Fluorenone imidazolium salts as novel de Vries materials

International audienceIn ionic liquid crystals (ILCs) tilted mesophases such as SmC required for electro-optic devices are quite rare. We report a design concept that induced the SmC phase and enabled de Vries-like behaviour in ILCs. For this purpose, we synthesized and characterized a library of ILC derivativesImR(On,Ym)Xwhich consist of a rigid central fluorenone core containing an alkoxy or thioether side chain and connectedviaa flexible spacer to an imidazolium head group. The mesomorphic properties were studied by differential scanning calorimetry (DSC), polarizing optical microscopy (POM) and X-ray diffraction (XRD). Temperature-dependent measurements of smectic layer spacingdby small-angle X-ray scattering (SAXS) and of optical tilt angles by POM demonstrate that ILCsImR(On,Ym)Xundergo SmA-SmC phase transitions with maximum layer contraction values between 0.4% and 2.1%. The lowest reduction factorRof 0.2 at the reduced temperatureT-T-AC= -10 K was calculated forIm(O12,S14)Br. Electron density calculations indicated a bilayer structure. Furthermore, temperature dependent emission studies show that self-assembling has a strong influence on the emission intensity of these ILCs

Novel Luminescent Diazafluorenone Liquid Crystals

International audienceIn this work, the synthesis, X-ray crystal structure analysis, studies on meso-morphism and luminescence spectroscopy of 2,7-diphenyl-4,5-diazafluorenones carrying 2, 4 or 6 peripheral alkoxy side chains of different lengths in the mesogenic unit are reported. The latter was attached to starting 2,7-dibromo-4,5-diazafluoren-9-one via Suzuki cross coupling of the respective 2-(alkoxyphenyl)-tetramethyl-1,2,3-borolane. The liquid crystalline properties were found to depend on both the number of side chains and their lengths. Derivatives with two short alkoxy chains (C6-C8) in the periphery formed nematic (N) and smectic C (SmC) mesophases while for the higher homologues only SmC mesophases were observed. Compounds carrying six alkoxy side chains with a minimum length of C8 assembled into columnar hexagonal phases. Homologues with C14 and C16 chain length displayed additionally two columnar rectangular mesophases. Four peripheral alkoxy chains, however, led to the loss of mesomorphism. Crystal structure data of a series of rod-shaped diazafluorenones helped to rationalize their liquid crystalline self-assembly and to understand geometry and thermal stability. Temperature-dependent luminescence spectra of diazafluorenone with two C12 chains revealed aggregation-induced emission (AIE) depending on the supramolecular order of the bulk phase. These studies suggested that AIE requires a lower degree of aggregation as compared to mesophase formation

Brain Region-Specific Differences in Amyloid-β Plaque Composition in 5XFAD Mice

Senile plaques consisting of amyloid-beta (Aβ) peptides are a major pathological hallmark of Alzheimer’s disease (AD). Aβ peptides are heterogeneous regarding the exact length of their amino- and carboxy-termini. Aβ1-40 and Aβ1-42 are often considered to represent canonical “full-length” Aβ species. Using immunohistochemistry, we analyzed the distribution of Aβ1-x, Aβx-42 and Aβ4-x species in amyloid deposits in the subiculum, hippocampus and cortex in 5XFAD mice during aging. Overall plaque load increased in all three brain regions, with the subiculum being the area with the strongest relative plaque coverage. In the subiculum, but not in the other brain regions, the Aβ1-x load peaked at an age of five months and decreased thereafter. In contrast, the density of plaques positive for N-terminally truncated Aβ4-x species increased continuously over time. We hypothesize that ongoing plaque remodeling takes place, leading to a conversion of deposited Aβ1-x peptides into Aβ4-x peptides in brain regions with a high Aβ plaque burden

Selective Requirement of PI3K/PDK1 Signaling for Kras Oncogene-Driven Pancreatic Cell Plasticity and Cancer

SummaryOncogenic Kras activates a plethora of signaling pathways, but our understanding of critical Ras effectors is still very limited. We show that cell-autonomous phosphoinositide 3-kinase (PI3K) and 3-phosphoinositide-dependent protein kinase 1 (PDK1), but not Craf, are key effectors of oncogenic Kras in the pancreas, mediating cell plasticity, acinar-to-ductal metaplasia (ADM), and pancreatic ductal adenocarcinoma (PDAC) formation. This contrasts with Kras-driven non-small cell lung cancer, where signaling via Craf, but not PDK1, is an essential tumor-initiating event. These in vivo genetic studies together with pharmacologic treatment studies in models of human ADM and PDAC demonstrate tissue-specific differences of oncogenic Kras signaling and define PI3K/PDK1 as a suitable target for therapeutic intervention specifically in PDAC