Seminars Archive

Fall 2019

New Frontiers in Cosmic Carbon

New Frontiers in Cosmic Carbon

Dr. Brett McGuire | National Radio Astronomy Observatory

Professor Ilse Cleeves

Abstract.

Molecular clouds of gas and dust pervade our galaxy, and are the birthplaces of stars and planets.  The temperature, density, and radiation conditions inside these clouds make them unique chemical laboratories for studying both fundamental reactions and the evolution of the molecular complexity that seeds primitive planets.  We have recently discovered a new regime of unexpected low-temperature aromatic chemistry in these sources that has far-reaching implications on the lifecycle of carbon in the universe.  These detections are demanding new analysis techniques to extract the maximum information content from increasingly large and complex datasets both observationally and in the laboratory.  Here, I will discuss novel applications of signal processing and analysis in both arenas.  Observationally, we are using Bayesian approaches combined with matched filtering techniques, while in the laboratory, we are conducting reaction screening analyses to try to understand the content and evolution of this new carbon chemistry in space.  I will describe the results of our new observational analysis techniques, as well as outline several new methods we have developed for rapidly screening complex chemical mixtures in the laboratory using pump-probe rotational spectroscopy in a (semi-)automated fashion to enable new molecular discovery.

Dr. Brett McGuire | National Radio Astronomy Observatory
Hosted by Professor Ilse Cleeves
Friday, November 22, 2019

Approaches to the Treatment of Alzheimer’s Disease: Two Targets; Two Modalities

Approaches to the Treatment of Alzheimer’s Disease: Two Targets; Two Modalities

Professor Richard Olson | Bristol-Myers Squibb

Professor Ken Hsu

ABSTRACT

Alzheimer’s disease remains a major unmet medical need representing a huge societal burden and a difficult event in the lives of patients and families. Current treatments do not offer hope for disease altering outcomes and recent attempts to bring forward new therapies have proven largely unsuccessful. This presentation will review two programs at Bristol-Myers Squibb spanning two therapeutic targets and two drug structural classes, or modalities: Small molecules and antisense oligonucleotides (ASOs). Efforts to improve the stereospecific synthesis of an important class of ASOs will be described.

Professor Richard Olson | Bristol-Myers Squibb
Hosted by Professor Ken Hsu
Friday, November 15, 2019

Main Group Lewis Acids for Applications in Catalysis and Anion Transport

Main Group Lewis Acids for Applications in Catalysis and Anion Transport

Professor François Gabbaï | Texas A & M University

Professor Robert Gilliard

ABSTRACT

Main group Lewis acids for applications in catalysis and anion transport

Research in the Gabbaï group has been dedicated to the synthesis and study of Lewis acidic main group compounds with the development of applications in molecular recognition and catalysis as the ultimate goals.  This seminar will highlight a series of recent results obtained in pursuit of these goals.  The first part of the presentation will focus on the chemistry of antimony- and carbon-based Z-type ligands and their demonstrated ability to modulate the catalytic reactivity of adjacent metal centers.  The second part of the presentation will show how boron and antimony-based Lewis acids can be deployed in aqueous media to effectively transport a range of anions across phospholipid bilayers in artificial vesicles as well as in live cells.

Professor François Gabbaï | Texas A & M University
Hosted by Professor Robert Gilliard
Friday, November 8, 2019

Proton-Coupled Electron Transfer by Copper-Oxygen Species Relevant to Enzyme Intermediates

Proton-Coupled Electron Transfer by Copper-Oxygen Species Relevant to Enzyme Intermediates

Professor William Tolman | Washington University in St. Louis

Professor Charlie Machan

Characterization of copper intermediates in enzymes and other catalysts that attack strong C-H bonds is important for unraveling oxidation catalysis mechanisms and, ultimately, designing new, more efficient catalytic systems. New insights into the nature of such intermediates may be obtained through the design, synthesis, and characterization of copper-oxygen complexes. Two key proposed examples contain [CuO2]+ and [CuOH]2+ cores, which have been suggested as possible reactive intermediates in monocopper enzymes such as lytic polysaccharide monooxygenase. Recent progress toward the characterization of the structures and properties of complexes with these cores that feature the same supporting ligand will be described, and detailed comparisons of their kinetics in reactions with C-H and O-H bonds will be discussed. Notable differences in their PCET reaction pathways with para-substituted phenols has been discovered that shed new light on the fundamental chemistry of these important core structures.

Professor William Tolman | Washington University in St. Louis
Hosted by Professor Charlie Machan
Friday, November 1, 2019

Chemical Biology and Chemistry for Translational Lipid Biology and Beyond

Chemical Biology and Chemistry for Translational Lipid Biology and Beyond

Professor Ken Hsu | UVA Department of Chemistry

Professor Linda Columbus

ABSTRACT

Lipids represent a rich model system for understanding how nature maintains cellular architecture (membrane building blocks), bioenergetics (energy stores), and communication (secondary messengers) through fine adjustments in enzyme metabolism. Embedded within lipid structures is chemical information that define their metabolic fate and function. Elucidating structure-function relationships of lipids in biological systems has been traditionally challenging because of the massive structural diversity of lipids in nature and lack of tools to selectively probe their function in vivo. I will describe efforts from my group to use chemical biology and mass spectrometry to gain fundamental insights into diacylglycerol (DAG) biology and the translational potential of modulating DAG pathways in inflammation and immuno-oncology.

Professor Ken Hsu | UVA Department of Chemistry
Hosted by Professor Linda Columbus
Friday, October 25, 2019

Magnesium(I) Dimers: Universal Reductants for the Synthetic/Catalytic Chemist?

Magnesium(I) Dimers: Universal Reductants for the Synthetic/Catalytic Chemist?

Professor Cameron Jones | Monash University: Director, Monash Centre for Catalysis

Professor Robert Gilliard

ABSTRACT

The renaissance that has occurred in main group chemistry over the last several decades has been largely driven by the realization that very low oxidation state p-block compounds can be stable species at ambient temperature, given the right ligand environment. Increasingly, such compounds are being shown to possess "transition metal-like" reactivity patterns in small molecule activations, and associated catalytic synthetic transformations.[1] In late 2007 we extended this field to the s-block with the preparation of the first room temperature stable molecular compounds containing magnesium-magnesium covalent bonds, viz. LMgMgL (L = bulky guanidinate or b-diketiminate, e.g. 1).[2] We have subsequently shown that the unique properties these species possess lend them to use as versatile reducing agents in both organic and inorganic synthetic protocols.[3] The products of such reactions are often inaccessible using more classical reducing agents. In this lecture an overview of what has been achieved with these remarkable reagents will be given, with an emphasis placed on the preparation of unprecedented examples of low oxidation state/low coordination number metal-metal bonded complexes involving metals from the s-, p- and d-blocks, e.g. 2-4.[4] The further chemistry of these highly reactive systems will also be discussed, as will our efforts to incorporate magnesium(I) dimers into catalytic cycles.[5]

 

REFERENCES

[1] Power, P. P. Nature 2010, 463, 171.

[2] Green, S. P.; Jones, C.; Stasch, A. Science 2007, 305, 1136.

[3] Jones, C. Nature Rev. Chem. 2017, 1, 0059.

[4] Bonyhady, S.J.; Collis, D.; Holzmann, N.; Edwards, A.J.; Piltz, R.O.; Frenking, G.; Stasch, A.; Jones, C. Nature Comm., 2018, 9, 3079.

[5] (a) Boutland, A. J.; Carroll, A.; Lamsfus, C. A.; Stasch, A.; Maron, L.; Jones, C. J. Am. Chem. Soc. 2017, 139, 18190; (b) Yuvaraj, K.; Douair, I.; Paparo, A.; Maron, L.; Jones, C. J. Am. Chem. Soc., 2019, 141, 8764.

Professor Cameron Jones | Monash University: Director, Monash Centre for Catalysis
Hosted by Professor Robert Gilliard
Wednesday, October 23, 2019

Annual Burger Lecture: Removing Organic Pollutants from Water Using Polymers Derived from Corn

Annual Burger Lecture: Removing Organic Pollutants from Water Using Polymers Derived from Corn

Dr. William Dichtel | Northwestern University

Professor Cassandra Fraser

Organic micropollutants, such as pesticides and pharmaceuticals, have raised concerns about negative effects on ecosystems and human health. These compounds are introduced into water resources by human activities, and current wastewater treatment processes do not remove them. Activated carbons are the most widespread adsorbents used to remove organic pollutants from water, but they have several deficiencies, including poor removal of relatively hydrophilic micropollutants, inferior performance in the presence of naturally occurring organic matter, and energy intensive regeneration processes. I will describe polymers based on β-cyclodextrin, an inexpensive, sustainably produced derivative of glucose, that binds these emerging contaminants from water. We also recently modified our original polymer design to target perfluorinated alkyl substances such as PFOA and PFOS, which are environmentally persistent and associated with negative effects at trace concentrations.

Figure: A porous polymer containing cyclodextrins (blue cups) binds organic pollutants from water.

 
Dr. William Dichtel | Northwestern University
Hosted by Professor Cassandra Fraser
Friday, October 18, 2019

Graham Lecture: Increasing Access to Global Healthcare through Process Intensification

Graham Lecture: Increasing Access to Global Healthcare through Process Intensification

Dr. Frank Gupton | Virginia Commonwealth University

Professor Brooks Pate

Abstract:   Access to global public healthcare is impacted by many technical, economic, and social factors. It is widely recognized that the resources required to deliver and improve global public health are currently constrained.  A powerful way to increase access is to lower the cost of products and services that have already proven to be effective.  Currently, the cost of producing a wide range of pharmaceutical products is higher than it needs to be. The mission of Medicines for All (M4All) is to transform active pharmaceutical ingredient (API) processes in order to reduce medication cost and improve patient access.  To fulfil this objective, M4ALL has developed a set of core principles for API process development, which are derived from fundamental elements of process intensification that are commonly known but often neglected. These principles have been applied to several global health drugs yielding dramatic improvements in chemical efficiency. The development of novel and highly efficient heterogeneous catalysts for cross-coupling reactions that support this effort will also be presented.

Dr. Frank Gupton | Virginia Commonwealth University
Hosted by Professor Brooks Pate
Thursday, October 10, 2019

The Unique Chemistry of Dying Stars: Organics, Metals, and Fullerenes

The Unique Chemistry of Dying Stars: Organics, Metals, and Fullerenes

Dr. Lucy Ziurys | University of Arizona

Professor Robin Garrod

ABSTRACT

The past 40 years of astrochemistry has showed that unusual molecules readily form in extreme interstellar environments. One of these interesting settings is the material lost from stars in their final stages. Here gas-phase material is ejected from the hot stellar photosphere, often at high velocities, and rapidly cools to create molecules and dust grains under competing thermodynamic and kinetic conditions. Using a combined program of high-resolution laboratory spectroscopy and astronomical observations, we have been investigating the chemistry of stellar ejecta. Measurements of rotational spectra of small, metal-bearing molecules using millimeter-wave and Fourier transform microwave methods have been conducted, such as simple oxides and dicarbides. Molecular-line observations have shown that some of these exotic species are present in circumstellar material, defying thermodynamic predictions, including such highly refractory molecules as VO and FeCN. At the very late stages of stellar evolution, the planetary nebula phase, a wide variety of carbon-containing molecules appear to be present, ranging from CCH and c-C3H2 to C60, despite the presence of very high ultraviolet radiation fields. The chemical formation of this wide variety of chemical compounds will be discussed, including a novel mechanism for fullerene production in circumstellar environments.

Dr. Lucy Ziurys | University of Arizona
Hosted by Professor Robin Garrod
Friday, October 4, 2019

Why does O-GlcNAc Transferase Matter?

Why does O-GlcNAc Transferase Matter?

Professor Suzanne Walker | Harvard University

Professor Ken Hsu

ABSTRACT

O-GlcNAc transferase (OGT) is essential for viability of all mammalian cells but no one knows why. OGT has two catalytic activities that take place in the same active site. In one, OGT attaches N-acetyl glucosamine to serine and threonine side chains of at least a thousand nuclear and cytoplasmic proteins. In the other, OGT cleaves a transcriptional co-activator involved in cell-cycle regulation. Because OGT is found in several stable protein-complexes, it is also proposed to act as a scaffolding protein. How do you dissect the cellular functions of an essential protein that has multiple biochemical activities and a thousand different substrates? I will argue that you need to start by understanding the chemistry –  mechanisms of catalysis and substrate recognition – so you can develop variants with some activities and not others. I will describe how we have done so and how we have used our knowledge to answer a fundamental question: What is the essential biochemical function of OGT for cell survival? I will also describe how we have developed and used a specific small molecule inhibitor of OGT to uncover an unexpected role in controlling RNA splicing.  

Professor Suzanne Walker | Harvard University
Hosted by Professor Ken Hsu
Friday, September 27, 2019

Ethylene Trimerization Using Chromium Pyridyl Amine Complexes: A Computational Study

Ethylene Trimerization Using Chromium Pyridyl Amine Complexes: A Computational Study

Professor Glen Alliger | ExxonMobil

Professor Charlie Machan

ABSTRACT

Selective trimerization of ethylene to produce 1-hexene is a commercially practiced process that yields valuable comonomer for linear low density polyethylene production. Several years ago, ExxonMobil chemists developed a family of chromium catalysts useful for ethylene trimerization, but a mechanistic understanding of the catalysis remained elusive. This talk presents a mechanistic proposal to explain the catalytic selectivity, supported by a computational exploration of proposed cycle. Results will be discussed in terms of geometric requirements for reaction and the fundamental steps involved in catalysis.

Professor Glen Alliger | ExxonMobil
Hosted by Professor Charlie Machan
Friday, September 20, 2019

Engineering Adaptive (bio) Materials from Functional Polymers and Peptide Stereocomplexes

Engineering Adaptive (bio) Materials from Functional Polymers and Peptide Stereocomplexes

Dr. Rachel Letteri | University of Virginia (Department of Chemical Engineering)

Professor Rebecca Pompano

ABSTRACT

Advancing highly tunable synthetic materials to operate in an increasingly cooperative fashion with biological systems and the environment provides a compelling opportunity to expand the repertoire and enhance the performance of critically needed technologies.  To this end, we are developing new building blocks for polymer biomaterials so as to access to a breadth of thermomechanical properties and promote productive interactions with biological systems.  The first part of this talk will describe our research on mirror image peptide complexes, or ‘stereocomplexes’, as tunable, transient junctions in synthetic polymer biomaterials.  Varying the primary structure of the peptides and solvent conditions were found to markedly impact the secondary structure, which in turn determined the macroscale properties of polymer-peptide conjugates.  These junctions are envisioned as molecular ‘VELCRO®’ strips and are anticipated to impart a myriad of adaptive properties, including self-healing and shear thinning, useful for 3D printing-based manufacturing processes and targeting biological proteins, among other applications.  Another approach to engineer adaptive materials involves controlling degradation rates, and the second part of this talk will describe the synthesis, thermomechanical characterization, and degradation profiles of poly(β-amino ester) networks.  By adjusting monomer composition, networks were obtained with degradation times scales that spanned hours to months.  Synthetically accessible and highly tunable, this polymer platform offers enormous opportunities, from sacrificial template materials for biomanufacturing to commodity materials that degrade after their useful lifetime.  Ultimately, by intertwining concepts from small molecule and peptide chemistry with polymer science and engineering, we aim to advance polymer and peptide building blocks, and thereby contribute to next generation materials and technologies for healthcare and beyond.

Dr. Rachel Letteri | University of Virginia (Department of Chemical Engineering)
Hosted by Professor Rebecca Pompano
Friday, September 13, 2019

SYNTHETIC COLLOQUIUM | Symmetry Making and Breaking in Seeded Growth of Metal Nanocrystals

SYNTHETIC COLLOQUIUM | Symmetry Making and Breaking in Seeded Growth of Metal Nanocrystals

Dr. Sara Skrabalak | Indiana University, Bloomington

Professor Sen Zhang

Crystal growth theory predicts that heterogeneous nucleation will occur preferentially at defect sites, such as the vertices rather than the faces of shape-controlled seeds. Platonic metal solids are generally assumed to have vertices with nearly identical chemical potentials, and also nearly identical faces, leading to the useful generality that heterogeneous nucleation preserves the symmetry of the original seeds in the final product. This presentation will discuss how this generality can be used to access stellated metal nanocrystals with high and tunable symmetries for applications in plasmonics. This presentation will also discuss the limits of this generality in the extreme of low supersaturation. A strategy for favoring localized deposition that differentiates between both different vertices and different edges or faces, i.e., regioselective deposition, will be demonstrated. Such regioselective heterogeneous nucleation was achieved at low supersaturation by a kinetic preference for high-energy defect-rich sites over lower-energy sites. This outcome was enhanced by using capping agents to passivate facet sites where deposition was not desired. Collectively, the results presented provide a model for breaking the symmetry of seeded growth and for achieving regioselective deposition.

Dr. Sara Skrabalak | Indiana University, Bloomington
Hosted by Professor Sen Zhang
Wednesday, September 11, 2019

Graphene-based Materials for Applications in Heterogeneous Catalysis, Water Treatment and Solar Water Desalination

Graphene-based Materials for Applications in Heterogeneous Catalysis, Water Treatment and Solar Water Desalination

Dr. Samy El Shall | Virginia Commonwealth University

Professor Eric Herbst

This talk will address the development of three classes of graphene-based materials as (1) support for metal nanoparticle catalysts in heterogeneous catalysis, (2) sorbent materials for the removal of heavy metal ions from polluted water, and (3) photothermal energy converter materials for efficient solar water desalination.

In heterogeneous catalysis, we will discuss the superior catalytic activity of Pd nanoparticles supported on reduced graphene oxide (RGO) nanosheets for carbon-carbon cross-coupling reactions. Second, the enhanced catalytic activity for the Fe-based nanoparticle catalysts supported on graphene in the Fischer-Tropsch Synthesis of liquid transportation fuels will be presented. Finally, the superior catalytic activity and selectivity of Pd nanoparticles supported on a sandwich-type nanocomposite consisting of Metal-Organic Frameworks (MOFs) wrapped with thin RGO nanosheets for the biomass-refining of liquids derived from lignocelluloisc sources will be presented.

For the removal of heavy metals from water, we will discuss the development of chemically modified graphene-based adsorbents containing highly efficient chelating groups such as diamine, imino and thiourea for the effective extraction of the toxic metal ions mercury (II), lead (II) and arsenic (V) from wastewater.

For photothermal energy conversion, we will discuss the development of a new generation of highly efficient, flexible, low weight, highly porous and cost effective Plasmonic Graphene Polyurethane (PGPU) nanocomposite materials for solar steam generation through the efficient evaporation of water surface pools. The PGPU nanocomposites contain metallic nanoparticles that exhibit very strong solar absorption. The polyurethane (PU) foam provides a hydrophilic surface with abundant microporous structure, excellent thermal insulation properties, and facile and scalable synthesis. The high solar thermal evaporation efficiency, excellent stability and long-time durability make the PGPU nanocomposites excellent candidates for solar-steam-generation applications and seawater desalination.

Dr. Samy El Shall | Virginia Commonwealth University
Hosted by Professor Eric Herbst
Friday, September 6, 2019

Escaping Flatland: Synthetic Innovation for the Future of Drug Discovery

Escaping Flatland: Synthetic Innovation for the Future of Drug Discovery

Professor Mike Hilinski | Department of Chemistry Kickoff Seminar

ABSTRACT

The majority of FDA-approved drugs are small organic molecules, generally defined as having a molecular weight below 900 g/mol. The speed and reliability with which one can synthesize complex bioactive small molecules is a major limiting factor in the race to discover new drugs. As a consequence of this, a historical overreliance on a small number of highly robust synthetic methods has limited the diversity of chemical structures generally pursued as drug leads. A long-term goal of our research program is to develop new synthetic methods that fill significant current gaps in the organic chemist’s toolbox, in order to work towards eliminating synthetic considerations as a barrier to the discovery of new therapeutics. Two major areas of research will be presented: (1) The development of new strategies and new modes of catalysis for the direct, site-selective functionalization of C–H bonds, and (2) The development of new methods for the synthesis and selective modification of nitrogen-containing heterocycles, which are present in the majority of FDA-approved small molecule drugs.

Professor Mike Hilinski | Department of Chemistry Kickoff Seminar
Friday, August 30, 2019

Spring 2019

Energy Conversion and Storage: Novel Materials and Operando Methods

Energy Conversion and Storage: Novel Materials and Operando Methods

Professor Héctor D. Abruña | Cornell University

Professor Sen Zhang
Professor Héctor D. Abruña | Cornell University
Hosted by Professor Sen Zhang
Friday, April 19, 2019

Two-Dimensional Carbides and Nitrides (MXenes) Challenge Graphene (Location: Monroe Hall Rm 110)

Two-Dimensional Carbides and Nitrides (MXenes) Challenge Graphene (Location: Monroe Hall Rm 110)

Dr. Yury Gogotsi | Drexel University

Professor Sen Zhang

ABSTRACT

Two-dimensional (2D) materials with a thickness of a few nanometers or less can be used as single sheets, or as building blocks, due to their unique properties and ability to assemble into a variety of structures. Graphene is the best-known example, but several other elemental 2D materials (silicene, borophene, etc.) have been discovered. Numerous compounds, ranging from clays to boron nitride (BN) and transition metal dichalcogenides, have been produced as 2D sheets. By combining various 2D materials, unique combinations of properties can be achieved which are not available in any bulk material. The family of 2D transition metal carbides and nitrides (MXenes) has been expanding rapidly since the discovery of Ti3C2 in 2011 [1]. Approximately 30 different MXenes have been synthesized, and the structure and properties of numerous other MXenes have been predicted using density functional theory (DFT) calculations [2]. Moreover, the availability of solid solutions on M and X sites, control of surface terminations, and the discovery of ordered double-M MXenes (e.g., Mo2TiC2) offer the potential for synthesis of dozens of new distinct structures.

This presentation will describe the synthesis of MXenes by selective etching of layered ceramic precursors, including various MAX phases. Delamination into single-layer 2D flakes and assembly into films and 3D structures, as well as their properties will be discussed. Synthesis-Structure-Properties relations of MXenes will be addressed on the example of Ti3C2.

The versatile chemistry of the MXene family renders their properties tunable for a large variety of applications [3]. Oxygen or hydroxyl- terminated Menes, such as Ti3C2O2, have been shown to have redox capable transition metals layers on the surface and offer a combination of high electronic conductivity with hydrophilicity, as well as fast ionic transport [4].  This, among many other advantageous properties, makes the material family promising candidates for energy storage and related electrochemical applications [5], but applications in plasmonics, electrocatalysis, biosensors, water purification/ desalination and other fields are equally exciting. In particular, capacitive deionization and membrane desalination and purification will be addressed.

 

Dr. Yury Gogotsi | Drexel University
Hosted by Professor Sen Zhang
Wednesday, April 17, 2019

Understanding Cardiac Calcium Signaling from Molecules to Systems

Understanding Cardiac Calcium Signaling from Molecules to Systems

Professor Peter Kekenes-Huskey | University of Kentucky

Professor Kateri DuBay

Abstract.

Calcium is critical to a wide range of physiological processes, including neurological function, immune responses, and muscle contraction in the heart. Calcium-dependent signaling pathways driving these functions enlist a variety of proteins and channels that must rapidly and selectively bind calcium against thousand-fold higher cation concentrations. Frequently these pathways further rely on co-localization of these proteins within specialized subcellular structures to function properly. Our lab has developed multi-scale simulation tools to understand calcium homeostasis and its dysregulation at the molecular through systems levels. Applications include molecular simulations to predict protein-protein interactions, reaction-diffusion simulations that leverage high-resolution microscopy data and computer vision techniques to characterize morphological differences in cells important to their function. In this seminar, I will describe these tools and their applications to a calcium-dependent signaling pathway driven by calmodulin and calcineurin activation, which is important in cardiac development and hypertrophy.

Professor Peter Kekenes-Huskey | University of Kentucky
Hosted by Professor Kateri DuBay
Friday, April 5, 2019

Hecht Lecture: Redesign of Vancomycin for Resistant Bacteria

Hecht Lecture: Redesign of Vancomycin for Resistant Bacteria

Professor Dale Boger | Scripps Research Institute; La Jolla, CA

Professor Sid Hecht

ABSTRACT

A summary of studies on the total synthesis and evaluation of the vancomycin family of glycopeptide antibiotics, their ligand binding pocket redesign to address the underlying molecular basis of resistance, and their subsequent peripheral tailoring to address the emerging public health problem of vancomycin resistance will be presented.

 

 

 

Professor Dale Boger | Scripps Research Institute; La Jolla, CA
Hosted by Professor Sid Hecht
Friday, March 29, 2019

Leveraging Chemistry for Biology and Therapy: New Amination Strategies to Access Biologically Important Molecules

Leveraging Chemistry for Biology and Therapy: New Amination Strategies to Access Biologically Important Molecules

Dr. Qui Wang | Duke University

Professor Jill Venton

Abstract:

Research in the Wang group aims to answer fundamental questions that lie at the interface of chemistry and biology. This talk will present her group’s recent efforts in developing new amination chemistry and strategies toward design and discovery of novel nitrogen-containing molecules for molecular labeling, imaging tools, and new antipsychotics. 

Dr. Qui Wang | Duke University
Hosted by Professor Jill Venton
Friday, March 1, 2019

Quantifying Oxygen’s Role in Promoting Aggressive Cancer Phenotypes With a Paper-Based 3D Culture Platform

Quantifying Oxygen’s Role in Promoting Aggressive Cancer Phenotypes With a Paper-Based 3D Culture Platform

Professor Matt Lockett | UNC Chapel Hill

Professor Rebecca Pompano

Abstract:

Oxygen is a master regulator of many cellular processes. In tissues, gradients of oxygen and nutrients extend radially from blood vessels. The gradients in these diffusion-dominated environments increase greatly when a blood vessel is occluded, or in the case of the tumors when the rate of proliferation outpaces the rate of vascularization. The extent of hypoxia in tumors has been correlated with cancer aggressiveness, drug resistance, and invasiveness. Gradients of oxygen are also believed to direct cellular invasion from the solid tumor mass to neighboring healthy tissue.

Despite the pivotal role that oxygen plays in tumor biology, there are a limited number of in vitro assays able to quantify cellular morphology, gene- and protein-expression, or drug sensitivities in well-defined oxygen gradients. Due to the lack of experimental tools, many studies compare cellular differences at a single normoxic (21% O2) and hypoxic (~0.2% O2) condition. Monolayer cultures are also commonly used in these normoxia-hypoxia comparisons. These experiments provide a simplified view of oxygen-mediated regulation, overlooking the importance of gradients by exposing cells to a single oxygen and nutrient concentration. Evaluating a limited number of oxygen tensions has led to the inadequate interpretation that cellular responses to oxygen are a binary phenomenon, eliciting a particular hypoxic phenotype or not.

We are developing a 3D culture platform utilizing paper-based scaffolds to prepare tissue- or organ-like structures. We are able to engineer extracellular environments with specific oxygen or nutrient gradients and to tease apart the nuanced responses of cells in gradients of different steepness and shape. In this talk, I will highlight the paper-based culture platform as well as other technologies we are developing to address three long-standing questions in tumor biology. First is the role that oxygen gradients play in directing cellular movement. We have recently shown that oxygen is a chemo-attractant in diffusion-dominated environments, and are exploring what additional extracellular conditions (e.g., gradient steepness, the presence of overlapping nutrient gradients) promote this directed invasion. Second is the oxygen-mediated mechanisms through which hypoxic cells become drug resistant. In particular, we use invasion assays and tumor-like structures to evaluate the relationship between oxygen tension, active resistance (upregulation of drug efflux pumps), and passive resistance (altered metabolism or halted proliferation). Third is the relationship between hypoxia and hormone responsiveness in estrogen receptor alpha-positive (ER+) breast cancers.

Professor Matt Lockett | UNC Chapel Hill
Hosted by Professor Rebecca Pompano
Friday, February 22, 2019

Electrochemical Conversion of CO2 and CO to C2+ Chemicals

Electrochemical Conversion of CO2 and CO to C2+ Chemicals

Dr. Feng Jiao | University of Delaware

Professor Sen Zhang

ABSTRACT

The rapid development of novel energy technologies has decreased renewable electricity prices significantly over the past decade. This foreseen cheap electricity has motivated significant research interest in the development of electrified pathways for chemical and fuel production. Compared to traditional chemical processes driven by fossil energy, electrochemical processes are often more environmentally friendly, can operate under relatively mild conditions, and can also be coupled with renewable electricity sources at remote locations. Recently, efforts have been devoted to the development of CO2 electrolysis devices that can be operated at industrially relevant rates; however, limited progress has been made, especially for valuable C2+ products. In this presentation, I will present our recent work on nanoporous copper as a CO2 reduction catalyst and its integration into a microfluidic CO2 flow cell electrolyzer. The CO2 electrolyzer exhibited a current density of 653 mA/cm2 with a C2+ product selectivity of ~62% at an applied potential of -0.67 V (vs. reversible hydrogen electrode). The highly porous electrode structure facilitated rapid gas transport across the electrode-electrolyte interface at high current densities. Further investigations on electrolyte effects revealed that the surface pH value was substantially different from the pH of bulk electrolyte, especially for non-buffering near-neutral electrolytes when operating at high currents.

 

In addition to CO2 electrolysis, CO electrolysis has also been reported to yield enhanced multi-carbon (C2+) Faradaic efficiencies up to ~55% but only at low reaction rates. This is due to the low solubility of CO in aqueous electrolytes and operation in batch-type reactors. In a recent study, we constructed a high-performance CO flow electrolyzer with a well-controlled electrode-electrolyte interface that can reach total current densities up to 1 A/cm2 together with improved C2+ selectivities. Computational transport modelling and isotopic C18O reduction experiments suggest that the enhanced activity is due to a higher surface pH under CO reduction conditions, which facilitated the production of acetate. At optimal operating conditions, we achieved a C2+ Faradaic efficiency of ~91% with a C2+ partial current density over 630 mA/cm2. Further investigations show that maintaining an efficient triple-phase boundary at the electrode-electrolyte interface is the most critical challenge to achieving a stable CO/CO2 electrolysis process at high rates.

Dr. Feng Jiao | University of Delaware
Hosted by Professor Sen Zhang
Friday, February 15, 2019

Screening, Isolation, and Characterization of Antibiotic Natural Products

Screening, Isolation, and Characterization of Antibiotic Natural Products

Professor Amanda Wolfe | University of North Carolina Asheville

Professor Mike Hilinski

Abstract

The increased emergence of bacterial resistance over the past two decades has greatly reduced the effectiveness of nearly all clinical antibiotics, bringing infectious disease to the forefront as a dire threat to global health. To combat these infections, new antibiotics need to be rapidly discovered, and bacterial natural products have reemerged as an abundant source of novel bioactive molecules. Herein, the isolation and evaluation of over 400 bacteria from bulk and rhizosphere soil native to western North Carolina and the southwestern U.S. in a novel and robust liquid-based high-throughput antagonism assay against Staphylococcus aureus and Escherichia coli is presented. Over 300 bacterial species were screened in monoculture, and 12% and 15% were found to produce antibiotics capable of ≥30% growth inhibition of Staphylococcus aureus or Escherichia coli respectively. 69 of those bacteria were subjected to 16s rRNA sequencing and found to be majority Pseudomonas (30%) and Serratia (17%) bacteria, and Aquitalea, Brevundimonas, Chryseobacterium, Herbaspirillum, and Microbacterium bacteria, which are currently not known to be antibiotic producers. More than 10 producing bacteria have been subjected to large scale culture and extraction techniques to isolate the produced antibiotic. One of those, a Pseudomonas sp., was found to produce the natural product pseudopyronine B, and we have further improved the antibiotic activity of this natural product through SAR evaluation of the alkyl side chains.

Professor Amanda Wolfe | University of North Carolina Asheville
Hosted by Professor Mike Hilinski
Friday, February 1, 2019

Electrocatalysis for Chemical Synthesis and Energy Conversion

Electrocatalysis for Chemical Synthesis and Energy Conversion

Professor Shannon Stahl | University of Wisconsin-Madison

Professor Charlie Machan

Abstract:

Oxidation and reduction reactions are crucial to the synthesis of organic chemicals, and they also provide the basis for energy production. Electrochemistry is the archetypal method for the removal and delivery of electrons in oxidation and reduction reactions, but electrochemical processes face numerous challenges. Most of the important redox processes involving organic molecules and energy-related small molecules (e.g., H2, O2, CO2, N2) feature the addition or removal of an even number of electrons and protons: 2e–/2H+, 4e–/4H+, 6e–/6H+. Such reactions are not well suited for a direct electrochemical processes, and catalysts are required to enable these reactions proceed with high efficiency and controlled selectivity. This talk will present our recent efforts to develop electrochemical transformations and electrocatalytic methods inspired by biological energy transduction and enzymatic redox processes. Specifically, we take advantage of electron-proton transfer mediators (EPTMs) that couple the movement of both electrons and protons. These mediators avoid unfavorable charge separation associated with independent electron and proton transfer steps, and they introduce new mechanistic pathways to achieve electrode-driven redox reactions. Quinones and organic nitroxyls are especially promising EPTMs, as they mediate hydrogen-atom or other proton-coupled electron transfer reactions with molecules or catalysts in solution, and then are capable of efficient regeneration via proton-coupled electron-transfer at an electrode. These mediator concepts and their use in electrocatalytic reactions will be illustrated through a series of case studies related to chemical synthesis (alcohol oxidation, C–H functionalization) and energy conversion (the oxygen reduction reaction).

 

Professor Shannon Stahl | University of Wisconsin-Madison
Hosted by Professor Charlie Machan
Friday, January 25, 2019

Micellar Electrokinetic Focusing Driven by Ion Concentration Polarization

Micellar Electrokinetic Focusing Driven by Ion Concentration Polarization

Professor Robbyn Anand | Iowa State University

Nathan Swami

Abstract 

We report selective electrokinetic focusing of neutral (uncharged) compounds from aqueous solution in a process driven by ion concentration polarization (ICP) at an ion permselective membrane. ICP is the simultaneous enrichment and depletion of ions at opposing ends of an ion permselective membrane or bipolar electrode when an electrical voltage is applied across it. In ICP, the electric field gradient present at the boundary of the ion depletion zone (IDZ) has been employed for concentration enrichment and separation of charged species for analysis. While ICP has proven to be a versatile means of focusing charged species, neutral compounds are unaffected by the electric field, thereby limiting its application. This limitation is of particular concern for the evaluation of the purity of food and pharmaceutical products, in which case the enrichment of uncharged compounds prior to analysis is often necessary. We have addressed this need by conferring a pseudo-charge to neutral compounds via their partition into an anionic micellar phase. In combination with ICP, this approach allows for neutral species to be electrokinetically enriched (stacked) and separated to an extent dependent upon the partition coefficient of the micelle-analyte pair. Initial results are presented including the quantitative characterization of micellar electrokinetic focusing by ICP.

Professor Robbyn Anand | Iowa State University
Hosted by Nathan Swami
Friday, January 18, 2019

Fall 2018

How does the Plasma Membrane Participate in Receptor-Mediated Cell Signaling?

How does the Plasma Membrane Participate in Receptor-Mediated Cell Signaling?

Professor Barbara Baird | Cornell University

Professor Andreas Gahlmann

Cells are poised to respond to their physical environment and to chemical stimuli in terms of collective molecular interactions that are regulated in time and space by the plasma membrane and its connections with the cytoskeleton and intracellular structures. Small molecules may engage specific receptors to initiate a transmembrane signal, and the surrounding system efficiently rearranges to amplify this nanoscale interaction to microscale assemblies, yielding a cellular response that often reaches to longer length scales within the organism. A striking example of signal integration over multiple length scales is the allergic immune response. IgE receptors (FceRI) on mast cells are the gatekeepers of this response, and this system has proven to be a valuable model for investigating receptor-mediated cellular activation. My talk will describe our efforts with quantitative fluorescence microscopy and modeling to investigate the poised, “resting state” of the plasma membrane and how signaling, initiated by an external stimulus and mediated by specific receptors, is regulated and targeted within this milieu.

Professor Barbara Baird | Cornell University
Hosted by Professor Andreas Gahlmann
Friday, November 16, 2018

Highly Sterically-Crowded Subvalent Group 14 Compounds: Unexpected Structures and High Reactivity with Small Molecules

Highly Sterically-Crowded Subvalent Group 14 Compounds: Unexpected Structures and High Reactivity with Small Molecules

Professor Philip Power | University of California at Davis

Professor Robert Gilliard

A series of new compounds, MAr2 (M = Ge, Sn, or Pb; Ar = terphenyl ligands) display structures and structural trends that are counter-intuitive with regard to steric effects. These trends are also reflected in their spectroscopic properties and in their reaction chemistry. It was found that the presence or absence of substituents at apparently-remote sites on the ligands can exert a large influence on the course of the reactions, as well as on the structural characteristics of the group 14 element environment. Their reactions with a range of olefins and carbon monoxide, which showed unexpected trends, will be shown. In addition, the reactions of the related subvalent hydrides, ArMH, with a range of olefins and alkyne molecules, as well as the unexpected compounds that are formed, will be presented. A notable feature of their behavior is their ability to induce unexpected isomerizations in the olefin substrates. Finally, it is proposed that many of the peculiar properties of the compounds is related to the presence of dispersion force interactions of their ligand substituents.

Professor Philip Power | University of California at Davis
Hosted by Professor Robert Gilliard
Friday, November 9, 2018

Chemistry and Biology of Nucleic Acid- and Nucleotide-Binding Proteins

Chemistry and Biology of Nucleic Acid- and Nucleotide-Binding Proteins

Professor Yinsheng Wang | University of California Riverside

Professor Huiwang Ai

The functions of nucleotides and nucleic acids involve their interactions with cellular proteins.  In this presentation, I will discuss about our recent efforts toward the development and applications of quantitative proteomic methods for unbiased, proteome-wide discovery of proteins that can recognize unique secondary structures of DNA. I will also discuss our recent development of targeted quantitative proteomic methods for interrogating ATP- and GTP-binding proteins at the entire proteome scale. The application of these methods for uncovering novel targets of clinically used kinase inhibitors and for revealing novel drivers and suppressors for melanoma metastasis will also be presented. Through this presentation, I hope to illustrate that quantitative proteomics constitutes a power tool for discovering novel nucleic acid- and nucleotide-binding proteins and for revealing their functions in cells.

Professor Yinsheng Wang | University of California Riverside
Hosted by Professor Huiwang Ai
Thursday, November 8, 2018

New Chemical Probe Technologies: Applications to Imaging, Target Identification and Drug Discovery

New Chemical Probe Technologies: Applications to Imaging, Target Identification and Drug Discovery

Professor Matthew Bogyo | Stanford University

Professor Ken Hsu

Hydrolases are enzymes that often play important roles in many common human diseases such as cancer, asthma, arthritis, atherosclerosis and infection by pathogens. Therefore tools that can be used to dynamically monitor their activity can be used as diagnostic agents, as imaging contrast agents and for the identification of novel classes of drugs. In the first part of this presentation, I will describe our efforts to design and synthesize small molecule probes that produce a fluorescent signal upon binding to tumor associated protease targets. We have identified probes that show tumor-specific retention, fast activation kinetics, and rapid systemic distribution making them useful for real-time fluorescence guided tumor resection and other diagnostic imaging applications. In the second half of the talk, I will present our recent advances using chemical probes to identify novel protease and hydrolase targets in pathogenic bacteria. This work has led to new imaging agents for Mycobacterium tuberculosis and the identification of novel virulence factors in Staphylococcus aureus that have the potential to be targeted with small molecules as a therapeutic strategy.

Professor Matthew Bogyo | Stanford University
Hosted by Professor Ken Hsu
Friday, November 2, 2018

Instrumented Tissue-in-a-Chip: A Bridge from In Vitro to In Vivo

Instrumented Tissue-in-a-Chip: A Bridge from In Vitro to In Vivo

Professor Chuck Henry | Colorado State University

Professor Rebecca Pompano

Abstract:

Microfluidic methods provide a promising path to mimicking human organ function with applications ranging from fundamental biology to drug metabolism and toxicity. The vast majority of these systems use dissociated, immortalized, or stem cells to create two and three-dimensional models in vitro. While these systems can provide valuable information, they are fundamentally incapable of recreating the three-dimensional complexity of real tissue. As a result, an important gap exists between in vitro models and in vivo systems. To address this gap, we have begun combining microfluidic devices with ex vivo tissue slices or explants to recreate model systems that capture the cellular diversity of real tissue and bridge the gap between in vitro models and in vivo systems. In this presentation two systems will be discussed. The first uses a high-density electrode array equipped with microfluidic flow to image chemical release profiles from living adrenal slices. The second uses a 3D printed microfluidic device with removable inserts to hold and perfuse fluids over intestinal tissue, enabling generation of differential chemical conditions on either side of this important barrier tissue.

Charles Henry, Stuart Tobet, David Dandy, Tom Chen

Colorado State University

Professor Chuck Henry | Colorado State University
Hosted by Professor Rebecca Pompano
Friday, October 26, 2018

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