Potent Antiplasmodial Derivatives of the Antitussive Drug Dextromethorphan Reveal the Ent-Morphinan Pharmacophore of Tazopsine-Type Alkaloids

The alkaloid tazopsine 1 was introduced in the late 2000's as a novel antiplasmodial hit compound active against Plasmodium falciparum hepatic stages, with potential to develop prophylactic drugs based on this novel chemical scaffold. However, the structural determinants of tazopsine 1 bioactivity, together with the exact definition of the pharmacophore, remained elusive, impeding further development. We found that the antitussive drug dextromethorphan (DXM) 3, although lacking the complex pattern of stereospecific functionalization of the natural hit, was harboring significant antiplasmodial activity in vitro despite suboptimal prophylactic activity in a murine model of malaria, which precluded its direct repurposing against malaria. The targeted N-alkylation of nor-DXM 15 delivered a small library of analogues with greatly improved activity over DXM 3 against P. falciparum asexual stages. Amongst these, N-2’-pyrrolylmethyl-nor-DXM 16i showed a 2- to 36-fold superior inhibitory potency compared to tazopsine 1 and DXM 3 against parasite liver and blood stages, with 760 ± 130 nM and 2.1 ± 0.4 µM IC50 values, respectively, as well as liver/blood phase selectivity of 2.8. Furthermore, cpd. 16i showed a 5 to 8-fold increase of activity relatively to DXM 3 against P. falciparum stages I-II and V gametocytes, with 18.5 µM and 13.2 µM IC50 values, respectively. Cpd. 16i can thus be considered a promising novel hit compound against malaria in the ent-morphinan series with putative pan-cycle activity, paving the way for further therapeutic development (e. g., investigation of its prophylactic activity in a mouse model of malaria).

Temperature Controlled Evolution of Pure Phase Cu9S5 Nanoparticles by Solvothermal Process

Copper sulphides are one of the most explored semiconductor metal sulphides because of their stoichiometric and morphological dependent optical and electrical properties, which makes them tunable for numerous optoelectronic applications. Stoichiometrically, copper sulphides exist in numerous structures which varies from the copper-rich phase (Cu2S) to the copper-deficient phase (CuS). Within these extreme stoichiometric phases lies numerous non-stoichiometric phases with interesting optical properties. Different solvothermal techniques have been explored for the synthesis of copper sulphides; however, the thermal decomposition of single source precursors provides a facile and tunable route to the synthesis of pure phase copper sulphides of different stoichiometries. In this study, copper (II) dithiocarbamate have been explored as a single source precursor compound to study the evolution of pure phase Cu9S5. Below 240°C, mixed phase of CuS and Cu9S5 were obtained, and as the temperature was increased beyond 240°C, keeping other reaction condition unchanged, the precursor yielded pure phase of Cu9S5. This phase selectivity at high temperature was attributed to the increased reducing ability of oleylamine (used as solvent) which enhance the evolution of the copper rich phase at high temperature. Optical and morphological studies of the pure phase Cu9S5, showed properties that varied considerably with the temperature of synthesis.

Anion Exchange Induced Formation of Kesterite Copper Zinc Tin Sulphide-Copper Zinc Tin Selenide Nanoheterostructures

We report the colloidal synthesis of quaternary kesterite CZTS-CZTSe heterostructures via anion exchange reactions on a kesterite CZTS template. The crystal phase selectivity during the synthesis (kesterite vs. wurtzite) is...

Laser Floating Zone Growth: Overview, Singular Materials, Broad Applications, and Future Perspectives

The Laser Floating Zone (LFZ) technique, also known as Laser-Heated Pedestal Growth (LHPG), has been developed throughout the last several decades as a simple, fast, and crucible-free method for growing high-crystalline-quality materials, particularly when compared to the more conventional Verneuil, Bridgman–Stockbarger, and Czochralski methods. Multiple worldwide efforts have, over the years, enabled the growth of highly oriented polycrystalline and single-crystal high-melting materials. This work attempted to critically review the most representative advancements in LFZ apparatus and experimental parameters that enable the growth of high-quality polycrystalline materials and single crystals, along with the most commonly produced materials and their relevant physical properties. Emphasis will be given to materials for photonics and optics, as well as for electrical applications, particularly superconducting and thermoelectric materials, and to the growth of metastable phases. Concomitantly, an analysis was carried out on how LFZ may contribute to further understanding equilibrium vs. non-equilibrium phase selectivity, as well as its potential to achieve or contribute to future developments in the growth of crystals for emerging applications.

Uniform spatial pooling explains topographic organization and deviation from receptive-field scale invariance in primate V1

Receptive field (RF) size and preferred spatial frequency (SF) vary greatly across the primary visual cortex (V1), increasing in a scale invariant fashion with eccentricity. Recent studies reveal that preferred SF also forms a fine-scale periodic map. A fundamental open question is how local variability in preferred SF is tied to the overall spatial RF. Here, we use two-photon imaging to simultaneously measure maps of RF size, phase selectivity, SF bandwidth, and orientation bandwidth—all of which were found to be topographically organized and correlate with preferred SF. Each of these newly characterized inter-map relationships strongly deviate from scale invariance, yet reveal a common motif—they are all accounted for by a model with uniform spatial pooling from scale invariant inputs. Our results and model provide novel and quantitative understanding of the output from V1 to downstream circuits.