A Doença de Chagas, endêmica na América Latina, é causada pelo parasito tripanossomatídeo Trypanosoma cruzi e atualmente já se espalha para o restante do mundo devido à migração humana. Os dois medicamentos disponíveis para o tratamento dessa doença, o Nifurtimox, (banido do Brasil), e o Benzonidazol, são eficazes somente na etapa aguda da doença e possuem efeitos colaterais severos. Recentemente, três novas substâncias para o tratamento chegaram à fase clínica de testes contra essa doença, mas ainda é necessária a pesquisa de novas moléculas contra esse parasito. A enzima Gliceraldeído-3-fosfato Desidrogenase (GAPDH) foi selecionada como alvo para busca de moléculas potencialmente tripanossomicidas. De forma a inibir essa enzima, a busca de moléculas baseou-se na abordagem de fragmentos moleculares para encontrar substâncias com elevada eficiência de ligante. A partir de um banco de dados comercial de 500 mil moléculas, filtros moleculares de solubilidade e da Regra dos Três foram aplicados para montar uma biblioteca focalizada de moléculas. Essa biblioteca foi submetida a estudos integrados baseados na estrutura do alvo macromolecular (docagem) e do substrato da enzima (similaridade química e eletrostática) e a inspeção visual dos fragmentos bem classificados em ambas técnicas foi realizada de modo a selecionar cinco compostos de classes químicas diversas. Essas substâncias foram submetidas a ensaios enzimáticos in vitro por meio de espectroscopia de fluorescência, sendo encontrado então um fragmento com Ki de (425 ± 53) μM e eficiência de ligante de 0,33, valor bastante promissor para abordagem baseada em fragmentos moleculares. Estudos de simulação por Dinâmica Molecular (MD) foram feitos para as cinco moléculas adquiridas, com energia de interação ligante-enzima calculada usando o método MM-GB/SA. A classificação das moléculas por essa energia foi idêntica à obtida experimentalmente. Além disso, a MD possibilitou a predição de modo de interação dos fragmentos no sítio ativo da TcGAPDH e a identificação de uma nova cavidade passível de modulação de sua atividade. Uma segunda série de fragmentos foi selecionada baseada no fragmento ativo de modo a construir uma relação estrutura-atividade (SAR) teórica por MD. A SAR sugere que a presença de um átomo nitrogênio capaz de doar ligações de hidrogênio é importante para a interação, com o resíduo de aminoácido Asp210. Este resíduo de aminoácido desponta como um possível ponto de seletividade para a enzima humana, que possui uma leucina nessa posição. Além disso, a posição na substituição do anel central também está diretamente relacionada à interação da molécula com a enzima, com uma substituição 2,3 em um anel de cinco membros a mais favorável. Este trabalho identificou pela primeira vez um fragmento molecular com alta eficiência de ligante para a enzima TcGAPDH, com o auxílio do uso conjunto de técnicas baseadas na estrutura do ligante e do alvo, para seleção de moléculas, e espectroscopia de fluorescência para identificação de atividade inibitória frente à enzima. Método de simulação por MD conseguiu reproduzir os resultados experimentais e prover informações teóricas de SAR para o composto ativo. / Chagas disease is a parasitic illness endemic in Latin America caused by the trypanosomatid parasite Trypanosoma cruzi that spreads around the world due to people migration. Nowadays, Benznidazole and Nifurtimox (banned in Brazil), are used for the treatment of this disease but causes severe side effects to patients. Recently, three new molecules have reached clínical trials phase in the development of drugs against Chagas disease but it is still necessary to develop new drugs. In this studies, the enzyme Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH) was used as a target for the search of new antitrypanosomatid molecules. It belongs to the glycolytic pathway, the major one for parasite\'s energy generation. With the aim searching a new molecule that inhibits this enzyme, the fragment-based approach guided the search of molecules with high ligand efficiency. A focused compound library was assembled from a database of 500,000 molecules using molecular and solubility filters and the Rule of Three. The integrated use of ligand (chemical and electrostatic similarity) and target (molecular docking) based drug design was carried out to rank the molecular fragments by a consensual score. Through visual inspection of the top 500 molecules five diverse fragments were selected for the in vitro enzymatic assays using fluorescence spectroscopy. One of these molecules shows a Ki equals to (425 ± 53) μM and ligand efficiency equals to 0,33, a promising value for the fragment-based approach. Additionally, Molecular Dynamics simulations (MD) were carried out with these fragments and the predicted energy of interaction for fragment-enzyme complex was able to rank the molecules as using the experimental results. Furthermore, the MD was useful to predict the mode of interaction of the fragments in the active site of enzyme and to reveal a new cavity close to the substrate binding site. A second generation of compounds was selected based on the structure of the active fragment to construct theoretical structure-activity relationship (SAR) using MD. SAR indicates that the presence of a nitrogen with hydrogen-bond donor property is important to the interaction, making hydrogen-bonding with the amino acid residue Asp210. In addition, MD shows the influence of different substituent posítion in the central ring in the energy of the interaction, with a 2,3 substitution at five-atom ring the most favorable. This study identifies the first molecular fragment with high ligand efficiency for the enzyme TcGAPDH, with the combined use of ligand and target-based tools and fluorescence spectroscopy, for selection and identification of active compounds against the enzyme. MD was able to reproduce experimental results and generate theoretical information of SAR to the active molecular fragment.

A Doença de Chagas, endêmica na América Latina, é causada pelo parasito tripanossomatídeo Trypanosoma cruzi e atualmente já se espalha para o restante do mundo devido à migração humana. Os dois medicamentos disponíveis para o tratamento dessa doença, o Nifurtimox, (banido do Brasil), e o Benzonidazol, são eficazes somente na etapa aguda da doença e possuem efeitos colaterais severos. Recentemente, três novas substâncias para o tratamento chegaram à fase clínica de testes contra essa doença, mas ainda é necessária a pesquisa de novas moléculas contra esse parasito. A enzima Gliceraldeído-3-fosfato Desidrogenase (GAPDH) foi selecionada como alvo para busca de moléculas potencialmente tripanossomicidas. De forma a inibir essa enzima, a busca de moléculas baseou-se na abordagem de fragmentos moleculares para encontrar substâncias com elevada eficiência de ligante. A partir de um banco de dados comercial de 500 mil moléculas, filtros moleculares de solubilidade e da Regra dos Três foram aplicados para montar uma biblioteca focalizada de moléculas. Essa biblioteca foi submetida a estudos integrados baseados na estrutura do alvo macromolecular (docagem) e do substrato da enzima (similaridade química e eletrostática) e a inspeção visual dos fragmentos bem classificados em ambas técnicas foi realizada de modo a selecionar cinco compostos de classes químicas diversas. Essas substâncias foram submetidas a ensaios enzimáticos in vitro por meio de espectroscopia de fluorescência, sendo encontrado então um fragmento com Ki de (425 ± 53) μM e eficiência de ligante de 0,33, valor bastante promissor para abordagem baseada em fragmentos moleculares. Estudos de simulação por Dinâmica Molecular (MD) foram feitos para as cinco moléculas adquiridas, com energia de interação ligante-enzima calculada usando o método MM-GB/SA. A classificação das moléculas por essa energia foi idêntica à obtida experimentalmente. Além disso, a MD possibilitou a predição de modo de interação dos fragmentos no sítio ativo da TcGAPDH e a identificação de uma nova cavidade passível de modulação de sua atividade. Uma segunda série de fragmentos foi selecionada baseada no fragmento ativo de modo a construir uma relação estrutura-atividade (SAR) teórica por MD. A SAR sugere que a presença de um átomo nitrogênio capaz de doar ligações de hidrogênio é importante para a interação, com o resíduo de aminoácido Asp210. Este resíduo de aminoácido desponta como um possível ponto de seletividade para a enzima humana, que possui uma leucina nessa posição. Além disso, a posição na substituição do anel central também está diretamente relacionada à interação da molécula com a enzima, com uma substituição 2,3 em um anel de cinco membros a mais favorável. Este trabalho identificou pela primeira vez um fragmento molecular com alta eficiência de ligante para a enzima TcGAPDH, com o auxílio do uso conjunto de técnicas baseadas na estrutura do ligante e do alvo, para seleção de moléculas, e espectroscopia de fluorescência para identificação de atividade inibitória frente à enzima. Método de simulação por MD conseguiu reproduzir os resultados experimentais e prover informações teóricas de SAR para o composto ativo. / Chagas disease is a parasitic illness endemic in Latin America caused by the trypanosomatid parasite Trypanosoma cruzi that spreads around the world due to people migration. Nowadays, Benznidazole and Nifurtimox (banned in Brazil), are used for the treatment of this disease but causes severe side effects to patients. Recently, three new molecules have reached clínical trials phase in the development of drugs against Chagas disease but it is still necessary to develop new drugs. In this studies, the enzyme Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH) was used as a target for the search of new antitrypanosomatid molecules. It belongs to the glycolytic pathway, the major one for parasite\'s energy generation. With the aim searching a new molecule that inhibits this enzyme, the fragment-based approach guided the search of molecules with high ligand efficiency. A focused compound library was assembled from a database of 500,000 molecules using molecular and solubility filters and the Rule of Three. The integrated use of ligand (chemical and electrostatic similarity) and target (molecular docking) based drug design was carried out to rank the molecular fragments by a consensual score. Through visual inspection of the top 500 molecules five diverse fragments were selected for the in vitro enzymatic assays using fluorescence spectroscopy. One of these molecules shows a Ki equals to (425 ± 53) μM and ligand efficiency equals to 0,33, a promising value for the fragment-based approach. Additionally, Molecular Dynamics simulations (MD) were carried out with these fragments and the predicted energy of interaction for fragment-enzyme complex was able to rank the molecules as using the experimental results. Furthermore, the MD was useful to predict the mode of interaction of the fragments in the active site of enzyme and to reveal a new cavity close to the substrate binding site. A second generation of compounds was selected based on the structure of the active fragment to construct theoretical structure-activity relationship (SAR) using MD. SAR indicates that the presence of a nitrogen with hydrogen-bond donor property is important to the interaction, making hydrogen-bonding with the amino acid residue Asp210. In addition, MD shows the influence of different substituent posítion in the central ring in the energy of the interaction, with a 2,3 substitution at five-atom ring the most favorable. This study identifies the first molecular fragment with high ligand efficiency for the enzyme TcGAPDH, with the combined use of ligand and target-based tools and fluorescence spectroscopy, for selection and identification of active compounds against the enzyme. MD was able to reproduce experimental results and generate theoretical information of SAR to the active molecular fragment.

Submitted by JOSIANE SANTOS DE OLIVEIRA (josianeso) on 2017-10-26T11:44:55Z No. of bitstreams: 1 Édson Flores_.pdf: 3781858 bytes, checksum: ecc6bea71a85c8419f9ea9400766fdf3 (MD5) / Made available in DSpace on 2017-10-26T11:44:55Z (GMT). No. of bitstreams: 1 Édson Flores_.pdf: 3781858 bytes, checksum: ecc6bea71a85c8419f9ea9400766fdf3 (MD5) Previous issue date: 2017-05-12 / CNPQ – Conselho Nacional de Desenvolvimento Científico e Tecnológico / Este trabalho tem como objetivo a modelagem de diferentes dissipadores de calor com resfriamento líquido em microcanais. A proposta é a utilização de softwares de dinâmica de fluidos para analisar o desempenho térmico em diferentes geometrias construtivas de microcanais. O software utilizado para a realização das simulações CFD foi o Ansys Fluent R . O trabalho aborda as etapas prévias necessárias para simulação CFD, destacando a etapa de geração de malha para as simulações, envolvendo o estudo de convergência de malha, os critérios de aceitação da simulação e as técnicas de refino na interface líquido-sólido, procedimento necessário para modelagem correta da física de transferência de calor. Foram estudadas geometrias de microcanais de seção retangular em paralelo, microcanais de estrutura pinada e microcanais em rede de fractal do tipo H. Este trabalho também apresenta o modelamento de um estudo de caso em que os microcanais em paralelo são formados pelas paredes de material adesivo fixado em um bloco de alumínio. Os resultados obtidos servem para auxílio em uma etapa de construção de um protótipo experimental. No estudo dos microcanais de seção retangular em paralelo e de microcanais de estrutura pinada, variou-se os aspectos dimensionais buscando a melhor resposta de desempenho térmico, sendo isso expresso em termos de resistência térmica. A simulação de microcanais em rede de fractal H foram realizadas para uma comparação qualitativa referente as demais geometrias estudadas. Um problema discutido no decorrer deste trabalho foi a necessidade de mudança do modelo de viscosidade laminar para um modelo de viscosidade turbulenta, apesar das velocidades do fluido no interior dos microcanais serem baixas e expressarem um número de Reynolds baixo. As técnicas de remoção de calor em microcanais podem colaborar de forma decisiva no gerenciamento térmico de um projeto, na menor energia empregada para o resfriamento e na diminuição das dimensões de um produto final. As geometrias estudadas podem ser construídas em uma camada metálica de uma placa de circuito impresso do tipo metal core, como também estarem presentes em uma estrutura de silício de um chip. O domínio das técnicas de modelagem térmica com softwares simuladores de dinâmicas de fluidos apresentados neste trabalho podem auxiliar na busca de soluções para a remoção de calor em micro-escala, reduzir a necessidade de produção de protótipos, e por consequência, diminuir custos. / This work has the objective of modeling different heat sinks with liquid cooling in microchannels. The proposal is the use of fluid dynamics software to analyze the thermal performance in different constructional geometries of microchannels. The software used to perform the CFD simulations was Ansys Fluent R . This work addresses the previous steps required for CFD simulation, highlighting the step of mesh generation for the simulations, involving mesh convergence study, simulation acceptance criteria and refining techniques at the liquid-solid interface, a procedure necessary for Modeling of heat transfer physics. The geometries studied were of rectangular section microchannels in parallel, microchannels of pinched structure and microchannels in fractal network of type H. A case study was also modeled in this work in which parallel microchannels were formed by walls of adhesive material In an aluminum block, in which the results obtained serve to aid in a stage of construction of an experimental prototype. In the study of the microchannels of rectangular section in parallel and microchannels of pinned structure, we varied the dimensional aspects seeking the best response of thermal performance, being expressed in terms of thermal resistance. The simulation of microchannels in fractal network H was performed for a qualitative comparison referring to the other geometries studied. A problem discussed in the course of this work was the need to change the laminar viscosity model to a turbulent viscosity model despite the velocity of the fluid inside the microchannels being low and expressing a low Reynolds number. Techniques for heat removal in microchannels can contribute decisively to the thermal management of a project, the lower energy used for cooling and the reduction of the dimensions of an end product. The geometries studied can be constructed in a metal layer of a metal core type printed circuit board, as well as being present in a one-chip silicon structure. The domain of thermal modeling techniques with fluid dynamics simulators presented in this paper can help in the search for technological solutions for micro-scale heat removal, reduce the need for prototype production, and consequently reduce costs.

Here we describe the fitting and testing, via molecular dynamics simulation, of a bond-order potential for water with a unique force field parameterization. Most potentials for water, including some bond-order (reactive) potentials, are based on a traditional, many-body decomposition to describe water's structure with bond stretch, angle bend, electrostatics, and non-bonded terms. Our model uses an expanded version of the Bond Valence Model, the Valence Multipole Model, to describe all aspects of molecular structure using multibody, bond-order terms. Prior work successfully related these multibody, bond order terms to energy, provided the structures were close to equilibrium. The success of this equilibrium energy model demonstrated the plausibility of adapting its parameterization to a molecular dynamics force field. Further, we present extensive testing of ab initio methods to show that the ab initio data we obtained, using the CCSD(t)/cc-pwCVTZ level of theory, to augment the fitting set of our parameters is of the highest quality currently available for the OH system. While the force field is not yet finished, the model has demonstrated remarkable improvement since its initial testing. The test results and the insights gleaned from them have brought us significantly closer to adapting our unique parametrization to a fully functional molecular dynamics force field. Once the water potential is finished, it is our intent to develop and expand the Valence Multipole Model into a fully reactive alternative to CLAYFF, a non-reactive potential typically used to simulate fluid interfaces with clays and other minerals.

In this dissertation, we introduce a framework for simulating the dynamics between liquid and thin structures, including the effects of buoyancy, drag, capillary cohesion, dripping, and diffusion. After introducing related works, Part I begins with a discussion on the interactions between Newtonian fluid and fabrics. In this discussion, we treat both the fluid and the fabrics as continuum media; thus, the physical model is built from mixture theory. In Part II, we discuss the interactions between Newtonian fluid and hairs. To have more detailed dynamics, we no longer treat the hairs as continuum media. Instead, we treat them as discrete Kirchhoff rods. To deal with the thin layer of liquid that clings to the hairs, we augment each hair strand with a height field representation, through which we introduce a new reduced-dimensional flow model to solve the motion of liquid along the longitudinal direction of each hair. In addition, we develop a faithful model for the hairs' cohesion induced by surface tension, where a penalty force is applied to simulate the collision and cohesion between hairs. To enable the discrete strands interact with continuum-based, shear-dependent liquid, in Part III, we develop models that account for the volume change of the liquid as it passes through strands and the momentum exchange between the strands and the liquid. Accordingly, we extend the reduced-dimensional flow model to simulate liquid with elastoviscoplastic behavior. Furthermore, we use a constraint-based model to replace the penalty-force model to handle contact, which enables an accurate simulation of the frictional and adhesive effects between wet strands. We also present a principled method to preserve the total momentum of a strand and its surface flow, as well as an analytic plastic flow approach for Herschel-Bulkley fluid that enables stable semi-implicit integration at larger time steps. We demonstrate a wide range of effects, including the challenging animation scenarios involving splashing, wringing, and colliding of wet clothes, as well as flipping of hair, animals shaking, spinning roller brushes from car washes being dunked in water, and intricate hair coalescence effects. For complex liquids, we explore a series of challenging scenarios, including strands interacting with oil paint, mud, cream, melted chocolate, and pasta sauce.

This work focuses on the emission processes of metal-organic clusters MmMen, (M is the organic molecule and Me the metal atom) ejected from self assembled monolayers (SAMs) of alkanethiols on gold after keV ion bombardment. These aggregates are often observed upon energetic ion bombardment of strongly bound molecules like SAMs. The explanation of this effect remains elusive, especially for large clusters as those observed in our study. The emission of these clusters is investigated using ToF-SIMS under 15 keV Ga+ bombardment. In particular, we have measured the energy distributions (KEDs), which are informative of the physical processes of sputtering. We have probed both the influence of the intermolecular forces and the adsorbate-metal bonding on the cluster ion emission. Importantly, our KEDs revealed that a significant fraction of MmMen clusters is formed via the metastable decay of larger aggregates in the acceleration section of the spectrometer. This is the experimental evidence that another cluster formation channel has to be considered in addition to the recombination mechanisms proposed by other groups. In parallel to these experiments, we have used classical molecular dynamics (MD) simulations to model an overlayer of octanethiols on gold. A realistic potential has been used including long-range forces between the hydrocarbon chains of the alkanethiols. Our key finding concerns the emission of large clusters which were not observed under sub-keV projectile impact. Statistically, they are predominantly formed in high yield events, where many fragments and (supra)molecular species are ejected. From the microscopic viewpoint, these events mostly stem from the confinement of the projectile and recoil atom energies in a finite nanovolume of the surface. As a result of the high local energy density, molecular aggregates desorb from an overheated liquid-like region surrounding the impact point. In summary, from a combined experimental and computational study we have shown that analytical models involving linear collision cascades and recombination processes are insufficient to describe metal-thiolate cluster emission from SAMs under keV ion bombardment. The detailed MD investigation have allowed us to obtain a general picture of the emission of these aggregates in which the mechanisms at play are reminiscent of those high yields events (megaevents) with non linear effects used usually to account for large (bio)molecule desorption.

Nanoporous carbons are among the widely studied and promising materials on hydrogen storage for on-board vehicles. However, the nature of nanoporous carbon structures, as well as the relationship between local structure and hydrogen adsorption are still unclear, and hinder the design of carbon materials for optimum hydrogen storage. This dissertation presents a systematic modeling effort of hydrogen storage in nanoporous carbon materials. Tight binding molecular dynamics simulations are utilized to simulate the amorphous carbons over a wide range of density. The resulting structures are in good agreement with experimental data of ultra-microporous carbon (UMC), a wood-based activated carbon, as indicated by a comparison of the microstructure at atomic level, pair distribution function, and pore size distribution. To estimate gas adsorption in complex geometries, an efficient numerical algorithm (based on a continuum gas adsorption model) is developed for calculating the gas uptake at room temperature and moderate pressures. This algorithm is a classical approximation of the quantum mechanical model by Patchkovskii et al.1 and proven to be much faster than other commonly used methods. The gas adsorption calculations in carbon structures from tight-binding simulations demonstrate both a promising hydrogen storage capacity (1.33 wt% at 298K and 5 MPa) and a reasonable heat of adsorption (12-21 kJ/mol). To our knowledge, this is the first work to directly calculate hydrogen adsorption capacity in amorphous carbon. This work demonstrates that increasing the heat of adsorption does not necessarily increase the hydrogen uptake. In fact, the available adsorption volume is as important as the isosteric heat of adsorption for hydrogen storage in nanoporous carbons.

Proton exchange membrane (PEM) fuel cells are an eco-friendly power source that has great potential to reduce our oil dependence for our stationary and transportation applications. In order to make PEM fuel cells an economically viable option, further effort is needed to improve proton conduction under wide operating conditions and reduce the cost of production. Design and synthesis of novel membranes that have superior characteristics require a fundamental molecular-level understanding of the relationship between the polymer chemistry, water content and proton conduction. The performance of a fuel cell is influenced by the electrochemical and molecular/proton transport processes that occur at the catalytic sites in the electrode/electrolyte interface. Therefore, understanding the molecular-level details of proton transport and structure of the multi-phase interfaces is critical. This work is subdivided into two main tasks. The first task is to model membrane/water vapor interfaces and to study their morphology and the transport properties of water and hydronium ions. Classical molecular dynamics simulation is used as the modeling tool for the characterization of the interface. The second task is to model proton transport through the aqueous domains of PEM. Such a model is inherently challenging since proton transport occurs through a combination of structural and vehicular diffusions that are associated with disparate time scales. Toward this end, we have developed and implemented a new reactive molecular dynamics algorithm to model the structural diffusion of proton that involves breaking and forming of covalent bonds. The proton transport through aqueous channels in PEM is governed by acidity and confinement. Therefore, systems in which the acidity and confinement can be independently varied, including bulk water, aqueous hydrochloric acid solutions and water confined in carbon nanotubes are also examined in addition to the application in PEM. We have developed an understanding of how acidity and confinement independently impact proton transport. The correlation between the two components of charge diffusion and their contribution to the total charge diffusion has also been explored for a basic understanding of the proton transport mechanisms. These studies will eventually help us establish the correlation between the morphology of the membrane and proton conduction.

Viscoelastic surfactant have found numerous application in the oil fields as fracturing and matrix acidizing fluid additives in the recent years. They have the ability to form long worm-like micelles with the increase in pH and calcium concentration, which results in increasing the viscosity and elasticity of partially spent acids. On one hand, concentration of surfactant in the fluids has profound effects on their performance downhole. Additionally, there is continuous debate in the industry on whether the gel generated by these surfactants causes formation damage, especially in dry gas wells. Therefore, being able to analyze the concentration of these surfactants in both live and spent acids is of great importance for production engineers who apply surfactant-based fluids in the oil fields. In the present work, a two-phase titration method was optimized for quantitative analysis of a carboxybetaine viscoelastic surfactant, and surfactant retention in calcite cores was quantitatively determined by two phase titration method and the benefits of using mutual solvents to break the surfactant gel formed inside the cores was assessed. On the other hand, high temperatures and low pH are usually involved in surfactant applications. Surfactants are subjected to hydrolysis under such conditions due to the existence of a peptide bond (-CO-NH-) in their molecules, leading to alteration in the rheological properties of the acid. The impact of hydrolysis at high temperatures on the apparent viscosity of carboxybetaine viscoelastic surfactant-based acids was evaluated in the present study, and the mechanism of viscosity changes was determine by molecular dynamics (MD) simulations. Our results indicate that, first, significant amount of surfactant has been retained in the carbonate matrix after acidizing treatment and there is a need to use internal breakers when surfactant-based acids are used in dry gas wells or water injectors. Second, hydrolysis at high temperatures has great impact on surfactant-acid rheological properties. Short time viscosity build-up and effective gel break-down can be achieved if surfactant-acid treatments are carefully designed; otherwise, unexpected viscosity reduction and phase separation may occur, which will affect the outcome of acid treatments.

Inter-molecular interactions have significant influences on linear and nonlinear optical properties of molecules including one- and two-photon absorptions, emissions, and various high order nonlinear polarizations. The related investigation has become an active and challenging research area. The theoretical structure-to-property relationship obtained from quantum chemical calculations of single organic conjugated molecules often can not be directly applied to real materials in condensed phases. One has to consider the effect of environment, that is, inter-molecular interactions, where the model systems experience in real experiments or applications. The change of molecular conformations under all kinds of interactions and its effects on linear and nonlinear optical properties are the central issue of this thesis. Special attentions have been paid to symmetrical diamino substituted distyrylbenzene chromophores with different torsional angles, two dipolar merocyanine dyes of various orientations, two isomers of a V-shaped 2-hydroxypyrimidine derivative and their various dimers, and the structural fluctuations of interacting polar chromophores in solutions. Quantum chemical methods in combination with molecular dynamics simulations have been employed to study molecular conformations and optical properties in solutions, in particular the solvent and aggregation effects on one- and two-photon absorption. More specifically, time-dependent density functional theory has been used for all electronic calculations, while the polarizable continuum model and supermolecule approach have also been employed to take into account solvent effects. Moreover, the propagation of an ultrashort laser pulse through a one-dimensional asymmetric organic molecular medium which possesses large permanent dipole moments has been simulated by solving full Maxwell-Bloch equations using predictor-corrector finite-difference time-domain method. We have focused on the supercontinuum generation of spectra and the formation of attosecond pulses. / QC20100630