Chemistry Commons^™

Synthesis And Characterization Of New Gd3+-Containing Complexes As Potential Targeted Contrast Agents For Magnetic Resonance Imaging, Sashiprabha Manjari Vithanarachchi

Wayne State University Dissertations

The focus of the research described in this thesis is the study of chemistry relevant to target-specific contrast agents for magnetic resonance imaging (MRI). MRI is a widely used technique in diagnostic medicine and biomedical research to obtain anatomical and physiological details of soft tissues. Contrast agents are used to enhance the contrast of MR images by causing changes to the chemical environment of water molecules. Clinically approved GdIII-containing contrast agents for MRI are non-specific, and consequently, have limited utility. Target-specific contrast agents represent one way to circumvent this limitation. In the research described in this thesis, myelin and Β-amyloid …

Hiv-1 Rna Dimerization At Single Molecule Level, Hansini R. Mundigala

Wayne State University Dissertations

The Dimerization Initiation Sequence (DIS) is a conserved hairpin-loop motif on the 5' UTR of the HIV-1 genome. It plays an important role in genome dimerization through formation of a "kissing complex" intermediate between two homologous DIS sequences. This bimolecular kissing complex ultimately leads to the formation of an extended RNA duplex. Understanding the kinetics of this interaction is key to exploiting DIS as a possible drug target against HIV. We wish to report a novel study that makes an important contribution to understanding the dimerization mechanism of HIV-1 RNA in vitro. Our work has employed single-molecule fluorescence resonance energy …

Experimental And Theoretical Studies Of Binding Interactions In Divalent Transition Metal Cation-N-Donor Ligand Complexes: Structures, Sequential Bond Dissociation Energies, Mechanisms And Energetics Of Collision-Induced Dissociation, Holliness Nose

Wayne State University Dissertations

The thesis research described here involves a series of experiments that have been designed to probe the influence of the electronic structure of the metal cation, the nature and number of ligands, as well as the effects of chelation and steric interactions on the geometry and binding strength of transition metal cation-ligand complexes. The experimental studies make use of energy-resolved collision-induced dissociation (CID) techniques that are carried out in a custom-built guided ion beam tandem mass spectrometer (GIBMS) to probe the structures, energetics, and fragmentation behavior of the complexes of interest. Electronic structure theory calculations including several density functional theory …

Evaluation Of Presynaptic Dopamine Dynamics After: Toluene Inhalation Or Trkb Receptor Activation, Aaron Kwaku Apawu

Wayne State University Dissertations

Dopamine (DA) neurons in the striatum mediate several functions of the brain and have been linked to a host of neurological disorders including Parkinson's disease and addiction, both of which occur as a result of dysfunction in the DA system. In the present study, our first objective was to understand how the striatal DA system adapts to acute and repeated administration of inhalant toluene. The use of toluene as inhalant, like other drugs of abuse, is known to perturb DA neurotransmission in the brain reward pathway. However, the exact mechanism underling toluene's influence on striatal DA neurotransmission is unknown. The …

Alterations In The Mouse Striatum Following Acute And Repeated Ethanol Exposure, Brooke D. Newman

Wayne State University Dissertations

Brain-derived neurotrophic factor (BDNF) is an important neuromodulator that has implicated in regard to several neurological disorders, including alcohol addiction. BDNF is also an important modulator of dopamine (DA), a neurotransmitter that is heavily implicated in addiction with one of the DA rich brain regions being referred to as the reward center of the brain. One of the focuses in alcohol dependence research includes determining risk factors that make an individual more susceptible to becoming dependent. BDNF has been of interest as a risk factor due to its involvement in ethanol consumption and addiction evidenced in a vast number of …

Investigation Into The Binding Interactions Of Klenow Fragment To Dna Modified With Carcinogens Af And Aaf Using Surface Plasmon Resonance, Ashley M. Floyd

Wayne State University Dissertations

The two major forms of DNA adducts from the carcinogen N-acetoxyacetyl-2-aminofluorene, N-(deoxygunanonsin-8-yl)-2-acetylaminofluorene (dG-C8-AAF) and N-(deoxyguanosin-8-yl)-2-aminofluorene (dG-C8-AF), are both known to impede replication, though in different ways. AAF is a strong block to replication leading to frameshift mutations, while the AF adduct is more easily bypassed, causing base substitutions. Surface plasmon resonance (SPR) was used to study the binding of exonuclease deficient E. coli polymerase I, Klenow fragment (KF), to DNA modified with AF or AAF at two locations: as a templating base or in the last formed base pair. KF binding to the modified DNA bases was also monitored to …

Development Of Elisa-Based Hdac Activity Assay For Identification Of Isoform Selective Hdac Inhibitors, Geetha Padige

Wayne State University Dissertations

Cancers are one of the leading causes of death in United States, effecting roughly 20% of the population. To develop effective anti-cancer agents, vast research is in progress that targets various factors leading to cancer. One such area of cancer research is developing drugs that inhibit histone deacetylase (HDAC) proteins. HDACs are histone modifying enzymes that regulate transcription of genes. Aberrant recruitment of HDACs to the transcription factors leads to tumor onset and growth. Because of their potential anti-cancer therapeutic interest, several HDAC inhibitors are in various stages of clinical trials. SAHA and Romidepsin are FDA-approved drugs for the treatment …

Lanthanide-Based Precatalysts For Carbon-Carbon Bond-Forming Reactions In Aqueous Media, Derek James Averill

Wayne State University Dissertations

The formation of carbon-carbon bonds is of great interest to synthetic chemists because these bonds make up the majority of biologically active compounds. The Mukaiyama aldol reaction is a Lewis-acid-catalyzed carbon-carbon bond-forming reaction that has the ability to produce optically active β-hydroxy carbonyls which can be found in many pharmaceuticals and natural products. Because of precatalyst instability towards hydrolysis, anhydrous solvents are commonly used. Recent efforts have focused on water-tolerant versions of enantioselective Mukaiyama aldol reactions because of the financial and environmental benefits of using aqueous media. Consequently, the Lewis-acidic and water-tolerant features of Ln³⁺ ions have aroused great …

Probing Proteasome Inhibition By Metal Copmplexes As A New Route For Anticancer Therapy, Dajena Tomco

Wayne State University Dissertations

The scope of this thesis is focused towards the development of metal-containing coordination compounds as potential therapeutic agents. Efforts of this research involve the design, synthesis, and purification of these complexes, as well as their evaluation by spectroscopic, spectrometric, and electrochemical characterization. The antineoplastic properties of these metal-containing pro-drugs are tested against the inhibition activity of the 26S proteasome. Selected metal ions ranging from transition to main group elements have been incorporated in various ligand systems containing phenolate and pyridyl donor sets. The mechanistic behavior of these complexes in solution has been thoroughly investigated along with their in vitro anticancer …

Theoretical And Experimental Studies Of Noncovalent Metal Cation Binding And Base Pairing Interactions Of Cytosine And Modified Cytosines, Bo Yang

Wayne State University Dissertations

ABSTRACT

THEORETICAL AND EXPERIMENTAL STUDIES OF NONCOVALENT METAL CATION BINDING AND BASE PARING INTERACTIONS OF CYTOSINE AND MODIFIED CYTOSINES

by

BO YANG

December 2014

Advisor: Professor Mary T. Rodgers

Major: Analytical Chemistry

Degree: Doctor of Philosophy

Binding of metal cations to the nucleobases can lead to formation of rare tautomers of the nucleobases. The infrared multiple photon dissociation (IRMPD) action spectroscopy of five alkali metal cation-cytosine complexes, M⁺(cytosine), where M⁺ = Li⁺, Na⁺, K⁺, Rb⁺, and Cs⁺, are examined using a Fourier transform ion cyclotron resonance mass …

Synthesis And Characterization Of Discrete Fexni2-Xp Nanoparticles; Assembly Of Phosphide Nanoparticles Into Porous Networks, Asha Hitihami Mudiyanselage

Wayne State University Dissertations

This dissertation research is focused on synthesis, characterization and assembly of metal phosphide nanoparticles of relevance to catalysis, magnetism, and optoelectronic applications. These include (1) synthesis of discrete FexNi2-xP ternary nanocrystals of relevance to hydrodesulfurization (HDS) catalysis and magnetism, and (2) 3-dimensional nanostructures (gels and aerogels) of InP and Ni2P.

A three-step solution-phase arrested precipitation method was employed for bimetallic nanocrystal synthesis. The synthesis of nanocrystals involves preparation of amorphous NixPy amorphous particles, introduction of the Fe precursor to form amorphous Fe-Ni-P particles, and high temperature conversion of Fe-Ni-P particles into crystalline ternary phosphide nanocrystals. Ternary FexNi2-xP nanocrystals crystalize in …

Characterization Of Initial Iron Binding Location And The Structure/Iron Binding Site On S.Cerevisiae Isu And On D.Melanogaster Frataxin, Andria V. Rodrigues

Wayne State University Dissertations

Iron-induced free radical damage has been implicated in the pathology of diseases of iron overload such as Friedreich's Ataxia, a genetic disorder characterized by an accumulation of iron in actively metabolizing tissues ultimately leading to cardio- and neuro- degeneration and cell death. It is caused by an inability to synthesize the mitochondrial protein, frataxin. Frataxin has been shown by numerous groups to be a part of the iron-sulfur cluster (ISC) multicomplex, where it functions in the capacity of a potential iron provider and an allosteric modulator of both the cysteine desulfurase and scaffold protein ISU. My research has been focused …

Structural And Functional Characterization Of Proteins Of Unknown Function (Hp0495, Hp0100 And Hp1259) In Helicobacter Pylori, Shirin Fatma

Wayne State University Dissertations

H. pylori is missing the glutaminyl- and asparaginyl-tRNA synthetases (GlnRS and AsnRS, respectively). Consequently, H. pylori uses an indirect aminoacylation pathway to generate Gln-tRNAGln and Asn-tRNAAsn. Within this process, Asn-tRNAAsn is produced by misacylation of tRNAAsn with aspartate by a non-discriminating aspartyl-tRNA synthetase (ND-AspRS). Next, the heterotrimeric, glutamine-dependent amidotransferase (called AdT or GatCAB) converts the misacylated Asp-tRNAAsn into Asn-tRNAAsn. A parallel pathway exists for the synthesis of Gln-tRNAGln, wherein misacylation of tRNAGln with glutamate is catalyzed by a tRNAGln-specific glutamyl-tRNA synthetase (GluRS2) to generate Glu-tRNAGln; this misacylated intermediate is converted to Gln-tRNAGln by the same AdT. This dependence on misacylated …

Precursors And Processes For The Growth Of Metallic First Row Transition Metal Films By Atomic Layer Deposition, Lakmal Charidu Kalutarage

Wayne State University Dissertations

As a result of the continuous miniaturization of microelectronics devices, atomic layer deposition (ALD) has gained much attention in the recent years. ALD allows the deposition of ultra-thin conformal films with accurate thickness control due to the self-limiting growth mechanism. The microelectronics industry requires the growth of metallic first row transition metal films by ALD. Due to the positive electrochemical potentials, the ALD growth of noble metal thin films has been well developed in the past. By contrast, the ALD growth of first row transition metal films remains poorly documented. The reasons for this scarcity include the lack of suitable …

Modulation Of Water-Exchange Rates Of Lanthanide(Iii)-Containing Complexes Using Polyethylene Glycol, Buddhima Nirodhi Siriwardena-Mahanama

Wayne State University Dissertations

MODULATION OF WATER-EXCHANGE RATES OF LANTHANIDE(III)-CONTAINING COMPLEXES USING POLYETHYLENE GLYCOL

by

BUDDHIMA N. SIRIWARDENA-MAHANAMA

May 2014

Advisor: Dr. Matthew J. Allen

Major: Chemistry

Degree: Doctor of Philosophy

A modular system of lanthanide(III)-containing polyethylene glycol (PEG) conjugates was synthesized and characterized to investigate the influence of length and density of PEG on water-exchange rates of lanthanide(III)-containing complexes. The water-exchange rates of lanthanide(III)-containing complexes contribute to the efficiency of these complexes as T₁-shortening and paramagnetic chemical exchange saturation transfer (PARACEST) contrast agents for magnetic resonance imaging (MRI). Because the mechanism of these two MRI methods is vastly different, there is …

Assembly And Function Of Macromolecular Complexes For Accurate Trna Aminoacylation In Helicobacter Pylori, Gayathri Niroshani Silva

Wayne State University Dissertations

ABSTRACT

ASSEMBLY AND FUNCTION OF MACROMOLECULAR COMPLEXES FOR ACCURATE TRNA AMINOACYLATION IN HELICOBACTER PYLORI

by

GAYATHRI SILVA

January 2014

Advisor: Dr. Tamara L. Hendrickson

Major: Chemistry (Biochemistry)

Degree: Doctor of Philosophy

Abstract

The aminoacylation of tRNA is a critical step in maintaining the accuracy of the genetic code. Many microorganisms are missing one or more aminoacyl tRNA synthetases (aaRSs) and rely on indirect pathways to produce certain aa–tRNAs. In Helicobacter pylori (H. pylori), the genes encoding both asparaginyl tRNA synthetase (AsnRS) and glutaminyl tRNA synthetase (GlnRS) are missing and the organism consequently relies on the indirect pathway for …

Redox-Active Trivalent Metallosurfactants With Low Global Symmetry For Molecule-Based Electronics: Spectroscopic, Electrochemical, And Amphiphilic Properties Of New Molecular Materials For Current-Voltage Measurements In M|Lb-Monolayer|M Devices, Lanka Dilruksi Wickramasinghe Wickramasinghe Arachchilage

Wayne State University Dissertations

LANKA D. W. WICKRAMASINGHE ARACHCHILAGE

August 2014

Advisor: Professor Cláudio N. Verani

Major: Chemistry (Inorganic)

Degree: Doctor of Philosophy

The silicon-based microelectronic industry has made remarkable technological advancements. Among these, new generation consumer electronics, telecommunication devices, and high performance data processing smart devices are of special interest. At present, electronic components existing on a single silicon chip grow rapidly, and soon the miniaturization process of electrical components will face limitations due to heat dissipation. Therefore, as an advanced alternative for silicon-based electronic components, the investigation of nanoscale molecular electronic devices is of great importance. This dissertation research is focused on …

Computational Studies Of Enzymatic Reactions And Inorganic Compounds, Dong Fang

Wayne State University Dissertations

Quantum mechanics (QM) calculations have been demonstrated to give very accurate results in studying a variety of chemical reactions. However, the current computing resources limits its use in large-size systems such as enzymes. Compared to QM, Molecular Mechanics (MM) have an advantage in computing time but disadvantage in accuracy, and MM cannot be used in reactions involving bonding forming and breaking. To combine the advantages of these two types of methods, QM/MM has been introduced to study reactions and processes in large-size systems, and it has been proven to give accurate results with moderate computational expense. When studying enzymatic reactions, …

New Carbohydrate-Based Anti-Cancer And Anti-Bacterial Vaccines, Zhifang Zhou

Wayne State University Dissertations

The unique carbohydrates expressed on the surface of cancer, bacterial, viral and fungal cells are excellent target antigens for the design of therapeutic or preventive vaccines. However, as antigens carbohydrates have problems. First, carbohydrates usually have low immunogenicity. Second, even if immunogenic, carbohydrates typically elicit T cell-independent immune responses. To overcome these problems and design useful vaccines based on carbohydrate antigens, they are usually coupled with carrier proteins to form conjugates to enhance the immunogenicity of the antigens. However, there are still some issues existing in glycoprotein vaccines, such as poor reproducibility of the conjugates, difficulties in quality control and …

Rydberg Time-Of-Flight And Imaging Probes Of The Velocity-Dependent Hydrogen Atom Spin Polarization, Bernadette Michlewicz Broderick

Wayne State University Dissertations

Insights into electron spin and nuclei are central to the field of chemical reaction dynamics. Of particular note is the study of spin-polarized hydrogen (SPH) atoms, which result from photodissociation of molecules. Examination of the detailed H-atom spin polarization is achieved by determining the projection of the electron spin onto the probe laser direction. In doing so, its angular distribution, complex dissociation pathways, and coherent excitation mechanisms may be revealed. Approaches to detect SPH atoms are experimentally challenging due to the difficulty associated with probing ground-state H atoms through isolated fine structure levels, which is the only direct way to …