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Julia-Kocienski Approach To 4-Substituted 1- Alkenyl-1h-1,2,3-Triazoles, Kunga Tsetan

Dissertations and Theses

A modular approach to the synthesis of 4-substituted N-vinyltriazoles was
developed. The triazole cores were assembled by copper-catalyzed 1,3-dipolar
cycloaddition of 1-phenyl-1H-tetrazol-5-yl (PT) azidomethyl sulfide with: pmethoxyphenyl, 2-pyridyl, and triisopropylsilyl alkynes. Subsequent oxidation of the sulfides furnished 4-substituted triazoles with a Julia-Kocienski olefination handle attached at the N1 atom of the triazole. Olefination reactions of triazole-derived Julia-Kocienski reagents with paraformaldehyde gave 1-ethenyl-1H-1,2,3-triazoles. Heck reactions of these products with phenyl or p-methoxyphenyl iodide led to further functionalization of the terminal carbon, with E/Z-olefin ratios ≥ 92%. Heck reaction with p-cyanophenyl iodide gave low conversion, and that with 2-thienyl iodide did not …

Quantitative Model For Rationalizing Solvent Effect In Noncovalent Ch-Aryl Interactions, Bright C. Emenike, Sara N. Bey, Brianna C. Bigelow, Srinivas V.S. Chakravartula

Publications and Research

The strength of CH–aryl interactions (ΔG) in 14 solvents was determined via the conformational analysis of a molecular torsion balance. The molecular balance adopted folded and unfolded conformers in which the ratio of the conformers in solution provided a quantitative measure of ΔG as a function of solvation. While a single empirical solvent parameter based on solvent polarity failed to explain solvent effect in the molecular balance, it is shown that these ΔG values can be correlated through a multiparameter linear solvation energy relationship (LSER) using the equation introduced by Kamlet and Taft. The resulting LSER …

Biolabeling Through The Use Of Water-Soluble Colloidal Quantum Dots, Cody Stombaugh

Honors Projects

Nanomaterials continues to be a growing field of study due to their wide range of potential applications. Quantum dots are artificially synthesized crystalline clusters of atoms able to confine electron motion as a result of their incredibly small size. Recently, medical applications of nanomaterials have expanded greatly. Quantum dots are ideal for biolabeling due to their rather narrow photoluminescence emission peaks. By synthesizing quantum dots of a specific diameter, it is possible to predetermine the peak photoluminescence wavelength of a sample. Through ligand exchange and immunoconjugation of the quantum dots with proteins, it is possible to use the quantum dots …

Functionalized Bodipy Dyes For Dye-Sensitized Solar Cells, Mahmoud A. Elkhalifa

Masters Theses

It is predicted that more than 20 terawatts of carbon-free energy will be demanded by 2050 to maintain a sufficient energy supply for the increasing global population, and photovoltaics are predicted to contribute significantly to the global energy needs. Dye-sensitized solar cells (DSCs) are an emerging class of photovoltaics (PV) that has produced promising power conversion efficiencies at low costs. Currently, electron recombination, dye aggregation, weak adsorption, and inefficient absorbance are among of the largest contributors to low DSC efficiencies.

BODIPY dyes are one of the most promising classes of dyes emerging for DSC application. These low molecular weight fluorophores …

Theoretical-Experimental Study Of The Two-Photon Circular Dichroism Of Helicenes And Aromatic Amino Acids In The Uv Region: From The Structure-Property Relationship To The Final Implementation, Yuly Katherine Vesga Prada

Electronic Theses and Dissertations

Two-photon circular dichroism (TPCD) has been recognized for its exceptional spectroscopic ability for the structural and conformational analysis of chiral systems due to its high sensitivity to small peptide structural distortions. In 2008, Hernandez and co-workers demonstrated TPCD experimentally by the development of the Double L-scan technique. Since then, we have been working on a systematic theoretical-experimental study of chiral molecules using TPCD. In this dissertation, I present my contribution to the continuation to the study of the structure-property relationship of TPCD in molecules with axial chirality in solution, as well as the implementation of the TPCD measurements in the …

Multidimensional Room-Temperature Fluorescence Microscopy For The Nondestructive Analysis Of Forensic Trace Textile Fibers, Nirvani Mujumdar

Electronic Theses and Dissertations

The purpose of this dissertation is to advance nondestructive methodology for forensic fiber examination. Non-destructive techniques that can either discriminate between similar fibers or match a known to a questioned fiber – and still preserve the physical integrity of the fibers for further court examination - are highly valuable in forensic science. A challenging aspect of forensic fiber examinations involves the comparison of fibers colored with visually indistinguishable dyestuffs. This is not an uncommon situation, as there are numerous indistinguishable fibers pre-dyed with commercial dyes of virtually identical colors. Minimal chemical structural variations are actually encouraged by the dye patent …

Small Molecule Proteostasis Regulators That Reprogram The Er To Reduce Extracellular Protein Aggregation, L. Plate, Christina B. Cooley, J. J. Chen, R. J. Paxman, C. M. Gallagher, F. Madoux, J. C. Genereux, W. Dobbs, D. Garza, T. P. Spicer, L. Scampavia, S. J. Brown, H. Rosen, E. T. Powers, P. Hodder, R. L. Wiseman, J. W. Kelly

Chemistry Faculty Research

Imbalances in endoplasmic reticulum (ER) proteostasis are associated with etiologically-diverse degenerative diseases linked to excessive extracellular protein misfolding and aggregation. Reprogramming of the ER proteostasis environment through genetic activation of the Unfolded Protein Response (UPR)-associated transcription factor ATF6 attenuates secretion and extracellular aggregation of amyloidogenic proteins. Here, we employed a screening approach that included complementary arm-specific UPR reporters and medium-throughput transcriptional profiling to identify non-toxic small molecules that phenocopy the ATF6-mediated reprogramming of the ER proteostasis environment. The ER reprogramming afforded by our molecules requires activation of endogenous ATF6 and occurs independent of global ER stress. Furthermore, our molecules phenocopy …

Fabricating Superhydrophobic And Superoleophobic Surfaces With Multiscale Roughness Using Airbrush And Electrospray, Karam N. Almilaji

Theses and Dissertations

Examples of superhydrophobic surfaces found in nature such as self-cleaning property of lotus leaf and walking on water ability of water strider have led to an extensive investigation in this area over the past few decades. When a water droplet rests on a textured surface, it may either form a liquid-solid-vapor composite interface by which the liquid droplet partially sits on air pockets or it may wet the surface in which the water replaces the trapped air depending on the surface roughness and the surface chemistry. Super water repellent surfaces have numerous applications in our daily life such as drag …

Continuous Stationary Phase Gradients For Planar And Column Chromatography, Veeren Dewoolkar

Theses and Dissertations

Surfaces that exhibit a gradual change in their chemical and/or physical properties are termed as surface gradients. Based on the changes in properties they are classified either as physical or chemical gradients. Chemical gradients show variations in properties like polarity, charge, functionality concentration and have found potential applications in fields of biology, physics, biosensing, catalysis and separation science. In this dissertation, surface gradients have been prepared using controlled rate infusion (CRI).

CRI is a simple method in which a surface gradient is formed by carrying out the infusion of organoalkoxysilane in a time-dependent fashion using a set infusion rate. Depending …

Towards An Understanding Of The Role Of Cation Packaging On Dna Protection From Oxidative Damage, Cody E. Gay

Theses and Dissertations--Chemistry

In sperm chromatin, DNA exists in a highly condensed state reaching a final volume roughly twenty times that of a somatic nucleus. For the vast majority (>90%) of sperm DNA in mammals, somatic-like histones are first replaced by transition proteins which in turn are replaced by arginine-rich protamines. This near crystalline organization of the DNA in mature sperm is thought crucial for both the transport and protection of genetic information since all DNA repair mechanisms are shut down. Recent studies show that increased DNA damage is linked to dysfunctions in replacing histones with protamines resulting in mispackaged DNA. This …

Towards An Understanding Of Pharmacologically Induced Intracellular Changes In Nicotinic Acetylcholine Receptors: A Fluorescence Microscopy Approach, Ashley M. Loe

Theses and Dissertations--Chemistry

Upregulation of nicotinic acetylcholine receptors (nAChRs) is a well-documented response to chronic nicotine exposure. Nicotinic acetylcholine receptors are pentameric ligand-gated ion channels consisting of alpha (α2-10) and beta (β2-4) subunits. Nicotine, an agonist of nAChRs, alters trafficking and assembly of some subtypes of nAChRs, leading to an increase in expression of high sensitivity receptors on the plasma membrane. These physiological changes in nAChRs are believed to contribute to nicotine addiction, although the mechanism of these processes has not been resolved. Recently, many studies have converged on the idea that nicotine induces upregulation by an intracellular mechanism. In this dissertation, expression …

Organometallic Materials: Ferroceno[C]Thiophenes And 1,2-Bisthienylmetallocenes, Surya R. Banks

Theses and Dissertations--Chemistry

Development of synthetic routes toward two general organometallic frameworks was undertaken. The first project involved synthetic attempts of substituted and unsubstituted ferroceno[c]thiophene while the second one was the synthesis of 1,2-dithienylmetallocenes. The long-term goal of this work is to lay the foundations for study of electronic, electrochromic, redox, and optical properties of thiophene-based materials integrated with organometallic systems such as ferrocene, ruthenocene and cymantrene. The synthetic pathway for the target molecule in the first project involved converting 1,2-bis(hydroxymethyl)ferrocene to 1,2-bis(thiouroniummethyl)ferrocene with thiourea under acidic conditions. Refluxing the salt in base followed by acidification resulted in 1,2-bis(mercaptomethyl)ferrocene, which is …

Design, Synthesis And Physicochemical Analysis Of Ruthenium(Ii) Polypyridyl Complexes For Application In Phototherapy And Nucleic Acid Sensing, Erin Melissa Wachter

Theses and Dissertations--Chemistry

Current chemotherapeutics exhibit debilitating side effects as a result of their toxicity to healthy tissues. Reducing these side effects by developing chemotherapeutics with selectivity for cancer cells is an active area of research. Phototherapy is one promising modality for selective treatment, where drug molecules are “turned on” when irradiated with light, reducing damage to healthy tissues by spatially restricting the areas exposed to irradiation. A second approach to improve selectivity is to exploit the differences in cancerous versus healthy cells, such as increased metabolism and/or upregulation of cell surface receptors. Ruthenium(II) polypyridyl complexes are candidates for phototherapy due to their …

Towards Catalytic Oxidative Depolymerization Of Lignin, Justin K. Mobley

Theses and Dissertations--Chemistry

Lignin is one of the most abundant and underutilized biopolymers on earth. Primarily composed on three monolignol units (sinapyl, coniferyl, and p-coumaryl alcohol), lignin is formed through a radical pathway resulting in an assortment of linkages, of which the β-O-4 linkage is the most prevalent (up to 60% in some hardwood species). In planta, lignin plays an important role in water transport and in protecting plants from chemical and biological attack. Traditional attempts to depolymerize lignin have focused on the cleavage of β-O-4 linkages via thermal or reductive routes. However these pathways lead to low-value, unstable product mixtures. Moreover, …

The Development Of Colorimetric Assays To Determine The Identity And Frequency Of Specific Nucleobases In Dna Oligomers, Elizabeth Marie Thomas

Theses and Dissertations--Chemistry

Colorimetric methods combined with color-changing chemical probes are widely used as simple yet effective tools for identifying and quantifying a wide variety of molecules in solution. For nucleic acids (DNA and RNA), perhaps the most commonly used colorimetric probe is potassium permanganate, which can be used to identify single-stranded pyrimidines (thymine and cytosine) in polymers. Unfortunately, permanganate is not an effective probe for identifying purines (adenine and guanine), especially in the presence of the more reactive pyrimidines. Therefore, robust methods for discriminating between the purines remain elusive, thereby creating a barrier toward developing more complex colorimetric applications. In this dissertation, …

The Synthesis Of Substituted Pentadentate Ligand Scaffolds And Their Future Application In Ruthenium-Catalyzed Water Oxidation, Manpreet Singh

Honors Theses

Rising global energy demands coupled with depleting natural resources have led to a strong emphasis on finding new sources of energy that are renewable and which limit the negative impact on the environment. One of the strongest candidates is utilizing solar energy to drive water oxidation to produce hydrogen as a fuel source. In order to do this, a better understanding of the mechanism involved in this process must be revealed. Homogenous molecular catalysts allow mechanistic studies and can be also used in Photoelectrochemical Cells (PECs) and other systems to produce chemical fuels. In this work, the new syntheses of …

The Evolution Of The Sugarcoated American Food Market And The Paradox Of Artificial Sweeteners, Mary Moses Hitt

Honors Theses

Living in present-day America makes it hard to imagine an era when sugar was not as inexpensive and readily available as it is now. It is in little colorful packets on restaurant tables, filled to the brim in jars at coffee shops, or mixed into candy products located at the beginning of every cash register. Today, sugar is one of, if not, the most widely consumed food products in the world, but our love for sugar is nothing new. Humans have been experiencing the bliss triggered by sweet-tasting foods since their earliest diets, which included fruits and honey. Our diets …

Nucleophile Promoted Gold Redox Catalysis With Diazonium: Cbr, C-S And C-P Bond Formation Through Catalytic Sandmeyer Coupling, Haihui Peng, Rong Cai, Chang Xu, Hao Chen, Xiaodong Shi

Faculty & Staff Scholarship

Gold-catalyzed C-heteroatom (C-X) coupling reactions are evaluated without using sacrificial oxidants. Vital to the success of this methodology is the nucleophile-assisted activation of aryldiazonium salts, which could be an effective oxidant to convert Au(I) to Au(III) even without the addition of assisting ligand or photocatalyst. By accelerating reaction kinetics to outcompete C-C homo-coupling or diazonium dediazoniation, gold-catalyzed Sandmeyer reactions were achieved with different nucleophiles, forming C-Br, C-S and C-P bonds in high yields and selectivity.

Echo Behavior In Large Populations Of Chemical Oscillators, Tianran Chen, Mark R. Tinsley, Edward Ott, Kenneth Showalter

Faculty & Staff Scholarship

Experimental and theoretical studies are reported, for the first time, on the observation and characterization of echo phenomena in oscillatory chemical reactions. Populations of uncoupled and coupled oscillators are globally perturbed. The macroscopic response to this perturbation dies out with time: At some time τ after the perturbation (where τ is long enough that the response has died out), the system is again perturbed, and the initial response to this second perturbation again dies out. Echoes can potentially appear as responses that arise at 2τ,3τ,... after the first perturbation. The phase-resetting character of the chemical oscillators allows a detailed analysis, …

Study Of An Active-State Cb1 Receptor Model And Jwh Compound Interactions To Predict New Emerging Synthetic Cannabinoids, Kelsey Leigh Pettus

Honors Theses

In recent years, a new class of compounds, called synthetic cannabinoids, have made their appearance in the market as a substitute for illegal marijuana or its constituent natural cannabinoids. These compounds, which are active at the same G- protein coupled receptors (GPCRS) as cannabinoids, are continuing to gain popularity because of the same cannabinoid-like effects they create. Though two cannabinoid receptors have been identified in humans, known as CB1 and CB2, synthetic cannabinoid activity at the CB1 receptor has been the focus of much research regarding synthetic cannabinoid ligand binding. In this study, the structure of the CB1 receptor is …

Optimization Of Rgd Containing Cyclic Peptides Against Αvβ3 Integrin, Yan Wang, Wenwu Xiao, Yonghong Zhang, Leah Meza, Harry Tseng, Yoshikazu Takada, James B. Ames, Kit S. Lam

School of Integrative Biological & Chemical Sciences (Formerly Dept. of Chemistry)

We have previously reported the use of one-bead-one-compound (OBOC) combinatorial technology to develop a disulfide cyclic, Arg-Gly-Asp containing octapeptide LXW7 (cGRGDdvc), that targets αvβ3 integrin with high affinity and specificity (Mol Cancer Ther, 9:2714–23, 2010). αvβ3 integrin is known to be over-expressed in many cancers and in tumor vasculature, and it has been established as a cancer therapeutic target. To further optimize LXW7, we have performed systematic structure activity relationship (SAR) studies. Based on the results, two highly focused OBOC peptide libraries were designed, synthesized and screened against αvβ3 integrin transfected K562 cells. One of the best …

Investigating Cross Talk Between The High And Low Iron Sensors In Saccharomyces Cerevisiae, John S. Hepburn

Theses and Dissertations

Iron is essential for nearly all life on earth. Cells must maintain sufficient levels of this important nutrient due its function as a central co-factor for many cellular processes. Although iron is extremely plentiful, its poor solubility requires specialized import. On the other side, too much iron inside the cell can lead to the generation of reactive oxygen species (ROS), which have deleterious effects on many cellular functions and have been implicated in a wide variety of diseases such as cancer and Alzheimer’s disease. Using the model eukaryote Saccharomyces cerevisiae, or budding yeast, our research group has accomplished much in …

Development Of Reactions And Methods For Labeling Biomolecules In Cells, Enoch Agbesi Adogla

Theses and Dissertations

The complexity of cellular environments presents a challenge to efforts at studying and elucidating biomolecules in cells. Covalent ligation of biomolecules with fluorescent molecules that have a reactive functional group that can react with a complementary functional group on biomolecules is one way that has been utilized to study biomolecules. It enables visualization and tracking of ligation and transportation of molecules within the cell. However, the myriad of functional groups within the cell makes achieving selectivity difficult. To circumvent this problem, reactions that do not interfere with biology have been developed. These reactions, referred to as bioorthogonal reactions must be …

The Development Of A Miniature Spatial Heterodyne Raman Spectrometer For Applications In Planetary Exploration And Other Extreme Environments, Patrick Doyle Barnett

Theses and Dissertations

Space exploration is arguably one of the most important endeavors our species has ever undertaken. Rapid advances in rocketry and robotics in recent years has allowed for positioning of complex scientific instruments on other planets with a precision that was previously thought impossible. This, along with the need for more sophisticated chemical measurements to achieve the goals of new, more ambitious missions and recent advances in in-situ and remote spectroscopic techniques, has led to a boom in the use of spectroscopic instruments for space exploration. However, future missions to the moons of Jupiter and Saturn, along with other planetary bodies …

Using Synthetic Lectins To Investigate Metastatic Potential In Colon Cancer, Erin E. Gatrone

Theses and Dissertations

Cancer is a disease that affects millions of people each year and it is well established that early diagnosis is a key factor towards improving survival rate, with that in mind there is a great need for better diagnostics. From the earliest onset of cancer, changes can be detected in the type and amount of carbohydrates expressed by the cancer cells, i.e., aberrant glycosylation. This process results in differing glycosylation patterns that can be used to detect cancer. Aberrant glycosylation can also greatly affect the potential of cancer cells to metastasize and can be used to stage the disease as …

Development Of Folate Directed, Protein Based Photodynamic Therapy Agents, Rojenia Jones

Dissertations

To attack cancer cells in a specific manner, we have developed a folate-targeted, photodynamic therapy (PDT) agent. The folate (FA) and the chlorin e6 (Ce6) photosensitizer were attached to bovine serum albumin (BSA) using carbodiimide chemistry. Since over 50% of cancers overexpress folate receptors, FA-BSA-Ce6 can be taken up by them and is an effective PDT agent. Hela cells exposed to FA-BSA-Ce6 in the dark showed no cytotoxicity. Upon exposure to light, the conjugate was dose (time and concentration) dependent. Concentrations less than or equal to 2 µM were not effective at killing Hela cells but concentrations of at 5 …

Development Of Protein-Polymer Core-Shell Nanoparticles (Ppcs-Nps) As Efficient Vehicles To Deliver Therapeutic Agents Across Blood Brain Barrier (Bbb), Napat Tandikul

Theses and Dissertations

Blood Brain Barrier (BBB) plays a main role as selective barrier which controls and limits access of chemicals, molecules and therapeutic agents from blood to brain. The BBB endothelial cells are connected by Tight Junctions (TJs) which close intracellular spaces between the endothelial cells and block the free diffusion of substances, therefore many potential drugs for treating human brain diseases cannot reach the brain in sufficient concentration. Recently, many studies have thrown an interest in development of nanoparticles for delivering drugs and imaging agents across BBB. Our research group has developed protein-polymer core-shell nanoparticles (PPCS-NPs) which demonstrate great potential for …

Physical Property Control In Core/Shell Inorganic Nanostructures For Fluorescence And Magnetic Targeting Applications, Stephen K. Roberts

Theses and Dissertations

Nanomaterials show immense promise for the future in numerous areas of application. Properties that are unique from the bulk material and are tunable allow for innovation in material design. This thesis will focus on controlling the physical properties of core/shell nanostructures to enhance the utility of the materials.

The first focus is on the impact of different solvent mixtures during the shell growth phase of SILAR based core/shell quantum dot synthesis is studied. Gaining insight into the mechanism for SILAR growth of core/shell nanoparticles allows improved synthetic yields and precursor binding, providing enhanced control to synthesis of core/shell nanoparticles. The …

Building And Optimizing A Spectroelectrochemical System For The Study Of Shewanella Putrefaciens, Jonathan Muscolino

Master's Theses

Shewanellaceae are among the most widely studied electroactive microorganisms. This study reports on Shewanella putrefaciens under anaerobic conditions during applied potential while monitored by spectroscopy. The attachment of the microbe Shewanella putrefaciens onto an indium tin oxide electrode was found to occur after 2 hr of +0.2 V applied potential. Microbial detachment occurred with a 5 mV/s scan rate cyclic voltammogram from +0.2 V to -0.5 V to +0.2 V. This was confirmed through use of a spectroelectrochemical apparatus utilizing a standard 3 electrode setup with evanescent wave spectroscopy.

Probing Allosteric, Partial Inhibition Of Thrombin Using Novel Anticoagulants, Stephen S. Verespy Iii

Theses and Dissertations

Thrombin is the key protease that regulates hemostasis; the delicate balance between procoagulation and anticoagulation of blood. In clotting disorders, like deep vein thrombosis or pulmonary embolism, procoagulation is up-regulated, but propagation of clotting can be inhibited with drugs targeting the proteases involved, like thrombin. Such drugs however, have serious side effects (e.g., excessive bleeding) and some require monitoring during the course of treatment. The reason for these side effects is the mechanism by which the drugs’ act. The two major mechanisms are direct orthosteric and indirect allosteric inhibition, which will completely abolish the protease’s activity. Herein we sought an …