This article describes the synthesis, spectroscopic studies, and theoretical calculations of nine original fluorophores based on the 2-(2′-hydroxyphenyl)benzazole (HBX) scaffold, functionalized at ...the 4-position of the phenol ring by ethynyl-extended aniline moieties. HBX dyes are well-known to display an excited-state intramolecular proton transfer (ESIPT) process, owing to a strong six-membered hydrogen bond in their structure that allows for an enol/keto tautomerism after photoexcitation. Appropriate electronic substitution can perturb the ESIPT process, leading to dual fluorescence, both excited tautomers emitting at specific wavelengths. In the examples described herein, it is demonstrated that the proton transfer can be finely frustrated by a modification of the constitutive heteroring, leading to a single emission band from the excited enol or keto tautomer or a dual emission with relative intensities highly dependent on the environment. Moreover, the nature of the functionalization of the N-alkylated aniline moiety also has a significant importance on the relative excited-state stabilities of the two tautomers in solution. To shed more light on these features, quantum chemical calculations by the density functional theory are used to determine the excited-state energies and rationalize the experimental spectroscopic data.
The synthesis of a series of push–pull dyes incorporating a functionalized benzo1,2-b:3,4-b′difuran moiety acting as a conjugated spacer is reported. The studies of their optical properties evidenced ...a strong ICT upon photoexcitation. As a consequence of their highly polarized nature, these dyes all display a sizeable solvatochromic emission. One example has been further incorporated onto a BODIPY fluorophore leading to a highly conjugated molecular scaffold.
Display omitted The synthesis of a series of push–pull dyes incorporating a functionalized benzo1,2-b:3,4-b'difuran moiety acting as a conjugated spacer is reported. The studies of their optical properties evidenced a strong ICT upon photoexcitation. As a consequence of their highly polarized nature, these dyes all display a sizeable solvatochromic emission. One example has been further incorporated onto a BODIPY fluorophore leading to a highly conjugated molecular scaffold.
The isotopic labelling of small molecules is integral to drug development and for understanding biochemical processes. The preparation of carbon-labelled α-amino acids remains difficult and time ...consuming, with established methods involving label incorporation at an early stage of synthesis. This explains the high cost and scarcity of C-labelled products and presents a major challenge in 11C applications (11C t1/2 = 20 min). Here we report that aldehydes catalyse the isotopic carboxylate exchange of native α-amino acids with *CO2 (* = 14, 13, 11). Proteinogenic α-amino acids and many non-natural variants containing diverse functional groups undergo labelling. The reaction probably proceeds via the trapping of *CO2 by imine-carboxylate intermediates to generate iminomalonates that are prone to monodecarboxylation. Tempering catalyst electrophilicity was key to preventing irreversible aldehyde consumption. The pre-generation of the imine carboxylate intermediate allows for the rapid and late-stage 11C-radiolabelling of α-amino acids in the presence of 11CCO2.Carbon-labelled α-amino acids are valuable compounds in drug development and nuclear medicine, but are difficult and time consuming to prepare. Now, an aldehyde-catalysed method has been developed for the direct C1-labelling of α-amino acids using *CO2 (* = 14, 13, 11), providing access to many proteinogenic and non-natural labelled α-amino acids.
Amides were prepared using rhodium-catalyzed coupling of organozinc iodides and carbon-11 (11C, t 1/2 = 20.4 min) isocyanates. Nonradioactive isocyanates and sp3 or sp2 organozinc iodides generated ...amides in yields of 13%–87%. Incorporation of cyclotron-produced 11CCO2 into 11C-amide products proceeded in yields of 5%–99%. The synthetic utility of the methodology was demonstrated through the isolation of 11CN-(4-fluorophenyl)-4-methoxybenzamide (11C6g) with a molar activity of 267 GBq μmol–1 and 12% radiochemical yield in 21 min from the beginning of synthesis.
Ces travaux de thèse concernent la synthèse et l’étude des propriétés optiques de fluorophores organiques appliqués à la détection de deux biomarqueurs de la maladie d’Alzheimer : la protéine kinase ...C (PKC) et les fibrilles de peptides amyloïdes Aβ42. La détection de la PKC est réalisée à l’aide de dyades comprenant un émetteur de type boradiazaindacène (BODIPY) relié de manière covalente à un inhibiteur de cette enzyme. Ces composés obtenus via une synthèse multi-étape présentent des coefficients d’absorption molaires et des rendements quantiques de fluorescence en solution importants. Ces sondes ont ensuite été utilisées en cytométrie de flux par la société Amoneta Diagnostics afin de détecter la PKC en surface des globules rouges et d’évaluer le potentiel de ces sondes dans le diagnostic de la maladie d’Alzheimer par test sanguin. Pour la détection des fibrilles de peptides amyloïdes, deux séries de fluorophores de la famille des 2-(2’-hydroxyphényl)-benzoxazoles ont été étudiées. Ces molécules présentent un phénomène de transfert de proton intramoléculaire à l’état excité (ESIPT) qui leur confère des propriétés optiques remarquables, telles que d’importants déplacements de Stokes et une émission duale. Enfin, un test de détection in vitro a été mis au point. Une interaction entre ces fluorophores et les fibrilles amyloïdes a pu être observée permettant la détection de ces peptides en solution.
This research concerns the synthesis and photophysical studies of organic fluorescent probes applied to the detection of two Alzheimer’s disease biomarkers: the protein kinase C and fibrils of amyloid Aβ42 peptides. PKC detection is achieved by dyads composed of boradiazaindacene dye (BODIPY) covalently linked to an inhibitor of this enzyme. These compounds afforded by a multistep synthesis display high molar absorption coefficients and quantum yields in solution. These probes were then used in flow cytometry by Amoneta Diagnostics to detect PKC on the surface of red blood cells in order to asses the potential of these molecules for the diagnostic of Alzheimer’s disease by blood test. Two series of fluorophores from the 2-(2’-hydroxyphenyl)-benzazole family have been studied for the detection of amyloid fibrils. These molecules display an excited state intramolecular proton transfer (ESIPT) phenomenon which confer them remarkable optical properties such as important Stokes shifts and dual emission. Finally, an in vitro detection test has been developed. Interactions between these dyes and amyloid fibrils has been observed, allowing the detection of these peptides in solution.
Amine‐functionalized squaramides 1 and 2 were prepared and shown to be suitable polymerization organocatalysts for the controlled ring‐opening polymerization (ROP) of l‐lactide (l‐LA) in the presence ...of an alcohol source such as BnOH (which acts as an initiator) to afford chain‐length‐controlled and narrow‐dispersion poly(l‐lactide) (PLLA) under mild reaction conditions. The ROP experimental and polymer analysis data are consistent with the action of 1 and 2 as bifunctional hydrogen‐bonding (HB) catalysts that are able to activate both the lactide monomer and initiator BnOH thanks to their dual HB acceptor and donor properties. As a comparison, aminosquaramide 3, a direct analogue of 1 but a weaker HB donor because of the absence of electron‐withdrawing NH substituents, displays little lactide ROP activity, which highlights the key role of monomer activation through HB in the present systems. Unlike aminosquaramides 1 and 2, related monofunctional squaramides 4 and 5 are inactive in l‐LA ROP in the presence of BnOH, but the addition of NEt3, as an external HB acceptor, allows the ROP to proceed with the production of well‐defined PLLA. A cooperative dual activation with an activated monomer/activated chain‐end mechanism is most likely operative in the lactide ROP mediated by 1 and 2 in the presence of BnOH.
One component or two: Single‐component aminosquaramides act as effective bifunctional hydrogen‐bonding catalysts for the controlled ring‐opening polymerization of lactide under mild conditions in the presence of BnOH. Such organocatalysts perform better in lactide ring‐opening polymerization than related squaramide/NEt3 two‐component catalysts.
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