Browsing by Subject "Chemistry"

Now showing 1 - 20 of 166
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    Access to Indoles via Diels-Alder reactions of vinylpyrroles.
    (2009-05) Lanzatella, Nicholas Peter
    The indole moiety is extremely common in biologically active natural and un-natural products. Exploration and discovery of methods for generating the indole nucleus provides new and potentially more efficient options for synthetic approaches to indole-containing compounds. Vinylpyrroles have electron-rich pi systems and perform well as dienes in normal electron-demand Diels-Alder reactions with sufficiently electron-deficient dienophiles. The resulting substituted dihydro- or tetrahydroindoles are dehydrogenated to the corresponding indoles. Tosylation of pyrrole promotes acylation under Friedel-Crafts conditions at the difficult-to-access 3-position, which after reduction and dehydration gives 3-vinylpyrroles. These partially deactivated stable crystalline pyrroles have sufficient electron density to provide a novel and advantageous [4+2] cycloaddition route to indoles. Due to the high reactivity and consequent tendency of pyrroles to undergo undesired side-reactions, protecting groups are often desirable in pyrrole chemistry. However, the requirement for a sufficiently electron-rich diene, along with the sensitive nature of pyrroles, restricts the use of traditional blocking groups. Methylthio-protected 2-vinylpyrroles are shown to act as effective dienes in Diels-Alder reactions, demonstrating new blocking group techniques for chemistry involving sensitive pyrroles.
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    Advances in nanostructured materials via templated sol-gel structure control and self-assembly
    (2015-04) Rudisill, Stephen Gabriel
    This dissertation describes a body of work focused on understanding and improving morphology control of nanoporous structures via their aqueous chemistry. Synthesis of materials was carried out primarily using the Pechini process with metal nitrates and colloidal crystal templates. CeO2 and CeO2-derived compounds were used for a substantial portion of the dissertation as they are useful for thermochemical cycling experiments. Templated CeO2 shows a tenfold improvement over an untemplated material as well as a nanoparticle powder under lab-scale thermochemical cycling experiments.The Pechini process itself was then investigated as a means to obtain greater structural control over colloidal crystal templated materials. The process was demonstrated to involve phase separation, which allowed for the production of microspheres and bicontinuous networks of templated CeO2-based solids. Microspheres produced were between 1-3 µm in size, with polydispersity less than 15%. Further experimentation demonstrated that this phase separation methodology was generalizable to Fe2O3 and Mn3O4, though higher polydispersities were obtained for these materials.The final research project accomplished in this dissertation involves a method to produce ordered collagen fibrils through the incorporation of nanocrystalline cellulose during fibrillogenesis. Results were verified via scanning electron microscopy and a mechanism was proposed based on infrared spectroscopy results indicating a decrease in collagen-collagen hydrogen bonding.
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    Application of molecular modeling techniques to study the structure, dynamics, and interactions of membrane proteins.
    (2011-08) Shi, Lei
    Membrane proteins constitute ~30% of all the genomes and ~70% of the drug targets. However, less than 1% of the entries in the protein data bank are membrane proteins. The underrepresentation of membrane protein structures limits our understanding of their functions. This thesis summarizes my effects to apply theoretical methods to understand the structure and function relationships of membrane proteins. Specifically, we developed computational techniques to interpret solution and solid-state NMR data of membrane proteins and determine their high resolution structures. We further performed molecular dynamics simulations to study their dynamics, interaction with other proteins and the lipid bilayer environment. We applied these approaches to phospholamban, which is a membrane protein that is involved in cardiac muscle relaxation by regulating Ca2+-ATPase activity. Our results provide new insights to understand how membrane proteins elicit their function.
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    Applications of substrate analogues for studies of prenyltransferase enzymes.
    (2010-04) DeGraw, Amanda Jane
    Prenyltransferase enzymes serve a variety of important biological functions from the creation of natural rubber to the modification of signal transduction proteins. The focus of this thesis is twofold; to understand better the isoprenoid chain elongation prenyltransferase enzymes, which catalyze the extension of isoprene units, and the protein prenyltransferases, which catalyze the transfer of an isoprenyl diphosphate to a protein or peptide. Substrate analogues have proven to be versatile tools for probing the identity, structure, mechanism, and function of various prenyltransferase enzymes. Described here are a variety of analogues of prenyltransferase substrates towards the study of prenyltransferase enzymes. A photoactive phosphonophosphate-containing analogue of farnesyl diphosphate (FPP) that can covalently modify proteins it is bound to upon irradiation with light was characterized and applied towards the identification of cis-prenyltransferase protein(s) involved in rubber biosynthesis. Kinetic and structural studies with this analogue and protein farnesyltransferase (PFTase) or protein geranylgeranyltransferase type-I (PGGTase-I) demonstrate that this probe is a good mimic of isoprenoid diphosphates. The phosphonophosphate linkage resulted in enhanced stability of the analogues, allowing it to be used as a label and identify a specific protein in rubber biosynthesis, rubber elongation factor (REF). The cross-linking of REF with a photoactivatible analogue of FPP suggests that REF can interact with isoprenoid diphosphates during rubber biosynthesis and this interaction may be key for the process. However, results indicated it is unlikely that REF is the sole protein responsible for rubber synthesis, thus prompting further work in the area. A caged compound is a biologically relevant molecule rendered inactive by a link to a chemical group (the "cage") through a photolabile bond. A series of photoactivatable protein prenyltransferase substrate analogues were created to achieve temporal control of prenyltransferase activity. Detailed characterization of these probes was performed to explore their applicability in protein prenylation studies. The first generation of caged PFTase analogues contain a nitrobenzyl-based photolabile group incorporated at the distal phosphate of the isoprenoid diphosphate substrate or the sulfhydryl side-chain of the cysteine residue in a CAAX peptide substrate. Kinetic studies of caged isoprenoid diphosphates demonstrated that they are poor substrates for PFTase but, upon irradiation, can efficiently release FPP upon irradiation which can be utilized for catalysis. The caged CAAX peptide photo releases the parent peptide with similar kinetics to the caged isoprenoid diphosphates. When caged the CAAX peptide does not function as a substrate, but is able to bind with efficient capacity and nearly identical conformation as compared to the photo-released peptide and does not interfere with the binding of the isoprenoid diphosphate substrate. These results lead to a wide variety of experiments where temporal control over protein prenylation is necessary. A second set of isoprenoid diphosphate analogues was created, bearing an azide or alkyne moiety. These analogues were applied as chemical proteomic probes for studying the mammalian protein prenylome. Cells were treated with either the alcohol, which is converted into the diphosphate by cellular kinases or the diphosphate isoprenoid analogue. These analogues were then appended onto prenylated proteins and through Cu(I)-catalyzed cycloaddition with a corresponding azide- or alkyne-modified fluorophore, direct visualization of prenylated proteins was accomplished. Application of this same reaction with a biotinylated capture reagent allowed for enrichment of the modified proteins and subsequent identification by liquid chromatography-tandem mass spectrometry (LC-MS). This work is still in progress.
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    Aptamer selection using capillary electrophoresis-SELEX
    (2008-10) Mosing, Renee Karen
    SELEX is a method used for the combinatorial selection of aptamers, or single stranded nucleic acid sequences that bind with high affinity and specificity to target molecules. Although successful, SELEX is a very time consuming, laborious process. We introduced a modification to this process called capillary electrophoresis-SELEX. This protocol proved to be significantly more efficient, which greatly decreased the time requirement of the process from weeks to days. This improvement was observed despite the lower loading capacity and resolution limited injections on CE which introduced approximately 1013 sequences to the separation instead of the 1015 sequences introduced in more traditional selections protocols. In fact, ssDNA aptamers with picomolar affinity for HIV-1 RT were identified in 4 rounds. Further sequence/structure characterization of these sequences demonstrated no homology, indicating that several sequences can bind with high affinity to the target. Interestingly, the aptamers were 10 fold more selective for the original target (HIV-1 RT) than other reverse transcriptases. Despite this result, the aptamers did not demonstrate inhibition of reverse transcriptase activity. The success of these collections prompted investigation of more challenging targets such as mitochondria and bacteria. These targets are difficult to purify and have surface chemistries that are constantly changing. Aptamers for these targets must identify a feature on the surface that is consistent in order to be conserved throughout the process. Our experiments indicated that the aptamers may have bound to features on the surface that are not very abundant, making affinity characterization cumbersome. Future experiments aim to determine if the aptamers are becoming more refined for specific features rather than just focusing on increase in affinity. Finally, initial experiments were performed for a model that will drive selections toward a specific binding site on the surface of the HIV assembly protein, capsid. Further experiments are proposed to allow aptamer binding to specific sites, and for aptamer characterization.
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    Atomic layer deposition of tin oxide and zinc tin oxide: understanding the reactions of alkyl metal precursors with ozone
    (2014-09) Warner, Ellis J.
    This work is focused on depositing thin films of transparent conducting oxides, namely tin oxide and zinc tin oxide. Atomic layer deposition was used as the method to deposit these materials from alkyl-metal precursors and ozone. In addition to depositing these materials and utilizing them in optoelectronic devices, significant computational and experimental resources were employed to understand the fundamental reaction chemistry between the alkyl-metal precursors and surface functional groups, as well as, the alkyl-metal precursors and ozone. The mechanistic insight gained from the theoretical work indicated that the surface acidity greatly affected the adsorption of certain alkyl-tin precursors on surface hydroxyls. In addition, it was also found that ozone could react with metal-alkyls resulting in the formation of hydroxide functional groups and the elimination of acetaldehyde which was observed experimentally.
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    Atomistic Simulations of High Temperature Air Chemistry Including Three-Body Collisions and Recombination
    (2023-05) Geistfeld, Eric
    This dissertation studies chemical reactions relevant to modeling high-speed flight through Earth’s atmosphere. Shock-heated mixtures of nitrogen and oxygen undergo gas phase chemical reactions that control the concentrations of O2, O, N2, N, and NO (aptly named five-species air) that impact the heat shielding of hypersonic craft. Predicting the extreme gas state surrounding the heat shield material is extremely complex because the time scales of fluid flow, internal energy relaxation, and chemical reactions all become similar. Experiments studying this process are difficult to perform, expensive, do not exactly reproduce flight conditions, and require assumptions to interpret the measured data. First-principles computational simulations are now being used to understand these chemical processes. Advances in computational chemistry techniques and high-performance parallel computing have made the comprehensive study of these processes in dilute gases possible. To date, these computational studies have focused heavily on reactions of oxygen and nitrogen and have focused on the dissociation of diatomic molecules. Because it is highly reactive, atomic oxygen is incredibly important to model correctly. The formation and destruction of nitric oxide (NO) is also important to understand because NO is liable to emit energy as radiation. This thesis uses first-principles molecular simulation in several ways to complete the study of reactions in five-species air. Potential Energy Surfaces (PESs) describing interatomic forces in oxygen are used to simulate reactions of oxygen atoms and diatoms, and the predictions are validated against new molecular beam experimental data. This study shows that the new PESs used to describe these reactions do a better job of reproducing experimental results than earlier efforts, and that this improvement results from a more complete description of the relevant chemical states of the oxygen system. A QuasiClassical Trajectory (QCT) study of reactions that form and destroy nitric oxide is performed using new PESs and compared to Direct Molecular Simulation (DMS). These comparisons show that dissociation reactions in air mixtures are biased towards high energy vibrational states of reactant diatoms, but exchange reactions (referred to as Zeldovic reactions) are not as strongly biased. This suggests that while reduced-order chemistry models for hypersonic flow simulations should account for vibrational bias in dissociation, they do not need to account for any vibrational bias in the Zeldovic reactions. A major contribution of this thesis is the development of a new QCT theory and simulation framework to study recombination processes that involve the collisions of three neutral heavy particles. This ternary kinetic approach is based on a definition of the lifetime of binary collisions that is consistent with hard-sphere models in the limit of instantaneous reactions, and does not require an explicit appeal to the principle of detailed balance. The aspects of different sampling strategies for this method and the convergence of recombination rate constants are investigated. The results of this method are compared to the predictions of detailed balance, the results of dissociation QCT simulations, and a reduced-order chemistry model formulated using dissociation data combined with detailed balance. These comparisons show that the ternary kinetic method reproduces similar trends to those seen in dissociation studies and a reduced-order model built from them. Further analysis shows that while long-lived binary collisions are more likely to be hit by a third particle when they occur, they occur extremely rarely, are not any more likely to cause recombinations than short-lived binary collisions, and do not produce molecules in vastly different states than those predicted by dissociation data and the principle of detailed balance.
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    An ATR-FTIR study of semiconductor-semiconductor and semiconductor-dielectric interfaces in model organic electronic devices.
    (2009-08) Mills, Travis
    Organic electronics offer many benefits to inorganic electronics such as the promise of cheap, large-scale processing on flexible substrates and incorporation into many household devices. Organic photovoltaic (OPV) devices and organic field effect transistors (OFETs) offer low-cost implementation which might compete in some applications with their inorganic counterparts. However, fundamental work is necessary to uncover the physics governing the operation of OPVs and OFETs, in order to improve the efficiency of the devices. Much of the fundamental understanding developed in this work occurs at buried interfaces, such as the donor acceptor interface in OPVs or the semiconductor dielectric interface in OFETs. This thesis first introduces the reader to the device physics and state of the art in the development of OPVs and OFETs. After describing the experimental techniques used, a discussion of interfacial electric fields in bulk heterojunction polymer/small molecular solar cells will follow. It was found using the vibrational Stark effect, that donor acceptor interfacial electric fields could be measured and related to previous experiments. The interfacial field hinders the dissociation of excitons but also prevents geminate pair recombination. In OFET devices, the semiconductor dielectric interface was studied and the rate limiting steps to device performance in polymer electrolyte gated OFETs were determined. The interfaces studied provide insight into the fundamental operation of both OPVs and OFETs, which should help produce more efficient and controllable production of organic electronic devices.
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    An Attempt to Make True Colored Lithopones
    (1923-06) Anderson, Winslow Samuel
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    Bioanalytical techniques for the analysis of mitochondrial heterogeneity
    (2013-10) Wolken, Gregory Gene
    In this thesis, techniques are described for the measurement of individual mitochondrial isoelectric point (pI) using capillary isoelectric focusing (cIEF) with laser-induced fluorescence detection, simulation of the contribution of mitochondrial surface compositions to pI, and determination of individual mitochondrial membrane potential and electrophoretic mobility using capillary electrophoresis with laser-induced fluorescence detection (CE-LIF). These techniques provide insight into mitochondrial heterogeneity, which could increase fundamental understanding of the role played by mitochondria in aging.A method was developed to determine the pIs of individual mitochondria by cIEF. This method provides reproducible distributions and accurate determination of individual mitochondrial pI by the use of internal standards, and was able to detect changes in mitochondrial pI distributions caused by changes to the mitochondrial surface by treatment with trypsin. Application of this method demonstrated the heterogeneity of mitochondrial pI, which reflects the heterogeneity of mitochondrial surface compositions.To model the effect of surface composition on mitochondrial pI heterogeneity, a method was developed to predict mitochondrial pI values using simulated surface compositions consisting of different percentages of amino acids and phospholipids found in the mitochondrial outer membrane. This method was validated by predicting the pI values of known mitochondrial outer membrane proteins then extended to isolated mitochondria and used to model a pI distribution determined experimentally by cIEF. Significant changes in the percentages of some amino acids and phospholipids were predicted for observed pI differences between individual mitochondria. This model provides insight into the heterogeneity of mitochondrial pI and contribution of surface compositions. Distributions of individual mitochondrial membrane potential and electrophoretic mobility were measured using CE-LIF. Mitochondria from cultured cells and mouse muscle and liver tissue were labeled with JC-1, a ratiometric dye which indicates membrane potential. Analysis of specific regions of interest defined by performing CE-LIF of depolarized samples makes this method capable of analyzing mitochondrial membrane potential even in preparations where depolarized mitochondria may be present due to biological variation or experimental factors that result in damage to mitochondria or may be insufficient to keep all mitochondria polarized. This analysis revealed additional differences between samples and an effect of membrane potential on electrophoretic mobility. This method allows for the characterization of mitochondrial heterogeneity in membrane potential and surface properties.In the future, these methods can be applied to biological models of aging to elucidate the role that mitochondrial heterogeneity plays in age-related dysfunction and disease.
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    Biophysical Methods to Study Bromodomain Interactions and 19F Nmr Analysis of Cbp/P300 Kix Domain Complexes
    (2020-01) Ycas, Peter
    Epigenetics is the study of heritable changes in genome expression which alter organism phenotype. Genome expression is controlled by access to specific DNA, which in turn is controlled by how DNA associates with the histone proteins it is wrapped around. The condensed complex of DNA and histones is known as a chromosome. A hallmark of epigenetics is post-translational modification of chromosomes, both of DNA and histones. One such post-translational modification is acetylation of lysines on histone tails, a modification associated with gene transcription. The first part of this thesis focuses on bromodomain and plant homeodomain (PHD) finger transcription factor containing protein (BPTF), a member of the bromodomain class of proteins. Bromodomains recognize histone lysine acetylation and recruit transcription factors and nucleosome remodelers to chromatin. BPTF is a multi-domain protein which is the largest part of the nucleosome remodeling factor. The second half of this thesis examines another transcriptional regulator, the KIX domain of CBP/p300, a protein domain which co-localizes transcription factors. In Chapter one, the role of BPTF in gene expression and disease progression is discussed. The success of using small molecule probes to study other bromodomain containing proteins is described, highlighting the need to develop probes for BPTF in order to further discern the role of the protein in healthy and disease states. The current advances in small molecule inhibitor and biophysical tool development are described. The second half of Chapter one introduces the role of the KIX domain of CBP/p300 and its’ interaction partners and focuses on the past methods of studying the domain with a variety of NMR techniques. Chapter two describes the development and ligand deconstruction analysis of the first BPTF bromodomain inhibitor, AU1. The structure activity relationship of the molecule is developed using protein-observed fluorine NMR (PrOF NMR) and the (S) enantiomer of the compound is identified as the active component. Treatment of a panel of cancer cell lines which were found to be BPTF dependent through gene knockdowns showed decreased cell viability when treated with AU1. Development of biophysical tools to rigorously characterize high affinity BPTF inhibitors is described in Chapter three. The progress of ligand development in Chapter two was hampered by the lack of tools to accurately determine tight binding affinities. To address these issues, SPR and AlphaScreen assays were developed which are capable of rank ordering compounds which previously could not be done with PrOF NMR. These biophysical assays were validated against a small panel of previously characterized small molecule inhibitors of BPTF. Following validation, these assays were used to discover two new BPTF scaffolds which were explored as possible starting points for BPTF ligand discovery. Finally, the development of conditions to co-crystallize ligands with BPTF and the solution to their X-ray structure is described providing BPTF-small molecule ligand structural information for the first time. Chapter four compares fluorine labeling strategies of the KIX domain of CBP/p300 with 2-, and 3-fluorotyrosine (2FY and 3FY). The response of small molecule mimics of five fluorinated aromatic amino acids to changes in solvent polarity is used as a barometer for their utility in PrOF NMR. The chemical shift anisotropy of polycrystalline samples of 2FY and 3FY are determined by magic angle spinning. Through incorporation of both fluorinated tyrosine derivatives into the KIX domain of CBP/p300, their influence on stability and pKa perturbation in a model protein is investigated. The response of both 19F labeling strategies to ligand binding is discussed using the protein-protein interaction partner, MLL, which shows an allosteric response with 2FY KIX which is not observed with 3FY KIX. Chapter five delves into the differences observed with 2FY and 3FY KIX. The 19F NMR response of both proteins to a positive allosteric regulator (MLL), a negative allosteric regulator (naphthol AS-E phosphate), and an as yet unknown small molecule (2) are measured with changes in D2O solvent composition to measure the solvent accessibility of 19F nuclei upon ligand binding. The role of aromatic amino acids in the allosteric communication network is interrogated through ternary complex formation with MLL and c-Myb, which bind concurrently at separate sites on KIX. Finally, efforts towards crystallizing a stabilized complex of 2FY and 3FY KIX to discern their differences in allosteric communication are described.
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    Block copolymer Ion gels for CO2 Separations
    (2013-08) Gu, Yuanyan
    Block copolymer ion gel is composed of a polymer network formed by self-assembly of triblock copolymers, and an ionic liquidIn this thesis project, the target is to study the gas separation performance of ion gels for CO2 separation, and seek ways to optimize their properties in terms of the gas separation performance and mechanical strength. Ionic liquids have shown great promise as novel CO2-separation media, largely due to their highly selective gas solubility and non-volatility. It is discovered that the polymer networks not only provides the mechanical support to the ionic liquid, but help improve the gas separation performance as well.To study the CO2 separation performance of block copolymer ion gels, model ion gel systems that comprise 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)amide ([EMI][TFSA]), and a triblock copolymer with a polymerized ionic liquid mid-block was prepared.. The gas separation performance was measured on a supported ion gel membrane. It was discovered that the polymerized ionic liquid gels exhibit high gas permeability due to the high liquid fraction. Moreover, the permeation selectivity is significantly increased from that of the neat ionic liquid. Comparisons with Robeson plots also indicate very promising separation performance for ion gels. Two other ion gels formed by self-assembly of poly(styrene-b-ethylene oxide-b-styrene) (SOS) and poly(styrene-b-methyl methacrylate-b-styrene) (SMS) in [EMI][TFSA] were also examined. The separation performance of ion gels was found to be strongly dependent on the polymer mid-block. It is also desirable to enhance the mechanical properties of ion gels. A novel ion gel based on poly[(styrene-r-vinylbenzyl azide)-b-ethylene oxide-b-(styrene-r-vinylbenzylazide)] (SOS-N3) was synthesized. Such a triblock copolymer ion gel can be chemically cross-linked by high temperature annealing and UV-irradiation. After cross-linking, the mechanical strength of the gel showed significant improvement, with 400% increase in the tensile strength and almost one order of magnitude increase in toughness. The mechanical stability of the supported ion gel membranes was also enhanced. More importantly, the mass transport properties are retained after the cross-linking. Overall, block copolymer ion gels represent a promising class of materials for CO2 separation applications. Through rational choice of ionic liquid and block copolymers, the properties of ion gels can be further optimized.
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    Block copolymers in ionic liquids.
    (2009-06) Simone, Peter Mark
    In this thesis the self-assembly behavior of block copolymers diluted with ionic liquids has been investigated. Initial experiments involved characterizing the selfassembly of poly(styrene-b-methyl methacrylate) (PS–PMMA) and poly(butadiene-bethylene oxide) (PB–PEO) copolymers at dilute concentrations (~1 wt%) in the ionic liquids 1-butyl-3-methylimidazolium hexafluorophosphate ([BMI][PF6]) and 1-ethyl-3- methylimidazolium bis(trifluoromethylsulfonyl)imide ([EMI][TFSI]). Dynamic light scattering and cryogenic transmission electron microscopy results showed that the ionic liquids behave as selective solvents for the PMMA and PEO blocks of the copolymers, and that the micelle morphology and self-assembly behavior of the block copolymers in the ionic liquids was analogous to that observed in conventional solvents. At increased solution concentrations (≥ 20 wt%) the lyotropic mesophase behavior for PB–PEO diluted with [BMI][PF6] and [EMI][TFSI], and poly(styrene-bethylene oxide) (PS–PEO) diluted with [EMI][TFSI] was investigated via small angle X-ray scattering. These experiments showed a microstructure phase progression with addition of ionic liquid that was analogous to that expected for an increase in the PEO volume fraction of the bulk copolymers. Additionally, an increase in the lamellar microstructure domain spacing with ionic liquid content indicated that both ionic liquids behave as strongly selective solvents for the PEO blocks of the copolymers. The ionic conductivity of the concentrated PS–PEO/[EMI][TFSI] solutions was measured via impedance spectroscopy, and found to be in the range of 10−3 S/cm at elevated temperatures (~100 °C). Additionally, the ionic conductivity of the solutions was observed to increase with both ionic liquid content and molecular weight of the PEO blocks of the copolymer. Finally, preliminary investigations of the microstructure orientation in thin films of a concentrated PS–PEO/[EMI][TFSI] solution were conducted. The copolymer microstructure was observed to align perpendicular to the film surface with short term (≤ 2 hours) thermal annealing. Longer term thermal annealing resulted in a transition to parallel alignment of the copolymer microstructure relative to the film surface.
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    C-X bond activation by low-valent first-row transition metal centers.
    (2011-11) Marlier, Elodie Eléonore Julie
    Low-valent metal centers have been of great interest for bond activation considering these species are highly reducing. In this work, two different ligand systems were used to create low-valent metal centers. In both cases, a family of metal complexes was made with each ligand to understand its binding properties and geometries. The first part of this thesis will focus on developing structural models for cobalamin, a cobalt metal center supported by the corrin, a monoanionic tetradentate nitrogen donor ligand. Our interest in modeling cobalamin stems from its ability to remediate chlorinated contaminants from groundwater. Specifically, the cobalt(I) oxidation state of cobalamin is responsible for its reactivity towards C-X bonds. Through the use of beta-diketiminate ligand with pendant donor arms, a successful structural model for cobalamin was created and its reduced cobalt(I) complex was reactive towards C-X bonds. The second part of this work will examine first-row transition metal complexes synthesized with the wide bite-angle disphophine, 4,6-bis(3-diisopropylphosphinophenyl)dibenzofuran. A reduced nickel(I) complex made with this ligand was characterized and its reactivity towards C-X bonds and metathesis was explored.
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    Carbon-carbon sigma bond activation: functionalizing C-C and C-CN Bonds via carboacylation and cyanoamidation
    (2015-01) Dreis, Ashley Michelle
    Chapter One. The content of this chapter broadly describes the growing area of carbon¬-carbon (C-C) sigma bond activation. The barriers to bond activation and the strategies employed to overcome these barriers will be summarized. Examples of stoichiometric and catalytic reactions utilizing strained systems and other thermodynamic driving forces are presented in addition to kinetic strategies enforced through cyclometalation.Chapter Two. The focus of the second chapter is on my discoveries in quinoline-directed C-C bond activation. A series of catalytic intramolecular carboacylation reactions with both alkenes and alkynes will be discussed. The mechanism(s) of such transformations were elucidated by researchers at Hope College and will be presented. The intermolecular carboacylation with norbornenes discovered by other Douglas group members will be acknowledged, and preliminary investigations into the idea of migratory insertion (or sigma-bond metathesis) across cyclopropane will be provided.Chapter Three. The third chapter of this thesis describes my efforts to uncover a synthetically viable directing group for C-C bond activation. Directing groups that are anticipated to be removable and reusable, such as quinoline esters, pyridyl esters, and azaindoles, will be described. Efforts to promote C-C activation with versatile triazene directing groups will be discussed. The strategy of metal-organic cooperative catalysis (MOCC) was explored with guanidines and 2-amino pyrimidine diol derivatives, and the concept of Lewis acid or hydrogen-bond-mediated directing groups will be proposed. Chapter Four. Chapter four provides a selected review of carbon-nitrile (C-CN) bond activation. Cleavage of alkyl, allyl, alkenyl, aryl, acyl, and carbamoyl C-CN bonds that undergo subsequent functionalization will be reported. Intramolecular variations of such reactions are highlighted in complex molecule syntheses.Chapter Five. The final chapter will explain my efforts in developing enantio- and diastereoselective routes to 3,3-disubstituted lactams via C-CN bond activation (cyanoamidation). β-, λ-, and δ-lactams are shown to be effectively prepared through this methodology, and attempts to access ε-lactams will be discussed.
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    Catalytic Substrate Oxidations by Iron/Hydrogen Peroxide: Generation of High-valent Iron-oxo Intermediates by Proton-Induced O-O Bond Cleavage
    (2011-08) Das, Partha
    Non-heme iron enzymes are responsible for various stereospecific hydroxylations under ambient conditions. Pterin-dependent hydroxylases hydroxylate the aromatic rings of aromatic amino acids while Rieske dioxygenases perform cis-dihydroxylation of aromatic double bonds. The most important step in the functioning of these enzymes is the cleavage of the O–O bond. The goal of this research is to investigate the reactivity of synthetic model complexes with H2O2 towards selective oxidative transformations. Iron complexes with tetradentate ligands (TPA, BPMEN where TPA = tris(2- pyridylmethyl)amine and BPMEN = N,N¢-bis(2-pyridylmethyl)-N,N¢-dimethyl-1,2- diaminoethane)) are synthesized and tested in the acid-catalyzed oxidation reactions with H2O2 as the oxidant. The addition of aliphatic acids is found to increase the yield of both alkane and olefin oxidations. Interestingly, the use of benzoic acids, instead, leads to the hydroxylation of the aromatic ring, which is found to be in competition with olefin oxidation. Further investigation reveals FeTPA/H2O2-catalyzed regioselective ortho- (producing salicylates) and ipso-hydroxylation (producing phenolates) of benzoates. Detailed kinetic studies of these reactions – to get a better understanding of the reaction mechanism – show an acid-induced H/D kinetic isotope effect, suggesting the involvement of proton in the rate limiting O–O bond heterolysis of iron(III)-peroxos towards the formation of the high-valent FeV=O species (postulated as the active oxidant). The tuning of ligand (TPA and BPMEN) electronics, by introducing electrondonating substituents in the backbone, exerts a 'push-effect' and increases the rate of O–O bond cleavage and affords a higher yield of catalytic oxidation products.