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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.

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.

Mechanism Of Action Of Kl-50, A Candidate Imidazotetrazine For The Treatment Of Drug-Resistant Brain Cancers, Eric D. Huseman, Anna Lo, Olga Fedorova, James L. Elia, Susan E. Gueble, Kingson Lin, Ranjini K. Sundaram, Jooneseok Oh, Jinchan Liu, Fabian Menges, Matthew G. Rees, Melissa M. Ronan, Jennifer A. Roth, Victor S. Batista, Jason M. Crawford, Anna M. Pyle, Ranjit S. Bindra, Seth B. Herzon

Chemistry Faculty Research and Publications

Aberrant DNA repair is a hallmark of cancer, and many tumors display reduced DNA repair capacities that sensitize them to genotoxins. Here, we demonstrate that the differential DNA repair capacities of healthy and transformed tissue may be exploited to obtain highly selective chemotherapies. We show that the novel N3-(2-fluoroethyl)imidazotetrazine “KL-50” is a selective toxin toward tumors that lack the DNA repair protein O⁶-methylguanine-DNA-methyltransferase (MGMT), which reverses the formation of O⁶-alkylguanine lesions. We establish that KL-50 generates DNA interstrand cross-links (ICLs) by a multistep process comprising DNA alkylation to generate an O⁶-(2-fluoroethyl)guanine (O⁶FEtG) …

Building Smart Textile Sensors From Bottom-Up: Chemically Precise Self Assembled Materials On Textiles As A Modular Platform For Electroanalysis, Lori-Ann Williams

Dartmouth College Master’s Theses

In this present work, we explore the metallization of textiles and sutures for the development of a wearable portable modular platform technology for non-invasive wound healing monitoring. Currently technology for the metallization of nonconductive materials have been mainly on a 2D surfaces which restricts the bulk metallization of textile surfaces which require specialized equipment and operators which are costly, energy ineffective, and prevents miniaturization. Metallization of nonconductive fabrics are achieved through a conventional electroless deposition of copper nanoparticle species on 3D surfaces to create electrodes. These conductive textiles and sutures were characterized by pXRD, ATR-IR, SEM-EDS, and XPS and were …

Extraction Of Capsaicin Using The Polyol Induced Extraction (Pie) Method, Orlando Herrera

All Student Theses and Dissertations

Polyol-induced extraction (PIE) is an extraction technique for separating organic solvents from water, using glycerol and polyol as separating agents. Glycerol binds water releasing the organic solvent as a separate liquid phase. this thesis, investigates how the PIE process may be used to separate caffeine and capsaicin. When acetonitrile and water are used as a 1:1 solvent mixture, two immiscible phases are created upon addition of the polyol, glycerol. Initially, for purposes of training on the PIE method, the studies primarly began with the extraction of pure caffeine. Using a 1:1 mixture of acetonitrile and water, 20 m/v % glycerol, …

Exploration Of Sulfonamides And Benzothiazoles As Peptide-Based Cleavable Linkers, Abigail Dalton

Honors Theses

Cleavable linkers have demonstrated great potential in various applications of medicinal organic chemistry, such as in modern therapeutic development. Linkers are stable compounds that cleave in specific conditions to release molecular cargo. We have developed cleavable linkers based on nucleophilic aromatic substitution reactions on sulfonamide and benzothiazole substrates in small molecule and in peptide studies. Sulfonamides, commonly with an electron-withdrawing group, reacted in high conversion of starting material to the sulfide product in small molecule studies, but was unable to successfully cleave the sulfonamide linker on peptide in mild conditions. Next, a benzothiazole sulfone substrate was analyzed and optimized in …

An Investigation Of The Correlation Between Polymer Solution Entanglement And Electrospun Polycaprolactone Fiber Mechanics, Manasa Sujatha Rajeev

Honors Theses

The aim of this study was to determine the role of entanglement in the mechanical properties of electrospun polycaprolactone (PCL) fibers. PCL is a useful polyester due to its favorable properties such as its biocompatibility and biodegradability. Multiple concentrations of PCL were dissolved in a 3:1 acetic to formic acid solvent. Fibers were formed using an electrospinning technique. Entanglement is a required parameter to produce fibers, thus the number of entanglements per polymer (ne) was calculated, as well as the corresponding concentrations. Smooth continuous fibers were found to form between 13 w/v% and 17 w/v%. Mechanical analysis, such as three-point …

The Effect Of Solvent Identity And Hydride-Donor On The Reduction Of Co2 Into Useful Fuels, Abigail Mcentire

Honors Theses

One possible strategy for decreasing CO2 emissions is through electrocatalytic reduction reactions to convert the CO2 back into combustible fuels , such as methane or methanol. However, it can be challenging to control the reaction to select one of these useful fuels as opposed to carbon monoxide or formate. Our strategy is to investigate a specific hydride donor and solvent combinations for which the reaction favors conversion to methanol. It was found that in acetonitrile , several hydride donors were capable of selective reduction of CO2 to the methanol oxidation state.

Chemical Reduction Of Curved Molecular Nanographenes: Metal Intercalation And Core Transformation, Yikun Zhu

Electronic Theses & Dissertations (2024 - present)

The promising lithium storage capacity and fast charge transport rate make graphene a great candidate for energy storage applications. However, the harsh synthetic conditions lead to uneven size distribution and poor solubility, posing limitations on further applications and modifications of graphene and its derivatives. Molecular nanographenes, as graphene cutouts, possess outstanding chemical and physical properties stemming from their parent graphene but also demonstrate such unique features as controllable synthetic conditions, defined molecular structures, uniform size, and relatively good solubility. The improved solubility enables the use of solution chemistry methods for design modifications of molecular nanographenes and for systematical investigation of …

Plasmid-Borne Biosynthetic Gene Clusters Within A Permanently Stratified Marine Water Column, Paraskevi Mara, David Geller-Mcgrath, Elizabeth A. Suter, Gordon T. Taylor, Maria G. Pachiadaki, Virginia P. Edgcomb

BCES: Faculty Publications

Plasmids are mobile genetic elements known to carry secondary metabolic genes that affect the fitness and survival of microbes in the environment. Well-studied cases of plasmidencoded secondary metabolic genes in marine habitats include toxin/antitoxin and antibiotic biosynthesis/resistance genes. Here, we examine metagenome-assembled genomes (MAGs) from the permanently-stratified water column of the Cariaco Basin for integrated plasmids that encode biosynthetic gene clusters of secondary metabolites (smBGCs). We identify 16 plasmid-borne smBGCs in MAGs associated primarily with Planctomycetota and Pseudomonadota that encode terpenesynthesizing genes, and genes for production of ribosomal and non-ribosomal peptides. These identified genes encode for secondary metabolites that are …

Synthesis And Characterisation Of Molecularly Imprinted Polymers On Functionalised Silica Gel Designed For The Selective Extraction And Detection Of Nitroaromatic Compounds Coupled With Colorimetric Methods, Raymond Tang

Masters

HPLC and LC-MS are analytical instruments used to detect the trace explosives, however, the instrumental methods are expensive and require specially trained operators to prepare the samples and interpret the results, and these methods are not suitable for use in conflict zones. The overall aim is to deliver a method for the selective, sensitive and rapid detection of trace explosives in the field.

Innovative Solutions In Medical Diagnostics, Seafood Industry, Environmental, And Forensic Applications Through Integrating Raman Spectroscopy And Machine Learning, Luis Perez Almodovar

Electronic Theses & Dissertations (2024 - present)

There is an urgent need for rapid and on-site analytical methods to address various environmental and forensic challenges. This dissertation explores the application of Raman spectroscopy combined with machine learning for three critical areas: evaluating perfluoroalkyl or polyfluoroalkyl substances (PFAS) exposure in wildlife, authenticating tuna species in the seafood industry, identifying body fluids at crime scenes, and medical diagnostics.

First, Raman spectroscopy and support vector machine discriminant analysis (SVMDA) were employed to detect PFAS levels in the blood plasma of smallmouth bass from two different tributaries, rivers, or streams that flow into larger bodies of water. The method achieved 100% …

Advancements In Forensic Analysis: Development Of Mass Spectrometric And Chemometric Approaches For The Identification Of Synthetic New Psychoactive Substances And Plant Materials, Mónica Ventura

Electronic Theses & Dissertations (2024 - present)

While forensic science is a well-established discipline, a number of federal agencies have highlighted challenges that continue to plague the field and the extent to which these challenges remain unaddressed. Examples are the illegal trade of wildlife timber and the drug epidemic. Characterization of these materials requires nuanced method development for compound determination, matrix material-specific protocols, and heavy use of expensive consumables. The application of a technique such as direct analysis in real time – high-resolution mass spectrometry (DART-HRMS) provides the opportunity to circumvent many of the challenges presented by conventional methods. In general, little to no sample preparation is …

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 …

Supply And Consumption Of Dissolved Organic Phosphorus Across The Subtropical Indian Ocean, Corinne Richard

Honors Theses and Capstones

The Indian Ocean is an understudied region for marine phosphorus (P) biogeochemistry. Emerging evidence indicates marine phytoplankton can adapt to decreasing supplies of inorganic P, a required nutrient for growth, by alternatively utilizing organic forms of P. Here we investigate the dissolved organic phosphorus concentration ([DOP]) distribution across the southern Indian Ocean using observations collected on the I05 US GO-SHIP Cruise (2023) across ~33ºS latitude. We quantify the longitudinal variability of [DOP] in the upper 350 m of the Indian Ocean and infer its rate of biological consumption from surface waters, contributing as an organic nutrient to sustain marine autotrophs …

Synthesis Of Hydroxycinnamate Derivatives And Characterization Of Bioactivity As Radical Scavengers And Α-Glucosidase Inhibitors, Cate Simmermaker

University of the Pacific Theses and Dissertations

Hydroxycinnamic acids (HCAs), a class of polyphenols commonly found in regularly consumed fruits and vegetables, have been investigated for efficacy as radical scavengers and glycosidase inhibitors. These compounds could mitigate the negative health effects of free radicals in oxidative stress diseases including neurodegeneration, cancer and diabetes. The HCAs investigated were caffeic acid (1), p-coumaric acid (2), ferulic acid (3), and sinapic acid (4). The compounds were derivatized with synthetically prepared amino acid esters through a four-step synthesis including protective acetylation, chlorination of the carboxylic acid, amidation, and subsequent deprotection of all applied protecting groups. The inclusion of diverse derivative groups …

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 …

Zno Varistors—Preparation Of Nano And Micro Sized Powders By Mechanical Methods For Low And High Voltage Varistors, Maura Kelleher

Books/Book Chapters

ZnO-Bi2O3-Sb2O3 varistors are as essential today as they have been since their discovery five decades ago. Their role is to protect other electronic components against oncoming surges of electrons and survive. The demands on varistors are increasing. Electronic components are becoming smaller and more sensitive, and the metal oxides from which varistors are made are precious. Every aspect of their structure (macro, micro, nano and atomic) determines how they perform and survive. Each stage and variable within the powder metallurgy process is important. The mechanical methods in preparing nano and micro sized metal oxide powders are outlined in this chapter.

Hybridization And Duplex Stability Of Peptide Nucleic Acid Containing An Azobenzene Switch, Carmen J. Velasquez

College of Graduate Studies: Theses & Dissertations

Light-driven molecular switches that can be turned on and off on demand have found many biological applications. For DNA, RNA, and synthetic derivatives, the switch can be used to interfere with a hybridization event with a complementary strand. To explore this potential, we have synthesized three light-sensitive PNA which have an azobenzene group (PNA-5azo5 and PNA-4azo4), and two azobenzene groups (PNA-2azo5azo2) as part of the PNA backbone. UV experiments were used to verify the conversion to the cis-isomer from the initial trans state for all of the single-stranded Azo-PNA ( PNA-5azo5, PNA-4azo4, and PNA-2azo5azo2) by irradiating at 365 nm …

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 …

Selected Trace Element Uptake By Rice Grain As Affected By Soil Arsenic, Water Management And Cultivar -A Field Investigation, Eric M. Farrow, Jianmin Wang, Honglan Shi, John Yang, Bin Hua, Baolin Deng

Chemistry Faculty Research & Creative Works

Accumulation of arsenic (As) in rice grain was reported in many regions of the world, including the United States, which has been a threat to human health. This field research investigated the grain as accumulation and its relationship with the uptake of selenium (Se), molybdenum (Mo), and cadmium (Cd) in soils with and without monosodium methane arsonate (MSMA) amended, as effects of selected rice cultivars and water management. Results indicated that MSMA increased the accumulation of as and Se but decreased Mo for all six cultivars under four irrigation management. MSMA also increased grain-Cd in some cultivars. in no MSMA-amended …

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 …

Terra-Lsd1 Phase Separation Promotes R-Loop Formation For Telomere Maintenance In Alt Cancer Cells, Nicholas J. Reiter

Chemistry Faculty Research and Publications

The telomere repeat-containing RNA (TERRA) forms R-loops to promote homology-directed DNA synthesis in the alternative lengthening of telomere (ALT) pathway. Here we report that TERRA contributes to ALT via interacting with the lysine-specific demethylase 1A (LSD1 or KDM1A). We show that LSD1 localizes to ALT telomeres in a TERRA dependent manner and LSD1 function in ALT is largely independent of its demethylase activity. Instead, LSD1 promotes TERRA recruitment to ALT telomeres via RNA binding. In addition, LSD1 and TERRA undergo phase separation, driven by interactions between the RNA binding properties of LSD1 and the G-quadruplex structure of TERRA. Importantly, the …

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 …

Tailored (La0.2pr0.2nd0.2tb0.2dy0.2)2ce2o7 As A Highly Active And Stable Nanocatalyst For The Oxygen Evolution Reaction, Sreya Paladugu, Ibrahim Munkaila Abdullahi, Palani Raja Jothi, Bo Jiang, Manashi Nath, Katharine Page

Chemistry Faculty Research & Creative Works

Designing highly active and robust catalysts for the oxygen evolution reaction is key to improving the overall efficiency of the water splitting reaction. It has been previously demonstrated that evaporation induced self-assembly (EISA) can be used to synthesize highly porous and high surface area cerate-based fluorite nano catalysts, and that substitution of Ce with 50% rare earth (RE) cations significantly improves electrocatalyst activity. Herein, the defect structure of the best performing nano catalyst in the series are further explored, Nd₂Ce₂O₇, with a combination of neutron diffraction and neutron pair distribution function analysis. It is …

Highly Dipole-Parallel Aligned Nonlinear Optical Organic Molecular Crystalline Materials: Rational Design, Experimental And Theoretical Studies Of Supramolecular Structures And Non-Covalent Interactions, Harmeet Singh Bhoday

Doctoral Dissertations

Highly dipole-parallel aligned donor-acceptor substituted organic molecules are attractive for a wide array of applications, including nonlinear optics. However, only a limited number of crystals are known to adopt polar non-centrosymmetric space groups. The concepts guiding the fabrication of these polar materials have been described. The study focused on unsymmetrical donor-acceptor substituted azines and butadiene's. An improved design over (MeO, Y)-azines led to the realization of three crystals perfectly aligned in dipole parallel orientation for (PhO, Y)-azines with Y = Cl, Br, I, and one nearly perfectly aligned crystal for Y = F (Paper I). The unique bonding properties associated …

The Effect Of Nanomorphology As Quantified Via The K-Index On The Drug Delivery Properties Of Isocyanate-Derived Aerogels, Stephen Y. Owusu, A. B.M.Shaheen Ud Doulah, Vaibhav A. Edlabadkar, Kamden J. George, Chariklia Sotiriou-Leventis

Chemistry Faculty Research & Creative Works

This study explores the potential to predict the drug-loading and release profiles of aerogels based on their morphologies: a milestone in drug delivery research, which can help save time and cost in formulating new aerogel drug carriers and cut-down evaluation of the drug delivery capabilities of aerogels to a few experimental runs. Polyurea (PUA) and poly(isocyanurate-urethane) (PIR-PUR) aerogels were used as model systems, while 5-fluorouracil (5-FU) and paracetamol (PM) were used as model drugs. These model systems were chosen because they can be synthesized into different morphologies, which can be quantified by the so-called K-index (water contact angle divided by …

Detection Of Micrornas In Blood Samples Using Biosensors For The Detection Of Early-Stage Lung Cancer, Nicholas Bruno

Honors Undergraduate Theses

Lung cancer kills more people in the U.S. a year than any other cancer. This is largely because patients often remain asymptomatic until stage 3, by which time the tumor is usually highly malignant. High radiation-producing screenings are the current method of lung tumor detection. These typically involve machinery for tumor visualization, such as computed tomography (CT) scans, positron emission tomography (PET scan), magnetic resonance imaging (MRI), and X-rays. Not only does radiation exposure from this equipment pose a risk to the patient, but any tumors detected by these scanning techniques are likely to be locally advanced. This suggests that …

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 …

Chemical Synthesis And Biological Application Of Sensitive Rna, Alexander T. Apostle

Dissertations, Master's Theses and Master's Reports

In the field of epigenetics - the dynamic collection of chemical modifications that overlay DNA/RNA - there is increasing interest in the potential for therapeutic and research-based utilization of the epitranscriptomics: those epigenetic modifications specific to RNA. Epitranscriptomics can give us a new approach to understanding and treating RNA viruses, like SARS-CoV-2. Given viruses are often found modified by human epitranscriptomic machinery, understanding how these modifications can modulate virulence is of high interest. We have shown that the N1-methyladensoine modification causes RNA synthesis termination in the SARS-CoV-2 replication complex, and thus may explain the differences in symptoms observed in individuals. …