Chemistry Commons^™

Striatal Dopamine Dynamics Upon Manganese Accumulation, Madiha Khalid

Wayne State University Dissertations

STRIATAL DOPAMINE DYNAMICS UPON MANGANESE ACCUMULATION

by MADIHA KHALID

August 2013

Advisor: Dr. Tiffany Mathews

Major: Chemistry (Analytical)

Degree: Doctor of Philosophy

Although manganese (Mn) is fundamental for many biological processes, exposure to excess amounts leads to a neurological disorder termed manganism. Due to its symptomatic similarity to Parkinson's disease, as well its preferential accumulation in dopamine rich brain regions, alterations in the dopamine system are implicated in the onset of manganism. In my research, Mn overexposure is mimicked via subcutaneous administration of manganese chloride to C57BL/6 mice over the course of seven days using a protocol that has been …

Synthesis And Application Of Atp Analogs For Phosphorylation-Dependent Kinase-Substrate Crosslinking, Satish Kumar Garre Venkata Raghavendra

Wayne State University Dissertations

Phosphorylation is an important post-translational modification that plays a key role in a variety of signaling cascades and cellular functions. Kinases phosphorylate protein substrates in a highly regulated manner and are promiscuous. Understanding kinase-substrate specificity has been challenging and there is a need for new chemical tools. To this end we developed -phosphate modified ATP photocrosslinking analogs ATP-ArN3 and ATP-BP, that crosslink substrate and kinase in a phosphorylation dependent manner. We have successfully demonstrated that ATP-ArN3 and ATP-BP can be used with natural kinase and substrates using cell lysates in vitro. We used our approach to identify novel kinases of …

Unveiling Dna Polymerase Synthesis And Proofreading Activities - One Molecule At A Time, Kyle Vrtis

Wayne State University Dissertations

DNA polymerases maintain the genome integrity from one generation to the next by faithfully synthesizing new DNA and by participating in DNA repair processes. The Klenow fragment of E. coli DNA polymerase I has served as a model polymerase for decades because it is straightforward to purify, well-characterized kinetically, and it is able to carry out DNA synthesis and proofreading. In 2009, Christian, et al. developed a single molecule Förster resonance energy transfer (smFRET) approach to monitor the polymerase position on the DNA with single base pair resolution.

We have worked to optimize nearly every aspect of that approach and …

Synthesis And Characterization Of A Biometric Model Of The Tricopper Binding Site Of Multicopper Oxidases, Haosen Wang

Honors Theses, 1963-2015

This research employs the principles of bioinorganic modeling, simplifying the extraneous structures of the molecule being mimicked and focusing only on the active components of the large biological molecules. Specifically, this project attempts to mimic the structure and reactivity of tri-copper active sites found in Multi-copper Oxidises, such as Laccase and Ceruloplasmin, that bind with oxygen and reduce it to water. After experimenting with various other structures that failed to mimic the active sites, we selected another potential ligand, 1,3,5-tri(2-pyridylmethyltriazole)-2,4,6-triethyl benzene, abbreviated L_tapma, to be the substrate for this research to bind with three Cu(I) ions and then …

Single-Cell Imaging And Spectroscopic Analyses Of Cr(Vi) Reduction On The Surface Of Bacterial Cells, Yuanmin Wang, Papatya C. Sevinc, Sara M. Belchik, Jim Fredrickson, Liang Shi, H. Peter Lu

Chemistry Faculty Publications

We investigate the single-cell reduction of toxic Cr(VI) by the dissimilatory metal-reducing bacterium Shewanella oneidensis MR-1 (MR-1), an important bioremediation process, using Raman spectroscopy and scanning electron microscopy (SEM) combined with energy-dispersive X-ray spectroscopy (EDX). Our experiments indicate that the toxic, highly soluble Cr(VI) can be efficiently reduced to less toxic, nonsoluble Cr2O3 nanoparticles by MR-1. Cr2O3 is observed to emerge as nanoparticles adsorbed on the cell surface and its chemical nature is identified by EDX imaging and Raman spectroscopy. Co-localization of Cr2O3 and cytochromes by EDX imaging and Raman spectroscopy suggests a terminal reductase role for MR-1 surface-exposed cytochromes …

Global Sampling Of The Photochemical Reaction Paths Of Bromoform By Ultrafast Deep-Uv Through Near-Ir Transient Absorption And Ab Initio Multiconfigurational Calculations, Alexander N. Tarnovsky, S. K. Pal, A. S. Mereshchenko, E. V. Butaeva, Patrick Z. El-Khoury

Chemistry Faculty Publications

Ultrafast deep-ultraviolet through near infrared (210-950 nm) transient absorption spectroscopy complemented by ab initio multiconfigurational calculations offers a global description of the photochemical reaction pathways of bromoform following 255-nm excitation in methylcyclohexane and acetonitrile solutions. Photoexcitation of CHBr3 leads to the ground-state iso-CHBr3 product in a large quantum yield (∼35), formed through two different mechanisms: concerted excited-state isomerization and cage-induced isomerization through the recombination of the nascent radical pair. These two processes take place on different time scales of tens of femtoseconds and several picoseconds, respectively. The novel ultrafast direct isomerization pathway proposed herein is consistent with the occurrence of …

1. Chromium(0)- Promoted Higher Order Cycloaddition Reactions: Studies Toward The Total Synthesis Of The Cyclocitrinols And Echinopines A And B 2. Total Synthesis Of (±)-Debromoflustramine B Via [4+1] Cyclization Of An Indole Isocyanate And A Bis(Alkylthio)Carbene, Saptarshi De

Wayne State University Dissertations

A facile and short stereoselective synthesis of the functionalized tetracyclic core structure of the cyclocitrinols, a family of unusual C25 steroid isomers, has been accomplished. The key structural unit, the bicyclo[4.4.1]A/B ring system, was constructed by a regioselective Cr(0)-promoted [6π + 4π] photochemical cycloaddition reaction.

A Bronsted acid catalyzed rearrangement of the 11-trimethylsilyl-tetracyclo[8.1.0.03,7.04,11]undeca-5,8-diene ring system to the unusual homotriquinacene ring system. The trimethylsilyl substitution on the cyclopropane moiety was found to be crucial for the rapid transformation which is believed to proceed via carbocation intermediates.

A short concise formal synthesis of Echinopines A and B is reported. The key [5.5.7] …

Protein-Protein Interactions In The Neocortex: Emx2 And Its Binding Partners, Cierra Miller

Undergraduate Honors Theses

The mammalian neocortex is divided into discrete functional areas that are marked by distinct boundaries and whose positions are assigned through a process called neocortical arealization. One of the proteins involved in this process is Emx2, a transcription factor (protein that turns genes on and off) that is expressed, or made, in a gradient along the axis of the neocortex and determines the positions of these areal boundaries. In order to determine how Emx2 carries out this function of assigning areas, we have identified the proteins QKl-7 and Cnot61 as binding partners of Emx2.

Current research involves confirming the interactions …

Uv-Visible Microscope Spectrophotometric Polarization And Dichroism With Increased Discrimination Power In Forensic Analysis, Dale Kevin Purcell

All Open Access Legacy Dissertations and Capstone Projects

Microanalysis of transfer (Trace) evidence is the application of a microscope and microscopical techniques for the collection, observation, documentation, examination, identification, and discrimination of micrometer sized particles or domains. Microscope spectrophotometry is the union of microscopy and spectroscopy for microanalysis. Analytical microspectroscopy is the science of studying the emission, reflection, transmission, and absorption of electromagnetic radiation to determine the structure or chemical composition of microscopic-size materials. Microscope spectrophotometry instrument designs have evolved from monochromatic illumination which transmitted through the microscope and sample and then is detected by a photometer detector (photomultiplier tube) to systems in which broad-band (white light) illumination …

Studies Of Mercury In Water, Sediment, And Fish In Mississippi: Concentrations, Speciation, Cycling, And Isotopic Composition, Garry Brown

Electronic Theses and Dissertations

The goal of this project is to better understand the biogeochemical cycle of mercury (Hg) in Mississippi to aid those managing the resources and developing related policy. To that end, Hg levels were determined in a total of 202 fish from Enid, Sardis and Grenada Lakes; Enid and Grenada have fish consumption advisories due to Hg. In addition, total-Hg and methylmercury (MeHg) levels were determined in the inflow and outflows from Enid and Sardis Lakes and in bottom sediment and suspended solids in Enid Lake. Potential sources of Hg to Enid Lake were investigated, including precipitation and runoff from urban, …

Online Learning In A Chemical Perceptron, Peter Banda, Christof Teuscher, Matthew R. Lakin

Computer Science Faculty Publications and Presentations

Autonomous learning implemented purely by means of a synthetic chemical system has not been previously realized. Learning promotes reusability and minimizes the system design to simple input-output specification. In this article we introduce a chemical perceptron, the first full-featured implementation of a perceptron in an artificial (simulated) chemistry. A perceptron is the simplest system capable of learning, inspired by the functioning of a biological neuron. Our artificial chemistry is deterministic and discrete-time, and follows Michaelis-Menten kinetics. We present two models, the weight-loop perceptron and the weight-race perceptron, which represent two possible strategies for a chemical implementation of linear integration and …

The Cloning And Expression Of Histone Genes From The Archaeal Organisms Pyrococcus Furiosus And Methanobrevibacter Smithii In The Polycistronic Vector Pst44., Doha Abdullah Alqurashi

Electronic Theses & Dissertations

The Euryarcheota branch of the Archaea contains histone proteins that are highly homologous to eukaryotic histones. Virtually all species within this group have two histone proteins (designated H1A and H2B). These proteins contain a canonical histone fold motif that stabilizes homo- and perhaps hetero-dimeric interactions. Molecular modeling calculations previously carried out in our laboratory revealed that both homo and hetero-dimers of histones from two euryarchaeal organisms are equally plausible. We have also shown through molecular modeling that inter-species hetero-dimers are structurally identical to existing solution structures archaeal histones. An interesting question that needs to be addressed is whether homo- and …

Synthesis And Characterization Of Metal Complexes Containing Tetrazolate, Poly(Tetrazolyl)Borate, And Poly(Azolyl)Aluminate Ligands As High Energy Density Materials, Christopher James Snyder

Wayne State University Dissertations

A series of heavy alkaline earth metal tetrazolate complexes has been synthesized that contain metal ions saturated by aqua ligands. Tetrazolates with small ring-core carbon substituents favor formation of two dimensional polymers with u3-coordination of the tetrazolate to the metal centers. Tetrazolates with bulkier groups block coordination to the 1- and 4-nitrogen atoms, resulting in monomer formation. The first example of a trihydro(tetrazolyl)borate was prepared, and its bonding is heavily influenced by the basic BH3 moiety. 18-Crown-6 adducts of dihydrobis(tetrazolyl)borate complexes have been prepared that contain B-N bonding to the 2-nitrogen atoms, due to bulky ring-core atom substituents. A series …

Synthesis And Characterization Of Transition Metal Arsenide Nanocrystals And The Metastability And Magneto-Structural Phase Transition Behavior Of Mnas Nanocrystals, Yanhua Zhang

Wayne State University Dissertations

This dissertation study focuses on (1) probing the magneto-structural phase transformation in nanoscale MnAs; (2) evaluation of the size-dependent phase stability of type-B MnAs (prepared by rapid injection); and (3) developing a general synthetic method for transition metal arsenide nanoparticles.

Discrete MnAs nanoparticles that adopt different structures at room temperature (type-A, α-structure and type-B, β-structure) have been prepared by the solution-phase arrested precipitation method. Atomic pair distribution and Rietveld refinement were employed on synchrotron data to explore the structural transitions of the bulk and nanoparticle samples, and these results were compared to AC magnetic susceptibility measurements of the samples. The …

Development And Optimization Of The First High Throughput In Vitro Fret Assay To Characterize The Saccharomyces Cerevisiae Gpi-T, Sandamali Amarasingha Ekanayaka

Wayne State University Dissertations

DEVELOPMENT AND OPTIMIZATION OF AN IN VITRO FRET ASSAY TO CHARACTERIZE THE SACCHAROMYCES CEREVISIAE GPI TRANSAMIDASE

By

SANDAMALI AMARASINGHA EKANAYAKA

December 2013

Advisor: Dr. Tamara L. Hendrickson

Major: Biochemistry

Degree: Doctor of Philosophy

The enzyme glycosylphosphatidylinositol transamidase (GPI-T) mediates the attachment of a glycosylphosphatidylinositol (GPI) anchor to the C-terminus of specific proteins to produce GPI anchored proteins. This post-translational modification is essential for viability of eukaryotic organisms. However, very little is known about GPI-T and its catalytic activity. Thus, the research described in this abstract was conducted to develop an in vitro assay to monitor GPI-T. A high-throughput assay for …

Characterization Of A Novel Fusion Protein Of Ipab And Ipad Of Shigella And Its Potential As A Pan-Shigella Vaccine, F. J. Martinez-Becerra, X. Chen, Nicholas E. Dickenson, S. P. Choudhari, K. Harrison, J. D. Clements, W. D. Picking, L. L. Van De Verg, R. I. Walker, W. L. Picking

Chemistry and Biochemistry Faculty Publications

Shigellosis is an important disease in the developing world, where about 90 million people become infected with Shigella spp. each year. We previously demonstrated that the type three secretion apparatus (T3SA) proteins IpaB and IpaD are protective antigens in the mouse lethal pulmonary model. In order to simplify vaccine formulation and process development, we have evaluated a vaccine design that incorporates both of these previously tested Shigella antigens into a single polypeptide chain. To determine if this fusion protein (DB fusion) retains the antigenic and protective capacities of IpaB and IpaD, we immunized mice with the DB fusion and compared …

The Magnitude And Mechanism Of Charge Enhancement Of Ch∙∙O H-Bonds, U. Adhikari, Steve Scheiner

Chemistry and Biochemistry Faculty Publications

Quantum calculations find that neutral methylamines and thioethers form complexes, with N-methylacetamide (NMA) as proton acceptor, with binding energies of 2–5 kcal/mol. This interaction is magnified by a factor of 4–9, bringing the binding energy up to as much as 20 kcal/mol, when a CH3+ group is added to the proton donor. Complexes prefer trifurcated arrangements, wherein three separate methyl groups donate a proton to the O acceptor. Binding energies lessen when the systems are immersed in solvents of increasing polarity, but the ionic complexes retain their favored status even in water. The binding energy is reduced when the methyl …

Oregon Nmr Consortium: A Collaboratory For Nmr Data Acquisition And Processing, R. Carlisle Chambers

Faculty Publications - Department of Biological & Molecular Science

The Oregon NMR consortium was created to provide access to a modern, high-field 400 MHz NMR spectrometer for students and faculty at several two-year and small four-year institutions. Students use both on-site and remote access to conduct their NMR experiments. Remote access involves connecting to the NMR console over the Internet. Features of the consortium are described, including the details of remote access, sample transport, and data processing. This paper also discusses the impact that the access to the NMR spectrometer has had on student achievement of several learning goals in the organic chemistry courses at the partner institutions.

Genetic Engineering Of Proteins For Biotechnology Applications, Yanbo Zhang

Chemistry & Biochemistry Dissertations - Archive

Heme b (protoporphyrin IX or protoheme) plays a major role in the structure and function in proteins such as myoglobin (Mb), hemoglobin (Hb), horseradish peroxidase (HRP), catalase, cytochrome P450 as well as catalase peroxidase (KatG). This highly conjugated porphyrin system forms the cradle for the iron containing prosthetic group of the hemeproteins. Although the surrounding chiral protein scaffold is important in protein reactivity and selectivity, the heme iron prosthetic group creates a focal point for the substrate reactivity.The genetic incorporation of unnatural amino acids (UAA) into proteins in vivo, using the same biosynthetic machinery used by living cells to synthesize …

Characterization Of Flavonoid Reactivities And Degradation Products Using Online Continuous Flow Kinetic Measurements And Higher Order Mass Spectrometry, Jeremy S. Barnes

Chemistry & Biochemistry Dissertations - Archive

Epidemiological studies offer strong evidence that diets rich in fruits and vegetables provide a defense against cardiovascular disease, cancer and other physiological disorders. One theory suggests that these hazards are due in part to an imbalance of the body's oxidative load, caused by an increase in biologically-relevant free radicals, such as reactive oxygen species (ROS). Flavonoids, a family of plant metabolites, are associated with an antioxidant capacity which could reduce oxidative stress and aging. Quercetin, a flavonol with one of the highest rated antioxidant characteristic, was used as a model system to evaluate the reactivity of flavonoids in the presence …

Studies Towards The Total Synthesis Of Haploscleridamine And Ceratinadin B, Xiaofeng Meng

Chemistry & Biochemistry Dissertations - Archive

In Chapter 1, we discuss the synthesis of haploscleridamine. Haploscleridamine is a novel tryptamine-derived alkaloid isolated from a sponge of the order Haplosclerida. This alkaloid inhibits cathepsin K, a cysteine protease, which is involved in the catabolism of elastin, collagen, and gelatin allowing the breakdown of bone and cartilage. Cathepsin K "blockers" show great potential in the treatment of osteoporosis. Building off earlier studies, we adopted a novel application of the Buchwald indole synthesis instead of a traditional Fischer indole synthesis to construct the â-carboline fragment. Starting from L-histidine, after several steps including a ring closing metathesis, a cyclohexanone was …

Crystalline Sico: Implication On Structure And Thermochemistry Of Ternary Silicon Oxycarbide Ceramics, Nelli Bodiford

Chemistry & Biochemistry Theses - Archive

The need for innovative refractory materials - materials that can sustain extreme temperatures - has been constantly growing within the modern industries. Basic requirements for usage at ultra-high-temperatures have been considered such as high melting point, high structural strength, exceptional resistance to oxidation, zero or almost zero creep. Monolithic ceramics alone cannot provide these properties, therefore, composite materials are sought to fulfill the demand. For example, silicon nitride and silicon carbide based ceramics have long been leading contenders for structural use in gas turbine engines. In the course of this work we are investigating amorphous SiCO formed via polymer-to-ceramic route. …

A Non-Heme Diiron Monooxygenase From Salmonella Typhimurium: Biochemical Characterization Of Trna-Modifying Miae, Siai Zhang

Chemistry & Biochemistry Theses - Archive

MiaE is a carboxylate bridged, non-heme diiron monooxygenase which catalyzes the O2-dependent hydroxylation of a hypermodified tRNA nucleoside at position 37 (2-methylthio-N-6-isopentenyl adenosine (37)-tRNA) [designated ms²i⁶A₃₇] to produce ms²i⁶A₃₇. In Salmonella typhimurium, synthesis of ms²i⁶A₃₇ requires a multi-step enzyme-catalyzed process that includes two other enzymes, MiaA and MiaB. Therefore, to study the hydroxylation step in this reaction pathway, all the elements within this reaction pathway (tRNA substrate, MiaA, MiaB, and MiaE) are required. In this work, methods for in vitro tRNA synthesis were developed for the biosynthesis of viable MiaA/MiaB/MiaE substrates. Additionally, the enzymes MiaA and MiaB were recombinantly cloned, …

Investigation Of The Role Of Polyelectrolytes In The Stabilization Of Reactive Redox Species, James Siegenthaler

Undergraduate Honors Theses

The stabilization of electrochemically reactive compounds can lead to new breakthroughs in energy storage technology. This study focused on the oxidation­reduction (redox) stabilization of indigo tetrasulfonate (ITS) from oxidation by oxygen, by forming a columbic complex with, poly(diallyldimethylammonium chloride) (poly(DADMAC)). Cyclic voltammetry was investigated as a tool to analyze such a complex solution of electrochemically active macromolecules. Complex scans were taken of poly(DADMAC) to ITS at 1 :20, 1 :6. 7 and 11: 13 molar ratios. Comparison of the redox potentials from the cathodic and anodic sweeps show that the redox of ITS is non­reversible. The presence of the polyelectrolyte …

Oil Pollution In Water Bodies Of Restricted Circulation, Michael A. Kruge

Department of Earth and Environmental Studies Faculty Scholarship and Creative Works

Coastal lagoons and embayments near urban centers around the world share many common characteristics and problems. Physical impediments to free water circulation (spits, barrier islands, internal islands, tombolos, submerged sills) often lead to water stagnation and, in the presence of excess nutrients, eutrophication. Urban and industrial activities provoke (usually accidental) spills of hazardous materials into these confined water bodies, such as crude petroleum and refined petroleum products, leading to difficulties for resident biota and potential hazards for human health. The sluggish turnover of these water bodies (or low-energy zones within them) may retard the natural attenuation of the spilled contaminants. …

Computational Approaches To Anti-Toxin Therapies And Biomarker Identification, Rebecca Jane Swett

Wayne State University Dissertations

This work describes the fundamental study of two bacterial toxins with computational methods, the rational design of a potent inhibitor using molecular dynamics, as well as the development of two bioinformatic methods for mining genomic data.

Clostridium difficile is an opportunistic bacillus which produces two large glucosylating toxins. These toxins, TcdA and TcdB cause severe intestinal damage. As Clostridium difficile harbors considerable antibiotic resistance, one treatment strategy is to prevent the tissue damage that the toxins cause. The catalytic glucosyltransferase domain of TcdA and TcdB was studied using molecular dynamics in the presence of both a protein-protein binding partner and …

Adding Gas Chromatography-Mass Spectrometry Data To A Melting Point And Thin-Layer Chromatography Laboratory, Adam M. Azman, Julie A. Barrett, Megan Darragh, John J. Esteb

Scholarship and Professional Work - LAS

The addition of gas chromatography–mass spectrometry (GC–MS) data interpretation to a thin-layer chromatography (TLC) and melting point (mp) laboratory for an introductory organic course is described.

Synthesis Of 1-Pyrenyldiazomethane For Derivatization Of Short-Chain Fatty Acids, Mary E. Kalvaitis

Senior Honors Theses and Projects

Use of I-pyrenyldiazomethane (PDAM) for derivatizing short-chain fatty acids (SCFA) is a successful way to analyze complex SCF A samples quickly and with minimal sample preparation. The costs associated with ordering PDAM from a commercial source can be high, typically more than $300 not including shipping costs. This project developed a simple two-step synthesis procedure that can be used in undergraduate chemistry laboratories. We found that the PDAM produced by this procedure is pure enough to use for our derivatization needs without further purification. This synthesis can be used to further explore the use of PDAM for fast and simple …

The Rich Chemistry Of Cyclotriveratrylene (Ctv) And Ct-Inspired Reactions: Anthracenes With Organic Light-Emitting Diode (Oled) Applications And The Discovery Of Cascade Reactions, Samuel Sarsah

Dissertations

Cyclotriveratrylene (CTV) is a supramolecular scaffold with applications in host-guest chemistry, analytical detection, drug delivery and liquid crystals. We have discovered that CTV rearranges to a highly functionalized anthracene derivative that is ideal for the synthesis of 9,10-disubstituted anthracene derivatives that are useful for the construction of organic light-emitting diodes (OLEDs). Several diaryl anthracene derivatives have been synthesized and analyzed, and were found to have excellent electroluminescent properties, including one analog that exhibits an exceptionally high quantum yield. Red, green and blue are the primary colors needed for full color display, but blue fluorescence emitting organic compounds used in OLEDs …

Revisiting The Fundamentals In The Design And Control Of Nanoparticulate Colloids In The Frame Of Soft Chemistry, Vuk Uskoković

Pharmacy Faculty Articles and Research

This review presents thoughts on some of the fundamental features of conceptual models applied in the design of fine particles in the frames of colloid and soft chemistry. A special emphasis is placed on the limitations of these models, an acknowledgment of which is vital in improving their intricacy and effectiveness in predicting the outcomes of the corresponding experimental settings. Thermodynamics of self-assembly phenomena illustrated on the examples of protein assembly and micellization is analyzed in relation to the previously elaborated thesis that each self-assembly in reality presents a co-assembly, since it implies a mutual reorganization of the assembling system …