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Antibacterial Drug Design And Discovery Via Vitamin B1 Biosynthetic Pathway, Abu Afzal Mohammad Shakar

Chemistry & Biochemistry Theses - Archive

Antibiotics play a vital role in fighting infectious disease caused by bacterial species. Antimicrobial resistance has been shown for every current antibiotic and poses a major health risk. To combat these growing threats to human health; new molecules must be investigated to treat bacterial infection. Chemical inhibition of the vitamin B1 biosynthetic pathway in the bacterial cell was hypothesized to inhibit the survival of bacteria. A series of synthetic molecules, which resemble metabolites of the vitamin B1 pathway, exhibit the inhibition of specific enzymes within this pathway and display initial activity against bacterial growth and survival. The beneficial activity of …

Synthesis, Characterization, And Application Of Magnetic Gold Nanoclusters, Naveen Reddy Kadasala

Open Access Dissertations

Au–Fe3O4 nanocomposites are of great interest for technological reasons due to their combined optical and magnetic properties. Nanosized Fe3O4 particles are superparamagnetic and can also be coated with a layer of Au, which supports localized plasmon resonances for useful optical properties. The dual properties of Au–Fe3O 4 nanoparticles have inspired chemists to design a variety of synthetic routes, some with good control of overall shape and size. However, most approaches require organic solvents, surfactants, or harsh chemical conditions. In this thesis we describe a simple and highly reproducible synthesis of magnetically active gold nanoclusters (MGNCs) with average particle sizes under …

Mass Spectrometric Characterization Of Remotely Charged Amino Acids And Peptides, Damodar Koirala

Open Access Dissertations

Ion–molecule reactions in a flowing afterglow are used to examine the electronic structure of 3- and 4-pyridinylnitrene-n-oxide radical anions. Reactions with nitric oxide are generally similar to those reported previously for other aromatic nitrene radical anions. In particular, phenoxide formation by nitrogen–oxygen exchange is observed with both isomers. Oxygen atom abstraction by NO is also observed with both isomers. Very significant differences in the reactivity are observed in the reactions of the two isomers with carbon disulfide. The reactivity of the 3-noxide isomer with CS2 is similar to that observed previously for nitrene radical anions, and reactions of the n-oxide …

Catalytic Conversion Of Chlorite To Chlorine Dioxide By Non-Heme Complexes, Manasa Ramachandra

Open Access Theses

The oxyanions of chlorine (ClOx-, x=1-4) have diverse applications and are used in a variety of commercial products. They are very stable in an aqueous environment leading to water contamination, thereby posing a concern for the environment and human health. At the microbial level, the enzyme perchlorate reductase catalyzes the reduction of perchlorate (ClO4-) to chlorite (ClO2-) and chlorite dismutase further reduces chlorite to innocuous chloride (Cl -) and dioxygen (O2). Two non-heme complexes [Fe III-TAML]- (Tetraamido Macrocyclic Ligand), and [Mn II-(BnTPEN)] in the presence of peracetic acid (PAA) have been studied as catalysts for chlorite dismutation under ambient conditions. …

Polymerizable Lipids For Controlled Functionalization Of Layered Materials, Kortney Kaye Rupp

Open Access Theses

Self-assembled monolayers (SAM’s) offer a straightforward approach to tailoring the interfacial properties of metals, metal oxides and semiconductors. Noncovalent functionalization of single-layer graphene offers the possibility to finely tune surface chemistry for future applications in electronics. Polymerization of photochemically reactive molecules in a lying-down phase has been used to increase the strength of intermolecular interactions between long alkanes and HOPG substrates. Long-chain fatty acid derivatives with internal diyne groups yield a conjugated ene-yne polymer upon UV irradiation. Diyne lipids with phosphocholine (diyne PC) and phosphoethanolamine (diyne PE) groups offer a charged form of the head group that is robust towards …

Metal-Promoted Self-Assembly Of Collagen Mimetic Peptides Into Biofunctional Scaffolds For Stem Cell Delivery With The Aim Of Tissue Regeneration, Kevin Strauss

Open Access Theses

Collagen is a strong, sturdy, but malleable, protein found abundantly in the extracellular matrix. Consequently, it has become an invaluable biomaterial for use in regenerative medicine. However, natural collagen poses difficulties when it comes to customization and structural control, as well as the risk of infectious prions from animal sources. Our approach utilizes shorter, synthetic collagen mimetic peptide sequences. These peptides retain the incredible triple helical stability of natural collagen but can be modified with versatile metal-binding ligands. In the presence of an appropriate metal ion, the peptides self-assemble into diverse, three-dimensional morphologies. The peptide NCoH, functionalized with N-terminal NTA …

Ultraviolet And Infrared Spectroscopy Of Synthetic Foldamers, Aib Homopeptides, And Solvated 1,2-Diphenylethane In The Gas Phase, Joseph R. Gord

Open Access Dissertations

The work presented here implements a supersonic jet expansion source to funnel the population of model peptides and solvated-bichromophore clusters into their low lying structural minima and to collisionally cool these minima to their respective zero-point vibrational levels. Single-conformation ultraviolet and infrared spectroscopy techniques are then used to probe these systems and investigate their electronic properties and uncover their intrinsic conformational preferences in the gas phase.

Model β/γ-peptides known as synthetic foldamers and aminoisobutyric acid (Aib) homopeptides incorporate structural constraints that are designed/known to impose particular structural motifs. Here the ability of a β/γ-dipeptide to replicate the backbone length of …

Synthetic Studies Of Heparan Derivatives: Glycosyl Couplings And Post-Glycosylative Modifications, Hari Raj Khatri

Open Access Dissertations

Heparan sulfate (HS) and closely related heparin are comprised of alternating units of D-glucosamine and either D-glucuronic acid (D-GluA) or L-iduronic acid (L-IdoA), and support variable degrees of sulfation which can interact with a large number of proteins with diverse biological functions. HS oligosaccharides can be constructed from readily accessible D-GlcN and D-GlcA derivatives, but the inclusion of L-IdoA is less straightforward. To address this, our laboratory has developed alternative synthetic strategies for HS-like oligosaccharides to incorporate either D-GlcA or L-IdoA in a synthetically efficient manner by nucleophilic ring opening of 4-epoxypyranosides, which can be made from readily available D-hexoses …

Advances In Raman Hyperspectral Compressive Detection Instrumentation For Fast Label Free Classification, Quantitation And Imaging, Bharat R. Makani

Open Access Dissertations

Multiple prototypes of hyperspectral compressive detection (CD) Raman spectrometers have previously been constructed in the Ben-Amotz lab and have proven to be useful for fast, label-free chemical identification, quantitation and imaging. The CD spectrometer consists of a volume holographic grating (VHG) that linearly disperses the Raman photons into its component wavelengths and all wavelengths are focused onto a digital micromirror devise (DMD). The DMD is an optical modulator that consists of an array of programmable 10μm mirrors that can reflect photons in either +12° or -12° to the incoming light. The DMD is tilted such that the +12° photons go …

Coupling Qualitative And Quantitative Analyses Of Pharmaceutical Materials Enabled By Second Harmonic Generation Microscopy, Paul D. Schmitt

Open Access Dissertations

The detection and characterization of crystallinity is critical throughout the drug development process. From the initial establishment of an active pharmaceutical ingredient’s (API) crystal structure to stability testing and quality control, the phase of an API affects the solubility, bioavailability, stability, and efficacy of a drug product. Second harmonic generation (SHG) microscopy has recently been developed as a selective and rapid method for imaging crystallinity in drug formulations. While SHG microscopy can enable the high signal-to-noise (SNR) detection of crystallinity, the intrinsic chemical information content within SHG images is relatively low. In cases of trace crystallinity and/ or small crystal …

Single-Conformation Spectroscopy Of Hydrogen Bonding Networks: Solvation, Synthetic Foldamers, And Neurodegenerative Diseases, Patrick S. Walsh

Open Access Dissertations

The hydrogen bond is one of the most important interactions in natural processes ranging from protein folding to chemical reactions. Two complementary methodologies are applied to understanding this important interaction: top-down and bottom-up. Top-down methods use large molecules, such as proteins, revealing secondary structure information. Bottom-up experiments are performed on small molecules, utilizing high-resolution spectroscopy to reveal underlying quantum mechanical effects. The complexity gap is formed between these two experimental regimes; between large and small molecules; between bulk and individual solvent molecules; between classical mechanics calculations and quantum chemical calculations. This dissertation will focus on the application of gas phase, …

Intact Protein Detection, Separation, And Quantitation Using Liquid Chromatography - Triple Quadrupole Mass Spectrometry, Evelyn Hsin-Yi Wang

Chemistry & Biochemistry Dissertations - Archive

There is an increasing demand for protein detection and quantitation in biological fluids for disease detection, protein therapeutics monitoring, and drug development response control. Current methods use highly sensitive and specific triple quadrupole mass spectrometry (QqQ-MS) to quantify protein digest peptides to predict original intact protein concentrations from the sample. The bottom-up protein quantitation format requires protein digestion which is often incomplete and can introduce errors into protein quantitation methods. Therefore, absolute protein quantitation is impossible without including expensive isotopically labeled protein standards. In our lab, a method that bypasses the protein digestion step to directly quantify intact protein on …

Advances In Separation Methodologies: Fatty Acid, Fatty Amine, Water, And Ethanol Determination By Ionic Liquid Gas Chromatography And D-Amino Acid Evaluation In Mammalian Brain By Liquid Chromatography, Choyce Asher Weatherly

Chemistry & Biochemistry Dissertations - Archive

This dissertation focuses on two chromatographic techniques, gas chromatography (GC) and high performance liquid chromatography (HPLC). The goal of the GC work is to describe advances in separation methodologies focusing on the separation and quantitation of commercially related compounds (i.e. fatty acids, fatty amines, water, and ethanol). Four ionic liquid (IL) columns were evaluated for rapid analysis and improved resolution of long-chain methyl and ethyl esters of omega-3, omega-6, and additional positional isomeric and stereoisomeric blends of fatty acids found in fish oil, flaxseed oil, and potentially more complicated compositions. The potential for improved resolution of fatty acid esters is …

Analysis Of Heme Iron Coordination In Dgcr8: The Heme-Binding Component Of The Microprocessor Complex, Hazel M. Girvan, Justin M. Bradley, Myles R. Cheesman, James R. Kincaid, Yilin Liu, Kazimierz Czarnecki, Karl Fisher, David Leys, Stephen E. J. Rigby, Andrew W. Munro

Chemistry Faculty Research and Publications

DGCR8 is the RNA-binding partner of the nuclease Drosha. Their complex (the “Microprocessor”) is essential for processing of long, primary microRNAs (pri-miRNAs) in the nucleus. Binding of heme to DGCR8 is essential for pri-miRNA processing. On the basis of the split Soret ultraviolet–visible (UV–vis) spectrum of ferric DGCR8, bis-thiolate sulfur (cysteinate, Cys^–) heme iron coordination of DGCR8 heme iron was proposed. We have characterized DGCR8 heme ligation using the Δ276 DGCR8 variant and combined electron paramagnetic resonance (EPR), magnetic circular dichroism (MCD), electron nuclear double resonance, resonance Raman, and electronic absorption spectroscopy. These studies indicate DGCR8 bis-Cys heme …

Mechanism Of Rapid Electron Transfer Reactions Involving Cytochrome Bc1, Cytochrome C And Cytochrome Oxidase, Jeremy Erik Durchman

Graduate Theses and Dissertations

Electron transfer between mitochondrial proteins complexes represents the primary means by which living things acquire the requisite energy for survival. The coupling of electron transfer to proton translocation creates an electrochemical gradient that drives the synthesis of highly energetic compounds such as ATP. The purpose of these studies is to measure rates of electron transfer and elucidate the important governing factors in the redox events involving cytochrome bc1, cytochrome c and cytochrome oxidase. Using rapid initiation of redox events triggered by laser flash excitation of ruthenium compounds, and strategically monitoring unique spectral properties of these proteins in the visible region …

Two Studies: Stereoselective C-C Bond Formations Of N-Boc-Piperidines Using Selected Organolithiums And Visible-Light-Mediated Synthesis Of Fused Indolines Using Tethered Styrenes, Scott Alan Morris

Graduate Theses and Dissertations

Chemists worldwide have accepted the challenge of developing methods to access a variety of compounds as single enantiomers, including the use of enzymes, chiral auxiliaries, and resolutions. In particular, dynamic resolutions offer a unique way to access chiral compounds using a few controllable steps, including the variation of both time and temperature. Many groups have implemented this methodology to generate various polysubstituted pyrrolidines and piperidines, which are substructures ranking high on the list of nitrogen–containing pharmaceuticals.

The Gawley group revealed a catalytic dynamic resolution (CDR) of N–Boc–piperidine using a chiral ligand. Impressively, the chemistry was tolerant of a variety of …

The Large-Scale Synthesis And Asymmetric Hydrosilylations Of Cuiphet, A C2-Symmetric N-Heterocyclic Carbene, Elizabeth Suzanne Spahn

Graduate Theses and Dissertations

CuIPhEt is a C2-symmetric N-heterocyclic carbene catalyst used in the asymmetric hydrosilylation of a variety of prochiral ketones with good yields and selectivities. The large-scale, five-step synthesis of this carbene has been devised. The second step of the synthetic plan includes a double asymmetric hydrogenation of a 1,1-diaryl alkene—a traditionally difficult transformation. The procedure for the use of CuIPhEt in asymmetric hydrosilylations has been optimized and used on both the originally published substrate scope and new compounds. This protocol for the hydrosilylation has been applied in a 10 g reduction to create an intermediate for use toward the total synthesis …

Investigation Of The Interaction Of Dimeric Ruthenium Complexes With Cytochrome B5, Christopher Dain Rupar

Graduate Theses and Dissertations

Photoreactive complexes to study the kinetics of electron transfer of proteins have been in use for a long time. It has always been speculated that complexes bind near the heme or the electron transfer reaction would not occur. But it is unkown exactly how the complex interacts with the protein. The structural, thermodynamic, and kinetic properties of rat liver microsomal cytochrome b5 were investigated when bound to ruthenium dimer complexes. Heteronuclear Single Quantum Coherence studies support a dynamic binding model of a dimer Ru complex bound near the protein’s heme involving residues H39, E44, G42, V61, G62, and H63. The …

Part 1: One Minute Peptoid Synthesis, From Peptoid Oligomers To Peptoid Polymers - Part 2: Synthesis Of Creatine Derivatives, Dan Y. Dong

All Theses

Part 1:

Peptoids are isomers of peptides where the side chains are on the nitrogens instead of the carbons, which have been developed for a variety of biomedical, nano, and materials applications. Conventional peptoid synthesis uses molar concentrations of reagents and hours of reaction time per residue, thus practically limiting the lengths of peptoids. Recently, we have managed to improve yields and make peptoids of unprecedented lengths while reducing the reaction times and concentrations of reagents. Indeed, we have demonstrated that the conventional longer reaction times degrade the peptoids and lead to lower purities. In addition, by using microwave conditions, …

A Library Of Coumarin-Enaminone Chemodosimeters For The Detection Of Analytes, Aaron Berrell Davis

Dissertations

Many anions and metal ions are of biological and environmental importance. This work describes our attempts to synthesize molecular probes to specifically target cyanide, zinc, cadmium and mercury as these species can often result in negative effects to the environment and the human body.

The work in this dissertation, describes the synthesis of a family of coumarin-enamine chemodosimeters, in a straightforward synthetic procedure, the reaction between 7-(diethylamino)-4-hydroxycoumarin and a primary amine. The work presented in this dissertation demonstrates that these molecules can play dual roles and therefore the work is split into two distinct parts: Part 1 describes one role …

The Synthesis Of Chemosensors For Toxic Analytes, Johnathan Hugh Broome

Dissertations

A number of chemosensors have been designed and synthesized to target cations (Zn²⁺ions), neutral molecules (cathinones), charged molecules (aminoindanes), and anions. The Zn²⁺ ion sensor featured bistriazole designed binding unit and ferrocene signaling units. Characterization of Zn²⁺ ion binding was carried out with electrochemical techniques (CV and DPV), ¹H-NMR, mass spectrometry, and molecular modelling. It exhibited a 1:1 binding stoichiometry with Zn²⁺ and had an affinity for ZnCl₂ (Log K_1:1 = 4.1 ± 0.02) over other Zn²⁺ salts.

The cathinone probe was designed to selectively bind mephedrone over common street drugs …

Assessing The Feasibility Of A One-Pot, Tandem Olefin Metathesis And Isomerization Sequence To Synthesize Conjugated Aromatic Olefins, Ajay D. Makwana

Honors Theses

The synthesis of substituted phenylpropene dimers using a one-pot, tandem olefin metathesis and isomerization sequence has been studied. This sequence relies on the facilitated, in-situ conversion of a ruthenium carbene species (Ru=C) to a ruthenium hydride species (Ru-H) upon addition of an inorganic hydride source. Three separate reactions occur within one reaction flask: 1) olefin metathesis of the starting phenylpropene to yield phenylpropene dimer via Ru=C catalyst, 2) conversion of Ru=C to Ru-H via addition of an inorganic hydride source, 3) isomerization of phenylpropene dimer via insertion and β-hydride elimination to yield conjugated product. The focus of the study has …

Preparation And Characterization Of Singlet-Oxygen Generating Thiol-Ene Networks Containing Fullerene And Metallofullerene Derivatives, Emily Matthews Barker

Dissertations

This work explores the derivatization of C₆₀ and Sc₃N@C₈₀ with S-, P-, and C- centered radicals, and is the first exploration into the functionalization of Sc₃N@C₈₀ with sulfur and phosphorous. The number of addends bound to C₆₀, as a function of reaction time and molar ratios, as well as, structure-property relationships including thermal stability, solubility, and singlet oxygen generation were explored. Fullerene derivatives exhibiting enhanced solubility were incorporated into two different thiol-ene polymer matrices at varying thiol-ene monomer concentrations (1:1 or 1:0.75 molar equivalents) and at different C₆₀ loadings (0, …

The San1 Ubiquitin Ligase Functions Preferentially With Ubiquitin-Conjugating Enzyme Ubc1 During Protein Quality Control, Rebeca Lea Ibarra

UNLV Theses, Dissertations, Professional Papers, and Capstones

Protein quality control (PQC) is a critical process wherein misfolded or damaged proteins are cleared from the cell to maintain protein homeostasis. In eukaryotic cells, the removal of misfolded proteins is primarily accomplished by the ubiquitin-proteasome system (UPS). In the UPS, ubiquitin-conjugating enzymes and ubiquitin ligases append poly-ubiquitin chains onto misfolded protein substrates signaling for their degradation. The kinetics of protein ubiquitylation are paramount since a balance must be achieved between the rapid removal of misfolded proteins versus providing sufficient time for protein chaperones to attempt refolding. To uncover the molecular basis for how PQC substrate ubiquitylation rates are controlled, …

Analysis Of The Intricacies Of Substrate Recognition Of High Mobility Group Proteins And Aminoacyl-Trna Synthetases Using Non-Cognate Substrates, Douglas Van Iverson Ii

Dissertations

The studies presented in section 1 (Chapters I-IV) focus on the design and development of nucleic acid four-way junctions (4WJs) to target a member of the high mobility group (HMG) proteins, the proinflammatory cytokine high mobility group box 1 protein (HMGB1). In the present study, hybrid PNA-DNA 4WJs based on a model DNA 4WJ were constructed to improve the thermal stability of 4WJs while maintaining strong binding affinity toward HMGB1. An electrophoretic mobility shift assay (EMSA) was used to examine the binding affinity of an isolated DNA binding domain of HMGB1, the HMGB1 b-box (HMGB1b), toward a set of PNA-DNA …

Molecular Docking, Synthesis And Evaluation Of Pyrrolo[2,1-C][1,4]Benzodiazepines Derivatives As Non-Β-Lactam Β-Lactamases Inhibitors, Joseph Osamudiamen Osazee

Electronic Theses and Dissertations

Our research aim was to design, synthesize, and study the competitive enzyme inhibition kinetics of pyrrolo[2,1-c][1,4]benzodiazepine (PBD) derivatives as potential non-²-lactam ²-lactamase inhibitors. All compounds (1-13) passed the Lipinski’s rule of 5 test and were docked into the active site of TEM-1 ²-lactamase. PBD derivatives 1-7 were synthesized in high yields and tested for their potency against TEM-1 and P99 ²-lactamases. Kinetic data showed that compounds 1, 4, 5, and 7 possessed inhibitory activity against TEM-1 ranging from 4-34 %. Docking results revealed significant interactive spanning of the active site of TEM-1 by PBDs. …

Synthesis, Characterization And Biological Evaluation Of Pyrrolo[2,1-C][1,4]Benzodiazepines For Cytotoxicity And Serine Β-Lactamases Inhibition, Joel K. Annor-Gyamfi

Electronic Theses and Dissertations

Pyrrolo[2,1-c][1,4]benzodiazepine (PBD) derivatives possess cancerostatic and anti-infective properties thus making them candidates of possible antibacterial agents. ²-lactam antibiotics are vital weapons for the treatment of bacterial infections, but their existence and effectiveness has been faced with resistance from ²-lactamases. Therefore, the need for new effective antimicrobial drugs is very crucial. In this work, we synthesized in high yields, PBD analogs 1−3, 5 and 7−9 in three to four synthetic steps from commercially available L-proline and isatoic anhydride. MTT Assay was employed to test the in vitro cytotoxicity of PBD analogs 1, 2, 5 …

Synthesis And Characterization Of Imidazolo 3,1- Tetrakis (N-Phenylacetamidato) Dirhodium (Ii) And A Crystallographic Study Of A Copper And Two Molybdenum Model Cofactors, Gabriel I.G. Thompson

Electronic Theses and Dissertations

Imidazole was reacted with 3,1-tetrakis (N-phenlyacetamidato) dirhodium (II) to explore the chemistry of asymmetric dirhodium catalysts. The imidazolo 3,1-tetrakis (Nphenlyacetamidato) dirhodium (II) complex was synthesized and then characterized by Nuclear Magnetic Resonance and Ultraviolet-Visible spectroscopies as well as by single crystal X-ray Diffraction. Additionally, one copper and two molybdenum model cofactors were characterized by XRD to better understand their structure/function relationships. NMR results gave evidence of the formation of the 3,1-imidazole complex, and UV-Vis indicated that even in large excess imidazole was coordinated only to one axial site. The structure of the 3,1-imidazole complex was confirmed by XRD with the …

Silver-Polymer Nanocomposites, Anita N. Paul

Electronic Theses and Dissertations

The objective of this research was the development of an efficient method for the preparation of silver-polymer nanocomposites containing finely dispersed silver nanoparticles. The surface of nanosilver was functionalized by thiolation with 2-aminoethanethiol. Amino-modified nanosilver was covalently bonded to polyacrylic acid, biodegradable polymers like acid terminated polylactic acid, ester terminated poly(DL-lactide-co-glycolide) and acid terminated poly(DL lactide-co-glycolide) in the presence of diisopropylcarbodiimide by carbodiimide method. Esterification of the carboxyl groups of Ag-polyacrylic acid by hydrochloric acid in methanol resulted in the formation of a stable colloidal dispersion of Ag nanoparticles in the polymer matrix. It was observed that not just acid …

Extraction, Purification And Characterization Of An Antibiotic-Like Compound Produced By Rhodococcus Sp. Mtm3w5.2, Pushpavathi Reddyvari Manikindi

Electronic Theses and Dissertations

The bacterium Rhodococcus is a potential source for novel antimicrobial metabolites. Recently, the Rhodococcus strain MTM3W5.2 was isolated from a soil sample collected from Morristown, East Tennessee and was found to produce an inhibitor molecule that is active against similar Rhodococcus species. The aim of this research is to extract, purify, and characterize the active compound. The compound was obtained from both agar and broth cultures of strain MTM3W5.2 and purified by primary fractionation of crude extract on a Sephadex LH-20 column, followed by semi-preparative reversed phase column chromatography. Final purification was achieved using multiple rounds of an analytical C …