Molecular docking assisted exploration on solubilization of poorly soluble drug remdesivir in sulfobutyl ether-tycyclodextrin.

Objective: To study structure-specific solubilization effect of Sulfobutyl ether-ß-cyclodextrin (SBE-ß-CD) on Remdesivir (RDV) and to understand the experimental clathration with the aid of quantum mechanics (QM), molecular docking and molecular dynamics (MD) calculations. Methods: The experiment was carried out by phase solubility method at various pH and temperatures, while the concentration of Remdesivir in the solution was determined by HPLC. The complexation mechanism and the pH dependence of drug loading were investigated following a novel procedure combining QM, MD and molecular docking, based on accurate pKa predictions. Results: The phase solubility and solubilization effect of RDV in SBE-ß-CD were explored kinetically and thermodynamically for each assessed condition. An optimal drug / SBE-ß-CD feeding molar ratio was determined stoichiometrically for RDV solubility in pH1.7 solution. The supersaturated solubility was examined over time after pH of the solution was adjusted from 1.7 to 3.5. A possible hypothesis was raised to elucidate the experimentally observed stabilization of supersaturation based on the proposed RDV Cation A /SBE-ß-CD pocket conformations. Conclusion: The computational explorations conformed to the experimentally determined phase solubilization and well elucidated the mechanism of macroscopic clathration between RDV and SBE-ß-CD from the perspective of microscopic molecular calculations.

Twist and sliding dynamics between interpenetrated frames in Ti-MOF revealing high proton conductivity.

We report the design and synthesis of a titanium catecholate framework, MOF-217, comprised of 2,4,6-tri(3,4-dihydroxyphenyl)-1,3,5-triazine (TDHT) and isolated TiO6 clusters, with 2-fold interpenetrated srs topology. The dynamics of the organic linker, breaking the C 3h symmetry, allowed for reversible twist and sliding between interpenetrated frames upon temperature change and the inclusion of small molecules. Introduction of 28 wt% imidazole into the pores of MOF-217, 28% Im-in-MOF-217, resulted in four orders of magnitude increase in proton conductivity, due to the appropriate accommodation of imidazole molecules and their proton transfer facilitated by the H-bond to the MOF structure across the pores. This MOF-based proton conductor can be operated at 100 °C with a proton conductivity of 1.1 × 10-3 S cm-1, standing among the best performing anhydrous MOF proton conductors at elevated temperature. The interframe dynamics represents a unique feature of MOFs that can be accessed in the future design of proton conductors.

Synergistic Mn-Co catalyst outperforms Pt on high-rate oxygen reduction for alkaline polymer electrolyte fuel cells.

Alkaline polymer electrolyte fuel cells are a class of fuel cells that enable the use of non-precious metal catalysts, particularly for the oxygen reduction reaction at the cathode. While there have been alternative materials exhibiting Pt-comparable activity in alkaline solutions, to the best of our knowledge none have outperformed Pt in fuel-cell tests. Here we report a Mn-Co spinel cathode that can deliver greater power, at high current densities, than a Pt cathode. The power density of the cell employing the Mn-Co cathode reaches 1.1 W cm-2 at 2.5 A cm-2 at 60 oC. Moreover, this catalyst outperforms Pt at low humidity. In-depth characterization reveals that the remarkable performance originates from synergistic effects where the Mn sites bind O2 and the Co sites activate H2O, so as to facilitate the proton-coupled electron transfer processes. Such an electrocatalytic synergy is pivotal to the high-rate oxygen reduction, particularly under water depletion/low humidity conditions.