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Abstract: Earth’s atmosphere is a multicomponent system comprising gases, aerosols, cloud, and their interaction with sunlight impacts radiative forcing. Biomass burning and anthropogenic emissions releases volatile phenolic compounds at the atmosphere as primary organic aerosol. These phenolic compounds can undergo atmospheric processing such as chemical oxidation, and photochemical aging providing precursors for the formation of secondary organic aerosol. This dissertation ensembles laboratory studies of oxidative processing of group of representative phenolic compounds by O3, HO•, and NO3 at the relevant environmental conditions. Aerosolized microdroplets of phenolic aldehydes undergoes electron transfer reaction generating HO• at the online electrospray mass spectrometry (OESI) reactor when exposed to 0.045 ppmv to 5 ppmv O3(g) at the microsecond contact time, generating hydroxy-substituents of the parent molecules. Ozonolysis of  phenolic compounds and ring-functionalized product phenols produces compounds containing carboxylic, and ester-like functionalities. These phenolic compounds were then deposited on ZnSe FTIR windows and exposed to 1 L min-1 of 0.20 ppmv to 800 ppmv O3(g) for a longer timescale in a flow through reactor and analyzed by FTIR spectroscopy, UV-visible spectroscopy, ultrahigh pressure liquid chromatography (UHPLC) with UV-visible and mass spectrometry (MS) detection, ion chromatography (IC) with conductivity and MS detection, and nuclear magnetic resonance (NMR) spectroscopy for 1H and 13C nuclei and tow-dimensional heteronuclear single quantum coherence (HSQC) experiments. The reaction products were dominated by functionalized and oligomeric compounds. Syringic acid was used as a common standard to compare the responses of UHPLC-MS, IC-MS and NMR analysis and quantify methoxy-aromatic product compounds and syringaldehyde was used to compare results from UHPLC-MS and NMR, and pseudo quantify aromatic aldehydic compounds. The uptake of O3(g) by the phenolic compounds increased with increasing relative humidity (RH). The decay kinetics showed non-linear dependence against increasing molar ratio of O3(g).  Phenolic compounds were also studied for oxidation with NO3. When aerosolized microdroplet of phenolic compounds such as catechols were exposed to NO3, produced from the mixing of NO2(g) and O3(g) at the OESI-MS reactor, nitroaromatic compounds (NAC) were produced. Under variable pH (4.05 to 8.07) conditions, all these compounds generated NAC. Catechol thin film was deposited over ZnSe windows and oxidized by 1 L min-1 of NO2(g) and O3(g) mix, in the flow through reactor for longer times scale. Formation of 4-nitrocatechol (4NC) was observed after exposure to oxidant mixture of 200 ppbv NO2(g) and 50 ppbv O3(g) at 0% RH. 4NC production was highest at 0% RH and at elevated RH the reaction was dominated by O3(g) as observed by the increased production of cis,cis-muconic acid. Exposure to high ppbv oxidant mix such as 10700 ppbv NO2(g) and 2500 ppbv O3(g) at 0% RH showed generation of NAC and oligomers. Decay of catechol against increasing oxidant molar ratio showed non-linear dependence at 0% RH. All these results show the crucial role of daytime oxidant O3(g), and HO•, and nighttime oxidant NO3 on the oxidative processing of phenolic compounds. Considering these reaction pathways and kinetics parameters in future climate modelling would reduce the gap between field observation and computer simulation predictions.

**CANCELLED**

Marco Bonizzoni

Department of Chemistry and Biochemistry, The University of Alabama, Tuscaloosa, AL, USA.
Alabama Water Institute, The University of Alabama, Tuscaloosa, AL, USA.

E-mail: marco.bonizzoni@ua.edu

Abstract: Artificial supramolecular receptors often rely on weak intermolecular interactions for their chemical recognition properties, so they may struggle to work in competitive media, chief among 

which are water solutions. However, aqueous media are very important in analytical, environmental, and biomedical applications, so it is valuable to adapt our supramolecular tools to them. With the right tools, even the weakest noncovalent interactions can be pressed into service in aqueous media. We have been using water-soluble polymers (e.g. dendrimers, hydrogels, conjugated polymers) as scaffolds to build multivalent supramolecular sensors that take advantage of the large number of interactions and of the preorganization of receptor sites afforded by such scaffolds, resulting in improved affinity in buffered aqueous solutions near neutral pH. We have successfully built systems for the detection of interesting guest families, including carboxylate anions, simple saccharides, heavy metal cations, and polycyclic aromatic hydrocarbons. These are examples of a general approach with two key advantages. On the one hand, installing known receptor chemistry on a polymer scaffold affords a modular approach to multivalency with minimal design and synthesis effort. This improves the apparent strength of weaker interactions and allows them to overcome desolvation costs in water. On the other hand, water-soluble macromolecular scaffolds impart solubility to water-incompatible receptor families.

This simple approach is particularly valuable when designing chemical fingerprinting systems (sometimes referred to as an “electronic nose” or “tongue”) that typically require many different receptors, each one poorly selective, and recovers selectivity from judicious interpretation of the ensemble response.

**CANCELLED**

Abstract:

Electron bifurcation is considered as a third fundamental mode of energy conservation mechanism, in which endergonic and exergonic redox reactions are coupled. The newly discovered flavin based electron bifurcation in Electron transfer flavoproteins (ETFs) helps to reduce low potential ferredoxin, which provides electrons to drive biologically demanding reactions such as atmospheric dinitrogen fixation in diazotroph and methane production in methanogens. Current research demonstrates the capacity for electron bifurcation in the Rhodopseudomonas palustris ETF (RpalETF) system. RpalETF contains two chemically identical but functionally different FADs: ET-FAD is bound in highly mobile domain II, which sits in a stable base created by domains I and III. Bf-FAD is buried in between domain I and III. The two flavins execute contrasting, complementary electron transfer reactions. Whereas one mediates single electron transfer (ET-FAD), the other accepts electrons pairwise (Bf-FAD), yet both flavins’ sites include a conserved Arg sidechain. R273 favors the ASQ of ET-FAD, whereas R165 near the Bf-FAD appears not to, possibly due to neutralization of its positive charge by nearby C174. R273 forms a pi- pi stacking interaction with ET-FAD whereas R165 appears to form hydrogen bond interactions with Bf-FAD. To learn whether the active site arginine residues each have different effects on their respective neighboring flavins, we replaced each of the Args in turn with chemically conservative, and divergent substitutions. Our data shows, R273 plays a vital role in BfETF by stabilizing the ASQ of the ET-FAD, whereas R165 favors binding of the Bf-FAD that is essential for electron bifurcation in RpalETF. Along with the electron bifurcation studies, we report an irreversible, pH dependent, site selective, enzyme mediated, anaerobic chemical modification of ET-FAD to a pink amino FAD, which opens a new perspective with which to understand the 726 nm band formed in bifurcating ETF.

Join the seminar here: https://uky.zoom.us/j/87175023115?pwd=dHlVZUtRRGVaY295eHVPWFJFa2l1dz09; Password: 764392

Abstract: Cancer is a worldwide public health crisis that requires new and improved drugs to be developed to extend survival rates and improve the quality of life for the patient. Platinum-based drugs are used in approximately 50% of cancer treatment regimens. These drugs are highly effective in many kinds of cancer; however, cancers can develop platinum resistance and these drugs have troubling side effects that reduced their use and efficacy. To overcome these disadvantages, many other metals have been studied for their anticancer properties. Notably, the anticancer properties of ruthenium-based agents have drawn considerable attention with multiple ruthenium complexes entering clinical trials. Unlike platinum complexes, which are flat (square planar), ruthenium compounds can adapt a multitude of 3D structures, which leads to many possible mechanisms of actions.

One of the most promising applications of ruthenium(II) complexes is their ability to act as photodynamic therapy (PDT) and photoactivated chemotherapy (PACT) agents. Both of these methodologies use light to “turn on” a non-toxic light-sensitive drug to form highly cytotoxic species that can kill cancer cells. These methods are appealing as they present a way to control the cytotoxic species to spatially isolated regions of the body. This control can reduce damage to healthy cells and reduce harmful side effects. Ruthenium(II) polypyridyl complexes are especially well suited for these applications as they have highly tunable excited states that can be tuned with careful ligand modification and selection.

Ruthenium complexes have also shown great promise as non-light-activated anticancer drugs. The coordination of small pharmacologically active molecules to ruthenium(II) polypyridyl complex is one promising method to develop potential ruthenium-based drugs. This strategy aims to create drugs that are greater than the sum of their parts by achieving synergistic mechanisms of action not achievable with either component individually.

Here we report on the synthesis and anticancer properties of Ru(II) complexes designed for PDT, PACT, and light-independent anticancer mechanisms. Highly potent lead compounds are identified and explored for PDT and light-independent anticancer applications. These lead compounds incorporated organometallic ligands with ruthenium(II) polypyridyl scaffolds to modulate their excited-state properties to produce improved PDT agents. The integration of O,O-chelating ligands into various ruthenium(II) scaffolds produced a range of complexes suitable for PDT, PACT, and light-independent mechanisms. Notably, the majority of these complexes possessed low submicromolar potency and low in vivo toxicity. Our results presented here show multiple new strategies for making new ruthenium(II) anticancer agents. These new methods have promising implications for bioinorganic research because they further expand our understanding of how to use ruthenium(II) complexes for biological applications.

Abstract: Protein-protein interactions (PPIs) are vital to many biological processes, including gene expression, and immune reactions to pathogens. There are approximately 650,000 PPIs in humans with pertinent physiological functions. Aberrant expression of PPIs leads to improper function and contributes to a plethora of disease conditions including cancer. Thus, PPIs represent an enormous target space for drug discovery and chemical probes. Direct targeting of clinically relevant PPIs with small molecules remains an unmet medical need. The development of small-molecule inhibitors of PPIs is a challenging enterprise and, in most cases, considered undruggable due to large protein surfaces, lack of deep binding pockets, and enzymatic activities. Despite these limitations, significant progress has been made in the area of compound development that selectively targets oncogenic PPIs and those underlying inflammation. This talk will focus on the identification and rational design of small-molecule inhibitors of PPIs, as applied to distinct protein targets, including the proto-oncogene product c-MYC, which dimerizes with MAX; the immunotherapeutic target programmed death receptor (PD-1) and programmed death ligand-receptor (PD-L1), and the epigenetic target AT-rich interacting domain 4B (ARID4B). The fundamentals of the small-molecule drug discovery process will be covered. More so, the use of in silico methods and synthetic chemistry to discover gold-based small-molecule covalent inhibitors of the intrinsically disordered protein, MYC, as well as the first-in-class small molecule inhibitors of ARID4B will be presented. This talk will also shed light on the medicinal chemistry of the recently identified dual-action small molecule inhibitors that perturb both Poly(ADP-ribose) polymerase (PARP) and PD-1/PD-L1 pathways.

Attend the seminar here.

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.

Attend the seminar via Zoom by clicking here.

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.

Attend the seminar here. Password 618011.

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.

Attend the seminar here.

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