Chemistry Commons^™

Studies Toward A Detailed Understanding Of The Intrinsic Properties Of Nucleic Acid Constituents: Gas-Phase Conformations, Energetics, And Glycosidic Bond Stability, Ranran Wu

Wayne State University Dissertations

The gas-phase conformations of the protonated forms of the nucleic acid constituents: nucleosides and mononucleotides, were characterized by infrared multiple photon dissociation (IRMPD) action spectroscopy and theoretical calculations. The IRMPD spectroscopy experiments were performed using a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) coupled to a free electron laser or a OPO/OPA laser system to measure the IRMPD action spectra over the IR fingerprint and hydrogen-stretching regions.

Theoretical calculations were performed using both mechanic dynamics and high level quantum chemical calculations to optimize structures, compute vibrational frequencies and IR intensities, and to obtain the relative stabilities of optimized …

Europium(Ii)-Containing Complexes For Responsive Magnetic Resonance Imaging, Levi Alexander Ekanger

Wayne State University Dissertations

The research projects described in this dissertation are focused on studying the oxidation of EuII-containing complexes within the context of responsive MRI. Prior to this research, EuII had not been explored within the context of oxidation-responsive MRI nor had the use of this ion been reported in vivo. The results of these studies enable predictions about the oxidation-responsive behavior of EuII-containing complexes in vitro and in vivo.

The EuII-containing cryptate 1.33 was used to evaluate EuII-based positive contrast enhancement after intravenous, intraperitoneal, and subcutaneous injections. The transitory behavior of the positive contrast enhancement correlated with reported levels of oxygenation and …

Crossed Beam Imaging Of The Reaction Dynamics Of Halogen Atoms With Selected Hydrocarbons, Yuanyuan Shi

Wayne State University Dissertations

This dissertation presents results of applying dc slice imaging in crossed molecular beams to probe the dynamics of the reactions of halogen atoms (chlorine and fluorine) with polyatomic hydrocarbons and alcohols such as deuterated propanes, butane isomers, pentane, alkenes and propanol. The full velocity-flux contour maps of the radical products were measured with 157nm single photon ionization at various collision eneriges. Secondary and tertiary abstractions were found in Cl with normal and deuterated propanes and butane isomers and show distinct differences. The differences were explained in terms of the nature of abstraction sites, energy disposal of the radical product, and …

Synthesis And Characterization Of Transition Metal Phosphide Nanoparticles For Catalytic Applications: Model Catalysts For Hydrodesulfurization And Electrocatalysts For The Oxygen Evolution Reaction, Don Malinda Ruchira Liyanage

Wayne State University Dissertations

Transition metal phosphides are emerging as efficient catalysts for different processes. Although binary phases have been extensively studied recently researchers have explored the synergism afforded by bimetallic ternary transition metal phosphides. The conventional catalyst preparation methods (temperature programmed reduction or solvothermal synthesis) yield inhomogeneous samples, preventing a detailed understanding of how active site density impacts catalytic activity and mechanism. In contrast, solution-phase arrested-precipitation reactions produce uniform nanoparticles with an excellent control on size, morphology and composition.

This dissertation describes the synthesis of ternary transition metal phosphide nanoparticles (Ni2-xCoxP and Ni2-xRuxP) by solution-phase arrested-precipitation reactions and evaluation of their composition-dependent catalytic …

Synthesis, Characterization, And Properties Of Peroxo-Based Oxygen-Rich Compounds For Potential Use As Greener High Energy Density Materials, Nipuni-Dhanesha Horadugoda Gamage

Wayne State University Dissertations

One main aspect of high energy density material (HEDM) design is to obtain greener alternatives for HEDMs that produce toxic byproducts. Primary explosives lead azide, lead styphnate, and mercury fulminate contain heavy metals that cause heavy metal poisoning. Leaching of the widely used tertiary explosive NH4ClO4 into groundwater has resulted in human exposure to ClO4– ions, which cause disruptions of thyroid related metabolic pathways and even thyroid cancer. Many research efforts to find replacements have gained little success. Thus, there is a need for greener HEDMs. Peroxo-based oxygen-rich compounds are proposed as a potential new class of greener HEDMs due …

Synthesis And Biological Evaluation Of Nitrile-Based Inhibitors Of Cysteine Proteases Caged With Ruthenium Complexes, Rajgopal Sharma

Wayne State University Dissertations

Light activated compounds can be used as tools for understanding and solving numerous biological problems. This dissertation focuses on developing ruthenium-based photocages for caging nitrile-based cysteine protease inhibitors. Four research areas pertaining to this dissertation, i) metals in medicine, ii) photocages in biological applications, iii) photodynamic therapy and iv) cysteine cathepsin proteases were briefly surveyed in the introductory chapter. Next, RuII(bpy)2 group was utilized for synthesizing nitrile-based caged CTSK and CTSB inhibitors. Light activated release of inhibitors, followed by toxicity and stability data were studied. Cathepsin enzyme activity inhibition in 2D and 3D assays were established. This work showcased the …

On The Nature Of Excited States In Ruthenium Complexes: Towards Renewable Energy, Ryan A. Thomas

Wayne State University Dissertations

The 77 K radiative properties (spectra, quantum yields and lifetimes) of ruthenium-polypyridyl complexes are investigated to better understand the effects of electronic mixing on metal-to-ligand-charge-transfer (3MLCT) excited state properties and how metal-centered (3MC) excited states affect the properties of potential ruthenium photosensitizers.The radiative rate of relaxation (kRAD) determines the maximum possible excited state lifetime when all other relaxation pathways are blocked (kn = 0 for all n  RAD). Thus, the excited state will relax only by means of an emission characteristic of the polypyridyl chromophore. kRAD is expected to increase as the excited state energy increases while the value …

Development Of New Algorithms For Exploring The Potential Energy Landscape Of Chemical Reactions, Adam Benjamin Birkholz

Wayne State University Dissertations

The research presented in this dissertation is divided into 5 chapters. In Chapter 2, a method for reducing the number of coordinates required to accurately reproduce a known chemical reaction pathway by applying principal component analysis to a number of geometries along the pathway (expressed in either Cartesian coordinates or redundant internal coordinates) is described and applied to 9 example reactions. Chapter 3 introduces new methods for estimating the structure of and optimizing transition states by utilizing information about the atomic bonding in the reactants and products. These methods are then benchmarked against a standard transition state optimization approach utilizing …

Noncovalent Interactions Between Alkali Metal Cation And Aza/Thia-Crown Macrocycles: Mass Spectrometric Techniques And Theoretical Studies, Calvin A. Austin

Wayne State University Dissertations

Macrocyclic complexes have been useful in understanding many systems encountered in biology, along with having widespread use in analytical, pharmaceutical, and synthetic chemistry. My goal was to provide a quantitative experimental and theoretical description of cation-aza-crown and thia-crown ether interactions with alkali metal cations. Infrared multiple photon dissociation (IRMPD) action spectroscopy and energy-resolved collision-induced dissociation (CID) techniques were used in conjunction with theoretical electronic structure calculations to characterize the structures, binding interactions, and stability of cation-aza-crown ether interactions. Quantum chemical calculations at several levels of theory were employed to characterize the structures and stabilities of the isolated cations and aza-crown …

Biological Evaluation Of The Vaccine Candidate Tf-Ps A1 And A One-Pot Multicomponent Coupling/Cyclization For Natural Product Herbicide (±)-Thaxtomin A, Jean Paul Bourgault

Wayne State University Dissertations

ABSTRACT

BIOLOGICAL EVALUATION OF THE VACCINE CANDIDATE TF-PS A1 AND A ONE-POT MULTICOMPONENT COUPLING/CYCLIZATION FOR NATURAL PRODUCT HERBICIDE (±)-THAXTOMIN A

By

JEAN PAUL BOURGAULT

August 2015

Advisor: Prof. Peter R. Andreana

Major: Chemistry (Organic)

Degree: Doctor of Philosophy

The -aminooxy derivative of the Thomsen–Friedenreich tumor associated carbohydrate antigen has been synthesized in 11 steps utilizing a D-GalN3 acceptor carrying a pre-installed -N-hydroxysuccinimidyl moiety. The natural  linkage was prepared in high selectivity employing a suitably protected D-GalN3-thioglycoside donor with N-hydroxysuccinimide. With access to -TF-ONH2, the preparation of the TF-PS A1 vaccine candidate ensued smoothly through oxime bond formation. This construct …

Development Of Inlet And Vacuum Ionization Methods For Characterization Of Biological Materials By Mass Spectrometry, Beixi Wang

Wayne State University Dissertations

Inlet ionization and vacuum ionization are novel ionization methods to produce electrospray ionization (ESI)-like ions from the solid or liquid states, operating from atmospheric pressure (AP) or vacuum, without the use of voltage or the necessity of high energy input such as a laser or particle beam. The fundamental aspects were probed for better understanding of the novel ionization processes. Initial applications were attempted to utilize the novel ionization methods for fast, robust, and quantitative analyses.

For inlet ionizations (laserspray ionization inlet, LSII; matrix assisted ionization inlet, MAII; and solvent assisted ionization inlet, SAII), small (e.g. drugs) to large (e.g. …

(I)Chromatographic Methods For Solute Descriptor Determinations (Ii)Ruthenium Substrate-Catalyzed Growth Of Nickel Nitride Thin Films By Atomic Layer Deposition, Thiloka Chandima Ariyasena

Wayne State University Dissertations

Determination of distribution levels of environmentally important compounds in various environmental compartments is a major procedure in many fields including environmental risk assessment, food and drug safety, and the perfumery industry. Models for direct estimation of environmental properties were developed using gas chromatography and liquid-liquid partitioning. The developed models were used to derive descriptor values for environmentally important organic compounds. The accuracy of the developed models and descriptor values were demonstrated by the application to the estimation of standard environmental properties and by comparison with experimental solute property values.

Quantitative structure property relationships were constructed for totally organic biphasic partition …

Developing A Toolbox To Probe Reaction Dynamics With Strong Field Ionization And Non-Linear Attosecond Spectroscopy, Thushani Nikeshala Herath

Wayne State University Dissertations

Electronic motions which happen in 10 to 100 of attoseconds are the heart of all processes in nature. Therefore monitoring and extracting details in this fundamental level will provide new prospect to the areas as information technology, basic energy science, medicine and life sciences. The challenge being, develop a tool to reach such a fast time scale for real time observation in atomic level. In this thesis work we have address this matter using two interesting approaches related to the laser matter interaction: strong field ionization and nonlinear attosecond spectroscopy. The first part is based on the studies related to …

Biochemical And Structural Characterization Of The Core Subunits Of Gpi Transamidase, Dilani G. Gamage

Wayne State University Dissertations

BIOCHEMICAL AND STRUCTURAL CHARACTERIZATION OF THE CORE SUBUNITS OF GPI TRANSAMIDASE

by

DILANI G GAMAGE

May 2015

Advisor: Prof. Tamara L. Hendrickson

Major: Chemistry (Biochemistry)

Degree: Doctor of Philosophy

Glycosylphosphatidylinositol transamidase (GPI-T) is a complicated, membrane-bound, multi-subunit enzyme that catalyzes an essential post-translational modification. This enzyme attaches GPI anchors to the C-termini of various proteins that contain a proper GPI-T signal sequence. Gpi8, Gaa1, Gpi16, Gpi17 and Gab1 are the five known subunits that may encompass the fungal GPI-T; Gpi8 is the catalytic subunit, but the functions of the other subunits remain essentially unknown. In humans, different GPI-T subunits are …

The Loss Of Genomic Uracil Homeostasis And Aid-Dependent Accumulation Of Dna Damage In B Cell Lymphomas, Sophia Shalhout

Wayne State University Dissertations

Activation-induced deaminase (AID) is a sequence-selective DNA cytosine deaminase that introduces uracils in immunoglobulin genes. This DNA mutator is required for somatic hypermutation and class switch recombination- processes involved in the affinity maturation and diversification of antibodies. AID, however, can also lead to deleterious mutations and translocations promoting lymphomagenesis. The introduction of uracils throughout the genome of activated B cells and the ability of UNG2 glycosylase to excise these uracils is examined here. This interplay was also studied in cancerous B cells, with different results emerging in transformed cells versus healthy cells. Genomic uracil levels are found to remain at …

Dna Aptamers Selected Against Wild-Type Helix 69 Ribosomal Rna And Their Implications In Combating Antibiotic Resistance, Sakina Miriam Hill

Wayne State University Dissertations

Outbreaks of advanced antibiotic-resistant strains of microbes have hastened the need to identify new viable molecular targets for the development of novel anti-infectives. For this purpose, helix 69 (H69, or m3a 19-nucleotide (nt) hairpin motif that is highly conserved throughout phylogeny and rich in modified nucleotides, including pseudouridine () and 3-methylpseudouridine (m3) was chosen as a potential target. Helix 69, which is located in domain IV of Escherichia coli 23S ribosomal RNA (rRNA), undergoes conformational changes when in close proximity to the decoding region of 16S rRNA and transfer RNAs (tRNAs) in the peptidyl-transferase center (PTC). Functionally, the exact biological …

Classical And Ab Initio Qm/Mm Simulations Of Bacterial Enzymes, Sajeewa Walimuni Dewage

Wayne State University Dissertations

This thesis describes analyses performed on three enzyme systems. Chapter 2, 3, and 4 involve studies carried out on the GatCAB enzyme of H. pylori and S. aureus. Since information at the electronic level was not required for these studies, sampling of the configuration space carried out at the molecular mechanics level was adequate. In Chapter 2, the snapshots sampled using MD were used as input for average correlation difference calculations and average RMSD difference calculations to ascertain the existence of a communication pathway between two subunits of GatCAB. Experimental and computational results obtained, suggest the existence of a communication …

Chirped-Pulse Fourier Transform Microwave Spectroscopy In Pulsed Uniform Supersonic Flows, Chamara S.W Abeysekera

Wayne State University Dissertations

This dissertation is focused on the development of a new experimental apparatus that combines two powerful techniques: Chirped-Pulse Fourier-Transform Microwave (CP-FTMW) spectroscopy and uniform supersonic flows. This combination promises a nearly universal detection method that can deliver quantitative isomer, conformer, and vibrational level specific detection; characterize unstable reaction products and intermediates; and perform unique spectroscopic, kinetics and dynamics measurements.

Thus, a new high-power Ka band (26 – 40 GHz) chirped pulse spectrometer with sub-MHz resolution was designed and constructed. In order to study smaller molecules, E-band (60 – 90 GHz) capabilities were also added to the spectrometer. A novel strategy …

Synthesis, Characterization, And Rna Reactivity Of Amino-Acid-Linked Cisplatin Analogues, Xun Bao

Wayne State University Dissertations

The essential role of ribosomal RNA (rRNA) in the cell life cycle is highlighted by protein synthesis; therefore, the ribosome is considered to be an ideal drug target. Ribosomal RNAs exhibit a high level of structural diversity. The well-known anticancer drug cisplatin was previously applied as a chemical probe of rRNA structure to determine solvent accessible purines (guanosine) in vivo and in vitro. Cisplatin accumulates faster on RNA than DNA, with less chance of repair. As such, designing new RNA-targeting Pt compounds is not only a promising direction for chemical-probing applications, but also for the design of anticancer drugs that …

Strong Field Ionization Of Radicals And Reaction Intermediates, Fadia Cudry

Wayne State University Dissertations

This work presents results of adapting SFI probe for detection of radicals and their isomers. Radicals and reaction intermediates were produced using an established method flash pyrolysis. This combination allows for new insight in studying radicals and provide complementary results to the other detection methods used. This is the first study reporting the use of SFI to detect radicals. This detection will also provide structural information of the radicals under study.

For acetone and isoprene, a detailed study shows the SFI flash pyrolysis mass spectra. These mass spectra were then compared to the spectra produced by other detection techniques. We …

Investigation Of New Ligand Architechtures Towards Proton And Water Reduction Catalysis By Cobalt Complexes, Debashis Basu

Wayne State University Dissertations

We designed several redox-active ligand architectures to optimize and understand the redox, electronic, and catalytic properties of their respective cobalt complexes. Ligand design was varied from pentadentate donor phenolate to tetradentate acceptor oxime in order to reduce the overpotential of hydrogen generation in organic solvents. We altered the substitution, axial ligands and axial ligand substitutions to vary electronic and catalytic properties for such tetra- or pentadentate ligand systems. Knowledge of the nature of the active species for catalysis enabled us to design the pentadentate oxime ligand which exhibited rich reaction chemistry along with suitable catalytic property in organic solvent. Presence …

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 …

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 …

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 …

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 …

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, …

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 …

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 …