Chemistry Commons^™

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 …

Why Are The Nitro And Sulfone Groups Poor Hydrogen Bonders?, Charles A. Kingsbury

Department of Chemistry: Faculty Publications

The interactions of water or methanol with nitromethane and dimethyl sulfone vs. comparison molecules, e.g. dimethylsulfoxide (DMSO), are reported. For nitromethane with water, the classical (edgewise) hydrogen bonded configuration is modestly stabilizing. However, the approach of water over the face of the nitro group is preferred in AM1 calculations. Generally, molecules such as sulfones and nitro compounds have lower energy bonding orbitals than sulfoxides. The energy of the n δ σ* interaction (e.g. nitro lone pair to O-H of water) thus is larger for the nitro and sulfone cases, and this interaction is less prevalent than other cases. Since …

Total Synthesis And Derivation Of Humulones And Lupulones As Possible Biologically Active Agents, Lucas R. Sass, Kristopher V. Waynant (Mentor)

Idaho Conference on Undergraduate Research

Humulones and lupulones have affirmed themselves as key ingredients in the multi-billion dollar brewing industry. Originally exploited for their bacteriostatic properties, these compounds also exhibit high levels of biological activity against a variety of diseases. Although quantifiable, the isolation and separation of specific humulones and lupulones has proven difficult, thus establishing efficient synthetic routes will be of value to those desiring exact bittering qualities and to the pharmaceutical community. Our investigations are towards developing a synthetic route to a library of humulones, lupulones, and their derivatives as possible biologically active agents against myriad diseases. The key step in our efficient …

Asymmetric Synthesis And Transition Metal-Catalyzed Cross-Coupling Arylations Of Selected Organolithiums, Barry Kyle Sharp

Graduate Theses and Dissertations

My former boss, Dr. Gawley, always loved to say, “The world is chiral” (à la Pasteur). From DNA and proteins to hands and feet, it is obviously true. Also, a wide variety of chemical products exist as single enantiomers. Advances in chemical technology have greatly accelerated asymmetric synthesis in the past quarter century, and namely, organolithiums, have been shown to provide a versatile route to chiral natural products and biologically active molecules. Versatility arises from the array of methods that produce a chiral organolithium. Dynamic thermodynamic resolution (DTR) is considered one of the most practical methods, but among the others …

Novel Azole-Based Rearrangements, Kolawole Folayele Ayinuola

Graduate Theses and Dissertations

This work describes efforts targeted at the development of novel reactivity modes for the Breslow intermediate, which was proposed by Breslow to explain the mechanism of action of thiamine-dependent enzymes. By employing this intermediate as a hydroxy-substituted N,S-ketene acetal, we successfully captured it via Claisen rearrangement towards the preparation of diaryl tertiary alcohol products that are isomers of the hitherto elusive intermediate. This strategy also constitutes an unusual disconnection for a Claisen rearrangement precursor.

We have also uncovered an unprecedented radical C-N bond scission of a Breslow intermediate when a fluorenyl group is installed on the azolium nitrogen atom. This …

Designing Fret Assays To Study Electrostatic Interactions Pertaining To The Binding Of Intrinsically Disordered Proteins, Ashley Ann Howard

Graduate Theses and Dissertations

Fibroblast growth factor receptor plays a major role in several biological processes. Without FGFR, a human cannot live. FGFR is involved in cell differentiation and wound healing. Of course, if FGFR signaling becomes unregulated, it causes severe distress in the body. Several cancers are contributed to high signaling levels, as well as developmental conditions like rickets and Kallmann’s syndrome. FGFR is thought to undergo an auto-inhibition (or self-regulatory) process in order to try to facilitate regulation. The exact method of this inhibition is currently unknown, but is proposed to involve the unstructured acid box region of FGFR. We developed a …

In Vitro Microdialysis Sampling Collection Of Volatile Organic Compounds (Voc's), Dodecafluoropentane (Ddfp) And Isoflurane, Valerie Shannon Mckinney

Graduate Theses and Dissertations

Death by stroke occurs every four minutes to human beings. Strokes cause necrosis within the tissue of the brain due to deprivation of oxygen. Perfluorocarbons have the ability to transport oxygen to tissue and in return decrease cell death. Dodecafluoropentane (DDFP) is a volatile fluorocarbon and collection in vivo can be a challenge since this compound evaporates at room temperature. There is currently not an efficient collection method in vivo for compounds that are volatile. Without a method to collect DDFP it is impossible to be approved for clinical use since exact concentrations of the drug within the body will …

Diol-Mediated Versus Water-Mediated Proton Transfer Reactions, Angela Moses

DePaul Discoveries

The triple-proton-transfer reactions of 8H-1,8-naphthyridin-2-one (8H-naph) have been investigated by employing different ab initio quantum mechanical methods. The proton transfer reactions studied were facilitated through an adjacent 1,3-propanediol molecule or two adjacent water molecules. Identical proton transfer reactions were studied using a model system of 8H-naph to investigate the validity of computational approaches that use model systems to study more complex systems. The solvent effects on the structures were investigated for comparison to the initial gas phase calculations. The potential energy, reaction force, and work profiles were studied along the intrinsic reaction coordinate to monitor the developing proton transfer reactions.

Investigations Of Thioether Generation For S-D-Ribosyl-L-Homocysteine Synthesis, Brendan Corcoran

Master's Theses

Creation of the thioether linkage is a fundamental step for the chemical preparation of the bacterial quorum sensing molecule S-D-ribosyl-L-homocysteine (SRH). Although previous preparations of SRH and its analogues have been reported in the literature, they employ assorted methods with varied results. Therefore, a reassessment of the methodology used for synthetic preparation of the thioether bond in SRH-like molecules is here considered. This work examines four methods of thioether generation following two mechanisms, bimolecular nucleophilic substitution (S_N2) and radical-initiated thiol-ene coupling, in an attempt to generate SRH in a more efficient and reproducible manner. Both mechanisms address …

The Synthesis And Study Of The Biological And Colloidal Properties Of Bolaamphiphiles, Louis M. Damiano

Senior Honors Projects, 2010-2019

Over the past decade, antibiotic resistant bacteria have caused infections in patients throughout the world.^[1] The rise in antibiotic resistance is primarily due to the misuse and overuse of antibiotics. ^[1] To counter the increase in antibiotic resistance, infection control mechanisms have been aggressively researched in recent years. In particular, drug delivery has become a focal point to fight antibiotic resistant infections.^[2] Amphiphiles have a wide range of applications in the clinical setting, including the ability to inhibit bacterial transference because of their bactericidal activity. ^[3] Bolaamphiphiles are a subclass of amphiphiles that possess two or more hydrophilic …

Applications Of Organic Probes For Imaging And Analysis Of Different Cancer Cell Models, Hong Guan

Theses and Dissertations

Novel techniques for better studying cancer cell behavior and progression are extremely important. Our lab is interested in synthesizing specifically designed organic reagents and applying them in the studies of cancers. In this dissertation, we used organic probes to investigate cancer cells in the following topics: determination of amino acid concentration in different types of cancers, tumor toxicity of organic probes towards HER2 positive breast cancer cells, glycoproteins identification in breast cancer cells and development of enzyme activity assay for colon cancer cells.

The first chapter was focused on the determination of cysteine/homocysteine concentrations using turn-on sensors in cancer cells. …

Impact Of Ocean Acidification On Aphotic Biogeochemical Production Of Reactive Oxygen Species, Sarah Ann Murphy

Theses and Dissertations

Reactive oxygen species (ROS) are critical to global maintenance of the global organic carbon cycle, sulfur cycle, oxygen cycle, and transition metal cycles. The primary source of ROS is commonly considered to be photolysis or photochemically driven reactions, however ROS also exist in aphotic zones. A geochemical mechanism for the same in dark environments based on the tidally driven, episodic movement of anoxic groundwaters through oxidized, Fe(III) rich sediments is shown. Predictive models were developed based on in vitro experiments and tested using sediment samples collected from a saline tidal creek in the estuary at Murrell’s Inlet, South Carolina. These …

Facile Method For Large Scale Alignment Of One Dimensional Nanoparticles And Its Biomedical Application, Sheng Feng

Theses and Dissertations

Topographical cues can profoundly affect cellular behaviors. This thesis investigate how to utilize the topographical cues generated by two techniques, flow assembly and electrospinning, to regulate cellular behaviors.

First of all, a facile and robust method to align one-dimensional (1D) nanoparticles (NPs) in large scale has been developed. Using flow assembly, representative rod-like nanoparticles, including tobacco mosaic virus (TMV), gold nanorods and bacteriophage M13, have been aligned inside capillaries by controlling flow rate and substrate surface properties. The properties of 1D NPs, such as stiffness and aspect ratio, play a critical role in the alignment. Furthermore, these hierarchically organized structures …

Tempo-Containing Romp Polymers As A Component For Treatment Of Traumatic Brain Injuries, Cameron H. Feriante

Honors College Theses

During a traumatic brain injury (TBI) sustained in combination with hemorrhagic shock the brain undergoes anoxic conditions resulting from swelling and blood loss. Traditional intravenous solutions are used to replace blood volume, but are unable to replace the blood’s oxygen carrying capacity. A proposed treatment based on isotonic solutions containing hemoglobin-based oxygen carriers (HBOC’s) which were intended to provide readily available oxygen was developed. However, cell-free hemoglobin was shown to have excessive oxidative potential. Polynitroxylated Pegylated Hemoglobin (PNPH) was developed to address this shortcoming. During PNPH synthesis a combination of polyethylene glycol (PEG) and (2,2,6,6-tetramethylpiperidin-1-yl)oxidanyl (TEMPO), is bound to the …

Fused Arene-Based Molecular Systems As Additives For Organic Photovoltaics, Rachana Neesu

Masters Theses & Specialist Projects

Organic photovoltaics (OPVs) are mainly based on organic semiconducting small molecules, macromolecules, and polymers, which form an active layer in photovoltaics. They act as an active material in absorbing light and causing charge mobility to generate electricity from sunlight. This thesis describes the molecular systems derived from fused arenes such as anthracene, pyrene, carbazole and thiophene for use as either a donor or an acceptor component of the active layer of OPVs. Two novel molecular systems (9- anthracenecarboxy-1-methylpyrene, (1) and Py-bi-TH-ANT, (2) were prepared using Steglich esterification and Grignard metathesis followed by Kumada coupling. The molecular structure of each was …

Methodology Development In Green Chemistry: Oxoammonium Salt Oxidations And Fluoroform Incorporation, Rebecca J. Wiles

University Scholar Projects

Central to the advancement of small molecule synthesis is the ability to develop methodologies that reimagine well known chemistry in a new, environmentally friendly manner. In this thesis two central themes emerge: oxoammonium salt oxidations and trifluoromethyl incorporation using fluoroform gas. Several projects have been developed surrounding oxoammonium salt chemistry, which are featured by their mild conditions, ease of use, and the metal-free, recyclable nature of the oxidant. Trifluoromethylation using fluoroform gas finds its utility in the use of a potent greenhouse gas waste product as a benchtop reagent.

Synthesis Of Diazonium Perfluoroalkyl(Aryl) Sufonimide (Pfsi) Zwitterions For Solid Acid Alkylation Catalysts, Husan Ahmad

Undergraduate Honors Theses

The final objective of this project is to create an environmentally friendly solid alkylation catalyst to replace the commercially available liquid acid catalysts, such as hydrofluoric acid and sulfuric acid, which are used in the petroleum industry. My research target is to synthesize the diazonium PFSI zwitterions, which can be chemically grafted on the silica as the solid alkylation catalyst. A 4-steps synthesis is designed to prepare the diazonium PFSI zwitterions. The first two steps were successfully completed in the lab. The first one is to prepare the starting material of 4-nitrobenzenesulfonamide from an ammonolysis reaction between 4-nitrobenzene sulfonyl chloride …