Submitted by Irene Nascimento (irene.kessia@ufpe.br) on 2016-09-08T19:08:46Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Tese_Karina_Final_CD.pdf: 2797138 bytes, checksum: 5e86db88edfdb58a92aceb27cf908735 (MD5) / Made available in DSpace on 2016-09-08T19:08:46Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Tese_Karina_Final_CD.pdf: 2797138 bytes, checksum: 5e86db88edfdb58a92aceb27cf908735 (MD5) Previous issue date: 2015-10-16 / A partir dos parâmetros eletrônicos obtidos com a Teoria do Funcional Densidade, realizamos um estudo Quantitativo da Relação Estrutura Atividade (QSAR) de derivados de cetonatiossemicarbazonas e de ácidos kójico e benzoico para analisar o potencial de inibição da melanogênese destes compostos. Utilizando técnicas computacionais em conjunção com uma Regressão linear múltipla, obtivemos uma expressão capaz de prever a concentração inibitória (IC50) destes compostos e dos demais aqui propostos. Para a previsão da IC50 foram utilizados os seguintes parâmetros eletrônicos e físico-químicos: afinidade eletrônica (EA), gap de energia (HHL), momento de dipolo (μ) e o logaritmo do coeficiente de partição [octanol/água](LogP). Para as cetonatiossemicarbazonas os descritores eletrônicos que proporcionaram uma boa correlação linear com a IC50 experimental foram: a carga atômica do nitrogênio N2 e a EA. Para as demais moléculas avaliadas nesta pesquisa, além desses parâmetros, foram incluídos o potencial de ionização (IP), a energia do atracamento molecular (G), eletronegatividade absoluta (), dureza (), maciez (S), logaritmo do coeficiente de solubilidade (LogS), volume molar (VM) e o coeficiente de Hansch (). Como resultado da QSAR, os descritores que proporcionaram a melhor correlação linear com a IC50 experimental foram: a HHL e o VM. Na análise QSAR dos derivados dos ácidos kójico e benzoico foi utilizado um conjunto de treinamento formado por dez moléculas e um grupo de teste constituído por duas moléculas para uma validação cruzada tipo boostrap. Os cálculos de G se restringiram a encontrar o valor da energia livre de interação dos derivados dos ácidos kójico e benzoico e da enzima tirosinase por meio da formação do complexo ligante-tirosinase. Os valores das energias de interação obtidos para as moléculas propostas se revelaram promissores, visto que apresentaram valores mais baixos do que o obtido para o complexo ácido kójico-tirosinase. Em todas as análises QSAR, os valores dos parâmetros estatísticos de validação, como coeficiente de correlação, desvio-padrão, teste de Fischer e do nível geral de confiabilidade do modelo, estão dentro do esperado para um bom modelo estatístico. Os modelos obtidos fornecem uma boa previsão das atividades biológicas investigadas neste trabalho apontam para novos compostos candidatos com potencial para inibição da melanogênese. / We have carried ant studies of QSAR using electronic structure derived parameters be the means of Density Functional Theory (DFT) calculations for derivatives of ketonethiosemicarbazones, kojic acid and benzoic acid. The aim was to evaluate the melanogenesis inhibiting potential of these compounds, by using this procedure and performing a Multiple Linear Regression we obtained an expression able to predict the inhibitory concentration (IC50) of the compounds studied here. In predicting the IC50 we used the electronic and physical-chemical parameters of electron affinity (EA), energy gap (HHL), dipole of moment (μ) and the [octanol/water] logarithm of the partition coefficient (LogP). For ketonethiosemicarbazones the electronic parameters that provide a good linear correlation with experimental IC50 are the atomic charge of nitrogen N2 and the EA. For the other molecules analyzed in this study, in addition to these parameters it is included ionization potential (IP), molecular docking of energy (G), absolute electronegativity (), hardness(), softness (S), partition coefficient of molar solubility (LogS), molar volume (VM) and Hansch coefficient (). We found that the parameters leading to the best linear correlation with experimental IC50 are the interaction energy and the molar volume. In the QSAR analysis of derivatives of the benzoic and kojic acids it is used a training group formed by ten molecules and a test group formed of two molecules to realize a bootstrap-type cross validation. The calculations of the molecular docking are restricted to values of free energy of derivatives of the benzoic and kojic acids and to the enzyme tyrosinase forming the tyrosinase-ligand complex. In all QSAR analysis, the statistical validation such as correlation coefficient, standard deviation, Fisher test and the model reliability are in that range expected for a good statistical model. As a conclusion, we show that our model gives a good prediction of the biological activities, which allow us to indicate new compounds with potential in inhibiting melanogenesis.

No description available.

The production of stable solid crystalline material is an important issue in the pharmaceutical industry and the challenge to control the desired active pharmaceutical ingredient (API) with the specific chemical and physical properties has led to more development in the drug industry. Increasing the solubility and the dissolution of the drug will increase its bioavailability; therefore the solubility can be improved with the change in the preparation method. The formation of co-crystals has emerged as a new alternate to the salts, hydrates and solvate methods since the molecules that cannot be formed by the usual methods might crystallise in the form of co-crystals. Co-crystals are multicomponent crystals which can be known as supramolecules and are constructed by the non covalent bonds between the desired former and co-former. Therefore the synthon approach was utilised to design co-crystals with the specific properties, this involves the understanding of the intermolecular interactions between these synthons. These interaction forces can be directed to control the crystal packing in the design of the new crystalline solid with the desired chemical and physical properties. The most familiar synthon was the amide group with its complementary carboxylic group, in this work isonicotinamide and benzoic acid were chosen to design co-crystal and much literature exist that introduce the determination of co-crystal growth from these two compounds. The growth of co-crystals was carried out in water, ethanol and ethanol / water mixed solvent (30 - 90 % ethanol) by utilising the Cryo-Compact circulator. Co-crystals (1:1) and (2:1) were grown in ethanol and water respectively and a mixture of both phases were grown in the mixed solvent. All the phases were examined by powder X-ray diffraction (PXRD), Raman, Infrared and 1H-NMR spectroscopy. The solubility of isonicotinamide, benzoic acid, co-crystals (1:1) and (2:1) in water, ethanol and ethanol/water mixed solvent (30 - 90 % ethanol) were determined at 25 °C, 35 °C and 40 °C by utilising the React-Array Microvate. It was important to understand some of the thermodynamic factors which control the formation of these polymorphs such as the change in the enthalpy and the change in the entropy. Also it was important to study the pH behaviour during dissolution of the former, co-former and co-crystals in water, ethanol and ethanol/water mixed solvent (30 - 90 % ethanol) in-order to examine the affect of the solvent composition on the solubility and to identify if some ions were formed during the dissociation and how this could affects the formation of co-crystals. A discussion has been introduced in this research of how similar solubility of the compounds maps the formation of the typical ternary phase diagram of the mixture of 1:1 while compounds with different solubility maps the formation of skewed phase diagram as shown in section 1.6.2.3. In this project an isotherm ternary phase diagram at 20 °C and 40 °C was constructed to map the behaviour of benzoic acid and isonicotinamide and to show all possible phases formed and the regions where all phases are represented in the ternary phase diagram were determined by the slurry method. The ternary phase diagram was used to design a drawn out and cooling crystallisation at 100 cm3 solution of 50 % ethanol / water mixed solvent and a study of the impact of seeds of co-crystals 1:1 on the cooling crystallisation method.

A ensilagem de grãos de milho reidratados é uma estratégia de armazenamento vantajosa, economicamente viável e que melhora a digestibilidade do amido. Este estudo foi dividido em dois experimentos - Experimento 1: Utilização de aditivos químicos e microbianos sobre aspectos fermentativos e estabilidade aeróbia de silagens de milho reidratado. Os tratamentos consistiram em silagens de milho tratadas com Lactobacillus buchneri (LB - 5×105 ufc/g da matéria natural); Bactérias homoláticas (Homo - 5×105 ufc/g MN); Lactobacillus buchneri + homoláticas (Combo - 1×106 ufc/g MN); Lactobacillus buchneri + nitrito de sódio (LB - 5×105 ufc/g MN + 1,5 g/kg MN de nitrito) e benzoato de sódio (Benz - 2,0 g/kg MN). Foi utilizado o delineamento experimental inteiramente casualizado com 6 tratamentos e 4 repetições. Experimento 2: Utilização de silagem de grãos de milho reidratados com ou sem a adição de benzoato de sódio sobre a digestibilidade e desempenho de vacas leiteiras. Foram utilizadas 18 vacas Holandês, alocadas em três quadrados latinos para avaliação dos tratamentos: Controle (silagem de milho reidratado); Benz (silagem de milho reidratado + benzoato de sódio - 2,0 g/kg MN) e MiS (milho seco moído). Em todas as dietas o nível de inclusão do milho foi de 17,3%. No primeiro experimento, a composição química das silagens foi adequada e as perdas fermentativas foram baixas (<1,6%) para todos os tratamentos. A presença de aditivos microbianos resultou em silagens bem fermentadas, enquanto silagens Benz preservaram carboidratos solúveis e resultaram em menor concentração de produtos de fermentação. A estabilidade aeróbia foi máxima para LB, Combo e Benz (240h) e intermediária para LBNit (151h). A silagem inoculada com bactérias homoláticas foi menos efetiva em promover estabilidade aeróbia (74,7h), comparada à controle (53,5h). Os melhores parâmetros de degradabilidade ruminal da MS foram obtidos para a silagens LB e Combo. Silagem Benz e Homo foram semelhantes à Controle e o LBNIT piorou a degrabilidade ruminal da MS. No segundo experimento, O CMS foi similar entre os tratamentos, com média de 21,1 kg/dia, ao passo que a digestibilidade do amido e CNF foi maior para os grãos fermentados. O maior aporte energético das silagens gerou tendência de aumento na produção de leite corrigido para 3,5% de gordura. Ao relacionar essa produção com o CMS, os animais alimentados com silagens de grãos reidratados tenderam a uma maior eficiência alimentar. Vacas leiteiras alimentadas com silagens apresentaram menor excreção de nitrogênio ureico no leite (11,9 vs 13 mg/dL), o que sugere um melhor uso de nitrogênio para produção de proteína microbiana. O uso dos aditivos benzoato de sódio, L. buchneri e L. buchneri combinado com bactérias homoláticas é aconselhável para promover a fermentação, estabilidade aeróbia e valor nutritivo de silagens de grãos de milho reidratados. / Rehydrated corn grain silage is an advantageous storage method, economically viable and improves starch digestibility. This study was carried out in two experiments - Experiment 1: Use of chemical and microbial additives on fermentation aspects and aerobic stability of rehydrated corn grain silage. The treatments consisted of rehydrated corn silage with different types of additives: control (no additive); Lactobacillus buchneri (LB - 5 × 105 cfu/g of fresh matter); homolactic bacteria (Homo - 5 × 105 cfu/g FM); Lactobacillus buchneri + homolactic bacteria (Combo LB - 5 × 105 cfu/g + LP - 5 × 105 cfu/g FM); Lactobacillus buchneri + sodium nitrite (LB - 5 × 105 cfu/g FM + nitrite - 1.5 g/kg FM) and sodium benzoate (Benz - 2.0 g/kg FM). The experiment was made in a completely randomized design with six treatments and four replications. Experiment 2: Use of rehydrated corn silage with or without sodium benzoate on the digestibility and performance of dairy cows. Eighteen Holstein cows were distributed in a replicated 3×3 latin square design with three periods (22-d) to evaluate the effect of control treatment (rehydrated corn silage); Benz (rehydrated corn silage plus sodium benzoate - 2.0 g/kg FM) and DGC (dry ground corn). In all diets the inclusion of corn was 17.3% in dry matter basis. In the first experiment, the chemical composition of silages was adequate and the fermentative DM losses were low (<1.6%) for all treatments. The presence of microbial additives resulted in well fermented silages, while Benz silages preserved WSC and showed lower concentration of fermentation products. The aerobic stability was highest for LB, Combo and Benz (240h) and intermediate for LBNit (151h). The Homo silages was less effective in promoting aerobic stability (74.7h), compared to the control (53.5h). The best parameters of ruminal DM degradability were obtained for LB and Combo silages. Benz and Homo silages were similar to the control, while LBNIT worsened the ruminal degrability of DM. In the second experiment, dry matter intake was similar across treatments with average of 21.1 kg/day, whereas starch and CNF digestibility was higher for fermented grains. The higher energy of silages tended to increase the production of 3.5 % fat-corrected milk. Therefore, animals fed rehydrated grain silages tended to present increased feed efficiency. Dairy cows fed silages had lower excretion of milk urea nitrogen, suggesting a better use of nitrogen for microbial protein synthesis. The use of additives sodium benzoate, L. buchneri and L. buchneri combined with homolactic bacteria is advisible to improve the fermentation, the aerobic stability and the nutritive value of rehydrated corn grain silages.

Dans ce travail, il est montré que les alkyl/vinyl/aryl lithiens et magnésiens réagissentavec les acides C-1(F/OMe) naphtoïques en l'absence de catalyseur métallique. Cette nouvelleréaction de substitution nucléophile aromatique permet potentiellement de préparer n’importequel biaryle tout en s'affranchissant des étapes de protection et de déprotection de la fonctionacide (CO2H). Les alkyllithiens linéaires et ramifiés réagissent avec la même efficacité que lesalkylmagnésiens même à basse température (–78 °C). Le déplacement d'un fluor ou d'unméthoxy s'effectue avec la même facilité. L'absence d'ortho-lithiation est confirmée par lepiégeage du milieu réactionnel en fin de réaction par l'iodométhane (après addition de n-BuLi,s-BuLi et t-BuLi). Le bromure de vinylmagnésium requiert un chauffage au reflux du THF.La méthode étudiée permet de préparer extrêmement facilement des 1- et 2-phénylnaphtalènes, 1,1’-binaphtalènes et 2,2’-binaphtalènes. Dans les exemples où lesaryllithiens donnent des rendements moyens-faibles en produits de couplage, les réactifs deGrignard sont beaucoup plus efficaces. Le o-tolyllithium, le bromure de o-tolylmagnésium, lebromure de (4-méthoxyphényl)magnésium, le bromure de (2,5-diméthylphényl)magnésium etle bromure de benzo[d][1,3]dioxol-5-ylmagnésium déplacent facilement le groupefluoro/méthoxy en ortho du groupe CO2M pour donner les produits de substitutioncorrespondants alors que la réaction du bromure de (2,6-diméthoxyphényl)magnésium estmoins efficace sans doute en raison de l'encombrement stérique causé par les deux groupesortho-méthoxy. L'acide 1-(2-méthoxyphényl)-2-naphtoïque est un produit particulièrementintéressant. La déprotection du groupe méthoxy suivie d'une cyclisation est réalisée par BBr3pour donner la 6H-naphtho[2,1-c]chromén-6-one qui est isolée avec un rendement de 97 %.Cette lactone est utile pour la préparation de composés atropoisomères optiquement actifsaprès ouverture énantiosélective du cycle lactone selon la technique mise au point parBringmann. / Alkyl as well as aryl substitution can be readily accomplished in generally excellentyields via a nucleophilic mode by displacement of an ortho-fluoro or methoxy group inunprotected naphthoic acids with lithium and Grignard reagents in the absence of a metalcatalyst.Alkyllithium reagents typically gave good-to-excellent yields, whether primary,secondary, or tertiary at –78 °C. Displacement of a fluoro or a methoxy group occurs withequal efficacy. The absence of ortho-lithiation was confirmed by quenching the reactionproduct with MeI after addition of n-BuLi, s-BuLi and t-BuLi. Alkyl Grignard reagentsEtMgBr and n-BuMgBr proved to be very reactive at –78 °C while vinyl magnesium bromiderequired refluxing in THF.The method provides excellent latitude with respect to the synthesis of 1- and 2-phenylnaphthalenes, 1,1’-binaphthalenes, and 2,2’-binaphthalenes. In those instances wherethe aryllithium reagents gave poor yields of coupling products, the corresponding Grignardreagents proved to be much more effective. o-Tolyllithium, o-tolylmagnesium bromide, (4-methoxyphenyl)magnesium bromide, (2,5-dimethylphenyl)magnesium bromide andbenzo[d][1,3]dioxol-5-ylmagnesium bromide smoothly displaced the fluoro/methoxy grouportho to the CO2M group to give the corresponding substitution products while reaction of(2,6-dimethoxyphenyl)magnesium bromide proceeded with less efficiency presumably due tosteric effects imparted by the two ortho-methoxy groups. Particularly useful is 1-(2-methoxyphenyl)-2-naphthoic acid which allows for further elaboration after the coupling isperformed. Deprotection of the methoxy group followed by cyclization was realized withBBr3 to afford 6H-naphtho[2,1-c]chromen-6-one which was isolated in 97% yield. Thislactone is the starting building block for the preparation of optically active atropisomers byenantioselective ring opening.

A ensilagem de grãos de milho reidratados é uma estratégia de armazenamento vantajosa, economicamente viável e que melhora a digestibilidade do amido. Este estudo foi dividido em dois experimentos - Experimento 1: Utilização de aditivos químicos e microbianos sobre aspectos fermentativos e estabilidade aeróbia de silagens de milho reidratado. Os tratamentos consistiram em silagens de milho tratadas com Lactobacillus buchneri (LB - 5×105 ufc/g da matéria natural); Bactérias homoláticas (Homo - 5×105 ufc/g MN); Lactobacillus buchneri + homoláticas (Combo - 1×106 ufc/g MN); Lactobacillus buchneri + nitrito de sódio (LB - 5×105 ufc/g MN + 1,5 g/kg MN de nitrito) e benzoato de sódio (Benz - 2,0 g/kg MN). Foi utilizado o delineamento experimental inteiramente casualizado com 6 tratamentos e 4 repetições. Experimento 2: Utilização de silagem de grãos de milho reidratados com ou sem a adição de benzoato de sódio sobre a digestibilidade e desempenho de vacas leiteiras. Foram utilizadas 18 vacas Holandês, alocadas em três quadrados latinos para avaliação dos tratamentos: Controle (silagem de milho reidratado); Benz (silagem de milho reidratado + benzoato de sódio - 2,0 g/kg MN) e MiS (milho seco moído). Em todas as dietas o nível de inclusão do milho foi de 17,3%. No primeiro experimento, a composição química das silagens foi adequada e as perdas fermentativas foram baixas (<1,6%) para todos os tratamentos. A presença de aditivos microbianos resultou em silagens bem fermentadas, enquanto silagens Benz preservaram carboidratos solúveis e resultaram em menor concentração de produtos de fermentação. A estabilidade aeróbia foi máxima para LB, Combo e Benz (240h) e intermediária para LBNit (151h). A silagem inoculada com bactérias homoláticas foi menos efetiva em promover estabilidade aeróbia (74,7h), comparada à controle (53,5h). Os melhores parâmetros de degradabilidade ruminal da MS foram obtidos para a silagens LB e Combo. Silagem Benz e Homo foram semelhantes à Controle e o LBNIT piorou a degrabilidade ruminal da MS. No segundo experimento, O CMS foi similar entre os tratamentos, com média de 21,1 kg/dia, ao passo que a digestibilidade do amido e CNF foi maior para os grãos fermentados. O maior aporte energético das silagens gerou tendência de aumento na produção de leite corrigido para 3,5% de gordura. Ao relacionar essa produção com o CMS, os animais alimentados com silagens de grãos reidratados tenderam a uma maior eficiência alimentar. Vacas leiteiras alimentadas com silagens apresentaram menor excreção de nitrogênio ureico no leite (11,9 vs 13 mg/dL), o que sugere um melhor uso de nitrogênio para produção de proteína microbiana. O uso dos aditivos benzoato de sódio, L. buchneri e L. buchneri combinado com bactérias homoláticas é aconselhável para promover a fermentação, estabilidade aeróbia e valor nutritivo de silagens de grãos de milho reidratados. / Rehydrated corn grain silage is an advantageous storage method, economically viable and improves starch digestibility. This study was carried out in two experiments - Experiment 1: Use of chemical and microbial additives on fermentation aspects and aerobic stability of rehydrated corn grain silage. The treatments consisted of rehydrated corn silage with different types of additives: control (no additive); Lactobacillus buchneri (LB - 5 × 105 cfu/g of fresh matter); homolactic bacteria (Homo - 5 × 105 cfu/g FM); Lactobacillus buchneri + homolactic bacteria (Combo LB - 5 × 105 cfu/g + LP - 5 × 105 cfu/g FM); Lactobacillus buchneri + sodium nitrite (LB - 5 × 105 cfu/g FM + nitrite - 1.5 g/kg FM) and sodium benzoate (Benz - 2.0 g/kg FM). The experiment was made in a completely randomized design with six treatments and four replications. Experiment 2: Use of rehydrated corn silage with or without sodium benzoate on the digestibility and performance of dairy cows. Eighteen Holstein cows were distributed in a replicated 3×3 latin square design with three periods (22-d) to evaluate the effect of control treatment (rehydrated corn silage); Benz (rehydrated corn silage plus sodium benzoate - 2.0 g/kg FM) and DGC (dry ground corn). In all diets the inclusion of corn was 17.3% in dry matter basis. In the first experiment, the chemical composition of silages was adequate and the fermentative DM losses were low (<1.6%) for all treatments. The presence of microbial additives resulted in well fermented silages, while Benz silages preserved WSC and showed lower concentration of fermentation products. The aerobic stability was highest for LB, Combo and Benz (240h) and intermediate for LBNit (151h). The Homo silages was less effective in promoting aerobic stability (74.7h), compared to the control (53.5h). The best parameters of ruminal DM degradability were obtained for LB and Combo silages. Benz and Homo silages were similar to the control, while LBNIT worsened the ruminal degrability of DM. In the second experiment, dry matter intake was similar across treatments with average of 21.1 kg/day, whereas starch and CNF digestibility was higher for fermented grains. The higher energy of silages tended to increase the production of 3.5 % fat-corrected milk. Therefore, animals fed rehydrated grain silages tended to present increased feed efficiency. Dairy cows fed silages had lower excretion of milk urea nitrogen, suggesting a better use of nitrogen for microbial protein synthesis. The use of additives sodium benzoate, L. buchneri and L. buchneri combined with homolactic bacteria is advisible to improve the fermentation, the aerobic stability and the nutritive value of rehydrated corn grain silages.

Made available in DSpace on 2015-05-14T12:59:56Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 8420094 bytes, checksum: e38d9fce0fc67703d2f3e878474b7c32 (MD5) Previous issue date: 2013-02-27 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The Piper L. genus is the largest one among the Piperaceae. Containing at least 1000 species, they are located mainly on the neotropical region of Earth and it draws our attention due to its medical, economical, chemical and cultural properties, such as anti-inflamatory, antibacterial and fungicide actions. Piper genus species have been becoming research sources for specific classes of secondary metabolites which play an important role concerning biological activities, including alkaloids, amides, chalcones, chromenes, flavonoids, lignans, terpenes, cyclopentanediones, steroids, porphyrin derivatives and benzoic acid derivatives. Piper caldense C. DC., which is commonly known as Pimenta D arda , is used in Paraíba as sedative, snake venom antidote, anti-toothache agent, and as active in located pain treatments through the use of compresses. This research reports the phytochemical study of P. caldense C. DC. leaves and fruits. Through usual chromatographic methods and spectroscopic techniques such as IR and one and two-dimensional ¹H and ³CNMR techniques and comparison with literature data it was possible to isolate and identify an mixture of the β-sitosterol and sitgmasterol steroids, besides porphyrin substances: 15-hydroxy-A-pophyrinlactone and a phaeophytin. Those fractions were obtained from crude ethanolic extract of P. caldense C. DC. leaves. Three benzoic acid derivatives were isolated from the hexane extract of P. caldense C. DC. fruits. From its leaves and fruits it was possible to obtain seven compunds commonly found it many vegetal species, but for the first time stated from P. caldense C. DC. The hexane and dichloromethane fruit extracts and isolated substances were submitted to microbiological assay and antifungal activites were detected concerning Candida genus yeast. This test is being done for the first time in the fruits of the studied species. / O gênero Piper L. é o maior da família Piperaceae, compreendendo pelo menos 1000 espécies, que se encontram distribuídas especialmente na região neotropical do globo terrestre e se destaca por suas propriedades medicinais, econômicas, químicas e culturais (anti-inflamatória, antibacteriana, anestésia e fungicida, dentre outros). Espécies do gênero Piper têm-se tornado fontes de pesquisa de classes específicas de metabólitos secundários com marcantes atividades biológicas, incluindo alcaloides, amidas, chalconas, cromenos, flavonoides, lignanas, terpenos e ciclopentanodionas, esteroides, derivados porfirínicos e derivados do ácido benzoico. Piper caldense C. DC., conhecida popularmente como pimenta d arda , é utilizada na Paraíba como sedativa, antídoto para picadas de cobras, para dores de dente, bem como na forma de compressa no local afetado para alívio da dor. Este trabalho reporta o estudo fitoquímico das folhas e frutos de P.caldense C. DC. Utilizando-se métodos cromatográficos usuais e técnicas espectroscópicas de IV e RMN de 1H e 13C uni e bidimensionais e a comparação dos dados com a literatura foi possível isolar e identificar do extrato etanólico bruto das folhas de Piper caldense C.DC., uma mistura de esteroides, o β-sitosterol e o estigmasterol, e duas substâncias porfirínicas, a 15-hidroxi-porfirionolactona A e a feofitina a, e, do extrato hexânico dos frutos, três derivados do ácido benzoico, compreendendo ao total sete substâncias, descritas pela primeira vez em Piper caldense C. DC. Os extratos hexânico e diclorometânico dos frutos e suas substâncias isoladas foram submetidos a ensaios microbiológicos, apresentando atividade antifúngica frente a leveduras do gênero Candida. Este ensaio está sendo feito pela primeira vez nos frutos da espécie estudada.

This master´s thesis is focused on simultaneous determination of sweeteners and preservatives in energy drinks by liquid chromatography coupled with DAD and ELSD detection. The method was optimized for determination of aspartame, acesulfame K, saccharin, sucralose, steviol glycosides, benzoic acid and sorbic acid. Analyses were carried out on the Poroshell 120 EC-C18 column (4.6 x 150 mm, 2.7 m, Agilent) using mixture of methanol, acetone and water with formic acid and trimethylamine as a gradient mobile phase at a flow rate 0,5 mL•min-1. Validation parameters were determined (limit of detection, limit of quantification, repeatability and recovery). The validated method was applied on real samples.

Abstract Food sustainability depends significantly on packaging since it helps maintainfood safe and fresh throughout its shelf life, resulting in the least amount ofwaste and the least negative environmental impact. The main objective of thisstudy is to determine the adsorbed and released amount of antimicrobial agents(benzoic acid and thymol) on modified calcium carbonate (MCC) by investigating adsorption isotherm at 25°C and desorption kinetics at both 22°C and5°C of anti-microbial to identify potential solutions to enhance the long-termsustainability of fresh products such as meat. These agents were incorporatedinto specialized food pads to mitigate bacterial growth in food packaging instead of being directly added to the food. Additionally, the study aimed to determine the amount of carbon dioxide generated when MCC, used as an adsorbent in combination with citric acid, comes into contact with the meat liquid,as this has an impact on the growth of aerobic microorganisms.The findings revealed that MCC adsorbed 44% and 55% of the initial quantities of benzoic acid (BA) and thymol, respectively. Furthermore, after 12 seconds from an initial adsorption amount of 19 mg/g, the maximum amount ofthymol released from MCC was measured at 0.120 mg/ml (approximately0.126%). Similarly, for an initial adsorption amount of 15 mg/g, the quantityof BA released was found to be 0.080 mg/ml (approximately 0.106%). TheUV-spectrophotometer was utilized to determine the amounts of adsorbed anddesorbed anti-microbial agents, while Checkmate 3 was used to assess the release of carbon dioxide.Significantly, the utilization of food pads demonstrated a significant enhancement in the release of carbon dioxide. Interestingly, the presence of anti-microbial agents did not have any influence on the generation of carbon dioxide.This research provides valuable insights into the potential application of foodpads and MCC as effective strategies for preserving fresh meat products bycontrolling microbial activity and promoting sustainability. / Sammanfattning Livsmedelshållbarhet beror i hög grad på förpackningar eftersom det hjälpertill att hålla maten säker och fräsch under hela dess hållbarhetstid, vilket resulterar i minskad mängd avfall och mindre negativ miljöpåverkan. Huvudsyftetmed denna studie var att bestämma den adsorberade och frigjorda mängdenantimikrobiella medel (bensoesyra och tymol) på modifierat kalciumkarbonat(MCC) genom att undersöka adsorptionsisoterm vid 25°C och desorptionskinetiken vid både 22°C och 5 °C av antimikrobiellt medel för att identifierapotentiella lösningar för att förbättra den långsiktiga hållbarheten för färskaprodukter som kött. Dessa medel inkorporerades i specialiserade food pad föratt mildra bakterietillväxt i livsmedelsförpackningar istället för att läggas direkt till maten. Dessutom syftade studien till att fastställa mängden koldioxidsom genereras när MCC, som används som adsorbent i kombination med citronsyra, kommer i kontakt med köttvätskan, eftersom detta har en inverkan påtillväxten av aeroba mikroorganismer.Resultaten visade att MCC adsorberade 44 % och 55 % av de initiala mängderna bensoesyra (BA) respektive tymol. Vidare, efter 12 sekunder från eninitial adsorptionsmängd på 19 mg/g, mättes den maximala mängden tymolsom frigjordes från MCC till 0,120 mg/ml (ungefär 0,126%). På liknande sätt,för en initial adsorptionsmängd på 15 mg/g, visade sig mängden frisatt BA vara0,080 mg/ml (ungefär 0,106%). UV-spektrofotometern användes för att bestämma mängderna av adsorberade och desorberade antimikrobiella medel,medan Checkmate 3 användes för att bedöma frisättningen av koldioxid.Betecknande nog visade användningen av food pad betydande förbättring avutsläppet av koldioxid. Intressant nog har närvaron av antimikrobiella medelinte haft någon inverkan på genereringen av koldioxid. Denna forskning gervärdefulla insikter om den potentiella tillämpningen av food pad och MCC someffektiva strategier för att bevara färska köttprodukter genom att kontrolleramikrobiell aktivitet och främja hållbarhet.

Dans le cadre d’un projet général concernant l’étude de la réactivité des acidesbenzoïques non protégés avec les organométalliques, la synthèse totale d’analoguesstructuraux de l’apogossypol mettant en jeu des réactions de métallation aromatique a étéétudiée ainsi que la réaction de substitution nucléophile aromatique des acides benzoïquesortho-fluorés et ortho-méthoxylés.Le gossypol, (1,1’,6,6’,7,7’-hexahydroxy-5,5’-di-iso-propyl-3,3’-diméthyl-2,2’-binaphtalène-8,8’-dicarboxaldéhyde), pigment principal des graines du cotonnier, existe sousla forme de deux atropoisomères et possède de multiples applications pharmaceutiques. Il estnotamment un inhibiteur efficace des protéines anti-apoptotiques de la famille Bcl-2. Legossypol déformylé ou apogossypol présente des propriétés similaires mais est plus stable,plus sélectif et moins toxique. Une méthode permettant de remplacer les groupes iso-propylesdu gossypol par des groupes structurellement proches a été mise au point. La stratégie retenuemet à profit les compétences du laboratoire dans le domaine des réactions de métallation etrepose sur la lithiation latérale de l’acide 4-hydroxy-6,7-diméthoxy-8-méthyl-2-naphtoïquepar le tétraméthylpipéridure de lithium. Divers dérivés 5,5’-didés-iso-propyl-5,5’-dialkylapogossypol racémiques ont été préparés selon cette méthode. La synthèse asymétriqued’analogues de l’apogossypol a également été étudiée et la voie de synthèse sélectionnéerepose sur le « concept lactone ». Un intermédiaire avancé de la synthèse, une lactonefonctionnalisée potentiellement réductible de façon asymétrique, a été préparée.La deuxième partie est consacrée à l’étude de la réaction de substitution nucléophilearomatique des acides benzoïques ortho-fluorés et ortho-méthoxylés (réaction SNArAB). Unerevue de la littérature des réactions de substitution nucléophile aromatique activée par lesesters est présentée. L’influence de substituants méthoxylés et halogénés (F, Cl, Br) sur lasélectivité SNAr/addition 1,2 a été évaluée. Il est montré que les acides 2-fluoro-6-halogénobenzoïques conduisent, par réaction avec les aryllithiens et les arylmagnésiens, auxproduits d’ipso-C2-substitution avec un excellent rendement et la réaction SNArAB permet unaccès efficace aux acides 3-halogéno-[1,1’-biphényl]-2-carboxyliques. Dans le cas de l’acide2,3-diméthoxybenzoïque, il a été découvert que la présence d’un substituant méthoxy enposition 3 permet de limiter la formation de cétone et le produit d’ipso-substitution est isoléavec un rendement correct. / As part of a program directed toward the study of the reactivity of unprotected benzoicacids with polar organometallics, the total racemic synthesis of apogossypol analogues bymetalation reactions was studied as well as the aromatic nucleophilic substitution reaction ofortho-fluoro- and ortho-methoxybenzoic acids (SNArAB reaction).Gossypol (1,1’,6,6’,7,7’-hexahydroxy-5,5’-di-iso-propyl-3,3’-diméthyl-2,2’-binaphtalène-8,8’-dicarboxaldéhyde) which is the main pigment of cotton seed, displaysmultiple pharmacological applications. It is a potent anti-apoptotic Bcl-2 protein inhibitor.The racemic route developed herein allows the replacement of the iso-propyl groups byvirtually any alkyl groups, providing a series of 5,5’-dides-iso-propyl-5,5’-dialkylapogossypolderivatives. Lateral metalation of 4-hydroxy-6,7-dimethoxy-8-methyl-2-naphthoic acid withLTMP is the key step of the synthesis. Atroposelective synthesis of apogossypol analoguewas also examined. The strategy relies on the “lactone concept” and involves a functionalizedlactone as a key intermediateThe influence of halogen atoms (F, Cl, Br) and methoxy groups on the 1,2-addition/SNArAB selectivity was examined. Treatment of 2-fluoro-6-halobenzoic acids withorganolithiums or Grignard reagents gives ipso-substituted products in excellent yields. Themethod allows the efficient preparation of 3-halo-[1,1’-biphenyl]-2-carboxylic acids and doesnot require protection of the carboxylate. Interestingly, the presence of an additional methoxyin C3 reduces the nucleophilic addition of the organometallic species to the carboxylate and2,3-dimethoxybenzoic acid affords ipso-substituted products in good yields.