abstract: One of the greatest problems facing society today is the development of a sustainable, carbon neutral energy source to curb the reliance on fossil fuel combustion as the primary source of energy. To overcome this challenge, research efforts have turned to biology for inspiration, as nature is adept at inter-converting low molecular weight precursors into complex molecules. A number of inorganic catalysts have been reported that mimic the active sites of energy-relevant enzymes such as hydrogenases and carbon monoxide dehydrogenase. However, these inorganic models fail to achieve the high activity of the enzymes, which function in aqueous systems, as they lack the critical secondary-shell interactions that enable the active site of enzymes to outperform their organometallic counterparts. To address these challenges, my work utilizes bio-hybrid systems in which artificial proteins are used to modulate the properties of organometallic catalysts. This approach couples the diversity of organometallic function with the robust nature of protein biochemistry, aiming to utilize the protein scaffold to not only enhance rates of reaction, but also to control catalytic cycles and reaction outcomes. To this end, I have used chemical biology techniques to modify natural protein structures and augment the H2 producing ability of a cobalt-catalyst by a factor of five through simple mutagenesis. Concurrently I have designed and characterized a de novo peptide that incorporates various iron sulfur clusters at discrete distances from one another, facilitating electron transfer between the two. Finally, using computational methodologies I have engineered proteins to alter the specificity of a CO2 reduction reaction. The proteins systems developed herein allow for study of protein secondary-shell interactions during catalysis, and enable structure-function relationships to be built. The complete system will be interfaced with a solar fuel cell, accepting electrons from a photosensitized dye and storing energy in chemical bonds, such as H2 or methanol. / Dissertation/Thesis / Doctoral Dissertation Biochemistry 2016

abstract: The exceptional mechanical properties of polymers with heterogeneous structure, such as the high toughness of polyethylene and the excellent blast-protection capability of polyurea, are strongly related to their morphology and nanoscale structure. Different polymer microstructures, such as semicrystalline morphology and segregated nanophases, lead to coordinated molecular motions during deformation in order to preserve compatibility between the different material phases. To study molecular relaxation in polyethylene, a coarse-grained model of polyethylene was calibrated to match the local structural variable distributions sampled from supercooled atomistic melts. The coarse-grained model accurately reproduces structural properties, e.g., the local structure of both the amorphous and crystalline phases, and thermal properties, e.g., glass transition and melt temperatures, and dynamic properties: including the vastly different relaxation time scales of the amorphous and crystalline phases. A hybrid Monte Carlo routine was developed to generate realistic semicrystalline configurations of polyethylene. The generated systems accurately predict the activation energy of the alpha relaxation process within the crystalline phase. Furthermore, the models show that connectivity to long chain segments in the amorphous phase increases the energy barrier for chain slip within crystalline phase. This prediction can guide the development of tougher semicrystalline polymers by providing a fundamental understanding of how nanoscale morphology contributes to chain mobility. In a different study, the macroscopic shock response of polyurea, a phase segregated copolymer, was analyzed using density functional theory (DFT) molecular dynamics (MD) simulations and classical MD simulations. The two models predict the shock response consistently up to shock pressures of 15 GPa, beyond which the DFT-based simulations predict a softer response. From the DFT simulations, an analysis of bond scission was performed as a first step in developing a more fundamental understanding of how shock induced material transformations effect the shock response and pressure dependent strength of polyurea subjected to extreme shocks. / Dissertation/Thesis / Doctoral Dissertation Mechanical Engineering 2017

Made available in DSpace on 2015-05-14T13:21:23Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 2208268 bytes, checksum: a713e84bf72b1325038dab0816e190d4 (MD5) Previous issue date: 2009-11-27 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / In this work the origin of the π−π-staking conformation stability of 5S in the 8-acrylate phenylmenthol 5 was revisiting. The geometries of 5S and 5T conformers were optimized from HF method and the MPW1B95 functional; and the geometries of the 11S and 11T conformers have been optimized from HF, MP2 methods and MPW1B95 functional. All calculations were performed on 6-311 + + G (2d, 2p) 6d as level of calculation. Using the optimized geometries of 5S, 5T, 11S and 11T (from MPW1B95/6-311 + + G (2d, 2p) 6d), were performed 15 energy single-point calculations, investigating various computational methods (ab initio, DFT and semiempirical). We also described the spectroscopic (1H NMR) and theoretical (DFT and ab initio) studies of 3-naphytylpropylcrotonate (12) and 3- naphytylpropylsorbate (21). The geometries of 12S and 12T conformers have been optimized from MP2, HF methods and B3LYP, LSDA and MPW1B95 functionals using 6-311+G(d,p) as calculation level. Finally, we describe the synthesis of 12 and 21 (the unpublished) in 3 steps of each synthesis (19% and 22% respectively of total yields) and the trans geometries of 12T and 21T were characterized as the most stable in the conformational equilibrium of 12 and 21. / Neste trabalho a origem do motivo para a maior estabilidade da conformação de 5S no acrilato de 8-fenilmentol 5 foi investigada. As geometrias dos confôrmeros 5S e 5T foram otimizadas nos métodos HF e no funcional MPW1B95; e as geometrias dos confôrmeros 11S e 11T foram otimizadas nos métodos HF, MP2 e o funcional MPW1B95. Todos os cálculos usaram 6-311++G(2d,2p)6d como nível de cálculo. Usando as geometrias otimizadas de 5S, 5T, 11S e 11T (por MPW1B95/6-311++G(2d,2p)6d), foram efetuados 15 cálculos de energia no ponto, investigando metodologias computacionais variadas (ab initio, DFT e semiempirico). Descrevemos também o estudo espectroscópico (RMN 1H) e teórico (DFT e ab initio) do crotonato de 3-naftilpropila (12) e o sorbato de 3-naftilpropila (21). As geometrias dos confôrmeros de 12S e 12T foram otimizadas com os métodos MP2, HF e os Funcionais B3LYP, LSDA e MPW1B95 usando 6- 311+G(d,p) como nível de cálculo. Finalmente, descrevemos a síntese total de 12 e 21 (inéditas na literatura) em 3 etapas de síntese cada (19% e 22% respectivamente de rendimentos globais) e caracterizamos por 1H RMN a geometria trans 12T e 21T como a mais estável no equilíbrio conformacional de 12 e 21.

Ante la evidente necesidad de comprender los frecuentes cambios negativos que experimenta el planeta Tierra en los suelos, los ríos y la atmosfera y con la idea de intentar mitigar el cambio climático, aparece la química computacional como una rama de la química que nos permite estudiar y predecir diversas propiedadesfisicoquímicas de sistemas moleculares complejos de interés ambiental las cuales son, algunas veces, imposibles de estudiar de forma experimental. El presente artículo muestra un panorama molecular del comportamiento y características fisicoquímicas de algunos contaminantes atmosféricos estudiados a través de la química computacional / The urgent need to understand the frequent negative changes that the planet Earth suffer on its soil, rivers and atmosphere and the need to mitigate climate change makes computational chemistry stand out as a branch of chemistry that allows thestudy and prediction of different physicochemical properties of several complex molecular systems of environmental significance which are sometimes impossible to study in a laboratory. The present article shows a molecular overview of the behavior and physicochemical characteristics of some atmospheric pollutants studied through computational chemistry.

El Premio Nobel de Química de 2013 ha sido otorgado a A. Warshel, M. Levitt y M. Karplus debido al desarrollo de métodos híbridos de cálculo para química computacional. En este artículo se presentará una breve introducción del uso de los métodos de química computacional. Se describirá cómo se desarrollaron, y por qué, los métodos híbridos de cálculo, conocidos como QM/MM (Quantum Mechanics/Molecular Mechanics) para el estudio de sistemas macromoleculares, sobre todo para el caso de su aplicación en enzimas y bioquímica. Finalmente, se comentarán los alcances y expectativas futuras para estos métodos, desarrollados en los años 70. / The 2013 Nobel Prize in chemistry was awarded to A.Warshel, M.Levitt and M.Karplus for their contribution to the development of hybrid methods for computational chemistry. In this article a brief introduction about computational chemistry methods is presented. This paper will show the order in which the QM/MM (Quantum Mechanics/Molecular Mechanics) methods were developed for the study of macromolecular systems and specially their application in enzymes and biochemistry. Finally, the reach and future prospects of these methods originally developed by A. Warshel, M.Levitt and M. Karplus in the seventies will be discussed.

No description available.

Abstract The present thesis investigates the electronic structure of selected atoms and molecules in vapor phase. Electron spectroscopy is applied for studying the electronic transitions following excitation and ionization with electron and photon bombardment. The work focuses on the photoionization and Auger decay of selected noble gasses, and on the photoionization and Auger decay of core ionized or resonant excited alkali halide molecules. The experimental results are compared with theoretical predictions.

This thesis is concerned with the simulation of various electrochemical experiments and its application to electroanalysis. Chapter 1 outlines the fundamental principles of electrochemistry which are of importance for the reading of this thesis. Chapter 2 then outlines the methods used in the numerical simulation of electrochemical experiments. Chapters 3 and 4 are concerned with the electrochemistry of nanoparticles, and how this is affected by the presence of near wall hindered diffusion. In Chapter 3, a computational model to simulate anodic particle coulometry of nanoparticles in the presence of hindered diffusion is developed, and the effect of this hindered diffusion investigated. The model is then applied to simulate experimental data. Chapter 4 looks at the effect of hindered diffusion on the adsorption of nanoparticles on electrode surfaces, and investigates the effects of this adsorption on electrochemical experiments with nanoparticles generally. Chapters 5, 6 and 7 are concerned with band electrodes in isolation, in a pair and in an array respectively. In Chapter 5, a model to simulate double potential step chronoamperometry at an individual band electrode is developed, and used to successfully simulate experimental data. Chapter 6 looks at dual band electrodes used in generator-collector mode, and how this can be used to simultaneously measure the concentration of two species in solution. Chapter 7 looks at interdigitated arrays of band and ring electrodes in generator-collector mode, and develops a model to simulate cyclic voltammetry in both cases, as well as investigating under what conditions interdigitated ring arrays may be modelled as interdigitated band arrays. Chapter 8 develops a model to simulate chronoamperometry and cyclic voltammetry at porous electrodes, and investigates the consequences for electroanalysis of having a porous layer. Finally, Chapter 9 investigates the Marcus-Hush theory of electron transfer kinetics, and looks at the effect of the kinetically limited currents resulting from this theory to the equivalence relation between microdisc electrodes and sphere-on-a-surface electrodes.

Ce travail de thèse vise à étudier l'endommagement de l'ADN, de la formation de lésions à leur réparation par des méthodes de modélisation moléculaire. Plusieurs projets ont pris forme dans ce contexte, lesquels peuvent être classés en trois grandes catégories. D'un côté, nous nous sommes intéressés la formation de lésions induites par des agents mutagènes. Nous avons étudié les mécanismes de formation de la 8-oxo-7,8-dihydroguanine (8oxoG), mais aussi le caractère de photosensibilisateur endogène de la pyrimidine 6-4 pyrimidone (6-4PP), et la photosensibilisation de l'ADN par deux anti-inflammatoires : le kétoprofène et l'ibuprofène. D'un autre côté, les propriétés mécaniques de l'ADN endommagé ont été simulées. La structure de lésions complexes est d'une importance capitale pour comprendre la manière dont elles sont réparées. Malheureusement, seulement peu de structures RMN et cristallographiques sont disponibles à ce jour. Pour pallier à ce manque et obtenir des informations sur leur dynamique, nous avons étudié un panel de lésions complexes : les clusters de sites abasiques, les pontages inter-brins, et la photolésion 6-4PP. De même, nous nous sommes penchés sur les modes d'interaction de certaines polyamines avec l'ADN, ces molécules étant connues pour interagir avec la double hélice. Enfin, latroisième partie de cette thèse concerne les interactions ADN-enzyme de réparation. En perspective avec l'étude de clusters d'abasiques, nous avons étudié le comportement dynamique du même système, cette fois-ci en interaction avec l'endonucléase APE1. Nous nous sommes également penchés sur les interactions entre la glycosylase Fpg avec un oligonucléotide contenant un tandem de lésions 8-oxoG d'un côté, etun cluster de lésions 8-oxoG - site abasique de l'autre. Ces multiples projets ont permis l'accumulation de nouvelles connaissances à propos des lésions complexes de l'ADN, et ont également apporté un appuicomputationnel aux expérimentations, qui peuvent se révéler très délicates dans ce domaine. Nos résultats ouvrent de larges perspectives dans le domaine de la pharmacologie, la cosmétique et plus généralementla compréhension du vivant / This thesis work is focused on the theoretical modelling of DNA damages, from formation to repair. Several projects have been led in this framework, which can be sorted into three different parts. One on hand, we studied complex DNA reactivity. It included a study about 8-oxo-7,8-dihydroguanine (8oxoG) mechanisms of formation, a project concerning the UV-induced pyrimidine 6-4 pyrimidone (6-4PP) endogenous photosensitizer features, and an other one about DNA photosensitizationby nonsteroidal anti-inflammatory drugs (ie ketoprofen and ibuprofen). On the other hand, we investigated mechanical properties of damaged DNA. The structural signature of a DNA lesion is of major importance for their repair, unfortunately only few NMR and X-ray structures of such systems are available. In order to gain insights into their dynamical structure, we investigated a series of complex damages : clustered abasic sites, interstrand cross-links, and the 6-4PP photolesion. Likewise, we studied the interaction modes DNA with several polyamines, which are well known to interact with the double helix, but also with the perspective to model DNA-protein cross-linking. The third part concerned the study of DNA interactions with repair enzymes. In line with the structural study about clustered abasic sites, we investigated the dynamics of the same system, but this time interacting with the APE1 endonuclease. We also studied interactions between the Fpg glycosylase with an oligonucleotides containing tandem 8-oxoG on one hand and 8-oxoG - abasic site as multiply damaged sites. Thus, we shed new lights on damaged DNA reactivity, structure and repair, which provides perspectives for biomedicine and life's mechanisms understanding as we begin to describe nucleosomal DNA

This work explores the use of computational methods to aid in the design of Metal Organic Frameworks (MOFs) for use as CO2 scrubbers in carbon capture and storage applications. One of the main challenges in this field is in identifying important MOF design characteristics which optimize the complex interactions governing surface adsorption. We approach this in a high-throughput manner, determining properties important to CO2 adsorption from generating and sampling a large materials search space. The utilization of MOFs as potential carbon scrubbing agents is a recent phenomenon, as such, many of the computational tools necessary to perform high-throughput screening of MOFs and subsequent analysis are either underdeveloped or non-existent. A large portion of this work therefore involved the development of novel tools designed specifically for this task. The chapters in this work are contiguous with the goal of designing MOFs for CO¬2 capture, and somewhat chronological in order and complexity, meaning as time and expertise progressed, more advanced tools were developed and utilized for the purposes of computational MOF discovery. Initial work towards MOF design involved the detailed analysis of two experimental structures; CALF-15 and CALF-16 using classical molecular dynamics, grand canonical Monte Carlo simulations, and DFT to determine the structural features which promote CO2 adsorption. An unprecedented level of agreement was found between theory and experiment, as we are able to capture, with simulation, the X-ray resolved binding sites of CO2 in the confined pores of CALF-15. Molecular simulation was then used to provide a detailed breakdown of the energy contributions from nearby functional groups in both CALF-15 and CALF-16. A large database of hypothetical MOF structures is constructed for the purposes of screening for CO2 adsorption. The database contains 1.3 million hypothetical structures, generated with an algorithm which snaps together rigid molecular building blocks extracted from existing MOF crystal structures. The algorithm for constructing the hypothetical MOFs and the building blocks themselves were all developed in-house to form the resulting database. The topological, chemical, and physical features of these MOFs are compared to recently developed materials databases to demonstrate the larger structural and chemical space sampled by our database. In order to rapidly and accurately describe the electrostatic interactions of CO2 in the hypothetical database of MOFs, parameters were developed for use with the charge equilibration method. This method assigns partial charges on the framework atoms based on a set of parameters assigned to each atom type. An evolutionary algorithm was used to optimize the charge equilibration parameters on a set of 543 hypothetical MOFs such that the partial charges generated would reproduce each MOFs DFT-derived electrostatic potential. Validation of these parameters was performed by comparing the CO2 adsorption from the charge equilibration method vs DFT-derived charges on a separate set of 693 MOFs. Our parameter set were found to reproduce DFT-derived CO2 adsorption extremely well using only a fraction of the time, making this method ideal for rapid and accurate high-throughput MOF screening. A database of 325,000 MOFs was then screened for CO2 capture and storage applications. From this study we identify important binding pockets for CO2 in MOFs using a binding site analysis tool. This tool uses a pattern recognition method to compare the 3-D configurations of thousands of pore structures surrounding strong CO2 adsorption sites, and present common features found amongst them. For the purposes of developing larger databases which sample a more diverse materials space, a novel MOF construction tool is devloped which builds MOFs based on abstract graphs. The graph theoretical foundations of this method are discussed and several examples of MOF construction are presented to demonstrate its use. Notably, not only can it build existing MOFs with complicated geometries, but it can sample a wide range of unique structures not yet discovered by experimental means.