Physical Sciences and Mathematics Commons^™

New Methods For Stereoselective Glycosylation In Application To Significant Biomedical Targets, Melanie L. Shadrick

Dissertations

Glycosyl halides have been utilized for glycosylation reactions since the early studies by Arthur Michael, nearing the end of the 19^th century. Koenigs and Knorr then utilized silver salts to activate glycosyl bromides and chlorides to create synthetic glycosides. Many efforts to improve the outcome of reactions with glycosyl halides have emerged. The key emphasis has traditionally been placed on reaction rates, product yields, and stereocontrol. Recently, our lab reported that silver(I) oxide-mediated Koenigs-Knorr glycosylation reaction can be dramatically accelerated in the presence of catalytic acid additives. Methods to improve glycosylation was explored using mannosyl and glucosyl bromides. However, …

Binding Interactions Of Biologically Relevant Molecules Studied Using Surface-Modified And Nanostructured Surfaces, Palak Sondhi

Dissertations

This research focuses on the field of surface nanobioscience, wherein different nanosurfaces that will be used as working electrodes in the electrochemical cell are manufactured and surface modified to understand the critical binding interactions between biologically significant molecules like proteins, carbohydrates, small drug molecules, and glycoproteins. This research is essential if we are to determine whether a synthetic molecule can serve as a therapeutic candidate or diagnose a disease in its early stages. In order to fully understand the binding interactions, the study begins with defining some of the fundamental concepts, principles, and analytical tools for biosensing.

Afterwards, we addressed …

High Resolution Intracavity Laser Absorption Spectroscopy Of Transition Metal-Containing Diatomic Molecules, Kristin Bales

Dissertations

Three transition metal-containing diatomic molecules have been studied using intracavity laser spectroscopy. Many of the transitions were recorded using a Fourier-transform spectrometer for detection, allowing collection at Doppler-limited resolution for the gas phase molecules. Several vibrational bands in two electronic transition systems of tantalum fluoride (TaF) have been analyzed, and new molecular constants provided. Transitions involving six electronic states of tungsten sulfide (WS) have been analyzed, with new and updated constants provided, including a deperturbation analysis of three vibrational bands in two of the states. Finally, a fresh perspective on two electronic states of tungsten oxide (WO) included a deperturbation …

Synthetic Amphiphiles As Antibiotic Potentiators, Helena Spikes

Dissertations

Antibiotic resistance has become a massive threat to modern medicine. Bacteria acquire resistance either through genetic mutations or mobile genetic elements, such as plasmids. The growing resistance crisis is exacerbated by over-prescription of antibiotics and improper use. As antimicrobial resistance becomes more widespread, superbugs (bacteria resistant to more than one class of drug) have evolved. Since few new drugs reach clinical trials and even fewer are approved by the FDA, we must find a way to make existing drugs more potent. One technique to accomplish this is by using combination therapy. By administering two or more drugs at a time, …

Ferrocenium Salt Aided Substitution Reactions And Synthesis Of Glycosylated Curcumin Derivatives, Deva Saroja Talasila

Dissertations

Organic synthesis has been significantly advanced with the employment of transition metal complexes. The discovery of transition metal catalysts provided the synthetic community with powerful tools for accelerating reactions and making them more selective and efficient. Many chemical reactions do not happen without a catalyst.

Iron-based catalysts have several advantages for the chemical industry because it is a non-toxic and ecologically friendly metal. Our group previously found that ferrocenium cations with a 3+ oxidation state of iron-catalyzed propargylic substitution reactions at low temperatures. The sandwich structure of ferrocenes allows substituents to be introduced on the cyclopentadienyl rings, which allows for …

Novel Thioglycosides As Versatile Glycosyl Donors For Oligosaccharide Synthesis, Ganesh Shrestha

Dissertations

This thesis is dedicated to the development of new methodologies for efficient synthesis of carbohydrate building blocks and their application to chemical glycosylation. S-Indolyl (SIn) anomeric moiety was investigated as a new leaving group. Understanding of the reaction pathways for the SIn moiety activation was achieved via the extended mechanistic study. The activation profile of indolylthio glycosides required large excess of activators. This drawback was partially addressed by the development of N-alkylated SInR derivatives. The activation process was studied by NMR and the increased understanding of the mechanism led to a discovery of different activation pathways taking place with …

Mechanism Of Sila- And Germafluorenes For Biological Applications, Shelby Jarrett

Dissertations

2,7-disubstituted silafluorenes and germafluorenes, originally designed for OLED applications, are a class of fluorescent dyes that have gained recent interest as probes for bioimaging and as biosensors to monitor cellular dynamics and interactions. Desirable biological probes absorb in the visible region, have high extinction coefficients, high quantum yield and excellent photostability. Here, their spectral properties are investigated under aqueous conditions for relevant biological applications. These molecules display intense blue fluorescence in the solid state and in solution, have high extinction coefficients, and exhibit appreciable solubility in aqueous solution. To better understand potential applications, the mechanism of fluorescence was investigated. It …

Bis(Tryptophan) Amphiphiles: Design, Synthesis And Efficacy As Antimicrobial Agents, Michael Mckeever

Dissertations

Amphiphiles play important roles in nature. These molecules contain both hydrophilic and hydrophobic regions, leading to some astonishing properties. The lipid bilayer of the cell membrane is a fascinating organization of amphiphilic phospholipids. Natural and synthetic amphiphiles, such as antimicrobial peptides, interact with the cell membrane. Such interactions can impact transport of molecules across the cell membrane, disrupting cell functions. In this work, a library of tryptophan-containing amphiphiles was synthesized and their antimicrobial properties were explored.

First, a library of bis(tryptophan) amphiphiles was synthesized. Preparation included a coupling reaction of a diamine with tryptophan residues, via their carboxy-termini, at …

New Methods For The Synthesis, Activation, And Application Of Thioglycosides, Samira Escopy

Dissertations

From their ubiquitous presence in Nature to their vital roles in biology and medicine, carbohydrates (sugars or glycans) are essential molecules of life, which are made and/or utilized by every living organism. Our cells are coated with sugars that are involved in almost every biological process and defensive mechanism in our body. To mention some of their crucial biological functions, carbohydrates are essential source of energy, they participate in blood coagulation, immune defense, cell growth, cell-cell interaction, and anti-inflammatory processes. Understanding of glycan functions and structure is crucial for the development of vaccines and therapeutics. Producing complex carbohydrates in sufficient …

Stereocontrolled Mannosylation By Hydrogen-Bond-Mediated Aglycone Delivery, Catherine Alex

Dissertations

Stereocontrolled Mannosylation by Hydrogen-Bond-Mediated Aglycone Delivery

Carbohydrates are the essential bio-molecules of life as they form the forefront of interactions with receptors, proteins, pathogens, or neighboring cells. On cell-surfaces, carbohydrates are mostly found as linear or branched glycoconjugates, and a majority of them are linked via either 1,2-cis or 1,2-trans O-glycosidic linkages. There is no template-driven pathway for achieving the synthesis of glycans unlike other biomolecules like proteins and nucleic acids. The synthesis of 1,2-trans glycosides can be reliably achieved via the neighboring group assistance. The synthesis of 1,2-cis glycosides is difficult because, beyond weak anomeric effects, there are …

Synthesis Of Biologically Active Phosphorus Heterocycles, Giri Gnawali

Dissertations

This dissertation work is divided into two parts. The first part is focused in the development of methodology for the synthesis of phostones and phosphonosugars and advancement thereof. The second part is focused in the development of affinity probes based on analogs of natural products cyclophostin and the cyclipostins.

Phostone (3) and phosphonosugars are cyclic phosphonates. The anomeric carbon of sugar is replaced by a phosphorus atom. The synthesis of phostones has been achieved starting form the key intermediate, γ,δ-epoxy vinyl phosphonate (1). The palladium catalyzed ring opening of γ,δ-epoxy vinyl phosphonates by a nucleophile results …

New Catalytic Reactions In Carbohydrate Chemistry, Scott Geringer

Dissertations

Carbohydrates or sugars are some of the most diverse and abundant biological molecules. They are involved in a multitude of processes in the body such as fertilization, cell-cell communication, and cancer metathesis. Because of these vital functions, the study of sugars is rapidly growing field. The field however is limited due to the complex nature of sugars which results in difficulties in obtaining large quantities for study.

Protecting group manipulation is a large emphasis area in carbohydrate chemistry due to the need to selectively protect different functional groups of each molecule during synthesis. Catalytic and selective cleavage of protecting groups …

Towards Completely Automated Glycan Synthesis, Matteo Panza

Dissertations

Carbohydrates are ubiquitous both in nature as biologically active compounds and in medicine as pharmaceuticals. Although there has been continued interest in the synthesis of carbohydrates, chemical methods require specialized knowledge and hence remain cumbersome. The need for development of rapid, efficient and operationally simple procedures has come to the fore. This dissertation focuses on the development of a fully automated platform that will enable both experts and non-specialists to perform the synthesis of glycans. Existing automated methods for the synthesis of oligosaccharides are highly sophisticated, operationally complex, and require significant user know-how. By contrast, high performance liquid chromatography (HPLC) …

Chemical Synthesis Of Oligosaccharides From Human Milk, Mithila Dulanjalee Bandara Weerasooriya Mudiyanselage

Dissertations

Human milk oligosaccharides (HMO) are a family of structurally related glycans that are highly abundant in breast milk. Oligosaccharide fraction is the third largest solid component in human milk after lactose and lipids. There is an accumulating evidence that HMO can provide significant benefits to the breast-fed infants. However, understanding of the exact HMO functions is still incomplete due to the lack of individual compounds in sufficient quantities. Therefore, development of expeditious strategies for the chemical synthesis of HMO has been increasingly important. Among all the methods available for oligosaccharide synthesis, armed-disarmed strategy introduced by Fraser-Reid is based on chemoselective …

Capabilities And Limitations Of The Spin Hamiltonian Formalism In Single Molecule Magnets, Philip Ferko

Dissertations

The rational design of molecular magnetic materials is an ongoing effort involving physics, materials science, and chemistry. A common approach to design of complexes and interpretation of magnetic data is the spin Hamiltonian formalism. In this approach, magnetic data is interpreted through constants extracted from the parameterization of data. In design, certain structural motifs are pursued, rationalized by the minimization or maximization of terms in the spin Hamiltonian. In this work, monometallic complexes were prepared to simplify magnetic behavior and allow the examination of specific factors that influence single molecule magnetism like coordination geometry, ligand identity, symmetry, and spin-orbit coupling. …

High Resolution Near-Infrared/Visible Intracavity Laser Spectroscopy Of Small Molecules, Jack Harms

Dissertations

Intracavity laser spectroscopy has been used to study the electronic structure of several small molecules. The molecules studied as part of this dissertation include germanium hydride (GeH), copper oxide (CuO), nickel chloride (NiCl), platinum fluoride (PtF), platinum chloride (PtCl), and copper hydroxide (CuOH). This work encompasses five peer-reviewed publications and two submitted manuscripts.

Application Of The Picoloyl Group In Carbohydrate Chemistry, Michael Mannino

Dissertations

Stereocontrol of glycosylation reactions is a constant struggle in the field of synthetic carbohydrate chemistry. The application of the picoloyl (Pico) substituent can offer numerous stereocontrolling avenues. The most popular application is the Hydrogen-bond-mediated Aglycone Delivery (HAD) method that provides excellent selectivity in the glycosylation of a variety of sugar substrates. The HAD method relies on the formation of an intermolecular hydrogen bond between the nitrogen atom of the Pico substituent on the glycosyl donor with the hydroxyl group of the glycosyl acceptor. This interaction provides a facial preference for the nucleophilic attack and hence provides powerful stereocontrol for the …

Application Of Glycosyl Imidates And Nitrates In Carbohydrate Synthesis, Tinghua Wang

Dissertations

Carbohydrates are the most abundant molecules among the four essential classes of biomolecules that also include nucleic acids, lipids and proteins. Unlike proteins and nucleic acids, which follow template-driven synthetic pathways, there is no general route to the synthesis of carbohydrates. The stereoselectivity of the formation of O-glycosidic linkages and the regioselectivity of protection and deprotection of specific hydroxyl groups over others represent two of the major challenges in carbohydrate chemistry. This thesis is dedicated to the development of novel strategies for efficient synthesis of carbohydrate building blocks and stereocontrolled glycosylations for step-economy oligosaccharide synthesis. Novel glycosyl donors with difluoro-3H-indol-2-yl …

Investigation Of Vaporization Enthalpies And Vapor Pressures Of Organic Compounds By Correlation Gas Chromatography, Carissa Nelson

Dissertations

Thermodynamic properties of organic compounds are useful to scientists and manufacturers in many areas of research and technology. This work focuses on measuring and reporting these properties on materials of commercial, environmental and scientific interest. Vaporization enthalpies and vapor pressures of several organic compounds have been studied using correlation gas chromatography (CGC) and are reported here as well as in recent publications. The CGC method allows for the indirect measurement of these properties in instances where these materials are available only in mixtures or in very small amounts.

The qualities of these measurements for any chosen target are directly related …

Development Of Rules Of Attraction For Intercalated Guest Molecules Inside Of A Hydrogen Bonded Framework, Matthew Fischer

Dissertations

Supramolecular chemistry has synthesized large and small molecules which host guest molecules for several decades. What started as a way to mimic of enzymes in nature, has exploded into a sea of materials such as porous coordination polymers, low-density metal-organic frameworks, inclusion compounds, and hydrogen bonded frameworks. We previously designed a layered framework consisting of a metal complex with coordinate covalent ligands. These ligands have peripheral carboxylic acid groups which hydrogen bond to organic pillars containing terminal amines. The layered structure is separated by these pillars, which are closed-packed, creating 1-dimensional channels able to co-crystallize molecules. There is interest in …

Cationic Ruthenium Complexes In Catalysis: The Activation Of Propargylic Alcohols Through Electronically Tuned Complexes, Matthew James Stark

Dissertations

With increasing complexity of metal complexes, it is of worthwhile interest to pursue systematic examinations of ligand modifications to study their impact on the reactivity of a catalyst. To that end, this study aimed to understand the effect electron-withdrawing ligands conveyed to catalytic activity in the etherification of propargylic alcohols and related reactions. A number of half-sandwich ruthenium complexes bearing ligands with varying electron–withdrawing properties were synthesized and structurally characterized. Their electronic and structural properties were investigated utilizing X-ray crystallography, revealing that the series of complexes did not vary significantly in structure. The complexes were studied electronically with cyclic voltammetry, …

Evaluation Of Vaporization Enthalpies And Vapor Pressures Of Various Aroma And Pharmacologically Active Compounds By Correlation Gas Chromatography, Daniel Simmons

Theses

Scientists in the pharmaceutical, food, and aroma industries can benefit from reliable thermochemical data. Vaporization enthalpy and vapor pressure data are not available for all compounds. Furthermore, some literature data is conflicting. The goal of this work was to use a method called correlation gas chromatography (CGC) to generate reliable vaporization enthalpy data in instances where other experimental methods are not applicable. Vapor pressures of the targets were also calculated in cases where the required literature data on the standards used in this technique were available.

CGC involves making a standard cocktail that includes a mixture of standards and one …

Steric Effects On The Formation Of Manganese Oxide Clusters And 2-Dimensional Ammonium Formate Architectures, Carl Oberle

Dissertations

It has been demonstrated by the Beatty group that altering the identity of the ortho-substituent of a dianiline counterion affects the assembly and dimensionality of a cadmium-chloride layer from 2-D to 0-D. This work seeks to extend this finding to metal oxide and organic hydrogen-bonded materials. By systematically increasing the ortho­-substituent’s size on the benzoate building block of reported manganese oxide clusters, of formula Mn_xO_y(O₂C-R)_zL_w (where R = Alkyl, L = neutral monodentate ligand), we aim to impact the self-assembly of these materials relative to their parent …

Chemical Synthesis Of Staphylococcal Oligosaccharides, Satsawat Visansirikul

Dissertations

The Gram positive, cluster forming bacteria Staphylococcus aureus belongs to the family of opportunistic pathogens that may cause blood stream infections when the integrity of skin is broken and the immune system can no longer fight the infection. S. aureus has become one of the most frequent causes of infections in newborns, surgical patients, trauma and burn patients, patients receiving an implant, and dialysis patients with high mortality rates. As a matter of fact, S. aureus has become one of the largest public health and economic impacts amongst all bacterial infectious diseases worldwide. This situation is further complicated by the …

Functionalized Nanoporous Carbon Scaffolds For Hydrogen Storage Applications, Christopher Carr

Dissertations

Recent efforts have demonstrated confinement in porous scaffolds at the nanoscale can alter the hydrogen sorption properties of metal hydrides, though not to an extent feasible for use in onboard hydrogen storage applications, proposing the need for a method allowing further modifications. The work presented here explores how the functionalization of nanoporous carbon scaffold surfaces with heteroatoms can modify the hydrogen sorption properties of confined metal hydrides in relation to non-functionalized scaffolds (FS). Investigations of nanoconfined LiBH₄and NaAlH₄indicate functionalizing the carbon scaffold surface with nitrogen can shift the activation energy of hydrogen desorption in excess of …

Interactions Between Amyloid-Beta And Microglial Cells, Lisa Gouwens

Dissertations

Alzheimer’s disease (AD), the most common cause of dementia, is a neurodegenerative condition characterized by loss of memory and intellectual abilities. Intracellular plaques of aggregated amyloid-beta (Ab) protein are a well-known pathology associated with AD. Although symptoms usually appear late in life, the accumulation of Ab begins decades earlier and causes activation of microglia, the brain’s immune cells. The ensuing inflammation contributes significantly to neurodegeneration. Determination of the particular form of Ab that causes the most damage in the brain is one of the major questions in the AD field. My research focused on the interactions of microglia with monomers, …

2-D Electrophoresis Modeling Of Multienzyme Cutting Of Polypeptides, Howard Mayes

Theses

2-Dimensional Electrophoresis is one of the tools in the identification of proteins by molecular weight and pH. The display of molecular weight allows the researcher to quickly identify whether a specific protein or peptide string is in the sample. The pH measurement allows even better resolution between different species in the sample. The MultiEnzyme ElectroPhoresis (MEEP) program tries to model that by providing a graph that displays separated protein strings by both molecular weight and pH. The ability to cleave the protein with 43 different enzyme variations allows the researcher to analyze appropriate enzymes to isolate a protein subsequence before …

Cadmium Chloride Dimensionality Changes From Ortho-Substituted Anilines, Stephanie Cernicek

Dissertations

Inorganic-organic hybrid metal halide materials have been of great interest recently due to the useful properties offered by such a combination. The inorganic portions usually consisting of MX₆^2- subunits, (M = Pb, Sn, Cd, Cu; X = Cl, Br, I) most often form 2-D perovskite layers where the metals are bridged by corner sharing halides. The organic portion, usually consisting of primary amines or anilines provides a template for the inorganic framework and in some cases, dictates the dimensionality (2-D, 1-D, 0-D) of the network. These materials have various applications in host-guest chemistry catalysis, and gas storage, or …

Rational Drug Design Directed At Blocking The Initial Signaling Events In Lipopolysaccharide-Induced Sepsis., Christopher A. Tipton

Theses

Systemic Inflammatory Response Syndrome (SIRS) is classified as an immune system response to an infectious state. If left untreated, SIRS leads to sepsis, septic shock, end-organ dysfunction, and death. As a patient progresses through these stages, associations of acute respiratory distress, disseminated intravascular coagulation, and acute renal failure persist, resulting in millions of deaths annually. Lipopolysaccharide (LPS), a bacterial endotoxin, is released into the blood stream, triggering SIRS. LPS is found in the outer cell-wall of Gram-negative bacteria and is responsible for initiation of a devastating cytokine storm. One of the regions of LPS, lipid A, is a polyacylated glucosamine …

Syntheses, Structures And Magnetic Properties Of Cyano-Bridged Transition Metal Compounds, Uma Prasad Mallik

Dissertations

To investigate the hypotheses, that systematically changing the electronic and relative sizes of tricyanido building blocks will tune magnetic properties of their cluster derivatives, we prepared two new tricyanido pyrazolylborate complexes, [NEt₄][(Tp*^Me)­Fe(CN)₃]­·H₂O and [NEt₄]­[(Tp^*Bn)­Fe^III(CN)₃]­·H₂O·MeOH, and investigated their self-assembly. The new building blocks were prepared, structurally characterized, and their coordination chemistry explored to prepare small molecule-based magnetic materials.

Three bent trinuclear ferromagnetic cluster derivatives of {[(Tp^*Me)­Fe^III(CN)₃]_2­[Ni^II(L)₂]}·n(solvent) [L = …