Physical Sciences and Mathematics Commons^™

Changes In Enzyme Structural Dynamics Studied By Hydrogen Exchange-Mass Spectrometry: Ligand Binding Effects Or Catalytically Relevant Motions?, Courtney S Fast, Siavash Vahidi, Lars Konermann

Chemistry Publications

It is believed that enzyme catalysis is facilitated by conformational dynamics of the protein scaffold that surrounds the active site, yet the exact nature of catalytically relevant protein motions remains largely unknown. Hydrogen/deuterium exchange (HDX) mass spectrometry (MS) reports on backbone H-bond fluctuations. HDX/MS thus represents a promising avenue for probing the relationship between enzyme dynamics and catalysis. A seemingly straightforward strategy for such studies involves comparative measurements during substrate turnover and in the resting state. We examined the feasibility of this approach using rabbit muscle pyruvate kinase (rM1-PK) which catalyzes the conversion of phosphoenolpyruvate and Mg-ADP to pyruvate and …

Adsorbed Gas Behaviour And Guest-Host Interactions In Ultramicroporous Metal-Organic Frameworks, Bligh Desveaux

Electronic Thesis and Dissertation Repository

Metal-organic frameworks (MOFs) are a class of porous materials that have attracted much attention due to their large surface areas, high tunability and their high selectivity for gas adsorption applications. In this work, solid-state nuclear magnetic resonance (SSNMR) experiments and single crystal X-ray diffraction (SCXRD) experiments are used to investigate carbon dioxide adsorption within the ultramicroporous MOFs SIFSIX-3-Zn (Chapter 2) and ZnAtzOx. (Chapter 3). Analysis finds that the CO₂ SIFSIX-3-Zn undergoes wobbling motions with a low temperature dependence, and in ZnAtzOx undergoes wobbling and hopping motions with a low temperature dependence. SCXRD is used to precisely determine the CO …

Fabrication And Modification Of Titania Nanotube Arrays For Harvesting Solar Energy And Drug Delivery Applications, Ahmed El Ruby Abdel Rahman Mohamed

Electronic Thesis and Dissertation Repository

The fast diminishing of fossil fuels in the near future, as well as the global warming caused by increasing greenhouse gases have motivated the urgent quest to develop advanced materials as cost-effective photoanodes for solar light harvesting and many other photocatalytic applications. Recently, titania nanotube arrays (TNTAs) fabricated by anodization process has attracted great interest due to their excellent properties such as: high surface area, vertically oriented, highly organized, one-dimensional, nanotubular structure, photoactivity, chemical stability and biocompatibility. This unique combination of excellent properties makes TNTAs an excellent photoanode for solar light harvesting. However, the relatively wide band gap energy of …

The Development Of Peptide Analogues As Potential Fluorescent And Pet Imaging Probes., Neha Sharma

Electronic Thesis and Dissertation Repository

Molecular imaging is a non-invasive way to diagnose disease. Molecular imaging probes consist of a targeting entity that has a high affinity for a biological target and a signaling source for external detection. Multimodality imaging combines the advantages of different imaging modalities, at the same time eliminating their shortcomings, thereby providing more accurate results. This thesis focuses on the development of novel dual PET/fluorescence imaging agents based on peptides as targeting entities.

Porphyrins are suitable for multimodality imaging applications due to their innate characteristics such as an ability to fluoresce and to coordinate metals. A gallium-protoporphyrin IX(PPIX)-ghrelin based analogue was …

Effect Of Counter Ions On The Self-Assembly Of Polystyrene-Polyphosphonium Block Copolymers, Benjamin Hisey, Jasmine V. Buddingh, Elizabeth R. Gillies, Paul J. Ragogna

Chemistry Publications

The ability to manipulate block copolymers on the nanoscale has led to many scientific and technological advances. These include nano-scale ordered bulk and thin films and also solution phase components, these are promising materials for making smaller ordered electronics, selective membranes, and also biomedical applications. The ability to manipulate block copolymer material architectures on such small scales has risen from thorough investigations into the properties that affect the architectures. Polyelectrolytes are an important class of polymers that are used to make amphiphilic block copolymers. In this context the authors synthesized polystyrene-b-polyphosphonium block copolymers with different anions coordinated to …

Studying Metal-Organic Frameworks Via Solid-State Nmr: Gas Dynamics, Structure Determination, And Phase Transition, Yue Zhang

Electronic Thesis and Dissertation Repository

Metal-organic frameworks (MOFs) are a class of microporous materials constructed from virtually endless combinations of metal centres and organic linkers. MOFs have attracted intense research interest in recent decades, since MOFs have outstanding properties such as extremely high surface area, tuneable pore topology, good stability, and many others. MOFs are also promising candidates for gas storage. In this work, solid-state NMR (SSNMR) spectroscopy has been investigated to study MOFs and their guest molecules, since SSNMR can provide information on the short-range environment about target nuclei and can also reveal the dynamics of guest molecules.

An introduction to MOFs and SSNMR …

1,6-Diphenyl-1,3,5-Hexatriene (Dph) As A Novel Matrix For Maldi Ms Imaging Of Fatty Acids, Phospholipids, And Sulfatides In Brain Tissues., Hanadi Ibrahim, Kristina Jurcic, Jasmine S-H Wang, Shawn N Whitehead, Ken K-C Yeung

Chemistry Publications

1,6-Diphenyl-1,3,5-hexatriene (DPH) is a commonly used fluorescence probe for studying cell membrane-lipids due to its affinity toward the acyl chains in the phospholipid bilayers. In this work, we investigated its use in matrix-assisted laser desorption/ionization (MALDI) as a new matrix for mass spectrometry imaging (MSI) of mouse and rat brain tissue. DPH exhibits very minimal matrix-induced background signals for the analysis of small molecules (below m/z of 1000). In the negative ion mode, DPH permits the highly sensitive detection of small fatty acids (m/z 200-350) as well as a variety of large lipids up to m/z of 1000, including lyso-phospholipid, …

Tip-Enhanced Raman Spectroscopy Of Amyloid Β At Neuronal Spines., Mohammadali Tabatabaei, Fabiana A Caetano, Farshid Pashee, Stephen S G Ferguson, François Lagugné-Labarthet

Chemistry Publications

The early stages of Alzheimer's disease pathogenesis are thought to occur at the synapse level, since synapse loss can be directly correlated with memory dysfunction. Considerable evidence has suggested that amyloid beta (Aβ), a secreted proteolytic derivative of amyloid precursor protein, appears to be a critical factor in the early 'synaptic failure' that is observed in Alzheimer's disease pathogenesis. The identification of Aβ at neuronal spines with high spatial resolution and high surface specificity would facilitate unraveling the intricate effect of Aβ on synapse loss and its effect on neighboring neuronal connections. Here, tip-enhanced Raman spectroscopy was used to map …

Tip-Enhanced Raman Spectroscopy Of Amyloid Β At Neuronal Spines., Mohammadali Tabatabaei, Fabiana A Caetano, Farshid Pashee, Stephen S G Ferguson, François Lagugné-Labarthet

Chemistry Publications

The early stages of Alzheimer's disease pathogenesis are thought to occur at the synapse level, since synapse loss can be directly correlated with memory dysfunction. Considerable evidence has suggested that amyloid beta (Aβ), a secreted proteolytic derivative of amyloid precursor protein, appears to be a critical factor in the early 'synaptic failure' that is observed in Alzheimer's disease pathogenesis. The identification of Aβ at neuronal spines with high spatial resolution and high surface specificity would facilitate unraveling the intricate effect of Aβ on synapse loss and its effect on neighboring neuronal connections. Here, tip-enhanced Raman spectroscopy was used to map …

Coordination And Organometallic Chemistry Of Novel Gallium Complexes: Synthesis, Reactivity And Spectroscopy, Jeremy L. Bourque

Electronic Thesis and Dissertation Repository

The work described in this thesis incorporates three main themes: the synthesis and reactivity of new coordination and organometallic gallium compounds, and the chemical state determination of molecular gallium complexes using XPS and XAS. The coordination chemistry of low valent gallium cations was explored using macrocyclic ethers as ligands. The experimental oxidation number, or chemical state, of newly synthesized low valent gallium cationic complexes was compared to known compounds to allow for the assessment of the electronic environment at gallium. The organometallic chemistry of gallium was examined using donor ligands to stabilize monomeric organogallium(III) compounds, demonstrating the ability to substitute …

Gamma-Radiation Induced Corrosion Of Alloy 800, Mojtaba Momeni

Electronic Thesis and Dissertation Repository

This thesis presents a newly developed mechanism and predictive model for the corrosion of Alloy 800. The Fe-Cr-Ni Alloy (Incoloy 800) is mainly used for steam generator (SG) tubing in CANDU and PWR reactors and is a candidate material for the proposed Canadian Supercritical Water Reactor (SCWR) in which it will be exposed to extreme conditions of high radiation flux and large temperature gradients. The influence of gamma radiation and water chemistry conditions on the corrosion behaviour of Alloy 800 are studied in this work. Ionizing radiation creates reducing (•e_aq^–, •H, •O₂^-) and oxidizing …

Cytochrome C As A Peroxidase: Activation Of The Precatalytic Native State By H, Victor Yin, Gary S Shaw, Lars Konermann

Chemistry Publications

In addition to serving as respiratory electron shuttle, ferri-cytochrome c (cyt c) acts as a peroxidase; i.e., it catalyzes the oxidation of organic substrates by H₂O₂. This peroxidase function plays a key role during apoptosis. Typical peroxidases have a five-coordinate heme with a vacant distal coordination site that permits the iron center to interact with H₂O₂. In contrast, native cyt c is six-coordinate, as the distal coordination site is occupied by Met80. It thus seems counterintuitive that native cyt c would exhibit peroxidase activity. The current work scrutinizes the origin of this …

Dendritic Plasmonics For Mid-Infrared Spectroscopy, Francois Lagugne-Labarthet, Gregory Q. Wallace, Hayden C. Foy, Scott M. Rosendahl

Chemistry Publications

Metallic nanostructures that exhibit tailored optical resonances spanning from the near to mid-infrared spectral range are of particular interest for spectroscopic and optical measurements in these spectral domains that can benefit from localized surface-enhancement effects. Plasmon resonances shifted in the near or mid-infrared range could be used to further enhance the excitation and/or the emission of an optical process. Surface-enhanced infrared absorption (SEIRA) is one of such processes and can particularly benefit from plasmon-enhanced local fields yielding an increase in sensitivity towards the detection of an analyte. Herein, we have fabricated a series of gold dendritic nanostructures, prepared by electron-beam …

Thermo-Responsive Self-Immolative Nanoassemblies: Direct And Indirect Triggering, Bo Fan, John F. Trant, Gauvin Hemery, Olivier Sandre, Elizabeth R. Gillies

Chemistry Publications

A thermo-responsive end-cap based on a retro-Diels-Alder and subsequent furan elimination reaction was developed. It was used to cap poly(ethyl glyoxylate), allowing end-to-end depolymerization upon thermal triggering. Using block copolymers, thermo-responsive micelles and vesicles were prepared and shown to disassemble upon heating. Thermal degradation could also be triggered indirectly by magnetic field hyperthermia after incorporation of iron oxide nanoparticles into the assemblies.

Dynamic Studies Of Guest Molecules In Metal-Organic Frameworks And Zeolites Via Solid-State Nuclear Magnetic Resonance, Bowei Wu

Electronic Thesis and Dissertation Repository

Metal-organic frameworks (MOFs) are synthetic compounds with crystalline microporous structures, consisting of metal centres joined by organic linkers. Zeolites are a class of crystalline porous materials featuring negatively charged aluminosilicate frameworks and charge-balancing cations.

In this work, solid-state nuclear magnetic resonance (SSNMR) is used to probe guest molecule locations and dynamics in MOFs and zeolites, yielding detailed informations of guest motion within these porous materials

Chapter 2 describes SSNMR dynamic studies of ¹³CO₂, ¹³CO and C₂D₄ adsorption behaviour in the α - zinc formate MOF, [Zn₃(HCOO)₆], which were performed …

Aluminum Complexes Of N2o23‒ Formazanate Ligands Supported By Phosphine Oxide Donors, Ryan Maar, Amir Rabiee Kenaree, Ruizhong Zhang, Yichen Tao, Benjamin D. Katzman, Viktor N. Staroverov, Zhifeng Ding, Joe Gilroy

Chemistry Publications

The synthesis and characterization of a new family of phosphine-oxide-supported aluminum formazanate complexes (7a, 7b, 8a, 9a) are reported. X-ray diffraction studies revealed that the aluminum atoms in the complexes adopt an octahedral geometry in the solid state. The equatorial positions are occupied by an N₂O₂^3‒ formazanate ligand, and the axial positions are occupied by L-type phosphine oxide donors. UV-vis absorption spectroscopy revealed that the complexes were strongly absorbing (ε ~ 30,000 M^‒1 cm^‒1) between 500 and 700 nm. The absorption maxima in this region were simulated using …

Determining The Reactivity And Oxidation Intermediates Of An Allylnickel (N-Heterocyclic Carbene) Chloride Complex, Scott W. E. Hendriks

Electronic Thesis and Dissertation Repository

The oxidation of C-H bonds to carbonyl functional groups using molecular oxygen (O₂) is a desirable process as O₂ is environmentally benign and inexpensive. However, oxidations that employ O₂ have lower product selectivity, making it industrially unappealing. The metal complexes NiCl(π-cinnamyl)(NHC) oxidize stoichiometrically with O₂ as the oxidant to selectively form the ketone and aldehyde products.

This thesis details the attempted catalysis with the NiCl(π-allyl)(NHC) complex and the stoichiometric reactivity of NiCl(π-allyl)(NHC) and NiCl(π-cinnamyl)(NHC) complexes upon O₂ exposure. An investigation of the intermediate and decomposition species of the NiCl(π-allyl)(NHC) complex was conducted. The complexes …

Investigations Into The Role Of Conformational Dynamics In Protein Function: Insights From Hydrogen/Deuterium Exchange-Mass Spectrometry, Courtney S. Fast

Electronic Thesis and Dissertation Repository

Deciphering protein structure and dynamics is a key prerequisite for understanding biological function. The current work aims to apply HDX-MS to improve the understanding of protein structure and dynamics for systems that remain challenging for other techniques. Following a general overview of the field (Chapter 1), Chapter 2 investigates the relationship between enzyme dynamics and catalysis. By conducting comparative HDX-MS measurements on rM1-PK during substrate turnover and in the resting state, catalytically active rM1-PK undergoes significant rigidification of the active site. However, virtually the same rigidification was seen upon exposing rM1-PK to substrate or product in the …

Boron Difluoride Adducts Of A Flexidentate Pyridine-Substituted Formazanate Ligand: Property Modulation Via Protonation And Coordination Chemistry, Stephanie M. Barbon, Jasmine V. Buddingh, Ryan R. Maar, Joe Gilroy

Chemistry Publications

The synthesis and characterization of a flexidentate pyridine-substituted formazanate ligand and its boron difluoride adducts, formed via two different coordination modes of the title ligand, are described. The first adduct adopted a structure that was typical of other boron difluoride adducts of triarylformazanate ligands and contained a free pyridine subsituent, while the second was formed via chelation of nitrogen atoms from the formazanate backbone and the pyridine substituent. Stepwise protonation of the pydridine-functionalized adduct, which is essentially non-emissive, resulted in a significant increase in the fluorescence quantum yield up to a maximum of 18%, prompting study of this adduct as …

Fabrication And Characterization Of Cuins₂ And Cuinse₂ Light-Absorbing Thin Films For Use In Solar Cells, Amy R. Tapley

Electronic Thesis and Dissertation Repository

Solar energy is free and globally abundant and harnessed cost-effectively, it has the potential to be the world’s main source of energy. CuInGa(S,Se)₂ solar cells have a very high efficiency of 20 %. However, gallium is a rare and expensive element. We have decided to work on its alternative CuInSe₂ (CISe) and CuInS₂ (CIS) by removing gallium or both gallium and selenium. The p-type CISe or CIS light-absorbing semiconducting layer is crucial for this type of solar cell. Preparation methods for CIS and CISe films were developed to reduce the costs and enhance the photoelectrochemical efficiency.

The …

Synthesis Of N-Heterocycles From Donor Acceptor Cyclopropanes And Progress Towards Flinderole A, B, And C, Joanne E. Curiel Tejeda

Electronic Thesis and Dissertation Repository

The first chapter of this thesis describes two projects, one explores the novel reactivity of quaternary donor acceptor cyclopropanes and the second one involves progress toward the total synthesis of the flinderoles A, B, and C. The first project involves the Lewis acid catalyzed nucleophilic ring opening of quaternary donor acceptor cyclopropanes with indoline. It was found that the ring opening reaction worked well with either Sc(OTf)₃ or Yb(OTf)₃ as the Lewis acids. The ring opened products were also able to be converted into pyrroloindoles via a manganese (III) oxidative radical cyclization reaction. Cyclopropanes bearing alkynyl, vinyl, and …

Investigating Growth Of Metal-Organic Frameworks Via Atomic Force Microscopy, Zitong Wang

Electronic Thesis and Dissertation Repository

Metal-organic frameworks (MOFs) are crystalline microporous materials that have drawn much attention in recent years for their promising applications in many fields of chemistry. To design MOFs with desired properties, a better understanding of how these frameworks self-assemble during crystallization is required. A useful technique for investigating the crystallization process of MOFs is atomic force microscopy (AFM). We have conducted AFM studies on four different MOFs: the gallium analog of the MIL-53 MOF, which exhibits the "breathing effect," and three Lead, Calcium and Cadmium-based MOFs that uses 4,4-sulfonyldibenzoate (SDB) as the organic ligand. Hydrothermal methods were used to prepare those …

Scanning Electrochemical Microscopy Of Human Bladder Cancer (T24) Cells, Michelle S. M. Li

Electronic Thesis and Dissertation Repository

Scanning electrochemical microscopy (SECM) employs a biased ultramicroelectrode (few nm to 25 µm diameter) as a probe that is scanned over a sample to electrochemically characterize its physical properties and chemical reactivity with high temporal and spatial resolutions. In this dissertation, SECM was used to investigate the membrane responses of single live human bladder cancer (T24) cells to obtain insights into their topography, physiology and pathology.

First, the membrane-impermeable ferrocene carboxylate was used as the SECM redox mediator to investigate the geometry and topography of these cells along with 3D finite elemental analysis (FEA) simulations. The use of 3D simulation …

Addressing A Common Misconception: Ammonium Acetate As Neutral Ph "Buffer" For Native Electrospray Mass Spectrometry., Lars Konermann

Chemistry Publications

Native ESI-MS involves the transfer of intact proteins and biomolecular complexes from solution into the gas phase. One potential pitfall is the occurrence of pH-induced changes that can affect the analyte while it is still surrounded by solvent. Most native ESI-MS studies employ neutral aqueous ammonium acetate solutions. It is a widely perpetuated misconception that ammonium acetate buffers the analyte solution at neutral pH. By definition, a buffer consists of a weak acid and its conjugate weak base. The buffering range covers the weak acid pK_a ± 1 pH unit. NH₄⁺ and CH₃-COO^- are …

Molecular Dynamics Simulations On Gas-Phase Proteins With Mobile Protons: Inclusion Of All-Atom Charge Solvation., Lars Konermann

Chemistry Publications

Molecular dynamics (MD) simulations have become a key tool for examining the properties of electrosprayed protein ions. Traditional force fields employ static charges on titratable sites, whereas in reality, protons are highly mobile in gas-phase proteins. Earlier studies tackled this problem by adjusting charge patterns during MD runs. Within those algorithms, proton redistribution was subject to energy minimization, taking into account electrostatic and proton affinity contributions. However, those earlier approaches described (de)protonated moieties as point charges, neglecting charge solvation, which is highly prevalent in the gas phase. Here, we describe a mobile proton algorithm that considers the electrostatic contributions from …

Calcium-Mediated Control Of S100 Proteins: Allosteric Communication Via An Agitator/Signal Blocking Mechanism., Yiming Xiao, Gary S Shaw, Lars Konermann

Chemistry Publications

Allosteric proteins possess dynamically coupled residues for the propagation of input signals to distant target binding sites. The input signals usually correspond to "effector is present" or "effector is not present". Many aspects of allosteric regulation remain incompletely understood. This work focused on S100A11, a dimeric EF-hand protein with two hydrophobic target binding sites. An annexin peptide (Ax) served as the target. Target binding is allosterically controlled by Ca²⁺ over a distance of ∼26 Å. Ca²⁺ promotes formation of a [Ca₄ S100 Ax₂] complex, where the Ax peptides are accommodated between helices III/IV and III'/IV'. …

Construction And Analysis Of Accurate Exchange-Correlation Potentials, Sviataslau V. Kohut

Electronic Thesis and Dissertation Repository

Practical Kohn–Sham density-functional calculations require approximations to the exchange-correlation energy functional, E_XC[ρ], or the exchange-correlation potential, v_XC(r), defined as the functional derivative of E_XC[ρ] with respect to the electron density, ρ. This thesis focuses on the following problems: (i) development of approximate exchange-correlation potentials by modelling the exchange-correlation charge distribution; (ii) accurate approximation of functional derivatives of orbital-dependent functionals; (iii) generation of exchange-correlation potentials from many-electron wavefunctions; (iv) analysis of accurate exchange-correlation potentials in atoms and molecules.

The advantage of modelling the exchange-correlation potential through the exchange-correlation …

Poly(Ethyl Glyoxylate) Solid-Core Particles For Drug Delivery, Michael Thomas Gambles

Electronic Thesis and Dissertation Repository

The ability to trigger the degradation of polymeric nanoparticles (NPs) by a specific stimulus can provide a method of improved drug targeting and selective release capabilities in vivo. The challenge for most polymeric drug delivery systems remains the necessity for many stimuli events to trigger the release of cargo. Polymeric nanotechnology containing “self-immolative polymers” looks to alleviate the reliance on high concentrations of stimuli by undergoing complete end-to-end depolymerization via a single stimulus-mediated reaction of an end-cap. Herein, NPs were developed using poly(ethyl glyoxylate) (PEtG) blended with poly(d,l-lactic acid) (PLA) to encapsulate a hydrophobic cargo to be released upon …

(Co)Polymers Containing Boron Difluoride 3-Cyanoformazanate Complexes: Emission Enhancement Via Random Copolymerization, Joe Gilroy, Samantha Novoa

Chemistry Publications

Ring-opening metathesis polymerization was used to produce polymers bearing an asymmetrically substituted boron difluoride 3-cyanoformazanate complex. The polymers were found to retain many of the unique characteristics of molecular boron difluoride complexes of 3-cyanoformazanates, including intense light absorption at ca. 560 nm and reversible electrochemical reductions implicating the radical anion and dianion forms of the formazanate complexes in the repeating unit of the polymer backbone. The polymers were also found to be emissive, with emission maxima centred at ca. 665 nm. The monomer employed in this study had a fluorescence quantum yield of 30%, while homopolymers were weakly emissive and …

Design And Synthesis Of Hyaluronan:Rhamm Interaction Inhibitors, Emily Rodrigues

Electronic Thesis and Dissertation Repository

A major component of the extracellular matrix is hyaluronan, a regulator of cell migration/survival and differentiation during response-to-injury processes. The receptor for hyaluronan-mediated motility (RHAMM) binds to HA and has limited constitutive expression but is upregulated during tissue injury. Blocking HA fragment:RHAMM interactions has therapeutic potential for treating cancer but truncation of RHAMM into peptides mimicking only the HA binding domains is predicted to lose their natural α-helical structure. The goal of this project is to explore the effects cyclizing each binding domain has on helicity and its biological effect. Eighteen peptides were synthesized and cyclized using lactam bridges. The …