Orientador: Douglas Soares Galvão / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Fisica Gleb Wataghin / Made available in DSpace on 2018-08-09T02:37:49Z (GMT). No. of bitstreams: 1 Autreto_PedroAlvesdaSilva_M.pdf: 14908796 bytes, checksum: 389f8f28e3d38fbfe32aeab511893f6e (MD5) Previous issue date: 2007 / Resumo: As melaninas constituem uma classe de pigmentos biológicos de destaque devido, sobretudo, a sua predominante presença nos tecidos dos mamíferos. Há fortes evidências que sugerem que a pigmentação por melanina tem por objetivo proteger a pele contra efeitos prejudiciais da radiação ultravioleta. Além deste papel de fotoproteção, outras funções biológicas são especuladas em razão da presença do pigmento em regiões não iluminadas do corpo como por exemplo no cérebro em que há uma aparente destruição preferencial das células que contém melanina quando ocorrem doenças como o mal de Parkinson. Apesar de décadas de investigações, nenhuma amostra de melanina foi estruturalmente bem caracterizada. Dentre os diversos obstáculos que são responsáveis pelo lento progresso que marca a pesquisa deste pigmento, o maior deles é que as melaninas naturais são altamente insolúveis e de presumido alto peso molecular. Pesquisas recentes desenvolvem sínteses alternativas para as melaninas utilizando outros solventes e demonstram que até 20 % da estrutura desta pode ser composta por água. Assim, neste trabalho investigamos, por métodos quânticos, a geometria e estrutura eletrônica das moléculas 5,6 indolquinona, suas formas reduzidas (semiquinona e hidroquinona) e 27 dímeros obtidos a partir destas, em seus estados neutros e iônicos ( ± 1 e ± 2), no vácuo e nos solventes DMF(dimetilformamida), DMSO (dimetilsulfóxido) e água. Verificamos como o solvente altera as propriedades eletrônicas e espectroscópicas destas estruturas e como este pode ser fundamental para a determinação de suas geometrias. Utilizamos dois modelos para simular o solvente: um modelo contínuo, COSMO (Conductor-like Screening Model) e um discreto, que considera explicitamente cada molécula do solvente e é baseado em simulações Monte Carlo. Notamos que o solvente altera a propriedade de aceitador de dois elétrons de diversas estruturas, fato até então não observado e de importante consequência biológica, visto as eumelaninas poderem ser base de um mecanismo de defesa celular contra radicais livres. Os picos dos espectros de absorção, de um modo geral, são deslocados para o vermelho e, em alguns casos, tem um alargamento. Isto poderia contribuir para a constrção da larga banda característica das eumelaninas. Diversos outros aspectos importantes, em excelente acordo com dados experimentais, são também apresentados ao se considerar o solvente. Um dos mais relevantes mostra que o solvente tem forte influência na geometria da molécula com o menor custo de dimerização, o que nos leva a concluir que esta pode ser de fato a semente de "nucleação" para a formação do polímero de melanina. / Abstract: Melanins belong to an important class of biological pigments due to its abundant presence in mamal tissues. There are strong evidences that suggest that the pigmentation due to melanin would protect the skin against the biochemical devastation induced by solar exposure. Besides the photo-protection feature, other biological functions have been speculated to melanin due to its presence in non-illuminated areas of the body and the apparent preferential destruction of melanin-containing cells in the substancia nigra of the brain in Parkinsonism. Unfortunately, in what concerns structural and chemical composition, no melanin sample has been fully and unambiguously characterized yet, despite the enormous amount of experimental work done so far. The main difficulty for that is that melanin is insoluble in most organic solvents and has high molecular weight. A new synthetic route for melanins, using organic solvents, has been recently achieved and it was demonstrated that about 20 % of the structure of the pigment is composed by water. In this work we have investigated using quantum methods the geometries and electronic structure of 5,6 indolquinone, their redox forms (semiquinone and hidroquinone) and 27 dimers associated, in their neutral and ionic states ( ± 1 e ± 2). The calculation were carried in vacuum and in the solvents dimethyl sulfoxide (DMSO), N,N-dimethyl formamide (DMF) and water. We study the effect of the solvent on the electronic and spectroscopic properties and its importance to determine eumelanin structure. Two models for solvents were used. The first was a continuum model, COSMO (Conductor-like Screening Model), and the second one (based on Monte Carlo simulations) explicitly considers each molecule of the solvent. The results showed that the solvents affected the electron accepton properties allowing the acceptance of two electrons. These aspects have been not been observed before from vacuum calculations and it is of important biological consequence because the melanins can be the base of mechanism of cellular defense against free radicals. The peaks of absorption spectra of the solvated structure are dislocated from red and broadened. This could contribute to the characteristic broad band of eumelanins. Many others important aspects are in better agreement with experimental data when solvent aspects are explicitly taken into account. One of most important results was the observation that solvent effects can alter the order of the lowest energy dimer configuration in relation to the structures in vacuum. This dimer was suggested to be the nucleation seed for the polymer formation. / Mestrado / Física Atômica e Molecular / Mestre em Física

Spin-orbit coupling (SOC) is a relativistic effect whose origin lies in the Dirac’s equation – a relativistic analogue of Schrödinger’s equation. SOC corrects the electronic states of a quantum mechanical system up to ~1 eV in case of semiconductors and ~ 2 – 3.6 eV in case of actinides and heavy elements by considering not only the coordinates but also the spin of the electrons in the system. Most of the applications of the present day technology are based on manipulating the electronic structure of a system with very high accuracy and precision. This demands availability of correct electronic structure of a material or molecule within a feasible computational time. Some direct consequences of SOC in materials can be noticed in analyzing the charge-transport properties of a semiconductor, evaluating the candidature of transition metal dichalcogenides (TMDCs) for spintronic, twistronic and valleytronic applications, and in the origin of topological properties of a material. Not only in materials but also in molecules the SOC effects can be observed. Fine-structure of atomic spectra was explained on the account of SOC. Several additional peaks and wavelength shift in UV-vis spectroscopy of Gold Superatoms can only be explained by correctly considering the energy level splittings caused by SOC. SOC allows intersystem and reverse intersystem crossing by mixing the spin states, ultimately opening various chemical reaction pathways which were spin forbidden before. Current advancements in computational power enrich us to work shoulder to shoulder with experiments where one can simulate the synthesized structures containing thousands of atoms using semi-empirical methods as in DFTB, GFN-XTB. These methods so far considered SOC effects but only as case studies in testing the implementation of SOC Hamiltonian rather than a systemic extension of SOC parameters to most part of the periodic table and studying SOC effects for different categories of materials and molecules. This motivated us to implement the SOC either in the form of highly accurate parameters throughout the periodic table or as addition in hamiltonian in such methods. Twisted van der Waals 2D materials as in twisted TMDC bilayers shows exciting electronic and optoelectronic properties and depending on the twist angle and chemical composition they can have thousands of atoms in their superlattices. A correct electronic analysis of such structures with SOC corrected DFT is computationally very expensive but is feasible at semi-empirical level. Here, we have applied our implementation on TMDC homo and heterobilayer twisted superlattices and studied the effect of SOC on the excitonic properties of the system. Therefore, this work opens the way for realizing various exotic applications of present day materials as well as molecules.:Table of Contents Abstract 4 1 Introduction 8 1.1 Quantum Chemistry: 8 1.2 HF based Semi-Empirical Methods 9 1.3 DFT based Semi-Empirical Methods 11 1.3.1 Density Functional based Tight-Binding Method (DFTB) 11 1.3.2 Geometry, Frequency, Non-Covalent, extended Tight Binding (GFN-xTB) 12 1.4 Spin-Orbit Coupling (SOC) 14 1.4.1 SOC in Materials 18 1.4.2 SOC in Molecular Structures 22 1.5 Theoretical Models for Accounting SOC 24 1.6 Motivation, Objective and Outline of thesis 26 2 Methodology 29 2.1 Quantum Chemistry 30 2.1.1 Schrödinger equation 30 2.2 Density Functional Theory 33 2.2.1 Generalized Gradient Approximations 39 2.3 Spin-orbit Coupling (SOC) 41 2.3.1 Classical Picture of SOC in LS model 42 2.3.2 Quantum Picture of SOC in LS model: 43 2.3.3 Calculation of SOC Paramentes 45 2.4 Density Functional Based Semi-empirical Quantum Mechanical Methods 48 2.4.1 Self-Consistent Charge Density Functional Based Tight Binding Method (SCC-DFTB) 48 2.4.2 Extended Tight-Binding (GFN1-xTB) 51 2.4.3 Addition of Spin-Orbit Coupling Hamiltonian in DFTB and GFN-xTB 54 3 Benchmarking Spin-Orbit Coupling Parameters for DFTB 56 3.1 Introduction 58 3.2 Computational Details of the DFT benchmark calculations 60 3.3 Benchmarking Spin-Orbit Coupling Parameters 60 3.3.1 III-V Bulk Semiconductor 61 3.3.2 Transition Metal Dichalcogenide 2D Crystals 65 3.3.3 Topological Insulators 68 3.4 Conclusions 70 4 Spin-Orbit Coupling Corrections for the GFN-xTB method 71 4.1.1 Introduction 73 4.2 Computational Details of The Benchmark Calculations 75 4.3 Results & Discussion 76 4.3.1 Geometries 76 4.3.2 Effect of SOC on Charge Transport Properties of Chromophores in MOFs 77 4.3.3 Superatoms 82 4.3.4 Effect of SOC on Binding of O2 on Ferrous Deoxyheme 85 4.4 Conclusions 86 5 Spin Orbit Coupling Effects on The Excitonic Properties of Twisted Moiré Transition Metal Dichalcogenides 88 5.1 Introduction 90 5.2 Computational Details 92 5.3 Results & Discussions 93 5.4 Excitons in Twisted Moiré Homobilayers 93 5.5 Excitons in Twisted Moiré Heterobilayers 102 5.6 Conclusions 109 6 Summary 112 A. Acronym 116 B. Appendices 120 SOC Parameters 120 7 References 147 C. Acknowledgement 173

Dans la recherche de nouveaux traitements des maladies broncho-pulmonaires comme l'asthme et la broncho-pneumopathie chronique obstructive, les inhibiteurs de PDE4 sont des cibles intéressantes. Dans cette voie, notre laboratoire s'intéresse à la synthèse d'une nouvelle famille d'inhibiteurs à base pyridazinone. Pour cela, cette thèse couple la modélisation moléculaire (docking : développement méthodologique et application), la synthèse organique ainsi que des tests biologiques.Dans un premier temps, le développement du logiciel d'amarrage moléculaire AlgoGen a été poursuivi. AlgoGen (créé initialement à l'université de Lorraine en 2009) est un logiciel qui couple un algorithme génétique pour la recherche conformationnelle à une évaluation de l'énergie protéine-ligand à un niveau quantique semi-empirique alors que les autres logiciels existant effectuent ce calcul à un niveau classique en général. Le calcul d'une énergie à un niveau quantique est très coûteux en temps. C'est pourquoi, nous avons apporté de nombreuses modifications à ce logiciel afin d'accroître son efficacité dans la recherche conformationnelle. Ce logiciel a ensuite été utilisé sur un jeu de 22 dimères (typiques des reconnaissances moléculaires biologiques) et à huit systèmes protéine-ligand.Dans un deuxième temps, huit inhibiteurs ont été synthétisés et testés in vitro sur la cible PDE4. Pour compléter ce volet expérimental, une étude de structure-activité a été effectuée grâce au docking moléculaire (AlgoGen, Autodock, Glide) pour rationaliser les activités mesurées (IC50). Pour terminer, des pharmaco-modulations guidées par docking ont été réalisées afin de proposer de nouveaux inhibiteurs de plus grandes affinités avec la protéine PDE4D. / For the research of new treatment of bronchopulmonary diseases such as asthma and chronic obstructive pulmonary disease (COPD), the PDE4 inhibitors are an attractive target. Our laboratory is interested in a new PDE4 inhibitors family based on the pyridazinone pattern. For this purpose, this thesis couples molecular modeling (docking: methodological development and application), organic synthesis and biological tests.First, the development of the molecular docking software AlgoGen was continued. AlgoGen (initially created at university of Lorraine in 2009) is a program which couples a genetic algorithm for the conformational research and a protein-ligand energy evaluation at the quantum semi-empirical level while other software do this evaluation at a classical level. Quantum energy calculations are very time consuming. That is the reason why some modifications have been made to improve its efficiency for the conformational search. This software was then used for calculations on a set of 22 dimers (typical in biological molecular recognition) as well on 8 ligand-protein complexes.Secondly, eight inhibitors were synthesized and tested in vitro on the PDE4 target. To complete the experimental part, a structure-activity relationship study was carried out through a molecular docking to rationalize the measured activity (IC50). Finally, pharmaco-modulations guided by docking were made to propose new inhibitors with more affinity with the protein.

<p>The absorption spectra of a recently designed low-bandgap conjugated polymer has been studied using the semi-empirical method ZINDO and TDDFT/B3LYP/6-31G. The vertical excitation energies have been calculated for monomer up to hexamer. Two main absorption peaks can be seen, the one largest in wavelength corresponding to a HOMO to LUMO transition, and one involving higher order excitations. TDDFT results are red-shifted compared to the ZINDO results. Comparison with experiment yields that short conjugation lengths are dominating. This is possibly due to steric interactions between polymer chains, breaking the conjugation length. Such effects are also studied.</p>

The absorption spectra of a recently designed low-bandgap conjugated polymer has been studied using the semi-empirical method ZINDO and TDDFT/B3LYP/6-31G. The vertical excitation energies have been calculated for monomer up to hexamer. Two main absorption peaks can be seen, the one largest in wavelength corresponding to a HOMO to LUMO transition, and one involving higher order excitations. TDDFT results are red-shifted compared to the ZINDO results. Comparison with experiment yields that short conjugation lengths are dominating. This is possibly due to steric interactions between polymer chains, breaking the conjugation length. Such effects are also studied.

Made available in DSpace on 2015-05-14T13:21:13Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 1246890 bytes, checksum: d8de4e92a3d9c573a9ad39ccb546aa71 (MD5) Previous issue date: 2008-11-13 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Lanthanide macrocyclic complexes, especially containing Gd(III) ions, are largely used as contrast agents in the medical diagnostic technique named Magnetic Resonance Imaging (MRI). Theoretical investigation of these compounds by molecular modeling methods is an emerging research area today. In this work we have performed a conformational study of the following supramolecular compounds: the macrocyclic ligands 1,4,7,10- tetraazacyclododecane (DOTA) and 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid (H4DOTA) and the macrocyclic complexes [Gd(DOTA).H2O]- and Gd(PhenHDO3A).H2O, where PhenHDO3A is (rel-10- [(5R,6R)-5,6-dihydro-6-hydroxy-1,10-Phenanthroline-5-yl)-1,4,7,10- tetraazacyclododecane-1,4,7-triacetic acid). For this, we have developed and carried out a procedure that involves: (1) the sampling of the conformation space of these compounds through some short molecular dynamics at different temperatures and (2) full geometry optimization in the geometries obtained in the previous stage using semi-empirical AM1 method for the macrocyclic ligands and Sparkle/AM1 model for the macrocyclic lanthanide complexes. Our results revealed that the high flexibility of non-coordinated macrocyclic ligands DOTA and H4DOTA, helped us to test the ability of our methodology to sample different regions of conformation space of these compounds. For the [Gd(DOTA).H2O]- complex, we were capable to find the same conformational isomers which were reported in published works as well as to comprehend relevant details about the mobility of the coordinated water molecule. Furthermore, we also were capable to identify some intermediate local minima related to the dynamics of rotation of the coordinated acetate groups in the studied complexes as well as to the dynamics of ring inversion of the coordinated tetraazadodecane moiety in the Gd(PhenHDO3A).H2O. In conclusion, we possess now an interesting strategy to conduct the search for conformational isomers of these compounds. This knowledge is very important to be applied in the rational design of new molecules to act as contrast agent in MRI. / Complexos macrocíclicos de lantanídeos, em especial com o íon Gd(III), são cada vez mais utilizados como agentes de contrastes na técnica médica de diagnóstico, imagem por ressonância magnética nuclear (MRI). O estudo teórico de novos agentes de contrastes através de modelagem molecular é uma área de pesquisa em grande expansão. No nosso trabalho fizemos um estudo conformacional dos seguintes compostos supramoleculares: os ligantes macrocíclicos 1,4,7,10- tetraazaciclododecano (DOTA) e ácido 1,4,7,10-tetraazaciclododecano- 1,4,7,10-tetraacético (H4DOTA), o complexo macrocíclico [Gd(DOTA)H2O]- e o complexo macrocíclico Gd(PhenHDO3A).H2O, onde PhenHDO3A é (rel-10-[(5R,6R)-5,6-dihidro-6-hidroxi-1,10-fenantrolina-5- il)-1,4,7,10-tetraazaciclododecano-1,4,7-ácido triacético). Para isso, elaboramos e executamos um procedimento que envolve o mapeamento ou amostragem do espaço conformacional desses compostos através de dinâmicas moleculares curtas em diferentes temperaturas para em seguida, essas geometrias serem usadas como pontos de partida para otimização de geometria usando tanto o método semi-empírico AM1 quanto o modelo Sparkle/AM1. Como resultado, podemos citar que a elevada flexibilidade dos ligantes macrocíclicos não coordenados DOTA e H4DOTA, serviu para testar a capacidade da nossa metodologia de visitar regiões distintas do espaço conformacional. Para o complexo [Gd(DOTA)H2O]-, conseguimos encontrar os mesmos isômeros conformacionais que já são reportados em outros estudos, bem como revelar detalhes relativos à mobilidade da molécula de água coordenada. Além disso, conseguimos identificar mínimos locais intermediários que estão relacionados com a dinâmica de rotação dos grupos acetato em ambos os complexos e a dinâmica de inversão do anel tetraazadodecano no complexo Gd(PhenHDO3A).H2O. A relevância desse trabalho está apoiada no fato de que agora temos uma estratégia interessante para realizar a busca de isômeros conformacionais desses compostos, sendo essas informações, muito importantes quando se deseja projetar uma nova molécula para atuar como agente de contraste em MRI.

The background in this study is that over the years analysis of grade 12 results in Ekurhuleni South District indicates that most secondary schools obtain 100% pass rate but not quality results isiZulu home language. IsiZulu home language quality results often range from 20% to 40%. The research findings point at two casual factors: (1) inside the classroom and (2) outside the classroom. Inside the classroom refers to quality of educators teaching isiZulu home language and outside the classroom refers to what is supposedly isiZulu home language’ yet a close analysis of the kind spoken in the township Zulu homes is in fact pidgin Zulu. In terms of quality evaluation this so called isiZulu home language can never pass quality assurance. The researcher recommends that educators of isiZulu home language be put through vigorous quality training in the teaching of isiZulu (HL). / African Languages / M.A. (African Languages)

Savannahs regulate an agro-ecosystem crucial for the production of domestic livestock, one of the main sources of income worldwide as well as in South African rural communities. Nevertheless, globally these ecosystem functions are threatened by intense human exploitation, inappropriate land use and environmental changes. Leaf area index (LAI) defined as one half the total green leaf area per unit ground surface area, is an inventory of the plant green leaves that defines the actual size of the interface between the vegetation and the atmosphere. Thus, LAI spatial data could serve as an indicator of rangeland productivity. Consequently, the accurate and rapid estimation of LAI is a key requirement for farmers and policy makers to devise sustainable management strategies for rangeland resources. In this study, the main focus was to assess the utility and the accuracy of the PROSAILH radiative transfer model (RTM) to estimate LAI in the South African rangeland on the recently launched Landsat 8 sensor data. The Landsat 8 sensor has been a promising sensor for estimating grassland LAI as compared to its predecessors Landsat 5 to 7 sensors because of its increased radiometric resolution. For this purpose, two PROSAIL inversion methods and semi- empirical methods such as Normalized difference vegetation index (NDVI) were utilized to estimate LAI. The results showed that physically based approaches surpassed empirical approach with highest accuracy yielded by artificial neural network (ANN) inversion approach (RMSE=0.138), in contrast to the Look-Up Table (LUT) approach (RMSE=0.265). In conclusion, the results of this study proved that PROSAIL RTM approach on Landsat 8 data could be utilized to accurately estimate LAI at regional scale which could aid in rapid assessment and monitoring of the rangeland resources. / Environmental Sciences / M. Sc. (Environmental Science)

The background in this study is that over the years analysis of grade 12 results in Ekurhuleni South District indicates that most secondary schools obtain 100% pass rate but not quality results isiZulu home language. IsiZulu home language quality results often range from 20% to 40%. The research findings point at two casual factors: (1) inside the classroom and (2) outside the classroom. Inside the classroom refers to quality of educators teaching isiZulu home language and outside the classroom refers to what is supposedly isiZulu home language’ yet a close analysis of the kind spoken in the township Zulu homes is in fact pidgin Zulu. In terms of quality evaluation this so called isiZulu home language can never pass quality assurance. The researcher recommends that educators of isiZulu home language be put through vigorous quality training in the teaching of isiZulu (HL). / African Languages / M.A. (African Languages)

Savannahs regulate an agro-ecosystem crucial for the production of domestic livestock, one of the main sources of income worldwide as well as in South African rural communities. Nevertheless, globally these ecosystem functions are threatened by intense human exploitation, inappropriate land use and environmental changes. Leaf area index (LAI) defined as one half the total green leaf area per unit ground surface area, is an inventory of the plant green leaves that defines the actual size of the interface between the vegetation and the atmosphere. Thus, LAI spatial data could serve as an indicator of rangeland productivity. Consequently, the accurate and rapid estimation of LAI is a key requirement for farmers and policy makers to devise sustainable management strategies for rangeland resources. In this study, the main focus was to assess the utility and the accuracy of the PROSAILH radiative transfer model (RTM) to estimate LAI in the South African rangeland on the recently launched Landsat 8 sensor data. The Landsat 8 sensor has been a promising sensor for estimating grassland LAI as compared to its predecessors Landsat 5 to 7 sensors because of its increased radiometric resolution. For this purpose, two PROSAIL inversion methods and semi- empirical methods such as Normalized difference vegetation index (NDVI) were utilized to estimate LAI. The results showed that physically based approaches surpassed empirical approach with highest accuracy yielded by artificial neural network (ANN) inversion approach (RMSE=0.138), in contrast to the Look-Up Table (LUT) approach (RMSE=0.265). In conclusion, the results of this study proved that PROSAIL RTM approach on Landsat 8 data could be utilized to accurately estimate LAI at regional scale which could aid in rapid assessment and monitoring of the rangeland resources. / Environmental Sciences / M. Sc. (Environmental Science)