Physical Sciences and Mathematics Commons^™

Minimalistic Peptide-Based Supramolecular Systems Relevant To The Chemical Origin Of Life, Daniela Kroiss

Dissertations, Theses, and Capstone Projects

All forms of life are based on biopolymers, which are made up of a selection of simple building blocks, such as amino acids, nucleotides, fatty acids and sugars. Their individual properties govern their interactions, giving rise to complex supramolecular structures with highly specialized functionality, including ligand recognition, catalysis and compartmentalization. In this thesis, we aim to answer the question whether short peptides could have acted as precursors of modern proteins during prebiotic evolution. Using a combination of experimental and computational techniques, we screened a large molecular search space for peptide sequences that are capable of forming supramolecular complexes with adenosine …

Probing The Gelation Phenomena In Molecular And Seed-Based Gels, Malick Samateh

Dissertations, Theses, and Capstone Projects

The interest in molecular gels has been gaining momentum as evident from being developed for a broad spectrum of applications. This impetus stems from several reasons that include: (i) molecular gels are highly stimuli responsive as they easily respond to thermodynamic changes, disintegrating into well-defined chemicals/building blocks because of the purely physical (in contrast to chemically cross-linked) nature of the interactions holding their 3D networks together; (ii) the sheer abundance of simple small molecules to choose starting materials from and the vast potential of tunability of the low molecular weight gelators (LMWGs) make the LMWGs and the molecular gels highly …

Synthesis And Characterization Of Multifunctional Transition Metal Oxide Nanoparticles Through A Modified Sol-Gel Method With Application In Energy Storage, Julien Lombardi

Dissertations, Theses, and Capstone Projects

The Synthesis of transition metal oxide nanoparticles has been studied in great detail over the many years. The most studied transition metal oxide nanoparticles are perovskites of the ABO₃ stoichiometry (A and B = transition metal) and more recently double perovskite crystal structures of the AA’BO₆ or A₂BB’O₆ stoichiometry due to the many different properties arising from the many different combinations of elements possible. These materials have proven potentially useful in many fields, but due to properties such as ferroelectricity and ferromagnetism, the desire to integrate these materials into electronics is ever growing. Many synthesis …

Electrochemical Carbon Nanoprobes For Biological And Chemical System Studies, Keke Hu

Dissertations, Theses, and Capstone Projects

The progress in the field of nanoelectrochemistry requires preparation and characterization of nanometer scale electrochemical probes. The focus of my Ph.D. research was on development of carbon nanopipette-based electrodes with versatile and controllable geometry and their applications to nanoscale studies of chemical and biological systems. Carbon nanopipette (CNP) electrodes offer important advantages, including high sensitivity and improved analytical selectivity. They can serve as nanoreactors for sampling ultra-small solution volumes and studies of individual nanoparticles. CNPs were prepared by chemical vapor deposition (CVD) of carbon into the pre-pulled quartz capillaries. By changing pulling parameters and CVD conditions, we fabricated several types …

Preparation Of Enantioenriched Alkyltin Species And Their Application In Stereospecific Transformations, Glenn O. Ralph

Dissertations, Theses, and Capstone Projects

Organometallic reagents containing the tin-carbon bond are used extensively in modern synthetic chemistry for the formation of new bonds to carbon. Over recent decades, transition metal catalyzed cross coupling reactions between two C(sp²) centers have been widely developed. However, the introduction of a C(sp³) center complicates the catalytic cycle, and opens unproductive chemical pathways which lead to isomerization, elimination, and racemization. Our lab has developed a modified-Stille reaction to combat the deleterious effects of β-hydride elimination. Our protocol enables unactivated 2° alkyl organotin nucleophiles to undergo efficient cross coupling reactions with C(sp²) electrophiles, avoiding …

Development Of Highly Efficient Catalyst And Reactions For Organic Synthesis: Monophosphine-Coordinated Palladacycle Complexes For Cross-Coupling Reactions/Polymerizations, Jie Dong

Dissertations, Theses, and Capstone Projects

Transition metal-catalyzed cross-coupling reactions such as Suzuki-Miyaura cross-couplings, are among the most powerful transformations in organic synthesis. They have been extensively used for the synthesis of a wide variety of organic compounds. Recently the Suzuki cross-coupling reaction has been extended to conjugated polymer synthesis, especially the controlled Suzuki cross-coupling polymerization for polymers with the desired length. My research is on developing highly efficient monophosphine-coordinated palladacycle complexes for cross-coupling reactions/polymerizations.

Based on the understanding of transition metal-catalyzed Suzuki cross-coupling reactions including polymerization, my dissertation started with Pd(0)- and Ni(0)-catalyzed borylation reactions of aryl halides and tosylates with bis(pinacolato)diboron to access arylboronates …

A Pretargeted Spect Imaging Strategy Employing Technetium-99m Based On Bioorthogonal Diels-Alder Click Chemistry, Justin H. Walsh

Dissertations, Theses, and Capstone Projects

A series of related N₃S ^99mTc-peptide complexes were synthesized and tested for use in pretargeting SPECT imaging that utilizes the bioorthogonal Diels-Alder click reaction between tetrazine (Tz) and transcyclooctene (TCO). The objective was to optimize the excretory pathways of the ^99mTc-peptide complexes for maximum tumor targeting with the in vivo “click” and minimum non-target uptake. The ^99mTc–tetrazine constructs were prepared by reaction of ^99mTc-peptide complexes (^99mTc-FKC, ^99mTc-FKCR, ^99mTc-DKC, and ^99mTc-SKC) with Tz-NHS or Tz-PEG₅-NHS to form ^99mTc FK(Tz)C, ^99mTc-FK(PEG₅-Tz)CR, ^99mTc-DK(PEG₅-Tz)C, …

Synthesis And Characterization Of Dielectric And Multiferroic Nanocrystalline Transition Metal Oxide Materials And Nanocomposites, Frederick A. Pearsall

Dissertations, Theses, and Capstone Projects

Nanocrystalline transition metal oxides with unique chemical, physical, magnetic and dielectric properties have very broad applications, ranging from photocatalysis, capacitor energy storage and 4-state memory. Frequency stable, high permittivity nanocomposite capacitors produced under mild processing conditions offer an attractive replacement to MLCCs derived from conventional ceramic firing. In one project reported herein, 0-3 nanocomposites were prepared using BaTiO₃ (barium titanate, BTO) nanocrystals, suspended in a poly(furfuryl alcohol) matrix, resulting in a stable, high effective permittivity, low and stable loss dielectric. Effective medium approximations were used to compare this with similar nanocomposite systems. The use of synthesized BTO nanocrystal photocatalysts …

Mild Synthesis Of Perylene Tetracarboxylic Monoanhydrides With Potential Applications In Organic Optoelectronics, Xizhe Zhao

Dissertations, Theses, and Capstone Projects

Perylene tetracarboxylic derivatives are considered good n-type semi-conductors. In past decades, there has been extensive study on their synthesis and electronic properties. Because of the high electron affinity, the ability to form π-π stacks, they have been widely utilized in organic photovoltaic solar cells, field-effect transistors and light-emitting diodes. Many of those applications prefer unsymmetrically substituted perylene tetracarboxylic derivatives. Perylene monoanhydrides are the most versatile intermediates for the preparation of unsymmetrically substituted perylene tetracarboxylic derivatives. In this thesis, I focused on introducing new synthesis methods for perylene monoanhydrides with labile functional group and their potential applications in organic optoelectronics.

In …

Raman And Surface Enhanced Raman Spectroscopy For Forensic Analysis: Case Studies On The Identification Of Illicit Substances And Artist Pigments, Abed Haddad

Dissertations, Theses, and Capstone Projects

Raman spectroscopy is an effective tool for detecting trace amounts of material by fingerprint-like vibrational spectra. At times, the weak intensity of Raman scattering can make it difficult to distinguish trace materials. This shortcoming is addressed by surface‐enhanced Raman spectroscopy (SERS), which produces strong signal enhancements when target compounds are near metal nanoparticles. For the first part of this thesis, the identification of fentanyl and carfentanil, main culprits in the opioid epidemic, was done using normal Raman and the SERS spectroscopy. As an aid in the assignment of the spectral lines, a computational model was built using Density Functional Theory …

Novel Heterocyclic Methodology For The Construction Of Natural Products, Robert C. Lapo

Dissertations, Theses, and Capstone Projects

The synthesis of heterocyclic compounds and their incorporation into total synthesis strategies are described. Three synthetic methodologies toward substituted indoles, isochromans, and fused multi-ring oxazolidinones have been examined. With the progress that has been made, further investigations will hopefully carry the concept to completion.

Chapter I is an introductory examination of the varied types and systematic nomenclature of heterocyclic structures, including common names. This continues on to their commercial and industrial usage, and their great importance in biological systems and natural product chemistry. Finally, examples of heterocycles in fused-ring natural products and examples of historical and/or commercial value are examined …

An Investigation Of Alkylboron Transmetallation In Palladium-Catalyzed Suzuki Reactions, Benjamin Murray

Dissertations, Theses, and Capstone Projects

Through the past 40 years, carbon-carbon cross-coupling reactions have greatly enhanced the ability of chemists to synthesize C(sp²)-C(sp²) bonds and more recently C(sp²)-C(sp³) bonds. In particular, the Suzuki reaction has proven to be invaluable with its high yields, good functional group tolerance, and low toxicity of reagents. One of the component steps of the catalytic cycle of this reaction is transmetallation, in which the nucleophilic species transfers its organic component to the metal center (generally palladium). The mechanism of transfer from primary alkylboron nucleophiles was studied in the 1990's via use of …

Peptide Mediated Co-Assembly Of Porphyrin: Towards Sustainable Biomaterials For Light Harvesting And Catalysis, Wsm Nadeesha K. Wijerathne

Dissertations, Theses, and Capstone Projects

The diverse molecular functions of naturally occurring biomaterials designed from proteins are fundamentally based on a set of conserved building blocks, namely the 20 gene coded amino acids. The supramolecular structures and functions of proteins dictates by the self-assembly, where the complexity of proteins arise from a large number of amino acids. Generation of biomimetic systems that resemble the structures and functions of proteins is of great interest yet challenging due to the tremendous complexity of the natural systems. It is important to investigate alternative strategies to design much simpler systems that exhibit the same or similar function as proteins. …

Solvation Thermodynamic Mapping In Computer Aided Drug Design, Steven Ramsey

Dissertations, Theses, and Capstone Projects

The displacement of water from surfaces upon biomolecular recognition and association makes a significant contribution to the free energy changes of these processes. We therefore posit that accurate characterization of local structural and thermodynamic molecular water properties can improve computational model accuracy and predictivity of recognition and association processes. In this thesis, we discuss Solvation Thermodynamic Mapping (STM) methods that we have developed using inhomogeneous fluid solvation theory (IST) to better characterize active site water structural and thermodynamic properties on protein surfaces and the open source tools that we have developed, GIST-CPPTRAJ and SSTMap, which implement these methods which we …

Bisthioether Stapled Peptides Targeting Polycomb Repressive Complex 2 Gene Repression, Gan Zhang

Dissertations, Theses, and Capstone Projects

Interactions between proteins play a key role in nearly all cellular process, and therefore, disruption of such interactions may lead to many different types of cellular dysfunctions. Hence, pathologic protein-protein interactions (PPIs) constitute highly attractive drug targets and hold great potential for developing novel therapeutic agents for the treatment of incurable human diseases. Unfortunately, the identification of PPI inhibitors is an extremely challenging task, since traditionally used small molecule ligands are mostly unable to cover and anchor on the extensive flat surfaces that define those binary protein complexes. In contrast, large biomolecules such as proteins or peptides are ideal fits …

Synthesis And Evaluation Of Novel Iodine-124 Labeled Nucleoside Analogs As Pet Imaging Agents To Predict Response To Gemcitabine Therapy, Kishore Kumar Gangangari

Dissertations, Theses, and Capstone Projects

Gemcitabine (gem) is a nucleoside analog that is used to treat pancreatic cancers (PaCa), which have dismal prognosis and low survival rate. Though gem is used as first line of treatment for PaCa, the response rate is quite low (~30%). Currently, there is no a priori way to determine a responder from a non-responder to gem therapy either invasively or non-invasively. Any biomarker that can act as a prognostic indicator of gem response will greatly aid in selecting responsive patients to gem therapy and provide alternative options such as Folfirinox or other treatments to resistant patient population. Amongst various known …

Pretargeted Radioimmunotherapy Utilizing The Inverse Electron Demand Diels-Alder Reaction, Rosemery Membreno

Dissertations, Theses, and Capstone Projects

Radioimmunotherapy capitalizes on the specificity and affinity of antibodies for their antigens to localize radioactivity at the tumor site. One limitation in using antibodies is their long circulation time, which can take days to weeks to fully clear from blood circulation. When a radioisotope is directly conjugated to this immunoglobulin vector, the red marrow and other healthy organs are receiving a constant radiation dose while it is in blood circulation. This not only harms healthy organs, but limits the dose of radioactivity that can be administered thus prolonging treatment. A promising alternative to limit the radiation dose to non-tumor tissue …

Potential Degradation Of Hexabromocyclododecane (Hbcdd) In Sediments: Stereoisomer Specific Reaction Of Hbcdd With Reduced Sulfur Species Or Fe(Ii) Bound To Iron Oxides, Xianmiao Zhang

Dissertations, Theses, and Capstone Projects

The individual degradation rates of the three dominant stereoisomers (alpha, beta, gamma) of hexabromocyclododecane (HBCDD) with bisulfide and polysulfides were investigated at pH 9-10 in methanol/water solutions at two different temperatures (25 °C and 40 °C). alpha-HBCDD reacts significantly slower than beta-HBCDD and gamma-HBCDD. It was also observed that the reaction of HBCDD with polysulfides is faster than with bisulfide. For the reaction of HBCDD with bisulfide, the experiments were performed in 20% water/80% methanol, 50% water/50% methanol and 80% water/20% methanol at 40 °C. It was determined that the solvent polarity affects the reaction and the second-order rate constants …

Development Of Palladium(0)-Catalyzed Suzuki Cross-Coupling Polymerizations, Wei Peng

Dissertations, Theses, and Capstone Projects

The synthesis of well-defined and high molecular weight π-conjugated polymers under mild condition within short reaction time is a challenging and important task in both organic chemistry and polymer chemistry. As one of the most efficient and high tolerance to solvents and reaction conditions, palladium(0)-catalyzed cross-coupling reactions would give us a good chance to achieve the goal. Thus, my Ph. D dissertation research projects focused on developing Pd(0)-catalyzed Suzuki cross-coupling polymerization reactions including controlled ones.

My research first studied t-Bu₃P-coordinated 2-phenylaniline-based palladacycle complex catalyzed Suzuki cross-coupling polymerization of aryl dibromides with aryldiboronic acids at room temperature. Based …