ÌÇÐÄvlog¹Ù·½Èë¿Ú

Abstract: Development of stable gold-based complexes has been a rapidly advancing field due to the popularity of gold complexes, particularly for use in biomedical applications and catalytic transformations. Given that auranofin, a gold(I) complex having FDA approval for the treatment of rheumatoid arthritis has been the only clinically relevant gold-based agent, the need for stable gold-based molecules is at an all-time high. Herein are reported synthetic strategies used for the development of new classes of gold(I) and gold(III) complexes for advancement in mitochondrial modulation for use as chemotherapeutics as well as application to gold catalysis due to the unique geometry of complexes presented within. Mitochondrial structure and function are integral to maintaining mitochondrial homeostasis and are an emerging biological targets in aging, inflammation, neurodegeneration, and cancer. Meanwhile, targeting cellular metabolism has emerged as a key cancer hallmark that has led to the therapeutic targeting of glycolysis. The study of mitochondrial structure and its functional implications remain challenging partially because of the lack of available tools for direct engagement, particularly in a disease setting. Furthermore, agents that target dysfunctional mitochondrial respiration for targeted therapy remain underexplored. Both the synthesis and characterization of highly potent organometallic gold(III) complexes supported by dithiocarbamate ligands as selective inhibitors of mitochondrial respiration and a gold-based approach using tricoordinate gold(I) complexes to perturb mitochondrial structure and function for selective inhibition cancer cells have been elucidated. Mitochondrial targeting and inhibitory effects are characterized using a plethora of both in vitro and in vivo experiments. While developing the tricoordinate framework, the unique geometry led to the pursuit of identifying other applications for these unique gold(I) complexes. The development of oxidant-free, gold-catalyzed, cross-coupling reactions involving aryl halides have been hampered by the lack of gold catalysts capable of performing oxidative addition at Au(I) centers under mild conditions or without some external oxidant. The catalytic method developed is insensitive to air or moisture. The asymmetrical character of the air-stable gold(I) complex is critical to facilitating this necessary orthogonal transformation. Taken everything together, rational design of novel gold complexes with unique binding motifs and geometry provide a building block for future applications with a diverse array of applications.

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Abstract: Secondary metabolites are organic compounds produced by an organism for reasons other than growth and development. In plants, secondary metabolites generally act as defense agents produced to deter predators and inhibit other competitive species. For humans, these compounds can often have a beneficial effect and are pursued and utilized as natural pharmaceuticals. The development of sensitive, high-throughput analytical screening methods for plant derived metabolites is crucial for natural pharmaceutical product discovery and plant metabolomic profiling. Here, metabolomic profiling methods were developed using a microfluidic capillary zone electrophoresis device and evaluated against traditional separation approaches. An alkaloid screening assay was constructed to analyze transgenic mutant plant extracts for novel metabolites. Putatively identified novel features were detected, elucidated, and then isolated and purified for pharmaceutical evaluation. Additionally, methods for the analysis of polyphenolic plant-derived secondary metabolites, such as cannabinoids, were also developed and evaluated. In this case, the occurrence of cross-instrumental variation was addressed, given the tight legal restrictions regarding commercialization the products in question. Lastly, the microfluidic CZE-MS methods were further applied for both primary and secondary metabolite profiling in a DMPK assay. This assay was developed to inclusively monitor metabolic changes as a response to varying concentrations of a therapeutic in circulation. The metabolomic methods developed and evaluated in this work displayed high sensitivity, efficiency, and accuracy and can be utilized across a wide variety of applications.

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Abstract: Small-molecule organic materials are of increasing interest for electronic and photonic devices due to their solution processability and tunability, allowing devices to be fabricated at low temperature on flexible substrates and offering utility in specialized applications. This tunability is the result of functionalization through careful synthetic strategy to influence both material properties and solid-state arrangement, both crucial variables in device applications. Functionalization of a core molecule with various substituents allows the fine-tuning of optical and electronic properties, and functionalization with solubilizing groups allows some degree of control over the solid-state order, or crystal packing. These combinations of core chromophores with varying substituents are systematically evaluated to develop structure-function relationships that can be applied to numerous applications. In this work, heteroacenes are investigated for singlet fission and triplet harvesting, with known crystal engineering strategies applied to optimize crystal packing and maximize relevant solid-state interactions. Further, a class of antiaromatic compounds are investigated using the same approaches to build up structure-function relationships and provide insight into the properties of a relatively understudied core molecule.

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Professor Andrew Gewirth

The University of Illinois at Urbana-Champaign

Understanding and Controlling Electrochemistry for Electrolyzers and Batteries

Abstract:

This talk addresses the electrochemical reactivity associated with electrolyzers and batteries.  Relevant to electrolyzers we show that electrodeposition of CuAg or CuSn alloy films under suitable conditions yields high surface area catalysts for the active and selective electroreduction of CO₂ to multi-carbon hydrocarbons and oxygenates.  Alloy films containing Sn exhibit greater efficiency for CO production relative to either Cu along or CuAg at low overpotentials.   In-situ Raman and electroanalysis studies suggest the origin of the high selectivity towards C₂ products to be a combined effect of the diminished stabilization of the Cu₂O overlayer and the optimal availability of the CO intermediate due to the Ag or Sn incorporated in the alloy.  Sn-containing films exhibit less Cu₂O relative to either the Ag-containing or neat Cu films, likely due to the increased oxophilicity of the admixed Sn.  Incorporation of a polymer into the Cu electrodeposit leads to very active CO₂ reduction electrocatalysis due to pH changes at the electrified interface.  Vibrational spectroscopy is used to evaluate the pH at the interface during electrolyzer operation.

Relevant to batteries, we discuss solid electrolytes (SEs) which have become a practical option for lithium ion and lithium metal batteries due to their improved safety over commercially available ionic liquids. The most promising of the SEs are the thiophosphates whose excellent ionic conductivities at room temperature approach those of commercially-utilized electrolytes. Hybrid solid-liquid electrolytes exhibit higher ionic conductivities than their bare solid electrolyte counterparts due to decreased grain boundary resistance, enhanced interfacial contact with electrodes, and decreased degradation at the interface. Spectroscopic and structural studies on these latter materials lead to new formulations and artificial SEI materials exhibiting advantageous properties.

Host: ECS UK chapter

Professor Marc T. M. Koper

Leiden University, Netherlands

Advances and challenges in understanding the electrocatalytic conversion of carbon dioxide to fuels

Abstract:

The electrocatalytic reduction of carbon dioxide is a promising approach for storing (excess) renewable electricity as chemicalenergy in fuels. Here, I will discuss recent advances and challenges in the understanding of electrochemical CO2 reduction. I will summarize existing models for the initial activation of CO2 on the electrocatalyst and their importance for understanding selectivity. Carbon–carbon bond formation is also a key mechanistic step in CO2 electroreduction to high-density and high-value fuels. I will show that both the initial CO2 activation and C–C bond formation are influenced by an intricate interplay between surface structure (both on the nano- and on the mesoscale), electrolyte effects (pH, buffer strength, ion effects) and mass transport conditions. This complex interplay is currently still far from being completely understood.

Y.Y.Birdja, E.Perez-Gallent, M.C.Figueiredo, A.J.Göttle, F.Calle-Vallejo, M.T.M.Koper, Nature Energy 4 (2019) 732-745

Host: ECS UK chapter

Abstract: Biological polymer networks such as mucus, extracellular matrix, nuclear pore complex, and bacterial biofilms, play a critical role in governing the transport of nutrients, biomolecules and particles within cells and tissues. The interactions between particle and polymer chains are responsible for effective selective filtering of particles within these macromolecular networks. This selective filtering is not dictated by steric alone but must use additional interactions such electrostatics, hydrophobic and hydrodynamic effects to control particle transport within biogels. Depending on chemical composition and desired function, biogels use selective filtering to allow some particles to permeate while preventing others from penetrating the biogel. The mechanisms underlying selective filtering are still not well understood yet have important ramifications for a variety of biomedical applications. Controlling these non-steric interactions are critical to understanding molecular transport in vivo as well as for engineering optimized gel-penetrating therapeutics. Fluorescence correlation spectroscopy (FCS) is an ideal tool to study particle transport properties within uncharged and charged polymer solutions. In this dissertation, our research focuses primarily on the role of electrostatics on the particle diffusion behavior within polymer solutions in the semi-dilute and concentrated regimes.

Using a series of charged dye molecules, with similar size and core chemistry but varying net molecular charge, we systematically investigated their diffusion behavior in polymer solutions and networks made up of polysaccharide and proteins. Specifically, we studied in Chapter 3 the probe diffusion in semidilute and concentrated dextran solutions. The hindered diffusion observed in attractive gels is dependent on the probe net charge and shows a dependence on the solution ionic strength. Using a biotinylated probe, we also show evidence of an additional non-electrostatic interaction between the biotin molecule and the dextran polymer chains. In contrast, comparisons to a highly charged, water soluble polyvinylamine (PVAm) semidilute solution shows that all probes, regardless of charge, were highly hindered and a weaker dependence on solution ionic strength was observed. In Chapter 4, we characterized the transport properties of our probe molecules within pure and mixed charge solutions of amino(+)-dextran and carboxymethyl(-)-dextran. We show that these mixed charge polymer solutions still have the potential to be efficient filters for interacting particles even with comparably few attractive interaction sites. By chemical modification of the amino dextran, we also compare these results to those obtained in polyampholytic solutions. Lastly, we investigate the transport properties of both probes and a much larger bovine serum albumin (BSA) protein molecule within liquid-liquid phase separated (LLPS) tau protein in chapter 5. Tau is an intrinsically disordered protein with both positive and negatively charged amino acids. We show that despite having a high local protein concentration, tau droplets are relatively low density and comparable to semi-dilute polymer solutions. Both probe molecules and BSA are observed by FCS to be recruited within the liquid droplet resulting in ~10x fold increase in particle concentration inside the tau droplet compared to outside. Probe transport within the phase separated tau is sensitive to probe net charge and solution ionic strength. Lastly, we show that BSA transport inside the tau droplet can be fairly well described by using Stokes-Einstein adjusted for the experimentally determined microviscosity within the tau droplet.

Keywords: diffusion, biological gels, fluorescence correlation spectroscopy, electrostatic, interaction filtering.

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The Department of ÌÇÐÄvlog¹Ù·½Èë¿Ú hosts a Graduation Celebration and Awards Ceremony to recognize the outstanding acheivements of our students on an annual basis. This year's event will be streamed via Facebook. !

We are delighted to recognize the following graduates of our PhD, Masters, and Undergraduate programs:

Abstract:

 

 ClpXP is an Escherichia coli protease that carryout energy-dependent intracellular proteolysis. In recent years, this system has been widely studied due to its importance as a protein regulatory machinery and a virulence factor.  Protein substrates of ClpXP contain degrons with a specific protein sequence. SsrA tag is one of the five degrons known to subject proteins for ClpXP degradation. SsrA is an 11 amino acid peptide added to the C-terminus of nascent polypeptide chains translated from aberrant messenger RNAs lacking stop codons via a process called trans-translation.

ClpXP was known to targets only cytosolic proteins with degrons until recently, AcrB, an E. coli membrane protein was found to be degraded by ClpXP when it is tagged by ssrA peptide, which leads to the speculation that ClpXP is capable of degrading membrane proteins.   However, this speculation was challenged with the finding that ssrA tagging of ProW1−182, a different inner-membrane protein resulted in degradation by AAA+ membrane protease FtSH. We report that the membrane substrates of ClpXP bear long c-terminal cytoplasmic domains while metastable proteins lacking cytoplasmic domains are degraded by FtsH. For instance, ssrA tagged Aquaporin-Z (AqpZ), a stable tetrameric membrane protein lacking a c-terminal cytoplasmic domain is subjected to degradation by neither ClpXP nor FtsH. Nevertheless, when the c-terminus of AqpZ is fused with ssrA tagged Cyan fluorescent protein ClpXP degrades the resulted fusion protein while truncated metastable version, AqpZ 1-155 is degraded by FtSH.

This presentation also emphasizes our attempt to unravel the possible effect of proton motive force on the activity of ClpXP. We used Carbonyl cyanide m-chlorophenyl hydrazone (CCCP) to disrupt the proton motive force. Our results suggest that degradation of soluble protein substrates such as GFP-ssrA, MurA-ssrA, Chloramphenicol acetyltransferase ssrA are not affected by CCCP. However, degradation of membrane protein substrates by ClpXP is diminished in the presence of CCCP. We speculate that either the proton motive force or ATP provided from oxidative phosphorylation is essential, or both are important for ClpXP to degrade membrane proteins. 

It has been shown that the TolC is not a good target for inhibition of multidrug efflux of antibiotic-resistant bacteria as the bacterial susceptibility to antibiotics was not affected even when a significant amount of TolC is depleted.  TolC is a membrane protein channel that functions in conjunction with transporters and membrane fusion proteins and provides a pathway to expel antibiotics across the E. coli outer membrane.  AcrAB-TolC multidrug efflux pump is one such example where TolC cooperates with AcrB transporter and AcrA membrane fusion protein.   We report that the depletion of the number of copies of AcrB makes bacteria highly susceptible to antibiotics. We utilized ClpXP degradation system to regulate the copy number of AcrB in the cell. Our results show that AcrB is an excellent target for inhibiting multidrug efflux, and ClpXP is an excellent tool to regulate antibiotic target proteins for research purposes.

Bio: Curtis P. Berlinguette is a Professor of ÌÇÐÄvlog¹Ù·½Èë¿Ú and Chemical & Biological Engineering at the University of British Columbia. He is also a CIFAR Program Co-Director and a Principal Investigator at the Stewart Blusson Quantum Matter Institute (SBQMI), and the CEO of Miru Smart Technologies.

Prof. Berlinguette leads a large, interdisciplinary team seeking ways to discover and scale disruptive clean energy materials. His academic group has advanced a range of clean energy applications including CO₂ utilization, next-generation solar cells, and self-driving labs. Prof. Berlinguette also likes to work on high-risk, high-impact clean energy projects like cold fusion. He has authored more than 100 scientific articles and 20 patent applications, and has participated in over 190 invited lectures at leading universities and international conferences. Prof. Berlinguette has been recognized with several awards, including an Alfred P. Sloan Research Fellowship and an NSERC E.W.R. Steacie Memorial Fellowship.

Abstract: The electrochemical conversion of CO₂ by the CO₂ reduction reaction (CO₂RR) is a promising strategy that enables renewable energy to be stored in carbon chemicals and fuels using atmospheric or emitted CO₂. Pilot-scale electrolyzers utilizing gaseous CO₂ feedstocks can mediate high rates of CO₂RR, however, this approach relies on several complex and energy-intensive steps required to produce purified, high-pressure CO₂ from carbon capture. This presentation will focus on the direct conversion of aqueous carbon capture solutions (i.e., those rich in bicarbonate anions) into useful chemicals (i.e., CO) over extended periods of time. I will show how to design an electrolyzer that converts liquid bicarbonate feedstocks into carbon products at comparable rates and greater efficiencies than reactors relying on pressurized CO₂. Our work demonstrates bicarbonate electrolysis as a practical strategy for storing renewable energy in carbon chemicals while bypassing CO₂ separation and pressurization processes in upstream CO₂ capture.

Find details of the event and registration here.

To view a copy of the 2019 abstract booklet, click here.

Note to UK students: Students in CHE 395 planning to graduate or otherwise conclude their research are required to participate in the Poster Session if they have not done so in the past. 

Schedule of Events:

10:00am - Zoom Check-In and Set Up

10:30 - 12:00pm - Group A Presents

1:00pm - 2:30pm - Group B Presents

3:30pm - Awards Presented

Recent winners include students from: