Physical Sciences and Mathematics Commons^™

Separating The R Vs. S Enantiomers Of A Quinoline Aimed At Inhibiting The Allosteric Binding Pocket Of Hiv-1 Integrase, Madison Canfield

Honors Theses

HIV-1 is a retroviral disease that infects CD4+ T cells in the body. Once inside the body, HIV-1 uses human cell machinery to replicate and reproduce using several enzymes to reverse transcribe viral RNA to DNA and integrate the viral DNA into the human genome to reproduce. Several drugs, such as NRTIs, INSTIs, NNRTIs, and PIs, have been created to inhibit specific parts of the viral life cycle and are used in combination to fight HIV-1. However, these medications face challenges of viral mutation and resistance, which increases the importance of creating more potent and effective drugs. Recently, a new …

Separating The R Vs. S Enantiomers Of A Quinoline Aimed At Inhibiting The Allosteric Binding Pocket Of Hiv-1 Integrase, Madison Canfield

Honors Theses

HIV-1 is a retroviral disease that infects CD4+ T cells in the body. Once inside the body, HIV-1 uses human cell machinery to replicate and reproduce using several enzymes to reverse transcribe viral RNA to DNA and integrate the viral DNA into the human genome to reproduce. Several drugs, such as NRTIs, INSTIs, NNRTIs, and PIs, have been created to inhibit specific parts of the viral life cycle and are used in combination to fight HIV-1. However, these medications face challenges of viral mutation and resistance, which increases the importance of creating more potent and effective drugs. Recently, a new …

Investigation Of N-Sulfonyliminium Ion Triggered Cyclizations For The Synthesis Of Piperidine Scaffolds, Kaitlyn Birkhoff

Honors Theses

In consideration of the on-going global pandemic, immediate access to Food and Drug Administration approved pharmaceutical medications and vaccines is a matter of utmost priority to our national healthcare system. One significant modality in managed care is the dispensation of prescription drugs for the prevention or treatment of illnesses and diseases. According to the Centers for Disease Control and Prevention, physicians order and provide over 2.9 billion prescriptions each year with analgesics, antihyperlipidemics, and dermatological agents being the most prescribed therapeutic classes. Within those classes exists a disparate variety of chemical structures that must be prepared on a metric ton …

Techniques For The Enantioselective Asymmetric Synthesis Of Benzyl Substituted Malonic Acid Esters, Madison Hansen

Honors Theses

A popular method for the enantioselective synthesis of substituted malonic half esters is hydrolysis via Pig Liver Esterase (PLE), however some substrates produce low enantiomeric excess, namely benzyl-substituted malonic esters. Presented here are alternative methods explored for this synthesis, the first being phase-transfer catalyzed hydrolysis via N-benzyl quaternary ammonium salts derived from cinchona alkaloids. The second method utilized chiral auxiliary directed benzylation with auxiliaries including menthol and oxazolidinones. Though unsuccessful, this research provided valuable groundwork in the investigation for the enantioselective asymmetric synthesis of benzyl-substituted malonic acid esters.

Keywords: Pig Liver Esterase, Enantioselectivity, Phase-Transfer Catalysis, Cinchona Alkaloids, Quaternary Ammonium …

Discriminating Azo Dyes: Conjugated Polymers, The Inner Filter Effect, And Array Sensors, Erin Crater

Honors Theses

Azo dyes are abundant pollutants that contaminate water supplies and threaten humans, biota, and ecosystem health. Their detection and discrimination are an incredible challenge due to the structural, chemical, and optical similarities between dyes, the complexity of the wastewater environment in which they are found, and their low environmental concentrations. In this work, the inner filter effect (IFE), combined with conjugated polymer array-based sensing, is utilized for the quantitative profiling of these pollutants. The array was constructed using three fluorescent, anionic conjugated polyelectrolytes whose varying spectroscopic properties led to distinct IFE patterns in the presence of the dyes. The unique …

Towards The Synthesis Of An Artificial Fluorescent Siderophore, Ashley Burns

Honors Theses

Siderophores are molecules capable of binding ferric ions with high affinity (Ka = 1052). This thesis outlines our attempts to synthesize an artificial siderophore, which incorporates a signaling group to help monitor the uptake of ferric ions. The artificial siderophore is a tripodal molecular receptor synthesized in a five-step procedure with a proposed final sixth step. Rhodamine 6G azide (95.0% yield) was formed from rhodamine 6G and the synthesis of 2-azidoethanamine was modified from the literature. The tripodal arm portion of the sensor was successfully synthesized by protecting the catechol of 2,3-dihydroxybenzaldehyde to form 3-formyl-1,2-phenylene dimethanesulfonate (98.8% yield). The reduction …

The Use Of Heterocycles As Important Structures In Medicinal Chemistry, Sayre Weast

Honors Theses

Heterocycles have many applications in the discipline of medicinal chemistry. These structures are found in various natural products with relevant biological activity. Our research group, in collaboration with two others, is particularly interested in one heterocycle, quinoline, as a scaffold for HIV-1 integrase inhibitors. A synthetic route has been developed to produce a derivatized structure on small scale. One goal of this thesis was to expand the scale of this route to provide increased quantities of the quinoline scaffold. Procedures were adapted to accommodate the increase in scale to convert commercially available anthranilic acids to quinolines via the isatoic anhydride. …

Synthesis, Characterization, And Utilization Of Iron Ii Ion Sensing Fluorescent Probes For Detection Of Early Onset Anodic Corrosion, Dane N. Wedgeworth

Honors Theses

Corrosion effects can be seen in infrastructure all around the world. From rusted bridges, ships, and other steel surfaces, the price of corrosion adds up quickly with repairs, maintenance, and complete replacement. Common approaches to corrosion detection and prevention require slow, optical inspection to begin the repair and maintenance process, which can also be very slow and costly. However, recent literature suggests that metal chelating probes can yield new understanding of the processes of corrosion faster and with greater specificity in location and diversity in mechanisms for early onset of corrosion. Earlier corrosion detection can be characterized by several ways. …

A Study On The Modifications Of [2.2]Paracyclophane And Their Effects On The Enantioselectivity Of The Copper Catalyzed Cyclopropanation Reaction, Yousef Dawoud

Honors Theses

The use of chiral [2.2]paracyclophane Schiff-base ligands has been shown to induce enantioselectivity in the copper catalyzed cyclopropanation of styrene with diazoesters. ¹ Previous research by Dr. Masterson tested Schiff-base ligands based on 4- amino[2.2]paracyclophane with moderate enantioselectivity. In this project, the Schiff-base N- salicylidene-4-amino[2.2]paracyclophane, was modified by way of Grignard addition to the imine carbon and its enantioselective properties were explored with the copper catalyzed cyclopropanation. The methyl Grignard addition to N- salicylidene-4-amino[2.2]paracyclophane was successful in producing the amino alcohol and the amino alcohol was characterized. The amino alcohol was produced from the R enantiomer of the Schiff-base and …

Pro-Antimicrobial Networks Prepared Via Degradable Thiol-Ene Acetal Photopolymerization, Sarah Swilley

Honors Theses

A degradable, antimicrobial polymer network with acetal crosslink junctions derived from p-anisaldehyde (pA), a common constituent found in star anise extract, is reported. The p-anisaldehyde was converted into a bis-functional acetal alkene monomer, which serves as a pro-antimicrobial form of the active aldehyde and a building block for materials referred to as pro-antimicrobial polymer networks via degradable acetals (PANDAs). Subsequently, the bis-functional acetal alkene monomer was photopolymerized with a multifunctional thiol to yield a thiol-ene network. PANDAs exhibit surface erosion behavior and yield sustained release of pA over 38 days when exposed to neutral or biologically relevant conditions. The pA …

Biocompatible, Responsive Polysoaps Via Raft Copolymerization For The Delivery Of Model Cancer Therapeutics, Mason Dearborn

Honors Theses

Many chemotherapeutic drugs are small, hydrophobic molecules that require water-soluble, biocompatible nanocarriers for enhanced vascular circulation. Existing polymeric carriers either conjugate the drug along a copolymer backbone or sequester drugs within a protected interior domain to be delivered to specific sites in the body. Such therapeutic systems must overcome a myriad of hurdles, beginning with complex, multi-step syntheses, followed by other inherent barriers that limit the efficiency of drug delivery at the targeted site. This work aims to circumvent a number of these issues using biocompatible, stimuli-responsive polysoaps that are capable of unimeric micelle formation, hydrophobic drug delivery, and triggered …

An Exploration Of Pyrrole Groups On The Enantioselectivity Of Pig Liver Esterase, Brian Long

Honors Theses

Pig Liver Esterase (PLE) is a serine protease enzyme that can interact with one side of a diester to hydrolyze the ester to a carboxylic acid, and research has found that the level of hydrophobicity of side groups can impact the enantioselectivity of PLE hydrolysis.1, 2 The Jones Model is what current researchers use to model the active site of PLE, but the nature of its binding pockets, namely the Hydrophobic Long (HL) pocket, has been called into question.3 Dimethyl 2-((pyrrole-2-yl)methyl)-2-methylmalonate was prepared to be subjected to PLE hydrolysis to see whether enantioselectivity was found. Chiral HPLC revealed 25.32% enantiomeric …

Understanding The Coating-Substrate Interface Changes And Degradation Caused By Environmental Acclimation With Water And Electrolytes, Russell Vick

Honors Theses

While it is well known that polymeric coatings are used to protect metals from corrosion, efficient and reliable protocols for quantifying and estimating protective coatings’ lifetimes have yet to match real-time results in rate or in detected mechanisms of material failure. Alkoxysilane pretreatments are widely utilized for substrate preparation and improved coating system performance by changing the metal substrate surface morphology to improve adhesion at the coating-substrate interface by creating a foundation and excluding water from the system. Three pretreatments used were 3-aminopropyltriethoxy silane (APS), tetraethylortho silicate (TEOS), N-[3-(trimethoxysilyl)propyl]ethylenediamine (DAS). They were investigated to improve the understanding of the relationships …

Diastereoselective Synthesis Of 2,4,6-Trisubstituted Piperidines Via Aza-Prins Cyclization, John A. Hood

Honors Theses

The nitrogen heterocycles are shared amongst 59% of Food and Drug Administration (FDA) approved small molecule pharmaceuticals with the six-membered piperidine representing the most common moiety. Given the versatility and potential to yield derivatives with broad biological activities, the discovery of new chemical methods to generate these heterocycles in a more time and cost-efficient manner is desired. While there are existing racemic methods to access this class of molecule, the objective of this research is to pioneer a new novel six-step method to generate 2,4,6-trisubstituted piperidines with stereoselective control.

The first step is a condensation between a nonenolizable aldehyde and …

Photoelectrochemical Investigations On Novel Earth Abundant Solid State Catalysts For Solar Water Oxidation, Nathaniel Branimir Kurtz

Honors Theses

In light of a looming fossil fuel scarcity, many forms of alternative, clean energy production are being researched in order to provide a more sustainable source of energy production for the future. One area of research is on using novel, abundant catalytic materials in conjunction with semiconducting materials to drive the splitting of water in order to produce hydrogen gas, an energy-rich fuel. Currently, efficiency is limited by the energy bottleneck posed by the oxygen evolution reaction (OER) half of water splitting. In this work, cobalt selenide (CoSe) catalyst paired with the semiconductor iron oxide (Fe2O3) has been identified as …

Investigation Of The Effects Of Hydrogen Bonding On The Enantiomeric Excess Of Pig Liver Esterase Hydrolysis Products, Matthew Hasler

Honors Theses

Pig Liver Esterase (PLE) is an effective enzyme used in the Masterson Research Group due to its ability to hydrolyze only one ester in a malonic diester. PLE is employed for creating chiral molecules for the synthesis of unnatural amino acid precursors. Previous research in the group found that malonic half esters with hydrogen bonding capable substrates yielded varying degrees of enantiomeric excess, and non-hydrogen bonding substrates yielded racemic mixtures.1,2 The compounds synthesized contained substrates consisting of thiophene rings in the second and third position, and these molecules act as a control for the other research done in the group. …

Synthesis Of A Thermally Reversible Cross-Linked System Using Electrophilic Cleavage/Functionalization Of Poly(Isobutylene-Co-Isoprene), Savannah H. Steadman

Honors Theses

Multifunctional polyisobutylenes (PIBs) are of great academic and commercial interest. Current methods to create these materials currently utilize prohibitively expensive synthetic strategies. Recently, Storey et al. reported a novel method for the synthesis of multifunctional PIB which is more commercially viable than the current methods. For this research, the material produced via this technique was utilized to create a thermally reversible crosslinked system using Diels-Alder chemistry. To achieve this, a bromide-functional polyisobutylene obtained via electrophilic cleavage and functionalization of butyl rubber was split into two portions and further functionalized. The first portion of the bromide-functional PIB was reacted with furfuryl …

Characterization Of Epoxy/Amine Networks With Glycidal Polyhedral Oligomeric Silsesquioxane Surface Modified Silica Nanoparticles, Reese K. Sloan

Honors Theses

Silica nanoparticles were surface modified with octa-functional glycidal polyhedral oligomeric silsesquioxane (G-POSS) and incorporated into an epoxy/amine system in an effort to increase the mechanical performance of the inorganic/organic hybrid material. The silica nanoparticles were first functionalized with 3-aminoprpyltrimethoxysilane (APTMOS) at 5 and 10 weight percent, and then modified with G-POSS at ratios of 1:10 and 1:5 (APTMOS: G-POSS). The modified particles were then incorporated into an epoxy/amine network consisting of diglycidyl ether of bisphenol A (DGEBA) and aromatic amine, diamine diphenyl sulfone (4,4’ DDS) at 1 and 5 weight percent, resulting in 8 different formulations. The incorporation of the …

Kinetic Study Of Conjugated Polymer Packing And Agglomeration, Skye R. Travis

Honors Theses

Although organic electronic materials are flexible, cheap to fabricate, and molecularly tunable, their performance has generally been less efficient than that of their inorganic counterparts. Chemical doping has been attempted as a method to increase the efficiency of organic materials. During this process, an organic material, typically a conjugated polymer, is exposed to an oxidant/reductant, called a dopant. Electron transfer between host polymer and dopant molecules increases the charge carrier density in the doped host material, making it a more efficient conductor. The effects of doping using 2,3,5,6-tetrafluoro-tetracyanoquinodimethane (F4TCNQ) on low molecular weight poly(3-hexylthiophene-2,5-diyl) (LMW P3HT) in varying ratios of …

Synthesis Of Polythioether Nanoparticles Via Thiol-Alkene/Alkyne Photopolymerization In Miniemulsion, Susan E. Walley

Honors Theses

Emulsion-based processes – such as miniemulsion polymerizations – provide well-studied synthetic routes to polymer nanomaterials. Miniemulsion polymerizations are characterized as aqueous dispersions of small, narrowly distributed monomer droplets created through high shear and stabilized against Ostwald ripening/collisional degradation by addition of an appropriate surfactant and costabilizer. In this work, thiol–alkene/alkyne photopolymerization in miniemulsion is demonstrated as a simple, rapid, and one-pot synthetic approach to polythioether nanoparticles with tuneable particle size and clickable functionality. Nanoparticles with mean particle diameters ranging from 45 nm to 200 nm were synthesized through simple modifications to the miniemulsion formulation and processing parameters. Facile access to …

Automated Data Acquisition Of Deet Time-Dependent Concentration Profiles, Ryan D. Coleman

Honors Theses

Spatial insect repellents must maintain a sufficient concentration in the vapor phase to successfully deter pests. However, little is known regarding correlation of concentration to efficacy nor does there exist a standard testing protocol to measure efficacy in air. Among existing spatial repellents, DEET is the most common active ingredient. This research focuses on application of sensor-based technologies to monitor the concentration levels of DEET under static conditions.

Metal oxide semiconductor sensors feature conductivity variance in response to absorption and desorption of volatile organic compounds. Advantages of these sensors include cost, versatility, and sensitivity. Metal oxide semiconductor sensors were chosen …

Using Intrinsic Properties Of Polyaniline To Sense Expression Of The Microrna Let-7, Jared N. Gloria

Honors Theses

MicroRNAs are approximately 22-nucleotide long RNA molecules that function through decay and translational repression of messenger RNA. The microRNA let-7 is found to play a role in maintaining the fate of differentiated cells in humans. Thus, expression level of this microRNA is a reliable biomarker of tumor cell phenotype. However, there are significant limitations in the current profiling techniques of microRNA. The current methods like northern blotting, microarrays, RT-PCR, or using locked nucleic acid (LNA) for in-situ hybridization are either laborious, semi-quantitative, or expensive. In this research we try to address this issue by developing a fast, specific, and inexpensive …

The Effect Of Acrylic Acid On Ring Formation In Polyacrylonitrile, Elisha Cade Willis

Honors Theses

The addition of comonomers into carbon fiber precursor, polyacrylonitrile (PAN), has shown to have effects on the extent of stabilization and thermal behavior.1 Acrylic Acid (AA) was added at varying initial apparent weight percent and added via semibatch reaction to copolymerize with acrylonitrile to form carbon fiber precursor. Accompanying batch reactions were synthesized for comparison. Degradation was found to be greater in the semibatch reactions although overall was comparable to the batch reactions. Differential scanning calorimetry (DSC) confirmed the addition of higher concentrations of AA into the reaction resulted in a less intense exotherm upon cyclization, along with a greater …

Synthesis And Application Of (R)-3-Methylpyrrolidine-3-Carboylic Acid, Shelby D. Dickerson

Honors Theses

L-Proline is an amino acid widely used in pharmaceutical and biotechnological research due to its catalytic activity and biological relevance. L-Proline has been recognized and utilized as an organocatalyst, which allows cleaner, more sustainable reactions. However, one issue with L-proline is its low solubility in organic systems, limiting its reactivity and efficiency, especially when considering industrial research. Two reactions that utilize L-Proline are the Michael and Aldol but require 100 mol% of L-Proline and 30 mol% of L-Proline, respectively. This research will focus on the synthesis of an analogue of L-Proline utilizing inexpensive, commercially available reagents. A variety of organic …

A Chemical Sensor For Cyanide, Rachel E. Lambert

Honors Theses

The cyanide ion and its gaseous form, hydrogen cyanide, are extremely toxic. Cyanide impairs cellular respiration by inhibiting cytochrome c oxidase, an enzyme in the electron transport chain, leading to cell death.

In a previous study, we synthesized an optical sensor that detects cyanide selectively. The aim of this project is to increase the sensitivity of this sensor. This can be achieved by utilizing the unique spectroscopic properties of lanthanide ions.

The lanthanide metal (europium or terbium) was added to a coumarin-glycine chemodosimeter in a DMSO solvent system. The sensor was titrated with several monodentate analytes including, nitrate, octylamine, 1-pentanethiol, …

Investigation Of How Hydrogen Bonding Affects The Enantiomeric Excess Of Pig Liver Esterase Promoted Hydrolysis Of Pro-Chiral Substrates, Jacob E. Pruett

Honors Theses

Pig Liver Esterase is a cost effective enzyme for ester hydrolysis. In our group, it is vital for creating chiral molecules for the synthesis of unnatural amino acids of potential biological importance. It has been previously found that the enantiomeric excess (%ee) of the PLE hydrolysis reaction increases drastically with the addition of co-solvents that are able to both accept and donate hydrogen bonds. This research endeavors to see if substrates of enhanced hydrogen bonding ability also increase the stereoselectivity of PLE hydrolyses. Diester malonate was covalently linked with a furan ring in both the third and second position from …

Synthesis Of Acceptors For Use In Donor-Acceptor Copolymers And Characterization Of These Polymers, William D. Walker

Honors Theses

In this thesis, a selenium-derivatized acceptor was synthesized to examine the heavy atom effects of selenium on the position of the frontier molecular orbitals (HOMO/LUMO band gap) as opposed to sulfur in a donor-acceptor copolymer for use in light harvesting and detection applications. Over the course of this research, standard operating protocols for ultraviolet-visible (UV-Vis-NIR) and Fourier transform infrared (FT-IR) spectroscopies, as well as cyclic voltammetry (CV) characterization techniques were established. Once synthesized, the polymers were characterized through use of the established characterization protocols. The selenium-derivatized polymer exhibited a bathochromic shift compared to the sulfur analogue, with a solid-state absorption …

Functionalizing Β-Cyano Oligo(P-Phenylene Vinylene) Chromophores For Use In Mechanochromic Materials, Alexander J. Wink

Honors Theses

Mechanochromic materials are materials that change color upon mechanical deformation. This concept can be applied in areas of quality control, since the knowledge of damaged parts will easily be detected due to a color change in the material that has undergone deformation. Typically these types of materials are enabled by employing functional small molecules. Often, these are conjugated organic molecules or chromophores, which fluoresce different colors determined by the stimulus (or lack thereof) acting upon the material. In this work, we explore a new avenue to elicit color changes in polymeric materials based on the process of restriction of intramolecular …

Polymerization Of Blocked Isocyanate Functional Polymer Surfaces And Post-Polymerization Modification By Thiol-Isocyanate Reactions, Chase A. Tretbar

Honors Theses

Direct polymerization of isocyanate-functional monomers has been achieved with controlled radical polymerizations (CRP) for precisely engineered modification platforms with highly reactive side chains. However, despite the success of these strategies, the inherent reactivity of isocyanates still leads to adverse side reactions, such as hydrolysis, that are difficult to suppress. Phenol, lactam, and oxime-based blocking agents have been used to limit the reactivity of isocyanates in applications such as multicomponent urethane coating systems. The reactivity of these blocked isocyanates can be restored by thermal deprotection of the blocking agent to achieve the desired reactions. In this work, we use blocked isocyanate-functional …

Analysis Of The Mechanical Properties Of Dgebf/4,4’-Dds Thermoset Systems As A Function Of Cure Rate, Chase B. Thompson

Honors Theses

The relationship between macroscopic mechanical and thermal properties and ramp rate during cure of epoxy-amine systems consisting of the epoxide resin digylcidyl ether of bisphenol F (DGEBF, provided Hexion specialty chemicals) and 4,4-diaminodiphenyl sulfone (4,4-DDS, provided by Atul Sulpho) were probed using Dynamic Mechanical Analysis (DMA), Positron Annihilation Lifetime Spectroscopy (PALS), and compression testing. These systems were cured in a programmable oven; the samples were heated from 35°C to 180°C at ramp rates of 0.5, 1.0, 1.5, 2.0, 2.5, 5.0, 10, and 15°C/min. Even as the ramp rates during the cure of these materials was changed, there was very little …