Digital Commons Network^™

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 …

Zn(Ii), Cu(Ii), Sn(Ii), And Ni(Ii) And Other Metal Cations Do Not Prevent The Aggregation Of Hiapp, Charles Hoying

Honors Thesis

The Zn(II) metal ion has been shown to interact with Islet Amyloid Polypeptide (IAPP), a protein implicated in the progression of Type II Diabetes Mellitus, in such a way as to prevent the protein from aggregating into toxic fibers. We set out to find whether other metal ions might similarly prevent IAPP aggregation. Using Thioflavin T (ThT) spectroscopic assays, which measure fluorescence of ThT upon binding to aggregated IAPP, we observed a decrease in aggregation when incubated with Zn(II), Cu(II), Ni(II), and Sn(II). Atomic Force Microscopy (AFM), which can visualize fibril formation, revealed that the metals were not inhibiting IAPP …

A Direct Mechanism Of Ultrafast Intramolecular Singlet Fission In Pentacene Dimers, Eric G. Fuemmeler, Samuel N. Sanders, Andrew B. Pun, Elango Kumarasamy, Tao Zeng, Kiyoshi Miyata, Michael L. Steigerwald, X.-Y. Zhu, Matthew Y. Sfeir, Luis M. Campos, Nandini Ananth

Publications and Research

Interest in materials that undergo singlet fission (SF) has been catalyzed by the potential to exceed the Shockley–Queisser limit of solar power conversion efficiency. In conventional materials, the mechanism of SF is an intermolecular process (xSF), which is mediated by charge transfer (CT) states and depends sensitively on crystal packing or molecular collisions. In contrast, recently reported covalently coupled pentacenes yield ∼2 triplets per photon absorbed in individual molecules: the hallmark of intramolecular singlet fission (iSF). However, the mechanism of iSF is unclear. Here, using multireference electronic structure calculations and transient absorption spectroscopy, we establish that iSF can occur via …

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

The Evolution Of The Surface Of The Mineral Schreibersite In Prebiotic Chemistry, Nikita L. La Cruz, Danna Qasim, Heather Abbott-Lyon, Claire Pirim

Faculty Articles

We present a study of the reactions of the meteoritic mineral schreibersite (Fe,Ni)3P, focusing primarily on surface chemistry and prebiotic phosphorylation. In this work, a synthetic analogue of the mineral was synthesized by mixing stoichiometric proportions of elemental iron, nickel and phosphorus and heating in a tube furnace at 820 °C for approximately 235 hours under argon or under vacuum, a modification of the method of Skála and Drábek (2002). Once synthesized, the schreibersite was characterized to confirm the identity of the product as well as to elucidate the oxidation processes affecting the surface. In addition to characterization of the …

Dynamics Of Prebiotic Rna Reproduction Illuminated By Chemical Game Theory, Jessica Anne Mellor Yeates, Christian Hilbe, Martin Zwick, Martin. A. Nowak, Niles Lehman

Chemistry Faculty Publications and Presentations

Many origins-of-life scenarios depict a situation in which there are common and potentially scarce resources needed by molecules that compete for survival and reproduction. The dynamics of RNA assembly in a complex mixture of sequences is a frequency-dependent process and mimics such scenarios. By synthesizing Azoarcus ribozyme genotypes that differ in their single-nucleotide interactions with other genotypes, we can create molecules that interact among each other to reproduce. Pairwise interplays between RNAs involve both cooperation and selfishness, quantifiable in a 2 × 2 payoff matrix. We show that a simple model of differential equations based on chemical kinetics accurately predicts …

Innovative Synthesis Of Diltiazem/Clentiazem Analogs, Emelyn Magtanong

Journal of Interdisciplinary Undergraduate Research

Cardiovascular disease defines disorders of the heart and blood vessels, and is the number one cause of death in America. Diltiazem and clentiazem are common calcium channel blockers incorporated into drugs used to treat various cardiovascular diseases. Methods to synthesize 5-[2-(dimethylamino)ethyl]-8-hydroxy-2,3,4,5-tetrahydro-1,5-benzothiazepin-4-one, an analog of the core of diltiazem and clentiazem, using cost-efficient starting materials allows for affordable treatment and increased availability to affected individuals. N-(N,N-dimethylethanamine)-4-aminophenol can be oxidized to form a quineoneimine, which can be further reacted with 3-mercaptopropionic acid via Michael addition. Subsequent addition of a coupling reagent, N,N'-dicyclocarbodiimide (DCC),¹ produces 5-[2-(dimethylamino)ethyl]-8-hydroxy-2,3,4,5-tetrahydro-1,5-benzothiazepin-4-one, analogous to the core …

Enhancing The Reduction Potential Of Quinones Via Complex Formation, Binod Nepal, Steve Scheiner

Chemistry and Biochemistry Faculty Publications

Quantum calculations are used to study the manner in which quinones interact with proton-donating molecules. For neutral donors, a stacked geometry is favored over a H-bond structure. The former is stabilized by charge transfers from the N or O lone pairs to the quinone’s π* orbitals. Following the addition of an electron to the quinone, the radical anion forms strong H-bonded complexes with the various donors. The presence of the donor enhances the electron affinity of the quinone. This enhancement is on the order of 15 kcal/mol for neutral donors, but up to as much as 85 kcal/mol for a …

Conversion Of Cafo Manure Into A Slow-Release Fertilizer, Richard Allan Williams Iii

Honors Projects

Alginate polymer is known to form gel through the process of Ionotropic gelation. By use of extrusion and diffusion setting manure was encapsulated into gel beads. These beads were then tested to determine their potential for further testing as a manure treatment process. From the limited data in this preliminary study, it appears as though there is potential for further testing of alginate beads as a treatment process for manure. The treatment is potentially valuable because of the ease of filtration of the alginate beads, the low cost of transportation of the dehydrated beads, and because the limited data suggests …

Wrinkled1 Rescues Feedback Inhibition Of Fatty Acid Synthesis In Hydroxylase-Expressing Seeds, Neil D. Adhikari, Philip D. Bates, John Browse

Faculty Publications

Previous attempts at engineering Arabidopsis (Arabidopsis thaliana) to produce seed oils containing hydroxy fatty acids (HFA) have resulted in low yields of HFA compared with the native castor (Ricinus communis) plant and caused undesirable effects, including reduced total oil content. Recent studies have led to an understanding of problems involved in the accumulation of HFA in oils of transgenic plants, which include metabolic bottlenecks and a decrease in the rate of fatty acid synthesis. Focusing on engineering the triacylglycerol assembly mechanisms led to modest increases in the HFA content of seed oil, but much room for …

Energy Transfer And Localization In Molecular Crystals, Mitchell A. Wood

Open Access Dissertations

With the aim of developing new technologies for the detection and defeat of energetic materials, this collection of work was focused on using simulations to characterize materials at extremes of temperature, pressure and radiation. Each branch of the work here is collected by which material response is potentially used as the detectable signal.

Where the chemical response is of interest, this work will explore the possibility of non-statistical chemical reactions in condensed-phase energetic materials via reactive molecular dynamics (MD) simulations. We characterize the response of three unique high energy density molecular crystals to different means of energy input: electric fields …

Rhenium(I) Complexes Of Tetraazatetrapyridopentacene (Tatpp): Synthesis, Characterization, Reactivity, Anticancer Potential And Luminescent Probe To Determine Cellular Localization, Pooja Ahuja

Chemistry & Biochemistry Dissertations - Archive

The ruthenium polypyridyl complexes [(phen)2Ru(tatpp)Ru(phen)2]4+ ([P]4+) and [(phen)2Ru(tatpp)]2+ ([MP]2+) are promising anti-tumor agents that arrest H358 NSCLC tumor growth in mouse tumor models and show cytotoxicity in the low micromolar range towards a number of platinum sensitive NSCLC lines (H358, H226, HOP62, H2087). Dose escalation toxicity studies in mice reveal that [MP]2+ and [P]4+ are tolerated without any short term side effects at levels up to 40 mg drug/kg mouse and >160 mg drug/kg mouse respectively with no obvious side effects, when administered as IP injection. Mechanistic studies reveal that much of the anti-tumor activity is primarily due to the …

Application Of Novel Heterosubstituted Vinylimidazoles: An Approach En Route To The Total Synthesis Of Axinellamine A, Abhisek Ray

Chemistry & Biochemistry Dissertations - Archive

Our group is primarily interested in the total synthesis of oroidin-based pyrrole-imidazole-containing marine sponge-derived alkaloids. These pyrrole-imidazole natural products are a growing class of alkaloids with exotic connectivity, unique topologies, and high nitrogen content. Presence of 2-aminoimidazole and pyrrolecarboxamide fragments in the structure represent their signature features. Due to their structural diversity and biological activity, many groups are interested in the total synthesis of these natural products. It has been proposed that many of the alkaloids in this family are produced in nature by dimerization of the simplest member, oroidin. In this dissertation we have explored a biosynthetic hypothesis disclosed …

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 …

Increasing Solubility Of Active Pharmaceutical Ingredients In Topical Creams Using Soluplus®, Roni Balzam

Graduate Theses/Dissertations

More than 40% of new chemicals developed in the pharmaceutical industry have poor solubility in aqueous solutions. Active Pharmaceutical ingredients (API) cannot reach their molecular targets in the body if the drug remains undissolved in the gastrointestinal system. One way to approach this problem is by using solubilizing agents. One such agent is a thermo-responsive, tri-block co-polymer which is marketed as “Soluplus®" (SP) by BASF Corporation. A part of this project is to thoroughly characterize various phase properties of SP such as cloud points and gel points temperatures. In current application, SP was incorporated into the creams formulations as an …

Increased Hydride Transfer Rates Within T09a Mutant Of F420:H2 Nadp+ Oxidoreductase, Md Hasmat Ullah

Chemistry & Biochemistry Theses - Archive

F420:H2 NADP+ oxidoreductase (Fno) is an F420 dependent enzyme found in methanogens and sulfate reducing archaea. Fno catalyzes the reversible reduction of NADP+ to NADPH through the transfer of a hydride involving F420 cofactor. The focus of our work is to study the hydride transfer mechanism of Fno from Archaeoglobus fulgidus using site directed mutagenesis, steady-state and pre steady-state kinetic methods. Threonine 09 (T09) is a conserved residue within Fno. The hydroxyl (–OH) group of T09 interacts with the phosphate and ribose of neighboring NADPH. Therefore, T09 was converted into an alanine (T09A) to study its functionality within Fno and …

E56h + E59h Mutation Affects Binding Of The Recombinant Haemphilus Influenza Carbonic Anhydrase To A Ni-Nta Column, Eric D. Lebel, Kathleen Cornely

Chemistry & Biochemistry Student Scholarship

The Haemophilus influenzae carbonic anhy- drase (HICA) is important in converting carbon dioxide to bicarbonate in bacteria. Endogenous cellular proteins, like Escherichia coli carbonic anhydrase (ECCA), have been observed to bind to a Ni-NTA column, which can be used as a means of protein purification. The possibility ex- ists that proteins that do not normally bind to Ni-NTA, like HICA, can be engineered using site directed mutagenesis to introduce histidine resi- dues that would give the protein the capability to bind, allowing for a one-step purification method. Site-directed mutagenesis was used to introduce the double mutation of E56H + E59H …

Role For Reactive Oxygen Species In Methamphetamine Modulation Of Dopamine Release In The Striatum, David Matthew Hedges

Theses and Dissertations

Methamphetamine (METH) is a highly addictive substance that is highly prevalent in today’s society, with over 1 in 20 adults over 26 having taken it at least once. While it is known that METH, a common psychostimulant, acts on both the mesolimbic dopamine (DA) and nigrostriatal DA systems by affecting proteins involved in DA reuptake and vesicular packaging, the specific mechanism of what is known as METH neurotoxicity remains obscure, but has been shown to involve oxidative stress. Studies have shown that reactive oxygen species act on the same proteins that METH affects. Oxidative species have also been known to …

An Analysis Of Environmentally-Persistent Free Radical Formation On Surrogate Soil Systems Containing Iron(Iii) And Copper(Ii) And The Potential Remediation Effects Of Laccases, Andrew Paul Mullet

Honors Capstones

No abstract provided.

The Effects Of Heavy Metals And Microbes On Extracellular Enzyme Activity At Liberty State Park, Eleanor Urenna Ojinnaka

Theses, Dissertations and Culminating Projects

The overall goals of this research were to 1) understand the influence of microbes and heavy metals on extracellular enzyme activity in soil environments and 2) explore the possibility of using living organisms, such as microbes, to improve the enzyme activity of contaminated, poor-functioning soil—bioremediation. Microbes exude enzymes into the soil, which are vital in the cycling of nutrients in soil communities. Thus, measuring extracellular enzyme activity can be used to quantify the health of soil. In this experiment, phosphatase enzyme was measured as a proxy for enzyme activity. The study site is a closed-off section of Liberty State Park …

Expression, Purification, Enzymatic And Inhibition Profile Of Brugia Malayi Dihydrofolate Reductase, Romy Perez-Abraham

Theses, Dissertations and Culminating Projects

Dihydrofolate reductase (DHFR) is an essential enzyme that plays an important role in the production of cofactors that are required in deoxyribonucleic acid (DNA) synthesis. The literature suggests that DHFR is a potential drug target for the elimination of the parasitic worm, B. malayi. B. malayi is one of the causative parasites of lymphatic filariasis, a globally neglected tropical disease. In this study, we expressed and purified B. malayi DHFR. Expression was carried out in E. coli with a His6-tagged construct, and purification was achieved through affinity chromatography using a special strain of E. coli cells called “LOBSTR.” The resulting …

Evaluating The Role That A Putative Fxiii Binding Site Plays In The Reactivity Of Three Glutamines Within The Coagulation Substrate Fibrinogen Aα (233-425)., Chad A. Stephens

College of Arts & Sciences Senior Theses

Formation of a stable thrombus in vivo depends on the interaction between fibrinogen and the transglutaminase factor XIII (FXIII). Characteristics of blood plasma, such as concentration of Ca2+, are well known to regulate the activation and subsequent reactivity of FXIII. Despite this knowledge, the role fibrin(ogen) plays in modulating FXIII activation and reactivity is not entirely delineated. Currently, the coagulation substrate fibrinogen Aα is proposed to contain a binding site for the active factor XIII with fibrinogen Aα E396 serving a major role. A series of mass spectrometry and NMR spectroscopy studies was conducted to assess whether putative interactions between …

Mechanism And Use Of Paired Ion Electrospray Ionization (Piesi) In High-Performance Liquid Chromatography-Mass Spectrometry (Hplc-Ms) For Sensitive Analysis Of Anionic Compounds, Hongyue Guo

Chemistry & Biochemistry Dissertations - Archive

In recent years, the paired ion electrospray ionization (PIESI) technique has been emerged as a promising alternative to overcome the inherent low sensitivity of negative ESI-MS. The current research focused on the further understanding of the mechanism of the enhanced sensitivity in PIESI based on previous studies, as well as novel applications of PIESI in sensitive and selective analysis of challenging anionic compounds. Specifically, this dissertation describes research in two areas: 1) The mechanism of PIESI in sensitive detection of anions was further investigated using two rational designed surface-active ion-pairing reagents. As compared to their corresponding non-surface-active ion-pairing reagents, the …

Highly Fluorinated, Coinage Metal Complexes Of Tris(Pyrazolyl)Borates With Additional Electron Withdrawing Groups And Pyrazolate Π-Stackings With Arenes, Naleen Bandupriya Jayaratna

Chemistry & Biochemistry Dissertations - Archive

Tris(pyrazolyl)borates are very popular ligands in inorganic chemistry, bioinorganic chemistry, and organometallic chemistry due to their attractive properties. It is possible to extensively modify the steric and electronic properties of these ligands by changing the pyrazolyl substituent groups. Taking into account the importance and current interest of fluorinated tris(pyrazolyl)borates and weakly coordinating anions in general, three new tris(pyrazolyl)borates, [HB(4-Cl-3,5-(CF₃)₂Pz)₃]-, [HB(3,4,5-(CF₃)3Pz)₃] and [HB(4-(NO₂)-3,5-(CF3)₂Pz)₃]- have been developed (Pz = pyrazolyl). Silver alkene adducts of the ligands have been isolated to evaluate the electronic properties of the ligands and to study their catalytic properties. These adducts found to be the most electron deficient …

Investigation Of The Tandem Alkylation-Cyclization Of Endocyclic Enol Ethers For The Preparation Of Unusual Oxygen Heterocycles, Sarah Mehdi

Renée Crown University Honors Thesis Projects - All

The purpose of this research is to study the alkylation and subsequent cyclization reaction of endocyclic enol ethers such as 2H-dihydropyran. This sequence is expected to yield oxygen heterocycles whose structures represent unique scaffolds with promising functionality.

A series of trichloroacetimidates were selected for the direct alkylation of 2H-dihydropyran. Following the alkylation, the addition of acid was expected to induce an intramolecular cyclization reaction that would yield the desired oxygen heterocycles. This stepwise scheme would then be converted into a tandem process in which the reaction would be expected to proceed in a single pot.

Studies showed that the alkylation …

Ruthenium Hydride Catalyzed Silylvinylation Of Terminal And Internal Alkynes And Synthesis Of Poly(Trimethylenecarbonate) And Poly(Dimethylacrylamide) Block Copolymer, Alec Beaton Jr.

Renée Crown University Honors Thesis Projects - All

Various propargyl alcohols were synthesized via Grignard reactions. These alkynic alcohols are tethered with dimethyl and biphenyl silicon tethers. These terminal alkyne substrates are reacted with RuHCl(CO)(H₂IMes)(PPh₃) as a catalyst under high pressure (80 psi) ethylene atmosphere to afford the 5-exo-dig trans-silylvinylation product in poor yield. Internal alkyne substrates are found to be much more efficiently transformed into the silylvinylation product, favoring one cycloisomer product over the other.

Comparing The Quantitation Of Opiates From Possible Drug Overdose Cases Using Results Of Blood Analysis And Liver Analysis, Lee Ann Garozzo

Forensic Science Theses

Currently the quantitation of opiates at the Erie County Medical Examiner’s Office Toxicology Laboratory is conducted through whole blood analysis. The objective of this thesis project was to determine if the analysis of opiates could be conducted through liver analysis, and if the analysis of opiates would provide a more accurate quantitation compared to the blood analysis. The quantitation of opiates was conducted from the livers of sixty-four possible overdose cases that were brought into the Erie County Medical Examiner’s Office between 2013 and 2015. Results showed that the opiate drugs could successfully be quantitated using the liver analysis. Generally …

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 …