PRISM :: Browsing by Author "Heyne, Belinda"

Browsing by Author "Heyne, Belinda"

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Open Access
Assessing Ryanodine Receptor Inhibition and Antioxidant Ability of Carvedilol and its Abilities
(2016) Malig, Thomas; Back, Thomas George; Ling, Chang-Chun; Derksen, Darren; Heyne, Belinda
The antioxidant ability of the commonly prescribed antiarrhythmic medication carvedilol was assessed using two distinct assays. The first assay monitored the depletion of the stable radical DPPH via hydrogen atom abstraction utilizing UV-VIS spectrophotometry. The second assay involved monitoring the inhibition of a radical chain reaction initiated by UV light. Three metabolites of carvedilol were synthesized and assessed in each assay along with carvedilol and several benchmark antioxidants to ensure assay validity. It was determined that carvedilol possessed negligible antioxidant ability in both assays, while the metabolites possessed moderate-high antioxidant strength. It is therefore concluded that the antioxidant ability of carvedilol originates from the phenolic metabolites and not from carvedilol itself. The primary function of carvedilol to regulate calcium handling in cardiac myocytes was also assessed for each metabolite using a mutant embryonic cell line. It was determined that metabolic deactivation via hydroxylation pathways is minimal.
Open Access
Assessment of r-process sensitivity studies and metrics
(2020-09-04) Osakwe, Carlton-James U.; Ouyed, Rachid; Hobill, David W.; Cully, Christopher M.; Heyne, Belinda
Understanding the r-process is essential to understanding the early Universe. Sensitivity studies are important to developing this understanding, but they are hindered by discrepancies in how their results are reported. The fundamentals of the r-process and sensitivity studies are described. These discrepancies are explored in detail. We primarily discuss the way sensitivity is quantified and the normalization of results. The need for consistent results is asserted, and the issues with inconsistent results are made evident. The discrepancies themselves suggest various future avenues of study. We conclude with several recommendations for consistent reporting of sensitivity studies.
Open Access
Biophysical analysis on the interaction of polymeric nanoparticles with biomimetic models of the human lung surfactant
(2019-11) Daear, Weiam; Prenner, Elmar J.; Anikovskiy, Max; Heyne, Belinda; Ildiko, Badea; Noskov, Sergei Yu
The human body offers many paths that could be used for drug delivery. The pulmonary route, which is delivery through the lungs, provides many advantages such as; 1) direct access to the lungs and blood circulation and 2) large surface area with a thin barrier of about 500 nm thick. These advantages, in addition to increased patient compliance with inhaled medications, have sparked interest in this route in the field of nanomedicine. Nanoparticles are drug delivery vehicles with many advantages over conventional drug delivery methods. These include the high surface area to volume ratio due to their small size and potential for specific targeting. In the pulmonary route, the air blood barrier is composed of three main layers. The top layer or first point of interaction is through the lung surfactant (LS). This monolayer is composed of 90% lipids and 10% proteins. The lung surfactant’s major role is to reduce surface tension experienced in the lung during breathing cycles in order to prevent lung collapse. Therefore, if nanoparticles are to pass through this monolayer, effects on its stability need to be assessed. In this thesis, a biomimetic model of the LS is developed and its interaction with two biodegradable and biocompatible nanoparticles is tested. Biophysical analysis on the interaction includes the use of Langmuir monolayer pressure-area isotherms, surface potential measurements and visualization through Brewster angle microscopy. Results show that interactions and effects on monolayer elasticity are strongly dependent on electrostatic interactions, charge density of the monolayer, lipid headgroup structure and acyl chain saturation.
Open Access
Biophysical Characterization of Nanoparticle Interactions with Lung Surfactant Models for Enhanced Pulmonary Drug Delivery
(2017) Lai, Patrick; Prenner, Elmar J.; Edwards, Robert Allan; Amrein, Matthias; Heyne, Belinda; Lavasanifar, Afsaneh
Inhalable nanoparticles for drug delivery has shown promising results in the treatment of lung disease. The impact of these small sized drug carriers on the lungs is remains unclear. One of the first barriers that nanoparticles will encounter upon inhalation is the lung surfactant that lines each alveolus. This is a single molecule layer of lipids and proteins that forms at the air-water interface on top of the alveolar lining fluid. Its main role is to lower surface tension preventing the collapse of the alveoli during the breathing cycle. Impairing surfactant function results in collapse of the alveolar sacs leading to respiratory distress. The aim of the thesis was to use in vitro studies to identify which components of lung surfactant that are potentially impacted or influenced by the presence of nanoparticles. This was conducted using a model system for lung surfactant made up for phosphatidylcholine, phosphatidylglycerol and the neutral lipid cholesterol. This was compared to a clinical surfactant BLES that is used in surfactant replacement therapy. Surface activity was measured using a Langmuir trough with two Teflon barriers to mimic the air-water interface and compress the surfactant monolayer. Imaging of the monolayer was conducted with Brewster angle microscopy to visualize changes in the organization of the surfactant models. Gelatin and polyisobutylcyanoacrylate nanoparticles are both biocompatible materials that have been tested for inhalable drug delivery and are used in these experiments. In vitro testing was done to evaluate three different methods of adding nanoparticles to the surfactant monolayer to develop a better in vitro model to study nanoparticle surfactant interactions. These nanoparticles were either mixed with surfactant before application on the trough, added to the subphase or sprayed from the air as dry powder. Cholesterol was found to play a major role in nanoparticle-surfactant interactions by enhancing the formation of spike-like structures from the surfactant monolayer. The Langmuir trough was shown to be a useful tool for studying in vitro interactions. Further optimization of the spraying dry powder nanoparticles onto the Langmuir trough can potentially be a useful tool in vitro tool to predict potentially harmful in vivo effects
Open Access
Chemical Modifications of Cyclodextrins for Ion Conduction, Sensing and Metal Sequestration
(2019-08-14) Champagne, Pier-Luc; Ling, Changchun; Derksen, Darren J.; Heyne, Belinda; Li, Quan; Shimizu, George K. H.
Supramolecular assemblies generally consist of molecules held together via non-covalent interactions of various strengths. These assemblies possess an astonishing variety of potential applications in numerous fields. In this thesis, several families of new cyclodextrin (CD) derivatives were synthesized, characterized and discussed. The novel derivatives were prepared with the intention to study their supramolecular assembly in solid states and solutions and develop novel applications. In the solid states, studies on structure-property relationships uncovered the influence of substitution patterns of amphiphilic CDs on their ability to form various liquid crystalline mesophases. A novel family of amphiphilic CD-based liquid crystals bearing O-acetylated oligoethylene glycol (OEG) chains at the secondary face is presented in Chapter Three. Unlike most of the previously reported liquid crystals based on chemically modified CDs which rely on H-bonding as the primary intermolecular force, the present CD derivatives self-assemble into highly ordered smectic liquid crystal phases via the weaker dipole-dipole intermolecular forces. The obtained materials were found to possess much improved properties, such as improved thermostability, reduced clearing temperatures and better fluidity. Chapter Four reports another family of amphiphilic CDs bearing O-acetylated oligoethylene glycol chain by inverting the substitution patterns on β-CDs by simply placing hydrophobic chains to the secondary face and O-acetylated OEG groups at the primary face; we showed that it is possible to transform the nature of mesophases from smectic to columnar. This investigation reveals some intriguing properties of CD scaffolds as a unique class of host mesogens. In addition to introducing OEG groups to CDs, we also attempted to introduce an OEG linker to the known cholesterol mesogen in Chapter Five to obtain either monomeric or dimeric cholesterol mesogens which showed interesting LC properties. A portion of this monograph focused on the potential applications of amphiphilic CD-based liquid crystalline materials. To this aim, we extended the design of our systems by introducing different functional groups at the end of OEG chains. For example, in Chapters Six to Eight, a group amphiphilic CD bearing non-polar alkyl chains at the primary face while multiple OEG groups of different lengths, terminated with a polar nitrile group, was developed; the addition of a nitrile functionality at the end of each OEG chain was found to increase the stability and temperature range of the mesophases; we found the smectic mesophases formed by these novel amphiphilic CDs have great ability to act as electrolytes for the conduction of lithium (Chapter Six and Eight) as well as sodium (Chapter Seven). Furthermore, when the terminal nitrile functionality was replaced with a carboxylic acid, a new family of amphiphilic CD polycarboxylic acids was obtained which constitutes the main topic of Chpater Nine; the introduction of numerous carboxylic acid functionalities at the secondary face of CD serves as a preorganization, that facilitate the formation of complex intra- and intermolecular hydrogen-bond networks in the formed smectic mesophases; introducing water molecules in the mesophases further strengthen H-bond networks by bridging adjacent carboxylic acids groups. We investigate the ability of this novel system for proton conduction and have found very encouraging results. Following our work using different amphiphilic CD-based LC materials for ion-conductions, we noticed that the room temperature crystalline phase can significantly affect the conductive properties of the material. Thus, we designed novel CD heptols displaying liquid crystalline phases at room temperature by inserting unconventional alkyl groups such as those containing cis-alkenic or/and branches at the secondary face. The newly synthesized series of amphiphilic CD derivatives were estimated to have crystal-liquid crystalline transitions below -40 °C. This research is the first to shed light on how to affect the mesomorphic properties of amphiphilic CDs with alkyl groups of bent conformation or containing branches. Copper (I)-mediated alkyne-azide 1,3-dipolar cycloaddition (CuAAC) reaction was used as the key reaction for the prepartion of all amphiphilc CD derivatives mentioned above. By taking adavantage of the methodology, Chapter Eleven reports an extension of my thesis work by investigating the synthesis of a novel chemically modified polyaminocarboxylate based on beta-CD scaffold using CuAAc and its coordination chemistry for lanthanides. A 1,2,3-triazolmethyl residue was created from each CuAAc reaction that advantageously serves as a competent chelating group while displacing the metal coordination center away from the primary rim of β-CD. With the participation of four N-acetate groups from two adjacent glucopyranosyl units of β-CD, a unique octavalent coordination sphere was created to bind each lanthanide with high affinity, while the lanthanide metal still has one open site available for dynamic water coordination. Furthermore, the CuAAC chemistry allowed us the synthesize another pyrene-appended β-CD fluorescent probe (Chapter Twelve), which self-assembles into nanoaggregates in water driven by hydrophobic π–π interactions. The formed fluorescent nanoaggregates were found to exhibit an efficient and selective ratiometric detection of pirimicarb, a potent toxic carbamate pesticide as well as differentiating nitro-aromatic explosives such as 2,4,6-trinitrotoluene (TNT), 1,3,5-trinitrobenzene (TNB) and picric acid (PA).
Open Access
Conjugated Organic Molecules Containing Imide Functional Groups for Organic Electronics
(2017) Hendsbee, Arthur; Welch, Greg; Sutherland, Todd; Heyne, Belinda; Li, Yuning; Ling, Chang-Chun
This thesis discusses the exploration of new, electron deficient molecular materials that can be used as active components in organic electronics. Chapter one of this thesis will introduce the concept of organic electronics and introduce preliminary design principles. In chapter two, the design and synthesis of an electron deficient small molecule based on a phthalimide-thiophene architecture (M1) is presented and physical properties pertinent to organic electronics are discussed. In chapter three, structurally related derivatives of the phthalimide-thiophene architecture are explored as electron transporting materials, where the number of thiophene units in the molecule as well as the alkyl chain lengths are varied (M2-M5). In chapter four, the M2 architecture is modified by changing the thiophene units for furan units, towards the goal of creating a more sustainable electron transporting material (M6). Chapters five and six discuss the effect of incorporating dye-fragments into the previously discussed molecular architecture to create a range of electron deficient dyes (M7-M17). Finally, in chapter seven, by making use of the combined knowledge obtained from previous work, an N-Annulated perylene diimide material (M18-M19) is presented which can be used as the electron accepting component in high organic solar cells that, depending on the choice of donor material, display power conversion efficiencies of up to 7.6 %.
Open Access
Cytotoxic, Cellular Uptake, and Photophysical Properties of Various Re(I) Tricarbonyl Complexes
(2019-09-20) Capper, Miles S.; Jalilehvand, Farideh; Heyne, Belinda; Roesler, Roland; Gailer, Jürgen; Derksen, Darren J.
A series of Re(I) tricarbonyl complexes with the general formula, fac-[Re(CO)3(2,2’-bipyridine)(X)]-/0 (X= L-cysteine; N-acetyl-L-cysteine; thiosulfate) were characterized using spectroscopic techniques and single-crystal X-ray diffraction. Photophysical, as well as singlet oxygen (1O2) generation and CO releasing properties were assessed. Cell viability of the complexes against the MDA-MB-231 breast cancer cell line were determined. Cellular localization and accumulation were investigated using synchrotron-based X-ray fluorescence microscopy (XFM). The results of this study show the cytotoxicity, cellular uptake and photophysical properties of fac-[Re(CO)3(bpy)X]+/0/- complexes (X= H2O, HCys-, NAC2-, S2O32-; bpy=2,2’-bipyridine). The cytotoxicity of fac-[Re(CO)3(bpy)(H2O)]+ is diminished when the aqua ligand is replaced by cysteine or thiosulfate.
Open Access
Cytotoxicity, cellular localization and photophysical properties of Re(I) tricarbonyl complexes bound to cysteine and its derivatives
(Springer Nature, 2020-06-24) Capper, Miles S.; Enriquez Garcia, Alejandra; Macia, Nicolas; Lai, Barry; Lin, Jian-Bin; Nomura, Masaharu; Alihosseinzadeh, Amir; Ponnurangam, Sathish; Heyne, Belinda; Shemanko, Carrie S.; Jalilehvand, Farideh
The potential chemotherapeutic properties coupled to photochemical transitions make the family of fac-[Re(CO)3(N,N)X]0/+ (N,N = a bidentate diimine such as 2,2'-bipyridine (bpy); X = halide, H2O, pyridine derivatives, PR3, etc.) complexes of special interest. We have investigated reactions of the aqua complex fac-[Re(CO)3(bpy)(H2O)](CF3SO3) (1) with potential anticancer activity with the amino acid l-cysteine (H2Cys), and its derivative N-acetyl-l-cysteine (H2NAC), as well as the tripeptide glutathione (H3A), under physiological conditions (pH 7.4, 37 °C), to model the interaction of 1 with thiol-containing proteins and enzymes, and the impact of such coordination on its photophysical properties and cytotoxicity. We report the syntheses and characterization of fac-[Re(CO)3(bpy)(HCys)]·0.5H2O (2), Na(fac-[Re(CO)3(bpy)(NAC)]) (3), and Na(fac-[Re(CO)3(bpy)(HA)])·H2O (4) using extended X-ray absorption spectroscopy, IR and NMR spectroscopy, electrospray ionization spectrometry, as well as the crystal structure of {fac-[Re(CO)3(bpy)(HCys)]}4·9H2O (2 + 1.75 H2O). The emission spectrum of 1 displays a variance in Stokes shift upon coordination of l-cysteine and N-acetyl-l-cysteine. Laser excitation at λ = 355 nm of methanol solutions of 1–3 was followed by measuring their ability to produce singlet oxygen (1O2) using direct detection methods. The cytotoxicity of 1 and its cysteine-bound complex 2 was assessed using the MDA-MB-231 breast cancer cell line, showing that the replacement of the aqua ligand on 1 with l-cysteine significantly reduced the cytotoxicity of the Re(I) tricarbonyl complex. Probing the cellular localization of 1 and 2 using X-ray fluorescence microscopy revealed an accumulation of 1 in the nuclear and/or perinuclear region, whereas the accumulation of 2 was considerably reduced, potentially explaining its reduced cytotoxicity.
Open Access
Decomposition of Hexamethyldisilazane on Hot Metal Filaments and its Gas-phase Chemistry in a Hot-wire Chemical Vapor Deposition Reactor
(2019-09-04) Ampong, Eric; Shi, Yujun; Marriott, Robert A.; Heyne, Belinda; Thurbide, Kevin B.
Hot-wire chemical vapor deposition (HWCVD) has been used to produce silicon-containing thin films, nanomaterials, and functional polymer coatings for applications in microelectronic and photovoltaic devices. Silicon carbonitride (SiCyNz) thin films, deposited by HWCVD, have found a wide range of applications due to their nonstoichiometric component that exhibits unique properties from a combination of SiC and Si3N4 binary compounds. Most CVD growth of SiCyNz proceeds through the use of separate Si-containing (SiH4), C-bearing (CH4) and NH3 precursors. Handling of pyrophoric silane is difficult, and the process optimization with multiple source gases is extremely complex. This has urged interest in exploring alternative single-source precursors for SiCyNz deposition. 1,1,1,3,3,3-Hexamethyldisilazane (HMDSZ), a non-pyrophoric and non-corrosive molecule, is one of the single-source precursors for use in HWCVD of SiCyNz thin films. In this work, single-photon ionization using vacuum ultraviolet wavelength at 118 nm coupled with time-of-flight mass spectrometry is employed to examine the products from primary decomposition on tungsten and tantalum filaments under collision-free conditions and from secondary gas-phase reactions in a HWCVD reactor. It has been shown that HMDSZ decomposes on the heated metal filaments to produce methyl radicals via Si-CH3 bond cleavage. The methyl radical formation is controlled by surface reactions at filament temperatures ranging from 1600 to 2400 oC. The activation energy for the formation of methyl radicals on the W and Ta filament has been determined to be 71.2 ± 9.1 to 76.7 ± 8.1 kJ/mol, respectively. A comparison with the theoretical energy (363 kJ/mol) required for the homolytic cleavage of Si-CH3 bond in the gas phase indicates that the dissociation of HMDSZ on the W and Ta surfaces to produce methyl radicals is a catalytic cracking process. Aside from the homolytic cleavages, other decomposition routes of HMDSZ, both concerted and stepwise ones, have been systematically explored in this work. The concerted formation of trimethylsilylamine and 1,1-dimethylsilene was found to be the most kinetically favorable route of all, with an activation barrier of 278 kJ/mol. It is also interesting to find that both the elimination of CH3 radical from a methylated silylamino radical and elimination of H atom from the C atom attached to a Si atom in a silyl radical site proceed without an activation barrier. In the secondary gas-phase reactions, radical-radical and radical-molecule reactions are dominant. Formation of 1,1-dimethylsilanimine ((CH3)2Si=NH) was detected from the HWCVD reactor when HMDSZ was introduced. 1,1-dimethylsilanimine undergoes head-to-tail cycloaddition and nucleophilic addition reaction with the abundant HMDSZ molecules to form 1,1,3,3-tetramethylcyclodisilazane and octamethyltrisilazane that were both detected in this work. The secondary gas-phase reactions are also characterized by a free radical short-chain reaction initiated by the primary decomposition of HMDSZ on the metal filaments to produce methyl radicals. Hydrogen abstraction by methyl radical is the main propagation step in the reactor, and biradical recombination reactions terminate the chain reaction to form various stable products with high molecular masses that were also detected in this work.
Open Access
Development of a new fluorescent tool box based on tocopherol
(2012) Sveen, Christopher Edward; Heyne, Belinda; Zaremberg, Vanina
Research into Vitamin E and its in-vivo function has recently exploded, focusing mostly on the biologically relevant isomer, a-tocopherol ( a-T). Although a-T is well known for its radical scavenger role in membranes, new roles of a-T not related to its antioxidant activity have been proposed. Much of this research has been slowed down due to the lack of readily accessible tools for the study of this Vitamin in vivo. Thus, our goal was to develop a toolbox of fluorescent tocopherol derivatives, either redox-active or silent, to be used for live studies. The fluorophore of choice was nitrobenzoxadiazole (NBD). After the successful synthesis and characterization of derivatives, the efficacy of several promising probes was tested in-vivo. Structural features relevant for intracellular localization were identified. In addition, the poorly understood photochemistry of NBD was investigated using laser flash photolysis on the simple probe NBD-hexane, revealing a novel phosphorescence process not previously described.
Open Access
Development of Poly (vinylidene fluoride) and Poly(vinyl pyrrolidone) based Solid Polymer Electrolyte for the Next Generation of Solid-state Sodium ion Battery
(2023-01-05) Bristi, Afshana Afroj; Thangadurai, Venkataraman; Shi, Yujun; Heyne, Belinda
Solid-state sodium-ion batteries (ss-SIBs) are a promising alternative to commercially available lithium-ion batteries for next-generation energy storage applications due to the abundance and cost-effectiveness of sodium over lithium. Good electrochemical, mechanical, electrode compatibility, interfacial, and thermal stability properties of the solid form of electrolytes are considered as prerequisites to develop ss-SIBs. Among the organic and inorganic solid electrolytes, solid polymer electrolytes (SPE) are being considered as the promising ones based on the versatility of polymer materials and their potential optimization scope. However, low ionic conductivity and high interfacial resistance are the key drawbacks of typical SPEs. In this thesis, using a facile solution casting fabrication process, a high sodium-ion conductive, filler-less composite solid polymer electrolyte (SPE) film based on poly (vinylidene fluoride) polymer, poly (vinyl pyrrolidone) (PVP) binder, and NaPF6 salt has been studied for ss-SIB. A systematic characterization was carried out to investigate the microstructure and electrochemical properties of PVDF and PVP based SPEs via electrochemical impedance spectroscopy (EIS), scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis (TGA), and Raman spectroscopy techniques. Total conductivities of 8.51 × 10–4 and 8.36 × 10–3 S cm–1 at 23 and 83 °C, respectively, were observed from the developed SPE. Obtained low activation energy (Ea) value suggests that in the composite polymer matrix Na-ion can easily be diffused. Identified β- and γ-phases of the PVDF polymer in the composite SPE matrix indicates the polar nature of the host polymer, which is believed to play an important role in decreasing the crystallinity as well as enhancing the Na+ conductivity. A hybrid symmetric half-cell assembly using Na electrode, 1 M NaClO4 in ethylene carbonate (EC) and propylene carbonate (PC) (EC/PC = 1:1 wt. %) and with SPE showed excellent Na plating–stripping performance at 10 mA cm–2 at 23 °C. A hybrid full cell with a SPE, a Na anode, and a Na3V2(PO4)3 cathode were assembled in a coin cell and electrochemical performance was evaluated.
Open Access
Discovering Compatible Environments for Dye Molecules: From the Spectroscopic Evaluation of Ionic Aggregates to the Enhancement of Singlet Oxygen
(2014-04-30) Mooi, Sara Michelle; Heyne, Belinda
The specific light absorbing capabilities of molecules has been taken advantage of numerous times in scientific literature, as interesting photophysical and photochemical phenomena can be easily recognized and characterized through optical spectroscopy. Consequently, small light absorbing molecules have shown to be valuable tools in the field of self-organization and aggregation as often these processes results in specific spectral signatures of these molecules. Cyanine dyes have been used predominantly in this regard as their photophysical properties are heavily influenced based on their environmental surroundings. This basic principle is the foundation for this work, where small cationic cyanine dyes are utilized to understand what drives the organization of molecules into aggregate structures. Herein, we present evidence that aggregation of multiple cyanine dyes can be encouraged by the addition of both simple and complex electrolytes, a phenomenon not fully investigated in the literature thus far. Specifically, the aggregation of cationic cyanine dyes seems to be a direct reflection of the molecular structure of the dye itself in addition to its ability to form a contact ion pair with a counter ion. The formation of a contact ion pair is pivotal in the aggregation process, and is a result of similarity between both the dye and the counter ion water affinity. Additionally, our work aimed at pushing the limits of soluble aggregates to form organic nanoparticles, which were found to maintain the redox ability of their ionic counterparts. From here we crossed into the field of metallic nanoparticles and where the light absorbing properties and subsequent photochemistry of a dye, Rose Bengal, was altered by covalently linking it to a core-shell nanoparticle. These experiments lead to the proof-of-principle that the singlet oxygen production of Rose Bengal could be enhanced in aqueous solution when in close proximity to a metal nanoparticle.
Open Access
Effects of manganese on the biophysical and biochemical properties of biologically relevant membranes and yeast
(2023-04-26) Sule, Kevin Charles Macam; Prenner, Elmar Josef; Zaremberg, Vanina; Fraser, Marie; Heyne, Belinda; Thewalt, Jenifer
Metal ion-membrane interactions have gained appreciable attention over the years with increasing interest in the mode of action of toxic and essential metals. Lipids are a potential metal binding targets leading to altered lipid-lipid interactions or lateral membrane organization. Despite its essentiality, manganese (Mn2+) stress can induce deleterious impact towards cell survival. The mechanisms by which Mn2+ exert damage at the biomolecular level are not fully understood. Thus, the goal of this thesis was to investigate the effects of the essential trace metal Mn2+ on model lipid systems comprised of zwitterionic and anionic glycerophospholipids, complex biological extracts and yeast (S. cerevisiae). The data shows that Mn2+ was able to rigidify bilayer membranes containing negatively charged lipids, in a dose dependent manner, in both simple and complex model membranes. In simple model membranes, liposome swelling, and extensive aggregation were also detected for some lipids. This documents that on top of electrostatic attraction, the detailed lipid structure in terms or charge location and side chain architecture needs to be considered. Moreover, Mn2+ caused both an expansion and condensation of phosphoinositide containing monolayers, whilst inducing lateral disorganization by abolishing lipid domains. The potential negatively impacting such domains that are essential for a multitude to signalling processes is an important result as well. Mn2+ was able to alter the impact of binary metal mixtures with Ca2+ and Mg2+ on selected liposomes. Metal induced changes in membrane rigidity depended on the details of lipid structure and differed for single metals or binary mixtures. This suggests that the impact of metals will depend on the localized lipid composition and the presence of other ions. Mn2+ was also found to catalyze lipid peroxidation in complex systems via Fenton reaction. Lastly, growth, organelle morphology, and lipid content were disrupted by Mn2+ stress on the model cell S. cerevisiae, suggesting both direct and indirect effects on membrane properties. This thesis contributed to a better understanding of Mn2+ effects on biological membranes and yeast that can be consequential for their proper structural and signalling functions and ultimately cell survival. This work also opens avenues for future research in these areas.
Open Access
Exploring the Factors Influencing the Plasmon-Enhanced Production of Singlet Oxygen by Developing Model Hybrid Photosensitizer-Metal Nanoparticles
(2020-01-20) Macia, Nicolas; Heyne, Belinda; Trudel, Simon; Anikovskiy, Max; Turner, Raymond Joseph; Boudreau, Denis
Singlet oxygen is arguably one of the most important and well-studied electronically excited species in the molecular realm. The photochemistry and photophysics of the lowest and most stable excited-state of molecular oxygen are remarkable from many perspectives, from its high reactivity against organic substrates to its emission signature in the near-infrared. Singlet oxygen is a ubiquitous, yet highly dichotomic reactive species, as it is both beneficial and harmful to life. To advance our comprehension of singlet oxygen’s complex biological roles and to expand and improve upon its applications, efficient production and detection of this reactive species are important prerequisites. However, the successful achievement of these goals is hindered by the forbidden character of the photophysical events leading to its production and emission. Plasmonics, the science of controlling light at subwavelength dimensions by excitation of surface plasmons in nanostructures, has emerged over the past few decades as a unique tool to boost the efficiency of a plethora of intrinsically weak phenomena, including the production of singlet oxygen. The overreaching goal of the work presented within this thesis is to advance our understanding of how plasmonic nanostructures enhance the production of singlet oxygen. To investigate the puzzling mechanisms governing this phenomenon, a model hybrid photosensitizer-metal nanoparticle which can efficiently enhance the production of singlet oxygen via plasmonic effects was developed. The design of this model system consists of a spherical metal core@silica shell nanoparticle, decorated with an efficient singlet oxygen photosensitizer, Rose Bengal. The robust and highly tunable architecture of this model system has allowed the synthesis of a library of hybrid nanoparticles made of different silica shell thicknesses, core shapes and core compositions. Through the numerous iterations of the hybrid nanoparticle’s design, a set of structure-property relationships was established. For instance, the dependence on the separation distance between the photosensitizer and the metal nanoparticle on the plasmon-enhanced singlet oxygen production was unveiled, revealing that an optimal effect is reached when the photosensitizer is located at approximately 10 nm from the nanoparticle. Furthermore, the greater amplification effect of plasmonic hot-spots on the production of singlet was demonstrated by changing the nanoparticle’s core shape from a symmetric spherical-based morphology to an anisotropic cubic-based one. Also, modifying the core composition by using Ag, Au and their AuAg alloy spherical nanoparticles made the model system an efficient tool to investigate for the first time the plasmon-enhancement of singlet oxygen production in terms of its intrinsic plasmonic near- and far-field properties. Finally, by performing a meta-analysis on the data obtained for a library of hybrid photosensitizer-metal nanoparticles, a quantification of the plasmonic effect on the singlet oxygen production was achieved. Altogether, these studies lead to an unprecedent interpretation of the plasmon-enhancement of singlet oxygen production in terms of the morphological parameters (shell and core size; core shape and composition) and the plasmonic properties (hot-spots, near- and far-fields) of a model system. Ultimately, this new applied and fundamental knowledge establish a first set of rules for a more rational design of hybrid photosensitizer-metal nanoparticles, which can extend to other photosensitizer’s nanoplatforms to boost singlet oxygen production.
Open Access
Generation and Transformations of Cationic Heteroaromatic Molecules
(2019-04-10) Hogan, David Thomas; Sutherland, Todd C.; Heyne, Belinda; Derksen, Darren J.; Shimizu, George K. H.
This thesis contains three chapters, each of which has been published in relevant journals. While the applications of each chapter are unrelated to one-another, the compounds involved fall under the broad class of cationic heteroaromatics either by using such systems directly (chapters one and two) or by forming them during investigation (chapter three). Instead of employing novel methods, the synthetic focus was to use the simplest and shortest possible routes, both to save material and extend the time available for characterization. Investigations in the first two chapters involved reduction electrochemistry, transforming the cationic heteroaromatic compounds into the analogous heteroatomic radicals or anions. How easily this could be accomplished and how long the nascent radicals/anions lived after generation drove the studies. The third chapter is unique because it involves no electrochemistry – instead solely photophysics – and starts with neutral organic compounds, generating the cationic analogues as a method of sensing metal cations.
Open Access
How to blow out a molecular lantern: interaction of aequorea victoria green fluorescent protein and its variants with singlet oxygen
(2012) Valencia-Perez, Adriana Zulema; Heyne, Belinda
Herein, we studied the interaction between Aequorea victoria Green Fluorescent Proetein and some of its mutants with exogenous single oxygen using spectroscopic and electrophoretic techniques. According to our results, exogenous 02 mainly oxidizes the ??-barrel of the proteins, resulting in formation of a covalent protein dimer. Further characterization of the underlying mechanism utilizing monomeric variants, suggested the interface of the natural occurring dimer as the initial area of oxidation, specifically the histidine in position 148 (H148). By mutating this residue to a less reactive side chain, its involvement in the 02 mediated mechanism was corroborated. The reactivity of endogenous 02 towards fluorescent proteins, was also analyzed by direct excitation of the proteins chromophores. Spectroscopy data suggested a variety of complex mechanisms, including generation of 02 and photodecarboxylation, occurring upon irradiation of the protein. Taken together, these results indicate that production of exogenous and/or endogenous 02 during standard imaging techniques influences fluorescent proteins, which could deteriorate the data obtained from the studied system.
Open Access
Mapping the Unexplored Reactivity Landscape of Benzo[ghi]perylene
(2024-04-16) Hogan, David Thomas; Sutherland, Todd Christopher; Derksen, Darren; Heyne, Belinda; Thurbide, Kevin; Zhao, Yuming
This thesis describes the learning opportunities, failures, and successes surrounding a polycyclic aromatic hydrocarbon of interest, benzo[ghi]perylene. Neglected in the chemical synthesis literature but fundamentally interesting due to its composition and molecular symmetry, the work contained herein contributes a small work to a small field. The efforts are found in three chapters for three chronologically and ideologically related topics: the construction and optimization of a flow photoreactor to produce benzo[ghi]perylene; the exploration of structure and reactivity of benzo[ghi]perylene; the development of a strategy to improve the flow photochemical productivity of benzo[ghi]perylene.
Open Access
Nonlinear Optics in III-V Photonic Resonators
(2021-12) McLaughlin, Blaine; Barclay, Paul; Barclay, Paul; Oblak, Daniel; Simon, Christoph; Heyne, Belinda
Nonlinear nanophotonics seeks to utilize the many useful nonlinear optical phenomena in integrated photonic devices. A particular field of interest is the use of resonant microcavities for nonlinear frequency generation in the telecommunication and visible ranges. The use of microresonator devices with high quality factors and small mode volumes allows for the considerable enhancement of nonlinear processes and high degrees of spatial overlap between resonator modes, leading to highly efficient conversion processes at low optical powers. Among the common photonic materials, the class of III-V semiconductor materials possess ideal properties for telecom-visible conversion, such as wide transparency windows leading to low absorption across these ranges, as well as large nonlinear electromagnetic susceptibilities. In addition, III-V materials with zincblende crystal structures allow for phase matched harmonic generation due to the crystal symmetry. In this work I study nonlinear harmonic generation processes in resonant microcavities made from gallium phosphide (GaP), a III-V semiconductor crystal with a zincblende structure. This study culminates in the simultaneous generation of second and third harmonic signals from a telecom pump in a GaP microdisk. Through resonance spectroscopy via a coupled fiber taper, we observe the generation of second and third harmonic signals at 778 and 519 nm from a 1557 nm telecom pump. Analysis of the resonant output power scaling and calculations of nonlinear inter-modal coupling factors via FDTD simulations allows us to attribute the signals to second harmonic and a cascaded sum frequency generation respectively. This work represents the first realization of efficient third harmonic generation in a GaP microresonator device.
Open Access
Novel Strategies using Micro Pressurized Liquid Extraction to Rapidly Prepare Solid Samples for Analysis
(2020-10-12) Taylor, Bradley Mark; Thurbide, Kevin B.; Heyne, Belinda; Marriott, Robert A.
This thesis will describe several advancements in solid-liquid extraction methods using new applications of a micro preparative technique. The overall aim is to reduce solvent consumption and analysis times to promote quick, low solvent approaches to solid sample preparation. Additionally, this technique will be shown to integrate directly with chromatographic instruments to promote a hands-free analysis approach. In particular, the first portion of this thesis explores a novel on-line micro pressurized liquid extraction method that directly interfaces solid sample preparation with high performance liquid chromatography. The technique employs rapid heating to remove analytes from milligram quantities of sample in as little as 20-40 seconds. As applications, the system was applied to a variety of solid samples including pharmaceutical tablets, green tea leaves, and samples containing polycyclic aromatic hydrocarbons. This micro preparative approach will be shown to provide rapid, quantitative extractions when compared to conventional methods. Frequently, total analysis times for a given sample can be as quick as 95 seconds which represents a large improvement over techniques such as Soxhlet or conventional pressurized liquid extraction. Next, a method that combines on-line micro pressurized liquid extraction with solid phase trapping will be introduced. Rapid heating will be again employed to extract analytes of interest from milligram quantities of solid samples before internally transferring this extract to a solid phase trap. Analyte will be shown to effectively absorb and concentrate on this solid phase material before it is subsequently desorbed/injected to high performance liquid chromatography for analysis. As a result, samples with low level analytes will be shown to have greatly improved detection limits which facilitates their characterization and analysis. Several applications of this method will be presented, and the results will indicate that on-line micro pressurized liquid extraction – solid phase extraction can facilitate coupling to high performance liquid chromatography and provide rapid sample preparation using little solvent.
Open Access
Perovskite-type Cathode Material for Intermediate Temperature Solid Oxide Fuel Cells
(2020-05) Abubaker, Orrsam Aadil; Thangadurai, V.; Birss, Viola; Heyne, Belinda
Solid oxide fuel cells (SOFCs) are an alternative energy device that transforms chemical energy to electrical energy without the conventional combustion step. SOFCs can do this with an efficiency of 60 - 80%. However, the temperature of operation (800 - 1000 oC) reduces the lifetime and puts sever restrictions on the material available for use. Ideally SOFCs would need to operate at a more intermediate temperature (IT) range between (500 – 750 oC) to maintain their fuel flexibility and have a reasonable lifetime to compete with conventional energy methods but, the reduction in temperature results in sluggish oxygen reduction reaction (ORR) activity for conventional SOFC cathodes. Due to the sluggish ORR of conventional cathodes, new materials are being introduced and studied to act as cathodes for SOFCs. The primary criteria for an SOFC cathode are the ability to act as a mixed ionic electronic conductor (MIEC), stability in an oxygen atmosphere, a porous microstructure, high catalytic activity towards the oxygen reduction reaction (ORR) and thermal cyclability. One material that has received attention is the perovskite-type structure because of its high tunability through doping while maintaining the same structure. The effect of Cu-substitution in Ba0.5Sr0.5Fe1-xCuxO3-δ (BSFCux, 0 ≤ x ≤ 0.20) on the phase, microstructure, cyclability and electrochemical performance was investigated using a series of methods to determine the feasibility of this material acting as a solid oxide fuel cell (SOFC) cathode. Powder X-ray diffraction showed the formation of a cubic perovskite (space group: Pm-3m, No. 221). This material has illustrated cyclable oxygen uptake and releasing properties that were studied using TGA. The microstructure was studied using SEM which showed a porous structure along with minor changes based on copper content. The symmetrical cells Ba0.5Sr0.5Fe1-xCuxO3-δ+LSGM|LSGM|Ba0.5Sr0.5Fe1-xCuxO3-δ+LSGM were tested for their electrochemical performance using EIS in ambient air. A trend of decreasing area specific resistance (ASR) with decreasing copper content was observed. 4-probe DC measurements were used to study the conductivity of Ba0.5Sr0.5Fe1-xCuxO3-δ in varying atmospheres. These measurements showed an increase in conductivity with increasing copper content and an increase in conductivity with an increasing pO2. The effect of sintering temperature (900-1100 °C) on the electrochemical performance and microstructure was studied for Ba0.5Sr0.5Fe0.95Cu0.05O3-δ+LSGM and Ba0.5Sr0.5Fe0.8Cu0.2O3-δ+LSGM. Plots of log ASR vs. pO2 were used to evaluate the rate determining steps in the oxygen reduction/oxygen evolution reactions (ORR/OER).