Dissertation/Thèse

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2024
Thèses
1
  • LEONARDO CENSI LEMOS
  • Planning and investigation of synthetic methodologies to obtain diimidazoline-pyrazoles derivatives with trypanocidal activity potencial

  • Leader : MAURICIO SILVA DOS SANTOS
  • MEMBRES DE LA BANQUE :
  • CRISTIANE FRANÇA DA COSTA
  • MARCOS ROBERTO DE ABREU ALVES
  • MAURICIO SILVA DOS SANTOS
  • Data: 29 févr. 2024


  • Afficher le Résumé
  • Chagas Disease (CD), an illness discovered by Carlos Chagas 115 years ago, remains a great
    public health problem. It has been reported 30 thousand new cases annually and causing 14
    thousand deaths during the same period of time. Currently, two drugs only are used in the
    chemotherapy, benznidazole (BZ) and nifurtimox (NF). The former is the unique commercially
    available in Brazil, but its major issue is a high treatment dropout rate (around 20%), due to
    severe side effects and long periods of administration, in addition to its lack of efficacy in the
    chronic phase of CD. In the search for new candidates with potential trypanocidal effect, our
    research group has been synthesizing several heterocyclic systems for their antiparasitic
    evaluation. In this work, the aim is to synthesize and evaluate the trypanocidal activity of 9 new
    1-aryl-3-(methyl(4,5-dihydro-1H-imidazol-2-yl))-4-(4,5-dihydro-1H-imidazol-2-yl)-1Hpyrazoles derivatives 1(a-i). Eighteen key intermediates were synthesized: 5-amine-1-aryl-4-
    cyane-3-(methylcyane)-1H-pyrazoles 2(a-i), 1-aryl-4-cyane-3-(methylcyane)-1H-pyrazoles
    3(a-c,e-i), 2-amine-1,1,3-tricyaneprop-2-ene 4, isolated in 31-85% yields. Regard to synthesis
    of the desired compounds 1(a-i), eleven methodologies were evaluated in attempt to obtain 1a
    and none of them generated this compound. However, when it was employed classical
    methodology, involving ethylenediamine (EDA) and carbon disulfide (CS2), an unexpected
    compound was obtained: 8-phenyl-2,3-dihydro-8H-imidazo[1,2-a]pyrazolo[4,3-c]pyridine-5-
    thiol 6a, in 29% yield. From similar experimental procedure more three compounds were
    obtained, 6(e,f,h), in 11-87% yields. All compounds had it structure confirmed by FourierTransform Infrared (FT-IR) Spectroscopy, High-Resolution Mass Spectrometry (HRMS), and
    Nuclear Magnetic Resonance (NMR) analysis.

Thèses
1
  • CYNTHIA NATHALIA PEREIRA
  • DESIGN AND SYNTHESIS OF HETEROCYCLIC SYSTEMS WITH POTENTIAL TRYPANOCIDAL ACTIVITY

  • Leader : MAURICIO SILVA DOS SANTOS
  • MEMBRES DE LA BANQUE :
  • EUGENIO URIARTE VILLARES
  • DANIEL CRISTIAN FERREIRA SOARES
  • LEONARDO DA SILVA LARA
  • MAURICIO FROTA SARAIVA
  • MAURICIO SILVA DOS SANTOS
  • Maria João Correia Pinto Carvalho de Matos
  • Data: 26 févr. 2024


  • Afficher le Résumé
  • Chagas Disease (CD) is a neglected tropical disease caused by the protozoan Trypanosoma cruzi, transmitted by triatomine insects. It is estimated that 6 million people are currently infected worldwide. Chemotherapy is based on two drugs, benznidazole and nifurtimox, which have limited efficacy and several side effects. Therefore, there is an imminent demand for the development of new compounds that are more active against T. cruzi. Over the years, especially compounds containing heterocyclic nuclei, have shown a wide spectrum of biological activities, including antiprotozoal, with emphasis on the pyrazole, imidazoline, pyrimidine, tetrahydropyrimidine, thiazole and coumarin nuclei, which were synthesized in this research project. In this study, 40 new compounds designated series 1(a-k), 2(a-k), 3(a,c-f,h-j) and 4(a-j) were designed, synthesized and evaluated their for trypanocidal activity, based on previously promising compounds synthesized by our research group. All final compounds were characterized by nuclear magnetic resonance (NMR) and mass spectrometry (HRMS) analyses. The yields of products 1(a-k) ranged from 28% to 77%. In series 2(a-k), derivatives were obtained in 27-91% yields. Derivatives 3(a,c-f,h-j) were isolated in yields ranging from 24-94%, while compounds 4(a-j) were synthesized in yields varying from 36-94%. In silico analyzes showed that all compounds obey Lipinski's rules, and presented a high probability of good oral bioavailability. The present study describes the biological activity of the final compounds 1(a-k), 2(a-k) and 3(a,c-f,g-j). In vitro phenotypic screening showed that among all compounds of series 1(a-k), 1h derivative displayed the highest biological activity (IC50 = 28.57 ± 4.70 µM) gainst trypomastigote forms, and all compounds displayed IC50 > 67 µM against amastigote forms. Among derivatives 2(a-k), compound 2g stood out as it exhibited the most promising results against both forms of the parasite, with an IC50 value equal to 11.66 ± 1.38 μM. The compounds of series 3(a,c-f,g-j) were tested against amastigote forms and demonstrated low efficacy (IC50 > 47 µM). In relation to compounds 4(a-j), 4f derivative has been the most active against both forms of T. cruzi, however trials are still ongoing. All compounds from series 1, 2, 3 and 4 did not show cytotoxicity (CC50 > 100 µM). The compound named MSD24 was synthesized on a larger scale and is currently undergoing in vivo testing. This work highlights the importance of searching for new drug candidates for the treatment of CD.

2023
Thèses
1
  • MATEUS VINÍCIUS NASCIMENTO DA SILVA
  • Computational study of the reduction mechanisms of Platinum(IV) compounds to Platinum(II) in aqueous solution.

  • Leader : JULIANA FEDOCE LOPES
  • MEMBRES DE LA BANQUE :
  • LEONARDO APARECIDO DE SOUZA
  • FABIO DA SILVA LISBOA
  • JULIANA FEDOCE LOPES
  • Data: 17 mars 2023


  • Afficher le Résumé
  • Platinum compounds are widely used as chemotherapeutics worldwide. One of the most important is cis-diamminedichloroplatinum(II), known as cisplatin. However, it has side effects and there are limitations on its administration. In this sense, a new class of platinum(IV) compounds has been studied following a prodrug approach in their development. It is believed that for these compounds to become therapeutically active, they must undergo prior reduction from Pt(IV) to Pt(II). However, what happens in this reduction process is still poorly explored in the literature, and there are several doubts. The prodrug approach indicates that in a reduction process, axial ligands leave the coordination sphere of platinum, forming a compound with irreversible characteristics. In this work, computational methods were used to investigate the reduction process of two platinum(IV) compounds: cis-diamminetetrachloroplatinum(IV) and bis(acetato)amino(n-butylamino)dichloroplatinum(IV), the latter in two different conformations. Their structural, electronic, and thermodynamic characteristics were studied to elucidate this reduction pathway. The MP2 and DFT levels of theory (M06-2x functional) were used for calculations in gas phase and with solvent inclusion by the IEFPCM method. The first compound has a LUMO orbital with dz2 symmetry, suggesting the traditional reduction mechanism for octahedral compounds, d6. The second compound has a LUMO orbital with dx2-y2 symmetry, which may indicate a different reduction mechanism from the traditional one, with the departure of equatorial ligands. The thermodynamic analyses performed indicate processes with a decrease in ΔG and an increase in entropy for most of the compounds studied. Other electronic and thermodynamic analyses were also performed and interpreted. Similar results were obtained with the inclusion of the solvent effect. Calculations were also performed with explicit solvation method by Monte Carlo methodology. These calculations yield results that indicate the stabilization of products in the aqueous phase, the formation of at least 2 solvation layers in the compounds studied, and possible hydrogen bonding. Statistical correlation analyses were performed to extract the smallest possible number of configurations that represent water-solute interactions. The results were obtained by combining functionals to find the best method, but limitations were found in the calculations, probably due to the high degree of freedom of the system and convergence problems.

2
  • PEDRO AUGUSTO DE ANDRADE NOVAES
  • Computational study of the thermodynamics and kinetics of cisplatin reactions with Glutathione

  • Leader : JULIANA FEDOCE LOPES
  • MEMBRES DE LA BANQUE :
  • FABIO DA SILVA LISBOA
  • JULIANA FEDOCE LOPES
  • LUCAS FAGUNDES ESTEVES
  • Data: 24 mars 2023


  • Afficher le Résumé
  • The studies on metal complexes for use in cancer chemotherapy have greatly increased since the discovery of the biological activity of cis-diamminedichloroplatinum(II), better known as cisplatin. Cisplatin is effective in cancer treatment, and its mechanism of action is based on the platinum-DNA binding, which interferes with cellular transcription and replication processes, leading to cell death or apoptosis. However, certain tumors originally sensitive to cisplatin develop chemoresistance, which is the main limitation in the clinical use of cisplatin and is generally multifactorial. Glutathione (GSH) is often considered the primary contributor to the sequestration of cisplatin due to its high intracellular concentration. Therefore, most of the interaction modulates toxicity, preventing cisplatin from interacting with DNA. In this work, the reactions of cisplatin and its hydrolyzed species with glutathione were studied, and the structures of the reacting species, products, and intermediate species, where the main intermolecular interactions involved in the reaction were observed, were characterized. To represent the studied processes, numerous DFT M062X calculations were performed, with the 6-31G(d,p) function and Lanl2dz as the pseudopotential for the platinum atom. Different conformers of glutathione were evaluated, and the GLUCα-C-C-C(COOH) and CYSN-C-C-N(CH2COOH) dihedrals and the terminal hydroxyls of glutamate and glycine were the parameters used to categorize and differentiate conformations. Three conformations were found, where the conformational population for the structures was I) 33.60%, II) 33.44%, III) 32.97%. The transition states of the first and second steps of the reactions were determined, where the conformations assumed by glutathione were directly related to the calculated energy parameters. Through the transition states, IRC calculations for reaction A were performed, and the conformation of GSH, the GLUCα-C-C-C(COOH)=-57.8° and CYSN-C-C-N(CH2COOH)=52.8° dihedrals, and the distances between the hydrogen atoms of the terminal hydroxyl groups (GLU-GLY) were evaluated, which was 9.444 Å. Comparatively, the product obtained via chemical intuition had GLUCα-C-C-C(=O)=-57.9° and CYSN-C-C-N(GLY)=58.21° and the distances between the glutamate and glycine acid groups were 3.970 Å, which is characteristic of a closed conformation.

3
  • ELINE BARBOSA FERREIRA
  • Hybrid materials formed by the Dithiocarbimate Anion [C7H7SO2NCS2]2- . 2 H2O and Layered Zinc Hydroxy salts: Synthesis, Characterization and Vulcanization Studies of Natural Rubber.

  • Leader : FABIO DA SILVA LISBOA
  • MEMBRES DE LA BANQUE :
  • EDER DO COUTO TAVARES
  • FABIO DA SILVA LISBOA
  • FREDERICO BARROS DE SOUSA
  • GEISE RIBEIRO
  • GREGÓRIO GUADALUPE CARBAJAL ARIZAGA
  • Data: 12 juin 2023


  • Afficher le Résumé
  • The study of layered materials has received much attention in recent decades due to the numerous possibilities of applications, such as the preparation of adsorbent materials, catalysts, devices for releasing drugs, and sensors. In this context, inorganic-organic hybrid materials stand out, which can be formed from the interaction between inorganic matrices, with the intercalation of organic molecules between the layers of the layered component. Dithiocarbimates (DCBI), organic anions that can be intercalated in suitable layered matrices, are known in the literature for their fungicidal and bactericidal properties and the capacity to form metallic complexes, which present activities as rubber vulcanization accelerators. It is noteworthy that, so far, there are no reports in the literature about zinc hydroxy salts (hydroxynitrate or hydroxyacetate) intercalated and/or functionalized with dithiocarbimate anions. The purpose of this work was the synthesis, characterization, and evaluation of the stability in the aqueous medium of these unpublished hybrid compounds and their tests as accelerators of rubber vulcanization. The compounds obtained were characterized by X-ray diffraction (XRD), vibrational spectroscopy in the infrared region (IR), electronic spectroscopy in the ultraviolet-visible region (UV-Vis), scanning electron microscopy, and energy dispersive X-rays (SEM /EDS). All synthesized compounds were tested as accelerators in the rubber vulcanization process. The XRD results indicated that the hydroxy salts, obtained without the presence of the dithiocarbimate anion, presented good crystallinity and, after being submitted to ion exchange reactions or having been synthesized via coprecipitation, products intercalated and/or functionalized with the organic anion were obtained, maintaining the basic structure of the layered structure. FTIR data suggest that acetate anions interact with the layers in a bidentate manner, nitrate anions are free in the interlayer spaces, and DCBI anions interact with the layers through the CS2 portion. The kinetic studies carried out from data obtained through UV-vis confirmed the instability of the DCBI anion in a basic medium, however the anion was more stable than when in an aqueous medium. The release study in an aqueous medium made from suspensions of the hybrid compounds HAcZ-iDCBI, HAcZ-fDCBI, and HNZ-iDCBI indicated greater stability of the anion due to its interaction with the matrices. In addition, the results indicated the presence of an anion in the reaction medium during the synthesis time and corroborate with the data of DRXP and DCBI size in the analysis of the integrity of the anion present in the intercalated structures. SEM/EDS techniques indicate morphologies with shapes without well-defined sizes and uniform distribution of elements over the surface. Tests of solids as accelerators in the rubber vulcanization process and mechanical tests were compared with the commercial accelerator ZEDC. The samples that showed better results were HNZ, HNZ-fDCBI, and HNZ-iDCBI. All samples were active as accelerators, although slower and with lower crosslinking levels, they had an advantage in terms of pre-cure time and minimum torque. Mechanical tests indicated that the synthesized samples have lower tear resistance and higher elongation at break when compared to ZEDC.

4
  • JOANE NÁTALY DE JESUS MARQUES
  • Synthesis, characterization and cytotoxic evaluation of thiosubstituted geraniol analogues in tumor cells of the U87MG lineage

  • Leader : MAURICIO FROTA SARAIVA
  • MEMBRES DE LA BANQUE :
  • DANIEL HENRIQUES SOARES LEAL
  • MARA RUBIA COSTA COURI
  • MARCUS VINICIUS NORA DE SOUZA
  • MAURICIO FROTA SARAIVA
  • Data: 24 août 2023


  • Afficher le Résumé
  • The cancer is a serious public health problem defined by a set of more than 100 diseases associated with disordered cell growth, which affects various organs and tissues of the body. This disease is responsible for about nine million deaths annually worldwide and, according to estimates, this number will rise to 11.5 million in 2030. Of this mortality rate, 70% is concentrated in developing countries, such as the Brazil. Therefore, in view of the high number of deaths caused annually by this disease, it becomes extremely important to develop new alternatives for the treatment of cancer. In this sense, the healing potential of medicinal plants, more specifically the substances found in the essential oils that are extracted from them, have shown to be good possibilities in the development of drugs for diseases in general. Among these essential oils, a compound called geraniol showed promising results in recent studies, in vitro and in vivo, evaluating the antineoplastic potential. Among the various types of cancer, glioblastoma multiforme (GBM) is considered one of the rarest and most lethal types, which belongs to the category of central nervous system (CNS) tumors. In general, patients diagnosed with this disease have a very low life expectancy. A significant challenge related to GBM lies in the scarcity of therapeutic options available, since only one drug has been approved by the Food and Drug Administration (FDA) and is used for the treatment of this disease. Considering the demand for new therapeutic alternatives in the treatment of cancer, especially in the case of glioblastoma, and motivated by the promising results obtained with geraniol, an attempt was made to develop derivatives with better properties, aiming at their improved effectiveness in inhibiting neoplastic cells. Therefore, this work describes the synthesis, characterization and evaluation of the cytotoxic activity of 11 thiosubstituted analogues of this monoterpene against glioblastoma tumor cells of the U87MG cell line. Of the 11 derivatives synthesized so far, only 9 were evaluated for cytotoxicity. The compounds were obtained in low to moderate yields ranging from 10 to 69%. The derivatives were characterized by Infrared (FT-IR), 13C and 1H NMR, DEPT-135 and high resolution mass spectrometry ESI-HRMS (ElectroSpray Ionization – High Resolution Mass Spectrometry). The evaluation of the cytotoxic activity of the 9 analogues was carried out in relation to cells of the U87MG lineage. IC50 values were compared to geraniol and Temozolomide, the standard drug used in the treatment of GBM. Notably, compound 3e stood out as the most active among all evaluated compounds, demonstrating an IC50 of 25 μM, being at least four times more effective than the monoterpenoid geraniol and approximately twenty times more potent than the reference drug used in the treatment of Glioblastoma U87MG. Conversely, compounds 3c, 3d, 3dsub, 3esub, and 5c yielded IC50 values ranging from 57,8 to 86,6 μM, whereas the remaining compounds exhibited values exceeding 100 μM.

5
  • Emily Pacelli Moreira Linhares
  • Development of potential ALDH1A3 inhibitors: a potential target in the fight against glioblastoma stem cells

  • Leader : MAURICIO FROTA SARAIVA
  • MEMBRES DE LA BANQUE :
  • CELSO DE OLIVEIRA REZENDE JÚNIOR
  • DANIEL HENRIQUES SOARES LEAL
  • MAURICIO FROTA SARAIVA
  • MAURICIO SILVA DOS SANTOS
  • Data: 25 août 2023


  • Afficher le Résumé
  • Glioblastoma is the most common, aggressive, and lethal type of brain tumor. Few treatments exist and the median survival period is less than 15 months after diagnosis. The permanence of subpopulations of glioma stem cells (GSCs) after treatments is a recent discovery that explains the high frequency of recurrences and metastases of this type of tumor. Aldehyde dehydrogenase family 1 member A3 (ALDH1A3) is an enzyme overexpressed in GSCs that has seen used as a biomarker and has been also pointed out as a potential pharmacological target for a selective and personalized therapy of Glioblastoma aiming at the elimination of tumor stem cells. In this context, the monoterpene citral (3,7-dimethyl-2,6-octadienal), presents itself as a promising natural product, as it can inhibit ALDH1A3. In attempt compounds more effective than citral, this work describes the synthesis and characterization of 20 compounds, 17 novel analogues of monoterpenes geraniol and geranial. The analogues consist of 4 final products, designed to inhibit ALDH1A3 (11a, 12a-b, 13a-c, and 14a) and 13 intermediates (1a, 2a, 3a, 4a, 5a, 6a, 7a, 8a, 9a, 10a beyond Intermediate I, Intermediate II and Intermediate III). Among all compounds, Intermediate III and consequently the final compounds derived from it (13a-c) could not be obtained. The final compounds 11a, 12a-b, and 14a were obtained in yields ranging from low to excellent (36-91%). The other intermediates (1a, 2a, 3a, 4a, 5a, 6a, 7a, 8a, 9a, 10a, Intermediate I, and Intermediate II) were obtained in yields ranging from low to excellent 35-98%. All products except 4a were characterized by spectroscopy in the infrared region (FT-IR). By 1H NMR, 13C NMR and DEPT-135, compounds 7a, 8a, 9a, 10a, Intermediate I, Intermediate II, 11a, 12a-b and 14a were characterized. Only intermediates I and II and two final products were forwarded to the high-resolution mass spectrometry technique (ESI-HMRS). The cytotoxic potential of Intermediate II was evaluated against glioblastoma tumor cells (U87MG) and IC50 values were calculated in comparison to geraniol and the reference drug used in GBM treatment, Temozolomide (IC50 = 1mM). The activity presented by Intermediate II showed IC50 value = 56.50 µM. The other compounds: Intermediate I, 11a, 12a, 14a, and the by-product derived from the attempted synthesis of Intermediate III, were sent for testing. In addition, the ability of the final products obtained and the intermediates to inhibit ALDH1A3 was also evaluated. Molecular modeling studies were performed to predict the docking of final products 11a, 12a-b, and 14a and Intermediates I, II, and III with the ALDH1A3 isoenzyme. Analysis of the results revealed 3 potential inhibitors of the enzyme. Intermolecular interactions by hydrogen bonds and hydrophobic interactions were identified between ALDH1A3 and most of the ligands, indicating the affinity of these compounds with the macromolecule. This is the first study focused on geraniol/geranial analogs for aldehyde dehydrogenase 1A3 inhibition, as a focus on tumor stem cell elimination.

6
  • RAFAEL TADEU SILVA
  • Bleaching of pine wood using hydrogen peroxide/ultraviolet radiation to produce transparent wood

  • Leader : MERCES COELHO DA SILVA
  • MEMBRES DE LA BANQUE :
  • ELIANE AYRES
  • GUILHERME OLIVEIRA SIQUEIRA
  • MERCES COELHO DA SILVA
  • Data: 28 août 2023


  • Afficher le Résumé
  • This study addresses the bleaching process of Pinus wood with the purpose of evaluating its application in the manufacture of transparent wood (MT), a composite made up of bleached wood and polymer resin. The removal of wood color was achieved by modifying the chromophore groups present in lignin, using hydrogen peroxide in conjunction with ultraviolet radiation. In this context, the parameters of the bleaching process were investigated, including the concentration of hydrogen peroxide, the immersion time of the wood samples in the solution and the period of exposure to ultraviolet radiation. A two-level experimental design (23) was used to evaluate the effect of these variables on the whiteness index (WI) of the samples. The chemical treatment applied to Pinus wood resulted in a significant increase in WI, from 13.30 to 60.55, as well as in porosity, which increased from 49.44% to 69.88%, consistent with the reduction in wood density, from 0.38 to 0.17 g/cm³. As predicted, the fundamental components of the wood were preserved after the bleaching process, which was evidenced by the characteristic absorption bands of the chemical structures of cellulose, lignin, and hemicellulose in the FTIR spectrum of the sample. This analysis corroborates the color changes resulting from the removal of chromophore groups from lignin and the chosen bleaching method. Bleached Pine wood was impregnated with epoxy resin under vacuum, resulting in a material with transmittance of 77.66%. The results obtained indicate the viability of this process to produce MT from Pine.

7
  • Hélder Inocêncio Ferreira Corrêa
  • PREPARATION AND CHARACTERIZATION OF SIZE-CONTROLLED MIXED OXIDES, OBTAINED FROM HETEROMETALLIC LAMELLAR MONOCARBOXYLATES OF Zn2+ AND Co2+ IONS

  • Leader : FABIO DA SILVA LISBOA
  • MEMBRES DE LA BANQUE :
  • FABIANO ROSA DA SILVA
  • ADHIMAR FLAVIO OLIVEIRA
  • FABIO DA SILVA LISBOA
  • JULIANA FEDOCE LOPES
  • Data: 31 août 2023


  • Afficher le Résumé
  • Saturated monocarboxylates of metal ions, also known as metallic soaps, are compounds that can be used as catalysts in esterification reactions, lubricants or as precursors of metal ion oxides, with the aim of acting in phenomena involving electrical semiconduction. In this work, heterometallic laurates and stearates containing Zn2+ and Co2+ ions in their composition were synthesized and, based on these, studies were carried out to obtain the oxides through calcination. Next, a study was carried out on the influence of the variables temperature and calcination time on the formation of mixed oxides, aimed at the formation of particles with uniform shape and size and on a nanometric scale. In addition to analyzes using X-ray powder diffraction, Fourier transform infrared with attenuated total reflectance and scanning electron microscopy, characterizations were carried out via diffuse reflectance between lengths of 200 and 1080 nm. Regarding the results obtained, it was found that the samples presented a profile to be used in photocatalysis reactions as they are dielectrics with direct and indirect band-gaps, which is a characteristic of a semiconductor.

8
  • DÉBORA ASSUMPÇÃO CUNHA
  • Evaluation of solvent effect: isomer MC-TTC of merocyanine in methanol.

  • Leader : JULIANA FEDOCE LOPES
  • MEMBRES DE LA BANQUE :
  • GEORGIA MARIA AMARAL JUNQUEIRA
  • FREDERICO BARROS DE SOUSA
  • JULIANA FEDOCE LOPES
  • Data: 28 sept. 2023


  • Afficher le Résumé
  • Spiropyrans (SP) isomerize to merocyanines (MC) when exposed to external factors such
    as radiation, temperature changes, different solvents, etc. The phenomenon that focuses on the influence of the solvent on changing electronic properties is called solvatochromism and can be observed by the change in color of a solution with the same solute in different solvents. In this study we started from a system containing an isomer of merocyanine, MC-TTC, in methanol solution, to verify the electronic interactions that explain this phenomenon.
    Computational chemistry was first used with the Gaussian 09 software, applying Density
    Functional Theory (DFT), carrying out simulations in the liquid phase implicitly, using the
    IEFPCM method. Geometry optimization, vibrational frequency and atomic charge calculations were performed with the M06-2X functional and 6-31G(d,p) basis function. With the results obtained, the simulations were followed explicitly. Using classical mechanics, Monte Carlo simulations were considered for explicit solvation, in which the DICE 3.0 software represented the solute-solvent system considering an NPT ensemble and OPLS force field. As result, radial distribution function was obtained, defining the
    distance and quantity of methanol in the solvation shells (1st: 8 molecules; 2nd: 17 molecules), as well as atom-atom interactions. In these, the behavior of the solvent distributions and its highest concentration in certain regions were predicted.
    Fifty statistically uncorrelated configurations were selected, directing them to quantum
    calculations using the TD-DFT methodology. At this stage, the M06-2X functional and 631-G(d,p) base function were maintained, such as the IEFPCM method, to represent long-distance interactions. UV-Vis spectra were generated, where a significant difference of approximately 40 nm was found between the maximum absorption values of these 50 configurations. The same analysis was carried out for the second solvation shell, and, as a summary of the results, it was confirmed that the explicit representation is efficient in presenting the phenomenon of solvatochromism, and consequently, in understanding the factors that influence solute-solvent interactions.

Thèses
1
  • FLÁVIO BASTOS MIGUEZ
  • Study of Polymeric Matrices with Spiropyra Derivates Incorporated for Applications in Chemical Sesnsing

  • Leader : FREDERICO BARROS DE SOUSA
  • MEMBRES DE LA BANQUE :
  • GUILHERME MAX DIAS FERREIRA
  • DANIEL CRISTIAN FERREIRA SOARES
  • EDER DO COUTO TAVARES
  • FREDERICO BARROS DE SOUSA
  • JOÃO PAULO CAMPOS TRIGUEIRO
  • Data: 2 juin 2023


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  • This work reports on the synthesis and characterization of six spirocyclic derivatives with potential incorporation into polymeric matrices for pH and lanthanide ion sensing. Among the various possible structural modifications that spiropyrans can undergo, those containing alkylsulfonate groups are commonly classified as photoacids. These molecules can be used to describe the acid/base equilibrium and to modify materials for use as sensors. Two synthesized spiropyrans containing this group (SON and SOH) had their acid- and photochromic properties studied by UV-Vis spectroscopy, and their pH and radiation dependent isomers were observed in the system. The other four synthesized spiropyrans (SPOH, SPOCH3, SPCOOH, and SPOCH3M) contain carboxylic acid or alcohol groups, commonly used for their interaction with metal ions. These two spiropyran derivate groups were structurally characterized by infrared spectroscopy, Raman spectroscopy, nuclear magnetic resonance, and mass spectrometry. To enable practical applications, it is essential to use materials such as high surface area polymeric matrices, which interact more efficiently with external media. Such materials can be obtained by electrospinning, in which the spiropyran derivatives were incorporated into biocompatible poly-ε-caprolactone (PCL) electrospun fibers with the aim of detecting acidic and basic vapors and lanthanide ions through colorimetric changes. The fibers obtained had their morphological aspects analyzed by scanning electronic microscopy and contact angle analysis. Apart from PLC-SPOCH3M fiber, the remaining PCL fibers containing spiropyran derivates showed surface properties compatible with hydrophobic systems. Materials designed for the detection of acid and base vapors can be reversibly reused according to the presented results. Moreover, these fibers showed efficient reversibility between acid and base vapors. The combination of results, containing the remaining spiropyrans, was fundamental to selectively identify and differentiate between all lanthanide ions, La3+ and Lu3+, by changes macroscopic changes (visible to the naked eye) and by emission analysis.

2
  • DIEGO CAPRONI DE MORAIS
  • Polymeric Fibers and Their Associations with Cyclodextrin for the Controlled Release of the Antimicrobial Sodium Sulfadiazine

  • Leader : FREDERICO BARROS DE SOUSA
  • MEMBRES DE LA BANQUE :
  • MICHELE FABIANE DE OLIVEIRA
  • DANIEL CRISTIAN FERREIRA SOARES
  • FREDERICO BARROS DE SOUSA
  • MARIA CECÍLIA RODRIGUES SIMÕES
  • SANDRO JOSE DE ANDRADE
  • Data: 31 août 2023


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  • The present work documents the production of polymeric matrices of poly-ε-caprolactone (PCL), polymethylmethacrylate (PMMA) and poly (lactic acid-co-glycolic acid) (PLGA), biocompatible polymers that are already commonly used in medical systems. Substances such as the anti-inflammatory and antibacterial drug sodium sulfadiazine (SDS) and the supramolecular compound formed by the drug and hydroxypropyl-β-cyclodextrin (HPCD) were added to these polymers, with the aim of assembling a delivery system. of drug transdermally. The technique used to obtain these polymeric membranes was electrospinning, with the formation of fibers and their morphological characteristics previously observed by optical microscopy. Then the formation of polymeric fibers and their average diameter distributions evaluated by scanning electron microscopy (SEM). The hydrophobic and hydrophilic characteristics of the materials were characterized by the technique of measuring the contact angle of the water with the surface of the materials, as well as by the analysis of permeability to water vapor. Prior to the release test, extractions were performed to quantify the presence of the drug in the polymeric membranes. After quantification, release tests were performed to discover the release profile that is associated with this material and whether the amount released during the test period will be effective for the main objective, which is to obtain a polymeric matrix for transdermal release. Subsequently, cell viability assessments were carried out to verify the possible toxicity of the material. The scratch test (wound healing) was also performed to simulate the healing process through fibroblast proliferation. Another biological analysis conducted was the antibacterial activity assay, to measure the material's ability to reduce the microbial load of Staphylococcus aureus and Escherichia coli bacteria. The characterization by SEM showed that the fibers obtained have diameters in nanometer and micrometer scale and the contact angle analysis indicate that the PCL and PMMA fibers, even with the presence of hydrophilic molecules, such as the drug and HPβCD, have a hydrophobic character, while the PLGA fibers have a hydrophilic character, both by the pure polymer and when the molecules are added. The quantification of the extractions showed an error that can be attributed to experimental issues or the non-uniformity of drug distribution across the membrane. The release values demonstrate that PLGA and PMMA fibers are promising to be used, as they have profiles demonstrate to be promise. The cell viability test showed that all polymeric membranes were found to be non-toxic. In the scratch test, the results showed that systems containing the supramolecular systems SDS/HPβCD particularly accelerated the cell proliferation process compared to the free polymer or SDS-only loaded systems. The membrane that yielded the best results was the PLGA SDS/HPβCD membrane. In the antimicrobial assays, once again, the PLGA SDS/HPβCD membrane showed lower microbial load values and a larger inhibition zone.

2022
Thèses
1
  • LUCAS PENHA DUTRA
  • synthesis and characterization of pyrazole-thiadiazole hybrid systems with potential trypanocidal activity

  • Leader : MAURICIO SILVA DOS SANTOS
  • MEMBRES DE LA BANQUE :
  • CELSO DE OLIVEIRA REZENDE JÚNIOR
  • MAURICIO FROTA SARAIVA
  • MAURICIO SILVA DOS SANTOS
  • Data: 25 févr. 2022


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  • Chagas Disease (CD) was discovered in 1909 by Dr. Carlos Chagas and it is, until today, a public health problem. According to WHO, CD is one of the 20 Neglected Tropical Disease and affects the poorest people who live in Latin American, where the disease is endemic. It is caused by Trypanosoma cruzi, transmitted to humans by the triatomine bugs. The treatment of CD is based on two drugs, benznidazole and nifurtimox, both were developed more than 50 years ago. They have limited efficacy on chronic phase and cause many side effects. Thus, there is an urgent need to develop new compounds more active against T. cruzi, in both phases of the disease, and with less side effects. In this sense, heterocycles are an attractive class to design new drugs, because they are present in a plethora of bioactive compounds. Especially, azolic heterocycles 1H-pyrazole and 1,3,4-thiadiazole have gained considerable attention in the development of antiparasitic agents. Thus, in this work two new series of pyrazole-thiadiazole hybrids 1(a-l) and 2(a-l) have been planned with potential trypanocidal activity. The final products were synthesized using the key intermediates 3(a-l) and 4(a-l). Initially, two alternative methodologies to the final products synthesis were investigated. The carbonitriles 4(a,c,g,i,j) and the carboxamides 5(a,f,j) were used as raw materials in the first and second attempt, respectively. However, the desired products could not be obtained and the unexpected products 5(a,c,g,i,j) were formed in the first case and 6(a,f,j) in the second one. Finally, employing thiosemicarbazide and trifluoroacetic acid, the intermediates 3(a-l) and 4(a-l) were successfully converted into 1(a-l) and 2(a-l), respectively, in yields of 26 to 72% and 20 to 91%, in this order. All the compounds were characterized by FT-IR and the 6(a,f,j), 1(a-l) and 2(a-l) were also analyzed by HRMS, 1H and 13C NMR. So far, the majority of the tested derivatives, 1(a-k) e 2(a,b,d,f-l), did not exhibit toxicity against Vero cells, with CC50 >500 uM, except for 1(c,d), which presented a CC50 in 118,77 and 341,65 uM, respectively.

2
  • Tainara Aparecida Nunes Ribeiro
  • SYNTHESIS OF IMIDAZO-PYRAZOLE-PYRIMIDINE DERIVATIVES FOR EVALUATION OF ANTIBACTERIAL ACTIVITY

  • Leader : MAURICIO SILVA DOS SANTOS
  • MEMBRES DE LA BANQUE :
  • DANIEL HENRIQUES SOARES LEAL
  • DANIELA SACHS
  • FABIO AGUIAR ALVES
  • MAURICIO SILVA DOS SANTOS
  • Data: 3 mars 2022


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  • Diseases caused by bacteria have been a major problem worldwide since they are responsible for many deaths every year around the world and high health-related costs. In addition, the drug resistance has been raised significantly. Therefore, it is very relevant the research in order to developing new classes of antibacterial. There are many reports in the literature showing that heterocyclic compounds containing nitrogen atom have great biological potential, specially pyrazole moiety, which has showed remarkable antimicrobial activity. Thus, in this work aimed to synthesize new seven pyrazole derivatives 7-aryl-2,3,6,7-tetrahydro-5H-imidazo[1,2-c]pyrazolo[4,3-e]pyrimidine-5-thiones 1(a-g). The raw materials 5-amino-1-aryl-1H-pyrazole-4-carbonitriles 3(a-g) and the key intermediates 5-amino-1-aryl-4-(4,5-dihydro-1H-imidazole-2-yl)-1H-pyrazoles 2(a-g) were obtained in 47 to 71 % and 24 to 88% yields, respectively. The final products 1(a-g) were synthesized in 31 to 91% yields and completely characterized by Infrared Spectroscopy (FT-IR), High Resolution Mass Sprectrometry (HRMS) and Nuclear Magnetic Resonance (NMR). The compounds 1(a-g) are being evaluted against Escherichia coli through Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC). These derivatives 1(a-g) did not show antibacterial activity against E. coli.

3
  • JULIANA CARONI SILVA GUIMARÃES
  • ELABORATION AND CHARACTERIZATION OF A SOLID EXTRACTOR BASED ON EXPANDED POLYURETHANE SYNTHESISTED WITH GROSS GLYCEROL AS A POTENTIAL SYSTEM FOR REMOVAL OF ANIONIC DYE

  • Leader : MERCES COELHO DA SILVA
  • MEMBRES DE LA BANQUE :
  • MARYS LENE BRAGA ALMEIDA
  • DANIEL CRISTIAN FERREIRA SOARES
  • MARCOS ROBERTO DE ABREU ALVES
  • MERCES COELHO DA SILVA
  • Data: 13 juil. 2022


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  • This work aimed to synthesize an expanded polyurethane (EPU) based on crude glycerol (CG), and another based on a mixture of vegetable oil (70%) and pure glycerin (PG) (30%), as an alternative to petroleum-derived polyol, and to evaluate its efficiency as an adsorbent of the anionic dye amaranth from aqueous solution. CG was obtained from a biodiesel plant and was characterized by Fourier Transform Infrared Spectrophotometer (FT-IV), determination of the hydroxyl number (IOH) and free glycerol content in the crude waste. The IOH and free glycerol values found for CG were, respectively, 505 mg KOH/g and 32.0±0.29%. EPUs were synthesized and characterized by apparent density, FT-IV, thermogravimetry (TGA) and zeta potential (pHpcz). The EPU synthesized with CG (EPU-CG) presented higher apparent density (130.80 Kg m-3) in relation to EPU synthesized with the mixture of vegetable oil and PG (EPU-Mist) (29.7 Kg m-3) , and proved to be less thermally stable. However, EPU-CG showed better performance in the adsorption tests, with more than 90% removal of amaranth (6 mg L-1) at pH 3 and room temperature, while EPU-Mist obtained 52.7% removal under the same conditions of study. The pHpcz values found were, respectively, 6.27 and 7.15 for EPU-Mist and EPU-CG. During the adsorption tests, the influence of pH, contact time and initial dye concentration were evaluated, and both EPUs obtained the best removal percentage at pH 2 and the lowest initial dye concentrations. The data obtained experimentally in the tests were adjusted to mathematical models of isotherm and adsorption kinetics. Both EPUs showed better fit to the Langmuir isotherm and to the pseudo-second order kinetics model. The maximum adsorption capacity (qmax) calculated for EPU-CG and EPU-Mist was 0.866 and 0.303 mg g-1, respectively. The reuse tests showed good performance for five consecutive cycles for EPU-CG and for three cycles for EPU-Mist. The results obtained suggest that glycerol is a raw material with great potential to replace petroleum-derived polyols in the synthesis of polyurethanes. However, its large-scale application still requires broader studies, in addition to the need for adjustments in the polyurethane formulation to increase the adsorption capacity.

4
  • GABRIEL DOS SANTOS E SILVA
  • Synthesis, characterization, and evaluation of the cytotoxic activity of Geraniol analogues against the Glioblastoma tumor cell line U87MG

  • Leader : MAURICIO FROTA SARAIVA
  • MEMBRES DE LA BANQUE :
  • MARCOS ROBERTO DE ABREU ALVES
  • MAURICIO FROTA SARAIVA
  • ÉRICO TOSONI COSTA
  • Data: 20 juil. 2022


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  • Cancer has long been a major public health problem and affects all countries around the world. By 2020, it is estimated that there will be approximately 19.3 million new cases and 10 million deaths from the disease. Cancer encompasses a wide variety of diseases, which differ in the regions of the body that are affected. One of the rarest and most lethal cancers is Glioblastoma multiforme (GBM), included in the class of central nervous system (CNS) cancers. Generally, patients with the disease live only 12 to 18 months after diagnosis. One problem with GBM is the lack of variety in the treatment of the disease: Only four drugs are approved by the FDA (Food and drug administration) and used in the treatment of the disease. Thus, the need arises for the development of new compounds that offer an effective and at the same time less aggressive treatment to healthy cells. In this context, products of natural origin have shown promise in fighting these cancerous cells. Among these products, some classes, such as terpenes, stand out. One of the most well-reported monoterpenes by the scientific community is Geraniol. Geraniol has shown interesting characteristics in the pharmacological field, especially when it comes to its anti-cancer activity. In this context, this research reports a proposal for the synthesis, characterization, and evaluation of the cytotoxic activity against glioblastoma tumor cells (U87MG strain) of 24 geraniol analogues, 16 of which are novel derivatives. The analogs consist of eight terpenic 1(a-h) amino alcohol derivatives and their four N,N-dialkenylated by-products (2a, 2c, 2e, and 2f), three acetylated 3a, 3b, and 3f derivatives, two mesylate intermediates 4a/4b, six derivatives from different nucleophiles 5(a-c) and 6(a-c) and two diamine derivatives 7a and 7b. The terpene amino alcohols 1a-h and their N,N-dialkenylated by-products 2a, 2c, 2e, and 2f were obtained with yields of 18-85%; the acetylated derivatives 3a, 3b, and 3f, 66-95%; the mesylate intermediates 4a and 4b, 90 and 96%, respectively; the derivatives 5b, 5c, and 5c(sub), 45-78%; the compounds 6a, 6b(sub) and 6c, 43-86% and the derivative 7a obtained with a yield of 81%. All products, except intermediates 4a and 4b (characterized by FT-IR only), were characterized by FT-IR and NMR (¹H, ¹³C, and DEPT-135). The novel derivatives were characterized by ESI-HRMS. The cytotoxic activity of 16 of the 24 analogues was evaluated against U87MG lineage cells, and IC50 values were calculated in comparison to Geraniol and the standard drug used in the treatment of GBM, Temozolomide (IC50 = 1mM or 1000 µM). The activity presented by the compound N,N-dialkenylated 2a with IC50 = 2.71 µM stands out, a value about 369 times higher than Temozolomide. Other derivatives (1e, 2e, 2f, 2c, 1a, and 7a) showed IC50 values ranging from 6.47 to 56.5 µM, also showing promise. The rest of the analogs evaluated presented IC50 >100 µM, the highest concentration value evaluated. Based on the results, it was possible to perform a structure-activity relation of the synthesized analogues.

5
  • PATRICIA MACIEL ALVES
  • Synthesis, characterization and evaluation of the antimicrobial activity of new terpenoids derived from farnesol

  • Leader : MAURICIO FROTA SARAIVA
  • MEMBRES DE LA BANQUE :
  • INÁCIO LUDUVICO
  • DANIEL CRISTIAN FERREIRA SOARES
  • DANIELA SACHS
  • MARA RUBIA COSTA COURI
  • MAURICIO FROTA SARAIVA
  • Data: 21 juil. 2022


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  • Bacteria are capable of becoming resistant to some drugs. With the increasing use of antibacterials, often administered indiscriminately, an increase in the speed with which this resistance occurs and propagates has been observed. Bacterial resistance becomes a problem for global health due to clinical complications that these pathogens cause, such as infections without adequate treatment, and aggravating or prolonging diseases. In addition to making current treatments often obsolete and inefficient. In this scenario, the research and development of new antimicrobial agents become important. Within this context, the present work describes the synthesis, characterization, and antibacterial evaluation of sixteen farnesol derivatives, eight of which are farnesylaminoalcohols (2a-h), two mesylate intermediates (3a and 3b), two azide derivatives (4a and 4b), two acetylated derivatives (5a and 5b) and an amine (6). The synthesized compounds were obtained in yields ranging from 21 to 92% and were characterized by infrared spectroscopy, 1H, 13C NMR, and high-resolution mass spectrometry (ESI-HRMS). The antibacterial action of compounds 2a, 2b, 2c, 2d, 2e, 2f, 5a, and 5b was tested, the tests performed for the evaluation were the minimum inhibitory concentration (MIC) and the minimum bacteriostatic concentration (CMB), all products showed some biological activity except for compound 5b, which did not show any bioactivity within the concentrations analyzed.

6
  • CAROLINE SERIANI MODENEZE
  • DEVELOPMENT AND VALIDATION OF GREEN ANALYTICAL METHODOLOGY FOR QUANTIFICATION OF ACETYLSALICYLIC ACID IN PHARMACEUTICAL FORMULATIONS

  • Leader : SANDRO JOSE DE ANDRADE
  • MEMBRES DE LA BANQUE :
  • CASSIANA CAROLINA MONTAGNER RAIMUNDO
  • FLAVIO SOARES SILVA
  • SANDRO JOSE DE ANDRADE
  • Data: 29 août 2022


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  • Themes of sustainability and productivity are increasingly on the rise, due to the constant increase in demands and global guidelines leading to an increasingly sustainable world, always considering the gain of time. In the pharmaceutical field, these themes are also present, requiring methodologies increasingly faster, less toxic and less harmful to the environment. Given this scenario, one of the drugs with the highest production and consumption worldwide is Aspirin®, one of the oldest drugs in the pharmaceutical market. With its high-volume production and high consumption, consequently large volumes of analyses, high solvent expenditure and time required for such analyses, it is necessary and important to develop more agile methodologies and with less use of solvents. In addition to the reduction in the use of organics, the acetonitrile crisis that has been going on for some years is well known, having intensified in the last year and continued in the current year. Therefore, it is also important to work with methodologies that reduce or eliminate the use of acetonitrile as a solvent, eliminating the risk of compromising the analyzes due to the lack of this solvent. Thus, the analytical methodology was developed with a Chromolith High Resolution RP-18 100mm x 4.6mm monolithic block column, with 2 mL.min-1 of flow in a composition of 38% ethanol and 62% acidified water phosphoric acid, temperature 30°C, 10 μL injection volume in a run time of 3.5 minutes. For validation, selectivity, linearity, precision, accuracy, detection limits and quantification tests were performed. The selectivity presented results within acceptable standards, using Parteck® SI 200 as placebo, since there was no interference in the same retention time of acetylsalicylic acid. The calibration curve was linear, with a correlation coefficient greater than 0.99. Precision tests were evaluated by repeatability and reproducibility, which showed coefficients of variation of 0.36% and 0.55%, respectively. The accuracy also presented results within the acceptance criteria stipulated by RDC No. 166/2017, where recovery was evaluated at 80, 100 and 120% (400, 500 and 600 mg/tablet). Limits of detection and quantification were also evaluated, presenting values of 0.04 mg.mL-1 and 0.52 mg.mL-1. Therefore, the developed method can be successfully applied to Aspirin® tablet content analysis. In addition, the methodology developed was measured for green character, being evaluated by four metrics: green star, NEMI, AGREE, analytical echo scale and cost and time analysis. By the green star, the methodology developed meets the 5 principles of Green Chemistry against the 2 principles met by the pharmacopeial methodology. By NEMI, 3 filled quadrants compared to 2 quadrants of the original method and a score of 93 on the analytical echo scale compared to 80 points of the pharmacopeia. According to AGREE, the green methodology presented a score of 0.67 versus 0.35 of the original method, also proving the greater green character of the developed methodology. In addition, it presented a 72.5% reduction (from R$51.78 to R$14.24 considering 15 runs) in cost and 65% in time (from 10 minutes to 3.5 minutes) in relation to the pharmacopeial methodology.

7
  • RALF RICARDO RAMALHO JÚNIOR
  • Removal of Ivermectin from aqueous matrices applying peanut shell biochar

  • Leader : SANDRO JOSE DE ANDRADE
  • MEMBRES DE LA BANQUE :
  • FABIO DA SILVA LISBOA
  • NATHALIA VIEIRA BARBOSA
  • SANDRO JOSE DE ANDRADE
  • Data: 19 déc. 2022


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  • The contamination of matrices in the environment by chemical compounds is a problem inherent to human development, since the generation of chemical residues is proportional to the techno-scientific advances of mankind, resulting in contamination of the most varied types of the most varied matrices. As for aquatic matrices, the class of emerging contaminants, compounds that have a potential ecotoxicological effect at low concentrations, in the order of ng L-1 and mg L-1, have gained the focus of researchers around the world. The presence of these kind of contaminants still aggravated by their persistence, since physicochemical characteristics can contribute to the fact that these compounds don’t degrade naturally or by conventional methodologies of treatment plants, culminating in the need to develop methodologies that can remove or degrade these compounds, such as the application of physical, biological or chemical methodologies. An example of material that can be applied for removal are the biochars, a type of charcoal obtained by the pyrolysis of biomass at high temperatures, producing a carbonaceous, amorphous material with characteristic porosity. In the present work, samples of biochar were applied for the removal of ivermectin, an antiparasitic quite representative in the veterinary market, in aqueous solutions. The material was obtained by Box-Behnken planning, seeking to explore biomass pretreatments. The same was characterized by the ATR-FT-IR techniques, which returned characteristic stretches of organic groups reported in the literature; SEM-EDS, in which the morphological variation of biochar types was observed; XRD, whose response was arrangements that varied according to the pre-treatment of the biomass. The removal assays were monitored by High Performance Liquid Chromatography and showed that higher pyrolysis and acidic treatment of biomass can improve the ivermectin removal. The average removal rate of the biomass pre-treated biochar, which obtaining method was optimized, was around 85%, fact that is assimilated with the characteristics of the obtained solid.

Thèses
1
  • ALLEY MICHAEL DA SILVA PROCÓPIO
  • SYNTHESIS AND CHARACTERIZATION OF CERIUM OXIDE THIN FILMS SUPPORTED ON POROUS TITANIUM OXIDE CERAMIC FILTER FOR CATALYTIC APPLICATION IN REDOX GAS SYSTEMS

  • Leader : FRANCISCO MOURA FILHO
  • MEMBRES DE LA BANQUE :
  • ANDRÉ FERNANDO DE OLIVEIRA
  • CESAR RENATO FOSCHINI
  • FABRÍCIO VIEIRA DE ANDRADE
  • FRANCISCO MOURA FILHO
  • MARCIO MARTINS LAGE JUNIOR
  • MERCES COELHO DA SILVA
  • Data: 18 févr. 2022


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  • Compounds based on titanium dioxide (TiO2) and cerium dioxide (CeO2) have aroused the interest of the world scientific community for presenting multifunctional technological applications related to their properties and characteristics. Due to its crystalline structure, size and particle morphology, TiO2 is widely used in catalysis, photocatalysis, sensors and air and water purifiers. While CeO2, due to its high thermal stability, oxygen mobility in the crystal lattice, oxygen storage capacity (OSC) and redox potential, has been applied mainly in catalysis and systems for the purification of automotive gaseous emissions. In this work, a porous TiO2 ceramic filter (TCF) was processed by the polymeric sponge method (PSM), which was coated with CeO2 nanoparticles (CNP) in the form of thin film by the dip coating technique from a stock polymeric solution of cerium obtained by the polymeric precursor method (PPM). Through analysis of X-ray diffraction (XRD), infrared absorption spectroscopy (FTIR), ultraviolet and visible optical spectroscopy (UV-Vis), thermogravimetric (TG), differential thermal (DTA) and dilatometric (DIL), it was found that the TiO2 powder showed high crystallinity, rutile phase, tetragonal structure, belonging to the P4/mnm space group, low reflectance rate in the UV region and high in the visible region with accentuated behavior between 350-430 nm, band gap energy (Egap) of 3.22 eV for a direct allowed electronic transition and thermostable up to 1500°C. TCF in powder form were characterized by XRD, FTIR, UV-Vis and Raman spectroscopy. In addition to the rutile phase, material presented a second phase Ti3O5, orthorhombic structure, CmCm space group, more gradual reflectance behavior in the region 400-1000 nm and Egap of 3.03 eV. CNP were characterized by the same techniques besides TG and DTA. From the results of thermal analysis the material was calcined at 600ºC, 700ºC, 800ºC and 900ºC with isotherms of 120 minutes. CeO2 powder showed an increase in the degree of crystallinity with heat treatment above 600ºC, fluorite-like cubic structure, Fm3m space group, low reflectance rate in the UV region and high in the visible, with an accentuated behavior between 350-550 nm and Egap of 3.44 eV for a direct allowable electronic transition. TCF coated with CNP in thin film form were characterized by scanning electron microscopy (SEM). Micrographs indicated for TCF an interconnected structure, fragile due to the presence of hollow rods, some cracks and a rough surface, while the occurrence of the formation of the CeO2 film on the surface of the material after 10 depositions followed by calcinations at 900ºC, formation of islands, scales and layers until obtaining the film. For identification and quantification of Ti and Ce elements, the material was macerated and the powder was characterized by energy dispersive X-ray spectroscopy (EDS) and total reflection X-ray fluorescence (TXRF) with concentrations of 486.2 mg L-1 and 6.61 mg L-1, respectively. For the catalysis study, a gasoline vehicle and a gas analyzer were used for instant measurements of the conversion of CO to CO2. Catalytic ceramic filter obtained between 11% and 17% efficiency, however, low reducibility of Ce4+ in Ce3+ and oxygen vacancies in the network, low reaction temperature (41ºC) and large formation of condensed water (reaction by-product) were the main factors attributed to the low catalyst/CO interaction.

2
  • NATHALIA VIEIRA BARBOSA
  • Spectroscopic, Chromatographic and Chemometric Evaluation of the Degradation of Insulating Oils of Transformer

  • Leader : FLAVIO SOARES SILVA
  • MEMBRES DE LA BANQUE :
  • ALBERTO CAMILO ALÉCIO
  • MARIANA RAMOS DE ALMEIDA
  • FLAVIO SOARES SILVA
  • MILADY RENATA APOLINARIO DA SILVA
  • ROSSANO GIMENES
  • SANDRO JOSE DE ANDRADE
  • Data: 30 juin 2022


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  • Concern about environmental issues, the need for installations employing safety dielectric fluids, and the search for new methodologies for fluid maintenance of electric power machines using environmentally friendly technology are increasingly pronounced. Although the characteristics and variations of the physicochemical and electrical properties of insulating oils are well established, less attention has been paid to the molecular level to understand the nature of the thermal and electrical aging processes of these fluids. Thus, the objective of this work was to develop a fast, simple, and environmentally safe method to evaluate and monitor the quality of vegetable insulating oil (IVO) through multivariate control charts and Fourier Transform Infrared (FTIR) spectroscopy, in addition to evaluating the evolution of chemical compounds formed during the degradation of IVO subjected to electrical and thermal stresses, comparing with insulating mineral oil (IMO). In order to simulate the internal environment of a transformer before and after energization, samples of IVO and IMO were kept in contact with paper and copper and subjected to accelerated electrical and thermal aging processes, in which the samples were subjected to disruptive discharges (from 10 at 1000 discharges) and heating to 130 °C for up to 1080 hours, respectively. Subsequently, the composition of the fluids before and after electrical and thermal treatments was studied through the techniques of gas chromatography coupled with mass spectrometry (GC-MS) and FTIR spectroscopy and the evaluation of acidity, viscosity, and density of the samples. The results obtained showed that the developed control chart was able to identify IVO samples at oxidation levels outside the acceptable quality standards for plant insulating fluids in transformers; and those new compounds were formed, due to the degradation process of mineral and vegetable oils, under the conditions studied. Partial discharges contribute to the degradation of oils, and this effect was more pronounced in the IVO and the factor that most influences the degradation of these fluids is heating. The insulating paper acts to delay the aging of mineral and vegetable oils, while copper acts as a catalyst for fluid oxidation. The degradation of the antioxidant 2,6-di-tert-butyl-p-cresol (DBPC) from IMO is heating dependent, while the antioxidants tocopherol, stigmasterol, and sitosterol from IVO degraded even in systems that were not subjected to heating. The viscosity and acidity values of the oils increased, demonstrating the degradation under the conditions studied, and this effect was more pronounced in the IVO. In this way, the potential of FTIR spectroscopy, together with the strategy of control charts as a quick and simple tool for monitoring the quality of insulating fluids, allowing to guide the transformer maintenance plan, was demonstrated. The results contribute to studies carried out on insulating fluids and to companies involved in energy generation since with the results obtained, it will be possible to predict the aging time of oils, as well as make proposals to increase their useful life and to promote in a secures the replacement of mineral-type insulating fluid in transformers with vegetable oils, as they are more environmentally viable and have dielectric properties equivalent to IMOs.

2021
Thèses
1
  • JORGE FERNANDES ZACHARIAS NETTO
  • Catalytic study of polymeric fibers incorporated with photochromic complexes of lanthanides

  • Leader : FREDERICO BARROS DE SOUSA
  • MEMBRES DE LA BANQUE :
  • FREDERICO BARROS DE SOUSA
  • MARCOS ROBERTO DE ABREU ALVES
  • MARIA CECÍLIA RODRIGUES SIMÕES
  • Data: 18 févr. 2021


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  • In this study, the synthesis and characterization of coordination complexes of Lanthanides: La, Ce, Eu, Er, Yb and Nd are reported, using the photochromic molecule spiropyran (SPCOOH) as a ligand. The complexes obtained were characterized by absorption spectroscopy in the UV-vis region and vibrational spectroscopy in the infrared region (FTIR), the results indicate that coordination occurs via the merocyanine and carbonyl isomer phenolate of the carboxylic acid group. A kinetic stability study of the merocyanine isomer was performed for all complexes with the acetonitrile solvent. Also, a solvatochromic study of them was carried out in different organic solvents, in which the merocyanine isomer showed different absorptions in the visible region. Through the electrospinning technique, uniaxial fibers were obtained, in which EuMC or ErMC complexes were immobilized on the polycaprolactone (PCL). Both fibers were characterized by the techniques of FTIR, emission electronic spectroscopy, scanning electron microscopy (SEM), measurements of the contact angle of the water with the material surface, and thermal analysis. The results indicate that hydrophobic microfibers were obtained and that the complexes are present in both. The PCL-EuMC fibers were used as a catalyst in the hydrolysis process of the organophosphate bis-2,4 dinitrophenylphosphate, the reaction was monitored by UV-vis and as a result the material achieved a 3-fold increase in the initial speed compared with the uncatalyzed process. Coaxial fibers were obtained using the polymer polymethylmethacrylate (PMMA) on the outside and PCL-EuMC on the inside and the same fiber without the complex. The fibers were characterized by contact angle measurements, in which the fiber-containing complex had a hydrophilic character and without the complex hydrophobic character, beside that the formation of fibers was proved with SEM images. Finally, monoaxial and coaxial fibers were subjected to leaching tests, in which it was observed that in the coaxial fiber the complex did not leach into a buffer solution.

2
  • ANA LAURA MARTINS MULKSON ALVES
  • Studies of the properties of hybrid matrices PMMA and PCL with H12PMo12O40 produced by electrospinning

  • Leader : FREDERICO BARROS DE SOUSA
  • MEMBRES DE LA BANQUE :
  • FABIO DA SILVA LISBOA
  • FREDERICO BARROS DE SOUSA
  • MARIA CECÍLIA RODRIGUES SIMÕES
  • Data: 22 févr. 2021


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  • In the present work were produced hybrid matrices of polymethylmethacrylate or polycaprolactone incorporated with phosphomolybdic acid in different concentrations by electrospun technique with the objective to verify the ability of the matrices to recover Ag+ ions in aqueous solutions by means of oxirreduction processes. Infrared spectroscopy was used to identify the interaction between the organic and inorganic parts of the matrices. This interaction was confirmed by the chemical shifting of the C=O bands of PMMA, C-O of PCL and Mo-Ob-Mo of phosphomolybdic acid. The morphological and surface aspects of the matrices were studied by scanning electron microscopy and contact angle measurements. From the microscopy results, it was observed that the fibers containing phosphomolybdic acid has smaller diameters compared to the pure polymeric fibers. The results of the contact angle demonstrated the influence of phosphomolybdic acid on the interaction of the surface of the PMMA matrices with water, showing that the presence of the inorganic compound provides less hydrophobic character to the matrices. To confirm the ability of the matrices to reduce Ag+ ions, the fibers were irradiated with ultraviolet light and subsequently immersed in a solution containing 0,1 mol/L AgNO3. UV-Vis absorption electron spectroscopy used to quantify the concentration of Ag+ remaining in aqueous solution after the oxirreduction process, from efficiency of the matrices in reducing/recovering Ag+ ions was proven. The presence of silver on the surface of the matrices was verified by scanning electron microscopy images. With the results obtained it was verified the presence of aggregates on the surface of the matrices that indicates the presence of metallic Ag.

3
  • Anderson Nogueira de Carvalho
  • Copper II, Zinc II, Manganese II and Lanthanum III carboxylates as adsorbents of the semiochemical undecan-2-one

  • Leader : FABIO DA SILVA LISBOA
  • MEMBRES DE LA BANQUE :
  • ANA CRISTINA TRINDADE CURSINO
  • FABIO DA SILVA LISBOA
  • MAURICIO SILVA DOS SANTOS
  • Data: 29 avr. 2021


  • Afficher le Résumé
  • Among the insects that attack common crops in Brazil, the Lobiopa insularis intensely damage strawberry plantations. To combat insects like the one mentioned above, a trap is generally used on which some type of bait is placed to specifically attract the insect. Pheromones are chemical compounds responsible for transmitting messages between same species individuals, among them, aggregation pheromones attract both genders to a certain place, which is the reason why it is ideal for use as bait. The main component on the aggregation pheromone for the L. insularis is undecan-2-one. Bait efficiency can be improved with a slow-release matrix such as one derived from lamellar materials. One of the characteristics of the lamellar compounds is their well-defined crystalline structure, organized in layers, in which the compound is joined by intralamellar covalent bonds, while the interlayer interaction is due to electrostatic interactions. Between one layer and another, guest compounds can be inserted. In this work, carboxylates derived from lauric acid and stearic acid with copper, zinc, manganese and lanthanum were synthesized by co-precipitation methodology and characterized. Gross reaction yield ranged from 87% to 99%. The X-ray diffractograms confirmed that the synthesized compounds are lamellar and the infrared spectra indicated that the conversion of the initial acid to the carboxylate was efficient. Zinc and manganese carboxylates showed a satisfactory interaction with the pheromone undecan-2-one, that was quantified in different experiment conditions. For the manganese laurate, some of those conditions are part of a design of experiment, a tool that enables experiment optimization. The carboxylates were tested on the following conditions: 2, 8 or 15 days for interaction time; 90°C, 100°C and 110°C for interaction temperature; 1:10, 1:30 and 1:50 for adsorbent proportion. The experimental condition that displayed best results were the one made in 15 days on 90°C with 1:50 of molar equivalent, on which 1,13mg of undecane-2-one was adsorbed per gram of solid. Then the design results suggest that the experimental conditions time and proportion positively affect results, while temperature negatively affects them. Other tests can be made in the future to better define which conditions is ideal for interaction.

4
  • RAYSSA THAINÁ DE PAIVA ALVES
  • Removal of Fipronil by Advanced Oxidative Processes using sulfite activated by cobalt immobilized on silica

  • Leader : SANDRO JOSE DE ANDRADE
  • MEMBRES DE LA BANQUE :
  • DANIELE SCHERES FIRAK
  • FABIO DA SILVA LISBOA
  • FLAVIO SOARES SILVA
  • SANDRO JOSE DE ANDRADE
  • Data: 12 juil. 2021


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  • Emerging contaminants are chemical compounds found in extremely low concentrations
    (micropollutants) that are unregulated or newly regulated in different countries in different
    environmental matrices and that are threatening human and animal health. Pesticides benefit
    food production by controlling unwanted pests, but overexposure and inappropriate
    application contaminate the environment. Among them, the insecticide Fipronil and its
    derivatives have shown great toxicity for insects, mammals and humans. Conventional water
    and sewage treatment techniques do not efficiently remove these contaminants, requiring
    alternative removal methods such as Advanced Oxidative Processes. In this work, sulfite
    auto-oxidation catalyzed by cobalt complexed with ammonia deposited on silica (CoNSi) was
    used to generate sulfate radicals. The material was characterized by ATR–FTIR, suggesting
    that the silica vibrational modes did not change, and MEV–EDS, indicating a uniform
    dispersion of cobalt over the surface of the material. BET analysis provided information on a
    mesoporous material (type IV isotherm) with regular morphology (H1 hysteresis). The DSC
    analysis showed that CoNSi is thermally stable under the conditions studied. Quantitative
    analyzes of Fipronil were performed by HPLC-DAD, where the applied method was linear.
    The Box–Behnken experimental design was used to define the best condition for removing
    the analyte in water, where in 60 min, 76% removal of 1.8 ppm of Fipronil was obtained by
    adding 0.30 g of the material and 0.30 g of the sulfite in a solution with stirring, aeration, pH
    8.0, room temperature and protected from visible radiation. This result demonstrates that the
    technique is very promising to be used as a complementary treatment in water and effluent
    treatment plants. However, analysis of cobalt leaching into the solution by FAAS showed a
    small amount of the metal (0.44 ppm) informing that the synthesis of the material must be
    improved.

5
  • THIAGO GOMES MENZONATTO
  • Theoretical analysis of the solvent influence in structural, thermodynamical and electronic properties of substituted merocyanines and their isomers

  • Leader : JULIANA FEDOCE LOPES
  • MEMBRES DE LA BANQUE :
  • LUCAS FAGUNDES ESTEVES
  • FREDERICO BARROS DE SOUSA
  • JULIANA FEDOCE LOPES
  • Data: 12 juil. 2021


  • Afficher le Résumé
  • Spiropyrans constitutes one of the most well-known and well-studied class of chromophores nowadays. This occurs since this class of compound undergoes a reversible isomerization which alters several of its properties, colors mainly, when submitted to a series of different stimuli, such as light, temperature, solvent, among others. Such versatility allowed spiropyrans to be utilized in several fields: optical storage, molecular switches, sensors.
    Herein, Density Functional Theory (DFT) level calculations of the thermal isomerization reaction SP→MC, where SP is the substituted 3-(3',3'-dimethyl-6-nitrospiro[chromene-2,2'-indole]-1'-yl) propanoic acid spyropiran in the closed-form and MC (merocyanine) is the corresponding open form are presented. Calculations were carried out using the CAM-B3LYP functional with the 6-31G(d,p) basis set. For the most stable conformers of the MC, an Atoms in Molecules (AIM) analysis was carried out to evaluate non-covalent intramolecular interactions. The influence of the carboxyl acid substituent group was evaluated through structural scan calculations. The solvents were treated implicitly using the Intrinsic Equation Formalism Polarizable Continuum Model (IEFPCM) method and by applying an electrostatic field upon the structure.
    The adopted methodology unveiled structural and thermodynamic parameters of the SP form and the several MC conformers both in the gas phase and in solution with the usage of a series of different solvents, their influence was computed within the analysis of properties such as bond length alternance (BLA), Gibbs Free Energy and dipole moment as a function of the dielectric constant of the solvents. A reactional mechanism proposal was made for the thermal pathway in the SP → MC ring-opening conversion. The NCI method allowed the elucidation of the relative stability of the different MC conformers in terms of intramolecular interactions and the results were in great agreement with experimental and theoretical data.
    Some of the obtained results provided a greater understanding of the conversion between the SP and MC isomers and extended the discussions upon the behavior of these structures in solution and the impact of the solvent effect in several of their properties. The applied electrostatic field upon the MC molecule unveiled a solvatochromic reversal in the UV-Vis spectrum and others electronic effects and structural changes.

6
  • DANIEL BRAGANÇA VIANA
  • Hybrid protein-polymer nanoparticles loaded with cisplatin: Synthesis and Characterization

  • Leader : MARLI LUIZA TEBALDI
  • MEMBRES DE LA BANQUE :
  • FERNANDA POLETTO
  • DANIEL CRISTIAN FERREIRA SOARES
  • FREDERICO BARROS DE SOUSA
  • MARLI LUIZA TEBALDI
  • Data: 24 août 2021


  • Afficher le Résumé
  • Nowadays, many research related tovhybrid materials and the advances in Reversible-Deactivation Radical Polymerization (RDRP) techniques have enabled the development of responsive materials. These compounds respond to specific stimuli and have been integrating many research projects involving different drug delivery systems. In particular, hybrid conjugates based on protein−polymer have been integrating different formulations already approved by the Food and Drug Administration. In general, protein-polymer conjugates can increase the drug plasmatic half-life, altering the drug biodistribution profile and opening the possibility to reduce the dose administrated, which is a relevant advantage for patients. In this work, poly (N-vinylcaprolactam) (PNVCL) and poly (2-dimethylamino-ethyl methacrylate) (PDMAEMA) polymers were grafted to the surface of a protein model, the bovine serum albumin (BSA), by grafting-from approach, using the Atom Transfer Radical Polymerization (ATRP) technique. Firstly, a macroinitiator (BSA-MI) was successfully obtained and characterized by Sodium dodecyl sulfate polyacrylamide gel electrophoresis and Matrix-Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry by modifying lysine groups present in the BSA. Then, the BSA-PNVCL-co-PDMAEMA hybrid was synthesized using BSA-MI as an initiator. The conjugate production was evaluated, revealing significant changes in the nanoparticles’ molecular mass and zeta potential . Additionally, it is demonstrated that altering the monomers' ratio can further adjust the lower critical solution temperature (LCST) of the protein-polymer conjugates. The results indicate the obtaining of a BSA-PNVCL-co-PDMAEMA able to encapsulate approximately 1.9 mg of cisplatin for each 1 mg of the hybrid, making this conjugate a very promising hybrid material with desirable properties for a possible application in smart drug delivery systems.

7
  • BIANCA BONIFÁCIO MONTEIRO VIEIRA
  • Study and characterization of inclusion compounds involving the drug Biperiden Hydrochloride and cyclodextrins.

  • Leader : FREDERICO BARROS DE SOUSA
  • MEMBRES DE LA BANQUE :
  • DANIEL CRISTIAN FERREIRA SOARES
  • FREDERICO BARROS DE SOUSA
  • JOEL JOSÉ PASSOS
  • Data: 17 déc. 2021


  • Afficher le Résumé
  • Biperiden Hydrochloride (BPR) is a drug indicated as an adjuvant in the treatment of Parkinson’s disease, assisting in managing symptoms such as tremors and muscle stiffness. However, it has a large amount of side effects, in addition to low water solubility and first-pass effect, limiting its bioavailability. One way to overcome these limitations is the use of an association of the drug with cyclodextrins (CDs) in supramolecular host-guest systems. Thus, in the present work, supramolecular systems linked by non-covalent interactions, formed by the association of guest molecules, β-cyclodextrin (βCD) and Hydroxypropyl-β-Cyclodextrin (HPβCD), with the drug BPR, were investigated. Solid state inclusion compounds for both systems (βCD:BPR e HPβCD:BPR) were prepared by lyophilization and characterized previously by infrared absorption spectroscopy (FTIR-ATR). In solution, isothermal titration calorimetry (ITC) was used to obtain the stoichiometric coefficients (n), the association constants (Ka) and the thermodynamic parameters involved in the process. Still in solution the phase solubility diagram was utilized to study the inclusion process on the solubility of the BPR. According to the ITC results, the formation process of inclusion compounds, both the HPβCD:BPR and the βCD:BPR system, was spontaneous and exothermic, however, the latter obtained a higher Ka, indicating stronger interactions between species. Furthermore, the ITC results indicated values of n corresponding to a 1:1 stoichiometry for the βCD:BPR system while for the HPβCD:BPR system fractional values of n were observed, suggesting the formation of multiple equilibria in solution. The 2D-ROESY correlation maps confirmed the inclusion of BPR for both systems, and also demonstrated the existence of stronger interactions between BPR and βCD. Additionally, solubility studies indicated that the solubility of inclusion compounds is superior in comparison with the free BPR drug, taking by example the AL-type solubility profile obtained for the two systems under study.

Thèses
1
  • Guilherme Augusto Batista Soares
  • Computational analysis of phosphate ester hydrolysis: An electronic and structural study of intermediate species and organolanthanides matrix as potential heterogeneous catalyst.

  • Leader : JULIANA FEDOCE LOPES
  • MEMBRES DE LA BANQUE :
  • DALVA ESTER DA COSTA FERREIRA
  • TIAGO ANTÔNIO DA SILVA BRANDÃO
  • DANIEL HENRIQUES SOARES LEAL
  • FABIO DA SILVA LISBOA
  • JULIANA FEDOCE LOPES
  • Data: 18 mars 2021


  • Afficher le Résumé
  • Phosphate esters are an important group of chemical compounds. They are naturally found and intrinsically related to life since are involved in genetic and energy storage. However, there is a concern about the use of anthropogenic phosphate esters emerges due to their persistence, toxicity especially to the nervous system and exponential rise of its uses. In this work phosphate esters with linear carbonic chain (methyl, ethyl, and propyl), were simulated in neutral and anionic forms using MP2, B3LYP, and M06-2X as methodology. Results point out that MP2 is the best methodology, since it was energetically more accurate compared to DFT. For conformational results, all methodologies give similar results. After the oxygen deprotonation, a structural and electronic rearrangement took place, pushing deprotonated oxygen away from each other, compensated by the approximation of oxygen esters (and consequently carbonic chains). Results of Monomethyl phosphate (MMP) indicate that the anomeric effect (hyperconjugation) has a great influence on species stability. Conformational analysis of neutral MMP allowed identifying maximum and minimum energy points, including second-order saddles points. Many pathways for reactions are possible with these configurations. The molecular description was performed characterizing atomic interaction and distance. This analysis involved many tools, such as topological or orbitals (Molecular or Natural) composition. No significant participation of P-d electrons was founded. Since phosphate ester hydrolysis occurs in water medium and this reaction could be catalyzed by metals, especially lanthanides. A polymeric base of polymethacrylate (maximum of 10 monomers) was simulated in neutral and anionic forms, with and without solvation, and linearly of consecutive constructed. These simulations indicated a consistent behavior regarding the chain size. Furthermore, high-charged chains tend to elongate more than lower ones. Concerning the lanthanide coordination to reference monomers, the use of semi-empirical software generates results compatible with the literature. The coordination seems to tend to an ideal number (9), where distances metal-ligand stabilizes. When the monomer is not able to supply the metal with ligands sites to reach the previously number, water molecules complete the coordination sphere.

2
  • FABIANA COSTA GUEDES
  • ProtCool: a Protocol Generator for Anchoring and Molecular Dynamics Simulations in Protein-Binder Complexes.

  • Leader : CARLOS HENRIQUE DA SILVEIRA
  • MEMBRES DE LA BANQUE :
  • LUCIANNA HELENE SILVA DOS SANTOS
  • ALETEIA PATRÍCIA FAVACHO DE ARAÚJO
  • CARLOS HENRIQUE DA SILVEIRA
  • DANIEL CRISTIAN FERREIRA SOARES
  • JULIANA FEDOCE LOPES
  • RAQUEL CARDOSO DE MELO MINARDI
  • Data: 11 juin 2021


  • Afficher le Résumé
  • In recent years, a significant evolution in the simulations in molecular dynamics (DM) has been noticed either in the precision of results compared to the real world or in the capacity to represent complex biological systems with thousands or millions of atoms. Despite all the advances in theories, algorithms, and computational infrastructure that give support and confidence to the current simulations, a serious practical issue persists: the reproducibility of experiments. Other concerning aspects are the lack of more standardized protocols, the lack of comprehensive documentation of what has been accomplished. In order to try to contribute to the solution to these challenges, this thesis aimed to develop, configure, structure and verify a tool that seeks the automation of protocols and workflows (called ProtCool) that enables the control, analysis and reproduction of experiments in molecular dynamics of proteins and molecular docking with multiple ligands. To achieve this main objective, it was necessary to go through the following specific objectives: Model and implement the workflow for preparing the molecular dynamics simulation; Model and implement the workflow for performing multi-molecule dockings; Perform workflow management script implementation; Implement the data source tool, allowing the researcher to have all the files and data generated during the simulation preparation; Automate the preparation of molecular dynamics; Run only part of the workflow; Perform the reproducibility of experiments and research methodologies; Integrate all this into a tool called ProtCool; Check the tool with case studies involving docking of ligands with human acetylcholinesterase and major protease (Mpro) from SARS-Cov-2. Human acetylcholinesterase, implicated in diseases such as Alzheimer's disease, and the main protease (Mpro) of SARS-CoV-2, the virus responsible for the current pandemic of the disease COVID-19, were used as targets in case studies for validating and demonstrating the use of the tool. For acetylcholinesterase, the same 4 ligands (galantamine, lycoramine, sanguinine and a hybrid ligand) and target (4EY6) studied by Rocha (2017) were used as a way to validate the implementation of ProtCool, producing equivalent results. As a way of indicating the potential use of ProtCool in the virtual screening of ligands on a large scale, in a relevant and current problem, the molecular docking of multiple ligands (19637 from ZINC, 8752 form Drugbank, and 8520 from SistematX, totaling 36909 ligands) on multiple targets (6 different conformations sampled by Metadynamics) involving the Mpro of SARS-CoV-2 was carried out, resulting in the generation 4427839 poses (using Vina and Smina docking systems). It was possible to show a new in silico strategy to indicate new ligands as candidates for antivirals against COVID19.

2020
Thèses
1
  • BYANCA SILVA FERREIRA
  • Synthesis of hybrid pyrazole-tetrazole, pyrazole-thiazoline and pyrazole-carboxamide systems with potential biological activity

  • Leader : MAURICIO SILVA DOS SANTOS
  • MEMBRES DE LA BANQUE :
  • AMANDA DANUELLO PIVATTO
  • EDER DO COUTO TAVARES
  • MAURICIO SILVA DOS SANTOS
  • Data: 6 févr. 2020


  • Afficher le Résumé
  • Chagas’ disease (CD) is a Neglected Tropical Disease that is endemic in Latin America and affects more than 6 million people worldwide, causing about 14 thousand deaths each year. This disease is caused by the protozoa Trypanosoma cruzi and only two drugs are available to treat CD: benznidazole and nifurtimox, which both have several side effects and inefficiency in the chronic phase, showing the relevance of developing safer and more potent drugs. Besides CD, diseases caused by bacteria have been highlighted since there are responsible for many deaths around the world. Infections by resistant bacteria cause almost 700 thousand deaths/year and will reach 10 million deaths/year by 2050. Therefore, the development of new substances against resistant strains is extremely important. In this context, the first objective of this work was to synthesize twelve 5-(1-aryl-1H-pyrazole-4-yl)-1H-tetrazoles 1(a-l), planned due to biological importance of pyrazole and tetrazole rings to evaluate them against Staphylococcus aureus and Pseudomonas aeruginosa. Since good results of protozoal activity have been obtained by our research group, including trypanocidal activity, the second objective was to synthesize new twelve 2-(1-aryl-1H-pyrazole-4-yl)-4,5-dihydrothiazoles 2(a-l) and twelve 5-amino-1-aryl-1H-pyrazole-4-carboxamides 3(a-l), being 3(h-k) published for the first time. All of compounds 2(a-l) and 3(a-l) are being evaluated for their trypanocidal activity. The key-intermediates 5-amino-1-aryl-1H-pyrazole-4-carbonitriles 4(a-l) and 1-aryl-1H-pyrazole-4-carbonitriles 5(a-l) were obtained in 69-98% and 80-98% yields, respectively. The final products 1(a-l) were synthesized in 10-78% yields and preliminary results, for 1b, 1c, 1e, 1g and 1j, showed poor activity against S. aureus. The desired products 2(a-l) were isolated in 71-91% while 3(a-l) were obtained in 26-84% yields. The compounds 3(a-l) were evaluate against trypomastigotes of T. cruzi and the IC50 results were more than 100 μM. Regarding the cytotoxicity, were found CC50 > 500 μM for all products. The corresponding hydrochlorides of 2(a-l) were obtained due to low solubility during the biologic tests and the trypanocidal activity has been investigated.

2
  • RAFAELA CORRÊA SILVA
  • Synthesis of pyrazole-tetrazole and pyrazole-carboxylic systems for evaluation of antibacterial activity

  • Leader : MAURICIO SILVA DOS SANTOS
  • MEMBRES DE LA BANQUE :
  • MARISI GOMES SOARES
  • MAURICIO FROTA SARAIVA
  • MAURICIO SILVA DOS SANTOS
  • Data: 17 févr. 2020


  • Afficher le Résumé
  • Bacteria are prokaryotic unicellular organisms living freely or in colonies being classified in two main groups: Gram-positive and Gram-negative. The chemotherapy against diseases caused by bacteria consists on different compounds classes, such as sulfonamides, penicillins and cephalosporines. Several drugs have been developed in attempt to solve the bacterial resistance problem, including heterocyclic derivatives. There are many reports showing drugs containing at least one heterocyclic nucleus, specially compounds containing nitrogen atoms, responsible for 60% of heterocycles with biological activity. Among several nitrogenated heterocycles, pyrazole and tetrazole nuclei should be highlighted since they present promising antibacterial activities. Therefore, in this work was planned to synthesize thirty derivatives: ten 5-amino-(1-aryl-1H-pyrazol-4-yl)-1H-tetrazoles 1(a-j), ten 5-amino-1-aryl-1H-pyrazole-4-carboxylics acids 2(a-j), and ten 1-aryl-1H-pyrazole-4-carboxylics acids 3(a-j). Until now, the derivative 1d of 1(a-j) series was obtained in 83% yield. The compounds 2(a-j) were obtained in two steps, obtained in yields from 29 to 97% and 2e and 2f described for the first time. The acids 3(a-j) were obtained in three steps, were synthesized with yields 75-99%. The compounds 3b and 3f are new. Until now, 2(b-e,g-j) were evaluated against Gram-positive Staphylococcus aureus bacterium for determination of the minimum inhibitory concentration (MIC). None of them showed MIC above 512 microg/mL. 2e e 2g were investigated with regard to bactericidal effect. The minimum bactericidal concentration (MBC) values were > 512 microg/mL. All derivatives will be evaluated against other bacteria species.

3
  • RYAN THAIRYK SILVA DE JESUS
  • Optimization of GC-MS/SIM method for the determination of PAHs

  • Leader : FLAVIO SOARES SILVA
  • MEMBRES DE LA BANQUE :
  • FLAVIO SOARES SILVA
  • Melina Espanhol Soares
  • SANDRO JOSE DE ANDRADE
  • Data: 20 févr. 2020


  • Afficher le Résumé
  • Polycyclic aromatic hydrocarbons (PAHs) comprise a large class of organic compounds, characterized by containing two or more fused aromatic rings in their structure. The study of this class of compounds is necessary because they are found in different environments and associated with the degradation of human health, attributed to a toxic potential, which can lead to mutagenesis and/or carcinogenesis of different cells. The present project was dedicated to the optimization and validation of a chromatographic method for the determination of 16 PAHs in atmospheric particulate matter.

4
  • FELIPE FARINATE LOPES DE SOUZA
  • Sinalized silica nanoparticles containing doxorubicin: a potential system for cancer treatment

  • Leader : DANIEL CRISTIAN FERREIRA SOARES
  • MEMBRES DE LA BANQUE :
  • CARLOS HENRIQUE DA SILVEIRA
  • DANIEL CRISTIAN FERREIRA SOARES
  • MARCOS ROBERTO DE ABREU ALVES
  • RENATA SALGADO FERNANDES
  • Data: 17 déc. 2020


  • Afficher le Résumé
  • The present work aimed to synthesize and functionalize silica Santa Barbara-16 (SBA-16) nanoparticles to study the incorporation rate and release kinetics of doxorubicin (DOXO), a potent antitumoral agent in order to reduce side effects and enhance efficiency for cancer treatment. The matrix of silica SBA-16 was synthesized through the sol-gel method, using tetraethyl orthosilicate as a precursor with the surfactant Pluronic® F-127. The product was functionalized with 3-aminopropyl triethoxysilane and characterized physiochemically and morphologically. The results revealed that the methodology applied yielded silica nanoparticles with a mesoporous matrix (SBA-16), with an average size of 296 ± 29 nm and zeta potential of -32.23 ± -2.5 mV and SBA-16 matrices functionalized with alkoxysilane groups (SBA-16- APTES) with the average size of 312 ± 31 nm and zeta potential of -8.3 ± -1.3 mV. HPLC-DAD was used to evaluate the doxorubicin load rate and release kinetics profile in the obtained matrices. The developed method presented parameters preconized by RDC n° 166 standard from the Brazilian Health Regulatory Agency (ANVISA), with a linear range from 1 to 250 μg/mL. The mean adsorption rate for SBA-16 was 92.77 % and 66.52 % for SBA-16-APTES. The release kinetics was studied using simulated body fluid (SBF) for both matrices at pH 4.5 and 7.4. Both matrices showed a controlled release profile for pH 4.5, reaching 26.50 %, after 696 hours for the SBA-16 matrices and 70.0 % after 696 hours for SBA-16-APTES. On the other hand, in physiological pH, the release rates were significantly reduced, reaching only 10.00 %, even after 696 hours for the SBA-16 matrix and 32.76 % after 72 hours for SBA-16-APTES. From all obtained results, SBA-16-APTES showed better and promising results for controlled release applications and may be considered a potential cancer treatment system.

5
  • BIANCA RODRIGUES SILVA BORGES
  • THERMOS-SENSITIVE HYBRID SILICA NANOPARTICLES CONTAINING DOXORUBICINE AS A POTENTIAL SYSTEM APPLIED TO CANCER TREATMENT

  • Leader : DANIEL CRISTIAN FERREIRA SOARES
  • MEMBRES DE LA BANQUE :
  • DANIEL CRISTIAN FERREIRA SOARES
  • EDUARDO HENRIQUE MARTINS NUNES
  • ERNESTO SOARES DE FREITAS NETO
  • MARLI LUIZA TEBALDI
  • Data: 18 déc. 2020


  • Afficher le Résumé
  • Cancer affects several people in the world and it is one of the diseases responsible for the main causes
    of death worldwide. Unfortunately, the therapies used to eliminate cancer cells also act against healthy
    cells, due to their low selectivity action. Inside this reality, the searches for more effective treatments
    that would cause less adverse effects have been encouraged, specially treatments involving the use of
    nanostructured carrier systems, considering their promising results. In this work, SBA-16 silica
    nanoparticles were synthesized and functionalized with 3-aminopropyltriethoxysilane and tests were
    performed on both matrices. The Fourier transform infrared spectroscopy (FTIR) technique made it
    possible to visualize characteristic bands of the synthesized materials such as: silane groups (Si-O-Si)
    and silanol groups (Si-OH) for SBA-16, ethyl group, silane groups and less intense hydroxyl band in
    the functionalized SBA-16 spectrum (APTES-SBA-16). The small angle X-ray scattering (SAXS) test
    revealed standard peaks from the samples, indicating the mesoporous and body cubic centered
    structure, of the Im3m spatial group. The study of adsorption and gas desorption, using Barrett-JoynerHalenda (BJH) method, showed a high surface area for SBA-16 (975 m²/g) and a significant reduction
    in the area of the funcionalized material (472 m²/g). The micrographs obtained by transmission electron
    microscopy (TEM) technique for SBA-16 and APTES-SBA-16 samples revealed a well-defined pore
    ordering in both matrices. The test also showed the modification of the material after functionalization,
    due to the use of electron energy loss spectroscopy (EELS), in which it was possible to observe the
    presence of nitrogen atoms in the functionalized material. Thermogravimetric analysis also helped to
    prove the functionalization of SBA-16 samples by the difference of mass between the samples
    obtained. The data showed average sizes (300 nm) on both matrices, size considered ideal for
    biomedical applications. After specified analysis had been made in the materials, the antitumor drug
    Doxorubicin was incorporated in the matrices SBA-16 and APTES-SBA-16. The rate of drug
    incorporation in both matrices was evaluated using high performance liquid chromatography (HPLC)
    7
    technique with a DAD (Diode Array Detector). To quantify the drug, a calibration curve was
    constructed with a coefficient of determination (r2
    ) equal to 0.993. The data obtained reveal there was
    an incorporation rate of 87 % for SBA-16 matrix and 29 % for APTES-SBA-16 samples. Subsequently,
    the functionalized silica was grafted with the thermosensitive copolymer [poli(Vinilcaprolactam) -co-
    (N-isopropylacrylamide)] (PVCL-co-PNIPAAm), obtaining a hybrid material that may control the
    drug release by means of heat. Finally, this hybrid material was characterized physically and
    chemically. The FTIR results revealed characteristic groups of polymers used. The dynamic light
    scattering (DLS) analysis showed that the sample has an average size of 447.5 nm  34 nm and a
    polydispersity index equal to 0.223. Such results indicate that it is a monodisperse material with an
    ideal size to be used as a biocarrier, due to the enhanced permeation and retention (EPR).

2019
Thèses
1
  • FLÁVIO BASTOS MIGUEZ
  • Obtenção e estudo das propriedades foto- e solvatocrômicas de complexos de metais de transição com espiropiranos.

  • Leader : FREDERICO BARROS DE SOUSA
  • MEMBRES DE LA BANQUE :
  • ELGTE ELMIN BORGES DE PAULA
  • FABIO DA SILVA LISBOA
  • FREDERICO BARROS DE SOUSA
  • Data: 26 juil. 2019


  • Afficher le Résumé
  • Herein, the synthesis and the electronic and structural characterization of the SPCOOH
    spiropyran are documented, being investigated as a photochromic ligand in coordinating
    complexes with some transition metals of the first series as Cr, Mn, Co, Ni, Cu, Zn. Moreover,
    the coordination complexes of the metals mentioned above were obtained using ultraviolet
    radiation-induced precipitation as a differential. The characterization of the synthesized
    complexes involved the techniques of electronic absorption spectroscopy in the UV-vis region,
    vibrational spectroscopy, nuclear magnetic resonance spectroscopy, mass spectrometry and
    emission spectroscopy depending of the complex. The results indicate that the binding sites of
    the SPCOOH ligand are present on the carbonyl of the carboxylic acid group and the phenolate,
    also showing a stoichiometry of 2:1 SPCOOH:metal for the Cobalt complex. Additionally, the
    solvatochromic properties of the complexes in various organic solvents were studied, showing
    the absorptions in the visible region of each complex varied up to 39 nm for the same solvent.
    These results were fundamental for the fluorescence property of the Zinc complex to be
    identified. A stability study of the Cobalt complex in solution in different organic solvents was
    carried out, in which the best stability in methanol was evidenced, with the possibility of
    detection of the same for up to 15 hours. Another property of the Co2+ complex studied was its
    ability to regenerate in alternating cycles of UV and visible radiation, demonstrating the best
    efficiency in isopropanol, with a loss of only 20 % of its initial absorbance when compared to
    tetrahydrofuran in which after 50 cycles the complex cannot be regenerated

2
  • Marina Guedes Fonseca de Souza
  • Thermosensitive Liposomes Containing Iron Oxide Nanoparticles as a Potential Anticancer System

  • Leader : DANIEL CRISTIAN FERREIRA SOARES
  • MEMBRES DE LA BANQUE :
  • ANDRE LUIS BRANCO DE BARROS
  • DANIEL CRISTIAN FERREIRA SOARES
  • ERNESTO SOARES DE FREITAS NETO
  • TIAGO HILÁRIO FERREIRA
  • Data: 29 nov. 2019


  • Afficher le Résumé
  • The cancer is nowadays one of the main causes of morbidity and mortality in the world. Despite the undeniable advances, the pharmacotherapy available today still presents many limitations. The current cancer treatments bring with them many collateral effects to the patient due to its unselectively nature. The main objective of this work was to develop formulations made of encapsulated iron oxide nanoparticles inside thermosensitive liposomes as an alternative for the selective treatment of cancer. The iron oxide nanoparticles were synthesized by coprecipitation, functionalized by citric acid and characterized by X-ray diffraction, Fourier-transform infrared spectroscopy (FTIR), thermogravimetry (TG/DTA), dynamic light scattering (DLS), and transmission electronic microscopy (TEM). The nanoparticles were then encapsulated in the thermosensitive liposomes obtained by the reverse phase evaporation method. The particles obtained were characterized by UV-Vis spectrophotometry (to check encapsulation), DLS, TEM and microcalorimetry. The liposomal samples obtained showed adequate characteristics for the in vitro tests. They were tested against 4T1, A549 and HEK-293 cells and it was observed selective character, where there was a reduction in cell viability in both tumor cells studied, with more than 70% cell death. Unlike the observed in the HEK-293 cells, where was obtained cell viability greater than 80%. These findings open perspective for the use of these liposomes in studies for the treatment of tumors in experimental models.

Thèses
1
  • MARIA CECÍLIA RODRIGUES SIMÕES
  • SYNTHESIS AND CHARACTERIZATION OF POLYACYLHYDRAZONES AND OBTAINING FIBERS ELETROFIATION POLYMERS FOR RELEASE CONTROLLED DRUG
  • Leader : FREDERICO BARROS DE SOUSA
  • MEMBRES DE LA BANQUE :
  • AMANDA NATALINA DE FARIA
  • DANIEL CRISTIAN FERREIRA SOARES
  • FREDERICO BARROS DE SOUSA
  • HERNANE DA SILVA BARUD
  • ROSSANO GIMENES
  • Data: 28 févr. 2019


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  • Molecules with nitrogen derivatives are widely reported in the literature due to the great
    biological potential predicted for these groups. Among the most cited molecular patterns are
    hydrazides, acylhydrazones and recently polymers of acylhydrazones called
    “polyacylhydrazones”, are cited too. Polycylhydrazones were synthesized and characterized
    from the condensation of dialdehydes and dihydrazides. This polyacylhydrazones could be
    associated with commercial polymers such as polymethylmethacrylate for the formation of
    polymeric fibers obtained by electrospinning technique. The morphologycal, thermal and
    mechanical properties of these fibers were studied, which provided important information about
    these systems as the protection of degradation provided by acylhydrazone to the
    polymethylmethacrylate fibers. Due to the low solubility of the proposed hydrazone polymers,
    only their dihydrazide intermediates have been studied for cytotoxicity and in vitro evaluation
    of antiinflammatory activity, providing promising results. In the other hand, polycaprolactone
    polymer fibers are very useful in various biological applications due their high mechanical
    properties, but because of their long degradation the use in controlled release systems is
    restricted. In contrast, polymethylmethacrylate fibers do not offer higher mechanical strength
    and are more used to form blends with other polymers or through the addition of composites.
    Thus, in this work the formation of blends between polymethylmethacrylate and
    polycaprolactone to generate monoaxial fibers or coaxial ones made by the same polymers was
    carried out using electrospinning process. These fibers were investigated through
    morphological, superficial and thermal analysis to propose the use of these systems in the
    release of hydrophobic drugs, for example Nimesulide. The above results as well as the
    cytotoxicity analysis and the in vitro release assay for the drug Nimesulide demonstrated that
    the proposed fibers exhibit potential for this action.

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