Chemistry Commons^™

Changes In Apoptotic Gene Expression Induced By Dna Cross-Linkers, Jordanne B. Dunn

Honors Theses

The Millard Research Laboratory is interested in the cytotoxic mechanisms of the bifunctional alkylators diepoxybutane (DEB), epichlorohydrin (ECH), and (1-chloroethenyl) oxirane (COX). Studies performed in the laboratory examine the dual nature of these DNA cross-linking compounds that can act as carcinogens or anti-cancer agents. The mechanisms through which these compounds induce cell death are explored in this study. Cells either undergo cell death due to necrosis or apoptosis. HL-60 cells were treated with varying concentrations of DEB, ECH, or COX. A caspase 3/7 assay was used to test for induction of apoptosis in the treated cells at varying incubation times. …

Upgrade Of A Raman Spectrometer With Modern Computer Control And Data Acquisition For Studies Of Hydrogen Bonding In Pyrimidine, Austin Howard

Honors Theses

The restoration of a Cold War era high resolution Raman spectrometer to working order as well as its control and data acquisition upgrade using a Labview program authored for this purpose are discussed. The restored Raman spectrometer was used in an investigation of intermolecular interactions involving pyrimidine. Following in this manuscript are three chapters. The first chapter is a brief description of the history and theory of Raman spectroscopy as well as some details of the instrumentation used in Raman spectroscopy. The second chapter contains technical details of the restoration and upgrade of the high resolution Raman spectrometer. The third …

Molecular Modeling Of Para-Benzyne And A Series Of Push-Pull [14]-Pyridoannulenes, Evan B. Wang

Honors Theses

Molecular modeling is vital for gaining insight into experimental results and discovering molecular properties not yet characterized by experiment. Depending on the type of molecule under investigation, certain methods will yield more accurate and revealing answers. In the first project, a state-averaged, multireference complete active space (CAS) approach was used for the determination of the vertical excitation energies of valence and Rydberg states of para-benzyne. Orbitals were generated with a 10- and 32-state averaged multiconfigurational self consistent field (MCSCF) approach. Electron correlation was included using multireference configuration interaction with singles and doubles (MR-CISD), including Pople correction for size extensivity (MR-CISD+Q), …

Foundations And Interpretations Of Quantum Mechanics, Cory Johnson

Honors Theses

The first famous thought experiment of Einstein gives rise to his theories of relativity, the bedrock of modern astrophysics and cosmology. His second famous thought experiment begins the investigation into the foundations of quantum mechanics. It leads to a paradox, inspiring various 'no-go' theorems proven by Bell, Kochen, and Specker. Physicists and philosophers worldwide become increasingly dissatisfied with the probabilistic complementarity interpretation (Born-Bohr) and eventually offer their own accounts of the theory. By the end of the 20th century two alternative approaches stand out as the best candidates: Both the hidden variables interpretation (de Broglie-Bohm) and the many worlds interpretation …

Temperature And Magnetic Field Dependence Of The Electronic Excitations In The Nickel Chain Compound Nino, Lucas Laviolet

Honors Theses

Temperature and magnetic field dependent absorbance spectra were taken on the Ni2+ chain compound NINO (Ni(C?H??N?)?NO?(ClO?)) in the range from 8,500 to 25,000 cm-?. The identification of an effective C?v symmetry about the nickel ions is supported by assignment of the low temperature absorbance bands. The intensity of many bands is found to be temperature dependent, and in several bands, a shift to higher energy is observed at lower temperatures. A correlation is noted between the field dependence of the spin forbidden electronic transitions and the magnetic properties of NINO. Below a crossover magnetic field, Hc ? 10 T, the …

Effects Of Context Of Natural And Artifactual Objects On Categorization, Linsey Walker

Honors Theses

Categorization of animals and vehicles in different contexts was investigated in three experiments using event related potentials (ERPs). The presence of a background and congruency of the background in relation to the object were both manipulated in order to determine the effects of context on visual processing. In Experiment 1, adults were presented with images of animals and vehicles in two conditions: situated in a congruent context (e.g. an animal in a field) and in the absence of a context (an animal in a white homogeneous background). In experiment 2, adults were presented with images of animals and vehicles in …

Inhibition Of Cellular Thioredoxin Reductase By The Anticancer Prodrug Cloretazine, Tyler R. Schleicher

Honors Theses

Sulfonylhydrazines are a class of DNA alkylating drugs which also produce carbamoylating activity in situ. The carbamoylating species is of significance because it has shown to inhibit important thiol-containing enzymes such as glutathione reductase (GR) and thioredoxin reductase (TrxR). TrxR catalyzes dithiol-disulfide exchange reactions on thioredoxin (Trx), which in turn catalyzes other reductive processes such as deoxyribonucleotide biosynthesis. In this study, we demonstrate that TrxR activity is strongly inhibited by the anticancer prodrug Cloretazine both in purified form and in leukemia cell lysates. This inhibition is specific to the carbamoylating activity of methylisocyanate (MiC). In contrast, another important oxidoreductase, glutathione …

Pressure Perturbation Calorimetry And Guest-Host Chemistry Of Ndmg And N-Map With P-Sulfonatocalix[6]Arene, Cassandra Newell

Honors Theses

The aim of this project is to provide an explanation for recently obtained binding constants for two similar guest molecules, NDMG and N-MAP, with a p-sulfonatocalix[6]arene host in ammonium acetate buffer. This work was done primarily using pressure perturbation calorimetry, which is a technique that determines the coefficient of thermal expansion, α, which is in turn related to the solute molecule's effect on the order of the surrounding water molecules. A series of experiments were designed to test the effects of suspected confounding variables on the validity of PPC data. PPC was then used to study NDMG and N-MAP in …

Photochemical Generation And Intramolecular Chemistry Of Β-Alkoxycarbenes, Kimberly Graves

Honors Theses

The photolytic phenanthrene-based precursors for both β-methoxycarbene and β-ethoxycarbene were synthesized with and without a deuterium label attached to the a carbon. The incorporation of this deuterium label allowed distinction between a 1, 2-H shift and a 1, 2-O shift pathway to the respective alkyl vinyl ether, without the influence of a primary kinetic isotope effect. Photolyses of these precursors gave rearrangement products of the expected β-alkoxycarbenes. In the case of β-methoxycarbene, no methyl vinyl ether was observed due to its volatility. However, the appearance of aldehyde peaks in the NMR spectra, from an apparent further rearrangement to acetaldehyde through …

The Selective Synthesis Of Oxacalix[6]Arenes And The Exploration Of Azacalix[N]Arenes, W. Christian Crannell

Honors Theses

Calix[n]arenes, cyclIc molecules composed of "n" benzene rings meta-linked by a methylene to form a macrocycle, are very prevalent jn the literature and enjoy a wide range of applications. However, the oxygen bridged and nitrogen bridged systems, oxacalllx[n)arenes and azacalix[n]arenes, respectively, are far less common because they are synthetically challenging. Furthermore, the selective synthesis of oxacalix[6]arene systems has not previously been well documented, but the systems can now be accessed in a facile approach disclosed here. The insight and knowledge gained from the synthesis of oxacalix{6]arenes has provided a foray into the synthesis of azacalix[nlarenes.

Effects Of The Anticancer Agent Cloretazine On Human Apurinic Endonuclease-1 Activity, Jennifer L. Bushee

Honors Theses

The carbamolyating activity of Cloretazine, a novel anticancer prodrug, modifies protein function and acts synergistically with the choroethyalting species, which a1kylales DNA. The reactive subspecies responsible for carbamolylating activity is methyl isocyanate, which reacts with sulfhydryl groups and amines. DNA repair enzymes have been identified as potential targets for the modification by methyl isocyanate; in particular, base excision repair enzymes. Enzymes in DNA base excision repair include DNA polymerase beta (Pol ?) and apurinic/apyrimidic endonucease-l (APE/Ref-1). APE/Ref-1 hydrolyzes the 5' -phosphodiester DNA backbone from an abasic DNA template, where the base was excised by a DNA glycosylase. The entire nucleotide …

Using Azahetercyclic Electrophiles To Synthesize Novel Bicyclooxacalixarenes And Oxacalix[2]N-Hexylnaphthalimide[2]Naphthyridines, Doug Rooke

Honors Theses

Various bicyclooxacalixarenes, tricyclooxacalixarenes and oxacalix[2]N-hexylnapthalimide[2]naphthyridines are synthesized via SnAr condensation. This research has involved synthesis optimization. The oxacalix[2]N-hexylnaphthalimide[2]naphthyridines have exhibited host-guest binding in fluorescence experiments. These compounds have been characterized by NMR spectroscopy as well as single crystal X-ray diffraction.

Reactions Of Atomic Carbon With Acid Chlorides, Daniel B. Herrick

Honors Theses

This thesis is the first report of reactions of atomic carbon with acid chlorides. Carbon is known to react with phosgene to afford dichlorocarbene. We report a similar reaction with carbon and acid chlorides, generating alkylchlorocarbenes. We examine both the nature of the carbene products generated through deoxygenation and the general reactivity of carbon with the acid chlorides. We report two ways in which carbon reacts with acid chlorides. First, as expected from prior work with phosgene, carbon deoxygenates the carbonyl group yielding alkylchlorcarbenes, which rearrange as expected. Second, carbon abstracts the chlorine, and generates the acyl radical, which, in …

Stability Testing Of Mint Oils Through Gas Chromatography Analysis, Sarah Wolf

Honors Theses

In this experiment, the stability of mint oil was measured through gas chromatography analysis. Eight different oils were tested. Levels of key components of mint oil, including menthol and menthone for peppermint oil, and carvone and limonene for spearmint oil, was compared over time. Several packaging materials were immersed in oils in order to determine their effects, if any, on the composition of the oils. Additionally, oil was subjected to either 25 degree or 40 degree Celsius temperatures to determine if temperature affected the oil composition.

Concomitant Polymorphism In 1,2-Bis(9-Anthryl)Acetylene, Rebecca Goldstein

Honors Theses

This thesis details the serendipitous discovery of the phenomenon of concomitant conformational polymorphism found to exist in 1,2-bis(9-anthryl)acerylene. 1,2-bis(9anthryl)acetylene is a previously published molecule. However, the published crystal structure showed the molecule to be completely planar, and to crystallize in the form of orange needles. While this form of the crystal was indeed found during the synthesis of 1,2-bis(9anthryl)acetylene, a new polymorph, crystallizing as yellow prisms, was also discovered. This yellow polymorph was found by X-ray crystallography to be monoclinic with an angle of 66.7 between the anthracene planes. The planar polymorph 1,2-bis(9-anthryl)acetylene was also found by X-ray crystallography to …

Detailed Mechanistic And Optimization Of The Photochemical Production Method Of Superoxide, Ta-Chung Ong

Honors Theses

The highly reactive nature of superoxide anion presents an analytical challenge to prepare stable standards for instrument calibration. McDowell et al. (1983) developed a convenient method of superoxide production based on continuous photolysis of benzophenone and acetone in oxygen saturated, alkaline, 2-propanol solution. In the McDowell reaction, ketones are photolyzed to their triplet state, and then reacted with alcohol to produce ketyl radicals that react with oxygen to produce superoxide. This study investigated the mechanism and rate of these reactions by Laser Flash Photolysis (LFP). Reaction rate constants for the reaction between the benzophenone triplet and ethanol was 5.5 x …

World Bank -Cpa Conflict: The Struggle To Define Human Rights And Development In The Philippines, Adam B. Robbins

Honors Theses

This thesis analyzes the interactions between the World Bank (hereafter, the Bank) and the Cordillera Peoples Alliance (CPA), an indigenous and environmental advocacy group based in the Cordillera region of Luzon, in the Philippines. Using data gathered through both text-based and participatory research methods, I analyze the discursive relationship and violent confrontations between the two organizations. Conflicting development and human rights values cause the majority of these conflicts. I focus on how each organization enacts development and human rights, and how this leads to conflict. Ultimately, I intend for this thesis to offer practical guidance for the reader involved in …

Intramolecular Chemistry Of Ss-Acetoxyethylidene And Photochemical Generation Of Vinylidenes, Jennifer M. Nguyen

Honors Theses

The parent carbene ß-acetoxyethylidene has been previously generated by the photolysis of its precursor, acetic acid 1a,9b-dihydro-1H-cyclopropa[l]phenanthren-1-yl methyl ester. Mechanistic studies on ß-acetoxyethylidene have indicated the possibilities of three rearrangement pathways to the formation of vinyl acetate: a proton shift, an acyl shift, and a cyclic rearrangement (see Figure 8). A deuterium labeling study involving the replacement of the hydrogens on the methylene carbon has indicated that the simple 1,2-H shift was the primary manner of rearrangement, with an 82% yield of product. However, a primary kinetic isotope effect may have occurred due to the greater strength of a C-D …

Synthesis Of 2-Oxo-16-(3', 4'-Methylenedioxyphenyl)-Trans-15-Hexadecene, Adelajda Zorba

Honors Theses

This work presents the progress made towards synthesizing 2-oxo-16-(3', 4'methylenedioxyphenyl)-trans-15-hexadecene, an antimycobacterial compound that was originally isolated from the leaves of Piper Sanctum. The hydrocarbon chain of the molecule was synthesized first by opening a 15-pentadecanolactone ring by means of HI, and performing an E2 elimination reaction on the molecule followed by an organolithium reaction with CH3Li. Hexadec-15-en-2-one that was afforded this way was later reacted with 5-bromobenzo[d][1,3]dioxole following the appropriate Heck reaction protocol that allows for the formation of a palladium catalyzed carbon-carbon bond.

The modes of action of 2-oxo-16-(3', 4'-methylenedioxyphenyl)-trans-15hexadecene are comparable to the ones of rifampicin, a …

Characterization Of The Wheat Grain Pkaba1-Interacting Protein Tawd40, Natalie Wayne

Honors Theses

Abscisic acid (ABA)-mediated gene expression is a critical component of plant responses to this important hormone, which affects plant growth, development, and responses to environmental stresses. Plant responses to ABA are mediated by a number of factors including PKABA 1> an ABA-induced protein kinase involved in ABA-suppressed gene expression in cereal grains, and TaWD40, which has previously been shown to physically interact with PKABA1. A full-length 1.9 kb TaWD40 cDNA, CK210682, was sequenced as part of this project. Based on the deduced protein sequence, it is thought that TaWD40 may belong to the family of E3 ubiquitin ligases, possibly targeting …

Investigating The Mechanisms Of A Novel Ribosomal Rna Degradation System, Daniel Fowler

Honors Theses

Nonfunctional ribosomal RNA decay (NRD) is a novel quality control system that eliminates defective ribosomal RNAs (rRNAs) from yeast cells. Plasmid-encoded rRNAs containing single nucleotide substitutions in the peptidyl transferase center of 25S rRNA or the decoding center of 18S rRNA are co-expressed with endogenous rRNAs in Saccharomyces cerevisiae. Quantitative northern blots reveal the steady-state levels of the resulting nonfunctional rRNAs are markedly decreased compared to wild-type rRNAs . Furthermore, the decreased expression is not the result ofdefects in rRNA transcription or processing, but instead is due to decreased stability ofthe mature, nonfunctional rRNAs. Mutations in other functionally important rRNA …

Guest-Host Chemistry Of P-Sulfonatocalix[6]Arene And Nizatidine, Galia Debelouchina

Honors Theses

This work investigates the guest-host chemistry in water of p-sulfonatocalix[6]arene and a number of guests related to the amino acids arginine and lysine. Two questions are particularly important: what are the interactions that drive guest-host binding and what is the role of the solvent. The answers to these questions are investigated with isothermal titration calorimetry (lTC), which gives K, ?H, and ?S, and pressure perturbation calorimetry (PPC), which allows the calculation of the thermal coefficient of expansion ? and relating it to a molecule's structure-breaking or structure-making properties. The ITC data suggests that hydrogen bonding and charge-charge interactions are the …

The Synthesis Of Biomimetic Tungsten And Molybdenum Complexes, John Sterling Cole Iii

Honors Theses

The synthesis of novel biomimetic molybdenum and tungsten compounds that are potential model complexes for molybdenum and tungsten oxidase enzymes is being pursued. Model complexes such as these provide a better understanding of the basic chemistry of a metal center in an environment similar to that found in particular enzyme active sites. This understanding provides a good starting point for biologists or biochemists studying those biological systems. The first target complex will incorporate a tetradentate-S4 ligand (L) that features two biphenyl-S2 fragments joined by a propyl linker. The second target complex will incorporate a bidentate ligand (L') with a singly …

An Analysis Of The Effect Of Carbon Dioxide On The Decay Rates Of Superoxide, Michael Jay Walsh

Honors Theses

The radical dioxygen anion, superoxide has been shown to react with carbon dioxide in nonprotic and aqueous systems. Indirect evidence suggests that superoxide also reacts with carbon dioxide and carbonate species dissolved in water. This study involved conducting experiments to determine the decay rate of superoxide in the presence of carbon dioxide and carbonate species. Experiments were conducted by sparging an alkaline bicarbonate buffer with carbon dioxide and measuring the decay rate of superoxide added to the solution. Although the specific reaction mechanism and rates have not been determined first order superoxide decay rates as high as 3.8x10-2s-1 were obtained …

Analytical Tools For Studying Phosphorus And Nitrogen Lake Nutrient Dynamics And Their Application To The Field, Ivan Mihajlov

Honors Theses

In order to evaluate the causes and conditions that lead to cyanobacteria blooms in northern temperate lakes, studies of nutrients such as total phosphorus, total nitrogen, phosphate, and nitrate are necessary. Sensitive, environmentally friendly and cost-effective techniques were developed to detect ppb-level nitrates and phosphates in the lake water. Phosphate was analyzed by luminol chemiluminescence, while the quantification of nitrate was performed by capillary electrophoresis (CE) using indirect UV detection, with a background electrolyte consisting of pyromellitic acid, hexamethonium hydroxide and triethanolamine. Sample injection methods for the CE were optimized for the analysis in Belgrade Lakes, Maine. Vertical profiles of …

Investigation Of Iron (Iii) Desferrioxamine B Oxalate Ligand Exchange By Uv-Vis Spectroscopy: The Next Step In Developing A Quantitative Analytical Method For Measuring Bioavailable Iron In Marine Ecosystems, Ken L. Pitter

Honors Theses

To date there are no analytical techniques designed to exclusively measure bioavailable iron in marine environments. The goal of this research is to develop such a technique by isolating the bioavailable iron using the terrestrial siderophore desferrioxamine B (DFB). This project contained many challenging aspects, but the specific goal of this study was to develop a robust analytical technique for quantification of Fe(III)-DFB complexes at nanomolar concentrations. Past work showed that oxalate (Ox) promotes photodissociation of Fe(III)-DFB to Fe(Il), and we are specifically interested in the mechanism of this process. A model was developed using known thermodynamic constants for Fe(III)-DFB …

Photochemical Generation Of 2-Methoxy-2methylpropylidene And Its Rearrangement Pathways, Stanislav Presolski

Honors Theses

2-methoxy-2-methylpropylidene was photochemically generated from a non-nitrogenous precursor, 1a,9b-Dihydro-IH-cyclopropa[1]phenanthrene-l-etbane 2-methoxy-2-methyl, available in two steps from phenanthrene. Two competing rearrangement pathways were observed for the p-methoxy carbene, 1,2-methyl shift and C-H insertion, which had varying weights depending on the solvent used. Nevertheless, the C-H insertion was always predominant, contrary to the current understanding of B-substituted carbenes, which apparently needs revision. An attempt was also made to measure by LFP the rate constant of rearrangement and lifetime of the stabilized l-chloro-2-methoxy-2-metbylpropylidene.

The Synthesis And Characterization Of Bicyclooxacalixarenes, Kevin J. Selby

Honors Theses

Bicyclooxacalixarenes were synthesized in high yield via a selective, room temperature Sn Ar reaction of phluoroglucinol with 2,6-dichloropyridines. Functionality on the 2,6-dichloropyridioe was varied by changing the electron-withdrawing groups in the 3 and 5 positions (using chlorine, nitro groups, and cyano groups) and the side-chains in the 4-position (using ethyl, butyl, phenyl and ρ-tolyl groups). The resulting cage-like molecules were studied by X-ray crystallography and tested for metal complexation.

Mapping Of Diepoxybutane Damage In The Cytochrome B Domain Of Mitochondrial Dna And The Β-Globin Domain Of Nuclear Chicken Dna Using Quantitative Pcr, Justin Juskewitch

Honors Theses

Diepoxybutane (DEB), a known industrial carcinogen, reacts with DNA primarily at the N7 position of deoxyguanosine residues and creates interstrand cross-links at the sequence 5'-GNC. Since N7-N7 cross-links cause DNA to fragment upon heating, quantative polymerase chain reaction (QPCR) is being used in this experiment to measure the amount of DEB damage (lesion frequency) with three different targets-mitochondrial (unpackaged), open chromatin region, and closed chromatin region. Initial measurements of DEB damage within these three targets were not consistent because the template DNA was not the limiting reagent in the PCR. Follow-up PCR trials using a limiting amount of DNA are …

Flanking Sequences Modulate Diepoxide Cross-Linking Efficiencies At The 5'-Gnc Sste, Gregory A. Sawyer

Honors Theses

Diepoxybutane, diepoxyoctane, and mechlorethamine are cytotoxic DNA crosslinking agents that vary in their carcinogenic versus chemotherapeutic potentials. Interstrand cross-linking occurs between the N7 positions of deoxyguanosine residues on opposite strands of the DNA duplex. Each synthetic DNA oligomer used in this study contained four 5'-N\GN2CN3 sites (within a 32 base sequence) and we have systematically varied the bases in the N1 and N2 positions to determine the resulting cross-linking efficiencies of each cytotoxic agent. Each duplex was 5' -end labeled and incubated with cross-linking agent. Interstrand cross-links were purified through denaturing polyacrylamide gel electrophoresis and then subjected to piperidine cleavage. …