Дисертації з теми "Electrostatic assemblies"

The coiled coil is a common and well-studied protein-folding motif. It is based on the seven-residue repeat abcdefg, where a and d residues are largely hydrophobic. Structurally, coiled coils comprise two or more a-helices that are brought together with the a and d residues packing in a well-defined manner to form a hydrophobic core. Interhelical electrostatic interactions are frequently observed between core-flanking g and e residues. There is debate as to whether these interactions are present solely to confer specificity, or whether they also have a role in stabilising the structures. A program, TRAWLER, was written to analyse the core-flanking interactions in a set of high-resolution structural data, and designed proteins were used to investigate the role of these interactions further. It is shown that the electrostatic interactions are stabilising in comparison to a state where the charged residues are present but not interacting. The strength of this stabilisation is strongly context dependent: pairs containing glutamic acid and lysine are more stabilising when the glutamic acid is placed at g and the lysine at e. It is proposed that this is due to the packing of these residues against the surface presented by the core a and d residues. It is noted that previous studies using different a residues in the core exhibit the opposite preference. Further designs include a histidine-based switch and a series of bi-faceted coiled coils. In the latter, coiled-coil repeats were overlaid within a sequence to produce two oligomerisation interfaces. Such sequences are seen in natural a-sheet and a-cylinder structures. Designed peptides were intended to form vertically staggered a-cylinders, leading to the formation of elongated nanotubes. The behaviours of these peptides are presented and the difficulties inherent in such designs are discussed.

Les hydrogels sont des réseaux 3D retenant de grandes quantités d'eau. Biocompatibles, ils sont utilisés pour la délivrance de médicaments. Dans le but de développer des hydrogels antibactériens, cette thèse présente deux études basées sur l'utilisation d'un tripeptide phosphorylé protégé par un fluorénylméthoxycarbonyle (Fmoc), qui peut s'auto-assembler en hydrogel. Dans la première étude, différentes conditions de préparation (pH, sel, présence de polysaccharide) ont été étudiées pour former un hydrogel autocicatrisant et antibactérien libérant un antibiotique, le florfénicol. Dans la seconde étude, des stratégies de synthèse peptidiques et de phosphoramidites en phase solide ont été combinées pour ajouter le florfénicol au phosphate de tyrosine protégé par le Fmoc via un phosphodiester, clivable par des nucléases produites par des bactéries. Des résultats encourageants ont montré la formation du composé ciblé, ouvrant la voie au design d'un peptide antibactérien auto-défensif
Hydrogels are 3D networks of fibers that retain large amounts of water when swollen. Due to their biocompatibility, they are increasingly used for drug delivery. To develop antibacterial peptide-based hydrogels, this dissertation presents two studies based on the use of a fluorenylmethoxycarbonyl (Fmoc)-protected phosphorylated tripeptide that can self-assemble into a hydrogel. In the first study, different preparation conditions (pH, salt, presence of polysaccharide) were investigated to obtain a self-healing and antibacterial hydrogel capable of releasing an antibiotic, florfenicol. In the second study, a solid-phase peptide and phosphoramidite synthesis strategies were combined to add florfenicol to the Fmoc-protected tyrosine phosphate via a phosphodiester, which can be cleaved by nucleases produced by bacteria. Encouraging results showed the formation of the targeted compound, paving the way for the design of a self-defensive antibacterial peptide

The ability of quantum dots to confine single charges at discrete energy levels makes them a promising platform for novel electronic and optoelectronic devices. Self-assembled quantum dots are of considerable interest because their size, shape, and material can be controlled during growth. These properties influence the confinement potential, thereby controlling the energy levels of the dot. However, the method of growth does not allow for positioning of the quantum dots which end up randomly distributed over the sample surface, making it difficult for lithographic techniques to access the quantum dots to perform either charge transport or charge sensing measurements so that single dot properties can be measured. An atomic force microscope (AFM) can be used to spatially access individual dots, and by applying a voltage between cantilever tip and back-electrode, the energy levels of individual dots can be measured as electrons are added to the dot one-by-one in the Coulomb blockade regime. The oscillating cantilever in these experiments is responsible for both loading the dots through electrical gating and also detecting tunneling events through a change in cantilever resonance frequency and/or cantilever dissipation. We use an AFM to measure the energy levels in few electron self-assembled InAs quantum dots. The charging energy, level spacing, and shell structure of single dots are extracted experimentally. We compare our results to a theoretical model that describes in detail the mechanism behind the dissipative electrostatic interaction due to the tunneling single-electrons.Examples of the electrostatic influence of the environment on the dots are also presented, and a method for using an AFM for characterizing electrostatic noise is demonstrated. Charge fluctuations are known to compromise the operation of electronic devices, especially for electrical components which are built in the micron and nano regime. Super bandgap irradiation leads to generation-recombination noise over the sample surface but not over the self-assembled quantum dots. We measure the generation-recombination noise with an AFM and compare the noise on and off the dot to show sub-20~nm spatial resolution, demonstrating the ability of AFM for characterizing noise arising from charge fluctuations within the sample with high spatial resolution.
La propriété qu'ont les points quantiques de confiner des charges élémentaires à des niveaux discrets d'énergie en font une plate-forme prometteuse pour la conception de nouveaux appareils électroniques et opto-électroniques. Les points quantiques auto-assemblés sont d'autant plus intéressants puisque leur taille, forme et matériau peuvent être contrôlés lors de leur croissance. Ces propriétés influencent le potentiel de confinement modifiant ainsi les niveaux d'énergies du point quantique. Toutefois, cette méthode de croissance ne permet pas de positionner les points quantiques et ceux-ci se retrouvent distribués aléatoirement sur la surface de l'échantillon. Cela rend difficile l'accès aux points quantiques par des techniques lithographiques pour effectuer des mesures de transport ou de détection de charge permettant d'en déterminer les propriétés.Un microscope à force atomique (AFM) permet d'accéder spatialement à des points quantiques individuels et en appliquant une tension électrique entre la pointe du cantilever et une électrode arrière, leurs niveaux d'énergies peuvent être mesurés au fur et à mesure que des électrons sont ajoutés dans un régime de blocage de Coulomb. Dans ces expériences, le cantilever oscillant est responsable simultanément du chargement des points par l'application d'une tension de grille et de la détection du passage d'électron par « effet tunnel » par un changement de fréquence de résonance et/ou de dissipation du cantilever.Nous utilisons un AFM pour mesurer les niveaux d'énergie dans des points quantiques à quelques électrons d'InAs auto-assemblés. L'énergie de chargement, l'espacement des niveaux et la configuration électronique de points individuels sont obtenus expérimentalement. Nous comparons nos résultats à un modèle théorique qui décrit en détail le mécanisme derrière l'interaction électrostatique dissipative due au passage d'électrons par « effet tunnel ».Des exemples de l'influence électrostatique de l'environnement sur les points quantiques sont aussi présentés, ainsi qu'une méthode pour utiliser l'AFM pour caractériser le bruit électrostatique. Les fluctuations de charge sont connues pour compromettre le bon fonctionnement des appareils électroniques et particulièrement des composants micro et nanométriques. L'irradiation de larges bandes d'énergie interdites produit un bruit de génération et de recombinaison à la surface de l'échantillon, mais pas sur les points quantiques auto-assemblés. Nous mesurons ce bruit avec un AFM et comparons les résultats obtenus sur la surface du point quantique et en dehors en démontrant qu'une résolution spatiale inférieure à 20 nm est réalisée. Nous démontrons ainsi qu'un AFM permet de caractériser le bruit provenant des fluctuations de charge d'un échantillon avec une haute résolution spatiale.

A novel cyclopentadienylruthenium(II) thiolato Schiff base, [Ru(SC6H4NC(H)C6H4OCH2CH2SMe)(&eta
5-C2H5]2 was synthesized and deposited as a selfassembled monolayer (SAM) on a gold electrode. Effective electronic communication between the Ru(II) centers and the gold electrode was established by electrostatically cycling the Shiff base-doped gold electrode in 0.1 M NaOH from -200 mV to +600 mV. The SAMmodified gold electrode (Au/SAM) exhibited quasi-reversible electrochemistry. The integrity of this electro-catalytic SAM, with respect to its ability to block and electro-catalyze certain Faradaic processes, was interrogated using Cyclic and Osteryoung Square Wave voltammetric experiments. The formal potential, E0', varied with pH to give a slope of about - 34 mV pH-1. The surface concentration, &Gamma
, of the ruthenium redox centers was found to be 1.591 x 10-11 mol cm-2. By electrostatically doping the Au/SAM/Horseradish peroxidase at an applied potential of +700 mV vs Ag/AgCl, a biosensor was produced for the amperometric analysis of hydrogen peroxide, cumene hydroperoxide and tert-butylhydroperoxide. The electrocatalytic-type biosensors displayed typical Michaelis-Menten kinetics with their limits of detection of 6.45 &mu
M, 6.92 &mu
M and 7.01 &mu
M for hydrogen peroxide, cumene hydroperoxide and tert-butylhydroperoxide respectively.

博士
崑山科技大學
機械與能源工程研究所
105
The mathematical model of the coupled system composed of two elastically restrained beams and probe-membrane (probe-ring typed membrane) system subjected to electrostatic force is constructed. It is different to the conventional clamped micro/nano actuator which is constructed by two independent fixed/mobile conducting electrodes. The formula of pull-in voltage is presented. The analytical method for the coupled vibration is presented. (1) the coupling system is only affected by the DC voltage. It is found that the critical ratio of the relative static displacement of the general system to the initial tip distance is 1/3. In the critical condition, pull-in instabilities will occur. In addition, a general formula for traction voltage is found. This is very helpful in designing micro / nano actuators, since the introduction voltage can be directly calculated by the formula. The relationship between the coupling frequency of the general system and the frequency of the individual beams is also found. (2) the effects of several parameters on the pull-in instability are studied. The analytical method for the coupled vibration is proposed. The effects of the probe tips and several differential boundary conditions of membrane on the coupled characteristics are investigated. The coupled characteristic mechanism is clearly described.

博士
國立交通大學
應用化學系碩博士班
103
Conventional cancer treatments have many limitations which often fail to completely eradicate the tumor and cause damages to normal cells. Photodynamic therapy (PDT), by the excitation of photosensitizers with light to generate reactive oxygen species (ROSs) such as 1O2, has emerged as a noninvasive technique for cancer theranostics. However, the clinical use of many photosensitizers has been challenged by their nonspecific damage to normal tissues, environmental degradation and hydrophobicity...etc. To overcome the existing limitation and to enhance the selectivity of photodynamic therapy, we developed a simple electrostatic adsorption strategy to fabricate silica nanocomposite (Apt-MB-Si NPs) by sequentially functionalizing MUC1 aptamer for tumor targeting and hydrophilic photosensitizer methylene blue (MB) for the PDT application. We found effective generation of singlet oxygen could be achieved with low PS dosage and short irradiation time by current strategy.

The key to theoretical prediction of the behaviour of self-assembling systems is an understanding of structure. This structure is the global spatial manifestation of the sum of all local interactions. As a consequence of the subtlety of this connection, prediction of structure from the basis of a detailed model of the specific molecular interactions is not feasible, as our mathematical limitations force the imposition of strict geometrical assumptions. Instead, such physical treatments are sacrificed for the freedom of description offered by simplified geometrical approaches. In this thesis two examples of such geometrical motivations, of particular reference to the phases observed in binary surfactant-water mixtures, are analysed and extended. Helfrich attributed the energy cost of fluctuation of the surfactant aggregate to the bending of the interface separating the hydrophilic and hydrophobic regions, and proposed a simple curvature energy function describing this. Applying simple stability considerations, we find that this functional form cannot be reconciled with the intuition of a preferred interfacial curvature, and propose an alternative phenomenological description which is consistent with this notion and with existing continuum models of the surfactant film. For the specific case of preferentially flat films (that is, zero spontaneous curvatures) the surfactant bilayers have a tendency to form lamellar phases, which exhibit interesting behaviour attributed to the bending energy. To investigate this, we calculate this energy directly for the specific case of ionic surfactants in aqueous electrolytes, thus permitting the inference of formulae for the bilayer bending modulus (characterising its degree of stiffness). Perhaps the most striking structural feature of surfactant-water systems is the observation of bicontinuous phases. The partitioning interface in these formations is found to be modelled in many cases by the class of triply periodic minimal surfaces. Here we derive new examples of these special surfaces and present an algorithm for the parametrisation of this class, thus facilitating a quantitative assessment of the degree to which these surfaces match the real surfactant interface.

In earlier research in our lab, the manipulation of microtubules on gold patterned silicon wafers was achieved by E-beam lithography, Poly (ethylene glycol) self assembled monolayers (PEG-SAMs) and electrophoresis. To develop a technique for delicate single microtubule manipulation, further studies need to be done on PEG-SAMs and electrophoresis. As a foundation of this goal, we examined the electric field in an aqueous solution between two planar electrodes and the compatibility of the antifouling property of PEG-SAMs with the electric field. For this purpose, the distribution of microbeads was analyzed using a Boltzmann distribution. The amount of adsorbed microtubules on a PEG-SAM was examined to test the compatibility of the antifouling property of a PEG-SAM with concomitant exposure to electric field. It is shown that the product of the electric field and the effective charge of the microbead does not have a linear relation with the applied electric potential but an exponentially increasing function with respect to the potential. The antifouling property of the PEG-SAM was not retained after an exposure to the electric field.

博士
國立清華大學
化學工程學系
102
Polyamidoamine (PAMAM) dednrimer bearing well-defined number of amine groups can be protonated under physiological or acidic condition to generate the macrocations capable of forming electrostatic complex (called “dendriplex”) with DNA for gene delivery. Using small angle X-ray scattering (SAXS) and small angle neutron scattering (SANS), here we constructed the morphological map of the complex of DNA with PAMAM dendrimer of generation four (G4) in terms of the dendrimer charge density and the nominal N/P ratio given by the feed molar ratio of dendrimer amine group to DNA phosphate group. With the increase of dendrimer charge density under a given nominal N/P ratio, the structure was found to transform from square columnar phase (in which the DNA chains packed in square lattice were locally straightened) to hexagonally-packed DNA superhelices (in which the DNA chains organizing in a hexagonal lattice twisted moderately into superhelices) and finally to beads-on-string structure (in which DNA wrapped around the dendrimer to form nuclesome-like array). The phase transition sequence was understood from the balance between the bending energy of DNA and the free energy of charge matching governed by the entropic gain from counterion release. Decreasing nominal N/P ratio under fixed dendrimer charge density was found to exert the same effect as increasing dendrimer charge density; that is, the structure with higher DNA curvature tended to form at lower nominal N/P ratio, in particular for the dendriplex with low dendrimer charge density. The effect of N/P ratio was attributed to the tendency of the system to increase the translational entropy of the counterions released to the bulk solution by reducing the concentration of free DNA or dendrimer remained in the solution. The experimental results presented here thus demonstrated the crucial role of counterion entropy in the structural formation of DNA-dendrimer complexes, and this entropic contribution was governed by the dendrimer charge density, the nominal N/P ratio, and the initial concentrations of DNA and dendrimer used for complex preparation. The dominant role of counterion entropy was further verified by examining the effect of protonic acid on the nanostructure of the dendriplex, where the dendrimer was also protonated by multivalent acids, including H2SO4 and H3PO4.

Layer-by-layer (LbL) is a self-assembly technique, proven to be a simplified method for the modification of material surfaces. The LbL multilayers are formed due to electrostatic attraction between opposite charged polymers. Substrates which can be utilised using this technique include dyes, enzymes, drugs and cells. In this study which comprise of three separate LbL studies, 1) compactible cellulose was nanocoated by means of LbL, 2) poly(amidoamine) dendrimer mediated synthesis of silver sulfadiazine nanoparticles and 3) four poorly water soluble drugs were nanocoated, i.e. furosemide, isoxyl, rifampicin, paclitaxel. In the first study Kraft softwood fibers was nanocoated using the LbL technique. This technique turned non-flowing, non-compacting cellulose into powders with positive tabletting properties which can be used in direct compression in the tabletting process. The cellulose microfibers which were coated with four PSS/PVP bilayers, display the best compaction properties. One of the major advantages of nanocoating is that the process adds less than 1% to the weight of the fibres. This process proved to be environmental friendly due to the type of materials used and the quantity. In the second study silver sulfadiazine (limited aqueous solubility) was used to synthesize highly soluble AgSD nanoparticles. In this particular study the nanoparticles were stabilized against crystal growth by LbL coating. PAMAM dendrimers were used to coat the particles. The dendrimers served as solubility enhancer for this poorly water soluble antibiotic. This study illustrated that nanotechnology based dosage forms can be create and that PAMAM dendrimers were crucial to the success of this dosage form. In the third study, a LbL nanocoat of chitosan and chondroitin sulfate was self-assembled step-wise onto drug nanoparticles. Furosemide, isoxyl, rifampin and paclitaxel were chosen to prepare these nanoparticles. All four of them display poor water solubility properties. Although the nanocoating reduced the dissolution proportional to the coat thickness, it still dissolved faster than the commercially available micronized powders of the drugs. Also this LbL nanocoating stabilizes the small particles against crystal growth and aggregation in suspension. The release patterns of the drugs were superior to that of the raw materials. This study proved that LbL coating can improve the performance of poorly water soluble drugs.
PhD (Pharmaceutics), North-West University, Potchefstroom Campus, 2015

A novel cyclopentadienylruthenium(II) thiolato Schiff base,[Ru(SC6H4NC(H)C6H4OCH2CH2SMe)(η5-C2H5]2 was synthesized and deposited as a selfassembled monolayer (SAM) on a gold electrode. Effective electronic communication between the Ru(II) centers and the gold electrode was established by electrostatically cycling the Shiff base-doped gold electrode in 0.1 M NaOH from -200 mV to +600 mV. The SAMmodified gold electrode (Au/SAM) exhibited quasi-reversible electrochemistry. The integrity of this electro-catalytic SAM, with respect to its ability to block and electro-catalyze certain Faradaic processes, was interrogated using Cyclic and Osteryoung Square Wave voltammetric experiments. The formal potential, E0', varied with pH to give a slope of about - 34 mV pH-1. The surface concentration, Γ, of the ruthenium redox centers was found to be 1.591 x 10-11 mol cm-2. By electrostatically doping the Au/SAM/Horseradish peroxidase at an applied potential of +700 mV vs Ag/AgCl, a biosensor was produced for the amperometric analysis of hydrogen peroxide, cumene hydroperoxide and tert-butylhydroperoxide. The electrocatalytic-type biosensors displayed typical Michaelis-Menten kinetics with their limits of detection of 6.45 μM, 6.92 μM and 7.01 μM for hydrogen peroxide, cumene hydroperoxide and tert-butylhydroperoxide respectively
Magister Scientiae - MSc