Physicochemical analysis of Bi2Te3 - (Fe, Eu) - Bi2Te3 junctions grown by molecular beam epitaxy method

Topological insulators (TI) are a class of materials gaining in importance due to their unique spin/electronic properties, which may allow for the generation of quasiparticles and electronic states which are not accessible in classical condensed-matter systems. Not surprisingly, TI are considered as promising materials for multiple applications in next generation electronic or spintronic devices, as well as for applications in energy conversion, such as thermo-electrics. In this study, we examined the practical challenges associated with the formation of a well-defined junction between a model 3D topological insulator, Bi2Te3, and a metal, Fe or Eu, from which spin injection could potentially be realized. The properties of multilayer systems grown by molecular beam epitaxy (MBE), with Fe or Eu thin films sandwiched between two Bi2Te3 layers, were studied in-situ using electron diffraction and photoelectron spectroscopy. Their magnetic properties were measured using a SQUID magnetometer, while the in-depth chemical structure was assessed using secondary ion mass spectroscopy. An examination of impact of Bi2Te3 structure on chemical stability of the junction area has been realized. For Fe, we found that despite room temperature growth, a reaction between the Fe film and Bi2Te3 takes place, leading to the formation of FeTe and also the precipitation of metallic Bi. For the Eu tri-layer, a reaction also occurs, but the Te chemical state remains intact

The search for new anticonvulsants in a group of (2,5-dioxopyrrolidin-1-yl)(phenyl)acetamides with hybrid structure - synthesis and in vivo/In vitro studies

Epilepsy belongs to the most common and debilitating neurological disorders with multifactorial pathophysiology and a high level of drug resistance. Therefore, with the aim of searching for new, more effective, and/or safer therapeutics, we discovered a focused series of original hybrid pyrrolidine-2,5-dione derivatives with potent anticonvulsant properties. We applied an optimized coupling reaction yielding several hybrid compounds that showed broad-spectrum activity in widely accepted animal seizure models, namely, the maximal electroshock (MES) test and the psychomotor 6 Hz (32 mA) seizure model in mice. The most potent anticonvulsant activity and favorable safety profile was demonstrated for compound 30 (median effective dose (ED50) MES = 45.6 mg/kg, ED50 6 Hz (32 mA) = 39.5 mg/kg, median toxic dose (TD50) (rotarod test) = 162.4 mg/kg). Anticonvulsant drugs often show activity in pain models, and compound 30 was also proven effective in the formalin test of tonic pain, the capsaicin-induced pain model, and the oxaliplatin (OXPT)-induced neuropathic pain model in mice. Our studies showed that the most plausible mechanism of action of 30 involves inhibition of calcium currents mediated by Cav1.2 (L-type) channels. Importantly, 30 revealed high metabolic stability on human liver microsomes, negligible hepatotoxicity, and relatively weak inhibition of CYP3A4, CYP2D6, and CYP2C9 isoforms of cytochrome P450, compared to reference compounds. The promising in vivo activity profile and drug-like properties of compound 30 make it an interesting candidate for further preclinical development

Quantum size effect on charges and phonons ultrafast dynamics in atomically controlled nanolayers of topological insulators Bi2Te3

This work was supported by the French Ministry of Education and Research, the CNRS, Region Pays de la Loire (CPER Femtosecond Spectroscopy equipment program) and the LIA-CNRS (Laboratoire International Associé) IM-LED. The partial financial support from National Science Center under project 2016/21/B/ST5/02531 is acknowledged. R. Rapacz was supported by FORSZT PhD fellowship.Heralded as one of the key elements for next generation spintronics devices, topological insulators (TIs) are now step by step envisioned as nanodevices like charge-to-spin current conversion or as Dirac fermions based nanometer Schottky diode for example. However, reduced to few nanometers, TIs layers exhibit a profound modification of the electronic structure and the consequence of this quantum size effect on the fundamental carriers and phonons ultrafast dynamics has been poorly investigated so far. Here, thanks to a complete study of a set of high quality molecular beam epitaxy grown nanolayers, we report the existence of a critical thickness of around ~6 nm, below which a spectacular reduction of the carrier relaxation time by a factor of ten is found in comparison to bulk Bi2 Te3 In addition, we also evidence an A1g optical phonon mode softening together with the appearance of a thickness dependence of the photoinduced coherent acoustic phonons signals. This drastic evolution of the carriers and phonons dynamics might be due an important electron-phonon coupling evolution due to the quantum confinement. These properties have to be taken into account for future TIs-based spintronic devices.Centre National de la Recherche Scientifiqu

Discovery of (R)-N-benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide [(R)-AS-1], a novel orally bioavailable EAAT2 modulator with drug-like properties and potent antiseizure activity in vivo

[Image: see text] (R)-7 [(R)-AS-1] showed broad-spectrum antiseizure activity across in vivo mouse seizure models: maximal electroshock (MES), 6 Hz (32/44 mA), acute pentylenetetrazol (PTZ), and PTZ-kindling. A remarkable separation between antiseizure activity and CNS-related adverse effects was also observed. In vitro studies with primary glia cultures and COS-7 cells expressing the glutamate transporter EAAT2 showed enhancement of glutamate uptake, revealing a stereoselective positive allosteric modulator (PAM) effect, further supported by molecular docking simulations. (R)-7 [(R)-AS-1] was not active in EAAT1 and EAAT3 assays and did not show significant off-target activity, including interactions with targets reported for marketed antiseizure drugs, indicative of a novel and unprecedented mechanism of action. Both in vivo pharmacokinetic and in vitro absorption, distribution, metabolism, excretion, toxicity (ADME-Tox) profiles confirmed the favorable drug-like potential of the compound. Thus, (R)-7 [(R)-AS-1] may be considered as the first-in-class small-molecule PAM of EAAT2 with potential for further preclinical and clinical development in epilepsy and possibly other CNS disorders

Identification of new compounds with anticonvulsant and antinociceptive properties in a group of 3-substituted (2,5-dioxo-pyrrolidin-1-yl)(phenyl)-acetamides

We report herein a series of water-soluble analogues of previously described anticonvulsants and their detailed in vivo and in vitro characterization. The majority of these compounds demonstrated broad-spectrum anticonvulsant properties in animal seizure models, including the maximal electroshock (MES) test, the pentylenetetrazole-induced seizure model (scPTZ), and the psychomotor 6 Hz (32 mA) seizure model in mice. Compound 14 showed the most robust anticonvulsant activity (ED(50) MES = 49.6 mg/kg, ED(50) 6 Hz (32 mA) = 31.3 mg/kg, ED(50) scPTZ = 67.4 mg/kg). Notably, it was also effective in the 6 Hz (44 mA) model of drug-resistant epilepsy (ED(50) = 63.2 mg/kg). Apart from favorable anticonvulsant properties, compound 14 revealed a high efficacy against pain responses in the formalin-induced tonic pain, the capsaicin-induced neurogenic pain, as well as in the oxaliplatin-induced neuropathic pain in mice. Moreover, compound 14 showed distinct anti-inflammatory activity in the model of carrageenan-induced aseptic inflammation. The mechanism of action of compound 14 is likely complex and may result from the inhibition of peripheral and central sodium and calcium currents, as well as the TRPV1 receptor antagonism as observed in the in vitro studies. This lead compound also revealed beneficial in vitro ADME-Tox properties and an in vivo pharmacokinetic profile, making it a potential candidate for future preclinical development. Interestingly, the in vitro studies also showed a favorable induction effect of compound 14 on the viability of neuroblastoma SH-SY5Y cells