Chemistry Commons^™

Methylation Markers In Hepatocellular Carcinoma, Avinash Gavicharla

ETD Archive

Hepatocellular Carcinoma is one of the major causes for mortality in the world and is usually asymptomatic until late stage decreasing the survival rate. There is an increase of incidence every year and current diagnostic and prognostic bio markers like AFP have their limitations in the wider context. Therefore, it is important to develop novel biomarkers. The aim of the Research is to understand the cytosine methylation and investigate the role of the p16 and SLIT-2 genes as biomarkers in Hepatocellular Carcinoma. The methylation profiles of the genes were assessed on bisulfite modified DNA samples with the aid of Real …

The Structural Requirements Of Histone Deacetylase (Hdac) Inhibitors: Suberoylanilide Hydroxamic Acid (Saha) Analogues Modified At C3, C6, And C7 Positions Enhance Selectivity, Sun Ea Choi

Wayne State University Dissertations

Histone deacetylase (HDAC) proteins are targets for drug design towards the treatment of cancers since overexpression of HDAC is linked to cancer. Several HDAC inhibitors, including the FDA approved drug suberoylanilide hydroxamic acid (SAHA, Vorinostat), have cleared clinical trials and emerged as anti-cancer drugs. However, SAHA inhibits all of the 11 metal ion-dependent HDAC proteins. Therefore, we synthesized several libraries of small molecule HDAC inhibitors based on SAHA to help understand the structural requirements of inhibitory potency and isoform selectivity.

In previous work, SAHA analogues functionalized at the C2 position (C2-SAHA analogues) near the metal binding hydroxamic acid displayed decreased …

Metal Chalcogenide Nanoparticle Gel Networks: Their Formation Mechanism And Application For Novel Material Generation And Heavy Metal Remediation Via Cation Exchange Reactions, Irina Ramona Pala

Wayne State University Dissertations

METAL CHALCOGENIDE NANOPARTICLE GEL NETWORKS: THEIR FROMATION MECHANISM AND APPLICATION FOR NOVEL MATERIAL GENERATION AND HEAVY METAL REMEDIATION VIA CATION EXCHANGE REACTIONS

by

IRINA R. PALA

February 2012

Advisor: Dr. Stephanie L. Brock

Major: Chemistry

Degree: Doctor of Philosophy

The dissertation research is focused on (1) uncovering the mechanism of metal chalcogenide nanoparticle gel formation; (2) extending the cation exchange reaction protocol to zinc sulfide gel networks, with the goal of accessing new aerogel chemistries and understanding the factors that drive the process; and (3) conducting a quantitative analysis of the ability of ZnS aerogels to remove heavy metal ions …

Synthesis, Spectroscopic, And Electrochemical Properties Of 3d Metal And Ruthenium Complexes With Phenolate And Catecholate Ligands, Frank Donald Lesh

Wayne State University Dissertations

The integration of amphiphilic properties into transition metal coordination systems is a pertinent step toward the development of candidate metallosurfactant precursors for the formation of responsive monolayer films. This concept is intended to preserve the solution-observed redox, spectroscopic, and magnetic responses onto solid surfaces for potential application. Selected metal ions and various ligand designs are investigated to address the effect of coordination and protonation preferences on amphiphilic behavior, the aspects of new modular approaches for Langmuir film precursors of differentiated topologies to extend amphiphilicity and redox behavior, and the introduction of photosensitizing properties into electroactive metallosurfactant precursors. In an attempt …

Probing The Dynamics Of Radical Reactions With Polyatomic Hydrocarbons By Crossed-Beam Dc Slice Imaging, Armando Dura Estillore

Wayne State University Dissertations

This work presents results of crossed molecular beam imaging studies on the reaction of radicals (Cl and CN) with polyatomic hydrocarbons of different functionalities such as pentane isomers, deuterated alkanes, alkenes, and alcohols. The reactively scattered alkyl radicals are probed as a function of collision energy using single photon ionization. The scattering results for pentane are quite similar for all reactants, suggesting that the nature of the abstraction site has surprisingly little influence on the dynamics studied at ~5 and ~9 kcal/mol. The angular distributions are broad with a backscattered peak at low collision energy and a sharp forward peak …

New Precursors And Chemistry For The Growth Of Transition Metal Films By Atomic Layer Deposition, Thomas Joseph Knisley

Wayne State University Dissertations

The advancing complexity of advanced microelectronic devices is placing rigorous demands on currently used PVD and CVD deposition techniques. The ALD deposition method is proposed to meet the film thickness and conformality constraints needed by the semiconductor industry in future manufacturing processes. Unfortunately, there is a limited number of chemical precursors available that have high thermal stability, reactivity, and vapor pressure suitable for ALD film growth to occur. These properties collectively contribute to the lack of suitable transition metal precursors available for use in ALD. In this thesis, we report the discovery of a series of novel transition metal diazadienate …

Genetic And Biochemical Studies Of Human Apobec Family Of Proteins, Priyanga Wijesinghe

Wayne State University Dissertations

The AID/APOBEC family of proteins in higher vertebrates converts cytosines in DNA or RNA into uracil. These proteins have essential roles in either innate immunity or adaptive immunity. Recently, AID has also been implicated in DNA demethylation in the context of early embryogenesis in mammals. This is partly based on the reported ability of AID to deaminate 5-methyl cytosine to thymine (5mC to T). I reexamined this proposed new role of AID (5mC deamination) with two members of the APOBEC family in a novel Escherichia coli based genetic system. My results confirmed that while all three enzymes are strong cytosine …

Synthesis And Characterization Of Size Controlled Transitionmetal Phosphide Nanoparticles And Their Hydrodesulfurization Catalytic Activity, Galbokka Hewage Layan Savithra

Wayne State University Dissertations

Transition metal phosphides are promising catalysts for hydrodesulfurization (HDS). The size-dependent catalytic activity of these metal phosphides for hydrodesulfurization (HDS) remains unstudied because the traditional temperature programmed reduction (TPR) method used in catalyst preparation results in highly polydisperse particles.

The main goals of this dissertation research are (1) synthesize metal phosphide nanoparticles (Ni²P, Rh²P, and Pd⁵P²) with control of size and morphology using a solution based arrested precipitation method; (2) develop large scale synthesis of mesoporous silica encapsulated nanoparticles (Ni²P and Pd⁵P²) with controlled loading to …

Synthesis And Á-Stereoselective Sialylation Of Kdn And Late Stage Modification Of Neuraminic Acid Sialosides, Chandra Sekhar Navuluri

Wayne State University Dissertations

ABSTRACT

SYNTHESIS AND á-STEREOSELECTIVE SIALYLATION OF KDN AND LATE STAGE MODIFICATIONS OF NEURAMINIC ACID SIALOSIDES

by

CHANDRA SEKHAR NAVULURI

December 2012

Advisor: Prof. David Crich

Major: Chemistry

Degree: Doctor of Philosophy

Keto deoxy nonulosonic acid has gained prominence in the recent years after the discovery of its presence in humans and the consequent appreciation of its role in human development and disease, and because of its potential as a marker of disease states. The development of efficient á-KDN sialylation methodology, an investigation of the mechanistic aspects of such sialylations, and the synthesis of this sparsely occurring sialic acid are the …

Synthesis And Characterization Of Group 5 Metal Complexes Containing Pyrazolate, Amidate, And Related Ligands As Potential Precursors For Thin Film Growth By Atomic Layer Deposition, Thuduwage Hiran Perera

Wayne State University Dissertations

Atomic Layer Deposition (ALD) is an advanced variant of Chemical Vapor Deposition (CVD) and is used to deposit smooth and conformal thin films for applications in the microelectronics industry. ALD requires metal precursors that are sufficiently volatile and thermally stable at elevated temperatures. Several group 5 ALD and CVD precursors were reported in the literature, which have been used to deposit TaN, NbN, Nb2O5, and Ta2O5 thin films. Synthesis of low and mid valent group 5 metal ALD precursors might give us access to deposit NbO2, Nb2O3, Ta2O3, and TaO2 thin films by low temperature ALD pathways upon applying mild …

Studies Toward The Total Synthesis Of Clavatadine A, Stephanie Conn

Undergraduate Honors Theses

Cardiovascular disease is a leading cause of death in humans. one cause of cardiovascular disease is excessive clot formation, or thrombosis. Although it can be fatal, thrombosis can be prevented or treated using inhibitors that target specific proteins in the blood coagulation pathway. Nevertheless, few targeted inhibitors of thrombosis have been reported. Clavatadine A is a specific and potent Factor XIa inhibitor (IC₅₀1.3uM) that was recently isolated from the Australian marine sponge Suberea clavata. Here, we report the completion of the synthesis for the synthetic stating materials, a dibrominated derivative of homogentisic acid lactone and an azidoiscyanate. We …

Characterization Of A Reductively-Activated Elimination Pathway Relevant To The Biological Chemistry Of The Kinamycins And Lomaiviticins, Seann P. Mulcahy, Christina M. Woo, Weidong Ding, George A. Ellestad, Seth B. Herzon

Chemistry & Biochemistry Faculty Publications

The lomaiviticins (1 and 2) and kinamycins (3–5) are bacterial metabolites with potent antimicrobial and antiproliferative activities. Herein we establish that 1–5 are capable of generating electrophilic acylfulvene intermediates (6) under mildly reducing conditions. These acylfulvenes 6 are formed by a multistep process comprising two-electron reduction and loss of dinitrogen to form an ortho-quinone methide, followed by elimination. Based on these studies, the structure of the product formed from 1 in DNA-cleavage assays is proposed (26). We also show that the bis(hydroxynaphthoquinone) substructures of the lomaiviticins activate the metabolites toward reduction. Finally, based on COMPARE and time-dependent cell response profiling …

Symmetry-Breaking Intramolecular Charge Transfer In The Excited State Of Meso-Linked Bodipy Dyads, Matthew T. Whited, Niral M. Patel, Sean T. Roberts, Kathryn Allen, Peter I. Djurovich, Stephen E. Bradforth, Mark E. Thompson

Chemistry Faculty Work

No abstract provided.

Trans-Acetyldicarbonyl(G5 -Cyclopentadienyl)(Methyldiphenylphosphane)- Molybdenum(Ii), Matthew T. Whited, Joseph W. Boerma, Michael J. Mcclellan, Christian E. Padilla, Daron E. Janzen

Chemistry Faculty Work

The title compound, [Mo(C5H5)(C2H3O)(C13H13P)(CO)2], was prepared by reaction of [Mo(CH3)(C5H5)(CO)3] with methyldiphenylphosphane. The MoII atom exhibits a fourlegged piano-stool coordination geometry with the acetyl and phosphane ligands trans to each other. There are several intermolecular C—HO hydrogen-bonding interactions involving carbonyl and acetyl O atoms as acceptors. A close nearly parallel – interaction between the cyclopentadienyl plane and the phenyl ring of the phosphane ligand is present, with an angle of 6.4 (1) between the two least-squares planes. The centroid-to-centroid distance between these groups is 3.772 (3) A˚ , and the closest distance between two atoms of these groups is 3.449 …

Histological Evaluation Of The Biocompatibility Of Polyurea Crosslinked Silica Aerogel Implants In A Rat Model: A Pilot Study, Firouzeh Sabri, J. D. Boughter Jr., D. Gerth, O. Skalli, T. C. N. Phung, G. R. M. Tamula, Nicholas Leventis

Chemistry Faculty Research & Creative Works

Background: Aerogels are a versatile group of nanostructured/nanoporous materials with physical and chemical properties that can be adjusted to suit the application of interest. In terms of biomedical applications, aerogels are particularly suitable for implants such as membranes, tissue growth scaffolds, and nerve regeneration and guidance inserts. The mesoporous nature of aerogels can also be used for diffusion based release of drugs that are loaded during the drying stage of the material. From the variety of aerogels polyurea crosslinked silica aerogels have the most potential for future biomedical applications and are explored here. Methodology: This study assessed the short and …

Development Of A Cargo Delivery System And Inhibition Studies Focused On Clostridium Difficile Toxin A, Stephanie Marie Kern

Wayne State University Dissertations

Virulence factors of pathogenic bacteria are to be blamed for life-threatening infections such as diphtheria, anthrax, botulism, and tentanus. In the case of enzymatic exotoxins, disease arises from cytotoxic proteins, and cytotoxicity is acheived only after cell entry. This intrinsic mechanism for cell entry is intriguing from research and medical views. Along with a review on existing cargo delivery systems utilizing protein toxins and the usefulness of such a system, here is described the first reported Clostridium difficile toxin A fusion protein, luciferase-TcdA, and evidence of the successful transport of an active enzyme, luciferase, into the cytosol of vero cells. …

Effects Of Carbon Chain Substituent On The P∙∙∙N Noncovalent Bond, U. Adhikari, Steve Scheiner

Chemistry and Biochemistry Faculty Publications

The effects of carbon chains placed on the electron-accepting P atom of a P⋯N bond are examined via ab initio calculations. Saturated alkyl groups have a mild weakening effect, regardless of chain length. In contrast, incorporation of double bonds into the chain strengthens the interaction, Ctriple bond; length of mdashC triple bonds even more so. These effects are only slightly enhanced by additional conjugated double bonds or an aromatic ring. Placing F atoms onto the carbon chains strengthens the P⋯N bond, but only by a small amount, which wanes as the F atom is displaced further from the P along …

Removal Of Uracil By Uracil Dna Glycosylase Limits Pemetrexed Cytotoxicity: Overriding The Limit With Methoxyamine To Inhibit Base Excision Repair, A. D. Bulgar, L. D. Weeks, Y. Miao, S. Yang, Yan Xu, C. Guo, S. Markowitz, N. Oleinick, S. L. Gerson, Lili Liu

Chemistry Faculty Publications

Uracil DNA glycosylase (UDG) specifically removes uracil bases from DNA, and its repair activity determines the sensitivity of the cell to anticancer agents that are capable of introducing uracil into DNA. In the present study, the participation of UDG in the response to pemetrexed-induced incorporation of uracil into DNA was studied using isogenic human tumor cell lines with or without UDG (UDG+/+/UDG−/−). UDG−/− cells were very sensitive to pemetrexed. Cell killing by pemetrexed was associated with genomic uracil accumulation, stalled DNA replication, and catastrophic DNA strand breaks. By contrast, UDG+/+ cells were >10 times more resistant to pemetrexed due to …

Early Lqt2 Nonsense Mutation Generates N-Terminally Truncated Herg Channels With Altered Gating Properties By The Reinitiation Of Translation, Matthew R. Stump, Qiuming Gong, Jonathan D. Packer, Zhengfeng Zhou

Faculty Publications - Department of Biological & Molecular Science

Mutations in the human ether-a-go-go-related gene (hERG) result in long QT syndrome type 2 (LQT2). The hERG gene encodes a K+ channel that contributes to the repolarization of the cardiac action potential. We have previously shown that hERG mRNA transcripts that contain premature termination codon mutations are rapidly degraded by nonsense-mediated mRNA decay (NMD). In this study, we identified a LQT2 nonsense mutation, Q81X, which escapes degradation by the reinitiation of translation and generates N-terminally truncated channels. RNA analysis of hERG minigenes revealed equivalent levels of wild-type and Q81X mRNA while the mRNA expressed from minigenes containing the LQT2 frameshift …

Isoform-Specific Dominant-Negative Effects Associated With Herg1 G628s Mutation In Long Qt Syndrome, Matthew R. Stump, Qiuming Gong, Zhengfeng Zhou

Faculty Publications - Department of Biological & Molecular Science

Background: Mutations in the human ether-a-go-go-related gene 1 (hERG1) cause type 2 long QT syndrome (LQT2). The hERG1 gene encodes a K+ channel with properties similar to the rapidly activating delayed rectifying K+ current in the heart. Several hERG1 isoforms with unique structural and functional properties have been identified. To date, the pathogenic mechanisms of LQT2 mutations have been predominantly described in the context of the hERG1a isoform. In the present study, we investigated the functional consequences of the LQT2 mutation G628S in the hERG1b and hERG1aUSO isoforms.

Methods: A double-stable, mammalian expression system was developed to characterize …

Electrolysis Of Coal And Carbon Slurry Suspensions, Moustafa Reda Aboushabana

Chemistry & Biochemistry Dissertations - Archive

In this dissertation study, different ranks of coal and carbons were tested as anode depolarizers in a three electrode electrochemical cell designed for hydrogen generation. The focus of this study was mainly Texas lignite coal (TXLC). For comparison purposes, other coals were carefully chosen to cover the range from high-rank, intermediate-rank, and to low-rank (TXLC). Carbon blacks and carbon nanotubes were also studied to gain more insight into the mechanistic aspects of the electrolysis process.The Fe3+/2+ redox couple was used as an oxidation mediator throughout the study. It shuttles the electrons between the coal or carbon particles and the anode …

Mixed Lineage Leukemia Histone Methylases In Hormonal Regulation Of Hox Genes And Their Disruption By Endocrine Disrupting Chemicals, Imran Hussain

Chemistry & Biochemistry Dissertations - Archive

Homeobox (HOX) genes are highly conserved family of genes that play vital roles during cell differentiation and embryogenesis. Of the 39 HOX genes present in human, HOXC6 is a critical players in mammary gland development, milk production and is over-expressed in breast and prostate cancer. I demonstrated that HOXC6 is transcriptionally regulated by estrogen (E2). The HOXC6 promoter contains two putative estrogen response elements (EREs). Promoter analysis using luciferase-based reporter assay demonstrated that both EREs are responsive to E2, ERE1_half being more responsive than ERE2_half. Estrogen receptors alpha and beta (ERα and ERβ) bind to these EREs …

Catalytic Hydro-Liquefaction Of Lignite Coals Under Mild Conditions, Mahir Alrashdan

Chemistry & Biochemistry Dissertations - Archive

A low-cost thermo-chemical process for the liquefaction of lignite coals is being developed at the University of Texas at Arlington (UTA). The coal-toliquids (CTL) project has focused of developing a liquefaction process which is made economically attractive by the combination of using a cheap coal feedstock, such as lignite, use of cheap disposable catalysts, and limiting the operating conditions to mild temperatures and pressures, at least relative to many existing CTL processes. The UTA-CTL process uses a solvent which is derived from the pyrolysis of lignite, an inexpensive iron-based catalyst and mild temperatures and pressures to hydrogenate and depolymerize the …

Increasing Lipophilicity Of Redox Active Ruthenium Complexes As A Means To Enhance Cytotoxicity And Reduce Animal Toxicity, Nagham Alatrash

Chemistry & Biochemistry Theses - Archive

The dinuclear and monomeric ruthenium(II) polypyridyl complexes [(phen)2Ru(tatpp)Ru(phen)2]Cl4 (P) and monomer [(phen)2Ru(tatpp)]Cl2 (MP) are promising candidates for anticancer drug development in terms of the observed anti-tumor activity in mouse models. These complexes contain the redox-active tatpp bridging ligand which seems to be the critical component for biological activity. Ruthenium complexes containing the tatpp ligand have been shown to cleave DNA with an inverse dependence on the [O2], exhibit selective and good cytotoxicity towards a number of cultured malignant cell lines, and have tolerable acute toxicity in mice. Significantly, the animal toxicity of P and MP is significantly less than simple …

Ruthenium(Ii) Polypyridyl Complexes As Potential Anticancer Drugs: Synthesis, Characterization, Cell Permeability And Investigation Of Their Hypoxia-Selectivity, Yanling Chen

Chemistry & Biochemistry Theses - Archive

Research on biological activity of ruthenium polypyridyl complexes (RPCs) continues to attract interest as these complexes have shown promising anti-cancer activity both in vitro and in vivo. The mononuclear RPC, [(phen)₂Ru(tatpp)]²⁺ (MP) and the related dinuclear complex [(phen)₂Ru(tatpp)Ru(phen)₂]⁴⁺ (P) have been shown to both intercalate with DNA and show potentiated DNA cleavage under anaerobic and reducing conditions¹ ² as well as show good selectivity and cytotoxicity towards malignant cell lines in vitro and tumors in vivo. Both complexes contain the redox-active tatpp ligand which is thought to be the essential component for the observed biological activity. This thesis is focused …

Applications Of Circular Dichroism (Cd) Spectroscopy As An Educational Tool For Undergraduate Students And Monitoring Protein Conformational Changes Induced By Ligand Binding, Catherine Ann Van Der Kar

Chemistry & Biochemistry Theses - Archive

The work reported here provides an overview on the applications of circular dichroism (CD) spectroscopy for the study of protein secondary structure. This project has two specific goals. First, to develop and validate an undergraduate experiment for CHEM 3175 (biophysical chemistry laboratory) to demonstrate the use of CD spectroscopy for the determination of protein secondary structure. In an extension of this work, the same principles of analysis were applied to the study and characterization of the protein-ligand interaction of MiaE (a non-heme iron hydroxylase) and its substrate, tRNA.

Towards The Synthesis Of (S)-(Acetamido9p-Tolyl)Methyl) Boronic Acid And Its Analogs As Precursors For Potential Boronated Hiv-1 Protease Inhibitors, Andrea Faulkner

Undergraduate Honors Theses

Currently more than 40 million people worldwide are suffering from HIV/AIDS. Despite the billions of dollars that have been put into research and development of HIV drugs, a cure has not been discovered. Protease inhibitors are a class of drugs that slow the progression of the disease. This research aims to create five boronated amino acid analogs that will be used in future synthesis of potential HIV-1 protease inhibitors. The purpose of including these amino acid analogs in potential inhibitors is to increase drug bioavailability by mimicking an amino acid structure. The amino acid analog also may help to create …

Plants Of The Western United States: Expanding The Collection And Biological Testing Of Extracts, Fernando N. Galvan

Undergraduate Honors Theses

The goal of this research was to find compounds with the potential for use as medicines. Many microorganisms use a mechanism known as active efflux to move antibiotics out of cells. As a result, the effectiveness of antibiotics may be partially or completely reduced allowing the pathogen to survive. A major theme of this research was to look for compounds in plants that inhibit active efflux processes and that are related to multi-drug resistance. After the diffusion of an antibiotic into a bacterial cell, an efflux pump inhibitor may prevent the antibiotic from being expelled from the organism, leading to …

Toward The Synthesis Of 5-Benzyl-3-Hydroxy-1,3-Azaborines As Potential Inhibitors Of Hiv-1 Protease, Julia Jennings

Undergraduate Honors Theses

Currently, approximately 33.3 million people are living with HIV/AIDS worldwide and each year an additional 2.1 million people become infected. The goal of this research is to develop 1,3-azaborines that could potentially inhibit HIV-1 protease. HIV-1 protease is an enzyme involved in the protein processing step of the replication cycle. By inhibiting HIV-1 protease, the drug would slow the progression of HIV into AIDS. The target compounds are expected to have both competitive and associative inhibition and may inhibit mutated HIV viruses as well. To synthesize these compounds, boronic acids were coupled with a chiral directing/protecting group. A homologation was …

Study Of The Gelling Process In The La-Co-Citric Acid System, Luminita Predoana, Andrei Jitianu, Barbara Malic, Maria Zaharescu

Publications and Research

The gelling process in the aqueous lanthanum-cobalt-citric acid system was studied using UV-VIS and IR spectroscopic methods, as well as viscosity measurements, to establish the gelling mechanism of transition metal ions (La3+ and Co2+) in the presence of chelating agent. Lanthanum and cobalt nitrates and lanthanum and cobalt acetates, respectively, were used as starting reagents, and the citric acid was used as chelating agent. The gelation process was investigated at room temperature and at 80°C. At elevated temperature, the gels were obtained after 30 h, whereas at room temperature, these were obtained in 1 month. Complex gels were formed for …