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Chemistry

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  • ItemOpen Access
    Structural Modifications of Dithienophospholes for Applications as Functional Materials
    (2024-03-16) Asok, Nayanthara; Baumgartner, Thomas
    Recent breakthroughs in synthetic chemistry have revolutionized main-group molecules, elevating them from mere laboratory curiosities to powerful materials with broad applications. A primary focus has been on electron-accepting or -deficient materials, driven by their historical limitations in availability and stability, which have hindered practical applications. The incorporation of heavier main-group elements, including Si, Ge, P, As, Sb, Bi, S, Se, and Te, has proven advantageous for electron-accepting materials due to their polarizable molecular orbitals (MOs) readily accessible to electrons and nucleophiles. This foundation has spurred research in materials chemistry across various applications, encompassing optoelectronic devices (OLEDs, OPVs), energy storage (batteries, capacitors), fluorescent sensors (biological, physiological), catalysis, and synthesis. Among main-group-element-based materials, organophosphorus compounds hold a privileged status, with their frontier orbitals easily modifiable through chemical, structural, or electronic means at the phosphorus center itself, without necessitating kinetic stabilization. The five-membered phosphorus-based heterocycle, phosphole, is particularly captivating in this context. Extensive studies have unveiled the intricate σ*-π* interaction within phospholes, endowing them with intriguing electron-accepting properties, while preserving morphological and physiological stability for practical utilization. Furthermore, phosphorus introduces easily accessible, low-lying antibonding orbitals, leading to Lewis acidic phosphorus species, a departure from the conventional perception of phosphorus as an electron-rich element. These species exhibit unconventional chemical reactivity through hypervalency. This thesis advances conjugated materials by employing the unique structures and electronics of organophosphorus compounds. It discusses how these materials can be harnessed to design functional materials with exceptional electronic, chemical, and structural properties, contributing to the realm of functional materials.
  • ItemOpen Access
    Machine Learning Estimation of Reaction Energy Barriers and its Applications in Astrochemistry
    (2024-03-16) Ji, Hongchen; Fournier, Rene Andre
    We developed a machine learning model for fast estimating reaction energy barriers. The model was trained on data for 11,730 elementary reactions and barriers computed with an estimated accuracy of 2.3 kcal/mol by Grambow and coworkers. Although it was trained, and then applied, only for reactions involving atoms of H, C, N and O, our model can readily be generalized to molecules and reactions involving other elements. We designed and tested many molecular representations. Our best model has 363 features calculated from the chemical composition, structure, and energy of products and reactants that can all be obtained at a small computational cost. A Kernel Ridge Regression with Laplacian kernel was found to give the best fit to the data. It makes predictions with a mean absolute error of 4.1 kcal/mol for barriers smaller than 40 kcal/mol. We used this machine learning model to estimate the barriers of 136,081 hypothetical association reactions between molecules known to exist in the circumstellar envelopes and interstellar medium, where temperatures range between 10 and 150 K. A screening procedure identified reactions likely to occur (those with near zero barriers) that could play a role in the formation of relatively complex organic molecules (those with at least one double bond and containing at least one atom each of the elements H, C, N and O). Reactions identified as the most promising were investigated with density functional theory and coupled cluster quantum chemical methods to obtain reaction pathways and energies of reactants, intermediates, transition states and products with an accuracy of roughly 1 kcal/mol. We found no barrierless reaction but found two reactions with low barriers leading to the formation of N-methyleneformamide (CH2NCHO) and imine acetaldehyde (NHCHCHO). These molecules have not yet been observed in space. The low barriers that we calculated, and the possibility that these reactions would be facilitated by adsorption on ice covered dust grains in the interstellar medium, suggest that these two molecules may exist in space and could be detected by determinations of rotational constants from spectroscopic lines in the microwave region.
  • ItemOpen Access
    Robust MircroRNA detection by Capillary Electrophoresis
    (2023-12-08) Hu, Liang; Krylov, Sergey N.
    MicroRNA (miRNA) are short single-stranded RNA molecules that function as post-transcriptional regulators in gene expression, The abnormal expression of small subsets of miRNAs, termed “miRNA fingerprints”, have been found as potential biomarkers in diagnosis of various diseases including cancers. However, none of miRNA-based biomarkers has been approved yet for clinical use due to the lack of a robust quantitative method for miRNA analysis. To address this issue, there have been significant efforts towards developing robust quantitative miRNA detection methods. Among a variety of initiatives, DQAMmiR is a promising approach developed by our lab which is capable of direct, quantitative analysis of multiple miRNAs in capillary electrophoresis (CE). In my PhD project, I have been focusing on investigating and improving the robustness of DQAMmiR to increase its applicability for practical use. Firstly, I demonstrated that DQAMmiR is capable of directly quantitating miRNA in crude cell lysates, indicating its robustness to the change of sample matrices, revealing its great potential to be used to analyzing miRNAs in biological samples directly without the need for complex sample processing. Secondly, I developed a second-generation DQAMmiR by replacing the ssDNA probes with the electrically neutral peptide nucleic acid (PNA) probes, which further improves the robustness of the assay by removing the need for single-stranded DNA binding protein (SSB) in the assay. Thirdly, to increase the applicability of the assay, I introduced a new sample preconcentration technique based on the integration of field-amplified sample stacking (FASS) and isotachophoresis (ITP) prior to CE separation in DQAMmiR, which successfully decreases its limit of quantification (LOQ) by 140 times. Lastly, I investigated the applicability of DQAMmiR for analyzing urinary miRNAs. I demonstrated that the concentration ratio of two miRNAs, miR-16 and miR-21, could be relative stable from different urine samples collected from the same person, although the individual concentrations of these miRNAs varied significantly in these samples. These findings suggests that the ratiometric measurements between multiple miRNAs in urine would serve as better biomarkers than individual miRNA concentrations for clinical diagnostic tests. And DQAMmiR would be an ideal analytical methodology for the development and use of such tests.
  • ItemOpen Access
    Instrumental Analysis of Pasylated Asparaginase, JZP-341, A Pre-Clinical Drug Candidate
    (2023-12-08) Ghaffari, Shakiba; Krylov, Sergey N.
    Bio-betters are second-generation biopharmaceutical drugs that aim to improve the original drug’s pharmacokinetic or pharmacodynamic properties through minor physical modifications. Bio-betters require extensive characterization. Here, we investigate: JZP-341, a long-acting asparaginase bio-better used to treat leukemia. JZP-341 has a disordered proline-alanine-serine (PAS) tail that increases the drug’s size and thereby its serum half-life. A long serum half-life decreases the dosage frequency, providing more freedom to the patient. We assess the structural heterogeneity, charge heterogeneity, and enzyme kinetics of JZP-341 to better understand the effects of the PAS tail on the drug via the methods of capillary electrophoresis (CE), mass spectrometry (MS), and chromatography. We observe size heterogeneity and charge heterogeneity. We also developed a native capillary gel electrophoresis assay and an automated label-free CE-MS enzyme activity assay to study JZP-341. A detailed understanding of the role of PAS tail on JZP-341 requires further assay development and sophisticated equipment.
  • ItemOpen Access
    Sustainable Synthesis of 4-acylpyridines through air oxidation of dearomatized 4-alkylpyridines
    (2023-12-08) Puzhitsky, Matthew; Orellana, Arturo
    Nitrogen containing heterocycles such as pyridines are a frequently encountered motif found in small molecule drugs approved by the FDA. Due to their prevalence in the pharmaceutical industry, green and effective synthetic routes towards these molecules are appealing. We detail a novel synthetic route towards 4-acypyridines via the ambient oxidation of alkylidene dihydropyridines (ADHPs). We then establish the robust and chemoselective nature of this oxidation by exploring substrates with various functional groups and multiple pyridylic sites. Finally, a series of time-course NMR studies reveal how to manipulate the stability of ADHPs by varying the nature of the chloroformate used to make these conjugated intermediates.
  • ItemOpen Access
    Mild Electrocyclization of Heptatrienyl Anions
    (2023-12-08) Guo, You Xuan Bill; Orellana, Arturo
    Carbocycles are prevalent in natural products and drug-like molecules. Despite their importance in medicinal chemistry, functionalized cycloheptanes remain a challenging scaffold to access. We have taken a keen interest in developing a strategy for cycloheptane formation through electrocyclization of heptatrienyl anions. Historically, this strategy has faced many challenges, including the use of strong bases to form the heptatrienyl anion, the lack of product selectivity, and low yields. We aim to overcome these deficiencies by the strategic use of electron withdrawing groups to activate both the heptatriene towards deprotonation and stabilize the resultant heptadienyl anion. In this report we detail the mild catalytic electrocyclization of functionalized heptatrienyl anions.
  • ItemOpen Access
    Exploring selected modern Mass Spectrometry techniques in applied sciences
    (2023-12-08) Taemeh, Maryam Yousefi; Ifa, Demian R.
    Mass Spectrometry (MS) is a powerful analytical technique that has revolutionized our ability to analyze complex mixtures and has diverse applications in various scientific disciplines. It is widely used in chemistry and biology to determine the molecular composition, structure, and quantification of samples. In this dissertation, we aimed to explore novel applications of mass spectrometry techniques, including electrospray ionization (ESI) and tandem mass spectrometry (MS/MS), as well as mass spectrometry imaging (MSI) techniques such as matrix-assisted laser desorption/ionization (MALDI) and desorption electrospray ionization (DESI). The objective was to strengthen our knowledge and skills in various MS methodologies and gain practical experience in using these techniques, for developing methods to chemically profile, separate, detect, map, and quantify a wide range of targeted and untargeted analytes from complex matrices. Given the versatility of MS-based techniques, we focused on specific applications within this field. First and foremost, forensic and pharmaceutical cannabis-related applications require accurate and sensitive analytical methods. Hence, we developed and validated a DESI-MS method for detecting cannabinoids in cannabis-infused chocolate, utilizing TLC-DESI-MS and QuEChERS extraction for THC quantification. Additionally, we investigated metabolic differences associated with soybean alleles (QTLs E and M) conferring resistance to leaf-chewing insects. Non-targeted mass spectrometry reveals distinct metabolite sets influenced by the QTLs, highlighting daidzein as a significant marker. This suggests a novel mechanism impeding the insects' ability to evolve tolerance. Moreover, we explored the sublimation technique for the application of a matrix coating in MALDI-MSI. Specifically, we investigated the optimal conditions for the sublimation of the 5-chloro-2-mercaptobenzothiazole (CMBT) matrix on mouse kidney samples. We successfully obtained high-quality MALDI-MSI images of phospholipids (PC, PG) and phosphatidylinositol (PI) in mouse kidney sections, providing valuable spatially resolved information. Lastly, we discussed the importance of phosphatidylinositols (PI) and phosphoinositides and their involvement in various diseases, emphasizing the need to optimize the MALDI-matrix type and thickness for enhanced sensitivity in detecting these molecules. The label-free data obtained through this optimized approach holds the potential for investigating the relative m/z factors associated with PI-related pathogenesis. Overall, this dissertation demonstrated the versatility and potential of mass spectrometry techniques. The findings lay the groundwork for future research in the field of MS analysis, particularly in the detection, quantification, and understanding of phosphatidylinositols and phosphoinositides in biological systems and disease pathologies.
  • ItemUnknown
    Investigating the Structural Dynamics of Therapeutic Proteins using Time resolved Hydrogen deuterium Exchange Mass Spectrometry
    (2023-12-08) ElSabaawy, Marwa Abdalla Abdelmaksoud Mohamed; Wilson, Derek
    Biopharmaceutical products have drastically grown as essential treatments in clinical settings. Hence, the drug industry is moving towards protein-based therapeutics with increasing demands for parallel advancement in bioanalytical technologies. This thesis centers around displaying the versatility of coupling front-end analytical methods to mass spectrometers. We implement time-resolved electrospray ionization hydrogen-deuterium exchange (TRESI-HDX) and ion mobility spectroscopy (IMS) MS for uncovering new and exciting insights into therapeutic protein dynamics and protein-substrate interactions on millisecond timescale. Using automated continuous flow injection (CFI) has enhanced the analytical throughput of our results. Collectively, the implications for these results widen the fundamental understanding of the studied proteins. Understanding the crosstalk between dynamics and function may help scientists to design new and improved therapeutics.
  • ItemOpen Access
    Quantification of Methane Emissions by Surface Mass Balance Method
    (2023-08-04) Kim, Yeuhyun; McLaren, Robert
    This thesis presents a surface mass balance method as a cost-effective top-down technique to conveniently validate the bottom-up inventories. Mobile methane measurements were performed for two large landfills, Keele Valley Landfill and Greenlane Landfill and the city of Sarnia which included petrochemical industries and residential areas by employing a Cavity Ringdown Spectrometer (CRDS) mounted in a vehicle to capture downwind enhancements of methane. Methane emission from the Greenlane landfill was estimated to be 3300 ± 730 kg h-1 by a mass balance approach. An estimation by a gaussian dispersion model provided a similar emission rate of 3320 ± 250 kg h-1. The regression analysis of the mixing ratios of CO2 and CH4 showed positive correlation with an average molar ratio of 0.99 ± 0.04 mole mole-1 which was used to estimate CO2 emission to be 7600 ± 1700 kg h-1. The city of Sarnia including its industrial complex and residential areas showed a total methane emission rate of 2450 ± 560 kg h-1. It is estimated the city emits 21.5 ± 4.9 kt CH4 annually accounting for 45% of Ontario’s oil and gas methane emission. These estimated source rates from facilities were consistently 9-10 times greater than the GHGRP estimates. The discrepancies confirmed in the study emphasizes that it is significant to reconcile top-down measurements with the bottom-up inventories to provide a more accurate understanding of methane sources and sinks in Canada.
  • ItemOpen Access
    Nanocrystals for Photocatalysis and Imaging Applications
    (2023-08-04) Malile, Brian; Chen, Jennifer I-Ling
    Nanocrystals, contrary to the bulk counterparts, can exhibit size-dependent optical, electronic, magnetic, and catalytic properties. These materials can be tailored for specific applications including sensing, bioimaging, drug delivery, optoelectronics, and catalysis. This dissertation explores two types of nanocrystals, namely CdS-based quantum dots (QDs) and DNA-conjugated gold nanoparticles (DNA-AuNPs), as photocatalysts for reductive organic transformations and high mass probes for the emerging Imaging Mass Cytometry bioanalytical platform, respectively. QDs are zero-dimensional semiconductor nanocrystals with attractive properties arising from quantum confinement effects. The tunable absorption and emission profiles make QDs desirable candidates in display technologies, lasing, and solar energy applications. On the other hand, non-radiative photophysical processes enhanced by quantum confinement in QDs are underutilised and often perceived as undesirable. One such process – Auger relaxation – can produce hot electrons with high reducing power and can be amplified further by doping the nanocrystal with Manganese (II). Part one of this thesis examines the photoreduction capabilities of Mn2+-doped CdS/ZnS core/shell QDs (Mn:CdS/ZnS QDs). The doped QDs were implemented as photocatalytic coatings on reaction vessels, and several model organic reactions were evaluated including the 6-electron reduction of nitrobenzene to aniline that reached an overall internal quantum efficiency of ~3%. The findings demonstrate several-fold increase in the photoreduction efficiency of Mn:CdS/ZnS over undoped CdS/ZnS QDs, and the film set up allows for facile post-reaction workup and a range of solvent compatibility. Additionally, surface characterizations were performed to probe the changes and address the reusability of the QDs. Lastly, the initial implementation of QD coatings in flow reactors showed success. This work presents new opportunities and diversifies the toolbox of heterogeneous photocatalysts for prospective use in organic reactions. Imaging Mass Cytometry (IMCTM) is a multiparametric imaging technique that utilizes metal-tagged antibodies as probes for investigating subcellular components via mass spectrometry. However, low-abundant cellular components can generate weak or no signals due to the small number of antibodies that bind to them. In the second part of this thesis, DNA-functionalized gold nanoparticles, each comprising >10 000 Au atoms, were examined as high mass probes for targeting low abundant microRNA. The interaction between the DNA strands on the AuNPs and microRNA-210, a biomarker for preeclampsia and hypertensive diseases, leads to the accumulation of DNA-AuNPs in cells as readily imaged with IMC. The results from IMC corroborated with traditional fluorescence-based methods, but with an enhanced sensitivity of a thousand-fold. This work is the first demonstration that DNA-AuNP can serve as high mass probes in IMC for detecting low-abundant nucleic acids.
  • ItemOpen Access
    An Evaluation of the Contributions of Short and Long Range Pollutant Transport on Southern Ontario's Atmospheric Sulfur Content
    (2023-08-04) Pritchard-Oh, Austin Michael; McLaren, Robert
    Sulfur dioxide (SO2), particle sulfate (p-SO4-2), and total sulfur (SOx) were evaluated at York University, in Toronto, Canada, using a ThermoFisher SO2 analyzer and an Aerodyne Aerosol Mass Spectrometer. These measurements were compared with a dataset from 2002-2020, which demonstrated a downward trend in atmospheric sulfur. Toronto’s atmospheric sulfur decline has plateaued in recent years. Current mean SO2 was 0.37 ppb, p-SO4-2 was 0.60 μg/m3, and SOx was 1.6 μg/m3. There were no significant seasonal or daytime/nighttime differences. The effects of pollutant transport and major contributors to Toronto’s sulfur were determined. Major contributors to SO2 included Hamilton metal refineries, Greater Toronto Area chemical production facilities, the Nanticoke petroleum refinery, and vehicle emissions. Major contributors to p-SO4-2 are Sarnia petroleum and chemical production, Sudbury metal refineries, and long-range transport from the Ohio River Valley. A field study mass-balance determination of Sarnia’s SO2 emissions was estimated at 0.18 tonnes/hr (4,300 kg/day).
  • ItemOpen Access
    Selective Chemical Reactions for Nucleic Acid Sequencing and DNA-Encoded Library Synthesis
    (2023-03-28) Mahdavi Amiri, Yasaman; Hili, Ryan
    Part One: The ability to map methylation sites in the human genome and epitranscriptome has transformed our understanding of how these modifications govern and influence a host of cellular processes and human diseases. Amongst the most widely studied methylations is N6-methyladenine, known as 6mA in DNA and m6A in RNA. While traditional methods to sequence these modifications have depended on antibody pulldowns, chemistry-based approaches are often less sequence dependent, can work on either DNA or RNA, and thus can provide a robust, inexpensive, and universal sequencing approach. In part one of this thesis, the first chemistry-based single-nucleotide resolution sequencing method for the detection of N6-adenine methylation sites in DNA and RNA is presented. This method takes advantage of the chemoselective deamination of unmodified adenines under acidic nitrite conditions, resulting in a (d)A to (d)G transition, while leaving methylated adenine sites unaffected. As changes in N6-adenine methylation of RNA and DNA have been implicated in a range of human diseases, especially cancers, the method has been rapidly adopted by researchers globally as an affordable and straightforward sequencing approach to assist in understanding the role and impact of the epigenome and epitranscriptome on human health. The ability of this method to detect other nucleotide modifications was also evaluated and described. Part Two: DNA-encoded libraries (DELs) comprise millions to billions of small-molecules covalently linked to a unique DNA barcode that can be read using standard next-generation sequencing (NGS). This technology has revolutionized the field of drug discovery as a method to rapidly identify small molecules that can serve as novel leads for drug development. The success of a drug discovery campaign involving a DEL depends on the chemical diversity presented within the DEL; methods that can generate DELs with new molecular architectures and with greater chemical diversity are critically needed to advance drug discovery efforts both within industry and academia. To this end, the use of photoredox chemistry as a facile method to generate DELs with drug-like properties is presented as part two of this thesis. An efficient approach for the photoredox-catalysed hydroaminoalkylation between on-DNA secondary N-substituted (hetero)arylamines and vinylarenes is explored as a method to generate DELs with known bioactive architectures. The developed reaction proceeds efficiently with a broad and well-explored substrate scope, working best with electron poor to neutral vinylarenes. This method is well suited for the construction of DELs enabling an expansion of drug-like chemical space.
  • ItemOpen Access
    Determining the Sampling Rates for a New Nylon Passive Sampler to Estimate the Atmospheric Concentrations of Nitric Acid and Perfluoroalkyl Acids Pollutants
    (2023-03-28) Carmichael, Lindy; Young, Cora; VandenBoer, Trevor C.
    Atmospheric pollutants such as gaseous nitric acid (HNO3) and perfluoroalkyl acids (PFAAs) are emitted or formed in the atmosphere as a result of anthropogenic activities. These acids could pose risks to organisms and the environment. The PFAAs are organofluorine chemicals that have been producing scientific and regulatory interest because of their persistence in the environment, toxicity, and bioaccumulation potential. They are detected in water, the atmosphere, human organs, and wildlife. There are scarce atmospheric measurements of PFAAs because of their low atmospheric concentrations. Nylon passive samplers are selective for sampling of atmospheric acids. They are well-validated for HNO3 but have never been used to collect PFAAs. The Nylasorb nylon filter, previously validated for HNO3 was discontinued and a new nylon filter was purchased from a different manufacturer. The new nylon filter has been characterized in this work for the monitoring of HNO3 and determination of PFAAs in the atmosphere.
  • ItemOpen Access
    Diversification of 4-Alkylpyridines: Mining for Reactivity with Alkylidene Dihydropyridines
    (2023-03-28) Doan, Brian Anh-Tuan; Orellana, Arturo
    Pyridines are valued structures in pharmaceutical development. Using a soft enolization approach, we can diversify alkyl pyridines under mild conditions via alkylidene dihydropyridines (ADHPs). Recent work in our group has demonstrated the utility of ADHPs in palladium-catalyzed reactions. However, the fundamental reactivity of ADHPs remains largely unexplored, with only scattered reports in the literature. We seek to further explore the reactivity of these electron-rich intermediates in different contexts, as new transformations can provide useful synthetic tools for pharmaceutical discovery. Herein we describe our investigations in this area, including the development of two new synthetic methods. Specifically, we describe the oxidation of ADHPs to the corresponding pyridylic ketones under mild conditions, and the iridium-catalyzed asymmetric alkylation of alkylidene dihydropyridines branch-allylated alkyl pyridines.
  • ItemOpen Access
    Design of Singlet Fission Chromophores through the Introduction of N-Oxyl Fragments.
    (2022-12-14) Dylan Shangrow James; Zeng, Tao
    Singlet fission is a highly desired phenomenon in photovoltaics. In the fission process, one short-lived singlet exciton splits to two long-lived triplet excitons. Generating a larger number of longer-lived excitons, singlet fission has the potential to enhance the photoelectric conversion efficiency. The exploitation of this phenomenon in the photovoltaic industry is however impacted by the small pool of existing singlet fission chromophores. Here, we report on the design of novel singlet fission chromophores through the substitution of N-oxyl fragments within the anthracene framework. The substantial diradical character brought on by the N-oxyl fragments located at specific positions on the anthracene pristine structure together with structural reorganization induced by excitation allows for a handful of chromophores to satisfy the thermodynamic requirements of singlet fission.
  • ItemOpen Access
    Electrophoretic Separations for Continuous Flow Synthesis
    (2022-12-14) Ivanov, Nikita; Krylov, Sergey N.
    The continuous-flow synthesis field has grown considerably in the last several decades. Converting a reaction from its batch synthesis to a continuous-flow alternative offers a long list of potential improvements. The latest advances make it possible for reactions to take place “on the chip’, where microscopic channels are used to propagate and mix different reactants. Continuously propagating discrete volumes of reactants inside a small capillary has the advantage of improved mass and heat transfers. These transport phenomena directly affect the kinetics and thermodynamics of the reaction, two factors that influence reaction yield over time. Having higher yields means that more product is made in a similar or lesser time frame, which can potentially lower the production cost of a pharmaceutical product, resulting in a monetary advantage for the early adopter. Another positive aspect of continuous flow chemistry is safety. By miniaturizing a reactor, we gain another level of control over the system. Since flow-reactor volumes are microscopic, the enthalpy of exothermic reactions can be easily dissipated. This is extremely important when reactions of interest possess high enthalpic contribution, especially if they are self-accelerating decomposition reactions. Since no reaction can ever achieve a hundred percent yield, a product purification mechanism is required at the end of each synthesis step. It runs naturally that a continuous-flow synthesis system should feed into a continuous-flow separation compliment without breaking the fundamental continuity concept. Up to this day, this remains the most problematic area of continuous-flow chemistry. Available continuous separation methods are either pseudo-continuous (simulated moving bed chromatography, SMBC) or severely limited in the number of concurrently separated analytes (Continuous liquid-liquid extraction, CLLE). The real solution to this problem are molecular stream separation (MSS) platforms. MSS approach allows for multiple analytes to be separated and analyzed simultaneously without disturbing the synthesis platform's continuous nature. Only two major MSS branches exist today, continuous-flow electrophoresis (CFE) and continuous annular chromatography (CAC). Although CAC has always been developed with the organic synthesis in mind, CFE has historically been reserved for water-soluble biological analytes such as DNA or proteins. By adapting CFE to the world of organic chemistry, we open the door to the field of electrophoretic separations for continuous-flow synthesis. The following manuscript will touch on the subject of fundamental engineering challenges imposed by the project and will serve to summarize our latest efforts at transforming CFE into a simple yet comprehensive platform for continuous chemistry separations.
  • ItemOpen Access
    Studying the Structural Dynamics and Aptamer-Ligand Interactions in the Cocaine-Binding Aptamer through Fluorescence Spectroscopy
    (2022-12-14) Shoara, Amin Aron; Johnson, Philip E.
    Since its first report in 1990, aptamers have been utilized in biosensor modeling technologies. One of the most important advantages of using aptamers is the structural flexibility and thermal stability of nucleic acids. These structural merits enable aptamers to be linked on solid surfaces, attached to chemical labels, or extended to build nanostructures for advanced therapeutic and diagnostic modeling purposes. The cocaine-binding aptamer was originally selected through a systematic evolution of ligands by exponential enrichment (SELEX) method to select cocaine molecules from cocaine metabolites in biological solutions. However, the aptamer showed binding to quinine and other antimalaria drugs tighter than its original ligand, cocaine. Work presented in this dissertation demonstrate how the cocaine-binding aptamer can be exploited as a model system for the structural analysis of aptamers using biophysical techniques including fluorometry methods. The results discussed in this study demonstrate how intrinsic fluorescence of ligands was exploited for aptamer-ligand binding and thermal stability analyses. Furthermore, photoisomerization of stilbene coupled with ligand-induced binding mechanism of the cocaine-binding aptamer were employed for the development of the Photochrome Aptamer Switch Assay. This research aims to gain insight into how aptamers interact with their ligands by utilizing the fluorescence properties of the ligands. Investigating the binding mechanisms of aptamers is essential in sensing technology since biosensors yield greater analytical sensitivity upon ligand-induced structural changes.
  • ItemOpen Access
    The Synthesis and Reactivity of Carbamoyl Fluorides
    (2022-12-14) Tiburcio, Tristan Redondo; Le, Christine
    Chapter 1 Herein we report a protocol for the synthesis of carbamoyl fluorides from secondary amines using inexpensive, and commercially available starting materials. This method employs the use of a difluorocarbene generated from the thermolysis of (triphenylphosphonio)difluoroacetate. This becomes oxidized by 4-methylpyridine N-oxide, generating difluorophosgene, which serves as the key intermediate to make the carbamoyl fluorides from secondary amine starting materials. This method allows access to carbamoyl fluorides with a vast functional group tolerance, including Lewis-basic heterocycles, alkenes, and alkynes. Chapter 2 We report a base-free, facile cross-coupling reaction of carbamoyl fluorides to silylated nucleophiles. This reaction utilizes an affordable and Earth-abundant nickel transition metal catalyst, with a common phenanthroline ligand (both of which see an exceptionally low loading), to synthesize ureas, carbamates, and alkynamides in moderate to excellent yields. The transmetallation step of the purported catalytic cycle generates a fluorosilane, providing the thermodynamic driving force for the reaction to progress, and circumventing the requirement of base.
  • ItemOpen Access
    Neutral Bidendate Guanidine-Based Zinc Complexes for the Ring Opening Polymerization of Lactide
    (2022-12-14) Khan, Brandon Sharaz; Lavoie, Gino G.
    Herein is reported the synthesis and structure elucidation of three novel zinc complexes bearing neutral bidentate guanidine ligands for the ring opening polymerization (ROP) of lactide to PLA. Ligand and complex structures were obtained computationally and leveraged against single-crystal studies to develop a method for predicting solid state structures of future complexes. The catalysts were tested for ring opening polymerization of lactide to PLA. The most active complex displayed a rate constant for propagation, kp, of 26 M-1h-1. The catalyst showed some stereoselectivity with a heterotactic bias in the polymer (Pr = 0.60). The polymer number average molecular weight was determined to be ~4700 g mol-1. The end analysis of the MALDI-TOF mass spectrum suggested water activation for the polymerization. The polydispersity index of the polymer was determined by gel permeation chromatography to be 1.10, indicating a well-behaved polymerization.
  • ItemOpen Access
    Developing an Automated Nitrous Acid (HONO) Platform to Detect Emerging Pollutants in a Commercial and Domestic Environment
    (2022-08-08) Lao, Melodie; Vandenboer, Trevor C.
    Nitrous acid (HONO) is an emerging household pollutant linked to adverse health effects, with levels reported higher indoors than outdoors. Under low light conditions, HONO can readily photolyze to form hydroxyl radicals, impacting our indoor air quality by generating harmful secondary pollutants. Thus, HONO formation processes must be well understood to improve indoor air quality. This work presents two new instruments: a HONO calibration source and an automated indoor HONO platform. The calibration source generates low HONO calibration mixing ratios from low ppt to tens of ppb, minimizing measurement uncertainty and identifying interferences for other HONO-detecting instruments. The source is integrated into an automated HONO platform, custom-built to perform modulated measurements of NOx and HONO in indoor air quality applications. The platform was deployed in a commercial kitchen to validate its measurements and investigate indoor chemical HONO processes in a setting that has not been previously measured at high-time resolution.