Chemistry & Biochemistry Masters Theses

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Diastereoselective Conjugate Radical Additions to ~-Pyrones
(North Dakota State University, 2009) Yu, Arvin Zillion
A convenient protocol for functionalization of ~-pyrones has been developed. Conjugate radical addition and tandem addition-trapping protocols allowed accessing highly substituted pyrones in a single operation with high selectivity. Different radical sources were utilized in the reaction. nOe experiments were performed to confirm the relative stereochemistry of the substituents in the conjugate addition products. Initial studies on the enantioselectivity of the reaction were carried out. Unfortunately, the catalysts chosen for the initial studies did not show any promise regarding enantioselectivity.
Regioselective and Enantioselective Nitrone Cycloadditions to Alkynones.
(North Dakota State University, 2010) Dunkle, Kelsey Lynn
There has been a need in agriculture, medicine, and organic chemistry for enantiopure isoxazolines. A direct method for their synthesis is from the cycloaddition of 1,3-dipoles and alkynes. Alkynones are difficult substrates to use in cycloadditions due to their high reactivity and sometimes instability. Due to their high reactivity it is often difficult to control regio- endo/exo, and enantioselectivities in dipolar cycloadditions of alkynones. This thesis details the cycloadditions of nitrones and alkynones using chiral Lewis acids leading to isoxazolines with high regio-and enantiocontrol. A chiral bisoxazoline-zinc(II) complex successfully catalyzed the enantioselective 1,3-dipolar cycloaddition reaction of nitrone and alkynone derivatives. This is the second successful reported method for the catalytic enantioselective 1,3- dipolar cycloaddition of nitrones and alkynone derivatives. Yields for the cycloadducts were good to near quantitative and enantioselectivities were generally good reaching a high of 86 % ee. The 4-isoxazolines were isolated as single reg101somers.
Interactions of Synthetic Metal Porphyrinates with PhuS, a Cytoplasmic Heme Trafficking Protein from Pseudomonas aeruginosa
(North Dakota State University, 2010) Moberg, Amber Elise
Pseudomonas aeruginosa is an opportunistic, Gram negative, bacterial pathogen that commonly establishes infection in immunocompromised individuals. It contains protein-based, iron uptake pathways that target both heme and nonheme iron sources in the host. When the Pseudomonas heme uptake system is compromised by genetic knockout of the cytoplasmic heme trafficking protein, PhuS, the ability to establish infection is lost. PhuS functions to transfer heme to a heme oxygenase, an 02 dependent heme metabolizing enzyme, so that it can be degraded to a usable form for the organism. Within the long-term goal of developing pharmaceutical agents to inhibit heme uptake by bacterial pathogens, this study aims to evaluate the general thermodynamic parameters of metalloporphyrin binding to PhuS. Two synthetic iron porphyrinates and the Ni(II) complex of protoporphyrin IX have been investigated and their binding constants have been determined. The implications of these results for inhibiting heme uptake will be discussed.
Synthesis and Photophysics of Platinum(II) Terdentate and Bidentate Complexes.
(North Dakota State University, 2010) Yi, Jing
Platinum(ll) terdentate and bidentate complexes possess square-planar d8 configuration. The moderate metal-to-ligand charge-transfer (1MLCT) absorption, 3MLCT emission, and broadband excited-state absorption are the unique spectroscopic features for these complexes. In my thesis work, two series of terdentate platinum(II) complexes and one bidentate platinum(II) complex were designed and synthesized. The photophysical properties, such as the electronic absorption, photoluminescence, and triplet excited-state absorption, are investigated systematically. Chapter I introduced the representative work on the synthesis and photophysical studies of the terdentate and bidentate platinum(II) complexes reported in the literature. The motivation for my thesis project was briefly discussed. In Chapter 2, the synthesis and photophysical properties of two platinum 6-phenyl-4- (9,9-dihcxylfluoren-2-yl)-2,2 '-bipyridine complexes with phenothiazinyl (PTZ) acetylide ligand were discussed. Their UV-vis absorption and emission characteristics in solutions and LB films were systematically investigated. The triplet transient difference absorption and reverse saturablc absorption were also studied for these complexes. Both complexes exhibit a broad metal-to-ligand charge-transfer / ligand-to-ligand charge-transfer / intraligand charge-transfer (1MLCTi1LLCTi11LCT) absorption band between 400 and 500 nm and a 'MLCT/'ILClill",ll"' emission band at -594 nm at room temperature, which blue shifts at 77 K. Both UV-vis absorption and emission spectra show negative solvatochromic effect. Both of the complexes also exhibit broad and moderately strong triplet transient absorption from the near-UV to the near-IR spectral region. In addition, LB films of them were prepared and characterized by AFM technique. The UV-vis absorption and emission spectra of the LB films of them were also investigated and compared with those obtained in solutions. In Chapter 3, the synthesis and photophysical studies of a series of platinum 6-phenyl- 4-(7-benzothiazolyl-9, 9-diethyltluoren-2-yl)-2,2' -bi pyridine complexes with different acetylides ligands, such as, nitrophenyl acetylide, tluorenyl acetylide, and benzothiazolyltluorenyl acetylide, were discussed. The complex bearing nitrophenyl acetylide ligand exhibited quite distinct photophysical properties compared to the other two complexes. In Chapter 4, one platinum bis(mesitylimino)acenaphthene complex was synthesized. The lowest-energy absorption band was attributed to 1MLCT transitions, which was much broader and red-shifted (extending from 490 nm to 800 nm) compared to those reported for other diiminc Pt(II) complexes.
A Metal Catalyzed Approach for Heterocycle Coupling Reactions
(North Dakota State University, 2021) Chhoun, Michael Robert
Heterocycles are cyclic compounds which contain atoms from at least two different elements. The work in this thesis describes methods we developed for the direct chemical transformation of indole heterocycles with various nitrogen heterocycles forming coupled heterocyclic compounds. The first chapter of this thesis introduces background information of the heterocycles worked with on in our research. The chapter will discuss why the synthesis of these compounds are an interesting research topic. The second chapter discusses the research of metal induced transformations of 4(3H)-quinazolinone. Specifically, the work that has been done in the literature to chemically transform these heterocycles. The last chapter will discuss the investigation indole transformations that our group has developed using various reaction conditions. This will lead into discussion of the various methods that were developed by our group, possible mechanistic pathways, and future direction for this project.
VIP Induces Snail1, A Master EMT Regulator: Upregulation in A375 Cancer Cells
(North Dakota State University, 2021) Al-Badrani, Sejaa
VIP is neurotransmitter with pleiotropic functions in mammals. It is expressed by a large number of tissues, including the CNS, PNS, innate and adaptive immune systems. VIP has two endogenous G-protein coupled receptors, termed VPAC 1 and VPAC2. VIP signaling through VPAC1 receptor has been documented to transactivate EGFR in healthy and cancerous cells leading to the activation of multiple downstream signaling pathways. EGFR signaling is a potent inducer of the master regulator EMT, called Snail1, which is a zinc-finger, transcription factor that is associated with downregulating epithelial markers like E-cadherin, while upregulating mesenchymal markers necessary for invasion and metastasis. We hypothesize that VIP upregulates Snail1expression in cancer cells. Our results showed that VIP treatment of epithelial cells increased Snail1 expression transiently at 1h and 4h then returned to basal levels at 24h. This research has implications in development of targeted therapies for cancer.
Palladium-Catalyzed Suzuki-Miyaura Cross-Coupling Reaction of Aromatic Esters and Aromatic Diesters with Arylboronic Acids
(North Dakota State University, 2020) Almowanas, Norah Abdulrahman
The palladium-catalyzed cross-coupling reactions for the functionalization of the ester bond provides a significant overall improvement in the catalytic system as compared to aryl halides/pseudo-halides electrophilic coupling partners. Several pathways have been developed to construct C-C or C-X (-O,-N,-S,&-P) bonds that avoid pre-functionalization, hard reaction conditions, and waste production. These pathways include decarboxylation, decarbonylative, and non-decarbonylative coupling reactions. The non-decarbonylative coupling reaction of aromatic esters with organoboron compounds has emerged as a novel and valuable solution, providing new methodologies and synthetics in organometallic chemistry. More specifically, this type of reaction has shown promising results for synthesizing biaryl compounds and aryl diketones from aromatic esters. This study found that a series of novel aryl ketone and aryl diketone moieties can be formed via a non-decarbonylative Suzuki-Miyaura coupling reaction using readily available and inexpensive starting materials (e.g., phenyl benzoate, 1,4-diphenyl 1,4-benzenedicarboxylate, and 1,3-diphenyl 1,3-benzenedicarboxylate) with aryl boronic acids in the presence of [Pd(IPr)(pi-4-CF3C6H4-C3H5)Cl] precatalysts.
The Development and Use of Chiral 4-Dimethylaminopyridine-N-Oxide as an Organocatalyst
(North Dakota State University, 2018) Joyce, Jesse Jo
Organocatalysis is a field that has bloomed over the last decades. With the field’s promise of being able to mimic nature and afford products in a synergistic manner to traditional Lewis acid catalysis, several interesting discoveries have been made. Owing to the vastness of the field as it exists today, this document will focus on two main aspects; cinchona alkaloid (and derivatives) as used in common carbon-carbon bond forming reactions and kinetic resolution via 4-dimethyl aminopyridine-N-oxide derivative driven acylation. Kinetic resolution via organocatalysis has the potential to react one enantiomer of a racemic mixture without affecting the other. The highlight of this screening was an s factor of 9 which was produced using optimized conditions using a catalyst designated DMAPO-IV. There remains much to do in improving the system and elucidating the scope of this catalytic system this report details the efforts made thus far.
Synthesis and Applications of Dialdehydes
(North Dakota State University, 2018) Grieger, Krystal Dawn
Due to their reactivity and ease of functional group interconversions, aldehydes have wide-ranging applications in polymer synthesis, such as polyacetals, epoxy resins, and polyurethanes. Recently, room temperature synthesis of polycarbamates using cyclohexanedicarboxaldehydes was reported by Dow Chemical, thus opening up a novel way of making non-isocyanate polyurethanes (NIPUs) with greater applicability. However, preparing NIPUs is limited by the available bio-based dialdehydes. Therefore, we prepared a series of bio-derived bis-furan and tris-furan dialdehydes through the condensation of furan with four readily available ketones, with subsequent formylation via the Vilsmeier-Haack reaction. The incorporation of structurally different spacers in otherwise structurally similar dialdehyde monomers resulted in a variety of melting points dependent on the relative symmetry and rigidity of the structures. Chapter 1 addresses the synthesis of aldehydes with a review of their current utility in polymer synthesis. Chapter 2 addresses our synthesis of the dialdehydes and their potential applications in polymer synthesis.
Synthesis of Precursors to Non-isocyanate Polyurethanes
(North Dakota State University, 2018) Wei, Manqing
Biobased diamines are excellent precursors for the synthesis of non-isocyanate polyurethanes (NIPUs). We have prepared several biobased diamines using three different reactions for their synthesis. In the first method, we have carried out chain elongation of cellulose-derived 2,5-diformylfuran by the Henry reaction followed by reduction of the nitroalkene. Yields of the key step: Hantzsch Ester reduction, were 70-80%. Method two involves the Friedel-Crafts alkylation of furfurylamine with different ketones under acidic conditions. Yields of large-scale alkylation reaction were 60-77%. In method three, we combined the Henry reaction and Friedel-Crafts alkylation techniques to access diamines from hemicellulose-derived furfural. These diamines can be reacted with carbonates to access hydroxyalkylcarbamates in good yields, around 80%. We have also developed a novel method for accessing biscarbamates directly from dialdehydes in good yields, 70-94%. The hydroxyalkylcarbamates and biscarbamates are valuable precursors to obtain polyurethanes via the phosgene-free route.
Identification of Aptamer Specific for Carcinoembryonic Antigen and its Analytical Applications
(North Dakota State University, 2017) Lund, Michelle
Carcinoembryonic Antigen (CEA) is an approved cancer biomarker by the Food and Drug Administration (FDA) for the early detection, diagnosis, and for the use in the regular screening of patients at high risk for the development of cancer. Traditional methods to determine the concentrations of CEA are based on utilizing antibodies. In this project, a graphene oxide (GO)–assisted systematic evolution of ligands through exponential enrichment (SELEX) was used to identify DNA aptamers specific for CEA. The dissociation constants of the identified aptamers were determined with surface plasmon resonance (SPR). Comparison of the dissociation constants of aptamers isolated from the GO-based SELEX and affinity SELEX found the dissociation constant of the aptamers isolated from GO-assisted SELEX was three times lower than aptamers isolated from the affinity SELEX. The analytical applications of the identified aptamers were studied by developing a colorimetric test for the determination of CEA with un-modified gold nanoparticles.
Carbon Nanotubes-Based Lateral Flow Biosensor for Sensitive and Rapid Detection of DNA Sequence
(North Dakota State University, 2017) Zhang, Xiaoguang
Sensitive detection for DNA has drawn great attention in plenty of different areas such as genetics therapy and basic discovery research. Recently, nucleic acid lateral flow biosensor (NALFB) has gained considerable attention for DNA analysis. Compared with the traditional immunoassays, NALFB has these advantages: short assay time and a low cost. In this thesis, we report a carbon nanotubes (CNTs)-based NALFB for rapid and sensitive detection of DNA. Amine-modified DNA detection probe was covalently immobilized on the CNTs via diimide-activated amidation between the carboxyl groups on the CNTs surface and amine groups on the detection DNA probes. Sandwich-type DNA hybridization reactions were performed and the captured MWCNTs on test zone and control zone produced the characteristic black bands. Based on the catalytic property of CNTs to enhance the Chemiluminescence intensity of the reaction between hydrogen peroxide and Lumigen APS-5, a rapid detection of DNA sequence with high sensitivity is achieved.
Novel Synthetic Routes to Complex Amines: the Catalytic Hydroamination of Alkynes and Hydroimination of Allenes
(North Dakota State University, 2016) Moran, Erik John
Amines are valuable targets for synthesis in contexts of both research and industrial applications. This work proposes two atom-economical methods—hydroamination (HAM) and hydroimination (HIM)—as C-N bond formation strategies. A nickel-(N-heterocyclic carbene) catalyst system was developed to carry out HAM of internal, unactivated alkynes with aryl amines and cyclic secondary amines. It was demonstrated that the Ni-NHC catalyst was capable of promoting both HAM at room temperature and transfer hydrogenation to produce α-branched aryl amines. These two procedures were performed by the same catalyst to demonstrate an elegant 1-pot, multi-transformation protocol. Separately, optimization of a Rh-HIM catalyst system for the combination of monosubstituted allenes and aromatic N-H-ketimine was carried out to favor high conversion of substrates to the linear HIM product rather than [3+2] annulation. Both HAM and HIM C-N bond formation methods were found to be successful and capable of good conversion and selectivity for their respective products.
Infrared Diode Laser Spectroscopic Study of Combustion Related Kinetics
(North Dakota State University, 2016) Janssen, Erik Lee
In the introduction section background into the subject of combustion chemistry is presented. The topics included are combustion mechanisms, combustion pollutants, and infrared absorption spectroscopy. Chapter two describes experiments that probe the kinetics of the reactions of CN radicals with several small primary alcohols, as well as the product channels of the reaction between the CN radical and methanol. It was found that all studied reactions were fast, and that CN preferentially abstracts the methyl hydrogen from methanol. Chapter three describes a study of the product channels of the reaction of the hydroxymethyl radical with nitric oxide. It was found that the primary product was the adduct, with minor channels yielding isocyanic acid and nitroxyl radicals.
Characterizing the Roles of Exit Tunnel Residues in Ligand Binding and Catalysis of Histone Deacetylase-8
(North Dakota State University, 2014) Gupta, Ruchi
Histone deacetylases are an important class of enzymes that catalyze the hydrolysis of acetyl-L-lysine side chains in histone and non-histone proteins to yield L-lysine and acetate, effecting the epigenetic regulation of gene expression. In addition to the active site pocket, the enzyme harbors an internal cavity for the release of acetate by-product. To probe the role of highly conserved amino acid residues lining this exit tunnel, site-directed alanine substitutions were made at tyrosine-18, tyrosine-20 and histidine-42 positions. These mutants were characterized by various biochemical and biophysical techniques to define the effect of mutations on ligand binding and catalysis of the enzyme. The mutations altered the catalytic activity of HDAC8 significantly. Y18A mutation dramatically impaired the structural-functional aspects of the enzymatic reaction. Our data reveal that there is long range communication between the exit tunnel residues and the active site pocket of HDAC8, presumably regulating the overall catalysis of the enzyme.
Applications of Dithieno [3,2-B2',3'-D] Pyrroles and its Analogues to Conjugated Materials
(North Dakota State University, 2014) Mccausland, Casey B.
The promise of semiconducting materials with tunable electronic and optical properties that share the same mechanical flexibility, low production costs and ease of processing displayed by traditional polymers fuels the intense interest seen in developing devices employing conjugated polymers (CPs). Many examples of -conjugated systems have been studied and reported in the literature, of which Rasmussen and coworkers have advanced the field with their work involving N-alkyl, N-aryl, and N-acyl-dithieno[3,2-b:2',3'-d]pyrroles (DTPs). Using DTP as a template current investigations are targeting two analogues: pyrrolo[3,2-d:4,5-d’]bisthiazole (PBTz) and difuro[3,2-b:2’,3’-d]pyrroles (DFP). In comparison to polymers of DTP, the electron-deficient nature of thiazoles is known to stabilize HOMO levels of PBTz-based polymers. Furan-based oligomers exhibit many of the properties displayed by DTPs and it is a reasonable assumption that the properties of DFPs would be comparable to DTPs. The synthesis and characterization of PBTz and DFPs and a comparison to DTP-based materials will be presented.
Identification of Novel RPA-Protein Interactions Using the Yeast Two Hybrid Assay and Identification of Regions Important for Interaction Between RPA and Rad24
(North Dakota State University, 2013) Piya, Gunjan
Replication Protein A (RPA) [Replication Factor A (RFA) in yeast] is an ssDNA binding protein composed of Rpa1, Rpa2, and Rpa3 and involved in numerous DNA processing pathways such as Replication, Recombination, and Repair. It participates in such diverse pathways by its ability to interact with numerous proteins. The goal of my project was to find novel RPA-protein interactions using the yeast two hybrid assay. Using this method, we identified several known and unknown proteins that interact with Rfa1 and showed that these interactions were dependent on the phosphorylation state of Rfa2. Next, we determine the region important for interaction between Rfa1 and Rad24. Rad24 is a checkpoint protein important for initiation of the DNA damage checkpoint signaling. By using the β- galactosidase assay, we determined the N-terminal region of Rfa1 (DBD-F) and the C-terminal region of Rad24 (460-660 aa) to be necessary for their interaction.
Supramolecular Functionalization of Single-Walled Carbon Nanotubes
(North Dakota State University, 2013) Yilmaz, Baris
Single-walled carbon nanotubes (SWNTs) possess extraordinary mechanical strength, thermal and electrical conductivity. These properties make them very attractive in many applications in the fields of nanotechnology, electronics, and optics. However, most of the SWNT syntheses methods result in different types of chiralities, which determine the electronic and optical properties of the sample. Thus, it is important to selectively solubilize and purify carbon nanotubes if one wants to use them in technological applications. Selective separation of SWNTs by chirality has been the research focus of many scientists. Here, a comparative study for the solubility of SWNTs with polyaromatic hydrocarbons and conjugated polymers was conducted. PEGylated corannulene derivative has been shown to disperse more metallic nanotubes than the commonly used sodium dodecyl sulfate dispersant. Phthalimide containing conjugated materials were found to be effective in solubilizing SWNTs. In addition, the structural and mechanistic implications for high solubility power were discussed for all dispersants.
Developing Platform Chemicals from Renewable Resources
(North Dakota State University, 2013) Wojciechowski, Kristin Lynn
The Department of Energy has listed 5-hydroxymethylfurfural (HMF) and 2,5-furandicarboxylic acid (FDCA) as two of the twelve building blocks derived from cellulosic biomass. HMF can serve as a renewable platform for the production of fuels and chemicals. Our research goal is to develop novel methods for the conversion of renewable resources to feedstock chemicals for polymer synthesis. The Diels-Alder reaction, the cycloaddition of alkenes and dienes, has become one of the most important synthetic methods used in organic chemistry. We were interested in carrying out Diels-Alder reactions with derivatives of HMF. Naphthalene analogs of terephthalic acid were synthesized by reacting HMF derivatives with benzyne which could lead to the formation of bio-based polyethylene terephthalate (PET) analogs.

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