Notch signaling has a pivotal role in numerous cell-fate decisions, and its aberrant activity leads to developmental disorders and cancer. To identify molecules that influence Notch signaling, we screened nearly 17,000 compounds using automated microscopy to monitor the trafficking and processing of a ligand-independent Notch-enhanced GFP (eGFP) reporter. Characterization of hits in vitro by biochemical and cellular assays and in vivo using zebrafish led to five validated compounds, four of which induced accumulation of the reporter at the plasma membrane by inhibiting γ-secretase. One compound, the dihydropyridine FLI-06, disrupted the Golgi apparatus in a manner distinct from that of brefeldin A and golgicide A. FLI-06 inhibited general secretion at a step before exit from the endoplasmic reticulum (ER), which was accompanied by a tubule-to-sheet morphological transition of the ER, rendering FLI-06 the first small molecule acting at such an early stage in secretory traffic. These data highlight the power of phenotypic screening to enable investigations of central cellular signaling pathways.
Numerous different photonics and biomedical applications depend on the fluorescent polymer micro- and nanoparticles. Besides optical or spectroscopic properties, the performance of the polymer nanoparticles is determined by their size, size distribution, and surface charge. Moreover, in order to realize a very uniform performance, the functional polymer nanoparticles should be of high homogeneity and demand for the preparation in a minimum number of synthesis steps. Here, we present a microfluidic-assisted synthesis of different types of reproducible fluorescent polymer nanoparticles with tuned size (40 nm up to 600 nm) and surface charge (ζ potential=-52 mV up to +45 mV). Four different preparation strategies were introduced for fluorophore-functionalized nanoparticles: (a) noncovalent binding of fluorophores with high loading, (b) covalent linking of fluorophores with enhanced stability, (c) surface-anchored fluorophores by hydrophobic interactions for triple function at the same time, and (d) surface immobilization of biomolecules and fluorophore by ionic as well as secondary interactions. In this way, four different classes of nanoparticles suited for different applications were prepared with a spherical shape as a model system. Moreover, the principle has been extended to the different types of nonspherical and composite polymer nanoparticles.
Morphologies crucially determine the optoelectronic properties of organic semiconductors. Therefore, hierarchical and supramolecular approaches have been developed for targeted design of supramolecular ensembles of organic semiconducting molecules and performance improvement of, e.g., organic solar cells (OSCs), organic light emitting diodes (OLEDs), and organic field-effect transistors (OFETs). We demonstrate how the photonic properties of fullerenes change with the formation of van der Waals aggregates. We identified supramolecular structures with broadly tunable absorption in the visible spectral range and demonstrated how to form aggregates with targeted visible (vis) absorption. To control supramolecular structure formation, we functionalized the C60-backbone with polar (bis-polyethylene glycol malonate-MPEG) tails, thus yielding an amphiphilic fullerene derivative that self-assembles at interfaces. Aggregates of systematically tuned size were obtained from concentrating MPEGC60 in stearic acid matrices, while different supramolecular geometries were provoked via different thin film preparation methods, namely spin-casting and Langmuir-Blodgett (LB) deposition from an air-water interface. We demonstrated that differences in molecular orientation in LB films (C2v type point group aggregates) and spin-casting (stochastic aggregates) lead to huge changes in electronic absorption spectra due to symmetry and orientation reasons. These differences in the supramolecular structures, causing the different photonic properties of spin-cast and LB films, could be identified by means of quantum chemical calculations. Employing supramolecular assembly, we propounded that molecular symmetry in fullerene aggregates is extremely important in controlling vis absorption to harvest photons efficiently, when mixed with a donor molecule, thus improving active layer design and performance of OSCs.
It is demonstrated that systematic and designated control of supramolecular nanostructures via interfacial engineering enables (opto)electronic C60‐material properties to be widely adjusted. Interestingly, the lowest unoccupied molecular orbital (LUMO) energies of the same amphiphilic fullerene species are tuned up to 120 meV using supramolecular assembly, competitive to complete molecular change; cf. PC61BM to PC71BM causes a change of 200 meV. Morphology control is achieved through different thin‐film production techniques involving molecular assembly at interfaces, including liquid–liquid interfacial precipitation (LLIP), and Langmuir–Blodgett technique at air–water interface. LLIP enables supramolecularly ordered extended surfaces, yielding the least electronically stable LUMO (ELUMO = −4.28 eV). After qualitatively explaining the observed electrochemical LUMO energy variation for these assemblies with varied molecular packing and aggregate dimensions, an analytical equation is proposed, connecting morphological parameters with LUMO energies with prospects in supramolecular chemistry. To demonstrate the applicability of supramolecular structure–electronic property relations and of supramolecular structure fabrication protocols established in this work to tailor device properties, amorphous‐Si/fullerene hybrid solar cells are built and characterized. It is found that the supramolecular structure variation can be successfully translated to the solar cells, giving rise to a prototype linear relation between LUMO energy and open‐circuit voltage.
This work describes the synthesis of five O‐silyloxy‐1,3‐thiazoles and their use as fast‐response “turn‐on” probes for fluoride ion detection in polar aprotic solvents and in aqueous cetyltrimethylammonium bromide micellar medium. The fluoride‐triggered deprotection of these silyl ethers results in ca. 180‐nm shifts in the fluorescence emission wavelengths. All compounds are suitable for the detection of fluoride ions with a detection limit in DMSO of 10–7 mol L–1; derivatives containing a 2‐pyridyl moiety in the thiazole system are more efficient than those with a 3‐ or 4‐pyridyl moiety. Typical anionic interferents, such as acetate or chloride, are not detected by O‐silyloxy‐1,3‐thiazoles, making these compounds very specific for fluoride.
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