Chemistry & Biochemistry
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Item Syntheses and characterizations of homoleptic and heteroleptic copper complexes with monocyclic and polycyclic azine ligands(Dec-23) Kouadio, Halima; Omary, Manal; Mirsaleh-Kohan, Nasrin; Salazar, GustavoThis thesis is concerned with the following ligands to use to coordinate and react to copper: a pyrimidine: niacinamide, the polyazine monocyclic triazine: cyanuric acid, and bicyclic N- donating hydrocarbons: quinoxaline and caffeine. When reacted with cuprous salts consisting of organic ligands they form multi-ligand coordination supramolecular architectures (1) or halides to form copper halide clusters. In the novel compounds, metal-metal interactions occur, which exhibit low-lying triplet state charge transfers, allowing the tunability of a photon-emitting compound which is expected to form the emission. Cuprous metal centers also possess the ability to self-assemble to form coordination polymers. Group 11 d10 coinage metals exhibit strong metal-to-ligand charge transfers (MLCT) as well.(50) Characterization of all compounds was completed using thermogravimetric analysis, X-ray crystallography, Fourier transform infrared spectroscopy (FTIR), and photoluminescence spectroscopy. The acquired data is analyzed and discussed further in the following thesis.Item Identifying chlorhexidine and sodium hypochlorite reaction products and the environmental implications of its interaction with cotton fibers(Dec-23) Huynh, Stacy 1997-; Beatty, John; Salazar, Gustavo; Lin, ShiruChlorhexidine is heavily used in the medical and dental field and is prescribed for multiple uses related to healthcare. When in contact with sodium hypochlorite, chlorhexidine breaks down into several toxic compounds that are not fully understood, and these compounds have impacts on the environment and human health, due to its heavy use in the medical field. Chlorhexidine breaks down into compounds that permanently adhere to and damage the cellulose fibers found in cotton fabrics and alter the visible quality of fabric, which leads to re-washing of fabrics or outright disposal of fabric due to the staining and damage. Chlorhexidine is also used in conjunction with sodium hypochlorite in dental procedures, such as root canals, and the toxic nature of this interaction is not fully understood. Previous studies have identified several products of this reaction, one being para-chloroaniline, suggesting that chlorhexidine should not be used in conjunction with chemical oxidizers like bleach until the toxic products are further studied and identified. Understanding how chlorhexidine interacts with textile fibers like cellulose will save water and cotton fabric from being prematurely disposed of and negatively impacting the environment. This project will work to understand the reaction between chlorhexidine and sodium hypochlorite, the toxic products that result from this reaction, and its interactions with cotton fiber textiles to reduce its impact on health and the environment.Item HPLC analysis to assess efficacy of cisplatin, nedaplatin, and oxaliplatin(Dec-23) Hernandez, Jessica 1990-; Mirsaleh-Kohan, Nasrin; Beatty, John; Salazar, GustavoPlatinum drugs are one of the most widely used agents against cancerous cells. Cisplatin’s chemotherapeutic efficacy is limited by the increase of tumor resistivity and unwanted side effects. Cisplatin’s cytotoxicity is linked to its ability of forming 1,2-intrastrand adducts with adjacent guanine (G) bases. An analytical method to detect and quantify the amount of platinum bound to DNA is necessary to enhance and develop anticancer drugs. In this work, High Performance Liquid Chromatography (HPLC) analysis was performed to assess the binding of cisplatin, nedaplatin, and oxaliplatin to the dinucleotide dGpdG. By examining the concentration ratios and incubation periods at 37 °C, we measured the amount of platinum drug reacted with DNA (platination rates) indicating the percentage of Platinum-DNA (Pt-DNA) adducts. Cisplatin proved to be the most effective, followed by nedaplatin, and then oxaliplatin. This research has implications in designing more efficient anticancer drugs.Item Synthesis and characterization of diverse copper halide complexes with a range of heterocyclic ligands(Dec-23) Diaby, Aminata 1988-; Dr. Manal Omary; Mirsaleh-Kohan, Nasrin; Dr. Richard SheardyThis study aimed to compare the stability, physical, and chemical attributes of Cu(I) and Cu(ACN) metals, investigating their resemblances and disparities. It comprises approximately 137 pages, encompassing 90 figures, 16 tables, and references. The research focused on synthesizing and characterizing Cu(I) complexes with azole family ligands. Two methodologies were applied: the first involving CuI and Cu(CH3CN) (where X = I or CH3CN) reacting with single ligands like 3,5-diisopropylpyrazole, 3,5-diphenolpyrazole, 3,5-(tert)-butylpyrazole, and 5-(4-chlorophenyl)-1H-tetrazole. The second utilized Cu(CH3CN) with mixed ligands specifically 3,5-diphenolpyrazole and pyrazine, as well as 3,5-(tert)-butylpyrazole and pyrazine. Complex synthesis occurred via solvent-mediated routes using the Schlenk technique and solvent-free reactions with mechanical grinding. Comprehensive characterization involved techniques such as melting point determination, solubility tests, luminescence spectroscopy, FT-IR, TGA, elemental analysis, NMR, and X-ray crystallography. Ligands were characterized using the same listed techniques to understand changes. All synthesized products underwent thorough characterization using diverse analytical tools.Item Preparation for college chemistry: high school and college perspectives(1998-05) Wood, KevinItem Synthesis of doxorubicin-protein conjugates via cobalt coordination chemistry(May-23) Colion, Sara; Petros, Robby; Beatty, John; Mirsaleh-Kohan, NasrinThe use of nanotechnology-based drug delivery systems in the context of cancer treatments has the potential to help target drug chemotherapeutics to tumor cells more precisely while simultaneously reducing off-target toxicity. One of the most prescribed chemotherapeutics, doxorubicin, is an anthracyclines drug that is effective in treating cancer; however, the drug exhibits dose-limiting cardiotoxicity. Dox intercalates DNA, resulting in the deterioration of DNA strands and the ultimate inhibition of DNA and RNA synthesis. Doxorubicin’s chemical structure contains a primary amine group that can be used to crosslink it to a protein. This project focuses on using cobalt coordination chemistry as a novel crosslinking strategy to synthesize conjugates of Dox bound human serum albumin (HSA). The synthesis of conjugates of Dox with HSA will be discussed along with methods for characterization via HPLC that allow the number of Dox molecules bound per protein molecule to be determined.Item The synthesis and mass spectral studies of t-butyl(deuterated) thiophenes(1968-06) Fowler, Rosemary; Ludeman, Helen; Foster, Norman; Mecay, WilliamThe synthesis and mass spectral studies of t-butyl (deuterated) thiophenes were undertaken to aid in elucidation of the mass spectral fragmentation routes of the unlabeled t-butylthiophenes. The desired 2-(t-butyl chloride-2H9) thiophene and 3-(t-butyl-2H9 thiophene were synthesized by the interaction of 2-theinylmagnesium bromide and the t-butyl chloride-2H9 forming both the 2- and 3-isomers. The isomers were separated by preparative gas chromatography/ The isotopic purity of the 2-(t-butyl-2H9) thiophene was 96.3% and for the 3-(t-butyl-2H9) thiophene was 96.7%. The 2, 5-di(t-butyl-5-2H9) thiophene and the 2, 4-di(t-butyl-4-2H9) thiophene were synthesized by the interaction of 5-t-butyl-2-thienyl magnesium bromide and the t-butyl chloride-2H9 forming both the 2, 4-isomer and the 2, 5-isomer. The isomers were separated by the preparative gas gas chromatography. The isotopic purity of the 2, 5-di(t-butyl-5-2H9) was 98.7% and the 2, 4-di(t-butyl-4-2H9) thiophene was 95.22% Mass Spectral studies of the 2-(t-butyl-2H9) thiophene and the 3-(t-butyl-2H9) thiophene confirmed the direct losses of methyl-2H9 groups from the t-butyl group. Preferred successive losses of methyl-2H3 groups occurred in the fragmentation of the 2-isomer, whereas loss of the t-butyl group is the preferred fragmentation route in the 3-isomer. Positional substitution is an important influence on the mode of fragmentation of the various isomers. The steric relationships of the t-butyl group to the rest of the molecule differs depending upon the location (2 or 3) of the t-butyl group. The favored interaction between the deuterium of the t-butyl group and the sulfur atom are related to the location of the t-butyl group. Mass spectral studies of the 2, 5-di(t-butyl-5-2H9) thiophene and the 2, 4-di(t-butyl-4-2H9) thiophene confirmed that two successive losses, one of methyl and one of methyl-2H3 occurred. Preferential losses of methyl and methyl-2H3 are favored in the 2, 5-isomer, whereas the loss of a t-butyl group is favored by the 2, 4-isomer to a considerable extent and apparently occurs with almost equal probability from either position. The fragmentation of the 2, 5-isomer differs from the 2, 4-isomer in ion production and in the intensity of the ions formed at high voltage. These differences may be related to the steric effects and the interaction of the deuterium of the t-butyl group with the sulfur atom. Additional study of the existing mass spectral data presented is expected to yield considerable information on the fragmentation pathways. The Friedel-Crafts alkylation of the 2-t-butylthiophene with t-butyl chloride-2H9 yielded 2, 5-di-t-butylthiophene, 2, 5-di(t-butyl-5-2H9) thiophene, 2, 5-di(t-butyl-2, 5-2H18) thiophene, 2, 4-di(t-butyl-2, 4-2H18) thiophene. The Friedal-Crafts alkylation of the 3-t-butylthiophene with t-butyl chlodide2H9 yielded a product containing equal amounts of 2, 4-di(t-butyl-2-2H9)thiophene and 2, 4-di(t-butyl-2-2H9)-thiophene 5-2H1. Studies to elucidate the mechanism of these reactions are in progress.Item Spectrometric studies of 4-substituted phthalic anhydrides and phthalimides(1971-10) Lee, DaisyItem Design and photophysical characterizations of new copper(I) and silver(I) mixed ligand complexes with “green chemistry” incorporation(1/25/2022) Jawaid, Ramsha; Rawashdeh-Omary, ManalThis thesis is a study of mixed ligand coinage metal complexes. It has 122 pages, 68 figures, 14 tables, and the references. It discusses one main project divided by three chapters describing in general the synthesis, structure and spectroscopic studies of silver (I) and copper (I) complexes. Chapter I discusses the introduction to trinculear pyrazolate complexes of d10 coinage metals, N-donor heterocyclic ligands, polycyclic aromatic hydrocarbon ligand, mixed-metal and mixed-ligand complexes. It also investigates the impact of structural factors and various synthetic conditions on photophysical properties as well as the potential applications including sensors for (VOCs), metal-organic frameworks (MOFs), solar cells and organic light emitting diodes (OLEDs). Chapter II involves both solvent-mediated and solvent-less synthetic routes of silver (I) and copper (I) complexes and mixed-metal and mixed-ligand complexes and their characterization through elemental analysis, x-ray crystallography, melting point, photoluminescence, 1H NMR, FT-IR, absorption spectroscopy and thermogravimetric analysis. Chapter III summarizes the conclusion of the results obtained in chapter II and the expected applications of similar compounds in the industry.Item Synthesis of doxorubicin-albumin conjugates via cobalt coordination chemistry: The effect of reaction conditions on overall protein stability(3/30/2022) Patel, Ashik; PETROS, ROBBYThe applications of nanotechnology in designing better treatments shows great promise in lessening the burden of chemotherapy while increasing therapeutic effect. Protein-drug conjugates are a rapidly expanding family of therapeutics that hold potential for ameliorating off-target toxic effects observed in chemotherapy. In this context, human serum albumin could act as a nanoscale delivery vector to alter the biodistribution of attached therapeutics. This research explored the use of cobalt coordination chemistry in the synthesis of Dox- albumin conjugates. Doxorubicin was chosen because it contains a primary amine that could be crosslinked to protein using cobalt coordination chemistry. The effect of pH and reaction time on the synthesis of conjugates was investigated. Samples were characterized by High Performance Liquid Chromatography, Dynamic Light Scattering, and Differential Scanning Calorimetry. Optimized reaction conditions for synthesizing conjugates with varying numbers of dox molecules per protein was a major focus of the research.Item Synthesis of doxorubicin-protein conjugates via cobalt coordination chemistry: Conjugates of transferrin and immunoglobulin G(11/8/2021) Carvajal de Luna, Juan JoseProtein-drug conjugates are a rapidly expanding family of therapeutics that hold significant potential to ameliorate off-target toxic effects commonly observed in patients undergoing chemotherapy. chemotherapy. In this context, the protein acts as a nanoscale delivery vector that alters the biodistribution of the drug upon administration by restricting its unhindered distribution in vivo. This thesis explores the use of cobalt coordination chemistry in the synthesis of doxorubicin-protein conjugates. Previous work has shown that cobalt can be used to crosslink amine-containing molecules in a reversible reaction that only utilizes the lone pair of electrons on nitrogen to form a dative bond with cobalt. Doxorubicin was chosen for initial studies because it contains a primary amine that could be crosslinked with lysine residues on a protein to form a protein-drug conjugate. Conjugates of dox with albumin, transferrin, and immunoglobulin G were investigated to demonstrate the broad applicability of the method for bioconjugation reactions. Drug loading was investigated by HPLC, and the conjugates further characterized by dynamic light scattering, calorimetry, and cytotoxicity. Details of the effects of reaction conditions on synthesis of stable conjugates will be discussed.Item Studies on the E-loop of human glutathione synthetase(9/15/2021) Haynes, Lindsey Cameron; Sheardy, RichardGlutathione (GSH; L-γ-glutamyl-L-cysteinylglycine), an abundant antioxidant, is synthesized intracellularly in two sequential ATP-dependent steps. Human glutathione synthetase (hGS), the second step, ligates γ-glutamylcysteine (γ-GC) to glycine forming GSH. hGS, an obligate homodimer, displays negative cooperativity to the γ-glutamyl-substrate; thus, binding of γ-GC to one subunit decreases its affinity in the second subunit. The recently found E-loop (A210-Q211-E212-K213-E214-R215-N216) is highly conserved (>66%) in mammals; however, only four residues are conserved in other eukaryotes (>49%). E-loop is near the carboxyl of the γ-GC substrate; therefore, we hypothesize it is important for binding and catalysis. Point mutations of these conserved E-loop residues (Q211A, E214S/A, R215A, N216A/V) were prepared (site-directed mutagenesis). After expression, purification and assays, our results show mutations on the E-loop cause changes in activity, γ-GC substrate binding, and negative cooperativity relative to wild-type hGS. Thus, E-loop is crucial to hGS function.Item Synthesis of doxorubicin-ablumin conjugates via cobalt coordination chemistry: The effect of reaction conditions on overall protein stability(7/23/2020) McGhee, Avione; Petros, RobbyPolymer-drug conjugates have become a common tool in therapeutics to reduce the chances of pharmacotoxicity, often seen in patients undergoing chemotherapy, and to enhance targeted drug delivery. The demand for more novel forms of drug delivery has increased the efforts to develop new drug designs. Our research utilizes cobalt coordination chemistry for the synthesis of protein-drug conjugates. More specifically, this researched was aimed at crosslinking human serum albumin (HSA) and Doxorubicin via cobalt coordination chemistry. In a reversible reaction, cobalt can be used to crosslink amine-containing molecules; such as the primary amine contained in Doxorubicin and the lysine residue of HSA, via coordinate covalent bonding. The ultimate goal of this research endeavor is to alter the biodistribution of Dox in vivo to reduce the systemic toxicity of the drug, which displays dose limiting cardiotoxicity. The use of high- performance liquid chromatography (HPLC) and dynamic light scattering (DLS) were used in identifying optimal reaction conditions for the synthesis of an HAS-Dox conjugateItem Characterizing the thermodynamic parameters of anti-cancer drug Carboplatin and DNA through Spectroscopic techniques(6/3/2020) Williams, Sara M; Mirsaleh-Kohan, NasrinSpectroscopic techniques have been employed to understand the interactions and thermodynamic parameters between the anti-cancer drug Carboplatin and the DNA oligomer COTAR 2: ATT AAT GGA TCC ATT AAT. This is a self-complementary sequence that has been previously shown to bind [Co(NH3)2(OH2)2]+3 with high specificity and is of interest because it contains two isolated G-G sites. Both Cisplatin and Carboplatin are known for binding preferentially to G-G sites. These anti-cancer drugs are commonly used in chemotherapeutic treatments and are known to have adverse side effects. In order to improve treatment options, it’s necessary to understand the molecular basis of their interactions with DNA. The binding of Carboplatin with COTAR 2 has been analyzed using Circular Dichroism (CD), Surface−Enhanced Raman Scattering (SERS), and UV-Vis Spectroscopy. The combination of these techniques allows for better understanding of structure and stability of platinum-DNA complexes, as well as binding kinetics. In this thesis, the results of these studies will be presented, and our current understanding of this interaction will be discussed.Item Employing chromatographic and spectroscopic methodologies to monitor DNA response to platinum-based chemotherapeutic drugs(6/16/2020) Wappes, Skylar C; Mirsaleh-Kohan, NasrinIn order to design platinum-based chemotherapeutic drugs that express low toxicity and high efficiency, their nature of interaction with DNA, effectiveness, as well as their mechanisms need to be better understood. This research investigates how Cisplatin, cis-diamminedichloroplatinum (II) and its derivatives, Carboplatin, Nedaplatin, and Oxaliplatin, effect DNA stability and structure. Two sensitive and selective analytical methodologies - Surface-Enhanced Raman Scattering (SERS) and High-Performance Liquid Chromatography (HPLC)- were applied to monitor the key concepts stated above. In this project, it was found that of all the drugs, Carboplatin did not significantly modify the DNA. Even though Carboplatin complexes were made at a 1:2 volume ratio it left more DNA unbound (5% unbound) compared to the other drug complexes which were ran at a 1:1 ratio (<2% unbound). Averaging the drug interactions, Cisplatin and Oxaliplatin left less DNA unbound than Nedaplatin did, but Carboplatin in all HPLC experiments left significantly more DNA unbound. In both SERS and HPLC experiments, Carboplatin modified each DNA less than Cisplatin.Item Synthesis and characterization of various copper halide complexes with pyrazole and pyridine-based ligands(2/26/2020) Alshammari, Nowyer G.; Rawashdeh-Omary, ManalThis thesis covers the following research areas: solvent-mediated, solvent-free synthesis and characterization of copper(I)halide complexes and coordination polymers with various pyrazole-based and pyridine-based ligands, analyzing the photophysical properties, focusing mainly on the luminescence of the copper(I)halide complexes and coordination compounds. It also investigates the impact of structural factors and various synthetic conditions on photophysical properties. This thesis consists of 85 figures, 31 tables, and 127 pages. several different compounds were synthesized in two different synthetic methods: solvent-mediated and solventless with different molar ratios. The characterization of all compounds was done using thermogravimetric analysis, elemental analysis, X-ray crystallography, Fourier transform infrared spectroscopy (FTIR), melting point, electronic absorption spectroscopy, and photoluminescence spectroscopy. The analysis for these data will be discussed in this thesis along with the potential application of similar complexes in the field of industry.Item Syntheses and characterizations of mixed-ligand copper(I/II) and silver(I) complexes and metallopolymers with pyrazolate- and phenanthroline-based ligands and poly(4-vinylpyridine)(12/2/2019) Kolek, Allan; Rawashdeh-Omary, ManalThis thesis focuses on the syntheses and characterizations of heteroleptic Cu(I/II) and Ag(I) complexes and coordination polymers with fluorinated-pyrazolate (FPz-) and phenanthrolines (phen) ligands, followed by that of copper(I) iodide-based Cu(I/II) complexes and metallopolyers with the fluorinated-pyrazolate (FPz-) ligand and poly(4-vinylpyridine) (PVP). Chapter I provides an introduction into the chemistry of homoleptic coinage metal-pyrazolate complexes, pyrazolate ligands, phenanthroline ligands, heteroleptic coinage metal complexes, solventless syntheses, copper(I) halide complexes, and poly(4-vinylpyridine), respectively, followed by the potential applications of coinage metal complexes/coordination polymers with the aforementioned ligands. Chapter II discusses the synthetic routes of the aforementioned Cu(I/II) and Ag(I) complexes and metallopolymers with the respective ligands. Chapter III discusses structural, physical, and photophysical properties of the resulting products. Chapter IV summarizes and concludes the effects of the different synthetic routes, the metal, and the ligand on the resulting products with regard to their aforementioned properties.Item Human glutathione synthetase reaction order and kinetics examined using spectroscopic and calorimeteric techniques(3/4/2019) Stopper, Anna Rachel; Anderson, Mary EGlutathione (GSH) is a tripeptide important in preventing cellular oxidative damage. Human glutathione synthetase (hGS) catalyzes the second stage of GSH biosynthesis. Homodimeric human glutathione synthetase is negatively cooperative with respect to its L-γ-Glu-Cys substrate. Although the allosteric effects of substrates binding to hGS have been studied, the order of substrate binding has not. GS in plants and prokaryotes are reported to exhibit opposing random ter and ordered ter ter reaction orders respectively; currently little is known about the reaction order in humans. Knowledge of the mechanism and reaction order of hGS is vital to understand how it contributes to the regulation of the levels of the limiting amino acid cysteine and of glutathione. Using ITC binding studies the mechanism of action and reaction order of hGS has been evaluated and suggests a semi-ordered reaction in human GS.Item Utilizing solventless and solvent mediated synthesis of novel coordination polymers based on copper bromide / chloride reactions with cyanopyridines(12/2/2019) Alkhazalah, Reyad Madee; Rawashdeh-Omary, ManalThis thesis covers the following research areas: solvent-mediated, solvent-free synthesis and characterization of copper(I)halides complexes and coordination polymers with various of cyanopyridine ligands, analyzing the photophysical properties, focusing mainly on the luminescence of the copper(I)halides complexes and coordination compounds. It also investigates the impact of structural factors and various synthetic conditions on photophysical properties. This thesis consists of 97 figures, 45 tables, and 125 pages. Eight different compounds have been synthesized in two different synthetic routes; solvent- mediated and solventless with various molar ratio. The characterization of all compounds was done by using elemental analysis, X-ray crystallography, melting point, thermogravimetric analysis, Fourier transform infrared spectroscopy (FTIR), electronic absorption spectroscopy, and photoluminescence spectroscopy. The analysis for these data will be discussed in this thesis in addition to the potential application of similar compounds in the field of industry.