Physical Sciences and Mathematics Commons^™

Synthesis And Characterization Of Two Sets Of Group 12 Complexes With Organic Ligands, Michelle Sturner

Dissertations, Theses, and Masters Projects

The complexes of group 12 elements are subjects of incredible interest due to differences in their bioactivity. Zinc is an essential element of life and is required for many bodily processes including gene production, growth, and the immune response. Cadmium and mercury are both toxic elements to humans. Part of their activity is due to their ability to replace zinc metal centers. Synthesis of new group 12 complexes can provide insight regarding their bioactivity and how replacement of metal centers can affect the structure of enzymes. In this thesis, the preparation and characterization of two sets of group 12 complexes …

Spectroscopy And Dynamics Of Atmospherically And Combustion-Relevant Collision Complexes, John Patrick Davis

Dissertations, Theses, and Masters Projects

Potential energy surfaces describing bimolecular collisions sensitively depend on the chemical functionality and the relative orientation of colliding partners, thus defining the accessibly reactive and nonreactive pathways. Herein, we investigate the peculiar product outcomes arising from Jahn-Teller distortion of the nitric oxide and methane complex (NO-CH4). We have reported an in-depth spectroscopic and dynamics study of NO-CH4 by utilizing conformation-specific and action spectroscopy, as well as velocity map imaging, to understand the fundamental dissociative mechanisms at play. Ultimately, we have gained information about how the Jahn Teller effect possibly impacts the potential product energy transfer pathways. There is a translationally …

Selectivity And Structure Of Chimeric Loop Swaps In Sh2 Domains, Sarah N. Smith

WWU Graduate School Collection

SH2 (Src Homology 2) domains are protein domains that bind to phosphorylated tyrosine residues within cell signaling cascades. They have been found to play a role in certain cancers and immunological disorders. Despite their importance in cell signaling and medical relevance, the structural basis of the various selectivity classes of SH2 domains is only partially understood. Previous research found that the EF and BG loops of the domains contribute to forming the peptide binding pocket, and thus impact their selectivity. To further understand the role of these loops in selectivity, we engineered chimeric SH2 domains by swapping the EF and …

New Synthetic Methods Based On Silicon-Tethered Nucleophilic Addition Reactions, Alexie W. Clover

WWU Graduate School Collection

With the recent discovery of an iodine mediated rearrangement of diallylsilanes, we set out to investigate a similar fluorine mediated rearrangement, aimed at introducing a new method for synthesizing organofluorine compounds. Interest in incorporating fluorine into organic molecules has grown significantly in recent years, primarily for medicinal applications. Since certain fluorination methods require the use of mCPBA, a common epoxidizing reagent, control experiments were performed on the reaction of several diallylsilanes with mCPBA, anticipating that a competing epoxidation of the diallylsilanes might occur. It was found that the formation of the hydroxy ester occurred through a regioselective epoxide opening from …

Regio- And Diastereoselective Samarium-Mediated Allylic Sulfone Reductions, Cody Schwans

WWU Graduate School Collection

A series of allylic sulfones were synthesized containing a stereodirecting group and chelating element and subjected to samarium diiodide reductions in the presence of a proton donor. The resulting products could be obtained with high regioselectivity (no less than 95:5) and high diastereoselectivity (>10:1) that correlated with the size of the stereodirecting group. A mechanism is proposed that includes loss of the sulfone and formation of a chelated organosamarium intermediate followed by intramolecular protonation by a samarium-bound proton source. In this way, both the regioselectivity and absolute stereochemistry of the resulting products are explained.

Tuned Gold Layer Growth Onto Plasmonic Sensing Silver Nanocubes Via Synthetic Control Of Reduction Potentials., Nicolas Hall

WWU Graduate School Collection

Metallic nanoparticles (mNPs) are commonly employed as sensors and detection tools due to their unique plasmonic properties. Silver NPs exhibit these properties in heightened capacity in comparison to other metals. However, Ag NPs are susceptible to oxidation, degradation over time and are biotoxic. These issues are commonly addressed by creating Ag-alloy NPs or by adding additional layers to Ag NPs. This work improves upon these methods by focusing on the growth of an Au layer onto Ag nanocubes (AgNCs), resulting in a layered Au-Ag NC (Au@AgNC). The resulting morphology of these Au@AgNCs are dependent on the synthetic pathway taken and …

Class A Sortases: Structures And Alternative Substrate Binding And Cleavage, Brandon Vogel

WWU Graduate School Collection

Sortases, consisting of classes A-F, are cysteine transpeptidases found in the cell wall of Gram-positive bacteria. They play a crucial role in ligating proteins to the cell wall that are responsible for cell adhesion, immune evasion, host cell invasion, and nutrient acquisition through a transpeptidation reaction. Consequently, they are an attractive therapeutic target. Class A sortases are also utilized in protein engineering applications such as sortase-mediated ligations and sortagging. Despite extensive research in the past two decades, gaps persist in understanding how class A sortases recognize their substrates, primarily due to a lack of structural information on sortases non-covalently bound …

Structural And Thermodynamic Studies Of Antibody Binding To Blood Coagulation Factor Viii, Jordan Vaughan

WWU Graduate School Collection

Blood coagulation factor VIII (FVIII) is a 2332 residue glycoprotein expressed in endothelial cells and plays a significant role in the formation of blood clots. Structurally, FVIII’s domains are organized as A1-A2-B-A3-C1-C2. The absence or deficiency of FVIII in the bloodstream gives rise to Hemophilia A; an X-linked bleeding disorder affecting 1 in 5000 males worldwide. To combat this deficiency, patients undergo FVIII replacement therapy which involves frequent injections of FVIII into the bloodstream in the form of blood, plasma, or protein concentrates. Although effective, this treatment commonly results in the development of anti-FVIII inhibitory antibodies in approximately 20-30% of …

Kinetic Analysis Of The Grafting Thermal Ring-Opening Polymerization Reaction Of Benzoxazine With Sulfonyl-Ester Functionalized Polymers, Tawakalt Adetoun Akinjobi

WWU Graduate School Collection

This project will explore the fundamental mechanistic details and kinetics of a grafting polymerization reaction that occurs with blended benzoxazine monomers (or resins) and polymers functionalized with reactive sulfonyl-ester leaving groups [such as tosylate (Ts), nosylate (Ns) or mesylate (Ms) groups]. Isoconversional analysis (ICA) is one of the most important methods for establishing the kinetics of the complex reactions associated with curing thermosets. In the case of ICA, activation energy is measured at fixed values of reaction conversion.²⁶ For thermosets the data are typically based on differential scanning calorimetry (DSC). The combinatorial approach not only provides uncertainty associated with …

Activity And Selectivity Of Class B Sortase Enzymes, Sophie Jackson

WWU Graduate School Collection

Gram-positive bacteria attach many proteins to their cell walls via sortase enzymes. Sortases are cysteine transpeptidases and are grouped into 6 classes, A-F. Sortase enzymes, particularly sortase A from Staphylococcus aureus, have been used extensively for in vitro protein ligations. Here, we investigate substrate-binding in sortase A from Streptococcus pyogenes. In addition, class B sortases are typically overlooked for research and development due to low in vitro activity and incomplete knowledge of substrate specificity. Here, we investigate the activity of class B sortases from Bacillus anthracis (baSrtB), Clostridioides difficile (cdSrtB), Listeria monocytogenes (lmSrtB), and Staphylococcus aureus (saSrtB). Of these, …

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 …

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 …

Ultrasensitive Tapered Optical Fiber Refractive Index, Erem Ujah, Meimei Lai, Gymama Slaughter

Electrical & Computer Engineering Faculty Publications

Refractive index (RI) sensors are of great interest for label-free optical biosensing. A tapered optical fiber (TOF) RI sensor with micron-sized waist diameters can dramatically enhance sensor sensitivity by reducing the mode volume over a long distance. Here, a simple and fast method is used to fabricate highly sensitive refractive index sensors based on localized surface plasmon resonance (LSPR). Two TOFs (l = 5 mm) with waist diameters of 5 µm and 12 µm demonstrated sensitivity enhancement at λ = 1559 nm for glucose sensing (5-45 wt%) at room temperature. The optical power transmission decreased with increasing glucose concentration due …

Investigation Of Oleic Acid As A Dispersant For Hydroxyapatite Powders For Use In Ceramic Filled Photo-Curable Resins For Stereolithography, Brendan Kennedy, Eamonn De Barra, Stuart Hampshire, Maura Kelleher

Articles

Stereolithography allows production of porous hydroxyapatite scaffolds for bone regeneration but is limited by the challenging rheology of ceramic filled resins. Oleic acid, a natural fatty acid, was applied in concentrations of 0.0–0.3 wt% to improve the rheological properties of HAp resins for the fabrication of solid cylinders and scaffolds by digital light processing (DLP) printing in a wiperless system. Bonding by chemisorption was confirmed by FTIR analysis. The powders were then incorporated into a photo-curable resin of 1–6 hexanediol diacrylate at 18–30 vol%. The shear viscosity and sedimentation rates of photocurable resins containing HAp powder decreased with increasing concentration …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

Electrodeposition Of Epitaxial Wide Bandgap P-Type Semiconductors And Copper Metal For Energy Conversion And Flexible Electronics, Bin Luo

Doctoral Dissertations

"Epitaxial electrodeposition is a simple, low-cost technology to produce highly ordered materials on single-crystal surfaces. This research focuses on the epitaxial electrodeposition of wide bandgap p-type semiconductors and epitaxial Cu thin films via a self-assembled monolayer for energy conversion and flexible electronics. Paper I introduces the epitaxial electrodeposition of hole conducting CuSCN nanorods onto Au (111) surface, and lift-off to produce flexible and transparent foils. Highly ordered CuSCN could serve as an inorganic transport layer in various opto-electronic devices such as perovskite solar cells, LEDs, and transistors. An ordered and transparent CuSCN foil was also produced by epitaxial lift-off following …

Fluorination Of Rubisco-Mimetic Co2 Capture Systems. Theoretical And Experimental Studies Of Ammonium Ion Acidity Depression And Carbamylation, Brian Michael Jameson

Doctoral Dissertations

"RuBisCO-inspired CO₂ capture and release (CCR) systems featuring amines have been developed for the purpose of reversable CO₂ capture from air. The enzyme active site consists of the tetrapeptide sequence Lys-Asp-Asp-Glu. The Lys sidechain amine undergoes carbamylation and an Mg²⁺ cation stabilizes the resulting carbamate. The N^a-acyl-lysinyl-aspratyl-aspartyl-glutamide (Lys-Asp-Asp-Glu, KDDE) peptide featured maximum capture at pH ≈ 10; a pH region too high for Mg²⁺ ions to remain in solution. This work aims to achieve pKa depression by introducing fluorine in the proximity of the lysine’s sidechain amine. A comparative analysis was made of butylamine, …

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 …

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 …

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 …

Interpretation Of The Tandem Mass Spectrum Of The Novel Psychoactive Substance 5f-App-Pinaca, Px-2, Christopher S. Poulos

Graduate Theses, Dissertations, and Problem Reports

Designer drugs and novel psychoactive substances (NPSs) are continuously entering the black market and causing serious health problems among users. NPSs present an especially difficult challenge to forensic chemists and toxicologists because they are not well characterized and often involve families of structurally related analogs. In crime laboratories, mass spectrometry is commonly used as a part of an analytical scheme to characterize and identify unknown analytes. Towards this end, tandem mass spectra of questioned analytes are often compared to reference spectra of standards that are either collected contemporaneously with the analyte or collected previously and stored in a database. However, …

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 …