Physical Sciences and Mathematics Commons^™

Synthetic Investigations In Chemical Probe Development Part 1: Design And Synthesis Of Novel Triton X-405 Adenosine Conjugates; Part 2: Synthesis Of 2,8-Dihydroxychrysene, Rachel Irene Hammond

Honors Theses

Although not drugs themselves, chemical probes are a necessary tool in biomedical research for the interrogation of biological systems. In the present synthetic investigation, two chemical probes were developed – a Triton X-405 adenosine conjugate (TX-405A) and 2,8-dihydroxychrysene. The designed TX-405A conjugate was generated in four steps through tosylation and amination of TX-405 such that EDC-coupling of TX-amine with 2’,3’-Isopropylidene adenosine-5’-carboxylic acid afforded TX-405A following acetonide deprotection. The development of TX-405A represents the first report of the synthesis and utilization of a detergent-linked dosimeter. The synthesis of 2,8-dihydroxychrysene provided an in-depth exploration on the unique reactivity of chrysene. The desired …

Fast Photochemical Oxidation And Footprinting Of Proteins Via Trifluoromethyl Radical Chemistry, Elaine Morrow

Honors Theses

Fast photochemical oxidation of proteins (FPOP) is a useful tool in proteomics because of the ability for modifications to occur on the scale of microseconds which reduces the modifications to tertiary and quaternary structure allowing for more accurate labeling of the protein. Labels for FPOP are generated from various radicals in our experiments which include hydroxyl radicals and trifluoromethyl radicals. Hydroxyl radicals are easily generated by using an excimer laser (KrF laser, 248 nm) or a UV flash lamp (as a part of the Fox™ System) by the photolysis of hydrogen peroxide. Trifluoromethyl radicals, however, need hydroxyl radicals to be …

One-Pot Synthesis Of Disubstituted Primary Amines From Nitriles Via Grignard Addition And Metal-Alcohol Reduction, Joshua Peltan

Honors Theses

The process of developing a working base case procedure for a novel one-pot-two-step synthesis of primary amines from Grignard reagents, nitriles, sodium metal or alkali metal loaded silica gel, and alcohol is described. Initial steps towards applying the process broadly are detailed. The process has the potential to be an affordable, convenient, safer, greener, and more accessible alternative to exiting methods of accomplishing the same transformation. The reaction scheme has been proven to provide yields and purity comparable to existing methods for certain pairs of substrates; however, its utility as a general-purpose method for transforming arbitrary pairs of Grignard reagent …

Applications Of Sodium Azide In The Synthesis Of Tetrazines And Hydrolysis Reactions, My Le

Honors Theses

The inverse electron demand Diels−Alder cycloadditions of heterocyclic azadienes have provided a robust methodology for synthesizing highly substituted and functionalized heterocycles. It is widely used in organic synthesis and the pharmaceutical industry in the divergent construction of screening libraries and bioorthogonal conjugation. Each heterocyclic azadiene was found to possess a unique reactivity toward different classes of dienophiles, display predictable modes of cycloaddition, and exhibit substantial substituent electronic effects impacting their intrinsic reactivity and cycloaddition regioselectivity. Synthesis of 1,2,4,5-tetrazine has been reported in the literature since the late 19th century, showing scientists' tremendous interest in its application.

Herein we attempt to …

Effects Of Halogen Bonding On 13c Nmr Shifts Of Various Tolan Species, Anthony Lybrand

Honors Theses

Halogen bonding is slowly becoming a more and more useful part of the world of chemistry and is beginning to be incorporated into various aspects of the chemical industry. This study’s purpose is to determine whether or not halogen bonding can cause any effect in the 13C NMR shifts. The specific purpose of this study is to determine whether these chemical shifts change when a Lewis Base is added to the dissolved sample. In order to do this, the tolan species (4-iodotolan and 4-chlorotolan) had to be synthesized. Once synthesized, the tolan species were analyzed via NMR. NMR data indicated …

End Group Modification Of Linear Dendritic Block Copolymers (Ldbcs), Chinwe Udemgba

Honors Theses

Linear dendritic block copolymers are amphiphilic molecules that consist of a dendritic hydrophilic portion and a linear hydrophobic portion. Its unique ability to self-assemble into spherical nanoaggregates while having the potential to uptake and transport both hydrophilic and hydrophobic drugs makes these polymers an item of interest in regard to the drug delivery field. The synthesis of polyamidoamine-polylactide linear dendritic block copolymers was designed to address the common issues in drug delivery systems, including problems in permeability, solubility, stability, specificity, and retention. Though this linear dendritic block copolymer has previously been synthesized in our lab with cationic amine surface functionalities, …

Synthesis Of A Dd-Π-Aa Organic Dye For Dye-Sensitized Solar Cells, Hope Lovell

Honors Theses

This project investigates the synthesis of a DD-π-AA (dual donor/dual acceptor) organic dye as a potential sensitizer for dye-sensitized solar cells (DSCs). The design of this dye was based off previous research that found dual donor/dual acceptor dyes exhibited promising results when used in a DSC. The donor groups, acceptor groups, and π-bridge were chosen for their stability, ability to absorb in the near-infrared (NIR) region, and intramolecular charge transfer (ICT) abilities.

While many components of the dye were synthesized, the final stages of the synthetic scheme were not completed due to the loss of time from COVID-19. Had the …

Preparation Of Perylene Bisimide Acceptors With Ethylcarboxyl And Pyrenylcyclohexyl Imide Groups, Michael Cashen Stark

Honors Theses

Multiple attempts were made to deprotect TBDMS-protected (tert-butyldimethylsilyl protected) serinol and swallowtailed PBI (Compound 2), synthesized by past researcher Tarrah Frederick, to generate Compound 1. The theoretical Compound 1 product is intended for use in molecular rectification of electricity because the perylene core acts as a good acceptor with high electron affinity, and it does not require an electron donor group. Many rectification molecules are amphiphilic Donor-σ-Acceptor compounds, which allow for electron transfer through localized molecular orbitals when placed between electrodes (Langmuir-Blodgett Method). However, PBIs can transfer electrons from one electrode, through the LUMO of perylene, and to the other …

Indolizine Donor-Based Dyes For Applications In Fluorescence Biological Imaging, William Meador

Honors Theses

NIR emissive fluorophores are intensely researched due to their potential to replace modern imaging procedures. Many molecular strategies have been employed in the literature to optimize fluorophores for deeper NIR absorption and emission, biocompatibility, and higher fluorescence quantum yields. Amongst the fluorophores studied to date, proaromatic indolizine donors are attractive alternatives to traditional alkyl amine and indoline based donors due to their 1) lower energy absorption and emission facilitated by proaromaticity, 2) large Stokes shifts due to increased dihedral angles about the π-system, 3) ease of functionalization and capacity for bioconjugation at the phenyl ring, and 4) potential for further …

Synthesis And Characterization Of Transition Metal Scorpionate Complexes For Redox Shuttle Applications In Dye-Sensitized Solar Cells, Chase Lance

Honors Theses

Given the rising global energy demands, alternative renewable energy sources are currently being investigated. The most appealing renewable energy source is solar energy, and dye-sensitized solar cells (DSSCs) in particular are an attractive technology. DSSCs have traditionally utilized iodide/triiodide as the redox mediator couple, which exhibits high efficiencies and fast regeneration of the oxidized dye with little recombination. Recently, the use of alternative redox couples based on transition metal complexes has been studied as a promising substitute due to the tunable design of these complexes. In this study, tridentate tris(pyrazolyl)borate and tris(pyrazolyl)methane ligands with first-row transition metals were designed and …

Synthesis Of Fluorinated Pyrazoles Via Intra- And Intermolecular Cyclization Reactions, Matthew Saucier

Honors Theses

Pyrazole-based pharmaceuticals treat a wide array of diseases and conditions including obesity, diabetes, cancer, microbial and viral infections, pain and inflammation, and many neurological disorders. Syntheses for this biologically significant substrate have been well developed, but current methods to afford fluorinated pyrazoles are limited by variability and selectivity. By 2013, over 25% of all drugs available on the market contained the element fluorine due to its unique characteristics leading to improved target protein binding, bioavailability, and metabolic stability. In order to harness these pharmaceutical benefits of fluorine and overcome its difficulty in handling and stability, we set out to develop …

Silver-Catalyzed Synthesis Of Disubstituted Fluorinated Isoxazoles, Micah Stewart

Honors Theses

The presence of fluorine can provide organic compounds with useful biological properties, such as increased metabolic stability and drug uptake. Because of these advantages, fluorinated compounds make up about 30% of the drug industry. However, fluorination of complex molecules is difficult due to fluorine’s high electronegativity.

Fluorinated isoxazoles are of particular interest in the pharmaceutical industry. Isoxazoles are five-membered heterocycles with oxygen and nitrogen in the 1, 2 positions that are able to engage in interactions unavailable to other ring structures, conferring advantageous biological properties upon compounds containing them. However, there are limited synthetic routes for fluorinated isoxazoles, and those …

A Study To Regioselectively Access Fluorinated Triazoles And Isoxazoles, Sweta Adhikari

Electronic Theses and Dissertations

The objective of the thesis is to develop regioselective methods for mono-fluorination of disubstituted triazoles, both 1,4- and 1,5-regioisomer, and isoxazoles. These strategies focus on one-pot direct access to final mono-fluorinated triazoles and isoxazoles. Eventually, these fluorinated substrates will be screened against various biological targets. Similarly, the optimization study of a regioselective method to generate 5-fluoro-1,4-disubstituted triazole was conducted. This reaction also utilized 1,3-dipolar cycloaddition to synthesize fluorinated triazole. However, difluoroalkene was used as a synthetic equivalent of fluoroalkyne for this method. This resulted into the inversion of polarity affording a different regioisomer. Here, fluoronitroalkene was identified as a synthetic …

High Voltage Dye-Sensitized Solar Cells And Molecular Photocatalysis For Co2 Reduction, Roberta Ramalho Rodrigues

Electronic Theses and Dissertations

The development of high voltage solar cells is an attractive way to use sunlight to power electrocatalysts for water oxidation, electrocatalysts for CO2 reduction, and consumer electronics. Through careful molecular dye engineering and redox shuttle pairing, our group has reported a single-junction dye-sensitized solar cell (DSC) employing, for the first time, an iron redox mediator (Fe(bpy)33+/2+) in conjunction with a novel wide band gap dye (RR9). This system generates a high photovoltage of 1.42 V. To the best of our knowledge, this system is the highest photovoltage achieved by a single-junction DSC device without metal oxide doping. The RR9/Fe(bpy)33+/2+ redox …

Theranostics Based On Linear Dendritic Block Copolymers, Jon Williams

Electronic Theses and Dissertations

When combining imaging and therapeutic motifs, known as theranostics, amphiphilic diblock copolymers have a strong precedent of success. These polymers can self-assemble into a variety of morphologies that are known to concentrate in areas of inflammation such as tumors. However, prediction of size and morphology from polymer structure still remains an open challenge. Another system with promise of therapeutic efficacy are tree-like struc- tures known as dendrimers, such as poly(amidoamine) (PAMAM) and bis-(hydroxymethyl) propionic acid (bMPA), which can uptake drugs and dyes into their branches. It is desireable to combine these two motifs, using linear-dendritic block copolymers (LDBCs). These represent …

Effects Of Halogen Bonding And Nir Tuning Of Dyes For Dye-Sensitized Solar Cells, Alexandra Baumann

Electronic Theses and Dissertations

With current energy demands being met through the utilization of energy sources such as petroleum, natural gas, and coal, the non-renewable nature of these sources will eventually approach depletion as world wide energy consumption increases yearly. As a result the need for a renewable energy alternative has become imminent. One appealing alternative that has gained considerable attention since its development due to a low cost and a high solar to electric conversion efficiency are dye-sensitized solar cells (DSCs). This dissertation describes efforts to design and synthesize improved organic dyes utilizing three analogous methods: first, through decreasing non-productive pathways such as …

The Development Of Novel Rhenium- And Copper-Based Molecular Catalysts For Applications In Energy Conversion Chemistry, Joseph Michael Lee

Electronic Theses and Dissertations

Since the Industrial Revolution, the consumption of fossil fuels has increased dramatically worldwide. The combustion of fossil fuels leads to the generation of carbon dioxide (CO2) emissions. CO2 is a greenhouse gas, but also a C1 feedstock that could be utilized for the generation of renewable fuels and commodity chemicals. However, CO2 is chemically inert and typically demands strong chemical reductants or very negative potentials before it undergoes conversion into reduced carbon products. The desire to carry out CO2 conversion in the presence of water presents a significant challenge, as protons may be reduced to hydrogen gas rather than facilitating …

Synthetic Study Of Karlotoxins And Investigation Of Alpha-Diaminoboryl Carbanion Chemistry, Yusuke Takahashi

Electronic Theses and Dissertations

Karlotoxins (KmTxs), produced by a toxic marine/estuarine phytoplankton, the dinoflagellate Karlodinium veneficum, are known to be ichthyotoxic, thus being associated with numerous fish deaths events worldwide. They have also been reported to show a variety of biological activities such as hemolytic, cytotoxic, and anti-fungal activities. Recently, the Hamann group successfully assigned the absolute configurations of KmTx2, the first complete structure elucidation among the congeners. In a structural sense, karlotoxins are a family of linear polyketides with three distinctive regions; a bis-tetrahydropyran core fragment, a long, highly oxygenated carbon chain, and a lipophilic chlorodiene unit. Such potent biological activities as well …

Efficient Utilization Of Solar Energy In Dye-Sensitized Solar Cells And In The Photocatalytic Reduction Of Carbon Dioxide, Aron Joel Huckaba

Electronic Theses and Dissertations

One of the most important questions humanity will face in the next 100 years is going to be "What will happen when oil runs out?" This dissertation describes efforts to utilize solar energy to improve renewable energy technology in two ways: First, through the improvement of dye sensitized solar cells by theimprovement of D-π-A dye subunits, the development of practical sensitizers, and progress towards stable, tunable redox shuttles. A novel indolizine donor subunit was synthesized that was shown to be the strongest reported donor. Dyes made from this novel donor and devices using the Γ-/I 3- reached up to 5.4% …

Donor-Sigma-Acceptor (D-Sigma-A) Molecules With Perylenebisimide Acceptors Having Alkyl Or Peg Swallowtails With Sulfur Or Hydroxyl Anchors: Synthesis And Applications In Langmuir-Blodgett Films, Single Molecule Spectroscopy (Sms), G-Quadruplex Studies And Passivation Of Gold Nanoparticles, Rajesh Kota

Electronic Theses and Dissertations

Use of single molecules as electronic devices is presently considered a potential alternative to semiconductor-based nanoscale electronics. The ability to study a single molecule or a small group of molecules provides a great opportunity to build electronic devices at the molecular level. It is vital to understand the parameters that control the device properties such as molecular structure, conformation and arrangement at the surface. Ari Aviram and Mark A. Ratner proposed the construction of a single organic molecule as an organic rectifier. Donor-Sigma-Acceptor (D-?-A ) molecules, when arranged with a proper orientation as Langmuir-Blodgett (LB) films and fixed between two …

Design And Synthesis Of Novel Agrofungicides Based On Naturally Occurring Pbdes, Robert Alexander Smith

Electronic Theses and Dissertations

Cyanobacterial symbionts of Indo Pacific marine sponges, e.g. Dysidea sp., produce hydroxylated (OH-) polybrominated diphenyl ethers (PDBEs) which likely function as chemical deterrents owing to their antifungal and antibacterial properties. Limiting the therapeutic potential and agricultural use of these antimicrobial natural products are the negative connotations associated with non hydroxylated anthropogenic PBDEs. Anthropogenic PBDEs are pervasive global pollutants used as flame retardant additives in many household goods, e.g. furniture, textiles, and electronics. These molecules have a propensity to bioaccumulate in living organisms, they easily traverse the trophic food chains, they are readily passed from mother to offspring, and many of …

Approaches Towards The Synthesis Of Bradyoxetin, Vanildo Martins Lima Braga

Electronic Theses and Dissertations

Quorum sensing bacteria produce and release chemical signal molecules (like N-acyl homoserine lactones, AHL) that increase in concentration as a function of cell density. The responses cover a large spectrum of process such as the virulence in Staphylococcus aureus, competence for DNA-uptake in Bacillus subtilis and Streptococcus pneumoniae, sporulation in Bacillus subtilis, conjugal plasmid transfer in Enterococcus faecalis, and bacteriocin production in lactic acid bacteria. The collapse of (AHL) signaling system in bacteria represents an attractive therapeutic approach towards the development of new antibiotics. Recently, a new extracellular modulator was isolated from a symbiotic bacterium (Bradyrhizobium japonicum) that nodulates soybean. …