Dissertations / Theses on the topic 'Bases de Schiff'

Dissertação (mestrado) - Universidade Federal de Santa Catarina. Centro de Ciencias Fisicas e Matematicas
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A reação de hidrólise das bases de Schiff N-benzildenoanilina, 4-metóxi-N-benzilidenoanilina, 2-metóxi-N-benzilidenoanilina e 2-(2-etoxi)etóxi-N-benzilidenoanilina foi estudada a 25oC, na presença de sais de metais alcalinos e alcalino-terrosos em diversas concentrações. A força iônica foi mantida constante no meio etanólico aquoso (88%) através da adição de tetrafluoroborato de tetrabutilamônio. Os resultados foram explicados em termos de três fatores: a) o efeito inibitório da complexação do íon metálico com o átomo ligado ao anel; b) o efeito provocado pela associação do cátion com o átomo de nitrogênio imínico; c) o efeito templato, envolvendo a associação do íon metálico com os átomos de oxigênio da cadeia lateral.

This study investigates the coordination modes of multidentate N,O-donor ligands toward the [ReVO]3+ and fac-[ReI(CO)3]+ cores. The reactions of trans-[ReOX3(PPh3)2] (X = Cl, Br) with 4-aminoantipyrine (H2pap) were studied, and the complexes cis-[ReX2(pap)(H2pap)(PPh3)](ReO4) were isolated. The X-ray crystal structures show that both complexes display a distorted octahedral geometry around the central rhenium atom, and are mirror images of each other. The ligand pap is coordinated monodentately through the doubly deprotonated amino nitrogen as an imide, and H2pap acts as a neutral bidentate chelate, with coordination through the neutral amino nitrogen and the ketonic oxygen. The attempted synthesis of the potentially hexadentate Schiff base ligand 1,2-bis(2-{(Z)- [(2-hydroxyphenyl)imido]methyl}phenoxy)benzene from the condensation reaction of 2- (2-((2-aminophenoxy)methyl)benzyloxy)benzenamine and salicylaldehyde produced the zwitterion derivative (H2ono) of 2-{(Z)-[2-(hydroxyphenyl)imino]methyl}phenol. The tridentate Schiff bases (Z)-2-(2-aminobenzylideneamino)phenol (H3onn) and (Z)-2-(2- (methylthio)benzylideneamino)phenol (Hons) were prepared in a similar manner. The reaction of H2ono with trans-[ReOBr3(PPh3)2] surprisingly led to the isolation of the rhenium(III) complex [ReBr(PPh3)2(ono)], in which ono acts as a dianionic tridentate ligand. The reaction of H3onn with trans-[ReOBr3(PPh3)2] produced the imidorhenium(V) complex salt [ReBr(PPh3)2(onn)]Br, in which onn is coordinated as a trianionic tridentate imidoiminophenolate. The reaction of Hons with [Re(CO)5Br] led to the further decomposition of the Hons ligand, and the rhenium(I) product fac- [Re(CO)3(ons)(Hno)] (Hno = 2-aminophenol) was isolated, with ons coordinated as a monoanionic bidentate chelate (with a free SCH3 group), and Hno present as a neutral monodentate ligand with coordination through the amino nitrogen atom. Abstract Nelson Mandela Metropolitan University vi The reactions of the potentially hexadentate ligand N,N’-{ethane-1,2- diylbis[nitrilomethylidenebenzene-1,2-diyl]}bis(2-aminobenzeneimine) (H2ted) with rhenium(V) starting materials resulted in the decomposition of the H2ted molecule to give different coordinated multidentate ligands coordinated to the rhenium(V) centers. In the reaction of H2ted with trans-[ReOBr3(PPh3)2] in ethanol, the highly unusual ‘3+3’ complex cation [Re(tnn)(Htnn)]Br2 was isolated, in which tnn is coordinated as a tridentate imido-imino-amine, and Htnn is present as a tridentate monoanionic amidoimino- amine chelate (H2tnn = N-(2-aminophenylmethylidene)ethane-1,2-diamine). With trans-[ReO2(py)4]Cl as starting material, the neutral complex [ReO(dne)] was found, in which the tetradentate chelate dne acts as a triamido-imine. The reaction of cis- [ReO2I(PPh3)2] with H2ted led to the formation of the monocationic complex salt [ReO(ane)]PF6, with ane acting as a tetradentate dianionic diamidodiimine (H2ane = N,N’-bis[(2-aminophenyl)methylidene] ethane-1,2-diamine). The seven-coordinate rhenium(III) complex cation [Re(dhp)(PPh3)2]+ (H2dhp = 2,6-bis(2- hydroxyphenyliminomethyl)pyridine) was isolated as the iodide salt from the reaction of cis-[ReO2I(PPh3)2] with H2dhp in ethanol and as the perrhenate salt from the reaction of trans-[ReOBr3(PPh3)2] with H2dhp in methanol. Both products result from a disproportionation reaction with perrhenate also being produced in the process. The complex fac-[Re(CO)3(H2dhp)Br] was prepared from [Re(CO)5Br] and H2dhp in toluene, where the H2dhp ligand acts as a neutral bidentate NN-donor chelate. The metal is coordinated to three carbonyl donors in a facial orientation, to a neutral imino nitrogen, a pyridinic nitrogen and a bromide.

Il y a de nos jours un besoin urgent de découvrir de nouveaux médicaments pour relever le défi de la multirésistance dans le traitement des infections bactériennes et le cancer. Dans cette perspective, des bases de Schiff dérivées de dithiocarbazates et leurs complexes métalliques correspondants sont des candidats intéressants puisqu'ils peuvent être facilement synthétisés et permettent une grande diversité de coordination. Dans cette étude, des complexes tetradentes et bidente ont été préparés. Les ligands et complexes synthétisés ont été entièrement caractérisés par différentes méthodes spectroscopiques et physico-chimiques dans le solide et en solution. L'activité antibactérienne de ces complexes a ensuite été étudiée et a permis de sélectionner un complexe " leader " (plus efficace, stable et fonctionnalisable). Ce complexe a alors été modifié afin d'augmenter sa stabilité en milieux biologique, sa solubilité dans l'eau ainsi que son activité. Il a été conjugué avec différentes entités : des peptides pénétrants, un polyéthylène glycol (PEG) et un peptide inhibiteur des pompes d'efflux bactériennes. Ces complexes ont montré une remarquable activité antibactérienne sur neuf souches de bactéries Gram-positives et Gram-négatives et en particulier, ils se sont avérés très efficaces contre S.aureus. L'activité anti-cancéreuse des complexes non-conjugués a également été étudiée et les complexes de cuivre sélectionnés et testés sur des cellules de cancer du sein ont montré une cytotoxicité élevée. Ceci met en évidence la pertinence d'utiliser les complexes métalliques, pour à la fois stabiliser les ligands et générer des composés plus actifs
There is an urgent need to discover new drugs with novel mechanisms of action, higher activity and improved selectivity to address the severe challenge of multidrug resistance in treating bacterial infections and cancer. In view of this, Schiff bases derived from S-substituted dithiocarbazate and their corresponding metal complexes with a plethora of potentially exciting biological activities and coordination chemistry are attractive candidates. Metal complexes of tetradentate NNSS and bidentate NS ligands have been prepared. The compounds were fully characterized with various physico-chemical and spectroscopic methods in solution and solid state. Conjugation of the most promising antimicrobial compound to various moities (polyarginine, polyethylene glycol (PEG) and an bacterial efflux pump inhibitor) was achieved to prepare improved therapeutic agents. The nanoarginines (R9) derivatives showed the most encouraging synergistic effect upon conjugation and complexation to copper ion with enhanced water solubility, bacteria cell membrane permeability and bioactivity. The Cu(II) R9 derivatives possess remarkable antibacterial activity against a wide spectrum of bacteria and in particular, highly efficacious against S. aureus. This show that the conjugation of polyarginine to dithiocarbazate compounds can greatly influence their therapeutic potential. Cytotoxic assay was also carried out for selected non-conjugated compounds. All the selected Cu(II) complexes assayed against breast cancer cells lines exhibited good cytotoxicity. This work highlights the relevance of the strategy that consists of using metal complexes to stabilize the ligands and improve their bioactivity

This study focuses on the antimicrobial activity of Cu(II) complexes of some orthohydroxybenzaldimines and its derivatives. Four different categories of Schiff base ligands were prepared by condensing salicylaldehyde, o-vanillin, p-vanillin and vanillin with p- and osubstituted anilines; 1-aminonaphthalene; 2- and 3-aminopyridine; 2- and 3- aminomethylpyridine as well as 2-aminobenzimidazole. The last category was prepared from ophenylenediamine and o-vanillin. The Schiff base ligands have been characterized by a combination of elemental analysis and spectral (¹H- and ¹³C-NMR, UV/Visible, infrared and Raman) data. The existence of strong intramolecular hydrogen bonding in the orthohydoxybenzaldimines was evident from the chemical shift values of the hydroxyl proton in the ¹H-NMR spectra of the Schiff base ligands. The hydroxyl proton resonates at high frequency and thus absorbed far downfield at 13.46-11.83 ppm, reflecting the presence of hydrogen bonding between the hydroxyl proton and the imine nitrogen. In the p-substituted aniline analogues of the Schiff base, a plot of the chemical shift values of the hydroxyl proton against the Hammett's substituent parameters gave a linear correlation between the electronegativities of the substituents and the chemical shift values. The nitro group with the highest electronegativity caused the least deshielding of the hydroxyl proton and thus absorbed upfield compared to the less electronegative substituents such as the CH3 and OCH3 analogues. Likewise, in the solid state infrared spectra of the ligands, the hydroxyl stretching band of the ortho-hydroxyl Schiff base ligands was observed as a very broad band and at much lower frequency, 3100-2100 cm⁻¹, indicating the existence of strong intramolecular hydrogen bonding. In the same vein, ¹H- and ¹³C-NMR spectral data for the Schiff base ligands indicated that the prepared compounds exist in the enol form in aprotic solvent, chloroform. The methine proton appeared as singlet and there was no carbonyl signal in the ¹³C-NMR spectra of the Schiff base ligands. This was supported by the infrared data having no vibrational band attributable to the carbonyl stretching of the keto-form of the Schiff base ligands in solid state. However, the UV/Visible study of the Schiff base ligands in protic solvent, methanol, suggested the existence of some of the Schiff base ligands in keto-enol form. A band at greater than 400 nm was observed in the UV/Visible spectra of the ligands and this has been attributed to the presence of the keto form of orthohydroxyl Schiff base ligands in solution. A plot of the molar absorptivity (ε) of the band at greater than 400 nm against Hammett substituent parameters revealed that the intensity of the bands increased with the electronegativity of the substituents. The Cu(II) complexes of salicylaldehyde, o-vanillin and a few p-vanillin based Schiff base ligands are reported in this work. It was observed that introduction of Cu(II) ions into the ligand system resulted in the hydrolysis of the imine band in few cases. All the isolated complexes have been characterized by elemental analysis, conductivity measurement, infrared and UV/Visible spectral data. The structures of three of the Cu(II) complexes were further confirmed by X-ray single crystal diffraction. The Schiff base ligands either coordinated as neutral base through the imine nitrogen or via the imine nitrogen and the phenolic oxygen atoms. In addition, the benzimidazole-based and ovan-2-pico analogues equally coordinated through the imidazole N-3 nitrogen and the azine nitrogen respectively; thus acted as tridentate. In general, the synthesized Cu(II) complexes fell into seven categories viz: [Cu(LH)Cl(H₂O)]Cl; [Cu(LH)₂Cl₂].xH₂O; [CuL₂]; [Cu₂L₂]; [Cu(LH)Cl(H₂O)]Cl; and [MLCl]. The Cu(II) complexes of the form, M(LH)₂Cl₂.xH₂O were either 1:1 or non-electrolyte in methanol and DMF. The third category, CuL₂, was however, non-electrolyte existing as neutral four coordinate Cu(II) complexes. X-ray single crystal structure of Cu(II) complexes derived from the ammonia-based Schiff bases revealed a square planar geometry for the complexes and this agreed with the planar geometry that has been reported for Cu(II) complexes of N-arylsalicylaldimines of the type studied in this work. The complexes, [Cu₂L₂], resulted from the ortho-hydroxyaniline analogues and were polymeric with the Schiff base ligands coordinating to the Cu(II) ions as tridentate dibasic via the imine nitrogen, phenolic oxygen and the aminophenolic oxygen atoms. Cu(II) complexes prepared from ovan-2-ampy and ovan-2-pico Schiff bases were of the forms [Cu(LH)Cl(H₂O)]Cl and [CuLCl] respectively. The X-ray crystal structure of [Cu(ovan-2- pico)Cl] revealed a four-coordinate square planar geometry for the complex. In the same vein, the o-phenylenediamine complexes were of the form [Cu(L)(H₂O)], with the X-ray crystal structure of [Cu(bis-ovanphen)(H₂O)] revealing a square pyramidal geometry. The Schiff base ligands and the isolated Cu(II) complexes have been evaluated for their antimicrobial activity against three bacterial strains (Escherichia coli ATCC® 8739™*, Staphylococcus aureus subsp. aureus ATCC® 6538™* and Bacillus subtilis subsp. spizizeni ATCC® 6633™*) and one fungal strain, Candida albicans ATCC® 2091™*, using agar disc diffusion and broth dilution techniques. It was observed that the presence of the methoxyl group at the ortho-position of the aldehyde moiety of the Schiff base ligands enhanced the activity of the ligand tremendously and thus the o-vanillin analogues showed the highest potency against the tested organisms. In addition, the hydroxyaniline analogues were equally the most promising of all the substituted aniline based Schiff bases. The o-vanillin analogues of the aminopyridines and aminomethylpyridines also exhibited significant activity against the tested organisms. All the 2-aminobenzimidazole series were active against the tested organisms. It should be noted that E. coli was the least susceptible of all the microorganisms while the highest potency was exhibited against the fungus of choice, Candida albicans. Lastly, chelation of the Schiff base ligands with Cu(II) ions did not have significant influence on the activity of the free ligands.

Bases de Schiff biopoliméricas à base de quitosana foram preparadas a partir do salicilaldeído e de seus derivados substituídos na posição 5 do anel aromático do salicilaldeído (5-bromo, 5-cloro, 5-metil, 5-metóxi e 5-nitrosalicilaldeído), utilizando condições de síntese otimizadas para aumentar o grau de substituição (GS). Durante a caracterização das bases foram observados GS (%) = 78,7; 51,3; 43,7; 28,1; 22,1 e 17,5, respectivamente para os derivados 5-metóxi, salicilaldeído, 5-nitro, 5-cloro, 5-metil e 5-bromo, tendo sido as diferenças atribuídas ao caráter indutivo e de ressonância de cada um dos grupos substituintes. A partir desses ligantes foram sintetizados os complexos de cobre (II) e níquel (II) com quitosana e todas as bases de Schiff biopoliméricas. A quitosana, os ligantes e os complexos foram caracterizados por espectroscopia vibracional na região do infravermelho com transformada de Fourier (FTIR) e técnicas termoanalíticas (termogravimetria, TG; termogravimetria derivada, DTG e análise térmica diferencial, DTA). A quitosana utilizada apresentou grau de desacetilação, GD = 75,6%, determinado por 1H RMN, e apresentou as bandas características para estes biopolímeros nos espectros FTIR e decomposição térmica em dois eventos exotérmicos, após desidratação. As curvas TG/DTG-DTA das bases revelaram que estas são menos estáveis que a quitosana de partida e a estabilidade mostrou-se mais uma função da natureza do ligante do que do GS. A partir das curvas TG e dos valores de GS foi possível prever a composição das bases em concordância com os dados de análise elementar. Os complexos mostraram coordenação com os átomos de oxigênio do anel aromático dos aldeídos e do nitrogênio imínicos, com base nos espectros FTIR, sendo os complexos de cobre aparentemente mais fortes que os de níquel, se considerados os deslocamentos nas frequências de vibração das ligações C=N e C-Ofen. Os complexos de cobre (II) e níquel (II) também apresentaram decomposição em duas etapas, após desidratação, tendo sido a primeira etapa observada em temperaturas inferiores às das bases. Em alguns casos foi possível observar que os processos de decomposição se dividem, sugerindo decomposição diferenciada para regiões do biopolímero contendo o complexo e aquelas não modificadas, pois tal fenômeno ocorreu principalmente nos complexos derivados das bases com menor GS. Os resíduos de decomposição desses complexos foram CuO e NiO, de acordo com difratogramas de raios X, cujos teores permitiram calcular a quantidade de metal presente em cada complexo, e concluir que praticamente todos os sítios contendo as bases biopoliméricas foram complexadas em ambos os casos.
Biopolymeric Schiff bases were prepared from chitosan and salicylaldehyde and its 5-bromo, 5-chloro, 5-methyl, 5-methoxy and 5-nitro derivatives, under conditions optimized to improve the degree of substitution (DS). From 1H NMR data, DS (%) = 78.7, 51.3, 43.7, 28.1, 22.1 and 17.5, for 5-methoxy, salicylaldehyde, 5-nitro, 5-chloro, 5-methyl, and 5-bromo derivatives, respectively. The differences had been attributed to inductive and resonance effects of each substituent. From these ligands, copper (II) and nickel (II) complexes were synthesized with chitosan and all the biopolymeric Schiff bases. Chitosan, ligands and complexes were characterized by Fourier transform vibrational spectroscopy in the infrared region (FTIR) and thermal analytical techniques (thermogravimetry, TGA; derivative thermogravimetry, DTG and differential thermal analysis, DTA). Chitosan presented a deacetylation degree, DD = 75.6%, determined by 1H NMR, presenting the characteristic bands of this biopolymer in the FTIR spectra as well as decomposition in two exothermic steps after dehydration. TGA/DTG and DTA curves of the bases revealed that they are less stable than chitosan. This stability is closely related to the nature of substituent than the DS. From TGA curves and DS values it was possible to calculate the bases composition which agreed with elemental analysis data. Complexes presented coordination via oxygen atom of aldehydes aromatic rings and the iminic nitrogen, based on the FTIR results, being the copper (II) complexes apparently stronger the those from nickel (II), if one consider the displacements in the vibration frequencies of the C=N and C-Ophen bonds. The copper (II) and nickel (II) complexes also presented decomposition in two steps after dehydration, being the first step observed in lower temperatures when compared to those of the free bases. In some cases it was possible to observe that the decomposition steps in the DTG curves are split suggesting different decomposition for regions of the biopolymer in which the complexes is present and for the unmodified ones, once such phenomena occurred mainly in complexes derived from the bases with lower DS. The residues of decomposition for such complexes were CuO and NiO, according to X-ray diffractograms and their contents permitted to calculate the amount of each metal present in the complex leading to conclude that almost all the sites containing the Schiff bases on the biopolymeric matrix was complexed in both cases.

La conception et la synthèse de nanomatériaux à base d'éléments de transition tardifs est d’un intérêt considérable pour des applications potentielles respectueuses de l’environnement en nanomédecine, pour la reconnaissance moléculaire, dans le domaine des capteurs, et en catalyse. Onze différents types de nanoparticules de métaux de transition (TMNPs) stabilisées par des dendrimères ont été synthétisées et caractérisées. Ces nanomatériaux ont été employés en tant que catalyseurs dans des réactions ''click'' et de réduction du nitrophénol en aminophénol dans le but d’établir une relation entre leurs activités catalytiques et la localisation de la nanoparticule qui peut être totalement ou partiellement encapsulée par le dendrimère. Par ailleurs, un complexe moléculaire base de Schiff organométallique de Cu(II) et le métallopolymère correspondant résultant de son greffage sur une matrice PMMA ont été préparés et utilisés comme précatalyseurs efficaces de réactions de cycloaddition [3+2] d’azotures organiques avec des alcynes terminaux. De plus, le dérivé supporté a été recyclé au moins trois fois sans perte d’activité ni de cuivre. Une réaction sélective de N-alkylation d’amines par des alcools en utilisant Pd/C comme catalyseur recyclable a également été développée
The design and synthesis of late transition-metal nanomaterials is of considerable interest towards applications in nanomedicine, molecular recognition, sensing and catalysis under environmentally friendly conditions. Eleven different kinds of dendrimer-stabilized TMNPs have been synthesized and characterized. They were employed as catalysts for “click” and 4-nitrophenol reduction reactions, to study the relationship between their catalytic activities and their ''inside vs. partly outside'' dendrimer localization. On the other hand, a new ferrocenyl-containing unsymmetrical CuII-Schiff-base complex, and its covalently poly(methyl) (methacrylate) (PMMA)-grafted counterpart were synthesized and employed as efficient precatalyst in the CuAAC “click reaction. The PMMA-supported catalyst has been reused at least three times without any lost of activity or copper leaching. A selective NAlkylation reaction of amines with alcohols using Pd/C as an efficient and reusable catalyst has also been developed

Neste trabalho inicialmente foi feita uma breve apresentação sobre a utilização de compostos de bases de Schiff e Cobre(II) como catalisadores na reação de oxidação de sulfetos. Foi feita a determinação das estruturas cristalinas dos compostos: N,N\'-bis(3-etoxisalicilideno)-(1,2etileno- diamina) Cu(II), sistema cristalino ortorrômbico grupo espacial Pbcn a = 7.639(5); b= 12.760(5); c= 19.733(5)Å; V = 1923.4(15) (3)Å3; Dcalc = 1.505 Mg/m3; MM = 435.96; e m = 1.170 mm-1, N,N\'-bis (4-dietilaminasalicilideno) - (1,2etilenodiamina) Cu(II), sistema monoclínico, C2/c, a = 19.571(2); b=9.8514(2)=; c=12.4552(4) Å; Beta = 93.705(9)o; V =2396.4(5) Å3; Dcalc=1.358 Mg.m-3; MM= 490.10; e m = 0.944 mm-1, N,N\'-bis(3-metoxisalicilideno)-(1,2etilenodiamina)Cu(II), sistema ortorrômbico, Pna21, a = 7.5140(6); b= 9.2629(9); c= 24.721(3)Å; V =1720.6(3) Å3; Dcalc = 1.575 Mg,m-1; MM = 407.91; e m = 1.302 mm1 e (SALAHE)Cu(II), monoclínico, P21/C, a = 18.3216(2) Å; b=4.804(3) Å; c=19.801(2)Å; Beta = 98.908(6)o; V =2396.4(5) Å3; Dcalc=1.358 Mg.m-3; MM= 490.10; e m = 0.944 mm-1. Os cálculos teóricos para as quatro moléculas foram efetuados partindo-se das coordenadas atômicas cristalográficas. Foram modeladas, para posterior estudo teórico, as moléculas de vinte e seis compostos de bases de Schiff e Cobre(II) análogos. Foram calculadas 104 variáveis para cada composto, e realizado o estudo de correlação estrutura-atividade catalítica através de métodos de Quimiometria. Foi obtido um modelo de correlação utilizando a classe de compostos de atividade catalítica pré-definida. Finalmente foi realizada a tentativa de previsão de atividade dos vinte e quatro compostos com atividade não conhecida, obtendo-se como resultado a probabilidade de vinte deles serem ativos como catalisadores da conversão sulfeto-sulfóxido .
Initially, in this work, a brief presentation about Schiff bases and their applications as catalysist. The crystalline structure determination was made for the compounds: N,N\'-bis(3-etoxysalicylidene)- (1,2ethylenediamine) Cu(II), crystal system orthorhombic spatial group Pbcn a = 7.639(5); b= 12.760(5); c= 19.733(5)Å; V = 1923.4(15) (3)Å3; Dcalc = 1.505 Mg/m3; MM = 435.96; e m = 1.170 mm-1, N,N\'-bis (4- diethylaminesalicilidene) - (1,2ethylenediamine) Cu(II), monoclinic, C2/c, a = 19.571(2); b=9.8514(2)=; c=12.4552(4) Å; B= 93.705(9)o; V =2396.4(5) Å3; Dcalc=1.358 Mg.m-3; MM= 490.10; e m = 0.944 mm-1, N,N\'-bis(3-metoxysalicilidene)- (1,2ethylenediamine) Cu(II), orthorhombic, Pna21, a = 7.5140(6); b= 9.2629(9); c= 24.721(3)Å; V =1720.6(3) Å3; Dcalc = 1.575 Mg,m-1; MM = 407.91; e m = 1.302 mm1 e (SALAHE)Cu(II), monoclinic, P21/C, a = 18.3216(2) Å; b=4.804(3) Å; c=19.801(2)Å; B= 98.908(6)o; V =2396.4(5) Å3; Dcalc=1.358 Mg.m-3; MM= 490.10; e m = 0.944 mm-1. The theoretical calculations for the four molecules had been effected starting of the crystallographic atomic coordinates. Twenty-six molecules without determined crystallographic structure had been shaped for theoretical study. 104 variables for each compound had been calculated, and carried through the correlation study structure-catalyst activity through chemometric methods. A separation model was gotten in one single class. Finally the attempt of forecast of activity of twenty four compounds with activity unknown was carried through, getting itself as resulted the probability of twenty in all to be able to become active.

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CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
A presente tese, intitulada "Preparação e avaliação biológica de conjugados esteroides/bases de Schiff" trata, sobretudo, da preparação, caracterização e avaliação do potencial biológico de compostos orgânicos contendo uma porção esteroidal associada a uma base de Schiff nos quais a conjugação se deu nas posições C-3 ou C-24 dos núcleos esteroidais cólico, desoxicólico ou colesterol. Além destes, encontra-se descrita também a preparação de derivados destas duas classes de compostos de forma não conjugada. Os compostos aqui descritos foram preparados através da utilização de metodologias clássicas em síntese orgânica, as quais envolvem a formação de amidas, reações de esterificação e formação de iminas; todas relacionadas à química de compostos carbonílicos. As estruturas químicas dos produtos obtidos, bem como as dos intermediários sintéticos, foram devidamente confirmadas por espectroscopia no infravermelho, de ressonância magnética nuclear de próton e de carbono, por espectrometria de massas, além de faixa de fusão e análise elementar. Os compostos sintetizados foram avaliados como potenciais antiparasitários (leishmanicidas e antimaláricos), antibacterianos (antituberculosos) e antioxidantes (inibidores do radical DPPH). Tais propriedades foram selecionadas por já serem atividades descritas para as duas classes de moléculas exploradas neste trabalho- derivados esteroidais e bases de Schiff. Baseado nas estruturas dos compostos descritos neste trabalho realizou-se também testes de avaliação da atividade fotoprotetora (fatores de proteção solar UVA e UVB e determinação do comprimento de onda crítico) de alguns dos conjugados obtidos. Grande parte dos compostos sintéticos apresentaram atividade biológica promissora.
The thesis entitled ―Preparation and biological evaluation of conjugated steroids/Schiff bases‖ deals mainly with the preparation, characterization and evaluation of the biological potential of organic compounds containing a steroid portion associated with a Schiff base in which the conjugation occurred the C-3 or C-24 positions of the steroid nucleus cholic, deoxycholic or cholesterol. In addition, is also described the preparation of derivatives of these two classes of compounds in non conjugated form. The compounds described herein were prepared by using classical methods of organic synthesis, which involves amide formation, sterification and imine formation; all related to chemistry of carbonyl compounds. The chemical structures of the obtained products, as well as synthetic intermediates were confirmed by infrared spectroscopy, nuclear magnetic resonance of proton and carbon, by mass spectrometry, elemental analysis and melting point. The synthesized compounds were evaluated as potential antiparasitic (antileishmanial and antimalarial), antibacterial (antituberculosis) and antioxidants (DPPH radical inhibitors). These properties have been selected by already being activities described for the two classes of molecules explored in this work-steroidal derivatives and bases Schiff. Based on the structures of the compounds described in this work also conducted evaluation tests of sunscreen activity (sun protection factor UVA and UVB, and determining the critical wavelength) of some of the conjugates. Much of the synthetic compounds showed promising biological activity.

Una de las áreas de la Química Organometálica que ha suscitado mayor interés en los últimos 25 años es el estudio de los procesos de activación de enlaces C-H, mediante compuestos de elementos de transición. Dentro de este contexto los procesos conocidos como reacciones de ciclometalación son unos de los más ampliamente estudiados, y en particular aquellos en los que se utilizan sales de paladio (II) y sustratos orgánicos que poseen nitrógeno como heteroátomo. El mecanismo que se propone en este caso concreto consiste en dos etapas sucesivas: a) la coordinación del heteroátomo y b) un ataque electrofilo de la especie formada al enlace C-H.

Por otra parte, si bien en la bibliografía se han descrito un gran número de reacciones de ciclopaladación de ligandos N-dadores derivados del benceno, los estudios que versan sobre substratos análogos con grupos ferrocenilo son sumamente escasos, a pesar de ser bien conocido que el ferroceno es mucho más proclive a experimentar reacciones del substitución electrofila. En consecuencia, parecía interesante llevar a cabo un trabajo paralelo basado en el estudio de los procesos de ciclopaladación de ferroceniliminas y ferrocenilazinas que permitiese obtener compuestos con Sigma(Pd-C/sp(2), ferroceno), que presentan el interés adicional de la quiralidad inherente a los derivados 1,2- disubstituidos del ferroceno.

El trabajo que se resume en esta Memoria está enmarcado dentro de este campo y tiene como objetivo fundamental abordar el estudio de los procesos de ciclopaladación de bases de Schiff con grupos ferrocenilo que permita:

a) comparar la facilidad de activación de los enlaces Sigma(C(sp)2, (ferroceno)-H) frente a los Sigma(C(sp)2, (fenilo)-H) e incluso Sigma(C(sp)3, (alifático)-H),

b) evaluar la importancia del llamado "efecto endo",

c) establecer la influencia del tamaño del paladociclo (y en particular, el número de átomos que lo constituyen) sobre la estabilidad de estos compuestos,

d) determinar la importancia del carácter básico del átomo de nitrógeno coordinado al paladio sobre la estabilidad y reactividad del enlace O'(Pd-N),

e) estimar la influencia de los efectos estéricos en estos procesos de activación de enlaces carbono-hidrógeno,

f) apreciar la incidencia de la posible formación de dos ciclos fusionados de cinco miembros, [5, 5] - el propio metalociclo y el anillo ciclopentadienilo - en el proceso de ciclometalación.

Con estas premisas iniciales, el trabajo que se resume en esta Memoria se ha dividido en dos partes marcadamente diferenciadas:

a) Preparación y caracterización de bases de Schiff mono- y difuncionales derivadas del ferroceno y,

b) Estudio de los procesos de ciclopaladación de derivados del ferroceno con el grupo funcional >C=N- del tipo iminas y azinas.
This Thesis deals with the synthesis and characterization of ferrocene derivatives containing the functional group >C=N-, and with the study of their cyclopalladation reactions. The work is divided in two parts:
a) Preparation and characterization of novel Schiff bases of general formulae.
b) The study of the cyclopalladation reactions of these derivatives as well as those of ferrocenylazines, which have aIlowed to isolate and characterize palladium (II) compounds with different sorts of Pd-C bonds (C(sp)(2) phenyl, C(sp)(2) ferrocene or C(sp)(3).

All the compounds have been characterized by elemental analyses, infrared spectroscopy, nuclear magnetic resonance, Mossbauer spectroscopy and electrochemical studies -based on cyclic voltammetries- on these compounds are also included and have allowed to elucidate the influence of the substituents -including the palladium (II)- on the Fe(II) environment.

The X-ray crystal structures of three imines of general formulae and four palladium compounds have been solved and refined.

Finally, the work summarized in this Thesis has also allowed to elucidate the relative importance of several factors, such as the "endo" effect, the different proclivity of benzene and ferrocene derivatives to undergo electrophilic substitution, and the size and structure of the metallacycle upon the nature of the final Pd (11) compound formed through activation of the Sgyma(C-H) bonds.

Des polymères supports de principes actifs (bases de Schiff) ont été synthétisés, caractérisés par RMN #1h, IR, DSC et microanalyse. Ces différents polymères supports de médicament ont été hydrolysés dans un milieu acide reproduisant l'acidité du milieu gastrique et dans un milieu basique reproduisant la basicité du milieu intestinal. Ces polymères sont ensuite dispersés dans une matrice polymère, très souvent employée en pharmacologie, l'eudragit rl: formant ainsi des formes galéniques sphériques à double effet retard. L'hydrolyse des formes galéniques a montré un double transfert de matière : le milieu liquide entre dans la matrice et le principe actif diffuse dans le liquide. Ces deux transferts sont interdépendants et sont gouvernes par la diffusion fickienne. Des modèles mathématiques très simples ont permis de simuler les phénomènes de diffusion au cours de la cinétique d'hydrolyse

A number of lead(II) complexes prepared from the reactions of various disalicylaldimines with lead(II) salts have been characterised spectroscopically, and in two cases have been analysed by X-ray diffraction. The reaction of N,N'-bis(salicylidene)ethane-1,2-diamine (H2salen) with Pb(ClO4)2·6H2O produced a novel complex [Pb3(salen)2][ClO4]2 in which the ligand bonds to the lead in two different modes. The interaction of N,N'-bis(3-methoxy-salicylidene)ethane-1,2-diamine with Pb(ClO4)2·6H2O yielded a mononuclear complex wherein the ligand bonds to the lead(II) atoms only through its phenolic oxygens.

Esta tese apresenta a síntese e a caracterização de novos complexos de rênio e tecnécio utilizando como agentes complexantes ligantes assimétricos do tipo base de Schiff e ligantes triaminas derivadas da dietilenotriamina. Os ligantes assimétricos foram sintetizados através de reações de condensação entre 2,2\'-dihidroxibenzofenona e as aminas alifáticas etilenodiamina e dietilenotriamina, formando, respectivamente, os ligantes 2,2\'-(((2-aminoetill)imino)metileno)difenol(HL1) e 2,2\'-(((2-((2-aminoetil)amino)etil)imino) metileno)difenol (HL2). Os ligantes simétricos foram sintetizados através de reações de condensação entre benzaldeído, 4-hidroxibenzofenona e 3- e 4-metoxibenzaldeído com a amina alifática dietilenotriamina, formando, respectivamente, os ligantes simétricos tridentados tricloridrato de N1-benzil-N2-(2-(benzilamino)etil)etano-1,2-diamina (HL3), 4,4\'-(((azanodiilbis(etano-2,1-diil))bis- (azanediil))bis(phenilmetileno))difenol (HL4), tricloridrato de N1-(4-metoxibenzil)-N2-(2-((4-metoxibenzil)amino)etil) etano-1,2-diamina (HL5) e tricloridrato de N1-(3-metoxibenzil)-N2-(2-((3-metoxibenzil)amino)etil)etano-1,2-diamina (HL6). Reações de complexação foram conduzidas com os precursores metálicos de ReI eTcI. O complexo [Re(CO)5Br] foi utilizado como precursor de ReI. Foi obtido o complexo neutro do tipo fac-[Re(CO)3(L1)] e complexos catiônicos do tipo fac-[Re(CO)3(HL2,3,4,5,6)]Br. Os ligantes e complexos foram caracterizados por ponto de fusão, análise elementar (CHN), espectroscopia de absorção na região do infravermelho, espectroscopia de absorção na região do ultravioleta visível, espectroscopia de ressonância magnética nuclear de 1H e 13C, espectrometria de massas (MS-ESI) e, no caso dos complexos com os ligantes HL1,2,5,6, difração de raios X pelo método do monocristal. Foi realizada a marcação do ligante HL3 com o complexo fac-[[99mTc](H2O)(CO)3]+, formando o complexo fac-[[99mTc](CO)3(HL3)]Br e outras espécies em solução, que foram separadas por HPLC. Adicionalmente, realizou-se um estudo comparativo entre o método convencional de síntese (aquecimento) com o método de síntese no qual microondas são utilizadas. O complexo de tecnécio foi caracterizado por HPLC e eletroforese em papel. Foram realizados testes de estabilidade em cisteína, histidina e tampão PBS. Os testes de estabilidade mostraram que o complexo apresenta boa estabilidade por período de 3 horas. Foi determinado o coeficiente de partição desse complexo, tendo sido observado o caráter lipofílico do mesmo. Foram também realizados testes biológicos in vitro de captação e extrusão com células B16F10 (melanoma murino), onde as células captaram o complexo fac-[[99mTc](CO)3(HL3)]Br,em torno de 4,2%, e mantiveram retidas em seu interior cerca de 20% do complexo, após 60 minutos de incubação. O teste de viabilidade celular por azul de Tripan, mostrou estabilidade das células, durante os experimentos de captação e extrusão, frente às espécies radioativas, apresentando uma viabilidade celular superior a 90% em todos os casos.
This thesis presents the synthesis and characterization of novel rhenium and technetium complexes using as complexing agents asymmetric ligands (Schiff\'s bases type ligands) and triamines ligands derived from diethylenetriamine. The asymmetric ligands were synthesized by condensation reactions between 2,2\'-dihydroxybenzophenone and the aliphatic amines ethylenediamine and diethylenetriamine, giving rise, respectively, to the ligands 2,2\'-(((2-aminoetill)imino) methylene)diphenol (HL1) and 2,2\'-(((2-((2-aminoethyl)amino)ethyl)imino) methylene) diphenol (HL2). The symmetrical ligands were synthesized by condensation reactions between benzaldehyde, 4-hydroxybenzophenone and 3- and 4-methoxybenzaldehyde with the aliphatic amine diethylenetriamine, resulting in the formation, respectively, of the symmetrical tridentated ligands trihydrochloride N1-benzyl-N2-(2-(benzylamino)ethyl)ethane-1,2-diamine (HL3), 4,4\'-(((azanodiilbis(ethane-2,1-diyl))bis(azanediil))bis(phenilmetileno))diphenol (HL4), trihydrochloride N1-(4-methoxybenzyl)-N2-(2-((4-methoxybenzyl)amino)ethyl)ethane-1,2-diamine (HL5) and trihydrochloride N1-(3-methoxybenzyl)-N2-(2-((3-methoxybenzyl)amino)ethyl)ethane-1,2-diamine (HL6). Complexation reactions were carried out using ReI and TcI as metal precursors. The complex [Re(CO)5Br] was used as ReI precursor. Neutral complexe of the type fac-[Re(CO)3(L1)] and cationic complexes of the type fac-[Re(CO)3(HL2,3,4,5,6)]Br were obtained. The ligands and complexes were characterized by melting point, elemental analysis (CHN), infrared absorption spectroscopy, UV-visible absorption spectroscopy, 1H and 13C nuclear magnetic resonance spectroscopy, mass spectrometry (MS-ESI) and for the complexes with the ligands HL1,2,5,6, single crystal X ray diffraction method. Labeling studies were carried out for the HL3 ligand with the complex fac-[[99mTc](H2O)(CO)3]+, forming the complex fac-[[99mTc](CO)3(HL3)]Br and other species in solution, which were separated by high performance liquid chromatography (HPLC). Additionally, a comparative study was done between the conventional (heating) and the synthesis method using microwaves. The technetium complex was characterized by HPLC and electrophoresis on paper. Stability tests were conducted on cysteine, histidine and PBS buffer. The stability tests showed that the compound presents good stability over a 3 hour period. The lipophilic character of the complex was confirmed by the determination of the partition coefficient. In addition, In vitro biolgical tests of captation and influx were performed on B16F10 cells (murine melanoma). The cells captured around 4.2% of the complex fac-[[99mTc](CO)3(HL3)]Br and retained 20% of the amount inside after 60 minutes of incubation. The Trypan blue exclusion test of cell viability showed stability of the cells during the influx and captation experiments, front of the radioactive species, showing cell viability greater than 90% in all cases.

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Universidade Federal de Sao Carlos
In order to find inorganic compounds with biological properties as chemotherapeutic agents that could increase the possibilities in the treatment of some diseases, copper complexes with Schiff base ligands were prepared and characterized. In this work we prepared 63 compounds, being 19 symmetrical tetradentate Schiff base ligands and their respective copper complexes, 16 copper complexes with unsymmetrical tetradentate Schiff base ligands and 9 copper complexes with tridentate Schiff base ligands derived from ethylenediamine, trans-1,2-diaminocyclohexane and orto-phenylenediamine, with salicylaldehyde or substituted salicylaldehyde. All were characterized by vibracional spectroscopy (infrared), electronic spectroscopy (ultraviolet-visible) and others methods such as solubility, melting points. Some complexes were studied by cyclic voltammetry and magnetic susceptibility. The structures of [Cu(3-MeOsalen)], [Cu(3- EtOsalen)] and [Cu(4-DEAsalen)], have been determined by single crystal X-ray diffraction. The cytotoxicity of the symmetrical complex [Cu(4-DEAsalen)], was evaluated using HPV-16 and HPV-18 infected cells. Cytotoxicity tests using spleen cells of BALB/c mice were performed using 5 tridentate complexes. The characterization results show that the synthesis had been successful with good yields. The effect of the substitution on the aromatic ring was compared for compounds within a series and between different series.
Em busca de compostos inorgânicos com propriedades biológicas que pudessem, através da atuação como agentes quimioterápicos, contribuir para aumentar as possibilidades no tratamento de algumas doenças, foram sintetizados e caracterizados complexos de cobre com ligantes bases de Schiff do tipo salen, foram estudados no total 63 compostos, sendo 19 complexos tetradentados simétricos com seus respectivos ligantes; 16 complexos tetradentados assimétricos e 9 complexos tridentados. Todos, complexos e ligantes, foram caracterizados pelas técnicas de espectroscopia vibracional (região do infravermelho) e eletrônica (região do ultravioleta-visível) entre outras técnicas como pontos de fusão e solubilidade, foram realizadas medidas de susceptibilidade magnética e estudos eletroquímicos para alguns complexos. Os complexos [Cu(3-MeOsalen)], [Cu(3-EtOsalen)] e [Cu(4-DEAsalen)], tiveram suas estruturas determinadas por difração de raios-x, método de monocristal. Foram realizados testes de toxicidade para o complexo simétrico [Cu(4-DEAsalen)], em relação à células infectadas com dois tipos de HPV e testes de toxicidade em células esplênicas com alguns complexos tridentados. Os meios de caracterização empregados indicam que as sínteses foram bem sucedidas com rendimentos bastante eficientes, foram feitas comparações com respeito aos efeitos dos substituintes no anel aromático dentro de uma mesma série de compostos e também foram comparados os resultados obtidos para as diferentes séries de trabalho.

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Universidade Federal de Sao Carlos
Salen complexes are an important class of coordination compounds, which have been used to catalyze a wide variety of reactions. The salen complexes have emerged as efficient and practical catalysts for the asymmetric oxidation of various organic substrates. In this thesis, copper(II) and oxovanadium(IV) complexes of the salcn type ligand [salcn= N, N -bis- (salicylidene)-1,2-cyclohexanediamine] have been investigated as catalysts for oxidation of organic sulfide. The first part of this work describes the synthesis and characterization of the free ligands and copper(II) and oxovanadium(IV) complexes. The combination of four complementary techniques (IR, UV-vis, 1HNMR-13CNMR and X-ray) made possible the characterization of the free ligands and complexes. Six unpublished crystallographic structures were determined: four ligands and two oxovanadium(IV) complexes . In the second part of this research were studied catalytic properties of some complexes in oxidation of phenyl methyl sulfide using acetonitrile as the solvent and hydrogen peroxide and t-butylperoxide as the oxidant. The [Cu(salcn)] and [VO(salcn)] with electrons donors and electrons withdrawing substituents were tested for catalytic oxidation. The effect of reaction conditions on activity with various oxidants gave distinctly different yields. The complex trans-(±)-[Cu(5- Clsalcn) showed the best result, with 73% of the sulfide conversion. This is result was showed with hydrogen peroxide as the oxidant. The yields obtained for the other compounds vary of 11-32%.
Os complexos de salen são uma classe importante dos compostos de coordenação e são utilizados como catalisadores em uma grande quantidade de reações. Os complexos salen tem mostrado ser catalisadores eficientes e práticos para oxidações assimétricas de vários substratos. Nesta tese, complexos do tipo salcn [salcn = N, N -bis- (salicilideno)-1,2-ciclohexanodiamina) foram investigados como catalisadores em oxidação de sulfetos orgânicos. A primeira parte deste trabalho, descreve a síntese e caracterização dos ligantes e complexos de cobre(II) e oxovanádio(IV). A combinação das quatro técnicas complementares (IV, UVvis, RMN e raios-X) possibilitou a caracterização dos ligantes e complexos quirais. Seis estruturas cristalográficas inéditas foram determinadas: quatro ligantes e dois complexos de oxovanádio(IV). A segunda parte desta pesquisa foi o estudo das propriedades catalíticas dos complexos na oxidação do metilfenilsulfeto utilizando acetonitrila como solvente e peróxido de hidrogênio e terc-butil peróxido como agente oxidante. [Cu(salcn)] e [VO(salcn)] com substituintes doadores de elétrons e retiradores de elétrons foram testados e os efeitos das condições de reações na atividade catalítica com a variação dos agentes oxidantes mostraram rendimentos bem distintos. O complexo trans-(±)-[Cu(5-Clsalcn) apresentou o melhor resultado, com 73,5% de conversão do sulfeto a sulfóxido e/ou sulfona. Este resultado foi alcançado quando utilizado como doador de oxigênio o peróxido de hidrogênio. Os rendimentos obtidos para os outros complexos variam de 11-32%.

Cette thèse décrit une méthodologie innovante d’extraction et d’hémisynthèse simultanée, dénommée SECheM (Simultaneous Extraction and Chemical Modification) sur une plante mauritanienne le Cienfuegosia digitata Cav. Cette méthodologie présente plusieurs avantages : (a) elle permet d’éviter les étapes critiques au niveau de la séparation et de la purification du gossypol, un polyphénol instable isolé de la plante ciblée (b) elle permet de stabiliser le gossypol thermiquement en le transformant en base de Schiff beaucoup plus stable. (c) elle présente un avantage en termes de réduction du nombre d’étapes et de temps. La même méthodologie a été utilisée pour accéder à des analogues bases de Schiff énantiomériquement pures du gossypol seulement en 2 étapes. Ces dernières transformées efficacement en complexes métalliques énantiomériquement purs se sont montrés être intéressants d’un point de vue catalytique
This PhD work describes an innovative methodology for simultaneous extraction and semisynthesis, named SECheM (Simultaneous Extraction and Chemical Modification) on a Mauritanian plant: Cienfuegosia digitata Cav. This methodology offers many advantages: (a) It is a perfect solution to circumvent critical steps in the extraction, separation and purification processes of gossypol that is unstable polyphenol isolated from the targeted plant (b) It allows an in-situ preparation of more stable gossypol Schiff base derivatives (c) It shows an important reduction of step number and also the time needed for the process. The same SECheM methodology was used to access enantiomerically pure Schiff base derivatives of gossypol in only two steps. The latters were efficiently transformed into enantiomerically pure metallic complexes that appear to be very interesting in a catalytic reaction

Tese (doutorado)—Universidade de Brasília, Instituto de Química, Programa de Pós-Graduação em Química, 2013.
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Neste trabalho está retratado a síntese e a caracterização de complexos de rênio(I) com ligantes escorpionatos derivados de tiobases e bases de Schiff derivadas da condensação de beta-aminoácidos (β-alanina, ácido 2-minobutírico e β-fenilalanina) com três aldeídos (2-hidróxi-1-salicilaldeído, 2-hidróxi-1-naftaldeído e 2-hidróxi-1-piperonal). Foram sintetizadas sete bases de Schiff (três inéditas) e dois ligantes escorpionatos (inéditos), dos quais quatro foram mais eficazes na complexação do fragmento fac-{Re(CO)3}+. Os complexos foram obtidos na proporção 1:1 (metal: ligante) e as estruturas cristalinas e moleculares dos complexos [fac-{Re(bala2hnH)(CO)3}2], (H3O)[Re(fac-bphala2hn)(CO)3]?CHCl3 ?H2O, K[fac-Re(bphala2hn)(CO)3]?⅓CHCl3?2H2O e fac-[Re{κ3-HB(btz)3)}(CO)3] foram determinadas por difração de raios X em monocristal que revelou que o íon ReI está hexacoordenado conferindo aos complexos geometria octaédrica distorcida. Os complexos obtidos foram caracterizados ainda por análise do ponto de fusão (P.F.), análise elementar (C, H, N), termogravimetria, espectroscopia de absorção no infravermelho e espectroscopia de ressonância magnética nuclear de 1H, 13C e 11B. Devido a baixa solubilidade e da reatividade dos ligantes escorpionatos, as análises de espectroscopia de ressonância magnética nuclear de 11B foram fundamentais na determinação da formação dos ligantes escorpionatos bem como dos complexos de rênio(I) com esses ligantes. _______________________________________________________________________________________ ABSTRACT
This work describes the synthesis of complexes of rhenium (I) with derivatives of escorpionate tiobases ligands. It also shows the synthesis and characterization of Schiff bases derived from the condensation of beta-amino acids (β-alanine, 2-β-phenylalanine and minobutírico acid) with three aldehydes (2-hydroxy-1-salicylaldehyde, 2-hydroxy-1-naphthaldehyde and 2 -hydroxy-1-piperonal). Seven Schiff bases (three new) and two “escorpionatos” binders (unpublished) were synthesized, four of which were more effective in complexing the fragment fac-{Re(CO)3}+. The complexes were obtained in the ratio 1:1 (metal: ligand). The crystal and molecular structures of the complexes [fac-{Re(bala2hnH)(CO)3}2], (H3O)[Re(fac-bphala2hn)(CO)3]?CHCl3?H2O, K[fac-Re(bphala2hn)(CO)3]?⅓CHCl3? 2H2O e fac-[Re{κ3-HB(btz)3)}(CO)3] were determined by X-ray diffraction crystallography. Analyses revealed that the ion ReI is hexacoordenate resulting in distorted octahedral complexes. The complexes were further characterized by analysis of melting point (mp); elemental analysis (C, H, N); thermogravimetry; infrared absorption spectroscopy and proton nuclear magnetic resonance of 1H, 13C and 11B. As “escorpianatos” ligands had low solubility and reactivity, analysis of nuclear magnetic resonance spectroscopy of 11B was essential in determining the escorpionates ligands and complexes of rhenium (I) with these binders.

La réaction de cycloaddition dipolaire [3+2] est un outil puissant pour la préparation de composés hétérocycliques. C'est une méthode facile à mettre en œuvre, tant ses conditions opératoires sont douces, qui nécessite, de plus des réactifs aisément accessibles et peu onéreux. Dans ce manuscrit, nous décrivons l'étude de la réaction de cycloaddition dipolaire à partir d'ylures d'azométhine sous irradiation micro-ondes. L'association de la cycloaddition dipolaire [3+2] avec la chimie des micro-ondes s'est révélée être d'une grande efficacité pour la préparation de plusieurs composés polycycliques en peu d'étapes. Les résultats intéressants obtenus, offrent une nouvelle approche synthétique applicable à la synthèse de nouvelles molécules bioactives. Par conséquent, nous avons préparé un grand nombre de composés potentiellement actifs, de type hydropyrrolique, comme des hydrochroménopyrroles, des hydrobenzoindoles, des hydroindénopyrroles et des oxochroménopyrroles. Ces composés ont pu être préparés dans des temps très courts, avec des rendements généralement très bons
The [3+2] dipolar cycloaddition reaction is a powerful tool for the preparation of heterocyclic compounds. It is a facile method, employing straight forward laboratory procedures, and easily accessible reagents. Herein we describe the study of the dipolar cycloaddition reaction from azomethine ylides under microwave conditions. The use of microwaves in this reaction is very efficient for the rapid synthesis of polycyclic compounds. The interesting results obtained permit the development of novel methodology for the synthesis of many molecules with pharmacological potential. As such, we prepared numerous families of compounds such as hydrochromenopyrroles, hydrobenzoindoles, hydroindenopyrroles and oxochromenopyrroles. These compounds were prepared rapidly, generally in very good yields

Several Schiff base ligands, N, N‟-(aryl)benzyaldiimine ligands (R-BEN); N, N‟-(aryl)benzyaldiamine dihydrochloride ligands (R-BENH•2HCl); N, N‟-(aryl)benzyaldiamine ligands (R-BENH); N, N‟-bis(cinnamaldiimine) ligands (R-CA2EN) were synthesized for the investigation of the electronic effect of the substituents at para-position of the Schiff base ligands and their copper complexes. The synthesis of Schiff bases was carried out by reacting a series of para-substituted benzyaldehyde, and para-substituted cinnamaldehyde with ethylenediamine. The imine group of Schiff bases, N, N‟-(aryl)benzyaldiimine ligands and N, N‟-bis(cinnamaldiimine)ligands were reduced to corresponding amines with sodium borohydride in methanol These ligands, N, N‟-(aryl)benzyaldiamine ligands (H-BENH), N, N‟-bis(cinnamaldiimine)ligands (CA2EN) were reacted with copper(II) dihalide and copper(I) monohalide ions respectively to form complexes. The ligands and their complexes were analysed using elemental analyses, FT-IR spectroscopy (mid-IR), UV/vis in aprotic and protic solvents,while mass spectrometry, 1H-NMR and 13C-NMR were used to further analyse the ligands. By using substituent parameters, both the single and dual substituent parameters with the spectroscopic data obtained from the spectroscopic techiques mentioned above, it was hoped to monitor and determine whether the electronic effects (resonance or inductive effcets) was predominantly within the Schiff base ligands and copper complexes. The NMR studies with dual substituent parameters suggest that the effects of the substituents are transimitted through the ligands, via resonance effects and that the phenyl group is nonplanar with the azomethine in N, N‟-(aryl)benzyaldiimine ligands. The presence of an extra double bond in Schiff base {(N, N‟-bis(cinnamaldiimine) ligand)} altered the electron density. The UV/vis studies showed that the symmetry of the N, N‟-bis(4-R-benzyl)-1, 2-diaminoethanedihalidecopper(II) complexes were predominantly tetrahedral for both chloro and bromo complexes. The correlation studies from mid-infrared were beneficial in monitoring the effect experienced by N, N‟-(aryl)benzaldiimine ligands, the studies suggest that the inductive effect is more pronounced at the C=N.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
The neglected diseases are a group of diseases with a higher incidence in poor regions and tropical or subtropical climate. The leishmanioses are listed in this group of diseases, which may present themselves in two ways: tegumentary leishmaniasis or Visceral Leishmaniasis (VL). The VL in the new world has as the etiology Leishmania chagasi, which is transmitted by the bite of the sandfly, especially Lutzomya longipalpis. There are some medications used for the treatment of VL, however, still there are recurrence rates and high mortality. In addition to the severe side effects related to these therapies, as Nephrotoxicity, hepatotoxicity and cardiotoxicity. Not long ago it was developed the amphotericin B encapsulated the Liposomes, associated with mild side effects, however still with an onerous cost, being hard to use in regions devoid of resources. In this work we aim to evaluate the activity of 15 compounds with Schiff bases complexed or not the metals (copper, nickel, zinc and iron), to inhibit promastigotes of Leishmania chagasi in vitro, as well as the cytotoxicity of these front of macrophages and fibroblasts in vitro. For tests with the promastigotas 24 hour incubation was carried out to evaluate the feasibility of resazurin method was used. To evaluate the cytotoxicity of compounds was incubated for 24 or 48 hours, using the colorimetric method with MTT. Of the 15 compounds evaluated, 11 showed good activity in inhibiting the promastigotas in the concentrations tested, the cytotoxicity performed with these 11 compounds. Copper complexes (D1, D2, D3) presented best activities when compared with their respective free ligands. However, they also showed cytotoxicity. The compounds complexed with iron (C1 and C3) also showed activity against the promastigotes, showing no or low cytotoxicity front cells, except the C1 that presented certain toxicity front of macrophages. The Methoxy group was what showed best activity when compared to the other free ligands. Generally the free ligands, without metals, were the ones who presented lower cytotoxicity.
As Doenças Negligenciadas são um grupo de doenças com maior incidência em regiões pobres e de clima tropical ou subtropical, para quais existem pouco investimento das indústrias farmacêuticas na busca por novos fármacos. As Leishmanioses estão listadas nesse grupo de doenças, podendo se apresentar de duas formas: Leishmaniose Tegumentar ou Leishmaniose Visceral (LV). A LV no novo mundo tem como etiologia a Leishmania chagasi, sendo esta transmitida pela picada do Flebotomíneo, principalmente a Lutzomya longipalpis, no Brasil. Alguns medicamentos são utilizados para o tratamento da LV. Contudo, ainda há taxas de recidiva e de letalidade altas. Além disso, apresentam efeitos colaterais severos relacionados a essas terapias, como nefrotoxicidade, hepatotoxicidade e cardiotoxicidade. Dessa forma, nesse trabalho tivemos como objetivo avaliar a atividade de 15 compostos de bases de Schiff complexados ou não a metais (cobre, níquel, zinco e ferro) em inibir promastigotas de Leishmania chagasi in vitro. E ainda, determinar a citotoxicidade destes compostos em macrófagos e fibroblastos, in vitro. Para os ensaios com as promastigotas foi realizado incubação de 24 horas e para avaliação da viabilidade foi utilizado o método da resazurina. Para avaliação da citotoxicidade dos compostos contra macrófagos e fibroblastos, a incubação foi durante 24 ou 48 horas, utilizando o método colorimétrico MTT. Nossos resultados demonstraram que dos 15 compostos avaliados, 11 apresentaram boa atividade em inibir as promastigotas nas concentrações testadas, sendo a citotoxicidade realizadas apenas com estes 11 compostos. Os complexos com cobre (D1, D2, D3) apresentaram melhores atividades quando comparados com seus respectivos ligantes livres. Todavia, estes também apresentaram citotoxicidade contra células avaliadas. Entretanto, os compostos complexados com ferro (C1 e C3) também apresentaram atividade contra as promastigotas, no entanto, apresentaram baixa citotoxicidade frente as células, exceto o C1 que apresentou toxicidade discreta frente a macrófagos. O grupo methoxy foi o que apresentou melhor atividade quando comparado com os outros ligantes livres. Assim, nossos dados sugerem que esses compostos complexados com Fe, principalmente o composto C3, podem ser promissores na busca por compostos para o tratamento da Leishmaniose Visceral. Estudos futuros in vitro, com formas amastigotas, e em animais poderão comprovar sua eficácia em ensaios pré-clínicos.

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciencias Fisicas e Matematicas
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Os compostos imínicos possuem reatividade semelhante a dos compostos carbonílicos, ambos apresentam ligações heteropolares insaturadas. No entanto, comparando-se os sistemas carbonílicos com os iminicos, observa-se que existem poucos estudos sobre a reatividade dos compostos iminicos. Investigou-se no presente trabalho reações de adição de um composto apresentando um grupo metilênico ativo a Bases de Schiff. O composto com metilênico ativo utilizado foi o ácido de Meldrum, que se destaca pela sua versatilidade em síntese orgânica. Foram preparadas Bases de Schiff aromáticas substituídas nas partes benzal e anilínica da molécula, sendo estes compostos utilizados nas reações de adição envolvendo o ácido de Meldrum. O produto obtido da reação de adição do ácido de Meldrum a N-benzilidenanilina foi submetido a reação de metanólise descarboxilativa. Todos os compostos obtidos foram caracterizados por técnicas espectroscópicas de IV, RMN de l H e quando necessário por análise elementar (CHN).

A enzima peroxidase (HRP) , agindo como uma oxigenase em substratos apropriados, promove a formação de espécies excitadas no estado triplete. Estes produtos excitados podem ser formados em sistemas bioquímicos e promover processos fotoquímicos no escuro. Nesta linha de estudos, investigamos a oxidação aeróbica, na presença de HRP, de substratos contendo ligações de Schiff. Esses compostos são de grande importância biológica, uma vez que participam como intermediários em diversas reações enzimáticas (transaminação, biossíntese de aminoácidos, biossíntese de profirinas), nas ligações cruzadas do colágeno e da elastina, na hemoglobina AlC, na rodopsina e bacterionodopsina e como produtos finais da lipoperoxidação. A oxidação aeróbica de quatro iminas alifáticas (BPA, i-BMA, sec-BMA e BVA) , catalisada por HRP, é quimiluminescente. A natureza triplete da espécie excitada foi sugerida pelo espectro de quimiluminescência, por meio de estudos de transferência de energia para DBAS e clorofila e pela supressão de quimiluminescência por oxigênio, sorbato, indol e p-benzoquinona. Com base nos altos valores de kETo encontrados, concluimos que a transferência de energia esteja ocorrendo provavelmente por um mecanismo a longa distância. A análise dos produtos da reação e os dados cinéticos indicam que a reação ocorre provavelmente segundo a via: (VER Esquema no arquivo) Ressalta-se que esta reação constitui um modelo mais adequado para sistemas bioluminescentes do que o proposto por McCapra e Burford (1976) com bases de Schiff aromáticas em t-butóxido e DMSO. Os sistemas aqui descritos também apresentam a possibilidade de desenvolvimento de método analítico, empregando quimiluminescência, para detectar formação de bases de Schiff em sistemas biológicos. Os estudos com base de Schiff alifáticos (sistemas modelo) foram estendidos para adutos contendo ligação de Schiff entre glicolaldeído e aminoácidos (Lys, Arg, His e Phe) ou proteínas (lisozima, BSA e protaminas). Todos os sistemas estudados são quimiluminescentes na presença de HRP; a fluorescência característica da formação do aduto decai concomitantemente com a emissão de luz; e, durante a reação, a peroxidase encontra-se principalmente na forma de composto II. Observa-se também transferência de energia dos sistemas glicolaldeído-lisozima/HRP/O2 e glicolaldeídoprotamina/HRP/O2 para clorofila. Estes estudos têm grande interesse do ponto de vista da toxicidade associada à ingestão de álcool etílico, a qual, segundo trabalhos recentes da literatura, é atribuída à formação de bases de Schiff entre proteínas de membranas e acetaldeído. E notável também, a formação de iminas durante o processo de lipoperoxidação e a quimiluminescência que o acompanha. Nossos dados levantam a possibilidade de que a toxicologia do álcool pode envolver espécies eletronicamente excitadas formadas na oxidação aeróbica dos adutos aldeído-proteínas.
Horseradish peroxidase (HRP) , acting as an oxigenase on various substracts, promotes the generation of electronically excited triplet species. These species can also be formed in many biochemical reactions and drive photochemical processes in the absence of light. Enlighted by this hypothesis (photobiochemistry in the dark) we have investigated the HRP-catalyzed aerobic oxidation of substrates containing Schiff linkage. These compounds are of utmost biological importance as they participate as intermediates of several enzymatic reactions (transamination, amino-acid biosyntheses, porphyrin biosyntheses, a.s.o.), in the crosslinking of collagen and elastin, in hemoglobin AlC, in rhodopsin and bacteriorhodopsin, and as final products from lipid peroxidation. The aerobic oxidation of four aliphatic imines (BPA, i-BMA, sec-BMA and BVA) , catalyzed by HRP, has been shown to be chemiluminescent. The triplet nature of the products is suggested by the chemiluminescence spectrum, by energy transfer studies to DBAS and chlorophyll a and by quenching of the chemiluminescence by molecular oxygen, sorbate ion, indol and p-benzoquinone. Based on the high values of ETTo found in these experiments we have concluded that the energy transfer process occur through a long range mechanism. Analyses of the products found in the spent reaction mixtures and the kinetic data indicate that the reaction follows the route: (SEE scheme file) We stress that this reaction constitutes a more realistic model for bioluminescent systems than that reported by McCapra and Burford (1976), which uses aromatic Schiff bases in DMSO/t-butoxi. In addition, the reaction described here point out for the possible development of chemiluminescent analytical procedure to detect the formation of Schiff bases in biological systems. Our studies on aliphatic Schiff bases were extended to adducts of both amino acids (Lys, Arg, His and Phe) and proteins (lyzozyme, bovine serum albumin and fish protamins) with glycolaldehyde. All these adducts are chemiluminescent when exposed to HRP in an aerated buffered solution. The fluorescence typical of the adducts decays concomitantly with light emission and, during the reaction, the enzyme remains predominantely in the form of HRP Compound II. Energy transfer to chlorophyll a from the systems glycolaldenyde-lyzozyme/O2/HRP and glycolaldehyde-protamine/ 02/HRP occur. These studies are relevant with respect to the toxicity associated to ethyl alcohol intake which, according to recent reports, is attributed to the formation of Schiff linkages between membrane proteins and acetaldehyde. Also noteworthy is the formation of imines along lipid peroxidation and the accompanying chemiluminescence. Our data raise the hypothesis that the alcohol toxicology may involve generated electronically excited species formed during aerobic oxidation of protein-aldehyde adducts.

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Fundação de Amparo a Pesquisa e ao Desenvolvimento Científico e Tecnológico do Maranhão
The vanadium complexes of the type [VO(acac)2], [VO(acac)(apftsc)], [VO(acac)(apmtsc)], [VO(acac)(aptsc)], [VO(acac)(apf)], vanadium (IV) and [VO2(apftsc)], [VO2(apmtsc)], [VO2(aptsc)] e [VO2(apf)], vanadium (V), were used as catalysts for cyclohexane oxidation using 30% hydrogen peroxide (H2O2) as oxidizing agent in acetonitrile at 40ºC. The cyclohexanol (OL) and cyclohexanone (ONA) were quantified by means of gas chromatography by the internal padronization method. Variation in the molar ratio of oxidizing, substrate and nitric acid with catalyst, as well as the effect of the addition of triphenylphosphine in catalytic properties were studied for all complexes. For the complex [VO(acac)(apftsc)], yielded the kinetic parameters with rate constant (k = 3,87 x 10-1 L.mol-1.min-1), reaction order relative to catalysts (nCat = 0,8) and to substrate (nS = 0,6); the thermodynamic parameters of activation Eap = 11 kcal.mol-1, ΔG# = + 0.6 kcal.mol-1, ΔH# = + 10.2 kcal.mol-1, ΔS# = + 30.8 cal.mol-1.K-1. The EPR spectrum data using 5,5-dimethyl-1-pyrroline Noxide (DMPO) as spin trap confirm that the mechanism the formation of radicals. The radicals ( acac) and hydroxyl ( OH) from the acetylacetonate e and hydrogen peroxide, respectively, was identified by forming the respective adduct, DMPO-Acac and DMPO-OH. From the mass spectrometry data it was possible to suggest a synthetic route for the formation of the oxo(peroxo)vanadate complex, an important intermediate in the catalytic cycle. It has been proposed also a mechanism for cyclohexane oxidation.
Os complexos de vanádio do tipo [VO(acac)2], [VO(acac)(apftsc)], [VO(acac)(apmtsc)], [VO(acac)(aptsc)], [VO(acac)(apf)] de vanádio (IV) e [VO2(apftsc)], [VO2(apmtsc)], [VO2(aptsc)] e [VO2(apf)] de vanádio (V), foram utilizados como catalisadores para a oxidação do cicloexano, utilizando o peróxido de hidrogênio (H2O2) a 30% como oxidante, em acetonitrila a 40ºC. O cicloexanol (OL) e a cicloexanona (ONA), foram quantificados por Cromatografia a Gás, por padronização interna. Variações nas razões molares entre oxidante, substrato e ácido nítrico com o catalisador, bem como o efeito da adição de trifenilfosfina nas propriedades catalíticas foram estudadas para todos os complexos. Para o complexo [VO(acac)(apftsc)], obteve-se os parâmetros cinéticos de constante de velocidade (k = 3,87 x 10-1 L.mol-1.min-1), ordem de reação em relação ao catalisador (nCat = 0,8 ) e ao substrato (nS = 0,6 ); os parâmetros termodinâmicos de ativação de Eap = 11 kcal.mol-1, ΔG# = + 0,6 kcal.mol-1, ΔH# = + 10,2 kcal.mol-1. ΔS# = + 30,8 cal.mol-1.K-1. Os espectros de EPR, utilizando 5,5 dimetil-1-pirrolina-N-óxido (DMPO) como spin trap confirmam um mecanismo radicalar. Os radicais ( acac) e ( OH) provenientes do acetilacetonato e H2O2, respectivamente, foram identificados através da formação dos respectivos adutos DMPO-Acac e DMPO-OH. A partir dos resultados de espectrometria de massas em modo positivo (ESI+) foi sugerida uma rota de síntese para o complexo oxo(peroxo)vanadato, intermediário importante no ciclo catalítico. Foi proposto também um mecanismo para a oxidação do cicloexano.

Neste trabalho estudamos propriedades estruturais, magnéticas e eletrônicas de complexos de cobre em duas classes de ligantes semelhantes com potenciais aplicações nas áreas de nanotecnologia e farmacologia. A primeira classe de ligantes é do tipo bases de Schiff, conhecidas por sua vasta gama de aplicações em química e biologia, aqui estudadas como miméticos de sítios de proteínas e também como potenciais metalo-fármacos. Procuramos investigar as características estruturais e eletrônicas buscando correlacionar as informações obtidas experimentalmente com as obtidas através de cálculos de estrutura eletrônica. Em especial, no estudo da competição pelo íon Cu entre as bases de Schiff e a proteína albumina, mostramos a influência de diversos fatores como, por exemplo, a geometria dos ligantes e a sua estrutura eletrônica. A segunda classe estudada é constituída de bases modificadas de DNA com a habilidade de complexar metais (espécie [M-DNA]) e formar estruturas com acoplamento ferromagnético. Observamos para as espécies [M-DNA] que o acoplamento ferromagnético é estabilizado através de dois efeitos: a) diferentes estados de carga que podem gerar distorções na coordenação quadrado planar; b) a adição do backbone do DNA. Utilizamos neste estudo o método Projector Augmented Wave (PAW) e também bases locais dentro da Teoria do Funcional da Densidade, atrav´es dos c´odigos computacionais CP-PAW e Gaussian03.
We studied structural, electronic and magnetic properties of copper complexes with two similar classes of ligands with potential applications in nanotechnology or pharmacology. The first class of compounds consists of Schiff bases and corresponding copper complexes. We investigated structural and electronic properties of these complexes searching for correlations among the information obtained experimentally and by electronic structure calculations. In special, in the study of the competition for the Cu ion between Schiff bases and the albumin protein, we show the influence of different factors such as the geometry of the ligands and their electronic structure. The second class of ligands focused in our studies are modified DNA bases coordinated to copper, where EPR studies have shown ferromagnetic interactions among the metal centers. We studied in this case the influence of the charge state and of the backbone in the magnetization of the Cu chain. In all cases presented here, we used ab-initio electronic structure calculations in the framework of the Density Functional Theory (DFT). This has been done using the CP-PAW code and the Gaussian03 code.

La double condensation de la 2-thénoyltrifluoroacétone (TTAH) avec les diamines primaires ne conduit pas aux bases de Schiff symétriques attendues mais dans le cas de l’éthylènediamine (en) à un mélange formé de l’éthylène-bis(trifluoroacétamide) et de la 7-(thiophène-2-yle)-5-(trifluorométhyle)-2,3-dihydro-1H-1,4-diazépine, alors qu’à partir de l’o-phénylènediamine seule la 4-trifluorométhyle-2-(thiophène-2-yle) -1,5-benzodiazépine est isolée. La réaction de condensation entre l’éthylènediamine et un complexe template [M(TTA)2(S)2] (M = Co, Ni, Cu) conduit exclusivement aux complexes octaédriques correspondants [M(TTA)2(en)], dans lesquels l’éthylènediamine est coordonnée au métal. Les coordinats bases de Schiff symétriques [H2N2O2], porteurs des unités 2-thiényles et trifluorométhyles, sont préparés en deux étapes : a) double condensation de l’acétyle thiophène avec l’éthylènediamine pour générer la diimine, puis b) traitement de cette dimine par l’acide trifluoroacétique. Dans les complexes bases de Schiff correspondants de Co(II), Ni(II) et Cu(II), le métal adopte une géométrie plan carré et est coordiné par les atomes d’azote et d’oxygène de l’entité dianionique tétradentate [N2O2]2-. Ces complexes, tout comme leurs homologues où le groupe CF3 a été substitué par l’entité 4-fluorophényle, sont inertes vis-à-vis de l’électropolymérisation. Par contre, la substitution du groupe CF3 par le groupe méthyle permet d’observer l’électropolymérisation des dérivés respectifs avec formation d’un dépôt isolant qui passive l’électrode et empêche la propagation de la polymérisation. En revanche, l’insertion d’une entité p-phénylène conjuguée entre le groupe thiophène et le fragment [M(N2O2)] porteur des substituants trifluorométhyles permet de mettre en évidence l’électropolymérisation de complexes bases de Schiff plan carré symétriques de Ni(II) et Cu(II) avec dépôt d’un film conducteur sur l’électrode
The one-pot double condensation reaction of 2-thenoyltrifluoroacetone (TTAH) with primary diamines does not lead to the formation of the expected symmetric Schiff bases, but in the case of ethylenediamine (en) to a mixture of bis(trifluoroacetamide)ethylene and 7-(thiophene-2-yl)-5-(trifluoromethyl)-2,3-dihydro-1H-1,4-diazepine derivatives, while only 4-trifluoromethyl-2-(thiophen-2-yl)-1,5-benzodiazepine was isolated starting from o-phenylenediamine. The templated condensation reaction between ethylenediamine and bis(β-diketonate)metal complexes [M(TTA)2(S)2] (M = Co, Ni, Cu) gave exclusively the corresponding octahedral compounds [M(TTA)2(en)], where the ethylenediamine ligand chelates the metal center. The symmetrical Schiff base ligands [H2N2O2] bearing the 2-thienyl and the trifluoromethyl groups were prepared in two steps by (i) double condensation of acetylthiophene and ethylenediamine to generate the expected diimine, and (ii) treatment of the diimine with trifluoroacetic acid. In their corresponding Schiff base complexes of Co(II), Ni(II) and Cu(II), the metal ion is tetracoordinated in a square-planar environment. The coordination sphere is formed by the nitrogen and oxygen atoms of the dianionic tetradentate [N2O2]2- ligand. Those complexes as well as their analogues in which the CF3 group has been substituted for the 4-fluorophenyl unit, are inert toward electropolymerization. By contrast, replacement of the CF3 group by the parent methyl one allows electrochemical oxydation of the respective complexes and formation of an isolating deposit with passivation of the electrode and inhibition of the propagation of the polymerization. Interestingly, insertion of a conjugated p-phenylene unit between the 2-thienyl group and the CF3-substituted [M(N2O2] core permits the generation of a polythienyl-containing square planar Schiff base complexes of Ni(II) and Cu(II) films, and their deposition on an electrode using an electrochemical oxidation process

La demarche suivie dans cette these a ete d'utiliser des reactions simples et bien connues de la chimie organique pour acceder a des molecules originales et particulierement complexes. Nous presentons dans le premier chapitre une mise au point bibliographique exhaustive sur les phosphorhydrazones puis nous abordons notre travail a travers trois chapitres qui montrent la complexite croissante des molecules que nous avons isolees. Le deuxieme chapitre decrit la synthese et la reactivite des molecules les plus simples, des n-methylenehydrazones stables que nous avons pour la premiere fois caracterisees par diffraction des rayons-x. Le troisieme chapitre concerne la synthese de divers types de macrocycles phosphores qui contiennent tous quatre enchainements phosphorhydrazone dans la chaine macrocyclique. Dans le quatrieme chapitre, nous decrivons les etapes de synthese qui permettent d'obtenir des polymeres possedant une architecture complexe mais parfaitement definie: des dendrimeres construits a partir de fragments phosphorhydrazone. Toutes les parties experimentales sont rassemblees dans le chapitre cinq

Pluisieurs molécules nouvelles ont été obtenues à partir du Gossypol, extrait des graines de cotonnier. Dans la première partie, de nouvelles bases de Schiff du gossypol et de la gossypolone ont été synthétisées, les énantiomères du gossypol et leurs bases de Schiff sont optiquement stables, tandis que, les énantiomères de la gossypolone ne sont pas stables à température ambiante, mais il est possible de les observer vers OʿC. La cytotoxicité de ces bases de Schiff a été évaluée principalement sur des cellules KB, la méthylimine et l'éthylimine de la gossypolone sont les plus toxiques (IC50= 0. 8 et 1. 2 mM). La toxicité du gossypol et de la gossypolone augmente quand les tests sont effectués en absence de sérum et elle diminue en présence de catalase ou de mannitol dans le milieu de culture. L'énantiomère (-)-gossypol est plus toxique que le (+)-qossypol; ceci est aussi valable pour les bases de Schiff des énantiomères du gossypol. Dans la deuxième partie, une nouvelle classe de dérivés du gossypol et de la gossypolone, les dithianes et les dithiolanes, a été développée. Les dithianes/dithiolanes du gossypol et de la gossypolone ont été synthétisés par action de dithiols en présence d'éthérate de trifluorobarate. La même réaction effectuée avec les monothiols, conduit à des mélanges complexes. L'action du propanedithiol ou de l'ethanedithiol sur le tetraméthyle ou l'hexaméthyle éthers du gossypol ne conduit pas aux dithianes ou dithiolanes attendus mais à de nouveaux dérivés cycliques. La toxicité de ces nouveaux thiodérivés sur les cellules KB est assez modeste, mais sous l'action de NO ou d'un sel de nitrosonium, ces dérivés se transforment en dérivés plus toxiques dans le ces du gossypol ou régénèrent la molécule de départ dans le cas de la gossypolone. Nous formulons l'hypothèse que dithianes et dithiolanes du gossypol et de la gossypolone pourraient être des modèles de prodrogues ciblées sur les cellules exprimant de fortes concentrations d'oxyde nitrique
New Schiff bases of racemic gossypol and gossypolone and of (+)- or (-)-gossypol enantiomers are described. Schiff bases obtained from gossypol enantiomers are optically stable at room temperature whereas gossypolone Schiff bases racemize quickly and may be observed only at lower temperatures. Their cytotoxic activities on KB human cancer cells were determined : the methylimine and ethylimine derivatives of racemic gossypolone were the most active compounds, and the cytotoxicity of racemic gossypol and gossypolone was increased when the tests were performed in the absence of serum and decreased when catalase as well as mannitol were added to the culture medium. (+)-gossypol and (-)-gossypol derivatives displayed higher toxicities on KS and MCF7 cells than the corresponding (+) isomers. New derivatives of gossypol and gossypolone: dithianes or dithiolanes, were synthesized using dithioethane or dithiopropane in the presence of BF3. Et2O. Furthermore, the same reaction conditions with tetramethyl or hexamethyl ethers of gossypol lead to cyclic thioderivatives. These thioderivatives exhibited very low toxicity in KB cells. This masking of the aldehyde groups may be reverted by the use of electrophiles such as nitroxide ions, nitrosonium tetrafluoroborate which regenerate gossypolone or transform thiogossypols in new compounds, more toxic. Since toxicities of the derivatives issued from nitrosonium tetraf luoroborate action or nitric oxide plus ferric ion are increased, these results support the hypothesis that gossypol and gossypolone dithiane and dithiolanes could be proposed as prodrugs targeted against cells that express or are surrounded by high concentrations of nitric oxide, for instance, tumor cells

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A investigação de sistemas catalíticos duais capazes de mediar as reações de polimerização por abertura de anel via metátese (ROMP) e de polimerização radicalar por transferência de átomo (ATRP) simultaneamente é de grande interesse e importância na obtenção de novos materiais com potencial de aplicação. Neste estudo, novos complexos de rutênio(II) coordenados a diferentes bases de Schiff derivadas de cicloalquilaminas (ciclopentil 1a, cicloexil 1b, cicloheptil 1c e ciclooctil 1d) foram sintetizados: [RuCl(CyPen-Salen)(PPh3)2] 2a, [RuCl(CyHex-Salen)(PPh3)2] 2b, [RuCl(CyHep-Salen)(PPh3)2] 2c e [RuCl(CyOct-Salen)(PPh3)2] 2d. As bases de Schiff e seus respectivos complexos de rutênio foram caracterizados por FTIR, UV-Vis, RMN e voltametria cíclica. Os complexos planejados foram avaliados como precursores catalíticos em reações de ROMP de norborneno (NBE) e em reações de ATRP de metacrilato de metila (MMA). As sínteses de polinorborneno (poliNBE) via ROMP com os complexos 2a-d como pré-catalisadores foram avaliadas sob diferentes condições de reação ([HCl]/[Ru], [EDA]/[Ru], [NBE]/[Ru] e temperatura). Os melhores rendimentos de poliNBE foram obtidos a 50 °C com razão molar [NBE]/[HCl]/[Ru] = 5000/25/1 na presença de 5 µL de EDA por 60 minutos. A polimerização de MMA via ATRP foi conduzida usando os complexos 2a-d na presença de etil-α-bromoisobutirato (EBiB) como iniciador. Os testes catalíticos foram avaliados em função do tempo de reação usando a razão molar [MMA]/[EBiB]/[Ru] = 1000/2/1. Todos os experimentos via ATRP foram conduzidos à 85 °C. A correlação linear do ln([MMA]0/[MMA]) em função do tempo na ATRP de MMA mediada pelos complexos 2a-d indica que a concentração de radicais permanece constante durante a polimerização. As massas moleculares aumentaram linearmente com a conversão com a diminuição dos valores de IPD, no entanto, as massas moleculares experimentais foram maiores do que as massas moleculares teóricas.
The investigation of dual catalytic systems able to mediate simultaneously ring-opening metathesis polymerization (ROMP) and atom-transfer radical polymerization (ATRP) reactions is of great interest and importance in obtaining new materials with potential for application. In the study, ruthenium(II) complexes of Schiff base derived from cycloalkylamines (cycloalkyl = cyclopentyl 1a, cyclohexyl 1b, cycloheptyl 1c and cyclooctyl) 1d were synthesized: [RuCl(CyPen-Salen)(PPh3)2] 2a, [RuCl(CyHex-Salen)(PPh3)2] 2b, [RuCl(CyHep-Salen)(PPh3)2] 2c and [RuCl(CyOct-Salen)(PPh3)2] 2d. The Schiff bases 1a-d and their respective RuII complexes 2a-d were characterized by FTIR, UV-Vis, NMR, and cyclic voltammetry. The complexes 2a-d were evaluated as catalytic precursors for ROMP of norbornene (NBE) and for ATRP of methyl methacrylate (MMA). The syntheses of polynorbornene (polyNBE) via ROMP with complexes 2a-d as pre-catalysts were evaluated under different reaction conditions ([HCl]/[Ru], [EDA]/[Ru], [NBE]/[Ru], and temperature). The highest yields of polyNBE were obtained with [NBE]/[HCl]/[Ru] = 5000/25/1 molar ratio in the presence of 5 µL of EDA for 60 minutes at 50 °C. MMA polymerization via ATRP was conducted using the complexes 2a-d in the presence of ethyl-α-bromoisobutyrate (EBiB) as initiator. The catalytic tests were evaluated as a function of the reaction time using the initial molar ratio of [MMA]/[EBiB]/[Ru] = 1000/2/1 at 85 °C. The linear correlation of ln([MMA]0/[MMA]) and time clearly indicates that the concentration of radicals remains constant during the polymerization and that the ATRP of MMA mediated by 2a-d proceeds in a controlled manner. Molecular weights increased linearly with conversion, however, the experimental molecular weights were higher than the theoretical ones.

Ce travail concerne l'etude d'especes organometalliques stables des types >m, >m = y (y = o, s, se, n-sime 3) et (>m) nm (m : metal de transition) a metal 14 a coordinence non usuelle. Le premier chapitre est une mise au point bibliographique concernant les basses coordinences stables des types > m et (> m) nm (m = ge, sn, pb). Le deuxieme chapitre concerne la synthese et l'etude physicochimique des nouvelles especes divalentes l 2m (m = ge, sn, pb ; l 2 = base de schiff). Les donnees spectroscopiques soulignent la coordination intramoleculaire n-m-n. Des reactions de cycloaddition et la structure rx de l'adduit (salen)sn-3,5-di-tert-butyl-1,2-benzoquinone sont presentes. Des insertions d'aldehydes ou de clivage par des acides organiques et des chlorures d'acides conduisent, a partir de (salen)m, a de nouveaux composes divalents heteroleptiques. Le troisieme chapitre concerne les complexes (salen)m nm(co) 6 - n (m = ge, sn, pb ; m = cr, w, n = 1, 2) 2. Les structures rx indiquent le caractere double de la liaison sn = m. Les complexes (salen)m = m(co) 5 (m = ge, sn ; m = cr, w) conduisent, par des reactions de cycloaddition et de substitution de ligands, a de nouvelles especes a enchainement p-w-sn ou a des composes trimetalles sn-m-sn (m = cr, w). Le quatrieme chapitre decrit les complexes (salen)m = mncp(co) 2 (m = ge, sn, pb), (salen)sn = fe(co) 4 et leurs structures rx. Le caractere double de la liaison (salen)m-ml n, du au caractere -donneur et au fort caractere -accepteur de (salen)m, est demontre par l'obtention de la plus courte liaison sn-mn connue dans (salen)sn = mn(cp)(co) 2. La position axiale de (salen)sn dans la structure de (salen)sn = fe(co) 4 demontre que (salen)sn est plus -donneur que -accepteur vis-a-vis du fer. Le cinquieme chapitre traite de la reactivite des especes divalentes (salen)m vis-a-vis d'oxydants conduisant a de nouvelles especes insaturees de type (salen)m = y (m = ge, sn ; y = s, se, n-sime 3) ; certains aspects de leur reactivite sont egalement presentes. La derniere partie concerne des transferts de ligands entre (salen)sn et des composes halogenes (bf 3. Me 2o, cp 2ticl 2, nicl 2. Dppe, pcl 3, tbupcl 2, cl 3p = x (x = o, s)) conduisant a de nouveaux composes lineaires ou cycliques a ligand salen du bore, du titane, du nickel et du phosphore (neutres ou cationiques).

Nos últimos anos, têm-se notado o aumento do número de pesquisas relacionadas aos complexos de metais de transição com base de Schiff devido a suas interessantes estruturas e amplas aplicações, isso se deve em parte a formação de complexos estáveis, apresentando um papel importante na química de coordenação. A determinação estrutural dos átomos nas moléculas é necessária para que suas propriedades químicas, físicas e biológicas possam ser compreendidas. Para esta finalidade, existe uma grande variedade de técnicas químicas e físicas, na qual podemos citar a Difração de Raios X. Os avanços computacionais dos últimos anos e sua agregação na ciência, proporcionou um crescimento nas pesquisas que utilizam métodos teóricos, pois possibilitou sua aplicação em diversas áreas que dependiam de tão evolução para continuação de seus estudos. Vale ressaltar, que o uso de cálculo teórico têm apresentado um grande interesse pelos pesquisadores da área da Química, seja para a compreensão das suas estruturas ou para o estudo dos mecanismos de reações. Logo, o objetivo desse trabalho é a investigação estrutural de bases de Schiff, através da determinação das estruturas cristalinas por difração de raios-X. A partir dos dados cristalográficos foram avaliados parâmetros geométricos, interações intermoleculares, onde ambos os dados foram comparados com os da literatura obtendo resultados satisfatórios. A estrutura ASZ, apresentou estrutura semelhante com a esperada, obtendo-se índices de discordância R = 0,0774, wR2 = 0,2302, o que caracteriza um refinamento eficiente. A molécula possui um eixo cristalográfico de ordem 2 e grupo pontual 2/m. O complexo Zn(apy-epy), obteve bons índices de discordância R = 0,0621, wR2 = 0,2172, centrossimétrica, apresentando grupo pontual mmm com eixo de ordem 2. O átomo central de zinco tem geometria bipiramidal ligada a 6 átomos de nitrogênio. O ligante CW2-10A, foi a estrutura que obteve o melhor valor de discordância R = 0,0348, wR2 = 0,0902 e grupo pontual 2/m. A estrutura determinada, estava de acordo com o esperado. A estrutura final do complexo com sigla CuDenim, estava de acordo com o proposto, com um índice de discordância satisfatório R = 0,0746, wR2 = 0,2122, também apresentou uma interação do metal Cu com átomos de oxigênio do íon perclorato. O complexo CW1-53A, possui alguns átomos desordenados e foi preciso que fossem refinados isotropicamente, apresentou índices de discordância dentro do ideal R = 0,0436, wR2 = 0,1227. Os cálculos de frequência vibracional não identificaram frequências imaginárias para nenhuma das estruturas otimizadas. A estabilidade química foi explicada pelo gap HOMO-LUMO, bem como os locais de interações intermoleculares foram explicados através dos mapas de superfície Hirshfeld e pelo mapa de potencial eletrostático.
In recent years, has been an increase in studies related with Schiff-bases transition metal complexes due to their interesting structures and wide applications. One reason for this is the formation of stable complexes, presenting an important role in coordination chemistry. The structural determination of the atoms in the molecules is necessary in understanding in their chemical, physical and biological properties. For this purpose, there is a great variety of chemical and physical techniques, in which we can mention X-ray Diffraction. The computational advances of the last years and their aggregation in science, provided to growth in the researches that use theoretical methods, as it allowed its application in several areas that depended on so to continue their studies. It is worth mentioning that the use of theoretical calculus has shown a great interest by researchers in the field of Chemistry, either to understand their structures or to study the mechanisms of reactions. Therefore, the objective of this work is the structural investigation of Schiff bases, through the determination of the crystalline structures by X-ray diffraction. Where all the structures presented good indexes of disagreement and the obtained structures were within the expected one. From the crystallographic data, geometric parameters, intermolecular interactions were evaluated, and both data were compared with those of the literature, obtaining satisfactory results. The structure ASZ, presented similar to the one expected, with discordance indices R = 0,0774, wR2 = 0.2302, therefore characterizing the refinement. The molecule has a crystallographic axis of order 2 and a point group 2 / m. The complex Zn (apy-epy), obtained good discordance indices R = 0.0621, wR2 = 0.2172, centrossimetric, presenting a point group mmm with axis of order 2. The central zinc atom has bipyramidal geometry attached to 6 nitrogen atoms. The ligand CW2-10A was the structure that obtained the best discordance value R = 0.0348, wR2 = 0.0902 and 2/m point group. The structure determined was as expected. The final structure of the complex with CuDenim acronym, was in agreement with the with satisfactory discordance index R = 0.0746, wR2 = 0.2122, also presented a Cu metal interaction with oxygen atoms of the perchlorate ion. The complex CW1-53A, has some disordered atoms and had to be refined isotropically. It presented disagreement indices within the ideal R = 0.0436, wR2 = 0.1277. The vibrational frequency calculations did not identify imaginary frequencies for any of the optimized structures. The chemical stability was explained by the HOMO-LUMO gap, as well as the sites of intermolecular interactions were explained through the Hirshfeld surface maps and the electrostatic potential map.

The present work involved the preparation and a study on the physicochemical properties and pharmacological activities of semicarbazones, thiosemicarbazones, hydrazones and their metal complexes. Since benzaldehyde semicarbazone (BS) presents anti-inflammatory and antinociceptive properties, including activities on central pain conditions, the analogues 2-, 3- and 4- hydroxybenzaldehyde semicarbazones (2-, 3- and 4-OHBS) were prepared in the present work. A study correlating NMR spectra, crystallography data and theoretical calculations of the conformational isomers energies and physicochemical properties of BS, 2-OHBS, 3-OHBS and 4-OHBS was performed. According to the results, 2-OHBS was the compound presenting the highest susceptibility to nucleophilic attack and subsequent hydrolysis. Besides, theoretical and experimental octanol-water partition coefficients are in accordance to higher hydrophobicity of BS and 2-OHBS in comparison with 3-OHBS and 4-OHBS. The antinociceptive and anti-inflammatory properties of 2-OHBS, 3-OHBS and 4- OHBS were evaluated in animal models using BS as positive control. Among the three isomers, only 2-OHBS presented statistically different antinociceptive effect in comparison to BS in Zymosan, formaldehyde and carrageenan-induced paw edema models. 2-OHBS inhibited exclusively the second phase of formaldehyde protocol, being characterized as an inhibitor of peripheral mechanisms of pain and inflammation. In contrast, BS acts on both, neurogenic (first) and inflammatory (second) phases of the formalin model. In order to correlate the biological activities of BS and 2-OHBS to their susceptibilities to hydrolysis and physicochemical properties, the immediate product of hydrolysis, semicarbazide, was evaluated in the formaldehyde and carrageenan-induced paw edema models. Semicarbazide is a well-known inhibitor of VAP-1, an enzyme strictly related to inflammatory processes. Results suggested that the peripheral activity of arilsemicarbazones, mainly in acute pain models, would be related to partial hydrolysis of the compounds, releasing semicarbazide in vivo. Besides, semicarbazide didnt present activity in neurogenic phase of the formaldehyde model, indicating that the activity of BS in first phase could be due to a particular mechanism, non-related to its hydrolysis. In a second step, the kinetics of hydrolysis of BS and 2-OHBS were evaluated in simulated gastric fluid in order to correlate their kinetic and thermodynamics (theoretical calculations) properties. Furthermore, the kinetics of hydrolysis of BS in its inclusion compound with .-cyclodextrin (BS.CD) and of BS mixed .CD were investigated in order to evaluate the influence of .CD on the semicarbazones pharmacokinetics. It was observed that the initial rate of hydrolysis of 2-OHBS was about 4-fold higher than that BS, confirming the tendency previously established by theoretical calculations. Thus, results suggest that 2-OHBS would be more susceptible to hydrolysis in comparison do BS, both kinetically and thermodynamically. The initial rate of hydrolysis of BS, BS.CD or a mixture of BS with .CD were statistically equivalent. Complexes of zinc(II) and gallium(III) with 2-OHBS were synthesized and evaluated as antifungal agents. Compounds were evaluated for their antifungal activities against Candida and Trychophyton rubrum strains and clinical isolates. The complex [Zn(2OBS)AcO] did not show significant activity. Besides, results for [Ga2(2OBS)3] suggested that the antifungal activity of the compound would be related to the metal itself. The antifungal activity of gallium nitrate decreased against four strains and clinical isolates of Trychophyton rubrum in the presence of increasing concentrations of iron nitrate suggesting that the mechanism of antifungal action of galium(III) could be related to replacement of iron(III) by galium(III) or to the disruption of iron-related redox processes in biological media. Results showed for the very first time the antifungal activity of galium(III) against Trychophyton rubrum. Since copper(II) and zinc(II) can be related to the aggregation process of amyloid. (A.) peptide in the brain of Alzheimers disease (AD) patients, the pentadentade chelators 2,6 diacetylpyridine bis(thiosemicarbazone) (DAPT), 2,6-diacetylpyridine bis(semicarbazone) (DAPS) and 2,6-diacetylpyridine bis(hydrazone) (DAPH) were prepared and evaluated in in vitro models of AD. DAPT and DAPH were insoluble in the turbidity test conditions, suggesting structural modifications of these compounds would be necessary in order to increase their solubility in aqueous medium. Results of the anti-aggregation assay using A.1-40 in the presence of metals showed that DAPS is able to inhibit peptides aggregation in turbidity test conditions. Transmission electron microscopy (TEM) images confirmed the results obtained in the turbidity test. These results showed the potential of bis(thiosemicarbazones), bis(semicarbazones) and bis(hidrazones) as promising chelating agents for AD therapy. The present work is an important contribution to the study of the role of Schiffs bases in Medicinal Chemistry, since these compounds proved to be potentially useful for the treatment of pain, inflammation, and Alzheimers disease.
O presente trabalho consistiu no preparo, estudo das propriedades físico-químicas e do perfil farmacológico de semicarbazonas, tiossemicarbazonas, hidrazonas e seus complexos metálicos. Uma vez que benzaldeído semicarbazona (BS) mostra atividades anti-inflamatória, antinociceptiva e contra a dor neuropática, foram preparados no presente trabalho os análogos 2-, 3- e 4-hidroxibenzaldeído semicarbazona (2-, 3- e 4-OHBS). Foi realizado um estudo correlacionando espectros de RMN, dados cristalográficos e resultados de cálculos teóricos das energias dos isômeros conformacionais mais estáveis e propriedades físico-químicas para BS, 2-OHBS, 3-OHBS e 4-OHBS. Concluiu-se que 2-OHBS seria o composto mais suscetível a um ataque nucleofílico e consequente à hidrólise. Valores de logP experimentais e calculados permitiram afirmar que BS e 2-OHBS são compostos mais hidrofóbicos que 3-OHBS e 4-OHBS. 2-OHBS, 3-OHBS e 4-OHBS foram avaliados em protocolos in vivo de caracterização das atividades antinociceptivas e anti-inflamatórias, utilizando BS como controle positivo. Apenas 2-OHBS induziu efeito antinociceptivo estatisticamente significativo quanto comparado a BS nos modelos do Zymosan, do formaldeído e do edema de pata induzido por carragenina. Na avaliação da atividade antinociceptiva no modelo do formaldeído, 2-OHBS inibiu apenas a segunda fase, caracterizando-se como um protótipo de fármaco com atividade anti-inflamatória e analgésica relacionadas a mecanismos periféricos, diferentemente de BS, que é ativo na fase neurogênica e na segunda fase do modelo. Com o objetivo de correlacionar as atividades biológicas de BS e 2-OHBS à suscetibilidade de hidrólise dos compostos e às suas propriedades físico-químicas, avaliou-se a atividade do produto de hidrólise semicarbazida nos modelos do edema em pata de rato e no modelo do formaldeído. A semicarbazida é um dos principais produtos de hidrólise das arilsemicarbazonas e um conhecido inibidor da enzima VAP-1, relacionada aos processos inflamatórios. Os resultados permitiram sugerir que a atividade periférica das arilsemicarbazonas, principalmente em modelos de dor aguda, estaria relacionada à hidrólise parcial do composto, formando semicarbazida in vivo. Paralelamante, a semicarbazida não apresentou atividade na fase neurogênica do modelo, reforçando a hipótese de que a atividade de BS na primeira fase estaria associada a um mecanismo não relacionado à hidrólise da semicarbazona. Em uma segunda etapa, foi avaliada a cinética de hidrólise de BS e 2-OHBS em meio gástrico simulado com o objetivo de relacionar os aspectos cinéticos aos termodinâmicos (cálculos teóricos) anteriormente discutidos. Além disso, avaliou-se a influência do composto de inclusão de BS em .-ciclodextrina (BS.CD) sobre a biodisponibilidade de BS após administração per os, na tentativa de elucidar a influência da .CD na farmacocinética da semicarbazona. Observou-se que a velocidade média de hidrólise de 2-OHBS foi aproximadamente quatro vezes superior à de BS, confirmando a tendência evidenciada nos cálculos teóricos e permitindo sugerir que, termodinâmica e cineticamente, 2-OHBS seria mais suscetível à hidrólise que BS. Na avaliação da influência de .CD no processo de hidrólise de BS, observou-se que as velocidades iniciais de hidrólise de BS, de BS no composto de inclusão BS.CD ou de BS simplesmente misturado a .CD são estatisticamente equivalentes. Complexos de 2-OHBS com zinco(II) e gálio(III) foram preparados, e avaliados quanto à sua atividade antifúngica em diferentes cepas e isolados clínicos de Candida e Trychophyton rubrum. O complexo [Zn(2OBS)AcO] não apresentou atividade significativa, ao passo que os resultados para o complexo [Ga2(2OBS)3] sugeriram que a atividade antifúngica do composto estaria relacionada exclusivamente ao metal. A atividade antifúngica de Ga(NO3)3 frente a quatro cepas/isolados clínicos de Trychophyton rubrum diminuiu na presença de concentrações crescentes de Fe(NO3)3, evidenciando que o mecanismo de ação antifúngica do gálio(III) poderia estar relacionado à substituição de ferro(III) por gálio(III) ou ao bloqueio de processos redox ferro-dependentes nos meios biológicos. Os resultados demonstraram, pela primeira vez na literatura, a atividade antifúngica do gálio(III) frente a Trychophyton rubrum. Uma vez que íons cobre(II) e zinco(II) poderiam estar associados à indução de agregação do peptídeo .-amilóide (.A) em cérebros de pacientes com a Doença de Alzheimer (DA), foram obtidos os agentes quelantes pentadentados 2,6 diacetilpiridina bis(tiossemicarbazona) (DAPT), 2,6 diacetilpiridina bis(semicarbazona) (DAPS) e 2,6 diacetilpiridina bis(hidrazona) (DAPH) para serem avaliados em modelos in vitro de DA. DAPT e DAPH mostraram-se insolúveis nas condições do teste de turbidez, sugerindo que modificações em suas estruturas seriam necessárias para aumentar a solubilidade. Os resultados dos testes de inibição da agregação do peptídeo .A1-40 induzida pelos metais mostraram que DAPS é capaz de inibir a agregação do peptídeo nas condições do teste. Imagens de microscopia eletrônica de trasmissão (MET) confirmaram a atividade anteriormente evidenciada pelo teste de turbidez. Estes resultados demonstraram o potencial de bis(tiossemicarbazonas), bis(semicarbazonas) e bis(hidrazonas) como agentes quelantes úteis na terapêutica da DA. O presente trabalho é uma importante contribuição ao estudo de bases de Schiff na Química Medicinal, uma vez que demonstrou que esses compostos seriam potencialmente úteis no tratamento da dor, inflamação e doença de Alzheimer (DA).

Some new acylpyrazolone Schiff bases have been synthesized from the condensation reaction of two acylpyrazolone diketone precursors with phenylhydrazine, 2,4-dinitrophenylhydrazine and sulfanilamide. They have been fully characterized by elemental analysis and spectroscopic techniques (IR,1H and 13C NMR, and mass-spectra). The single crystal structure of the benzoyl derivative acylpyrazolone Schiff bases have been obtained and analyzed by X-ray crystallography technique. Solid state X-ray diffraction revealed a keto tautomer Schiff base in solid state. Mn(II), Co(II), Ni(II) and Cu(II) complexes with the Schiff bases have been synthesized and characterized by elemental analysis, IR and UV-VIS spectroscopy, magnetic susceptibility measurements, and thermal studies (TGA and DTG). An octahedral geometry around the transition metal ion, consisting of two bidentate Schiff base ligands bonding through the azometine nitrogen and ketonic oxygen have been proposed based on careful interpretation of available analytical and spectroscopic characterization results. Two water molecules as ligands complete the octahedral geometry in all cases. Using the invitro disc diffusion method for screening synthesized compounds against selected gram positive and gram negative bacterial at 40 mg/mL, and the DPPH free radical scavenging methods at 0.50, 0.25 and 0.13 mg/mL, the synthesized Schiff base and metal complexes showed varying biological activities. 4-benzoyl-3-methyl-1-phenyl-2-pyrazolin-5-one sul29 fanilamide showed more activity generally, exhibiting a broad spectrum activity against all selected bacterial in some cases. Mn(II), Co(II) and Ni(II) complexes of sulfanilamide Schiff base with the acetylpyrazolone derivative 4-acetyl-3-methyl-1-phenyl-2-pyrazolin-5-one sulfanilamide, exhibited a stronger and very good DPPH radical scavenging activity as good as ascorbic acid on comparing, but not with Cu(II). As such they could be important antitumour candidates.

Orientador: Marcos Fernando de Souza Teixeira
Banca: Luiz Henrique Dall'Antonia
Banca: Maria Valnice Zanoni
Resumo: A presente dissertação de mestrado apresenta o estudo da eletropolimerização de monômeros à base de Schiff na ausência de cátions metálicos (N,N'-bis(5-aminosalicilidenoimina) - NH2 -salen) e do monômero a base de Schiff contendo níquel como cátion metálico no centro ligante tetradentado (N,N',N'',N'''-tetrabis(salicilideno)3,3',4,4'-bifenileno tetramino de níquel (II)) - Ni2 (Bisalphen). A obtenção do monômero NH 2 -salen foi realizada pela redução metálica em meio ácido do monômero NO 2 -salen (N,N'-bis(5-nitrosalicilidenoimina)), sendo confirmada pela técnica de espectroscopia no infravermelho (FTIR), espectrofotometria na região de UV-vís e por espectroscopia de massa (MS-EI). As análises dos voltamogramas de eletropolimerização, e dos perfis voltamétricos em solução aquosa, demonstram um mecanismo de por acoplamento C-N. O mecanismo foi confirmado pelo estudo de velocidade de varredura e número de ciclos de potenciais, como também pela caracterização por espectroscopia Raman. Em solução aquosa o filme de poli(NH-salen) apresentou um único par redox na ausência de oxigênio molecular, atribuído ao par redox R 1 -NH-C-R 2 /R 1 -N=C-R 2 , onde um aumento da concentração de espécie eletroativa foi obtida em função do aumento da razão [carga do íon]/[raio iônico] dos ânions presentes em solução, que pode ser atribuído a necessidade da difusão dos ânions no processo de transferência eletrônica. Para comparação dos mecanismos de formação, a obtenção do filme polimérico do complexo metálico Ni 2 (Bisalphen) foi realizada de modo semelhante, modificando apenas o solvente e eletrólito suporte utilizado. Na etapa de eletropolimerização, os resultados foram satisfatórios somente em solvente THF contendo... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: This dissertation presents the study of electropolymerization of monomers to the Schiff base in the absence of metal cations (N, N'-bis (5-amine-salicylideneimine) - NH2 -salen) and the Schiff base monomer containing nickel as metallic cation in the tetradentate center (N,N',N'',N'''-tetrabis(salicylidene) 3,3',4,4'-biphenylene-tetramine of nickel (II) - Ni2 (Bisalphen)). The NH 2 -salen monomer synthesis was realized by metallic reduction in acid medium from NO2 -salen (N,N'-bis(5-nitro-salicylideneimine)), being confirmed by the infrared spectroscopy (FTIR), UV-Vis spectrophotometry, and mass spectroscopy of electronic impact (MS-EI). The voltammetric profiles obtained on electropolymerization stage and in aqueous solution show the mechanism formation based on C-N coupling. This mechanism was confirmed by scan rate, potential cycle number study, and by the Raman characterization. In aqueous solution the poli(NH-salen) film showed one redox couple in absence of molecular oxygen, which was ascribed to R 1 -NH-C-R 2 /R 1 -N=C-R 2 redox couple. The increase of surface coverage was obtained in function of [ion charge]/[ionic radius] ratio of the anions present in aqueous solution, which can be ascribed to necessity of anion diffusion on electronic transfer. In order to compare the electropolymerization mechanism, the polymeric film of Ni2 (Bisalphen) was also obtained by electropolymerization technique. However, the solvent and supporting electrolyte were different. In the electropolymerization stage, the results were satisfactory only in THF solvent using the TBAP as supporting electrolyte, which can be ascribed to low solubility of complex in other solvents, as well as the low dipole value, necessary to propagation of the reaction. Due to presence of the metallic cation on monomer structure, the electropolymerizatiom... (Complete abstract click electronic access below)
Mestre

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A presente dissertação de mestrado apresenta o estudo da eletropolimerização de monômeros à base de Schiff na ausência de cátions metálicos (N,N’-bis(5-aminosalicilidenoimina) – NH2 -salen) e do monômero a base de Schiff contendo níquel como cátion metálico no centro ligante tetradentado (N,N’,N’’,N’’’-tetrabis(salicilideno)3,3’,4,4’-bifenileno tetramino de níquel (II)) – Ni2 (Bisalphen). A obtenção do monômero NH 2 -salen foi realizada pela redução metálica em meio ácido do monômero NO 2 -salen (N,N’-bis(5-nitrosalicilidenoimina)), sendo confirmada pela técnica de espectroscopia no infravermelho (FTIR), espectrofotometria na região de UV-vís e por espectroscopia de massa (MS-EI). As análises dos voltamogramas de eletropolimerização, e dos perfis voltamétricos em solução aquosa, demonstram um mecanismo de por acoplamento C–N. O mecanismo foi confirmado pelo estudo de velocidade de varredura e número de ciclos de potenciais, como também pela caracterização por espectroscopia Raman. Em solução aquosa o filme de poli(NH-salen) apresentou um único par redox na ausência de oxigênio molecular, atribuído ao par redox R 1 -NH-C-R 2 /R 1 -N=C-R 2 , onde um aumento da concentração de espécie eletroativa foi obtida em função do aumento da razão [carga do íon]/[raio iônico] dos ânions presentes em solução, que pode ser atribuído a necessidade da difusão dos ânions no processo de transferência eletrônica. Para comparação dos mecanismos de formação, a obtenção do filme polimérico do complexo metálico Ni 2 (Bisalphen) foi realizada de modo semelhante, modificando apenas o solvente e eletrólito suporte utilizado. Na etapa de eletropolimerização, os resultados foram satisfatórios somente em solvente THF contendo...
This dissertation presents the study of electropolymerization of monomers to the Schiff base in the absence of metal cations (N, N'-bis (5-amine-salicylideneimine) - NH2 -salen) and the Schiff base monomer containing nickel as metallic cation in the tetradentate center (N,N',N'',N'''-tetrabis(salicylidene) 3,3',4,4'-biphenylene-tetramine of nickel (II) - Ni2 (Bisalphen)). The NH 2 -salen monomer synthesis was realized by metallic reduction in acid medium from NO2 -salen (N,N'-bis(5-nitro-salicylideneimine)), being confirmed by the infrared spectroscopy (FTIR), UV-Vis spectrophotometry, and mass spectroscopy of electronic impact (MS-EI). The voltammetric profiles obtained on electropolymerization stage and in aqueous solution show the mechanism formation based on C-N coupling. This mechanism was confirmed by scan rate, potential cycle number study, and by the Raman characterization. In aqueous solution the poli(NH-salen) film showed one redox couple in absence of molecular oxygen, which was ascribed to R 1 -NH-C-R 2 /R 1 -N=C-R 2 redox couple. The increase of surface coverage was obtained in function of [ion charge]/[ionic radius] ratio of the anions present in aqueous solution, which can be ascribed to necessity of anion diffusion on electronic transfer. In order to compare the electropolymerization mechanism, the polymeric film of Ni2 (Bisalphen) was also obtained by electropolymerization technique. However, the solvent and supporting electrolyte were different. In the electropolymerization stage, the results were satisfactory only in THF solvent using the TBAP as supporting electrolyte, which can be ascribed to low solubility of complex in other solvents, as well as the low dipole value, necessary to propagation of the reaction. Due to presence of the metallic cation on monomer structure, the electropolymerizatiom... (Complete abstract click electronic access below)

Les travaux realises au cours de cette these ont pour but de modeliser le centre actif de la metalloproteine a manganese du photosysteme ii vegetal. Pour ce faire, nous avons prepare et etudie deux familles de complexes incorporant des bases de schiff pentadentees a sites donneurs n#2o#3 comme ligands binucleants. Parmi les dix neuf complexes prepares, nous avons determine la structure moleculaire d'un complexe dinucleaire du mn(iii), de trois complexes tetranucleaires mn(ii)#2mn(iii)#2 et d'un complexe tetranucleaire mn(iii)#4, par diffraction des rx. Dans la premiere partie de notre travail, les ligands de type 1,3-bis(z-salicylideneamino)propane-2-ol ont conduit a six nouveaux complexes polynucleaires du mn(ii) et trois nouveaux complexes du mn(iii) dont deux sont binucleaires. La deuxieme partie concerne l'etude des complexes du manganese avec les ligands de type 1,5-bis(z-salicylideneamino)pentane-3-ol. En milieu rigoureusement anaerobe, les complexes precurseurs de cette deuxieme serie, mn#i#i#2(l#2)(-oac)#n, reagissent avec le methanol pour conduire a des especes tetranucleaires a valence mixte mn(ii)#2mn(iii)#2 et, pour certains, avec l'eau de melanges methanol/eau ou ethanol/eau pour conduire a des especes tetranucleaires mn(iii)#4. Au cours de ces reactions les deux anions methanolate ou oxo formes sont stabilises sous forme de ligands -3 pontants. Les etudes electrochimiques mettent en evidence l'accessibilite de six etats d'oxydation allant de mn(ii)#4 a mn(iii)#2mn(iv)#2. Associees a la caracterisation des especes bisdinucleaires a valence mixte, elles suggerent que la deuxieme reaction fait intervenir deux etapes successives a deux electrons. L'etude et l'interpretation des proprietes magnetiques de ces complexes par rpe et variation thermique de la susceptibilite magnetique ont permis d'approfondir la connaissance des correlations magneto-structurales dans les edifices polynucleaires du manganese

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Os metais, bem como seus compostos, têm sido utilizados na medicina há mais de 5000 anos. Atualmente há vários fármacos que contém, como centro ativo, um íon metálico. Particularmente, os compostos contendo os íons metálicos Ag(I), Au(I) e Au(III) têm demonstrado bons resultados no tratamento e no combate a alguns tipos de enfermidades. Estes compostos possuem atividade biológica contra alguns tipos de vírus e bactérias, por exemplo, contra o vírus HIV, plasmodium falciparium, protozoário parasita causador da malária, e contra a M.tuberculosis, bactéria causadora da tuberculose. Também, os compostos de Au(I) e Au(III), têm sido usados no tratamento dos sintomas da artrite reumatóide e do câncer, respectivamente. Bases de Schiff estão entre os compostos orgânicos mais amplamente estudados e utilizados na pesquisa de novos produtos e fármacos, em função de sua facilidade de síntese e versatilidade de suas propriedades estéricas e eletrônicas. Muitos compostos descritos na literatura estão relacionados complexos metálicos com ligantes deste tipo, pois, além de apresentar grande afinidade para complexar aos íons metálicos Ag(I), Au(I) e Au(III), têm apresentado uma gama de atividades biológicas, incluindo, antifúngica, anti-bacteriana, anti-malárica, antiproliferativa, propriedades anti-inflamatórias, anti-virais e anti-piréticas. O objetivo deste projeto é sintetizar, caracterizar e estudar as propriedades físico-químicas de complexos de Ag(I) e Au(I) com bases de Schiff e estudar, posteriormente, suas atividades biológicas. Os ligantes foram sintetizados a partir da reação de condensação de aminas (2-aminotiofenol, 2-aminofenol e ácido 2-aminobenzóico) com o 2-carboxi-aldeídotiofeno. O ligante BTT foi sintetizado empregando-se a técnica de reação em forno de microondas, utilizando sílicagel como suporte e livre de solventes. Os complexos foram sintetizados adicionando-se aos ligantes o respectivo sal do íon metálico. Os ligantes IminaOH, BTT, IminaSH e IminaCOOH, foram caracterizados por análise elementar, espectroscopia vibracional na região do infravermelho, espectroscopia eletrônica na região do ultravioleta visível e ressonância magnética nuclear. O ligante IminaOH teve sua estrutura cristalina determinada e refinada por técnica de análise de difração de raios X. Com base nos resultados obtidos, foram propostas as seguintes fórmulas moleculares: C11H9NOS, para a IminaOH, C11H7NS2, para o BTT e C12H9NO2S, para a IminaCOOH. Os complexos obtidos foram caracterizados por um conjunto de técnicas analíticas e espectroscópicas e, a partir desses dados coletados, as seguintes fórmulas moleculares foram propostas: [Ag(C11H7NS2)2NO3], para o complexo do ligante BTT com o íon metálico Ag(I), no qual a proporção metal/ligante é de 1:2, nomeado de AgBTT, [Au(C11H7NS2)Cl], para o complexo com Au(I), intitulado AuBTT, com proporção 1:1 metal/ligante e [Ag(C12H8NO2S)NO3]. H2O, para o complexo de prata com o ligante IminaCOOH, chamado de AgIminaCOOH, em que sugere-se a proporção de um íon metálico Ag(I) para um ligante IminaCOOH e meia molécula de H2O, sendo este um complexo hemi-hidratado. O ligante BTT, bem como seus complexos com ouro e prata, foram testados contra bactérias do tipo M.tuberculosis e demonstraram certa atividade. O ligante BTT apresentou CIM de 230 µM, enquanto os complexos AgBTT e AuBTT, apresentaram CIM de 20,7 e 34,7 µM, respectivamente, sendo os valores obtidos para o complexo com prata comparáveis a valores de CIM para a sulfadiazina de prata, composto utilizado como antibacteriano. Nota-se também a sinergia existente entre o ligante BTT e os íons metálicos.
The metals and their compounds have been used in medicine for over 5000 years. Currently there are several drugs containing as active center, a metal ion. Particularly, the compounds containing the metal ions Ag (I), Au (I) and Au (III) have shown good results in treatment and to fight certain types of diseases. These compounds have biological activity against some viruses and bacteria, for example, against the HIV virus, plasmodium falciparum, which causes malaria, and against M.tuberculosis that causes tuberculosis. Also, the compounds of Au (I) and Au (III) have been used to treat the symptoms of rheumatoid arthritis and cancer, respectively. Schiff bases are among the compounds most widely studied and used in research of new products and drugs, due to their easy of synthesis and versatility of their steric and electronic properties. Many compounds described in the literature are related metal complexes with ligands of this type, because, besides having great affinity for complexing the metal ions Ag (I), Au (I) and Au (III), have shown a range of biological activities, including, antifungal, anti-bacterial, anti-malarial, antiproliferative, anti-inflammatory, anti-viral and anti-antipyretic properties. The objective of this project is to synthesize, characterize and study the physicochemical properties of complexes of Ag (I) and Au (I) with Schiff bases and study later, their biological activities. The ligands were synthesized from the condensation reaction of amine (2aminotiofenol, 2-aminophenol and 2-aminobenzoic acid) with 2-carboxy-thiophene aldehyde. The BTT ligand was synthesized employing the reaction technique in a microwave oven, using silica gel as a support and solvent-free. The compounds were synthesized by adding ligands to their metal ion salt. The ligands IminaOH, BTT and IminaCOOH, were characterized by elemental analysis, vibrational, electronic and nuclear magnetic resonance spectroscopies. The ligand IminaOH had its crystal structure determined and refined by analysis technique X-ray diffraction. Based on the results obtained, we propose the following molecular formulas: C11H9NOS, for IminaOH, C11H7NS2 for BTT and C12H9NO2S, for IminaCOOH. Abstract Dissertação de Mestrado Guilherme Alves Pereira The complexes were characterized by a set of analytical and spectroscopic techniques, and data collected from these, the following molecular formulas have been proposed: [Ag(C11H7NS2)2NO3] for the complex of the ligand BTT with metal ion Ag (I) in which the ratio metal / ligand is 1:2, named AgBTT, [Au (C11H7NS2) Cl] for the complex with Au (I), entitled AuBTT, with a ratio of 1:1 metal / ligand and [Ag ( C12H8NO2S) NO3] .1/2H2O for the silver complex with the ligand IminaCOOH, called AgIminaCOOH, suggests that the proportion of 1:1:1/2 metal ion Ag (I):IminaCOOH:H2O. The ligand BTT, as well as their complexes with gold and silver, were tested against bacteria such M.tuberculosis and they demonstrated some activity. That ligand had a MIC values of 230 µM, while the complexes AgBTT and AuBTT showed MIC values of 20.7 and 34.7 µM, respectively, the MIC value obtained for the silver complex is comparable to silver sulfadiazine, used as an antibacterial compound. Note also the synergy between the ligand BTT and metal ions.

Au-delà de son importance dans l'industrie nucléaire, la chimie d'oxydoréduction de l'uraniumretient de plus en plus l'attention des chercheurs. En effet, la capacité toute particulière descomplexes d'uranium à bas degré d'oxydation à promouvoir des réductions originales par desvoies inhabituelles suscite actuellement un grand intérêt, tout particulièrement leur aptitude àactiver dans des conditions douces des petites molécules telles CO, CO2, N2, ou encore descomposés aromatiques et des azotures. Les composés d'uranium, de part leurs propriétés decoordination tout à fait uniques pourraient offrir une alternative aux métaux de transitionclassiques pour la conception de catalyseurs. Cependant, comparativement aux métaux du bloc d,les processus polyélectroniques sont rares dans la chimie de l'uranium à bas degré d'oxidation quiest dominée par les transferts monoélectroniques. C'est pourquoi le développement de nouveauxcomplexes d'uranium capables de réaliser des réductions poly-électroniques est particulièrementintéressant. Le premier objectif de ce travail était d'associer à l'uranium des ligands non-innocentsservant de réservoir d'électrons. Ainsi nous avons utilisé des bases de Schiff p-conjuguées pourexplorer la chimie de cet élément à bas degree d'oxydation. Cela nous a permis d'isoler descomplexes riches en électrons dans lesquels des électrons sont stockés sur le ligand via laformation de liaisons C-C. Ces mêmes liaisons sont rompues en présence d'agent oxydant, et lesélectrons sont libérés pour réaliser des transformations polyélectroniques. Ce procédé a étéobservé pour plusieurs bases de Schiff, permettant de moduler les propriétés des composés. Dansune seconde approche, nous nous sommes intéressés à la synthèse et à l'étude de la réactivité denouveaux complexes d'uranium trivalent supportés par des ligands silanolates. De nouveauxcomposés dinucléaires d'uranium à basse valence ont été obtenus. Ces composés très réactifsdécomposent spontanément en clivant des groupements tertiobutyls des ligands, conduisant à laformation de complexes d'uranium(IV). En parallèle, un complexe monoanionique mononucléaired'U(III) a été isolé, nous permettant de comparer la réactivité de l'uranium trivalent dans différentsenvironnements stériques et électroniques. Ces études de réactivité ont permis de stabiliser unexemple rare de dimère d'uranium ponté par un groupement CS22- et ont mis en évidence lacapacité de l'uranium trivalent à promouvoir la dismutation de CO2 en carbonate et CO. La réactionde ces composés d'uranium trivalent vis-à-vis d'azotures organiques et inorganiques a produit denouveaux nitrures et nitrènes d'uranium originaux. Enfin, la capacité de ces agents réducteurspuissants à transférer des électrons au toluène a permis d'isoler une famille de complexessandwiches inversés où deux cations uranium sont liés de part et d'autre d'un cycle aromatique.

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O objetivo deste trabalho foi o de sintetizar MOFs com ligantes mistos, N- e O- doadores, utilizando alguns cátions metálicos da primeira série de transição como conectores de rede. Foram obtidas as redes de coordenação CoPDC2D e ZnPDC2D, que são isoestruturas as quais se estendem bi-dimensionalmente. Essas formam laços com 16-circuitos (circuitos mais curtos que contemplam 16 átomos), e incluem apenas o ligante 2,5-piridinodicarboxilato 2,5-pdc e os cátions (Co2+ e Zn2+) na coordenação. Algumas diferenças entre as sínteses aqui reportadas e aquelas publicadas são mostradas. Este trabalho também reporta brevemente o estudo topológico dessas redes bidimensionais. Todavia, foi obtida uma nova rede de coordenação ZnPDC1D, envolvendo a formação de laço (circuitos mais curtos de átomos), os quais se estendem unidimensionalmente, e envolvem os cátions Zn2+ e o ligante 2,5-pdc. Além disso, foi reportada uma série de novos complexos CuPDC0D, MnPDC0D, CuPDC0Dq e CuPDC0Dr, aniônicos, envolvendo apenas o ligante 2,5-pdc e os íons Cu2+ e Mn2+. Estes sistemas formam monômeros, MnPDC0D e CuPDC0Dr, ou dímeros oxo-metalatos, CuPDC0D e CuPDC0Dq, e contemplam cátions etilenodimina na rede cristalina, formando complexos metálicos (no caso do CuPDC0Dq. Finalmente, faz-se uma discussão sobre os ligantes nitrogenados 1,2-bis(2-piridil)etilenediamina 2-bpen e 1,2-bis(4-piridil)etilenediamina 4-bpen, que foram sintetizados, porém não foi observada a coordenação destes em nenhum dos sistemas aqui reportados. Tal fato foi atribuído à hidrólise dos ligantes nitrogenados (Bases de Schiff) e, portanto, foi proposto um mecanismo para essa hidrólise nos sistemas obtidos. A estrutura cristalina do ligante 2-bpen, ainda não reportada na literatura, foi discutida.
The aim of this work was the synthesis of MOFs with mixed ligands N- and O- donors from some metal cations of first series transition, as connectors of the net. In this work has been obtained coordination networks CoPDC2D and ZnPDC2D, that are iso-structures, which extend two-dimensionally forming loops with 16-shortest circuits, including the ligand 2,5-pyridinedicarboxylate 2,5-pdc and the Co2+ and Zn2+ cations, respectively. Both structures were recently published, however there some differences between the syntheses and the yield. Moreover, this work reports briefly the topological study of these two-dimensional networks. Additionally, were obtained a new coordination network ZnPDC1D, including loops formation, which extend one-dimensionally containing the cation Zn2+ and 2,5-pdc ligand. Here, were reported a series of new complexes CuPDC0D, MnPDC0D, CuPDC0Dq and CuPDC0Dr, anionic, including just the 2-5-pdc ligand and some this having Cu2+ e Mn2+ ions. This systems are monomers MnPDC0D and CuPDC0Dr or oxometalates dimmers CuPDC0D and CuPDC0Dq, including etilenodiamine on the crystalline network and, in some cases, participating on coordination CoPDC0Dq. Finally, are discussed about the nitrogenous ligands 1,2-bis(2-pyridil)etilenediamine 2-bpen and 1,2-bis(4-pyridil)etilenediamine 4-bpen, that were synthesized and characterized but not was observed the coordination in any system here reported. This has been attributed to the hydrolysis of nitrogenous ligands and, therefore, was proposed a mechanism for hydrolysis of these systems. The crystal structure of ligand 2-bpen, not yet reported in literature, was discussed.

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Certos íons metálicos bem como seus complexos estão presentes em sistemas biológicos exercendo importantes funções biológicas. No entanto, a utilização dos íons metálicos e de seus compostos, no início, era de modo empírico. A investigação sistemática científica de complexos parece ter vindo somente após os estudos de Paul Ehrlich e Robert Koch. Bases de Schiff diimínicas, assim como seus derivados benzimidazóis, possuem atividades biológicas conhecidas. Alguns complexos contendo vanádio (IV ou V) e de ouro (I ou III) também possuem reconhecidos usos biológicos. Portanto, complexos envolvendo as Bases de Schiff diíminicas e benzimidazóis com íons metálicos de vanádio e de ouro é um importante tema de estudo dentro do campo da Química Bioinorgânica. Dentro deste contexto, este trabalho tratou da síntese e caracterização de bases de Schiff diimínicas e benzimidazóis obtidos a partir da condensação entre 1,2-fenilenodiamina e benzaldeído ou seus derivados. Este trabalho também relata a síntese, caracterização e estudo biológico de complexos envolvendo bases de Schiff diimínicas e benzimidazóis obtidos com os íons de vanádio (IV) e de ouro (I e III). Ao final, são relatados quatorze compostos, sendo seis ligantes e oito complexos. Sete destes compostos ainda não foram relatados na literatura. Os compostos, exceto IMOH e [AuIIMOMeCl], foram testados contra protozoários do gênero Leishmania na etapa promastigota, sendo as espécies L. amazonesis, L. braziliensis, L. chagasi e L major. Os resultados mais expressivos foram encontrados para os compostos envolvendo o íon AuIII. Os complexos de AuIII também foram testados contra a fase amastigota do parasita contra as espécies L. amazonesis, L. braziliensis e L major.
The metal ions and their complexes are present in biological systems exersing important biological functions. However, the use of metal ions and their compounds, it was empirically. Systematic investigation of metals complexes seems to have come only after the studies of Paul Ehrlich and RobertKoch. Diiminics Schiff bases, as well as benzimidazole derivatives, have known biological activities. Some complexes containing vanadium (IV or V) and gold (I or III) also have recognized biological uses. Therefore, complexes involving Schiff Bases diíminicas and benzimidazole metal ions vanadium and gold is a major field of study within the field of Bioinorganic Chemistry. Within this context, this paper deals with the synthesis and characterization of Schiff bases and diimínicas benzimidazole obtained from the condensation between benzaldehyde and 1,2-phenylenediamine or its derivatives. This paper also reports the synthesis, characterization and biological study of complexes involving Schiff bases and diimínicas benzimidazole obtained with ions of vanadium (IV) and gold (I and III). In the end, fourteen compounds are reported, six and eight ligand complexes. Seven of these compounds have not been reported in the literature. The compounds, except IMOH and [AuIIMOMeCl], were tested against the protozoa of the Leishmania promastigote stage, with the species L. amazonesis, L. braziliensis, L. chagasi and L major. The most significant results were found for compounds involving ion AuIII. The AuIII complexes were also tested against the amastigote stage of the parasite species against L. amazonesis, L. braziliensis and L major.

Title from PDF of title page (University of Missouri--Columbia, viewed on Feb. 23, 2010). The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file. Dr. Steven W. Keller, Dissertation Supervisor. Vita. Includes bibliographical references.

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In the present work, several compounds derived from monosacharide D-Glucosamine were synthetized. These compounds were used successfully against gram-positive and gram-negative microorganisms. In the synthesis of compounds, classical methods in organic chemistry were used.The products were readily prepared from D-Glucosamine in few easy steps. In the first step, we have obtained he imine derivatives 2a or 2b. The resultant imines were protected in the OH groups at C1, C3, C4 and C6 positions with acetyl group. Selective desprotection of C2 aminogroup and coupling with cmnamic acid fford compound 5. All compounds were tested as antimicrobial agents against gram-positive and gram-negative microorganisms. Best results were obtained when compound 2b was used.
No presente trabalho, foram sintetizados vários compostos derivados da D-Glucosamina. Estes compostos foram usados com sucesso contra microorganismos grampositivos e gram-negativos. Na síntese dos compostos, foram utilizados métodos clássicos em química orgânica. Os produtos foram facilmente preparados a partir da D-glucosamina em poucas etapas. Na primeira etapa, foram obtidas as iminas derivadas 2a ou 2b. As iminas resultantes foram protegidas nos grupamentos OH ligados nas posições C1, C3, C4 e C6, por grupos acetila. Desproteção seletiva do grupamento amino ligado na posição C2, e posterior acoplamento com ácido cinâmico, forneceu o composto 5. Todos os compostos foram testados como agentes antimicrobiannos contra microorganismos gram-positivos e gram-negativos. Os melhores resultados foram obtidos quando o composto 2b foi utilizado.