School of Molecular Sciences


Seminar schedules

Departmental Seminars are held on Fridays in PSH-151 at 3:40pm unless otherwise specified.

Current Seminars


Sheryl L. Wiskur
University of South Carolina  
Asymmetric Silylation: Understanding catalyst substrate interactions and reaction selectivity

Asymmetric silylation has been employed recently to obtain enantiomercially enriched alcohols that have been difficult to obtain otherwise. We have also been exploring the mechanism of this reaction and the supramolecular interactions that control the selectivity of the reaction. Specifically, electrostatic interactions, such as cation-pi interactions are hypothesized to be one of many controlling factors in reaction selectivity, and we are interested in obtaining a better understanding of this supramolecular interaction as it relates to asymmetric catalysis. Our group uses physical organic techniques, such as linear free energy relationships, to understand reaction mechanisms which includes the intermolecular interactions that aid in controlling these reactions. In this talk we will show how we use our silylation-based kinetic resolution as a model reaction to explore how changes in the pi system of the substrate affect the selectivity of the reaction. Since the hypothesized intermediate is a silylated cationic catalyst, changes in the substrate’s pi system should affect the affinity to the catalyst which ultimately affects the selectivity. This talk will focus on some of these aspects, and some other new areas we are working in. Host: Ryan Trovitch

Claudia Turro
Ohio State University  
Dual Action Photoactive Transition Metal Complexes for Photochemotherapy

The use of light to activate the action of a drug has become important as mode of cancer therapy, in some cases superior to traditional treatments, because it significantly less invasive and poses low levels of systemic toxicity to the patient. Photoinduced ligand exchange, which can be used to release drugs with spatiotemporal control, together with the production of 1O2, represent important reactions initiated by light with potential applications in photochemotherapy (PCT). These photoinduced reactions of Ru(II) complexes will be presented, along with their activity towards biological targets and cancer cells. Importantly, Ru(II) complexes were recently discovered to undergo multiple photochemical pathways following activation with light, and this property was used to design new dual-action compounds. These new complexes are able to both release a medically relevant compound and to produce 1O2 from the same molecule. These dual-action compounds were shown to exhibit significant enhancement of activity stemming from their ability to target cancer and/or induce cell death via two different, independent pathways. New strategies developed for the photoinduced exchange of pyridine-containing drugs and methods to selectively target cancer tissue. These new dual- action complexes provide a new platform for drug delivery and enhanced therapeutic activity upon excitation with low energy light. Host: Gary Moore

Paul Weiss
Technical Lecture - Precise Chemical, Physical, and Electronic Nanoscale Contacts

Two seemingly conflicting trends in nanoscience and nanotechnology are our increasing ability to reach the limits of atomically precise structures and our growing understanding of the importance of heterogeneity in the structure and function of molecules and nanoscale assemblies. By having developed the “eyes” to see, to record spectra, and to measure function at the nanoscale, we have been able to fabricate structures with precision as well as to understand the important and intrinsic heterogeneity of function found in these assemblies. The physical, electronic, mechanical, and chemical connections that materials make to one another and to the outside world are critical. Just as the properties and applications of conventional semiconductor devices depend on these contacts, so do nanomaterials, many nanoscale measurements, and devices of the future. We discuss the important roles that these contacts can play in preserving key transport and other properties. Initial nanoscale connections and measurements guide the path to future opportunities and challenges ahead. Band alignment and minimally disruptive connections are both targets and can be characterized in both experiment and theory. I discuss our initial forays into this area in a number of materials systems. Host: Neal Woodbury
6:30 PM
Paul Weiss
University of Southern California  
General Lecture - Nanotechnology Approaches to Biology and Medicine

Biology functions at the nanoscale. Thus, there are special opportunities not only to make biological measurements using nanotechnology, but also to interact directly in order to influence biological outcomes. Nanoscience and nanotechnology developed from chemistry, physics, biology, engineering, medicine, toxicology, and a host of other fields. Along the way, we taught each other our problems, challenges, and approaches. The interdisciplinary communication skills that were developed and are now part of our training remain unique to the field. As a result, nanoscience contributes to a wide range of other fields, such as neuroscience and the microbiome. Host: Ian Gould

Anne Co
Ohio State University  
Understanding Fundamental Reactions Involved in Energy Storage Materials Using In-Situ Methods

In this seminar, I will discuss our recent efforts in developing analytical methods to decouple the chemical processes involved in lithiation and delithiation in battery materials. Specifically, I will present our work on neutron depth profiling (NDP) method to visualize and quantify Li atom position in real-time, as well as derivative operando (dOp) NMR voltammogram to identify chemical processes and preferential Li nucleation, trapping and transport in energy storage materials. Host: Candace Chan

Kim See
The Subtleties of Redox Chemistry with Multivalent Cations for Next-Generation Batteries

Rechargeable Li-ion batteries revolutionized energy storage but the fundamental limitations imposed by intercalation chemistry and the cost associated with common components in Li-ion cells drive the need for new, less expensive batteries. The search for these so called “beyond Li-ion” technologies include systems based on alternative charge storage mechanisms that promise high theoretical capacity including multielectron redox and redox-induced solid-state phase transitions. To this end, we study sulfur conversion electrodes, multi-electron intercalation cathodes, and metal anodes based on new working ions. This talk will focus on chemistries based on divalent working ions as promising alternatives to lithium-based chemistry. Divalent cations open the door to reversible metal anodes while using abundant and inexpensive resources. The intricacies of divalent cation electrochemistry range from the complex coordination complexes in electrolyte solutions, to unstable interfaces, to difficulties in divalent cation conduction in the solid-state. We will explore aspects of these key challenges in the context of pursuing a new chemistry based on a divalent working ion and a conversion cathode. Host: Christina Birkel

Spring Break


Lian Yu
University of Wisconsin - Madison  
Fast surface diffusion of molecular glasses and its role in crystallization and formation of ultrastable glasses by vapor deposition

Glasses are remarkable materials that combine the mechanical strength of crystals and the spatial uniformity of liquids, finding applications in telecommunication, organic electronics, and drug delivery. A central issue in this area is the stability of glasses against crystallization and structural relaxation (aging). We report that surface diffusion can be extremely fast in molecular glasses, outpacing bulk diffusion by up to 8 orders of magnitude at T¬g. This high surface mobility enables fast crystal growth on free surfaces, fast crystal growth in the bulk through micro-fracture, and the formation of ultrastable glasses by vapor deposition with density and energy expected for ordinary glasses aged for millennia. Unlike bulk diffusion, surface diffusion exhibits greater system-to-system variation, slowing down with molecular size and intermolecular hydrogen bonds; this property is associated with the mobility gradient beneath the free surface. Host: Ranko Richert

Justin Sambur
Colorado State University  
Nanoscale imaging of electrochemical energy conversion and storage systems

Energy needs and environmental trends demand a large-scale transition to clean, renewable energy. Nanostructured materials are poised to play an important role in this transition. However, nanomaterials are chemically and structurally heterogeneous in size, shape, and surface structural features. My research group focuses on understanding the correlation between nanoparticle chemistry/structure and functional properties. The first part of my talk will focus on characterizing charge storage mechanisms in single nanoparticles. My lab has developed a high-throughput electro-optical imaging method to selectively probe the battery-like and capacitive-like (i.e., pseudocapacitive) contributions to overall charge stored in single metal oxide nanoparticles. Pseudocapacitors are a promising class of electrochemical energy storage materials that behave electrochemically like capacitors even though the underlying charge storage mechanism is faradaic in nature (like a battery). Pseudocapacitors have the potential to charge/discharge at capacitor-like rates and maintain high energy density. A major challenge in the field is to demonstrate that pseudocapacitors behave electrochemically like a capacitor and the charge storage process is faradaic in nature. It is challenging to do so because pseudocapacitive charging has the same electrical signatures as non-faradaic electrical double layer charging. I will present our recent single particle-level measurements that show (1) individual particles exhibit different charge storage mechanisms at the same applied potential and (2) particle size-dependent pseudocapacitive charge storage properties. The second part of my talk will focus on solar energy conversion using ultrathin semiconductors such as monolayer-thick (ML) two-dimensional (2D) materials such as MoS2 and WS2. ML semiconductors represent the ultimate miniaturization limit for lightweight and flexible power generation applications. However, the underlying solar energy conversion processes in 2D materials is not entirely understood. We developed a correlated laser reflection and scanning photocurrent microscopy approach to study how layer thickness and surface structural features (edges versus basal planes) influence solar energy conversion efficiency. I will highlight our recent wavelength-dependent photocurrent microscopy and current-voltage measurements that revealed charge separation, transport, and recombination pathways in monolayer heterojunction ITO/MoS2/WS2 and ITO/WS2/MoS2 photoelectrodes. Host: Gary Moore

Visitation weekend: No seminar


Leslie Schoop
Princeton University  
From chemical bonds to high mobility in layered materials

In the discipline of chemistry, it is common to have guidelines and heuristics that help to predict how chemical reactions will proceed. We are interested to expand these heuristics to understand electronic properties of inorganic solids. In this talk, I will show how delocalized chemical bonds in certain structural networks allow us to define chemical descriptors that predict so-called topological materials, which is a new form of quantum matter, of interest for their exotic electronic and optical properties. Using these descriptors, we found a layered, antiferromagnetic van der Waals material with very high mobility. These properties have preciously not coexisted in a material that can be mechanically exfoliated. We further implemented our heuristics to discover novel complex topological phases, including magnetic ones, and phases that are in competition with complex structural distortions. The second part of my talk will focus on the concept of chemical exfoliation. With this method, we can exfoliate materials for which the scotch tape method fails. I will show how we were able to synthesize a new chromium chalcogenide this way, which might be a new 2D magnetic material. Host: Christina Birkel

Emily Pentzer
Texas A&M University  
Using Fluid-Fluid Interfaces and Fundamental Organic Chemistry Reactions to Build Better Materials

Research in the Pentzer lab focuses on using fundamental organic chemistry reactions to dictate materials properties and assemblies. We use the interface between two fluids to prepare higher order hybrid structures and dictate the interfacial properties and intimate connection of dissimilar materials. This talk will report our use of 2D particle surfactants and interfacial polymerization to address composite formation for a number of different applications- from the preparation of Janus nanosheets to the encapsulation of active materials for solvent remediation and imaging. We will show that based on modification of graphene oxide nanosheets, that oil-water, oil-oil, ionic liquid-oil, ionic liquid-water, etc. emulsions can be prepared and that interfacial polymerization results in the formation of capsules with a core of, e.g., ionic liquid, and shell, e.g., of polymer and nanoparticle. We will describe the benefits of these tailored materials, as well as current limitations. Moreover, we will highlight the application of these capsules for: enhanced uptake of carbon dioxide, overcoming mass transfer limitations, removing the need for handling controls upon volume change, as a column packing material for contaminant removal, and as the active material for super capacitors. This work gives access to unique structures and assemblies of interest in a scalable fashion. Host: Anne Jones

Derek Pratt
University of Ottawa  
Mechanisms of Free Radical Oxidation and their Inhibition: from Hydrocarbons to Lipid Bilayers and Living Organisms

The free radical mediated oxidation of hydrocarbons (autoxidation) limits the longevity of all petroleum-derived products. The most important strategy in slowing this process is via the intervention of radical-trapping antioxidants, which are included as additives to most hydrocarbon-based commercial products. Over the years, we have developed new methods to study autoxidation and its inhibition, carried out detailed mechanistic investigations to elucidate how the 4 most common classes of antioxidants (phenols, diarylamines, hindered amines and organosulfur compounds) function, and have used this knowledge to develop new compounds with significantly increased efficacy that are under development for several different applications. In parallel with these efforts, we have strived to apply our knowledge in biological contexts, where lipid autoxidation (peroxidation) has been implicated in virtually every degenerative disease. Yet, the hundreds of clinical trials intended to probe the potential of antioxidants for the treatment and/or prevention of disease have been disappointing at best. Most recently we have developed chemical tools that can be deployed to rigorously quantify the reactivity of antioxidants and investigate the mechanisms that underlie their activity under physiological conditions. These methods, along with advances in chemical and cell biology that enable the specific initiation and monitoring of cellular lipid peroxidation, have enabled us to demonstrate very clearly that the vast majority of the most celebrated compounds simply aren’t very potent – and for very basic chemical reasons. We have identified the molecular characteristics that contribute to potent antioxidant activity under relevant conditions, which underlie the activity of several recently-identified cytoprotective agents that are being advanced to the clinic to treat neurodegeneration and ischemia reperfusion injury. These insights have also enabled the bottom-up design of promising new chemical entities under active investigation. Host: Sid Hecht

Milica Radisic
University of Toronto  
Towards heart and kidney on-a-chip

Recent advances in human pluripotent stem cell (hPSC) biology enable derivation of essentially any cell type in the human body, and development of three-dimensional (3D) tissue models for drug discovery, safety testing, disease modelling and regenerative medicine applications. However, limitations related to cell maturation, vascularization, cellular fidelity and inter-organ communication still remain. Relying on an engineering approach, microfluidics and microfabrication techniques our laboratory has developed new technologies aimed at overcoming them. Since native heart tissue is unable to regenerate after injury, induced pluripotent stem cells (iPSC) represent a promising source for human cardiomyocytes. Here, biological wire (Biowire) technology will be described, developed to specifically enhance maturation levels of hPSC based cardiac tissues, by controlling tissue geometry and electrical field stimulation regime (Nunes et al Nature Methods 2013, Zao et al Cell 2019). We will describe new applications of the Biowire technology in engineering a specifically atrial and specifically ventricular cardiac tissues, safety testing of small molecule kinase inhibitors, potential new cancer drugs, and modelling of left ventricular hypertrophy using patient derived cells. For probing of more complex physiological questions, dependent on the flow of culture media or blood, incorporation of vasculature is required, most commonly performed in organ-on-a-chip devices. Current organ-on-a-chip devices are limited by the presence of non-physiological materials such as glass and drug-absorbing PDMS as well as the necessity for specialized equipment such as vacuum lines and fluid pumps that inherently limit their throughput. An overview of two new technologies, AngioChip (Zhang et al Nature Materials 2016) and inVADE (Lai et al Advanced Functional Materials 2017) will be presented, that overcome the noted limitations and enable engineering of vascularized liver, heart and kidney as well as studies of cancer metastasis. These platforms enable facile operation and imaging in a set-up resembling a 96-well plate. Using polymer engineering, we were able to marry two seemingly opposing criteria in these platforms, permeability and mechanical stability, to engineer vasculature suitable for biological discovery and direct surgical anastomosis to the host vasculature. Host: Steve Presse

Elena Galoppini
Rutgers University Newark  
Synthetic Design of Porphyrin/Metal Oxide Semiconductor Interfaces for Solar Energy Applications: the influence of surface dipoles

The exchange of charges between photo-excited molecules and a metal oxide semiconductor such as TiO2 or ZnO is a process of great importance for solar energy conversion research on photovoltaics, artificial photosynthesis, and photocatalysis. Molecular design of chromophore-linker-anchor compounds plays an important role to control, at the molecular level, charge transfer at hybrid organic-inorganic systems and to gain a fundamental understanding of these important interfaces. The talk will address several aspects of molecular design that our group has focused on, including ways to control the energy level alignment between the LUMO and HOMO of Zinc Tetraphenylporphyrin (ZnTPP) chromophores and the conduction band of TiO2 or ZnO surfaces through the presence of permanent dipoles built in the linker unit. Host: Ana Moore

Steven Boxer
Stanford University  
Electric Fields and Enzyme Catalysis

We have developed the vibrational Stark effect to probe electrostatics and dynamics in organized systems, in particular in proteins where vibrational probes can report on functionally important electric fields. The strategy involves deploying site-specific vibrational probes whose sensitivity to an electric field is measured in a calibrated external electric field. Once calibrated, these probes, typically nitriles or carbonyls, can be used to probe changes in electric field due to mutations, ligand binding, pH effects, light-induced structural changes, etc. We can also obtain information on absolute fields by combining vibrational solvatochromism and MD simulations, checked by the vibrational Stark effect calibration. This frequency-field calibration can be applied to quantify functionally relevant electric fields at the active site of enzymes. Using ketosteroid isomerase as a model system, we correlate the field sensed at the bond involved in enzymatic catalysis with the rate of the reaction it catalyzes, including variations in this rate in a series of mutants and variants using non-canonical amino acids. This provides the first direct connection between electric fields and function: for this system electrostatic interactions are a dominant contribution to catalytic proficiency. Using the vibrational Stark effect, we can now consistently re-interpret results already in the literature and provide a framework for parsing the electrostatic contribution to catalysis in both biological and non-biological systems. Extensions of this approach to other classes of enzymes, to effects of electrostatics on pathways of photoisomerization in proteins, and to the evolutionary trajectories of enzymes responsible for antibiotic resistance will be described if time permits. Host: Neal Woodbury
6:30 PM
PSH 153
Stephen Boxer
Stanford University  
GFP - the Green Revolution Continues

Bioluminescence has fascinated scientists since ancient times – the green fluorescence from agitated jellyfish is an example and this comes from Green Fluorescent Protein (GFP). Since the discovery in the mid-1990’s that GFP can be expressed in essentially any organism, GFPs have become indispensable tools as genetically encoded fluorescent reporters. A bewildering array of variants has been developed leading to a wide pallet of colors and photo-switching characteristics that are essential for super-resolution microscopy. Our lab was involved in early studies of excited state properties of GFP that led to the discovery that the GFP chromophore is a photoacid – this has many consequences for further protein design and is related to the natural function of this unusual protein. Beyond applications in imaging, GFPs are a wonderful model system for probing the spectroscopic and functional consequences of the interaction between a prosthetic group and the protein surrounding it. I will discuss several examples related to photoisomerization of the chromophore. (1) We have systematically altered the electrostatic properties of the GFP chromophore in a photo-switchable variant using amber suppression to introduce electron-donating and -withdrawing groups to the phenolate ring. The contributions of sterics and electrostatics can be evaluated quantitatively and used to demonstrate how electrostatic effects bias the pathway of chromophore isomerization. (2) Split GFPs are made from protein fragments whose reassembly leads to a fluorescent readout. By chance, we discovered that split -strands can be photo- dissociated, i.e. split GFP is a genetically encoded caged protein. The mechanism of this unusual process will be discussed along with possible applications as optogenetic tools. Host: Neal Woodbury

Jeff Hartgerink
Rice University  
Self-assembly of collagen triple helices and b-sheet nanofiber hydrogels: applications in peptide design

Nature uses self-assembly to generate nearly every complex structure from the DNA double helix to the lipid membrane to the intricate folding of the ribosome; a huge number of individually weak non-covalent interactions are used to direct the assembly of life’s machinery. This approach allows for easy reversibility and self-healing properties that are commonplace in nature but difficult to engineer. Our lab has focused on mimicking nature’s approach to the preparation of nanostructured materials through the design of peptides. In this talk I will describe our work with MultiDomain Peptides (MDPs) which self-assemble into b-sheet nanofibers and Collagen Mimetic Peptides (CMPs) which self-assemble into triple helices. MDPs self-assemble into nanofibers approximately 8 nanometers wide and many microns in length through the interplay of several non-covalent interactions including hydrogen bonding and the hydrophobic effect, which drive assembly, and ionic repulsion which can act as a controlling switch to turn assembly on or off. As nanofibers grow, they entangle with one another and, in water, will form a viscoelastic hydrogel at concentrations at or above 0.5% by weight. These hydrogels can be loaded with small molecule drugs, proteins, cells or a combination of all these to achieve syringe directed deliver with control over release kinetics. However, the nanofibrous hydrogel can also be used unloaded where we have found that free of any bioactive agents it is rapidly infiltrated with cells in vivo and remodeled into highly vascularized tissue. CMPs differ in critical ways from other well studied proteins in that they lack a hydrophobic core and require a glycine every third amino acid creating a characteristic (Xaa-Yaa-Gly)n repeat. Design of synthetic triple helices which can mimic collagen are extremely challenging for many reasons, but one of the most apparent is that a system of three peptides A, B and C can self-assemble into at least 27 different compositions and registers (AAA, AAB, AAC, ABA, etc). Proper design therefore must stabilize one of these while destabilizing the other 26. I will describe the design, synthesis and characterization of several AAB and ABC heterotrimers and computational methods which allow us to both predict their stability, the stability of natural collagens and improve design of new systems. Beyond supramolecular assembly of triple helices I will also describe how these systems can be selectively covalently captured and the applications these types of covalently stabilized helices will allow. Host: Nicholas Stephanopoulos

Victor Batista
Yale University  
Studies of Natural and Artificial Photosynthesis

Mechanistic investigations of the water-splitting reaction are fundamentally informed by structural studies of the oxygen-evolving complex (OEC) of photosystem II (PSII) and biomimetic catalytic complexes. Many physical techniques have provided important insights into the OEC structure and function, including X-ray diffraction (XRD) and extended X-ray absorption fine structure (EXAFS) spectroscopy as well as mass spectrometry (MS), electron paramagnetic resonance (EPR) spectroscopy, and Fourier transform infrared spectroscopy applied in conjunction with mutagenesis studies. However, experimental studies have yet to yield consensus as to the nature of the reaction mechanism responsible for oxygen evolution. Computational modeling studies, including density functional (DFT) theory combined with quantum mechanics/molecular mechanics (QM/MM) hybrid methods for explicitly including the influence of the surrounding protein provide powerful modeling tools to explore reaction mechanisms for the fully ligated OEC within PSII and examine whether they are maximally consistent with experimental data. The computational models are useful for rationalizing spectroscopic and crystallographic results and for building a complete structure-based mechanism of water-splitting as described by the intermediate oxidation states of oxomanganese complexes. This talk summarizes our recent advances in studies of water oxidation catalyzed by the OEC of PSII and biomimetic catalysts for artificial photosynthesis. Host: Ana Moore

Thom LaBean
NC State University  
Engineering Biomolecular Assembly for Medical Applications

The ability to design and program complex molecular interactions between synthetic biomolecules (especially polynucleotides and polypeptides) has led to a revolution in artificial nanomaterials capable of self-assembly. For example, DNA-based nanotech entails the design of artificial nucleotide sequences capable of self-assembling into desired geometric shapes, patterns, and architectures with nanometer-scale precision. These synthetic DNA nanostructures have been shown useful for organizing other materials including inorganic nanoparticles (metals and semiconductors), nucleic acid aptamers, and even carbon nanostructures. We are working with DNA self- and directed-assembly to expand our molecular assembly toolbox for use in a wide variety of applications, especially in nanoelectronics and medicine. One promising recent development is a chemically modified RNA origami-based anticoagulant [See Ref. 1 and schematic below] with potential to treat complex, life-threatening conditions such as disseminated intravascular coagulation (DIC). Host: Nicholas Stephanopoulos

Kit Bowen
Johns Hopkins  
Adventures in Anion Photoelectron Spectroscopy

Host: Scott Sayres

Jun Wang
University of Arizona  
Medicinal Chemistry and Pharmacology of Antivirals

My lab focuses on developing antivirals targeting drug-resistant and emerging viruses such as influenza virus and the enterovirus. In addition, we are interested in studying the pharmacology of antivirals, specifically their mechanism of action and mechanism of resistance. The goal is to develop antivirals with a high genetic barrier to drug resistance. In this seminar, I will present two projects: one is the development inhibitors targeting the influenza virus polymerase subunit PA-PB1 protein-protein interactions through either rational design or split-luciferase based high-throughput screening; another is the discovery of enterovirus D68 (EV-D68) antivirals by targeting the viral capsid protein VP1, the 2C protein, as well as the newly identified 2A protease. Host: Wei Liu

Paul Braun
University of Illinois at Urbana-Champaign.  
High Energy and Power Density Electrodeposited Lithium and Sodium Battery Electrodes

Electrodeposition of electrode materials has the potential to grow anode and cathode materials with unprecedented energy and power densities for both Li-ion and Na-ion rechargeable batteries and to broaden the scope of available electrode form factors. I will present our work on the electrodeposition of high performance silicon and tin-based Na and Li-ion anodes and LiCoO2, NaCoO2, LiMn2O4, and Al-doped LiCoO2-based Na and Li-ion cathodes. The electrolytically active materials were formed either as solid films, or where significant volume changes upon cycling are present, as a 3D mesostructured film. The capacities are near-theoretical, and in the case of the electroplated oxides, the crystallinities and electrochemical capacities are comparable, or in some cases, even better than powders synthesized at much higher temperatures. Time permitting, I will also discuss some of our recent work on the fundamentals of energy transport in redox-active materials for flow batteries. Host: Neal Woodbury

Jean-François Masson
Université de Montréal  
Plasmonic nanobiosensors: From therapeutic drugs and environmental monitoring to optophysiology of living cells

This presentation will provide an overview of our research activities in plasmonic nanobiosensing. Our research lies in the areas of plasmonic materials, low-fouling surface chemistry and instrumental design for biosensing. This presentation will focus on applying these concepts for several classes of sensors for monitoring biomolecules, therapeutic drugs, pheromones and for environmental contaminants. We have developed a SPR and LSPR sensing platform based on a small and portable instrument that can be field-deployed. In the first example, this SPR chip was integrated with a RDX-selective molecularly imprinted polymer to detect RDX at ppb levels directly in natural waters. The system was deployed to a Canadian army base for monitoring the level of RDX in proximity of training grounds. This system was tested on several trips in different environmental conditions and results were in good agreement with HPLC performed in a laboratory. Clinical sensing in crude biofluids is a common challenge to different biosensing platforms. To prevent nonspecific adsorption of serum, a series of peptide monolayers were synthesized and tested in crude serum. Based on this, competition assays were validated for therapeutic drug quantitation, such as methotrexate with the SPR sensors. The methotrexate assay was tested at a local hospital and was cross-validated with the current state-of-the-art FPIA analyzer commercially available. Lastly, we are currently exploring the concept of optophysiology using plasmonic nanopipettes for monitoring living cell secretion events. Due to the lack of analytical techniques for detecting metabolites near living cells, developing tools to monitor cell secretion events remains a challenge to overcome in chemical analysis. Plasmonic nanopipettes were developed based on the decoration of patch clamp nanocapillaries with Au nanoparticles. The plasmonic nanopipette is thus competent for dynamic SERS measurements in the liquid environment near cells. This nanobiosensor was tested with the detection of small metabolites near living cells and of neurotransmitters released by neurons. Host: Mark Hayes

John Peters
Washinton State University  
The diverse catalytic reactivity of hydrogenases reveals a simple model for tuning catalytic bias in oxidation-reduction catalysis

Hydrogenases display a wide range of catalytic rates and biases in reversible hydrogen gas oxidation catalysis. The interactions of the iron-sulfur containing catalytic site with the local protein environment are thought to contribute to differences in catalytic reactivity, but this has not been demonstrated. The microbe Clostridium pasteurianum produces three [FeFe]-hydrogenases that differ in their “catalytic bias” exerting a disproportionate rate acceleration in one direction or the other spanning a remarkable six orders of magnitude. The combination of high-resolution structural work, biochemical analyses, and computational modeling indicate that protein secondary interactions directly influence the relative stabilization/destabilization of different oxidation states of the active site metal cluster. This selective stabilization or destabilization of different oxidation states can promote preferentially hydrogen oxidation or proton reduction and represent a simple yet elegant model for how a protein catalytic site can confer catalytic bias. Host: Anne Jones

Phil Castellano
NC State University  

The generation and transfer of triplet excitons across semiconductor nanomaterial-molecular interfaces will play an important role in emerging photonic and optoelectronic technologies and understanding the rules that govern such phenomena is essential.1 The ability to cooperatively merge the photophysical properties of semiconductor quantum dots, with those of well-understood molecular chromophores is therefore paramount. CdSe semiconductor nanocrystals, selectively excited by green light, engage in interfacial Dexter-like triplet-triplet energy transfer with surface-anchored polyaromatic carboxylic acid acceptors, thereby extending its excited state lifetime by 5 orders-of-magnitude.2 Net triplet energy transfer also occurs from surface anchored molecular acceptors to freely diffusing molecular solutes, further extending the triplet exciton lifetime while sensitizing singlet oxygen in aerated solution. The successful translation of triplet excitons from semiconductor nanoparticles to bulk solution implies a general paradigm that such materials are effective surrogates for molecular triplets. Inspired by the notion that semiconductor nanocrystals present molecular-like photophysical and photochemical properties, 1-pyrenecarboxylic acid (PCA)-functionalized CdSe quantum dots are shown to undergo thermally activated delayed photoluminescence.3 This phenomenon results from a near quantitative triplet-triplet energy transfer from the nanocrystals to PCA, producing a molecular triplet-state ‘reservoir’ that thermally repopulates the photoluminescent state of CdSe through endothermic reverse triplet-triplet energy transfer. The resultant photoluminescence properties are systematically and predictably tuned through variation of the quantum dot–molecule energy gap, temperature, and the triplet-excited-state lifetime of the molecular adsorbate. The concepts developed here appear to be generally applicable to semiconductor nanocrystals interfaced with molecular chromophores enabling potential applications of their combined excited states. Host: Gary Moore

Jia Guo
Novel Fluorescent Probes For Single Cell In Situ Genomics And Proteomics Analysis


Gary Moore
Make Like a Leaf: Bioinspired Architectures for Application in Solar-to-Fuels and Green Chemistry

11:00 AM
Gilad Haran
Understanding Microsecond Dynamics of Protein Machines

Host: Steve Presse
Alexandra Ros
Separations and Serial Crystallography in Microenvironments

10:30 am
Wolfram Sander
Taming the Beast-Controlling Spin and Reactivity of Reactive Intermediates

Host: Matthias Heyden

Chengde Mao
Programmed DNA Self-Assembly

Molecular self-assembly promises an effective approach for nanoconstructions. DNA, in particular, has been used as a programmable 'smart' building block for the assembly of a wide range of nanostructures. Here, I will first introduce the general field of structural DNA nanotechnology and my own philosophy: striving to use minimal number of component molecules to assemble complex nanostructures. Then, I will discuss the development in programmed DNA self-assembly in my research group, including: DNA polyhedra, DNA 2D arrays and 3D crystals, and our exploration in RNA nanostructures. Host: Nicholas Stephanopoulos

Kamil Godula
Chemical editing of the glycocalyx to influence cellular functions

Glycans (also known as carbohydrates, saccharides or, simply, sugars) are among the most intriguing carriers of biological information in living systems. The structures of glycans not only convey the cells’ physiological state, but also regulate cellular communication and responses by engaging receptors on neighboring cells and in the extracellular matrix. Despite their structural complexity, individual glycans rarely engage their protein partners with high affinity. Yet, glycans modulate biological processes with exquisite selectivity and specificity. To correctly evaluate glycan interactions and their biological consequences, one needs to look beyond individual glycan structures and consider the entirety of the cell-surface landscape. There, glycans are presented on protein scaffolds, or are linked directly to membrane lipids, forming a complex, hierarchically organized network with specialized functions, called the glycocalyx. Our research program focuses on the development of nanoscale glycomaterials, which can mimic the various components of the glycocalyx, together with chemical methods for cell surface engineering to reveal how the presentation of glycans within the glycocalyx can influence their biological functions. In my presentation, I will describe our recent efforts in this area, placing emphasis on the applications of glycomaterials to provide new insights into the mechanisms through which glycans mediate cellular differentiation and host-pathogen interactions. Host: Nicholas Stephanopoulos

Marino Resendiz
University of Colorado Denver  
Exploring the structural and functional impact of 8-oxo-7,8-dihydropurines (8-oxoG, 8-oxoA, 8-oxoI) on RNA. Ribonucleases and Aptamers.

The relationship between oxidatively damaged RNA and disease is of wide interest. Mechanisms regarding how cells cope with oxidized RNA have been proposed, however, little is known in this area. In this work, 8-oxo-7,8-dihydropurines were incorporated into oligonucleotides of RNA to explore their impact on structure and function. In addition, ribonucleases of different specificities, common in RNA structure-probing, were used to understand structural aspects and reactivity, i.e., RNase T1, RNase H, RNase A, Xrn-1. Duplexes, hairpins and pseudoknots were used to determine structural changes and the aptamers for preQ1 and theophylline were used to understand function, via small-molecule – RNA interactions. We found that positioning these lesions in duplex regions leads to decreased stability, while modification of single stranded regions, i.e., hairpin loops, internal loops, often times resulted in increased stability. Furthermore, the effect on small-molecule interactions resulted in loss of recognition, decreased recognition, or changes in selectivity towards other small molecules in a position dependent manner. Ribonucleases were used to characterize overall changes in structure and we found that the modifications are not recognized by RNase T1, while being recognized by RNase A with the following preference: C > 8-oxoG > U. The changes in reactivity are now guiding our efforts to predict local (H-bonding, conformation) and global (secondary/tertiary) structural and functional aspects of RNA. Understanding this behavior will shed light into possible mechanisms by which these lesions are recognized for their subsequent enzymatic degradation, thus allowing us to understand the potential role between oxidized RNA and the development/ progression of disease. Host: Marcia Levitus
6:30 PM
Paul Weiss
University of Southern California  
General Lecture - Nanotechnology Approaches to Biology and Medicine

Biology functions at the nanoscale. Thus, there are special opportunities not only to make biological measurements using nanotechnology, but also to interact directly in order to influence biological outcomes. Nanoscience and nanotechnology developed from chemistry, physics, biology, engineering, medicine, toxicology, and a host of other fields. Along the way, we taught each other our problems, challenges, and approaches. The interdisciplinary communication skills that were developed and are now part of our training remain unique to the field. As a result, nanoscience contributes to a wide range of other fields, such as neuroscience and the microbiome. Host: Ian Gould

Thomas Record
University of Wisconsin - Madison  
Interpreting and Predicting Effects (m-values) of Solutes and Hofmeister Salts on Protein Folding and other Processes

Solutes and salt ions are used in vitro at concentrations above 0.1 M to favor or disfavor the thermodynamics and perturb the kinetics of protein processes. Hofmeister series describe the relative effectiveness of different salt cations and anions as protein stabilizers/destabilizers, precipitants/solubilizers, and assembly/disassembly agents. An analogous series exists for uncharged solutes. Typically the standard free energy change for the process varies linearly with solute or salt concentration; the slope is called the m-value. Effects of salt ions on surface tension and protein processes follow similar series. I’ll discuss a unified quantitative interpretation of these solute and salt ion effects in terms of their partitioning between the local water of hydration of the protein surface that is exposed or buried in these processes. Model compound data allow a quantitative interpretation of these solute and salt ions effects with predictive capability. Analysis of these data also provides quantitative information about strengths of the different noncovalent interactions of protein unified atoms (e.g.amide N – amide O) in water. Host: Marcia Levitus
6:30 PM
Emily A. Carter
Eyring Lecture - Sustainable Energy Material from First Principles

I believe that we scientists and engineers have a responsibility to use our skills to improve life for all Earth’s inhabitants. To this end, for the past dozen years, I have used my skills - in developing and applying quantum mechanics simulation methods aimed at complex phenomena difficult to probe experimentally - to help accelerate discovery, understanding, and optimization of materials for sustainable energy conversion processes. These range from materials for converting sunlight and other renewable energy sources to fuels and electricity, to biodiesel fuels, to clean electricity production from solid oxide fuel cells and nuclear fusion reactors, to lightweight metal alloys for fuel-efficient vehicles. During this talk, I will focus on potential technological advances in materials science, nanoscale optics, and electrochemistry that could someday create a virtuous cycle, exploiting energy from sunlight and molecules in air, water, and carbon dioxide to synthesize the fuels and chemicals needed to sustain future generations. Host:



Spring Break


John Matson
Virginia Tech  
Therapeutic Delivery of Hydrogen Sulfide: Small Molecules, Polymers, and Materials

Despite its reputation as a foul-smelling and toxic pollutant, hydrogen sulfide (H2S) is a vital biological signaling agent, and it is of interest as a therapeutic for a variety of diseases and conditions. We focus on developing new small molecules, polymers, and supramolecular materials for the delivery of H2S. The majority of biological studies on this gasotransmitter have been carried out with systemically administered sulfide salts, which have no tissue specificity, fast release, and the potential for off-target effects. We address these shortcomings by developing new H2S-releasing small molecules with controllable triggers and release kinetics. These small molecules are then incorporated into new materials, which can offer localized H2S delivery with tunable kinetics. Our platforms include soluble polymers and peptide-based gels designed to release therapeutically relevant concentrations of H2S with controllable kinetics. We focus on using these materials as therapeutics for treating cardiovascular disease and cancer. Host: Nicholas Stephanopoulos

No seminar- visitation weekend







2:00 PM
Biodesign auditorium
Shannon S. Stahl
University of Wisconsin-Madison, Madison, Wisconsin  Dept of Chemistry
Electrocatalysis for Chemical Synthesis and Energy Conversion

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 enzmatic 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). Host: BioDesign

Peng Yin
Harvard University  
Nanoscale Construction and Imaging with DNA

Dr. Peng Yin will be discussing how to use DNA/RNA to construct nanostructures and develop applications especially for bioimaging. We have developed a framework to synthesize DNA/RNA nanostructures with user-specified geometry or dynamics. By interfacing these nanostructures with other functional materials, we have introduced digital programmability into diverse application areas, e.g. fabrication of inorganic nanoparticles with arbitrary prescribed shapes for future nanoelectroics, robust DNA probes with near optimal binding specificity for molecular diagnostics, and RNA-based genetically encodable translation regulators with large dynamic range and orthogonality for programming biology. In particular, I will describe DNA-based techniques for high precision super-resolution imaging using diffusing fluorescent DNA strands, multiplexed in situ signal amplification for high throughput and sensitivity tissue imaging, and a biochemical DNA nanoscope that encodes the spatial arrangement of molecular targets in autonomously produced DNA proximity records. I will also discuss current and prospective biological applications of these techniques, including single-cell nucleus architecture study, single molecule proteomics, and biomarker tissue mapping. Host: Nicholas Stephanopoulos



Thanksgiving-no seminar


Ke Zhang
Northeastern University  

Host: Nicholas Stephanooulos

Edgar Arriaga
University of Minnesota  Department of Chemistry
Blame it on the satellites: mass cytometric analysis of single cells

Host: Alexandra Ros

Yogesh Surendranath
Bridging Molecular and Heterogeneous Catalysis Through Graphite Conjugation

Host: Gary Moore
6:00 PM
Sunney Xie
Harvard University  Department of Chemistry and Chemical Biology
Eyring General Lecture: Life at the Single Molecule Level: From Single Molecule Enzymology to Single Cell Genomics

Since the 1990s, developments in room-temperature single-molecule spectroscopy, imaging, and manipulation have allowed studies of single-molecule behaviors in vitro and in living cells. Unlike conventional ensemble studies, single-molecule enzymology is characterized by ubiquitous fluctuations of molecular properties. The understanding of such single-molecule stochasticity is pertinent to many life processes. DNA exists as single molecules in an individual cell. Consequently, gene expression is stochastic. Single-molecule gene expression experiments in live single cells have allowed quantitative description and mechanistic interpretations. The fact that there are 46 different individual DNA molecules (chromosomes) in a human cell dictates that genomic variations, such as copy-number variations (CNVs) and single nucleotide variations (SNVs), occur stochastically and cannot be synchronized among individual cells. Probing such genomic variations requires single-cell and single-molecule measurements, which have only recently become possible. These studies are difficult since they require the amplification of the minute amount of DNA of a single cell, and existing single-cell whole genome amplification (WGA) methods have been limited by low accuracy of CNV and SNV detection. We have developed transposase-based methods for single-cell WGA, which have superseded previous methods. With the improved genome coverage of our new WGA method, we developed a high-resolution single-cell chromatin conformation capture method, which allows for the first 3D genome map of a human diploid cell. We have also developed a method for single-cell transcriptome with better detection efficiency and accuracy, revealing intrinsic correlations among all detected mRNAs in a single-cell. Host: Neal Woodbury and Jia Guo
3:30 PM
Biodesign Auditorium BDB105
Sunney Xie
Harvard University & Peking University  Department of Chemistry and Chemical Biology
Stimulated Raman Scattering Microscopy: Seeing the Invisible in Biology and Medicine

Stimulated Raman scattering (SRS) microscopy is a label-free and noninvasive imaging technique using vibration spectroscopy as the contrast mechanism. Recent advances have allowed significant improvements in sensitivity, selectivity, robustness, and cost reduction, opening a wide range of applications. This is particularly relevant in biology since SRS microscopy does not affect cell function, and is best suited for imaging small metabolite molecules. For medicine, SRS microscopy provides instant tissue examination without the need of previous histological staining procedures. Host: Neal Woodbury and Jia Guo

Steffen Lindert
Ohio State University  
Computational Protein Structure Prediction Guided by Covalent Labeling and SID Mass Spectrometry Data

Host: Wade Van Horn

Mariana Bertoni
ASU  School of Electrical, Computer and Energy Engineering
Across Dimensions and Scales: How X-ray Microscopy Can Help Design Better Solar Absorbers

Host: Marcia Levitus

Jane Richardson
Early protein design, and our circuitous route to current model validation for cryoEM

Host: Jeremy Mills

Julius Lucks
Northwestern University  
Uncovering How RNA Molecules ‘Make Decisions’ On the Fly: Towards Understanding and Engineering Cotranscriptional RNA Folding

RNAs are emerging as a powerful substrate for engineering gene expression and cellular behavior since they are now known to control almost all aspects of gene expression. As with all biomolecules, RNA function is intimately related to its structure, since RNA can adopt structures that selectively modulate gene expression. Central questions in biology and bioengineering then are: How do RNAs fold inside cells?; and How can we engineer these folds to control gene expression? In this talk, I will present our work at the interface of these two questions and share results that are beginning to uncover design principles for understanding natural RNAs and engineering RNAs for an array of applications. I will start by presenting our work on engineering RNA molecular switches that control transcription. The desire to uncover design principles for engineering these RNAs motivates our development of SHAPE-Seq, a technology that couples chemical probing with next-generation sequencing and that helps characterize RNA structures on an ‘omics’ scale. I will then describe our exciting recent developments in using SHAPE-Seq to help break open one of the frontiers of RNA structure-function relationships by uncovering at nucleotide resolution how RNAs fold cotranscriptionally. Specifically I will highlight new data on uncovering the ligand-dependent folding pathways of riboswitches, and how we are beginning to use these datasets to computationally reconstruct cotranscriptional folding pathways. This new ability is allowing us to ask deep questions about how RNA molecules make regulatory decisions ‘on the fly’ during the dynamic process of transcription. By probing the fundamental processes of RNA folding and function, these studies are expected to greatly aid RNA engineering. Host: Petr Sulc

Vicente Talanquer
University of Arizona  
Reconceptualizing the Chemistry Curriculum to Foster Chemical Thinking

The chemistry curriculum at many universities is still mostly fact-based and encyclopedic, built upon a collection of isolated topics, oriented too much towards the perceived needs of chemistry majors, and detached from the ways of thinking and applications of chemistry in the 21st century. Research in chemistry education has shown that this curriculum does not help many students to develop meaningful understandings and connections between core concepts and ideas. Our own educational research has revealed that many chemistry students finishing college chemistry courses still rely on intuitive assumptions and fast and frugal heuristics to build explanations and make decisions in chemistry relevant contexts. This presentation will summarize core findings of our research on student reasoning and show how we have used these results to develop an alternative way of conceptualizing the chemistry curriculum by shifting the focus from learning chemistry as a body of knowledge to understanding chemistry as a way of thinking. This new curricular and teaching approach has been implemented in all General Chemistry sections at our university for the past three years. Analysis of students' performance in ACS standardized tests, conceptual questionnaires, and in subsequent Organic Chemistry courses shows a significant positive effect on student understanding and achievement. Host: Ian Gould and Marcia Levitus

Nancy Levinger
Colorado State University  Department of Chemistry
Sweet Confinement: Glucose and Other Osmolytes in Reverse Micelles

Confinement to nanoscopic proportions can have dramatic impact on the properties of materials. We explore the impact that soft nanoconfinement in reverse micelle has on water properties. This presentation will focus on the effects of water on carbohydrates and carbohydrates on water in reverse micelles. When introduced to reverse micelles, carbohydrates such as glucose, sorbitol, and trehalose result in smaller particles than those prepared with only water. Through a range of measurements we are developing a model to explain the reverse micelle size variations. At the same time, we explore the impact of carbohydrates on water in the reverse micelle nanoconfined environment, where we measure dramatic slowing of chemical exchange rates between carbohydrates hydroxyl groups and water. This presentation will discuss implications of these results for interfacial chemistry and implications for cryopreservation of cells. Host: Dmitry Matyushov

Rhiju Das
Stanford University  
Molecular machines through rational RNA design

Host: Petr Sulc

Yan Liu
DNA nanotechnology and rational control of self-assembly

Host: Neal Woodbury

Chad Borges
Albumin Oxidizability as a Forensic Marker of Blood Plasma/Serum Exposure to Thawed Conditions

Host: Neal Woodbury

Ryan Trovitch
Utilization of Donor-Functionalized Redox Non-Innocent Ligands to Promote Manganese- and Molybdenum-Based Catalysis

Host: Neal Woodbury

Ayusman Sen
Penn State University  
Fantastic Voyage: Designing Self-Powered Nanobots

Self-powered nano and microscale moving systems are currently the subject of intense interest due in part to their potential applications in nanomachinery, nanoscale assembly, robotics, fluidics, and chemical/biochemical sensing. One of the more interesting recent discoveries has been the ability to design nano/microparticles, including molecules, which catalytically harness the chemical energy in their environment to move autonomously. These "bots" can be directed by chemical and light gradients. Further, our group has developed systems in which chemical secretions from the translating micro/nanomotors initiate long-range, collective interactions among the particles. This behavior is reminiscent of quorum sensing organisms that swarm in response to a minimum threshold concentration of a signaling chemical. In addition, an object that moves by generating a continuous surface force in a fluid can, in principle, be used to pump the fluid by the same catalytic mechanism. Thus, by immobilizing the nano/micromotors, we have developed nano/microfluidic pumps that transduce energy catalytically. These non-mechanical pumps provide precise control over flow rate without the aid of an external power source and are capable of turning on in response to specific analytes in solution. Host: Steve Presse
12:30 P.M.
BioDesign Auditorium B105
Nicholas Seyfried
Emory University School of Medicine  Department of Biochemistry
Integrative Proteomics for Novel Target Discovery in Alzheimer’s Disease

The proteome is the “executioner” of the effects of aging, genetics, the environment and other risk factors that cause human disease. In Alzheimer’s disease (AD), amyloid-beta (Aß) and Tau were identified with classical biochemical methods, enabling breakthroughs from discovery as proteins directly altered in AD pathology. Nicholas Seyfried’s team hypothesizes the AD proteome undoubtedly contains many other proteins that play key roles in initiation and progression of AD. To further understand AD pathophysiology and to identify new targets for early intervention, he employs unbiased large-scale quantitative proteomic discovery methods utilizing mass spectrometry platforms. Seyfried will discuss systems biology approaches that resolve highly conserved networks of proteins, many of which correlate strongly with clinical and pathological AD phenotypes, including those reflecting key mechanisms strongly correlated with impaired synaptic function, RNA binding and neuroinflammation. These comprehensive proteomic datasets of brain-based protein changes linked to AD and other neurodegenerative diseases are currently being leveraged as protein biomarkers in human cerebrospinal fluid for the diagnosis, staging and therapeutic response to treatment. Host:
10:30-11:30 AM
PSC 101/103
David L. Osborn
Sandia National Laboratories  Combustion Research Facility
Hunting for Intermediates in Complex-Forming Reactions: Better Hounds for an Elusive Quarry

Complex-forming reactions have at least one deep well on their potential energy surface, where the well represents a reactive intermediate on the pathway to products. Just as in direct reactions, where the observation of a transition state complex provides important clues to the reaction mechanism, the characterization of reactive intermediates is enormously useful in discovering the mechanism of complex-forming reactions. Most reactive intermediates are short-lived, elusive molecules that are difficult to catch and challenging to detect. In this presentation, I’ll discuss the first observation of one of these key species: a hydroperoxyalkyl radical (denoted •QOOH) that plays an important role in autoignition and autooxidation. As reaction complexity increases, many more intermediates may be energetically and entropically feasible, making the hunt for reactive intermediates increasingly difficult. To address these challenges, I’ll present a new breakthrough in an old technique: photoelectron photoion coincidence spectroscopy (PEPICO). By teaching PEPICO a new trick, the ability to identify and reject false coincidences, we have extended its dynamic range by a factor of 100, promising a potent new method to unravel chemical reaction mechanisms. Host: Tim Steimle

Juan Alfonzo
Ohio State University  
Bridging the Gap between RNA Editing and Modification: 10-year Solution to a 25-Year Problem

Host: Julian Chen

Jing Yang
Epithelial-Mesenchymal Plasticity in Carcinoma Metastasis

During metastasis, epithelial tumor cells dissociate from each other, disseminate into the systemic circulation, and then establish secondary tumors in distant sites. A developmental program termed Epithelial-Mesenchymal Transition (EMT) is implicated in promoting the dissemination of single carcinoma cells during metastasis. Both the Twist and Snail families of transcription factors are key inducers of EMT and tumor metastasis. Using an inducible Twist1 mouse model, we show that activation of Twist1 is sufficient to promote carcinoma cells to undergo EMT and disseminate into blood circulation. Importantly, in distant sites, turning off Twist1 to allow reversion of EMT is essential for disseminated tumor cells to proliferate and form macrometastases. These data indicate that EMT is dynamically regulated during tumor metastasis: carcinoma cells undergo EMT to disseminate; once reaching distant site, they need to revert to an epithelial identity to form macrometastases. I will also present our ongoing studies that aim to understand how EMT is dynamically regulated in response to signals from the tumor microenvironment and from the intracellular machineries to impact EMT and tumor metastasis. Host: Jia Guo

David Baker
University of Washington  
Eyring Technical Lecture: Protein design for medicine and technology

The advances in de novo protein design described in my first talk are opening up many new exciting areas of application. I will describe our efforts towards designing next generation therapeutics, vaccines and functional nanomaterials with applications ranging from computing to light harvesting. Host: Neal Woodbury and Jeremy Mills
PSH 150
David Baker
University of Washington  
Eyring General Lecture: The Coming of Age of De Novo Protein Design

Proteins mediate the critical processes of life and beautifully solve the challenges faced during the evolution of modern organisms. Our goal is to design a new generation of proteins that address current day problems not faced during evolution. In contrast to traditional protein engineering efforts, which have focused on modifying naturally occurring proteins, we design new proteins from scratch based on Anfinsen’s principle that proteins fold to their global free energy minimum. We compute amino acid sequences predicted to fold into proteins with new structures and functions, produce synthetic genes encoding these sequences, and characterize them experimentally. I will describe the design of ultra-stable idealized proteins, flu neutralizing proteins, high affinity ligand binding proteins, and self-assembling protein nanomaterials. I will also describe the contributions of the general public to these efforts through the distributed computing project Rosetta@Home and the online protein folding and design game Foldit. Host: Neal Woodboury and Jeremy Mills

Malcolm Forbes
Bowling Green State University  
Photons, Radicals, Bubbles and Beer: Using Photochemistry and Electron Paramagnetic Resonance Spectroscopy to Understand the Universe

Our laboratory has a long-standing interest in the structure, reactivity, and dynamics of free radicals in both homogeneous and heterogeneous media. In this lecture, the basic tenets of steady-state and time-resolved (CW) electron paramagnetic resonance spectroscopy (SSEPR and TREPR) are explained, and their use in understanding the physical and chemical behavior of free radicals is outlined. Examples to presented include the use of stable nitroxide spin probes to investigate the drying and curing of architectural coatings, and to probe the physical properties structured (non-Newtonian) fluids at the molecular level. Chemical reactivity involving free radicals can be studied directly using TREPR, for example in the study of the mechanism for the lightstruck flavor (so-called “skunking”) of beer. Reactivity can also be investigated using spin trapping techniques. Two different trapping methods will be presented: nitrones can be used to confirm the mechanism of action of biocompatible polymer initiators, and the reaction of hindered amines with singlet oxygen can be used to quantify the kinetics and topology of such reactions in confined media. Finally, two applications of EPR spectroscopy to study molecular dynamics are presented: modulation of the exchange interaction in two Cu-Cu porphyrin dimers, and long-range radical-triplet state pair interactions in acrylic polymers in liquid solution. Host: Gary Moore

Wenwan Zhong
UC Riverside  
Chemical Tools for Study of Epigenetic Markers

Protein modifications such as methylation play important roles in regulation of gene transcription, strongly impacting cellular development, and they also respond to different stimulations leading to the development of pathological conditions.1 Synthetic receptors could provide diverse solutions for analysis of protein PTM, because their structures can be judiciously designed to provide selectivity against various modification situations and they are much cheaper and easier to be obtained than antibodies. They can be used to design sensors for specific recognition of methylated peptides; and can also act as the additives in the matrix of column separation for separation of the unmethylated and methylated peptides. Both directions have been explored by our group. A series of displacement sensors formed by various deep cavitands were employed to form a sensor array for detection of methylated peptides in solution and enzyme mix. The array was also applied for monitoring enzyme activity and screening for specific enzyme substrates. In addition, several synthetic receptors including tetrasulfonatocalixarene (CX4), cavitand, and cucurbit[7]uril (CB7) were used to separate histone peptides with or without methylation using capillary electrophoresis (CE). Our work proves the great potential of synthetic receptors in enabling the study of protein methylation. Host: Jia Guo


PSH 132
Tracy A. Schoolcraft
Shippensburg University  
So, do you miss teaching?

Faculty who take positions in administration are often asked “Don’t you miss teaching?” as an entry point for a conversation.  What do administrators do?  Why would a tenured faculty member respond to encouragement to apply for an administrative position?  What is the learning curve like for a first-time administrator?  How is life at universities other than ASU? Come and hear one person’s journey and ask questions to inform your own career path regardless of your plans.     Tracy Schoolcraft is the Associate Provost at Shippensburg University of Pennsylvania. In the Associate Provost role, she leads and manages new program development, program review, assessment, accreditation, and academic transformation initiatives; and participates in strategic planning and budgeting, enrollment management, student success, distance education, and institutional research initiatives; and interfaces with the faculty union. For the first eleven years in this position, she also served as Dean of Graduate Studies where she led the Graduate Council which approves graduate curriculum and policy. Thus far, she has overseen the development of the university’s first four engineering programs and first three professional doctorate programs.  Previously at Shippensburg, Tracy served as faculty member and Chair of the chemistry department. She has also been a faculty member at Millersville University and Gettysburg College. Tracy has held local leadership roles in the American Chemical Society, as well as national roles with the society’s Chemical Education Program Committee.  Among her academic achievements, she was a co-editor of the society’s book Physical Chemistry Curriculum Reform: Where Are We Now and Where Are We Going? Host: Scott Sayres

No seminar-spring break


Lan Cheng
Johns Hopkins University  
Relativity Throughout the Periodic Table: Scalar Relativity, Spin-Orbit Coupling, and Spin-Vibronic Interaction

Special relativity plays an important role in heavy-element chemistry and is also relevant in theoretical description of light elements when aiming at high accuracy. In this presentation, the role of relativistic effects in chemistry and spectroscopy is reviewed together with recent developments of relativistic quantum-chemical methods. The applicability of state-of-the-art relativistic quantum chemistry is demonstrated using selected example applications. Studies of low-lying electronic states for actinide-containing molecules are used as examples containing elements in the far reaches of the periodic table. In addition, high-accuracy calculations are presented for core-level spectroscopy involving elements cross the periodic table, including K-edge spectra for first-row elements, L-edge spectra for sulfur-containing compounds and M-edge spectra for Xenon-containing molecules. Host: Timothy Steimle

Ronald Zuckermann
Lawrence Berkeley National Lab  
New Biomimetic Nanomaterials at the Intersection of Structural Biology and Polymer Science

A fundamental challenge in materials science is to create synthetic nanoarchitectures that rival the structural complexity found in nature. A promising bioinspired approach is to synthesize sequence- defined polymer chains that fold into precise protein-like structures. In order to efficiently produce such information-rich polymer sequences, we use the automated solid-phase submonomer synthesis method to generate sequence-defined peptoid polymers up to 50 monomers in length. The method uses readily available primary amine synthons, allowing hundreds of chemically diverse sidechains to be cheaply introduced. We use this method, along with with computational modeling, to design, synthesize, assemble and engineer a variety of protein-mimetic nanostructures. Here we examine peptoid sequences that can form highly ordered supramolecular assemblies of nanosheets and nanotubes, and compare their molecular structures to the fundamental structures found in biology. Host: Neal Woodboury

Hannah Shafaat
Ohio State University  
Rebuilding Ancient Pathways: Model Metalloenzymes for Energy Conversion

Nature has evolved diverse systems to carry out energy conversion reactions. Metalloenzymes such as hydrogenase, carbon monoxide dehydrogenase, and acetyl coenzyme A synthase use earth-abundant transition metals such as nickel and iron to reversibly generate and oxidize small-molecule fuels such as hydrogen, CO, and acetate. These processes are implicated in chemoautotrophic origins of life and play a key role in the metabolisms of ancient bacteria and archaea. However, while these enzymes are highly functional within their native environment, most are costly to isolate, sensitive to external conditions, and generally poorly suited for large-scale application. Additionally, the multimetallic active sites and auxiliary cofactors obscure distinguishing spectroscopic features and render detailed analyses challenging. As a result, the molecular mechanisms of catalysis remain relatively poorly understood, thwarting efforts to build biomimetic synthetic systems that act with the efficacy of native enzymes. We have approached this problem from a metalloprotein engineering perspective. Azurin and rubredoxin are two of the most well studied proteins within the bioinorganic community. Both are robust platforms, known for their unique spectroscopic features and representative coordination geometries. By introducing non-native metals and redesigning the primary and secondary coordination spheres, we have been able to install novel activity into these simple electron transfer proteins, including catalytic hydrogen evolution, carbon dioxide fixation, and carbon monoxide activation. Optical, vibrational, and magnetic resonance spectroscopic techniques have been used in conjunction with density functional theory calculations to probe the active-site structures across different states in order to determine the catalytic mechanisms. These findings will be discussed in the context of identifying the fundamental principles underlying highly active native enzymes and applying those principles towards engineering effective model metalloproteins for energy conversion reactions. Host: Anne Jones

Daphne Klotsa
University of North Carolina  
A Touch of Non-Linearity at Intermediate Reynolds Numbers: Where Spheres “Think” Collectively and Swim Together

From crawling cells to orca whales, swimming in nature occurs at different scales. The study of swimming across length scales can shed light onto the biological functions of natural swimmers or inspire the design of artificial swimmers with applications ranging from targeted drug delivery to deep-water explorations. In this talk, I will present experiments and simulations of how oscillating spheres, universally simple geometric objects, can utilize non-linearities to demonstrate complex pattern formation in a granular system, or different swimming behaviors in a spherobot (robot made out of spheres) when placed in a fluid at intermediate Reynolds numbers, 1 < Re. Host: Nicholas Stephanopoulos

Brian Chait
 Rockefeller University
Towards a “Molecular Microscope” for the Cell

The myriad events that occur in living cells (replication, organellar assembly, transport, genome organization, transcription etc.) are to a large extent carried out through dynamic associations and assemblies of macromolecules. I will describe our efforts to develop and integrate sets of tools that are designed to throw light on the evolution, structure and function of these macromolecular machines. To do this, we are developing approaches for elucidating proximal, distal, and transient protein-protein interactions in cellular milieus, as well as for determining distance restraints between amino acid residues within large protein assemblies by chemical cross-linking and mass spectrometry. The long-term goal of this research is to develop what I loosely term a “molecular microscope” for defining cellular systems with scales spanning all the way from dimensions of the cell to atomic resolution of molecules. Host: Chad Borges

Bill Graves
ASU  Physics
Compact XFEL Light Source

We are pursuing development of a very compact XFEL based on inverse Compton scattering (ICS) from a nanopatterned electron beam. CXFEL depends on a novel method to produce transform-limited x-ray output in all dimensions, i.e., with all photons in a single degenerate quantum state. This method avoids the noise amplification of SASE by imprinting a well-defined coherent modulation on the electrons via diffraction in a thin crystal grating. The method allows for coherent control of the phase, frequency, bandwidth, pulse length and amplitude of the x-ray pulses, and enables a variety of 2-color or multi-color experiments with precisely tunable femtosecond delays for pump-probe experiments, and perhaps even sub-cycle phase-locking of the multiple colors. This source is ideal for emerging techniques such as coherent diffractive imaging, stimulated x-ray Raman spectroscopy and Fourier transform resonant inelastic x-ray scattering for studying molecular dynamics and correlated electron effects. Host: Neal Woodbury

William Shih
Harvard University  
DNA-Origami Barrels

DNA origami, in which a long scaffold strand is assembled with a large number of short staple strands into parallel arrays of double helices, has proven a powerful method for custom nanofabrication. Although diverse shapes in 2D are possible, the single-layer rectangle has proven the most popular, as it features fast and robust folding and modular design of staple strands for simple abstraction to a regular pixel surface. Here we introduce a barrel architecture, built as stacked rings of double helices, that retains these appealing features, while extending construction into 3D. We demonstrate hierarchical assembly of a 100 megadalton barrel that is ~90 nm in diameter and ~270 nm in height, and that provides a rhombic-lattice canvas of a thousand pixels each, with a pitch of 9 nm, on its inner and outer surfaces. Complex patterns rendered on these surfaces were resolved using up to twelve rounds of exchange PAINT super-resolution fluorescence microscopy. We envision these structures as versatile nanoscale pegboards for applications requiring complex 3D arrangements of matter. Host: Nicholas Stephanopoulos

Adam Barb
Iowa State University  
Asparagine-linked Glycosylation of Immunoglobulin G and the Fc γ Receptors Impacts Immune System Activation

Immunoglobulin G1 (IgG1) is the major circulating human antibody and also the primary scaffold for therapeutic monoclonal antibodies (mAbs). The interaction between IgG-coated targets and membrane-bound Fcy receptors (FcyRs) requires the presence of an asparagine-linked (N-)glycan on the Fc. Our laboratory determined the Fc N-glycan stabilizes a single polypeptide loop in a conformation compatible with FcyR binding and explains how changes to the Fc N-glycan termini affect affinity. N-glycans on the primary receptor responsible for the efficacy of mAbs, FcyRIIIa or CD16a, also impact antibody binding affinity. We isolated natural killer cells from peripheral human blood to determined that FcyRIIIa N-glycans represent minimally-processed forms that promote high affinity IgG1 Fc binding and are radically different from the N-glycans found on recombinant FcyRIIIa. Host: Xu Wang

Veterans Day-No seminar


Thomas Meade
Northwestern University  
Seeing is Believing: Coordination Chemistry and Molecular Imaging: A Marriage made In Vivo

MR imaging offers a non-invasive means to map structure and function by sampling the amount, flow or environment of water protons in vivo. Such intrinsic contrast can be augmented by the use of paramagnetic contrast agents in both clinical and experimental settings; however, these agents are typically anatomical reporters that label individual fluid compartments and distinguish tissues that are magnetically similar but histologically distinct. To permit a direct imaging of the physiological state of cells or organs, we have synthesized and in vivo tested new bio-activated MR imaging contrast probes that change their influence on nearby water protons in a conditional fashion. The agents modulate fast water exchange with the paramagnetic center, yielding distinct "strong" and "weak" relaxivity states and are modulated by two types of biological events: i. self-immolative enzymatic processing of the complex that is a reporter probe for lacZ (b-galactosidase and ii. binding of the intracellular messenger, Ca(II). These agents provide the ability to monitor gene expression and intracellular second messenger activity in the form of acquired 3D MR images. Host: Anne Jones

Ron Orlando
University of Georgia  
Challenges Associated with Glycoprotein Characterization: The More We Learn, the More We Realize How Much We Don’t Know

The ability to accurately quantitate the glycan chains attached to glycoproteins has wide-ranging implications. Numerous studies over the past 40 years have demonstrated that abnormal glycosylation occurs in virtually all types of human cancers, and show the potential of using glycan markers in either a diagnostic or a prognostic manner. The glycosylation on recombinant protein therapeutics is also known to have profound effects, with one of the better-known examples being the increased serum half-life of erythropoietin (EPO) resulting from glycoengineering. Hence, the quantification of glycoprotein glycans plays important roles from the discovery of new diagnostic/prognostic markers to the development of therapeutic agents. A particularly challenging aspect is the identification and accurate quantitation of low abundance glycans that are present as minor components in complex isomeric mixtures. We are developing analytical strategies to overcome the limitations encountered in traditional glycan profiling/glycomic analysis. The use of hydrophilic interaction liquid chromatography (HILIC) is a central component as this allows for the separation of isomeric glycan structures. To facilitate identification and discovery of low-level glycans, we have created a HILIC retention model for native glycans, peptides, and glycopeptides, which also facilitates the analysis of other hydrophilic post-translational modifications such as deamidation and isomerization. This presentation will highlight our approach and demonstrate its utility for the detection and quantitation of individual linkage isomers and other PTMs in complex mixtures such as human serum glycans and therapeutic IgGs. Host: Chad Borges

Richard Royce Schrock
Eyring Technical Lecture: Recent Advances in Olefin Metathesis by Molybdenum and Tungsten Catalysts

Advances in applications of the chemistry of Mo and W olefin metathesis catalysts in the last two years include the synthesis of monoaryloxide chloride imido catalysts, kinetically Z- or E-selective catalytic macrocyclic ring-closing metathesis, stereoselective (Z or E) olefin metathesis reactions that use electron-poor olefins (ClCH=CHCl and CF3CH=CHCF3), and ROMP reactions that yield cis,syndiotactic-A-alt-B copolymers from enantiomerically pure monomers. New applications rely on synthetic advances that include new approaches to monoaryloxide chloride complexes, to rare molybdenum oxo alkylidene complexes, and to previously unknown Mo=CHCl and Mo=CHCF3 complexes, which must be involved in reactions with the electron-poor olefins ClCH=CHCl and CF3CH=CHCF3. Host: Neal Woodbury
Richard Royce Schrock
Eyring General Lecture: A Discovery and a Nobel Prize 30 years Later

A catalytic reaction discovered in the 1960s allows one to break carbon-carbon double bonds and form new ones with remarkable ease. This "metathesis" reaction began to attract the interest of organic, inorganic, and polymer chemists because of its great potential in manipulating carbon-carbon bonds, which is a fundamental goal of organic chemistry. The metathesis reaction has continued to change how chemistry that involves carbon-carbon double bonds, in particular, is practiced in the laboratory and industry. In 1974 I was in the right place at the right time to make a discovery that helped us understand how this reaction works and have spent my career developing catalysts for it. In the process I also discovered catalysts that "metathesize" carbon-carbon triple bonds and one that will "break" the triple bond in dinitrogen (to give ammonia catalytically), a reaction that is crucial to all life on earth. Host: Neal Woodbury

Paul Cremer
Penn State University  
Metallomembranes: Exploring the Interactions of Metal Ions with Lipid Bilayers

Phosphatidylserine (PS) and phosphatidylethanolamine (PE) are major components of numerous cellular membranes. Both these lipids contain amine moieties in their head groups that can strongly interact with first row transition metal ions such as Cu2+. This is significant because copper is a redox active metal ion and causes lipid oxidation in the presence of oxidants such as hydrogen peroxide. To explore both the binding and oxidation chemistry of these systems, we have employed a combination of spectroscopic techniques (e.g. vibrational sum frequency and infrared spectroscopy), microfluidic platforms, fluorescence microscopy, as well as monolayer and planar supported bilayer architectures. This includes the development of a novel analytical tool that employs fluorescence quenching upon resonance energy transfer from a fluorophore to Cu2+ to quantitatively monitor metal ion binding at the bilayer surface. Both thermodynamic and molecular level details of these systems have been obtained. The results reveal that Cu2+ binding can be highly dependent on the concentration of PS within the membrane, the pH of the bulk solution, as well the ionic strength of the solution. Moreover, the presence or absence of various charged lipids can also greatly influence the binding properties. The interactions of transition metals with lipid membranes may play a role in neurodegenerative diseases such as Alzheimer’s as well as in Autism, where metal ion homeostasis is not maintained. Host: Jia Guo

Thomas E. Mallouk
Penn State University  
Assembly and Disassembly of Layered Materials

Layered solids – which have strong bonds in two dimensions and weaker links in the third - are interesting building blocks for materials and devices because they potentially offer control over structure at the molecular level. Our research in this area began with the question of whether such compounds could be built up one layer at a time in controlled sequences on surfaces. This was possible by using either molecular precursors, in the case of metal phosphonates, or exfoliated sheets derived from lamellar microcrystals. Many layered oxides consist of negatively charged sheets interleaved by exchangeable cations. These oxides are particularly amenable to exfoliation (and to other topochemical reactions) by simple ion-exchange and acid-base reactions. Recently we have found that van der Waals solids such as graphite, hexagonal BN, and MoS2 can also be intercalated and exfoliated without incurring damage to the sheets by means of acid-base and redox reactions. An interesting consequence of the layer-by-layer assembly processes is the overcompensation of the surface charge of nanosheets. This effect can be exploited to invert the layer charge of nanosheets (which is typically negative for sheets derived from early transition metal oxides) and enable the intercalation of negatively charged molecules and nanoparticles. While studying these reactions, we observed surprisingly strong bonding between late transition metal oxide nanoparticles and early transition metal oxide nanosheets. Calorimetric measurements and electronic structure calculations suggest that d-acid/base interactions – originally proposed by Leo Brewer to explain the anomalous stability of early-late transition metal alloys – contribute to the strength of nanoparticle/nanosheet covalent bonding. This finding helps us understand the strong metal support interaction (SMSI) in catalysis and provides a prescription for stabilizing catalytically active late transition metal nanoparticles. Host: Gary Moore

Qinghai Zhang
Scripps Research Institute  
Chemical Tools Enabled ABC Transporter Structural Studies

ATP-Binding Cassette (ABC) transporters constitute a large protein family that transport diverse molecules across cell membranes. These transporters play pivotal roles in normal physiology and drug pharmacokinetics and multidrug resistance. I will present recent structural studies of multidrug ABC transporters conducted in our lab and through collaborations, all enabled by the development of novel chemical tools including ligands and amphiphiles. These include X-ray crystallographic studies of MsbA and P-glycoprotein in complex with ligands and substrates as well as single particle electron microscopic analyses of the flexible conformations of these transporters. Structural and mechanistic insights into the conformational flexibility and ligand binding for these transporters will be discussed. Host: Wei Liu

Dennis Dougherty
California Institute of Technology  
Chemistry on the Brain: Understanding the Nicotine Receptor

The human brain is the most complex object known to man. It presents daunting challenges at all levels, from the anatomical, to the cellular, to the molecular. Our work seeks to provide a chemical-scale understanding of the molecules of memory, thought, and sensory perception; of Alzheimer’s, Parkinson’s, and schizophrenia. An area of particular interest has been the chemistry of nicotine addiction. The initial chemical event of nicotine addiction involves nicotine binding to and activating acetylcholine (ACh) receptors in the brain. Using the mindset and methodologies of physical organic chemistry, we have probed these complex membrane proteins with a precision and subtlety normally associated with small molecule studies. We have established that the cation-π interaction plays a pivotal role in promoting the high potency of nicotine in the brain, leading to its addictive properties. We have also discovered key hydrogen bonding interactions that uniquely contribute to the binding of nicotine to ACh receptors. These chemical studies provide a high-precision structural model for the interaction of potent drugs at brain receptors. Host: Jeremy Mills

Carlos Castro
Ohio State Universty  
Design and Control of Dynamic DNA Nanomechanical Devices

Structural DNA nanotechnology is a rapidly emerging field with exciting potential for applications such as single molecule sensing, drug delivery, and manipulating molecular components. However, realizing the functional potential of DNA nanomachines, and ultimately nanorobots, requires the ability to design dynamic mechanical behavior such as complex motion, conformational dynamics, or force generation. Our lab has developed approaches to design and construct DNA nanostructures with programmable 1D, 2D, and 3D motion as well as dynamic nanostructures with programmed or externally controlled conformational dynamics. We have also recently developed methods to manipulate dynamic DNA nanodevices via external magnetic fields. This approach relies on coupling the motion of micron-scale magnetic beads to nanoscale DNA machines via a long mechanical lever arm made from an array of highly stiff DNA origami structures. We demonstrated the ability to drive continuous or oscillating rotational motions up to several Hz. Moving forward, we aim to develop devices where nanoscale dynamic behavior (i.e. motion, conformational distributions, and kinetics) can be exploited to probe physical properties or manipulate nanoscale components or molecular interactions in real time. I will highlight two ongoing projects in our lab to develop DNA nanodevices to probe the structure and dynamics of nucleosomes and to engineer cell surface functions such as intercellular adhesion and biomolecule sensing. Host: Nicholas Stephanopoulos

Xin-Yun Huang
Weill Cornell Medical College, Cornell University  
Fascin, Filopodia and Tumor Metastasis

Tumor metastasis is responsible for ~90% of all cancer deaths. One of the key steps during tumor metastasis is tumor cell migration and invasion. However, currently there is no anti-migration drug in clinical uses. Filopodia are finger-like cell surface extensions that are critical for cell migration. Fascin is the main actin-bundling protein in filopodia. Metastatic tumor cells are rich in filopodia, and the numbers of filopodia correlate with their invasiveness. From cancer genomics, fascin gene is amplified in patients with many types of cancers. Studies on samples from cancer patients demonstrate that elevated levels of fascin are correlated with clinically aggressive phenotypes, poor prognosis, and shorter survival. Mouse genetic studies showed that deletion of fascin gene delayed tumor development, slowed the tumor growth, reduced metastatic colonization, and increased overall survival. Transgenic expression of fascin in mice increased the tumor incidence, promoted tumor progression, and decreased the overall survival. We have developed small-molecule compounds that specifically inhibit the biochemical function of fascin. Fascin inhibitors block tumor cell migration, invasion and metastasis. These inhibitors alone, in combination with surgery, chemotherapy, or immunotherapy, all prolong the overall survival of tumor-bearing mice. Host: Wei Liu
Don Seo
Arizona State University  School of Molecular Sciences
Porous Sol-Gel Metal Oxides for Sustainability Applications – From Bio/Nano Hybrid-Based Solar Energy Conversion to Carbon Capture

There is a great demand for developing new high-performance functional materials for human sustainability in the areas of energy, water, human health and global warming. Challenges are still overwhelming as any practical solutions would need to be as holistic as possible to avoid the tyranny of scale in the order of “mega” or “giga”. Considerable attention has been given to porous sol-gel metal oxides where introduction of a three-dimensional open pore network to the structure can realize new or efficient utilization of innate functionalities of the oxides. Relatively straightforward and scalable synthetic schemes make the materials an ideal candidate for large-scale production and applications. In this presentation, we will introduce two different types of new porous metal oxides and their applications. In the first part, it is demonstrated that transparent conducting metal oxides (TCOs) can be produced in a highly mesoporous or macroporous form through sol-gel-based synthetic routes, without compromising their surface-chemical, optical and electronic properties. The materials are further used to fabricate bio/nano hybrid systems in which DNA superstuctures and proteins are stabilized and can function. Reaction center proteins from purple bacteria could be embedded with cytochrome c protein in the macroporous TCO films and showed the largest photocurrent to date with a remarkable stability. In the second part, we introduce our recent synthetic effort in creating three kinds of new nanostructured aluminosilicate materials with different pore structures and physical dimensions, based on geopolymer gel chemistry. The new developments have led us to highly-crystalline hierarchical zeolites with an exceptional CO2 sorption kinetics, selectivity and regenerability and hence may realize cost-effective CO2 separation. Other materials have a great potential as a superb solid base catalyst in biodiesel production, high-performance reinforcing white fillers for rubber and an antibacterial silver zeolite agent with a superior efficacy against antibiotics-resistant bacteria. Host: Neal Woodbury

Xu Wang
Arizona State University  School of Molecular Sciences
New Insights from Old GAGs: Studies in Glycosaminoglycans and Their Protein Partners

Glycosaminoglycans (GAG) are a unique class of linear, sulfated polysaccharides produced by many organisms. In humans, GAG act as receptors for numerous signaling proteins, allowing the glycan to control vital cellular processes such as migration, differentiation and regeneration. However, the structure-activity relationships of GAG-protein interactions are rarely clear, nor is there any way to determine the fine structures of intact GAG chains. These deficiencies have hampered our understanding of GAG’s biological role. Our group focuses on investigating biophysical factors governing GAG-protein interactions as well as on developing techniques to determine fine structures of intact GAG chains. So far, we have studied several important GAG-binding proteins, including the pro-inflammatory chemokine RANTES, the Lyme disease bacterium adhesin decorin-binding protein and the mitogenic cytokine pleiotrophin. Our results revealed mechanisms GAG use to regulate activities of these proteins and explained how structures of these proteins’ control their interactions with GAG. In addition, these studies shed light on the diverse nature of GAG-protein interactions and provide insights into the dynamic and adaptable qualities of these glycan-protein complexes. Host: Neal Woodbury

Wade Van Horn
Arizona State University  School of Molecular Sciences
Dissecting the Polymodal Gating and Modulation of TRP Channels

Transient receptor potential (TRP) ion channels serve as polymodal regulated sensors, which are widely expressed in diverse tissues of higher organisms. This class of membrane proteins functions in diverse physiological roles in health and disease. As a result, TRP channels have emerged as a target for therapeutic intervention for diverse indications, including a number of significant pathophysiologies such as pain, cancer, and obesity. A subset of the TRP channel family senses biological temperature, where changes in thermal energy are converted to conformational change (work), a feature that is central to thermosensing and thermoregulation. In addition to functioning as molecular thermometers, these proteins are regulated by a variety of other stimuli including modulatory proteins, voltage, pH, chemical ligands, and lipids. This seminar will detail our efforts to untangle and understand the molecular mechanisms of TRP channel stimulatory integration and regulatory modes through structural, functional, and thermodynamic approaches. The data will focus on our studies of TRPV1 and TRPM8 ion channels and the emerging view of the mechanistic interplay in TRP channel structure and function. Host: Neal Woodbury

Steven Carr
Broad Institute  Proteomics Platform
Quantitative Proteomics in Biology and Medicine

A new era of quantitative biology enabled by mass spectrometry based proteomic technologies has arrived. We can now define the content, relative abundance, modification states and interaction partners of proteins in a dynamic and temporal manner on a near-global basis in organelles, whole cells and clinical samples, providing information of unprecedented detail. At the Broad Institute we are developing and applying these technologies in a wide array of studies including defining the subcellular locations of proteins in health and disease, connecting cancer genotype to molecular phenotype, unraveling the basis of the innate-immune response, identifying the mechanism of action of drug-like molecules and to discover and verify protein biomarkers of disease. I will present the results of several recent studies that convey a sense of the breadth and depth of application of modern proteomics to biology and medicine. Host: Chad Borges

Gerhard Wagner
Harvard Medical School  Department of Biological Chemistry and Molecular Pharmacology
Eyring Technical Lecture: Engineering Phospholipid Nanodiscs for Membrane Protein Studies

Biophysical studies of membrane proteins face multiple obstacles, including low expression yield, sample heterogeneity and the need for a membrane mimetic that resemble the native environment. When using NMR spectroscopy, additional problems are the large size of the systems and the need of incorporating stable isotope 13C, 15N and 2H. Micelles, or bicelles, which are frequently used for structural studies of membrane proteins, but have the disadvantage of the destabilizing effect of the detergents, in particular when the membrane proteins have water-soluble domains or interact with soluble proteins. Therefore, we embraced the use of phospholipid nanodiscs for membrane protein studies. Nanodiscs are patches of phospholipid bilayer surrounded by two copies of a membrane-scaffolding protein (Msp1), which is derived from apolipoprotein A1. We had shown that the Voltage-Dependent Anion Channel (VDAC1) can be inserted into nanodiscs and can be analyzed both in EM images and in NMR spectra. However, embedding was heterogeneous and prevented detailed NMR analysis. To address this problem and adapt nanodiscs to different size membrane proteins we first engineered Msp1 variants that yield nanodiscs at diameters of 9.5, 8.1, 7.8 and 6.8 nm, and we could determine an NMR structure of OmpX in the 8.1 nm nanodisc. However, the diameter distribution of these nanodiscs is rather wide. To further optimize nanodiscs, we developed procedures to covalently circularize the scaffolding protein and make nanodiscs of exactly defined diameters. We could extend the cND sizes from as low as 8 nm to as high as 50 nm each exhibiting a very narrow size distribution. We are able to insert membrane protein into the covalently circularized nanodiscs, record NMR spectra for smaller systems and obtain negative stain or cryo EM images from nanodisc-bound membrane proteins. We pursued applications from small mitochondrial membrane proteins to GPCRs and larger systems. Host: Neal Woodbury
6:30 PM
Gerhard Wagner
Harvard Medical School  Department of Biological Chemistry and Molecular Pharmacology
Eyring General Lecture: Solution NMR from a Chemist’s Tool to Solving Protein Structures

When I became interested in biophysics little had been done in protein NMR. Mainly chemists used NMR to check the success and purity of their reaction products. As undergraduate physics student at the Technical University of Munich, I had worked on Mössbauer effect studies hemoglobins and ferredoxins. While this technology yields spectra with a small number of resonance lines, I learned that NMR spectroscopy of the same class of proteins could yield spectra with numerous resonances as was shown at Bell Labs in the Shulman group. The discoverer of the paramagnetically shifted heme resonances, Kurt Wüthrich had just moved to the ETH in Zürich, and I decided to join his group as a graduate student. Thus, I entered the field of protein NMR at an early stage. First, I focused on internal motions of proteins and discovered that aromatic side chains of the basic pancreatic trypsin inhibitor (BPTI) rotate fast or slowly depending on their location, and NMR could measure rotation rates. Fast ring flipping was unexpected since aromatic side chains appeared rigidly oriented in the high-resolution crystal structures becoming available at that time. With new NMR instruments available I developed procedures for sequentially assigning the entire 1H NMR spectrum of BPTI, the first NMR assignment of a protein, and it appeared possible that with a skillful use of the nuclear Overhauser effect (NOE) it should be possible to determine protein structures with NMR. However, the first structure of BPTI I determined together with Werner Braun was of very low resolution due to the lack of better reconstruction software and was never published. When more powerful software packages were developed by Werner Braun and Tim Havel, I determined the structure of the protein metallothionein-2, which appeared entirely different from a X-ray structure of the same protein just published in Science; however, after much checking our NMR structure was found to be correct. After my time at the ETH I moved to the University of Michigan where we developed the first 1H-15N-13C triple resonance experiments and also started to measure 13C and 15N relaxation rates to characterize backbone dynamics of proteins. In 1990 I moved to Harvard Medical School and became very interested in tackling biological problems including proteins related to T-cell activation. Soon I became interested in translation initiation, and my group determined structures of several proteins that play key roles in protein synthesis. Subsequently, we discovered small molecule inhibitors of translation initiation that have anti-tumor activity, and we still pursue this research activity. More recently, my group focused on membrane proteins and we developed new procedures for covalently circularizing membrane scaffolding proteins to create well-defined membrane surrogates for structural and functional studies of membrane proteins. Host: Neal Woodbury

Steven A. Soper
University of Kansas  Department of Chemistry
New Tools for Liquid Biopsies: Microfluidic Platforms for the Efficient Isolation and Molecular Profiling of Circulating Tumor Cells (CTCs), Cell Free DNA (cfDNA) and Nanovesicles (Exosomes)

Liquid biopsies are generating great interest within the biomedical community due to the simplicity for securing important biomarkers to manage complex diseases, such as many of the cancer-related diseases. These circulating markers consist of CTCs, cfDNA and exosomes. We are developing a suite of microfluidic devices that are can process whole blood directly and engineered to efficiently search for a variety of disease-associated liquid biopsy markers from divergent subpopulations comprising the tumor microenvironment that can supply complementary clinical information. Each microfluidic device can isolate the target with recovery >90% and sufficient purity (>80%) to enable downstream molecular analysis of the particular biomarker. The microfluidic devices are made from thermoplastics via injection molding to allow for mass-production of devices with tight compliancy to accommodate clinical implementation. In this presentation, information will be shared on the operational parameters of these devices for the selection of liquid biopsy markers, and the downstream molecular information that can be garnered from the isolated markers in diseases such as colorectal, ovarian, breast, pancreatic and prostate cancers as well as some of the liquid-based cancers (acute myeloid leukemia). Host: Jia Guo

Scott Fraser
University of Southern California  Biological Sciences and Biomedical Engineering
Eavesdropping on the Signals, Lineages and Motions that Build Embryos

The challenge of modern embryology is to draw upon the growing body of high-throughput molecular data to better understand the cellular and molecular events underlying embryonic development. This wealth of data now presents the challenge of integrating a working knowledge of how these molecular components, often present at vanishingly small concentrations, generate reliable patterns of cell migration and cell differentiation. In typical cell biology approaches, cultures of isolated cells have been used reveal mechanism. What is needed to understand development is to carry out studies on cells in their normal context interacting with other cells and signals in the intact embryo. Imaging techniques are challenged by major tradeoffs between spatial resolution, temporal resolution, and the limited photon budget. We are attempting to advance this tradeoff by constructing faster and more efficient light sheet microscopes that maintain subcellular resolution. Our two-photon light-sheet microscope, combines the deep penetration of two-photon microscopy and the speed of light sheet microscopy to generate images with more than ten-fold improved imaging speed and sensitivity. As with other light sheet technologies, the collection of an entire 2-D optical section in parallel offers dramatically speeds acquisition rates. By adopting two-photon SPIM is far less subject to light scattering, permitting subcellular resolution to be maintained far better than conventional light sheet microscopes. The combination of attributes permits cell and molecular imaging with sufficient speed and resolution to generate unambiguous tracing of cells and signals in intact systems. Multispectral imaging offers the chance of asking multiple questions of the same embodied cells. Multiplex analyses permit the variance and the “noise” in a system to be exploited by asking about the analytes that co-vary with a selected gene product. These approaches allow straightforward prediction of draft gene regulatory networks. In parallel, label-free approaches offer an important approach for molecular sensing, but the low concentrations and low sensitivity of the techniques can make single cell approaches challenging. We have refined a new technology for enhancing these signals and have achieved gains that make the analysis of single cells possible. Host: Jia Guo

Angela Gronenborn
University of Pittsburgh School of Medicine  
Synergy Between NMR, Cryo-EM and Large-Scale MD Simulations - An All Atom Model of a Native HIV Capsid

HIV and other retroviruses use a Trojan horse style of infection, taking advantage of a cloak that shields its genome till the time is ripe to open the shield. Once HIV gets inside the cell, it takes over the cellular machinery, turning it into a factory for its own reproduction. This entails a derailment of the normal host defense pathways, rendering HIV resistant to cell-mediated destruction responses. In mature HIV-1 particles a conical-shaped capsid core encloses the viral RNA genome. Using the high-resolution NMR structure of the CA C-terminal domain (CTD) dimer permitted the construction of a model for a tubular CA assembly that fit extremely well into the cryoEM density map. A novel CTD-CTD interface at the local three-fold axis in the cryoEM map was identified and confirmed to be essential for function by mutagenesis. Refinement by large-scale molecular dynamics (MD) simulation permitted the construction of all-atom models for the hexamer-of-hexamer and pentamer-of-hexamer elements which, in combination with cryo-electron tomography (Cryo-ET) of a native HIV-1 core, allowed us to derive a realistic all-atom model for the entire capsid. Furthermore, we also showed that solution and solid state NMR chemical shifts can successfully guide cryoEM structure model refinement by MD. Host: Xu wang

Yossi Weizmann
University of Chicago  Department of Chemistry
Synthetic Nucleic Acid Topology and Colloidal LEGO-Like Nanoparticles for Biological and Plasmonic Applications

The iconic double helical structure of DNA has excited the imagination of both scientists and non-scientists for more than six decades. In recent times, the programmable nature of DNA has redefined its use as a powerful building material for the construction of precisely defined 2D and 3D nanoscale assemblies. The term “DNA structure” combines the chemical, stereochemical and biological advantages into one focus that can be applied to a wide range of scientific fields. The Weizmann group aims to demonstrate novel approaches that take DNA philosophy to a new level, with the potential application of DNA structure in biology, material science and nanomedicine studies. We focus on the fundamental design, functions and applications of highly programmable nucleic acids nanostructures. Our main research objective is the development of novel strategies and approaches providing versatile tools to form composite, nano-scaled, precisely-controlled structures and ultra-sensitive DNA machineries. The following research fields will be represented: (a) Design and applications of novel synthetic molecular topologies from programmable nucleic acids and their biological consequences for enzyme mechanisms, drug discovery, and drug delivery. (b) Synthesis of programmable assemblies of colloidal LEGO nanoparticles with specific and anisotropic bonding directionality for applications in self-assembly, plasmonics, and photothermal energy conversion for nucleic acids amplification. Host: Hao Yan

No Seminar-Spring Break


Sharona Gordon
University of Washington  Physiology & Biophysics
Chemistry at the Membrane: Unnatural Approaches in a Natural Setting

The study of ion channel and transporters is at a technological apex, with high-resolution structural studies using cryoEM joining better-established high-resolution functional studies with patch-clamp electrophysiology. Limitation of these approaches, however, have left a gap in our understanding of membrane protein dynamics, particularly outside the ion-conducting pore. Using amber codon suppression to introduce a fluorescent, noncanonical amino acid along with transition metal ion FRET, we have developed a system to measure short-distance rearrangements within a membrane protein in a native cellular environment. This approach has the power to reveal the mechanisms of agonist-dependent activation and inactivation in the pain-transducing ion channel TRPV1. Host: Wade Van Horn

Gerald Meyer
University of North Carolina at Chapel Hill  Department of Chemistry
Dye-Sensitization for Sustainable Energy

There exists a critical need to identify materials that can be utilized to convert sun light into a sustainable energy source. A molecular approach has been to sensitize wide bandgap semiconductor mesoporous thin films to visible light with dyes. Such dye-sensitized nanostructures can provide electrical power generation as well as gaseous hydrogen fuel through water splitting. This presentation provides an overview with recent highlights of research directed towards sustainable electrical power and solar fuel generation. Dye-sensitized solar cells have received considerable attention since the advent of mesoporous TiO2 thin films described by Grätzel and O’Regan [1]. Recently a kinetic pathway for electron transfer from the semiconductor to the oxidized dye was identified through the rational design of molecules where the distance and driving force were held near parity and only a bridge unit was varied [2]. These molecules were comprised of a Ru chromophore linked through a rigid xylyl- or phenyl- thiophene bridge. Spectroscopic analysis revealed that electronic coupling through the phenyl bridge was a factor of ten greater than through the xylyl bridge. Taken together the data indicated an interfacial electron transfer pathway by a super-exchange hole-transfer mechanism. Visible water splitting has been demonstrated for chemically linked Ru(II) polypyridyl chromophore-catalyst molecules in dye-sensitized photoelectrosynthesis cells [3]. In these cells, water oxidation requires the absorption of four photons and transient absorption measurements have provided insights into the first two light driven steps with both nanocrystalline TiO2 and core-shell SnO2-TiO2 electrodes. An interesting observation was that light excitation of the mixed-valent molecule, [RuII-RuIII-OH2]5+, at pH = 1 resulted in excited state injection followed by a slow one electron, two proton transfer reaction that occurred on the seconds time scale: TiO2|-[RuIII-RuIII-OH2]5+ TiO2|-[RuII-RuIV=O]3+ + 2 H+. Under more alkaline conditions, electrolyte buffers enhance water oxidation by a proposed atom-proton transfer reaction. The importance of proton coupled electron transfer reactions for light driven water oxidation as well as the utility of core-shell nanostructures for charge recombination inhibition will be discussed. Host: Gary Moore

No seminar-Visitation Weekend


Tijana Grove
Virginia Polytechnic Institute and State University  Chemical Biology, Biomaterials, Bioanalytical
Protein Engineering – From Nature to Nanotechnology

Proteins and protein assemblies are the biological workhorses that carry out vital functions in all living organisms. The Grove lab is interested in translating fundamental knowledge and principles of how proteins operate in nature to the growing field of nanotechnology for the design of multifunctional materials. This seminar will focus on materials for tissue-device interfaces and materials for sensing and catalysis. Host: Giovanna Ghirlanda

Umesh R. Desai
Virginia Commonwealth University  Institute for Structural Biology, Drug Discovery and Development
The Interplay of Specific and Non-Specific Interactions of Glycosaminoglycans in Modulation of Human Physiology

Glycosaminoglycans (GAGs) affect human physiology and pathology by interacting with more than 500 proteins. These interactions do not involve a particular GAG sequence but thousands of sequences. In fact, the bounty of millions of GAG sequences generated by nature’s biosynthetic machinery is likely to contribute in an important way. However, GAG-protein interactions have been generally assumed to be ionic, non-specific, and not of much value. Specific interactions do exist and can lead to discovery of therapeutic agents but the science of identification of such specific interactions is still in its infancy. This talk will present aspects of identifying specific and non-specific interactions with the goal of discovering therapeutics of use in cancer, thrombosis, and other diseases. Host: Xu Wang

Hanadi Sleiman
McGill University  Department of Chemistry
DNA Nanostructures for Cellular Delivery of Therapeutics

DNA nanotechnology can assemble materials on the nanoscale with exceptional predictability and programmability. In a sense, this field has reduced the self-assembly space into a simple ‘language’ composed of four letters (A, T, G, C). Nature, on the other hand, relies on many more supramolecular interactions or ‘languages’ to build its functional structures. Over the last 50 years, supramolecular chemistry has taken advantage of these interactions to assemble materials with highly diverse structures and functions. This talk will summarize our efforts to merge the field of supramolecular chemistry with DNA nanotechnology. This approach results in new motifs and functionalities that are unavailable with base-pairing alone. Starting from a minimum number of DNA components, we create 3D-DNA host structures, such as cages, nanotubes and micelles, that are promising for targeted drug delivery. These can encapsulate and selectively release drugs and materials, and accomplish anisotropic 3D-organization. We find that they readily enter mammalian cells, resist nuclease degradation, they silence gene expression to a significantly greater extent than their component oligonucleotides and have a favorable in vivo distribution profile. We designed a DNA cube that recognizes a cancer-specific gene product, unzips and releases drug cargo as a result, thus acting as a conditional drug delivery vehicle. We will also describe a method to ‘print’ DNA patterns onto other materials, thus beginning to address the issue of scalability for DNA nanotechnology. Finally, we will discuss the ability of small molecules to reprogram the assembly of DNA, away from Watson-Crick base-pairing and into new motifs. Host: Nicholas Stephanopoulos

Vincent Remcho
Oregon State University  Department of Chemistry
Low-Cost Diagnostics Enabled by Novel Hybrid Microsystems

Microfluidic paper-based analytical devices (μPADS) have drawn much interest as platforms for analysis in a variety of complex biological and environmental systems. μPADS offer many advantages including low cost, high surface area to support capillary and sorptive action, reagent compatibility, and widespread availability. Plastic materials likewise have gained popularity and seen widespread application owing to their optical properties, solvent compatibility, and structural integrity. Fabrication methods are many and varied; the most compelling methods enable rapid prototyping. No single material is perfect, though; drawbacks in building microfluidic devices include high production cost, difficult post processing, unstable reagents, poor biocompatibility and non-biodegradability. We are working to address these problems by designing and building hybrid (open channel/wicking; glass microfiber/paper/plastic) devices with both on-and offline detection protocols. In most instances, a biocompatible material widely used in the pharmaceuticals industry with nearly ideal working properties enables our devices: polycaprolactone (PCL). We will share an update on our progress using PCL as a hydrophobic barrier in porous media (such as paper), an adhesive agent (for layering dissimilar materials), and a structural element (in multilamellar architectures). Hybrid microfluidic devices comprising both open channels and paper wicking regions were modeled, designed, prepared and applied for several assays, including colorimetric diagnostic assays for clinical biomarkers such as glucose, bilirubin, and creatinine as well as environmental markers of fracking fluid and heavy metal ions in environmental and biological samples. Assay results were analyzed using a smartphone and a custom application for detection, data handling, quantitative and statistical analysis, and data sharing without the need for a computer or network connection, and using custom-built devices of a form factor that is readily accommodated in a standard plate reader. Host: Mark Hayes

Rebecca Schulman
Johns Hopkins University  Chemical and Biomolecular Engineering
Dynamic, Reconfigurable Materials and Nanostructures Built with DNA

Materials within living systems have a complex structure that constantly reorganizes in order to continue to function reliably as the environment changes. Commonly, this structure arises because a simple set of components are assembled and reorganized by control over assembly kinetics, sensors and signal transduction cascades that translates information about the state of the environment to direct assembly and reorganization processes. These rules not only allow a material to take on a particular number of fixed states but also, through feedback between the environment and the assembly process, adapt to its surroundings and improve its function. For example, tubulin can be organized into cilia, fibrous networks or machines such as the spindle, and the extracellular matrix, an extended matrix composed of a relatively small number of principle protein components, is continually growing and being digested and remodeled in response to interaction with cells within a tissue. Could we build materials that can, like biological materials, respond and adapt in a myriad of ways to multiple features of the environment? Such responsiveness could lead to the design of soft robots, self-healing materials, or biomaterials that can continue to improve their function over time. To build such materials we need both structural components that can receive signals from the environment in chemical form and respond to these signals in ways that can be combined to engineer complex global behaviors. I’ll describe work in my laboratory toward building a range of DNA nanostructures that can interpret the shape of the physical environment through kinetic engineering of assembly processes, and that can dynamically respond to a range of environmental signals using different sets of local rules for assembly, disassembly and reorganization. I’ll also show how we can build “online” molecular circuits that can respond to inputs, time multistage responses and enable feedback between the state of the circuits and the state of the material. Finally, the ability to readily functionalize DNA-based materials and integrate them with other chemical components allows us to translate these ideas into the design of functional systems. Host: Hao Yan

Veteran's day- no seminar


Thomas R Cech
University of Colorado Boulder  Department of Chemistry and Biochemistry
Eyring Technical Lecture: LncRNAs, Histone Modification, and Epigenetic Silencing in Cancer

Polycomb repressive complex 2 (PRC2) is a multi-subunit complex, catalyzing trimethylation of H3K27 of nucleosomes. Such methylation marks promote epigenetic silencing of chromatin during embryonic development and cancer. Long noncoding (lnc) RNAs have been suggested to recruit PRC2 to its sites of action on chromatin. By studying the binding of PRC2 to RNA in vitro and in vivo, we and others have found that it binds RNA promiscuously – almost any RNA will bind. Yet we also find some special RNAs that have huge differences in affinity. How can we reconcile these observations, and what might they mean for epigenetic silencing? Host: Neal Woodbury and Julian Chen
Thomas R. Cech
University of Colorado Boulder  Department of Chemistry and Biochemistry
Eyring General Lecture: The Long Road to Precision Medicine: How Mutations Activate an “Immortality Gene” and Help Drive Cancer

The practice of medicine has continually evolved towards greater precision. Now in the last decade, the availability of genomic and other –omic information has provided the opportunity for a quantum leap in precision. Yet the road towards precision medicine is long, and many obstacles interfere. Dr. Cech will give an example involving his own work on telomerase, which may perhaps contribute to more precise cancer treatment in the future. Host: Neal Woodbury and Julian Chen

Jeffrey Esko
University of California at San Diego  Department of Cellular and Molecular Medicine
Ups and Downs of Heparan Sulfate

All cells are covered by a glycocalyx. Multiple types of glycoconjugates make up the glycocalyx, including glycoproteins, glycolipids, and proteoglycans. Many of the proteoglycans contain heparan sulfate, a type of glycosaminoglycan. The heparan sulfate proteoglycans (HSPGs) interact with many cell surface receptors and secreted proteins and play fundamental roles in cell proliferation, differentiation, and organ development and physiology. The HSPGs are dynamic, undergoing shedding at the cell surface and endocytosis with subsequent lysosomal degradation. Degradation is an orderly process, involving a series of enzymes that process the non-reducing end of the chain. Patients deficient in any of the degradative enzymes results in Mucopolysaccharidoses (MPS), a subclass of lysosomal storage disorders. The non-reducing ends of the glycans that accumulate provide a set of biomarkers and allow diagnosis of MPS, monitoring of therapy, and discovery of novel enzymes in the pathway. Normally considered a neurodegenerative disorder, recent data shows that the MPS also results in neurodevelopmental defects. Techniques for treating MPS consist of symptomatic care and enzyme replacement therapy (ERT). ERT has proven useful for treating the somatic aspects of the disease, but its utility for treatment of neurological aspects of the disease is limited by the blood brain barrier. A new technique for enzyme delivery based on conjugation of recombinant enzyme to a carrier glycoside allows delivery of enzyme to lysosomes by way of cell surface proteoglycans. Nose-to-brain delivery is enhanced by glycoside conjugation, based on restoration of enzyme activity and reduction of pathological biomarker. Host: Xu Wang

Jonathan Sweedler
University of Illinois  Department of Chemistry
The Chemical Characterization of the Brain: from New MS-based Measurement Tools to New Insights

In the postgenomic era, one expects the suite of chemical players in a brain region to be known and their functions uncovered. However, many cell-to-cell signaling molecules remain poorly characterized and for those that are known, their localization and dynamics are oftentimes unknown. A suite of small-scale measurement approaches are described that allow the investigation of individual neurons and small brain regions; these approaches include capillary scale separations, direct mass spectrometric-based profiling and mass spectrometry imaging. A key to successful measurement involves optimized tissue and cell sampling protocols. Depending on the sample being assayed and metabolites being measured, we use mechanical isolation, optical tweezers, patch pipettes, dialysis probes and microfluidics, all of which have advantages for specific experimental goals and samples. Several applications of single cell microanalysis are highlighted including the discovery of unusual metabolites to characterizing the peptides in single cells. Single cell assays allow differences in the metabolomics and peptidomics from supposedly homogeneous populations of cells to be explored. As a further example, a unique matrix assisted laser desorption / ionization time of flight mass spectrometry approach is used to probe thousands of endocrine cells for their neuropeptide content. Current technology efforts involve extending the depth of metabolome coverage and adapting our approaches to high throughput single cell assays. By obtaining information from tens of thousands of individual cells, rare cells are found and subtle differences in cell populations can be measured. Imaging mass spectrometry and dynamic sampling of the extracellular environment also provide a functional context for the discovery of novel cell to cell signaling molecules. Our overarching goal is to uncover the complex chemical mosaic of the brain and pinpoint key cellular players in physiological and pathological processes. Host: Jia Guo

Greg Gillen
National Institute of Standards and Technology (NIST)  
Surface and Trace Chemical Analysis Using SIMS and Ambient Mass Spectrometry for Homeland Security and Forensics

Several years ago we began a pilot study at the National Institute of Standards and Technology (NIST) to explore the potential use of cluster SIMS for spatially resolved analysis of contraband materials (explosives and narcotics). These experiments led to the growth of a new research program focused on the development and optimization of surface trace chemical analysis techniques for characterization of contraband materials to support civil aviation and military checkpoint security screening applications as well as forensics. This metrology and standards program has evolved to include the use of cluster SIMS on both magnetic sector and TOF SIMS instruments as well as various ambient ionization mass spectrometry approaches. In addition, we make use of various complementary techniques including optical, surface enhanced Raman and ion mobility spectrometry. Technique development and optimization, especially for ambient MS techniques, is supported by a range of novel flow visualization and high speed video microscopy techniques. This presentation will provide a look “inside” the science of trace contraband detection technologies with an emphasis on measurement tools, standards and protocols we have developed in our laboratory. Included in the presentation will be a discussion of the critical role of standards in homeland security, the application of SIMS and related techniques to address problems in forensics and homeland security including trace drug analysis, chemical imaging, age dating of fingerprints and analysis of narcotics, explosives, paints and gunshot residues. Finally, we will provide a description of the production of test articles including simulated fingerprints produce by 3D printing and chemical standards containing explosives, narcotics, drugs and gunshot residues that are fabricated using advanced materials deposition inkjet printer systems. Host: Peter Williams

Chang-Guo Zhan
University of Kentucky  
Understanding Molecular Mechanisms of Biological Processes and Developing Novel Therapeutics via Integrated Computational and Experimental Studies

In this talk, I will first briefly discuss the general strategies and integrated computational-experimental approaches used to understand the detailed molecular mechanisms of increasingly complex biological systems (such as those related to cancers, HIV virus, neurodegenerative diseases, inflammation, cardiovascular diseases, and drug addiction) and perform mechanism-based design, discovery, and development of novel drugs. I will also discuss the general trend of rational drug design and discovery through specific examples of our integrated efforts from understanding molecular mechanism to clinical development. The presentation will show how powerful understanding the detailed molecular mechanism and mechanism-based computational design are in the current drug design, discovery, and development. The integrated computational-experimental approaches are of great value not only for small-molecule drug discovery, but also for discovery and development of novel therapeutic proteins. Integrated computational-experimental drug design and discovery efforts have led to exciting discovery of promising drug candidates, including our designed novel drugs in Phase II clinical trials; one has received the Breakthrough Therapy Designation by the FDA. Host: Wei Liu

Catherine Murphy
University of Illinois at Urbana-Champaign  Department of Chemistry
Surface (Bio)Engineering of Gold Nanorods

The promise of nanotechnology encompasses the energy, health care, defense, and chemical manufacturing sectors of the global economy. Gold nanorods are a class of nanomaterials that have tunable optical properties depending on particle shape, and these optical properties are key to sensor and imaging technology that directly impact these sectors of the global economy. In this talk I will detail how these nanomaterials are made and characterized; how the surface chemistry can be tuned to manipulate nanomaterial properties; and how the nature of the nanomaterial surface influences biological response at the molecular, cellular, and ecosystem levels. Host: Dan Buttry

Tracy Handel
University of California at San Diego  UCSD Skaggs School of Pharmacy & Pharmaceutical Sciences
Structure, Activation and Inhibition of Metastasis-Promoting Chemokine Receptors

What do structures tell us about chemokine receptor activation and antagonism? Chemokine receptors are G Protein-Coupled Receptors (GPCRs) best known for their role in controlling cell migration in the context of immune system function. However, inappropriate regulation of chemokine-mediated processes contributes to the pathology of many diseases. Although CXCR4 plays a role in numerous inflammatory diseases and is an HIV co-receptor, it is best known as one of the most important chemokine receptors involved in many aspects of cancer, particularly cancer metastasis. As such, it has become an important oncology target both for directly inhibiting tumor growth and metastasis and for blocking the development of an immunosuppressive microenvironment to achieve better efficacy with chemo- and immunotherapy. We recently solved the structure of chemokine receptor CXCR4 in complex with the viral chemokine vMIP-II. Along with additional data, it formed the basis for experimentally guided models of several other receptor chemokine complexes including CXCL12 with CXCR4 and ACKR3, a trio of proteins that work together to promote the cancer phenotype. In this presentation, I will describe these structures, as well as experimental data that reveals a path of interconnected residues between chemokine binding on the extracellular face of the receptor, and the intracellular face where G proteins bind. These structures along with structures of chemokine receptors with small molecule antagonists reveal the extra challenges that these receptors pose as drug targets relative to other GPRCs as well as strategies for inhibiting them. Host: Wei Liu

Yi Lu
University of Illinois  Department of Chemistry
Design and Selection of Metalloenzymes and their Applications as Biocatalysts in Alternative Energies and as Biosensors in Environmental Monitoring, Medical Diagnostics and Imaging

Metalloenzymes play important roles in numerous biological processes. Designing metalloenzymes is an ultimate test of our knowledge about metalloenzymes and can result in new biocatalysts for practical applications such as in alternatives energies. We have been focusing ways to design heteronuclear metalloenzymes involved in multiple electron redox processes, such as heme-copper oxidase, heme-non-hem iron nitric oxide reductase and heme-[4Fe4S] cluster sulfite reductase. In the process, we demonstrate, while reproducing the primary coordination sphere may be good enough to make structural models of metalloproteins, careful design of the non-covalent secondary coordination sphere interactions, such as hydrophobicity and hydrogen bonding interactions, including those involving waters, are required to create functional metalloenzymes with high activity and turnover numbers comparable to those of native enzymes. While metalloproteins have been the major focus of metalloenzyme research for decades, metallo-DNAzymes, DNA molecules containing metal ions at the active site and displaying enzymatic activities, have emerged as a new class of metalloenzymes. We have been using in vitro selection to obtain from a large DNA library DNAzymes that are specific for metal ions and use spectroscopic methods to elucidate how and why DNAzymes can recognize metal ions selectively. We have also converted these DNAzymes into highly sensitive and selective sensors for metal ions, including those metal ions that are difficult to design using other methods, and demonstrated their applications in environmental monitoring, food safety, and medical diagnostics. The use of these metal-DNAzymes for imaging metal ions in living cells has also been established. Host: Jeremy Mills

Arjan van der Vaart
University of South Florida  Department of Chemistry
Probing (protein-) DNA Conformational Dynamics by Computer Simulations

DNA-binding proteins exploit subtle sequence-dependent differences in DNA flexibilities for binding, and DNA flexibility also plays a role in the recognition of methylated and damaged DNA. We have developed efficient methods to systematically assess the free energy cost of bending and other DNA deformations from computer simulations. Applications of these methods have helped quantify and rationalize the thermodynamics of bare and protein-bound DNA bending and its role in binding, and revealed important differences in inherent flexibilities between normal, methylated and damaged DNA. We will also discuss recent advances in the confinement method, and show that this technique holds great promise for assessing free energies between wildly different chemical or conformational states. Host: Jeff Yarger and Marcia Levitus

David C. Muddiman
North Carolina State University  Department of Chemistry
Innovative Chemistries and Technologies to Read the Complex Language of Biology

Mass spectrometry offers the most robust platform to discover and characterize biological species across all molecular classes, including xenobiotics. We developed bioanalytical tools to characterize structurally challenging analytes that are critical to a systems-level analysis. To increase the electrospray response of N-linked glycans, we synthesized novel hydrophobic tagging reagents which have the added benefit of being able to incorporate a stable-isotope label for relative quantification experiments (INLIGHTTM). Furthermore, we developed a novel ionization technique for tissue imaging of lipids, metabolites, and bioactive peptides (IR-MALDESI). These innovative strategies will be presented in the context of ovarian cancer and treatment and adherence of HIV drugs. Host: Jia Guo

Robert Fischetti
Argonne National Laboratory  X-ray Science Division
The Bright Future for Macromolecular Crystallography on 4th Generation Storage-Ring Based Sources

The development of microcrystallography capabilities on 3rd generation storage-ring based sources has enabled the determination of many important biological problems to atomic resolution. Some of the recent developments that have improved data quality, reduced primary radiation damage at liquid nitrogen temperatures, or improved user friendliness include: user-selectable micro-beams, raster mapping, vector data collection, shutter-less data collection, multiple crystal strategy and SONICC alignment of crystals. The Linac Coherent Light Source, an XFEL, has also driven the development of new technologies and enabled “serial crystallography.” These new technologies such as viscous jet sample injectors are now being implemented on storage-ring-source beamlines. Another very exciting but controversial topic is the potential for outrunning secondary radiation damage at room temperature at storage-ring sources. In the near future, 4th generation storage-ring sources based on multibend achromatic (MBA) lattices will increase brightness by at least two orders of magnitude. In this talk, I will present the current state of microcrystallography and the potential game-changing future for structural biology enabled by the APS-MBA source. Host: Wei Liu

Dennis Salahub
University of Calgary  
Beyond Structure - Molybdenum Carbide Nanoparticles as Catalysts for Oil Sands Upgrading - Between Clusters and the Bulk

My talk will focus on reactions catalyzed by transition-metal-containing nanoparticles. I will show that, under working conditions (in the context of oil sands upgrading), it is necessary to go beyond the concept of structure, minima on a potential energy surface, to include dynamics, entropy and free-energy surfaces. I will describe a multiscale modelling approach to study benzene hydrogenation on molybdenum carbide nanoparticles (MCNPs) [1]. The QM DFTB method is coupled with an MM force field to yield a quantum mechanical/molecular mechanical (QM/MM) model describing the reactants, the nanoparticles and the surroundings. Umbrella sampling (US) is employed to calculate the free energy profiles for benzene hydrogenation in a model aromatic solvent under realistic conditions. Comparisons are made with traditional methodologies; the results reveal new features of the metallic MCNPs. Under working conditions, rather than being rigid, they are very flexible due to the entropic contributions of the MCNPs and the solvent, which greatly affect the free energy profiles. Host: Dmitry Matyushov

Karena Chapman
Argonne National Laboratory  X-ray Science Division
Accelerating the development of energy materials through hard X-ray tools

Our energy needs drive widespread materials research, from energy storage in lithium-ion batteries to novel catalysts for natural gas conversion to selective capture of radiological gases within porous media for safer nuclear energy. Breakthroughs in performance can be driven by advances in the materials themselves or in the tools that we use to understand their function and limitations. By exploiting advanced crystallographic tools that allow us to probe the atomic structure of energy materials in-situ, as they function, we can identify how their structure is linked to their functional properties and performance. These fundamental insights serve as a road map to enhance performance in the next-generation of advanced energy materials. This presentation will describe examples of recent work demonstrating the valuable insights that synchrotron-based experiments can provide into the structure-function relationship in energy-relevant materials, focusing on identifying the processes that lead to capacity loss in battery electrodes, and temperature and the pressure-induced distortions of novel metal-organic framework-based with applications in catalysis and gas capture. These examples will highlight the new levels of understanding provided by recent developments in in-situ and operando measurement capabilities for synchrotron powder diffraction and pair distribution function analysis. Host: Don Seo

Emily Weinert
Emory University  Department of Chemistry
Investigating the Mechanism and Role of O2-Dependent Globin Coupled Sensor Signaling

Recent studies have suggested that heme proteins play roles in sensing the bacterial environment and controlling the switch between motile and sessile (biofilm) states. Globin coupled sensors are heme proteins that consist of a globin domain linked by a central domain to an output domain. Diguanylate cyclase-containing globin coupled sensors are found in a number of bacteria, including human and plant pathogens and environmental bacteria. Current efforts to elucidate the signal transduction mechanism of these enzymes have found that cyclase activity is controlled by ligand binding to the heme within the globin domain. In addition, both ligand binding to the heme and c-di-GMP binding to an inhibitory site control the oligomerization state of the enzyme. Furthermore, our work on a plant pathogen suggests that these sensor proteins control O2-dependent bacterial virulence. These studies provide insight into the mechanism by which heme ligand binding controls activity of globin coupled sensors, as well as highlights the biological relevance of the pathways they control. Host: Anne Jones

Nam-Gyu Park
SungKyunKwan Univ., Korea  
How to Get to 20% Efficient Perovskite Solar Cells

The solid-state perovskite solar cell with power conversion efficiency (PCE) of 9.7% was first reported in 2012 by Park’s group. Its PCE reaches now 21% that was produced by EPFL. It is believed that perovskite solar cell is promising next-generation photovoltaics due to superb performance and very low cost. In this talk, chemical routes to reaching more than 20% efficient perovskite solar cells will be presented. We have found that Lewis acid-based adduct route is an effective methodology for high quality perovskite layer. In the solution process to form the perovskite layer, PbI2 and CH3NH3I or HC(NH2)2I are dissolved in polar aprotic solvents. Since polar aprotic solvents bear oxygen, sulfur or nitrogen, they can act as Lewis bases. In addition, the main group compound PbI2 is known to be Lewis acid. Thus PbI2 has a chance to form adduct by reacting with Lewis base. By taking advantage of weak dative covalent bonding characteristics in the adduct, high quality perovskite film was achieved. We have successfully fabricated the highly reproducible CH3NH3PbI3 perovskite solar cells with PCE as high as 20.4% via adduct of PbI2 with oxygen-donor N,N’-dimethyl sulfoxide and grain boundary healing process. This adduct approach can be extended to formamidinium lead iodide HC(NH2)2PbI3, in which large grain with high crystallinity and long-lived carrier life time is successfully fabricated via adduct of PbI2 with sulfur-donor thiourea. Host: Don Seo

Hongfei Wang
Pacific Northwest National Laboratory  
Complex Molecular Surface/Interface Sciences and Applications with Novel Nonlinear Vibrational Spectroscopy

In the past three decades or so, there have been many applications of surface nonlinear vibrational spectroscopy, i.e. sum-frequency generation vibrational spectroscopy (SFG-VS), for its interface selectivity and sub-monolayer sensitivity, in obtaining chemical structure and bonding, as well as dynamic interactions, of molecular surfaces/interfaces. The potentials of SFG-VS in studies of complex molecular systems at surfaces/interfaces can be greatly expanded with the recent development of the high-resolution broadband sum-frequency generation vibrational spectroscopy (HR-BB-SFG-VS). HR-BB-SFG-VS is realized by combining the infrared and visible pulses at both the time and the frequency resolution limit, as it allows measurement of the nearly intrinsic lineshape of the SFG vibrational spectra. In this talk, the new opportunities and applications of such a unique quantitative spectroscopic tool for complex molecular surfaces/interfaces in energy, environmental and biological sciences and technologies are to be discussed. Host: Yan Liu

Spring Break


Ivan Korendovych
Syracuse University  Department of Chemistry
De Novo Design of Catalytic Function

Host: Giovanna Ghirlanda

Visitation Weekend. No seminar


Steven Gygi
Harvard Medical School  Department of Cell Biology
Systematic mapping of the human interactome

Protein-protein interactions form a network whose structure drives cellular function and whose organization informs all biological inquiry. Using high-throughput affinity-purification mass spectrometry, we identify interacting partners for 2,594 human proteins in HEK293T cells. The resulting network (BioPlex) contains 23,744 interactions, 86% unknown, among 7,668 proteins. BioPlex accurately depicts known complexes, attaining 80-100% coverage for most CORUM complexes. Network structure reveals 4 key features: 1) BioPlex subdivides into >300 communities, uniting proteins with shared function. 2) Interactions predict 2,968 associations among co-occurring Pfam domains. 3) Attributes including localization, biological process, and molecular function were determined for thousands of proteins - many uncharacterized. 4) BioPlex reveals interactions of biological or clinical significance. To demonstrate complementary studies inspired by BioPlex, we interrogated interactions of wild-type and mutant VAPB variants implicated in familial Amyotrophic Lateral Sclerosis. The network provides a framework for hypothesis generation and refinement as applied to protein function, mechanism, and activity. Host: Chad Borges

John Turner
National Renewable Energy Laboratory  
Semiconductor Systems and Catalysis for Photoelectrochemical Water Splitting

Forty years after the first reported photoelectrochemical (PEC) water splitting experiment, commercial hydrogen production from PEC is still a dream. Literally 100’s of millions of dollars and thousands of papers later and still no semiconductor system has been identified that has the potential for economical hydrogen production from PEC water splitting. Recent technoeconomic analysis studies indicate that a >15% solar-to-hydrogen PEC conversion efficiency is necessary for a commercially viable system. Additional requirements of lifetime (years), and cells costs (<$400/m2) make a working device extremely challenging. To achieve such high efficiencies, semiconductors with superior electronic properties are required as well as highly active catalysts. Clearly then one must decide whether to use an existing PV-based semiconductor or search for a new semiconductor with the necessary electronic properties. The majority of the research has been directed at metal oxides due to their expected low costs, ease of synthesis and stability, but their poor electronic structure prevents them from reaching the high efficiencies necessary for a working device. The III-V-based solar cells show the highest solar PV efficiency and thus are excellent candidates for a PEC system, but cell costs are high and lifetime is limited. Incorporation of proper electrocatalysts onto the illuminated SC surface is necessary to both stabilize the PEC interface and increase catalysis, thus enhancing the overall device performance. Noble metals, particularly platinum, are mostly commonly applied as they are the most active for the water redox reactions. The branching ratio between catalysis and corrosion must be extremely high (>106) in order for the system to have the necessary lifetime, thus the catalysts must have a very high turnover frequency (TOF) and turnover number (TON). Nobel metals are neither earth abundant nor low-cost, so identifying catalytic systems that can match the activity and stability of platinum but are based on earth abundant materials are clearly a high-priority area of research. Such materials for SC surface modification are particularly beneficial if they are potentially low-cost and scalable, transparent and conductive while also highly catalytically active and stable. Work on hydrogen evolution catalysts has been a very active area of research where numerous molecular, nanomaterial, and bulk catalysts have been developed. This presentation will discuss some of the challenges and opportunities facing PEC community in our search for a workable PEC solar water-splitting system that could lead to a commercial device. The discussion will include tandem cells for PEC water splitting and the importance of surface treatments for band edge control and the advantage of a visible-light transparent hydrogen evolution catalyst Host: Gary Moore

Carlos Garcia
Clemson University  Chemistry Department
Micro/Nano…Does it Make a Difference?

The field of miniaturization in chemical analysis has seen tremendous growth in the last few decades enabling the collection, pretreatment, separation, and detection of minute amounts of materials with minimal human intervention. Despite these advances, a key shortcoming of miniaturization is the lack of integration of many analytical steps into a single device. Aiming to address this gap in current technology, part of our group is focused on the development of simple strategies leading to the development of low-cost microfluidic devices. As examples of the outcomes of these projects, the development of devices using CO2 laser engraving from plastic, paper, and glass will be discussed. In addition, the seminar will describe recent results obtained with carbon electrodes developed by pyrolysis of paper substrates and the development of a robotic platform to perform remotely-controlled analyses. The presentation will also address the outcomes of a project focused on the adsorption of proteins to nanostructured surfaces. The hypothesis is that a detailed understanding of the interaction process will lead to rational methodologies to fabricate biosensors with improved performance. In this regard, examples of the interaction of enzymes with carbon nanotubes will be complemented with results related to the characterization and potential biomedical uses of optically transparent carbon electrodes. Host: Mark Hayes

Erica Forzani
Arizona State University  School for Engineering of Matter, Transport, and Energy
Mobile Chemical Sensors Based on Nanomaterials, Bridging the Gap from the Lab to Real World

Host: Marcia Levitus

PSH 151
Wenyu Huang
Iowa State University  Department of Chemistry
Control Heterogeneous Catalysts for Superior Catalytic Properties

Catalysis—the essential technology for accelerating and directing chemical transformation—is the key to realizing environmentally friendly and economical processes for the conversion of fossil energy feedstocks. Catalysis is also the key to developing new technologies for converting alternative feedstocks, such as biomass, carbon dioxide, and water to chemicals and fuels.1 The two grand challenges of heterogeneous catalysis, understanding mechanisms and dynamics of catalyzed reactions as well as the design and controlled synthesis of catalyst structures, require an atomic and electronic-level understanding of catalysts and catalytic processes. However, due to the structure complexity, especially under reaction conditions (high temperature and pressure), the exact catalytic active site and the molecule-catalyst interaction are extremely difficult to describe. In this presentation, I will discuss the synthesis, characterization, reaction study, and modeling of heterogeneous catalysts precisely synthesized at atomic level using intermetallic compounds2 and metal-organic frameworks3-5, which provide the means for meeting the two grand challenges of heterogeneous catalysis. The synthesis of these heterogeneous catalysts is based on nanoscience and nanotechnology. Host: Don Seo

Daniel Chiu
University of Washington  Department of Chemistry
Technologies for Studying Individual Rare Cells in Circulation and Tissue

Host: Jia Guo

James Bowie
UCLA  Department of Chemistry and Biochemistry
Learning How Membrane Proteins Fold

Protein folding is a fundamental process of life with important implications throughout biology. Elaborate mechanisms exist to regulate and assist folding. Moreover, tens of thousands of mutations have now been associated with diseases and it is thought that most of these mutations affect protein folding and trafficking rather than function. Consequently, there has been an enormous effort over the years to understand how proteins fold. Essentially all of the effort has been directed at soluble proteins, however, and membrane proteins have been largely shunted aside. As a result it has usually only been possible to examine the folding and misfolding of biologically and medically interesting membrane proteins in qualitative terms. Quantitative and mechanistic studies have been restricted to a handful of model membrane proteins, in artificial systems, far from natural conditions. Our goal is to bring quantitative protein folding studies to biologically and medically relevant proteins. Model membrane proteins like bacteriorhodopsin have provided important insights into the folding process of membrane proteins in general. I will summarize the state of folding of studies with bacteriorhodopsin and then describe single molecule methods we are developing that we hope will allow us to examine the folding of complex human membrane proteins, and the causes of misfolding in disease states. Host: Wade Van Horn

PS H-151
Cynthia Burrows
University of Utah  Department of Chemistry
Eyring Technical Lecture - “Single-Molecule Analysis of the Effects of Oxidative Stress on G:C-rich Sequences in DNA”

Oxidative stress in the cell results in modifications to DNA and RNA bases and downstream events including effects on transcription and replication as well as signaling for repair. Ultimately, unrepaired damage in DNA leads to mutagenesis that is a contributing factor to cancer and other diseases. Our studies focus on base modifications arising from guanine (G) oxidation, including how and where they form in the genome. To investigate this, we have developed a single-molecule nanopore approach that is complementary to other biophysical techniques for interrogating nucleic acid structure. Specifically, the electrophoretic capture of DNA strands, either Watson-Crick duplexes or folded G-quadruplexes, inside a protein nanopore (alpha-hemolysin) embedded in a lipid bilayer provides information about the presence of oxidized bases as well as the dynamics of unfolding. In order to adapt this methodology to sequencing DNA for modified bases, we have developed a protocol for PCR amplification using a third base pair to mark the site of DNA modification. Host: Dan Buttry
6:30 PM
PS H-152
Cynthia Burrows
University of Utah  Department of Chemistry
Eyring General Lecture -“Peering into the Dark Matter of DNA: Structures and Functions beyond Watson & Crick”

Less than 2% of the human genome codes for the amino acid sequence of proteins. Why is all the rest of the DNA there? Some of it participates in orchestrating replication, some in the protection of the ends (telomeres), and some sections upstream of transcription start sites (promoters) control whether or not a gene is expressed as protein. All of these functions of DNA include guanine-rich sequences capable of folding into G-quadruplexes, four-stranded folds of DNA that differ dramatically from the classical base-pairing scheme of the Watson-Crick double helix. Furthermore, the G-rich sequences are sensitive to oxidative stress, converting to modified structures including 8-oxo-7,8-dihydroguanine (OG) and the hyperoxidized lesions spiroiminodihydantoin (Sp) and guanidinohydantoin (Gh). Both the overall reactivity of a G residue in DNA or RNA and the final oxidized G product formed are highly dependent on sequence, solvent exposure and mechanism. For example, oxidation of G in G-quadruplex folds leads to very different outcomes compared to those in Watson-Crick B-helical duplexes. The location of G damage in turn has a profound effect on the stability of duplex vs. quadruplex structures. We propose that G-rich sequences respond to oxidative stress by selecting a secondary structure that can best accommodate the damaged base, and that ‘shape-shifting’ may be used as a signaling mechanism to affect transcription and repair. The implications are that nucleotide identity beyond the exome may be important in gene expression and disease, and that the definition of epigenetic modifications should be expanded to include guanine oxidation. Host: Dan Buttry

Eric Xu
Van Andel Research Institute  
Structures and Drug Discovery of Nuclear Hormone Receptors and GPCRs

Hormone signaling is essential to eukaryotic life. Our research is focused on the signaling mechanisms of physiologically important hormones, striving to solve fundamental questions that have a broad impact on human health and disease. The overall goal of my research program is to seek new biological paradigms through structural and functional analysis of key hormone signaling complexes and to develop therapeutic applications using the structural information we obtain. My current research programs are focused on two families of proteins, the nuclear hormone receptors and the G protein–coupled receptors, because these proteins, beyond their fundamental roles in biology, are important drug targets for treating major human diseases. In this seminar, I will focus on drug discovery of glucocorticoid receptor and structure determination of rhodopsin-arrestin complex. See more at: Host: Wei Liu

Daniel Alkon
Blanchette Rockefeller Neurosciences Institute  
Bryostatin: Restoring Synaptic Balance in Neurodegenerative Diseases

Host: Bob Pettit

Chia-Kuang (Frank) Tsung
Boston College  Department of Chemistry
“Controlled Encapsulation of Catalysts in Metal-Organic Frameworks”

Controlled Encapsulation of Catalysts in Metal-Organic Frameworks Towards our long-term vision of precisely controlling active sites, our group focuses on incorporating catalysts into crystalline nanoporous materials, metal-organic frameworks (MOFs). Our hypothesis is that the precise molecularly-defined pores intrinsic to the MOFs will provide a new tool to control the catalytic transformations on the catalysts. We have developed methods to combine organometallic catalysts, enzymes, and nanoparticle catalysts with MOFs of precisely tuned pore structures to manipulate the reactions. Host: Candace Chan

Haitao Liu
University of Pittsburgh  Department of Chemistry
“Wetting at the Nanoscale: Fundamental Science and Applications”.

Abstract Graphitic surfaces (e.g., graphite, graphene, carbon nanotubes) have long been believed to be hydrophobic. However, our recent work showed that such surfaces are in fact mildly hydrophilic. The previously observed hydrophobicity is caused by adsorption of airborne hydrocarbon contamination (Figure 1). This talk will discuss these related issues, with a special focus on the wetting transition and its implications in carbon materials research Host: Hao Yan

David Kramer
Michigan State University  
The Knife-Edge of Photosynthesis: How the Proton Motive Force Enables, Regulates and Limits Photosynthesis

Life, death, electrons and the PMF This talk will cover new advances in understanding how the chloroplast balances its energy budget to optimize the efficiency and robustness of photosynthesis. The photosynthetic machinery of is finely tuned to balance the needs for efficient light capture with an avoidance of photodamage. The thylakoid proton motive force (PMF) plays a central role in this balancing, producing ATP and regulating the capture of light energy and subsequent electron transfer reactions. A key component of this balancing involves a process called cyclic electron flow (CEF). I will discuss recent results that indicates CEF involves a reversible proton-pumping complex called NDH, that enables the chloroplast to conduct a new pathway for electron transfer that consumes PMF to transfer electrons “uphill” in energy to NADPH. I will also discuss very recent work on the limits of pmf, and how elevated pmf accelerates photoinhibition under fluctuating environmental conditions. Host: Gary Moore

Kirill Kovnir
UC Davis  Department of Chemistry
Novel Approaches for Thermoelectric and Strongly Correlated Magnetic Materials

Novel Approaches for Thermoelectric and Strongly Correlated Magnetic Materials Kirill Kovnir Department of Chemistry, University of California, Davis The phenomenon of thermoelectricity is attributed to the interconversion of thermal and electrical forms of energy. We developed a new class of bulk thermoelectric materials based on clathrates with a three dimensional framework comprised of oversized transition metal-phosphorus polyhedral cages that encapsulate guest cations. Transition metal-based clathrates have the following advantages over conventional Si-, Ge-, and Sn-based clathrates: i) a larger variety of framework topologies; ii) a higher tunability of the electronic properties via framework substitutions. The correlation between the crystal structure, distribution of the metal and phosphorus atoms over the clathrate framework and thermoelectric properties will be discussed. Exploration of chemical factors that affect magnetic interactions in solids is one of the major steps in the development of novel magnetic materials. We have developed a synthetic approach that granted access to novel well-crystalline materials containing an infinite Fe-chalcogenide sublattice where correlated magnetic interactions are expected. On the example of the solution synthesis of the simplest superconductor, tetragonal iron(II) selenide (â-FeSe), we will consider main advantages and pitfalls of the solution synthesis of superconductors and highly correlated materials. Perspectives of this method for the design and synthesis of new materials will be discussed. Host: Don Seo

Daron Freedberg
US Food and Drug Administration  
NMR Studies of Glycan Structure ON and OFF Cells

NMR Studies of Glycan Structure ON and OFF cells Carbohydrates are ubiquitous in nature and participate in a wide variety of cellular processes. They make up bacterial capsules, play roles in cell-cell interactions such as immune responses, fertilization, inflammation, and cell growth, influence protein folding and stability, and may be involved in signal transduction. Given the variety of monosaccharides, linkage types, and functional group modifications, oligosaccharides alone have potential structural complexity unmatched by any other biomolecule. Despite their importance, carbohydrate structure-function relationships, or ¡§glycan code¡¨, are poorly understood. Our group is delineating carbohydrate three-dimensional solution structure to gain insight into how carbohydrates function, which should facilitate development of vaccines, drug delivery systems, and antibiotics of the future. Our goal is to unveil carbohydrate structure-function relationships using heteronuclear multidimensional NMR to delineate conformation and dynamics of 15N, 13C enriched oligo- and polysaccharides. In recent research, we sought to understand why ƒÑ, 2->8 polysialic acid induces almost no immune response in humans, while other polysaccharides induce a stronger immune response. We hypothesized that a three-dimensional structural difference between polysaccharides on and off cells may be the source of this difference. To test this hypothesis, we deciphered the structure of 15N, and 13C polysialic acid on bacteria and found that the structure is quite similar to purified polysialic acid. In a continuing effort to address this question, we are studying ƒÑ, 2->8 tetrasialic acid in solution. Our recent studies of the labeled tetramer show evidence for a helix with two residues per turn. Finally, we recently developed methods to observe hydrogen bonding involving hydroxyl groups in carbohydrates. We are able to directly detect hydrogen bonds and assign directionality. We also recently developed methods to measure hydroxyl group H/D exchange rates in glycans, to infer hydrogen bonds in systems in which we cannot directly detect them . Direct detection of hydrogen bonds is a powerful structural descriptor since only certain conformations can explain their presence. Therefore, hydrogen bonds, in opposition to other NMR observables, provide evidence of unique three-dimensional structures even when coexisting with other conformations in solution. Together, these experiments are helping to expand the repertoire of methods available to determine carbohydrate three-dimensional solution structures. Host: Xu Wang

Giovanna Ghirlanda
To Boldly Go Where Nature Has Not Gone: Design and Application of Novel Proteins

A pressing challenge facing society is the development of sustainable alternatives to carbon-based fuels, ideally using solar light to produce carbon-neutral fuels such as hydrogen or methanol derived from reduction of carbon dioxide. In nature, metalloenzymes are at the center of redox processes that carry out those transformations. For example, natural hydrogenases catalyze the reduction of protons to molecular hydrogen reversibly under mild conditions. Unfortunately, several obstacles prevent the direct use of hydrogenases in technological applications. To address this challenge, our group has designed artificial hydrogenases consisting of hybrid systems by which the chemistry of simple, relatively inefficient organometallic centers can be enriched through second-sphere and long-range interactions provided by a protein scaffold. Our strategy builds on using unnatural amino acids with dithiol side chains to coordinate and stabilize diiron sites of biomimetic organometallic catalysts. Using this strategy we have demonstrated nascent hydrogen production activity by a small helical peptide in water at mild pH, and designed complex, evolvable four-helix bundle that shows significant improvements in activity. Another approach to generate evolvable hybrid proteins for sustainable fuel production utilizes cobalt porphyrins as prosthetic active sites. We recently repurposed an abundant globin with an unnatural porphyrin containing cobalt instead of iron; the hybrid is able to efficiently catalyze hydrogen production under aerobic conditions, a property uncommon to other catalysts. Our strategy enhances the activity of the cobalt porphyrin ten-fold by providing critical secondary-shell interactions to the catalyst. We are currently exploring the use of these hybrid system as catalysts for carbon dioxide reduction. Host: Daniel Buttry

Julian Chen
Structure and Mechanism of Telomerase: A Fast-Evolving and Highly Specialized Reverse Transcriptase

Telomerase is a highly specialized reverse transcriptase that adds simple DNA repeats onto linear chromosome ends in eukaryotes to maintain genomic integrity and sustain cellular immortality. In humans, telomerase is expressed at an insufficient level in adult stem cells, leading to progressive telomere shortening and cellular aging in the elderly. Mutations in telomerase genes have been linked to numerous telomere-mediated disorders such as dyskeratosis congenita, aplastic anemia, and idiopathic pulmonary fibrosis. Telomerase functions as a ribonucleoprotein (RNP) complex, requiring minimally the catalytic telomerase reverse transcriptase and essential telomerase RNA. Since its discovery in 1985, telomerase has been intensively studied in select model organisms, which has led to the realization that the telomerase RNP is remarkably divergent in size, composition, biogenesis pathway and even the mechanism of DNA repeat synthesis. In recent years, my lab has studied telomerases identified from several novel groups of eukaryotes, advancing our understanding of the essential core of the telomerase enzyme and its evolution along distinct phylogenetic lineages. In addition to the comparative structural studies of telomerase, we have developed novel systems and tools to understand the inner workings of telomerase. In my talk, I will discuss our recent progress in understanding the structural diversity of telomerase RNP complex and the molecular mechanism of telomerase function. Host: Daniel Buttry

Rebekka Wachter
Proteins in Motion: From Chemical to Mechanical Work

Proteins in Motion: From Chemical to Mechanical Work Rebekka Wachter This talk will focus on two distinct research projects in my laboratory, each aimed at understanding the relationship between protein structure, function and dynamics. First, I will discuss the use of photoconvertible GFPs as a model system to study the role of dynamics in protein evolution. Recently, we have uncovered a direct experimental link between large-scale collective motions and phenotypic change. Our data suggest that the relocation of a rigid anchoring region diagonally across the beta barrel fold sets the stage for the acquisition of red color. Based on structural, computational and kinetic work, we have proposed a novel mechanism for the light-triggered reaction specific to a class of GFPs frequently used in super-resolution microscopy. Second, I will discuss our efforts to unravel the structural and dynamical features of the ring-forming ATPase Rubisco activase (Rca). Rca is a chemo-mechanical motor protein thought to undergo large-scale domain motions to regulate the activity of the CO2-fixing enzyme Rubisco. Recent results concerning its structure, assembly and regulation indicate that site asymmetry may play a critical role in function. Mechanistic work suggests that hydrolytic activity may be tuned by fluctuating magnesium in response to changes in available light. Our work has led to the development of a preliminary model for Rca-mediated regulation of higher plant carbon assimilation under changing environmental conditions. Host: Daniel Buttry

William M. Gelbart
UCLA  Dept of Chemistry and Biochemisty UCLA
Making Viruses (and Virus-Like Particles) From Scratch

Viruses are overwhelmingly – by many orders of magnitude – the simplest of evolving organisms. Typically their genomes code for only a few proteins (as compared with thousands in the case of bacteria and yeast) and their “parts list” consists of just two or three molecules. Related to this fact, they are the only living disease agents that can be formed by spontaneous self-assembly from their purified components. Finally, they are the only evolving organisms whose genome need not be DNA; indeed, most viruses use RNA – not DNA – as their genetic material In my talk I focus on a pair of plant and insect viruses that we argue are the simplest possible viruses. Their genomes are ready-to-translate messenger RNA molecules, involving 3 or 4 genes, whose first protein products are enzymes that replicate the RNA one-million-fold. We use purified capsid protein from the plant virus to package in vitro a range of RNA molecules of interest, one at a time. In particular, we package the self-replicating genome of the insect virus, which we have genetically engineered to be non-infectious and to contain various mammalian genes of interest. We do so by controlling conditions of ionic strength and pH, thereby directing assembly of perfectly icosahedrally-symmetric, single-protein-thick, shells (capsids) that contain a single copy of the RNA gene of interest. Host: Austen Angell

Mark Akeson
UC Santa Cruz  
Nanopore DNA Sequencing Comes of Age

Nanopore DNA strand sequencing was conceived in the 1980s, but it was not until 2014 that several hundred laboratories received courier packages containing the first commercial 'MinION' nanopore sequencers. In this seminar I will discuss key experiments that set the stage for implementation of this 100-gram device. I will then discuss our analysis of the MinION's performance using M13 genomic DNA as a reference sample. By pairing a new high confidence sequence alignment strategy with long MinION reads (36-42 kilobases), we used nanopore data to determine the copy number for a cancer-testis gene family (CT47) within an unresolved region of human chromosome Xq24. In the third part of my seminar, I will discuss recent advances at UC Santa Cruz focused on nanopore detection of epigenetic modifications on genomic DNA, and linear analysis of individual proteins. Host: Stuart Lindsay

Amanda Morris
Virginia Tech  
Exploring Metal Organic Frameworks for Use as Integrated Artificial Photosynthetic Assemblies

The finite supply of fossil fuels and the possible environmental impact of such energy sources has garnered the scientific community’s attention for the development of alternative, overall carbon-neutral fuel sources. The sun provides enough energy every hour and a half to power human civilization for an entire year. However, two of the remaining challenges that limit the utilization of solar energy are the development of cheap and efficient solar harvesting materials and advances in energy storage technology to overcome the intermittent nature of the sun. In the seminar, the research projects to be discussed focus on the development of an integrated artificial photosynthetic array for solar energy storage. Photosynthetic systems consist of light harvesting arrays and redox mediators that can funnel the electrochemical potential stored in a molecular excited states to catalytic centers to drive the oxidation of water and the reduction of CO2 to sugars. Many artificial approaches to this chemistry have been reported. In the Morris group, we investigate porous coordination networks (PCNs) as both light harvesters and high surface area catalysts as photosynthetic mimics. PCNs combine the synthetic diversity possible with molecular catalysts and the ease of recovery of heterogeneous catalysis. Theoretically, the high surface area of PCNs can be exploited to produce a higher catalytic rate per geometric area than those realized by other approaches. Additionally, the incorporation of molecular chromophores into networks has been show to lead to enhanced luminescence quenching. Our studies span the scope of artificial photosynthetic chemistry and include mechanistic investigations of homo-resonance energy transfer, electron transport, and catalysis within PCNs. Host: Ana Moore

Gordana Dukovic
University of Colorado, Boulder  
Photophysics and photochemistry of nanoscale semiconductors and implicatons for solar fuel generation

Colloidal semiconductor nanocrystals are remarkably versatile materials that exhibit a high degree of tunability in electronic structure, optical spectra, and surface properties. My research group is focused on the photophysics and photochemistry of nanoscale semiconductors with a particular emphasis on light-driven reactions involved in solar water splitting. To photochemically drive reduction of H+ to H2, we have coupled CdS nanorods with hydrogenase, an enzyme that catalyzes reduction of H+ to H2 generation. Similarly, we have functionalized CdS nanorods with molecular water oxidation catalysts. Using time-resolved spectroscopy over a broad range of timescales (100 fs – 10 ìs), we have examined the kinetics of charge transfer between photoexcited nanorods and these redox catalysts and identified structural and chemical parameters that govern the overall photochemical reactivity. The second part of the seminar will focus on nanoscale (Ga1-xZnx)(N1-xOx), a semiconductor that has demonstrated intriguing water splitting activity under visible irradiation. I will discuss the relaxation dynamics of photoexcited states in this material and their implications for solar fuel generation. Host: Gary Moore

Vicki Lundblad
Salk Institute  
Telomere Length Maintenance: The Intersection Between Telomerase and Replication Fork Dynamics

Telomeres, the specialized structures found at the ends of linear chromosomes, help ensure long-term cellular proliferation. When the enzyme telomerase – which replenishes these ends through the addition of telomeric repeats - is deficient, the resulting erosion of chromosome termini eventually results in a block to cell division. The Lundblad group, which pioneered the identification of protein subunits of telomerase, is currently identifying novel regulatory patches on the surface of the telomerase complex that regulate telomere length in vivo. In parallel, they have identified a telomere-dedicated replication complex that helps ensure high fidelity replication of the duplex region of telomeric DNA. Dr. Lundblad’s seminar will address both complexes, and how their coordinated activity helps ensure full telomere function. Host: Julian Chen

Eric Kool
Stanford University  
Designer DNA Bases: Probing Molecules and Mechanisms in Biology

Designer DNA Bases: Probing Molecules and Mechanisms in Biology Although highly successful in Nature, the DNA bases are – in chemical terms – quite limited in their properties. The tools of synthesis and physical analysis allow us to design a wide variety of DNA base replacements, conferring properties in nucleic acids that can lead to surprising and useful outcomes. For example, we have designed dozens of novel fluorescent DNA bases, and are incorporating them into short oligomers of thousands of distinct sequences. From these we are developing agents for imaging specific proteins and enzyme activities in living cells and organisms. We have also developed broad classes of these DNA-like molecules as chemosensors that can detect many different molecules and ions in air and water, with applications ranging from biomedicine to environmental remediation. Host: John Chaput

Spring Break-No seminar


Blake Hill
Medical College of Wisconsin  
Converging on Fis1 Mechanism in Mitochondrial Fission: Evolution Meets Intelligent Design

Mitochondrial fission helps to maintain proper mitochondrial homeostasis in a poorly understood manner despite its association with human disease. Several proteins have been identified in this process, but only two -- FIS1 and DNM1L -- are found in every species that contain mitochondria. A lethal mutation (A395D) in human DNM1L was reported in a neonate with microcephaly, abnormal brain development, optic atrophy, and lactic acidemia (Waterham et al., 2007, N. Engl. J. Med.356, 1736–1741). Another Drp1 mutation (C446F) was reported to cause severe cardiomyopathy in mice (Ashrafian et al., 2010, PLoS Genet 6, e1001000). We are using multidisciplinary approaches to uncover how these mutants affect mechanoenzyme activity and reveal the molecular basis of fission. For A395D, we found impaired localization, recruitment, assembly, and GTP hydrolysis. For C446F, we found enhanced GTP hydrolysis and assembly. These mutations impair Drp1 in different manners yet both lead to decreased fission, elongated mitochondria, and altered cellular distribution of mitochondria. Curiously, these mutants show enhanced in vitro interactions with the mitochondrial protein Fis1, a possible recruiter of Drp1. To determine the consequences of disrupting these interactions, we devised an unbiased and general method to rapidly identify residues critical to protein interfaces and applied this technology to yeast Fis1 interactions. Of the >3000 Fis1 alleles screened, ~9% selectively disrupted interactions with one of the three protein partners including yeast Drp1. To test the functional consequences, each allele was parsed into its corresponding point mutation and tested for mitochondrial fission. Of 211 yeast Fis1 mutants tested to date, 97 resulted in nonfunctional fission indicating that our method identifies residues essential for mitochondrial fission. Orthologous mutations were introduced into human Fis1 and also found to impair interactions with Drp1 and mitochondrial fission in mammalian cells. Combining our data from yeast and mammalian systems, we propose a new model for Drp1 assembly in fission and its role in maintaining mitochondrial homeostasis. Host: G. Ghirlanda

Elena Jakubikova
North Carolina State University  Department of Chemistry
Toward Computational Design of Iron-Based Chromophores for Solar Energy Conversion

Photoactive transition metal complexes anchored to semiconductor surfaces play an important role as chromophores in artificial systems for solar energy conversion, such as dye-sensitized solar cells (DSSCs). Fe(II)-polypyridines share many properties with Ru(II)-polypyridines, which have been successfully used as photosensitizers in DSSCs. Visible light excitation in both types of compounds results in the population of photoactive metal-to-ligand charge transfer states (MLCT). The main obstacle to the utilization of Fe(II)-based compounds as photosensitizers is the short lifetime of the initially populated MLCT states due to their de-activation by ultrafast intersystem crossing events into photo-inactive metal centered (MC) ligand-field states. We employ density functional theory and quantum dynamics simulations to investigate how various modifications to the polypyridine ligands as well as semiconductor anchor groups influence the relative energies of the MC and MLCT states and relative rates of the intersystem crossing and interfacial electron transfer events. The results obtained lead to better understanding of structure-property relationships in these complexes and have implications for development of photosensitizers based on first-row transition metals Host: Don Seo

PS H 151
Tobin Marks
Northwestern University  
Eyring Technical Lecture - Thermochemically Leveraged Strategies for Biofeedstock Catalysis

Thermodynamic Strategies for New Catalytic Process Design. Biofeedstock Processing via Tandem C-O Hydrogenolysis Tobin J. Marks Northwestern University, Evanston IL 60208 USA Abstract This lecture focuses on thermodynamics/mechanism-based strategies for converting abundant biofeedstocks into useful chemicals. Thus, new approaches to the hydrogenolysis of C-O bonds are discussed with the ultimate goal being the processing of diverse biomass feedstocks. It is shown that selective hydrogenolysis of cyclic and linear etheric C-O bonds is effected by a tandem catalytic system consisting of recyclable metal triflate Lewis acids and supported palladium nanoparticles or related catalysts in either “green” ionic liquid solvents or in the neat substrates. In this tandem process, the metal homogeneous triflates catalyze the endothermic retro-hydroalkoxylation of the ether, with the supported palladium catalyst subsequently catalyzing the hydrogenation of the resulting intermediate alkenols, to afford saturated alkanols with high overall activity and selectivity. Kinetic and DFT computational studies show that the turnover-limiting step in these reactions is the retro-hydroalkoxylation, followed by rapid alkenol hydrogenation. Furthermore, the metal triflate catalytic activity scales approximately with the DFT-computed charge density on the triflate metal ion. With the most active of these catalysts, ethereal substrates are rapidly converted, via the alkenol, to the corresponding saturated hydrocarbons. In similar tandem processes, it is shown that esters and triglycerides are also rapidly and selectively converted to alcohols and, ultimately, to saturated hydrocarbons. The kinetics and mechanism of these ester hydrogenolysis processes, as deduced by experimental results and DFT computation, are compared and contrasted with those of the corresponding ethers Host: Dan Buttry
6:30 pm
PSH 150
Tobin Marks
Northwestern University  
Eyring General Lecture - Interface Science of Plastic Solar Cells

Interface Science of Organic Photovoltaics Tobin J. Marks Department of Chemistry, Materials Research Center, and the Argonne-Northwestern Solar Research Center Northwestern University, Evanston IL 60208, USA The ability to fabricate molecularly tailored interfaces with nanoscale precision offers means to selectively modulate charge transport, molecular assembly, and exciton dynamics at hard matter-soft matter and soft-soft matter interfaces. Such interfaces can facilitate transport of the “correct charges” while blocking transport of the “incorrect charges” at the electrode-active layer interfaces of organic photovoltaic cells. This interfacial tailoring can also suppress carrier-trapping defect densities at interfaces and stabilize them with respect to physical/thermal de-cohesion. For soft matter-soft matter interfaces, interfacial tailoring can also facilitate exciton scission and photocurrent generation in such cells. In this lecture, challenges and opportunities in organic photovoltaic interface science are illustrated for four specific and interrelated areas of research: 1) controlling charge transport across hard matter(electrode)-soft matter interfaces in organic photovoltaic cells, 2) controlling charge transport by specific active layer nano/microstructural organization in the bulk active material and at the electrodes, 3) controlling exciton dynamics and carrier generation at donor-acceptor interfaces in the active layer, 4) designing transparent conducting electrodes with improved properties. It will be seen that such rational interface engineering along with improved bulk-heterojunction polymer structures guided by theoretical/computational analysis affords exceptional fill factors, solar power conversion efficiencies greater than 9%, and enhanced cell durability. Host: Dan Buttry

PS H-151
Mu-Hyun Baik
Indiana University  
Redox Non-Innocent Ligands: What do they do? The Role of Non-Classical Ligands in Small Molecule Activation Catalysis

Redox Non-Innocent ligands have attracted much attention lately, as they appear to play a major role in small molecule activation catalysis: During catalysis ligands participate in redox event by accepting or donating electrons, which affords non-classical electronic structures wherein standard electron counting rules produce misleading clues about the redox state of the metal center. Whereas the existence of this non-classical metal-ligand bonding has now been widely acknowledged, there is only a few examples where the micromechanistic role of these unusual bonding has been precisely identified. I will discuss two examples where redox non-innocence plays a major role in promoting a difficult chemical transformation: (i) Water oxidation by a dinuclear Ru-complex, where the reactive species contains a (IV)Ru–O• moiety, the redox non-innocent resonant form of the classical (V)Ru=O fragment. (ii) Dioxygen activation in gas phase by [Ni(H)(OH)]+ complex, where a redox non-innocent ligand helps to protect the reactive state against decomposition Host: Ryan Trovich

PS H-151
Wei-Jen Tang
University of Chicago  
Two tales of human amyloid-â degrading metalloproteases, IDE and PreP

Title: Two tales of human amyloid-â degrading metalloproteases, IDE and PreP Type 2 diabetes mellitus and Alzheimer’s disease are human chronic diseases that affect millions of people in US alone. Aberrant levels of insulin and improper responses to insulin and other hormones that control glucose levels are the primary causes of T2DM. Aâ peptide, the primary component in amyloid plaques, plays a central role in the progression of AD. Insulin Degrading Enzyme (IDE) and Presequence Protease (PreP) are structurally related, ~110 kDa M16 Zn2+-metalloproteases that use an enclosed catalytic chamber to recognize and degrade peptide substrates into fragments. IDE is involved in the clearance of peptides diverse in structure and sequence, including three glucose-regulating hormones (insulin, amylin, and glucagon), Aâ, and other bioactive peptides <80 aa. The involvement of IDE in the clearance of insulin and Aâ links IDE to the progression of Type 2 diabetes mellitus and Alzheimer’s disease. PreP is localized at mitochondrial matrix, where it degrades presequences cleaved from proteins imported into the organelle. PreP also effectively degrades Aâ in vitro and may degrade Aâ imported into mitochondria to prevent Aâ toxicity in mitochondria. We have used structural, biochemical, and biophysical analyses to construct a working model to how human IDE and PreP use their catalytic chambers to recognize the <80 aa substrates in a distinct manner. We also have developed potent inhibitors of human IDE and PreP to probe the biological functions of these enzymes and explore the therapeutic potential of IDE. My talk will discuss our efforts to elucidate the molecular basis of how IDE and PreP recognize their substrates and our effort in IDE-based therapy. Host: Xu Wang

Scott Sayres
Arizona State University  
Intense Light-Matter Interaction on the Ultrafast Timescale: Electron Correlation and Molecular Fireworks

Host: Tim Steimle