Carnegie Mellon University Department of Chemistry

About the Department

Abstracts for Seminars — Spring 2017

Thursday, January 19, 2017

Matthew Becker, The University of Akron

Functional Polymers that Enable Post Printing Derivatization of 3D Scaffolds with Bioactive Groups

Abstract

Efforts in additive manufacturing are focused on designing patient specific solutions for tissue repair. Key to the design elements are materials that stimulate specific cellular responses at the molecular level and degrade at the rate in which the tissue is repaired. These efforts are hindered by a lack of resorbable polymer resins that are bioactive and can be designed to degrade under well defined conditions. While synthetic advances have yielded polymers designed to elicit specific cellular functions and to direct cell-cell interactions, further advances in both synthetic methodology and scaffold fabrication are needed to drive these efforts forward. Many strategies have involved doping polymers with proteins or peptides or decorating the substrates with covalently tethered peptides that mimic the extracellular matrix or growth factors. While these approached have been demonstrated to aid the biochemical signaling and integration into host tissues, they generally reduce the mechanical properties of the material. This presentation will describe the use of several translationally relevant functionalization strategies for 3D printed scaffolds.

Biography

Matthew L Becker is the W. Gerald Austen Professor of Polymer Science and Polymer Engineering at The University of Akron. He holds appointments in the Departments of Polymer Science and Biomedical Engineering. He completed his PhD in organic chemistry in 2003 at Washington University in St. Louis under the direction of Professor Karen L Wooley as an NIH Chemistry-Biology Interface Training Fellow. In 2003, Dr Becker moved to the Polymers Division of the National Institute of Standards and Technology for a NRC Postdoctoral Fellowship in biophysics. He joined the permanent staff in 2005 and led projects in bioimaging and combinatorial methods for tissue engineering. Professor Becker joined the University of Akron in 2009 and to date, his multidisciplinary research group has published more than 100 papers and has 25 patents pending focus on translationally relevant chemical strategies for functionalizing degradable polymers with bioactive groups. He is the founder of two start-up companies, 3D Bioresins & 3D Bioactives. In 2015, Professor Becker was one of two scientists worldwide under 40 named Macromolecules-Biomacromolecules Young Investigators.

Tuesday, January 24, 2017

Karla Arias, Crowell and Moring

Patents from the Chemist’s Perspective

Abstract

A discussion on how to protect chemical inventions and how to journey into the field of patents.

Biography

Karla is a patent agent in the Intellectual Property Group in Crowell & Moring's Washington D.C. office. Karla focuses on patent prosecution and provides technical analysis in the fields of organic chemistry and pharmaceutics, in support of patent counseling, opinion work and litigation for the pharmaceutical industry.

Prior to joining Crowell & Moring, Karla worked as a Swiss National Science Foundation postdoctoral fellow at Carnegie Mellon University, investigating the degradation of endocrine-disrupting contaminants in water and the formation and reactivity of iron complexes.

She received her doctorate from the University of Zurich, where her research focused on the synthesis of supramolecular architectures and the study of fluorescent and phosphorescent properties of supramolecular building blocks. In addition, Karla holds a M.Sc. in organic chemistry from the University of Zurich and a B.S. in chemistry from the University of California, San Diego.

Karla is registered to practice before the United States Patent and Trademark Office (USPTO).

Thursday, January 26, 2017

Brian K. Long, University of Tennessee

Utilizing Coordination-Insertion Based Polymerizations for the Synthesis of Tailored Polyolefins and Gas Separation Membranes

Abstract

Coordination-insertion based polymerization methods provide a multitude of opportunities for enhanced control over catalytic activity, selectivity, and reactivity. Through tailored catalyst development and macromolecular design, the Long Research Group leverages these advantages to synthesize unique and/or tailored polymeric structures for a variety of applications. In this talk, we will demonstrate the potential power of these coordination-insertion based polymerization methods through two studies. First, we will provide fundamental evidence that redox-active olefin polymerization catalysts can be effectively used to modulate polyolefin microstructure and copolymer composition via simple in situ changes in a catalyst's oxidation-state. Second, we will demonstrate that careful catalyst selection can enable access to a unique class of polymers that was previously believed to be inaccessible, and that those materials are extremely attractive as highly efficient gas separation membranes.

Biography

Brian studied chemistry as an undergraduate at North Georgia College & State University and as an REU student at Furman University. After completion of his B.S. degree in 2003, Brian attended the University of Texas at Austin for his doctoral studies with Professors C. Grant Willson and Christopher W. Bielawski. After graduating in 2009, he moved to Ithaca, NY to begin his postdoctoral studies at Cornell University under the supervision of Professor Geoffrey W. Coates. Brian has since returned to the southeast and is currently an assistant professor of chemistry at the University of Tennessee. Brian received an Army Research Office Young Investigator Award in 2013 and received the Ffrancon Williams Endowed Faculty Award in 2015 and 2016. Brian's current research interests include the synthesis of tailored polymers, design of advanced polymerization catalysts, and development of next-generation gas separation membranes.

Tuesday, January 31, 2017

Arsalan Mirjafari, Florida Gulf Coast University

Biomimetic Development of Amphiphilic Ionic Liquids with Enhanced Fluidity and Diverse Functionalities

Abstract

Over the past decade, there has been a phenomenal rise in activity in the field of ionic liquids as measured by many metrics, including publication rates and the introduction of both ionic liquids as commercial products and commercialized ionic liquids-enabled processes. And, like any field, that of ionic liquids is constantly evolving, with new concepts and applications continuously emerging. Among the areas of rapidly increasing interest and importance is the use of highly hydrophobic ionic liquids containing functionalities. However, lack of accurate structure-properties relationships studies represent a major obstacle to the synthesis/preparation functionalized ionic liquids with precisely engineered structures and properties for specific needs.

We focused on the purposeful development of novel classes of amphiphilic ionic liquids with profoundly lower melting points (more fluid) and outstanding oxidative stability as such. “Click” chemistry-mediated strategies will be utilized to incorporate a diverse array of functionalities into the structures of ionic liquids. Due to the highly amphiphilic character and low-melting nature of the synthesized ionic liquids, they are desirable for a wide range of applications from liquid crystals to gene delivery.

Tuesday, February 7, 2017

Genevieve Sauve, Case Western Reserve University

Alternative Molecular Acceptors for Bulk Heterojunction Organic Solar Cells

Abstract

Organic photovoltaics (OPVs) are promising candidates for providing a low cost, widespread energy source by converting sunlight into electricity. Solution-processable active layers have predominantly consisted of a conjugated polymer donor blended with a fullerene derivative as the acceptor. Although fullerene derivatives have been the dominant electron acceptors in organic photovoltaics, they have limitations, including poor absorption in the visible to near-IR and limited tuning of the energy levels. There is strong interest in discovering new electron acceptors that may overcome these limitations. Here, we present our work in developing non-fullerene acceptors based on 2,6-dialkylamino core-substituted naphthalene diimides (cNDI) and azadipyrromethenes (ADP). Based on our results and those in the literature, we hypothesize that non-fullerene acceptors should be large conjugated systems that are nonplanar to promote nanoscale phase separation, charge separation and charge transport in blend films with conjugated polymer donors.

Thursday, February 9, 2017

Brian V. Popp, West Virginia University

Mild Strategies for Catalytic Olefin Carboxylation

Abstract

Carbon dioxide is an attractive C1 synthon in chemical synthesis due to its abundance, availability, non-toxicity, and inherent renewability. However, it has been undervalued and underutilized for the synthetic installation of carboxyl functionality because of its unreactive nature, owing to its inherent thermodynamic stability and kinetic inertness. Given the frequency and utility of carboxylic acids in all areas of chemistry and biology, there is a need for and high potential value in mild, functional group tolerant, atom-economical approaches to the installation of CO2 in organic molecules. This seminar will discuss our recent synthetic and mechanistic work on olefin hydro- and hetero(element)-carboxylation.

Thursday, February 16, 2017

Dennis Bong, The Ohio State University

Bifacial Peptide and Polymer Nucleic Acid: Functional Integration of Abiotic Molecules with DNA and RNA

Abstract

We have recently reported the synthesis of bifacial peptide nucleic acid (bPNA), a peptide that uses aminotriazine heterocycles to interface with oligo T/U domains. Triazines readily form from prebiotic reaction conditions, raising the intriguing possibility of their role as informational precursors to the native bases. Bifacial PNA engages two oligo T/U strands simultaneously to form a unique triple stranded structure. Thus, bifacial PNA binding is an associative operation, bringing together non-interacting poly-T/U strands to form a bPNA triplex hybrid. We demonstrate functional compatibility of bPNA with functional non-coding DNA and RNA scaffolds by the use of bPNA as an allosteric trigger of aptamer protein-binding, ribozyme catalytic self-cleavage and aptamer small-molecule binding. The biotechnological applications of bPNA and related scaffolds in nucleic delivery and biosensing will be discussed.

Thursday, February 23, 2017

Severin Schneebeli, University of Vermont

En-route to Shape-defined Precision Polymers

Abstract

Precise sequence and shape control of macromolecules, which functions under a variety of experimental conditions — e.g. different solvents and temperatures — is important for selective molecular recognition, self-assembly, and catalysis. I will therefore discuss our recent advances toward this fundamental goal in synthetic organic/polymer chemistry. Inspired by chirality-assisted synthesis (CAS) at the example of Pd-catalyzed aminations (see also: Liu, X.; Weinert, Z. J.; Sharafi, M.; Liao, C.; Li, J.; Schneebeli, S. T. Angew. Chem. Int. Ed. 2015, 54, 12772–12776), methods for universal shape control will be introduced. Next, I will demonstrate how large chiral strips, created efficiently with CAS, take part in allosteric, supramolecular regulation of synthetic receptors, hinting at new forms of catalyst control. Shape control can also be extended to three dimensions with molecular strips, for instance to create molecular claws as well as single-handed, freeform molecular spirals. The utility of such structures for chiral catalysis will be discussed, followed by concluding remarks on how universal shape-control can be achieved with sequence-controlled macromolecules, built with exponential amplification schemes.

Thursday, March 2, 2017

Mark Bathe, MIT

Programming and Probing Biomolecular Machines

Abstract

Nucleic acids offer a high degree of programmability that enables the rational design and synthesis of structured three-dimensional molecular architectures that mimic aspects of highly evolved, natural protein assemblies, as well as the interrogation of messenger RNA and protein structure and dynamics in living systems using super-resolution fluorescence imaging. In the first part of my seminar I will present work in our group to enable the design [1, 2, 3] and synthesis [3] of structured nucleic acid assemblies to engineer synthetic viral capsid mimics [3] for high-resolution imaging, metallic nanoparticle synthesis [4], and therapeutic delivery. In the second part of my seminar I will present the application of nucleic acids to the super-resolution fluorescence imaging of neuronal messenger RNA transport and translation dynamics [5, 6], as well as the characterization of neuronal synapse structure using an approach that overcomes the four-color spectral limit of conventional fluorescence imaging [7]. Together, these examples will illustrate the application of synthetic nucleic acids and fluorescence imaging to program and probe complex biomolecular machines.

References
  1. Castro, C.E., Kilchherr, F., Kim, D.N., Lin Shiao, E., Wauer, T., Wortmann, P., Bathe, M., Dietz, H. A primer to scaffolded DNA origami. Nature Methods, 8: 221 (2011).
  2. Lattice-free prediction of three-dimensional structure of programmed DNA assemblies. Pan, K., Kim, D.N., Zhang, F., Adendorff, M., Yan, H., Bathe, M. Nature Communications, 5: 5578 (2014).
  3. Designer nanoscale DNA assemblies programmed from the top down. Veneziano, R., Ratanalert, S., Zhang, K., Pan, K., Zhang, F., Yan, H., Chiu, W., Bathe, M. Science, 352: 1534 (2016).
  4. Casting inorganic structures with DNA molds. Sun, W., Boulais, E., Hakobyan, Y., Wang, W., Guan, A., Bathe, M., Yin, P. Science, 346: 717 (2014).
  5. Inferring transient particle transport dynamics in live cells. Monnier, N., Barry, Z., Park, H.Y., Su, K.C., Katz, Z., English, B., Dey, A., Pan, K., Cheeseman, I., Singer, R., Bathe, M. Nature Methods, 12: 838 (2015).
  6. Mapping translation in live cells by tracking single molecules of mRNA and ribosomes. Katz, Z.B., English, B.P., Lionnet, T., Yoon, Y.J., Monnier, N., Ovryn, B., Bathe, M., Singer, R.H. eLife, e10415 (2016).
  7. Multiplexed super-resolution neuronal synapse imaging using probe exchange. Guo, S.M., Gordonov, S., Veneziano, R., Kulesa, T., Park, D., Blainey, P., Boyden, E., Bathe, M. In preparation (2017).

Thursday, March 9, 2017

Amanda C. Bryant-Friedrich, University of Toledo

Elucidation of the Nucleic Acid-Derived Endogenous Exposome

Abstract

The Center for Disease Control and Prevention defines the exposome as “the measure of all the exposures of an individual in a lifetime and how those exposures relate to health”. Exposure in this context and from the perspective of toxicology, generally and chemical toxicology, specifically are the chemical entities found in our environment. This environment is both external (diet, lifestyle, medical interventions, etc.) as well as internal (oxidative stress, metabolism, etc.). These exposures span the lifetime of the individual, from conception to death. The identity of these chemical entities is only one part of a larger equation. The interaction of our life long exposures with our unique characteristics (genetics, physiology, epigenetics, etc.) determine health outcomes. Contributors to the unique constituents of an individual exposome are characterized by many factors, which have been divided into four general categories. These areas are the general external, specific external and internal. The focus of our laboratory is on the internal.

Among many things, the internal exposome is made up of chemical constituents which are the result of metabolism, inflammation, oxidative stress and the gut microflora, just to name a few. Common to many of these internal processes is the production of reactive species, in particular reactive oxygen species (ROS). The work to be presented will reveal our identification and study of chemical compounds which result from oxidative damage to nucleic acids. Using modified nucleic acids as precursors to intermediates that result from the reaction of ROS with nucleosides and nucleotides, we have determined the identity of several small reactive molecules which result from the degradation of nucleic acids via radical mechanisms.

Thursday, March 23, 2017

Katherine Seley-Radtke, University of Maryland, Baltimore County

Flex-Nucleosides — A Strategic Approach to Antiviral Therapeutics

Abstract

Replication is intrinsic to the lifecycle of all viruses, thus their survival relies on DNA or RNA polymerases. As a result, the polymerase is considered one of the most important targets for antiviral drug design. A highly effective strategy to target polymerases is through the use of nucleos(t)ide analogues. In an effort to explore flexibility as a design approach to increase polymerase recognition, as well as to develop a possible strategy against resistance mechanisms, a novel flexible nucleoside scaffold was designed in our laboratories. The “fleximers” as we named them, featured a "split” heterocyclic purine base that retained the requisite hydrogen bonding elements necessary for recognition, but allowed free rotation around a single carbon-carbon bond. This endows the nucleoside scaffold with the ability to adjust and adapt when encountering point mutations in enzyme binding sites. Various types of fleximer nucleosides have been designed, synthesized and investigated in our laboratories over the years. Many of the fleximers have shown promise as antiviral, anticancer and antiparasitic therapeutics. Most recently a new series of “doubly” flexible analogues was pursued, by combining our fleximer base modification with various modified sugars found in several FDA-approved antiviral nucleoside drugs, including the acyclic sugar found Acyclovir. This has led to potent biological activity against a number of viral targets, including MERS, SARS, Ebola, Sudan and other neglected viruses. The history and progress of some of these projects will be discussed.

Thursday, March 30, 2017

Yugang Sun, University of Wisconsin-Madison

How Pt Nanoparticles Behave in Photocatalytic HER?

Abstract

Platinum (Pt) nanocrystals are usually used in chemical reactions because of their excellent catalytic performance, for example, photocatalytic water splitting of water. In a typical design, Pt nanocrystals can accept photo-excited electrons from light absorbers such as semiconductor quantum dots (QDs) to catalyze hydrogen evolution reaction (HER) [1]. Charge transfer from QDs to Pt nanocrystals is very inefficient, and shuttle molecules (e.g., methylviologen) or other shuttle species are necessary to facilitate the charge transfer. In this presentation, a binary superparticles made of Pt nanocrystals and AgCl nanocrystals [2] will be discussed as a new class of Pt-based nanostructures that can directly accept photoexcited electrons from QDs without assistance of mediate molecules to efficiently catalyze HER with internal quantum yield of 8.6%. In addition to receiving electrons from semiconductor QDs, Pt nanocrystal can also absorb visible light to generate energetic electrons, which can inject to conduction band of a semiconductor to drive chemical reactions including HER. Depositing Pt nanocrystals on spherical SiO2 particles can significantly enhance visible absorption coefficient of the Pt nanocrystals due to the unique scattering modes near the SiO2 particles. In SiO2@Pt nanocrystals@TiO2 core-shell nanostructures, the enhancement in visible absorption enables the efficient generation of energetic electrons in photoexcited Pt nanocrystals, which can easily transfer to the TiO2 surface layer to drive HER and many other chemical reactions [3].

References
  1. Rasamani, K. D.; Li, Z.; Sun, Y. Nanoscale 2016, 8, 18621-18625.
  2. Hu, Y.; Liu, Y.; Sun, Y. Adv. Funct. Mater. 2015, 25, 1638-1647.
  3. Zhang, N.; Han, C.; Xu, Y.-J.; Foley, J. J., IV; Zhang, D.; Codrington, J.; Gray, S. K.; Sun, Y. Nat. Photon. 2016, 10, 473-482.

Biography

Dr. Yugang Sun obtained his B.S and Ph.D degree from University of Science and Technology of China (USTC) in 1996 and 2001, respectively. He then worked as a postdoctoral fellow with Prof. Younan Xia at University of Washington and Prof. John A. Rogers at University of Illinois at Urbana-Champaign. In 2006, Dr. Sun joined the Center for Nanoscale Materials at Argonne National Laboratory (ANL) to start his independent research career. He moved to Chemistry Department of Temple University in January 2016. He received the Presidential Early Career Award for Scientists and Engineers (PECASE) in 2007 and DOE’s Office of Science Early Career Scientist and Engineering Award in 2008. His work has significant impact the field of nanomaterials and he was listed in the top 100 chemists (#62) and top 100 Materials scientists (#5) analyzed by Thomson Reuters in 2011. His research is centered in the design/synthesis of hybrid nanostructures as well as investigation of novel properties of the synthesized nanostructures in the context of nanophotonics, photocatalysis, sensing, and energy storage/conversion.

Thursday, April 6, 2017

Rinku Jain, Icahn School of Medicine at Mount Sinai

Towards Small Molecule Therapeutics for Treating Zika Infections

Abstract

The Zika virus has emerged as a major health concern over the past year. Its rapid spread across the Americas and link to microcephaly in newborn infants has invigorated efforts to develop antivirals to curb infection in the event of an outbreak. To aid the design of zika specific antivirals, we have determined several high-resolution structures of enzymes central to the life cycle of the virus. We have used these structures to identify features that lend to structure-based antiviral drug discovery. Specifically, we have designed and characterized an analog of the zika RNA methyltransferase that has the potential to exhibit enhanced selectivity relative to the human methyltransferases.

Biography

Dr. Jain is a Structural Biologist working on biochemical and structural characterization of proteins involved in DNA replication and repair, with a long-term goal to develop drug-like molecules targeting oncogenic and viral proteins for treatments of infectious diseases and cancer. Dr. Jain received her Ph.D in Biophysics and Biochemistry from the Ohio State University, Columbus, Ohio and further pursued her Postdoctoral training in structural & chemical Biology in the laboratory of Dr. Aneel Aggarwal at Mount Sinai, New York. Dr. Jain recently solved the 3D structure of the NS3 helicase protein of Zika Virus which plays essential role in viral genome replication.

Thursday, April 20, 2017

Stephan Friderich, Lawrence Livermore Laboratory

Superconducting High-resolution X-ray Detectors for Chemical Analysis at the Synchrotron

Abstract

Solid state X-ray detectors with operating temperatures below 0.1K are being developed because they offer an order of magnitude higher energy resolution than conventional silicon or germanium detectors. These cryogenic detectors increase the sensitivity of soft X-ray analysis in cases where semiconductor detectors lack energy resolution and grating spectrometers lack detection efficiency. We have developed superconducting tunnel junctions (STJs) as high-resolution X-ray detectors for chemical analysis of dilute samples at the synchrotron. They have an energy resolution between ~2 and ~10 eV FWHM in the soft X-ray range, and can be operated at several 1000 counts/s per detector pixel. For synchrotron applications, we have also built refrigerators to operate these detectors at ~0.1K within ~2 cm of a sample inside the UHV endstation of a synchrotron beamline. This seminar will give an overview about STJ X-ray detector operation and performance at the synchrotron. For typical applications, we will discuss spectroscopy on transition metals in the active site of metalloproteins, and chemical changes of dopants in novel semiconductor materials during processing.

Thursday, April 27, 2017

Kathleen Farley, Pfizer

Impact on the Drug Design of Cyclic Peptides using NMR Spectroscopy

Abstract

Incorporation of favorable pharmaceutical properties is a prominent design feature of many successfully developed peptide based drugs. NMR spectroscopy is an essential tool in this process since it can be used to determine the intramolecular hydrogen bonding pattern as well as the secondary and tertiary structure of a small cyclic peptide. This talk will review some of the NMR techniques that we are currently using at Pfizer in the drug design of cyclic peptides.

Biography

Kathleen Farley is a Principal Scientist in the R&D division at Pfizer Inc with over 25 years of experience in the pharmaceutical industry. She has extensive experience in managing NMR facilities and currently provides NMR support for medicinal chemistry research. Kathleen has over 30 publications including a book chapter and two patents. Additionally, she has experience in optimizing lead compounds through fragment based NMR screening and in supporting library chemistry with HT-NMR. Her current research includes structural characterization of small molecules and peptides using residual dipolar coupling. She is a founding member and organizer of the Practical Applications of NMR in Industry Conference (PANIC) and has taught a 2D NMR class for the American Chemical Society for the last five years.