Chemistry Commons^™

Polymeric Porphyrins As Solar Photocatalysts, Nicholas Upton Day

Dissertations and Theses

Research concentrated on the absorption, transformation, and storage of light energy is useful for the energy challenges faced by humanity. In particular, photocatalysis using solar energy to generate useful fuels has become a primary research goal in the drive to replace fossil fuels for the future. In this dissertation it is shown that poly-tetra(4-aminophenyl)porphyrin (pTAPP) can be oxidatively polymerized using a variety of methods, including electropolymerization, chemical oxidation, and interfacial polymerization and that pTAPP has photocatalytic ability to reduce O₂ to H₂O₂ for a storable fuel.

Organic conductive polymers such as pTAPP are attractive catalysts because …

Design And Synthesis Of Novel Chloroquine-Based Antimalarials, Kevin Vincent Murphy

Dissertations and Theses

Malaria is an infectious, often fatal disease that afflicts nearly 200 million people every year. The disease, characterized by recurring and extreme flu-like symptoms, is caused by the protozoan parasite Plasmodium falciparum. Victims usually contract the disease through a mosquito vector. Chloroquine is a chemotherapeutic that was introduced in the 1940s. For many years the drug was the foremost treatment of malaria, being effective and producing few side effects. Unfortunately, tolerance to chloroquine developed when the parasite evolved a resistance mechanism. Newer drugs have been developed and implemented, but these medicines also show a decreasing effect with continued administration. …

Antimalarial Drug Discovery Using Triazoles To Overcome Chloroquine Resistance, Elias Sibhatu Tesfaselassie

Dissertations and Theses

Malaria is considered as one of the most prevalent and debilitating diseases affecting humans. Plasmodium falciparum is the most virulent form of the parasite which developed resistance to several antimalarial drugs. Chloroquine is one of the most successful antimalarials developed that is safe, effective, and cheap. However, its use has been limited due to the emergence of drug resistance. Click chemistry, particularly, the copper(I)-catalyzed reaction between azides and alkynes has shown to have a cutting-edge advantage in medicinal chemistry by its reliability, selectivity and biocompatibility.

Triazole-based antimalarials were synthesized via copper(I)-catalyzed alkyne-azide cycloaddition reaction by modifying the aliphatic chains terminal …

Rational Design Of Materials For The Protection Of Outdoor Metalworks, Natasja Alexandria Swartz

Dissertations and Theses

Protective coatings are commonly used to protect culturally significant works, such as outdoor sculptures and architectural elements. Given the valuable nature of such metalworks, there is a surprising lack of environmentally sustainable coatings available for their conservation. High performance clear coatings are not developed or thoroughly tested for compatibility and longevity on outdoor sculptures. This can make the implementation of both methods and materials, no matter how promising in a lab, a significant hurdle for the conservation science community. This dissertation work initially aims to replace high-VOC formulations such as acrylic lacquers and waxes currently used as protective coatings for …

The Influence Of Surface Chemistry On The Photoelectrochemical Properties Of Fes(2) Photoanodes, Qi Tong

Dissertations and Theses

The recurring theme of this dissertation is the correlation between FeS₂ surface chemistry and key electrical and electronic properties of FeS₂. Efforts have been made to identify and characterize the FeS₂ surface, investigate the photoelectrochemistry of FeS₂ photoanodes under anhydrous and anoxic conditions, and investigate the influence of deliberate surface chemistry on FeS₂ photoelectrochemistry.

Infrared reflection-absorption spectroscopy (IRRAS) was used to investigate a thin adsorbate layer on pyrite. The results showed that the combination of angle-dependent studies and computational efforts are a powerful tool for characterizing the pyrite surface.

The photoelectrochemistry of FeS_{2 …}

Characterization, Dna Binding And Cleavage Activities Of New Prodigiosin And Tambjamine Analogues And Their Cu²⁺ And Zn²⁺ Complexes, Karen Chichetu

Dissertations and Theses

Prodigiosins and tambjamines are natural compounds from bacterial and marine sources belonging to a family containing a common 4-methoxy-2,2'-bipyrrole core. These compounds have received a lot of interest due to their promising biological activities. Studies have suggested DNA as a potential therapeutic target for the natural prodigiosin and tambjamine due to their ability to facilitate oxidative DNA cleavage in the presence of Cu²⁺. Based on this we sought to study the metal binding activity of new prodigiosin and tambjamine analogues. A new prodigiosin analogue was synthesized and complexed with Cu²⁺. This revealed 1:1 complex formation between …

Steps Towards Deciphering The Post-Polyketide Synthase Tailoring Steps In The Phoslactomycin Biosynthesis Pathway, Patience Marimo

Dissertations and Theses

Phoslactomycins (PLMs) are a group of natural products belonging to a polyketides class. These polyketides are synthesized by sequential reaction catalyzed by a collection of enzymes activities called polyketide synthases. A polyketide is a large class of diverse compounds that are characterized by more than two carbonyl groups connected by single intervening carbon atoms. In other words, a polyketide is a polymer whose monomer is a ketide. The PLMs are also known as phosphazomycins or phospholines. These compounds were isolated based on antifungal and antitumor activities. This array of promising biological activities has stimulated research into the field of PLMs …

Development Of An Optical Method For The Detection Of Homocysteine As A Disease Biomarker Using Fluorescein-Aldehydes, Aabha Barve

Dissertations and Theses

Homocysteine is a natural occurring aminothiol. It is an intermediate product in the metabolism of methionine. Methionine is an essential amino acid required for protein synthesis. Metabolic irregularities disrupt homocysteine levels in plasma. Elevated homocysteine levels are directly linked to folate and cobalamin (vitamin B12) deficiencies, and are an independent risk factor for cardiovascular diseases. High homocysteine levels have also been associated with Alzheimer's, osteoporosis, renal failure, cancer, birth defects and pregnancy complications. The association of elevated homocysteine levels with cardiovascular disease and other diseases has generated great interest in the detection of homocysteine.

An optical method for the detection …

Facile Methods For The Analysis Of Lysophosphatidic Acids In Human Plasma, Jialu Wang

Dissertations and Theses

Lysophosphatidic acid (LPA) influences many physiological processes, such as brain and vascular development. It is associated with several diseases including ovarian cancer, breast cancer, prostate cancer, colorectal cancer, hepatocellular carcinoma, multiple myeloma atherosclerotic diseases, cardiovascular diseases, pulmonary inflammatory diseases and renal diseases. LPA plasma and serum levels have been reported to be important values in diagnosing ovarian cancer and other diseases. However, the extraction and quantification of LPA in plasma are very challenging because of the low physiological concentration and similar structures of LPA to other phospholipids. Many previous studies have not described the separation of LPA from other phospholipids, …

Spectroscopy, Nmr, And Electrochemistry Studies Of Protonated Aminophenyl/Pyridyl Porphyrins And Their Application In Hydrogen Evolution, Chenyi Wang

Dissertations and Theses

Spectrophotometric titrations for a full series of 4-aminophenyl/4-pyridyl meso-substituted porphyrins were carried out using methanesulfonic acid in DMSO to study the hyperporphyrin effect across different substitution patterns. The series included zero, one, two (cis and trans), three, and four meso(4-aminophenyl) groups, with the remaining meso substituents being 4-pyridyl groups. The peripheral pyridyl groups consistently protonate before the interior porphyrin pyrrole nitrogens, which protonate before the aminophenyl groups. Aminophenyl substituents increase the basicity of the pyrrole nitrogens and lead to distinctive hyperporphyrin spectra with a broad Soret band and a strong red absorption. The structure proposed to give rise to these …

Enzymatic Control Of The Related Pathways Of Fatty Acid And Undecylprodiginine Biosynthesis In Streptomyces Coelicolor, Renu Singh

Dissertations and Theses

Streptomyces coelicolor produces fatty acids for both primary metabolism and for production of the components of natural products such as undecylprodiginine. Primary metabolism makes the longer and predominantly branched-chain fatty acids, while undecylprodiginine utilizes shorter and almost exclusively straight chain fatty acids. The first step in fatty acid biosynthetic process is catalyzed by FabH (β-ketoacyl synthase III), which catalyzes a decarboxylative condensation of an acyl-CoA primer with malonyl-acyl carrier protein (ACP). The resulting 3-ketoacyl-ACP product is reduced by NADPH-dependent FabG into 3-hydroxyacyl-ACP, which is dehydrated by FabA to form enoyl-ACP. The NADH-dependent FabI (InhA) completes the cycle. Subsequent rounds of …

Degradation Of Carbon Tetrachloride Using Hydrophobic Green Rust, Sheena Bowman

Dissertations and Theses

Hydrophobic green rusts (GR) were produced using aerial oxidation of solutions containing bis (2-ethylhexyl) sulfosuccinate (BIS) and sodium N-lauroylsarcosinate (SNLS), iron (II) sulfate and sodium hydroxide. The synthesis was conduced at constant pH 8.0±0.1 for the duration of 1-3 hrs. Partition tests showed GRBIS and GRSNLS suspended in the organic phase (tetrachloroethylene). Through X-ray diffraction analysis both GRs exhibit similar patterns to Green Rust II, an inorganic form of GR. The kinetics of GR reductive dechlorination of carbon tetrachloride (CT) was investigated. CT at high concentrations was degraded at high percentages for GRBIS-3, 88.5% and GRSNLS-5, 97.6%. Their reactions were …

New 4-Aminoquinoline Compounds To Reverse Drug Resistance In P. Falciparum Malaria, And A Survey Of Early European Antimalarial Treatments, Katherine May Liebman

Dissertations and Theses

Intermittent fevers caused by Plasmodium parasites have been known for millennia, and have caused untold human suffering. Today, millions of people are afflicted by malaria each year, and hundreds of thousands die. Historically, the most successful synthetic antimalarial drug was chloroquine, as it was safe, inexpensive, and highly efficacious. However, plasmodial resistance to chloroquine now greatly limits its utility. Previously in our laboratories it has been shown that attachment of a "reversal agent moiety" to the side chain of chloroquine can result in the restoration of activity against chloroquine-resistant strains of P. falciparum malaria. In the first part of the …

Selective Indicators For Optical Determination Of Disease Biomarkers, Lovemore Hakuna

Dissertations and Theses

The most abundant biological thiols, homocysteine (Hcy), cysteine (Cys) and glutathione (GSH) have been the subject of intense research due to their association with a wide range of diseases. They play a key role in maintaining the redox status of biological systems. Selective detection methods for these thiols are challenging due to their similar structures and properties. Current commercially available detection methods use separations, fragile and expensive enzymatic or immunogenic materials and complex instrumentation. This has led to a global effort towards developing simple and inexpensive optical probes and indicators selective for specific biological thiols.

Highly selective chemical probes and …

Mimicking Metabolism Of A Reversed Chloroquine Antimalarial, Kelsie Lynn Kendrick

Dissertations and Theses

The aim of this study was to elucidate the oxidation products of a candidate antimalarial drug, PL69, using a porphyrin system and to determine the accuracy of the oxidation products produced, as compared to what is expected in metabolism. PL69 is a reversed chloroquine (RCQ) that is active against chloroquine resistant malaria. Porphyrin oxidation systems have been shown to mimic in vitro enzymatic metabolism reactions. PL69 and its known metabolite, PL16, were incubated with the porphyrin system, and then the oxidation products were collected and separated by HPLC. The oxidation products were characterized by NMR and mass spectrometry and compared …

Translational Fidelity Of A Eukaryotic Glutaminyl-Trna Synthetase With An N-Terminal Domain Appendage, Aaron Bethea Rogers

Dissertations and Theses

Several Saccharomyces cerevisiae mutant tRNA^Q2 species (glutamine isoacceptor, CUG anticodon) were synthesized and assayed for aminoacylation activity with Saccharomyces cerevisiae glutaminyl-tRNA synthetase. The derived steady state parameters were compared to similar datasets from the literature. The mutants behaved analogously to similar mutant species based on tRNA from Escherichia coli, but with slightly relaxed specificity as revealed by comparison of k_cat/K_M values relative to wild type in vitro transcribed tRNA. Additionally the eukaryotic N-terminal domain appendage, as found in Sce glutaminyl-tRNA synthetase, is considered in light of the discovery of non-canonical aminoacyl-tRNA synthetase functions, including …

Characterization Of Methylene Diphenyl Diisocyanate Protein Conjugates, Morgen Mhike

Dissertations and Theses

Diisocyanates (dNCO) such as methylene diphenyl diisocyanate (MDI) are used primarily as cross-linking agents in the production of polyurethane products such as paints, elastomers, coatings and adhesives, and are the most frequently reported cause of chemically induced immunologic sensitization and occupational asthma (OA). Immune mediated hypersensitivity reactions to dNCOs include allergic rhinitis, asthma, hypersensitivity pneumonitis and allergic contact dermatitis.

There is currently no simple diagnosis for the identification of dNCO asthma due to the variability of symptoms and uncertainty regarding the underlying mechanisms. Immunological sensitization due to dNCO exposure is traditionally thought to require initial conjugation of the dNCO to …

Interpretation Of Chemical Environments By Rna And The Implications To The Origins Of Life, Brian Larson

Dissertations and Theses

We describe the initial realization of behavior in the biosphere, which we term behavioral chemistry. If molecules are complex enough to attain a stochastic element to their structural conformation in such a way as to radically affect their function in a biological (evolvable) setting, then they have the capacity to behave. This circumstance is described here as behavioral chemistry, unique in its definition from the colloquial chemical behavior. This transition between chemical behavior and behavioral chemistry need be explicit when discussing the root cause of behavior, which itself lies squarely at the origins of life and is the foundation of …

Biobased Amphiphiles As Molecular Gelators, Nneoma C. Ezeude

Dissertations and Theses

No abstract provided.

The Study Of The Degradation Rates Of The Hexabromocyclododecane Isomers With Polysulfides At 25 Oc And Ph 9 In 80% Water / 20% Methanol, John H. Wilson

Dissertations and Theses

No abstract provided.

Investigation Of The Structure And Dynamics Of Regioisomeric Eu³⁺ And Gd³⁺ Chelates Of Nb-Dotma: Implications For Mri Contrast Agent Design, Benjamin Charles Webber

Dissertations and Theses

The detection of disease and abnormal pathology by magnetic resonance imaging (MRI) has been aided significantly by the use of gadolinium (Gd³⁺)-based contrast agents (CAs) over the past three decades. MRI and MRI CAs play a critical role in diagnosing tumors and diseases of the central nervous system. The agents used clinically have been shown to safely increase MRI contrast despite the toxicity of Gd³⁺, owing to the high kinetic and thermodynamic stability of these chelates. However, current CAs enhance contrast at a small fraction of what is theoretically possible. This leads to the necessity of …

Substituent Effects On Reactivity And Allergenicity Of Benzoquinone, Wilbes Mbiya

Dissertations and Theses

Benzoquinone (BQ) is an extremely potent electrophilic contact allergen that haptenates endogenous proteins through Michael addition (MA). It is also hypothesized that BQ may haptenate proteins via free radical formation. The objective of this study was to assess the inductive effects (activating and deactivating) of substituents on BQ reactivity and the mechanistic pathway of covalent binding to nucleophilic thiols. The BQ binding by Cys34 on human serum albumin was studied, and for reactivity studies, nitrobenzenethiol (NBT) was used as a surrogate for protein binding of the BQ and benzoquinone derivatives (BQD). Stopped flow techniques were used to determine pseudo-first order …

Developing Thyronamine Analog Pharmaceuticals Targeting Taar1 To Treat Methamphetamine Addiction, Troy Andrew Wahl

Dissertations and Theses

As a part of the overall program in the Grandy laboratory at Oregon Health & Science University (OHSU), studying the underlying chemical biology of methamphetamine (Meth) addiction, this dissertation reports on the development of six new thyronamine analogs which were synthesized and assayed against trace amine associated receptor 1 (TAAR1), giving preliminary results consistent with the analogs being inverse agonists. Due to highly variable TAAR1 expression levels in the assays, based on inter-assay response to control Meth stimulation as well as other possible factors, kinetic models were developed to qualitatively explain the assay results. The models set approximate limits on …

Use Of Soybean Lecithin In Shape Controlled Synthesis Of Gold Nanoparticles, Benjamin Robert Ayres

Dissertations and Theses

The work presented in this dissertation is a composite of experiments in the growth of gold nanoparticles with specific optical properties of interest. The goal is to synthesize these gold nanoparticles using soybean extract for not only shape control, but for propensity as a biocompatible delivery system. The optical properties of these nanoparticles has found great application in coloring glass during the Roman empire and, over the centuries, has grown into its own research field in applications of nanoparticulate materials. Many of the current functions include use in biological systems as biosensors and therapeutic applications, thus making biocompatibility a necessity. …

Supercharging: An Investigation Into The Effects Of External Amino Acid Residue Charge On The Solubility And Internal Electric Character Of Bound Ligands In A Heme-Binding De Novo-Designed Protein, Cooper French

Dissertations and Theses

De novo protein design offers many interesting prospects both as a means to better understand natural protein dynamics and as a potential resource in biomedical and industrial applications. In this work I describe the modification of a simple, well-characterized heme-binding protein by altering side chain residue identities on the hydrophilic surface of the protein to produce variants with a range of net external charges. These charge modifications had a significant impact on nearly every measurable character of the protein. This work establishes the hard limits of supercharging within our experimental protein scaffold system, demonstrating that excessive positive charge increased the …

An Investigation Of Urban Mobile Source Aerosol Using Optical Properties Measured By Crdt/N: Diesel Particulate Matter And The Impact Of Biodiesel, Monica Elizabeth Wright

Dissertations and Theses

Mobile source emissions are a major contributor to global and local air pollution. Governments and regulatory agencies have been increasing the stringency of regulations in the transportation sector for the last ten years to help curb transportation sector air pollution. The need for regulations has been emphasized by scientific research on the impacts from ambient pollution, especially research on the effect of particulate matter on human health. The particulate emissions from diesel vehicles, diesel particulate matter (DPM) is considered a known or probable carcinogen in various countries and increased exposure to DPM is linked to increased cardiovascular health problems in …

Studies On Sucralose-Based Low Molecular Weight Gelators, Malick Samateh

Dissertations and Theses

Amphiphiles are molecules with both hydrophilic head and hydrophobic tail groups. Examples of amphiphiles include surfactants, detergents, soaps, bile acids/salts and lipids. Due to their amphiphilic nature, they tend to self-assemble in solution via non-covalent interactions such as hydrogen-bonding, π-π stacking and donor–acceptor interactions to form hierarchical morphologies like micelles, lamellae and fibers. The ones capable of subsequently forming gels are known as low molecular weight gelators (LMWGs). LMWGs usually form “polymer-like” fibers that interact to form a three-dimentional network known as a Self-Assembled Fibrillar Network (SAFIN), which entraps and immobilizes the entire solvent pool to form a viscoeslatic material …

Effects Of Arsenic And Uvb Radiation On Induction Of Cyclin D1 In Human Keratinocytes., Julian Gonzalez

Dissertations and Theses

Arsenic and Ultraviolet radiation B (UVB) are environmental toxins that have been linked to various epithelial cancers. Arsenic metabolism in humans leads to its collection in the skin, where it encounters and can act with known carcinogen UVB. Epidemiological evidence of the two toxins demonstrates their potential to affect signaling pathways, with various consequences. Here we employ an in vitro model system using Normal Human Epidermal Keratinocytes (NHEK) to identify the effect of arsenic and UVB on humans and whether they work synergistically. We find that although both cause induction of cyclin D1, culturing cells with both co-mutagens does not …

Azide-Benzyne Cycloaddition And Olefination To Vinyl Benzotriazoles, Singh Govindra

Dissertations and Theses

No abstract provided.

Spontaneous Cooperative Assembly Of Replicative Catalytic Rna Systems, Nilesh Vaidya

Dissertations and Theses

The RNA World hypothesis proposes a period of time during the origins of life in which RNA molecules were the only source of both genotypes and phenotypes. Although a vast amount of evidence has been obtained in support of this hypothesis, a few critical demonstrations are lacking. A most crucial one is a demonstration of self-replication of RNA molecule from prebiotic soup. Previously in the Lehman laboratory, it has been demonstrated that a 198-nucleotide molecule derived from the Azoarcus group I intron can self-assemble from up to four fragments of RNA via recombination. Furthermore, the covalent full-length molecules are catalytically …