Chemistry Commons^™

Pyrimethamine Based Anti-Protozoan Agents From Isostere And Heuristic Structure-Similarity Search, Ronald Bartzatt

Chemistry Faculty Publications

Aims: To generate new medicaments for control and treatment of the parasitic protozoan Toxoplasma gondii.

Study Design: Structure similarity search and isostere search was conducted over a broad range of structure categories. Correlation and highest similarity scores were implemented to select the best drug candidates.

Place and Duration of Study: University of Nebraska, Department of Chemistry, Durham Science Center, 6001 Dodge Street, Omaha Nebraska 68182, from June 2016 to February 2017.

Methodology: Utilizing pyrimethamine as the parent compound, a broad range of similar structures and isosteres were found by applying search methods. The compounds having the highest correlation and …

The Study Of Zirconium Hydroxide And Zirconium (Iv) Metal-Organic Frameworks As Reactive Substrates For The Decomposition Of Chemical Warfare Agents, James W. Kollar

Master of Science in Chemical Sciences Theses

Nerve agents have been described by the Center for Disease Control and Prevention to be the most toxic and rapidly acting of chemical warfare agents. The present study investigates the efficacy of zirconium hydroxide, Zr(OH)₄, and Zr(IV) Metal-Organic Frameworks (MOFs) in the uptake and decomposition of the gas phase nerve agent simulant dimethyl methylphosphonate, DMMP. This investigation was carried out using two different methods: 1) with the use of Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFTS) to examine the surface reaction between DMMP and the solid; and 2) using a flow reactor system that monitored gas phase reaction …

Discovery Of A Diaminopyrimidine Flt3 Inhibitor Active Against Acute Myeloid Leukemia, Jamie A. Jarusiewicz, Jae Yoon Jeon, Michele C. Connelly, Yizhe Chen, Lei Yang, Sharyn D. Baker, R. Kiplin Guy

Pharmaceutical Sciences Faculty Publications

Profiling of the kinase-binding capabilities of an aminopyrimidine analogue detected in a cellular screen of the St. Jude small-molecule collection led to the identification of a novel series of FMS-like tyrosine kinase 3 (FLT3) inhibitors. Structure–activity relationship studies led to the development of compounds exhibiting good potency against MV4-11 and MOLM13 acute myelogenous leukemia cells driven by FLT3, regardless of their FLT3 mutation status. In vitro pharmacological profiling demonstrated that compound 5e shows characteristics suitable for further preclinical development.

Design, Synthesis And Biological Evaluation Of Novel Hedgehog Inhibitors For Treating Pancreatic Cancer, Vinod Kumar, Amit Kumar Chaudhary, Yuxiang Dong, Haizhen Zhong, Goutam Mondal, Feng Lin, Virender Kumar, Ram I. Mahato

Chemistry Faculty Publications

Hedgehog (Hh) pathway is involved in epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) maintenance resulting in tumor progression. GDC-0449, an inhibitor of Hh pathway component smoothened (Smo) has shown promise in the treatment of various cancers including pancreatic cancer. However, the emergence of resistance during GDC-0449 treatment with numerous side effects limits its use. Therefore, here we report the design, synthesis and evaluation of novel GDC-0449 analogs using N-[3-(2-pyridinyl) phenyl] benzamide scaffold. Cell-based screening followed by molecular simulation revealed 2-chloro-N1-[4-chloro-3-(2-pyridinyl)phenyl]-N4,N4-bis(2-pyridinylmethyl)-1,4- benzenedicarboxamide (MDB5) as most potent analog, binding with an extra interactions in seventransmembrane (7-TM) domain of Smo due to …

A Perspective On How To Improve Undergraduate Research Education In The Physical Sciences At Usc, Michael Caleb Bagley

Senior Theses

My years at the University of South Carolina have been some of the most challenging and edifying periods of my life. I have been blessed by having a great professional and chemistry mentor in Dr. John L. Ferry who has helped me engage in scientific research in a meaningful way. As I watched other chemistry students, in particular, struggle with understanding what research really was and even how to understand the results and methodologies of it I felt that this was a huge issue that could be rather simply fixed. I have been privileged to apply for and receive a …

Synthesis Of Α, Β-Substituted Alkenylphosphonates From Α-Phosphonovinyl Triflates: I) Palladium Catalyzed Suzuki-Miyaura Cross-Coupling With Aryl Boronic Acids Ii) Palladium Catalyzed Reduction, Ronald Laryea Mensah

Master of Science in Chemical Sciences Theses

Alkenylphosphonates (vinylphosphonates) are important targets for R & D because they have interesting chemical, biological and pharmacological properties. Vinylphosphonates are used in synthesis, polymer applications, and have demonstrated potential as anticancer and antimicrobial agents.

Vinyl triflates are useful in organic synthesis and are referred to as pseudo-halides because they react in a manner similar to halides. Vinyl triflates have a broad range of synthetic utility because they undergo nucleophilic substitutions and transition metal-mediated reactions. There is a growing interest in using α-phosphonovinyl pseudo-halides in transition metal-mediated cross-coupling reactions as a means to synthesize α, β-substituted alkenylphosphonates. Over the past three …

Spectroscopy And Formation Of Lanthanum-Hydrocarbon Radicals Formed By C—C Bond Cleavage And Coupling Of Propene, Dilrukshi C. Hewage, Wenjin Cao, Sudesh Kumari, Ruchira Silva, Tao Hong Li, Dong-Sheng Yang

Chemistry Faculty Publications

La reaction with propene is carried out in a laser-vaporization molecular beam source. Three La-hydrocarbon radicals are characterized by mass-analyzed threshold ionization (MATI) spectroscopy. One of these radicals is methylenelanthanum [La(CH₂)] (C_s), a Schrock-type metal carbene. The other two are a five-membered 1-lanthanacyclopent-3-en [La(CH₂CHCHCH₂)] (C_s) and a tetrahedron-like trimethylenemethanelanthanum [La(C(CH₂)₃)] (C_3v). Adiabatic ionization energies and metal-ligand stretching and hydrocarbon-based bending frequencies of these species are measured from the MATI spectra, preferred structures and electronic states are identified by comparing the experimental measurements and spectral …

Catalytic Acceptorless Dehydrogenation Of Amines With Ru(PR2nR′2) And Ru(Dppp) Complexes, James M. Stubbs, Richard J. Hazlehurst, Paul D. Boyle, Johanna M. Blacquiere

Chemistry Publications

[Ru(Cp)(PPh2NBn2)(MeCN)]PF6 (1; PPh2NBn2 = 1,5-benzyl-3,7-phenyl-1,5-diaza-3,7-diphosphacyclooctane) and [Ru(Cp)(dppp)(MeCN)]PF6 (2; dppp = 1,3-bis(diphenylphosphino)propane) are both active toward the acceptorless dehydrogenation of benzylamine (BnNH2) and N-heterocycles. The two catalysts have similar activities but different selectivities for dehydrogenation products. Independent synthesis of a [Ru(Cp)(PPh2NBn2)(NH2Bn)]PF6 adduct (3) reveals the presence of a hydrogen bond between the bound amine and the pendent base of the PPh2NBn2 ligand. Preliminary mechanistic studies reveal that the benzylamine adduct is not an on-cycle catalyst intermediate.

Effects Of Processing Parameters On Properties Of Novel Silica-Filled Polysiloxane Materials, Kyle W. Schwenker

Electronic Theses & Dissertations

Polysiloxanes are a class of materials that possess high temperature stability and the ability to remain flexible at extremely low temperatures. Their elastomers generally exhibit low strength and have poor mechanical properties unless reinforced with fillers. Reinforcement can be accomplished by compounding reinforcing silica fillers with polysiloxanes via twin-screw extrusion compounding that vigorously mixes the fillers into a polymer matrix. In this thesis, a lab-scale twin-screw extruder was utilized to compound thermoplastic materials to determine the effects of processing on thermoplastics material properties, as well as to determine the extruder’s compounding effectiveness. Processing via lab-scale twin-screw extrusion did not negatively …

Analysis Of Structural Stability Of Human Prosecretory Mitogenic Lacritin By Circular Dichroism, Anna P. Desmarais, Casey Q. Ramirez Cortes

Senior Honors Projects, 2010-2019

Purpose: Lacritin is a human tear glycoprotein that has high thermal stability. When cleaved, lacritin has antimicrobial activity resulting from the C-terminus amphipathic alpha helical region. The alpha helices contain three salt bridges; ionic bonds between neighboring oppositely charged amino acids. The purpose of this research was to investigate the hypothesis that the salt bridges within the alpha helices contribute to the high thermal stability.

Methods: To determine the role of salt bridges in the thermal stability of lacritin, point mutants were prepared for each salt bridge by site directed mutagenesis that replaced the oppositely charged amino acids with serine. …

Carbon Particles, Stephen M. Lipka, Christopher R. Swartz

Center for Applied Energy Research Faculty Patents

A composition generally includes carbon particles. The particles are prepared by dissolving a carbohydrate-based precursor in water to form a precursor solution and placing the precursor solution in a pressure vessel. The precursor solution is placed in a pressure vessel. The pressure vessel is heated to a reaction temperature to form carbon particles. The carbon particles are subjected to a chemical activation and a physical activation. The composition includes, by weight, about 5% to about 30% oxygen.

Development Of Neurotensin-Based Radiopharmaceuticals For Neurotensin-Receptor-1-Positive Tumors Targeting, Yinnong Jia

Theses & Dissertations

The neurotensin receptor 1 (NTR1) is overexpressed in many cancers, due to its role as a growth pathway. These NTR1-positive cancers include pancreatic, colon, prostate and breast cancers. In the radiopharmaceutical field, the overexpression of NTR1 in cancer has prompted the development of NTR1-targeted diagnostics and therapeutics. The neurotensin (NT) peptide exhibits low nanomolar affinity for NTR1 and has been the paradigm for NTR1-targeted agents. Since the 1980’s, radiolabeled NT analogs have been developed and evaluated for targeting NTR1-positive cancers. Since native NT is rapidly degraded in vivo by a variety of peptidases, a tremendous amount of effort has been …

Elucidation Of Active Sites For The Reaction Of Ethanol On Tio2/Au(111), David T. Boyle

Senior Honors Projects, 2010-2019

Obtaining a molecular-level understanding of the reaction of alcohols with heterogeneous model catalysts is critical for improving industrial catalytic processes, such as the production of H₂ from alcohols. Gold has been shown to be an excellent oxidation catalyst once oxygen is added to it. The use of reducible oxides provides a source of oxygen on Au(111) for the reaction of ethanol, which is easily regenerated in the presence of an oxygen background. In this work, ethanol operates as a probe molecule to investigate the role of Au(111), TiO₂ nanoparticles, and TiO₂/Auinterfacial surface sites on the catalytic …

Real Time Monitoring Of Photocatalysis: An Application And Expansion Of The Quartz Crystal Microbalance, Perrin Godbold

Senior Honors Projects, 2010-2019

There are many applications of photocatalytic chemistry, with hundreds of researchers investigating photocatalytic materials. Another method of investigation could aid these researchers and contribute significantly to this field. This study attempts to develop a new method of analysis by expanding the capabilities of the Quartz Crystal Microbalance (QCM) into the realm of photocatalysis. We coated QCM crystals with the stable and well-known photocatalyst, titanium dioxide, and utilized these coated crystals to begin to develop an analysis procedure for our modified instrument. Some indication of the QCM’s sensitivity was seen, but the UV irradiation elicited a frequency change independent of the …

Synthesis Of Oxidative Metabolites Of Di(2-Ethylhexyl) Phthalate, Kelly Mcdaniel

Departmental Honors & Graduate Capstone Projects

Di(2-ethylhexyl) phthalate (DEHP) is a chiral persistent organic pollutant that is used as a plasticizer in polyvinyl chloride (PVC). Humans are exposed to DEHP through inhalation, ingestion, and intravenous exposure; it has shown toxicity as an endocrine disrupter and carcinogen. In the body, DEHP is broken down into mono(2-ethylhexyl) phthalate (MEHP), which is subsequently oxidized in various locations on the ethylhexyl chain. Since previous studies of DEHP have ignored chirality, the purpose of this research is to synthesize enantiomerically pure oxidative metabolites of DEHP. One of the oxidative metabolites of DEHP, 2cx-MMHP, was produced by a malonic ester synthesis followed …

Paper Microzone Plates As Analytical Tools For Studying Enzyme Stability: A Case Study On The Stabilization Of Horseradish Peroxidase Using Trehalose And Su-8 Epoxy Novolac Resin, Kirsten A. Ganaja, Cory Chaplan, Jingyi Zhang, Nathaniel W. Martinez, Andres W. Martinez

Chemistry and Biochemistry

Paper microzone plates in combination with a noncontact liquid handling robot were demonstrated as tools for studying the stability of enzymes stored on paper. The effect of trehalose and SU-8 epoxy novolac resin (SU-8) on the stability of horseradish peroxidase (HRP) was studied in both a short-term experiment, where the activity of various concentrations of HRP dried on paper were measured after 1 h, and a long-term experiment, where the activity of a single concentration of HRP dried and stored on paper was monitored for 61 days. SU-8 was found to stabilize HRP up to 35 times more than trehalose …

A Complex Stereochemical Relay Approach To The Antimalarial Alkaloid Ocimicide A1. Evidence For A Structural Revision, H. Nikolayevskiy, M. K. M. Tun, Paul R. Rablen, C. B. Mamoun, S. B. Herzon

Chemistry & Biochemistry Faculty Works

Ocimicide A1 (1) and the semisynthetic derivative ocimicide A2 (2) are highly potent antimalarial agents efficacious against chloroquine-sensitive and -resistant Plasmodium falciparum strains with IC50 values in the nanomolar and picomolar range, respectively. Members of this family have demonstrated radical cure in rhesus monkeys, without detectable toxicity, but their structure–function relationships and mechanism of action are unknown. Herein we describe a twelve-step synthesis of an advanced N-acylated pentacyclic precursor to the proposed structure of 1 (11% overall yield). Instability and poor P. falciparum growth inhibition of the corresponding free donor–acceptor cyclopropylamine, and large discrepancies between reported and both experimental and …

Solid Phase Extraction Of Herbicides From Groundwater And Soils, Ken Overway, Garrett George

Chemistry Faculty Scholarship

The purpose for this experiment was to compare relative concentrations of the herbicide atrazine in soil and ground water samples. Atrazine is commonly found in groundwater and is known to be toxic to aquatic life with long lasting effects. This experiment aims to identify whether or not atrazine is present in the groundwater as well as to examine how long atrazine can persist in soil. Previous studies have shown atrazine and other related herbicides persisting with little to no degradation for up to 16 weeks. Soil and groundwater samples were obtained from a farm where atrazine is used seasonally to …

Extraction Of Protoporphyrin Ix For Use In Dye-Sensitized Solar Cells, Ken Overway, Carleigh Studtmann

Chemistry Faculty Scholarship

Dye-sensitized solar cells (DSSC) are a possible alternative to traditional solar energy technologies. Metal-free organic dyes such as porphyrins seem to be an especially promising option as a sensitizer due to their characteristic Soret band and smaller Q-bands in the visible spectrum. Protoporphyrin IX (PPIX) is a naturally occurring porphyrin found in sources hemoglobin, chlorophyll, and brown egg shells. PPIX exhibits typical porphyrin absorbance spectrum, and the carboxylic acid substituents make it ideal for direct attachment to the TiO2 of the DSSC. The purpose of this research is to extract PPIX at a high enough concentration from brown eggshells that …

Acid Rain Kinetics On Calcareous And Silicate Soils, Ken Overway, John Oates

Chemistry Faculty Scholarship

Calcareous, silicate, and aluminosilicate minerals are common constituents of inorganic soil. These minerals act as buffers against acid attack, either through carbonate neutralization or cation exchange. Previous studies focusing on potassium observed that cations occur in four separate phases: the solution phase, exchangeable phase, non–exchangeable phase, and the mineral phase. Each phase represents a different kinetic mechanism that is incrementally slower for cations deposited deeper in the mineral.

We have observed that when soil is exposed to acid, the pH of the soil slurry drops drastically, followed by a recovery curve on the order of seconds

to minutes. These recovery …

Development Of New Routes For The Synthesis Of Carbaporphyrins And Carbachlorins, Navneet Sahota

Theses and Dissertations

Carbaporphyrins and carbachlorins are porphyrin analogs in which one of the nitrogens is replaced with a carbon atom within a porphyrin-like cavity. These systems form stable organometallic derivatives and exhibit unusual chemical reactivity. In the monocarbaporphyrinoids such as benzocarbaporphyrins, one of the pyrrole rings is replaced by an indene unit. Although syntheses of monocarbaporphyrins with fused rings have been widely investigated over the past 20 years, a few examples of carbaporphyrins without fused rings have been reported in the literature.

In this thesis, two projects were conducted to further explore carbaporphyrin and carbachlorin chemistry. The first project utilized a ‘3+1’ …

Ion-Specific Ice Recrystallization Provides A Facile Approach For The Fabrication Of Porous Materials, Shuwang Wu, Chongqin Zhu, Zhiyuan He, Han Xue, Qingrui Fan, Yanlin Song, Joseph S. Francisco, Xiao Cheng Zeng, Jianjun Wang

Xiao Cheng Zeng Publications

Ice recrystallization is of great importance to both fundamental research and practical applications, however understanding and controlling ice recrystallization processes remains challenging. Here, we report the discovery of an ion-specific effect on ice recrystallization. By simply changing the initial type and concentration of ions in an aqueous solution, the size of ice grains after recrystallization can be tuned from 27.4±4.1 to 277.5±30.9 mm. Molecular dynamics simulations show that the ability of the ion to be incorporated into the ice phase plays a key role in the ultimate size of the ice grains after recrystallization. Moreover, by using recrystallized ice crystals …

Pro- And Antioxidant Activity Of Selenomethionine: Preventative Measures Against Metal-Mediated Dna Oxidation, Austin Mroz

Graduate Theses - Chemistry and Biochemistry

DNA damage by reactive oxygen species (ROS) has been linked to several diseases.

Antioxidants are one method of combating the effects of ROS; selenium-containing antioxidants have shown promise in alleviating in vitro DNA damage. This study aims toelucidate the effects of selenomethionine (SeMet) on DNA damage mediated by Cu(II),Fe(II), or Cr(III) metal ions. HPLC analysis was used to probe the oxidative effects of SeMet by quantifying the oxidative damage marker, 8-hydroxy-2’-deoxyguanosine. Prior literature indicates that the antioxidant activity of SeMet is potentially concentration dependent; however, HPLC results in this study indicate a metal-ion dependency. In order to better understand the …

Do Halogenated Natural Products Bioaccumulate In Narragansett Bay?, Christine Gardiner, Anna Robuck, Rainer Lohmann

Senior Honors Projects

In recent decades, a new family of chemical compounds has begun to garner research attention—halogenated natural products, or HNPs. These chemicals are produced by algae, bacteria, worms, and sponges, and many are structurally similar to harmful manmade compounds, such as polychlorinated diphenyls (PCBs), or brominated flame retardants (PBDEs), which are known to cause cancer, reproduction issues, endocrine disruption, and death. While HNPs are produced naturally, they are still considered pollutants because of their bioaccumulative behavior and apparent toxicity.

Currently, there is limited research on their presence and effects, with a few studies from Europe and the Pacific highlighting their importance …

Abca' Tetrablock Terpolymers: Synthesis And Morphology, Madalyn Radlauer, Seijiro Fukuta, Megan Matta, Joshua Van Benschoten, Marc Hillmyer

Faculty Publications, Chemistry

No abstract provided.

Phosphomolybdic Acid Catalysis Of Cellulose Hydrolysis, Troy R. Dolmetsch

Undergraduate Honors Theses

Renewable sources such as cellulose derived biofuels are sought after in order to replace fossil fuel sources that are currently used to meet energy demands. Cellulose is a biological polymer composed of a chain of glucose molecules. Hydrolysis of cellulosic materials then has potential to serve as a source of renewable energy in the form of biofuels. The crystalline structure of cellulose is very stable, and current methods of catalyzed hydrolysis are inefficient for industrial application. This project explores the use of phosphomolybdic acid (PMA) in water to catalyze hydrolysis of microcrystalline cellulose. Temperature of hydrolysis was varied from 40 …

Synthesis And In-Vitro Cell Viability/Cytotoxicity Studies Of Novel Pyrrolobenzodiazepine Derivatives, John M. Jarrett

Undergraduate Honors Theses

Pyrrolobenzodiazepines (PBDs) are a group of naturally occurring compounds that were discovered in the cultures of Streptomyces in the 1960s. Some natural PBDs discovered in these cultures, such as anthramycin and sibiromycin, were shown to possess a broad spectrum of anti-tumor activity. Since cancer is still a leading cause of death globally, the development of novel anti-proliferative derivatives of PBDs is essential for human welfare worldwide. Further synthesis and structure-activity relationship (SAR) studies of the parent natural products and their tetracyclic analogs will lead to the discovery of drug candidates. In this work, thirteen PBD analogues were synthesized using no …

Fundamental Studies On Ultrafast Chiral And Achiral Separations In Liquid Chromatography And Sub/Supercritical Fluid Chromatography, Chandan L. Barhate

Chemistry & Biochemistry Dissertations - Archive

This thesis is based on fundamental contributions in the field of ultrafast chiral and achiral separations using liquid and sub/supercritical fluid chromatography. The high efficiency sub-2 μm particles of narrow particle size distribution (NPSD) and 2.7 μm superficially porous particles (SPP) were used as a support for bonding various chiral selectors. The chiral selectors used in this thesis are teicoplanin (T), teicoplanin aglycone (TAG) and vancomycin (V) cyclofructan-6 derivatized isopropyl carbamate (CF6-P), cyclofructan-7 dimethylphenyl carbamate (CF7-DMP), tert-butyl carbomoylated quinine and hydroxypropyl-β cyclodextrin (HPRSP) . These high efficiency particles were packed in 0.5, 2.0, 3.0 and 5 cm long columns As …

Application Of Dft-Derived Relationships Between Chemical Environment And ²⁹Si Nuclear Magnetic Resonance Spectroscopy To Determine Structure In Silicon Oxycarbide Ceramics, John Paul Nimmo

Chemistry & Biochemistry Theses - Archive

Silicon oxycarbide (SiCO) is an amorphous ceramic material widely used in industrial applications, for its useful electronic and biologically-compatible properties.1-3 SiCO is resistant to crystallization, remaining amorphous even above temperatures at which amorphous SiO2 would crystallize. Though silica (SiO2¬) and silicon carbide (SiC) are almost immiscible, it is useful to consider the material as a phase composition of these along with carbon, according to the formula below. The first two terms in braces can be considered as being the “SiCO glass” into which a third term representing excess or “free” carbon is incorporated as graphite-like nano-flakes and bands. SiC_x O_y={y/2 …

Mid-Scale Instrumentation: Regional Facilities To Address Grand Challenges In Chemistry, Robert Hamers, Sophia Hayes, Graham Peaslee

Chemistry Faculty Research

A regional workshop sponsored by the National Science Foundation, Arlington, Virginia, September 29-30, 2016. To determine what needs and opportunities might exist for mid-scale instrumentation (MSI), two workshops were held in fall of 2016 to explore opportunities within the discipline that could be provided by such investment. One workshop was convened to explore the need for co-localization of existing instrumentation at a regional or cyber-enabled facilities (addressed in this report, “Mid-Scale Instrumentation: Regional Facilities to Address Grand Challenges in Chemistry”). In this report, we identify different areas where investment in such MSI facilities would be highly beneficial. These appear as …