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Synthesis, Design, And Biological Evaluation Of Inhibitors And Activators Of Src Homology 2 Domain-Containing Inositol Phosphatase (Ship) And Synthetic Studies Of Apicularen A And Maoecrystal V, Dennis Racca Viernes

Chemistry - Dissertations

This dissertation involves work both on the syntheses of small molecules with potential therapeutic applications and synthetic studies on natural products with unusual core skeletons.

The first part of this work involves the synthesis, design, and biological evaluation of aminosteroids as inhibitors for the SH2-containing inositol phosphatase 1 (SHIP1). SHIP1, a 145 kDa protein, is involved in regulating the formation of new blood cells. High- throughput screening identified several SHIP inhibitors including NSC23922, a mixture of 3a- and 3β-aminocholestane. Both 3a- and 3β-aminocholestane were synthesized from dihdyrocholesterol and the 3a- form was verified as …

The Path To An Orally Administered Protein Therapeutic For The Treatment Of Diabetes Mellitus, Susan Clardy James

Chemistry - Dissertations

Protein therapeutics like insulin and glucagon-like peptide-1 analogues are currently used as injectable medications for the treatment of diabetes mellitus. An orally administered protein therapeutic is predicted to increase patient adherence to medication and bring a patient closer to metabolic norms through direct effects on hepatic glucose production. The major problem facing oral delivery of protein therapeutics is gastrointestinal tract hydrolysis/proteolysis and the inability to passage the enterocyte. Herein we report the potential use of vitamin B₁₂ for the oral delivery of protein therapeutics.

We first investigated the ability of insulin to accommodate the attachment of B₁₂ at …

Synthesis And Biological Activity Of Aminoglycosides And 1,4-Naphthoquinone Derivatives, Marina Fosso Yatchang

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

The research described in this dissertation is at the interface of organic chemistry and biology, and it aimed at designing and synthesizing biologically active molecules for the possible development of therapeutic agents.

Spinal muscular atrophy is an incurable disease that affects 1 in every 6000 babies, making it the leading genetic cause of infant mortality. While no treatment is available, efforts are being taken to solve this issue. Part of the work outlined in this dissertation was carried out in collaboration with researchers from the University of Missouri to investigate a potential therapeutic for this disease.

In addition, the continuous …

Elemental Contributions From Minor And Major Constituents Of Bone On The Separation Of Radiostrontium, Ashlee Rae Dailey

UNLV Theses, Dissertations, Professional Papers, and Capstones

While many methods exist to separate and analyze radionuclides from a variety of environmental matrices, the performance of all of these methods is often limited by other interfering constituents that are consistently found in most of these samples. The presence of such constituents can significantly reduce the recovery of the radioisotopes of interests and lead to incomplete separations.

Strontium has the same oxidation state and a similar atomic radius as calcium and is therefore readily able to substitute for calcium in lattice sites. This similarity in behavior leads to the preferential accumulation of strontium in newly formed bone. The study …

Anti-Germinants As A New Strategy To Prevent Clostridium Difficile Infections, Amber Janece Howerton

UNLV Theses, Dissertations, Professional Papers, and Capstones

Clostridium difficileinfections (CDI) have emerged as a leading cause of hospital-associated complications. CDI is the major cause of antibiotic-related cases of diarrhea and nearly all cases of pseudomembranous colitis. The infective form of C. difficileis the spore, a dormant and hardy structure that forms under stress. Germination of C. difficile spores into toxin producing bacteria in the GI tract of susceptible patients is the first step in CDI establishment. Patient susceptibility occurs with a disruption of the natural gut microbiota by broad-spectrum antibiotics. Antibiotic treatments usually resolve CDI but refractory cases are on the rise. Of great concern is the …

Recycling And Reuse Of Radioactive Materials, Thomas Joseph O'Dou

UNLV Theses, Dissertations, Professional Papers, and Capstones

The Radiochemistry Program at the University of Nevada, Las Vegas (UNLV) has a Radiation Protection Program that was designed to provide students with the ability to safely work with radioactive materials in quantities that are not available in other academic environments. Requirements for continuous training and supervision make this unique program capable of turning out graduates that have an understanding of contamination and dose control techniques that complement their knowledge of the elements that they work with. The Program has also adopted a radionuclide recovery and reuse program that has provided materials from other universities, government agencies, and private companies …

Controlling Nanoparticle Dispersion For Nanoscopic Self-Assembly, Nathan S. Starkweather

Master's Theses

Nanotechnology is the manipulation of matter and devices on the nanometer scale. Below the critical dimension length of 100nm, materials begin to display vastly different properties than their macro- or micro- scale counterparts. The exotic properties of nanomaterials may trigger the start of a new technological revolution, similar to the electronics revolution of the late 20^th century. Current applications of nanotechnology primarily make use of nanoparticles in bulk, often being made into composites or mixtures. While these materials have fantastic properties, organization of nano and microstructures of nanoparticles may allow the development of novel devices with many unique properties. …

Synthesis And Luminescence Properties Of Core-Shell Structured (Lanthanum(1-X)Europium(X))(2)Zirconium Heptoxid[At]Yttrium Orthoborate Spherical Nanoparticles, Suresh Babu Alaparthi

Theses and Dissertations - UTB/UTPA

Many rare earth compounds have photoluminescent characteristics for various important applications. In this study, europium doped La2Zr2O7 nanoparticles were first synthesized morphology-controllably by using a molten-salt synthesis method. These nanoparticles were used as the core for coating with YBO3 shell. We then explored the effect of different experimental processing parameters, such as annealing temperatures, reaction times and different ratios of salt mixtures on the structure and morphology of these nanoparticles. The overall core size and shell thickness can be controlled by varying the reactant concentration both the core and shell material. These core@shell nanoparticles were then characterized mainly using power …

Understanding Corrosion Protection And Failure Through Model Polymers In Thin Films, Joshua Smith Hanna

Dissertations

When developing a model polymeric system to facilitate in the detection of molecular and microscopic events that preface macroscopic corrosive failure; a better understanding of how polymers can indicate corrosion was accomplished. Initially, the thought that molecular chain scission as a necessity for corrosion to occur had to be tested. Through the utilization of high molecular weight thermoplastic (HMWTP) model polymers, it was found that corrosion protection did not correlate to the quantity of weak bonds within an epoxy-amine polymer matrix. Therefore more sensitive methods of detecting corrosion had to be developed since changes within the polymer matrix did not …

Polymer Surface Engineering Via Thiol-Mediated Reactions, Ryan Matthew Hensarling

Dissertations

Synthesis of polymer brushes to decorate a surface with desired functionality typically involves surface-initiated polymerization (SIP) of functional, but non-reactive monomers. This approach suffers major drawbacks associated with synthesizing sufficiently thick polymer brushes containing surface-attached polymer chains of high molecular weight at high grafting density (i.e. cost, synthetic effort and functional group intolerance during polymerization). The research herein seeks to circumvent these limitations by the decoration of surfaces with polymer chains bearing specific pendent functional groups amenable to post-polymerization modification (PPM). In particular, this dissertation leverages PPM via a specific class of click reactions – thiol-click – that 1) enables …

Synthesis And Characterizations Of Pyridinium Salts Including Poly(Pyridinium Salt)S And Their Applications, Tae Soo Jo

UNLV Theses, Dissertations, Professional Papers, and Capstones

Pyridinium salts, both molecular and polymeric, are an interesting class of multifunctional materials that exhibit liquid-crystalline and light-emitting properties. Moreover, their properties can be easily tuned by introducing new types of anions or by modifying their chemical structures. This dissertation describes synthesis and characterization of poly(pyridinium salt)s containing macrocounterions and fluorene moieties in their backbones, synthesis and characterization of nanocomposites of poly(pyridinium salt)s with single-walled carbon nanotubes via non-covalent interactions, and synthesis and characterizations of pyridinium salts having different aliphatic linkages and their application in organic acid sensing.

First, all of these ionic polymers were prepared by either ring-transmutation or …

Solvation Energy Of Biomolecular Structures: A Study Of The Effect Of Salt On Biomolecules Through Implicit As Well As Explicit Solvation Methods, Mihir Date

All Dissertations

In the current dissertation, studies related to solvation energy of protein structures using implicit as well explicit solvation methods have been discussed. Special focus is given to explore effect of salt on the fold stability of proteins and enzymes. Salt plays a crucial role in the functioning of all proteins, enzymes and nucleic acids. Change in salt concentration of the medium has large impact on stability and activity of these biological macromolecules. Therefore exploring mechanism of salt effect on them and development of an efficient model to calculate the salt effect has fundamental as well as practical importance in the …

Sample Preparation Techniques For The Improvement Of Analytical Measurements: Capillary-Channeled Polymer Fibers Employed In Protein Solid Phase Extraction Applications And Characterization Of Active Components In Botanical Dietary Supplements, Carolyn Burdette

All Dissertations

The task of sample preparation encompasses many challenges and demands for analytical techniques. Appropriate preparative steps can be the determining factor between successful measurements and failures. Too little preparation can lead to the inability to detect analytes due to low concentrations, insufficient extraction of analytes, and/or strong matrix effects; exhaustive preparation steps increases analysis times, the potential for analyte losses, and the difficulty to obtain consistent reproducible results. Discussed here are several examples of analytical techniques where sample preparation is critical and can be used to improve existing techniques. Capillary-channeled polymer (C-CP) fibers used for solid phase extraction (SPE) protein …

New Applications Of Mass Spectrometry For Drug And Lipid Analysis, Elizabeth Lauren Emerson

Graduate Theses and Dissertations

Mass spectrometry is an important tool used in many different disciplines and settings that include forensics, drug discovery, environmental analysis, and proteomics. Gas chromatography - mass spectrometry (GC-MS) and matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI - TOF MS) are two of the most important instruments used for analysis of compounds. Chapters 1 and 2 of this discussion use GC-MS for the investigation of synthetic cannabinoids in `K2' incense products and the detection of metabolites in urine samples from individuals suspected of consuming these mixtures. Analytical standards were synthesized and used for identification and confirmation of structures. Detection of …

Lack Of P53 Affects The Expression Of Several Brain Mitochondrial Proteins: Insights From Proteomics Into Important Pathways Regulated By P53, Ada Fiorini, Rukhsana Sultana, Eugenio Barone, Giovanna Cenini, Marzia Perluigi, Cesare Mancuso, Jian Cai, Jon B. Klein, Daret K. St. Clair, D. Allan Butterfield

Chemistry Faculty Publications

The tumor suppressor protein p53 has been described "as the guardian of the genome" for its crucial role in regulating the transcription of numerous genes responsible for cells cycle arrest, senescence, or apoptosis in response to various stress signals. Although p53 promotes longevity by decreasing the risk of cancer through activation of apoptosis or cellular senescence, several findings suggest that an increase of its activity may have deleterious effects leading to selected aspects of the aging phenotype and neurodegenerative diseases. There is the link between p53 and oxidative stress, the latter a crucial factor that contributes to neurodegenerative processes like …

Preparation Of Nitrogen-Containing Heterocycles Via Cyclization Of Pyridine-Tethered Organolithiums, Elizabeth Archer

Master's Theses

No abstract provided.

Microfabrication, Characterization, And Application Of Carbon Nanotube Templated Thin Layer Chromatography Plates, And Functionalization Of Porous Graphitic Carbon, David S. Jensen

Theses and Dissertations

This dissertation contains the following sections. Chapter 1 contains a detailed description of the theory of thin layer chromatography (TLC). Chapter 2 describes the benefits and practical considerations of elevated temperatures in liquid chromatography (LC). The porous graphitic carbon (PGC) I modified as part of my work is often used in elevated temperature LC. Chapter 3 shows a thermodynamic analysis of chromatographic retention at elevated temperature, and Chapter 4 contains a closer look at the van 't Hoff equation in LC and how it can be used in retention modeling. In Chapter 5, I describe a new procedure for microfabricating …

Deposition And Characterization Of Hydrophobic Coatings, Vipul Gupta

Theses and Dissertations

Hydrophobic coatings find application in various sectors of the economy including to electronics, textiles, optical devices, and in scientific and commercial equipment. These different applications demand that different hydrophobic coatings posses a range of properties that may include smoothness or roughness, thicknesses on the order of a monolayer or a micron, robustness or the ability to dissolve quickly, transparency or opacity, water resistance or water permeability, electrical conductivity, oleophobicity, etc. However, whatever the final/desired properties, deposition via dry-deposition processes offers significant advantages, including greater reproducibility, increased environmental friendliness, and cost effectiveness on an industrial scale. Herein I explore the chemical …

A Cucurbit[8]Uril Sponge, Vijayakumar Ramalingam, Sharon K. Kwee, Lisa M. Ryno, Adam R. Urbach

Chemistry Faculty Research

This paper describes a convenient approach to quantitative removal of the synthetic host cucurbit[8]uril (Q8) from aqueous mixtures using a sepharose resin coated in memantine groups to selectively sequester Q8 in the presence of competing hosts and guests. The “Q8 sponge” can separate Q8 from Q6 and reverse the Q8-mediated dimerization of peptides.

Proposed Coherent Trapping Of A Population Of Electrons In A C60 Molecule Induced By Laser Excitation, Thomas George, G.P. Zhang

Chemistry & Biochemistry Faculty Works

This Letter demonstrates the possibility of generating coherent population trapping in C60. Similar to a three-level Λ system, C60 has a forbidden transition between the highest occupied molecular orbital (HOMO) (|a⟩) and the lowest unoccupied molecular orbital (LUMO) (|c⟩), but a dipole-allowed transition between HOMO and LUMO+1 (|b⟩) and between |b⟩ and |c⟩. We employ two cw laser fields, one coupling and one probe. The strong coupling field is switched on first to resonantly excite the transition between |b⟩ and |c⟩. After a delay, the probe is switched on; the coherent interaction between the coupling and probe fields traps the …

Design And Synthesis Of Fluorescence Turn-On Probes For Iron, Randy K. Jackson

Master's Theses

No abstract provided.

Flexural Rigidity Measurements Of Biopolymers Using Gliding Assays, Douglas S. Martin, Lu Yu, Brian L. Van Hoozen Jr.

Chemistry and Physics Faculty Articles

Microtubules are cytoskeletal polymers which play a role in cell division, cell mechanics, and intracellular transport. Each of these functions requires microtubules that are stiff and straight enough to span a significant fraction of the cell diameter. As a result, the microtubule persistence length, a measure of stiffness, has been actively studied for the past two decades. Nonetheless, open questions remain: short microtubules are 10-50 times less stiff than long microtubules, and even long microtubules have measured persistence lengths which vary by an order of magnitude.

Here, we present a method to measure microtubule persistence length. The method is based …

Nanoporous Gold As A Solid Support For Protein Immobilization For The Development Of Immunoassays, And For Biomolecular Interaction Studies, Binod Prasad Pandey

Dissertations

Nanoporous gold (NPG) is a versatile material of high surface area to volume ratio that can be readily modified with self-assembled monolayers of alkanethiols to which biomolecules can be linked. NPG presents new opportunities for the development of immunoassays, and for the development of carbohydrate based assays. This thesis explores the use of NPG as a support for self-assembled monolayers, their linkage to antibody-enzyme conjugates for immunoassay development, and for the study and application of carbohydrate-protein interactions. Direct kinetic electrochemical immunoassays were developed on NPG for prostate specific antigen (PSA) and carcinoembryonic antigen (CEA). The decrease in enzymatic conversion of …

Capturing Fleeting Intermediates In A Catalytic C-H Amination Reaction Cycle, Richard H. Perry, Thomas J. Cahill Iii, Jennifer L. Roizen, Justin Du Bois, Richard N. Zare

Chemistry and Physics Faculty Articles

We have applied an ambient ionization technique, desorption electrospray ionization MS, to identify transient reactive species of an archetypal C–H amination reaction catalyzed by a dirhodium tetracarboxylate complex. Using this analytical method, we have detected previously proposed short-lived reaction intermediates, including two nitrenoid complexes that differ in oxidation state. Our findings suggest that an Rh-nitrene oxidant can react with hydrocarbon substrates through a hydrogen atom abstraction pathway and raise the intriguing possibility that two catalytic C–H amination pathways may be operative in a typical bulk solution reaction. As highlighted by these results, desorption electrospray ionization MS should have broad applicability …

Mechanism Of Action Studies On A New Class Of Anticancer Nucleosides, Megan E. Browning

Theses and Dissertations

We have completed mechanism of action studies on a new class of anticancer nucleosides typified by a novel nucleoside discovered in our lab, MAP-870. In order to study the mechanism of MAP-870, several experiments were completed on a colorectal adenocarcinoma cell line, HT-29, including trypan blue cell count, sulforhodamine B assays, flow cytometry of cell cycle, propidium iodide incorporation, and phosphatidylserine externalization, Caspase-Glo3/7 assays, DNA fragmentation gel, cyclophilin A release gel, PAMPA, and confocal imaging. Sulforhodamine B assays show that MAP-870 does indeed cause growth inhibition and cell death in the model tested. PAMPA assays show that MAP-870 does not …

Conformations Of Islet Amyloid Polypeptide Monomers In A Membrane Environment: Implications For Fibril Formation, Mojie Duan, Jue Fan, Shuanghong Huo

Chemistry

The amyloid fibrils formed by islet amyloid polypeptide (IAPP) are associated with type II diabetes. One of the proposed mechanisms of the toxicity of IAPP is that it causes membrane damage. The fatal mutation of S20G human IAPP was reported to lead to early onset of type II diabetes and high tendency of amyloid formation in vitro. Characterizing the structural features of the S20G mutant in its monomeric state is experimentally difficult because of its unusually fast aggregation rate. Computational work complements experimental studies. We performed a series of molecular dynamics simulations of the monomeric state of human variants in …

New Multidetector Solution Could Lead To Safer Alternatives To Faulty Silicone Breast Implants, Judit D. Puskas, Geof Wyatt

Chemical, Biomolecular, and Corrosion Engineering Faculty Research

The article discusses the effort of the University of Akron's Department of Chemical and Biomolecular Engineering to pursue research which aims to reduce or eliminate capsular contracture associated with breast implants. It notes that the new multidetector nanotechnology developed by researchers can be better alternative to silicone gel-filled breast implants. It mentions that the new technology can also help in early diagnosis and imaging of breast cancer.

Differential Effects Of The Hydrophobic Surfactant Proteins On The Formation Of Inverse Bicontinuous Cubic Phases, Mariya Chavarha, Ryan W. Loney, Kamlesh Kumar, Shankar B. Rananavare, Stephen B. Hall

Chemistry Faculty Publications and Presentations

Prior studies have shown that the biological mixture of the two hydrophobic surfactant proteins, SP-B and SP-C, produces faster adsorption of the surfactant lipids to an air/water interface, and that they induce 1-palmitoyl-2-oleoyl phosphatidylethanolamine (POPE) to form inverse bicontinuous cubic phases. SP-B has a much greater effect than SP-C on adsorption. If the two proteins induce formation of the bicontinuous structures and faster adsorption by similar mechanisms, then they should also have differential ability to form the cubic phases. To test this hypothesis, we measured small angle X-ray scattering on the individual proteins combined with POPE. SP-B replicated the doserelated …

Electronic Communication Across Diamagnetic Metal Bridges: A Homoleptic Gallium(Iii) Complex Of A Redox-Active Diarylamido-Based Ligand And Its Oxidized Derivatives, Brendan J Liddle, Sarath Wanniarachchi, Jeewantha S. Hewage, Sergey Lindeman, Sergey V. Lindeman, James R. Gardinier

Chemistry Faculty Research and Publications

Complexes with cations of the type [Ga(L)₂]ⁿ⁺ where L = bis(4-methyl-2-(1H-pyrazol-1-yl)phenyl)amido and n = 1, 2, 3 have been prepared and structurally characterized. The electronic properties of each were probed by electrochemical and spectroscopic means and were interpreted with the aid of density functional theory (DFT) calculations. The dication, best described as [Ga(L^–)(L⁰)]²⁺, is a Robin-Day class II mixed-valence species. As such, a broad, weak, solvent-dependent intervalence charge transfer (IVCT) band was found in the NIR spectrum in the range 6390–6925 cm^–1, depending on the solvent. Band shape …

On Pi-Stacking, Ch/Pi, And Halogen Bonding In Halobenzene Clusters: Resonant 2-Photon Ionization Studies Of Chlorobenzene, Lloyd Muzangwa, Silver Nyambo, Brandon Uhler, Scott A. Reid

Chemistry Faculty Research and Publications

Noncovalent interactions such as hydrogen bonding, π-π stacking, CH/π interactions, and halogen bonding play crucial roles in a broad spectrum of chemical and biochemical processes, and can exist in cooperation or competition. Here we report studies of the homoclusters of chlorobenzene, a prototypical system where π-π stacking, CH/π interactions, and halogen bonding interactions may all be present. The electronic spectra of chlorobenzene monomer and clusters (Clbz)_n with n = 1-4 were obtained using resonant 2-photon ionization in the origin region of the S₀–S₁ (ππ*) state of the monomer. The cluster spectra show in all cases a …