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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 …

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 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.

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 …

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 …

The Behavior Of Cerium Oxide Nanoparticles In Polymer Electrolyte Membranes In Ex-Situ And In-Situ Fuel Cell Durability Tests, Benjamin Pearman

Electronic Theses and Dissertations

Fuel cells are known for their high efficiency and have the potential to become a major technology for producing clean energy, especially when the fuel, e.g. hydrogen, is produced from renewable energy sources such as wind or solar. Currently, the two main obstacles to wide-spread commercialization are their high cost and the short operational lifetime of certain components. Polymer electrolyte membrane (PEM) fuel cells have been a focus of attention in recent years, due to their use of hydrogen as a fuel, their comparatively low operating temperature and flexibility for use in both stationary and portable (automotive) applications. Perfluorosulfonic acid …

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 …

Exploring Conformational Variability Of An Rna Domain In The Ribosome: From Structure And Function To Potential Antibiotic Targeting, Yogo Sakakibara

Wayne State University Dissertations

RNA in nature is modified at many specific sites to order to gain extra functions or to expand the genetic code. One of such RNAs is ribosomal RNA (rRNA), which contains several modified bases, particularly around the functionally significant sites. We have focused on understanding the influences of modified base on RNA structure and function by employing helix 69 (H69), which is a good region to evaluate the roles of modified bases since it contains three pseudouridines in the loop region and exists at the core of the ribosome.

Previous model studies using small hairpin H69 showed the conformational differences …

Analysis Of Illicit Drugs, Their Metabolites And Other Micropollutants In Water By Liquid Chromatography Tandem Mass Spectrometry, Deepika P. Panawennage

Dissertations

The goal of this project is to develop liquid chromatography tandem mass spectrometry (LC/MS/MS) methods for the analysis of different, novel micropollutants in waste water and natural water. Micropollutants are compounds that can exert adverse environmental and human health effects at low concentrations. Most of these compounds include personal care products and pharmaceuticals, such as antibiotics and controlled substances. In the first part of this study, we focused in the analysis of illicit drugs and drug metabolites because these analyses have the potential to serve as markers of drug abuse. We have detected over sixteen different illicit drugs and their …

Profiles In Science: John Bennett Fenn, Kimberly Brady, Roy Brown, Emily Johnson, Shannon D. Jones, Margaret Henderson, Dana Ladd, Irene Lubker, Jennifer A. Mcdaniel

VCU Libraries Faculty and Staff Publications

“Don’t ever try to be a scientist or engineer!” Had John Bennett Fenn listened to this advice given by his ninth grade teacher, he might not have gone on to pursue a career in analytical chemistry which would culminate in the attainment of the Nobel Prize in 2002. Gathered from interviews, publication analyses, glowing tributes, and his reminiscences, this paper outlines the academic and professional life of John Fenn from childhood through the end of his career in 2010.

Molecular Engineered Myoglobin With Unnatural Amino Acids As A Peroxidase, Kananke Sriyani Liyanage

Chemistry & Biochemistry Theses - Archive

Myoglobin (Mb) has been used as a model system to mimic other biologically important heme proteins like cytochrome P450 due to its ability to prepare mixed ligand complexes with different valencies, such as ferric, ferrous and ferryl species. It has been engineered to perform peroxidase, peroxygenase, monooxygenase and catalase activities. However, previous work on this area has shown that the distal histidine (H64) in the active of wild-type Mb is a critical residue, which destabilizes compound I, the reactive intermediate of the catalytic cycle (a ferryl ð-porphyrin radical cation). Therefore in this study we replaced H64 with a smaller residue, …

Pegylated Silicon Nanowire Coated Silica Microparticles For Drug Delivery Across Intestinal Epithelium, Vuk Uskoković, Phin-Peng Lee, Laura Walsh, Kathleen Fischer, Tejal Dasai

Pharmacy Faculty Articles and Research

Composite particles made by growing nanoscopic silicon wires from the surface of monodispersed, microsized silica beads were tested in this study for their ability to affect the integrity and permeability of an epithelial cell layer. Polyethylene glycol (PEG) is known to sterically stabilize particles and prevent protein binding; as such, it is a routine way to impart in vivo longevity to drug carriers. The effect of the silica beads, both with and without silicon nanowires and PEG, on the disruption of the tight junctions in Caco-2 cells was evaluated by means of: (a) analysis of the localization of zonula occludens-1 …

Understanding Fracture, Allison Marsh

Section 3: Imaging the Fast Moving

No abstract provided.

Wall_1.6 — Acknowledgements, Allison Marsh

Section 1: Introduction

No abstract provided.

Design, Synthesis, And Biological Evaluation Of Novel Polyamine Transport System Probes And Their Application To Human Cancers, Aaron Muth

Electronic Theses and Dissertations

The mammalian polyamine transport system (PTS) has been of interest due to its roles in cancer and maintaining cellular homeostasis. Polyamines are essential growth factors which are tightly controlled via a balance of biosynthesis, metabolism, import, and export. This work focused on the development and biological testing of polyamine transport probes to help understand the molecular requirements of the PTS. This was mediated through the use of a CHO (PTS active) and CHO-MG* (PTS deficient) screen, where compounds demonstrating high toxicity in CHO and low toxicity in CHO-MG* were considered PTS selective. The first chapter focused on the development of …

Use Of An Activated Magnesium/Cosolvent System For The Desorption And Degradation Of Polycyclic Aromatic Hydrocarbons And Their Oxygenated Derivatives In Contaminated Soils, Marc Elie

Electronic Theses and Dissertations

The contamination of soils, with polycyclic aromatic hydrocarbons (PAHs), remains a widespread environmental concern. In the past two decades, many physical, chemical and biological methods have been developed and evaluated for the degradation of PAHs. However, due to their low aqueous solubility, high sorption affinity, hydrophobicity and recalcitrance, the environmental remediation of PAHs in soil continues to be economically challenging. In addition to PAH contamination, the presence of oxygenated derivatives of PAHs (OPAHs), in soils, has increasingly become a concern due to their greater toxic properties compared to parent PAH compounds. To date, no investigations on OPAH-remediation methods have been …

New Bonded Phase Materials For Separtions, Sirantha Perera

Chemistry & Biochemistry Dissertations - Archive

Separations play an important role in day to day life as well as in science and technology. This dissertation focuses on novel and versatile techniques involving synthesizing new bonded chiral stationary phases (CSPs) and using existing CSPs for the separation of target chiral analytes in HPLC. It also includes development of new ionic liquid (IL) based silica bonded polymeric coatings for solid phase microextraction gas chromatography (SPME-GC) in headspace and direct immersion for polar analytes and finally, coupling new MALDI matrix bonded SPME fibers and laser desorption for rapid identification of biological materials. Enantiomerically pure Ru complexes were introduced as …

Development Of Mass Spectrometric Methods For The Analysis Of Serotonin And Related Compounds In Biological Matrices, Merisa Moriarty

Theses

Serotonin is a major neurotransmitter in the brain and affects various functions both in the brain and in the rest of the body. It has been linked to depression, migraines, and aggression, as well as many psychiatric disorders including schizophrenia, dementia and anorexia nervosa. It also has been associated with conditions like Alzheimer’s disease along with other neurotransmitters such as dopamine.

The aim of this research project is to develop various mass spectrometric methods for the analysis of serotonin, dopamine and similar indoles in both urine and serum matrices. This thesis provides extensive reviews detailing a general overview of serotonin …