Physical Sciences and Mathematics Commons^™

Implementation Of A Constraint And Configuration Interaction Methodology Into Density Functional Tight Binding, Gunnar J. Carlson

WWU Graduate School Collection

This research aims to implement a charge constraint in conjunction with a small configuration interaction scheme into a density-functional tight-binding (DFTB) method within the DFTB+ quantum mechanical software package. This method aims to model the electron transfer rate of chemical systems by calculating the electronic couplings between two constrained states more efficiently. Electronic couplings are directly proportional to electron transfer, making them important parameters to efficiently compute the optimal minimum or maximum of an electron transfer rate, for example, when screening chemical systems based on their ability as a conductor. Other methods such as constrained density-functional theory followed by a …

Signaling And Trafficking In Choanoflagellates And Humans: A Study Of Conserved Peptide-Binding Domains, Haley Wofford

WWU Graduate School Collection

Many crucial cellular processes are regulated by signaling and trafficking pathways, which are largely dependent on protein interactions in the cell. These networks are thought to play a crucial role in the evolution of multicellular organisms from their unicellular ancestors. Choanoflagellates are unicellular organisms that can adopt a multicellular state, called a rosette. Though they evolved independently from and prior to the diversification of metazoans, they are the closest extant nonmetazoan ancestor to animals, making them a compelling model for the study of early multicellularity. Here, we look at two structurally conserved peptide-binding domains that both play important roles in …

Pyridinediimine Complexes With Coordination Sphere Interactions Relevant To Copper And Non-Heme Iron Enzymes, Pui Man Audrey Cheung

WWU Graduate School Collection

Primary and secondary coordination sphere interactions with proximal Brønsted-Lowry acid/base sites were investigated using a family of pyridinediimine (PDI) complexes. The PDI ligands used in this project could be easily prepared by the Schiff base reactions with commercially available diamines as proton relays. Upon activation, the pendant Bronsted site and accessible electrons were arranged in a single scaffold that allowed the transportation of both protons and electrons to occur.

Two new PDI complexes with morpholine and pyrrolidine derivatives were introduced to the pendant PDI family. Their proton dissociation constant in acetonitrile were 17.1 and 18.3, respectively. The PDI complexes were …

Computational Design Of Novel Materials For Solar Energy Conversion And Catalysis, Corey Teply

WWU Graduate School Collection

As synthetic chemists and materials scientists increasingly gain the ability to precisely arrange the atoms in solids, computation can provide guiding insight toward designing materials for a variety of applications. This work focuses on two distinct projects: 1) the use of biaxial strain in all crystallographic directions to tune the structural and electronic properties of perovskites for solar energy conversion, and 2) the extension of the concept of single-atom alloys to design stable motifs of multiple catalyst atoms on metal surfaces.

Perovskite solar cells have been shown to have band gap tunability when compressive or tensile-biaxial strain is enacted on …

Structural Studies Of The Von Willebrand Factor D’ Domain And Its Binding Mechanism To Factor Viii, Ap Wang

WWU Graduate School Collection

Hemophilia A is an X-linked disorder that results in uncontrolled bleeding, which is caused by a lack of activity for blood coagulation factor VIII, an essential protein cofactor in the clotting cascade. Factor VIII consists of multiple domains, and binding disruptions between factor VIII and its circulatory partner, von Willebrand Factor, may cause von Willebrand disease. Von Willebrand Disease type 2N is an autosomal recessive disease, and it is caused by binding disruptions between the D’ domain (also known as TIL’E’) of von Willebrand Factor and a3 domain of factor VIII. A 2.9Å Cryoelectron microscopy structure of the FVIII:vWF complex …

Synthesis Of Guaipyridine Alkaloids Rupestines C, D And K With Studies Toward The Synthesis Of Rupestines B, J, L And M, Briana J. Mulligan

WWU Graduate School Collection

Hepatocellular carcinoma (HCC) is a type of primary liver cancer that is responsible for roughly 700,000 deaths around the world each year. While invasive treatment methods for HCC have proven to be limited, there are drug treatments available that show promising features. The structural elements of these drugs have given rise to an interest in guaipyridine alkaloids, specifically a family of naturally occurring guaipyridine alkaloids known as the rupestines. The rupestines have previously been isolated from the flowers of the plant Artemisia rupestris. This plant has been known for its reported antitumor, antiviral and antibacterial properties when used in traditional …

Enhancing Plasmonic Nanomaterials: Colorimetric Sensing And Sers, John Crockett

WWU Graduate School Collection

Nanomaterials, materials with at least one dimension on the nanoscale have become an area of extreme scientific interest due to their many unique properties with applications in catalysis, optics, and sensing, just to name a few. Metal nanoparticles are particularly interesting because of the interactions between light and surface electrons in the metal’s conduction band, called localized surface plasmons. In anisotropic metal nanoparticles these plasmons are especially exciting due to the highly responsive quality of the plasmonic resonance associated with their varied nano dimensions. Gold nanorods and nano dendrites in particular exhibit electromagnetic effects which are specifically associated to the …

Organic Crystal Nucleation In Ultrathin Liquid Films: Applications Of Computational And Experimental Methods For The Exploration Of Dynamic Spatial Relationships And Controlled Growth, Haley Doran

WWU Graduate School Collection

The advancement of semiconducting materials is paramount to the future of electronics. Organic semiconducting materials are of particular interest due to their significantly lower processing cost compared to traditional inorganic semiconducting materials, such as silicon. However, the present toolkit for solution-based controlled growth of polycrystalline thin films is lacking. Therefore, the purpose of this research is to build such a toolkit, wherein tunable parameter relationships of organic thin-film growth are evaluated and compared both experimentally and computationally. A multi-scale model has been developed, which combines mean field rate equations with a self-consistent treatment of the critical stable monomer cluster size, …

Synthesis And Reactions Of Medium-Ring Silyl Ethers, Inna A. Fomina

WWU Graduate School Collection

Olefin metathesis is a reaction that creates new carbon-carbon double bonds by rearranging two alkenes. The reaction has undergone significant development since its discovery in the 1950s, from first reports to new catalysts and industrial uses, culminating in the 2005 Nobel Prize in chemistry. Grubbs ruthenium-based catalysts are widely used for such reactions, including ring closing metathesis (RCM) that involves the rearrangement of two alkenes on a single molecule to form a ring. During the course of investigating RCM reactions to produce eight-membered ring silyl ethers, we observed double bond isomerization when using the second-generation Grubbs catalyst and the Hoveyda-Grubbs …

Exploring Biochemical Mechanisms With Hybrid Quantum Mechanics/Molecular Mechanics And Enhanced Sampling Methods, Edwin Enciso

WWU Graduate School Collection

In the field of molecular dynamics (MD), a long-standing issue is the time frame required in order to fully observe a chemical reaction. Enhanced sampling methods have been the primary way of overcoming this issue for the past 40 years. In this experiment our goal was to combine new and existing sampling methods in order to create an efficient and accurate way of retrieving kinetics data from simulations. In order to do this, we examined two test cases: the enzymes chorismate mutase and cytosine deaminase. We did this using hybrid quantum mechanics/molecular mechanics simulations coupled with enhanced sampling methods. The …

Engineering Class A Sortases: Activity And Selectivity Of Hybrid And Ancestral Variants, Sarah Struyvenberg

WWU Graduate School Collection

Bacterial sortases are cysteine transpeptidases that anchor virulence factors to the surface of bacterial cells. Sortases are a powerful tool utilized for protein engineering that allow researchers to modify proteins at the protein level, not the DNA level. However, important limitations to utilization of sortases for engineering purposes exist; namely, SrtA from S. aureus is a relatively modest enzyme compared to other SrtA enzymes and is very specific for the LPXTG motif. Previous work from our collaborators and others revealed that sortases from different species can recognize alternative sequences and that activities can vary widely. We were curious about how …

Synthesis And Characterization Of Earth Abundant Metal Phosphide Photocatalysts For The Reverse Water Gas Shift Reaction, John D. Springer

WWU Graduate School Collection

This thesis work focuses on the synthesis and characterization of photocatalysts composed of metal phosphide nanoparticles on a titania (TiO2) support for the conversion of carbon dioxide (CO2) to carbon monoxide (CO) via the reverse water gas shift (RWGS) reaction. The CO product can be subsequently converted to solar fuels such as methanol (CH3OH), thus lowering the carbon footprint associated with the combustion of liquid fuels. The photocatalysts are composed of a tunable light absorber, indium-gallium phosphide (InxGa1-xP), and nickel phosphide (Ni2P) as a co-catalyst, on TiO2. The photocatalysts are characterized using diffuse reflectance ultraviolet-visible (UV-Vis) spectroscopy to determine band …

Lsc Fabrication And Design: Bulk Polymerization And Ultrathin Architectures, Justin T. Doyle

WWU Graduate School Collection

Renewable energy technologies that access underutilized spaces in the built environment will need to be implemented, on a large scale, to curtail trending increases in global temperature. Luminescent Solar Concentrators (LSCs) are one such technology. They employ luminophores doped into polymer sandwiched in between glass plates, that redirect sunlight to the device periphery where photovoltaics are attached, producing power. Current devices do not have high enough efficiencies for commercialization. One of the biggest barriers is fluorophore aggregation which causes waveguide refractive index fluctuations which result in parasitic losses from the waveguide. In this work Copper Indium Disulfide/Zinc Sulfide (CIS/ZnS) quantum …

Polybenzoxazine-Grafted Composites: Accelerated Polymerization Of Benzoxazine Resins From Bulk- To Microscale Mesylated Materials, Cassidy L. Crickmore

WWU Graduate School Collection

Benzoxazine-based resins often afford high modulus and high glass transition polymers that are desirable for creating safe and reliable thermoset parts and composites. However, benzoxazine resins have had limited widespread deployment into industry due to their high cure temperature. By blending functionalized glass substrates with the benzoxazine monomer, we hypothesize that the cure temperature of thermosetting resin can be lowered. The structure and purity of the particles, determined by NMR and FTIR, will be presented. DSC studies on the stability and cure accelerating properties of blends composed of functionalized glass substrates and benzoxazine monomer will be determined and compared against …

Activation Of Nitrite And Carbon Dioxide By Cobalt Centered Redox Active Ligand Featuring A Hemilabile Pendant Amine, Douglas F. Baumgardner

WWU Graduate School Collection

Carbon dioxide (CO₂) and bioavailable nitrogen in the form of nitrates (NO₃^-) and nitrites (NO₂^-) are serious environmental pollutants. However, without economic incentives there is little interest in remediation of these pollutants outside of laboratory scale experiments. CO₂ can be converted to carbon monoxide (CO), a valuable building block in Fischer-Tropsch sourced fuel, and NO₃^- and NO₂^- can be converted to ammonia, another important chemical building block. However, both require effective, low-cost catalysts to be financially viable options. This thesis seeks to demonstrate the conversion of CO …

Allylic Benzoate Reductions: A Study On Stereospecificity, Michael A. Leitch

WWU Graduate School Collection

Herein we report results from experiments aimed at better understanding SmI2(H2O)n reductions of allylic benzoates adjacent to a trisubstituted alkene. When flanked by both a chelating group and stereodirecting group, these reactions can occur with complete regioselectivity and good diastereoselectivity (up to 90:10). Initial experiments suggested that the reaction was stereospecific to alkene geometry. However, further experimentation has revealed that the alkene stereospecificity is substrate dependent. For instance, if the geminal alkene substituents are alkyl, results show the reaction to be stereospecific, but if one of the substituents is a phenyl group the reaction is still stereoselective but not stereospecific. …

Carbodiimides: Templates For Covalent Adaptable Networks And Post Polymerization Modification, Alberto J Melchor Bañales

WWU Graduate School Collection

The global increase in plastic waste has negatively impacted the environment, human health, and economy. Plastics that lack recyclability, such as thermosets are some of the main culprits. To help address this issue, reactive functional groups can be incorporated in macromolecules, enabling straightforward post-polymerization modification (PPM) that can enhance their ability to be recycled. This thesis studied carbodiimides as a reactive functional group for facile PPM with amines through a catalyst-free transformation to N,Nʹ,Nʺ-trisubstituted guanidines. Small molecule studies showed that N,Nʹ,Nʺ-trisubstituted guanidines underwent a reversible thermal exchange reaction without a catalyst. The newly found thermal exchange reaction, termed thermal guanidine …

Plasmonic-Based Hybrid Nanomaterial: From Synthesis To Application, Maggie Wang

WWU Graduate School Collection

Gold nanoparticles, particularly gold nanorods, have been widely used as sensors and imaging agents due to their unique and tunable morphology-dependent properties and intriguing plasmonic resonance. However, the increasing need of new materials with enhanced properties and functionality led scientists to discover novel hybrid nanomaterials, which involves the formation of two or more components into one nanoplatform. Hence, gold nanorod-based hybrid nanomaterials exhibit simultaneous synergistic effects between the phenomenal plasmonic properties from gold nanorods and the intrinsic properties of the other constituents. The functionality of gold nanorod-based hybrid nanomaterials greatly increases due to its enhanced performance characteristics, which directly impacts …

Organic Molecular Crystal Engineering Via Organic Vapor-Liquid-Solid Deposition, Griffin Reed

WWU Graduate School Collection

Control over the size, shape, topology, orientation, and crystallographic phase of organic molecular materials is critical for a wide array of applications ranging from optoelectronics to pharmaceutical development. Herein, we demonstrate a relatively low-cost approach for fabricating single crystals with controlled sizes, shapes, microscale periodic features, preferred orientations and specific molecular packing modes. These features allow for the fabrication of intricate arrangements of single crystals for incorporation into complex device architectures, and potentially the endowment of tailored optical, electronic, thermal, and mechanical properties onto these materials. Patterning is achieved by utilizing an organic-vapor-liquid-solid (OVLS) deposition scheme paired with traditional photolithography …

Synthetic Studies On Guaipyridine Alkaloids: Rupestines B And C, Evangeline Starchman

WWU Graduate School Collection

The rupestines, a family of guaipyridine alkaloids, are isolated from the plant Artemisia rupestris. Historically, this plant was used intraditional Chinese medicine due to its reported antitumor, antibacterial, and antiviral activities as well as reported protection of the liver. The rupestines can only be isolated from their parent plant in small quantities, making the total synthesis of these guaipyridine alkaloids of particular interest. Cananodine, anotherguaipyridine alkaloid, is a biologically active compound that can be isolated in small quantities from the fruits of Cananga odorata and displays activity against two types of hepatocellular carcinoma cell lines. It is hypothesized that the …

Development Of Ti-Dftb: Transition Dipole Moment Calculations In A Time-Independent Density Functional Tight-Binding Framework, Megan Deshaye

WWU Graduate School Collection

Here we discuss the development of a time-independent excited state computational method that consists of three augmentations to the semi-empirical electronic structure package, DFTB+ 19.1. The density functional based tight binding method (DFTB) is an approximation of Kohn-Sham (KS) density functional theory (DFT) wherein the energy functional is expanded to second order with respect to density fluctuations. Application of a delta self-consistent field (delta-SCF) approach within DFTB has allowed for the variationally optimized calculation of spin-purified excited state (ES) properties, and forms the foundation of our time-independent DFTB (TI-DFTB) framework. Selection of KS spin orbitals based on the character of …

Synthesis Of A Stimulus Responsive Phosphine Ligand And Metal Binding Studies, Gabriel Bourne

WWU Graduate School Collection

Cations have been shown to modify a variety of properties of transition metals, including bite angle, isomerization, substrate control, and catalytic activation. Herein describes the synthesis of a novel stimulus responsive phosphine ligand. Ligand binding studies by NMR salt titration show a preference in the order of Na⁺ > Li⁺ > K⁺. Platinum dimethyl and dichloride complexes with the phosphine ligand were also synthesized. Isomerization of the platinum chloride complex between cis and trans is reported.

Synthesis Of An Archazolid Based Enzyme Inhibitor, Cooper A. Vincent

WWU Graduate School Collection

The archazolids are a family of natural products that display powerful growth inhibitory activity against a number of human cancer cell lines. This activity has been linked to inhibition of the vacuolar-type ATPase (V-ATPase) and more recently cyclooxygenase (COX) enzymes. Using the archazolid structure as a starting point, several simplified analogues have been prepared and assayed for their V-ATPase and COX inhibitory activity. These simplified analogues were prepared using a novel Suzuki coupling with yields over 80%. They were assayed to investigate both their V-ATPase and COX inhibitory activity. In our assays there was no COX inhibition, while there was …

Progress Towards The Substrate-Bound Structure Of Streptococcus Pneumoniae Sortase A, Nicholas M. Horvath

WWU Graduate School Collection

Sortases are cysteine transpeptidases found primarily on the cell surface of Gram-positive bacteria. Sortase-mediated ligations have become an attractive option for protein modification chemistry, enabling the synthesis of a wide range of non-natural polypeptide derivatives. Attempts at understanding how these enzymes recognize and bind substrates are integral to furthering their usefulness in protein engineering and, potentially, treatment of bacterial diseases. However, the variable substrate specificity and activity between homologs of these enzymes is not yet fully understood. Of specific interest to us is sortase A from Streptococcus pneumoniae (SrtA_pneu), as it demonstrates a broad substrate tolerance not …

Surface Modified Gold Nanorods Based Mercury Sensor, Tianqi Luan

WWU Graduate School Collection

The high toxicity of mercury in the form of inorganic vapor and organic compounds has become a major concern leading scientists to investigate more accurate and effective methods for the quantification of residue mercury in drinking water, aquaculture products and industrial wastes. In this research, we designed a mercury sensor based on the amalgamation between mercury and gold nanorods (AuNRs) which relate the longitudinal surface plasmon resonance (LSPR) peak shift induced by aspect ratio (AR) change after amalgamation. However, most of AuNRs synthesized based on seed mediated methods use either citrate or hexadecyl trimethyl ammonium bromide (CTAB) as surface stabilizing …

Isopeptide Ligations Catalyzed By Streptococcus Suis Sortase A, Sarah Bowersox

WWU Graduate School Collection

Chemically modified proteins are critical components of modern therapeutics and basic research. To generate non-natural protein derivatives, bacterial sortase enzymes have been effective due to their ability to catalyze selective ligations between protein targets and functional groups that are uncommon in nature. Thus far, the enzymatic approach using sortase has been limited to modifications at the termini of peptide chains. Here we describe efforts to develop a sortase-mediated strategy for the formation of isopeptide bonds at the side chains of internal lysine residues. To this end, we have identified a sortase A homolog from Streptococcus suis (SrtA_suis) that …

Structural Studies On The Mechanism Of Argyrin B And The L12 – L11 Ribosomal Protein Interface, Christopher Swanson

WWU Graduate School Collection

The mechanism of action of argyrin B and the molecular interactions of L11 and L12 has been undetermined and underrepresented in the research of bacterial translation. This work seeks to examine the mechanism of action of argyrin B by performing in vitro structural studies of its interaction with its specific target protein elongation factor-G. We demonstrate that argyrin B inhibits translation, and allows GTPase activity to proceed, contrary to assumptions made in prior research. We determine that ribosome recycling is the likely step through which argyrin B acts as an antibiotic, since translocation is unaffected by argyrin B and association …

Multifunctional Microgels For Nanoparticle-Based Detection Methodologies, Alyson Silva

WWU Graduate School Collection

In this study, pH-responsive microgel particles, comprised of 2-vinyl pyridine (P2VP) and styrene (PS), are explored as scaffolds to assemble metallic nanoparticles (NPs) for ultrasensitive detection strategies. Microgel particles serve as size-tunable scaffolds to assemble metal (silver or gold) NPs for surface-enhanced Raman scattering (SERS) vibrational spectroscopy. The high sensitivity of SERS arises from the enormous enhancement of the Raman scattering cross sections of molecules adsorbed to roughened metal surfaces, such as metal NPs. Using a sterically stabilized latex of random copolymers of PS and P2VP (PSxP2VPy), this polymer is capable of transitioning to a microgel state through acid-base titration. …

The Atomic And Electronic Structure And Tunability Of Ruddlesden-Popper Phases For Photovoltaic Applications, Britt A. Tyler

WWU Graduate School Collection

There is an increasing need for alternative energy sources that reduce the global reliance on fossil fuels. Since their demonstration in 2009, perovskite solar cells (based on compounds with the formula ABX₃, such as CH₃NH₃PbI₃) have become an extremely promising and active research area. Still, there are obstacles to the widespread use of these technologies, including their instability and the environmental impacts of lead. It is therefore important to find ways to modify and tune the structure and properties of perovskites to optimize their stability and photovoltaic performance. This research explores a …

Structural Studies Of Complexes Of Blood Coagulation Factor Viii, Joseph S. Gish

WWU Graduate School Collection

Factor VIII (FVIII) is a 2332 amino acid glycoprotein with domain organization of A1-A2-B-A3-C1-C2 which is a crucial component of the blood coagulation cascade. After secretion, FVIII circulates in the bloodstream at a concentration of one nanomolar bound to von Willebrand Factor (vWF) which protects FVIII from clearance. In the event of an injury to the bloodstream, FVIII is proteolytically cleaved, releases from vWF and binds to both activated platelet surfaces and activated Factor IX with nanomolar affinity. These interactions increase the rate of blood clot formation 100,000 fold. Hemophilia A is an x-linked recessive disease affecting 1 in 5000 …