Exploring Multi-Anion Chemistry in Yttrium Oxyhydrides: Solid-State NMR Studies and DFT Calculations

Rare earth oxyhydrides REOxH(3–2x), with RE = Y, Sc, or Gd and a cationic FCC lattice, are reversibly photochromic in nature. It is known that structural details and anion (O2–:H–) composition dictate the efficiency of the photochromic behavior. The mechanism behind the photochromism is, however, not yet understood. In this study, we use 1H, 2H, 17O, and 89Y solid-state NMR spectroscopy and density functional theory (DFT) calculations to study the various yttrium, hydrogen, and oxygen local environments, anion oxidation states, and hydride ion dynamics. DFT models of YOxH(3–2x) with both anion-ordered and anion-disordered sublattices are constructed for a range of compositions and show a good correlation with the experimental NMR parameters. Two-dimensional 17O–1H and 89Y–1H NMR correlation experiments reveal heterogeneities in the samples, which appear to consist of hydride-rich (x ≈ 0.25) and hydride-poor domains (x ≈ 1) rather than a single composition with homogeneous anion mixing. The compositional variation (as indicated by the different x values in YOxH(3–2x)) is determined by comparing static 1H NMR line widths with calculated 1H–1H dipolar couplings of yttrium oxyhydride models. The 1D 17O MAS spectrum demonstrates the presence of a small percentage of hydroxide (OH–) ions. DFT modeling indicates a reaction between the protons of hydroxides and hydrides to form molecular hydrogen (H+ + H– → H2). 1H MAS NMR indicates the presence of a mobile component that, based on this finding, is attributed to trapped molecular H2 in the lattice

Structural insights into the interactions of repositioning and known drugs for Alzheimer’s disease with hen egg white lysozyme by MM-GBSA

Six drugs (dapsone, diltiazem, timolol, rosiglitazone, mesalazine, and milnacipran) that were predicted by network-based polypharmacology approaches as potential anti-Alzheimer’s drugs, have been subjected in this study for in silico and in vitro evaluation to check their potential against protein fibrillation, which is a causative factor for multiple diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington disease, cardiac myopathy, type-II diabetes mellitus and many others. Molecular docking and thereafter molecular dynamics (MD) simulations revealed that diltiazem, rosiglitazone, and milnacipran interact with the binding residues such as Asp52, Glu35, Trp62, and Asp101, which lie within the fibrillating region of HEWL. The MM-GBSA analysis revealed −7.86, −5.05, and −10.29 kcal/mol as the binding energy of diltiazem, rosiglitazone, and milnacipran. The RMSD and RMSF calculations revealed significant stabilities of these ligands within the binding pocket of HEWL. While compared with two reported ligands inhibiting HEWL fibrillation, milnacipran depicted almost similar binding potential with one of the known ligands (Ligand binding affinity −10.66 kcal/mol) of HEWL. Furthermore, secondary structure analyses revealed notable inhibition of the secondary structural changes with our candidate ligand; especially regarding retention of the 3/10 α-helix both by DSSP simulation, Circular dichroism, and FESEM-based microscopic image analyses. Taking further into experimental validation, all three ligands inhibited fibrillation in HEWL in simulated conditions as revealed by blue shift in Congo red assay and later expressing percentage inhibition in ThioflavinT assay as well. However, dose-dependent kinetics revealed that the antifibrillatory effects of drugs are more pronounced at low protein concentrations. Communicated by Ramaswamy H. Sarma</p