Organic Chemistry Commons^™

[3+2] Annulation Of Cyclopropylanilines With Alkynes Under Photocatalysis, Theresa Ha Nguyen

Graduate Theses and Dissertations

Over the past decade, pharmaceutical industries have prioritized their focus on discovering new innovative drugs, yet the syntheses are often either inefficient or the approach of environmental sustainability presents a great deal of concern. Moreover, the methodology developments for amine syntheses have continued to flourish due to their important role and wide use in pharmaceutics. Yet their syntheses often lack sustainability and efficiency. Synthetic chemists have continued to explore potential innovative avenues for conducting chemical reactions more effectively and efficiently. One of the most abundant, renewable natural resources is solar energy and to harvest, use, and store it directly is …

Investigation Of The Interaction Of Dimeric Ruthenium Complexes With Cytochrome B5, Christopher Dain Rupar

Graduate Theses and Dissertations

Photoreactive complexes to study the kinetics of electron transfer of proteins have been in use for a long time. It has always been speculated that complexes bind near the heme or the electron transfer reaction would not occur. But it is unkown exactly how the complex interacts with the protein. The structural, thermodynamic, and kinetic properties of rat liver microsomal cytochrome b5 were investigated when bound to ruthenium dimer complexes. Heteronuclear Single Quantum Coherence studies support a dynamic binding model of a dimer Ru complex bound near the protein’s heme involving residues H39, E44, G42, V61, G62, and H63. The …

The Large-Scale Synthesis And Asymmetric Hydrosilylations Of Cuiphet, A C2-Symmetric N-Heterocyclic Carbene, Elizabeth Suzanne Spahn

Graduate Theses and Dissertations

CuIPhEt is a C2-symmetric N-heterocyclic carbene catalyst used in the asymmetric hydrosilylation of a variety of prochiral ketones with good yields and selectivities. The large-scale, five-step synthesis of this carbene has been devised. The second step of the synthetic plan includes a double asymmetric hydrogenation of a 1,1-diaryl alkene—a traditionally difficult transformation. The procedure for the use of CuIPhEt in asymmetric hydrosilylations has been optimized and used on both the originally published substrate scope and new compounds. This protocol for the hydrosilylation has been applied in a 10 g reduction to create an intermediate for use toward the total synthesis …

Mechanism Of Rapid Electron Transfer Reactions Involving Cytochrome Bc1, Cytochrome C And Cytochrome Oxidase, Jeremy Erik Durchman

Graduate Theses and Dissertations

Electron transfer between mitochondrial proteins complexes represents the primary means by which living things acquire the requisite energy for survival. The coupling of electron transfer to proton translocation creates an electrochemical gradient that drives the synthesis of highly energetic compounds such as ATP. The purpose of these studies is to measure rates of electron transfer and elucidate the important governing factors in the redox events involving cytochrome bc1, cytochrome c and cytochrome oxidase. Using rapid initiation of redox events triggered by laser flash excitation of ruthenium compounds, and strategically monitoring unique spectral properties of these proteins in the visible region …

Two Studies: Stereoselective C-C Bond Formations Of N-Boc-Piperidines Using Selected Organolithiums And Visible-Light-Mediated Synthesis Of Fused Indolines Using Tethered Styrenes, Scott Alan Morris

Graduate Theses and Dissertations

Chemists worldwide have accepted the challenge of developing methods to access a variety of compounds as single enantiomers, including the use of enzymes, chiral auxiliaries, and resolutions. In particular, dynamic resolutions offer a unique way to access chiral compounds using a few controllable steps, including the variation of both time and temperature. Many groups have implemented this methodology to generate various polysubstituted pyrrolidines and piperidines, which are substructures ranking high on the list of nitrogen–containing pharmaceuticals.

The Gawley group revealed a catalytic dynamic resolution (CDR) of N–Boc–piperidine using a chiral ligand. Impressively, the chemistry was tolerant of a variety of …

Mida Boronates Are Hydrolysed Fast And Slow By Two Different Mechanisms, Jorge A. Gonzalez, O. Maduka Ogba, Gregory F. Morehouse, Nicholas Rosson, Kendall N. Houk, Andrew G. Leach, Paul H.-Y. Cheong, Martin D. Burke, Guy C. Lloyd-Jones

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

MIDA boronates (N-methylimidodiacetic boronic acid esters) serve as an increasingly general platform for building-block-based small molecule construction, largely due to the dramatic and general rate differences with which they are hydrolysed under various basic conditions. Yet the mechanistic underpinnings of these rate differences have remained unclear, hindering efforts to address current limitations of this chemistry. Here we show that there are two distinct mechanisms for this hydrolysis: one is base-mediated and the other neutral. The former can proceed more than three orders of magnitude faster, and involves rate-limiting attack at a MIDA carbonyl carbon by hydroxide. The alternative ‘neutral’ hydrolysis …

Synthesis Of A Small Molecule Nitrosocysteine Inhibitor To Reduce The Activity Of Caspase-1, Catherine A. Shamblen, Caitlin E. Karver

DePaul Discoveries

Caspase-1 is an enzyme that is overactive in autoimmune and autoinflammatory diseases cleaving pro-interleukin-1β to the cytokine interleukin-1β (IL-1β), which leads to inflammatory symptoms. The inhibition of caspase-1 will cause a decrease in the concentration of interleukin-1β (IL-1β), resulting in the reduction of inflammatory symptoms. Recent research has revealed that the appending of a nitric oxide (NO) or nitroxyl (HNO) donating group to non-steroidal anti-inflammatory drugs (NSAIDs) reduced, or avoided, the side effects caused by currently available treatments. A small molecule based on a known caspase-1 inhibitor with a nitrosocysteine appended on was synthesized to look at the effect of …

Serendipitous Discovery Of A New Method For The Catalytic Synthesis Of Indole-Fused Benzazepanes, Edward Gluzman, Paul A. Vadola

DePaul Discoveries

We report here on our investigations into the application of 1,5-hydride transfer cyclization mechanisms to the synthesis of 2,3-disubstituted benzofurans and indoles. We found that PtI₄ in MeCN at 120 ºC was indeed capable of activating the alkyne, however, the expected 2,3-disubstituted indole product was not observed. Instead we isolated an indolyl-3-benzazepane via an unexpected intramolecular Steven’s rearrangement/ring expansion. While this transformation has been previously reported our method may prove to have increased substrate scope and more practical reaction conditions. Further studies are underway to optimize the reaction conditions and to fully explore the scope and mechanism of the …

Spatially Directional Resorcin[4]Arene Cavitand Glycoconjugates For Organic Catalysis In Aqueous Media, Ali Husain Husain

USF Tampa Graduate Theses and Dissertations

Resorcin[4]arenes and their rigid structures “cavitands” offer a unique molecular structure scaffolds suitable for attaching and orienting multi-ligands on their upper rims. Their remarkable structure properties, the relative ease of chemical modification on their either rims or through the multiple phenolic hydroxyl (-OH) groups, manipulating their cavity size and the role of spatial directionality provided by their cores, led synthetic chemist to explore their utilities in the synthesis of valuable resorcin[4]arene/cavitand assemblies with wide range of applications in many research areas such as supramolecular chemistry, host-guest chemistry, glycoconjugates, polymer chemistry, host-guest chemistry, micro-reactors in chemical catalysis and others. In particular, …

Ionic Liquid Extraction Unveils Previously Occluded Humic-Bound Iron In Peat Soil Pore Water, Timothy J. Veverica, Evan S. Kane, Amy Marcarelli, Sarah A. Green

Department of Biological Sciences Publications

Globally, peatland ecosystems store tremendous amounts of C relative to their extent on the landscape, largely owing to saturated soils which limit decomposition. While there is still considerable uncertainty regarding CO₂ production potential below the water table in peatland ecosystems, extracellular Fe reduction has been suggested as a dominant pathway for anaerobic metabolism. However, colorimetric methods commonly used to quantitate Fe and partition between redox species are known to be unreliable in the presence of complex humic substances, which are common in peatland pore water. We evaluated both the standard o-phenanthroline (o-P) Method and an ionic …

Synthesis And Biological Activity Of Novel Quorum Sensing Compounds, Joseph Nicholas Capilato

Theses and Dissertations

Bacteria communicate with chemical signals in a process known as quorum sensing. This population density-dependent process involves the bacterial production, release and detection of structurally specific small molecules and enables the bacterial pathogen to regulate its virulence on a population-wide level. Using a variety of chemical and biological techniques, I have studied various quorum sensing systems in several bacteria, including Vibrio cholera and Pseudomonas aeruginosa. A key principle of this research involves the design, synthesis and testing of novel compounds for their biological activity. These molecules are typically based off of an initial lead target, which is often identified …

Rotamer-Restricted Fluorogenicity Of The Bis-Arsenical Reash, A. S. Walker, Paul R. Rablen, A. Schepartz

Chemistry & Biochemistry Faculty Works

Fluorogenic dyes such as FlAsH and ReAsH are used widely to localize, monitor, and characterize proteins and their assemblies in live cells. These bis-arsenical dyes can become fluorescent when bound to a protein containing four proximal Cys thiols—a tetracysteine (Cys4) motif. Yet the mechanism by which bis-arsenicals become fluorescent upon binding a Cys4 motif is unknown, and this nescience limits more widespread application of this tool. Here we probe the origins of ReAsH fluorogenicity using both computation and experiment. Our results support a model in which ReAsH fluorescence depends on the relative orientation of the aryl chromophore and the appended …

Photooxidation Chemistry And Photodynamic Therapy: Pointsource Delivery Of Singlet Oxygen, Sensitizer And Nitrosamine Drugs, Ashwini Anil Ghogare

Dissertations, Theses, and Capstone Projects

Eradication of residual tumor cells that are directly adjacent to vital tissue is a daunting challenge to surgeons. Because the field needs advances in intraoperative settings and a means for high-precision delivery of singlet oxygen for photodynamic therapy (PDT) of cancers, this dissertation outlines the development and application of a “pointsource” fiber optic device. The device offers highly localized and simultaneous delivery of sensitizer drug, light, and oxygen (components necessary for PDT) for cancer cell eradication in-vitro and in-vivo. The following chapters describe (a) the photokilling activity and precision of pointsource PDT in monolayer ovarian and brain cancer cells …

Aqueous Photochemistry Of Glyoxylic Acid, Alexis J. Eugene, Sha-Sha Xia, Marcelo I. Guzman

Chemistry Faculty Publications

Aerosols affect climate change, the energy balance of the atmosphere, and public health due to their variable chemical composition, size, and shape. While the formation of secondary organic aerosols (SOA) from gas phase precursors is relatively well understood, studying aqueous chemical reactions contributing to the total SOA budget is the current focus of major attention. Field measurements have revealed that mono-, di-, and oxo-carboxylic acids are abundant species present in SOA and atmospheric waters. This work explores the fate of one of these 2-oxocarboxylic acids, glyoxylic acid, which can photogenerate reactive species under solar irradiation. Additionally, the dark thermal aging …

Oleanolic Acid Inhibits High Salt-Induced Exaggeration Of Warburg-Like Metabolism In Breast Cancer Cells, Suneetha Amara, Mu Zheng, Venkataswarup Tiriveedhi

Chemistry Faculty Research

Cancer cells have a proliferative advantage by utilizing intermediates of aerobic glycolysis (Warburg effect) for their macromolecule synthesis. Although the exact causes of this Warburg effect are unclear, high osmotic stress in solid tumor microenvironment is considered one of the important factors. Oleanolic acid (OA) is known to exert anti-inflammatory and anti-cancer effect. In our current studies, using breast cancer cell lines, we determined the protective role of OA in high salt-mediated osmotic stress-induced cancer growth. Hypertonic (0.16 M NaCl) culture conditions enhanced the cancer cell growth (26 %, p < 0.05) and aerobic glycolysis as marked by increased glucose consumption (34 %, p < 0.05) and lactate production (25 %, p < 0.05) over untreated cells. This effect was associated with increased expression and activity of key rate-limiting enzymes of aerobic glycolysis, namely hexokinase, pyruvate kinase type M2, and lactate dehydrogenase A. Interestingly, this high salt-mediated enhanced expression of aerobic glycolytic enzymes was efficiently reversed by OA along with the decreased cancer cell proliferation. In cancer cells, enhanced aerobic glycolysis is associated with the decreased mitochondrial activity and mitochondrial-associated caspase activity. As expected, high salt further inhibited the mitochondrial related cytochrome oxidase and caspase-3 activity. However, OA efficiently reversed the high salt-mediated inhibition of cytochrome oxidase, caspase activity, and pro-apoptotic Bax expression, thus suggesting that OA induced mitochondrial activity and enhanced apoptosis. Taken together, our data indicate that OA efficiently reverses the enhanced Warburg-like metabolism induced by high salt-mediated osmotic stress along with potential application of OA in anti-cancer therapy.

Synthesis And Evaluation Of Biological Activity Of A Potential Immunomodulatory Zwitterionic Polysaccharide, Vikram Basava

Seton Hall University Dissertations and Theses (ETDs)

The gram-negative anaerobic bacterium Bacteroides fragilis is an integral component of the normal gastrointestinal flora. The bacterium colonizes the intestinal tract of human beings as it has no reservoir other than mammals. An unprecedented proportion of the genomic DNA of B. fragilus is involved in the production of capsular polysaccharides. These capsular polysaccharides are important virulence factors in most extracellular bacterial pathogens. Eight of these polysaccharides have been identified thus far, out of which two were found to be zwitterionic polymers, PSA1 and PSA2. PSA1 was found to stimulate T-cell lineage of the immune system because of the dual charge …

The Synthesis Of 1,3-Difluoro-2-Methyl-4-Phenylbenzene From A One-Pot Reaction Of Difluorocarbene And 1-Phenyl-2-Methylcyclobutene, Ruth Felicitas Menger

Senior Honors Projects, 2010-2019

Previous studies show that 1,2-disubstituted cyclobutenes can be used in reaction with difluorocarbene to produce 1,3-difluorobenzenes. A pathway to the synthesis of these types of compounds is of interest due to their presence in fluoroquinolone antibacterials, resins, and insecticides. The synthesis is unique because the fluorine atoms from the difluorocarbene are not adjacent to each other when the ring expands to a benzene ring. This study focuses on the reaction of difluorocarbene with 1-phenyl-2-methylcyclobutene, which was synthesized in one-pot in 4 steps starting from 1-phenyl-1-propyne and zirconocene dichloride.

The Synthesis And Colloidal Characterization Of Several Triscationic Amphiphilic Antibacterial Agents, Kristin R. Mckenna

Senior Honors Projects, 2010-2019

M-P,12,12, a triscationic amphiphile, was characterized for its antibacterial and colloidal properties as well as its ability to associate with sodium dodecyl sulfate (SDS). This amphiphile has a mesitylene core, one pyridinium headgroup, and two dimethyldodecylammonium tails. The critical aggregation concentration (CAC) for M-P,12,12 was determined by three different methods. According to isothermal titration calorimetry (ITC), the CAC is 2.54 mM, conductivity studies determined the CAC to be 2.07 and the degree of ionization to be 0.188, and nuclear magnetic resonance (NMR) spectroscopy yielded a CAC value of 1.73 mM. The NMR study of the water-insoluble solid formed by M-P,12,12 …

The Effect Of Hofmeister Series Counterions On The Colloidal And Antimicrobial Properties Of Triple-Headed Cationic Amphiphiles, Kirstie A. Thompson

Senior Honors Projects, 2010-2019

Antibacterial resistance is becoming increasingly prominent, causing a great need for novel antibacterial products. This work focuses on developing an understanding of the relationship between counterion identity on colloidal and antibacterial activity for cationic amphiphiles. In an amphiphile series with three hydrophilic quaternary ammonium bromide head groups and one hydrophobic tail, the amphiphile with a linear hydrocarbon chain with 18 carbons is more antibacterial than those with longer or shorter tails. Counterion exchange of the bromide counterions with various Hofmeister series anions significantly affects both antibacterial and colloidal activity. The logarithm of critical aggregation concentration [log(CAC)] was found to have …

The Synthesis Of Angucyclines Using An Intramolecular Bradsher Cycloaddition, Abdullah Allaoa, Tony E. Nicolas

Publications and Research

The Angucyclines are natural products which possess a broad spectrum of biological properties. Of particular interest are the natural products which contain the cis-hydroxyl motif at the AB ring junction. Their synthesis is particularly challenging. Our model study has resulted in the synthesis of a model of the angucyclines with the required cis-hydroxyl features. The present work will apply the previously developed chemistry to an intramolecular version which will lead to the synthesis of the ABC ring system

Improving Photocatalytic Activity By Appending A Quinone To Ruthenium Polypyridyl Complex, Amy N. James

Chemistry & Biochemistry Undergraduate Honors Theses

By converting natural light energy into chemical energy, chemists are studying ways to take advantage of clean energy. The rising precedence of “green chemistry” has led to academic interest in the activity of photocatalysts and harnessing visible light in an efficient, accessible, and safe manner. Photochemistry is an upcoming and fascinating field of study that has made significant progress, but also has great potential for future work. By utilizing light as a natural energy source, many reaction processes in chemistry can be viewed with a new perspective. Ru(bpy)₃²⁺ is one of the most widely used photocatalysts. An efficient …

The Effects Of Hydrogen Bonding On The Reactivity Of Synthetic Ada Repair Protein Analogues, Josiah G. Elsberg

Boise State University Theses and Dissertations

The study of bioinorganic chemistry is an important field, as it can provide insight as to why Nature has chosen certain active sites and structures within different kinds of metalloproteins. Ada repair protein, a zinc-containing metalloprotein, is one such topic of interest. Although it is known that Ada RP is able to repair methyl-phosphotriester backbone damage by self-methylation of one of its cysteine groups, the mechanism is not fully understood. Two pathways have been proposed: a dissociative pathway where the Zn-S bond becomes a zinc/sulfur ion pair, and an associative pathway where a four ringed σ-metathesis occurs. Previous research has …

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 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 …

Synthesis Of Microgel Polymers As Catalysts, Hannah N. Miller

Chemistry & Biochemistry Undergraduate Honors Theses

New developments in organic synthesis show promise in achieving the best catalytic properties for the hydrolysis of glycosidic bonds through microgel polymers and transition metal complexes. A monomer mix of ethylene glycol dimethacrylate, butyl acrylate, and styrene form miniemulsion polymers after sonication and exposure to UV light. Gravimetrical analysis is used to determine the most suitable polymerization conditions by performing experiments at varying pH values, temperatures, monomer amounts, initiator amounts, and lamp heights. The final data show that the best polymerization conditions are a pH of 10.50 at 0°C with a high monomer ratio, 20% initiator amount, and a lamp …

Curing Of Polymer Thermosets Via Click Reactions, Mark Richard Brei

Dissertations

In the first project, an azide functional resin and tetra propargyl aromatic diamines were fabricated for use as a composite matrix. These systems take already established epoxy/amine matrices and functionalize them with click moieties. This allows lower temperatures to be used in the production of a thermoset part. These new systems yield many better mechanical properties than their epoxy/amine derivatives, but their T_gs are low in comparison.

The second project investigates the characterization of a linear system based off of the above azide functional resin and a difunctional alkyne. Through selectively choosing catalyst the linear system can show …

Synthesis And Characterization Of "Click Inspired" Thiol-Ene-Fullerene Nanocomposites, Amber Danielle Windham

Dissertations

This work explores the covalent incorporation of C₆₀ and Sc₃N@C₈₀ fullerenes into thiol-ene networks by a facile, one-pot photochemical reaction with multifunctional thiol and alkene monomers. Synthesis of disulfide bonds within the tri-functional thiol monomer served to photochemically initiate the reaction when cleaved. This was followed by thermal curing of the pre-polymer for preparation of fullerene-containing thiol-ene films. Films were characterized by standard techniques including infrared spectroscopy, gel percent, and thermogravimetric analysis. The role of C₆₀ and Sc₃N@C₈₀ as suitable alkenes for free-radical reaction with multifunctional thiols was investigated by preparing a …

Synthesis Of Two Monomers For Proton Exchange Membrane Fuel Cells (Pemfcs), Abdulmajeed A. Alayyaf

Electronic Theses and Dissertations

The overall goal of this research is to synthesize two different monomers for proton exchange membrane (PEM) Fuel Cells. Such monomers are proposed to be polymerized to improve the efficiency and compatibility of electrodes and electrolytes in PEM fuel cells.

The first target is to synthesize 4-diazonium-3-fluoro PFSI zwitterionic monomer. Three steps were carried out in the lab. First one was the ammonolysis of 3-fluoro-4-nitrobenzenesulfonyl chloride. Second reaction was the bromination of Nafion monomer. The next coupling reaction, between brominated Nafion monomer and the 3-fluoro-4-nitrobenzenesulfonamide, was failed. The obstacles involve the harsh reaction condition and troublesome purification procedure.

The second …

Synthesis Of Diazonium (Perfluoroalkyl) Arylsulfonimide Monomers From Perfluoro (3-Oxapent-4-Ene) Sulfonyl Fluoride For Proton Exchange Membrane Fuel Cell, Faisal Ibrahim

Electronic Theses and Dissertations

Two diazonium perfluoroalkyl arylsulfonimide (PFSI) zwitterionic monomers, 4-diazonium perfluoro(3-oxapent-4-ene)benzenesulfonimide (I) and 4-(trifluoromethyl)-2-diazonium perfluoro(3-oxapent-4-ene)benzenesulfonimide (II) have been synthesized from perfluoro(3-oxapent-4-ene) sulfonyl fluoride (POPF) for proton exchange membrane fuel cells. PFSI polymers are proposed as new electrolytes due to their better thermal stability, inertness to electrochemical conditions, and lower susceptibility to oxidative degradation and dehydration. For a better integration between the electrode and the electrolyte, the PFSI polymers are expected to be grafted onto the carbon electrode via the diazonium moiety.

All the reaction intermediates and the final product were characterized with 1H NMR, 19F NMR and IR …

Chemoselective Reactions And Their Applications In Metabolite Isolation And Analysis., Sadakatali Shokatali Gori

Electronic Theses and Dissertations

Chemoselectivity is the preferential reaction of a reagent with a select functional group among other plausible reactions. This dissertation describes chemoselective reagents and methods explored to develop more accurate, efficient and high-throughput means to quantify metabolites containing either thiol, carboxylic acid or 1,2-diol moieties directly from biological mixtures. Chapter 1 discusses how dysregulation of thiol- or carboxylic acid-containing metabolites is either the cause or effect of cellular dysfunction. Quantifying such metabolites is important in discovery of pathways to understand etiology of diseases. Chapter 1 also discusses the need for sustainable syntheses using renewable resources and describes the traditional methods for …