Betalaínas são alcalóides coloridos e com alta capacidade antioxidante que são encontrados em plantas e fungos. A biossíntese destes produtos naturais baseia-se na conversão enzimática da L-tirosina em ácido betalâmico e na condensação aldimínica deste com aminoácidos. A semissíntese de betalaínas naturais para aprofundar o estudo desta classe de pigmentos estimulou o desenvolvimento de betalaínas artificiais, incluindo derivados funcionais. Uma betalaína cumarínica foi criada para ser usada como sonda fluorescente para marcação de Plasmodium falciparum em glóbulos vermelhos. Esta Tese de Doutorado apresenta a semissíntese e estudo de três betalaínas cumarínicas (cBeets) e uma carboestiril-betalaína (csBeet). Procurou-se estabelecer relações entre as estruturas destes compostos e suas propriedades físico-químicas e fotofísicas como ponto de partida no desenvolvimento de uma nova classe de betalaínas funcionais. São apresentados dados sobre a lipofilicidade, estabilidade frente à hidrólise, potencial redox, absorção de um e dois fótons e fluorescência. Interações intermoleculares destes compostos foram investigadas por medidas de fluorescência em misturas binárias de solventes polares, albumina sérica bovina e micelas reversas de AOT em heptano/água. / Instituto de Química, Universidade de São Paulo, São Paulo, 2017. Betalains are colorful alkaloids with high antioxidant capacity that are found in plants and fungi. The biosynthesis of these natural products is based on the enzymatic conversion of L-tyrosine into betalamic acid and aldimine condensation thereof with amino acids. The semisynthesis of natural betalains improved the knowledge on this class of pigments and stimulated the development of artificial betalains, including functional derivatives. A coumarinic betalain was created to be used as a fluorescent label for Plasmodium falciparum on red blood cells. This Doctoral Thesis presents the semisynthesis and study of three coumarin betalains (cBeets) and one carbostyril betalain (csBeet). It was sought to establish relationships between the structures of these compounds and their physical-chemical and photophysical properties as a starting point in the development of a new class of functional betalains. Data on lipophilicity, hydrolysis stability, redox potential, one- and two-photon absorption and fluorescence are presented. Intermolecular interactions of these compounds were investigated by fluorescence measurements in binary polar solvent mixtures, bovine serum albumin and AOT reverse micelles in heptane/water.

Neste trabalho estudamos o espectro de absorção da clorofila d, incluindo os efeitos do solvente metanol, utilizando a Teoria do Funcional da Densidade Dependente do Tempo em combinação com o método s-QM/MM. Diferentes abordagens para a descrição do meio solvente, que vão desde o modelo contínuo polarizável até a inclusão de moléculas explícitas do solvente, são utilizadas. Observamos que a inclusão do solvente desloca o espectro, em relação ao calculado em vácuo, para o vermelho. A inclusão de 20 moléculas explícitas de metanol e 880 representadas como as cargas pontuais do seus átomos para a descrição do meio solvente foi a que melhor concordou com os valores experimentais. Mediante cálculos de mecânica quântica obtivemos para o complexo composto por a molécula de clorofila d e apenas uma de metanol explícita um deslocamento do átomo de magnésio da clorofila d em relação ao anel de 0,31 Å. Mediante a analise da função de distribuição radial de pares obtida da simulação clássica comprovamos que esse átomo de magnésio é penta-coordenado. Além disso, é usada uma estrutura simplificada da clorofila d baseado na localização dos orbitais moleculares participantes das transições eletrônicas com o objetivo de diminuir o custo computacional dos cálculos de mecânica quântica. Os espectros calculados para a clorofila d não apresentaram diferenças significativas com os calculados para a simplificação proposta. Como complementação o espectro Raman da clorofila d isolada é calculado mediante DFT e alguns dos modos normais são caracterizados. / In this work we study the absorption spectrum of chlorophyll d, including the effects of the solvent methanol, using the Time Dependent Density Functional Theory in combination with the method s-QM/MM. Different approaches for the description of the solvent medium, ranging from the polarizable continuum model to the inclusion of explicit solvent molecules, are used. We note that the inclusion of solvent shifts the spectrum, relative to that calculated in vacuum, to the red side of the spectrum. The inclusion of 20 explicit molecules of methanol and 880 represented as point charges of their atoms for the description of the solvent medium was the one that best agreed with the experimental values. By quantum mechanics calculations we obtained for the complex composed of the molecule of chlorophyll d and only one explicit methanol molecule a displacement of the magnesium atom of chlorophyll d in relation to the ring of 0,31 Å. By means of the analysis of the radial distribution function obtained from the classic simulation we can see that this atom of magnesium is penta-coordinated. In addition, a simplified structure of chlorophyll d is used based on the location of the molecular orbitals involved in the electronic transitions in order to reduce the computational cost of quantum mechanics calculations. The spectra calculated for chlorophyll d did not show significant differences with those calculated for the proposed simplification. As a complement the Raman spectrum of isolated chlorophyll d is calculated by DFT and some of the normal modes are characterized.

A arilação seletiva de compostos orgânicos confere-lhes propriedades com amplas aplicações: em compostos de atividade biológica, inibidora da protease do vírus HIV-1, e de interesse como agroquímicos ou na engenharia de materiais. Em razão disso, novos métodos e reagentes tem sido desenvolvidos com essa finalidade. Sabe-se que a N-arilação de várias aminas, catalisadas por paládio, com haletos de arila e triflatos é tida como ferramenta importante a disposição do químico sintético. Do mesmo modo, publicou-se que a N-arilação de certos -amino ácidos por haletos de arila, procede-se facilmente quando catalisada por CuI. Alternativamente, a literatura cita outros métodos eficientes usando ácidos borônicos, compostos arilbismuto e compostos organochumbo. Neste trabalho foi estudada a arilação seletiva de ânions ambidentados pelo sal de iodo polivalente cloreto de difenil iodônio, em diferentes condições de reação, visando a otimização da síntese: 1) reação térmica (agitação magnética), sem catalisador, e em diferentes solventes, ou mistura de solventes; 2) reação sonoquímica, sem catalisador e em diferentes soluções; 3) reação térmica e sonoquímica na presença de catalisador CuCl (10%). Sacarinato de sódio, acesulfame de potássio, e ftalimida potássica foram escolhidos como ânions ambidentados derivados de sulfoimidas e imidas a serem arilados. No caso de N-fenil sacarina a quemiosseletividade e o melhor rendimento são observados com acetonitrila/água (1:1, v/v), sob refluxo para formação do par iônico intermediário (ou o iodano correspondente), seguido por fusão térmica na ausência de solvente. O acesulfame potássico, por sua vez, forneceu seletivamente produtos de N- ou O-fenilação, de acordo com as seguintes condições estabelecidas: 1) produto de fenilação por via térmica ou sonoquímica em etanol; 2) produto de O-fenilação, por via térmica ou sonoquímica em acetonitrila. A ftalimida potássica, na ausência de catalisador, é arilada em baixos rendimentos. A melhor condição de síntese é encontrada com acetonitrila e CuCl (10%), sendo 92% o rendimento por via sonoquímica e 78% por via térmica. A seletividade verificada foi analisada em termos das interações dos ânions ambidentados e dos solventes em questão. / The arylation of organic compounds gives place to a wide number of applications: concerning to their biological properties as HIV-1, protease inhibitor, as well as synthetic intermediates in pharmaceuticals, agrochemical and polymer chemistry. New methodologies and reagents have been developed as consequence of this. It is already known that N-arylation of several amines, catalyzed by palladium, with aryl halides and trifflates is a valuable tool to various reported organic synthesis. In the same way, it has been published that the N-arylation of certain -amino acids by aryl halides, proceeds smoothly when catalized by CuI. Alternatively, the literature reports other efficient methods using boranic acids, arylbismuth and organolead compounds. In the present work, it was studied the selective arylation of ambident anions by hypervalent iodine salts (chloride of diphenyl iodonium), in a different set of conditions, seeking the synthesis optimizations: 1) thermal reactions (silent mode, magnetic stirring), without catalyst, and, in different solvents or mixture of then; 2) sonochemical reactions, without catalyst, and in a different solvent composition; 3) thermal and sonochemical reactions carried out in the presence of (10%) CuCl as the catalyst. Sodium saccharinate, acessulfame K and potassium phthalimide were chosen as the ambident anions (derived from sulfonimides and imide functional groups) to be studied. In the N-phenyl saccharin case the chemioselectivity was achieved along the best yields when water/acetonitrila (1:1, v/v) solvent was employed in the step to form the ion pair (or the 3-iodane, intermediate), followed by the thermal fusion in the absence of solvent. The acessulfame K, for its turn, supplied selectively products of N- and O-arylation under the following established conditions: 1) N-phenylation in etanol through thermal and sonochemical approach; 2) O-phenylation product, in acetonitrila, by thermal and sonochemical method. Finally, arylation of potassium phthalimide with diaryliodonium is sluggish and gives low yields without catalyst. The best protocol to this synthesis was found with the solvent acetonitrile and (10%) CuCl catalyst addition, being 92% the yield of sonochemical reaction and 78% of the thermal one. The selectivity achieving was analyzed in accord with the solution interaction between the ambident anion and the solvent molecules.

Um procedimento baseado no uso sequencial de simulação Monte Carlo e cálculos de Mecânica Quântica é proposto e usado para o tratamento de efeitos de solvente, com especial atenção parao sovatocromismo no espectro de absorção molecular. A ideia básica é realizar simulações clássicas com o método Monte Carlo para gerar estruturas supermoleculares do sistema em solução e em seguida tratar estas supermoléculas (soluto, solvente e suas interações) com cálculos quânticos. Um modelo totalmente discreto do solvente é utilizado e, portanto, o uso de meios dielétricos contínuos é dispensado. Neste procedimento, as supermoléculas são compostas por uma molécula do soluto rodeada pela primeira camada de solvatação definida através da função distribuição. Os efeitos de solvente são calculados usando médias configuracionais sobre estruturas supermoleculares descorrelacionadas obtidas através de análises estatísticas das simulações. Como aplicação, os deslocamentos espectrais da primeira banda de absorção do benzeno 1B2u(- *), devido a presença de diversos solventes, foram analisados e calculados. Boa concordância com os resultados experimentais foram obtidos. / A approach based on the sequential use of Monte Carlo simulation and Quantum Mechanics is proposed and use for the treatment of solvent effects with special attention to solvatochromic shifts. The basic Idea is to perform a classical Monte Carlo simulation to generate supermolecular structures of the system, then to treat these supermolecules (solute, solvent and all its interaction) by quantum mechanics. This is a totally discrete modelo f the solvent that avoids the use of a dielectric continuum. In this approach, the supermolecules are composed by the solute molecule surrounded by the first solvation Shell as determined by the distribution function. The solvent effects are calculated using ensemble average over uncorrelated supermolecular structures obtained by statistical analysis. As na application, the spectral shifts of the 1B2u(- *) trnsition of benzene in different solvents are investigated. Good agreement with the experimental results are obtained.

Nucleophilic substitution reactions of alkylamines, cyclic alkylamines, and hydroxyalkylamines with 5-substituted-1,4-naphthoquinones have been studied. It has been found that the nature of the solvent employed in the reaction influences the position of mono-substitution at either the 2- or 3-position. Although both regioisomers were produced in all the reactions, protic polar solvents favoured the formation of the 3-regioisomer, whereas non-protic solvents favoured the formation of the 2-regioisomer. It has also been found that formation of 2,3-diaminoalkyl derivatives is normally unlikely. A series of hydroxyalkylamino-1,4-naphthoquinones were also synthesised. The collision-induced dissociation mass spectra of protonated hydroxyalkylamino-1,4- naphthoquinones showed fragmentation patterns which were dependent on the nature and length of the side chain and the presence and nature of the adjacent group on the 3-position on the 1,4-naphthoquinone ring. A total of 27 novel compounds were synthesised during the course of this research, the structures of which were confirmed via 1D and 2D NMR spectroscopy, mass spectrometry (ESI), IR spectroscopy and high resolution mass spectrometry (HRESIMS and HREIMS).

No description available.

No description available.

The work described in this thesis focuses on the effects that adsorption processes on catalytic surfaces pose in controlling key steps that can affect and control reaction pathways. To that, the development of Nuclear Magnetic Resonance (NMR) relaxometry methods and the comparison with traditional catalytic was performed with a series of C5 and C6 unsaturated hydrocarbons on two different alumina supports, γ- and θ-Al2O3. The developed techniques were applied in the study of liquid phase selective hydrogenation of citral on 5% Pt/SiO2. Infrared (IR) spectroscopy, volumetric adsorption isotherms, dynamic isotherms via a Tapered Element Oscillating Microbalance (TEOM), temperature programmed desorption (TPD) as well as 13C T1 NMR and 1H 2D T1-T2 relaxometry methods were employed. Energies of adsorption as a function of coverage were obtained via adsorption isotherms and the particular surface adsorbate interactions were described with IR spectroscopy. For example, 1-pentyne showed the strongest interaction with the alumina (94 kJ mol-1) while 1-pentene presented a weaker interaction (46 kJ mol-1) on θ-Al2O3. Desorption energies obtained from TPD ranged 85 – 130 kJ mol-1, irrespective of the adsorbate. Reactivity of the aluminas was captured with TPD, TEOM and NMR relaxometry. Interaction of adsorbates with hydrocarbon occurred predominantly on weak adsorption sites. 13C NMR T1 relaxometry provided in addition atom-specific adsorbate-adsorbent interaction strengths, showing the molecular geometry of adsorption, and applied in co adsorption measurements. The selective hydrogenation of citral as a model α,β-unsaturated aldehyde and the effect of different solvents on the activity and product distribution was studied at 298 and 373 K. A series of polar protic, polar aprotic and non polar solvents was investigated. Results showed higher initial reaction rates in non polar solvents but higher selectivities towards desired products on polar protic solvents. Solvent used also affected by product formation. The strong variations in reaction rates and selectivities reported were related with adsorbate catalyst interactions, as well as solvent reactant interactions. For example, adsorption isotherms showed that ethanol notably reduced the adsorption capacity of citral as compared with hexane, related with the rate differences observed. ATR-IR measurements indicated solvent citral interactions were solely present in polar protic solvents in line with higher yields of geraniol and nerol. Finally, 13C T1 NMR and 1H 2D T1-T2 correlation experiments determined that the geometry of adsorption of citral, influenced by solvent, affected product selectivity, and that product adsorption affected selectivity and deactivation.

This work entails efforts to understand effects of solvent choice on paracetamol crystallization. Various techniques have been developed and implemented to study aforementioned. A clear-cut, direct evidence of two-step nucleation mechanism is demonstrated using a bench top Raman spectrometer and a novel method named as OSANO. / Polymorphismus ist die Eigenschaft vieler anorganischer und insbesondere organischer Moleküle, in mehr als einer Struktur zu kristallisieren. Es ist wichtig, die Faktoren zu verstehen, die den Polymorphismus beeinflussen, da er viele physikochemische Eigenschaften wie Stabilität und Löslichkeit beeinflusst. Nahezu 80 % der vermarkteten Medikamente weisen Polymorphismus auf. In dieser Arbeit wurde der Einfluss der Wahl des organischen Lösungsmittels auf den Polymorphismus von Paracetamol untersucht und verschiedene Methoden entwickelt und angewandt, um den Einfluss genauer zu verstehen. Es wurde festgestellt, dass Ethanol viel stärker auf Paracetamol-Kristallisation als Methanol wirkt. Nichtgleichgewichts-Molekulardynamiksimulationen mit periodischer, simulierter Abkühlung (Simulated Annealing) wurden verwendet, um Vorläufer der metastabilen Zwischenprodukte im Kristallisationsprozess zu untersuchen. Es wurde festgestellt, dass die Strukturen der Bausteine der Paracetamol-Kristalle durch geometrische Wechselwirkungen zwischen Lösungsmittel und Paracetamol bestimmt werden. Die statistisch häufigsten Bausteine in der Selbstassemblierung definieren die finale Kristallstruktur. Ein speziell angefertigter akustischer Levitator hat die Proben zuverlässig gehalten, wodurch die Untersuchung des Einflusses von Lösungsmitteln ermöglicht, heterogene Keimbildung abgeschwächt und andere Umgebungsfaktoren stabilisiert wurden. Die Kristallisation wurde in diesem Aufbau mit zeitaufgelöster In-situ-Raman-Spektroskopie verfolgt und mit einer neuen Zielfunktion basierenden Methode der nichtnegativen Matrixfaktorisierung (NMF) analysiert. Orthogonale Zeitrafferfotografie wurde in Verbindung mit NMF verwendet, um eindeutige und genaue Faktoren zu erhalten, die sich auf die Spektren und Konzentrationen verschiedener Anteile der Paracetamol-Kristallisation beziehen, die als latente Komponenten in den unbehandelten Daten vorhanden sind. / Polymorphism is the property exhibited by many inorganic and organic molecules to crystallize in more than one crystal structure. There is a strong need for understanding the influencing factors on polymorphism, as it is responsible for differences in many physicochemical properties such as stability and solubility. Nearly 80 % of marketed drugs exhibit polymorphism. In this work, we took the model system of paracetamol to investigate the influence of solvent choice on its polymorphism. Different methods were developed and employed to understand the influence of small organic solvents on the crystallization of paracetamol. Non-equilibrium molecular dynamics simulations with periodic simulated annealing were used as a tool to probe the nature of precursors of the metastable intermediates occurring in the crystallization process. Using this method, it was found that the structures of the building blocks of crystals of paracetamol is governed by solvent-solute interactions. In situ Raman spectroscopy was used with a custom-made acoustic levitator to follow crystallization. This set-up is a reliable method for investigating solvent influence, attenuating heterogeneous nucleation and stabilizing other environmental factors. It was established that as a solvent, ethanol is much stronger than methanol in its effect of driving paracetamol solutions to their crystal form. The time-resolved Raman spectroscopy crystallization data was processed using a newly developed objective function based non-negative matrix factorization method (NMF). An orthogonal time-lapse photography was used in conjunction with NMF to get unique and accurate factors that pertain to the spectra and concentrations of different moieties of paracetamol crystallization existing as latent components in the untreated data.