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Probing the dynamics and conformational landscape of neuronal nitric oxide synthaseSobolewska-Stawiarz, Anna January 2014 (has links)
Rat neuronal nitric oxide synthase (nNOS) is a flavo-hemoprotein that catalyses the NADPH and O2-dependent conversion of L-arginine (L-arg) to L-citrulline and nitric oxide (NO) via the intermediate N-hydroxyarginine. nNOS is a homodimer, where the subunits are modular and are comprised of an N-terminal oxygenase domain (nNOSoxy) that binds iron protoporphyrin IX (heme), (6R)-5,6,7,8-tetrahydro-biopterin (H4B) and L-arg, and a C-terminal flavoprotein or reductase domain (nNOSred) that binds NADPH, FAD and FMN. Regulation of NO biosynthesis by nNOS is primarily through control of interdomain electron transfer processes in NOS catalysis. The interdomain electrons transferred from the FMN to the heme domain are essential in the delivery of electrons required for O2 activation (which occurs in the heme domain) and the subsequent NO synthesis by NOS. Both spectroscopic and kinetic approaches have been used in studying the nature and control of interdomain electron transfer, reaction mechanism and structural changes during catalysis in WT and R1400E nNOS in both full length (FL) and nNOSred. Cytochrome c reduction activity of nNOS was used to determine kinetic parameters for NADPH for FL and nNOSred, WT and R1400E nNOS in the presence and absence of calmodulin (CaM). FL nNOS, where both domains (nNOSred and nNOSoxy) were present, was proven to be more stable and more catalytically efficient than nNOSred by itself. Additionally it was observed that R1400E is still promoting electron transfer despite being thought to lower the affinity of the enzyme to the substrate (NADPH); R1400E also showed lower catalytic efficiency and lower dependence on CaM/Ca2+ compared to the WT. The structure of the functional output state has not yet been determined. In the absence of crystallographic structural data for the NOS holoenzyme, it was important to experimentally determine conformational changes and distances between domains in nNOS. A pulsed EPR spectroscopy (PELDOR) approach has been utilised to gain important and unique information about the conformational energy landscape changes in nNOS. In the presence of CaM, PELDOR results for FL WT nNOS shows a complex energy landscape with multiple conformational states, while in the absence of CaM the interflavin distance distribution matches that exhibited by nNOSred CaM- in the presence of NADP+, suggesting that CaM binding affects some major large-scale conformational changes which are involved in internal electron transfer control in nNOS. A high-pressure stopped-flow technique was also used to perturb an equilibrium distribution of conformational states, to observe the effect of the pressure on the internal electron transfer and to study the kinetics of NADPH oxidation, flavin reduction by NADPH and NO formation. It was shown that high pressure is forcing major changes in the conformational energy landscape of the protein, affecting internal electron transfer. NO formation studies under pressure show that the R1400E mutation in FL nNOS may be affecting protein/NADPH affinity and flavin reduction, but it has no effect on the heme reduction step.
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Size-controllable growth of ZnO nanorod arrays and their surface modifications =: ZnO納米柱陣列可控生長與表面修飾. / ZnO納米柱陣列可控生長與表面修飾 / CUHK electronic theses & dissertations collection / Size-controllable growth of ZnO nanorod arrays and their surface modifications =: ZnO na mi zhu zhen lie ke kong sheng zhang yu biao mian xiu shi. / ZnO na mi zhu zhen lie ke kong sheng zhang yu biao mian xiu shiJanuary 2010 (has links)
At last, a thermal evaporation method that modifies the surface of ZnO nanorods and forms core shell structure is developed, which structure constitutes the photoelectrode for solar energy application. Single crystal ZnO nanorods are uniformly covered by wurtzite polycrystalline CdxZn1-x SySe1-y layer. The band gap of the shell can be systematically tuned from 2.5 to 1.7 eV by varying its composition, as suggested by the optical extinction measured of the samples. The type II band alignment between the ZnO core and the alloy shell enables effective photo-generated charge carrier separation, and the single crystalline ZnO nanorod array provides a direct electrical pathway for the photo-injected electron transport. The nanocable solar cells exhibited short-circuit current ∼0.2 mA/cm 2 and open-circuit voltages of 0.45 V when illuminated with 100 mW/cm 2 simulated AM 1.5 spectrum. / Green emission is observed from the ZnO nanorods synthesized by both methods, which is commonly attributed to the surface defect emission from the nanostructure. We modify surface of the nanorods with SiO 2 and investigate the relation between green emission and the surface defect. However, the surface passivation fails to reduce the green emission significantly, suggesting that surface defects of ZnO are not necessarily responsible for the green emission, but the interior structure quality of the ZnO nanorods decides the luminescence behavior. / In this study, a solution chemistry based method to grow aligned ZnO nanorod arrays on Zn foil is developed at first. Effects of various growth parameters, including the temperature, solution composition and the concentration of individual components on the morphology, structural quality, and properties of the ZnO nanorods are studied. The average diameter of the nanorods in the array can be tuned from ∼20 nm to ∼150 nm by systematically changing the growth conditions. Nanorods with larger diameters are found to be of better structural quality as compared to the smaller diametered ones, as suggested by the cathodoluminescence measurement. Following similar logic, a vapor transport deposition route on controllable fabricating of the ZnO nanorod arrays is investigated. The average diameter of the ZnO nanorods can be tuned from less than 40 nm to larger than submicron, by controlling the fabrication conditions. Larger-diametered nanorods that grow on higher temperature zone are found to possess higher band edge to defect emission ratio. / One dimensional (1D) ZnO nanostructure becomes a research focus in recent years. On the one hand, ZnO itself possesses structural, electrical and optical properties that make it useful for a diverse range of technological applications. On the other hand, semiconductor nanowire owns many advantages, such as superiority in electron transport and its high surface to volume ratio. Aligned ZnO 1D nanostructures on conducting substrates are of special interests, as they are easy to be integrated into devices, directly working as functional unit. / Jiao, Yang. / Adviser: Li Quan. / Source: Dissertation Abstracts International, Volume: 72-04, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 107-109). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / Jiao, Yang.
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First principles study of ZnO and graphene based interfacial electronic structures for nanoelectronics. / 面向納米電子學的基於氧化鋅和石墨烯界面電子結構的第一性原理計算 / First principles study of zinc oxide and graphene based interfacial electronic structures for nanoelectronics / CUHK electronic theses & dissertations collection / Mian xiang na mi dian zi xue de ji yu yang hua xin he shi mo xi jie mian dian zi jie gou de di yi xing yuan li ji suanJanuary 2010 (has links)
Advances in experimental techniques such as nanofabrication, characterization and synthesis have resulted in the development of many novel and interesting materials and devices. Surfaces and interfaces play an indispensible role for nanoelectronics development. ZnO and graphene have drawn tremendous research interests in recent years, due to their exceptional merits in electrical, optical and magnetic applications. This thesis attempts to ferret out the current experimental research progress, particularly, the frontiers of ZnO and graphene based surfaces and interfaces, and employs first principles to explore their electronic structures, to acquire mechanistic understanding of experimental findings, and to shed light on rational design of functional devices. / Finally, the magnetic properties of graphene by organic molecule modification are investigated by first principles method. For the first time, we demonstrate that methoxyphenyl group can introduce a delocalized p-type ferromagnetism into graphene sheet, with the Curie temperature (T c) above room temperature. Each aryl group can totally induce 1 muB into molecule/graphene system. Moreover, an around 1.1 eV direct band gap is introduced into both majority and minority spin bands of graphene by methoxyphenyl group modification. Zigzag graphene nanoribbon (GNR) shows strong site-specific magnetism by aryl group adsorption near the edge. At specific site of GNR, each molecule could totally induce 3∼4 mu B into molecule/GNR hybrid system. / First, we study the controllable modulation of the electronic structures of ZnO(10 1¯ 10) surface functionalized by various types of carboxylic acids. The calculated structural results are consistent with the experimental ones attained by the Fourier transform infrared attenuated total reflectance (FT-IR-ATR). Mercapto-acetic acid molecules are found to contribute an abundance of band gap states into ZnO. Mercapto-acetic monolayer functionalized ZnO (10 1¯ 10) is on the verge of metal-to-insulator transition, which is consistent with the experimental finding of an conductivity increase by 6 orders of magnitude. Mercapto-acetic acid functionalized ZnO (10 1¯ 10) surface shows a strong configuration-dependence for both electronic structure and adsorption energy. Moreover, mercapto-acetic acid molecule functionalized ZnO also shows facet-dependent characteristic in which the monolayer functionalized ZnO (2 1¯ 1¯ 0) does not show metal-to-insulator transition. Acetic acid does not contribute to the band gap states of ZnO (10 1¯ 10), whereas benzoic acid and 9-anthracenecarboxylic acid do contribute an abundance of band gap states to ZnO(10 1¯ 10). / Second, we study the band gap opening of graphene bilayer by F4-TCNQ doping and externally applied electric filed effects. With F4-TCNQ concentration of 8.0x1013 molecules/cm2, the electrostatic charge transfer between each F4-TCNQ molecule and graphene is 0.45 e, and the built-in electric field Ebi between the graphene layers could achieve 0.070 V/A. The charge transfer and band gap opening of the F4-TCNQ doped bilayer graphene can be further modulated by externally applied electric field (Eext ). At 0.077 eV/A, the gap opening at the Dirac point ( K) DeltaEK = 306 meV and the band gap Eg 253 meV are around 71% and 49% larger than those of the pristine bilayer under the same Eext. By combining F4-TCNQ molecular doping and Eext, the p-type semiconductor bilayer graphene are attained, with the band gap and hole concentration varied in a wide range. / These four theoretical sub-topics stem from the experimental advances in ZnO and graphene based surfaces and interfaces. They form the mechanistic understanding of the respective surfaces and interfaces down to the molecular level. / Third, the self-assembly mechanism of PTCDA ultrathin films on graphene with the coverage in a range of 0.3∼3 monolayers (MLs) are interrogated by first principles method. For alpha modification mode, with critical thickness of 1 ML, the growth of PTCDA on graphene follows the Stranski-Krastanov (SK) growth mode. In contrast, for beta modification mode, the PTCDA can form two complete MLs on graphene substrate. From the thermodynamical viewpoint, alpha modification mode is more stable than beta modification mode. At 1 ML, the PTCDA follows a continuous and planar˙ packing arrangement on graphene, which is almost unperturbed by typical defects in graphene substrate. This is in consistentcy with the experimental findings. For alpha modification mode with 2 and 3 ML coverage, the bulk-like phases appear. At the same time, the total charge transfer between PTCDA and graphene per 5✓3x5 super cell at 2 MLs saturates with 0.42e, which is larger than those of 1 or 3 ML coverage. / Tian, Xiaoqing. / Adviser: Jianbin Xu. / Source: Dissertation Abstracts International, Volume: 73-03, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.
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Vanadium(V)-peroxo complexes : a study of their specific DNA-photocleavage activities and NMR spectral propertiesShek, Lai Kuen 01 January 2001 (has links)
No description available.
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Inorganic nitrate supplementation improves diastolic function in cancer survivors treated with anthracycline chemotherapyLovoy, Garrett M. January 1900 (has links)
Master of Science / Department of Kinesiology / Carl Ade / Background: Cancer survivors treated with anthracycline-based chemotherapy have a high risk of developing anthracycline-induced cardiotoxicities, including cardiac abnormalities, endothelial dysfunction, and dilated cardiomyopathy. Notably, the imbalance of decreased nitric oxide (NO) production and increased reactive oxygen species has been shown to cause significant damage to cardiac tissue and mitochondria. Therefore, the aim of the current investigation was to determine if an inorganic dietary nitrate (NO3-) supplementation period could restore normal cardiac function in cancer survivors with a history of anthracycline chemotherapy. Methods: Ten cancer survivors, 9 with breast cancer and 1 with lymphoma, completed the experiment. Standard and Tissue Doppler echocardiography were used to assess LV and carotid artery function during systole and diastole at rest. Results: There were no differences in ventricular-arterial coupling (p=0.10), arterial stiffness (p=0.38) or strain of the LV (p=0.49). However, NO₃- supplementation improved strain rate in early filling, early mitral septal wall annular velocity, and mitral A-wave velocity or late diastolic filling. Conclusion: Following NO₃- supplementation, cancer survivors with a history of anthracycline chemotherapy showed significant improvements in diastolic function compared to placebo treatments. These findings add support to the literature of the therapeutic benefits of inorganic dietary NO₃- supplementation on cardiovascular function in clinical populations.
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Synthesis and study of ZnO nanostructures and ZnO based quasi-1d dilute magnetic semiconductors. / 氧化鋅的納米結構以及准一維氧化鋅稀磁半導體的合成及研究 / Synthesis and study of ZnO nanostructures and ZnO based quasi-1d dilute magnetic semiconductors. / Yang hua xin de na mi jie gou yi ji zhun yi wei yang hua xin xi ci ban dao ti de he cheng ji yan jiuJanuary 2008 (has links)
Rao, Yangyan = 氧化鋅的納米結構以及准一維氧化鋅稀磁半導體的合成及研究 / 饒洋燕. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references. / Abstracts in English and Chinese. / Rao, Yangyan = Yang hua xin de na mi jie gou yi ji zhun yi wei yang hua xin xi ci ban dao ti de he cheng ji yan jiu / Rao Yangyan. / Abstract --- p.1 / 摘要 --- p.3 / Acknowledgments --- p.4 / Table of contents --- p.5 / Chapter Chapter 1 --- Introduction --- p.7 / Chapter 1.1 --- Zinc oxide --- p.7 / Chapter 1.2 --- Mn doped ZnO diluted magnetic semiconductors --- p.7 / Chapter 1.3 --- Motivations --- p.9 / Chapter 1.4 --- Our Work --- p.10 / Chapter 1.5 --- Overview of the thesis --- p.11 / References --- p.11 / Chapter Chapter 2 --- Experimental set-up and conditions --- p.15 / Chapter 2.1 --- Chemical Vapor Deposition --- p.15 / Chapter 2.1.1 --- Key Steps in Chemical Vapor Deposition --- p.15 / Chapter 2.2 --- Experiments on the synthesis of ZnO nanostructures --- p.16 / Chapter 2.2.1 --- Set-up --- p.17 / Chapter 2.2.2 --- Growth mechanism --- p.18 / Chapter 2.2.3 --- Experimental conditions --- p.20 / References --- p.23 / Chapter Chapter 3 --- Characterization of pure ZnO --- p.25 / Chapter 3.1 --- Morphology of ZnO nanowires --- p.25 / Chapter 3.2 --- Lattice structure --- p.30 / Chapter 3.3 --- Photoluminescence property (PL) --- p.32 / Chapter 3.4 --- Lattice dynamics´ؤRaman spectra --- p.33 / References --- p.35 / Chapter Chapter 4 --- Properties of Mn doped ZnO nanowires --- p.37 / Chapter 4.1 --- Morphology and composition --- p.37 / Chapter 4.2 --- Lattice structure of Mn-doped ZnO --- p.40 / Chapter 4.3 --- Lattice dynamics´ؤRaman study of Mn-doped ZnO nanowires --- p.46 / References --- p.48 / Chapter Chapter 5 --- Magnetic properties of Mn doped ZnO nanowires --- p.50 / Chapter 5.1 --- Theory of DMS --- p.50 / Chapter 5.2 --- Magnetic results of Mn doped ZnO nanowires --- p.52 / Chapter 5.2.1 --- Paramagnetism of Mn doped ZnO --- p.52 / Chapter 5.2.2 --- Ferromagnetism of Mn doped ZnO --- p.58 / References --- p.65 / Chapter Chapter 6 --- Conclusions --- p.67
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Towards functional oxide heterostructures / Funktionelle oxidische HeterostrukturenMüller, Andreas January 2012 (has links) (PDF)
Oxide heterostructures attract a lot of attention as they display a vast range of physical phenomena like conductivity, magnetism, or even superconductivity. In most cases, these effects are caused by electron correlations and are therefore interesting for studying fundamental physics, but also in view of future applications. This thesis deals with the growth and characterization of several prototypical oxide heterostructures. Fe3O4 is highly ranked as a possible spin electrode in the field of spintronics. A suitable semiconductor for spin injection in combination with Fe3O4 is ZnO due to its oxide character and a sufficiently long spin coherence length. Fe3O4 has been grown successfully on ZnO using pulsed laser deposition and molecular beam epitaxy by choosing the oxygen partial pressure adequately. Here, a pressure variation during growth reduces an FeO-like interface layer. Fe3O4 films grow in an island-like growth mode and are structurally nearly fully relaxed, exhibiting the same lattice constants as the bulk materials. Despite the presence of a slight oxygen off-stoichiometry, indications of the Verwey transition hint at high-quality film properties. The overall magnetization of the films is reduced compared to bulk Fe3O4 and a slow magnetization behavior is observed, most probably due to defects like anti-phase boundaries originating from the initial island growth. LaAlO3/SrTiO3 heterostructures exhibit a conducting interface above a critical film thickness, which is most likely explained by an electronic reconstruction. In the corresponding model, the potential built-up owing to the polar LaAlO3 overlayer is compensated by a charge transfer from the film surface to the interface. The properties of these heterostructures strongly depend on the growth parameters. It is shown for the first time, that it is mainly the total pressure which determines the macroscopic sample properties, while it is the oxygen partial pressure which controls the amount of charge carriers near the interface. Oxygen-vacancy-mediated conductivity is found for too low oxygen pressures. A too high total pressure, however, destroys interface conductivity, most probably due to a change of the growth kinetics. Post-oxidation leads to a metastable state removing the arbitrariness in controlling the electronic interface properties by the oxygen pressure during growth. LaVO3/SrTiO3 heterostructures exhibit similar behavior compared to LaAlO3/SrTiO3 when it comes to a thickness-dependent metal-insulator transition. But in contrast to LaAlO3, LaVO3 is a Mott insulator exhibiting strong electron correlations. Films have been grown by pulsed laser deposition. Layer-by-layer growth and a phase-pure pervoskite lattice structure is observed, indicating good structural quality of the film and the interface. An electron-rich layer is found near the interface on the LaVO3 side for conducting LaVO3/SrTiO3. This could be explained by an electronic reconstruction within the film. The electrostatic doping results in a band-filling-controlled metal-insulator transition without suffering from chemical impurities, which is unavoidable in conventional doping experiments. / Oxidische Heterostrukturen besitzen verschiedenste physikalische Eigenschaften wie Leitfähigkeit, Magnetisums oder sogar Supraleitung. Diese Effekte, die meist von elektronischen Korrelationen verursacht werden, zu verstehen und ihren fundamentalen Ursprung zu erklären, machen diese Materialsysteme ebenso interessant wie ihr zukünftiges Anwendungspotential. Diese Arbeit beschäftigt sich mit verschiedenen prototypischen Schichtsystemen. Fe3O4 könnte zukünftig als Spinelektrode im Bereich der Spintronik dienen. ZnO ist ein Halbleiter, der durch seinen oxidischen Charakter und einer hinreichenden Spinkohärenzlänge gut zur Spininjektion geeignet ist. Das Wachstum von Fe3O4 auf ZnO wurde erfolgreich mittels gepulster Laserdeposition und Molekularstrahlepitaxie durchgeführt. Dabei ist der Sauerstoffpartialdruck entscheidend und eine Variation des Drucks während des Wachstums wirkt der Bildung einer FeO-artigen Grenzschicht entgegen. Die Filme wachsen inselartig und ihre Gitterstruktur ist fast vollständig relaxiert. Trotz einer Sauerstofffehlstöchiometrie wird die hohe Qualität der Filme durch einen Verwey-Phasenübergang bestätigt. Im Vergleich zu Einkristallen ist die Magnetisierung der Filme reduziert. Durch das Inselwachstum verursachte Antiphasengrenzen könnten zu dieser Reduzierung führen. Die leitfähige Grenzschicht, die in LaAlO3/SrTiO3 Heterostrukturen ab einer bestimmten LaAlO3 Filmdicke auftritt, kann höchstwahrscheinlich durch eine elektronische Rekonstruktion erklärt werden. Im entsprechenden Modell wird der Aufbau eines elektrischen Potentials auf Grund der Polarität des LaAlO3 Films durch eine Ladungsumordnung kompensiert. Die Eigenschaften dieser Heterostruktur sind jedoch von den Wachstumsparametern abhängig. Diese Studie zeigt erstmals, dass die makroskopischen Eigenschaften maßgeblich vom Gesamtdruck, die Anzahl der Ladungsträger dagegen stark vom Sauerstoffpartialdruck während des Wachstums abhängen. Leitfähigkeit auf Grund von Sauerstofffehlstellen wurde für sehr kleine Sauerstoffpartialdrücke beobachtet. Ein zu hoher Gesamtdruck hingegen verhindert die Leitfähigkeit der Grenzschicht. Dies ist vermutlich durch eine Änderung der Wachstumskinematik erklärbar. Ein Nachoxidieren der Proben führt überdies zu einem metastabilen Zustand, der die Vergleichbarkeit von Proben verschiedener Arbeitsgruppen gewährleistet. LaVO3/SrTiO3 zeigt ähnliches Verhalten wie LaAlO3/SrTiO3 und Leitfähigkeit tritt ab einer gewissen LaVO3 Schichtdicke auf. Im Gegensatz zu LaAlO3 ist LaVO3 ein Mottisolator, dass heißt, Korrelationseffekte spielen eine Rolle. LaVO3/SrTiO3 wurde mittels gepulster Laserdeposition hergestellt, Phasenreinheit und die strukturellen Eigenschaften mit verschiedenen Methoden überprüft. Zusätzliche Elektronen wurden für leitfähige Proben auf der LaVO3-Seite der Grenzfläche nachgewiesen. Eine Erklärung hierfür wäre eine elektronische Rekonstruktion im Film selbst. Dieses elektrostatische Dotieren führt zu einem bandfüllungsinduzierten Mott-Phasenübergang, der nicht durch chemische Verunreinigungen, die in konventionellen Dotierexperimenten unvermeidbar sind, beeinflusst ist.
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Graphene-Based ‘Hybrids’ as High-Performance Electrodes with Tailored Interfaces for Alternative Energy Applications: Synthesis, Structure and Electrochemical PropertiesVan Meveren, Mayme Marie 01 July 2017 (has links)
Technological progress is determined to a great extent by developments of novel materials from new combinations of known substances with different dimensionality and functionality. We investigate the development of 3D ‘hybrid’ nanomaterials by utilizing graphene based systems coupled with transition metal oxides (e.g. manganese oxides MnO2 and Mn3O4). This lays the groundwork for high performance electrochemical electrodes for alternative energy owing to their higher specific capacitance, wide operational window and stability through charge-discharge cycling, environmental benignity, cost effective, easily processed, and reproducible in a larger scale.
Thus far, very few people have investigated the potential of combining carbon sheets that can function as a supercapacitor in certain systems with transition metals that have faradaic properties to create electrochemical capacitors. Previous work by Wang et al. has focused on the structural combination of Mn3O4 and graphene based materials,1 and research by Jafta et al. studied the electrochemical properties of MnO2 with GO.2
We find that both physical and chemical attachment of manganese oxide on graphene allows for electrical interplay of the materials as indicated in electrochemical analysis and Raman spectroscopy. Attachment of the two materials is also characterized by scanning electron microscopy and X-ray diffraction.
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Consciousness, neurons, and laughing gasOrendurff, Dody Michelson 01 January 1979 (has links)
Psychological and physiological effects of nitrous oxide resemble those of eight other drug categories. Lipid solubility or hydrate microcrystal theories correlate behavioral measures with measurable parameters of the molecule N20. N20, a spindle poison, halts mitosis in metaphase, producing widespread physiological consequences. N20 affects the microtubules of the spindle in a number of specific ways. Microtubules are utilized in other parts of eukaryotic cells, in a wide variety of functions. In neurons, microtubules build and maintain dendritic sensory processes. Since microtubules are built of two dissimilar proteins, constantly assemble and disassemble, and maintain a more negative interior potential, they would be responsive to changes in summed post-synaptic dendritic potential. Microtubules respond to N20 with a loss of communication between subcellular components, and between cells. Chromosomes, proteins, and ATP are no longer transported efficiently. Such fundamental changes might explain nitrous oxide's effects in "potentiating" other drugs, and upon perception and memory.
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S-Nitrosothiols: Formation, Decomposition, Reactivity and Possible Physiological EffectsMorakinyo, Moshood Kayode 01 January 2010 (has links)
Three biologically-active aminothiols cysteamine (CA), DL-cysteine (CYSH) and DL-homocysteine, were studied in this thesis. These aminothiols react with nitrous acid (HNO2), prepared in situ, to produce S-nitrosothiols (RSNOs): S-nitrosocyteamine (CANO), S-nitrosocysteine (CYSNO) and S-nitrosohomocysteine (HCYSNO). They also react with S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylpenicillamine (SNAP) through a transnitrosation reaction to produce their corresponding RSNOs. A detailed kinetics and mechanistic study on the formation of these RSNOs and their subsequent decomposition to release nitric oxide (NO) were studied. For all three aminothiols the stoichiometry of their reaction with nitrous acid is strictly 1:1 with the formation of one mole of RSNO from one mole of HNO2. In all cases, the nitrosation reaction is first order in nitrous acid, thus implicating it as a nitrosating agent in mildly acidic pH conditions. Acid catalyzes nitrosation after nitrous acid has saturated, implicating another nitrosating agent, the nitrosonium cation, NO+ ( which is produced from the protonation of nitrous acid) as a contributing nitrosating species in highly acidic environments. The acid catalysis at constant nitrous acid concentrations suggests that the nitrosonium cation nitrosates at a much higher rate than nitrous acid. Nitric oxide itself was not detected as a nitrosant. Bimolecular rate constants for the nitrosation of CA, CYSH and HCYSH were deduced to be 17.9, 6.4, 0.09 M-1 s-1 for the nitrosation by nitrous acid and 8.25 x 1010, 2.89 x 1010 and 6.57 x 1010 M-1 s-1 for the nitrosation by nitrosonium cation respectively. A linear correlation was obtained between the rate constants and the pKa of the sulfur center of the aminothiols for nitrosation by NO+. The stabilities of the three RSNOs were found to be affected by metal ions. They were unstable in the presence of metal ions, with half-lives of few seconds. However, in the presence of metal ion chelators, they were found to be relatively stable with half-lives of 10, 30 and 198 hours for CYSNO, CANO and HCYSNO respectively. The relative stability of HCYSNO may be an advantage in the prevention of its metabolic conversion to homocysteine thiolactone, the major culprit in HCYSH pathogenesis. This dissertation has thus revealed new potential therapeutic way for the modulation of HCYSH related cardiovascular diseases.
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