DNA scaffolds self-assembled by short-stranded synthetic DNA can be tailored to build thermally reversible hydrogels with target binding sites. These hydrogels exhibit highly selective binding properties due to the specificity of DNA and also provide an aqueous environment for various reactions to happen within the network constraints. Hence, a careful study on the assembly mechanism and other physical aspects of DNA hydrogels is required to facilitate the future design and construction of such materials at the precise control. In this thesis, I present the work on well-designed DNA nano-stars as scaffolds for functional bulk materials with potential applications in bio-sensing. Chapter 1 starts with introducing the fundamental properties of DNA molecules, focusing on the advantages of utilising short-stranded DNA to programme and engineer micro- and macro- materials. Then it briefly reviews the field of rheology and micro-rheology, with the diffusing wave spectroscopy (DWS) technique illustrated explicitly as an example passive micro-rheology tool. Afterwards, a critical literature review on computational modelling of DNA systems is present, followed by the thesis outline at the end. Chapter 2 describes a simple DNA dendrimer system self-assembled from three-armed DNA nano-stars. The characterisation tools such as UV-vis spectroscopy, gel electrophoresis and dynamic light scattering (DLS) are introduced to verify the final production of the complex DNA structures. From this practice, we develop a routine for designing DNA scaffolds that yield optimal productivity. Chapter 3 investigates the mechanical properties of DNA hydrogels made of three-armed DNA nano-stars and how they change upon cooling and heating empolying DWS micro-rheology. The resulting viscoelastic moduli over a broad range of frequencies reveal a clear, temperature-reversible percolation transition coinciding with the melting temperature of the system's sticky ends. This indicates that we can achieve precise control in mechanical properties of DNA hydrogels, which is beneficial for designing more sensitive molecular sensing tools and controlled release systems. Chapter 4 develops a coarse-graining computational model of DNA hydrogels that resembles the system in Chapter 3 using LAMMPS, a classical molecular dynamics code. Thermodynamics, structural analysis and rheology tests were taken, qualitatively reproducing the physical phenomena of DNA assembly of the hydrogel network. Chapter 5 studies the internal behaviours of three-armed DNA complexes using oxDNA model also implemented in LAMMPS, with particular focus on the effect of the inert bases in the core and between double-stranded branches and single-stranded sticky ends. A deep insight into sequence-dependent behaviour of such complex structures can guide the parameter optimisation of the individual building blocks for the model described in Chapter 4. Chapter 6 concludes the thesis and presents an outlook for the future work that emerged out of my experimental and numerical studies.

Bioactive glass is a type of third generation bioactive material that can bond to both soft and hard tissue with applications ranging from bone defect repair, coatings for metallic implants, to scaffolds for tissue engineering. Design of bioactive glasses for these applications rely on a detailed understanding of the structures of these glasses which are complicated and multicomponent. In this thesis, I have applied molecular dynamics (MD) simulations with interatomic potentials developed in our group to understand the effect of modifier cation substitution on the structures and properties of two series of bioactive glasses. Particularly, MD simulations are used to understand K2O to Na2O and MgO to CaO substitution on the short and medium range structures (such as cation coordination number, pair distribution function, Qn distribution, and ring size distribution) and properties (such as bulk and Young's moduli and CTE) of 55S4.1 bioactive glasses. As Na2O is incrementally substituted with K2O in 55S4.1, a decrease of the glass transition temperature (Tg) and an increase of CTE was observed, as well as a decreasing trend in the moduli. For the MgO to CaO substitution series, Mg2+ is mainly four-fold coordinated that suggests that it can play a role as a network former in this series. Results of both series showed characteristics of the phenomena of the mixed alkali effect (MAE) that has been known to show non-linear variations in trends like Tg in glasses with alkali and alkali earth ion substitution.

No description available.

Apresentamos uma série de estudos, baseados em simulações de Dinâmica Molecular no vácuo e em solução, sobre o processo de complexação das supramoléculas tetraethylester p-tert-butyl calix[4]arene (CLE) e tetramethylketone p-tert-butyl calix[4]arene (CLC) com os íons Pb2+ e Cd2+ e espécies neutras. Os modelos para as moléculas de calixareno e do solvente foram baseados no campo de forças OPLS-AA. Os parâmetros para os íons foram desenvolvidos a partir de uma metodologia de ajuste de valores de modo a reproduzirem simultaneamente propriedades termodinâmicas e estruturais obtidas experimentalmente ou por cálculos de QM/MM. As simulações no estado líquido nos mostraram que o CLE aprisiona os íons de maneira mais eficiente que o CLC, formando complexos mais estáveis. A complexação do íon desencadeia um efeito alostérico em ambos os calixarenos estudados, permitindo a complexação de uma molécula de acetonitrila na cavidade hidrofóbica estabilizando o complexo. Nas simulações com o CLC observamos que a complexação da acetonitrila é necessária para manter o íon ligado à cavidade hidrofílica, evidenciando a dependência desses complexos com esse solvente em específico. Apesar de observarmos que o CLE apresenta maior afinidade com os íons Pb2+ e Cd2+ que o CLC, somente futuras simulações utilizando a água como solvente poderão confirmar a viabilidade do uso desta molécula em sistemas destinados à despoluição ambiental. / We report a series of Molecular Dynamics simulations, in vacuum and in acetonitrile solution, on the complexation process of the calixarens tetraethylester p-tert-butyl calix[4]arene (CLE) and tetramethylketone p-tert-butyl calix[4]arene (CLC) with Pb2+ and Cd2+ anions and neutral species. The solvent and calixarene molecules were modeled based on the OPLS-AA force field. The parameters for the ions were adjusted to simultaneously reproduce some structural and thermodynamic properties obtained either experimentally or from QM/MM calculations. The simulations in the liquid phase show CLE to be more efficient than CLC in trapping the studied metal ions, leading to more stable complexes. Ion complexation gives rise to an allosteric effect by which a solvent molecule is trapped in the hydrophobic cavity giving rise to further stabilization of the complex. Simulations on CLC show that formation of the calixarene-acetonitrile adduct is essential to the stabilization of the ionic complex, thus exhibiting the influence of this particular solvent in the very existence of the complex. In spite of the conclusion that CLE has higher affinity than CLC for Pb2+ and Cd2+ ions, only further studies in water solution will permit to evaluate the real potential of this molecule as an efficient scavenger of environmental heavy metal pollution.

Apresentamos uma série de estudos, baseados em simulações de Dinâmica Molecular no vácuo e em solução, sobre o processo de complexação das supramoléculas tetraethylester p-tert-butyl calix[4]arene (CLE) e tetramethylketone p-tert-butyl calix[4]arene (CLC) com os íons Pb2+ e Cd2+ e espécies neutras. Os modelos para as moléculas de calixareno e do solvente foram baseados no campo de forças OPLS-AA. Os parâmetros para os íons foram desenvolvidos a partir de uma metodologia de ajuste de valores de modo a reproduzirem simultaneamente propriedades termodinâmicas e estruturais obtidas experimentalmente ou por cálculos de QM/MM. As simulações no estado líquido nos mostraram que o CLE aprisiona os íons de maneira mais eficiente que o CLC, formando complexos mais estáveis. A complexação do íon desencadeia um efeito alostérico em ambos os calixarenos estudados, permitindo a complexação de uma molécula de acetonitrila na cavidade hidrofóbica estabilizando o complexo. Nas simulações com o CLC observamos que a complexação da acetonitrila é necessária para manter o íon ligado à cavidade hidrofílica, evidenciando a dependência desses complexos com esse solvente em específico. Apesar de observarmos que o CLE apresenta maior afinidade com os íons Pb2+ e Cd2+ que o CLC, somente futuras simulações utilizando a água como solvente poderão confirmar a viabilidade do uso desta molécula em sistemas destinados à despoluição ambiental. / We report a series of Molecular Dynamics simulations, in vacuum and in acetonitrile solution, on the complexation process of the calixarens tetraethylester p-tert-butyl calix[4]arene (CLE) and tetramethylketone p-tert-butyl calix[4]arene (CLC) with Pb2+ and Cd2+ anions and neutral species. The solvent and calixarene molecules were modeled based on the OPLS-AA force field. The parameters for the ions were adjusted to simultaneously reproduce some structural and thermodynamic properties obtained either experimentally or from QM/MM calculations. The simulations in the liquid phase show CLE to be more efficient than CLC in trapping the studied metal ions, leading to more stable complexes. Ion complexation gives rise to an allosteric effect by which a solvent molecule is trapped in the hydrophobic cavity giving rise to further stabilization of the complex. Simulations on CLC show that formation of the calixarene-acetonitrile adduct is essential to the stabilization of the ionic complex, thus exhibiting the influence of this particular solvent in the very existence of the complex. In spite of the conclusion that CLE has higher affinity than CLC for Pb2+ and Cd2+ ions, only further studies in water solution will permit to evaluate the real potential of this molecule as an efficient scavenger of environmental heavy metal pollution.

This dissertation presents a numerical study using molecular dynamic simulations that interrogates the polymer structure as it is strained continuously in time and correlates it with the stress developed in it. We investigate the role of external control variables such as temperature, strain-rate, chain length, and density. At temperatures higher than glass transition, stress anisotropy is reduced even though bond stretch is greater at higher temperatures. There is a significant increase in stress level with increasing density. At faster rates of loading stress anisotropy increases. Deformation is mostly due to bond stretch and bond bending rather than overall shape and size. Stress levels increase with longer chain length. Cross-linkers beyond a critical value of functionality cause increased constraint on the motion of monomers and uniaxial stress developed increases. Stacking of chains also plays a dominant role in terms of excluded volume interactions. Low density, high temperature, low values of functionality of cross-linkers, and short chain length, facilitate chain uncoiling and chain slipping in crosslinked polymers. Uniaxial stress in linear polymers, on the other hand, is only mildly in uenced by temperature. Sinusoidal strain loading clearly reveals the viscoelastic nature of polymers. Internal structural parameters of the chains such as bond length, bond angle show hysteresis during loading and unloading. However, parameters representing overall size and shape of chains do not display any hysteresis. Small size magnetic particles and their small volume fractions in polymers show no signi cant e ect of applied external magnetic eld on anisotropic stress. Stress increases with lowering temperature, increasing density, decreasing volume fraction of magnetic particles, and increasing chain length

Au cours d’un traitement de surface de type dépôt assisté par plasma, les caractéristiques et propriétés de l’interface entre le dépôt et le substrat sont déterminées par la première couche atomique du dépôt, voire les premiers atomes qui commencent à recouvrir la surface du substrat. Aussi, la parfaite connaissance du comportement des particules incidentes et du réarrangement des atomes suite à l’impact d’une particule du plasma est-elle un élément essentiel à la description du comportement de la surface en cours de traitement et donc de ses propriétés ultérieures. Au cours de cette thèse, nous avons entrepris d’étudier, par une approche combinant expériences et simulation numérique par dynamique moléculaire, l’interaction d’espèces (C, Ti, W) avec une surface de silicium en fonction de paramètres tels que l’énergie, la fluence ou encore l’incidence des particules arrivant sur la surface. Une part importante de ce travail a consisté à adapter les codes de dynamique moléculaire (utilisation des champs de force réactifs) aux systèmes étudiés. La partie expérimentale a nécessité la mise en place de procédures spécifiques pour l’utilisation de l’équipement Storing Matter. Les résultats montrent que, quelles que soient l’espèce incidente, parmi celles étudiées, le coefficient de collage (SC) est dans la gamme [0.7 – 1] ; dans le cas de W, quasiment tous les atomes incidents restent sur la surface (SC~~1). Outre la détermination du coefficient de collage, pour différentes conditions initiales des espèces incidentes (énergie, incidence, fluence) les modifications apportées à la surface ont également été déterminées en termes d’implantation et de trajectoire dans le matériau des espèces incidentes, et de pulvérisation de la surface du substrat / During plasma assisted deposition, properties of the coating substrate interface depend on the first atomic layer of the deposit, or the atoms that first start to cover the surface. Therefore the good knowledge of the sticking coefficient and the reorganization of the surface following particle impact is an essential issue to achieve the description of the behavior of the processed surface and, therefore, its expected properties. Consequently, we investigated the interaction between incoming particles (C, Ti, W) and a silicon surface by using an approach combining molecular dynamic simulations and experiments. Various initial conditions were studied, energy, fluence and incidence angle of the incoming particles. An important part of this work has consisted in adapting the molecular dynamic codes (using reactive force fields) to the investigated systems. Meanwhile, experimental procedure specifically devoted to the use of the Storing Matter facility was also developed. Results show that the sticking coefficient (SC) value is in the range [0.7 – 1] irrespectively of the incoming species; in the case of W, almost all atoms stick on the surface (SC~~1). Besides the determination of sticking coefficient, the surface modification resulting from the particles impingement were determined for various initial conditions (energy, fluence, angle) in terms of implantation and displacement of the incoming species, and surface sputtering as well

No description available.

Poorly water-soluble drugs (PWSDs), to date, require advanced formulation techniques to improve solubility and achieve the required plasma concentration to show a therapeutic effect when orally administered. Lipid-based formulations (LBFs) are an enabling strategy that is being used to improve the oral delivery of PWSDs. The aim of this study was to investigate the effect of lipid-based formulation, Type IIIA-LC, on the solubilization patterns of PWSDs, namely, carvedilol and felodipine. Solubility studies, for both drugs, were performed with LBF dispersed in -1) dog intestinal fluid (DIF), and 2) water, to identify and compare the extent of solubility in different matrices, and in silico to identify interesting patterns with any correlations in experimental and computational data. Solubility studies showed that carvedilol had better solubility in LBF when compared to felodipine. Computational studies showed that both drugs solubilized in the colloid in both digested and undigested states. Effect of drug loading had no significant difference on the solubilization patterns of both drugs. The maximum drug loading done was for 100 molecules though there is the possibility of the colloid having a higher capacity. Digestion did not seem to have a significant effect on the distribution of both drugs. In vitro and in silico data were in qualitative agreement and therefore, this computational model can be further used to study the specific processes causing solubilization, improvement, and development of new LBFs.

No description available.