TiO2. Structural and electronic properties of TiO2 polymorphs denser than rutile, i.e. £\-PbO2-, baddeleyite, fluorite, and cotunnite-type were calculated by a first-principle pseudo-potential method based on density functional theory with local density approximation. Using experimental and theoretical lattice parameters of ambient TiO2, i.e. anatase and rutile as standard, the fluorite-type TiO2 has the narrowest band gap among the post-rutile phases. This character is important for the potential applications as visible-light-responsive photocatalyst. In additional to the bulk properties of dense TiO2 polymorphs the surface energies of

No description available.

Polymers containing bulky tetraphenylthiophene (TP) moieties were prepared by different coupling reactions. Firstly, 2,5-bis(4-bromophenyl)-3,4-diphenylthiophene (TP-Br) was coupled together by either NiCl2/PPh3 or n-BuLi to form polymers with TP as the repeat unit. The resulting polymers (PTP-NiCl2 and PTP-BuLi) are easily soluble in organic solvents and are photoluminescent (PL) materials (

Synthesis of five-membered heteroaromatic compounds such as pyrazoles, isoxazoles and 1,2,4-oxadiazoles are important for pharmaceutical industry and material science due to their applications. Although there are many methods to prepare such compounds, new variants continue to appear since they exhibit a wide range of biological and medicinal activities. In this thesis, new methods were developed for the synthesis of 4-iodopyrazoles, pyrazoles, isoxazoles, 1,2,4-oxadiazoles and/or 1,2,4-oxadiazepines. In the first part of the study, electrophilic cyclization of &alpha / ,&beta / -alkynic hydrazones by molecular iodine and copper iodide were investigated as new ways for the synthesis of 4-iodopyrazoles and pyrazoles, respectively. Initially, &alpha / ,&beta / -alkynic hydrazones were prepared by the reactions of propargyl aldehydes and ketones with hydrazines. Then &alpha / ,&beta / -alkynic hydrazones were treated with molecular iodine in the presence of NaHCO3, which afforded 4-iodopyrazoles in good to excellent yields. Subsequently, the same reactions were carried out with CuI in the presence of NEt3, which furnished corresponding pyrazoles in good yields. Moreover, ferrocenyl-substituted 4-iodopyrazoles and pyrazole derivatives were synthesized from corresponding

Conselho Nacional de Desenvolvimento Científico e Tecnológico / This study describes the attainment of twenty three (23) bis-heterocycles derived from the Levulinic Acid: Bis-Pyrazoles (6a-k) by the reaction of cyclecondensation between the 3-(5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-3-il)propanohidrazidamand a series of replaced β-alcoxiviniltrifluorometilcetonas. 1,3,4-oxadiazole 2-5-disubstituted (8-11) by reactions like [4 + 1] [OCNN+C], through the reactions of cyclecondensation between the 3-(5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-3-yl)propanohidrazida with different orthoesters as well as with carbon disulfide. It was also produced hydrazides (16c-d, g-h e 17c-d, g-h) derived of synthesized pyrimidines, to be used as precursorsn in the synthesis of bis-heterocycles, derivatizated of the reaction of those with some β- Ketones alcoxiviniltrifluormetil. The bis-heterocycles were obtained by the ordinary methodology, with efficiency between 61-97%.It was also gotten other original compounds (3i-k, 5), used as precursors in this study. The structure of these synthesized compounds were confirmed by the data of RMN 1H, 13C, besides the data of mass spectrometry. / Este trabalho descreve a obtenção de 23 novos bis-heterociclos derivados do Ácido Levulínico: Bis-Pirazóis (6a-k) a partir da reação de ciclocondensação entre o 3-(5-(trifluorometil)-4,5-dihidro-1H-pirazol-3-il)propanohidrazida e uma série de β-alcoxiviniltrifluorometilcetonas substituídas; 1,3,4-oxadiazóis 2-5-dissubstituídos (8-11) via reações do tipo [4 + 1] [OCNN+C], através de reações de ciclocondensação entre a 3-(5-(trifluorometil)-4,5-dihidro-1H-pirazol-3-il)propanohidrazida com diferentes ortoésteres, bem como com dissulfeto de carbono. Foram produzidas ainda, hidrazidas( 16c-d, g-h e 17c-d, g-h) derivadas de pirimidinas sintetizadas, para serem utilizadas como precursores na síntese de bis-heterociclos, derivatizados da reação destas com algumas β-alcoxiviniltrifluormetil cetonas. Os bis-heterociclos foram obtidos por metodologia convencional, com rendimentos entre 61-97%. Foram obtidos ainda outros compostos inéditos (3i-k, 5) utilizados como precursores nesse trabalho. As estruturas dos compostos sintetizados foram confirmadas por dados de RMN 1H, 13C, além de dados de espectrometria de massas.

No description available.

L'enveloppe cellulaire des bactéries à Gram négatif constitue la première ligne de défense contre les antibiotiques. Sous l’effet, d’une part, de la faible perméabilité de la membrane externe qui s'oppose à la pénétration des agents antibactériens, d’autre part des pompes d'efflux qui favorisent leur expulsion, elle empêche nombre de composés potentiellement actifs in vitro d'atteindre leur cible, limitant l’effet antibactérien. Un enjeu important pour restaurer l’activité de ces molécules est de trouver une stratégie pour en augmenter la concentration intracellulaire. L'objectif de cette thèse est de développer des métallodrogues comme nouvelle stratégie de vectorisation de drogues dans les cellules. Cette stratégie repose sur l’association d'une drogue active in vitro, et d’un ligand auxiliaire ayant des propriétés perméabilisantes ou inhibitrices de pompe d’efflux, dans un complexe qui jouera le rôle de chaperone. Les agents antibactériens utilisés sont des inhibiteurs (dérivés d’acides hydroxamiques) de peptide déformylase (PDF) et de méthionine aminopeptidase (MetAP) développés au laboratoire. Tout d’abord, une étude globale de la stratégie de vectorisation a été réalisée (i) étude de stabilité de métallodrogues modèles : en utilisant un acide hydroxamique fluorescent, nous avons montré que, seules, des métallodrogues à Co(III), à la différence de celles à Cu(II) et Fe(III), satisfaisaient aux conditions de stabilité compatibles avec les conditions de tests biologiques. (ii) Etude de la libération de la drogue : nous avons établi par une étude RMN 1H et UV-vis qu’en milieu tampon pH = 7,4, la libération de la drogue se faisait par échange de ligand avec un thiol exogène. Récemment, une nouvelle série d’inhibiteurs de PDF a été synthétisée au laboratoire. Elle est basée sur un squelette hétérocyclique à 5 chaînons fonctionnalisé par une chaîne en C4, puis via un espaceur monocarboné, à un acide hydroxamique. Les meilleurs résultats ont été obtenus avec un oxadiazole (AT002 16 µg/ml sur E. coli en présence de perméabilisant PMBN). Au cours de cette thèse, pour améliorer la lipophilie, des groupements aromatiques ont été fixés sur cet hétérocycle. Les MICs sur la souche d’E. coli sauvage n’ont pas été améliorées mais en présence de PMBN, le dérivé présentant la meilleure activité est le composé AT015 (2 µg/ml sur E. coli en présence de PMBN) qui a donc été choisi pour concevoir des métallodrogues. La métallodrogue réunit autour d’un métal deux parties: (i) un ligand auxiliaire fonctionnalisé via un espaceur par un perméabilisant peptidique analogue de peptide antimicrobien ou par un modulateur de l’efflux (ii) un acide hydroxamique inhibiteur de PDF. Au cours de la SAR réalisée en faisant varier la drogue, le ligand auxiliaire et le métal, nous avons montré que les meilleures métallodrogues permettent d’améliorer l’activité de la drogue sur la souche d’E. coli sauvage d’un facteur 16. Un des ligands auxiliaires fonctionnalisé par un tétrapeptide présente, seul, une activité sur une souche d’E. aerogenes résistante aux fluoroquinolones. Sur ce cas, l’activité biologique a été reliée, par des expériences de mapping par fluorescence, à son accumulation intracellulaire, en utilisant un analogue fluorescent de ce composé. / The gram negative bacterias’ cell envelopes are the first line of defense against antibiotics. First thanks to the low permeability of the external membrane that prevents the penetration of the antibiotics, but also thanks to the efflux pumps that help expelling the antibiotics from the cell. These mechanisms prevent many compounds, potentially active in vitro, from reaching their targets, thus limiting the antimicrobial effect. To increase the molecules’ intracellular concentration is one of the means to restore their activity. This thesis’ objective is to develop metallodrugs as a new drug vectorization strategy in cells. We here associate an active drug in vitro and an auxiliary ligand with permeabilization or efflux pumps inhibition abilities in a complex playing the role of a chaperone. We used peptide deformylase (PDF) and methionine aminopeptidase (MetAP) inhibitors (derived from hydroxamic acids) developed at the laboratory as antimicrobial agents. I’ll begin with a global study of the vectorization strategy we’ve adopted (i) Stability study of the metallodrugs models: using a fluorescent hydroxamic acid, we showed that only Co(III) metallodrugs are in agreement with the stability conditions compatible with the biological tests, in opposition with the Cu(II) and Fe(III) ones. (ii) Drug release study: we showed in 1H NMR and UV-vis studies that in a buffer solution pH 7.4, a ligand exchange with an exogenous thiol is responsible for the drug release. Recently, a new series of PDF inhibitors was synthesized at the laboratory. It is composed of a 5 membered heterocyclic skeleton functionalized by a chain in C4 followed by an hydroxamic acid via a monocarbonated spacer. The best results were obtained with an oxadiazole (AT002 16 µg/ml with E. coli and PMBN as permeabilizing agent). During this thesis, to enhance lipophilicity, we attached aromatic groups on the heterocycle. CMIs on the E. coli strain have not been increased but the compounds displaying the best activity in presence of PMBN (AT015, 2 µg/ml with E. coli and PMBN) was chosen to conceive metallodrugs. The metallodrug is composed of a metal center and two other parts: (i) an auxiliary ligand functionalized via a spacer by a permeabilizing peptide, an antimicrobial peptide analogue, or by an efflux modulator. (ii) An hydroxamic acid PDF inhibitor. We showed that the best metallodrugs enhance the drug activity on the wild E.coli strain by a 16 factor, with the SAR we realized, changing the drug, the auxiliary ligand and the metal. One of the auxiliary ligands functionalized by a tetrapeptide show an activity on a fluoroquinolone-resistant E. aerogenes strain while alone. Utilizing a fluorescent analogous of this compound, we linked the biological activity to its intracellular accumulation with fluorescence mapping experiments.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / In the present work, a series of 2-alkyl/arylchalcogenide-N-(4-aryl-1,3-thiazol-2-yl)acetamide was prepared via addition of aryl or alkyl chalcogenides. This methodology allowed the preparation of new derivatives of 2-amino-1,3-thiazoles in good yields. The compound synthesized is intended to evaluate the biological potential from the antioxidant activity by scavenging capacity of the assay by ABTS and DPPH. Was also developed a methodology for obtaining the compounds (S)-N-(alkyl-1-(3-aryl-1,2,4-oxadiazol-5-yl)-2-(phenylchalcogenide)acetamide derived from (S)-2-(2-(phenylchalcogenide)acetamido)alkanoic acids and arylamidoximes employing microwave irradiation. This synthesis was carried out in three conditions by varying the reaction time, temperature and solvent. The reactions employing microwave irradiation exhibit advantages against reactions using conventional method. These compounds were characterized by 1H NMR, 13C NMR and techniques high resolution mass spectrometry. / No presente trabalho, uma série de 2-alquil/arilcalcogeno-N-(4-aril-1,3-tiazol-2-il)acetamidas foi preparada via adição de calcogenetos de alquila ou arila. Essa metodologia permitiu a obtenção de derivados de 2-amino-1,3-tiazois em bons rendimentos. A proposta dessa síntese tem a finalidade de avaliar o potencial biológico a partir da atividade antioxidante por meio da capacidade sequestradora dos compostos sintetizados através de ensaios de ABTS e DPPH. Também foi desenvolvido uma metodologia para a obtenção dos compostos (S)-N-(1-(3-aril-1,2,4-oxadiazol-5-il)alquil)-2-(calcogenofenil)acetamidas derivados de ácidos (S)-2-(2-(calcogenofenil)acetamido)alcanoicos e arilamidoximas, empregando irradiação de micro-ondas. Para essa síntese foram desenvolvidas três condições reacionais variando o tempo reacional, temperatura e solvente. As reações conduzidas em micro-ondas apresentaram vantagens frente às reações em método convencional. Estes compostos foram caracterizados por técnicas de RMN 1H, RMN 13C e por espectrometria de massas de alta resolução.

Made available in DSpace on 2015-05-14T13:21:26Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 8587505 bytes, checksum: 3dc99b05c6b4e46c71e2ec550261f7cf (MD5) Previous issue date: 2013-01-18 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Among the heterocyclic compounds, 1,3,4-oxadiazole represents an important unit for the development of new drugs, since compounds containing this unit present a broad spectrum of biological activities such as antibacterial, antifungal, analgesic, anti- inflammatory, antiviral, antitumor, antihypertensive, anticonvulsant, etc. We describe the synthesis, characterization and antimicrobial activity of heterocyclic compounds of class 2,3-dihydro- 1,3,4-oxadiazole, specifically, 3-acetyl-2,5-diaryl-2,3-dihydro-1,3,4-oxadiazole, that were obtained as racemic mixture from the reaction of cyclization of N-acylhydrazones using acetic anhydride. Compounds were divided into three sets congeners as follows: series 1 (2-aryl-3- acetyl-5-(pyridin-4-yl)-2,3-dihydro-1,3,4-oxadiazol), series 2 (2-(5-nitrofuran-2-yl)-3-acetyl- 5-aryl-2,3-dihydro-1,3,4-oxadiazol) and series 3 (2-(4-acetoxyphenyl)-3-acetyl-5- aryl-2,3- dihydro-1,3,4-oxadiazol). All compounds were characterized by spectroscopic techniques IR, 1H-NMR, 13C-NMR and mass spectrometry. In the evaluation of the in vitro antimicrobial activity, compounds of the series 2 exhibit efficient activity against several strains of Staphylococcus aureus with minimum inhibitory concentration in the range of 8 to 32μg/mL, being more potent than the standard drug chloramphenicol, and good antifungal activity against six Candida strains with minimum inhibitory concentration values ranging from 64 to 512 μg/mL. / Entre os compostos heterocíclicos, 1,3,4-oxadiazol representa uma importante unidade de construção para o desenvolvimento de novos fármacos, uma vez que compostos que contém esta unidade possuem um amplo espectro de atividades biológicas tais como: antibacteriana, antifúngica, analgésica, anti-inflamatória, antiviral, antitumoral, antihipertensiva, anticonvulsivante, etc. Neste trabalho, descreve-se a síntese, caracterização e atividade antimicrobiana de compostos heterocíclicos da classe 2,3-diidro-1,3,4-oxadiazol, especificamente, 3-acetil-2,5-diaril-2,3-diidro-1,3,4-oxadiazol, que foram obtidos como mistura racêmica a partir da reação de ciclização de N-acilhidrazonas usando anidrido acético. Os compostos foram divididos em três séries congêneres como: série 1 (2-aril-3-acetil-5- (piridin-4-il)-2,3-diidro-1,3,4-oxadiazol), série 2 (2-(5-nitrofuranil)-3-acetil-5-aril-2,3-diidro- 1,3,4-oxadiazol) e série 3 (2-(4-acetoxifenil)-3-acetil-5-aril-2,3-diidro-1,3,4-oxadiazol). Todos os novos compostos foram devidamente caracterizados por técnicas espectroscópicas de IV, RMN de 1H e 13C e espectrometria de massa. Na avaliação da atividade antimicrobiana in vitro, os compostos da série 2 exibiram eficiente atividade frente a diversas linhagens de Staphylococcus aureus ensaiadas com concentração inibitória mínima na faixa de 8-32μg/mL, sendo mais potente do que o fármaco padrão cloranfenicol, e boa atividade antifúngica contra seis linhagens de Candida com concentração inibitória mínima na faixa de 64 a 512μg/mL.

The literature surrounding organic small-molecule donor-acceptor systems is summarised for a range of optoelectronic applications (OLEDs, OPVs, OFETs etc.). There is a focus on the key building blocks: 1,3,4-oxadiazole (OXD), diphenylamine (DPA), carbazole (Cbz) and fluorene (F). The incorporation of such moieties into various donor-acceptor systems is discussed with further reference to selected alternative organic donor and acceptor systems. The syntheses of novel bipolar molecules based on a donor-spacer-acceptor (DPA/Cbz-F-OXD) structure and the incorporation of these molecules into single-layer OLEDs is presented. It is demonstrated how the emission colour can be tuned from green to deep blue by systematic manipulation of the structure. A significant result is that high efficiency accompanied with pure, deep blue emission in single-layer OLEDs can be achieved with this structural motif. The incorporation of these materials as part of a simple two-component blend to produce white OLEDs is presented and the modification of the materials to improve electron-transport properties is discussed. The synthesis of DPA-bridge-OXD wire systems is presented with the use of oligo-p-phenyleneethynylene units as a bridge of varying length to investigate the effect on charge transfer between the donor and acceptor. Photophysical studies demonstrate the change in absorption, emission and fluorescence lifetimes as the length scale of the molecules is altered. The synthesis of a series of planarised and twisted DPA-bridge-OXD systems based upon phenylene linkers is discussed. Finally, a series of DPA-F-OXD-anchor molecules is presented for incorporation into DSSC devices. The synthesis of these materials is described and the suitability of various anchoring groups for DSSCs is analysed through photophysical and device studies.