Kateri H. DuBay

Assistant Professor of Chemistry
Room 388C, Chemistry Building
434-243-2159

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-scale, 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.

Recent Publications

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).

. 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).

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Andreas Gahlmann

Assistant Professor of Chemistry and Molecular Physiology and Biological Physics
Room 129, Chemistry Building
434-924-3624

One key area in understanding bacterial cell biology is spatiotemporal phenomena: Wherewhen, 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 live 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.

Recent Publications

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 DimensionsA. 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 DiffractionA. 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 GuanineA. 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 ResolutionsA. Gahlmann, S.T. Park, and A.H. Zewail.  Phys. Chem. Chem. Phys., 2008, 10, 2894

Michael Hilinski

Assistant Professor of Chemistry
Room 288C, Chemistry Building
434-924-0159

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. molecular, synthetic, 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.

Recent Publications

Chemoselective Hydroxylation of Aliphatic sp3 C–H Bonds Using a Ketone Catalyst and Aqueous H2O2. C. J. Pierce, M. K. HilinskiOrg. Lett. 201416, 6504–6507.

Improving the Affinity of SL0101 for RSK Using Structure-Based Design. R. M. Mrozowski, R. Vemula, B. Wu, Q. Zhang, B. R. Schroeder, M. K. Hilinski, D. E. Clark, S. M. Hecht, G. A. O’Doherty, D. A. Lannigan, ACS Med. Chem. Lett. 20134, 175–179.

Insights into the Inhibition of the p90 Ribosomal S6 Kinase (RSK) by the Flavonol Glycoside SL0101 from the 1.5 Å Crystal Structure of the N-Terminal Doman of RSK2 with Bound Inhibitor. D. Utepbergenov, U. Derewenda, N. Olekhnovich, G. Szukalska, B. Banerjee, M. K. Hilinski, D. A. Lannigan, P. T. Stukenberg, Z. S. Derewenda, Biochemistry 201251, 6499–6510.

Analogues of the RSK Inhibitor SL0101: Optimization of In Vitro Biological Stability. M. K. Hilinski, R. M. Mrozowski, D. E. Clark, D. A. Lannigan, Bioorg. Med. Chem. Lett. 201222, 3244–3247.

Function-Oriented Synthesis: Biological Evaluation of Laulimalide Analogues Derived from a Last Step Cross Metathesis Diversification Strategy. S. L. Mooberry, M. K. Hilinski, E. A. Clark, P. A. Wender Mol. Pharmaceutics 20085, 829–838.

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Brooks H. Pate

William R. Kenan, Jr. Professor of Chemistry
Room 207B, Chemistry Building
434-243-0384

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 universitys 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.

Recent Publications

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).

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Lin Pu

Professor of Chemistry
Room 250, Chemistry Building
434-924-6953

Organic, Polymer and Organometallic Chemistry; Asymmetric Catalysis; Chiral Sensors; Optically Active materials

pu-spiderMulti-disciplinary research programs involving organic synthesis, polymer chemistry, dendrimers, organometalic chemistry, asymmetric catalysis, and molecular recognition are conducted in our laboratory. Our main interests focus on the design and synthesis of novel chiral molecules and macromolecules for applications in asymmetric catalysis, chiral sensors, polarized light emission and nonlinear optics.

We have chosen the derivatives of (R)- and (S)-1,1′-bi-2-naphthol (BINOL) to build novel main chain chiral conjugated polymers since these molecules have exhibited remarkably stable chiral configuration as well as high chiral induction in many asymmetric processes. We expect that incorporation of the optically active binaphthyls in the main chain of conjugated polymers may lead to efficient and stable chiral induction or chiral discrimination when these materials are used to carry out asymmetric electrosynthesis, polarized light emission and other applications. Efficient electroluminescent properties have been observed for these materials. Chiral conjugated nonlinear optical polymers are also synthesized and studied.

pu-structureWe 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. Using the chiral polymers has the advantage of easy recovery of the catalysts and simplified product purification. We have further synthesized optically active polymers that contain both BINOL and BINAP ligands. The BINOL ligands are used to make Lewis acid catalysts and the BINAP ligands are used to make late transition metal catalysts. Such novel multifunctional chiral catalysts have been used to catalyze tandem asymmetric reactions with high enantioselectivity as well as diastereoselectivity.

We have synthesized novel rigid and optically active dendrimers. Efficient energy migration from the cross-conjugated light harvesting dendrons to the chiral binaphthyl core has been observed. The fluorescence intensity of these dendrimers is dramatically increased over that of the small parent molecule BINOL. The greatly enhanced fluorescence of the dendrimers makes them more useful as fluorescent sensors than BINOL. We have discovered that the fluorescence of the dendrimers can be enantioselectively quenched by chiral amino alcohols. Thus, the dendrimers can serve as highly sensitive as well as enantioselective fluorescent sensors. Enantioselective hosts for the fluorescent detection of other chiral organic molecules such as a-hydroxycarboxylic acids have also been designed and synthesized. Further study of these materials aims at developing enantioselective fluorescent sensors for rapid determination of the enantiomeric composition of chiral compounds. One application of such sensors will be in the combinatorial search of chiral catalysts.

Recent Publications

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. 134:20282-5 (2012).

A novel near-infrared fluorescence imaging probe for in vivo neutrophil tracking. Xiao L, Zhang Y, Berr SS, Chordia MD, Pramoonjago P, Pu L, Pan D. Mol Imaging. 11:372-82 (2012).

Optical properties of solution-processable semiconducting TiOx thin films for solar cell and other applications. Li J, DeBerardinis AM, Pu L, Gupta MC. Appl Opt. 51:1131-6 (2012).

Characterization of novel synthesized small molecular compounds against non-small cell lung cancer. Zhao Y, Turlington M, LaPar DJ, Jones DR, Harris DA, Kron IL, Pu L, Lau CL. Ann Thorac Surg. 92:1031-7 (2011).

Enantioselective fluorescent sensors: a tale of BINOL. Pu L. Acc Chem Res. 45:150-63 (2012).

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Books

pu_book

B. Jill Venton

Professor of Chemistry
Room 108, Physical Life Sciences Building
434-243-2132

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 DrosophilaDrosophila larva. Current projects involve characterizing electrochemically-detected dopamine and serotonin release and comparing the control of neurotransmission in the fly to mammalian systems. larva is only 8 nL in volume! In collaboration with the Condron lab (UVa Biology), we have developed the first method to measure real-time changes in neurotransmitter concentrations in the CNS of a single

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. serotonin-dopamine-codetectionDifferent 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.

Recent Publications

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).

Fast scan cyclic voltammetry as a novel method for detection of real-time gonadotropin-releasing hormone release in mouse brain slices. Glanowska KM, Venton BJ, Moenter SM. J Neurosci. 32:14664-9 (2012).

Rapid, sensitive detection of neurotransmitters at microelectrodes modified with self-assembled SWCNT forests. Xiao N, Venton BJ. Anal Chem. 84:7816-22 (2012).

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