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Evaluation Of Earth-Abundant Monometallic And Bimetallic Complexes For Catalytic Water Splitting, Kenneth Kwame Kpogo

Wayne State University Dissertations

The development of affordable water splitting catalysts from Earth-abundant transition metal ions such as Co and Mn is of immense scientific interest. Aiming to develop an efficient water splitting catalyst, a Co(II) complex featuring an asymmetric, pentadentate quinolyl-bispyridine ligand with a phenylenediamine backbone was synthesized and characterized by spectroscopic, spectrometric, and X-ray analysis. The Co ion was selected because of its ability to undergo redox conversions from 3d5 CoIV through 3d8 CoI thereby making it a suitable catalyst that can withstand harsh structural and electronic changes during catalysis. The electrocatalytic water reduction activity of the catalyst at neutral pH gave …

Differential Activation Of Dead Box Rna Helicases Rhlb And Rhle By Hfq/Srnas And Their Target Mrnas, Amit Kumar

Wayne State University Theses

Number of small RNA (sRNA) gene regulators have mounted in E. coli over the years whereas the number of validated protein partners has not changed considerably. Hfq has remained the only well studied global regulatory partner of sRNAs in E. coli. However, direct or indirect involvement of other protein partners has always been speculated. Study from Blasi lab has shown that CsdA, one of the five DEAD-box RNA helicases of E. coli, is required for the DsrA mediated upregulation of rpoS under cold stress condition. Previous study from our lab has identified two other DEAD-box RNA helicases, RhlB and RhlE, …

Design, Synthesis And Analysis Of Potential Photo-Activatable Cathepsin K Inhibitors, Khalin Evania Nisbett

Wayne State University Theses

Abstract

DESIGN, SYNTHESIS AND ANALYSIS OF POTENTIAL PHOTO-ACTIVATABLE CATHEPSIN K INHIBITORS

by

KHALIN NISBETT

May 2017

Advisor: Dr. Jeremy Kodanko

Major: Chemistry

Degree: Master of Science

Tightly regulated cysteine CA proteases play a major role in maintaining the homeostasis within cells. Subsequently, when these proteases are dysregulated and mislocalized they disrupt healthy cell dynamics and contribute to many life-threatening pathologies such arteriosclerosis, osteoporosis and cancer. As such many pharmaceutical companies and research teams are highly interested in these proteases as targets. One emergent strategy is the spatiotemporal control of biological processes. In relation to this, a series of spatiotemporally controlled …

Chalcogenide Nanocrystal Assembly: Controlling Heterogeneity And Modulating Heterointerfaces, Jessica Davis Davis

Wayne State University Dissertations

This dissertation work is focused on developing methods to facilitate charge transport in heterostructured materials that comprise a nanoscale component. Multicomponent semiconductor materials were prepared by (1) spin coating of discrete nanomaterials onto porous silicon (pSi) or (2) self-assembly. Spin-coating of colloidal quantum dot (QD) PbS solutions was employed to create prototype PbS QD based radiation detection devices using porous silicon (pSi) as an n-type support and charge transport material. These devices were initially tested as a photodetector to ascertain the possibility of their use in high energy radiation detection. Short chain thiolate ligands (4-fluorothiophenolate) and anion passivation at the …

The Development Of Chemical Methods To Discover Kinase Substrates And Map Cell Signaling With Gamma-Modified Atp Analog-Dependent Kinase-Catalyzed Phosphorylation, Dissanayaka Mudiyanselage Maheeka Madhubashini Embogama

Wayne State University Dissertations

Kinase-catalyzed phosphorylation plays an important role in cell physiology by regulating a myriad of cellular functions. Thus aberrant kinase activity is implicated in various diseases. Methods are needed to discover kinase substrates and map signaling pathways to explore biology and to help drug discovery. A few techniques are currently available to discover kinase substrate and map cell signaling. However, to augment kinase substrate discovery approaches, it is essential to develop alternative techniques. Pflum has recently discovered cosubstrate promiscuity of protein kinases with gamma-modified ATP analogs. Here, kinase-catalyzed biotinylation with ATP-biotin was used to develop novel tools to discover kinase substrates …

Elucidation Of The Cation And The Anion Doping Mechanism Of Nanoparticulate Manganese Arsenide: Effect Of Doping On The Magnetostructural Properties, Surangi Hasitha Roshini Pimmachcharige

Wayne State University Dissertations

The mechanism of solution-phase synthesis of P-doped type-B MnAs nanoparticles has been quantitatively assessed and the knowledge obtained is extended to independently control nanoparticle size and P incorporation in order to understand the roles of size and dopant concentration on the magnetostructural properties. During the solution-phase synthesis, the dimensions of the nanoparticles change as the monomer concentration in the bulk solution is depleted and the particles become uniform in size and shape when the temperature stabilizes. The temperature at which the nanoparticles were isolated controls the particle size and polydispersity. High temperature isolation of nanoparticles is required to achieve narrow …

Gas-Phase Ion Spectroscopy Of Nucleobases And Mononucleotides: Models For Higher Order Nucleic Acids, Yuan-Wei Nei

Wayne State University Dissertations

Experiments examining the structures and stabilities of protonated and sodium cationized nucleobases, and deprotonated DNA and RNA mononucleotides are presented and discussed in this dissertation. These studies were carried out using the infrared multiple photon dissociation (IRMPD) action spectroscopy technique that utilizes a Fourier transform ion cyclotron mass spectrometer (FT-ICR MS) coupled to a free electron laser (FEL) located at the Radboud University Nijmegen. Ionic species of these biologically important complexes were generated using an electrospray ionization source and then mass isolated to have their infrared (IR) spectra measured by the experimental apparatus. Detailed analysis of the IR spectra measured …

Water Splitting Using Cobalt-Based Amidopyridine Complexes, Habib Baydoun

Wayne State University Dissertations

As part of the ongoing search for clean energy sources, splitting water into oxygen and hydrogen has emerged as a promising source of alternative energy. We are interested in developing electrocatalysts capable of performing water reduction and water oxidation. In this dissertation, a variety of catalytic platforms based on an amidopyridine framework are studied. A novel monomeric cobalt complex in an amidopyridine ligand environment, ([CoIII(L1)(pyrr)2]PF6), was investigated for electrocatalytic water reduction and found to have an onset overpotential of 0.54 V and an observed TOF of 23 min-1. The catalytic decomposition pathway was explored with the aim of designing more …

Design, Synthesis And Biological Evaluation Of Histone Deacetylase (Hdac) Inhibitors: Saha (Vorinostat) Analogs And Biaryl Indolyl Benzamide Inhibitors Display Isoform Selectivity, Ahmed Negmeldin

Wayne State University Dissertations

HDAC proteins have emerged as interesting targets for anti-cancer drugs due to their involvement in cancers, as well as several other diseases. Several HDAC inhibitors have been approved by the FDA as anti-cancer drugs, including SAHA (suberoylanilide hydroxamic acid, Vorinostat). Unfortunately, SAHA inhibits most HDAC isoforms, which limit its use as a pharmacological tool and may lead to side effects in the clinic. In this work we were interested in developing isoform selective HDAC inhibitors, which may decrease or eliminate the side effects associated with non-selective inhibitors treatment. In addition, isoform selective HDAC inhibitors can be used as biological tools …

Development Of Chemical Tools To Investigate Protein S-Glutathionylation In Response To Metabolic Alteration, Kusal Theekshana Gayan Samarasinghe

Wayne State University Dissertations

Oxidative stress is a common characteristic of age-related diseases such as vascular diseases, diabetes and cancer. Many diseases are known to be regulated by glutathionylation. Glutathionylation is referred to as the formation of disulfide bond between a protein cysteine and a glutathione. To understand the molecular mechanisms behind the disease initiation and progression, identification of such glutathionylated proteins is important. Even though existing methods have been widely used, several limitations of these methods hinder the identification of such proteins in disease conditions. Therefore, we developed a versatile chemical method that generates clickable glutathione inside the cells. In this method, we …

Synthesis Of Netilmicin And Apramycin Derivatives For The Treatment Of Multidrug-Resistant Infectious Diseases, Amr Sayed Motawi Sonousi

Wayne State University Dissertations

The ever-growing bacterial resistance to existing antibiotics is alarming to humanity. Many researchers decided to revisit aminoglycosides with renewed emphasis on chemical modification as they have long been used as highly potent antibiotics for treating severe bacterial infections. The bactericidal effect of aminoglycosides is mainly due to protein synthesis inhibition by binding to the A-site of the bacterial ribosomes. However, the high potency and the broad spectrum of aminoglycosides has been outweighed by their side effects, especially ototoxicity, and by the resistance of pathogens. The goal of this research was the modification of existing aminoglycosides to develop derivatives which are …

Exploring Potential Energy Surfaces Of Chemical Reactions Using Electronic Structure Methods, Bishnu Thapa

Wayne State University Dissertations

This dissertation includes three topics: molecular dynamics in strong laser fields, pKa’s and redox potential calculations of bio–organic molecules, and oxidative damage of the nucleobases. Electronic structure calculations are used to provide a deeper understanding of experimental observations as well as to predict new results.

Chapters 2, 3 and 4 investigate the fragmentation and isomerization reactions of small monocations in the presence of strong laser fields. In the presence of intense laser pulses with 800 nm wavelengths, Born-Oppenheimer classical trajectory simulations were performed to investigate the dynamics of methanol monocation on the ground state potential energy surface (Chapter 2). With …

Synthesis Of Low-Coordinate Transition Metal Bis(Alkoxide) Complexes And Their Reactivity Toward Small Molecules, Maryam Yousif

Wayne State University Dissertations

This dissertation focused on the synthesis of new transition metal complexes in bis(alkoxide) ligand environments and the investigation of their reactivity in nitrene-group transfer catalysis and small molecule activation. Treatment of Cr(N(SiMe3)2)2(THF)2 with two equivalents of HOR (OR = OCtBu2Ph) led to the formation of the chromium(II) alkoxide dimer, Cr2(OR)4. Upon the reaction with bulky aryl and alkyl azides, Cr2(OR)4 led to the stable Cr(IV) mono(imido) complexes, Cr(OR)2(NR), featuring trigonal planar metal centers. In contrast, less bulky aryl azides led to the formation of chromium (VI) bis(imido) complexes Cr(OR)2(NR)2, independent of the amount of azide used. Chromium(IV) mono(imido) species Cr(OR)2(NR) …

Ln(Ii)-Containing Cryptates: Synthesis And Properties, Akhila Nuwan Wijerathne Kuda-Wedagedara

Wayne State University Dissertations

LNII-CONTAINING CRYPTATES: SYNTHESIS AND PROPERTIES

by

AKHILA N. W. KUDA-WEDAGEDARA

May 2016

Advisor: Dr. Matthew J. Allen

Major: Chemistry

Degree: Doctor of Philosophy

Research projects described in this dissertation are focused on studying the physicochemical properties, including the photochemical, redox, and magnetic properties, of LnII-containing cryptates and how ligand structure influences metal–ligand interactions that in turn influence physicochemical properties. The results of these studies enable tailoring of the coordination properties of metal complexes that are important in applications including luminescent materials, chemical reductions, catalysis, and imaging.

A EuII-containing cryptate 2.1-EuII synthesized with an amine-rich ligand displayed bright yellow luminescence in …

A New Three-Dimensional (3d) Particle Coincidence Imaging System And Its Applications In Strong Field Studies Of Reaction Dynamics In Atoms And Molecules, Yunfei Lin

Wayne State University Dissertations

Electron‐electron interaction is an important and interesting research theme both in chemistry and physics. Experimental study of electron correlation is hindered by the long dead time (the time within which no more than two electrons can be detected) of electron detection system. We developed a new three‐dimensional (3D) particle coincidence imaging system to remove this restriction. The detection system employs a new strategy: It uses a fast‐frame camera to record positional information on 2D MCPs/phosphor detector (so the particle velocities in two dimensions can be measured); It utilizes a high‐speed digitizer to pick up the signal from MCP lead, off‐line …

Selective Atomic Layer Deposition Of Transition Metal Thin Films, Marissa Marie Kerrigan

Wayne State University Dissertations

Atomic layer deposition (ALD) affords highly conformal thin films with precise thickness control due to its self-limited growth mechanism. ALD enables the increasing demands for smaller feature sizes in microelectronics devices to be met. Area-selective ALD growth is receiving attention in the fabrication of microelectronic devices, since it can eliminate complicated etching steps from the fabrication process and minimizes expensive and toxic reagent use. Selectivity can be achieved by tailoring the surface chemistry of the precursor and substrate. To date, few area-selective ALD processes have been reported for metallic films. Thin films of cobalt metal deposited selectively are of considerable …

Synthesis Of Discrete Transition Metal (Ni, Fe, Co, Mn) Phosphide Nanoparticles: Compositional Effect On Catalytic And Magnetic Properties, Da Li

Wayne State University Dissertations

This dissertation research is focused on the synthesis, characterization of binary and ternary transition metal (Ni, Co, Fe, Mn) phosphide nanomaterials and their catalytic and magnetic properties.

A phase-control strategy enabling the arrested-precipitation synthesis of nanoparticles of Ni5P4 and NiP2 is presented. The composition and purity of the product can be tuned by changing key synthetic levers, including the metal precursor, the oleylamine (OAm) and Trioctylphosphine (TOP) concentrations, temperature, time and the presence or absence of a moderate temperature soak step to facilitate formation of Ni and/or Ni-P amorphous nanoparticle intermediates.

New CoxFe2-xP nanoparticles (0 ≤ x ≤ 2), Co2-xMnxP …

Real-Time Investigation Of Bulky Lesion Bypass By Y-Family Dna Polymerase, Dpo4, Using Single Molecule Fret, Pramodha Liyanage

Wayne State University Dissertations

DNA is constantly exposed to various DNA damaging agents that are generated by various internal and external sources. Some of this damage may not be able to be repaired by cellular machineries causing DNA replication to be blocked. Once the replication fork is blocked by a DNA adduct, damage tolerance DNA polymerases, mainly Y-family, are able to restore the DNA replication by synthesizing past the DNA adduct. Benzo[a]pyrene (B[a]P) is one of the most studied environmental carcinogens. It is known to make covalent DNA adducts after metabolic activation and the bulkiness of the B[a]P adducts impose a strong barrier to …

Ligand Binding Studies Of A Peptide Targeting Helix 69 Of 23s Rrna In Bacterial Ribosomes, Hyosuk Seo

Wayne State University Dissertations

In the development of finding a peptide targeting H69 of 23S rRNA in bacterial ribosomes, phage display was employed at pH 5.5, a buffer condition previously reported of H69 preferring a closed conformation. After sequencing, several peptides were chosen through sequence alignment, followed by preparation using solid-phase peptide synthesis. The peptides were characterized using MALDI-TOF and purified with HPLC. A truncated peptide TARHIY was selected from FID assay. Through binding studies using ESI-MS, SPR, BLItz, and NMR, the binding properties of the peptide to H69 were determined, such as binding affinity, stoichiometry, and interaction site. The peptide exhibited moderate binding …

Classical And Quantum Mechanical Simulations Of Condensed Systems And Biomolecules, Hedieh Torabifard

Wayne State University Dissertations

This work describes the fundamental study of two enzymes of Fe(II)/-KG super family enzymes (TET2 and AlkB) by applying MD and QM/MM approaches, as well as the development of multipolar-polarizable force field (AMOEBA/GEM-DM) for condensed systems (ionic liquids and water).

TET2 catalytic activity has been studied extensively to identify the potential source of its substrate preference in three iterative oxidation steps. Our MD results along with some experimental data show that the wild type TET2 active site is shaped to enable higher order oxidation. We showed that the scaffold stablished by Y1902 and T1372 is required for iterative oxidation. The …

Attosecond Spectroscopy Probing Electron Correlation Dynamics, Alexander Heinecke Winney

Wayne State University Dissertations

Electrons are the driving force behind every chemical reaction. The exchange, ionization, or even relaxation of electrons is behind every bond broken or formed. According to the Bohr model of the atom, it takes an electron 150 as to orbit a proton[6]. With this as a unit time scale for an electron, it is clear that a pulse duration of several femtoseconds will not be sufficient to understanding electron dynamics. Our work demonstrates both technical and scientific achievements that push the boundaries of attosecond dynamics. TDSE studies show that amplification the yield of high harmonic generation (HHG) may be possible …