Master of Science in Chemistry

Series

Master of Science in Chemistry

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https://hdl.handle.net/1853/73608

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Degree Series

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Organizational Unit

School of Chemistry and Biochemistry

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Now showing 1 - 10 of 413

Metabolomics of Inflammatory Bowel Disease in African American Patients

(Georgia Institute of Technology, 2024-11-20) Gray, Jada Simone

Inflammatory Bowel Disease (IBD) in African American (AA) and individuals of European Ancestry (EA) is steadily growing. Unfortunately, IBD studies underrepresent AA, compromising our understanding of disease etiology and progression in the subpopulation. IBD affects 96 of 100,000 AA every year, so generation of numerous well-balanced and matched biospecimens for metabolomic studies is challenging. Metabolomics provides the most immediate snapshot of the IBD phenotype, showing contrasting pathogenesis in AA vs. EA individuals. We here present a new Dynamic SQUAD approach where LC-MS experiments are performed in a sequential fashion as more biospecimens become available. This approach builds a targeted metabolite panel that reflects IBD pathway alterations from the non-targeted data block produced by the previous SQUAD LC-MS batch. We conducted SQUAD LC-MS experiments on biopsies from IBD patients to measure targeted and non-targeted data for different analytes using a Thermo ID-X tribrid mass spectrometer. A literature metanalysis indicated specific metabolic reactions that can differentiate Crohn’s disease (CD) from healthy patients. Pathways altered included amino acid metabolism, tryptophan metabolism, microbial metabolism, and energy metabolism, indicating dysbiosis of the gut microbiome, showing a decrease in the diversity of microbes/metabolites in the gut1. Additionally, metabolic modeling indicated that inflamed CD patient ileal tissue displays a distinct metabolic signature compared with non-inflamed tissue2. Subsequently, we sought to experimentally confirm whether the CD ileum contained metabolic changes versus controls using non-targeted LC-MS of a small external pilot cohort, complementary to in silico metabolic modeling to characterize whether the changes in metabolic pathways correlate to specific changes in specific lipids and/or metabolite composition. The top discriminant analytes were also added to the first targeted SQUAD panel. These ongoing studies will help us probe metabolomics alterations in the mucosal tissue to further our insights on IBD differences across populations.
A New Luminescence-Based Assay for Monitoring Mutant Myocilin Cellular Localization

(Georgia Institute of Technology, 2024-07-30) Harris, Ethan Foley

Glaucoma is a heterogenous eye disease that is the leading cause of irreversible blindness worldwide, caused by a blockage in the outflow of aqueous humor from the eye, leading to an increase in intraocular pressure. The most common glaucoma subtype is primary open angle glaucoma, affecting ~60 million people worldwide. 2-4% of primary open angle glaucoma (POAG) and 10% of juvenile open angle glaucoma (JOAG) cases are attributed to mutations in the gene encoding for the protein myocilin. One of the key characteristics of a pathogenic variant is its inability to be secreted from trabecular meshwork cells. Instead of secretion, pathogenic myocilin variants accumulate in the endoplasmic reticulum and causes cell death. Mutant myocilins are studied in the lab using cellular secretion assays. In the past, different cellular fractions were detected using immunoblot, which has sensitivity limitations. In this thesis, we implement a new method that utilizes HiBiT, a luciferase-based assay, which we hypothesized would be more sensitive than immunoblot. The myocilin mutants tested using HiBiT (T377K, T377R, D384G, D395ins, C433Y, T455K, and L486F) to detect myocilin cellular localization exhibited negligible secretion when compared to WT. In addition, all the mutants except for L486F accumulated intracellularly. Unexpectedly, L486F was not detected intracellularly to the same degree as the other mutants, as evidenced by low band intensity in both the western and HiBiT blots for all three fractions. HiBiT blotting provides more sensitive detection than traditional immunoblotting, as evidenced by increased band intensity in the HiBiT blots for the same sample and lower quantities of cells needed for robust detection. Further studies on L486F will be required to determine whether it is poorly expressed or being degraded intracellularly. Overall, HiBiT detection of mutant myocilin enables new insights to be made into the mechanism of myocilin-associated POAG.
A Comparison Of Two Uranium Oxo Dimers Featuring Diamond Core Geometry

(Georgia Institute of Technology, 2023-12-18) Barker, Tiffany

Two bis-(µ-O)2 uranium dimers [(μ-O)2(UV(NPC)3)2] (A, NPC [NP(tBu[pyrr]2]-) and [(μ-O)2(UIV(NPC)3)2 [K(THF)x]2, (B) were synthesized and structurally characterized by single-crystal X-ray diffraction (SC-XRD), spectroscopically analyzed via nuclear magnetic resonance (NMR), Fourier-transfer infrared (FTIR), and ultraviolet-visible/near-infrared (UV-Vis/NIR) spectroscopies, and electrochemically analyzed via cyclic voltammetry (CV). Both compounds feature a diamond-shaped inner core geometry that, while common for transition metal dimers, is less prevalent in uranium chemistry. All bond lengths and angles for the diamond cores of A and B are in good agreement with reported data for previously published diamond-core uranium complexes. The UV-Vis spectrum of A exhibited a broad charge transfer feature at ~300 nm that tails into the visible region with ε ≈ 29000 M-1∙cm-1. Compound B showed also showed a charge transfer feature at 310 nm that tailed into the visible region that was comparatively weaker with ε ≈ 8686 M-1∙ cm-1. B showed several f→f transitions in the near-IR spectrum as well, with ε ranging from ~45 M-1∙cm-1 to ~76 M-1∙cm-1. The voltammogram of A exhibited two reversible redox events at E1/2 = -1.15 V, and -0.47 V vs. Fc/Fc+ and a quasireversible event at -2.4 V vs. Fc/Fc+. The difference between these two potentials was used to estimate the comproportionation constant, Kc, giving an approximate value of 3.13 x 1011, suggesting strong electronic communication between the central uranium atoms. Cyclic voltammetry of B was drastically different with one quasireversible event at E1/2 = -1.25 V and one irreversible event at +0.26 V vs. Fc/Fc+. Compound B was also electrochemically unstable and decomposed rapidly during scanning. Magnetic measurements for A displayed antiferromagnetic behavior with a Néel temperature of 40 K, a moderate value compared to other similar compounds who typically have Néel temperatures of ~15 – 70 K. Compound B exhibited paramagnetic behavior, and neither compound showed any evidence of magnetic hysteresis.
Interlaboratory Comparison of a Complex Targeted Assay: Improving Consistency and Reliability in Metabolomics Analyses

(Georgia Institute of Technology, 2023-12-07) Phillips, Emily R.

Ideal isotope-labeled internal standards for analysis via targeted metabolomics approaches are presented for negative and positive ion modes for both hydrophilic interaction liquid chromatography (HILIC) and reverse phase liquid chromatography (RPLC) chromatography coupled to mass spectrometry. These best performing analytes (BPA) were deduced after experimentation from a collaborative research project involving six top metabolomics research laboratories in the country. These results are detailed in this work, supported by observed behaviors of included chemical classes and chromatographic behaviors, and align with the group hypothesis and expectations
The Role of Space Weather in Forming Water from the Potential Lunar Regolith Simulant Rhyolite

(Georgia Institute of Technology, 2022-08-26) Castarlenas, Aintzane

The potential role of the solar wind and space weathering in the formation of water on a lunar surface has been studied by deuteron ion implantation followed by electron bombardment on a silica rich glass surrogate, rhyolite. The electron bombardment stimulates chemistry and leads to water formation and ion desorption. The latter process, electron stimulated desorption (ESD) probes the role of electrons from the solar wind in both producing and desorbing ionic and neutral products. Prolonged electron excitation of deuteron dosed rhyolite samples induces defects on the sample, opening paths for diffusion of molecules to the surface. These experiments lead to the conclusion that solar wind in conjunction with electron bombardment of the lunar soil can generate water and other volatile products such as molecular hydrogen. These processes should be considered when modeling the lunar hydrogen and water pathways or cycles.
Synthesis and Characterization of Imidophosphorane Ligand Derivatives For Crystalline, Low Coordinate F-Element Complexes

(Georgia Institute of Technology, 2022-08-03) Tateyama, Haruko

This thesis describes the development of imidophosphorane ligand derivatives in order to access low coordinate, crystalline complexes of lanthanides and actinides. Chapter 1 provides a general overview of the low-coordinate f-block complexes and ligands used in achieving such systems. Chapter 2 describes the synthesis of four imidophosphorane ligand derivatives, including synthetic challenges encountered. These ligand derivatives were developed to address synthetic challenges of limited solubility and crystallinity from the ligand developed in the group. The availability of these four ligand derivatives will give us a toolbox of ligands in addressing such synthetic challenges, eventually with the goal of accessing low-coordinate, crystalline f-element complexes. Chapter 3 showcases the crystallographic analyses of the four imidophosphorane derivatives.
Homopolymer and block polymer materials derived from highly reactive thionolactone monomers

(Georgia Institute of Technology, 2022-05-03) Tennyson, Simone Lena

Thionolactones are a recently discovered sub-class of radical ring-opening monomers that are notable for their ability to impart labile thioester units into polymer backbones when used as a comonomer. The simple scaffold allows for structural changes to further tune the monomer’s reactivity in order to change rates of copolymerization with different monomer families and can even lead to systems capable of homopolymerization. Thionolactones also demonstrate high degrees of control with reversible addition-fragmentation chain-transfer (RAFT) polymerizations, and rapid reactivity with acrylates. In this thesis, the introduction of the furan heterocycle into a 7-membered thionolactone monomer scaffold is described, and the resulting homopolymerization behavior is studied (Chapter 2). Additionally, a thermally responsive amphiphilic diblock polymer of N,N-dimethylacrylamide and N-isopropylacrylamide with a cleavable thioester junction is prepared using a new 6-membered thionolactone derivative with ultra-fast copolymerization behavior (Chapter 3).
Expression, Purification, and Activity of Putative Intramembrane Aspartyl Proteases From Diverse Species

(Georgia Institute of Technology, 2022-04-27) Thomas, Gwendell Michelle

Intramembrane aspartyl proteases (IAPs) cleave peptide bonds within the hydrophobic lipid membrane. The best characterized IAP is presenilin, the catalytic subunit of γ-Secretase, which is known for cleaving amyloid precursor protein into the amyloid-β peptide that aggregates in the brains of Alzheimer’s patients. More than 100 substrates have been documented for γ-Secretase, yet no consensus recognition sequence has emerged, at least in part due to the technical complexities of studying this membrane-embedded proteolytic system. To date, the presenilin homolog from Methanoculleus marisnigri JR1 (MCMJR1) has been the sole microbial model of non-eukaryotic IAPs for in vitro molecular studies. A recent bioinformatic study uncovered over 1000 putative IAP sequences lurking in archaeal and bacterial organisms. Here, we report recombinant expression, purification, and enzymatic activity of selected new IAPs. These new IAPs express well and are from noted archaea such as H. volcanii and Lokiarchaeota. These putative IAP orthologs share key structural and cleavage preference similarities with MCMJR1 IAP and presenilin. By studying the molecular biochemistry of more IAP family members, additional trends and insights regarding cleavage preferences and peculiarities will emerge. Such knowledge will further illuminate the fascinating fundamental and complex chemistry occurring within the lipid membrane.
PEG (Polyethylene Glycol)-PCL (Polycaprolactone) Block Copolymers For 3D Printing Of Medical Devices

(Georgia Institute of Technology, 2022-01-18) Yang, Ruyi

PCL polymers have been widely used in 3D printing of scaffolds over the past few decades, which can be applied in a variety of medical devices. However, PCL has intrinsic defects, such as high hydrophilicity which causes low biocompatibility. The research reported in this thesis aims to modify existing PCL polymers by developing a series of PEG-PCL block copolymers with different ratios of blocks and investigate their potential as implants for soft tissue engineering and airway reconstruction. The introduction of PEG blocks to PCL enhanced biocompatibility towards mammalian cells compared to the commercially available PCL with same molecular weight, without compromising the 3D printability. Moreover, some PEG-PCL copolymers showed significantly better resistance towards bacterial adhesion, which is desirable for both applications. The various mechanical properties of these copolymers make them promising candidates to devise patient-specific medical devices with various needs.
Analysis of Adenosine Triphosphate in Spatially Distributed Planetary Analog Field Samples to Inform Biosignature Detection Missions

(Georgia Institute of Technology, 2021-05-11) Novak, Carlie Marie

New discoveries of potentially habitable environments elsewhere in our solar system, and at the extremes here on Earth, have reopened the imagination to possibilities for extraterrestrial life. Planetary field analog research enables us to study the impact of similar extreme environmental stressors and the bioactivity of an ecosystem. This thesis research was designed to better understand biosignature detection in extreme environments by exploring distributions and patterns of biosignatures in harsh planetary environments. Adenosine triphosphate (ATP) was used as a proxy of bioactivity due to its ubiquitous role in terrestrial metabolism and can be quantified easily by a bioluminescence assay. Observing variations in concentrations of ATP can provide insight on where bioactivity becomes concentrated, or evenly distributed which is essential in the search for life outside of Earth. A variety of chemical and physical studies of samples from analog locations aids in understanding the limits of life terrestrially, and therefore can help make more informed predictions about the potential habitability on other planetary bodies.