Disertacijoje nagrinėjamas galimas aplinkos poveikis organinių molekulių elektroninių būsenų savybėms. Tam tikslui yra naudojami kompiuterizuotieji kvantinės mechanikos metodai, kuriais remiantis nagrinėjamos įvairių molekulių savybės. Ištirtos 2-(N-metil-α-iminoethyl)-fenol ir N-triphenylmethylsalicylidene imine molekelulių, esančių poliniame tirpiklyje, struktūros pagrindinėje ir sužadintose elektroninėse būsenose. Pirmą kartą parodyta, kad, norint gauti teisingą kokybinį ir artimą kiekybiniam vidujmolekulinės protono pernašos potencinės energijos paviršių, būtina atsižvelgti į polinių tirpiklio molekulių kuriamą vandenilinių ryšių tinklą bei į nulinių svyravimų energijas. Pastarieji ir nulemia protono pernašos vyksmo kryptį bei efektyvumą. Parodyta, kad anilų klasės molekulių konformerų susiformavimas priklauso nuo tirpiklio poliškumo, o jų susidarymas savo ruožtu konkuruoja su klasterių iš tirpiklio molekulių susiformavimo galimybėmis. Pirmą kartą parodyta, kad dipolinio momento vertė bakteriorodopsine yra nulemta membranos paviršiuose esančių radikalų. Pademonstruota, kad stilbazolio molekulė deformuojasi ir sudaro naujus konformerus (pademonstruota dviejų formų atsiradimo galimybė) tik esant molekulėms tirpalo apsuptyje. Šis rezultatas paaiškino eksperimente stebimus skirtuminių spektrinių pokyčių evoliucijos prigimtį. Apskaičiuotos ir išanalizuotos karotinoidų - luteino, violaksantino ir zeaksantino molekulių - žemiausios sužadintos elektroninės būsenos. Parodyta... [toliau žr. visą tekstą] / To explore changes caused by the environment on the internal characteristics of an organic molecule is the objective of the thesis. For this purpose we investigate a variety of organic molecules. Using various methods of quantum mechanics calculations possible influence of a polar solvent on the ground and excited states of 2-(N-metil-α-iminoethyl)-fenol and N-triphenylmethylsalicylidene imine is considered. It is shown for the first time that in order to obtain the correct qualitative and quantitative interpretation of possible pathways of the intermolecular proton transfer the hydrogen network of the polar solvent molecules together with the zero point energy have to be taken into consideration. It is also shown that conformational variability of anil-type molecules in polar solvents is competing with clusters formation of solvent molecules. It is shown for the first time that the dipole moment of bacteriorhodopsin is mainly defined by cytoplasmic and extracellular coils on the surfaces of the membrane. It is also demonstrated that the stilbazole molecule experiences the deformation resulting in formation of new conformers (at least two forms are present) in the solvent surrounding. The experimental data of the transient spectroscopy were explained in the basis of these model calculations. The lowest excited states of carotinoids, such as lutein, zeaxanthin and violoxantin are calculated and analyzed. Sensitivity of the excited electronic state on the polar environment is... [to full text]

Disertacijoje nagrinėjamas galimas aplinkos poveikis organinių molekulių elektroninių būsenų savybėms. Tam tikslui yra naudojami kompiuterizuotieji kvantinės mechanikos metodai, kuriais remiantis nagrinėjamos įvairių molekulių savybės. Ištirtos 2-(N-metil-α-iminoethyl)-fenol ir N-triphenylmethylsalicylidene imine molekelulių, esančių poliniame tirpiklyje, struktūros pagrindinėje ir sužadintose elektroninėse būsenose. Pirmą kartą parodyta, kad, norint gauti teisingą kokybinį ir artimą kiekybiniam vidujmolekulinės protono pernašos potencinės energijos paviršių, būtina atsižvelgti į polinių tirpiklio molekulių kuriamą vandenilinių ryšių tinklą bei į nulinių svyravimų energijas. Pastarieji ir nulemia protono pernašos vyksmo kryptį bei efektyvumą. Parodyta, kad anilų klasės molekulių konformerų susiformavimas priklauso nuo tirpiklio poliškumo, o jų susidarymas savo ruožtu konkuruoja su klasterių iš tirpiklio molekulių susiformavimo galimybėmis. Pirmą kartą parodyta, kad dipolinio momento vertė bakteriorodopsine yra nulemta membranos paviršiuose esančių radikalų. Pademonstruota, kad stilbazolio molekulė deformuojasi ir sudaro naujus konformerus (pademonstruota dviejų formų atsiradimo galimybė) tik esant molekulėms tirpalo apsuptyje. Šis rezultatas paaiškino eksperimente stebimus skirtuminių spektrinių pokyčių evoliucijos prigimtį. Apskaičiuotos ir išanalizuotos karotinoidų - luteino, violaksantino ir zeaksantino molekulių - žemiausios sužadintos elektroninės būsenos. Parodyta... [toliau žr. visą tekstą] / To explore changes caused by the environment on the internal characteristics of an organic molecule is the objective of the thesis. For this purpose we investigate a variety of organic molecules. Using various methods of quantum mechanics calculations possible influence of a polar solvent on the ground and excited states of 2-(N-metil-α-iminoethyl)-fenol and N-triphenylmethylsalicylidene imine is considered. It is shown for the first time that in order to obtain the correct qualitative and quantitative interpretation of possible pathways of the intermolecular proton transfer the hydrogen network of the polar solvent molecules together with the zero point energy have to be taken into consideration. It is also shown that conformational variability of anil-type molecules in polar solvents is competing with clusters formation of solvent molecules. It is shown for the first time that the dipole moment of bacteriorhodopsin is mainly defined by cytoplasmic and extracellular coils on the surfaces of the membrane. It is also demonstrated that the stilbazole molecule experiences the deformation resulting in formation of new conformers (at least two forms are present) in the solvent surrounding. The experimental data of the transient spectroscopy were explained in the basis of these model calculations. The lowest excited states of carotinoids, such as lutein, zeaxanthin and violoxantin are calculated and analyzed. Sensitivity of the excited electronic state on the polar environment is... [to full text]

Fourier transform infrared difference spectroscopy (FTIR DS) is widely used to study the structural details of electron transfer cofactors in photosynthetic protein complexes. In photosynthetic proteins quinones play an important role, functioning as a cofactor in light-driven electron transfer. In photosystem I (PS I) phylloquinone (PhQ) functions as an intermediary in electron transfer. To investigate the properties of PhQ that occupies the, so called, A1 binding site in PS I, time-resolved step-scan FTIR DS, with 5µs time resolution at 77K has been used. By replacing PhQ in the A1 binding site with specifically isotope labeled version, information on the vibrational frequencies associated specifically with the quinone in the binding site were obtained, which could be compared to the vibrational properties of quinone in solution or quinones in other protein binding sites. To further aid in assessing the origin of bands in the spectra, quantum mechanics /molecular mechanics (QM/MM) ONIOM type calculations were undertaken. ONIOM is an acronym for Our own N-layered Integrated molecular Orbital and molecular Mechanics. We find that the phytyl tail of PhQ does not play an important role in the orientation of PhQ in the A1 binding site. We also find that PhQ, in both neutral and reduced states, is strongly hydrogen bonded. To test and verify the applicability of our QM/MM approach, ONIOM calculations were also undertaken for ubiquinone and a variety of other quinones incorporated into the, so called, QA binding site in purple bacteria photosynthetic reaction centers. The calculated and experimental spectra agree well, demonstrating the utility and applicability of our ONIOM approach. Hydrogen bonding to the carbonyl groups of quinones in the QA binding site was shown to be relatively weak, and it was found that hydrogen bonding to neutral ubiquinone in purple bacterial reaction centers can be considered in purely electrostatic terms, contrary to the widely held belief that the hydrogen bonding amino acids should be treated quantum mechanically.

High-resolution magic angle spinning (HRMAS) NMR spectroscopy is used to study solid samples that are normally difficult to analyze due to broadening of peaks. Solid-phase peptide synthesis can bind peptides to an insoluble resin that can be analyzed with HRMAS NMR spectroscopy. A combination of HRMAS NMR and IRMPD spectroscopy, along with computational chemistry, was applied to analyze and evaluate the structure of resin-bound glutathione. Two-dimensional 1H-1H NMR experiments such as COSY, TOCSY, and ROESY were employed to assign and predict the structure of the resin-bound peptide. IRMPD results were used along with calculated protonated structures and spectra to evaluate the conformation of the peptide. The experimental spectrum was compared to the spectra and structures of the protonated species to hypothesize the most favoured structure. Molecular mechanics, molecular dynamics and DFT calculations were implemented to collect structures that best resembled the free and resin-bound glutathione peptide. The results from these methods were compared to determine the structure that is most probable for the glutathione peptide. A semi-folded conformation is the structure the resin-bound GSH most preferred as concluded from the NMR and DFT results. The IRMPD results were analyzed as separate from the resin-bound experiments and suggested protonated GSH had a folded conformation. FK-13 was another peptide synthesized using the solid-phase peptide synthesis technique. The peptide was synthesized using a modified technique different from conventional methodology used in the past. The peptide was also analyzed using COSY, TOCSY, and ROESY to confirm that the synthesis was done correctly and hypothesize a structure. The low substitution of the peptide on the resin gave rise to minimal NOE interactions, but there was some evidence suggesting that the synthesis was successful and the peptide adopted a cyclic conformation. These initial results are useful for future analyses and conformational studies of this resin-bound peptide. Further work needs to be done for both peptides to explore the structures in more detail. The explicit model of solvation should be used to explore the effect of solvent molecules on the conformation of the glutathione peptide as opposed to the implicit model that PCM provides. FK-13 could be synthesized better so that a higher substitution is achieved and better NMR results are obtained. The IRMPD results obtained by the McMahon group can then be compared to the NMR results and computational calculations can be performed to obtain realistic structures of the peptide.

El objetivo de esta tesis se centra en el estudio de la transferencia de electrones (ET), una de las reacciones más simples y cruciales en bioquímica. Para dichos procesos, obtener información directa de los factores que lo promueves, asi como del camino de transferencia electronica, no es una tarea trivial. Dicha información a un nivel de conocimiento detallado atómico y electrónico, sin embargo, es muy valiosa en términos de una mejor comprensión del ciclo enzimático, que podría conducir, por ejemplo, a un diseño más eficaz de inhibidores. El objetivo principal de esta tesis es el desarrollo de una metodología para el estudio cuantitativo de la ET en los sistemas biológicos. En este sentido, hemos desarrollado un nuevo método para obtener el camino de transferencia electrónico, llamado QM/MM e-­‐ Pathway, que se puede aplicar en sistemas complejos con ET de largo alcance. El método se basa en una búsqueda sucesiva de residuos importantes para la ET, utilizando la modificación de la región quantica en métodos mixtos QM/MM, y siguiendo la evolución de la densidad de espín dentro de la zona de transferencia. Hemos demostrado la utilidad y la aplicabilidad del algoritmo en el complejo P450cam/Pdx, identificando el papel clave de la Arg112 (en P450cam) y del Asp48 (en Pdx), ambos conocidos en la literatura. Además de obtener caminos de ET, hemos cuantificado su importancia en términos del acoplamiento electrónico entre el dador y aceptor para los diferentes caminos. En este sentido, se realizaron dos estudios de la influencia del solvente y de la temperatura en el acoplamiento electrónico para sistemas modelo oligopéptidos. Ambos estudios revelaron que los valores del acoplamiento electrónico fluctúan fuertemente a lo largo de las trayectorias de dinámica molecular obtenidas, y el mecanismo de transferencia de electrones se ve ampliamente afectado por el espacio conformacional del sistema. La combinación del QM/MM e-­‐pathway y de los cálculos de acoplamiento electronico fueron utilizados finalmente para investigar la ET en el complejo CCP/Cytc. Nuestros hallazgos indican el papel fundamental del Trp191 en localizar un estadio intermedio para la transferencia electronica, así como el camino ET principal que incluye Ala194, Ala193, Gly192 y Trp191. Ambos hallazgos fueron confirmados a través de la literatura. Los resultados obtenidos para el muestro de manios de ET, junto con su evaluación a través de cálculos de acoplamiento electrónico, sugieren un enfoque sencillo y prometedor para investigar ET de largo alcance en proteínas. / The focus of this PhD thesis lies on electron transfer (ET) processes, belonging to the simplest but most crucial reactions in biochemistry. Getting direct information of the forces driving the process and the actual electron pathway is not a trivial task. Such atomic and electronic detailed information, however, is very valuable in terms of a better understanding of the enzymatic cycle, which might lead, for example, to more efficient protein inhibitor design. The main objective of this thesis was the development of a methodology for the quantitative study of ET in biological systems. In this regard, we developed a novel approach to map long-­‐range electron transfer pathways, called QM/MM e-­‐Pathway. The method is based on a successive search for important ET residues in terms of modifying the QM region following the evolution of the spin density of the electron (hole) within a given transfer region. We proved the usefulness and applicability of the algorithm on the P450cam/Pdx complex, indicating the key role of Arg112 of P450cam and Asp48 of Pdx for its ET pathway, both being known to be important from the literature. Besides only identifying the ET pathways, we further quantified their importance in terms of electronic coupling of donor and acceptor incorporating the particular pathway residues. Within this regard, we performed two systematic evaluations of the underlying reasons for the influence of solvent and temperature onto electronic coupling in oligopeptide model systems. Both studies revealed that electronic coupling values strongly fluctuate throughout the molecular dynamics trajectories obtained, and the mechanism of electron transfer is affected by the conformational space the system is able to occupy. Combining both ET mapping and electronic coupling calculations, we finally investigated the electron transfer in the CcP/Cytc complex. Our findings indicate the key role of Trp191 being the bridge-­‐localized state of the ET as well as the main pathway consisting of Ala194, Ala193, Gly192 and Trp191 between CcP and Cytc. Both findings were confirmed through the literature. Moreover, our calculations on several snapshots state a nongated ET mechanism in this protein complex. The methodology developed along this thesis, mapping ET pathways together with their evaluation through electronic coupling calculations, suggests a straightforward and promising approach to investigate long-­‐range ET in proteins.

No description available.

As vias de sinalização celular por meio de moléculas são um dos principais meios de controle funcional de um organismo. O entendimento das funções de moléculas sinalizadoras facilita a compreensão das vias metabólicas de um organismo, assim possibilitando uma melhor compreensão de vários eventos biológicos e também de várias doenças. A sinalização pelo ácido retinóico (AR), e seus derivados, é responsável pelo controle de várias funções, por exemplo: crescimento celular, diferenciação celular, formação da retina, desenvolvimento cardíaco e também relacionado a várias patologias como diabetes, obesidades, cânceres, e doenças cardiovasculares. A ação do ácido retinóico é controlada em dois níveis: no metabolismo de síntese/degradação e na sua utilização na sinalização para a expressão gênica. A maquinaria que controla o metabolismo inclui as enzimas de síntese do AR (aldeído desidrogenase ALDH) e as enzimas de degradação do AR (Cyp26), que controlam a distribuição espaço-temporal do AR durante a embriogênese. As ALDHs são enzimas NAD(P)+ dependentes, que oxidam uma ampla gama de aldeídos para os seus correspondentes ácidos carboxílicos, sendo ALDH1A2 a principal enzima na transformação de retinal em ácido retinóico. A maquinaria da sinalização celular por AR contém os receptores nucleares controlados por AR (RARs) que estão envolvidos com o controle da transcrição gênica. Os mecanismos de controle de expressão mais comuns são os que ocorrem na fase transcricional. Um desses mecanismos envolve proteínas que se ligam às regiões promotoras de transcrição, representadas por trechos de DNA que geralmente estão localizados próximo à região de início da transcrição, mas que também podem estar a centenas ou até milhares de pares de bases desse início. Essas proteínas modulam a maquinaria transcricional, podendo ativá-la ou inibi-la. A associação de várias técnicas como a biologia molecular, bioinformática, filogenia, análises estruturais de biomoléculas, mecânica molecular e métodos termodinâmicos tem se mostrado uma poderosa abordagem para compreensão de sistemas biológicos simplificando e agilizando o desenvolvimento do conhecimento científico. Nessa direção, esse estudo desenvolveu duas análises: a primeira estudando a evolução das funções das enzimas ALDH, utilizando-se de técnicas de genômica combinatória, filogenia, bioinformática, estrutura de biomoléculas e de biologia do desenvolvimento, tentando compreender o modo como as ALDHs, que apresentam as seqüências de aminoácidos bastante similares, puderam divergir para gerar funções diversas como a destoxificação e a sinalização. Para este estudo foram analisados os genomas de 487 organismos em busca de seqüências de ALDHs e também o genoma do organismo modelo Branchiostoma floridae. Foram obtidas 190 seqüências que foram utilizadas em uma análise filogenética para tentar compreender a função primordial e também para definir grupos de aminoácidos candidatos a marcadores das diferentes famílias de ALDHs. Essas 190 seqüências também foram modeladas estruturalmente e analisada a forma e o volume do canal onde se aloja o aldeído a ser oxidado. A partir dessas informações foi possível prever que as ALDHs passaram das funções ancestrais de controle do padrão corporal para algo mais abrangente como funções protetoras. A segunda análise, utilizando-se das estruturas tridimensionais dos fatores de transcrição ligados ao DNA em diferentes posições e submetendo esses complexos a processos de mecânica molecular, cálculos termodinâmicos e análises das ligações de hidrogênio para tentar prever os mais prováveis sítios de interação entre os receptores e o DNA. O modelo escolhido para essa análise foram os fatores de transcrição regulados por ácido retinóico o RAR e RXR utilizando a região promotora do gene RARE-2 para avaliar as mais prováveis regiões de ligação desses fatores. Para esse estudo foram construídos 71 complexos proteína-DNA que foram submetidos a processos de mecânica molecular e cálculos termodinâmicos. A partir dessas informações foi possível prever uma região de maior afinidade entre o fator de transcrição e o DNA. As análises de ligações de hidrogênio possibilitaram definir exatamente a região de interação entre os fatores de transcrição e o DNA, e também descrever as interações moleculares responsáveis pela especificidade da interação. / Cellular signaling paths through molecules are one of the main processes of functional control of an organism. The comprehension of signaling molecules functions enables one to understand the metabolic pathways of an organism, along with related biological events and several diseases. The signaling through retinoic acid (RA) and its secondary products is responsible for controlling several functions, such as cellular growth and differentiation, retinas formation and cardio development, and is also related to several pathologies such as diabetes, obesity, cancers and cardiovascular disorders. There are two levels of control of retinoic acid activity: synthesis/degradation metabolism and its use in gene expression signaling. The machinery that controls the metabolism includes RAs synthesis (aldehyde dehydrogenase ALDH) and degradation (Cyp26) enzymes, which control the space-temporal distribution of RA during the embryogenesis. The ALDHs are NAD(P)+ dependent enzymes that oxidize many types of aldehydes into the related carboxylic acids, being the ALDH1A2 the main enzyme involved in the process of transformation of retinal into retinoic acid. The machinery of cellular signaling through RA contains the nuclear receptors controlled by RA (RARs) that are involved in the control of gene transcription. The most common mechanisms of expression control are the ones that occur during the transcriptional phase. One of these mechanisms involves proteins that bind to the transcription promoter regions, represented by DNA sequences that are usually located close to the region where the transcription starts, but can also be hundreds or thousands of base pairs apart from the starting point. These proteins modulate the transcriptional machinery, being responsible for both its activation and inhibition. The association of several techniques as molecular biology, bioinformatics, phylogeny, structural analysis of biomolecules, molecular mechanics and thermodynamic methods has been shown as a powerful tool for the understanding of biological systems, simplifying and speeding up the production of related scientific knowledge. Facing this direction, the present study developed two analyses. The first one studied the evolution of ALDH enzymes functions, using the techniques of combinatory genomic, phylogeny, bioinformatics, structure of biomolecules and developmental biology, in the attempt of understanding how the ALDHs could diverge and acquire different functions as detoxification and signaling, despite the fact that they have very similar aminoacid sequences. For this study, ALDHs sequences were searched for in the genome of 487 organisms plus the model organisms, Branchiostoma floridae. All 190 sequences obtained were used in a phylogenetic analysis, in the attempt of understanding the primordial function of the enzyme and defining possible groups of conserved aminoacids in the different families of ADLHs. These 190 sequences were also structurally modeled and the shape and volume of the channel where the aldehyde is placed to be oxidized were analyzed. Based on this information, it became possible to predict that the ALDHs moved from ancestral functions of corporal pattern control to a wider spectrum of protection functions. For the second analysis we submitted the complex formed by tridimensional structures of the transcriptional factors bond to DNA in different positions to processes of molecular mechanics, thermodynamic calculi and analysis of the hydrogen bonds, in order to predict the most probable sites of interaction between the receptors and the DNA. The model chosen for this analysis were the transcription factors regulated by retinoic acid, RAR and RXR, using the promoter region of the gene RARE-2 to assay the most probable binding regions of these factors. For this study, 71 protein-DNA complexes were built and submitted to processes of molecular mechanics and thermodynamic calculi. Based on the resulting data, it became possible to predict a region of greater affinity between the transcription factor and the DNA. The analyses of hydrogen bonds enabled us to define the exact region where the interaction between the transcription factor and the DNA takes place and also enabled us to describe the molecular interactions responsible for the specificity of this interaction.

Nanotubos de carbono e polímeros condutores são fortes candidatos à miniaturização dos componentes eletrônicos disponíveis atualmente. Estudos teóricos afirmaram que 1/3 dos nanotubos seriam metálicos, enquanto que os outros seriam semicondutores, mas alguns grupos reportaram medidas experimentais evidenciando um pequeno gap eletrônico em tubos considerados metálicos. Protótipos de transístores compostos de nanotubos e moléculas orgânicas conjugadas foram propostos e foi observado que o recobrimento dos tubos por moléculas de pentaceno tornava os dispositivos menos suscetíveis à deposição de impurezas, o que diminuía a histerese na curva característica i x V, ao mesmo tempo que a formação de cristais de pentaceno era favorecida. Neste trabalho estudamos a estrutura eletrônica dos nanotubos (5,5) e (9,0) través de DFT e observamos presença de um gap nesses sistemas, assim como uma deformação de suas estruturas de ligações químicas, evidenciando a distorção de Peierls. O efeito do termo de troca de Hartree-Fock introduzido no funcional B3LYP foi avaliado variando-se seu peso e observando as propriedades destes sistemas. Em uma segunda etapa, utilizamos mecânica molecular e dinâmica molecular clássica com o campo de forças CVFF 950 e observamos a formação de estruturas de pentaceno em volta dos tubos, evidenciando o favorecimento da formação de cristais do mesmo quando depositado sobre os nanotubos. / Carbon Nanotubes and conducting polymers are strong candidates for use in nanoscale electronic devices. Theoretical studies claimed that 1/3 of the nanotubes are metallic, while the others are semiconductors, but some groups have reported experimental measurements of a small electronic gap in tubes considered metallic. Prototype transistors made of nanotubes and organic conjugated molecules were proposed and it has been noticed that the coverage of the tubes by pentacene molecules made those trasistors less susceptible to impurity deposition, reducing the hysteresis in the characteristic I x V curve, while the formation of pentacene cristals was favored. In this work, we studied the electronic structure of the nanotubes (5,5) and (9,0) using DFT and noticed an electronic gap in those systems, as well as a deformation of their structures, similar to a Peierls distortion. The effect of the Hartree-Fock exchange included in the B3LYP functional was studied, as we varied its weight to obtain some properties of those systems. Later, we used molecular mechanics and classical molecular dynamics with the CVFF 950 force field and obtained structures compatible with pentacene crystals around the tubes, showing that the tubes in fact favor the formation of of these structures around them.

Made available in DSpace on 2016-08-18T18:19:26Z (GMT). No. of bitstreams: 1 Nilton Ferreira Frazao.pdf: 1298809 bytes, checksum: 5aca0b703a735a7fb605b7bdee658bdd (MD5) Previous issue date: 2009-03-30 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Recently, the existence of nanoribbon of Boron Nitride with finite size was discovered experimentally, in porous nanoesferas of BN (100-400 nm of diameter), synthesized for the reaction of B2O3 with carbon spheres contend nanoporos filled for Nitrogen to a temperature of 17500C. However a theoretical inquiry of the properties of this nanometerial did not exist. Then, in this present work, we carry through simulation of molecular mechanics using field of universal force (forcefild) to optimize the structure of some of these nanoribbon of Boron Nitride, with objective to find a conformation more steady, that is, of lesser energy for these nanostructures. Later, we investigate the electronic properties of these nanoribbon of Boron Nitride (NRBN) in the finite form (not-periodic) of two types: nanoribbon of Boron Nitride of the type to armchair (a-NRBN) and nanoribbon of Boron Nitride of the type zigzag (z-NRBN). The study of these properties they had been carried through of calculations of first principles based in the Density Functional Theory, with the local density approximation (LDA). Through our calculations, we observe that all the nanoribbon are metallic when we made the analysis of the density of states (DOS). Result not waited, but surprising, therefore of literature we know that material nanostructuralized of Boron Nitride they are always semiconductors. However, our calculations had shown that as much a-NRBN as z-NRBN had presented a conducting electronic character. The simulations had been carried through for many cases of nanoribbon of width (L) and length (C), forming a pair of indices (L, C), with the objective to facilitate the identification of these nanostructures. However we will present the results of but twelve of these, being: (1,3), (1,6), (1,9), (2,3), (2,6) e (2,9) in such a way of the types a-NRBN and z-NRBN. / Recentemente, foi descoberto experimentalmente a existência de Nanofitas de Nitreto de Boro (BN) de tamanho finito, em nanoesferas porosas de BN (100-400 nm de diâmetro), sintetizada pela reação de B2O3 com esferas de carbono contendo nanoporos preenchidos por Nitrogênio a uma temperatura de 17500C. No entanto não existia uma investigação teórica das propriedades desses nanocompósitos. Então, neste presente trabalho, realizamos simulações de mecânica molecular usando campo de força universal (forcefild) para otimizar a estrutura de algumas destas nanofitas de Nitreto de Boro, com objetivo de encontrar uma conformação mais estável, ou seja, de menor energia para essas nanoestruturas. Depois, investigamos as propriedades eletrônicas dessas nanofitas de Nitreto de Boro (NRBN) na forma finita (não-periódica) de dois tipos: nanofitas de Nitreto de Boro do tipo armchair (a-NRBN) e nanofitas de Nitreto de Boro do tipo zigzag (z-NRBN). O estudo destas propriedades foram realizados através de cálculos de primeiros princípios baseados na Teoria do Funcional da Densidade, com a aproximação da densidade local (LDA). Através de nossos cálculos, observamos que todas as nanofitas são metálicas quando fizemos a análise da densidade de estados eletrônicos (DOS). Resultado não esperado, mas surpreendente, pois da literatura sabemos que materiais nanoestruturados de Nitreto de Boro são sempre semicondutores. No entanto, nossos cálculos mostraram que tanto as a- NRBN como as z-NRBN apresentaram um caráter eletrônico condutor. As simulações foram realizadas para muitos casos de nanofitas de largura (L) e comprimento (C), formando um par de índices (L, C), com o objetivo de facilitar a identificação dessas nanoestruturas. No entanto apresentaremos os resultados de apenas doze dessas, sendo: (1,3), (1,6), (1,9), (2,3), (2,6) e (2,9) tanto dos tipos a-NRBN e z-NRBN.

Orientador: Prof. Dr. Maurício Domingues Coutinho Neto / Coorientador: Prof. Dr. Rodrigo Luiz Oliveira Rodrigues Cunha / Tese (doutorado) - Universidade Federal do ABC, Programa de Pós-Graduação em Ciência e Tecnologia/Química, Santo André, 2018. / Recentemente completaram-se dois séculos da descoberta do selênio, um elemento controverso que pode ser considerado tóxico e ao mesmo tempo essencial. Apesar de suas propriedades antagônicas, compostos de selênio possuem um grande apelo biológico desde o relato de sua incorporação em enzimas, através da selenocisteína. Neste contexto, os compostos de selênio e telúrio tem se destacado devido às suas propriedades anti-inflamatória, antioxidante, antiviral e antimicrobiana. E portanto, como potenciais quimioterápicos contra doenças cardiovasculares, infecciosas, neurológicas e parasitárias. Esses compostos também tem se mostrado promissores na inibição de cisteína-catepsinas. Essas enzimas são ubíquas e participam de diversas funções no organismo humano. Porém, a atividade desregulada de cisteína proteases está relacionada com o desenvolvimento de diversas patologias, que as fazem importantes alvos terapêuticos no planejamento de novos fármacos. Ensaios experimentais com calcogenuranas mostraram bons resultados na inibição de cisteína proteases. Embora o mecanismo de reação desses compostos ainda não tenha sido completamente esclarecido, a literatura propõe que a inibição ocorre através da reação de troca de ligante entre o grupo tiol e o átomo de calcogênio em sua forma hipervalente. Nesta abordagem, cálculos de mecânica quântica foram utilizados para a investigação do mecanismo de reação através da análise da energia livre de Gibbs envolvida em trocas de ligantes, utilizando a teoria do funcional de densidade (DFT), com o funcional B3LYP e base 6311-G+(d), considerando efeitos de dispersão e correção de ponto zero. Cálculos híbridos com metodologia quântica acoplada à dinâmica molecular (Quantum Mechanics / Molecular mechanics - QM/MM) foram desenvolvidos para avaliar a energia envolvida na inibição de papaína por selenurana utilizando o software AMBER em interface com o software Orca. Para a dinâmica molecular utilizou-se o campo de força geral do Amber (General Amber Force Field - GAFF) e o modelo de solvatação explícita TIP3P, enquanto que a os cálculos quânticos usaram abordagem semi-empírica com o funcional PM3 e teoria do funcional da densidade com o funcional BLYP e base def2-SV(P) incluindo efeitos de dispersão. Ensaios de docking molecular também foram realizados para determinar uma configuração de atracamento inicial para os cálculos de QM/MM. Os resultados propõem que as reações de troca de ligante ocorrem em duas etapas distintas, dependentes da acidez do meio. As selenuranas dicloradas eliminam cloro, em meio aquoso, e formam espécies tricoordenadas (DMeSeO, DMeOH+, DMeSH+, DMeCl+) que podem interagir com tiolato provinente de cisteína proteases provocando sua inibição em ambientes ácidos, com barreiras de energia muito pequenas (menor que 3 kcal) ou inexistentes. / Recently two centuries of the discovery of selenium have been completed, a controversial element that can be considered toxic and at the same time essential. Despite their antagonistic properties, selenium compounds have a great biological appeal since the report of their incorporation into enzymes, through selenocysteine. In this context, selenium and tellurium compounds have been prominent due to their anti-inflammatory, antioxidant, antiviral and antimicrobial properties. And therefore, as potential chemotherapeutics against cardiovascular, infectious, neurological and parasitic diseases. These compounds have also been shown to be promising in cysteine-cathepsin inhibition. These enzymes are ubiquitous and participate in various functions in the human body. However, the unregulated activity of cysteine proteases is related to the development of several pathologies, which make them important therapeutic targets in the planning of new drugs. Experimental trials with calcogenurans showed good inhibition of cysteine proteases. Although the mechanism of reaction of these compounds has not yet been fully elucidated, the literature proposes that inhibition occurs through the bound between the thiol group and the calcogen atom in its hypervalent form. In this approach, quantum mechanics calculations were used to investigate the reaction mechanism through the Gibbs free energy analysis involved to ligand exchanges reactions, using for this the density functional theory (DFT) with the B3LYP functional and base 6311-G+(d), considering dispersion effects and zero point correction. Hybrid calculations with Quantum Mechanics/Molecular Mechanics (QM/MM) were developed to evaluate the energy involved in the inhibition of papain by selenuran using AMBER software in interface with Orca software. For the molecular dynamics, the general Amber force field (GAFF) and the explicit solvation model TIP3P were used, while the quantum calculations used a semi-empirical approach with the PM3 functional and the DFT with the functional BLYP and base def2-SV (P) including dispersion effects. Molecular docking assays were also performed to determine an initial docking configuration for the QM/MM calculations. The results suggest that the ligand exchange reactions occur in two distinct steps, depending on the acidity of the medium. The dichlorinated selenuranes eliminate chlorine in aqueous medium and form tricoordinated species (DMeSeO, DMeSeOH+, DMeSeSH+, DMeSeCl+) which can interact with thiolate from cysteine proteases causing their inhibition in acid environments, with very small energy barriers (less than 3 kcal) or nonexistent.