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Oxidative C–C And C–Heteroatom Reactivity Of High-Valent Nickel Complexes, Sofia Marie Smith

Arts & Sciences Electronic Theses and Dissertations

ABSTRACT OF THE DISSERTATION

Oxidative C–C and C–Heteroatom Reactivity of High-Valent Nickel Complexes

by

Sofia M. Smith

Doctor of Philosophy in Chemistry

Washington University in St. Louis, 2019

Professor Liviu M. Mirica, Chair

Professor Kevin D. Moeller, Co-Chair

Nickel catalysts are commonly used for cross-coupling reactions such as Negishi, Kumada and Suzuki couplings. While Ni(0), Ni(I), and Ni(II) intermediates are most relevant in these transformations, Ni(III) and Ni(IV) species have also been recently proposed to play a role in catalysis. The formation of C–C and C–heteroatom bonds plays a fundamental role in organic transformations, and today cross-coupling reactions are one …

Use Of Self-Assembled Monolayers To Tailor Surface Properties: From Lubrication To Neuronal Development, Natalie Ann Lafranzo

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The subsequent work describes advances in modifying the chemical properties of various substrates to tailor the surface properties for specific applications. This is achieved by making use of a molecular assembly known as self-assembled monolayers, or SAMs. SAMs are composed of tightly packed organic molecules that form a well-ordered structure on a substrate. Typically, the head group of the monomer is covalently anchored to the substrate, and monolayer order and self-assembly is achieved through van der Waals interactions between the long alkyl chains of the monomer's tail group. Monolayers containing head groups consisting of thiols, siloxanes, and phosphonates have been …

A Specialized Citric Acid Cycle Requiring Succinyl-Coenzyme A (Coa):Acetate Coa-Transferase (Aarc) Confers Acetic Acid Resistance On The Acidophile Acetobacter Aceti, Elwood Mullins

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The characteristic ability of acetic acid bacteria to aerobically oxidize ethanol to acetic acid has been harnessed for millennia to produce vinegar. Acetic acid permeates cell membranes at low pH and generally inhibits bacterial growth at low millimolar concentrations. The strains used for vinegar production, however, thrive in near-molar concentrations. This remarkable resistance results from the combined contributions of several molecular mechanisms. This study examines the inherent acid stability of proteins from the industrial vinegar-production strain Acetobacter aceti 1023 and the process by which cytoplasmic acetic acid is "overoxidized" to carbon dioxide. Acetate overoxidation in A. aceti strain 1023 is …

Investigation Of The Structure Of Alkyne Self-Assembled Monolayers On Gold And The Development Of Matrix-Enhanced Secondary Ion Mass Spectrometry Methods, Jennifer Dertinger

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Characterization of thin films is critical to the understanding of many technological and biological processes. The focus of this dissertation is to develop methods to characterize very low concentration species present on surfaces. A reflection adsorption infrared spectroscopy: RAIRS) system was constructed and tested. The instrument comprises an Fourier transform infrared: FTIR) spectrometer, an optical pathway and a vacuum chamber. The RAIRS system is designed to investigate in situ the interaction of vapor-deposited metals and gases, such as CVD precursors, with organic thin films, and so a vacuum chamber is required. To accommodate the vacuum chamber, an external IR optical …

Part I Development Of Nucleophilic Acylation Catalysts Part Ii Chiral Brønsted Acid Catalyzed Enantioselective Alcoholysis, Guojian Lu

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Chiral bicyclic amidines and isothioureas developed in our group have been showed as a new type of nucleophilic acyl transfer catalysts. Based on the previous achievement in our group, several aza-analogues and a 5,7-menbered ring bicyclic analogue of THTP were prepared. Its synthesis proved to be more laborious than that of the THTP analogue derivative, and the enantioselectivity was substantially lower. Based on the previous discovery in our group that 1,2,4-triazole anion, as an active acyl transfer catalyst, can promote aminolysis and transesterification of moderately activated or even unactivated esters, a systematic study of pyrazole derivatives in this transformation was …

Quantitative Perfusion-Sensitive Mri Phantoms, Jeff Anderson

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Perfusion-sensitive MR methods are increasingly utilized in preclinical and clinical MR research studies with the promise of providing quantitative estimates of parameters that describe in vivo microvasculature. One of these techniques, dynamic contrast enhanced: DCE) MRI, has found particularly common use in oncology for the detection, staging, and monitoring of highly vascularized tumors. DCE-MRI has been qualitatively validated by various studies that show a high correlation between modeled parameters from DCE and histologically measured microvascular density: MVD). However, in the absence of a matching "gold-standard" technique, DCE-MRI has not yet been quantitatively validated: i.e., the accuracy of the estimated parameters …

Design, Synthesis And Characterization Of Lipidated Pna-Peptide Conjugates As Potentialtherapeutic And Diagnostic Reagents, Yinyin Song

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Peptide Nucleic Acids: PNAs), are an ideal choice for antisense and antigene tools and probes because of their stability and high binding affinity, but have limited application as therapeutic and diagnostic agents because of poor membrane permeability. To increase membrane permeability, we conjugated hydrophobic lipids or phospholipid molecules and hydrophilic cell penetrating peptides to the N and C terminus of PNAs, and studied their physical and biological properties. After solid-phase automated synthesis, PNA-CPPs: TAT/Arg9) were coupled with lipids or phospholipids before cleavage from the support and then purified by HPLC. The conjugates were characterized by UV-vis and MALDI, and by …

Well-Defined Molecular Brushes: Synthesis By A "Grafting Through" Strategy And Self Assembly Into Complicated Hierarchical Nanostructures, Zhou Li

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This dissertation focuses on the development of a "grafting through" methodology to synthesize molecular brushes with well-defined structures, as an attempt to construct nanostructures by covalent bonds totally. Detailed synthetic procedures for and characterization of molecular brushes, as well as complicated hierarchical nanostructures resulted from their self-assembly are reported. The synthesis of molecular brushes is achieved by combining orthogonal living polymerization techniques rationally, such as living/controlled radical polymerization, ring opening polymerization and ring opening metathesis polymerization. Generally, the strategy can be divided into two steps: the first step involves the preparation of linear macromonomers whose chain ends are functionalized with …

Novel Plasmonic Nanostructures For Applications In Sensing, Imaging, And Controlled Release, Weiyang Li

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This research placed emphasis on engineering the properties of novel plasmonic nanostructures, especially silver: Ag) and gold: Au) nanostructures with well-defined shapes, for biomedical applications in sensing, imaging and drug delivery. The first part of this work focused on the development of novel dimeric nanostructures of Ag for surface-enhanced Raman scattering: SERS) applications. In this section, I successfully demonstrated the synthesis of well-defined Ag dimers consisting of nanospheres with a broad range of sizes by using two methods. The first method was based on polyol process and the second was based on wet etching. The key for the dimerization process …

Mass Spectrometry-Based Structural Proteomics: Bottom-Up Protein Footprinting And Top-Down Native Electrospray Of Protein Assemblies, Hao Zhang

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Converting gene-sequence information into functional information about a protein is a major challenge of post-genomic biology. Proteins have a variety of functions from serving as catalysts to acting as structural components; all these functions are closely related to protein structure. The first step to understand protein function is often a structural study of that protein. Two major approaches, NMR spectroscopy and X-ray crystallography, can provide an atomic-level, 3D structural model of a protein. The applications of these high resolution approaches, however, are limited by protein size, conformational flexibility, and aggregation propensity. To obtain complementary structural information about proteins, a variety …

Examination Of Uv-Cross-Linkable Di-Block Copolymer Strategy For Functionalized Reaction Surface On Microelectrode Arrays, Libo Hu

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Microarrays are powerful tools for high-throughput screening of small molecule libraries. Our group is using a microelectrode array variant on these efforts that allows us to construct and screen the libraries in a rapid, cost effective fashion. In this approach, the small molecules are attached to polymer-coated microelectrodes, which can be used to detect ligand-receptor interactions as they happen by means of impedance. Impedance experiment work by monitoring the current associated with a redox couple in solution. When a protein binds a ligand on the array, it sterically prevents the redox couple from reaching the electrode surface and thus causes …

Studies Of Fluorescent Imaging For Mrna Detection In Living Cells, Zhenghui Wang

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This dissertation focuses on the study of imaging mRNA in living cells. To achieve this research objective, three approaches have been utilized:: 1) Imaging of a transgenic mRNA tagged by multiple repeats of malachite green: MG) binding aptamer.: 2) Imaging of inducible nitric oxide synthase: iNOS) mRNA by strand-displacement activated Peptide Nucleic Acid: PNA) probes.: 3) Imaging of iNOS mRNA by binary fluorescently labeled PNA probes. The first approach was based on the work of our former lab member Dr. Huafeng Fang, who had constructed a multiple MG binding aptamer tagged transgene: Flag-mβ2AR-GFP-MGVI), which could also express a green fluorescence …

Surface Passivation Of Colloidal Ii-Iv Semiconductor Quantum Belts And Quantum Wires: Synthesis, Mechanism And Optical Studies, Yi-Hsin Liu

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My research aims to study the formation mechanism of CdSe quantum belts: QBs) and the surface passivation of CdTe quantum wires: QWs). Investigation of QB morphology and QW passivation are fundamentally important to avoid nonradiative recombination and to increase electron-transport efficiency in semiconductor solar-cell devices. The origin of CdSe QBs is a lamellar structure of cadmium-octylamine precursor complex, with an intermediate state of stripe-like assembly of CdSe magic-sized nanoclusters. Transformation of: CdSe)13 nanoclusters to CdSe quantum belts: QBs) is conducted by higher annealing-temperature and confirmed by their optical and structural characterization. The QBs possess a thickness of 1.5-2.0 nm with …

Studies Toward The Synthesis Of Lomaiviticins A And B And Englerin A, Srinivas Achanta

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Part I: Studies toward the central core of lomaiviticins A and B Lomaiviticins A and B are novel C2-symmetric dimeric molecules with profound cytotoxic activity. The most challenging feature of these molecules is the densely functionalized central core. Despite the effort by several research groups, the total synthesis of lomaiviticins has not been reported so far. We envisioned the synthesis of the lomaiviticin core by an unprecedented Diels-Alder dimerization of ortho-quinols and masked ortho-benzoquinones, followed by the fragmentation of the extra carbon-carbon bond. This chapter describes the stereoselective elaboration of the ortho-quinol and masked ortho-benzoquinone dimers to the fragmentation precursors …

Synthesis And Investigation Of Uv-Cured, Complex Amphiphilic Polymer Films For Use In Anti-Biofouling Applications, Jeremy Bartels

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The overall emphasis of this dissertation research included the development of novel amphiphilic anti-fouling coatings having complex surface topography and compositional heterogeneity and a fundamental investigation of their properties. These films were cultivated as non-fluorinated or non-fluorinated/non-PEGylated analogs to the hyperbranched fluoropolymer-poly(ethylene glycol): HBFP-PEG) film system. The coating compositions consisted of the mixing and crosslinking of either two disparate polymers or a complex amphiphilic block copolymer with crosslinking agents. A variety of crosslinking methods was analyzed, including vulcanization and UV-promoted thiol-ene reactions. The coatings were analyzed using a variety of advanced methods, including thermomechanical techniques, tensile testing and surface analysis. …

Design, Synthesis And Characterization Of Synthetic Ion Receptors As Biologically Functional Ion Carriers And Channels, Carl Yamnitz

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The study of proteins and natural molecules that transport cations and anions across biological membranes has been a major focus of biochemistry and cellular biology for more than a century. The function of ion transporters is vital for all known forms of life. Natural and synthetic transporters can have applications as antimicrobial agents, in nerve impulse transduction and cell signaling. The current work was performed to further the understanding of a diverse array of novel and previously-studied synthetic molecules as membrane-active ion transporters. In the process, important facets such as ion binding capacity, aggregation behavior, ion transport functionality, and antimicrobial …

Intramolecular Anodic Olefin Coupling Reactions: Synthesis Of Nitrogen- And Oxygen-Heterocycles, Haichao Xu

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Anodic oxidation has been shown to be a powerful method for initiating umpolung reactions that allow the coupling of two nucleophilic functional groups. Most of the work in this area concentrates on making carbon-carbon bond. Hence, the reactions are usually terminated with olefin nucleophiles. The use of heteroatom-based coupling partners to form carbon-heteroatom bond is less explored despite the wide occurrence of heterocyclic compounds as natural products, pharmaceuticals, and synthetic building blocks. Therefore, this thesis focuses on the application of heteroatom-based coupling partners in intramolecular anodic olefin coupling reactions for the synthesis of N- and O-heterocyclic compounds. First, a synthesis …

Fcs Analysis Of Pore Formation By The Human Protein Bax In Lipid Membranes, Olena Ivashyna

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Bax is a pro-apoptotic member of the BCL-2 protein family and its paramount function during apoptosis is to form pores in the mitochondrial outer membrane: MOM). In a simplified apoptosis model, upon apoptotic stimulation, Bax is activated via an unresolved mechanism, translocates to the MOM, where it changes conformation, inserts into the membrane as a monomer, and finally undergoes in-membrane oligomerization to form a pore. Once the Bax pore is formed, cytochrome c and other mitochondria-resident proteins escape into the cytoplasm where they activate the cascade of caspases, which dismantle the cell. To date, the structure of the inactive cytoplasmic …

Synthesis, Structure And Spectroscopy Of Heteropentadienyl-Cobalt Complexes, Bryn Lutes

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A heteropentadienyl ligand is a molecule in which the terminal carbon of a pentadienyl ligand has been replaced with a heteroatom: O, PR, NR, S, SiR2). The study of heteropentadienyl-transition metal complexes has been an active area of research in the last decade, and has recently received significant attention in the chemical literature. These molecules can now be synthesized by generalized methods, allowing their unique reactivity to be the focus of current research. These molecules have shown the ability to adopt and shift between a variety of bonding modes, opening coordination sites at the metal center and showing promise for …

Examination Of Molecular Recognition In Protein-Ligand Interactions, Yat Tang

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This dissertation is a compilation of two main projects that were investigated during my thesis research. The first project was a prospective study which identified and characterized drug-like inhibitors of a prototype of bacterial two-component signal transduction response regulator using computational and experimental methods. The second project was the development and validation of a scoring function, PHOENIX, derived using high-resolution structures and calorimetry measurements to predict binding affinities of protein-ligand interactions. Collectively, my thesis research aimed to better understand the underlying driving forces and principles which govern molecular recognition and molecular design. A prospective study coupled computational predictions with experimental …

Transient-State Kinetic Studies Of The Mechanisms Of Dna Unwinding And Translocation Of The E. Coli Recbc And Recbcd Helicases, Colin Wu

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This thesis presents mechanistic studies of the E. coli RecBC and RecBCD helicases using transient-state kinetic approaches to understand the relationship between DNA unwinding and ssDNA translocation. RecBC initiates unwinding from duplex DNA ends with pre-existing 5'-(dT)6 and 3'-(dT)6 ssDNA tails using a series of repeated rate-limiting steps with a rate of 345 ┬▒ 8 bp/sec and an average kinetic step-size of ~4 bp: 20 mM Mops-KOH, pH 7.0 at 25°C, 30 mM NaCl, 10 mM MgCl2, 5% glycerol, 1 mM 2-mercaptoethanol) while RecBCD unwinds these same DNA substrates with a rate of 745 ┬▒ 18 bp/sec using a more …

Tandem, Oxidative Cyclizations By Anodic Electrochemistry And The Use Of Solar Power As An Alternate Energy Source, Laura Anderson

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Cyclization reactions are a significant pursuit in organic synthesis. Unfortunately, many cyclization reactions are either reductive in nature or redox neutral. This can force post-cyclization manipulations to add functional groups and continue the total synthesis. These additional reactions create excess waste and decrease the efficiency of a synthetic scheme. In these cases, it would be nice to do the cyclization in an oxidative fashion. Oxidative cyclizations have been performed, but are currently limited in nature and scope. One way to address this issue is with the use of organic electrochemistry. Electrochemistry appears to be an ideal choice for initiating oxidative …

Nucleation Control In Size And Dispersity In Metallic Nanoparticles: The Prominent Role Of Particle Aggregation, Vernal Richards

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The aim of this project is to investigate the effect of aggregative nucleation and growth on the final size and dispersity in metallic nanoparticle systems. Aggregative nucleation functions are determined for the first time for three nanocrystal systems, namely gold: Au), silver: Ag) and bismuth: Bi). These nucleation functions give critical information that correlates closely with the size and dispersity of t+X123he nanocrystals synthesized. The aggregative nucleation functions and growth kinetics of pre-synthesized Au nanoparticles as a function of tetra-n-octylammonium bromide: n-octyl4NBr) is investigated. For each kinetic trial, the time dependence of the aggregative nucleation rate is extracted from the …

Discovery And Identification Of New Dna Photoproducts And Investigation Of The Redox Mechanism Of Human Apurinic/Apyrimidinic Endonuclease 1 (Hape1) Protein, Dian Su

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Exposure of cells to ultraviolet light results in the formation of DNA photoproducts, many of which have been linked to skin cancer. The majority of these photoproducts arise from a photoreaction between two pyrimidines. Irradiation of double stranded B form DNA under physiological conditions mainly produces adjacent dimers. Nonadjacent photodimers of both intrastrand and interstrand types are much rarer. Intrastrand-type nonadjacent dimers form when one or more nucleotides between two pyrimidines become extrahelical owing to the formation of single strand DNA or a slipped structure. This allows the two pyrimidines to photodimerize in a colinear arrangement, as if the intervening …

Quantitative Phosphoproteomics Through Β-Elimination And Michael Addition With Natural Abundance And Stable Isotope Labeled Thiocholine, Meng Chen

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The reversible covalent phosphorylation of cellular proteins is widely believed to be the most important mechanism for the regulation of multiple signal transduction pathways in cell growth, division, and death by acting as a molecular switch at multiple nodes in metabolic networks. In this dissertation, first, a novel mass spectrometric strategy is reported that exploited the unique chemical properties of thiocholine that was introduced into protein phosphosites through alkaline beta-elimination and Michael addition: BEMA), allowing the specific detection, identification and quantitation of phosphorylated serine/threonine containing peptides. Through replacement of the phosphate with thiocholine as the Michael donor, this strategy resulted …

Synthetic Ion Transporters: New Analytical Approaches For The Investigation Of Ion Binding And Transport, Ionut Carasel

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Synthetic ion transporters: new analytical approaches for the investigation of ion binding and transport by Ionut Alexandru Carasel Doctor of Philosophy in Chemistry Washington University in St. Louis, 2010 Dr. George W. Gokel, co-Chair Dr. Kevin Moeller, co-Chair The work reported in this dissertation focuses on synthetic ion transporters: SATs). SATs have a relatively simple chemical structure but they aggregate, self-assemble and insert in biological membranes much in the same way as their much more complex naturally occurring analogs. This makes SATs valuable tools for the investigation of these supramolecular and membrane related processes with the final goal of developing …

Synthesis Of Complex Plasmonic Nanostructures For Applications In Surface-Enhanced Raman Spectroscopy And Biomedicine, Claire Cobley

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This research centers around techniques to engineer the properties of noble-metal nanostructures for applications in surface-enhanced Raman spectroscopy: SERS) and biomedicine. Many of these potential applications are made possible by the strong localized surface plasmon resonance: LSPR) of noble-metal nanostructures, which is heavily influenced by the particle's morphology. The first part of this work focuses on the solution-phase synthesis of Ag nanostructures. In this section, I demonstrate the synthesis of Ag nanostructures with two different morphologies that are interesting for fundamental SERS studies: anisotropically truncated octahedrons and large, single-crystalline spheres. In both syntheses, control over etching was critical to morphological …

Development Of Atomistic Potentials For Silicate Materials And Coarse-Grained Simulation Of Self-Assembly At Surfaces, Brian Barnes

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This thesis is composed of two parts. The first is a study of evolutionary strategies for parametrization of empirical potentials, and their application in development of a charge-transfer potential for silica. An evolutionary strategy was meta-optimized for use in empirical potential parametrization, and a new charge-transfer empirical model was developed for use with isobaric-isothermal ensemble molecular dynamics simulations. The second is a study of thermodynamics and self-assembly in a particular class of athermal two-dimensional lattice models. The effects of shape on self-assembly and thermodynamics for polyominoes and tetrominoes were examined. Many interesting results were observed, including complex clustering, non-ideal mixing, …

Light-Harvesting And The Primary Photochemistry Of Roseiflexus Castenholzii, Aaron Collins

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Photosynthetic organisms have evolved diverse antennas to harvest light of various qualities and intensities. Anoxygenic phototrophs can have bacteriochlorophyll Q_y antenna absorption bands ranging from about 700-1100 nm. This broad range of usable wavelengths has allowed many organisms to thrive in unique environments. Roseiflexus castenholzii is a niche-adapted, filamentous anoxygenic phototroph: FAP) that lacks chlorosomes, the dominant antenna found in all green bacteria. Light-harvesting is realized only in the membrane with BChl a and a variety of carotenoids. Through biochemical and spectroscopic methods, a model for the size and organization of the photosynthetic antenna is presented. Despite the wide …

Structure And Function Of The Fmo Protein From The Photosynthetic Green Sulfur Bacteria, Jianzhong Wen

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The Fenna-Matthews-Olson: FMO) bacteriochlorophyll a protein has served as a model antenna system for understanding pigment-protein interaction and the energy transfer mechanism. The FMO protein has been extensively studied by a wide range of spectroscopic and theoretical techniques due to its stability, spectral resolution of pigments, water-soluble nature and availability of high-resolution structural information. A new 1.3 ├à FMO structure: PDB: 3EOJ) revealed an 8th pigment at the monomer connection region with partial occupancy. To understand the nature and stoichiometry of this new pigment, the molecular weight of the whole FMO complex was measured by the recently developed mass spectrometry: …