Synthesis of 5-aryl-5´-formyl-2,2´-bithiophenes as new precursors for nonlinear optical (NLO) materials

A series of formyl-substituted 5-aryl-2,2´-bithiophenes 5 were synthesized using two different methods: Vilsmeier-Haack-Arnold reaction (VHA) or through Suzuki coupling. The synthesis of compounds 5 through the Vilsmeier-Haack-Arnold reaction, starting from inexpensive and easily available precursors such as acetophenones, gave the title compounds in low yields after four reaction steps. On the other hand Suzuki coupling of functionalized aryl boronic acids 7 and the 5-bromo-5´-formyl-2,2´-bithiophene 6 gave compounds 5 in good yields in only one step.Fundação para a Ciência e a Tecnologia (FCT

Synthesis and characterization of novel efficient and thermally stable 2-aryl-5-dicyanovinylthiophenes and 5-aryl-5´-dicyanovinyl-2,2´-bithiophenes as potentially promising nonlinear optical (NLO) materials

Two series of dicyanovinyl-substituted compounds namely 2-aryl-5-dicyanovinyl-thiophenes 4 and 5-aryl-5´-dicyanovinyl-2,2´-bithiophenes 6 were synthesized through Knoevenagel condensation of the corresponding 2-aryl-5-formyl-thiophenes 3 and 5-aryl-5´-formyl-2,2´-bithiophene 5 precursors. On the other hand, precursors 3 were prepared through the Vilsmeier-Haack-Arnold reaction (VHA) starting from inexpensive and easily available precursors such as acetophenones. This method produced the title compounds in higher yields than the recently reported synthesis via Suzuki coupling of functionalized aryl boronic acids with 5-bromo-2-formyl-thiophene. Electrochemical studies and characterization of the optical (linear and nonlinear), and thermal properties for compounds 5-6 indicate that, good nonlinearity is complemented by exceptional thermal stability for chromophores 6, making them potential candidates for several optoelectronic applications such as solvatochromic probes and nonlinear optical materials.Fundação para a Ciência e a Tecnologia (FCT) - PTDC/QUI/66251/2006, programa “Acções Integradas Luso-Francesas/CRUP-CP

Theoretical and experimental studies of aryl-bithiophene based push-pull pi-conjugated heterocyclic systems bearing cyanoacetic or rhodanine-3-acetic acid acceptors for SHG nonlinear optical applications

A series of push-pull aryl-bithiophene based systems 2-3 were designed and synthesized in order to understand how structural modifications influence the electronic, linear and nonlinear optical properties. The push-pull conjugated chromophores 2-3 bear a bithiophene spacer conjugated with a phenyl ring functionalized with N,N-dialkylamino electron-donor groups together with cyanoacetic or rhodanine-3-acetic acid acceptor groups. Theoretical (DFT calculations) and experimental studies were carried out to obtain information on conformation, electronic structure, electron distribution, dipolar moment, and molecular nonlinearity response of the push-pull bithiophene derivatives. This multidisciplinary study revealed that chromophore 2e exhibits the highest value for hyperpolarizability beta (10440 × 10-30 esu) due to the strong electron donating ability of the N,N-diethylamino group, and the ethyne linker that not only lengthens the pi- conjugation path but also grants less distortion to the system.Thanks are due to Fundação para a Ciência e Tecnologia (FCT) for a PhD grant to S. S. M. Fernandes (SFRH/BD/87786/2012) and FEDERCOMPETE for financial support through the CQ/UM (Ref. UID/QUI/ 00686/2013 and UID/QUI/0686/2016). The NMR spectrometer Bruker Avance III 400 is part of the National NMR Network and was purchased within the framework of the National Program for Scientific Reequipment, contract REDE/1517/RMN/2005 with funds from POCI 2010 (FEDER) and FCT. The pulsed laser system was acquired within the framework of the grant (PTDC/CTM/105597/2008) from the Fundação para a Ciência e Tecnologia (FCT) with funding from FEDERCOMPETE. This work was also supported by the Associated Laboratory for Sustainable Chemistry - Clean Processes and Technologies - LAQV which is financed by Portuguese national funds from FCT/MEC (UID/ QUI/50006/2013) and co-financed by the ERDF under the PT2020 Partnership Agreement (POCI-01-0145-FEDER–007265).info:eu-repo/semantics/publishedVersio

Fluorescence and two-photon absorption of push-pull aryl(bi)thiophenes: structure-property relationships

Special Issue in honor of Jean-Pierre SauvagePhotophysical and TPA properties of series of push-pull aryl(bi)thiophene chromophores bearing electron-donating (D) and electron-withdrawing (A) end-groups of increasing strength are presented. All compounds show an intense Intramolecular Charge Transfer (ICT) absorption band in the visible region. Increasing the D and/or A strength as well as the length of the conjugated path induces a bathochromic and hyperchromic of the absorption band as reported for analogous push-pull polyenes. Yet, in contrast with corresponding push-pull polyenes, a significant increase in fluorescence is observed. In particular, chromophores built from a phenyl-bithienyl conjugated path and bearing strong D and A end-groups were found to combine very large one and two-photon brightness as well as strong emission in the red/NIR region. These molecules hold promises as biphotonic fluorescent probes for bioimaging.Fundação para a Ciência e a Tecnologia (FCT

Synthesis, fluorescence and two-photon absorption properties of push-pull 5-aryl[3,2-b]thienothiophene derivatives

Three series of novel push-pull 5-aryl[3,2-b]thienothiophene derivatives functionalized with potent electron-withdrawing terminal moieties) were synthesized in moderate to excellent yields through Suzuki coupling followed by Knoevenagel condensation. These novel chromophores combine intense absorption in the near-UV down to the orange visible region in relation with a strong intramolecular charge transfer transition. By combining strong donor and acceptor, large fluorescence quantum yield are achieved as well as large two-photon absorption responses. Interestingly, due to the improved rigidity and electronic delocalization provided by the thienothiophene moiety (compared to the bis-thiophene one) larger one- and two-photon brightness values are achieved. As a result, a library of new fluorescent dyes showing enhanced brightness (up to and tunable fluorescence (ranging from blue to the NIR region) has been obtained which offer interesting promises for bioimaging applications.FCT, FEDER, QREN PEst-C/QUI/UI0686/2013 (FCOMP-01-0124-FEDER-037302

Kallikrein 5 induces atopic dermatitis–like lesions through PAR2-mediated thymic stromal lymphopoietin expression in Netherton syndrome

Netherton syndrome (NS) is a severe genetic skin disease with constant atopic manifestations that is caused by mutations in the serine protease inhibitor Kazal-type 5 (SPINK5) gene, which encodes the protease inhibitor lymphoepithelial Kazal-type–related inhibitor (LEKTI). Lack of LEKTI causes stratum corneum detachment secondary to epidermal proteases hyperactivity. This skin barrier defect favors allergen absorption and is generally regarded as the underlying cause for atopy in NS. We show for the first time that the pro-Th2 cytokine thymic stromal lymphopoietin (TSLP), the thymus and activation-regulated chemokine, and the macrophage-derived chemokine are overexpressed in LEKTI-deficient epidermis. This is part of an original biological cascade in which unregulated kallikrein (KLK) 5 directly activates proteinase-activated receptor 2 and induces nuclear factor κB–mediated overexpression of TSLP, intercellular adhesion molecule 1, tumor necrosis factor α, and IL8. This proinflammatory and proallergic pathway is independent of the primary epithelial failure and is activated under basal conditions in NS keratinocytes. This cell-autonomous process is already established in the epidermis of Spink5−/− embryos, and the resulting proinflammatory microenvironment leads to eosinophilic and mast cell infiltration in a skin graft model in nude mice. Collectively, these data establish that uncontrolled KLK5 activity in NS epidermis can trigger atopic dermatitis (AD)–like lesions, independently of the environment and the adaptive immune system. They illustrate the crucial role of protease signaling in skin inflammation and point to new therapeutic targets for NS as well as candidate genes for AD and atopy

Triesters non symétriques de l'acide tétrathiophosphorique : synthèse et réactivité

Development of a general synthetic method for unsymmetrical triesters of the phosphorotetrathioic acid is described in this thesis. The method is based on the reaction of triethylammonium salts of phosphorotetrathioic diesters with electrophiles. Using the reactivity of the triethylammonium salts allows the synthesis of various functionnalized triesters as well as new polyheterocyclic (P, O, S, N) systems. Spectral data (1H, 13C and 31P NMR) for all the synthesized compounds have been determined and are discussedCette étude a permis de développer une méthode générale de synthèse de triesters non symétriques de l'acide tétrathiophosphorique, basée sur la préparation de sels de triéthylammonium de diesters de cet acide. L'étude de la réactivité de ces intermédiaires a conduit à l'obtention d'un grand nombre de triesters non symétriques fonctionnalisés de cet acide ainsi que divers composés polyhétérocycliques. Les caractéristiques spectroscopiques en RMN 1H, 13C et 31P de ces produits, non décrits pour la plupart, ont été déterminées et discutée

Développement de nouvelles sondes photoactivables pour la caractérisation des cibles cellulaires du glutathion

Le glutathion (GSH et GSSG) joue un rôle prédominant dans l apoptose (mort cellulaire programmée) un phénomène déficient dans certains cas de cancer. L action du glutathion est étroitement liée à plusieurs protéines qui ont une affinité pour ce tripeptide ( Glu-Cys-Gly sous sa forme réduite) et qui constituent le système du glutathion. Une méthode de marquage par photoaffinité n utilisant pas de radioisotopes a été choisie pour identifier ces nouvelles protéines. Pour cela nous avons synthétisé de nouvelles sondes photoactivables dont le but est de se lier à différentes molécules biologiques notamment, dans notre cas, le glutathion. L irradiation de ce matériel biologique en présence de ces sondes photoactivables va permettre la formation d une liaison covalente entre les protéines ayant une affinité pour le glutathion et le glutathion lui-même. L étape suivante qui consiste en une ligation de Staudinger avec la biotine ou en une réaction de Click Chemistry avec une biotine modifiée, va permettre la visualisation et l identification de ces protéines cibles ainsi que de leur site de liaison. Deux méthodes de détection ont été envisagées¡: - La chimiluminescence : la présence de la biotine permet une détection aisée via une procédure bien connue qui utilise le complexe streptavidin-peroxydase et le luminol - La fluorescence : le couplage d un composé fluorescent à la sonde permet une détection.Glutathione (GSH and GSSG) takes a predominant part in apoptosis (programmed cell death), a process which is deficient in many cancers. The action of glutathione is closely related to the activity of several proteins having an affinity for the tripeptide ( Glu-Cys-Gly when reduced) and which are constituting the so-called glutathione system. A radioisotope-free photoaffinity labeling method was chosen for the identification of novel glutathione-binding proteins. We prepared news photoaffinity probe which can be connected to different biological molecules including, in our case, glutathione. Irradiation of a biological sample with this probe should lead to the formation of a covalent bond with proteins having an affinity for GSH. In a second step, a Staudinger ligation with biotin or a Click Chemistry reaction with modified biotin should allow the visualization and identification of the target proteins and the binding sites. Two detection methods are envisaged: - Chemiluminescence : the presence of biotin can be easily detected by a well known procedure using streptavidin-peroxydase and luminol - Fluorescence : coupling the probe with a fluorescent comMETZ-SCD (574632105) / SudocSudocFranceF