Development of a selective inhibitor for Kv1.1 channels prevalent in demyelinated nerves.

Members of the voltage-gated K+ channel subfamily (Kv1), involved in regulating transmission between neurons or to muscles, are associated with human diseases and, thus, putative targets for neurotherapeutics. This applies especially to those containing Kv1.1 α subunits which become prevalent in murine demyelinated axons and appear abnormally at inter-nodes, underlying the perturbed propagation of nerve signals. To overcome this dysfunction, akin to the consequential debilitation in multiple sclerosis (MS), small inhibitors were sought that are selective for the culpable hyper-polarising K+ currents. Herein, we report a new semi-podand - compound 3 - that was designed based on the modelling of its interactions with the extracellular pore region in a deduced Kv1.1 channel structure. After synthesis, purification, and structural characterisation, compound 3 was found to potently (IC50 = 8 µM) and selectively block Kv1.1 and 1.6 channels. The tested compound showed no apparent effect on native Nav and Cav channels expressed in F-11 cells. Compound 3 also extensively and selectively inhibited MS-related Kv1.1 homomer but not the brain native Kv1.1- or 1.6-containing channels. These collective findings highlight the therapeutic potential of compound 3 to block currents mediated by Kv1.1 channels enriched in demyelinated central neurons.

Suzuki-Miyaura Micellar Cross-Coupling in Water, at Room Temperature, and under Aerobic Atmosphere.

Recently, oxygen-equilibrated water solutions of Kolliphor EL, a well-known surfactant, have been seen to form nanomicelles with oxygen-free cores. This has prompted the successful testing of the core environment as a green medium for palladium-catalyzed Suzuki-Miyaura cross couplings. The versatility of these conditions is endorsed by several examples, including the synthesis of relevant molecular semiconductors. The reaction medium can also be recycled, opening the way for an extremely easy and green chemistry compliant methodology.

Near-infrared roll-off-free electroluminescence from highly stable diketopyrrolopyrrole light emitting diodes.

Organic light emitting diodes (OLEDs) operating in the near-infrared spectral region are gaining growing relevance for emerging photonic technologies, such as lab-on-chip platforms for medical diagnostics, flexible self-medicated pads for photodynamic therapy, night vision and plastic-based telecommunications. The achievement of efficient near-infrared electroluminescence from solution-processed OLEDs is, however, an open challenge due to the low photoluminescence efficiency of most narrow-energy-gap organic emitters. Diketopyrrolopyrrole-boron complexes are promising candidates to overcome this limitation as they feature extremely high photoluminescence quantum yield in the near-infrared region and high chemical stability. Here, by incorporating suitably functionalized diketopyrrolopyrrole derivatives emitting at ~760 nm in an active matrix of poly(9,9-dioctylfluorene-alt-benzothiadiazole) and without using complex light out-coupling or encapsulation strategies, we obtain all-solution-processed NIR-OLEDs with external quantum efficiency as high as 0.5%. Importantly, our test-bed devices show no efficiency roll-off even for high current densities and high operational stability, retaining over 50% of the initial radiant emittance for over 50 hours of continuous operation at 10 mA/cm2, which emphasizes the great applicative potential of the proposed strategy.