Chemistry Commons^™

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 …

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 …

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 …

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) …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

New Approaches To Chalcogenide Materials For Thermoelectrics: Lead Telluride-Based Nanostructures And Facile Synthesis Of Tetrahedrite And Doped Derivatives, Derak Justin James

Wayne State University Dissertations

The overall purpose of this work is to address several of the roadblocks to use of thermoelectric materials for generation of electricity, namely inefficient processing of materials and low performance, commonly rated by the figure of merit, ZT=T2/tot. The ZT includes  as the Seebeck coefficient,  as electrical resistivity, T as the average temperature, and tot as total thermal conductivity. tot is the sum of electronic charge carrier (C) and lattice (L) contributions to thermal conductivity. Attempts to increase ZT in the literature to values >1 have focused on decreasing the thermal conductivity via nanostructuring or optimizing the electrical …

Use Of 17o-Nmr Spectroscopy To Study The Coordination Chemistry Of Trivalent Lanthanide Ions In Solution, Zhijin Lin

Wayne State University Dissertations

Trivalent lanthanide (Ln3+)-containing complexes have a number of important applications in molecular imaging, catalysis, medical diagnosis, information storage, and environmental sensing. The properties of Ln3+-containing complexes that are useful for these applications are influenced by coordination chemistry, including the number of coordinated ligands and ligand-exchange rates. The coordination numbers for water molecules bound to Eu3+ and Tb3+ have been studied by luminescence-decay measurements; however, the coordination numbers of other important oxygen-containing functional groups such as ketones, esters, ethers, sulfonyls, amides, phosphine oxides, and aldehydes have not been as thoroughly studied in solution because of the lack of hydroxyl groups that …

Studying The Atp Cosubstrate Promiscuity Of Nucleotide And Lipid Kinases, Thilani Murium Anthony

Wayne State University Dissertations

The kinase family consist of a large assortment of enzymes that phosphorylate a variety of substrates, including proteins, nucleosides, polynucleotides, lipids, sugars, and other small molecules. The Pflum lab recently found that protein kinases promiscuously accept an ATP analog containing a biotin at the γ-phosphate (ATP-biotin) as a cosubstrate to label the hydroxyl side chains of Ser, Thr and Tyr residues with biotin. The main goal of this new project is to extend the use of kinase-catalyzed biotinylation towards polynucleotides. Crystallographic studies of T4 polynucleotide kinase (T4 PNK) that phosphorylates the 5’-hydroxyl termini of DNA and RNA show a solvent …

Design Of First-Row Transition Metal Bis(Alkoxide) Complexes And Their Reactivity Toward Nitrene And Carbene Transfer, James Bellow

Wayne State University Dissertations

The novel alkoxide ligand [OCtBu2Ph], or [OR], was synthesized in a single step as a lithium salt. It was then reacted with a series of first-row transition metal(II) halides, with widely varying results. Upon reaction with chromium, manganese, iron, or cobalt(II) chloride, dimeric complexes of the form M2(OR)4Li2Cl2 were formed, which displayed rare seesaw geometry at the metal. This unusual geometry was confirmed by various spectroscopic and computational studies. Computational studies also indicate that the steric bulk of the ligand, as well as the inclusion of lithium atoms in the molecules, are what lead to the seesaw geometry. Reaction of …

State Resolved Sliced Imaging Of Infrared Multiphoton Dissociation, Ravin Lakshitha Fernando

Wayne State University Dissertations

This dissertation focuses on unimolecular dissociations of molecules under colissionless conditions with IRMPD. IRMPD was used as the dissociation technique in these studies since roaming type dissociations predominates from the ground electronic state. DC slice imaging was used with REMPI as the detection technique to study the products in a state selective manner to understand the nano scale dynamics of unimolecular dissociations. In the investigation of photodissociation dynamics of nitromethane and methyl nitrite with IRMPD, nitromethane show very low translational energy release of the photofragments and resemble the “roaming” pathway in the dissociation of nitromethane. The difference in the intensities …

Synthesis Of Dinucleating Ligands And Their Dinuclear Metal Complxes:Applications In Sensing And Small Molecule Activation, Jeffrey William Beattie

Wayne State University Dissertations

Dinuclear metal complexes provide a route to interesting structure and reactivity. Two common uses of dinuclear metal complexes are sensing and activation of small molecules. Herein we describe a series of dinuclear metal complexes capable of sensing of oxalate and activation of carbon disulfide.

Sensing of oxalate is of great interest because high oxalate concentration (hypooxaluria) is a major cause of kidney stones. Dinuclear metal complexes can act as sensors for oxalate because the oxalate can bridge between the metal centers. Herein we describe a colorimetric oxalate sensor capable of regeneration. Upon addition of oxalate to a pink solution of …

Development Of Gamma-Modified Atp Analogs To Study Kinase-Catalyzed Phosphorylations, Ahmed Eid Fouda

Wayne State University Dissertations

Kinase-catalyzed protein phosphorylation is one of the most important post-translational modifications that controls cascades of biochemical reactions. Irregularities in phosphorylation result in many diseases, such as diabetes mellitus, Parkinsons, and cancer. The development of new methods to monitor kinase-catalyzed phosphorylation is needed to decipher details of normal and diseased cell signaling. The Pflum lab recently developed several -modified ATP analogs to study kinase catalyzed phosphorylation reactions. The -modified ATP analogs have different tags, such as biotin for substrate labeling or aryl-azide for kinase substrates identification. Unfortunately, use of -modified ATP analogs was limited to in vitro studies due to the …

Synthesis Of Apramycin And Paromomycin Derivatives As Potential Next Generation Aminoglycoside Antibiotics And Chemistry Of Isothiocyanato Sialyl Donors, Appi Reddy Mandhapati

Wayne State University Dissertations

AGAs are clinically important antibacterials for human therapy and have long been used as highly potent antibiotics for treating several bacterial infections. The fidelity of protein synthesis is affected by AGAs in the course of binding to specific sites of the bacterial rRNA. The clinical use of AGAs and their applications as therapeutics is restricted by toxicity (irreversible ototoxicity and reversible nephrotoxicity) and by the resistance of pathogens. The objective of this research was the development of proficient AGAs that are less toxic (i.e., more selective) and that evade resistance. The first three chapters of this thesis are aimed towards …

How Geometric Distortions Scatter Electronic Excitations In Conjugated Macromolecules: Towards Photoinduced Relaxation And Energy Transfer, Tian Shi

Wayne State University Dissertations

The exciton scattering (ES) approach has been developed to study electronic excitations in large branched conjugated molecules. It attributes excited states to standing waves in the quasi-one-dimensional system by assuming a quasi-particle picture of optical excitations. Tight binding models extend capability of the ES approach to investigate the exciton-phonon coupling.

The topological counting method plays a substantial role in constructing tight binding models. It depicts the ES equations as a topological intersection problem. Then, by applying the index theorem, we can get the total number of excited states, which is equal to the number of repeat units plus topological charges …

Novel Approaches For Assessment Of Copper Toxicity: Fast Scan Cyclic Voltammetry And Optical Bioassays, Annette R. Tremonti

Wayne State University Dissertations

Anthropogenic activities negatively impact fresh water ecosystems through toxic contaminants that are released into the environment. Copper (Cu) is a water contaminant that is fundamentally persistent once introduced into the environment that has the potential for bioaccumulation. Although Cu toxicity has been studied for decades, there is still a continuing problem with new sources and pathways. New approaches are needed to understand distribution and transport of Cu and its potential for complex biological impacts beyond the simple assessment of lethality. Several novel approaches were used in this research project to advance our understanding of Cu toxicity, including fast scan cyclic …

A Novel, Ultra-Fast Electrochemical Tool To Study Speciation Of Trace Metals In Aqueous Solution, Pavithra Pathirathna

Wayne State University Dissertations

Trace metals play important roles in biological and ecological systems. In biology, trace metals act as catalytic or structural cofactors and regulate biochemical processes. In the environment, natural and anthropogenic sources of trace metals mobilized into natural waters where they can create harmful and persistent pollution. Trace metal chemistry in physiological and environmental systems can fluctuate rapidly which makes it difficult to clearly define trace metals’ roles in these systems with traditional analytical methods. Furthermore, these systems are often chemically harsh and physically delicate (e.g. the brain), factors that add to the challenge of analysis in real systems. Fast scan …

The Development Of Peptide Ligands To Target H69 Rrna, Danielle Nicole Dremann

Wayne State University Dissertations

ABSTRACT

THE DEVELOPMENT OF PEPTIDE LIGANDS TO TARGET H69

by

DANIELLE NICOLE DREMANN

December 2015

Advisor: Prof. Christine S. Chow

Major: Chemistry (Biochemistry)

Degree: Doctor of Philosophy

In the development of peptide ligands to target H69, SPPS and ESI MS was used to determine if 1) peptides could bind to modified H69 and 2) if increased affinity for the target RNA could be enhanced with modification. An alanine and arginine scan was synthesized and tested for this determination. Selected peptides were then tested using biophysical techniques such as circular dichroism and isothermal titration calorimetry. An assay was also designed to …

Development Of Single And Array Electro-Chemical Sensors For Real-Time Trace Metal Analysis In Aqueous Environmental Media, Yuanyuan Yang

Wayne State University Dissertations

Detection of trace metals has great importance in environmental and biological applications. While traditional electrochemical techniques have played critical roles in this field, their usefulness is limited by temporal resolution, Hg toxicity and stability concerns. Recently, we developed a method using fast-scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes (CFMs) to achieve rapid measurement of metal ions with high sensitivity, selectivity, and stability. Through optimizations this method showed strengths in real-time trace metal analysis. ‬‬‬‬‬‬

‪Analytical selectivity was improved via covalent functionalization on CFMs. We employed diazonium electrochemical reduction followed by click chemistry to create robust covalent attachments. We showcased its …

Electron Transfer Studies In Langmuir-Blodgett Films Of Metallosurfactants For Current Rectification, Corrosion Mitigation, And Water Oxidation, Sunalee Gonawala Jayasundara Mudiyanselage

Wayne State University Dissertations

The work presented in this dissertation is focused on the design and synthesis of new redox-active amphiphilic architectures to optimize and understand the redox, electronic, and film formation properties for applications in current rectification, corrosion mitigation, and water oxidation. As such, new redox-active, and amphiphilic iron(III), cobalt(III), nickel(II), copper(II), and zinc(II) complexes were synthesized as precursors for Langmuir-Blodgett films used for the aforementioned applications.

For the use in molecular rectification, amphiphilic copper(II) and nickel(II) complexes with [N2O2] ligand environment were synthesized. Homogeneous film formation ability was observed between ~20-25 mN/m pressure, with a film collapse observed at ~35 mN/m for …

Synthesis And Heteroallene Reactivity Of Bis(Aldimino)Pyridine Nickel Complexes In Four Different Oxidation States, Blake Reed

Wayne State University Dissertations

A series of redox non-innocent bis(aldimino)pyridine ligands were synthesized. These were then reacted with nickel(II) salts to form Ni[NNN]X2 complexes. Cyclic voltammograms of these nickel(II) complexes suggest that more reduced states can be achieved. Reduction of these nickel(II) complexes lead to distorted square planar complexes with the halide bent ~20° out of the plane. EPR suggests that spin density is located on the metal as g-values of >2.01 were obtained. This differs from previously reported analogous bis(ketimino)pyridine complexes, which show a ligand-based radical and nickel(II). DFT confirms that as the Npyr-Ni-X angle decreases, spin density on the nickel increases. Because …

New Chemistry For The Growth Of First-Row Transition Metal Films By Atomic Layer Deposition, Joseph Peter Klesko

Wayne State University Dissertations

Thin films containing first-row transition metals are widely used in microelectronic, photovoltaic, catalytic, and surface-coating applications. In particular, metallic films are essential for interconnects and seed, barrier, and capping layers in integrated circuitry. Traditional vapor deposition methods for film growth include PVD, CVD, or the use of plasma. However, these techniques lack the requisite precision for film growth at the nanoscale, and thus, are increasingly inadequate for many current and future applications. By contrast, ALD is the favored approach for depositing films with absolute surface conformality and thickness control on 3D architectures and in high aspect ratio features. However, the …