Digital Commons Network^™

Benzoquinone Ligand-Enabled Ruthenium-Catalyzed Deaminative Coupling Of 2-Aminoaryl Aldehydes And Ketones With Branched Amines For Regioselective Synthesis Of Quinoline Derivatives, Krishna Prasad Gnyawali, Aldiyar Shakenov, Pandula T. Kirinde Arachchige, Chae S. Yi

Chemistry Faculty Research and Publications

The catalytic system generated in situ from the cationic Ru–H complex [(C₆H₆)(PCy₃)(CO)RuH]⁺BF₄– (1) with 2,3,4,5-tetrachloro-1,2-benzoquinone (L1) was found to be highly effective for promoting the deaminative coupling reaction of 2-aminoaryl aldehydes with branched amines to form 2-substituted quinoline products. The analogous deaminative coupling reaction of 2-aminoaryl ketones with branched amines led to the regioselective formation of 2,4-disubstituted quinoline products. A number of biologically active quinoline derivatives including graveolinine and a triplex DNA intercalator have been synthesized by using the catalytic method.

Anticancer Drugs Of Lysine Specific Histone Demethylase-1 (Lsd1) Display Variable Inhibition On Nucleosome Substrates, Dulmi Senanayaka, Danyun Zeng, Emre Deniz, Indunil K. Priyankara, Joceline Helmbreck, Owen Schneider, Aashay Mardikar, Aykut Uren, Nicholas J. Reiter

Chemistry Faculty Research and Publications

Lysine specific demethylase-1 (LSD1) serves as a regulator of transcription and represents a promising epigenetic target for anticancer treatment. LSD1 inhibitors are in clinical trials for the treatment of Ewing’s sarcoma (EWS), acute myeloid leukemia, and small cell lung cancer, and the development of robust inhibitors requires accurate methods for probing demethylation, potency, and selectivity. Here, the inhibition kinetics on the H3K4me2 peptide and nucleosome substrates was examined, comparing the rates of demethylation in the presence of reversible [CC-90011 (PD) and SP-2577 (SD)] and irreversible [ORY-1001 (ID) and tranylcypromine (TCP)] inhibitors. Inhibitors were also subject to viability studies in three …

Autoregulatory Mechanism Of Enzyme Activity By The Nuclear Localization Signal Of Lysine-Specific Demethylase 1, Dulmi Senanayaka, Danyun Zeng, Sahar Alishiri, William J. Martin, Khadijah I. Moore, Roshni Patel, Zigmund Luka, Alexander Hirschi, Nicholas J. Reiter

Chemistry Faculty Research and Publications

The N-terminal region of the human lysine-specific demethylase 1 (LSD1) has no predicted structural elements, contains a nuclear localization signal (NLS), undergoes multiple posttranslational modifications (PTMs), and acts as a protein-protein interaction hub. This intrinsically disordered region (IDR) extends from core LSD1 structure, resides atop the catalytic active site, and is known to be dispensable for catalysis. Here, we show differential nucleosome binding between the full-length and an N terminus deleted LSD1 and identify that a conserved NLS and PTM containing element of the N terminus contains an alpha helical structure, and that this conserved element impacts demethylation. Enzyme assays …

Efficient Synthesis Of Thiazole-Fused Bisnoralcohol Derivatives As Potential Therapeutic Agents, Subrata Roy, Hansa Raj Kc, Sanjay Adhikary, Alexander N. Erickson, Mohammad Abrar Alam

Chemistry Faculty Research and Publications

Thiazole derivatives are known for a wide range of therapeutic properties. Bisnoralcohol is an inexpensive natural product obtained by the biodegradation of sterols. This article describes an efficient synthesis of a library of thiazole-fused bisnoralcohol derivatives. These novel compounds have been studied for their antineoplastic and antibacterial properties, which led to the discovery of hit compounds with therapeutic potential. The antibacterial compound is noncytotoxic and nonhemolytic against cancer cell lines and sheep red blood cells, respectively. Several of the antineoplastic compounds showed activity against human cancer cell lines with growth inhibition at submicromolar concentration.

Additive-Dependent Regioselective Boracarboxylation Of Alkenes Using Low Valent Copper And Co2, Carly H. Gordon Ph.D.

Graduate Theses, Dissertations, and Problem Reports (ETD)

As a major greenhouse gas, carbon dioxide (CO₂) is an abundant and renewable C₁ feedstock, and developing methods for fixing CO₂ into high-value products is a major interest for the movement of greener chemistry. The boracarboxylation of alkenes provides access to difunctionalized products containing pharmaceutically relevant motifs, including carboxylic acids and boron-containing moieties. Significant work has been done to improve the versatility and efficiency of this methodology, with the recent expansion into a wide variety of terminal alkenes. The use of different phosphine and alkene additives have demonstrated positive effects on reaction rates and productivity, indicating …

Spiral Wave Teleportation And Multiplex Network Synchronization In Light Sensitive Belousov-Zhabotinsky Systems, Shannyn Alicia Tyler

Graduate Theses, Dissertations, and Problem Reports (ETD)

We experimentally and computationally investigate dynamical behaviors in excitable and oscillatory media using light sensitive Belousov-Zhabotinsky (BZ) systems. These systems are not in a state of thermodynamic equilibrium, and have been proven to show various interesting phenomena including spatiotemporal patterns, self-organization, and chaos. We utilize the BZ reaction, a nonlinear chemical reaction, known for its relaxation-type oscillations, to explore the dynamics of these systems.

We examine spiral wave teleportation in an excitable media as an effective alternate defibrillation method. Spiral waves have emerged as a key phenomenon associated with the initiation and persistence of cardiac arrhythmias. Using a light sensitive …

A Portable, Digital Nucleic Acid Amplification Test For Use At The Point Of Care, Bethany J. Fike

Graduate Theses, Dissertations, and Problem Reports (ETD)

Nucleic acid tests are key tools for the detection and diagnosis of many diseases. In many cases, the amplification of nucleic acids is required to reach a detectable level. Although nucleic acid tests have great success, there is a need to make nucleic acid amplification tests more accessible to a point-of-care (POC) setting for diagnosis, prognosis, and monitoring of infectious diseases. Traditionally, these tests are performed through bulk Polymerase Chain Reaction (PCR) and are monitored in real time with a change in fluorescence intensity. With these bulk testing methods, only a qualitative or semi-quantitative result is possible. For more exact …

Photoinduced Alpha-Hydroxy C–H Alkylation Of Mono-Alcohols Via Hydrogen Atom Transfer (Hat) Of An Activated Boron-Containing Complex, Courtney Deanna Glenn

Graduate Theses, Dissertations, and Problem Reports (ETD)

Hydroxy (-OH) groups are one of the most abundant functional groups found in natural products and pharmaceuticals with many of these compounds containing multiple alcohol classes. The ability to selectively functionalize a specific α-OH C–H bond in the presence of other competitive sites would provide straightforward access to new, potentially bioactive compounds. In recent literature, photoredox catalysis has been implemented to perform site and stereoselective α-OH C–H functionalization of cis-diol containing substrates. Incorporating an organoboron cocatalyst into these systems have proven to be crucial in decreasing the bond dissociation energy (BDE) and increasing hydricity of the α-OH C–H bond …

Chemical Synthesis Of Sensitive Dna, Komal Chillar

Dissertations, Master's Theses and Master's Reports

Over the past decades, researchers have tried various chemical methods to synthesize modified oligodeoxynucleotides (ODNs, i.e. short segments of DNAs). Traditional ODN synthesis methods require strong basic, and nucleophilic conditions for the deprotection and cleavage of the ODN from the solid support. However, the sensitive ODNs containing labile functionalities are vulnerable to such harsh conditions. Sensitive ODNs have a wide range of applications in research and pharmaceuticals. To synthesize sensitive ODNs, researchers devised different strategies but no practical methods have been developed. To overcome these challenges, we developed alkyl Dim alkyl Dmoc technology. This innovative technology uses weakly basic and …

Establishing A Two-Color Fluorescence Probe Assay For The Simultaneous Screening Of Glut5 And Glut2 Fructose Transporters In Live Cells, Oluwanifesimi Mary Afolabi

Dissertations, Master's Theses and Master's Reports

The mammalian facilitative glucose transporter (GLUT) family comprises 14 members that mediate the transport of hexoses across cell membranes. GLUT5 is the only member specific to fructose, and together with GLUT2, which transports fructose in addition to glucose, they make up the primary fructose transporters in humans. This study introduces a novel two-color fluorescence assay designed to simultaneously monitor the activity of GLUT5 and GLUT2 in live cells. 2,5-anhydro-D-mannitol (2,5-AM) a GLUT5 targeting compound has facilitated the development of various fructose-mimicking probes with a wide range of properties, such as radioactive imaging, fluorescent, photoactive, and drug delivery capabilities. Effective and …

A Physicochemical Characterization Of Protein Aggregates: Influence Of Lipid Membranes And Surfaces, Connor J. Hall

Dissertations, Master's Theses and Master's Reports

Protein aggregation is a hallmark of neurodegenerative diseases (NDs). Although there has been a greater emphasis in the past decade or more on the correlation between the physicochemical characteristics of aggregates and their cellular toxicity, it is still unclear what specific features of an aggregate render it toxic. To better understand that, there has been a renewed focus on the characterization of unique biochemical and biophysical properties of protein aggregates. Elucidation of these unique characteristics can help to better understand disease pathogenesis in vivo. Furthermore, the lipid-rich nature of the brain sets it apart from all other organs, and numerous …

Synthesis Of Long Oligodeoxynucleotides, Yipeng Yin

Dissertations, Master's Theses and Master's Reports

Synthetic long oligodeoxynucleotides (ODNs) have found wide applications in diverse fields such as chemical biology, synthetic biology, and genes and genomes synthesis. Those applications leading to a significant demand for their production. However, traditional methods for purifying synthetic ODNs present notable drawbacks, particularly their inability to purify long ODNs, rendering long ODN synthesis challenging. To address these issues, chemical synthesis techniques for long ODNs coupled with non-chromatographic purification methods have been developed. This technology makes the purification of long synthetic ODNs feasible and offers a viable pathway for producing genes and genomes with extensive repeats or stable secondary structures, which …

The Surface Chemistry And Binding Interactions Of Lignin With Polymer-Encapsulated Gold Nanoparticles Acting As Model Microplastics, Oluwaseun Ayodeji Akinsola

All Master's Theses

This study investigates the surface chemistry and molecular-level interactions between lignin, a special type of natural organic matter, and polymer-capped gold nanoparticles, shedding light on the strength of adsorption between lignin and nanoscale polymer surfaces. Specifically, the study presents a variety of nanoscale polymer surfaces displaying different charged functional groups, using layer-by-layer assembly of three polyelectrolytes (polyallylamine hydrochloride (PAH)), polyacrylic acid (PAA), and poly(diallyldimethylammonium chloride (PDADMAC)) on 90 nm citrate-stabilized gold nanoparticles (AuNPs). This approach provides a library of polymer-encapsulated AuNPs for investigating the binding interactions of lignin to nanoscale polymers via spectroscopic techniques. ζ-potential, dynamic light scattering (DLS), …

Stereocontrolled Synthesis Of Lactam-Fused Tetrahydropyrans As Potential Antidiabetic Agents, Ifeyinwa Stella Anosike

All Master's Theses

Functionalized tetrahydropyrans are structural motifs in diverse natural products, including polyether antibiotics, marine toxins, pheromones, and pharmaceuticals. They are frequently used as versatile building blocks for accessing stereochemically sophisticated biologically active compounds. Specifically, functionalized bicyclic tetrahydropyrans bearing contiguous stereocenters have garnered interest in the synthesis and medicinal chemistry communities. Thus far, some synthetic methods have been developed for their construction and functionalization. These methods include Prins' cyclization reactions, intramolecular oxa-Michael reactions, hetero-Diels-Alder cyclization, ring-closing metathesis, radical cyclization, and halocycloetherification. However, these methods have some drawbacks such as the need for expensive reagents and catalysts, substrate limitations, and environmentally unfriendly conditions. …

Unexpected Ring Opening Reactions, Solid-State Structures, And A Chemiluminescent Reaction, L Hiscock

Theses and Dissertations (Comprehensive)

Functional π-materials involve the use of an aromatic π-system to carry out a function such as electron transport (organic electronics), absorbing and emitting photons (dyes, fluorescent materials), self-assembly (discotic liquid crystals), or sensors for various analytes. Our lab has recently published the syntheses of heteroaromatic derivatives of tetrafluoroterephthalonitrile (TFTP, 2.24) synthesised via nucleophilic aromatic substitution chemistry. The prepared derivatives have displayed fluorescent (e.g. 2.2)1 and liquid crystalline (1.0)2 properties, as well as displaying close π-π interactions in the solid state (2.8).3 As the materials we are synthesising all belong to the class of aromatic compounds, an introduction to aromaticity and …

Problems In Chemical Graph Theory Related To The Merrifield-Simmons And Hosoya Topological Indices, William B. O'Reilly

College of Graduate Studies: Theses & Dissertations

In some sense, chemical graph theory applies graph theory to various physical sciences. This interdisciplinary field has significant applications to structure property relationships, as well as mathematical modeling. In particular, we focus on two important indices widely used in chemical graph theory, the Merrifield-Simmons index and Hosoya index. The Merrifield-Simmons index and the Hosoya index are two well-known topological indices used in mathematical chemistry for characterizing specific properties of chemical compounds. Substantial research has been done on the two indices in terms of enumerative problems and extremal questions. In this thesis, we survey known extremal results and consider the generalized …

A Simple, Inexpensive Alkaline Method For Bacterial Dna Extraction From Environmental Samples For Pcr Surveillance And Microbiome Analyses, Abdulkarim Shwani, Bin Zuo, Adnan Alrubaye, Jiangchao Zhao, Douglas D. Rhoads

Poultry Science Faculty Publications and Presentations

DNA extraction for downstream molecular diagnostic applications can be an expensive, time-consuming process. We devised a method to quickly extract total bacterial DNA from environmental samples based on the sodium hydroxide lysis of cells with or without capture by magnetic beads for subsequent PCR or quantitative PCR. The final DNA extraction method using NaOH is extremely low-cost and can be completed in as little as 10 min at room temperature with dilution, or the DNA can be further purified using silica-coated paramagnetic beads. NaOH extraction was effective for Gram-negative and Gram-positive bacteria in samples from air, soil, sewage, food, laboratory …

Synthetic Elaboration Of Β-Carbonyl Alkylboronic Esters, Mason D. Hamilton Ph.D.

Graduate Theses, Dissertations, and Problem Reports (ETD)

Organoboron compounds are some of the most synthetically versatile compounds in organic chemistry due to the many valuable transformations of the C-B bond. This synthetic versatility combined with the pharmacophoric nature of carboxylic acids has led to an increased interest in the one-pot difunctionalization of vinyl arenes using CO₂ and pinacol boranes. Recently, much progress has been made to improve the scope and versatility of boracarboxylation reactions to now include electron-deficient and α-methyl substituted vinyl arenes. However, the potential transformations of boracarboxylated products have remained unexplored. Here, methodologies to transform the β-aryl alkylboronic ester into new C-C, C-N, and …

Stabilizing Bulk Lead-Free Tin Halide Perovskites, William Rice

Electronic Theses & Dissertations (2024 - present)

Tin halide perovskites are a growing candidate in the semiconducting materials field due to their band gap, and ability to be doped (specifically p-type doped). Halide perovskites are sensitive to light and air which causes the degradation of the material from its preferred cubic perovskite lattice. This thesis introduces a way of stabilizing bulk CsSnCl3 through the Goldschmidt tolerance factor. It will also introduce potential new ways to p-type dope halide perovskites. We attempted to p-type dope our halide perovskite by substitutional, interstitial, and vacancy doping to increase the carrier concentration to compete with current perovskites. During our trials of …

Intrinsic Lipid Curvature And Bilayer Elasticity As Regulators Of Channel Function: A Comparative Single-Molecule Study, Mohammad Ashrafuzzaman, Roger E. Koeppe Ii, Olaf S. Andersen

Chemistry & Biochemistry Faculty Publications and Presentations

Perturbations in bilayer material properties (thickness, lipid intrinsic curvature and elastic moduli) modulate the free energy difference between different membrane protein conformations, thereby leading to changes in the conformational preferences of bilayer-spanning proteins. To further explore the relative importance of curvature and elasticity in determining the changes in bilayer properties that underlie the modulation of channel function, we investigated how the micelle-forming amphiphiles Triton X-100, reduced Triton X-100 and the H_II lipid phase promoter capsaicin modulate the function of alamethicin and gramicidin channels. Whether the amphiphile-induced changes in intrinsic curvature were negative or positive, amphiphile addition increased gramicidin channel …

Weak Effects Of Prebiotically Plausible Peptides On Self-Triphosphorylation Ribozyme Function, Joshua T. Arriola, Shayan Poordian, Estefanía Martínez Valdivia, Tommy Le, Luke J. Leman, Joan G. Schellinger, Ulrich F. Müller

Chemistry and Biochemistry: Faculty Scholarship

Catalytic RNAs (ribozymes) were central to early stages of life on earth. The first ribozymes probably emerged in the presence of prebiotically generated peptides because amino acids can be generated under abiotic conditions, and amino acids can oligomerize into peptides under prebiotically plausible conditions. Here we tested whether the presence of prebiotically plausible peptides could have aided the emergence of ribozymes, by an in vitro selection of self-triphosphorylation ribozymes from random sequence in the presence of ten different octapeptides. These peptides were composed of ten different, prebiotically plausible amino acids, each as mixture of D- and L-stereoisomers. After five rounds …

Geochemistry Of Rare Earth Elements In Simulated Natural Waters: Experiments And Modelling Of Precipitation, Complexation, And Bioavailability., Samantha Zulian

Theses and Dissertations (Comprehensive)

Rare earth elements (REEs) are an important part of modern technology and used for many applications. Mining, agriculture, improper recycling and medical applications can increase the concentration of these elements in surface waters. Metals in the environment including REEs can be found naturally but understanding the implications increase concentrations from anthropogenic inputs is important. REE mobility, persistence and toxicity is imperative to risk assessment as Canada begins to mine REE. Ultimately, as with other metals, the impacts of REEs in the environment should be dependent on the specific physical and chemical forms of the elements. Fractionation provides a practical method …

Coordination Chemistry Using Strategic Design Of Ligands For Switchable Properties, Delara Joekar

Theses and Dissertations (Comprehensive)

Coordination-driven self-assemblies are multifunctional molecular systems that provide an efficient method for miniaturization towards functional devices with diverse applications. Herein, the synthesis of novel pyrazole-based ligands suitable for construction of coordination assemblies is reported. These were designed using a strategy that incorporates the presence of both cationic and anionic coordination sites, and a third site for further functionalization. This design strategy has been used because there is still a knowledge gap for controlling the directionality of weak molecular forces in the presence of stronger competing forces. The structural characterization of these ligands, their Hirshfeld surface analysis, and select coordination complexes …

Development Of Novel Protein Digestion And Quantitation Methods For Mass Spectrometic Analysis, Yongling Ai

Dissertations

Proteins are the workhorses of biology, playing multifaceted roles in maintaining cellular function, signaling, and response to environmental cues. Understanding their abundance and dynamics is pivotal for unraveling the complexities of biological processes, which underpins the foundations of molecular and cellular biology. Accurate measurement of protein quantities provides insights into cellular homeostasis, facilitates the discovery of biomarkers, and sheds light on the molecular mechanisms of diseases, bridging the gap between the molecular intricacies of proteins and their functional consequences in health and disease. The evolution of protein quantitation methodologies, from classical colorimetric assays to sophisticated mass spectrometry-based approaches, has expanded …

The Influence Of Predict, Observe, And Explain (Poe) Learning Accompanied By Formative Assessment On Misconceptions And Mastery Of Students’ Concepts Of Temperature And Heat Material, Ahmad Ilmar, Sentot Kusairi, Khusaini Khusaini

Jurnal Pendidikan Sains

High misconceptions and students’ mastery of concepts that are low enough are detected in temperature and heat material. To overcome this, teachers must apply learning strategies that are able to actively involve students in observation activities, namely the POE learning strategy. However, POE learning is not always easy to apply, students are still weak in communicating the results of their experiments. Therefore, a way is needed that helps students during the learning process to be more confident and not afraid when asked to argue, namely with formative assessment. POE learning accompanied by formative assessment aims to enable students to understand …

Ipq Descriptor

Level 3

No abstract provided.

Balancing Quality Assurance & Innovation In Pharma, Emma Ramnarine

Level 3

At the Pharmaceutical Regulatory Science Team (PRST) workshop on ICH Q9(R1), held at the Technological University Dublin in early June 2023, Boehringer Ingelheim US Biopharma Operations Product Management & Development Operations Head Emma Ramnarine shared her insights on balancing quality assurance and innovation in pharmaceutical manufacturing. She addressed: ● patient-centered transformation ● a watershed moment in her career ● understanding the drug shortage problem ● disruptive collaboration, and ● systems thinking

approaches. Click here for the slides accompanying Ramnarine’s remarks. She connected some of her remarks for the pharmaceutical industry to those made in the previous talk by Ed Hoffman, …

Achieving Warranted Acceptance Of Biotechnologies, Emily Grayek, Baruch Fischhoff

Level 3

The U.S. has faced long-standing shortages of generic drugs, causing negative health effects and spikes in drug costs. To address these shortages, investments in critical technologies and policies to support their adoption will be needed. The success of these technologies and policies depends on public acceptance. We studied public acceptance using the mental model approach, which identifies gaps in understanding that can be addressed with communications. We began with semi-structured interviews with experts in pharmaceutical manufacturing. Based on these interviews, we developed and conducted surveys of the general public, physicians, and pharmacists. Similar strategies could be applied to improve communications …

Speaker Bios

Level 3

No abstract provided.

Ipq Bibliography Pac Km Qrm 2010 - 2023

Level 3

No abstract provided.