Seminars Archive

Expanding the Chemical Toolbox for Acoustic-based Imaging of Cancer

Dr. Jefferson Chan | University of Illinois, Urbana-Champaign

Professor Clifford Stains

Many disease states are characterized by molecular level changes that occur before detectable symptoms have begun to manifest. In order to maximize treatment outcomes it is essential to accurately detect such alterations at an early stage. Chemical probes designed to selectively image such molecular processes have the potential to not only aid in disease diagnosis but can also provide unique insights into disease progression. As an important step toward these goals we have developed a palette of activatable probes for photoacoustic imaging and apply these to visualize changes in the tumor microenvironment. Briefly, photoacoustic imaging is a state-of-the-art technique that generates ultrasound signals from light, which can be detected and converted into high-resolution 3D images. Since sound scattering is three orders of magnitude less than light in tissue, photoacoustic imaging can be employed to image up to 8 cm in depth while achieving micron resolution. To image deeper regions of the body in real-time, we have recently developed the first activatable ‘smart bubbles’ for ultrasound imaging. Like our photoacoustic probes, smart bubbles respond selectively to a disease property to provide signal enhancements via enhancement of their echogenic properties. In this seminar, we will discuss the strategies employed to construct both photoacoustic and ultrasound probes, as well as highlight notable examples from our laboratory.      

Brief Bio:

Professor Chan received his BSc degree in chemistry from the University of British Columbia in 2006 and his PhD from Simon Fraser University (Prof. Andrew Bennet) in 2011. For his graduate research, he received the Boehringer Ingelheim (Canada) Doctoral Research Award for the top Canadian thesis in the areas of organic and bioorganic chemistry. From 2011-2014 he was a Human Frontiers Science Program Postdoctoral Fellow at the University of California, Berkeley (Prof. Christopher Chang). In the fall of 2014 he joined the faculty at the University of Illinois, Urbana-Champaign.

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ABSTRACT

The brain is a complex organ, with billions of neurons and more than 30 distinct neurochemicals (possibly up to 100), involved in all aspects of a human life, including cognition, movement, sleep, appetite, and fear responses. For some neurological diseases/conditions, changes in neurochemical concentrations could be predictors of early onset disease or disease progression. While there are a variety of sampling techniques which can detect neurotransmitters in biofluids at low concentrations, these techniques often involve multi-step sample preparations coupled with long measurement times, and are not suited for in vivo detection. There is a need for the development of sensors for the detection of neurotransmitters that are selective, rapid, and label-free with little to no sample processing. Our group focuses on the detection of biomarkers for neurological activity in biofluids and through the skull.

Our approach is to apply surface enhanced Raman spectroscopy (SERS), a highly specific and selective vibrational spectroscopy, for the detection of neurochemicals. Raman scattering is an inherently weak phenomenon. To enhance the weak Raman scattering signal, we incorporate noble metal nanoparticles in our sensors, which when excited with a laser generate an oscillating electric field, referred to as the localized surface plasmon resonance (LSPR), at the surface of the nanoparticles. The molecules of interest are adsorbed to the nanoparticle surface, and the Raman scattered light is enhanced by the LSPR of the nanoparticles. SERS is surface selective, highly sensitive, rapid, label-free and requires little to no sample processing. We are developing SERS-based sensors for in vitro neurotransmitter sensing at physiologically relevant concentrations in biofluids. For in vivo detection, we combine SERS with spatially offset Raman spectroscopy (SORS), where Raman scattering spectra is obtained from subsurface layers of turbid media.  We demonstrate low concentration detection of neurotransmitters in the micromolar (µM) to nanomolar (nM) concentration ranges with SESORS in a brain tissue mimic through the skull.

Electrochemical Energy Storage through Ligand-Based Charge Manipulation

Dr. Mitch Anstey | Davidson College

Professor Charlie Machan

ABSTRACT

Public and private investments in energy storage have created a 100 billion dollar industry, and this industry is now converging on grid-scale applications due to the urgent need for resource conservation and our ever-increasing global demand for energy. Redox flow batteries (RFBs) are one method for grid-scale energy storage, being used for peak-shaving and renewable energy incorporation into the grid. Our lab has been using molecular structure as one method to influence electrolyte performance metrics such as Coulombic efficiency, charge-recharge cycling, and voltage window. This talk will describe the work in our lab that focuses on molecular design to address these specific issues in nonaqueous redox flow battery electrolytes.

Using N-Heterocyclic Olefins (NHOs) and Frustrated Lewis Pairs (FLP) to Promote Small Molecule Activation and Nanomaterial Deposition in the Main Group

Dr. Eric Rivard | University of Alberta

Professor Robert Gilliard

ABSTRACT

This presentation will describe our recent application of Frustrated Lewis Pairs (FLPs) to gain access to inorganic methylene EH2 complexes (E = Group 14 element) and their use to deposit bulk metal films from solution.[1] This will be followed by a highlight of our studies on anionic N-heterocyclic olefin (NHO) ligands, leading to rare examples of acyclic two-coordinate silylenes (R2Si:). I will also describe the ability of our silylenes to activate strong homo- and heteroatomic bonds under mild conditions.[2]

[1] For reviews of EH2 complexes, see: E. Rivard, Chem. Soc. Rev. 2016, 45, 989-1003.

[2] a) M. M. D. Roy, E. Rivard, Acc. Chem. Res. 2017, 50, 2017-2025; b) C. Hering-Junghans, P. Andreiuk, M. J. Ferguson, R. McDonald, E. Rivard, Angew. Chem., Int. Ed. 2017, 56, 6272-6275; c) M. M. D. Roy, M. J. Ferguson, R. McDonald, Y. Zhou, E. Rivard, Chem. Sci. 2019, 10, 6476-6481.

Examining the Dynamics of Glucose Regulation

Dr. Mike Roper | Florida State University

Professor James Landers

ABSTRACT

Islets of Langerhans are the endocrine portion of the pancreas responsible for maintaining glucose homeostasis via the regulated secretion of numerous hormones, most notably insulin and glucagon. Defects in the secretion of these hormones are associated with a number of metabolic diseases, including diabetes and the metabolic syndrome. The ability to measure these glucose-regulating peptides with high time resolution and sensitivity is necessary to fully resolve the secretion dynamics of these factors and to understand how they change at various disease stages.

In this talk, a number of analytical strategies our group has developed which enable monitoring of secretion with high time resolution will be discussed. These assays include multi-color electrophoretic affinity assays, electrochromatographic separations for small molecule transmitters, and fluorescence anisotropy immunoassays. A number of these assays have been integrated into microfluidic systems to enable monitoring of secretions as a function of time. Select applications of these devices will also be discussed including how groups of islets can coordinate their secretion in vivo into pulses that are necessary for proper glucose utilization.

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

Professor Richard Olson | Bristol-Myers Squibb

Professor Ken Hsu

ABSTRACT

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

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

Professor William Tolman | Washington University in St. Louis

Professor Charlie Machan

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

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

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

Professor Robert Gilliard

ABSTRACT

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

REFERENCES

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

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

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

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

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

Graham Lecture: Increasing Access to Global Healthcare through Process Intensification

Dr. Frank Gupton | Virginia Commonwealth University

Professor Brooks Pate

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