Organic Chemistry Commons^™

Synthesis Of Medicinally Relevant Thiazolyl Aryl Ketones Under Mild Conditions, Danielle M. Gardner

Health, Human Performance and Recreation Undergraduate Honors Theses

Purpose: The growing amount of clinical resistance observed in current antifungal drugs and in anti-HIV pharmaceuticals is a concern in the medical community. The purpose of this study is to develop a mild synthetic process for biomedically relevant thiazolyl aryl ketones that can be used to develop antifungal and anti-HIV drugs. We hypothesized that the proposed synthetic technique would be more efficient, produce fewer unwanted byproducts, and be more tolerant of functional groups than existing methods.

Methods: Prior to each of the ketone reactions, the necessary salt was synthesized by mixing thiazole and 9-bromofluorene neat in a reaction tube heated …

Toward The Probing Of Dhqs Activity By Protein Engineering Through The Introduction Of Unnatural Amino Acids And The Selection Of Trna/Trna Synthetase Pairs, Shaina E. Ives

Department of Chemistry: Dissertations, Theses, and Student Research

Protein engineering is a valuable tool that allows scientist to explore how an enzyme works by mutation of key residues. This method has been used to improve function or stability of enzymes, thus allowing their use in both the lab and in industry to be expanded. Genetic incorporation of unnatural amino acids (unAA) can be used with protein engineering to exceed the current limitations, due to the limited number of functional groups of the 20 common amino acids.

The majority of this thesis will discuss the progress on incorporating the various unAA into the active site of the enzyme, Dehydroquinate …

Asymmetric Synthesis Of Cα-Methyl-Γ- And Δ-Amino Acids From A Common Synthon And Evaluation Of Thionyl Chloride Assisted Peptide Esterifications, Emily Rose Vogel

Dissertations

C^α-methyl-γ- and δ-unnatural amino acids (UAAs) are important class of biomolecules used extensively as structural scaffolds, peptidomimetics, and in the development of pharmaceuticals. Due to steric congestion surrounding the quaternary center, asymmetric preparation of α,α-disubstituted UAAs are synthetically challenging. Herein, two methods for the synthesis of chiral synthons to prepare C^α-methyl-γ- and -δ-UAAs are reported. A crucial step in both strategies includes an enzymatic hydrolysis of prochiral malonic esters with pig liver esterase (PLE). The first method utilizes the Meyer Schuster rearrangement to prepare α,β-unsaturated diesters synthons, but the preparation of the precursor propargyl alcohol decomposes …

Influence Of Shelling Temperature And Time On The Optical And Structural Properties Of Cuins2/Zns Quantum Dots, Colette Robinson

Graduate Theses and Dissertations

CIS/ZnS core/shell QDs are an important class of nanomaterials for optoelectronic, photovoltaic and photoluminescence applications. They consist of lower toxicity materials than the prototypical II-VI Cd-based QDs and show long fluorescence lifetimes, which generates prospective in biological imaging applications. It is vital to develop reproducible synthetic methods for this new class of nanomaterials in order to maintain small sizes with high QYs. CIS core QDs have been shelled with ZnS at various temperatures from 90-210°C for reaction times ranging from 20-140 minutes to examine the role of thermodynamics and kinetics on the shell growth. Using HR-TEM and ICP-MS, it was …

Production And Harvest Of Microalgae In Wastewater Raceways With Resource Recycling, Alexander Colin Roberts

Master's Theses

Microalgae can be grown on municipal wastewater media to both treat the wastewater and produce feedstock for algae biofuel production. However the reliability of treatment must be demonstrated, as well as high areal algae productivity on recycled wastewater media and efficient sedimentation harvesting. This processes was studied at pilot scale in the present research.

A pilot facility was operated with nine CO₂-supplemented raceway ponds, each with a 33-m² surface area and a 0.3-m depth, continuously from March 6, 2013 through September 24, 2014. The ponds were operated as three sets of triplicates with two sets continuously fed …

Synthesis Of Agents For The Treatment And Analysis Of Tropical Diseases, Jeanine Yacoub

USF Tampa Graduate Theses and Dissertations

Toxoplasmosis is an opportunistic disease caused by the protozoan parasite Toxoplasma gondii. The parasite is usually staved off by a healthy immune system and remains dormant in the body. In immunocompromised patients, the parasite can become active and spread throughout the body causing symptoms such as encephalitis, cognitive disorders, seizures, and death. Combination drug therapy is the usual treatment for toxoplasmosis; however, patients suffer from problems of intolerance, allergic reactions, and cytotoxicity. In an effort to identify new drug targets for toxoplasmosis, a series of compounds have been synthesized that can be used as tools to probe the unique …

Synthesis And Characterization Of Neo-Confused Porphyrins And Related Systems, Arwa Salem Almejbel

Theses and Dissertations

Carbaporphyrins have been the focus of many studies, and a wide variety of related carbaporphyrinoid systems have been reported. N-confused porphyrins are a class of carbaporphyrins where one pyrrole unit has been inverted. In this work, a newly discovered family of porphyrin isomers where one of the pyrrolic subunits is connected to the meso-bridges in a 1,3-fashion, called neo-confused porphyrins, has been investigated.

Reaction of pyrrole-3-carbaldehydes with acetoxymethylpyrroles and NaH in DMF gave neo-confused dipyrrylmethane dialdehydes. The resulting dialdehydes underwent an acid catalyzed condensation with a dipyrrylmethane to give neo-confused phlorins, and following oxidation with FeCl3 afforded new neo-confused porphyrins. …

Progress Toward A Structure-Function Relationship For Novel, Small-Molecule Inhibitors Of Plasminogen Activator Inhibitor-1, Sarah Burke

Master's Theses and Doctoral Dissertations

Plasminogen activator inhibitor-1 (PAI-1) is a serpin protein whose function is to inhibit tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA), and hence, fibrinolysis. This inhibition leads to decreased plasminogen to plasmin conversion, which results in deleterious effects on the organism, such as blood clots. Elevated levels of PAI-1 are implicated in a variety of diseases and conditions. We have synthesized a variety of novel, small-molecule PAI-1 inhibitors in order to establish a structure-function relationship throughout the compounds. This goal was accomplished through an iterative process in which only one aspect of the molecule was altered at a time. …

Viral Infection Causes A Shift In The Self Peptide Repertoire Presented By Human Mhc Class I Molecules, Charles T. Spencer, Jelena S. Bezbradica, Mireya G. Ramos, Chenoa D. Arico, Stephanie B. Conant, Pavlo Gilchuk, Jennifer J. Gray, Mu Zheng, Xinnan Niu, William Hildebrand, Andrew J. Link, Sebastian Joyce

Chemistry Faculty Research

Purpose

MHC class I presentation of peptides allows T cells to survey the cytoplasmic protein milieu of host cells. During infection, presentation of self peptides is, in part, replaced by presentation of microbial peptides. However, little is known about the self peptides presented during infection, despite the fact that microbial infections alter host cell gene expression patterns and protein metabolism.

Experimental design

The self peptide repertoire presented by HLA-A*01;01, HLA-A*02;01, HLA-B*07;02, HLA-B*35;01, and HLA-B*45;01 (where HLA is human leukocyte antigen) was determined by tandem MS before and after vaccinia virus infection.

Results

We observed a profound alteration in the self …

Selective Iodination Using Diaryliodonium Salts, William H. Miller Iv

Department of Chemistry: Dissertations, Theses, and Student Research

Aryl iodides have become widely recognized as versatile synthetic intermediates, owing to aromatic iodine’s excellent ability to participate in oxidative addition reactions. Iodoarenes readily undergo a variety of synthetic transformations including metal catalyzed cross-coupling reactions, diaryliodonium chemistry, formation of organometallics through reduction or metal-halogen exchange, as well as classical S_N2 type chemistry. Because a wide array of transformations are available for aryl iodides, organic molecules containing this moiety often serve as vital precursors to highly desirable pharmaceuticals.

This thesis describes a simple and selective two-step approach to the formation of aryl iodides. This method proceeds through an easily …

Steroid Receptor Isoform Expression In Drosophila Nociceptor Neurons Is Required For Normal Dendritic Arbor And Sensitivity, Aidan L. Mcparland, Taylor L. Follansbee, Gwendolyn D. Vesenka, Alexandra E. Panaitiu, Geoffrey K. Ganter

Biology Student Publications

Steroid hormones organize many aspects of development, including that of the nervous system. Steroids also play neuromodulatory and other activational roles, including regulation of sensitivity to painful stimuli in mammals. In Drosophila, ecdysteroids are the only steroid hormones, and therefore the fly represents a simplified model system in which to explore mechanisms of steroid neuromodulation of nociception. In this report, we present evidence that ecdysteroids, acting through two isoforms of their nuclear ecdysone receptor (EcR), modulate sensitivity to noxious thermal and mechanical stimuli in the fly larva. We show that EcRA and EcRB1 are expressed by third instar larvae in …

Bis(Spirolactam) 1,3-Double-Armed Calix[4]Arene Compounds And Their Application As Extractants For The Determination Of Heavy Metal Ions, Fintan Kelleher, Mary Deasy, James Ward, Li Li, Fiona Regan

Articles

A number of double-armed calix[4]arene compounds, with proline-derived spirolactam ligating groups on the lower rim, have been synthesised and investigated as extractants of toxic heavy metal ions from aqueous solution. Pedersen’s extraction technique was employed to determine the capability of these new 1,3-distal derived calix[4]arene spiroalactams to extract selected heavy metal ions (e.g. Pb²⁺, Cd²⁺, Zn²⁺, Cu²⁺, Ni²⁺, Co²⁺) from an aqueous phase into an organic phase. The percentage extraction was calculated using UV-vis spectroscopy. All of the compounds synthesised demonstrated good selectivity for the heavy metals selected …

Temporal Variation In Optical Properties Of Chromophoric Dissolved Organic Matter (Cdom) In Southern California Coastal Waters With Nearshore Kelp And Seagrass, Catherine D. Clark, Warren J. De Bruyn, Paige Aiona

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Optical properties of chromophoric dissolved organic matter (CDOM) were measured in surf zone waters in diurnal field studies at a Southern California beach with nearshore kelp and seagrass beds and intertidal plant wrack. Absorption coefficients (aCDOM(300 nm)) ranged from 0.35 m21 to 3.7 m21 with short-term variability<1 h, increases at ebb and flood tides and higher values (6 m21) during an offshore storm event. Spectral slopes (S) ranged from 0.0028 nm21 to 0.017 nm21, with higher values after the storm; S was generally inversely correlated with aCDOM(300 nm). 3-D excitation–emission matrix spectra (EEMs) for samples with lower S values had humic-type peaks associated with terrestrial material (A, C), marine microbial material (M) and protein peaks, characteristic of freshly produced organic material. Samples with high S values had no or reduced protein peaks, consistent with aged material. Fluorescent indexes (f450/f500 >2.5, BIX>1.1) were consistent with microbial aquatic sources. Leachates of senescent kelp and seagrass had protein and humic-type EEM peaks. After solar simulator irradiation (4 h), protein peaks rapidly photochemically degraded, humic-type peak C increased in intensity and peak M disappeared. Optical characteristics of kelp leachates were most similar to field samples, …

Small Molecule Inhibitor Design For Anaplastic Lymphoma Kinase Inhibition, Theodore D. Hansel, David J. Grabovsky

Interface Compendium of Student Work

The Anaplastic Lymphoma Kinase (ALK) gene has been linked to tumorigenesis in a number of human cancers, including anaplastic large cell lymphoma (ALCL) and neuroblastoma. While ALK mutations in ALCL and many other cancers occur as a result of gene fusions with wild type kinase domains, those in neuroblastoma stem from single nucleotide polymorphisms (SNPs) in the kinase domain. These lead to autophosphorylation and constitutive signaling by ALK for cell growth and division, ultimately causing cancer. Crizotinib, an ATP-competitive ALK inhibitor, has proven to be an effective inhibitor of both ALKWT and ALKMutant kinase domains, and is in the middle …

Oxidative Cyclization Of Tertiary Pentenol Derivatives Forming 2,5,5-Trisubstituted Thf Rings And The Total Synthesis Of Cyclocapitelline, Geoffrey A. Phillips, Cory Palmer, Andrew C. Stevens, Mattew L. Piotrowski, Daryyl Sr Dekruyf, Brian Pagenkopf

Chemistry Publications

The synthesis of 2,5,5-trisubstituted tetrahydrofuran rings was accomplished via the Mukaiyama aerobic oxidative cyclization of tertiary 5-pentenols employing the Co(nmp)₂catalyst. A variety of THFs were formed in moderate to good yield and diastereoselectivity. The method developed herein was successfully applied to an enantioselective total synthesis of cyclocapitelline.

Asymmetric Transfer Hydrogenation Of Secondary Allylic Alcohols, Christopher Olugbenga Olusegun Shoola

Seton Hall University Dissertations and Theses (ETDs)

This dissertation highlights the developments and optimization of a new reaction method that transforms racemic secondary allylic alcohols into optically active secondary alcohols. The key step in this methodology occurs through a ruthenium catalyzed tandem isomerization and asymmetric transfer hydrogenation reaction. This reaction is a one pot, two-step process, which utilizes the unique ability of a transition metal catalyst to effect a combined reduction of the C-C double bond and the carbonyl group in a selected class of secondary allylic alcohols.

With a-vinyl benzyl alcohol as substrate, the optimal catalyst for this reaction was generated in situ from a …

Accessing Medicinally-Relevant Scaffolds Via Organocatalyzed Cascade Reactions, Joshua Hadley Jones

Dissertations, Theses, and Capstone Projects

The field of asymmetric catalysis embodies the efforts of chemists to mimic the stereoselectivity routinely achieved by biological systems. Asymmetric organocatalysis, a sub-field of asymmetric catalysis, is broadly based on the catalytic activity of non-transition metal, small molecules that transmit chirality to substrates. This dissertation describes experimental work towards the construction of versatile, medicinally-relevant molecular scaffolds using chiral, diarylprolinol silyl ether organocatalysts. Specifically, these catalysts were used in 1-pot, iminium-enamine catalyzed cascade reactions to functionalize α,β-unsaturated aldehydes. A comprehensive review of iminium and enamine organocatalysis is provided, including its development towards iminium-enamine cascade reactions. This review provides background for the …

Studies Toward A General Synthesis Of Poly-Substituted Alpha-Hydroxytropolones, Christine Marie Meck

Dissertations, Theses, and Capstone Projects

Chapter 1: This chapter gives a brief history of α-hydroxytropolones, how they were discovered and unique properties of these substrates. Included is a background on the bioactivity of these substrates in cellular targets such as bacteria, fungi, parasites, tumors and toxicity, as well as their ability to inhibit various metallo-based enzymes. Structure activity relationships studies are reviewed on important metalloenzymes HIV-Reverse Transcriptase (RT) and Inositol monophosphatase (IMPase). Finally the chapter finishes with a synthetic overview of α-hydroxytropolones including natural product targets such as puberulic acid, puberulonic acid, β-thujaplicinol, and β-hydroxytropolone.

Chapter 2: A brief review on β-hydroxy-γ-pyrone based oxidopyrylium cycloadditions …

Assessing The Impacts Of Inorganic And Organic Fertilizer On Crop Performance Under A Microirrigation-Plastic Mulch Regime, Niyi S. Omidire, Raymon Shange, Victor Khan, Russell Bean, Jewel Bean

Professional Agricultural Workers Journal

Abstract

This study was conducted at S & B Farm located in Eufaula, AL in 2014. The treatments were Inorganic fertilizer/“Farmer’s Mix” (NPK 13:13:13 + ammonium nitrate mixed in 3:1 ratio); Inorganic fertilizer/“Farmer’s Mix” (NPK 13:13:13 + ammonium nitrate mixed in 3:1 ratio + Bio-grow) plus microbe mix; and Organic Fertilizer – Mighty Grow (4-3-4) with a microbe mix. All fertilizers were applied prior to mulch application after which the following crops squash (Cucurbita pepo L.), cucumber (Cucumis sativus L.), and okra (Abelmoschus esculentus L. Moench) were directly seeded in a complete randomized …

Heterogeneous Oxidation Of Catechol, Elizabeth A. Pillar, Ruixin Zhou, Marcelo I. Guzman

Chemistry Faculty Publications

Natural and anthropogenic emissions of aromatic hydrocarbons from biomass burning, agro-industrial settings, and fossil fuel combustion contribute precursors to secondary aerosol formation (SOA). How these compounds are processed under humid tropospheric conditions is the focus of current attention to understand their environmental fate. This work shows how catechol thin films, a model for oxygenated aromatic hydrocarbons present in biomass burning and combustion aerosols, undergo heterogeneous oxidation at the air–solid interface under variable relative humidity (RH = 0–90%). The maximum reactive uptake coefficient of O₃(g) by catechol γ_O3 = (7.49 ± 0.35) × 10^–6 occurs for …

Effect Of Quercetin, Genistein And Kaempferol On Glutathione And Glutathione-Redox Cycle Enzymes In 3t3-L1 Preadipocytes, William Y. Boadi, Paul K. Amartey, Andrew Lo

Chemistry Faculty Research

Context and objective: Many studies have shown that cellular redox potential is largely determined by glutathione (GSH), which accounts for more than 90% of cellular nonprotein thiols. The aim of this study was to delineate the effect of three flavonoids – namely, quercetin, kaempferol and genistein – and exogenous GSH on oxidative damage by the Fenton’s pathway through the GSH and GSH-redox cycle enzymes in 3T3-L1 cells. Materials and methods: 3T3-L1 preadipocytes were exposed to each flavonoid and GSH at concentrations of 0, 5, 10, 15, 20 and 25 µM and then GSH levels and activities of glutathione peroxidase (GSH-Px), …

Fluorinated Metallo Phthalocyanines For Chemical And Biological Catalysis, Hemantbhai H. Patel

Seton Hall University Dissertations and Theses (ETDs)

The rational design of robust oxidation catalysts based on organic molecules is hindered by the presence of labile C-H bonds. We have shown recently that replacing all C-H bonds by a combination of fluoro- and perfluoro-groups in a bioinspired Cytochrome P450 model based on a phthalocyanine, Pc, scaffold results in a stable yet reactive oxidation catalyst. The Pc cobalt complex catalyzes, for example, the aerobic oxidation of thiols to disulfides, a reaction of both biological significance and industrial importance.

The presence of robust C-F bonds, however, renders the catalyst unsuitable for attachment to solid-state supports, except via van der Waals …

Understanding The Backlog Problems Associated With Requests For Continued Examination Practice, Sean Tu

Duke Law & Technology Review

One of the greatest problems facing the current patent administration is a long patent pendency period. This study focuses on Request for Continued Examination (RCE) practice, and its effects on the current patent application backlog problem. RCEs are used to continue prosecution after a patent examiner has issued a final rejection. However, now that RCEs are placed on an examiner’s special docket, some examiners may pick up prosecution one to two years after the last action. Accordingly, there are great inefficiencies that may be created by this delay, such as relearning issues and questions from the previous action, diminished value …

Applications Of Green Chemistry In Asymmetric Transfer Hydrogenation And Chiral Separations, Ruoqiu Wu

Seton Hall University Dissertations and Theses (ETDs)

Green chemistry has been applied to all aspects of the life cycle of chemically related products, including design, usage, manufacturing, analysis, and disposal. In this thesis, I focus on the green chemistry applications in organic synthesis and analytical chemistry. More specifically, allylic and chiral alcohols are abundant in natural sources such as in essential oils, and widely utilized as starting materials. They are also major components in food, fragrance, biocides and the pharmaceutical compounds. In this thesis, I report the first Ru-catalysed asymmetric transfer hydrogenation (ATH) of prochiral allylic alcohols. This reaction provides chiral secondary alcohols in excellent enantioselectivities and …

Analysis Of The Fabrication Conditions In Organic Field-Effect Transistors, Rachel M. Rahn, Yan Zhao, Jianguo Mei

The Summer Undergraduate Research Fellowship (SURF) Symposium

Polymer-based organic field-effect transistors have raised substantial awareness because they enable low-cost, solution processing techniques, and have the potential to be implemented in flexible, disposable organic electronic devices. The performance of these devices is highly dependent on the processing conditions, as well as the intrinsic properties of the polymer. Processing conditions play an important role in semiconductor film formation and device performance. These factors may provide an important link between structure and performance. In this study, an empirical analysis tool, Process Scout, was applied to assess processing factors such as polymer concentration and silicon modification. This sanctioned the creation of …

Development Of A Scalable Synthesis Of Hp-Β-Cd Pluronic Polyrotaxanes, Joseph L. Skulsky, Elizabeth A. Slepko, Bradley P. Loren, David H. Thompson

The Summer Undergraduate Research Fellowship (SURF) Symposium

Polyrotaxanes are polymers that have macrocycles threaded onto them, analogous to beads threaded onto a string. These materials are used for a variety of different biomedical applications.^1-3 The Thompson group has been developing 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) polyrotaxanes as therapeutics for the treatment of Niemann-Pick Type C (NPC) disease. NPC is a debilitating genetic disorder where cholesterol accumulates in the lysosomes of cells.⁴ Developing a scalable process is crucial for the advancement of these materials as NPC therapeutics. The goal of this project is to optimize the only protocol for the synthesis of HP-β-CD/Pluronic polyrotaxanes in order to develop a …

Synthesis And Flammability Testing Of Epoxy Functionalized Phosphorous-Based Flame Retardants, Vladimir Benin, Xuemei Cui, Alexander Morgan, Karl Seiwert

Chemistry Faculty Publications

Several potential new phosphorus-containing flame retardant molecules were evaluated for heat release reduction potential by incorporation of the molecules into a polyurethane, generated from methylene diphenyl diisocyanate and 1,3-propane diol. The heat release reduction potential of these substances was evaluated using the pyrolysis combustion flow calorimeter (PCFC). The polyurethanes were prepared in the presence of the potential flame retardants via solvent mixing and copolymerization methods to qualitatively evaluate their potential reactivity into the polyurethane prior to heat release testing. The functionality of the flame retardants was epoxide based that would potentially react with the diol during polyurethane synthesis. Flammability testing …

A Structurally-Tunable 3-Hydroxyflavone Motif For Visible Light-Induced Carbon Monoxide-Releasing Molecules (Corms), Stacey N. Anderson, Jason M. Richards, Hector J. Esquer, Abby D. Benninghoff, Atta M. Arif, Lisa M. Berreau

Chemistry and Biochemistry Faculty Publications

Molecules that can be used to deliver a controlled amount of carbon monoxide (CO) have the potential to facilitate investigations into the roles of this gaseous molecule in biology and advance therapeutic treatments. This has led to the development of light-induced CO-releasing molecules (photoCORMs). A goal in this field of research is the development of molecules that exhibit a combination of controlled CO release, favorable biological properties (e.g., low toxicity and trackability in cells), and structural tunability to affect CO release. Herein, we report a new biologically-inspired organic photoCORM motif that exhibits several features that are desirable in a next-generation …

Characterization, Dna Binding And Cleavage Activities Of New Prodigiosin And Tambjamine Analogues And Their Cu²⁺ And Zn²⁺ Complexes, Karen Chichetu

Dissertations and Theses

Prodigiosins and tambjamines are natural compounds from bacterial and marine sources belonging to a family containing a common 4-methoxy-2,2'-bipyrrole core. These compounds have received a lot of interest due to their promising biological activities. Studies have suggested DNA as a potential therapeutic target for the natural prodigiosin and tambjamine due to their ability to facilitate oxidative DNA cleavage in the presence of Cu²⁺. Based on this we sought to study the metal binding activity of new prodigiosin and tambjamine analogues. A new prodigiosin analogue was synthesized and complexed with Cu²⁺. This revealed 1:1 complex formation between …

Antioxidant Mechanisms Of Glutathione Against Metal-Mediated Oxidative Dna Damage, Elias Eteshola

Graduate Theses - Chemistry and Biochemistry

Oxidative damage of DNA strands has been strongly linked with the development of diseases such as certain cancers, cystic fibrosis and Parkinson’s, as well as aging. In intercellular reactions involving hydrogen peroxide endogenous metals have been shown to increase the generation of site-specific base modifications through their formation of reactive oxygen species (ROS). The damage markers measured via HPLC are the 8-hydroxy-2’-deoxyguanosine (8-OHdG) and the dA-N1 oxide markers. The current study deals with the reduced form of the sulfur antioxidant glutathione (GSH) and elucidating its ameliorating effects against ROS formation. Comparative studies with the known radical-scavenging sulfur antioxidant dimethyl sulfoxide …