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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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

(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 …

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 …

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 …

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 …

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. …

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 …