Potential-induced phase transition of low-index Au single crystal surfaces in propylene carbonate solution

In situ scanning tunneling microscopy (STM) was employed to examine the surface structures ofAu(111), Au(100), and Au(110) single crystals in propylene carbonate (PC) containing tetrabutylammonium perchlorate (TBAP). All three electrodes exhibited potential-induced phase 10 transition between the reconstructed and unreconstructed (1 ´ 1) structures at negative and positive potentials, respectively. The potential-induced phase transition of the Au electrode surfaces is attributed to the interaction of TBA cation and perchlorate anion at the electrode surface, which is similar to that which takes place in aqueous solutions. In addition to static atomic structures, dynamic processes of both the reconstruction and the lifting of the reconstruction were investigated 15 by means of in situ STM. The lifting of reconstructed Au(111)–(Ö3 ´ 22) on Au(111) to the (1 ´ 1) structure is completed within 1 min at a positive potential. The diffusion of Au atoms on Au(100) plane in the PC solution proceeds more rapidly than that in the aqueous solution, suggesting that the PC solvent plays an important role in accelerating the diffusion of Au atoms

¹¹³Cd Nuclear Magnetic Resonance as a Probe of Structural Dynamics in a Flexible Porous Framework Showing Selective O₂/N₂ and CO₂/N₂ Adsorption

Two new isomorphous three-dimensional porous coordination polymers, {[Cd­(bpe)_0.5(bdc)­(H₂O)]·EtOH}_<i>n</i> (<b>1</b>) and {[Cd­(bpe)_0.5(bdc)­(H₂O)]·2H₂O}_<i>n</i> (<b>2</b>) [bpe = 1,2-bis­(4-pyridyl)­ethane, and H₂bdc = 1,4-benzenedicarboxylic acid], have been synthesized by altering the solvent media. Both structures contain one-dimensional channels filled with metal-bound water and guest solvent molecules, and desolvated frameworks show significant changes in structure. However, exposure to the solvent vapors (water and methanol) reverts the structure back to the as-synthesized structure, and thus, the reversible flexible nature of the structure was elucidated. The flexibility and permanent porosity were further reinforced from the CO₂ adsorption profiles (195 and 273 K) that show stepwise uptake. Moreover, a high selectivity for O₂ over N₂ at 77 K was realized. The framework exhibits interesting solvent vapor adsorption behavior with dynamic structural transformation depending upon the size, polarity, and coordination ability of the solvent molecules. Further investigation was conducted by solid state ¹¹³Cd nuclear magnetic resonance (NMR) spectroscopy that unambiguously advocates the reversible transformation “pentagonal-bipyramidal CdO₆N → octahedral CdO₅N” geometry in the desolvated state. For the first time, ¹¹³Cd NMR has been used as a probe of structural flexibility in a porous coordination polymer system

Deep learning driven de novo drug design based on gastric proton pump structures

Abstract Existing drugs often suffer in their effectiveness due to detrimental side effects, low binding affinity or pharmacokinetic problems. This may be overcome by the development of distinct compounds. Here, we exploit the rich structural basis of drug-bound gastric proton pump to develop compounds with strong inhibitory potency, employing a combinatorial approach utilizing deep generative models for de novo drug design with organic synthesis and cryo-EM structural analysis. Candidate compounds that satisfy pharmacophores defined in the drug-bound proton pump structures, were designed in silico utilizing our deep generative models, a workflow termed Deep Quartet. Several candidates were synthesized and screened according to their inhibition potencies in vitro, and their binding poses were in turn identified by cryo-EM. Structures reaching up to 2.10 Å resolution allowed us to evaluate and re-design compound structures, heralding the most potent compound in this study, DQ-18 (N-methyl-4-((2-(benzyloxy)-5-chlorobenzyl)oxy)benzylamine), which shows a K i value of 47.6 nM. Further high-resolution cryo-EM analysis at 2.08 Å resolution unambiguously determined the DQ-18 binding pose. Our integrated approach offers a framework for structure-based de novo drug development based on the desired pharmacophores within the protein structure

Physiological skin FDG uptake: A quantitative and regional distribution assessment using PET/MRI.

PurposeTo retrospectively assess the repeatability of physiological F-18 labeled fluorodeoxyglucose (FDG) uptake in the skin on positron emission tomography/magnetic resonance imaging (PET/MRI) and explore its regional distribution and relationship with sex and age.MethodsOut of 562 examinations with normal FDG distribution on whole-body PET/MRI, 74 repeated examinations were evaluated to assess the repeatability and regional distribution of physiological skin uptake. Furthermore, 224 examinations were evaluated to compare differences in the uptake due to sex and age. Skin segmentation on PET was performed as body-surface contouring on an MR-based attenuation correction map using an off-line reconstruction software. Bland-Altman plots were created for the repeatability assessment. Kruskal-Wallis test was performed to compare the maximum standardized uptake value (SUVmax) with regional distribution, age, and sex.ResultsThe limits of agreement for the difference in SUVmean and SUVmax of the skin were less than 30%. The highest SUVmax was observed in the face (3.09±1.04), followed by the scalp (2.07±0.53). The SUVmax in the face of boys aged 0-9 years and 10-20 years (1.33±0.64 and 2.05±1.00, respectively) and girls aged 0-9 years (0.98±0.38) was significantly lower than that of men aged ≥20 years and girls aged ≥10 years (pConclusionPET/MRI enabled the quantitative analysis of skin FDG uptake with repeatability. The degree of physiological FDG uptake in the skin was the highest in the face and varied between sexes. Although attention to differences in body habitus between age groups is needed, skin FDG uptake also depended on age