at Albany College of Pharmacy and Health Sciences and at Rensselaer Polytechnic Institute. She currently lives in Culpeper, Virginia with her husband and son and enjoys endurance running in her free time.
Structure, Function & Evolution of Ribonucleoprotein Assemblies
The Mura lab employs experimental and computational approaches to understand the structure, function/dynamics, and evolution of RNA- and DNA-based protein assemblies. In particular, we seek a deeper understanding of Sm-based ribonucleoprotein (RNP) assemblies; what these protein/RNA complexes look like at atomic resolution (structure, such as shown below), their assembly pathways and dynamical behavior (function), and the interrelationships between Sm and Sm-like systems (evolution).
Discovered as the antigens in the autoimmune disease lupus, Sm proteins are now known to form a broad, evolutionarily-conserved family that play key roles in most aspects of RNA metabolism (including mRNA splicing), as well as in bacterial cell-cell communication networks (“quorum sensing”). Sm-based complexes such as the spliceosome exceed the ribosome in terms of both size and architectural complexity, thereby providing an immensely rich area for ongoing studies. Current work focuses on Sm systems drawn from both a well-established context (splicing) and a more recently emerging area (quorum sensing) that is of major biomedical significance because of its involvement in biofilm-mediated bacterial pathogenesis. The research program being developed to pursue this work is necessarily highly interdisciplinary, relying particularly heavily on methods from structural biology (e.g., crystallography) and computational chemistry (e.g., molecular dynamics simulations), in addition to traditional wet-lab biochemistry.
Crystal Structure and RNA-binding Properties of an Hfq Homolog from the Deep-branching Aquificae: Conservation of the Lateral RNA-binding Mode
Stanek KA, Patterson-West J, Randolph PS & C Mura. Acta Crystallographica Section D: Structural Biology (2017), in press.
Toward a Designable Extracellular Matrix: Molecular Dynamics Simulations of an Engineered Laminin-mimetic, Elastin-like Fusion Protein
Tang JD, McAnany CE, Mura C & K Lampe. Biomacromolecules (2016), 17(10), pp 3222–3233.
Claws, Disorder, and Conformational Dynamics of the C-terminal Region of Human Desmoplakin
McAnany CE, & C Mura. The Journal of Physical Chemistry B (2016), 120 (33), pp 8654–8667.
An Introduction to Programming for Bioscientists: A Python-based Primer
Ekmekci B†, McAnany CE†, & C Mura. PLOS Computational Biology (2016), 12(6): e1004867, pp 1–43. [†equal authors]
Known Structure, Unknown Function: An Inquiry-based Undergraduate Biochemistry Laboratory Course
Gray C, Price CW, Lee CT, Dewald AH, Cline MA, McAnany CE, Columbus L & C Mura. Biochemistry & Molecular Biology Education (2015), 43(4), pp 245–262.
An Introduction to Biomolecular Simulations and Docking
Mura C & CE McAnany. Molecular Simulation (2014), 40(10-11), pp 732–764.
Michael Palmer, Associate Director and Associate Professor, joined the Teaching Resource Center in the Fall of 2003. As an Associate Director, he presents interactive workshops locally, nationally and internationally; he regularly consults with faculty, graduate student instructors, departments, and administrative units about teaching and learning matters; and he designs and administers professional development programs, such as the TRC’s graduate student professional development program, Tomorrow’s Professor Today, and the Center’s annual Course Design Institute. His educational development research centers on teaching consultation techniques, graduate student professional development, and the impact of intense professional development activities on teacher beliefs and practices. Published accounts of his work can be found in To Improve the Academy, Practically Speaking: A Sourcebook for Instructional Consultants in Higher Education (2nd Ed, 2012; editor Kate Brinko), and Studies in Graduate and Professional Student Development. He was the 2011 Professional and Organizational Development Network in Higher Education’s (POD Network) conference co-chair and has served on the core faculty of the 2009, 2011, and 2013 New Faculty Developers Institutes. He is currently a member of the POD Network’s Core Committee, the organization’s Board of Directors, and chair of the Membership Committee.
Michael’s pedagogical interests include course design, active learning, student motivation, creative thinking, and teaching large enrollment courses, particularly in STEM disciplines. He teaches a highly interdisciplinary course on infinity and a large-enrollment, inquiry-based laboratory course for first-year chemistry students. In 2012, he won one of UVa’s All-University Teaching Awards.
Born and raised in Wyoming, Michael obtained his B.S. and Ph.D. in chemistry at the University of Wyoming in Laramie. There he won both the University of Wyoming Outstanding Dissertation Award and the Sara Jane Rhoads Award for Outstanding Research for the Ph.D. Degree in Chemistry. Upon completing his graduate studies, Michael accepted a postdoctoral research position in the Chemical Engineering Department at the University of Virginia. Michael’s research focused on environmentally and industrially important catalytic processes, from the desulfurization of petroleum feedstocks and the conversion of natural gas to liquid fuels to the selective oxidation of aromatic compounds. Published accounts of his chemical research can be found in the Journal of the American Chemical Society, Journal of Physical Chemistry B, and Organometallics.
Brooks H. Pate
Vibrational Dynamics and the Spectroscopy of Highly Excited Molecules
Our group studies the dynamics of molecules with significant amounts of vibrational energy. The flow of vibrational energy in a molecule, a process known as intramolecular vibrational energy redistribution (IVR), lies at the heart of chemical reactivity. We study the kinetics of energy flow in isolated molecules and molecules in solution. A major emphasis of our work is understanding the spectroscopy of molecules as the IVR process, and possibly reaction, occurs. In particular, we are interested in how coherent excitation of highly excited molecules can be used to influence reaction products.
We have developed a new type of molecular spectroscopy called dynamic rotational spectroscopy to study isomerization reactions of isolated molecules. The basis of rotational (or microwave) spectroscopy is that the geometry determines the measured rotational frequencies. When the molecule has more energy than the barrier to isomerization, reaction can occur and the geometry becomes time dependent. As a result, the rotational frequency is modulated by the reaction rate. When the reaction causes the frequency to switch between the characteristic values of the reactant and product, the spectrum undergoes the phenomenon known as coalescence. Therefore, the isomerization kinetics can be investigated through the changes in the line shape of the rotational spectrum. We have developed new high-resolution, molecular-beam spectroscopy techniques to obtain the rotational spectrum of single quantum states of a highly excited molecule. These measurements combine ultrasensitive infrared laser spectroscopy methods with strong-field microwave excitation. Application of this technique to conformational isomerization reactions has shown that this class of reactions violates the predictions of quantum transition state theory. We are presently developing new techniques to improve our sensitivity for single quantum state measurements and to extend our measurements to higher energy. A more complete description of the projects we are currently pursuing can be found on our research group web pages.
The second area of research in our group investigates the vibrational dynamics of molecules in dilute solution. Using our molecular-beam spectroscopy techniques we can quantitatively measure energy flow rates for the isolated molecule. Our goal for solution phase studies is to understand how solvent molecules modify the dynamics and reactivity of the isolated molecule. This work is performed in the Ultrafast Laser Facility that is part of the university's SELIM program. We have an impressive array of laser tools available for this work including a two-color femtosecond laser system, a two-color picosecond laser system, and a 32-element infrared array detector for multichannel detection. Our first studies have shown that the basic features of isolated molecule IVR dynamics are preserved in solution. In particular, we have found that a new relaxation channel opens for large molecules that correlates with the onset of fast IVR in the isolated system. From this work, we can identify a time window where the molecule in solution retains the energy deposited by the laser (i.e., before interaction with the solvent causes conversion of the internal energy to heat). Knowing this time scale gives us a window of opportunity to study the spectroscopy and kinetics of the vibrationally hot molecule. Examples of our recent work in this area, as well as descriptions of projects planned for the near future, can be found on our research web pages.
Broadband Fourier transform rotational spectroscopy for structure determination: The water heptamer. Perez C, Lobsiger S, Seifert NA, Zaleski DP, Temelso B, Shields GC, Kisiel Z, Pate BH. Chem. Phys Let. 571:1-15 (2013).
High-Resolution Electronic Spectroscopy of the Doorway States to Intramolecular Charge Transfer. Fleisher AJ, Bird RG, Zaleski DP, Pate BH, Pratt DW. J. Phys. Chem B. 117:4231-4240 (2013).
. Pate BH, Seifert NA, Guirgis GA, Deodhar BS, Klaassen JJ, Darkhalil ID, Crow JA, Wyatt JK, Dukes HW, Durig JR. Chemical Physics. 416: 33-42 (2013).
The detection of interstellar ethanimine (CH3CHNH) from observations taken during the GBT PRIMOS survey. Loomis RA, Zaleski DP, Steber AL, Neill JL, Muckle MT, Harris BJ, Hollis JM, Jewell PR, Lattanzi V, Lovas FJ, Martinez O, McCarthy MC, Remijan AJ, Pate BH, Corby JF. Astrophysical Journal Letters. 765:L9 (2013).
Detection of E-cyanomethanimine towards Sagittarius B2(N) in the Green Bank Telescope PRIMOS Survey. Zaleski DP, Seifert NA, Steber AL, Muckle MT, Loomis RA, Corby JF, Martinez O, Crabtree KN, Jewell PR, Hollis JM, Lovas FJ, Vasquez D, Nyiramahirwe J, Sciortino N, Johnson K, McCarthy MC, Remijan AJ, Pate BH. Astrophysical Journal Letters. 765:L10 (2013).
Rebecca R. Pompano
Our lab develops methods based on microfluidic culture systems, bioanalytical techniques, and spatially resolved simulations to quantify the spatiotemporal dynamics of the inflammatory cascade and develop targeted therapies. This work is part of a broad interest in the dynamics of complex biological systems. Specifically, we study the kinetics of immunity and inflammation, and we develop chemically targeted methods to control these processes in the context of vaccination, autoimmunity, and chronic inflammatory disease.
The immune system is a fascinating topic for physical scientists to study, and one where novel analytical tools can make a significant impact. The system consists of a highly structured network whose components include a set of specialized cell types and secreted signals, which organize themselves into dynamic spatial arrangements. These components interact with all of the characteristics of mathematical complexity, including nonlinearity, thresholds for activation, and multiple length scales, and they exhibit emergent behaviors that are difficult to predict from knowledge of the individual components. As a result of this complexity, protective immune responses against invading pathogens and injected vaccines are only a small perturbation away from the non-productive inflammation that characterizes autoimmunity, heart disease, Alzheimer’s disease, and solid tumors. Despite a wealth of information about individual proteins and cells in the immune system, it is challenging to predict the effects of a given stimulation of the immune system. One reason is that chemical stimulation of individual clusters of cells is still difficult to achieve in vitro or in vivo. Spatially resolved readout of secreted molecules is also difficult, unless the molecules can be fluorescently labeled. Without such tools, it remains unclear how to stop an autoimmune disease without suppressing the entire immune system, or how to design potent vaccines that work for any disease target without unwanted inflammatory side effects.
We are developing new methods to study the kinetics and the spatial behavior of cells and secreted signals during immune responses. For example, we are designing microfluidic devices to test the effects of spatial distribution and local delivery of signals. We also are developing new ways to measure the secretions of cells in living tissues with high spatial and temporal resolution. To do so, we combine activities from a variety of disciplines, including microfabrication and device design; quantitative analysis of chemical and biochemical signals using immunoassays, HPLC, mass spectrometry, and fluorescence microscopy (widefield and confocal); live cell and tissue imaging using samples from mouse models of health and disease; and, finally, spatially-resolved time-dependent numerical simulations. Eventually, we will use the information from these experiments to design spatially targeted nanoparticles that abrogate inflammation. Our goal is that the methods we develop will enable experiments that contribute to the fundamental understanding of both immunity and complex chemical kinetics, and that they will help guide the design of highly targeted vaccines and immunotherapies.
Materials-based modulation of inflammation and immune responses:
The use of self-adjuvanting nanofiber vaccines to elicit high-affinity B cell responses to peptide antigens without inflammation. Chen J*, Pompano RR*, Santiago FW, Maillat L, Sciammas R, Sun T, Han H, Topham DJ, Chong AS, Collier JH. Biomaterials. 2013; 34(34):8776-85. *Equal contributions.
Device design for microfluidic analyses:
Control of initiation, rate, and routing of spontaneous capillary-driven flow of liquid droplets through microfluidic channels on SlipChip. Pompano RR, Platt CE, Karymov MA, Ismagilov RF. Langmuir. 2012; 28(3):1931-41.
Toward mechanistic understanding of nuclear reprocessing chemistries by quantifying lanthanide solvent extraction kinetics via microfluidics with constant interfacial area and rapid mixing. Nichols KP, Pompano RR, Li L, Gelis AV, Ismagilov RF. J Am Chem Soc. 2011; 133(39):15721-9.
Microfluidics using spatially defined arrays of droplets in one, two, and three dimensions. Pompano RR, Liu W, Du W, Ismagilov RF. Annu Rev Anal Chem. 2011; 4:59-81. (review)
Microfluidics for analysis of complex biological systems:
Confinement regulates complex biochemical networks: initiation of blood clotting by “diffusion acting”. Shen F, Pompano RR, Kastrup CJ, Ismagilov RF. Biophys J. 2009 Oct 21;97(8):2137-45.
Spatial localization of bacteria controls coagulation of human blood by ‘quorum acting’. Kastrup CJ, Boedicker JQ, Pomerantsev AP, Moayeri M, Bian Y, Pompano RR, Kline TR, Sylvestre P, Shen F, Leppla SH, Tang WJ, Ismagilov RF. Nat Chem Biol. 2008; 4(12):742-50.
Rate of mixing controls rate and outcome of autocatalytic processes: theory and microfluidic experiments with chemical reactions and blood coagulation. Pompano RR, Li HW, Ismagilov RF. Biophys J. 2008; 95(3):1531-43.
Organic, Polymer and Organometallic Chemistry; Asymmetric Catalysis; Chiral Sensors; Optically Active Materials
Multi-disciplinary research programs involving organic synthesis, molecular recognition, fluorescent sensing, asymmetric catalysis, and polymers are conducted in our laboratory. The 1,1′-bi-2-naphthol (BINOL) and its derivatives are chosen as the chiral building blocks to construct novel chiral molecules and macromolecules for diverse applications. We have developed a family of enantioselective fluorescent sensors for the recognition of organic molecules such as alpha-hydroxycarboxylic acids, amino acids, amino alcohols, and amines. These sensors are potentially useful for rapid assay of the enantiomeric composition of chiral compounds and for high throughput chiral catalyst screening. They are also potentially useful for biological analysis and imaging. New chiral conjugated polymers and dendrimers are prepared for applications in materials, catalysis, and sensing. We have discovered that the Lewis acid complexes of the optically active binaphthyl molecules and polymers can carry out highly enantioselective organic reactions such as organozinc additions to aldehydes, hetero-Diels-Alder reactions, 1,3-dipolar cycloadditions, reductions of ketones, Michael additions, epoxidations, and others. Interesting chiral organic molecules including those of biological functions are prepared by using these catalysts.
Enantioselective Fluorescent Sensors
Simultaneous Determination of Concentration and Enantiomeric Composition in Fluorescent Sensing. Lin Pu. Acc. Chem. Res. 2017, 50, 1032-1040.
Regiospecific Hydration of N-(Diphenylphosphinoyl)propargyl amines: Synthesis of b-Amino Ketones by Au(III) Catalysis. Ying, J.; Pu, L. J. Org. Chem. 2016, 81, 8135−8141. A Featured Article. Highlight on the cover.
Conjugated polymer-enhanced enantioselectivity in fluorescent sensing. Zhang, X. –P.; Wang, C.; Wang, P.; Du, J. –J.; Zhang, G. –Q.; Pu, L. Chem. Sci. 2016, 7, 3614–3620.
Rational Design of a Fluorescent Sensor to Simultaneously Determine Both the Enantiomeric Composition and Concentration of Chiral Functional Amines. Wen, K. –L.; Yu, S. –S.; Huang, Z.; Chen, L. –M.; Xiao, M.; Yu, X. –Q.; Pu, L. J. Am. Chem. Soc. 2015, 137, 4517-4524.
Asymmetric Functional Organozinc Additions to Aldehydes Catalyzed by BINOLs. Pu, L. Acc. Chem. Res. 2014, 47, 1523–1535.
Zn(II) Promoted Dramatic Enhancement in the Enantioselective Fluorescent Recognition of Chiral Amines by a Chiral Aldehyde. Huang, Z.; Yu, S. S.; Yu, X. Q.; Pu. L. Chem. Sci. 2014, 5, 3457-3462.
Enantioselective Fluorescent Sensors: A Tale of BINOL. Pu, L. Acc. Chem. Res. 2012, 45, 150–163.
Simultaneous Determination of Both the Enantiomeric Composition and Concentration of a Chiral Substrate with One Fluorescent Sensor. Yu, S.; Plunkett, W.; Kim, M.; Pu, L. J. Am. Chem. Soc. 2012, 134, 20282–20285. A spotlight article reported in J. Am. Chem. Soc., 2013, 135 (3), 949–950.
Professor Serbulea is teaching organic chemistry courses, including the accelerated organic chemistry lectures and laboratories. She is actively involved in the development of the organic chemistry curriculum, focusing on improving the coordination between the topics in the lecture course and the experiments that are carried out in the laboratory. In the accelerated organic chemistry laboratories, students gain hands-on experience in the synthesis, purification, and characterization of organic compounds using modern analytical instruments and laboratory equipment.
Laura Serbulea earned her undergraduate degree at the University of Bucharest, Romania, and received her Ph.D. in Chemistry from University of California, Los Angeles. She joined the faculty at the University of Virginia in 2012. Her research interests are in the area of computational drug design targeting G-protein coupled receptors, and investigation of organic reaction mechanisms using computational methods.
Diane M. Szaflarski
My work focuses on considering what Chemical Education should look like today and in future decades. Chemistry, “the central science” has many important pillars that have to be established in order to understand advanced applications and mechanisms. It is essential that as chemical educators we continuously and critically evaluate whether our curricula are current in applications and technologies that are relevant to today’s science and industry, and will be applicable for our students as they encounter their future.
I define Chemical Education broadly and am interested in the range of students including chemistry, science and chemical education majors as well as non-science majors. The focus of the non-majors course that I teach, Chem 1210, is to address college science literacy and to explore the question of what every college student should know about chemistry and impact of chemical issues. In my courses, I strive to establish student centered learning environments in the classroom to maximize the student involvement and focus.
My consideration of curricula parallels my interest in building support networks, especially for those students taking college level chemistry for the first time. It is important that the appropriate supports are in place so that student’s interest does not wane as a result of frustration. I have been involved in departmental efforts to establish support for students.
I am interested in bridging the Chemistry Department with other areas on campus, and have done this with the Curry School and the School of Nursing. These connections encourage facile flow of information on teaching methods and current chemistry content which allows us superior approaches to serving the needs of today’s students. I currently teach in the Chemistry Department and the School of Nursing.
B. Jill Venton
The Venton group is interested in the development and characterization of analytical techniques to measure neurochemical changes. Measurements in the brain are challenging because tiny quantities of neuroactive molecules must be detected in a chemically-complex sample while disturbing the tissue as little as possible. In addition, fast time resolution measurements are needed to track the fast dynamics of neurotransmitter release and uptake. Our lab develops both electrochemical and separations methods to monitor these rapid changes in neurotransmitters in model systems. The development of new analytical tools will enable a better understanding of the central nervous system and facilitate the development of new treatments for neurological disorders. Several specific projects are highlighted below:
Electrochemical Detection of Adenosine
Adenosine is a neuromodulator that has a variety of actions including regulation of cerebral blood flow, modulation of neurotransmission, and protection against neuronal injury during stroke. We are studying the regulation of adenosine release in vivo and changes in adenosine in a brain slice model of stroke using cyclic voltammetry at carbon-fiber microelectrodes. We are also developing new methods for ATP and adenosine detection.
Detection of Neurotransmitter Release in Drosophila
Drosophila melanogaster (the fruit fly) is a favorite model organism for biologists, but the central nervous system of a Drosophila larva is only 8 nL in volume! Current projects involve characterizing electrochemically-detected dopamine and serotonin release and comparing the control of neurotransmission in the fly to mammalian systems. We have developed the first method to measure real-time changes in neurotransmitter concentrations in the CNS of a single larva or adult. We also use capillary electrophoresis to measure tissue content of single brains.
Development of Carbon Nanotube-Based Electrodes
Carbon nanotubes have interesting electrical, chemical and mechanical properties and have been shown to promote electron transfer in electrochemical experiments. Our aim is to characterize carbon nanotube-based electrodes with fast-scan cyclic voltammetry. We are exploring different ways to add nanotubes to a carbon-fiber microelectrode surface as well as fabricate new electrodes our of carbon nanotubes.
Mechanisms of Drugs of Abuse using Capillary Electrophoresis
We are also developing capillary electrophoresis instrumentation for making rapid separations. We are interested in using this separations based technique to monitor both neurotransmitter and drug concentrations simultaneously. For example, the effect of amphetamine on amino acid concentrations could be studied in vivo. Different fluorescent tags will be examined to study secondary amines such as Ecstasy.
Figure: Codetection of serotonin and dopamine in the rat brain using a nanotube coated electrode.
Transient Adenosine Release Is Modulated by NMDA and GABAB Receptors. M.D. Nguyen, Y. Wang, M. Ganesana, B.J. Venton. ACS Chemical Neuroscience, 8(2):376–385 (2017).
Analytical techniques in neuroscience: Recent advances in imaging, separation, and electrochemical methods. M. Ganesana, S.T. Lee, Y. Wang, B.J. Venton. Analytical Chemistry, 89(1): 314-341 (2017).
O2 plasma etching and antistatic gun surface modifications for CNT yarn microelectrode improve sensitivity and antifouling properties. C. Yang, Y. Wang, C.B. Jacobs, I. Ivanov, B.J. Venton. Analytical Chemistry, 89:5605-5611 (2017).
Fast-scan cyclic voltammetry (FSCV) detection of endogenous octopamine in Drosophila melanogaster ventral nerve cord. P. Pyakurel, E. Privman Champaloux, B.J. Venton. ACS Chemical Neuroscience, Aug 17;7(8):1112-1119 (2016).
Quantitation of dopamine, serotonin and adenosine content in a tissue punch from a brain slice using capillary electrophoresis with fast-scan cyclic voltammetry detection. Fang H, Pajski ML, Ross AE, Venton BJ. Anal Methods. 5:2704-2711 (2013).
Kinetics of the dopamine transporter in Drosophila larva. Vickrey TL, Xiao N, Venton BJ. ACS Chem Neurosci. 4:832-7 (2013).
The mechanism of electrically stimulated adenosine release varies by brain region. Pajski ML, Venton BJ. Purinergic Signal. 9:167-74 (2013).
Professor Kevin Welch is interested in developing curricula for undergraduate instruction in general chemistry and organic chemistry. In particular, his focus is on updating these courses to accommodate the diverse educational background in chemistry of the students enrolling in chemistry at the University of Virginia, as well as providing a strong chemical foundation for the students as they continue on in their educational and post-educational careers in a variety of fields. In the past, he has taught undergraduate courses in general chemistry, organic chemistry, inorganic chemistry, environmental chemistry, and scientific writing.
In addition to a focus on undergraduate education, Kevin’s interests in chemistry involve research investigating metal-ligand bonding interactions and the use of transition metal complexes to address challenges in fuel generation and energy storage.
A native of northern Virginia, Kevin received his B.S. in chemistry from Gettysburg College in 2002, and his Ph.D. in chemistry from the University of Virginia in 2007, where he focused on synthetic organometallic chemistry. He spent three years in central Washington as a Department of Energy Postdoctoral Researcher at the Pacific Northwest National Laboratory, working on the development of transition metal catalysts for energy storage and fuel cell technology. From 2010 to 2016, Kevin was a visiting assistant professor at Swarthmore College outside of Philadelphia, Pennsylvania, where he taught and conducted research with undergraduate students. He returned to the University of Virginia in the fall of 2016 and currently teaches courses in general chemistry and laboratories for organic chemistry.
Professor Lindsay Wheeler is the instructor for the Teaching Methods courses for undergraduate and graduate TAs in the chemistry, physics, biology, and astronomy departments, with the goal of expanding these courses to all STEM departments at the University. She worked with Dr. Charles Grisham to redesign the General Chemistry laboratory curricula (Chem 1411/1611/1421/1621) to a project-based guided inquiry approach where students work collaboratively to design, implement, analyze, and communicate their approach to solving a real-world problem. Dr. Wheeler has also previously taught Chem 1400 using a Process Oriented Guided Inquiry Learning (POGIL) curriculum. Her current role is the Assistant Director of STEM education innovations in the Center for Teaching Excellence (CTE), where she supports STEM instructors in the teaching and implementation of evidence-based practices.
Dr. Wheeler’s research explores the impact of various teaching interventions on instructors’ beliefs, confidence, and practice in undergraduate STEM classrooms. Dr. Wheeler directs a university-wide observation project of STEM undergraduate classrooms to characterize STEM instructional practices at UVA. As part of this large-scale research endeavor, Dr. Wheeler also seeks to understand the impact of CTE Ignite and Course Design Institute programs on faculty instructional practices. She also investigates the impact of TA training and Teaching Methods courses on TAs’ content knowledge, beliefs, confidence, and instructional practice as well as how these TAs influence the students they teach.
Dr. Wheeler is active in the science education and educational development professional communities and presents regularly at national and international conferences. She runs teaching and research workshops at UVA and other universities and also works collaboratively with STEM faculty across campuses to support teaching innovations.
Do teaching assistants matter? Investigating relationships between teaching assistants and student outcomes in undergraduate science laboratory classes, Wheeler, L.B., Maeng, J.L., Chiu, J.L., & Bell, R.L. Journal of Research in Science Teaching, 54, 463-492 (2017). DOI: 10.1002/tea.21373
Engineering or not? Whitworth, B.A., & Wheeler, L.B. The Science Teacher, July 2017, 25-29.
Elementary science teachers’ integration of engineering design into science instruction: Results from a randomized controlled trial, Maeng, J.L., Whitworth, B.A., Gonczi, A.L., & Wheeler, L.B., International Journal of Science Education, 39, 1529-1548 (2017). DOI: 10.1080/09500693.2017.1340688.
Transforming a traditional laboratory to an inquiry-based course: Importance of training TAs when redesigning a curriculum, Wheeler, L.B., Clark, C.P., & Grisham, C.M., Journal of Chemical Education (2017)
Teaching assistant (TA) professional development within an inquiry-based general chemistry context: Characterization of TA knowledge and beliefs, Wheeler, L.B., Maeng, J.L., & Whitworth, B.A., Journal of Chemical Education, 94, 19-28 (2017). DOI: 10.1021/acs.jchemed.6b00373
The Zhang group focuses on developing well-defined nanostructured materials with controls at atomic levels for highly efficient energy conversion and chemical transformation. We are interested in a broad range of nanomaterials systems, including single-component nanoparticles (NPs), multi-component heterostructured NPs, self-assembled NPs superlattices, and other complex nanoscale architectures. We take advantage of our synthetic control over those nanomaterials’ physical dimensions and structures, to understand and optimize their functions in catalysis, with the overarching objective of addressing our society’s most critical challenge: a sustainable and green energy future. Major directions include:
Controlled Synthesis and Assembly of Well-Defined NPs: We are exploring the critical parameters applied in solution based chemical syntheses to direct NP nucleation and growth, and identifying their mechanisms in bridging atomic species and NPs with precisely controlled size, shape, composition, and crystal structure. We also exploit the inter-particle interactions that lead to the formation of binary and ternary NPs superlattices with unique collective physicochemical properties. This research requires a technical combination of chemical synthesis, in-situ electron microscopic and X-ray structural analysis, and computational modeling, to advance the understanding of NPs hierarchical control at multiple length scales.
Nanocatalyst for H2/O2-H2O Electrochemical Energy Conversion: The sustainable use of energy is built on highly efficient and environmentally friendly schemes of energy storage and conversion. Energy conversion and chemical transformation between H2/O2 and H2O is specifically important for future energy applications. H2O can be electrolyzed into H2 and O2 through the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER), respectively. This electrochemical water splitting allows stationary electrical energy to be converted and stored in H2 as a clean fuel to power energy devices such as polymer electrolyte membrane fuel cells (PEMFCs) via hydrogen oxidation reaction (HOR) and oxygen reduction reaction (ORR). We seek to understand the correlation of NP’s architecture to the desired catalytic properties, and develop highly active, durable and cost-effective nanoparticle catalysts for these four reactions.
Nanocatalyst for CO2-to-fuel and Biomass Conversion: CO2 and biomass offer the sustainable and inexpensive carbon feedstocks for commodity chemicals and fuels, and can reduce or even eliminate our society’s dependence on non-sustainable carbon resources such as petroleum. Their efficient conversion to high-value chemicals and fuels can significantly impact the chemical industry, and advance the development of the carbon-neutral energy cycle. We integrate the efforts in nanomaterials synthesis, structural characterization, catalytic analysis, and computational modeling, to exploit the design rule and optimized approach to electrocatalysts and photocatalysts for CO2 reduction and biomass conversion with high selectivity, activity, and stability.
- He*, S. Zhang*, J. Li, X. Yu, Q. Meng, Y. Zhu, E. Hu, K. Sun, H. Yun, X. Yang, Y. Zhu, H. Gan, Y. Mo, E. A. Stach, C. B. Murray, D. Su. Nat. Comm. 7, 11441 (2016). (* equal contribution)
- Zhang, Y. Hao, D. Su, V. V. T. Doan-Nguyen, Y. Wu, J. Li, S. Sun, C. B. Murray. J. Am. Chem. Soc. 136, 15921 (2014).
- Zhang, X. Zhang, G. Jiang, H. Zhu, S. Guo, D. Su, G. Lu, S. Sun. J. Am. Chem. Soc. 136, 7734 (2014).
- Zhang, O. Metin, D. Su, S. Sun. Angew. Chem. Int. Ed. 52, 3681 (2013).
- Zhang, S. Guo, H. Zhu, D. Su, S. Sun. J. Am. Chem. Soc. 134, 5060 (2012).
- Guo*, S. Zhang*, D. Su, S. Sun. J. Am. Chem. Soc. 135, 13879 (2013). (* equal contribution)
- Zhu*, S. Zhang*, S. Guo, D. Su, S. Sun. J. Am. Chem. Soc. 135, 7170 (2013). (* equal contribution)
- Guo*, S. Zhang*, S. Sun, Angew. Chem. Int. Ed. 52, 8526 (2013). (* equal contribution)
Ralph O. Allen
Trace Analysis: Environmental, Archaeological, and Forensic Applications
Professor Allen is not currently accepting graduate students.
The development of sensitive analytical methods has helped provide more detailed information about the small chemical differences between materials which seem similar but have different histories. In some cases, like geological samples, the large scale geochemical processes can give rise to subtle yet understandable differences in those elements which are present at trace levels. We have used instrumental neutron activation analysis and X-ray fluorescence to study several types of geological materials. These materials have been investigated as part of an ongoing effort to interpret the migration of trace elements during geochemical processes. In some cases, these same geological materials have been used by prehistoric humans and hence our studies have had archaeological implications.
To provide accurate trace element data on large numbers of samples, we have investigated several other analytical methods. The inductively coupled plasma emission source used to provide ions for a quadrupole mass spectrometer (ICP-MS) holds considerable promise. This method is also being used to study soil and glass samples for applicability in the forensic laboratory. Our efforts in the forensic science field are part of a continuing cooperative effort with scientists at the FBI’s research facilities. In the past, traces of explosive residues and epoxies have been analyzed to differentiate the sources of the materials. The latest forensic science efforts have been directed toward the important new area of DNA “fingerprinting.” This major forensic tool allows small amounts of genetic material to be used to match the DNA from a suspect.
Forensic determination of ricin and the alkaloid marker ricinine from castor bean extracts. Darby SM, Miller ML, Allen RO. J Forensic Sci. 6, 1033-42 (2001).
A mass spectrometric method for quantitation of intact insulin in blood samples. Darby SM, Miller ML, Allen RO, LeBeau M. J Anal Toxicol. 25, 8-14 (2001).
Analysis of two multiplexed short tandem repeat systems using capillary electrophoresis with multiwavelength fluorescence detection. Isenberg AR, Allen RO, Keys KM, Smerick JB, Budowle B, McCord BR. Electrophoresis. 19, 94-100 1998 .
Lester S. Andrews
Spectroscopy and Photochemistry of Matrix Isolated Species
Normally inaccessible chemical species including free radicals, hydrogen-bonded complexes, unusual inorganic species, transition metal containing intermediates, metal hydrides, and molecular ions are under investigation using infrared matrix-isolation spectroscopy. These transient molecules are prepared by reactions of suitable atoms and/or molecules prediluted in argon by precursor photolysis, or by microwave discharge of the reagents during condensation at 7 K in a vacuum chamber. Solid argon isolates the reaction or photolysis products and preserves them for spectroscopic study at 7 K. Neon is used to isolate new reactionproducts on a 4 K substrate. Pure H2 and D2 are also be employed as a reagent and matrix for the investigation of novel metal hydrides. A new source of atoms that require high temperatures to generate, namely pulsed laser ablation from solid samples, has been developed for use in matrix-infrared spectroscopy in this laboratory. This method exploits two advantages: first, the ablated atoms contain excess energy which can activate reactions with small molecules, and second, collisions with matrix atoms during the condensation process relax energetic product molecules and allow them to be trapped in the solid matrix for spectroscopic study. In addition, laser-ablation also produces cations and electrons for reactions to make charged products.
The experimental apparatus used in hydrogen matrix investigations is sketched in the figure. Infrared spectra are recorded after co-depositing reagent and host matrix gases on the cold sample window and rotating by 90 degrees to face the infrared light beam.
These infrared spectroscopic matrix-isolation studies characterize the bonding and structure of chemical intermediates, interesting new inorganic molecules and complexes and molecular ions and often provide a useful complement and guide to high resolution gas phase work. Stable isotopes are used to determine assignments of the observed infrared absorptions to fundamental vibrational frequencies. Comparison of vibrational energies within related chemical species provides conclusions about the bonding of these newly observed chemical intermediates. Selection rules based upon molecular symmetry and vibrational analysis help determine the molecular geometry. Ab initio electronic structure calculations are done to find molecular structures compatible with the infrared spectrum. Agreement between calculated and observed isotopic vibrational spectra provides further evidence for the discovery of new transient molecular species.
Please click here for a full list of publications.
Robert F. Bryan
Robert Bryan was a faculty member of the U.Va. Chemistry Department for 36 years. During his career, Professor Bryan established an international reputation in crystallography and published more than 150 papers in the area. He was born in Rhu, Scotland in 1933, and earned his B.Sc. (1954) and Ph.D. (1957) from the University of Glasgow. His postdoctoral training was at ETH (BAttelle Fellow) and MIT (Alfred P. Sloane Fellow and a NIH Fellow) from 1957 – 1961. In 1961, he joined the faculty at Johns Hopkins University School of Medicine in the Biophysics Department. He joined U.Va. in 1967 as an Associate Professor of Chemistry and became a Full Professor in 1982. He held several offices in the international Union of Crystallography and was an editor of Acta Crystallographica and The Journal of Applied Crystallography. In addition to a very active research career (over 150 publications), Prof. Bryan was the Associate Dean for the Graduate School of Arts and Sciences from 1970 – 1973.
Robert G. Bryant
Nuclear Magnetic Resonance in Chemistry
The Bryant laboratory utilizes a wide range of nuclear and electron spin resonance methods to characterize intra and intermolecular dynamics. A primary focus is the rich information available from the study of the magnetic field dependence of the nuclear spin-lattice relaxation rate as a function of the magnetic field strength or what is called the magnetic relaxation dispersion (MRD). We have constructed unique instrumentation that permits acquisition of MRD profiles for a variety of nuclear resonances in high resolution. These measurements provide a direct measure of the time fluctuations in various nuclear or nuclear-electron dipolar couplings. The resulting MRD profile reports relative inter and intramolecular motions over the time range from about ten microseconds to one picosecond. We are developing methods for probing the fluctuation spectrum of specific vectors defined in structurally interesting proteins and are trying to understand how these fluctuations affect molecular function. In related work, we apply the nuclear spin relaxation induced by freely diffusing paramagnetic solutes in cosolutes to define how one molecule samples the local environment of another and explores the surface or even penetrates into a complex structure like a folded protein. The measurements are sensitive to relatively weak intermolecular interactions and permit definition of highly localized intermolecular free energy differences in solutions. Multinuclear studies of proteins in a number of dynamical environments provide a fundamental characterization of how the protein structure fluctuates in time and how energy is redistributed in the folded structure. The practical implications range from understanding protein catalytic function to developing new techniques for diagnostic medicine in the context of magnetic resonance imaging or MRI.
Water-proton-spin-lattice-relaxation dispersion of paramagnetic protein solutions. Diakova G, Goddard Y, Korb JP, Bryant RG. J Magn Reson. 208:195-203 (2010).
Water and backbone dynamics in a hydrated protein. Diakova G, Goddard YA, Korb JP, Bryant RG. Biophys J. 98:138-46 (2010).
Dynamics of water in and around proteins characterized by 1H Spin-Lattice Relaxometry. Bryant RG. Comptes Rendus Physique. 11(2), 128-135(2010).
Dimensionality of diffusive exploration at the protein interface in solution. Grebenkov DS, Goddard YA, Diakova G, Korb JP, Bryant RG. J Phys Chem B. 113, 13347-13356 (2009).
Water molecule contributions to proton spin-lattice relaxation in rotationally immobilized proteins. Goddard YA, Korb JP, Bryant RG. J Magn Reson. 199, 68-74 (2009).
Francis A. Carey
Francis A. Carey is a native of Pennsylvania, educated in the public schools of Philadelphia, at Drexel University (B.S. in chemistry, 1959), and at Penn State (Ph.D. 1963). Following postdoctoral work at Harvard and military service, he was appointed to the chemistry faculty of the University of Virginia in 1966. Prior to retiring in 2000, he regularly taught the two-semester lecture courses in general chemistry and organic chemistry. With his students, Professor Carey has published over forty research papers in synthetic and mechanistic organic chemistry. In addition to this text, he is coauthor (with Robert C. Atkins) of Organic Chemistry: A Brief Course and (with Richard J. Sundberg) of Advanced Organic Chemistry, a two-volume treatment designed for graduate students and advanced undergraduates. He was a member of the Committee of Examiners of The Graduate Record Examination in Chemistry from 1993-2000.
Professor Gerrans is primarily engaged in teaching and chemical education. He has taught undergraduate chemistry at the University of the Witwatersrand, South Africa and here at the University of Virginia. He has held visiting professorships at the California Institute of Technology (1972), the University of Illinois (1979), the University of East Anglia, England (1986) and the University of Virginia (1990). Amongst the awards that he has received are the Convocation Distinguished Teacher’s Award (University of the Witwatersrand) and the Education Medal (South African Chemical Institute). He has published over 80 papers and is the co-author, together with P and R Hartmann-Petersen, of “Encyclopedia of Science and Technology,” (New Africa Books, 2007).
Most recently, Professor Gerrans was a faculty in the Spring 2009 UVA Semester at Sea Program.
Russell N. Grimes
Russ Grimes was raised in Pennsylvania and is a B.S. Chemistry alumnus of Lafayette College He received his Ph.D. in Chemistry from the University of Minnesota as a student of Professor William Lipscomb, although his thesis research was conducted at Harvard University where he was a Harvard Fellow. Following postdoctoral work at Harvard and with Professor M. F. Hawthorne at the University of California, Riverside, he was a faculty member in the Department of Chemistry from 1963 to 2003, becoming a Full Professor in 1973 and serving a term as Department Chair from 1981 to 1984. Over a 40-year period he and his students were among the pioneers in the synthesis and study of polyhedral molecular cage compounds of boron, along the way discovering metal-promoted oxidative cage fusion, tricarbon and large tetracarbon carboranes, stable triple-decker sandwich complexes (which were also the first electrically neutral triple-deckers), isolable tetra-, penta-, and hexadecker molecular sandwiches, linked multidecker complexes, polyhedral metallaboranes, and many novel clusters ranging from C2B3H7 to 14-vertex M2C4B8 systems. A major theme in their work was the development and exploration of small carborane ligands in the designed synthesis of novel transition-metal organometallic systems, especially those having electrically conducting or catalytic properties. The Grimes group together with William Hutton, in work initially reported in the Journal of the American Chemical Society in 1980 and 1981, developed the first successful 2D COSY (correlated spectroscopy) NMR technique involving a quadrupolar nucleus (11B) and in a 1984 JACS full paper detailed its use in both homonuclear 11B-11B) and heteronuclear (11B-1H) spectroscopy.
Professor Grimes was a Senior Fulbright Scholar at the University of Canterbury, New Zealand, in 1974-75, a Guest Professor at the University of Heidelberg, Germany, in 1986, a Humboldt Scholar there in 1997-98, and a Visiting Scholar at the Korea Advanced Institute for Science and Technology in 1997. He received a Boron U.S.A. (BUSA) Award for Distinguished Achievements in Boron Science in 1990 and was elected a Fellow of the American Association for the Advancement of Science in 1981. He served as an American Chemical Society Tour Speaker on six occasions. He is the author or co-author of 240+ research publications and the books Carboranes (Academic Press, 1970, Russian translation 1974) and Carboranes Second Edition, (Elsevier, 2011). He edited the book Metal Interactions with Boron Clusters (Plenum, 1982) and is Editor-in-Chief of Inorganic Syntheses, Vol. 29 (John Wiley, 1992). He has served on the editorial board of Inorganic Chemistry and the editorial review panel of Dalton Transactions, and is a past president of the Board of Directors of Inorganic Syntheses.
The Third Edition of Carboranes was published by Elsevier in August, just 5 years following the Second Edition. The book reflects the rapid pace of development in this field, which is generating hundreds of publications each year in areas as diverse as nanomaterials, pharmacology, diagnostic and therapeutic medicine, extraction of radioactive metals from nuclear waste, catalysis, and organic synthesis. Professor Grimes was recently honored by a special issue of the Journal of Organometallic Chemistry, featuring over 40 contributed papers from international scientists in recognition of his contributions to boron chemistry throughout his 50-year career.
Sidney Hecht was the John W. Mallet Professor of Chemistry and a Professor of Biology at UVA from 1978 – 2008. During his thirty years he led a very productive research group in the areas of synthesis and mechanism of action of bleomycin family antitumor antibiotics, peptidyltransferase as a source of synthetic enzymes, mechanism of action/inhibition of mammalian DNA topoisomerase I, and inhibition of signal transduction at the level of p90RSK. He is the recipient of numerous awards icluding the Alfred P. Sloan Research Fellowship (1975-79), a National Institutes of Health Research Career Development Award (1975-80), a John Simon Guggenheim Memorial Fellowship (1977-78), the 1996 Arthur C. Cope Scholar Award, the Virginia’s Outstanding Scientist Award (1996), a 1998 Research Achievement Award, American Society of Pharmacognosy and in 2004 he was elected as a Fellow of the American Association for the Advancement of Science. In a career spanning more than three decades, Sidney Hecht has held both academic and industrial research positions. From 1981 to 1986 in addition to his professorship at UVA, he held concurrent appointments at Smith Kline & French Laboratories, first as Vice President Preclinical R&D, then Vice President Chemical R&D. He is currently Director of the Center for BioEnergetics in the Biodesign Institute and Professor of Chemistry at Arizona State University.
James A. Marshall
In our research we identify natural products with interesting, often novel, structures and useful biological properties that may lead to medicinal agents for treatment of cancer, cardiovascular disorders and infectious diseases. We focus on key structural and stereochemical features present in these target natural products and devise mechanism or analogy based methodology for efficient construction of potentially useful subunits. Finally, we assemble the foregoing subunits by a combination of new and known reactions to synthesize the target substance and/or analogues thereof. Our overall program is thus target directed but methods driven.
A cascade cyclization route to adjacent bistetrahydrofurans from chiral triepoxyfarnesyl bromides. Marshall JA, Hann RK. J Org Chem. 73, 6753-7(2008).
A formal synthesis of the callipeltoside aglycone. Marshall JA, Eidam PM. Org Lett. 10, 93-6 (2008).
Chiral allylic and allenic metal reagents for organic synthesis. Marshall JA. J Org Chem. 72, 8153-66 (2007).
ABC synthesis and antitumor activity of a series of Annonaceous acetogenin analogs with a threo, trans, threo, trans, threo-bis-tetrahydrofuran core unit. Marshall JA, Sabatini JJ, Valeriote F. Bioorg Med Chem Lett. 17, 2434-7 (2007).
Palladium- and copper-catalyzed 1,4-additions of organozinc compounds to conjugated aldehydes. Marshall JA, Herold M, Eidam HS, Eidam P. Org Lett. 8, 5505-8 (2006).
Synthesis of a bistetrahydrofuran C17-C32 fragment of the polyether antibiotic ionomycin. Marshall JA, Mikowski AM. Org Lett. 8, 4375-8 (2006).
R. Bruce Martin
A wide ranging investigator, Bruce Martin has published studies in physical, inorganic, biophysical, bioinorganic, physical organic, and bioorganic chemistry. Born in Chicago, he undertook undergraduate studies leading to a B.S. degree in chemistry at Northwestern University and received a Ph.D. degree in photochemistry from the University of Rochester. as a postdoctoral fellow at both the California Institute of Technology and Harvard University, he developed his career interest of investigating the chemistry of problems of biological importance. He came to the University of Virginia in 1959, served a term as chairman, and at retirement 35 years later in 1994 had published more than 200 research papers, one of which was the most widely quoted departmental paper over a recent twelve year period. He authored one of the first textbooks of its kind “Introduction to Biophysical Chemistry” that was translated into Russian and Japanese. Professor Martin describes himself as using the approach of a physical chemist for investigating problems of biological inspiration regardless of the kind of chemistry involved. He continues a strong interest in metal ion interactions, currently those of neurotoxic aluminum. As Associate Director of the Center for Liberal Arts he recently directed two National Science Foundation supported televised chemistry and physical science courses to secondary school science teachers throughout Virginia. Professor Martin has received the President’s and Visitors’ Research Prize of the University three times, the J. Shelton Horsley Research Award of the Virginia Academy of Science, and recognition as a fellow of the AAAS.
Frederick S. Richardson
Professor Frederick S. Richardson earned his B.S. degree at Dickinson College summa cum laude in 1961. In 1966, he received his Ph.D. at Princeton University working with Walter Kauzmann. He served in the US Army for two years before starting his NSF Postdoctoral Research Fellowship at the University of California, San Diego. In 1969, he joined the faculty in the Chemistry Department at the University of Virginia. Prof. Richardson served as chair of the department from 1983 – 87 and 1992 – 1997. In 1991, he was appointed a Commonwealth Professor. Prof. Richardson is an exceptional physical chemist and is known for his research, teaching, and mentorship.
He was appointed as a Henry Dreyfus Foundation Teacher-Scholar from 1973-78. He taught undergraduate general, physical, and biophysical chemistry, as well as, graduate courses in all areas of physical chemistry. He research supervised 36 Ph.D. students, 6 M.S. students and 28 postdoctoral fellows.
Prof. Richardson has published over 220 papers in scientific journals or books. His principal research interests are:
- Electronic structure and spectroscopy of molecules and ions in solution and in crystals.
- Natural and magnetic chiroptical properties of molecular systems.
- Intermolecular chiral recognition and discrimination phenomena.
- Spectroscopic probes of metal-ion coordination sites in biomolecular systems.
- Rare-earth chemistry and spectroscopy.
- Theory and measurement of nonlinear optical processes in condensed-phase materials.
Paul N. Schatz
Paul N. Schatz has published widely in spectroscopic areas ranging from the study of absolute infrared intensities to Magnetic Circular Dichroism (MCD) measurements on matrix isolated species using Synchrotron Radiation in the vacuum ultraviolet, as well as on the theory of mixed valence compounds.
He was a pioneer along with Professor Philip J. Stephens in the development of Magnetic Circular Dichroism (MCD) spectroscopy. This included development of one of the first MCD instruments along with the theoretical interpretation of the novel data produced. These studies started with symmetrical inorganic molecules in solution, then moved on to symmetrical organic molecules, and then to crystals doped with such molecules at pumped liquid helium temperatures (~2.7 K) and as a function of temperature. In later years, matrix isolated species were studied, and pioneering studies on these species were carried out using far ultraviolet frequencies available at the Synchrotron Radiation Center in Stoughton Wisconsin.
Along with Professor S. B. Piepho, a comprehensive book emphasizing the group theoretical aspects of MCD was published in 1983.
In 1978, along with Professors S.B. Piepho and Elmars Krausz, the first rigorous theoretical treatment of the spectroscopy of mixed valence compounds was published. In what later became known as the PKS model, both spectroscopic and dynamic aspects of these compounds were explored in detail.
T. Y. Shen
Professor Shen was born in Peking, China in 1924. He graduated from National Central University of China in 1946, and a year later traveled to England to study organic chemistry on an Overseas Scholarship form the Chinese Ministry of Education. In 1950, he came to the United States for a postdoctoral position at Ohio State University, followed by a research associateship at MIT. From MIT, he joined Merck & Co. in 1956. He was appointed to the U.Va. Chemistry Department in 1986 as Commonwealth Professor of Chemistry, and in 1986 he was named the Alfred Burger Professor of Medicinal Chemistry. Professor Shen’s research focused on the development of three antiinflammatory – analgesic drugs (indomethacin, clinoril®, Dolobid®), and potential chemo-therapeutic agents for viral infections, immunolgical, neoplastic, and other metabolic disease. He also synthesized and characterized molecular probes for biomembrane receptors and receptor ligands for targeted drug delivery. Professor Shen served on many editorial boards including the Journal of Medicinal Chemistry. He received many awards throughout his career, including the Rene Descartes Medal, the Galileo Medal of Scientific Achievement, and an Achievement Award from the Chinese Institute of Engineers-USA. He was also a fellow of the AAAS.
Richard J. Sundberg
Research: Organic chemistry of nitrogen heterocyclic compounds, especially indoles. Biological activity of organic compounds.
Professor Sundberg is primarily engaged in teaching and chemical education. Along with Francis A. Carey he is the author of “Advanced Organic Chemistry,” a two-part text, which was recently published in its fourth edition. Professor Sundberg is also interested in synthetic methodology in heterocyclic chemistry and is the author of “Indoles” in the Best Synthetic Methods Series (Academic Press, 1996).
Electrophilic Substitution Reactions of Indoles. Sundberg RJ. Reactions and Applications of Indoles, G. W. Gribble, editor, Springer, 2010, pp 47-115.
The Iboga Alkaloids and their Role as Precursors of Anti-neoplastic Bisindole Catharanthus Alkaloids, The Alkaloids, Sundberg RJ and Smith SQ. Vol 59, G. A. Cordell, editor, Academic Press, 2002 281-376.
Diethyl formylmethylphosphonate as an acetaldehyde synthon for quinoline synthesis. Wllz AJ, Sundberg RJ. Synlett. 1, 75-76 (2001).
Synthesis of 8-methoxy-1-methyl-1H-benzo[de][1,6]naphthyridin-9-ol (isoaaptamine) and analogues. Walz AJ, Sundberg RJ. J. Org. Chem. 65, 8001-8010 (2000).
Bis-cationic heteroaromatics as macrofilaricides: Synthesis of bis-amidine and bis-guanylhydrazone derivatives of substituted imidazio[1,2-a] pyridines. Sundberg RJ, Biswas S, Murthi KK, Rowe D. J. Med. Chem. 41, 4317-4328 (1998).
Research in Computational Modeling and Theoretical Chemistry
In the past twenty-five years molecular mechanics and quantum mechanical methods have become essential helpers to experimental chemists of all kinds. Modern software systems teamed with powerful computers now make possible practical representation of many aspects of chemical structure and reactivity. I help newcomers to modeling to develop good judgment in their use of these techniques, and apply some of the most powerful techniques to chemical problems.
I use computer modeling to study reaction pathways in organic systems, structures and energetics of systems likely to possess low-lying states of high spin, and the bonding and reactivity of metal-organic complexes. Much of my work is done in collaboration with graduate students conducting experimental investigations with other UVA faculty.
Some projects I am pursuing now:
- Modeling of aryl carbenes, so to characterize Tomioka’s long-lived methylene species (Presented at the International Symposium on Reactive Intermediates and Unusual Molecules [ISRIUM], Nara Japan, Sept 2001.)
- Characterization of Dearomatization induced by complexation with Osmium, Rhenium, and Tungsten species (presented at the Faraday Discussion York University, April 2003)
- Stereochemical consequences of weak interactions loosely termed “hydrogen bonding” (presented in preliminary form at Rutgers University, February, 2004)
- Characterization of Closed shell and open shell dianions stable with respect to autoionization and dissociation (Presented at ISRIUM, Edinburgh UK August 2005)
- TDDFT characterization of circular dichroism spectra of high symmetry organic species (presented at the ACS National Meeting in New Orleans, April 2008
- Structural characterization of organic cations which bind protons and the resulting dications (to be presented at the Int Conf of Quantum Chemistry, Helsinki June 2009
- TDDFT characterization of fluorescence spectra of Iridium and Ruthenium systems
Computed anharmonic frequencies for Formic Acid Dimers can guide experimental detection of short-lived isomers [figure by Ilhan Yavuz].
Environmental Sensitivity of Ru (II) Complexes: The Role of the Accessory Ligands, Eileen N. Dixon †, Michael Z. Snow †, Jennifer L. Bon †, Alison M. Whitehurst †, Benjamin A. DeGraff *†, Carl Trindle ‡, and James N. Demas ‡, Inorg. Chem., 2012, 51 (6), pp 3355–3365
Communication: Frequency shifts of an intramolecular hydrogen bond as a measure of intermolecular hydrogen bond strengths, Q Gu, C Trindle, JL Knee, J. Chem. Phys. 2012 137, 091101
Structure and energetics of cyclopropane carboxaldehyde. Trindle, C., Bleda, E. A. and Altun, Z. (2012), . Int. J. Quantum Chem.. doi: 10.1002/qua.24201
Computational thermochemistry of glycolaldehyde. Bleda, E. A., Yavuz, I., Altun, Z. and Trindle, C. (2012), . Int. J. Quantum Chem.. doi: 10.1002/qua.24200
Photophysical and Analyte Sensing Properties of Cyclometalated Ir (III) Complexes, Leavens BB, Trindle CO, Sabat M, Altun Z, Demas JN, DeGraff BA., J Fluoresc. 2012 , 22:163-74
Chuck Arrington, Ph.D.
Dina Bai, Ph.D.
I design, develop and test software for the acquisition and analysis of mass-spectrometry data in the Hunt laboratory.
Jeff Ellena, Ph.D.
Tao received his B.S. from Wuhan University in China and earned his Ph.D. in medicinal chemistry from the University of Virginia, under the supervision of Professor Timothy Macdonald. His Ph.D. work focused on chemical biology study of Sphingosine 1-Phosphate (S1P) receptors and Sphingosine Kinases for immune modulation, which is directly relevant to human diseases such as autoimmune disorder and cancer. During his post-doc training in UVA’s School of Medicine, he extended his expertise into molecular imaging and nanotechnology for cancer diagnosis and therapy. In the Hsu lab, Tao will be working on immunotherapy for cancers.
Delphine Le Roux, Ph.D.
Carol Price, Ph.D.
Mark Ross, Ph.D.
Jeffrey Shabanowitz, Ph.D.
I work with Professor Hunt’s group to develop new methods and instrumentation in mass spectrometry to determine the primary structure of proteins and peptides and apply these methods to the structural characterization of proteins in complex mixtures and to peptides presented to the immune system in association with class I or class II molecules of the major histocompatibility complex.
Christopher Birch, Ph.D.
Sayanti Chatterjee, Ph.D.
Mallikarjunarao Ganesana, Ph.D.
Jackie Corbitt, Ph.D.
Jennifer Martin, Ph.D.
Dan Nelson, Ph.D.
Balaram Raya, Ph.D.
Charles Richardson, Ph.D.
Sang Jo Shim, Ph.D.
Gwendoline Stephan, Ph.D.
Zhiyong “Jerry” Zhang, Ph.D.
Development and application of BINOL-based chiral catalysts and enantioselective fluorescent sensors.
Chemical Biology; Fluorescence and Bioluminescence Imaging; Protein Engineering
Our lab develops novel molecular probes to peer into cells and brains to understand their communications. We use a collection of innovative techniques, such as protein engineering, fluorescence and bioluminescence imaging, synthetic chemistry, and mass spectrometry, to dissect signaling pathways involving redox-active molecules, neurotransmitters, and protein post-translational modifications (PTMs). Our immediate goal is to monitor biological signaling in real time with excellent spatial resolution and molecular precision in physiologically relevant environments. Our long-term goal is to apply these new probes to live cells and rodent models to understand communications relevant to toxicity of chemicals, cancer development and progression, cognition and behavior, and neurological disorders. Moreover, these basic research efforts are actively being translated to develop novel protein-based diagnostics and therapeutics.
Yeh HW, Karmach O, Ji A, Carter D, Martins-Green MM, and Ai HW*, “Red-shifted luciferase-luciferin pairs for enhanced bioluminescence”, Nature Methods, DOI:10.1038/nmeth.4400. PMID: 28869756
Fan Y, Makar M, Wang MX, Ai HW*, “Monitoring thioredoxin redox with a genetically encoded red fluorescent biosensor”, Nature Chemical Biology, 2017, doi:10.1038/nchembio.2417. PMID: 28671680
Chen Z, Ai HW*, Single Fluorescent Protein-Based Indicators for Zinc Ion (Zn2+)., 2016; Analytical Chemistry. 88(18) 9029-36. PMID: 27539450
Chen ZJ, Tian Z, Kallio K, Oleson AL, Ji A, Borchardt D, Jiang DE, Remington SJ, Ai HW*, The N-B Interaction through a Water Bridge: Understanding the Chemoselectivity of a Fluorescent Protein Based Probe for Peroxynitrite., 2016; Journal of the American Chemical Society. 138(14) 4900-7. PMID: 27019313 | PMCID: PMC4958459
Ren W, Ji A, Ai HW*, Light activation of protein splicing with a photocaged fast intein., 2015; Journal of the American Chemical Society. 137(6) 2155-8. PMID: 25647354
Professor Mattson is a member of the faculty at Randolph College in Richmond, VA. He spends his summers here at UVA teaching Introductory College Chemistry.
My passion is teaching. I am one of the richest people on the planet in that I get paid for doing something I thoroughly enjoy.
In all of my classes, I expect my students to work hard and to strive for excellence.
Accomplishments are not measured in how many details are memorized or in how many processes are mastered. What is important is that a true, quality understanding is achieved, such that the student both sees the world with different eyes and can deal with the challenges in her or his future.
To improve my ability to communicate an understanding of chemistry, I have spent the previous fifteen summers teaching general chemistry at the University of Virginia. A memorable piece of student feedback: “I took the chemistry test. I did not know the answers to all of the questions, but what I did not know I could figure out. I made a perfect 800.”
I was invited to present an ACS Webinar on Creative Problem Solving in Chemical Research(May 5, 2011). The ACS weekly webinar series is designed to connect ACS members and scientific professionals with subject matter experts and global thought leaders in chemical sciences, management, and business on relevant professional issues. In addition to presenting the webinar, I have participated in numerous weeklong ACS Speakers Tours, been invited multiple times to speak to several local ACS sections, was invited to be the 27th Annual Harold Hammond Garretson Speaker at Lynchburg College, and have been invited back dozens of times to talk about problem solving in research to undergraduate students at the University of Virginia. In each case, the audience response has been positive, reflecting both their improved insights and abilities in problem solving and the entertaining nature of the talk.
In addition to teaching general, analytical, and instrumental chemistry and to working both on and off campus with students on research projects, I offer a popular course in creative and critical problem solving. The students greatly improve their abilities to think and to solve problems. A memorable piece of student feedback came from a student after a summer: “After I was working on my job for two weeks everyone was calling me MacGyver because I was so good at problem solving.”
I have spent 23 of the past 25 summers teaching or conducting research at the University of Virginia, James Madison University, the University of North Carolina, and the University of Tennessee. I served as a senior reviewer charged with helping to audit all Advanced Placement chemistry courses in the nation, a consultant for the South Carolina Course Alignment Project, a question writer for the American Dental Exam, an Educational Testing Service chemistry Advanced Placement reader, a National Science Foundation panel member for grant evaluation, a director of the Central Virginia Regional Science Fair, and a master of ceremonies for a high school Academic Competition for Excellence program.
It is very important to me that my students like me, but what is most important is that, 10 years into their futures, they are grateful for what they have learned.
Organic molecules are found in a diverse set of astronomical environments, demonstrating that there are efficient astrochemical pathways to molecular complexity. Interstellar grains and their icy mantles are proposed to be important formation sites of many of these molecules. Understanding the structure, dynamics and chemistry of ices is thus key to advance our understanding of the chemistry in space.
In the Öberg Astrochemistry Lab we pursue laboratory ice experiments and astronomical observations that address how astrochemically important molecules form, and how they may evolve into larger molecules associated with the origins of life. An important aspect of this research is to constrain the fundamental physical chemical processes that underpin ice chemistry. In addition to exploring the chemical evolution in space, our research forms a basis for developing molecular probes of different astrophysical phenomena.
Öberg, K.I., Qi, C., Wilner, D. and Hogerheijde, M., Evidence for Multiple Pathways to Deuterium Enhancements in a Protoplanetary Disk, ApJ, 2012, 749, 162
Öberg, K.I., Murray-Clay, R., Bergin, E.A., The effects of snowlines on C/O in planetary atmospheres, ApJL, 2011, 743, L16
Öberg, K.I., Boogert, A.C.A., Pontoppidan, K.M., van den Broek, S., van Dishoeck, E.F., Bottinelli, S., Blake, G.A., and Evans II, N.J., The Spitzer Ice Legacy: Ice Evolution from Cores to Protostar, ApJ, 2011, 740,109
Öberg, K.I., van der Marel, N., Kristensen, L.E., and van Dishoeck, E.F., Complex Molecules toward Low-Mass Protostars: the Serpens Core, ApJ, 2011, 740, 14
Öberg, K.I., Qi, C., Fogel, J.F.J, Bergin, E.A., Andrews, S.M., Espaillat, C., Wilner, D.J., Pascucci, I., Kastner, J., Disk Imaging Survey of Chemistry with SMA (DISCS): II. Southern Sky Protoplanetary Disk Data, ApJ, 2011, 734, 98
Transitioning lab-bench technologies into commercial products. Focusing on system automation and subcomponent manufacturability to yield prototypes that are ready for the final stage of productization.
Robert Ellsworth Ireland
Robert Ellsworth Ireland (Bob) passed away on Saturday, February fourth at Sarasota Memorial Hospital in Sarasota Florida. He is survived by his wife Margaret, brother Andrew, and children Mark and Richard. Bob, a world-renowned chemistry professor resided in Sarasota these past seventeen years after retiring from the University of Virginia in 1995.
Bob received an A.B. degree from Amherst College in 1951, followed by a Ph.D. degree under the direction of William S. Johnson from the University of Wisconsin in 1954. He then studied as a NSF postdoctoral fellow in the group of William G. Young at the University of California, Los Angeles, from 1954-56. He joined the University of Michigan faculty in 1956 and, subsequently moved to the California Institute of Technology in 1965 as Professor of Organic Chemistry. In 1985, he left Cal Tech to become Director of the Merrell-Dow Research Institute in Strasbourg, France. After a year in that position he came to the University of Virginia as Chairman of the Chemistry department and was selected as the inaugural Thomas Jefferson Chair Professor of Chemistry. He assumed emeritus status in 1995. Among his noteworthy achievements as Chair of the Department was a substantial new addition to the Chemistry Building, completed in 1995.
Bob Ireland received numerous awards in recognition of his contributions to organic synthesis. These include a Sloan Fellowship, the Ernest Guenther Award in the Chemistry of Essential Oils, and the ACS Award for Creative Work in Synthetic Organic Chemistry. He was the first to demonstrate the awesome synthetic potential of the enolate Claisen rearrangement, a reaction that now bears his name. His significant impact on synthetic organic chemistry reflected not only his scientific achievements, but also his style of presentation both in seminars and the scientific literature. His publications are a model of clarity and thoroughness. Early in his career he wrote Organic Synthesis (Prentice Hall, 1969), the first-ever textbook on synthetic strategy. In it one finds the oft quoted passage “Stereochemistry Raises its Ugly Head” as the title of Chapter 5. The final chapter, “Multistage Synthesis: Logistics and Stereochemistry Combine to Produce Nightmares,” presages the present era of complex molecule construction. Though nearly 40 years old, the book can still serve as a text for a modern mid-level course in synthetic organic chemistry.
Bob’s lucid and often entertaining lectures in the classroom and at industrial organizations graphically illustrated the power and beauty of multistage organic synthesis and inspired generations of chemists, both young and old. It is worth noting that many of his former students and postdoctoral associates have become successful chemists themselves and now hold leadership positions in industry, government, and universities, both in the U.S. and abroad. His many contributions to education and science will be long remembered.
James A. Marshall, Charlottesville Virginia
John T. Yates, Jr.
John Thomas Yates, Jr.
August 3, 1935 – September 26, 2015
John T. Yates, Jr., Professor of Chemistry at the University of Virginia, member of the US National Academy of Sciences, and a pioneer of modern surface science, passed away at his home on Saturday morning September 26, 2015, from a recurring glioblastoma. John was both courageous, pragmatic and forthright about his diagnosis right to the end. His wife, Kerin, related that John, upon learning of his diagnosis, said that he had had a great life and was not going to ‘let the last 1.25%’ define him. It did not. He had a wonderful family and a stellar career.
Born in Winchester, Virginia on August 3, 1935, he received his B.S. degree in chemistry from Juniata College in Huntingdon, Pennsylvania in 1956, and his Ph.D. in physical chemistry from the Massachusetts Institute of Technology in 1960 — working with Professor Carl W. Garland. Following three years as an Assistant Professor at Antioch College in Yellow Springs, Ohio, he joined the National Bureau of Standards, Gaithersburg, Maryland (now the National Institute of Standards and Technology), first as an NRC Postdoctoral Research Fellow and then, from 1965 until 1982, as a member of its scientific staff. He was a Senior Visiting Scholar at the University of East Anglia, Norwich, UK in 1970-71, and the Sherman Fairchild Distinguished Scholar at the California Institute of Technology in 1977-78. He joined the University of Pittsburgh in 1982 as the first R.K. Mellon Professor of Chemistry, and as the Founding Director of the University of Pittsburgh Surface Science Center. In 1994 he received a joint appointment in the Department of Physics. In 2006, he retired from the University of Pittsburgh and moved to the University of Virginia as Professor and Shannon Research Fellow.
Throughout his career, his research was in the fields of surface chemistry and physics, including interests in the structure and spectroscopy of surface species, the dynamics of surface processes, and the development of new methods for research in surface chemistry. When he moved to the University of Virginia, he also became professionally active in the field of astrochemistry. He was an accomplished amateur astronomer and woodworker. He had a passionate lifelong interest in clocks, accuracy in timekeeping, and precision instrumentation, both antique and modern. To his core, he was “a measurer” with accuracy and precision. His colleagues and competitors alike knew that they could always trust, without question, the measured quantities in his published works.
John Yates was an exceptional scientist and gifted communicator. He had a knack for making complex problems seem simple after he studied them in depth and communicated his results so beautifully, typically with his own meticulously hand-drawn diagrams. He published more than 750 scientific papers on surface chemistry and physics, and is among the 100 most-cited chemists in the world. His professional accomplishments have been recognized by many prestigious awards and honors, including: Silver Medal – U.S. Department of Commerce (1973); Sherman Fairchild Distinguished Scholar – Caltech (1977-78); Stratton Award for Distinguished Research – NBS (1978); Gold Medal, U.S. Department of Commerce’s Highest Award (1981); Kendall Award for Colloid or Surface Chemistry of the American Chemical Society (1987); Inaugural President’s Distinguished Research Award – University of Pittsburgh (1989); E.W. Morley Medal of the Cleveland ACS (1990); Fellow of the American Physical Society (1992); Medard Welch Award –American Vacuum Society’s highest technical award (1994); Fellow of the American Vacuum Society (1994); Alexander von Humboldt Senior Research Award (1994); Member of the National Academy of Sciences (1996); Pittsburgh-Cleveland Catalysis Society Award (1998); Pittsburgh Award of the Pittsburgh ACS (1998); Arthur W. Adamson Award for Distinguished Service in the Advancement of Surface Chemistry of the ACS (1999); J.W. Linnett Visiting Professorship – Cambridge University (2000); Outstanding Alumnus of Juniata College (2000); G.N. Lewis Lecturer, University of California-Berkeley (2002); Japan Society for the Promotion of Science Fellowship (2002); Gwathmey Visiting Professor, University of Virginia (2002-03); Fellow of The Institute of Physics (2004); and the Peter Debye Award in Physical Chemistry of the ACS (2007); Theodore Madey Award of the AVS (2011); Gerhard Ertl Lecturer Award for Surface Chemistry and Catalysis (2013).
Professor Yates was a kind, patient, trusted and generous mentor and advisor to the more than 1000 students, postdocs and collaborators with whom he interacted. He was an inspirational undergraduate and graduate teacher and mentor. He demonstrated and conveyed an excitement about science, the wonders of scientific discovery, and a love of learning that encouraged and helped many to pursue scientific careers. In addition, he developed strong professional relationships with a number of surface science research programs in academic, government, and industrial research laboratories throughout the world. He served on the editorial boards of six scientific journals and two book series in surface science and catalysis. He was Associate Editor of the ACS journal, Langmuir. He also served on the Advisory Board of Chemical & Engineering News and on the International Advisory Board of Chemistry World.
Yates was generous in his service of scientific societies such as the American Vacuum Society, the American Physical Society, and the American Chemical Society, including past service as a member of the AVS Board of Directors, AVS Trustee Chair, and twice as the AVS Surface Science Division Chair. He was the past chairman of the APS Division of Chemical Physics, and the ACS Division of Colloid and Surface Chemistry. He organized many symposia for ACS and APS national meetings, and was Chairman of three Gordon Research Conferences. He co-edited two books, Vibrational Spectroscopy of Molecules on Surfaces, Plenum, 1987 and Chemical Perspectives of Microelectronic Materials, Materials Research Society, 1989. He co-authored a book entitled, The Surface Scientists Guide to Organometallic Chemistry, ACS, 1987. He also co-authored a textbook, Molecular Physical Chemistry for Engineers, University Science Books, published in 2007. His book, Experimental Innovations in Surface Science, was originally published by Springer-Verlag and The American Institute of Physics in 1998; a second edition, his last major project, was published in 2015.
John is survived by Kerin – his wife of 57 years, his sons Geoffrey (Michelle), and Nathan (Jan), and six grandchildren, Andrew, Steven, Caitlin, Lauren, Hannah and Sara. His passing is a loss for his family and for science, but he has left a lasting legacy in his published work, and in the generations of scientists he mentored.
John N. Russell, Jr., Ph.D.
Head, Surface Chemistry Branch, Naval Research Laboratory, Washington DC
Thomas P. Beebe, Jr., Ph.D.
Professor of Chemistry, University of Delaware, Newark DE
(former graduate students)
William H. Myers
Bill Myers was a strict teacher teaching a tough subject — chemistry. He expected discipline. However, he would do everything to help his students succeed. He offered review and practice sessions for his exams. He posted every test he ever administered online so students could practice on old tests right before upcoming tests. He recorded his lectures and told stories in class – often funny ones — to help students relate to and understand his subject matter. In a University of Richmond post, Bruce Matthews, assistant athletic director for academics, noted, “He wasn’t going to let you go until you had it. … He just cared.”
Dr. Myers, who retired last May as professor of chemistry at UR after teaching and researching for 43 years, died Sept. 14 at home in Richmond at age 70. Doctors diagnosed an aggressive brain tumor in August. Family members say that chemistry was in his blood from the beginning. William Howard Myers was born Jan. 26, 1946, in a hospital in the shadow of nuclear reactors at Oak Ridge, Tenn., the secret “Fenced City” that housed the Manhattan Project, which the previous year had produced the atomic bomb that won World War II for the Allies.
His chemist father, Albert Myers, who had overseen the chemical aspects of the site’s uranium enrichment program, left to teach at various universities, including Carson-Newman in Jefferson County, Tenn., where Dr. Myers grew up and graduated with honors from high school in 1963. That summer, his father moved the family to Houston, where he helped establish a new Houston Baptist University. Dr. Myers lived at home and attended HBU, majoring in chemistry, physics and math and taking every science course the school offered. After running out of classes to take, he spent his final semester as an intern at Argonne National Laboratory in Chicago, where he decided he never wanted to live again in a cold city.
In Texas, he met Barbara Sue McElvany, whom he married after graduation from HBU in 1967. They moved to the University of Florida at Gainesville, where she finished earning a sociology degree and he began work on his doctorate in inorganic chemistry. When he drew a low draft number during the Vietnam War, Florida put him on staff to teach freshman chemistry, which deferred him long enough to join the Reserve Officer Training Corps and transition into the officers’ Chemical Corps. In 1972, when he earned his doctorate, he was an Army captain. He served in the Army Reserve until 1981.
In fall 1973, he came to the University of Richmond as an associate professor of chemistry, becoming one of five members of his family to teach college chemistry. Dr. Myers chose teaching over research because he loved people and relished encouraging them to reach their potential, according to family. He had a special spot in his heart for student-athletes in his class.
Leland Melvin, a UR football standout who became a NASA astronaut, noted that, “The whole time I was in space, I reflected on people who had not given up on me. … And he was one of them. Dr. Myers was that person who molded me and guided me and helped me understand what chemistry was all about and brought it to life. “All those traits you want your kids to have, he tried to instill them in us: having good character, being a strong person, believing in yourself. It wasn’t just chemistry but in life.”
When former UR offensive lineman Chris Kondorossy became anxious about passing his dental school entrance exam, Dr. Myers invited him to his home, according to the UR post. “I went out there every Saturday for a whole summer at 7 a.m.,” he said. “He privately tutored me for two or three hours. His wife would make us coffee, and we’d sit at the dining room table. “He would go through the textbook front to back. I’d take practice exams with him. I’d get stuck, and he’d tell me why. That’s probably the only reason I was able to get into VCU [Dental School]. … I’ll never forget that. He was looking out for me. That’s who he was.”
Growing up in a family that loved everything from hymns to symphonic music, Dr. Myers developed a love of music and the arts. Playing the lead in “Amahl and the Night Visitors” as a child in Tennessee started him on his way. In Richmond, he sang in the Richmond Symphony Chorus under James Erb and also had lent his voice to the bass sections of church choirs.
In a letter to Dr. Myers on Sept. 6, Jim Hall, a former UR colleague of Dr. Myers, wrote, “I am so glad that you and Barbara took the time this summer to see your families. There’s nothing more important than family this side of Jordan.”
The family archivist, Dr. Myers converted his grandfather’s weekly family newsletters to print and digital formats, preserving more than 25 years of family history. He also collected, organized and preserved family photos and slides.
With Southern Baptist roots running deep on both sides of his family, “he loved his church,” wrote his brother, James “Jim” Myers of Knoxville, Tennessee. “Bill’s life was spent in service to people.”
A self-taught Bible scholar, Dr. Myers found great joy in leading others to more deeply experience God’s word, family members wrote. He taught everywhere he could – at churches, in Kenya, as well as at seminars and conferences. One Thursday per month since 2012, he had led a Bible study group at Deep Meadow Correctional Center. “He was a remarkable teacher of the Bible, of patience, of compassion, of inclusiveness, of love for all people, of ethical/forthright behavior, of clear thinking, of the importance of organization and scholarship, and of unbridled love for God and his family,” another brother, John Myers of Durham, North Carolina, wrote. “His main concern was about each person’s faith in God and their journey with Christ. His gift to each of them was helping them on that journey.”
Please click here to read more on Bill’s life and legacy.
In addition to his brothers, survivors include his wife of 49 years, Barbara Sue McElvany Myers; a daughter, Kathy Burnette; and a son, Bryan Myers, both of Midlothian; and one grandson.
September 20, 2016, Ellen Robertson, Richmond Times Dispatch
Jack Cronk grew up in Charlottesville, Virginia and graduated from Western Albemarle High School. He is currently pursuing a Bachelors of Science in Chemistry with a specialization in Biochemistry along with ACS certification. Jack conducts research in the School of Medicine in the laboratory of Dr. Michael Brown, Ph.D. Over the last 3 semesters, Jack has designed and utilized genetic approaches to systematically and specifically induce mutations in the genes of natural killer (NK) cell receptors. NK cells play an essential role in the innate immune response as cytotoxic lymphocytes that recognize cells infected with virus. Jack’s research investigates genetic mutations in NK cell receptors, the effects of which will ultimately be evaluated with respect to how these mutations impact receptor functionality. His thesis focuses on the validation of a meticulous experimental approach to study the immediate impact of these gene disruptions. Current and future work will involve testing his experimental design and evaluating the effects of the receptor mutations at the genomic level. Following graduation, Jack plans to continue his research at UVa, spend time with his two miniature dachshunds, Piper and Elly, and eventually pursue a Ph.D in Immunology.
Nikki grew up in Fairfax, Virginia and attended Robinson Secondary School. She will be graduating from UVA with a Bachelor of Arts in Chemistry and a Minor in Psychology. Since August 2015, Nikki has been working in Dr. Thurl Harris’ lab in the Pharmacology Department in the School of Medicine. Dr. Harris’ lab studies how the enzymes involved in lipid metabolic pathways are regulated and how their deregulation can lead to pathological conditions such as obesity and Type II Diabetes. Over the last two years, Nikki has been exploring the stability of lipin-1, a phosphatidic acid phosphatase enzyme in the Kennedy pathway of lipid synthesis and an essential component of triacylglycerol synthesis in adipose tissue. She is working to identify critical residues that regulate lipin-1 ubiquitination and degradation by the proteasome. In light of the obesity epidemic, understanding what regulates lipin-1 stability and its ability to synthesize triacylglycerol may help to illustrate the mechanisms at play in metabolic derangements that physicians see every day. Following graduation, Nikki will be pursuing a Ph.D. in Pharmacology at Columbia University in New York City.
Victoria is from Herndon, Virginia and is studying chemistry with a minor in Russian language and literature. She began research with Dr. Landers in the fall of 2015, working with Shannon Krauss on an explosives detection project. The project is working to develop a portable device in which colorimetric reactions occur in the presence of various explosive materials. Reactions for nitrates, hydrogen peroxide, perchlorates, TNT, DNT, and tetryl have been implemented on the device. Victoria focused most of her work on the nitrates. By modifying the Griess reaction, which turns bright pink when reagents form an azo dye with nitrate, the reaction and limits of detection were optimized for use in the field.
When she isn’t working in the lab, Victoria loves to dance, read, and cook. She has been a member of University Dance Club throughout her college career, and joined University Salsa Club during her third year. She also volunteered as an elementary school tutor through Madison House and was a fundraiser for Dance Marathon for UVA Children’s Hospital.
Maggie grew up in Yorktown, VA, but went to high school at the International School of Provence-Alpes-Cote-D’azur in Manosque, France. She is pursuing a Bachelor of Science with Specialization in Biochemistry and a Minor in Religious Studies with a concentration in Islam.
Since May 2015, Maggie has been conducting research with Dr. Cassandra Fraser in the Department of Chemistry. The Fraser Lab studies the synthesis and applications of dual-emissive polymeric materials for oxygen sensing and imaging in biomedical contexts such as tumors, wounds and the brain. The dyes are luminescent difluoroboron b-diketonates that are covalently linked or blended with a biocompatible polymer, such as poly(lactic acid), and precipitated into nanoparticles. Maggie’s projects in the Fraser Lab have a focus on the molecular design of the luminescent boron dyes, with efforts to elucidate the trends for tuning their optical properties.
Outside of the lab, Maggie is an active member of Club Swim as well as Alternative Spring Break at UVA. She has also worked as an Organic Chemistry Lab TA for the past two years. Next year, she will begin pursuing a PhD in Materials Science at the University of North Carolina at Chapel Hill.
I am from Atlanta, GA, and I went to The Lovett School. I will graduate with a BSc in Chemistry and a BA in Studio Art, painting concentration. I stated research with the Demas lab Spring 2016, focusing on fluorescence anisotropy. I have worked with the oxygen sensor Ru(bpy)3, Fraser’s promising boron complex nanoparticles, and fluorescent dye-polymer equilibria that model biological binding systems. Measuring the anisotropy of these compounds gives valuable information about the excited state(s) and information about binding. Fluorescence anisotropy is the study of emission polarization and is commonly used to measure the binding of biological equilibria. When a polarized excitation source excites a fluorophore, that fluorophore can emit in the same orientation, or it can rotationally diffuse before it has the chance to emit, thus producing an unpolarized emission. Anisotropy is a ratiometric measurement of the extent of the emitted polarization.
In addition to painting, I sing in two different groups on Grounds, the Harmonious Hoos co-ed a cappella group and the Virginia Women’s Chorus.
Youlim was born in Seoul, South Korea and grew up in Nanjing, China. She is graduating with the Bachelor of Science in Chemistry with the ACS certification from the University.
Youlim is doing research with Professor Ku-Lung (Ken) Hsu in the Department of Chemistry. In order to understand protein function in human disease and physiology, the lab develops novel small molecules that enable molecular analysis of proteins with mechanistically-related reactivity and activity. Her research is focused on the synthesis of new chemical probes to identify novel small molecule binding pockets present in proteins that were previously undetected due to a lack of suitable chemical biology approaches.
She received the Undergraduate Poster Session Award from the American Chemical Society for her research. She also received the Department of Chemistry Award for Excellence in Chemistry. In the fall, she is moving to London for studying Advanced Chemical Engineering.
Ellen Howerton grew up in Fairfax, Virginia and graduated from Thomas Jefferson High School for Science and Technology. She will graduate from UVa with a Bachelor of Science in Chemistry with a biochemistry specialization.
Ellen joined the Bushweller lab group in the Molecular Physiology and Biological Physics department in January, 2015. For her distinguished major, she focused on the Ets-domain family of transcription factors, which are deregulated in multiple cancers. Many Ets-domain proteins exhibit autoinhibition, a phenomenon that occurs when a separate portion of a protein inhibits the function of another domain. As the autoinhibitory domain is likely unique between Ets family members, it provides a promising target for therapeutics.
Outside of her studies, Ellen is a violinist and an active member of Radio Music Society, a student-run group that writes and performs string quartet covers of popular songs. She is also a Soprano 1 with the Virginia Women’s Chorus and a member of the Washington Literary Society and Debating Union. After graduation, Ellen will be working at the National Human Genome Research Institute at the NIH and later hopes to pursue graduate study in Public Health.
Daniel grew up in Arlington, Virginia and attended Washington-Lee High School. He will be graduating UVA with a Bachelor of Science in Chemistry with a Specialization in Chemical Physics and a Bachelor of Arts in Physics.
Since August of 2013 Daniel has been working for the Demas research group. His primary focus has been using fluorescence anisotropy to determine binding constants between fluorescent dyes and polyelectrolytes. This method has been shown to allow for more types of binding constants to be measured than using other fluorescent techniques. It also has shown that more complex binding occurs when the polymer concentration is much greater than that of the fluorescent dye.
Outside of lab, Daniel is very involved with UVA’s honor fraternity Phi Sigma Pi as well as being a First Year Seminar Facilitator for the Orientation and New Student Programs office at UVA. He has also served as a physical chemistry teaching assistant for the past year. After graduation, Daniel will be pursuing a Ph.D in nuclear/physical chemistry.
Joshua attended Franklin County High School in Rocky Mount, VA. He is pursuing a B.Sc. in Chemistry with a Specialization in Biochemistry with ACS certification.
His research is in the lab of Dr. Lin Pu where he worked on a project with graduate student Shifeng Nian synthesizing a bimetallic catalyst to control the tacticity in atomic transfer radical polymerizations (ATRP) of functional alpha-olefins (e.g. acrylamide) by synthesizing a salen-derived macrocyclic ligand to coordinate a Lewis acidic metal and copper. Previous research showed that addition of a Lewis acid to Cu-mediated ATRP was promising for producing steroregular polymers. We confined the Lewis acidic center and the copper center in close proximity on a macrocyclic ligand to couple their roles in the polymerization and enhance the catalytic efficiency. Our work has provided evidence that these bimetallic catalyst systems incorporate a cooperative effect utilizing the Lewis acidic monomer activation with the copper-chlorine radical generation and stabilization process in order to provide stereocontrol and catalysis to the ATRP processes. Following the introduction of chirality into the catalyst system, the reaction of the Lewis acid coordinated monomer with the adjacent transient free radical, generated from the copper-chlorine abstraction at the polymer end, proceeds with significant stereocontrol to give the desired isotactic polymers. We are still working to optimize the degree of monomer conversion and stereocontrol.
In addition to research, Joshua has been a teaching assistant for CHEM 3410 and CHEM 3420 (physical chemistry, thermodynamics and quantum chemistry) under Dr. Dave Metcalf. Though still undecided on his particular focus, he will study organic, organometallics, or polymer chemistry in graduate school.
Andrew was born in Silver Spring, MD but attended Oakton High School in Vienna, VA. He will be graduating from UVA with a Bachelors of Science in Chemistry. Since January 2012, Andrew has worked in the research group of Dr. W. Dean Harman.
For the majority of his time in the Harman group, Andrew’s project has been to separate the two enantiomers of a chiral tungsten dearomatization core. To do so, a tartaric acid derivative was first used to create two diastereomeric salts. From there, the salts were separated via a finely tuned precipitation reaction and then returned to their original state by removing the asymmetric anion with a base. This research presents a novel approach for the enantio enrichment of chiral organometallic complexes. Andrew is in the process of submitting a first author publication of this research and hopes to have it published before he graduates.
Outside of academics, Andrew is a dedicated fan of UVA basketball and religiously attends all home games. After graduation, Andrew will be pursuing a Ph.D in inorganic chemistry.
Nick Lee is a fourth-year Distinguished Major in Biochemistry from Winchester, Virginia. He conducts research in the School of Medicine in the laboratory of Anindya Dutta, M.D., Ph.D., where he investigates the function of the CRL4(Cdt2), an E3 ubiquitin ligase, in the cell cycle. The complex is responsible for marking cell cycle regulators for degradation by the proteasome. Previously, he worked to elucidate the stabilizing role that 14-3-3 exerted over Cdt2. His thesis is focused on characterizing the interaction between BRAF35 and Cdt2. BRAF35 is relatively uncharacterized in the literature, but it interacts with BRCA2, the breast cancer susceptibility protein. For his research endeavors, he has received a U.Va. Summer Scholars Award, a Harrison Undergraduate Research Award, a College Council Fall Research Grant, and a Small Research and Travel Grant, along with being a published co-author in Molecular and Cellular Biology.
Currently, he serves as the Vice Chair for Trials for the Honor Committee, the Chair of the Undergraduate Research Network, and the President of the College Science Scholars Council. Outside of those commitments, Nick has taught his own CavEd class, Current Topics in Neuroethics, served as a TA for Organic Chemistry, and is an Echols Scholar, College Science Scholar, a member of the Raven Society, and a Lawn Resident. After graduation, he will be pursuing his M.D. with the desire to become a professor of medicine.
Emily M. Schutzenhofer is from Stafford, Virginia and is a graduate of Colonial Forge High School. She is an Echols Scholar double majoring in Chemistry with a Specialization in Biochemistry (including the ACS certificate) and Global Development Studies with a concentration in Global Public Health.
Emily conducts research in the lab of Dr. Gary K. Owens in the Robert M. Berne Cardiovascular Research Center. She studies the molecular mechanisms controlling the expression of an embryonic stem cell pluripotency gene, Oct4, in adult smooth muscle cells. Of particular interest to her are those mechanisms involving the vessel environmental cues typically associated with the development and progression of atherosclerotic lesions. The implications of her research include increasing understanding of the development of atherosclerosis, a condition characterized by the hardening of arteries due to the buildup of plaque. End-stage, catastrophic clinical events associated with atherosclerosis include myocardial infarction and stroke, provoked by plaque rupture and major thrombotic events. In addition, her research contributes to the field of knowledge surrounding smooth muscle cell phenotypic switching— control of which could constitute even more widely applicable clinical interventions related to cardiovascular diseases.
Outside of her academic pursuits, Emily proudly serves as the President of the National Leadership Council of the National Society of Collegiate Scholars, one of the nation’s largest and most prestigious college honor societies. She also serves on the Board of Directors for the Society. Emily is an aspiring physician and, as such, is passionate about health, wellness, and service— in addition to her research at the CVRC, she volunteers at the Charlottesville Free Clinic and Remote Area Medical Clinics in underserved regions of the state, has led the Women in Medicine Initiatives interest and advocacy group at UVA, has studied and participated in research on public health interventions in developing nations to improve chronic asthma management, and has founded and leads a service organization, the Virginia Cyber Leo Club at UVA, to help people with disabilities in the local community.
Dr. Collins earned a B.S. in Chemistry at the University of Virginia in 1970 (mentor Carl Trindle). He went on to attain a Ph.D. in physical chemistry at Yale University in 1974. He then enrolled in medical school at the University of North Carolina at Chapel Hill, earning there an M.D. in 1977. rom 1978 to 1981, Dr. Collins served a residency and chief residency in internal medicine at North Carolina Memorial Hospital in Chapel Hill. He then returned to Yale, where he was named a Fellow in Human Genetics at the medical school from 1981 to 1984. During that time, he developed innovative methods of crossing large stretches of DNA to identify disease genes. In 1984, Dr. Collins joined the University of Michigan in a position that would eventually lead to a Professorship of Internal Medicine and Human Genetics. Dr. Collins accepted an invitation in 1993 to succeed James Watson as Director of the National Center for Human Genome Research, which became NHGRI in 1997. As Director, he oversaw the International Human Genome Sequencing Consortium. Dr. Collins’ accomplishments have been recognized by numerous awards and honors, including election to the Institute of Medicine and the National Academy of Sciences, and the Presidential Medal of Freedom. On July 8, 2009, President Barack Obama announced he will nominate Dr. Collins to lead the National Institutes of Health.
Professor Crews earned his Chemistry B.A. at the University of Virginia in 1986. He then studied in Germany at the University Tübingen with a German Academic Exchange Service (DAAD) fellowship. He earned his Ph.D. in Biochemistry at Harvard University in 1993. After a postdoctoral fellowship with Stuart Schreiber at Harvard he joined the Yale Molecular, Cellular, and Developmental Biology Department faculty. He is also a faculty in the Departments of Chemistry and Pharmacology at Yale. His laboratory investigates chemical approaches to the study of biological questions and is specifically interested in the modes of action of biologically active natural products in order to investigate intracellular signaling pathways and identify novel targets for drug design. In 2006, Prof. Crews received the Friedrich Wilhelm Bessel Award from the Alexander von Humboldt Foundation and, in 2009, he received a Grand Challenges Exploration grant from the Bill & Melinda Gates Foundation.
Cynthia S Dowd
Professor Dowd earned her B.A. degree from the University of Virginia and her Ph.D. in Medicinal Chemistry from Virginia Commonwealth University (working with Richard Glennon). Following postdoctoral work at the University of Pennsylvania (with Irwin Chaiken), she joined the NIH where she directed a synthetic chemistry group finding novel small molecules against Mycobacterium tuberculosis. In 2007, she joined the Chemistry Department of George Washington University as an assistant professor. Her research interests broadly include anti-infective drug discovery, structure-based ligand design, and the development of chemical tools to understand important biological processes.
Christopher B. Ferenc
After graduating from UVa with a B.S in Chemistry, Christopher Ferenc received his law degree from Seton Hall University School of Law, in Newark, NJ. His background in chemistry motivated him to pursue a career in the field of intellectual property law. His professional experience in this field includes interning with a U.S. Magistrate Judge and serving as legal support staff for a U.S. Congressional Committee. Currently, he is employed as a Patent Attorney in Washington, D.C. His practice focuses on the preparation and prosecution of U.S. and foreign patent applications in the chemical arts, as well as providing counsel to clients on issues relating to invalidity, infringement and patentability of U.S. patents.
J. Christopher Love
Professor Love is an assistant professor in chemical engineering at MIT. He is also an associate member at the Eli and Edythe L. Broad Institute, and associate faculty at the Ragon Institute of MGH, MIT, and Harvard. He was named a Dana Scholar for Human Immunology and a Keck Distinguished Young Scholar in Medical Research in 2009.
Professor Love graduated with a B.S. degree in chemistry from the University of Virginia in 1999 (conducted research with Cassandra Fraser). He received his Ph.D. in 2004 in physical chemistry at Harvard University under the supervision of George Whitesides. Following completion of his doctoral studies, he extended his research into immunology at Harvard Medical School with Hidde Ploegh from 2004-2005, and at the Immune Disease Institute from 2005-2007. His current research uses microsystems to characterize heterogeneity among single cells with specific studies in HIV/AIDS, autoimmunity, and biopharmaceutical manufacturing. He was selected as on of a Brilliant 10 for 2010 in PopSci.
Brian Pollok, Ph.D., is Life Technologies’ Chief Scientific Officer and Head of Global Science & Innovation based in Carlsbad, CA. He oversees the allocation of more than $350M in R&D funds annually, which has yielded innovative new products in the areas of DNA sequencing, cell analysis, and molecular biology. Dr. Pollok has been with Life Tech since 2003, previously serving as CSO and Head of Global R&D for Invitrogen, and as VP of R&D for the company’s Discovery Sciences unit in Madison, WI. Prior to joining Life Tech, Dr. Pollok served as Sr. VP of R&D and Co-Founder at Ansata Therapeutics in La Jolla (2002-03), as VP of Discovery Biology at Aurora Biosciences/Vertex Pharmaceuticals in San Diego (1997-2002), as Sr. Research Investigator at Pfizer Central Research in Groton, CT (1993-97), and as Assistant Professor of Microbiology and Immunology at Wake Forest University in Winston-Salem, N.C. (1987-93). Dr. Pollok received his B.A. in biology and chemistry from UVa, and his Ph.D. from UAB. Dr. Pollok held a Damon Runyon Cancer Fund postdoctoral fellowship at the Fox Chase Cancer Center, Philadelphia. He is a member of the editorial board of the journal ASSAY, and is an advisor for several non-profit disease organizations. Dr. Pollok is also a past recipient of an American Cancer Society Faculty Research Award and an Arthritis Foundation Investigator Award.
Christian M. Rojas
Professor Rojas earned his B.A. from the University of Virginia in 1989, where he did research with Ralph O. Allen on neutron activation analysis of archaeological artifacts. He received a Ph.D. in organic chemistry from Indiana University, working with David R. Williams. Following a postdoc with Julius Rebek at both MIT and The Scripps Research Institute, Professor Rojas joined the faculty at Barnard College, a liberal arts college for women in New York City. His research involves the development of nitrogen atom transfer reactions and their application to the synthesis of 2-amino sugars.
Eric A. Rohlfing
Dr. Rohlfing is the division director of the Chemical Sciences, Geosciences and Biosciences Division in the Office of Basic Energy Sciences (BES), Office of Science, U.S. Department of Energy. He joined BES in 1997 and served as program manager for the Atomic, Molecular and Optical Sciences program from 2000 to 2003 and as team leader for Fundamental Interactions from 2003 until October 2006, when he became division director. Dr. Rohlfing received his B.S. in Chemistry from the University of Virginia in 1977 and his Ph.D. in Physical Chemistry from Princeton University in 1982. He was a postdoctoral fellow at Exxon Research and Engineering Company and Los Alamos National Laboratory before joining the staff at the Combustion Research Facility at Sandia National Laboratories in 1986.
His research interests include the experimental characterization of transient molecules relevant to combustion processes, linear and nonlinear laser spectroscopies, trace detection of pollutants, molecular beam and mass spectrometric studies of carbon and metal clusters, and vibrational relaxation dynamics. He is the author of approximately 50 peer-reviewed articles, holds membership in the American Chemical Society and the American Physical Society, and is a fellow of the American Association for the Advancement of Science.
Stuart L. Schreiber
Director of Chemical Biology at and Founding Member of the Broad Institute of Harvard and MIT, where he is a Investigator. He is also the Morris Loeb Professor of Chemistry and Chemical Biology at Harvard University. He is a member of the National Academy of Sciences and the American Academy of Arts & Sciences (1995).
Dr. Schreiber was born February 6, 1956 and raised in Virginia. After receiving a B.A. degree (conducting research with Richard Sundberg) at the University of Virginia in June of 1977, he carried out graduate studies at Harvard University under the supervision of R. B. Woodward and Y. Kishi. Following completion of his doctoral studies, he joined the faculty at Yale University in May of 1981. He was promoted to Associate Professor with tenure in 1984 and to Full Professor in 1986. In 1988, he returned to Harvard.
Dr. Schreiber is known for having developed systematic ways to explore biology, especially disease biology, using small molecules and for his role in the development of the field of chemical biology. Currently, the Schreiber group research is focused on:
- Development of next-generation synthetic chemistry affording a transformative small-molecule screening collection.
- Investigating small molecules using human primary cells in an environment that mimics their in vivo niche.
- Exploiting the remarkable ability of genetic approaches to illuminate the roles of genes in biology and disease
- Attempting to discover small molecules that increase pancreatic beta cell numbers and function using organ cultures of human primary pancreatic islets
Professor Santos earned his B.S. degree from the University of Virginia and continued at UVA for his Ph.D. studies with Timothy Macdonald. After graduating in 2002, he was an NIH Postdoctoral Fellow at Harvard University in the Department of Chemistry and Chemical Biology with Professor Gregory L. Verdine. He is now an assistant professor at Virginia Tech.
After Robert Sell earned his B.S. in Chemisty with High Distinctions from UVA in 1975, he worked for four years in the U.S. Navy as an instructor at the Naval Nuclear Power School teaching Chemistry, Radiological Fundamentals, and Materials Science. From 1979 to 2009, he worked with Corning Incorporated in a wide variety of positions in manufacturing, process engineering, product and market development, strategy development, intellectual property, product line management. During his time at Corning, he obtained a Masters in Business Administration from West Virginia University in 1987. Over the 30 years he worked at Corning , he participated in the areas of glass products for the pharmaceutical industry, environmental laboratory analysis, and semiconductor manufacturing. He is now retired from Corning and instructing at Corning Community College.
Dr. Toney’s career has spanned both the pharmaceutical industry and academia. His academic training is in Chemistry (B.S., University of Virginia; M.S. and Ph.D., Northwestern University) and included research experience as a postdoctoral fellow in Molecular Biology (Dana Farber Cancer Institute, Harvard Medical School) and in Chemical Biology (Massachusetts Institute of Technology).
While at UVA, Dr. Toney conducted research with James Demas, which resulted in a publication (Toney, J.H., Demas, J.N. “Low frequency computerized lock-in amplifier”, Rev. Sci. Inst., 53: 1082-1085 (1982)).
His current scholarship is focused on drug discovery using an interdisciplinary approach. As a Senior Research Fellow at Merck Research Laboratories, he studied a variety of therapeutic targets for which high throughput biochemical assays were developed. He has held the Herman and Margaret Sokol Professorship in Chemistry at Montclair State University and served as Department Chairperson of Chemistry and Biochemistry. During this time, he developed a new graduate course, “Biomolecular Assay Development” that emphasizes teaching of the drug development process, including laboratory and in silico molecular modeling techniques. He is a member of the Editorial Board of Assay and Drug Development Technologies and is a Section Editor of Current Opinion in Investigational Drugs. He has served ten times as a member of the review panel, “Assay Development for High Throughput Molecular Screening” (R03, R21) of the National Institutes of Health, Molecular Libraries and Imaging Initiative. He has published 51 peer reviewed articles and holds six U.S. patents. Dr. Toney joined Kean University in 2008 as Dean of the College of Natural, Applied and Health Sciences. Dr. Toney is Vice President for Academic Affairs (2011- present) at Kean University. He is currently serving as the Chief Academic Officer (since 2011) and Provost and Vice President for Academic Affairs at Kean University and is continuing interdisciplinary research in drug discovery.
Professor Kian Tan graduated with a B.S. in chemistry with a specialization in biochemistry from the University of Virginia in 1999. At UVa, Kian performed research in the group of Professor Dean Harman working on the development of an osmium-mediated asymmetric Diels-Alder reactions and the synthesis of epibatidine derivatives as analgesics. Subsequently, Kian worked jointly with Professors Robert Bergman and Jonathan Ellman at the University of California Berkeley on novel metal-mediated C-H activation reactions. He obtained his Ph. D. from UC-Berkeley in 2004. Working as a postdoctoral researcher in Professor Eric Jacobsen’s group at Harvard University, Kian focused on bifunctional urea catalysts for the enantioselective allylation of hydrazones. In 2006, Kian began as an Assistant Professor at Boston College where he enjoys teaching organic chemistry and guiding a research program focused on the new catalysts for the transformation of organic molecules.
Ann M. Valentine
Professor Valentine earned her B.S. in Chemistry from the University of Virginia. She conducted undergraduate research with Timothy Macdonald on aluminum inhibition of magnesium-dependent enzymes. After graduating in 1993, she went to MIT to earn a Ph.D. with Steve Lippard. She then conducted her postdoctoral research at Penn State University and, in 2001, joined the Yale Departmet of Chemistry faculty. Her research explores the use of metals in nature and the development of potential titanium-based anticancer drugs. She has received numerous awards including the American Chemical Society PROGRESS/Dreyfus Lectureship Award in 2007 and the Paul D Saltman Award for Metals in Biology in 2009.
Erskine Williams was born and raised in Richmond, Va. He graduated from the University of Virginia in 1996 with degrees in Biochemistry & Cognitive Science. After graduating, he moved to Hood River, OR for two years to windsurf. In 1998, he moved to Portland, OR and started software engineering for Intel. From 2000 -2001, he rode the dot.com bubble with a small consulting firm in San Francisco. When the bubble popped, Erskine worked for Barclays Global Investors as a software engineer in San Francisco from 2001 – 2003. In 2003, he married and moved back to Portland working with Fujitsu Biosciences to write 3D molecular modeling software. Then, in late 2005, Erskine joined a company which brings social networking software to businesses.
Henry A. Boyter, Jr.
Henry Boyter Jr. is the Director of CESTAB (Center for Environmentally Sustainable Textile and Apparel Businesses). His research and industry service is directed at the application of green chemical techniques to textile processes. He is the past Chair of the AATCC RA100 Global Sustainability Technology Research Committee. He is a former member of the Peer Review Group for the American Apparel & Footwear Association (AAFA) Restricted Substances List Task Force and was a Joint Committee (JC) member developing a “Sustainability Assessment for Commercial Furnishings Fabric – NSF/ANSI 336 – 2011” under the Association for Contract Textiles (ACT) and NSF International and was Leader of the Water Group. He is currently involved with an industry task force under the direction of NTA to Update the VPEP form used by industry for chemical information exchange and is working on the Outdoor Industry Association’s (OIA) Eco-Index as a member of the Toxics Subgroup.He is the author of “Environmental Legislation USA” In Environmental Aspects of Textile Dyeing; Woodhead Publishing Limited.
John M. Butler
John M. Butler is NIST Fellow and Group Leader of Applied Genetics at the National Institute of Standards and Technology. He is author of the internationally acclaimed textbook Forensic DNA Typing—now in its third edition—as well as more than 100 scientific articles and invited book chapters. His book was also been translated into Chinese (2007) and Japanese (2009). He earned his Ph.D in 1995 from the University of Virginia with Ralph Allen (Analytical Chemistry). His Ph.D. research was conducted in the FBI Laboratory, involved pioneering the techniques now used worldwide in modern forensic DNA testing. Over the past 15 years, Dr. Butler has worked in government and industry. He designed and maintains STRBase (http://www.cstl.nist.gov/biotech/strbase), an information resource for short tandem repeat DNA markers. As a member of the World Trade Center Kinship and Data Analysis Panel, he aided the New York City Office of Chief Medical Examiner in their work to identify the remains of victims of the 9/11 terrorist attacks. He also serves on the Department of Defense Quality Assurance Oversight Committee for DNA Analysis and advises numerous national and international forensic DNA efforts. Dr. Butler has received numerous awards during his career including the Presidential Early Career Award for Scientists and Engineers (2002), the Department of Commerce Gold Medal (2008) and Silver Medal (2002), the Arthur S. Flemming Award (2007), Brigham Young University’s College of Physical and Mathematical Sciences Honored Alumnus (2005), and the Scientific Prize of the International Society of Forensic Genetics (2003). In August 2011, ScienceWatch.com announced that Dr. Butler was number one in the world as a high-impact author (number of citations per paper published) in legal medicine and forensic science for the decade of 2001-2011.
Christopher D. Claeboe
After earning his Ph.D. with Sidney Hecht at the University of Virginia in 2003, Dr. Christopher Claeboe joined the laboratory of David R. Williams at Indiana University for a post-doctoral fellowship that was focused upon the total synthesis of Peloruside A. In 2005, Dr. Claeboe began his industrial career as a process chemist with Albemarle Corporation, working at their Baton Rouge, LA facility. He then transferred to their South Haven, MI facility in 2008 where he currently resides. While responsible for the completion of a variety of interesting side projects for the company including the pursuit of his MBA through Indiana University, his work is centered upon the process development and scale-up of custom active pharmaceutical ingredients ().
Dr. Frazier graduated from Harvey Mudd College with a B.S. in Applied Chemistry. In 2003, she earned her Ph.D. from the University of Virginia Chemistry Department with Prof. David Cafiso. She works at Pro-Cure Therapeutics (a Prostate Cancer Stem Cell Company) where she performs two roles. She is the Commercial Operations Manager and a research scientist. She manages business relationships with corporate partners and tests and develops assays for novel prostate cancer stem cells.
Benjamin A. Garcia
Professor Garcia received his B.S. degree from the University of California, Davis and then went on to earn his Ph.D. from the University of Virginia under Donald Hunt in 2005. Ben then was an NIH NRSA Postdoctoral Fellow at the Institute for Genomic Biology at the University of Illinois, Urbana-Champaign with Professor Neil Kelleher. Currently, he is an Assistant Professor of Molecular Biology and Chemistry, and a member of the Quantitative and Computational Biology program at Princeton University where he has received a 2010 NIH Director’s New Innovator award.
Dr. McWhorter earned a Ph.D. in Chemistry (with Brooks H. Pate) from the University of Virginia and a B.S. in Chemistry from Washington and Lee University. As a Principal of Catalyst Partners, work focuses on helping clients navigate US Department of Homeland Security’ (DHS; especially the SAFETY Act) and helping DHS navigate his clients. Dr. David McWhorter spent over seven years at the Institute for Defense Analyses (IDA), a Federally Funded Research and Development Center (FFRDC). Most recently he served as the deputy project leader for IDA on the DHS SAFETY Act (the Support Anti-terrorism by Fostering Effective Technologies Act of 2002). In this position he led the technical evaluations of anti-terrorism products and services across a broad spectrum of countermeasures for chemical, biological, explosive, nuclear, cyber and human threats, including services. He was also instrumental in the implementation of the SAFETY Act including orchestrating the creation of the evaluation process, the drafting of the application kits, and the coordination of several government procurements, and the identification of Subject Matter Experts (SMEs). In 2007, Dr. McWhorter became a member of the US Chamber of Commerce’s SAFETY Act committee, and in 2008 he was appointed to the Executive Board of NDIA’s Homeland Security Division.
Seth W. Snyder
Seth W. Snyder, Ph.D. received a B.A. from University of Pennsylvania in Chemistry and Environmental Studies (1980), a M.S. in Physical Chemistry (1985) and a Ph.D. in Biophysics (1989) from the University of Virginia in James Demas‘ laboratory. He completed a postdoctoral fellowship at Argonne National Laboratory in Photosynthesis. In 1989, he joined Abbott Laboratories, first in Alzheimer’s Disease Research and later in Pharmaceutical Discovery Research. In 1998, Seth rejoined Argonne as the Associate Director of the Chemistry Division where he developed new programs in nanoscience and applied biotechnology. In 2001, he joined the Energy Systems Division as the Section Leader of Chemical and Biological Technology and now Process Technology Research. His team develops new process technologies ranging from tree growth through conversion technologies and product separations. The goal is to improve energy efficiency in production of biofuels and biobased products, CO2 capture, and water treatment. In other technology areas, his team works on plastic recycling, PV materials, geothermal energy, and now battery materials.
He serves as the President of the Council for Chemical Research and as Argonne’s Lab Relationship Manager for the DOE Office of the Biomass Program. He is on the advisory board for several academic centers including: the University of Illinois Urbana-Champaign’s “Center for Advanced Bioenergy Research”, South Dakota’s “Center for Bioprocessing Research”, and the NSF “Center for Bioenergy R&D”. He has published about fifty papers, has twelve patents (issued and pending), has presented or co-authored his research at 75 conferences over the past nine years. He has received three R&D 100 awards and an Outstanding Mentor Award from the DOE FAST Program.
Professor Shipman received his B.A. from Rice University and earned his Ph.D. from the University of California-Berkeley under Charles Harris in 2005. He was then a post-doctoral researcher from 2006 until 2008 at the University of Virginia with Professor Brooks Pate. He is currently an Assistant Professor of Physical Chemistry at New College of Florida, a small liberal arts college in Sarasota, FL. His research is concerned with the study of the rotational spectra of molecules in vibrationally-excited states at room temperature.
Scott C. Bailey-Hartsel
Professor Scott C. Bailey-Hartsel received his B.S. degree from Ohio University and then went on to earn his Ph.D. from the Ohio State University in 1985. He worked as an American Heart Association postdoctoral fellow under David Cafiso from 1985-1987 at UVa and was an NSF/CNRS research fellow at Universite Pierre et Marie Curie and Institut Curie in Paris in 1995 and 96. Scott is currently Professor and immediate past Chair of Chemistry at the University of Wisconsin-Eau Claire, a member of the ACS Committee on Professional Training (CPT) and was a past member of the Council on Undergraduate Research (CUR). He has received over $1,000,000 of external research funding in drug delivery and peptide research and has published numerous research articles with over 35 different undergraduate co-authors. He was named CASE Professor of the Year for the State of Wisconsin in 2001.
Professor Zhou received his B.S.and Ph.D degrees from Fudan University in 1990 and 1995, respectively. He was a postdoctoral fellow at the University of Virginia with professor Lester Andrews from 1997 to 1999. He then joined the chemistry department of Fudan University and became a professor of physical chemistry in 2000 and Cheung Kong Scholar in 2002. He is currently a member of the editorial advisory board of the Journal of Physical Chemistry.
Mi Wha Jin
Bradley McKeown, Ph.D.
Brandon Thompson, Ph.D.
Jeff Myers, Ph.D.
Robert J. Gilliard, Jr.
Synthetic Chemistry: Main-Group and Organometallic Chemistry, Bond Activation and Catalysis, Hybrid Materials
The Gilliard Research Laboratory focuses its efforts on the synthesis, structure, reactivity and applications of main-group and late transition metal species. We develop novel synthetic methods to access molecules that are relevant to a wide range of energy-related problems. In many cases, the compounds of interest contain reactive or unstable components (e.g., radicals, hydrides, multiple bonds, etc.). Accordingly, we utilize various anaerobic synthetic procedures including Schlenk techniques and inert atmosphere gloveboxes.
Current research themes under investigation include:
Bond Activation and Catalysis Mediated by Main-Group Elements - we are targeting catalysts and catalyst precursors which activate relatively inert chemical bonds (e.g., C-H, N-H, Si-H), critically important processes for tackling our current energy problems. We are also concerned with the interaction of these compounds with important energy-related small molecules such as CO, CO2, and H2.
Hybrid Materials - we are developing novel hybrid inorganic-organic polymers which contain unconventional d- and p-block element components in their structure for advancements in organic light emitting diode (OLED) technologies and molecular electronics.
Heterocycles and Bioactive Organometallics - we are synthesizing novel conjugated heterocycles which contain heavier main-group elements, mimicking the structural features of bioactive transition metal species. The physio-chemistry of these new complexes will be explored for future applications in medicinal chemistry.
An Isolable Magnesium Diphosphaethynolate Complex. Gilliard Jr., Robert J.; Heift, Dominikus; Benkő, Zoltán; Kieser, Jerod M.; Rheingold, Arnold; Grützmacher, Hansjörg; Protasiewicz, John D. Dalton Trans. 2018, DOI: 10.1039/C7DT04539E.
Synthesis of P2C2O2 and P2CO via NHC-Mediated Coupling of the Phosphaethynolate Anion. Gilliard Jr., Robert J.; Suter, Riccardo; Schrader, Erik; Benkő, Zoltán, Rheingold, Arnold; Grützmacher, Hansjörg; Protasiewicz, John D. Chem. Commun. 2017, DOI:10.1039/C7CC07654A.
Insertion of Sodium Phosphaethynolate, Na[OCP], into a Zirconium-Benzyne Complex. Kieser, Jerod M.; Gilliard Jr., Robert J.; Rheingold, Arnold; Grützmacher, Hansjörg, Protasiewicz, John D.; Chem. Commun. 2017, 53, 5110-5112.
From the Parent Phosphinidene-Carbene Adduct NHC=PH to Cationic P4-Rings and P2-Cycloaddition Products. Beil, Andreas; Gilliard Jr., Robert J.; Grützmacher, Hansjörg Dalton Trans. 2016, 45, 2044-2052.
Oxidation of Carbene-Stabilized Diarsenic: Diarsene Dications and Diarsenic Radical Cations. Abraham, Mariham Y.; Wang, Yuzhong; Yaoming, Xie; Gilliard Jr., Robert J.; Wei, Pingrong; Vaccaro, Brian J.; Johnson, Michael K.; Schaefer III, Henry F.; Schleyer, Paul v. R.; Robinson, Gregory H. J. Am. Chem. Soc. 2013, 135, 2486-2488.
Carbene-Stabilized Beryllium Borohydride. Gilliard Jr., Robert J.; Abraham, Mariham Y.; Wang, Yuzhong; Wei, Pingrong; Yaoming, Xie; Quillian, Brandon; Schaefer III, Henry F.; Schleyer, Paul v. R.; Robinson, Gregory H. J. Am. Chem. Soc. 2012, 134, 9953-9955. This manuscript was featured as a JACS Spotlight Article: J. Am. Chem. Soc. 2012, 134, 11299-11300.
Alicia J. Frantz
Alicia Frantz is an instructor for Organic Chemistry lecture. She earned a B.S. in Forensic Chemistry and a Ph.D. in Chemistry from Ohio University, Athens, Ohio. She is currently focusing on implementation of guided inquiry based learning in courses with large enrollment. Attending a large school herself, Alicia understands the importance for dedicating more of class time to group work and evidence-based techniques than the traditional lecturing. She is also updating her courses to reflect the growing diversity seen in the classroom, especially nontraditional and first generation students.
Alicia has taught general chemistry and organic chemistry at the University of Rio Grande and Kalamazoo College. She also spent a year as a medicinal chemistry intern at GlaxoSmithKline (GSK) in Research Triangle Park, North Carolina, synthesizing novel compounds in an effort to combat HIV/AIDS.
Changcheng Jiang, Ph.D.
Boobalan received his Master’s Degree in Chemistry from Virginia Tech, and his Ph.D. in Medicinal Chemistry from the University of Illinois at Chicago. He is a trained medicinal chemist whose research interests lie on the interface of computer-assisted drug design methods and organic synthesis. During his research years, he worked in several therapeutic areas, including Alzheimer's, oncology, infection (antibacterial and antimalarial) and epilepsy. Boobalan published his findings in 13 peer-reviewed journals. Owing to his contributions to the field of medicinal chemistry, the American Chemical Society bestowed upon him the highly prestigious Robert M. Scarborough Post-Graduate Excellence award in Medicinal Chemistry.
In the Hsu lab, Boobalan will be engaged in activities involving synthesis of all activity-based probes and small molecular inhibitors.