Organic Chemicals Commons^™

Investigations Of The Mechanism Of Action For Lung Cancer Cell Death By A 4-Trifluoromethoxy Substituted Chalcone, Trevor M. Stantliff

Undergraduate Theses

Chalcones are a diphenyl compound that serves as a natural precursor to flavonoids in plants. Chalcones have been shown to have anticancer and antimicrobial activities. Chemoprevention activity of chalcones are of high interest in medicinal chemistry because of the simple laboratory synthesis and modification via Claisen-Schmidt condensation. Previously this lab created and screened a library of synthetic chalcones against A549 lung adenocarcinoma cell line for antiproliferation properties. We identified a strong drug candidate (4-trifluoromethoxy substituted chalcone) for A549 growth inhibition. However, the cause of inhibition by the substituted chalcone remains to be identified We began to explore the mechanism of …

Mechanistic Studies And Derivative Effects In 1, 3, 4- Oxadiazole Synthesis Via Cyclodehydration Reactions, Evan Huggins

Undergraduate Honors Thesis Projects

In the world of pharmaceutical synthesis, research to combat foreign pathogens is always necessary. Scientists have been exploring different methods in order to synthesize the most effective compounds in antibacterial, anticancer, anti-inflammatory, and many other treatments. A key component within these versatile compounds are 1,3,4-oxadiazoles. Current methods to synthesize these compounds are inefficient. This research seeks to improve oxadiazole synthesis; however, the mechanism of this reaction is unknown. The goal of this project was to study the mechanistic pathway in the discovered, one-pot cyclodehydration synthesis of 1,3,4-oxadiazoles. In the first part of this study, a diacylhydrazine intermediate was proposed. This …

The Chemical Analysis And Biological Activities Of The Secondary Metabolites From Dalea Mollis And Dalea Albiflora, Nicholas Peter Hansen

All Master's Theses

Multidrug resistance has increased since the introduction of drugs used to prevent growth and kill microorganisms in a host. This has caused a worldwide search to discover new drugs effective against microorganisms. Mechanisms of drug resistance include, but are not limited to, the production of biofilms and efflux pumps. Efflux pumps prevent antimicrobial drugs from reaching their biological target, so the coordinated use of efflux pump inhibitors and antimicrobial drugs has been identified as a potential treatment for multidrug-resistant microorganisms. The secondary metabolites of Dalea mollis and Dalea albiflora were tested against multidrug-resistant (MDR) and engineered strains of the fungi …

1h And 13c Nmr Assignments For (N-Methyl)-(−)-(Α)-Isosparteinium Iodide And (N-Methyl)-(−)-Sparteinium Iodide, Kavoos Kolahdouzan, O. Maduka Ogba, Daniel J. O'Leary

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

(‒)-Sparteine (1) and (–)-(α)-isosparteine (2) are members of the lupine alkaloid family.^[1-2] Sparteine has found extensive use in asymmetric organic transformations, including lithiations^[3] and Pd-catalyzed oxidations.^[4-7] (α)-Isosparteine, which can be made from sparteine, has been utilized as a chiral ligand for a limited number of stereoselective reactions.^[8-9] The two compounds differ in that 1 displays an exo-endo arrangement of the bridgehead hydrogens at C-11 and C-6, respectively, while 2 retains an exo-exo arrangement of these atoms (Figure 1). This study is focused on assigning 1H chemical shifts and coupling constants and 13C chemical shifts for N-methyl …

Photochemical Investigation Of High-Valent Metal-Oxo Intermediates Containing Corrole And Light-Harvesting Porphyrin Ligands, Jonathan Malone

Masters Theses & Specialist Projects

In enzymatic and synthetic catalytic oxidations, high-valent iron-oxo intermediates play a vital role as the active oxidant. In this regard, many synthetic metal catalysts are designed as biomimetic models to resemble the active site of Cytochrome P450 enzymes (P450) which are the predominant oxidation catalysts in nature. Vitamin B12 cofactors, with a corrole-like structure corrin, are also utilized in some of the more difficult reactions in nature such as rearrangement and reductase reactions.

In this work, application of the promising photochemical method to corrolecontaining ligands systems showed much success in the generation of manganese(V)-oxo corrole intermediates using two electron-deficient corrole …

Do Paraben Derivatives Alter T Cell Immunity?, Hailey Kintz

Spring Presentation of Undergraduate Research

T cells immunity is linked to a complex system of cytokines that determine differentiation of naïve T cells into Th1, Th2, Th17, and Treg cells. Estrogen production or periods of elevated production have been correlated with an anti-inflammatory state in which Th2 and Treg cells are up-regulated. Such responses in the immune system are capable of supporting pre-cancerous activity. We are investigating the tie between the xenoestrogen compounds found in cosmetics, parabens, and their ability to regulate T cell immunity. Testing parabens and paraben derivatives with weaker estrogen receptor association will allow for a better understanding of the interplay between …

Inactivation Of Myeloma Cancer Cells By Helium And Argon Plasma Jets: The Effect Comparison And The Key Reactive Species, Zeyu Chen, Qingjie Cui, Chen Chen, Dehui Xu, Dingxin Liu, H. L. Chen, Michael G. Kong

Bioelectrics Publications

In plasma cancer therapy, the inactivation of cancer cells under plasma treatment is closely related to the reactive oxygen and nitrogen species (RONS) induced by plasmas. Quantitative study on the plasma-induced RONS that related to cancer cells apoptosis is critical for advancing the research of plasma cancer therapy. In this paper, the effects of several reactive species on the inactivation of LP-1 myeloma cancer cells are comparatively studied with variable working gas composition, surrounding gas composition, and discharge power. The results show that helium plasma jet has a higher cell inactivation efficiency than argon plasma jet under the same discharge …

Cellular And Molecular Targets Of Menthol Actions, Murat Oz, Eslam El Nebrisi, Keun-Hang Susan Yang, Frank Christopher Howarth, Lina T. Al Kury

Mathematics, Physics, and Computer Science Faculty Articles and Research

Menthol belongs to monoterpene class of a structurally diverse group of phytochemicals found in plant-derived essential oils. Menthol is widely used in pharmaceuticals, confectionary, oral hygiene products, pesticides, cosmetics, and as a flavoring agent. In addition, menthol is known to have antioxidant, anti-inflammatory, and analgesic effects. Recently, there has been renewed awareness in comprehending the biological and pharmacological effects of menthol. TRP channels have been demonstrated to mediate the cooling actions ofmenthol. There has been new evidence demonstrating thatmenthol can significantly influence the functional characteristics of a number of different kinds of ligand and voltage-gated ion channels, indicating that at …

Recent Advances On Iron Oxide Magnetic Nanoparticles As Sorbents Of Organic Pollutants In Water And Wastewater Treatment, Angela M. Gutierrez, Thomas D. Dziubla, J. Zach Hilt

Superfund Research Center Faculty Publications

The constant growth in population worldwide over the past decades continues to put forward the need to provide access to safe, clean water to meet human needs. There is a need for cost-effective technologies for water and wastewater treatment that can meet the global demands and the rigorous water quality standards and at the same maximizing pollutant efficiency removal. Current remediation technologies have failed in keeping up with these factors without becoming cost-prohibitive. Most recently, nanotechnology has been sought as the best alternative to increase access to water supplies by remediating those already contaminated and offering ways to access unconventional …

Synthesis Of Multifunctional Polyacrylates And A Binding Group To Hemoglobin For The Treatment Of Traumatic Brain Injuries, Marina Michaud

Honors College Theses

Hemoglobin based oxygen carriers (HBOCs) hold promise as an effective emergency treatment of severe traumatic brain injuries (TBI). In the latest generation of HBOCs, polynitroxyl-pegylated hemoglobin (PNPH), cell-free hemoglobin is modified with TEMPO and PEG which reduce the toxicities associated with earlier generations of HBOCs. In our efforts to optimize the economic and therapeutic impacts of PNPH’s we have synthesized polydimethylaminoethyl methacrylate (poly-DMAEMA) under controlled living conditions via reverse addition-fragmentation chain transfer (RAFT) polymerization. The poly-DMAEMA was then successfully functionalized via quaternization of its NMe₂ groups using chloroacetate derivatives of the TEMPO and PEG. This process was quantitative and …

A Diversity-Oriented Synthesis Approach To Functionalized Azaheterocycles Using Cyclic Alpha-Halo Eneformamides, Spencer A. Langevin

All Master's Theses

Functionalized piperidines, azepanes, azamacrocycles, morpholines, and thiomorpholines are common structural motifs found in a wide range of pharmaceuticals such as carmegliptine, levofloxacin, thioridazine, claviciptic acid, and azithomycin. As a result, there is a strong desire to construct highly functionalized nitrogen-bearing ring scaffolds in order to construct a wide range of drug possibilities. There are several non-modular and step-uneconomical synthetic methods used in the construction of these aforementioned motifs such as ring closing metathesis, ring expansions, and intramolecular reductive amination. In this research, we present a step-economical, cost-effective, scalable, and diversity-oriented synthesis approach to highly functionalized N-heterocycles through the intermediacy of …

Assembly Of Nucleic Acid-Based Nanoparticles By Gas-Liquid Segmented Flow Microfluidics, Matthew L. Capek, Ross Verheul, David H. Thompson

The Summer Undergraduate Research Fellowship (SURF) Symposium

The development of novel and efficient mixing methods is important for optimizing the efficiency of many biological and chemical processes. Tuning the physical and performance properties of nucleic acid-based nanoparticles is one such example known to be strongly affected by mixing efficiency. The characteristics of DNA nanoparticles (such as size, polydispersity, ζ-potential, and gel shift) are important to ensure their therapeutic potency, and new methods to optimize these characteristics are of significant importance to achieve the highest efficacy. In the present study, a simple segmented flow microfluidics system has been developed to augment mixing of pDNA/bPEI nanoparticles. This DNA and …

The Synthesis Of 1,3-Difluoro-2-Methyl-4-Phenylbenzene From A One-Pot Reaction Of Difluorocarbene And 1-Phenyl-2-Methylcyclobutene, Ruth Felicitas Menger

Senior Honors Projects, 2010-2019

Previous studies show that 1,2-disubstituted cyclobutenes can be used in reaction with difluorocarbene to produce 1,3-difluorobenzenes. A pathway to the synthesis of these types of compounds is of interest due to their presence in fluoroquinolone antibacterials, resins, and insecticides. The synthesis is unique because the fluorine atoms from the difluorocarbene are not adjacent to each other when the ring expands to a benzene ring. This study focuses on the reaction of difluorocarbene with 1-phenyl-2-methylcyclobutene, which was synthesized in one-pot in 4 steps starting from 1-phenyl-1-propyne and zirconocene dichloride.

Probing Allosteric, Partial Inhibition Of Thrombin Using Novel Anticoagulants, Stephen S. Verespy Iii

Theses and Dissertations

Thrombin is the key protease that regulates hemostasis; the delicate balance between procoagulation and anticoagulation of blood. In clotting disorders, like deep vein thrombosis or pulmonary embolism, procoagulation is up-regulated, but propagation of clotting can be inhibited with drugs targeting the proteases involved, like thrombin. Such drugs however, have serious side effects (e.g., excessive bleeding) and some require monitoring during the course of treatment. The reason for these side effects is the mechanism by which the drugs’ act. The two major mechanisms are direct orthosteric and indirect allosteric inhibition, which will completely abolish the protease’s activity. Herein we sought an …

The Synthesis And Study Of The Biological And Colloidal Properties Of Bolaamphiphiles, Louis M. Damiano

Senior Honors Projects, 2010-2019

Over the past decade, antibiotic resistant bacteria have caused infections in patients throughout the world.^[1] The rise in antibiotic resistance is primarily due to the misuse and overuse of antibiotics. ^[1] To counter the increase in antibiotic resistance, infection control mechanisms have been aggressively researched in recent years. In particular, drug delivery has become a focal point to fight antibiotic resistant infections.^[2] Amphiphiles have a wide range of applications in the clinical setting, including the ability to inhibit bacterial transference because of their bactericidal activity. ^[3] Bolaamphiphiles are a subclass of amphiphiles that possess two or more hydrophilic …

Total Synthesis Of Biologically Active Natural And Unnatural Products, Julia Heimberger

College of Graduate Studies: Theses & Dissertations

Herbarin A and B were isolated from the fungal strains of Cladosporium herbarum found in marine sponges Aplysina aerophoba and Callyspongia aerizusa. Total synthesis of Herbarin A and B was achieved by carrying out a multi-step synthesis approach, and the antioxidant properties were evaluated using FRAP assay. Toxicity of these compounds was determined using a zebrafish embryo model. Furthermore, synthesis of C-6 alkyl-azaarene derivatives of nucleosides by Csp3-H bond functionalization were investigated. Effective incorporation of 2-methylazaarene moiety at the C-6 position of the protected inosine nucleoside provided a new class of compounds with anticipated enhanced biological activity.

Chemoenzymatic Studies To Enhance The Chemical Space Of Natural Products, Jhong-Min Chen

Theses and Dissertations--Pharmacy

Natural products provide some of the most potent anticancer agents and offer a template for new drug design or improvement with the advantage of an enormous chemical space. The overall goal of this thesis research is to enhance the chemical space of two natural products in order to generate novel drugs with better in vivo bioactivities than the original natural products.

Polycarcin V (PV) is a gilvocarcin-type antitumor agent with similar structure and comparable bioactivity with the principle compound of this group, gilvocarcin V (GV). Modest modifications of the polyketide-derived tetracyclic core of GV had been accomplished, but the most …

Design, Synthesis And Biological Evaluation Of Novel Compounds With Cns-Activity Targeting Cannabinoid And Biogenic Amine Receptors, Alexander M. Sherwood

University of New Orleans Theses and Dissertations

This work seeks to contribute to the discipline of neuropharmacology by way of structure activity relationship from the standpoint of an organic chemist. More specifically, we sought to develop robust synthetic methodology able to efficiently produce an array of compounds for the purpose of systematic evaluation of their interaction with specific sights within the central nervous system (CNS) in order to better understand the mind and to develop drugs that may have beneficial effects on neurological function.

The focus of these studies has been toward the development of novel molecules, using a structure-activity relationship approach, that exhibit binding affinity at …

Polyethylene Glycol Containing Rompolymers For The Modification Of Neuro-Protective Hemoglobin, Andrea L. Mccollum

Honors College Theses

Polyethylene glycol (PEG) has shown the ability to improve compatibility when used in combination with cell-free hemoglobin in the treatment of traumatic brain injuries. It has been demonstrated that the covalently bonded PEG increases the hydrodynamic radius of the hemoglobin and hence generates a physical barrier while slowing down the oxygen delivery of the strongly oxidative hemoglobin. In this context, I have been working on the development of synthetic pathways to incorporate PEG into monomers and polymers through both direct modification of (7-oxa)norbornene derivatives and post polymerization modification. Starting from the (7-oxa)norbornene anhydride derivatives, we have developed pathways to cationic …

Atrazine And Nitrate In Public Drinking Water Supplies And Non-Hodgkin Lymphoma In Nebraska, Usa, Martha G. Rhoades, Jane L. Meza, Cheryl L. Beseler, Patrick J. Shea, Andy Kahle, Julie M. Vose, Kent M. Eskridge, Roy F. Spalding

School of Natural Resources: Faculty Publications

A secondary analysis of 1999–2002 Nebraska case-control data was conducted to assess the risk of non-Hodgkin lymphoma (NHL) associated with exposure to nitrate- and atrazine-contaminated drinking water. Water chemistry data were collected and weighted by well contribution and proximity of residence to water supply, followed by logistic regression to determine odds ratios (OR) and 95% confidence intervals (CI). We found no association between NHL risk and exposure to drinking water containing atrazine or nitrate alone. Risk associated with the interaction of nitrate and atrazine in drinking water was elevated (OR, 2.5; CI, 1.0–6.2). Risk of indolent B-cell lymphoma was higher …

The Morbidity & Mortality Of Prevalent Heart Failure, Jennifer Kwon

Loma Linda University Electronic Theses, Dissertations & Projects

The first study population included 292 unselected consecutive patients from the LLUMC heart failure clinic who were enrolled in the study from January to July 2006 and were followed up through the end of December 2010. The treatment policy at the clinic was to uptitrate dosages of beta-adrenergic blockade (β-blockers), angiotensin-converting-enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) to the most tolerable levels in order to reach target dosages, as recommended by the Heart Failure Society of America (HFSA). Patients were classified into systolic heart failure (ejection fraction (EF) < 40%) or diastolic heart failure (EF≥40%). All dosages of β-blockers, ACEi and ARB were extracted through chart reviews and were used as the main predictors of the patients' survival. Results from analyses showed that reaching target dosages of β-blockers and ACEi/ARB may increase survival when compared to not reaching target among the systolic HF population (HR_{β_biockers}= 0.64, 95% CI 0.26-1.56 and HR_ACEi/ARB=0.50, …

The Reaction Of Methionine With A Non-C2-Symmetrical Platinum (Ii) Diamine Compound, Nilesh Sahi

Mahurin Honors College Capstone Experience/Thesis Projects

The research that we have conducted has allowed us to discover that the amino acids, methionine (Met) and N-acetyl methionine (N-AcMet), will react in a 1:1 and 1:2 molar ratio with platinum complexes containing bulky diamine ligands. Previous research has allowed us to gain a plethora of information on the experimentation and results of specific bulky diamine ligands such as N,N,N',N'-tetramethylethylenediamine and N,N-diethylethylenediamine. In the current study, we have investigated the bulky diamine ligand of N,N-dimethylethylenediamine, or Me₂en. With our focus on the bulk of the Me₂en ligand, we have been able to synthesize a platinum …

Comparing The Epa Indoor Air Quality Personal Computer Model And Field Data, Arash Behravesh, Wilbur A. Spaul

RISK: Health, Safety & Environment (1990-2002)

The authors recommend caution in using an EPA model for reconstructing past exposure events as well as for predicting future exposures.

Bulletin 4307 - Grass Control In Pastures Using Herbicides, Alexandra Wallace

Bulletins 4000 -

This Bulletin discusses three methods for herbicide control of grasses in pastures:

• pasture manipulation, in the early stages of pasture growth;
• spray-topping late in the growing season; and
• hay freezing, late in the growing season.

The Isolation And Identification Of Polyphenolics From Grape Seeds And Their Activity Towards Specific Cell Lines, Joseph A. Reddy

Chemistry & Biochemistry Theses & Dissertations

Grape seed extract is being marketed in France for cardiovascular use and skin care. The active constituents of both these drugs are certain polyphenols called procyanidins. A similar seed extract has now been obtained from Virginia Chardonnay grape seeds. Ten of the major components in this extract have been isolated in their pure form by the semi-preparative HPLC separation on a YMC ODS-AQ (Octadecylsilane-AQ) column. The ODS-Aq column has been shown to have a better resolving capacity compared to the Spherisorb ODS (Octadecylsilane) column previously described in the literature. This has been attributed to the ODSAQ support which has both …

Replicated Single Row Evaluation., C. M. Saunders

Experimental Summaries - Plant Research

Trial 89AB12

Great Southern Agricultural Institute - Paddock B15

This trial was of similar design to the single row evaluation, except four replications and pesticide treatments were also included.
However the trial had to be abandoned due to severe phytotoxic responses seen in the medics due to repeated spraying of 'Lorsban' (used at recommended rates).
Intended to repeat this work in 1990, bulk seed where possible and to eventually assess these lines, under such conditions, in large plots.

Serradella Evaluations, L. Cransberg

Experimental Summaries - Plant Research

Trial 85AL56

Location: South Sterlings.

Serradella line evaluation - Stage 3.

To evaluate five promising lines selected from variety trials, in terms of herbage production and long term persistence.

Trial 88AL32

Location: Walpole.
Long season serradella evaluation.

To select productive and persistent serradella lines for the deep acidic sands in the very high rainfall zone on the south coast.

Trial 88AL31

Location: Takalarup.

Ryegrass species evaluation.

To investigate the potential of a range of ryegrasses, from short term to long term perennial, in the south coast environment.

Grass species evaluation

Location: Greenrange.

To identify both productive and persistent grasses for …

The Synthesis And Evaluation Of The Cardiovascular Activity Of Novel Imidazole Ring Systems, Joseph E. De Los Angeles

Chemistry & Biochemistry Theses & Dissertations

An investigation was undertaken to synthesize and evaluate the cardiovascular activity of two imidazole ring systems. Imidazoles with hypotensive activity would provide novel potential antihypertensive drugs. These novel structures may also find use as chemical probes in the study of the cardiovascular system and as prototypes for other potential cardiovascular agents.

The histamine derivative, 7,7-dipyridyl-4,5,6,7-tetrahydroimidazo-[4,5-c]pyridine (ligand l), was demonstrated to possess significant hypotensive activity in laboratory rats. A 15 mg/Kg dose of ligand 1 produces a statistically significant decrease in blood pressure when injected IP. This hypotensive effect is also associated with marked increase in heart rate. Although compound 1 …

The Aquatic Toxicity Of Organic Compounds To Embryo-Larval Stages Of Fish And Amphibians, Jeffrey A. Black, Wesley J. Birge, Willaim E. Mcdonnell, Albert G. Westerman, Barbara A. Ramey, Donald M. Bruser

KWRRI Research Reports

Aquatic toxicity tests were conducted on 11 organic compounds considered hazardous to water resources. The toxicity of each compound was evaluated using embryo-larval stages of two to eight fish and amphibian species. Exposure was initiated at fertilization and maintained through 4 days posthatching. The animal test species exhibited varying degrees of sensitivity to the selected toxicants. Combined frequencies for mortality and teratogenesis at 4 days posthatching gave LC₅₀ ranges of 3.66 to 8.25 mg/L for benzene, 1.16 to 22.42 mg/L for carbon tetrachloride, 0.11 to 1.20 mg/L for chlorobenzene, 2.03 to > 68 mg/L for chloroform, 3.01 to 5.56 mg/L …

Effects Of Organic Compounds On Amphibian Reproduction, Wesley J. Birge, Jeffrey A. Black, Robert A. Kuehne

KWRRI Research Reports

Aquatic toxicity tests were conducted with atrazine, carbon tetrachloride, chloroform, methylene chloride, trisodium nitrilotriacetic acid (NTA), and phenol. Each compound was administered to developmental stages of three to five amphibian species. Exposure was initiated at fertilization and maintained through 4 days posthatching. Test responses included lethality and teratogenesis. Different amphibian species exhibited varying degrees of tolerance to the selected compounds. Greatest tolerance usually was observed for the more broadly adapted semi-aquatic and terrestrial species (e.g., Bufo americanus, Bufo fowleri). The more sensitive amphibians usually included those species which normally are restricted to aquatic or moist habitats (e.g., Rana …