Chemistry & Biochemistry Theses and Dissertations
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Item ACYCLIC CUCURBIT[N]URIL MOLECULAR RECEPTORS: SEQUESTRANTS FOR DRUGS, MICROPOLLUTANTS, AND IODINE(2024) Perera, Wahalathanthreege Sathma Suvenika; Isaacs, Lyle; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Molecular containers are extensively utilized for their exceptional molecular recognition capabilities, making them suitable for use as sensors and sequestration agents. Cucurbit[n]urils, in particular, are recognized for their strong binding affinities, especially towards cationic guest molecules. These applications can be further enhanced by adjusting the size and shape of the host and incorporating functional groups.In Chapter 1, the concept of supramolecular chemistry is introduced, with a specific focus on cucurbit[n]urils. The chapter provides an overview of the development of cucurbit[n]urils and their potential applications. It also addresses the challenge of poor water solubility of cucurbit[n]urils, and discusses the enhancement of water solubility through the development of acyclic CB[n]s. Furthermore, the potential application of these containers as sequestration agents is explored. Chapter 2 describes the synthesis of a novel sulfated acyclic CB[n] receptor (Me4TetM0) and its recognition properties towards a panel of drugs of abuse. The obtained results were compared with two other sulfated acyclic CB[n]s (TetM0 and TriM0). Furthermore, in vivo studies were conducted with TetM0 to assess its efficacy as a sequestration agent for methamphetamine. Chapter 3 presents the synthesis of a series of water insoluble acyclic CB[n]-type receptors and studies their function as solid state sequestrants for organic micropollutants. The results are compared with CB[6] and CB[8]. The time course experiments performed with H4 show a rapid sequestration ability of the five micropollutants studied. Furthermore, under identical conditions, the micropollutant removal efficiency is higher than activated charcoal. Chapter 4 investigates the use of water-insoluble acyclic CB[n]-type receptors for the reversible capture of iodine from the vapor phase. H2 exhibits an iodine capture of 2.2 g g-1, equivalent to 12 iodine atoms per H2 molecule. Following iodine uptake, H2 undergoes partial oxidation, and the uptake of I3- and I5- was confirmed through Raman spectroscopy. Chapter 5 details the synthesis of glycoluril dimer bis(cyclic) ether-based hosts with diverse aromatic side walls. The chapter presents a comparative analysis of dye removal from a solid state and delves into the influence of distinct aromatic walls and various attached substituents.Item EXAMINING QUINONE CONTRIBUTION TO THE OPTICAL PROPERTIES OF CHROMOPHORIC DISSOLVED ORGANIC MATTER(2024) Ashmore, Rachel; Blough, Neil; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Chromophoric Dissolved Organic Matter (CDOM) in natural waters is largely responsiblefor absorption of light and photochemistry in the water, impacting environmental reactions and aquatic life. The composition of CDOM is greatly varied based on source, photochemical reactions, and natural cycles. The impact of quinone moieties on this structure and photochemical and redox reactions involving CDOM remains the subject of controversy. To investigate the impact of quinone structure on optical properties, model quinone compounds were thoroughly characterized by their optical properties and reactions with sodium dithionite and sodium sulfite. A series of methyl-substituted p-benzoquinones, a methoxy p-benzoquinone, and a range of napthoquinones and anthraquinones were investigated. These model compounds were characterized according to their quinone and hydroquinone molar absorptivities and fluorescence quantum yields. Sodium dithionite reduction of quinones and the impact of structure on the products of this reaction was investigated by reducing the quinones with both sodium dithionite and sodium sulfite and comparing the optical properties of the products to those of the quinone and hydroquinone. The spectra of dithionite reduced p-benzoquinones and napthoquinones suggested the presence of products other than the hydroquinone. Sulfite is produced in solution as a result of dithionite reduction of quinones. Model quinones were therefore also reduced with sodium sulfite to investigate the impact of this side reaction on the dithionite reduction products. High performance liquid chromatography (HPLC) was used to further investigate and quantify the products of dithionite reduction of quinones and the importance of sulfite interference. Although some of the model quinones react with sulfite to form a proposed sulfonated hydroquinone product, based on the observed extent of this reaction in dithionite reductions, the structures of quinones likely to be found in CDOM, and their relatively small contribution to CDOM optical properties, the sulfite reaction was determined to not significantly impact the study of quinone moieties in CDOM. Dithionite selectively reduces quinones, while borohydride reduces ketones, aldehydes, and quinones. Therefore, in CDOM samples, dithionite can be used to isolate the effects of quinone moieties on the optical properties. Dithionite reduction was used to analyse CDOM standards and natural water extracts from the North Pacific Ocean and the Chesapeake Bay to investigate quinone contribution to their optical properties. These results are compared to borohydride reduction results from Cartisano and McDonnell to compare the contribution of quinones to that of ketones and aldehydes. (1, 2) Dithionite reduction showed small impacts on absorbance and fluorescence, whereas significant changes in both were observed for borohydride reduction. Therefore, the optical changes observed under borohydride reduction are attributed to primarily ketones and aldehydes rather than quinones. Model quinones showed significant changes in fluorescence intensity due to dithionite reduction, which are largely not observed for CDOM standards and natural water extracts, further supporting the conclusion that their role in CDOM optical properties is small.Item DIRECTED AND ELLIPTIC FLOW MEASUREMENTS: A COMPARISON BETWEEN THE PARTICIPANT AND SPECTATOR PLANES IN Pb+Pb COLLISIONS AT √sNN = 5.02 TeV WITH CMS AT THE LHC(2024) Lascio, Samuel Andrew; Mignerey, Alice C.; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Directed and elliptic flow of unidentified charged hadrons at mid-rapidity are measured as a function of transverse momentum (pT) and pseudorapidity (η) in ultra-relativistic PbPb collisions at √sNN = 5.02 TeV with the Large Hadron Collider (LHC) at CERN. The reaction plane (RP) angle is approximated using participants and spectator neutrons measured with the Compact Muon Solenoid (CMS) detector and the newly installed Spectator Reaction Plane Detector (SRPD), respectively. The SRPD is the latest addition to the existing Zero Degree Calorimeter (ZDC) designed to measure spectator neutrons +/- 140 m from the interaction point at CMS. The Event Plane (EP) Method is used to calculate the v1odd, v1even, and v2 harmonic flow parameters as functions of η and pT. The directed flow measurements using participants and spectators with CMS are compared and contrasted. Overall results are in good agreement between participants and spectators, however v1even(pT) measurements using spectators begin to show the opposite trend to those using participants at pT > 2 GeV/c. Results are compared to those obtained by A Large Ion Collider Experiment (ALICE), which is another experiment at the CERN LHC. Directed flow results do not agree with those obtained by ALICE. Additionally, the first elliptic flow measurements using the EP Method and mixed harmonics with the SRPD are reported. A slight asymmetry in v2(η) is observed using spectators. The elliptic flow results do agree with ALICE. Tracking efficiency as determined by the CMS collaboration is applied to the data and potential corruption as a result is discussed. Results strongly support continued use of the SRPD as a spectator neutron detector for reaction plane determination within the CMS ZDC.Item USING VIBRATIONAL SUM-FREQUENCY-GENERATION SPECTROSCOPY TO EXPLORE THE ROLE OF SOLVENT ORGANIZATION IN DETERMINING ION LOCATIONS NEAR SILICA SURFACES(2024) Singh, Siddharth; Fourkas, John; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Chemical processes occurring at liquid–solid interfaces are fundamental to applications in fields such as energy storage and nanofluidic transport. In this thesis I establish that the general framework used to describe and understand these systems, the electrical double-layer model, is insufficient in describing interfacial electrolyte solutions in polar, aprotic organic solvents. Using vibrational sum-frequency-generation (VSFG) spectroscopy, a nonlinear optical technique that is indispensable for exploring interfacial organization and dynamics, I study different polar aprotic solvents at silica interfaces. These studies highlight the importance of the organization of such solvents in dictating the interfacial distribution of ions. In the first part of this dissertation, I compare electrolyte experiments in acetonitrile (MeCN) and propionitrile (EtCN) to determine how an increase in alkyl chain length can influence solvent organization at a liquid–solid (LS) interface, and thereby influence the interactions of ions with the interface. In the second part of the dissertation, I focus on a solvent mixture of EtCN and deuterated MeCN at a silica interface. VSFG data for solutions with different molar ratios of the two solvents indicate that there is preferential partitioning of each liquid at this surface. In the third part of this dissertation, I examine the effects of solvent chirality on the organizational behavior at an LS interface, and consequently on the effects of this organization on ion partitioning. The key result of my research is that a polar, aprotic, organic solvent’s structure, chirality, and mixing with other solvents, can drive the partitioning of ions in interfacial electrolyte systems, in contradiction to the predictions of the EDL.Item INVESTIGATION OF AMBIENT METHANE CONCENTRATION, SOURCES, AND TRENDS IN THE BALTIMORE-WASHINGTON REGION(2024) Sahu, Sayantan; Dickerson, Russell Professor; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Methane, an important and not yet fully understood greenhouse gas, has a global warming potential 25 times that of carbon dioxide over 100 years, although with an atmospheric lifetime much shorter than carbon dioxide. Controlling methane emissions is a useful way to avoid some of the adverse effects of climate change at least on short time scales. Natural sources include wetlands, ruminants, and wildfires, while anthropogenic sources include the production, transmission, distribution, and use of natural gas, livestock, and landfills. In the US, natural gas and petroleum systems, anthropogenic sources, are the second-largest source of methane emissions. Urban areas are a significant source of anthropogenic methane emissions, primarily fugitive emissions from natural gas distribution and usage.We studied methane observations from five towers in the Baltimore-Washington (BWR) region – two urban towers ARL (Arlington, VA), NEB (Northeast Baltimore, MD), and one rural tower, BUC (Bucktown, MD). Methane measurements from these three towers displayed distinct seasonal and diurnal cycles with maxima at night and in the early morning, which indicated significant local emissions. We concluded from our analysis that anthropogenic methane emissions dominate at the urban sites whereas wetland emissions dominate at the rural site. We compared observed enhancements (mole fractions above the 5th percentile) to simulated methane enhancements using the WRF-STILT model driven by two EDGAR inventories – EDGAR 4.2 and EDGAR 5.0. We did a similar comparison between model and observations with vertical gradients. We concluded that both versions of EDGAR underestimated the regional anthropogenic emissions of methane, but version 5.0 had a more accurate spatial representation. We ran the model with WETCHARTs to account for wetland emissions which significantly reduced the bias between model and observations especially in summer at the rural site. We investigated winter methane observations from three towers in the BWR including a ten-year record, 2013-2022, from BUC, located ~100 km southeast of these urban areas. We combined the observations with a HYSPLIT clustering analysis for all years to determine the major synoptic patterns influencing methane mixing ratios at BUC. For methane concentrations above global background, the cluster analysis revealed four characteristic pathways of transport into BUC – from the west (W), southwest (SW), northwest (NW), and east (E) and these showed significant differences in methane mixing ratios. We corroborated our conclusions from BUC using 2018-2022 data from towers in Stafford, Virginia (SFD), and Thurmont, Maryland (TMD); results confirmed the influence of synoptic pattern, typically associated with frontal passage, on methane. No significant temporal trend over the global background was detected overall or within any cluster. For BUC, low concentrations were observed for air off the North Atlantic Ocean (E cluster) and flowing rapidly behind cold fronts (NW cluster). High methane mixing ratios were observed, as expected, in the W cluster due to the proximity of the BWR and oil and gas operations in the Marcellus. Less expected were high mixing ratios for the SW cluster – we attribute these to agricultural sources in North Carolina. Swine production, ~500 km to the SW, impacts methane in eastern Maryland as much or more than local urban emissions plus oil and gas operations 100–300 km to the west; this supports the high end of emission estimates for animal husbandry and suggests strategies for future research and mitigation.Item NONEQUILIBRIUM STATISTICAL PHYSICS OF FEEDBACK-CONTROLLED AND AUTONOMOUS INFORMATION-THERMODYNAMIC SYSTEMS(2024) Bhattacharyya, Debankur; Jarzynski, Christopher; Chemical Physics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)This thesis investigates the nonequilibrium dynamics of a variety of systems evolving under control protocols. A control protocol can involve feedback based on measurements performed by an external agent, or it can be a predefined protocol that does not rely on explicit measurements of the system’s state. In the context of information thermodynamics, the former setup belongs to the paradigm of non-autonomous or feedback-controlled Maxwell's demons, and the latter to the paradigm of autonomous demons. The thesis begins with a framework for analyzing non-autonomous feedback control, when the control protocol is applied by an agent making continuous measurements on the system. A multiple-timescales perturbation theory, applicable when there exists an appropriate separation of timescales, is developed. This framework is applied to a classical two-state toy model of an information engine – a device that uses feedback control of thermal fluctuations to convert heat into work. Additionally, quantum trajectory simulations are used to study a feedback-controlled model of Maxwell's demon in a double quantum dot system. Next, a modeling scheme for converting feedback-controlled Maxwell's demons to autonomous (non-feedback) systems is developed. This scheme explicitly accounts for the thermodynamic costs of information processing, by incorporating an information reservoir, modeled as a sequence of bits. This modeling scheme is then applied for converting the classical analogue of the non-autonomous double quantum dot Maxwell's demon, discussed previously, to an autonomous model. Using analytical, semi-analytical and stochastic simulation-based approaches, it is shown that the obtained model can act either as an information engine, or as a “Landauer eraser”, and then the phase diagrams that identify these regimes of behavior are constructed. Finally, fast-forward shortcuts to adiabaticity for classical Floquet-Hamiltonian systems is developed, and applied to a periodically driven asymmetric double well (without feedback control). Tools from dynamical systems theory are then used to characterize the system’s angle-variable dynamics.Item USING DNA LOOPING PROTEINS TO ENHANCE HOMOLOGY DIRECTED REPAIR IN VIVO FOLLOWING A CAS9 INDUCED DOUBLE STRAND BREAK(2024) Ferencz, Ian Theodore; Kahn, Jason D; Biochemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Genome engineering methods that start with a CRISPR/Cas9 targeted genomic DNA double strand break proceed through cellular DNA repair mechanisms after the induction of the break. Imprecise nonhomologous end-joining (NHEJ) is useful for knockouts, but precise homology-directed repair (HDR) is necessary for gain of function changes. NHEJ tends to be more efficient, so directing the cell to knock in a precise sequence via HDR is an active area of research. The system we have designed uses a bivalent protein to recruit HDR donor DNA to the site of a specific DNA double strand break induced by a Cas9/sgRNA nuclease. Previously described leucine zipper dual-binding (LZD) proteins areused because they are small and stable. The system was designed to reduce the effort needed for screening, shorten the time required for the repair process, and/or decrease the amount of donor DNA needed, reducing potential off-target effects. We developed a model system in Saccharomyces cerevisiae to measure gene disruption and HDR frequencies in yeast that contain combinations of non-replicating donor DNA plasmid or linear DNA, expression plasmids of four LZD variants, and a plasmid expressing Cas9 and an sgRNA targeting either the AGC1 or ADE2 genes. The donor DNA includes a gene coding for G418 resistance in yeast. It also includes an INV-2 site recognized by the C-terminal DNA binding domain of LZDs adjacent to suboptimal regions of homology to the target gene. The N-terminal DNA binding domain of the LZDs recognizes an endogenous CREB site near the target gene. The desired recombinants are scored by their inability to grow on acetate as a sole carbon source (for AGC1) or their red color (ADE2), accompanied by resistance to G418. We believe that LZD enhancement can become a simple and valuable adjunct to any other method of improving the efficiency of HDR, in any system. We were able to show that the inclusion of LZD73 in recombination experiments increased the number of colonies presenting with the desired phenotype and genotype nearly eight-fold in the absence of a designed DNA break. We also provide evidence suggesting that the presence of LZD73 has a slight positive effect on the efficiency of Cas9 targeting. Desired recombinants were recovered after Cas9/sgRNA cleavage in an experiment where there was no apparent recombination in the absence of LZD73. Future work on this project includes optimization of the homologous sequences to improve background recombination so a more quantitative measure of the improvement observed in the presence of LZD proteins. This work can be transferred laterally to enhance other recombination-based methods in other organisms: the LZD proteins could be analogous to an adjuvant that increases overall efficiency.Item Controlled Nucleation and Growth of Carbon Nanotubes(2024) Alibrahim, Ayman; Wang, YuHuang; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Single-walled carbon nanotubes (SWCNTs) exhibit exceptional electrical, mechanical, and optical properties, making them potential game changers for diverse applications. However, the synthesis of SWCNTs faces significant challenges, including low yield, inadequate control over catalyst particle size, and prevalent impurities. This dissertation focuses on elucidating SWCNTs' nucleation and growth mechanisms to address these challenging issues. First, I applied in-situ absorption spectroscopy to monitor the SWCNT production by chemical vapor deposition. Second, I investigated the factors affecting metal catalyst nucleation and introduced a confinement strategy that enabled a record-breaking growth rate of 4500 meters per hour for SWCNTs. Furthermore, I developed a novel “seed doping” technique to control the nucleation of metal catalysts, significantly reducing catalyst particle size and producing purer, smaller-diameter SWCNTs continuously. Finally, I explored the role of ethanol in enabling the controlled growth of double-walled carbon nanotubes by building on SWCNTs as templates.Item TOWARDS FULLY AUTOMATED ENHANCED SAMPLING OF NUCLEATION WITH MACHINE-LEARNING METHODS(2024) Zou, Ziyue; Tiwary, Pratyush; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Molecular dynamics (MD) simulation has become a powerful tool to model complex molecular dynamics in physics, materials science, biology, and many other fields of study as it is advantageous in providing temporal and spatial resolutions. However, phenomena of common research interest are often considered rare events, such as nucleation, protein conformational changes, and ligand binding, which occur on timescales far beyond what brute-force all-atom MD simulations can achieve within practical computer time. This makes MD simulation difficult for studying the thermodynamics and kinetics of rare events. Therefore, it is a common practice to employ enhanced sampling techniques to accelerate the sampling of rare events. Many of these methods require performing dimensionality reduction from atomic coordinates to a low-dimensional representation that captures the key information needed to describe such transitions. To better understand the current challenges in studying crystal nucleation with computer simulations, the goal is to first apply developed dimensionality reduction methods to such systems. Here, I will present two studies on applying different machine learning (ML) methods to the study of crystal nucleation under different conditions, i.e., in vacuum and in solution. I investigated how such meaningful low-dimensional representations, termed reaction coordinates (RCs), were constructed as linear or non-linear combinations of features. Using these representations along with enhanced sampling methods, I achieved robust state-to-state back-and-forth transitions. In particular, I focused on the case of urea molecules, a small molecule composed of 8 atoms, which can be easily sampled and is commonly used in daily practice as fertilizer in agriculture and as a nitrogen source in organic synthesis. I then analyzed my samples and benchmarked them against other experimental and computational studies. Given the challenges in studying crystal nucleation using molecular dynamics simulations, I aim to introduce new methods to facilitate research in this field. In the second half of the dissertation, I focused on presenting novel methods to learn low-dimensional representations directly from atomic coordinates without the aid of a priori known features, utilizing advanced machine learning techniques. To test my methods, I applied them to several representative model systems, including Lennard Jones 7 clusters, alanine dipeptide, and alanine tetrapeptide. The first system is known for its well-documented dynamics in colloidal rearrangements relevant to materials science studies, while the latter two systems represent problems related to conformational changes in biophysical studies. Beyond model systems, I also applied my methods to more complex physical systems in the field of materials science, specifically iron atoms and glycine molecules. Notably, the enhanced sampling method integrated with my approaches successfully sampled robust state-to-state transitions between allotropes of iron and polymorphs of glycine.Item DECIPHERING THE MOLECULAR MECHANISM BEHIND THE SARS-COV-2 FUSION DOMAIN(2024) Birtles, Daniel; Lee, Jinwoo; Biochemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)SARS-CoV-2 is an extremely infectious virus, yet despite a plethora of research the viral lifecycle is still not well understood, particularly the process of membrane fusion. The traditional means by which viral glycoproteins facilitate fusion is that of the six-helix bundle, within which a short, conserved sequence known as the fusion domain (FD) initiates the process as it embeds within and perturbs the target cell membrane, in turn lowering the energetic barrier necessary to coalesce two opposing membranes. Furthermore, the highly conserved coronavirus FD is found to be available on the SARS-CoV-2 spike protein surface, which along with its integral role within the viral lifecycle makes it an ideal therapeutic target. However, limited knowledge of the exact molecular mechanism by which the SARS-COV-2 FD conducts its role within the fusion process has prevented the production of antiviral treatments. Here we describe the elucidation of key molecular details regarding how the SARS-CoV-2 FD initiates the process of membrane fusion. Firstly, the FD was found to contain a unique assembly of fusogenic regions, known as a fusion peptide (FP) and fusion loop (FL), which operate in synergy to elicit efficient fusion. This was followed by the discovery of a preference for the FD to fuse within conditions akin to the late endosomal membrane, with both pH and lipid composition significantly impacting fusion. It was found that the endosomal resident anionic lipid BMP imparts a negative impact on lipid packing within the membrane, which positively correlates with fusion. The unique mechanism by which the coronavirus FD initiates fusion was cemented when we uncovered the importance of several positively charged residues towards the FDs function. This also led to unearthing a mutant of the FD (K825A), which if found to have naturally occurred within the full spike protein, has the potential to produce a more virulent strain of SARS-CoV-2.