Various gold complexes were computationally investigated, to probe their photophysical, geometric, and bonding properties. The geometry of AuI complexes (ground state singlet) is very sensitive to the electronic nature of the ligands: σ-donors gave a two-coordinate, linear shape; however, σ-acceptors yielded a three-coordinate, trigonal planar geometry. Doublet AuIIL3 complexes distort to T-shape, and are thus ground state models of the corresponding triplet AuIL3. The disproportionation of AuIIL3 to AuIL3 and AuIIIL3 is endothermic for all ligands investigated, however, σ-donors are better experimental targets for AuII complexes. For dimeric AuI complexes, only one gold center in the optimized triplet exciton displays a Jahn-Teller distortion, and the Au---Au distance is reduced versus the ground state distance (i.e., two reasons for large Stokes' shifts).

Mycobacterium tuberculosis (Mtb) is the causative agent of Tuberculosis (TB), a life-threatening disease primarily affecting the lungs that infects about one third of the world's population and causes 1.3 million deaths annually. It is estimated that TB has been infecting humans for around 70,000 years and has killed more people than any other infectious disease. The highly effective, persistent, and multifaceted virulence strategies that have allowed Mtb to continue to spread and thrive for so long are still poorly understood at the molecular level. This lack of knowledge contributes to ongoing challenges to curing TB. Although drugs capable of killing Mtb exist, even strains that are susceptible to these drugs remain so difficult to treat that stringent six- to nine-month courses of four-drug cocktails are required. Practical difficulties in administering full treatments and patient noncompliance have contributed to a rise in drug-resistant TB cases globally. To combat this increasing world health problem, new antibiotic treatments that kill Mtb and drug-resistant Mtb more effectively via new mechanisms of action are necessary. Discovering these antibiotics expediently requires that innovative Mtb-specific drug-screening assays are developed. An ideal and innovative TB drug screening method would target validated protein-protein interactions (PPI) essential to Mtb's pathogenesis and would be performed on whole Mtb cells under relevant in vivo-like conditions. This project focused on engineering several tools relevant to creating an ideal TB drug screen. A protein fragment complementation assay capable of studying PPI of the TB gyrase complex was created, and this assay was assessed for future HTS applications. To streamline the readout, this assay was re-engineered to include green fluorescent protein.

A Curcumin há muito tempo é utilizada como condimento, colorífico e na medicina tradicional asiática. Conhecida como açafrão-da-índia, recentemente tem chamado a atenção devido ao grande potencial medicinal. Surgiram trabalhos principalmente sobre seus supostos efeitos benignos no tratamento de câncer e Alzheimer porém não limitados a estas enfermidades. Na tentativa de otimizar as propriedades medicinais surgiu a Dimethoxy Curcumin, um composto sintético que apresenta maior citotoxicidade e estabilidade biológica que a Curcumin. A maioria das reações químicas e biológicas ocorrem em soluções e os efeitos dos solventes são de extrema importância e complexidade. Neste trabalho nós estudamos os efeitos dos solventes ciclohexano e acetonitrila nos espectros de absorção e emissão da Dimethoxy Curcumin. Consideramos a contribuição de diferentes isômeros e estados excitados usando a Teoria do Funcional Densidade Dependente do Tempo (TD-DFT) utilizando a aproximação Modelo Contínuo Polarizável para o solvente. Nós observamos que as energias de emissão dos estados singletos sofrem um deslocamento para o vermelho enquanto que os estados tripletos sofrem um deslocamento para o azul. Respondemos estas questões analisando a variação do momento de dipolo durante a transição. Neste trabalho encontramos boa concordância com os valores experimentais dos espectros de absorção, emissão, deslocamento espectral e deslocamento Stokes. / The Curcumin has long been used as a condiment, pigment and in the traditional Asian medicine. Known as turmeric, recently has attracted attention because of the large medical potential. Several studies were made mainly about the supposed benign effects in the treatment of cancer and Alzheimer but not limited to these diseases. Attempt to optimize their medicinal properties there appeared the Dimethoxy Curcumin, a synthetic compound that has a higher cytotoxicity and biological stability than Curcumin. Most of the chemical and biological reactions occur in solutions and the solvent effects are of great importance and complexity. In the present work, we study the effects of the solvents cyclohexane and acetonitrile in the absorption and emission spectra of Dimethoxy Curcumin. We consider the contribution of various isomers and excited states using the Time Dependent Density Functional Theory (TD-DFT) with the Polarizable Continuum Model (PCM) approximation for the solvent. We observe that the emission energy of the singlet states are red shifted while the triplet states are blue shifted. We address this by analyzing the dipole moment variation after the transition. We find good agreement with the experimental values for the absorption, emission, spectral shift and Stokes shift

In this thesis methodological developments have been made for the description of flexible conjugated dyes in room temperature spectrum calculations. The methods in question target increased accuracy and efficiency by combining classical molecular dynamics (MD) simulations with time-dependent response theory spectrum calculations. For absorption and fluorescence spectroscopies a form of conformational averaging is used, where the final spectrum is obtained as an average of spectra calculated for geometries extracted from ground and excited state MD simulations. For infrared and Raman spectroscopies averaged spectra are calculated based on individual spectra, obtained for zero-temperature optimized molecular structures, weighted by conformational statistics from MD trajectories. Statistics for structural properties are also used in both cases to gain additional information about the systems, allowing more efficient utilization of computational resources. As it is essential that the molecular mechanics description of the system is highly accurate for methods of this nature to be effective, high quality force field parameters have been derived, describing the molecules of interest in either the MM3 or CHARMM force fields. These methods have been employed in the study of three systems. The first is a platinum(II) actylide chromophore used in optical power limiting materials, for which a ultraviolet/visible absorption spectrum has been calculated. The second is a family of molecular probes called luminescent conjugated oligothiophenes, used to detect and characterize amyloid proteins, for which both absorption and fluorescence spectra have been calculated. Finally, infrared and Raman spectra have been calculated for a group of branched oligothiophenes used in organic solar cells. In addition, solvation effects have been studied for conjugated poly\-eletrolytes in water, resulting in the development of two solvation models suitable for this class of molecules. The first uses a quantum meachanics/molecular mechanics (QM/MM) description, in which the solute mole\-cule is described using accurate quantum mechanical methods while the surrounding water molecules are described using point charges and polarizable point dipoles. The second discards the water entirely and removes the ionic groups of the solute. The QM/MM model provides highly accurate results while the cut-down model gives results of slightly lower quality but at a much reduced computational cost. Finally, a study of protein-dye interactions has been performed, with the goal of explaining changes in the luminescence properties of the LCO chromophores when in the presence of amyloid proteins. Results were less than conclusive.

A Curcumin há muito tempo é utilizada como condimento, colorífico e na medicina tradicional asiática. Conhecida como açafrão-da-índia, recentemente tem chamado a atenção devido ao grande potencial medicinal. Surgiram trabalhos principalmente sobre seus supostos efeitos benignos no tratamento de câncer e Alzheimer porém não limitados a estas enfermidades. Na tentativa de otimizar as propriedades medicinais surgiu a Dimethoxy Curcumin, um composto sintético que apresenta maior citotoxicidade e estabilidade biológica que a Curcumin. A maioria das reações químicas e biológicas ocorrem em soluções e os efeitos dos solventes são de extrema importância e complexidade. Neste trabalho nós estudamos os efeitos dos solventes ciclohexano e acetonitrila nos espectros de absorção e emissão da Dimethoxy Curcumin. Consideramos a contribuição de diferentes isômeros e estados excitados usando a Teoria do Funcional Densidade Dependente do Tempo (TD-DFT) utilizando a aproximação Modelo Contínuo Polarizável para o solvente. Nós observamos que as energias de emissão dos estados singletos sofrem um deslocamento para o vermelho enquanto que os estados tripletos sofrem um deslocamento para o azul. Respondemos estas questões analisando a variação do momento de dipolo durante a transição. Neste trabalho encontramos boa concordância com os valores experimentais dos espectros de absorção, emissão, deslocamento espectral e deslocamento Stokes. / The Curcumin has long been used as a condiment, pigment and in the traditional Asian medicine. Known as turmeric, recently has attracted attention because of the large medical potential. Several studies were made mainly about the supposed benign effects in the treatment of cancer and Alzheimer but not limited to these diseases. Attempt to optimize their medicinal properties there appeared the Dimethoxy Curcumin, a synthetic compound that has a higher cytotoxicity and biological stability than Curcumin. Most of the chemical and biological reactions occur in solutions and the solvent effects are of great importance and complexity. In the present work, we study the effects of the solvents cyclohexane and acetonitrile in the absorption and emission spectra of Dimethoxy Curcumin. We consider the contribution of various isomers and excited states using the Time Dependent Density Functional Theory (TD-DFT) with the Polarizable Continuum Model (PCM) approximation for the solvent. We observe that the emission energy of the singlet states are red shifted while the triplet states are blue shifted. We address this by analyzing the dipole moment variation after the transition. We find good agreement with the experimental values for the absorption, emission, spectral shift and Stokes shift

Orientador: Lázaro Aurélio Padilha Junior / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Física Gleb Wataghin / Made available in DSpace on 2018-09-02T09:51:28Z (GMT). No. of bitstreams: 1 Nagamine_Gabriel_M.pdf: 6846623 bytes, checksum: 1daab6ac65771517c50786728dfce86e (MD5) Previous issue date: 2017 / Resumo: Pontos quânticos coloidais (QDs) ternários de CuInS2 (CIS) surgiram como uma alternativa não tóxica, altamente promissora, aos já bem estabelecidos QDs binários de CdX e PbX (X=Se,S). Além de não possuírem metais pesados em sua composição, esses novos materiais apresentam diversas características desejáveis, o que os torna fortes candidatos a serem aplicados em novas tecnologias, tanto em biologia quanto na geração de nova fontes de energia renovável. Além disso, esses QDs apresentam diversas propriedades ópticas que os diferem radicalmente dos QDs binários já conhecidos e ainda são pouco compreendidas. Dentre elas, podemos citar um largo espectro de fotoluminescência (PL), com decaimentos longos e multi-exponenciais e um espectro de absorção pouco definido, com uma longa cauda que vai para o infravermelho. Adicionalmente, esses nanomateriais apresentam um grande Stokes shift, de até 500 meV, cuja origem ainda é desconhecida e amplamente debatida na literatura. Com o intuito de desvendar os mecanismos por trás dessas propriedades distintas, nesse trabalho, realizamos uma série de estudos da sua dinâmica ultrarrápida e de espectroscopia não-linear para revelar a estrutura eletrônica desses QDs. Das medidas de dinâmica ultrarrápida, mostramos uma maneira alternativa de medir-se o tamanho dessas nanopartículas, por meio da sua seção de choque de absorção em 3,1 eV, que seria independente da variabilidade morfológica apresentada por elas. Adicionalmente, fazendo um estudo da dependência das interações multi-éxciton desses QDs com o tamanho, reportamos que esses nanomateriais apresentam interações Coulombianas reduzidas em relação aos QDs binários já conhecidos. Das medidas de espectroscopia não-linear, mostramos a primeira comprovação experimental de que a transição óptica entre os níveis fundamentais da banda de valência e condução é proibida por paridade em partículas esféricas. Além disso, comparando o espectro de absorção de 2 fótons das amostras estudadas com imagens de microscopia eletrônica de transmissão (TEM), mostramos que quebras na simetria das funções de onda dos portadores nesses QDs alteram as suas regras de seleção para transições ópticas. Adicionalmente, verificamos que, controlando a composição e tamanho desses QDs, é possível obter seções de choque de 2PA de até 13.500 GM dentro da janela de transparência óptica do tecido do corpo humano / Abstract: Ternary CuInS2 (CIS) Colloidal Quantum Dots (QDs) have emerged as a non-toxic promising alternative to the CdX and PbX (X=Se,S) binary QDs. Besides not having heavy metals on their composition, these new materials show several desirable features, which makes them strong candidates to be applied in new technologies, from biology to the new generation of renewable energy sources. Furthermore, these QDs present various optical properties that radically differs from the already well studied binary QDs and yet are not well understood. Among them, we can cite a large photoluminescence (PL) spectra, with long and multi-exponential decays and a poorly defined absorption spectra, with a long infrared tail. Additionally, these nanomaterials present large Stokes shift, up to 500 meV, whose origin is still not well understood and largely debated on the literature. To reveal the mechanism behind these distinguished properties, here, we perform a series of ultrafast spectroscopy and non-linear spectroscopy studies to reveal the electronic band structure of these QDs. From the ultrafast dynamics measurements, we show an alternative way to measure the size of these nanoparticles, through their absorption cross section in 3,1 eV, which would be independent from the morphologic variability presented by them. Additionally, by performing studies of the size dependent multi-exciton interactions, we report that these kind of nanomaterials present reduced Coulombic interactions in relation to de already known binary QDs. From the non-linear spectroscopy measurements, we show the first experimental confirmation that the optical transition between the electron and hole ground state are parity forbidden in the spherical particles. In addition, comparing the two-photon absorption (2PA) spectra of the studied samples with their transmission electron microscopy images, we show that symmetry breaking of the electronic wave functions in these QDs change their optical transition selection rules. Additionally, we verify that, by controlling the size and composition of these QDs, it is possible to obtain 2PA cross section as high as 13,500 GM inside the transparency window of the human tissue / Mestrado / Física / Mestre em Física / 1547612/2015 / 13/16911-2 / CAPES / FAPESP

Cette thèse décrit l’exploration de techniques de catalyse et de flux continu pour faciliter la fermeture de molécules cycliques tendues. En premier lieu, un catalyseur de palladium permet de fermer un hétérocycle aromatique tendu, la structure benzo[a]imidazo[2,1,5-c,d]indolizine.16 La tension de cycle contribue à donner au système  hautement délocalisé de ces molécules des propriétés photophysiques intéressantes, différentes de celles de leurs analogues non tendus.21,33 Il a été démontré que leur longueur d’onde d’émission maximale peut être modulée de manière prévisible en modifiant les groupes fonctionnels conjugués au système aromatique. Le potentiel d’application en biochimie de ces fluorophores à déplacement de Stokes élevé a été exploré en étiquetant deux protéines en milieu biocompatible. En second lieu, une version catalytique de la cycloaddition de Simmons-Smith a été optimisée. Dans cette transformation, une quantité catalytique d’un sel de zinc permet de former un carbénoïde hautement réactif à partir d’un composé aryldiazométhane. Ce carbénoïde peut réagir avec une grande variété d’alcènes pour former les arylcyclopropanes correspondants. Un catalyseur modifié permet même à la réaction d’avoir lieu en présence d’alcools primaires. Enfin, la manipulation des composés aryldiazométhanes utilisés dans la cyclopropanation décrite ci-haut peut s’avérer risquée vu la toxicité et l’instabilité de ces composés. Pour minimiser ces risques, une méthode pour générer et purifier ces réactifs en flux continu a été développée. De cette manière, le composé dangereux est consommé à mesure qu’il est généré, dans un système fermé. Un large éventail d’aryldiazométhanes peut être produit en solution dans un solvant non-coordinant. La compatibilité de ces solutions avec des systèmes catalytiques requérant des réactifs propres et secs a été démontrée. / This thesis describes the exploration of catalysis and continuous flow techniques towards the formation of strained cyclic molecules. First, a palladium catalyst enables the ring closure of a strained aromatic heterocycle, the benzo[a]imidazo[2,1,5-c,d]indolizine.16 Ring strain gives these molecule’s highly delocalized  system interesting photophysical properties that differ from those of unstrained analogs.21,33 Their emissive properties can be predictably modulated by modifying functional groups conjugated to the aromatic core. These high Stokes-shift fluorophores’ application potential in biochemistry was explored by the biocatalyzed labelling of two proteins in biocompatible media. Second, a catalytic version of the Simmons-Smith cycloaddition was optimized. In this transformation, a catalytic amount of zinc salt allows the formation of a highly reactive carbenoid from an aryldiazomethane precursor. This intermediate can then react with a variety of alkenes, forming the corresponding arylcyclopropanes. A modified catalyst even enables the reaction to proceed in the presence of a primary alcohol group. Finally, the handling of the aryldiazomethane precursors used in the above reaction can be hazardous due to these compound’s instability and toxicity. To minimise these risks, a method to synthesise and purify these reagents in continuous flow was developed. This way, the dangerous chemical is consumed as it is generated, in a closed system. A large array of aryldiazomethane solutions in a non-coordinating solvent can be produced. These solutions’ compatibility with sensitive catalytic systems requiring clean and dry reagents was demonstrated.

In this licentiate thesis the luminescence properties of two flexible conjugated dyes have been studied. The first, Pt1, is a platinum(II) acetylide chromophore used in optical power limiting materials. The second is a set of optical probes known as luminescent conjugated oligothiophenes (LCOs), which are used to detect and characterize the protein structures associated with amyloid diseases such as Alzheimer’s disease. MM3 and CHARMM force field parameters have been derived for the Pt1 chromophore and LCOs, respectively, based on potential energy surface references calculated at the density functional theory (DFT)/B3LYP level of theory. The parameters have been used to perform room temperature molecular dynamics simulations of the chromophores in solvent, where tetrahydrofuran was used for Pt1 and water for the LCOs. Conformationally averaged absorption spectra were obtained, based on response theory calculations at the time-dependent DFT(TDDFT)/CAM-B3LYP level of theory for a selection of structures from the simulations. For one of the LCOs, p-HTAA, force field parameters were also created describing the dominant first excited state, based on TDDFT/B3LYP reference potential energy surfaces. These were used for molecular dynamics simulations of the chromophore in the excited state, allowing the creation of an emission spectrum. A theoretically obtained Stokes shift of 112 nm could be computed based on the absorption and emission spectra, which is in good agreement with the experimental value of 124 nm. In addition, a quantum mechanics/molecular mechanics study of the effects of solvation on the absorption properties of the p-HTAA chromophore in water has been conducted, resulting in two models for including these effects in the averaged spectra. The first includes explicit water molecules in the form of point charges and polarizable dipole moments, and results in an absorption wavelength that is blueshifted by 2 nm from a high quality reference calculation. The second model involves the complete removal of the solvent as well as the ionic groups of the chromophore. The resulting absorption wavelength is blueshifted by an additional 4 nm as compared to the first model, but requires only one fifth of the computational resources.

No description available.