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Study Of The Insulin Mimetic Sodium Orthovanadate In Glucosamine Induced Insulin Resistnace In Primary Rat Hepatocytes, Kalan Mcpherson

Masters Theses

Insulin resistance and type II diabetes is a disease state characterized by a lack of sensitivity of insulin to provoke a proper response in insulin sensitive tissues. Currently, we utilize glucosamine to increase flux through the Hexosamine Biosynthetic Pathway (HBP) to induce an insulin resistance like state in primary rat hepatocytes. We tested the effectiveness of the insulin mimetic sodium orthovanadate to determine if it could elicit an insulin-like response under these conditions. Mixed results were obtained on the effectiveness of vanadate as an insulin mimetic in this insulin resistant model.

One-Pot Reactions Of Ethyl Propiolate, Ana Maria Neferu

Honors Theses

Through an efficient one-pot reaction sequence, ethyl propiolate can be transformed into a complex, usefully functionalized bicyclic product. Thioconjugate addition yielding Z-selective enoates has been developed for both aromatic thiols (trialkylamine-catalyzed) and aliphatic thiols (KOt-Bu-catalyzed). The oxidation of the thioenoates thus generated is followed by Li-catalyzed oxidation to sulfones using mCPBA, and Li-catalyzed Diels–Alder addition of cyclopentadiene. These subsequent steps are performed in situ, without any purification of intermediates. The yields obtained using the described synthesis are acceptable for a one-pot three-step sequence. Preliminary conjugate addition results with alcohols and amines as nucleophiles are also presented.

Expulsion Of Leaving Groups From Zwitterionic Intermediates Generated Via Photochemical Electrocyclic Ring Closure Reactions And An Investigation On Tpe Oligomers, Tasnuva Shahrin

Dissertations (1934 -)

Photochemical cleavage reactions have been found widespread use in biological applications that require intracellular photochemical release of biologically active substrates such as peptides, proteins, neurotransmitters, or nucleotide phosphates. The research is to devise photoremovable protecting groups (cage compounds) that can be used to deprotect those biological substrates by irradiation. A number of photocleavage reactions have been developed in recent years which release chlorides, hydroxides, carboxylates, thiolates, and phenolates leaving groups for use in such applications. Nevertheless, photochemical elimination reactions that expel such leaving group anions remain quite uncommon. The cleavage of cage compounds via photolysis requires heterolysis of a bond …

Studies On The Diastereoselctive Synthesis Of Spiroketals And Bis-Spiroketals Utilizing A Planar Chiral Sulfinyl Diene Iron(0) Tricarbonyl Scaffold, Jacob S. Tracy , '13

Senior Theses, Projects, and Awards

Spiroketals are chemical motifs found in a range of natural products, many of which possess important biological activity. The stereochemistry of the spiro center of a spiroketal can be controlled by an enantiomerically pure planar chiral ƞ⁴-iron(0) tricarbonyl scaffold. This planar chiral scaffold is prepared through the Stille coupling of an appropriately substituted β-stannylenone to an enantiomerically pure iodo vinyl p-tolyl sulfoxide. Planar chirality is installed by preferential complexation of an iron(O) tricarbonyl fragment to the less hindered face of the sulfinyl diene. An appropriately substituted planar chiral spiroketal precursor was treated with acid to result in diastereoselective spiroketalization. …

Cycling Of Molecular Hydrogen In Subarctic Sweden, Victoria Ward

Honors Theses and Capstones

No abstract provided.

Volume 05, Ian Karamarkovich, Jessica Cox, Kyle Fowlkes, Allison Pawlowski, Kaitlin Major, Carrie Dunham, Kelsey Scheitlin, Kathryn Grayson, Ashley Johnson, Jennifer Nehrt, Kelsey Stolzenbach, Kristin Mcquarrie, Sara Nelson, Melisa Michelle, Jessica Sudlow, Perry Bason, Danielle Dmuchawski, Mariah Asbell, Matthew Sakach, Timothy Smith Jr., Annaliese Troxell, T. Dane Summerell, Sarah Ganrude, Malina Rutherford, Hannah Hopper, John Berry Jr., James Early, Colleen Festa, Chelsea D. Taylor, Michelle Maddox, Kaitlyn Smith, Sarah Schu, Cabell Edmunds, Katherine Grayson, Kayla Tornai

Incite: The Journal of Undergraduate Scholarship

Introduction from Dean Dr. Charles Ross

The Tallis House as an Extension of Emily Tallis in McEwan's Atonement by Ian Karamarkovich

Graphic Design by Jessica Cox

Graphic Design by Kyle Fowlkes

Graphic Design by Allison Pawlowski

Incorporating Original Research in The Classroom: A Case Study Analyzing the Influence of the Chesapeake Bay on Local Temperatures by Kaitlin Major, Carrie Dunham and Dr. Kelsey Scheitlin

Graphic Design by Kathryn Grayson

Graphic Design by Ashley Johnson

Facing the Music: Environmental Impact Assessment of Building A Concert Hall on North Campus by Jennifer Nehrt, Kelsey Stolzenbach And Dr. Kelsey Scheitlin

Art by Kristin …

Solution Structures Of Mycobacterium Tuberculosis Thioredoxin C And Models Of Intact Thioredoxin System Suggest New Approaches To Inhibitor And Drug Design, Andrew Lawrence Olson, Terrence S. Neumann, Sheng Cai, Daniel S. Sem

Chemistry Faculty Research and Publications

Here, we report the NMR solution structures of Mycobacterium tuberculosis (M. tuberculosis) thioredoxin C in both oxidized and reduced states, with discussion of structural changes that occur in going between redox states. The NMR solution structure of the oxidized TrxC corresponds closely to that of the crystal structure, except in the C-terminal region. It appears that crystal packing effects have caused an artifactual shift in the α4 helix in the previously reported crystal structure, compared with the solution structure. On the basis of these TrxC structures, chemical shift mapping, a previously reported crystal structure of the M. tuberculosis …

Interaction Of Ruthenium Polypyridyl Complexes With Human Telometric Dna, Vienna Tran , '13

Senior Theses, Projects, and Awards

The goal of this thesis work was to explore the interactions between a series of ruthenium complexes and the human telometric DNA sequence. Specifically, this work investigated the ability of [Ru(bpy)₂L]²⁺ and [Ru(phen)₂L]²⁺ complexes to act as G-quadruplex (GQ) stabilizing ligands (bpy = bipyridine, phen = phenanthroline, L = a polypyridyl derivative of dipyridophenazine (dppz)). [Ru(bpy)₂(dppz)]²⁺ and [Ru(phen)₂(dppz)]²⁺ are known to bind to GQ DNA, though not selectively and also to display molecular light switch activity upon interaction with DNA. The ruthenium complexes were studied in this work with several UV-visible and fluorescent techniques to determine the ability of each …

Mass Spectral Imaging For Analysis Of Pharmaceutical Ingredients, Abdul Majid Mohammed

All Student Theses and Dissertations

Mass spectral imaging (MS-imaging) is a modern technique used for the analysis and characterization and distribution of pharmaceutical ingredients , drugs, peptidies, lipids, and other bioactive species in tissue section/ Tissue prints. Although now widely accepted, there remains a host of competing and complementary techniques including DESI, MALDI, SIMS, and DART ionization techniques that allow the researchers to obtain appreciable ion intensities for mapping purposes. Instrumentation further is, rapidly advancing with significant progress in TOF, ion trap, and quadrupole instrumentation for mapping. In this review, I will examine the current status and role of MS-imaging with emphasis on analysis of …

Investigating G-Quadruplex Formation And Its Structural Perturbation By And Interactions With N-Methyl Mesoporphyrin Ix, Steven P. Barrett , '13

Senior Theses, Projects, and Awards

G-quadruplexes (GQs) are noncauonical secondary structures of DNA that can adopt a multitude of different topologies. Here, we explore the factors that drive the formation of these structures and favor the specific topologies they adopt. Our discussion of this topic begins with an investigation of the interactions of N-methyl mesoporphyrin IX (NMM), a small aromatic molecule, with Tel22, a 22-nucleotide DNA sequence that serves as a model for the putative quadruplex formed by the human telomeric repeat sequence. NMM is exceptionally selective for GQ DNA over all other types of nucleic acid secondary structure and specifically prefers the parallel …

Analysis Of Beetle Cuticular Hydrocarbons, Elizabeth A. Williams , '13

Senior Theses, Projects, and Awards

The insect cuticle, commonly known as the exoskeleton, consists of two layers: a bottom layer called the procuticule and a thin outer waxy coating called the epicuticle. The epicuticle contains hydrocarbons that prevent desiccation and are used for chemical communication both inter- and intra- specifically. For some insects, these compounds are important sociochemicals involved in recognizing nestmates and predators as well as identifying the sex of other insects. The established procedure to extract cuticular hydrocarbons is lethal, directly introducing the insects to toxic solvents. The goal of this study is to develop a non-lethal procedure to extract the cuticular hydrocarbons …

Utilizing Enantiopure Planar Chiral Sulfinyl And N-Oxazolidinyl Iron(O) Tricarbonyl Diene Complexes For The Installation Of Adjacent Stereocenters, Alice R. Wong , '13

Senior Theses, Projects, and Awards

Enantiomerically pure planar chiral iron(0) tricarbonyl diene complexes were used as a template for the diastereoselective spiroketalization of four spiroketals. As an additional complication, these substrates contained an additional methyl substituent (both the (R) and (S) configurations) at the C6 position along the B ring of the spiroketal; these substituent effects were examined for both the 2-iodovinyl sulfoxide and l-iodovinyl sulfoxide series. These spiroketalization reactions demonstrated clear "matched"/"mismatched" effects as predicted, affording "matched" spiroketalization diastereomeric ratios of 46:1 and 24:1, and "mismatched" spiroketalization diastereomeric ratios of 10:1 and 9:l. These diastereoselectivities were supported by computational information. As a step away …

Patent: Fusion Proteins For Treating Metabolic Disorders, Brian R. Boettcher, Shari L. Caplan, Douglas S. Daniels, Norio Hamamatsu, Stuart Licht, Stephen Craig Weldon

Chemistry Faculty Publications

The invention relates to the identification of fusion proteins comprising polypeptide and protein variants of fibroblast growth factor 21 (FGF21) with improved pharmaceutical properties. Also disclosed are methods for treating FGF21 associated disorders, including metabolic conditions.

Rapid, Efficient And Versatile Strategies For Functionally Sophisticated Polymers And Nanoparticles: Degradable Polyphosphoesters And Anisotropic Distribution Of Chemical Functionalities, Shiyi Zhang

All Theses and Dissertations (ETDs)

The overall emphasis of this dissertation research included two kinds of asymmetrically-functionalized nanoparticles with anisotropic distributions of chemical functionalities, three degradable polymers synthesized by organocatalyzed ring-opening polymerizations, and two polyphosphoester-based nanoparticle systems for various biomedical applications.

Inspired by the many hierarchical assembly processes that afford complex materials in Nature, the construction of asymmetrically-functionalized nanoparticles with efficient surface chemistries and the directional organization of those building blocks into complex structures have attracted much attention. The first method generated a Janus-faced polymer nanoparticle that presented two orthogonally click-reactive surface chemistries, thiol and azido. This robust method involved reactive functional group transfer by …

Facile Synthesis And Improved Pore Structure Characterization Of Mesoporous Γ-Alumina Catalyst Supports With Tunable Pore Size, Baiyu Huang

Theses and Dissertations

Mesoporous γ-alumina is the most extensively used catalysts support in a wide range of catalytic processes. The usefulness of γ-alumina relies on its favorable combination of physical, textural, thermal, and chemical properties. Pore structure properties are among the most important properties, since high surface area and large pore volume enable higher loading of active catalytic phases, while design of pore size and pore size distribution is critical to optimize pore diffusional transport and product selectivity. In addition, accurate determination of surface area (SA), pore volume (PV) and pore size distribution (PSD) of porous supports, catalysts, and nanomaterials is vital to …

Use Of Self-Assembled Monolayers To Tailor Surface Properties: From Lubrication To Neuronal Development, Natalie Ann Lafranzo

All Theses and Dissertations (ETDs)

The subsequent work describes advances in modifying the chemical properties of various substrates to tailor the surface properties for specific applications. This is achieved by making use of a molecular assembly known as self-assembled monolayers, or SAMs. SAMs are composed of tightly packed organic molecules that form a well-ordered structure on a substrate. Typically, the head group of the monomer is covalently anchored to the substrate, and monolayer order and self-assembly is achieved through van der Waals interactions between the long alkyl chains of the monomer's tail group. Monolayers containing head groups consisting of thiols, siloxanes, and phosphonates have been …

Part I: An Artificial Neural Network Model Of Tuberculosis Patient Data, Part Ii: A Dft Computational Model Of Metal Hydrides, William Orson Griffin

Theses and Dissertations

PART I -- The data of tuberculosis patients and a control group were analyzed with the artificial neural network in order to find genetic factors which inhibit and promote the patient to developing drug resistant tuberculosis. The data came from populations in Kyrgyzstan containing genetic and physical records as well as the type of tuberculosis they had contracted. Three models based on the data were developed: first, a model which differentiates TB from control patients, second, a model which differentiates both TB and control patients, and finally, a model which distinguishes infiltrative from chronic type tuberculosis. Factors which influenced the …

Renewable Resource-Based Magnetic Nanocomposites For Removal And Recovery Of Phosphorous From Contaminated Waters, Sunil Kumar Ramasahayam

Theses and Dissertations

Water pollution by dissolved phosphorous (P) is a serious water related issue being faced by mankind during the past two decades. Several technologies already exist to remove P from contaminated water but each has its own drawbacks. This project provides a novel microwave assisted synthesis of reduced iron oxide containing renewable resource-based media for P removal from contaminated waters. It provides a fast, easy, and economical way to produce reduced iron oxide nanocomposites without requiring the need for hydrogen or inert gas during the transformation. A wide range of other metal/ carbon nanocomposites can also be synthesized using this technology …

Resorcinarene-Based Cavitands: From Structural Design And Synthesis To Separations Applications, Na Li

Theses and Dissertations

Resorcinarenes are cyclic tetramers that are synthesized by the condensation of resorcinol and various aldehydes. The upper and lower rims can be modified with substituents that provide specific selectivity and other chemical features. In this work, resorcinarene-based macrocyclic ligands with specific selectivities have been designed, synthesized and applied to chiral amine discrimination and transition metal ion separations.These resorcinarenes fall into two categories. In the first type, the upper rims of resorcinarenes were modified with amino acid groups, including chiral alanine groups. The lower rims were modified with --CH3, or --C11H23 groups. The structures were studied by nuclear magnetic resonance (NMR), …

Monolayer-Protected Nanoparticle Doped Xerogels As Functional Components Of Amperometric Glucose Biosensors, Michael Hartley Freeman, Jackson R. Hall, Michael C. Leopold

Chemistry Faculty Publications

First-generation amperometric glucose biosensors incorporating alkanethiolate-protected gold nanoparticles, monolayer protected clusters (MPCs), within a xerogel matrix are investigated as model systems for nanomaterial-assisted electrochemical sensing strategies. The xerogel biosensors are comprised of platinum electrodes modified with composite films of (3-mercaptopropyl)trimethoxy silane xerogel embedded with glucose oxidase enzyme, doped with Au225(C6)75 MPCs, and coated with an outer polyurethane layer. Electrochemistry and scanning/transmission electron microscopy, including cross-sectional TEM, show sensor construction, humidity effects on xerogel structure, and successful incorporation of MPCs. Analytical performance of the biosensor scheme with and without MPC doping of the xerogel is determined from direct glucose injection during …

Nanoparticle Film Assemblies As Platforms For Electrochemical Biosensing – Factors Affecting Amperometric Signal Enhancement Of Hydrogen Peroxide, Adrienne R. Schmidt, Natalie D. T. Nguyen, Michael C. Leopold

Chemistry Faculty Publications

Factors affecting the enhanced amperometric signal observed at electrodes modified with polyelectrolyte–gold nanoparticle (Au-NP) composite films, which are potential interfaces for first-generation biosensors, were systematically investigated and optimized for hydrogen peroxide (H2O2) detection. Polyelectrolyte multilayer films embedded with citrate-stabilized gold nanoparticles exhibited high sensitivity toward the oxidation of H2O2. From this Au-NP film assembly, the importance of Au-NP ligand protection, film permeability, the density of Au-NPs within the film, and electronic coupling between Au-NPs (interparticle) and between the film and the electrode (interfacial) were evaluated. Using alternative Au-NPs, including those stabilized with thiols, polymers, and bulky ligands, suggests that the …

Insights Into The Roles Of Desolvation And Π-Electron Interactions During Dna Polymerization, Edward A. Motea, Irene Lee, Anthony J. Berdis

Chemistry Faculty Publications

This report describes the use of several isosteric non-natural nucleotides as probes to evaluate the roles of nucleobase shape, size, solvation energies, and π-electron interactions as forces influencing key kinetic steps of the DNA polymerization cycle. Results are provided using representative high- and low-fidelity DNA polymerases. Results generated with the E. coli Klenow fragment reveal that this high-fidelity polymerase utilizes hydrophobic nucleotide analogues with higher catalytic efficiencies compared to hydrophilic analogues. These data support a major role for nucleobase desolvation during nucleotide selection and insertion. In contrast, the low-fidelity HIV-1 reverse transcriptase discriminates against hydrophobic analogues and only tolerates non-natural …

Use Of Soybean Lecithin In Shape Controlled Synthesis Of Gold Nanoparticles, Benjamin Robert Ayres

Dissertations and Theses

The work presented in this dissertation is a composite of experiments in the growth of gold nanoparticles with specific optical properties of interest. The goal is to synthesize these gold nanoparticles using soybean extract for not only shape control, but for propensity as a biocompatible delivery system. The optical properties of these nanoparticles has found great application in coloring glass during the Roman empire and, over the centuries, has grown into its own research field in applications of nanoparticulate materials. Many of the current functions include use in biological systems as biosensors and therapeutic applications, thus making biocompatibility a necessity. …

Effects Of The Protein Environment On The Spectral Properties Of Tryptophan Radicals In Pseudomonas Aeruginosa Azurin, Caterina Bernini, Tadeusz AndrunióW, Massimo Olivucci, Rebecca Pogni, Riccardo Basosi, Adalgisa Sinicropi

Chemistry Faculty Publications

Many biological electron-transfer reactions involve short-lived tryptophan radicals as key reactive intermediates. While these species are difficult to investigate, the recent photogeneration of a long-lived neutral tryptophan radical in two Pseudomonas aeruginosa azurin mutants (Az48W and ReAz108W) made it possible to characterize the electronic, vibrational, and magnetic properties of such species and their sensitivity to the molecular environment. Indeed, in Az48W the radical is embedded in the hydrophobic core while, in ReAz108W it is solvent-exposed. Here we use density functional theory and multiconfigurational perturbation theory to construct quantum-mechanics/molecular-mechanics models of Az48W* and ReAz108W* capable of reproducing specific features of their …

Oxidation Of Adenosine And Inosine: The Chemistry Of 8-Oxo-7,8-Dihydropurines, Purine Iminoquinones, And Purine Quinones As Observed By Ultrafast Spectroscopy, Denis I. Nilov, Dmitry Y. Komarov, Maxim S. Panov, Kanykey E. Karabaeva, Andrey S. Mereshchenko, Alexander N. Tarnovsky, R. Marshall Wilson

Chemistry Faculty Publications

Oxidative damage to purine nucleic acid bases proceeds through quinoidal intermediates derived from their corresponding 8-oxo-7,8-dihydropurine bases. Oxidation studies of 8-oxo-7,8-dihyroadenosine and 8-oxo-7,8-dihydroinosine indicate that these quinoidal species can produce stable cross links with a wide variety of nucleophiles in the 2-positions of the purines. An azide precursor for the adenosine iminoquinone has been synthesized and applied in ultrafast transient absorption spectroscopic studies. Thus, the adenosine iminoquinone can be observed directly, and its susceptibility to nudeophilic attack with various nucleophiles as well as the stability of the resulting cross linked species have been evaluated Finally, these observations indicate that this …

Site-Specific Inter-Strand Cross-Links Of Dna Duplexes, Miao Ye, Johan Guillame, Yu Liu, Ruojie Sha, Risheng Wang, Nadrian C. Seeman, James W. Canary

Chemistry Faculty Research & Creative Works

We report the development of technology that allows inter-strand coupling across various positions within one turn of DNA. Four 2'-modified nucleotides were synthesized as protected phosphoramidites and incorporated into DNA oligonucleotides. The modified nucleotides contain either 5-atom or 16-atom linker components, with either amine or carboxylic acid functional groups at their termini, forming 10 or 32 atom (11 or 33 bond) linkages. Chemical coupling of the amine and carboxylate groups in designed strands resulted in the formation of an amide bond. Coupling efficiency as a function of trajectory distance between the individual linker components was examined. For those nucleotides capable …

Kinetic And Spectroscopic Studies Of Bicupin Oxalate Oxidase And Putative Active Site Mutants, Ellen W. Moomaw, Eric Hoffer, Patricia Moussatche, John C. Salerno

Faculty Articles

Ceriporiopsis subvermispora oxalate oxidase (CsOxOx) is the first bicupin enzyme identified that catalyzes manganese-dependent oxidation of oxalate. In previous work, we have shown that the dominant contribution to catalysis comes from the monoprotonated form of oxalate binding to a form of the enzyme in which an active site carboxylic acid residue must be unprotonated. CsOxOx shares greatest sequence homology with bicupin microbial oxalate decarboxylases (OxDC) and the 241-244DASN region of the N-terminal Mn binding domain of CsOxOx is analogous to the lid region of OxDC that has been shown to determine reaction specificity. We have prepared a series of CsOxOx …

Iapp Aggregation And Cellular Toxicity Are Inhibited By 1,2,3,4,6-Penta-O-Galloyl-Β-D-Glucose, Edward Bruno, Catalina Pereira, Karla P. Roman, Marisa Takiguchi, Pei-Yu Kao, Luiza A. Nogaj, David A. Moffet

Chemistry and Biochemistry Faculty Works

The polyphenol, 1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG) has been found to exhibit a host of positive pharmacologic activities, including anti-cancer and anti-diabetic. Little is known about the mode of action of PGG in yielding these positive activities. We show here that PGG is a potent inhibitor of IAPP (islet amyloid polypeptide, amylin) aggregation. Preventing the initial aggregation event of IAPP is one strategy for slowing, and possibly preventing, the toxic effects of IAPP oligomeric intermediates. Equal molar ratios of PGG to IAPP substantially reduced the ability of IAPP to bind thioflavin T. Atomic force microscopy revealed that PGG prevented amyloid-based fiber formation under …

Affinity Monolith Chromatography: A Review Of Principles And Recent Analytical Applications, Erika L. Pfaunmiller, Marie Laura Paulemond, Courtney M. Dupper, David S. Hage

David Hage Publications

Affinity monolith chromatography (AMC) is a type of liquid chromatography that uses a monolithic support and a biologically-related binding agent as a stationary phase. AMC is a powerful method for the selective separation, analysis or studies of specific target compounds in a sample. This review discusses the basic principles of AMC and recent developments or applications of this method, with particular emphasis being given to work that has appeared in the last five years. Various materials that have been used to prepare columns for AMC are examined, including organic monoliths, silica monoliths, agarose monoliths and cryogels. These supports have been …

Rearrangement Of Cyclotriveratrylene (Ctv) Diketone: 9,10-Diarylanthracenes With Oled Applications, Samuel R. Sarsah, Marlon R. Lutz Jr., Matthias Zeller, David S. Crumrine, Daniel Becker

Chemistry: Faculty Publications and Other Works

Electroluminescent 9,10-diaryl anthracenes have been shown to be promising host and hole-transporting materials in organic electroluminescence due to their high thermal stability, electrochemical reversibility, and wide band gap useful for organic light-emitting diodes (OLEDs), especially blue OLEDs. Oxidation of cyclotriveratrylene (CTV) to the corresponding diketone and subsequent bromination resulted in an unexpected rearrangement to a highly functionalized 9-aryl-10-bromoanthracene derivative, which was employed in Suzuki couplings to synthesize a series of 9,10-diaryl compounds that are structural analogues of anthracene derivatives used in the preparation of OLEDs but are more highly functionalized, including electron-donating methoxy groups in addition to substitution by a …