Dynamics of superionic Rb3H(SeO4)2 single crystals studied by H and Rb spin-lattice relaxation

The ¹H and ⁸⁷Rb spin-lattice relaxation and spin-spin relaxation times in superionic Rb₃H(SeO₄)₂ single crystals grown by the slow evaporation method were measured over the temperature range 160-450 K. The temperature dependencies of the ¹H T₁, T_1ρ, and T₂ are measured. In the ferroelastic phase, T₁ differs from T_1ρ, which is in turn different from T₂, although these three relaxation times converge to similar values near 410 K. This transition seems to occur at temperature which is about 40 K lower than the superionic transition temperature. The observation of liquid-like values of the ¹H T₁, T_1ρ, and T₂ in the high temperature is compatible with the phase being superionic, indicating that the destruction and reconstruction of hydrogen bonds does indeed occur at high temperature. In addition, the ⁸⁷Rb T₁ and T₂ values at high temperature were similar (on the order of milliseconds), a trend that was also observed for ¹H T₁ and T₂. This behavior is expected for most hopping-type ionic conductors, and could be attributed to interactions between the mobile ions and the neighboring group ions within the crystal. The motion giving rise to this liquid-like behavior is related to the superionic motion.     

Scaffold-based molecular design with a graph generative model

Searching for new molecules in areas like drug discovery often starts from the core structures of known molecules. Such a method has called for a strategy of designing derivative compounds retaining a particular scaffold as a substructure. On this account, our present work proposes a graph generative model that targets its use in scaffold-based molecular design. Our model accepts a molecular scaffold as input and extends it by sequentially adding atoms and bonds. The generated molecules are then guaranteed to contain the scaffold with certainty, and their properties can be controlled by conditioning the generation process on desired properties. The learned rule of extending molecules can well generalize to arbitrary kinds of scaffolds, including those unseen during learning. In the conditional generation of molecules, our model can simultaneously control multiple chemical properties despite the search space constrained by fixing the substructure. As a demonstration, we applied our model to designing inhibitors of the epidermal growth factor receptor and show that our model can employ a simple semi-supervised extension to broaden its applicability to situations where only a small amount of data is available.

We propose a scaffold-based graph generative model for designing novel drug candidates that include the desired scaffold as a substructure.     

Lewis-Base Adducts of Group 11 Metal(I) Compounds. LXXVI Structural Studies in the Copper(I) Halide : Norbornadiene System

The structural characterizations of some copper(I) halide (CuX) adducts with norbornadiene (nbd) are recorded. CuCl : nbd (1:1)₄ (a redetermination), (2:1)_2(|), are systems both based around Cu₄Cl₄ cubane-type cluster arrays. CuBr : nbd (7:3)_(|)( 0.5 MeOH), a complex polymer with 3-symmetry, is believed to be the complex previously described as an adduct of 2:1 stoichiometry. Attempts to obtain an iodide counterpart have resulted in the definition of an ephemeral adduct CuI : MeCN (3:2)_(|). 0.5 C₇H₈ in which, remarkably, the nbd is uncoordinated; the complex is a polymer, related to the [AgX(quinoline)]_(|) (X = Cl, Br) saddle polymer.     

A facile synthesis of (6S,1′S)-(+)-hernandulcin and (6S,1′R)-(+)-epihernandulcin

A facile total synthesis of (+)-hernandulcin (1) was accomplished from (−)-isopulegol in 6 steps with 15% overall yield. Epoxidation of (−)-isopulegol with m-chloroperbenzoic acid followed by opening of the epoxide 3a with prenyl Grignard afforded the tertiary alcohol 4a with correct C-6 and C-1′ stereochemistry as a major product. Oxidation of the secondary alcohol in compound 4a to the ketone 5a was accomplished in high yield by using TPAP and N-methylmorpholine N-oxide. Conversion of the ketone 5a to α,β-unsaturated ketone via organoselenium intermediate gave (+)-hernandulcin (1). This method was also successfully applied to the synthesis of (+)-epihernandulcin (2).     

Effect of steps on the decomposition of CH3O at PdZn alloy surfaces

The decomposition of methoxide (CH(3)O) on a PdZn alloy is considered to be the rate-limiting step of steam re-forming of methanol over a Pd/ZnO catalyst. Our previous density functional (DF) studies (Langmuir 2004, 20, 8068; Phys. Chem. Chem. Phys. 2004, 6, 4499) revealed only a very low propensity of defect-free flat (111) and (100) PdZn surfaces to promote C-H or C-O bond breaking of CH(3)O. Thus, we applied the same DF periodic slab-model approach to investigate these two routes of CH(3)O decomposition on PdZn(221) surfaces that expose Pd, (221)(Pd), and Zn, (221)(Zn), steps. C-H bond cleavage of CH(3)O is greatly facilitated on (221)(Pd): the calculated activation energy is dramatically reduced, to approximately 50 kJ mol(-1) from approximately 90 kJ mol(-1) on flat PdZn surfaces, increasing the rate constant by a factor of 10(8). The lower barrier is mainly due to a weaker interaction of the reactant CH(3)O and an enhanced interaction of the product CH(2)O with the substrate. The activation energy for C-O bond scission did not decrease on the (221)(Pd) step. On the (221)(Zn) step, the calculated reaction barriers of both decomposition routes are even higher than on flat surfaces, because of the stronger adsorption of CH(3)O. Steps (and other defects) appear to be crucial for methanol steam re-forming on Pd/ZnO catalyst; the stepped surface PdZn(221)(Pd) is a realistic model for studying the reactivity of this catalyst.     

An Fc variant with two mutations confers prolonged serum half-life and enhanced effector functions on IgG antibodies

The pH-selective interaction between the immunoglobulin G (IgG) fragment crystallizable region (Fc region) and the neonatal Fc receptor (FcRn) is critical for prolonging the circulating half-lives of IgG molecules through intracellular trafficking and recycling. By using directed evolution, we successfully identified Fc mutations that improve the pH-dependent binding of human FcRn and prolong the serum persistence of a model IgG antibody and an Fc-fusion protein. Strikingly, trastuzumab-PFc29 and aflibercept-PFc29, a model therapeutic IgG antibody and an Fc-fusion protein, respectively, when combined with our engineered Fc (Q311R/M428L), both exhibited significantly higher serum half-lives in human FcRn transgenic mice than their counterparts with wild-type Fc. Moreover, in a cynomolgus monkey model, trastuzumab-PFc29 displayed a superior pharmacokinetic profile to that of both trastuzumab-YTE and trastuzumab-LS, which contain the well-validated serum half-life extension Fcs YTE (M252Y/S254T/T256E) and LS (M428L/N434S), respectively. Furthermore, the introduction of two identified mutations of PFc29 (Q311R/M428L) into the model antibodies enhanced both complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity activity, which are triggered by the association between IgG Fc and Fc binding ligands and are critical for clearing cancer cells. In addition, the effector functions could be turned off by combining the two mutations of PFc29 with effector function-silencing mutations, but the antibodies maintained their excellent pH-dependent human FcRn binding profile. We expect our Fc variants to be an excellent tool for enhancing the pharmacokinetic profiles and potencies of various therapeutic antibodies and Fc-fusion proteins.Subject terms: Antibody therapy, Molecularly targeted therapy, Drug development     

Enhanced output voltage of nano energy harvester with diverse textiles

Abstract

We demonstrate the electrical properties of nano energy harvesters (NEHs) with various textiles for smart textiles that can be applied to the next generation wearable electronics. Output voltages and currents of NEHs with various fabrics, such as a cotton, rayon and wool that have different triboelectricity were measured. Cotton, rayon and wool shows the maximum output voltages of 1.250, 3.313 and 4.063 V, respectively. In addition, output currents of those textiles were 0.75, 4.4, 1.063 μA, respectively. Wool, in particular, which has the highest triboelectricity of 350 V exhibits the highest output voltage.     

Chemistry of novolac resins. X. Polymerization studies of HMTA and strategically synthesized model compounds

The reactions between hexamethylenetetramine (HMTA) and compounds which model novolac resins have been studied by ¹³C‐ and ¹⁵N‐NMR techniques. The dimer and tetramer compounds vary in molecular size and structure and react with HMTA to yield benzylamines and benzoxazine as the major initial‐formed intermediates and convert to methylene linked compounds at increased temperatures. The reaction of the compounds with only ortho reactive sites paralleled the 2,4‐xylenol–HMTA case reported by us previously; however, increasing molecular weight favored the formation of benzylamines and not benzoxazines. Those compounds with only para reactive sites paralleled the 2,6‐xylenol–HMTA case. The reactivity of the systems containing both ortho and para reactive sites depends on the ratio of ortho/para sites and various aspects such as the chemical structure and molecular weight of the compound, the HMTA level, and the melting point and pH of the system. These results parallel those obtained from novolac/HMTA systems. The xylenol/HMTA reactions formed similar products but showed quite different relative reaction rates by varying the HMTA ratio and structures of the materials. The importance of careful selection of model systems is also discussed. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 1347–1355, 1999     

Prediction of African Swine Fever Virus Inhibitors by Molecular Docking-Driven Machine Learning Models

African swine fever virus (ASFV) causes a highly contagious and severe hemorrhagic viral disease with high mortality in domestic pigs of all ages. Although the virus is harmless to humans, the ongoing ASFV epidemic could have severe economic consequences for global food security. Recent studies have found a few antiviral agents that can inhibit ASFV infections. However, currently, there are no vaccines or antiviral drugs. Hence, there is an urgent need to identify new drugs to treat ASFV. Based on the structural information data on the targets of ASFV, we used molecular docking and machine learning models to identify novel antiviral agents. We confirmed that compounds with high affinity present in the region of interest belonged to subsets in the chemical space using principal component analysis and k-means clustering in molecular docking studies of FDA-approved drugs. These methods predicted pentagastrin as a potential antiviral drug against ASFVs. Finally, it was also observed that the compound had an inhibitory effect on AsfvPolX activity. Results from the present study suggest that molecular docking and machine learning models can play an important role in identifying potential antiviral drugs against ASFVs.