Physical Sciences and Mathematics Commons^™

Investigating The Interactions Of The Iron-Sulfur Mitochondrial Protein, Mitoneet With Its Binding Partners, Ebenezer Osei Newton

Graduate Theses, Dissertations, and Problem Reports

MitoNEET belongs to the CDGSH Iron-Sulfur Domain (CISD)-gene family of proteins and is a [2Fe-2S] cluster-containing protein found on the outer membrane of mitochondria. The specific functions of mitoNEET/CISD1 remain to be fully elucidated, but the protein is involved in regulating mitochondrial bioenergetics in several metabolic diseases. Unfortunately, drug discovery efforts targeting mitoNEET to improve metabolic disorders are hampered by the lack of ligand-binding assays for this mitochondrial protein. We have developed a protocol amenable for high-throughput screening (HTS) assay, by modifying an ATP fluorescence polarization method to facilitate drug discovery targeting mitoNEET. Based on our observation that adenosine triphosphate …

Exogenous Factors That Impact Huntingtin Aggregation, Adam Skeens

Graduate Theses, Dissertations, and Problem Reports

While expansion of a polyglutamine (polyQ) domain is the immediate cause of huntingtin (htt) aggregation associated with Huntington’s Disease (HD), other cellular factors modify aggregation. These include interactions with cellular membranes, protein biding partners, molecular crowding, and proteinaceous seeds. Here, two important factors are biophysically characterized: 1) the interaction of htt with endomembranes and 2) proteinaceous seeds obtained from a variety of htt-derived peptides. In the first project, the aggregation of htt at bilayer interfaces and in the presence of divalent cations was investigated. A major cellular factor implicated in altered htt aggregation is the binding of lipids. Furthermore, the …

Enabling Technologies For Chemical Synthesis: I. Selective Microwave Heating; Ii. Synthesis And Regioselective Cyclotrimerizations Of Tethered 1,6-Diynes, Amir Tavakoli

Graduate Theses, Dissertations, and Problem Reports

Reaction discoveries, method developments, and technology advancements lie at the heart of synthetic organic chemistry. These innovations are essential for creating and manipulating complex molecules, which are the building blocks of many important chemical compounds, including pharmaceuticals, materials, and agrochemicals. Here, we first describe new methods to prepare neopentylene-tethered (NPT) 1,6-diynes which are valuable substrates for reaction discovery and target-oriented synthesis, especially in benzannulation strategies toward illudalane natural products. NPT 1,6-diynes have been employed as coupling partners in cyclotrimerization reactions for the synthesis of highly substituted benzene rings which present a persistent challenge in chemical synthesis and are underrepresented scaffolds …

Enantioselective Dearomatization Facilitated By Non-Covalent Interactions Of N-Heterocyclic Carbene Catalysts And Pyridinium Salts, Jack A. Patterson

Graduate Theses, Dissertations, and Problem Reports

Dihydropyridines are a practical organic scaffold commonly used for their pharmaceutical properties. Nucleophilic dearomatization of pyridines has proven to be a useful method in obtaining dihydropyridines. By using N-heterocyclic carbene (NHC) organocatalysts, dihydropyridines can be synthesized with high regioselectivity of the 1,4 regioisomer over the 1,2- regioisomer but often with low enantioselectivity. By incorporating non-covalent interaction contact points, we hypothesize that enantioselectivity can be enhanced. By synthesizing numerous NHCs, each proposed to exhibit a different type of non-covalent interaction (i.e., hydrogen bonding or ion pairing), an understanding of the secondary interactions within this reaction system can be studied and …

Copper-Catalyzed Dehydrogenative Decarboxylation Reactions Of Carboxylic Acids To Alkenes, Michael P. Stanton

Graduate Theses, Dissertations, and Problem Reports

Linear alpha olefins (LAOs) are important building blocks in the production of linear low-density polyethylene, a plastic used in products such as shrink wraps, plastic bags, tubing, plasticizers, among others. Commercial methods for generating LAOs utilize ethylene oligomerization, but this method is reliant on fossil fuels and leads to unselective product formation. Synthesis of LAOs from renewable resources, namely carboxylic acids, by decarbonylative dehydration strategies has been well studied, however, this method has inherent drawbacks rooted in the formation of internal olefin side-products through isomerization pathways. With the goal of avoiding internal isomerization, this thesis explores a dehydrogenative decarboxylation strategy …

Application Of Computational Biophysics Techniques To Characterize Cell Membrane-Associated Events, Kyle Billings

Graduate Theses, Dissertations, and Problem Reports

Cell membranes are crowded environments which can modulate protein structure-function relationships through interaction with lipids, other proteins, carbohydrate structures and so on. This work focuses the impact of the membrane environment on two varieties of peptides: Microbial rhodopsin proteins, and cyclic peptides.

Life on Earth is dependent on the ability of plants and microbes to harness sunlight for energy production. Their ability to transform light into carbohydrates requires tailor-made machinery, and for a wealth of microorganisms, microbial rhodopsin proteins (MR) are critical for maintaining the concentration gradients used to produce the energy molecule Adenosine triphosphate (ATP). The central retinal molecule …

Solid State Nmr Analysis Of Insect Wing Membranes, Samuel Eddy

Graduate Theses, Dissertations, and Problem Reports

Solid State NMR is a powerful tool for analyzing the chemical composition of insects. Previous studies have used Solid State NMR to investigate the chemical composition and investigate the sclerotization (tanning) process of insect exoskeletons. Acquiring sufficient exoskeleton sample for analysis has been relatively simple. This is however not the case for other components of an insect’s physiology, particularly the wing membrane material. The wings of an insect only compose a small percentage of their overall body mass, and many hundreds to thousands of insects must be processed in order to achieve a few milligrams of wing membrane sample. The …

Enhancing The Forensic Comparison Process Of Common Trace Materials Through The Development Of Practical And Systematic Methods, Meghan Nicole Prusinowski

Graduate Theses, Dissertations, and Problem Reports

An ongoing advancement in forensic trace evidence has driven the development of new and objective methods for comparing various materials. While many standard guides have been published for use in trace laboratories, different areas require a more comprehensive understanding of error rates and an urgent need for harmonizing methods of examination and interpretation. Two critical areas are the forensic examination of physical fits and the comparison of spectral data, which depend highly on the examiner’s judgment.

The long-term goal of this study is to advance and modernize the comparative process of physical fit examinations and spectral interpretation. This goal is …

Synthesis And Pharmacology Of Illudalic Acid And Analogous Chemical Structures, Robert Gaston Jr

Graduate Theses, Dissertations, and Problem Reports

Natural products are the foundation of modern medicine and an inspiration for chemical innovation. Developing new synthetic strategies to complex natural products drives synthetic innovation and promotes pharmacological exploration. As bioactive secondary metabolites of fungi, illudalic acid and associated analogs have unrealized medicinal potential due to synthetic limitations. Illudalic acid is notably the first selective covalent inhibitor of the LAR-PTPs, a class of enzymes linked to many human illnesses, including stimulant addiction. The chemistry herein focuses on optimizing synthetic routes to illudalic acid and associated analogs toward exploring their pharmaceutical potential. We report a second-generation synthesis of illudinine (55% overall …

Ambient Ammonia Synthesis Via Microwave-Catalytic Materials And Plasma Chemistry, Siobhan Brown

Graduate Theses, Dissertations, and Problem Reports

Ammonia is critical to supporting human life on earth because of its use as fertilizer. The Haber-Bosch process to produce ammonia has been practiced for over 100 years. This process operates at high pressure and temperature to overcome the thermodynamic and kinetic limitations of the ammonia synthesis reaction thus researchers have tried to overcome it for decades. At present this process represents 1% of global energy usage and 2.5% of global CO₂ emissions. The proposed chemical looping ammonia synthesis approach seeks to reduce the environmental impact of this critical process and to elucidate microwave-catalytic principles.

This research aims to …

Investigation Of Early Complex Formation Of Huntingtin Protein With And Without Lipids, Alyssa R. Stonebraker

Graduate Theses, Dissertations, and Problem Reports

Huntington’s disease (HD) is a fatal neurodegenerative disease caused by the expansion of the polyglutamine (polyQ) domain of the huntingtin protein (htt). The expansion of the polyQ domain beyond a threshold of approximately 35 repeats triggers complex toxic aggregation mechanisms and results in altered interactions between htt and lipid membranes. Many factors modulate these processes. One such modulator includes sequences flanking the polyQ domain, most notably the first 17 amino acids at the N-terminus of the protein (Nt17), and environmental factors including the presence of membranous structures. Nt17 has the propensity to form an amphipathic a-helix in the presence of …

The Influence Of Instrumental Sources Of Variance On Mass Spectral Comparison Algorithms, Isabel Cristina Galvez Valencia

Graduate Theses, Dissertations, and Problem Reports

Current search algorithms for the identification of substances based only on their electron ionization mass spectra provide the correct compound as their top result approximately 80% of the time. One contributing factor to the ~20% deviation in the first-hit recognition rate is that traditional algorithms work by comparing the unknown spectrum to an ‘ideal’ or consensus spectrum of each reference compound. The inclusion of replicate reference spectra in a database has been shown to improve the probability of ranking the correct identity in the number one position, but the variance in ion abundances caused by different conditions or different instruments …

Exploration Of Metal-Carbonyl Complexes For Decarbonylation Reactions, Rebekah C. Krupa

Graduate Theses, Dissertations, and Problem Reports

In recent years, transition metal-mediated decarbonylation reactions have emerged as an alternative to conventional cross-coupling methods due to the advantages associated with the use of carbonyl-containing functionalities as coupling electrophiles instead of organohalides found in traditional cross-coupling reactions. This, coupled with the ubiquity of carbonyl-containing compounds in pharmaceuticals and non-biodegradable chemicals, has led to the interest in developing efficient systems for transition metal-catalyzed decarbonylation. However, these reactions are commonly limited to stoichiometric amounts of metal reagents due to the strong metal-carbonyl bond formed during transition metal-mediated decarbonylation. With the goal of gaining a better mechanistic understanding of CO dissociation in …

Analysis Of ‘Touch’ Dna Recovered From Metal Substrates: An Investigation Into Cfdna-Metal Interactions And The Efficacy Of Different Collection Techniques On Dna Yield, Jessica E. Thornton

Graduate Theses, Dissertations, and Problem Reports

While several improvements have been made in recent years to optimize the recovery of ‘touch’ DNA, relatively little research has been conducted to understand the relationship between ‘touch’ DNA and the binding affinity of that DNA to metal surfaces, specifically those with a significant copper presence. Furthermore, characterization of cell-free DNA (cfDNA) and its contribution to ‘touch’ samples and those cfDNA-metal interactions from objects commonly identified at crime scenes (cartridge casings, knives, doorknobs) have been lacking. Research has identified the tendency of copper ions to intercalate with DNA helices, resulting in sample degradation among other damaging conformational changes; however, while …

Strengthening The Interpretation Of Glass And Paint Evidence Through The Study Of Random Frequency Of Occurrence And Analytical Information, Lauryn C. Alexander

Graduate Theses, Dissertations, and Problem Reports

Glass and paint particles are frequently discovered at crime scenes as valuable trace evidence. Often, these fragments are transferred from a crime scene to a victim or person-of-interest, and can subsequently be evaluated, analyzed, and classified according to their physical and optical measurements, and chemical properties, each of which can provide important information to the analyst to assist in the determining if a recovered particle is distinguishable or indistinguishable from a known source. Moreover, these minute materials can provide information about how the events took place, leading to the reconstruction of crime scenes and the identification of valuable clues for …