Chemistry Commons^™

Analogues Of (-)-Picropodophyllin, Synthesis And Uses Thereof, David B. Berkowitz, Sylvain Broussy

Department of Chemistry: Faculty Publications

Analogs of (-)-Picropodophyllin, synthesis thereof, and uses in pharmaceuticals as inhibitors of IGF1RK.

Further Characterization Of A Secreted Lipase From The Human Pathogen Leishmania Donovani By Determining The Effect Of Various Metal Ions On Its Enzymatic Activity., Lana Hoertz

Pell Scholars and Senior Theses

Leishmania donovani, a protozoan parasite, is the causative agent of the often fatal disease visceral leishmaniasis. The current treatments available are minimal and toxic to the patient. It has been shown that these organisms exhibit lipolytic activity during their growth in vitro. Lipases are enzymes that are known to aid in the development and virulence of several pathogenic organisms such as Candida albicans and Staphylococcus warneri. Little information is known, however, about the role of lipases in Leishmania species. We hypothesize that lipase may play a part in Leishmania's ability to survive within the human host as well as its …

Proton Pump Inhibitors: Omeprazole, Paulina N. Ongkowijoyo

A with Honors Projects

Characteristics and uses of proton pump inhibitors are discussed, specifically, the drug omeprazole, a type of proton pump inhibitor, is discussed, including the chemistry, it's uses and side effects.

Probing The Human Estrogen Receptor-Α Binding Requirements For Phenolic Mono- And Di-Hydroxyl Compounds: A Combined Synthesis, Binding And Docking Study, Christopher Mccullough, Terrence S. Neumann, Jayapal Reddy Gone, Zhengjie He, Christian Herrild, Julie Lukesh, Rajesh K. Pandey, William A. Donaldson, Daniel S. Sem

Chemistry Faculty Research and Publications

Various estrogen analogs were synthesized and tested for binding to human ERα using a fluorescence polarization displacement assay. Binding affinity and orientation were also predicted using docking calculations. Docking was able to accurately predict relative binding affinity and orientation for estradiol, but only if a tightly bound water molecule bridging Arg394/Glu353 is present. Di-hydroxyl compounds sometimes bind in two orientations, which are flipped in terms of relative positioning of their hydroxyl groups. Di-hydroxyl compounds were predicted to bind with their aliphatic hydroxyl group interacting with His524 in ERα. One nonsteroid-based dihdroxyl compound was 1000-fold specific for ERβ over ERα, and …

High Resolution X-Ray Diffraction Analysis Of Cb1 Receptor Antagonists As A Means To Explore Binding Affinity, Steven P. Fournet

LSU New Orleans Theses and Dissertations

Abstract

Charge density studies have been conducted on ten CB₁ cannabinoid receptor antagonists via high resolution x-ray crystallography. Bond critical point values and various other properties derived from these studies including the electrostatic potential were analyzed in correlation to the affinity of each compound with the CB₁ receptor. Correlation/anti-correlation was found between several properties and K_i. The data was also interpreted by principal component analysis with three principal components accounting for 85% of the data variation. Data mining was limit due to the low sample count and the requirements set for the inclusion of correlated/anti-correlated variables …

The Spontaneous Formation Of Selenium Nanoparticles On Gallic Acid Assemblies And Their Antioxidant Properties, Stacey Barnaby Fcrh '11, Nazmul Sarker Fcrh '13, Aaron Dowdell Fcrh '12, Ipsita Bannerjee

The Fordham Undergraduate Research Journal

Gallic acid (GA) is a naturally occurring plant phenol known for its anti-inflammatory and antioxidant properties. In this work, we probed the molecular self-assembly of GA for the development of GA based nanocomposites for potential device fabrications and enhanced antioxidant applications. We found that the formation of GA nanostructures was pH dependent. Further, we examined the interactions of selenite with GA and subsequently examined the biomimetic formation of selenium (Se) nanoparticles. We found that in the presence of selenite, the yield of nanofibers was significantly higher, and selenium nanoparticle coated nanofibers were formed. The ability of the nanocomposites to scavenge …

Fluorination Of Aromatic Ring Systems, Stephen G. Dimagno

Department of Chemistry: Faculty Publications

This disclosure relates to reagents and methods useful in the synthesis of aryl fluorides, for example, in the preparation of ¹⁸F labeled radiotracers. The reagents and methods provided herein may be used to access a broad range of compounds, including aromatic compounds, heteroaromatic compounds, amino acids, nucleotides, and synthetic compounds.

Molecular Level Interaction Of Human Fibroblast Growth Factor-1 (Hfgf-1) With Phloridzin, Rammohan Paripelly

Masters Theses & Specialist Projects

Fibroblast growth factors (FGFs) are a family of growth factors which includes twenty three proteins. FGFs work as modulators for various cellular activities like mitosis, differentiation and survival. Among the FGF family, human fibroblast growth factor-1 (hFGF-1), which is also known as acidic fibroblast growth factor, is a potent angiogenic agent, involved in the formation of new blood vessels in various tissues. hFGF-1 is regarded as a prototype of the FGF family. It serves as one of the potential targets in tumor inhibition and obesity due to its involvement in new blood vessel formation in cancerous regions and adipose tissues. …

Phosphate Esters, Thiophosphate Esters And Metal Thiophosphates As Lubricant Additives, David W. Johnson, John E. Hils

Chemistry Faculty Publications

Phosphate esters, thiophosphate esters and metal thiophosphates have been used as lubricant additives for over 50 years. While their use has been extensive, a detailed knowledge of how they work has been a much more recent development. In this paper, the use of phosphate esters and thiophosphate esters as anti-wear or extreme pressure additives is reviewed with an emphasis on their mechanism of action. The review includes the use of alkyl phosphates, triaryl phosphates and metal containing thiophosphate esters. The mechanisms of these materials interacting with a range of iron and steel based bearing material are examined.

Nmr And Computational Characterization Of Protein Structure And Ligand Binding, Terrence Neumann

Dissertations (1934 -)

Nuclear magnetic resonance (NMR) techniques combined with computational methods such as docking and cheminformatics were used to characterize protein structure and ligand binding. The thioredoxin system of Mycobacterium tuberculosis consists of a thioredoxin reductase and at least three thioredoxins. This system is responsible for maintaining the cellular protein thiol redox state in normal state. This maintenance is important as the bacterium is engulfed by the human macrophage. Here it is bombarded by reactive oxygen and nitrogen species in an attempt to disrupt normal cellular function in part by perturbing the protein thiols. To this end, the solution structures of the …

Novel Modulation Of Adenylyl Cyclase Type 2, Jason Michael Conley

Open Access Dissertations

Adenylyl cyclase isoforms are distinctly modulated by G protein subunits and are therefore hypothesized to be uniquely regulated by proteins that influence G protein signaling. Activator of G protein signaling 3 (AGS3) is a G protein modulator that binds Gαi subunits in the GDP-bound state, implicating AGS3 as an important regulatorof Gi-coupled receptor signaling. We studied the ability of AGS3 to modulate recombinant adenylyl cyclase(AC) type 1 and 2 signaling in HEK293 cells following both acute and persistent activation of the D _2Ldopamine receptor (D_2L DR). AGS3 expression modestly enhanced the potency of acute quinpirole-induced D _2LDR …

A Novel Mglur5 Antagonist, Mfz 10-7, Inhibits Cocaine-Taking And Cocaine-Seeking Behavior In Rats, Thomas Keck, Mu-Fa Zou, Gui-Hua Bi, Hai-Ying Zhang, Xiao-Fei Wang, Hong-Ju Yang, Ratika Srivastava, Elliott L. Gardner, Zheng-Xiong Xi, Amy Hauck Newman

College of Science & Mathematics Departmental Research

Pre-clinical studies suggest that negative allosteric modulators (NAMs) of the metabotropic glutamate receptor subtype 5 (mGluR5), including 2-methyl-6-(phenylethynyl)pyridine (MPEP), 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) and fenobam are highly effective in attenuating drug-taking and drug-seeking behaviors. However, both MPEP and MTEP have no translational potential for use in humans because of their off-target effects and short half-lives. Here, we report that 3-fluoro-5-[(6-methylpyridin-2-yl)ethynyl]benzonitrile (MFZ 10-7), a novel mGluR5 NAM, is more potent and selective than MPEP, MTEP and fenobam in both in vitro binding and functional assays. Similar to MTEP, intraperitoneal administration of MFZ 10-7 inhibited intravenous cocaine self-administration, cocaine-induced reinstatement of drug-seeking behavior and …

Structure, Theoretical Studies And Coupling Reactions Of Some New Cyclic Boronic Esters, Andrew Kuttler, Sravanthi Durganala, Albert Fratini, Alexander Morgan, Vladimir Benin

Chemistry Faculty Publications

The present report describes the X-ray structural and theoretical studies of some new pinacolboronate esters, and it also outlines the use of the target structures in Suzuki coupling reactions to produce new aromatic or heteroaromatic esters and amides. X-ray structural analysis of the studied compounds revealed that the pinacolborane ring's position with respect to the benzene ring varies, depending on the particular environment. An ortho-positioned carboxylic ester (methyl ester) causes a nearly perpendicular orientation of the pinacolborane unit with respect to the benzene ring, whereas an ortho-positioned amide (N,N-dimethylamide) causes the pinacolborane unit to orient itself nearly coplanar. A plausible …

A Supramolecular Strategy To Assemble Multifunctional Viral Nanoparticles, Limin Chen, Xia Zhao, Yuan Lin, Yubin Huang, Qian Wang

Faculty Publications

Using a one-pot approach driven by the supramolecular interaction between β-cyclodextrin and adamantyl moieties, multifunctional viral nanoparticles can be facilely formulated for biomedical applications.

Selective Catalytic Oxidation Of Organic Sulfides By Iron (Iii) Porphryin Catalysts And Generation Of Iron (Iv)-Oxo Prophyrin Radical Cations, Nawras A. Asiri

Masters Theses & Specialist Projects

Macrocyclic ligand-complexed transition metal-oxo intermediates are the active oxidizing species in a variety of important biological and catalytic oxidation reactions. Many transition metal catalysts have been designed to mimic the predominant oxidation catalysts in nature, namely the cytochrome P450 enzymes. Iron porphyrin complexes have been the center of research as catalysts. In this study 5,10,15,20- tetramesitylporphyrin (H₂TMP) and its corresponding iron complexes Fe^III(X)TMP (X= Cl, ClO₄, ClO₃, NO₃, NO₂, and BrO₃) have been successfully synthesized and fully characterized by UV-vis and NMR spectroscopies. For the catalytic …

Ionic Conductivity In Non-Ionic Compounds, Usha Kranthi Avala

Masters Theses & Specialist Projects

The main objective of this work is to investigate the ionic conductivity of the drugs under certain conditions and also to compare the ionic conductivities of drugs determined by single surface sensors and parallel plate sensors. The ionic conductivity of various materials at their pre-melt and melt states are studied in order to further study a recently discovered phenomenon. Polar solids like Lidocaine, Ketoconazole, Procainamide and Nifedipine were examined in this study. Experimental studies show an increase in ionic conductivity in both pre-melt (20 -30 °C below melting temperature) and melt transition regions. Results of ionic conductivity of both parallel …

Developing Thyronamine Analog Pharmaceuticals Targeting Taar1 To Treat Methamphetamine Addiction, Troy Andrew Wahl

Dissertations and Theses

As a part of the overall program in the Grandy laboratory at Oregon Health & Science University (OHSU), studying the underlying chemical biology of methamphetamine (Meth) addiction, this dissertation reports on the development of six new thyronamine analogs which were synthesized and assayed against trace amine associated receptor 1 (TAAR1), giving preliminary results consistent with the analogs being inverse agonists. Due to highly variable TAAR1 expression levels in the assays, based on inter-assay response to control Meth stimulation as well as other possible factors, kinetic models were developed to qualitatively explain the assay results. The models set approximate limits on …

Characterization By Nmr Of Reactants And Products Of Hydrofluoroether Isomers, Cf3(Cf2)3och3 And (Cf3)2c(F)Cf2och3, Reacting With Isopropyl Alcohol, Howard Knachel, Vladimir Benin, William E. Moddeman, Janine C. Birkbeck, Thomas A. Kestner, Tayna L. Young

Chemistry Faculty Publications

The 3M Company product Novec™ 71IPA DL, a mixture of methoxyperfluorobutane, methoxyperfluoroisobutane and 4.5 wt.% isopropyl alcohol, has been found to be very stable at ambient temperature, producing fluoride at the rate of ~1 ppm/year. Our earlier kinetic and theoretical studies have identified the reaction mechanism. This paper identifies the ¹H and ¹⁹F NMR chemical shifts, multiplicities, and coupling constants of reactants and the major products that result from aging the mixture in sealed Pyrex NMR tubes for periods up to 1.8 years at temperatures from 26 °C to 102 °C. Chemical shifts and coupling constants of fluorine …

A, Catalysis Of Co-Prox By Water-Soluble Rhodium Fluorinated Porphyrins. B, Studies Toward Fluorination Of Electron Rich Aromatics By Nucleophilic Fluoride, Shri Harsha Uppaluri

Department of Chemistry: Dissertations, Theses, and Student Research

The rhodium(III) derivative of a water soluble, heavily fluorinated porphyrin is shown to catalyze the low temperature, low pressure selective oxidation of carbon monoxide in hydrogen gas streams for use in fuel cell applications. The catalytic activity is a direct result of the removal of electron density from the metal center. Selectivity for CO oxidation is a direct consequence of fluorination of the porphyrin periphery, since these substituents enhance the rate of the reaction and prevent the formation of Rh(II)-Rh(II) dimmers. Significantly, the dramatic increase in rhodium hydride acidity caused by fluorination precludes hydrogen activation and generation, thereby permitting preferential …

Synthesis And Antifungal Evaluation Of Barbiturate Saponins And Progress Towards Cysteinyl Metal Peptides, Monika Madhav

LSU New Orleans Theses and Dissertations

Invasive fungal infections are a major threat to immune-compromised patients. There is a critical need to develop new antifungal agents because of increasing resistance to the common antifungal drugs.

In the first part of this dissertation, methods for preparation of novel barbiturate saponin as antifungals and their biological activities would be described. Barbiturates and steroidal saponins have shown remarkable antifungal activity in the biological assays. Therefore, attempts were directed to combine the barbiturate with the steroid to give novel antifungal agents. The need for extensive SAR studies and to better understand these compounds efforts were directed to synthesize novel saponin …

Synthesis Of Rhenium And Manganese Pyridazoal Complexes, Jesse Evans

Masters Theses & Specialist Projects

Pyridazines are a heterocyclic aromatic compound containing a characteristic N-N bond that are utilized in many fields, including medicine and electronics. It is this latter field that Dr. Snyder's research group is focused upon. Organometallic compounds are a better conducting material than the current inorganic compounds used in electronics due to better conductance of electricity, lower production cost, and the ability to be formed into thin films. With this in mind, Dr. Snyder's research group has set out to synthesize organometallic compounds for this purpose. Following procedures set forth by Snyder etc, and altered to form an off-metal route, we …

Reactions Of Platinum(Ii) Compounds With Selenium Containing Amino Acids, Stephanie Robey

Masters Theses & Specialist Projects

Platinum(II) anticancer medications essentially react with DNA forming kinks in
the double helix of DNA and causing apoptosis. It has also been noted that these
anticancer medications react with methionine and cysteine in the body. With the new discoveries of selenium containing amino acids including selenomethionine and selenocysteine, new research is ongoing to see what types of products can be formed from these amino acids. Our research reacts [Pt(Met-S,N)Cl₂] ²⁺ with selenomethionine to determine what types of products are produced. Monochelates including [Pt(SeMet-Se,N)Cl₂] ²⁺ have formed two isomers, …

Effects Of Cisplatin Analog Size On The Reaction With Dna Bases, Swathi Nandala

Masters Theses & Specialist Projects

Cancer is the second leading cause of death in the United States. Cisplatin is one of the well-known anti-cancer agents used to treat testicular and ovarian cancers. It mainly binds to the DNA bases, which leads to cell death. The cytotoxic activity of the cisplatin analogs is due to the interaction of platinum with nucleotides like adenine at N₇ or N₁ position and guanine at N₇ position. Guanine is the primary target for cisplatin analogs whereas adenine is the secondary target. Cisplatin analogs, [Pt(Me₅dien)(D₂O)]²⁺[Me₅dien = N,N,N’,N’,N’’-pentamethyl diethylene triamine] and …

The Role Of Type-2 Cannabinoid Receptors In Calcification Of Atherosclerotic Lesions., Kaitlyn Hinshaw

Undergraduate Honors Theses

Introduction: Atherosclerosis is a chronic inflammatory disease characterized by the buildup of cholesterol, fat and other debris within arterial walls. Atherosclerotic lesions undergo a calcification process with similarities to bone remodeling. In mice, the type-2 cannabinoid receptor (CB2) is known to regulate bone remodeling processes and has also been shown to alter atherosclerotic lesion characteristics. However, the role of CB2 in lesion calcification is still unclear. CB2 modulates bone remodeling by affecting differentiation of osteogenic precursor cells; thus we hypothesize that CB2 alters lesion calcification by altering osteoblastogenesis and osteoclastogenesis of precursor cells of vascular origin. To test this hypothesis, …

Interaction Between Lubricants Containing Phosphate Ester Additives And Stainless Steels, David W. Johnson, Matthew Bachus, John E. Hils

Chemistry Faculty Publications

One way to improve fuel efficiency in today’s jet aircraft engines is to create an environment for higher operating temperatures and speeds. New and improved lubricants and bearing materials must be developed to remain stable in these elevated operating temperatures. Three lubricants, with varying amounts of tricresyl phosphate added as an anti-wear/extreme pressure additive were tested on two different stainless steels at varying temperatures ranging from 300 °C to 350 °C in vacuum. Significant decomposition of the lubricant base-stocks and the phosphate ester additive did occur in most of the trials resulting in the formation of carboxylic acids and phenols. …

Study Of The Insulin Mimetic Sodium Orthovanadate In Glucosamine Induced Insulin Resistnace In Primary Rat Hepatocytes, Kalan Mcpherson

Masters Theses

Insulin resistance and type II diabetes is a disease state characterized by a lack of sensitivity of insulin to provoke a proper response in insulin sensitive tissues. Currently, we utilize glucosamine to increase flux through the Hexosamine Biosynthetic Pathway (HBP) to induce an insulin resistance like state in primary rat hepatocytes. We tested the effectiveness of the insulin mimetic sodium orthovanadate to determine if it could elicit an insulin-like response under these conditions. Mixed results were obtained on the effectiveness of vanadate as an insulin mimetic in this insulin resistant model.

Dimethyl Sulfoxide (Dmso) Exacerbates Cisplatin-Induced Sensory Hair Cell Death In Zebrafish (Danio Rerio), Phillip M. Uribe, Melissa A. Mueller, Julia S. Gleichman, Matthew D. Kramer, Qi Wang, Martha Sibrian-Vazquez, Robert M. Strongin, Peter S. Steyger, Douglas A. Cotanche, Jonathan I. Matsui

Chemistry Faculty Publications and Presentations

Inner ear sensory hair cells die following exposure to aminoglycoside antibiotics or chemotherapeutics like cisplatin, leading to permanent auditory and/or balance deficits in humans. Zebrafish (Danio rerio) are used to study drug-induced sensory hair cell death since their hair cells are similar in structure and function to those found in humans. We developed a cisplatin dose-response curve using a transgenic line of zebrafish that expresses membrane-targeted green fluorescent protein under the control of the Brn3c promoter/enhancer. Recently, several small molecule screens have been conducted using zebrafish to identify potential pharmacological agents that could be used to protect sensory hair cells …

Overexpression Of Human Fatty Acid Transport Protein 2/Very Long Chain Acyl-Coa Synthetase 1 (Fatp2/Acsvl1) Reveals Distinct Patterns Of Trafficking Of Exogenous Fatty Acids, Elaina M. Melton, Ronald Cerny, Concetta C. Dirusso, Paul N. Black

Ronald Cerny Publications

In mammals, the fatty acid transport proteins (FATP1 through FATP6) are members of a highly conserved family of proteins, which function in fatty acid transport proceeding through vectorial acylation and in the activation of very long chain fatty acids, branched chain fatty acids and secondary bile acids. FATP1, 2 and 4, for example directly function in fatty acid transport and very long chain fatty acids activation while FATP5 does not function in fatty acid transport but activates secondary bile acids. In the present work, we have used stable isotopically labeled fatty acids differing in carbon length and saturation in cells …

Interaction Of Pyrimoidiazolium Ions With Calf Thymus Dna, Stormy Rene Gibson

Theses, Dissertations and Capstones

A new class of fluorescent dyes, pyridoimidiazolium cations, is being considered for their possible use in the biochemical field because of their interactions with DNA. Binding of low molecular weight fluorophores has been proven to cause a wide variety of biological responses in DNA. The dyes used here have been synthesized using α-diimine type compounds. The reaction used has the capability to produce many fluorescent cations. Binding constants of these compounds in acetonitrile with calf thymus DNA have been determined by measuring emission intensity. Emission intensity showed the degree to which binding is occurring. The experimental results show that binding …

A Facile, Low-Cost Route For The Preparation Of Calcined Porous Calcite And Dolomite And Their Application As Heterogeneous Catalysts In Biodiesel Production, Rui Wang, Hu Li, Fei Chang, Jiafeng Luo, Milford A. Hanna, Daoyang Tan, Deyu Hu, Yuping Zhang, Baoan Song, Song Yang

Department of Chemistry: Faculty Publications

Despite their potential for biodiesel synthesis, directly calcined minerals rich in magnesium/calcium carbonates are used at the expense of large amounts of the catalyst, high alcohol loading, long processing times, and severe conditions. We report a facile and low-cost route for preparing calcined porous calcite (CPC) and dolomite (CPD) via simple thermal decomposition of the reaction mixtures of natural calcite and dolomite with stearic acid. CPC and CPD, both of which have porous structures, were compared with previously reported catalysts and examined as promising heterogeneous base catalysts under mild conditions. A 40% increase in conversion through CPC and CDC was …