Seminars Archive

Spring 2019

DATE IS AVAILABLE

DATE IS AVAILABLE

Friday, April 26, 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

ACS Poster Session

ACS Poster Session

Friday, April 12, 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

GRADUATE RECRUITMENT WEEK: NO SEMINAR

GRADUATE RECRUITMENT WEEK: NO SEMINAR

Friday, March 22, 2019

No Seminar: Spring Break Week!

No Seminar: Spring Break Week!

Friday, March 15, 2019

No Seminar: Friday before Spring Break

No Seminar: Friday before Spring Break

Friday, March 8, 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

Ireland Lecture: Catalyst-Controlled Site-Selective and Enantioselective C–H Functionalization

Ireland Lecture: Catalyst-Controlled Site-Selective and Enantioselective C–H Functionalization

Professor Huw Davies | Emory University

Professor Mike Hilinski
Professor Huw Davies | Emory University
Hosted by Professor Mike Hilinski
Friday, October 19, 2018

Jefferson Lecture: New Photoredox Reactions

Jefferson Lecture: New Photoredox Reactions

Professor David MacMillan | Princeton University

Graduate Student Council

Abstract

This lecture will discuss the advent and development of new concepts in chemical synthesis, specifically the application of visible light photoredox catalysis to the discovery or invention of new chemical transformations.  This lecture will explore a strategy the discovery of chemical reactions using photoredox catalysis.  Moreover, we will further describe how mechanistic understanding of these discovered processes has led to the design of new yet fundamental chemical transformations that we hope will be broadly adopted.  In particular, a new catalysis activation mode that allows for the development of C–H abstraction and decarboxylative coupling reactions that interface with organometallic catalysis.

Professor David MacMillan | Princeton University
Hosted by Graduate Student Council
Wednesday, October 17, 2018

Spontaneous Formation of Oligomers and Fibrils in Large Scale Molecular Dynamics Simulations of the Alzheimer’s Peptides

Spontaneous Formation of Oligomers and Fibrils in Large Scale Molecular Dynamics Simulations of the Alzheimer’s Peptides

Professor Carol Hall  | North Carolina State University

Professor Kateri DuBay

Spontaneous Formation of Oligomers and Fibrils in Large-Scale Molecular Dynamics Simulations of the Alzheimer’s Peptides

Protein aggregation is associated with serious and eventually-fatal neurodegenerative diseases including Alzheimer’s, Parkinson’s and the prion diseases.  While atomic resolution molecular dynamics simulations have been useful in this regard, they are limited to an examination of either oligomer formation by a small number of peptides or analysis of the stability of a moderate number of peptides placed in trial or known experimental structures. We describe large-scale molecular dynamics simulations of the spontaneous formation of fibrils by systems containing large numbers of peptides. The simulations are fast enough to enable us to follow the steps in the aggregation process from an initial configuration of random coils to oligomers and then to proto-filaments with cross-β structures. In simulations of Aβ17-42 peptides, we uncovered two fibrillization mechanisms that govern their structural conversion from disordered oligomers into protofilaments.  We also investigate the influence of crowding agents on oligomerization and fibrillization for Aβ16-22. Simulations are conducted which allow examination of the impact of naturally-derived inhibitors (resveratrol, curcumin, vanillin, and curcumin) on the oligomerization and fibrillation of A β17-36. Finally, we describe simulations of human, mouse and Syrian Movies of the aggregation process on a molecular level will be shown.

Professor Carol Hall  | North Carolina State University
Hosted by Professor Kateri DuBay
Friday, October 12, 2018

Incorporating Functional Nanomaterials in Layer-by-Layer Amperometric Sensor Designs: Adaptable Templates for Clinically Relevant Measurements

Incorporating Functional Nanomaterials in Layer-by-Layer Amperometric Sensor Designs: Adaptable Templates for Clinically Relevant Measurements

Professor Michael Leopold | University of Richmond

Professor Rebecca Pompano

Abstract

Research and development of materials and strategies for real-time, amperometric sensors and biosensors with potential in-vitro or in-vivo applications for clinically relevant physiological agents continues to be a relevant scientific endeavor.  Within this field of study, a large number of reports continue to focus on enzyme-based glucose detection because it serves both as a well-understood fundamental model system and as a clinically relevant sensing goal for diabetics.  It is, however, relatively rare that the same strategies and materials utilized for glucose sensing prove to be robust and versatile enough to be readily adapted to different target molecules with clinical relevance.  It follows then that a significant achievement would be the demonstration of a strategy and the use of materials that offer this type of versatility while maintaining superior performance toward a molecule with bioanalytical implications and possible medical applications.  Our work explores layer-by-layer (LbL) strategies for amperometric biosensor and sensor designs, where each layer or material within the composite film, including the incorporation of different nanomaterials, is functional with respect to sensing sensitivity and/or selectivity.  Additionally, this research also involves sensor development toward practical and effective clinical usage where the LbL strategies must be successfully adapted and miniaturized to needle or wire electrodes that can potentially function in vitro as a bedside device, within catheters for continuous, real-time measurements, or as an in vivo implant operating in biological media and physiologically relevant concentrations.     Fundamental studies proceed with a glucose model system before adapting the strategy and materials to specifically targeted clinical measurements including early detection/monitoring for sepsis, pregnancy-induced hypertension, and prostate cancer among others.   

Professor Michael Leopold | University of Richmond
Hosted by Professor Rebecca Pompano
Friday, September 28, 2018

Indole Alkaloids and Phenazine Antibiotics: New Platforms for Discovery

Indole Alkaloids and Phenazine Antibiotics: New Platforms for Discovery

Professor Robert Huigens | University of Florida

Professor Mike Hilinski

Abstract:

Various natural products, such as taxol, morphine and vancomycin, play a prominent role in medicine due to their ability to modulate biological targets critical to human disease. Our lab has two natural product inspired synthetic medicinal chemistry programs, driven by the structural complexity of indole alkaloids and the biological function of phenazine antibiotics. Each program aims to address major biomedical problems, including: (1) enhancing the chemical diversity of screening libraries used to drive drug discovery in high throughput screening campaigns and (2) the discovery of small molecules capable of targeting and eradicating surface-attached bacterial biofilms. Our first program aims to rapidly generate diverse and complex compounds, which can be accessed through short synthetic sequences motivated by the dramatic alteration of the inherent complex ring system of indole alkaloids. From these efforts, we have generated a library of >200 complex and diverse small molecules, which are producing an array of interesting hit compounds in diverse disease areas. Our second program aims to target bacterial biofilms, which contain specialized persister cells that are metabolically dormant and demonstrate tolerance towards every class of conventional antibiotic currently available. Biofilms are the underlying cause of chronic and recurring bacterial infections. Our lab has discovered that the marine phenazine antibiotic 2-bromo-1-hydroxyphenazine is a tunable molecular scaffold that provides access to highly potent antibacterial agents that are able to eradicate drug-resistant and antibiotic-tolerant bacterial biofilms. 

Professor Robert Huigens | University of Florida
Hosted by Professor Mike Hilinski
Friday, September 21, 2018

Graham Lecture: Increasing Access to Global Healthcare: The Medicines for All Institute

Graham Lecture: Increasing Access to Global Healthcare: The Medicines for All Institute

Professor Frank Gupton - NOTE: Lecture is on Thursday at 7:00 PM | 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 fulfill this objective, M4ALL has developed a set of core principles for API process development, which is 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 heterogeneous cross-coupling that support this effort will also be presented.

Professor Frank Gupton - NOTE: Lecture is on Thursday at 7:00 PM | Virginia Commonwealth University
Hosted by Professor Brooks Pate
Thursday, September 13, 2018

Reductive Carboxylation of Unsaturated Hydrocarbons with CO2

Reductive Carboxylation of Unsaturated Hydrocarbons with CO2

Professor Brian Popp | West Virginia University

Professor Mike Hilinski

ABSTRACT

Carbon dioxide is an attractive C1 synthon in chemical synthesis due to its abundance, obtainability, 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. Traditionally the carboxyl group is accessed by organic chemists through redox manipulation and protection/deprotection reactions or through the use of strong nucleophiles that have limited functional group tolerance. By fixing carbon dioxide with unsaturated organic molecules through C–C bond formation, rapid and redox-economic synthesis of carboxylic acids and their derivatives can be realized. Nevertheless, these transformations remain rare, are poorly understood, and generally limited to more energetic alkyne substrates. The Popp Research Group uses methodological and mechanistic approaches to expand the versatility and usefulness of transition metal-catalyzed reductive olefin carboxylation. Two approaches that will be discussed in this seminar are transfer hydrometallation–carboxylation and hetero(element)carboxylation. Recent mechanistic work will be presented on an iron-catalyzed variant of the former reaction class that has revealed new details, and possibly new opportunities, for this poorly understood class of reaction. The latter manifold was only recently extended by our group to include olefins (vinyl arenes) for the first time (ACS Editors’ Choice–Org. Lett. 2016, 18, 6428). The mild method uses redox-neutral copper catalysis and a single atmosphere of CO2 to obtain boron-functionalized α-aryl carboxylic acids, including novel functionalized-NSAIDs such as bora-ibuprofen and bora-naproxen. Recent progress toward the preparation of new bora-olefin compounds, subsequent synthetic elaboration of the carbon-boron bond, and complementary experimental/computational studies to improve our mechanistic understanding of the reaction will also be presented.

Professor Brian Popp | West Virginia University
Hosted by Professor Mike Hilinski
Friday, September 7, 2018

2018

2018-19 Kick-off Seminar: A Taste of Space: New Recipes for Making Complex Interstellar Molecules

2018-19 Kick-off Seminar: A Taste of Space: New Recipes for Making Complex Interstellar Molecules

Professor Robin Garrod | UVA Department of Chemistry

Professor Eric Herbst

ABSTRACT

Interstellar space is replete with molecules, ranging from the very simple (e.g. molecular hydrogen), to more complex and exotic species such as the cyanopolyynes (e.g. HC9N). However, young star-forming regions in particular demonstrate the richest chemistry observed outside the solar system, and are host to many molecules that are familiar from the terrestrial chemistry lab, including alcohols, aldehydes, esters and ethers; it is still a matter of debate how much of this interstellar material can survive intact to the planet-formation stage and beyond. Recent millimeter-wavelength spectral observations of high-mass star-forming regions, using the new ALMA telescope, have identified a range of new, and yet more complex molecules, whose formation mechanisms are just beginning to be fully explored. Diffusive chemistry on cold dust-grain surfaces and the energetic processing of the resultant ice mantles seem to play a critical role for many.

I will outline the chemical and physical processes that take place in interstellar clouds and star-forming cores, and will discuss new astronomical observations of organic molecules. I will also show how new chemical kinetics simulations, combined with astrophysical spectral-emission models, can help us understand both the chemistry of star formation, and the laboratory experiments that aim to reproduce its conditions.

Professor Robin Garrod | UVA Department of Chemistry
Hosted by Professor Eric Herbst
Friday, August 31, 2018

Spring 2018

Phosphorus-Element Bond-Forming Reactions

Phosphorus-Element Bond-Forming Reactions

Professor Christopher Cummins | Massachusetts Institute of Technology

Professor Robert Gilliard

White phosphorus (P4) has been the traditional entry point into phosphorus chemistry. The thirteenth element to have been isolated, it can be oxidized with elemental oxygen or chlorine, or reduced in a variety of ways. We investigated its reduction using early transition metal systems and breakdown to produce complexes with terminal metal-phosphorus triple bonds. Such terminal phosphide complexes possess nucleophilic phosphorus atoms, paving the way to new phosphorus-element bonded systems. This opened the door to the study of reactive diphosphorus molecules, the naked P2 molecule being otherwise a high-temperature species. Subsequently, it proved possible to deliver P2 into organic molecules using photochemical “cracking” of white phosphorus, the P2 serving as an effective dienophile with 1,3-dienes. An alternative pathway to the generation of unsaturated, P-containing reactive intermediates is through the use of anthracene as a delivery platform as illustrated for aminophosphinidenes, the interstellar molecule HCP, and diphosphorus. The raw material serving as a phosphorus source for global agriculture is not white phosphorus, but rather apatite in phosphate rock. White phosphorus is made in the legacy “thermal process”, accounting for ca. 5% of global phosphate rock consumption but ca. 30% of the energy utilized in phosphate rock upgrading. Now we are seeking routes to value-added phosphorus chemicals that leverage the “wet process”, in which phosphate rock is treated with sulfuric acid en route to phosphoric acid and phosphate fertilizers. 

Professor Christopher Cummins | Massachusetts Institute of Technology
Hosted by Professor Robert Gilliard
Friday, April 27, 2018

Supramolecular Approaches to Advanced Functional Materials

Supramolecular Approaches to Advanced Functional Materials

Professor Davita Watkins | University of Mississippi

Professors Robert Gilliard & Jill Venton
Professor Davita Watkins | University of Mississippi
Hosted by Professors Robert Gilliard & Jill Venton
Friday, April 20, 2018

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