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The protocol for simple, efficient, and mild synthesis of oxazolyl sulfonyl fluorides was developed through Rh2(OAc)4-catalyzed annulation of methyl-2-diazo-2-(fluorosulfonyl)acetate (MDF) or its ethyl ester derivative with nitriles. This practical method provides a general and direct route to a unique class of highly functionalized oxazolyl-decorated sulfonyl fluoride warheads with great potential in medicinal chemistry, chemical biology, and drug discovery.This work considers strategies to develop accurate and reliable graph neural networks (GNNs) for molecular property predictions. Prediction performance of GNNs is highly sensitive to the change in various parameters due to the inherent challenges in molecular machine learning, such as a deficient amount of data samples and bias in data distribution. Comparative studies with well-designed experiments are thus important to clearly understand which GNNs are powerful for molecular supervised learning. Our work presents a number of ablation studies along with a guideline to train and utilize GNNs for both molecular regression and classification tasks. First, we validate that using both atomic and bond meta-information improves the prediction performance in the regression task. Second, we find that the graph isomorphism hypothesis proposed by [Xu, K.; et al How powerful are graph neural networks? 2018, arXiv1810.00826. arXiv.org e-Print archive. https//arxiv.org/abs/1810.00826] is valid for the regression task. Surprisingly, however, the findings above do not hold for the classification tasks. L-Ascorbic acid 2-phosphate sesquimagnesium supplier Beyond the study on model architectures, we test various regularization methods and Bayesian learning algorithms to find the best strategy to achieve a reliable classification system. We demonstrate that regularization methods penalizing predictive entropy might not give well-calibrated probability estimation, even though they work well in other domains, and Bayesian learning methods are capable of developing reliable prediction systems. Furthermore, we argue the importance of Bayesian learning in virtual screening by showing that well-calibrated probability estimation may lead to a higher success rate.We present an optimized density-functional tight-binding (DFTB) parameterization for iron-based complexes based on the popular trans3d set of parameters. The transferability of the original and optimized parameterizations is assessed using a set of 50 iron complexes, which include carbonyl, cyanide, polypyridine, and cyclometalated ligands. DFTB-optimized structures predicted using the trans3d parameters show a good agreement with both experimental crystal geometries and density functional theory (DFT)-optimized structures for Fe-N bond lengths. Conversely, Fe-C bond lengths are systematically overestimated. We improve the accuracy of Fe-C interactions by truncating the Fe-O repulsive potential and reparameterizing the Fe-C repulsive potential using a training set of six isolated iron complexes. The new trans3d*-LANLFeC parameter set can produce accurate Fe-C bond lengths in both geometry optimizations and molecular dynamics (MD) simulations, without significantly affecting the accuracy of Fe-N bond lengths. Moreover, the potential energy curves of Fe-C interactions are considerably improved. This improved parameterization may open the door to accurate MD simulations at the DFTB level of theory for large systems containing iron complexes, such as sensitizer-semiconductor assemblies in dye-sensitized solar cells, that are not easily accessible with DFT approaches because of the large number of atoms.The initial drug release from in situ forming implants is affected by factors such as the physicochemical properties of the active pharmaceutical ingredient, the type of the excipients utilized, and the surrounding environment. The feasibility of UV-vis imaging for characterization of the initial behavior of poly(d,l-lactide-co-glycolide) (PLGA)/1-methyl-2-pyrrolidinone (NMP) in situ forming implants was investigated. The in vitro release of leuprolide acetate (LA) and implant formation in real time were monitored using dual-wavelength imaging at 280 and 525 nm, respectively, in matrices based on agarose gel and hyaluronic acid (HA) solution emulating the subcutaneous matrix. Three hours upon injection of the pre-formulation, approximately 15% of the total amount of LA administered was found in the agarose gel, while 5% was released from the implant into the HA solution. Concurrently, more extensive swelling of the implants in the HA solution as compared to implants in the agarose gel was observed. Transport n interesting approach in the development of in situ forming implant delivery systems.The toughness and the durability under a high humidity condition of the interfaces in dissimilar adhesive joints of carbon-fiber-reinforced thermoplastic with a polyamide-6 matrix and Al alloy were evaluated by two test methods, in which a tensile opening load was applied to the specimens to cleave the interfaces apart in two different ways. In the double cantilever beam (DCB) test, the specimens were continuously pulled apart at a constant velocity, while in the wedge test, the specimens are pulled apart at a constant displacement. The crack growth along the interface in the DCB test was dynamically monitored with the assistance of mechanoluminescence for the accurate detection of the phenomena at the crack tip. The wedge test was employed for the evaluation of the durability of the interfaces under high humidity conditions. It was found that the adhesive joints were failed by various failure modes depending on the surface pretreatment and environmental conditions. Throughout the work, discussion was made concerned with the interfacial structures and the adhesion mechanism of dissimilar adhesive joints.The synthetically challenging and highly functionalized azabicyclo[6.4.1] ring system, which is found in lycopodium alkaloid lycoclavatumide and some natural molecules, was synthesized for the first time. The key reaction was a diastereoselective type II [5+2] cycloaddition with excellent functional group compatibility. We tried to install the desired eight-membered ring in the final product by RCM reaction.Psoriasis is an inflammatory disease of the epidermis based on an immunological mechanism involving Langerhans cells and T lymphocytes that produce pro-inflammatory cytokines. Genetic factors, environmental factors, and improper nutrition are considered triggers of the disease. Numerous studies have reported that in a high number of patients, psoriasis is associated with obesity. Excess adipose tissue, typical of obesity, causes a systemic inflammatory status coming from the inflammatory active adipose tissue; therefore, weight reduction is a strategy to fight this pro-inflammatory state. This study aimed to evaluate how a nutritional regimen based on a ketogenic diet influenced the clinical parameters, metabolic profile, and inflammatory state of psoriasis patients. To this end, 30 psoriasis patients were subjected to a ketogenic nutritional regimen and monitored for 4 weeks by evaluating the clinical data, biochemical and clinical parameters, NMR metabolomic profile, and IL-2, IL-1β, TNF-α, IFN-γ, and IL-4 concentrations before and after the nutritional regimen. Our data show that a low-calorie ketogenic diet can be considered a successful strategy and therapeutic option to gain an improvement in psoriasis-related dysmetabolism, with significant correction of the full metabolic and inflammatory status.Here we reported a hierarchical self-assembly approach toward well-defined superlattices in supramolecular liquid crystals by fullerene-based sphere-cone block molecules. The fullerenes crystallize to form monolayer nanosheets intercalated by the attached soft hydrocarbon cones. The frustration caused by cross-sectional area mismatch between the spheres and the somewhat oversize cones leads to a unique lamellar superlattice whereby each stack of six pairs of alternating sphere-cone sublayers is followed by a cone double layer. While such areal mismatch problems in soft matter are usually solved by interface curvature, the lamellar superlattice solution is best suited to systems with rigid layers. Meanwhile, formation of the superlattice significantly improves the material’s transient electron conductivity, with the maximum value being among the highest for π-conjugated organic materials. The design principle of solving steric frustration by forming a superlattice opens a new avenue toward self-assembled optoelectronic materials.A new approach is theoretically proposed to study the glass transition of active pharmaceutical ingredients and a glass-forming anisotropic molecular liquid at high pressures. We describe amorphous materials as a fluid of hard spheres. Effects of nearest neighbor interactions and cooperative motions of particles on glassy dynamics are quantified through a local and collective elastic barrier calculated using the elastically collective nonlinear Langevin equation theory. Inserting two barriers into Kramer’s theory gives the structural relaxation time. Then, we formulate a new mapping based on the thermal expansion process under pressure to intercorrelate particle density, temperature, and pressure. This analysis allows us to determine the pressure and temperature dependence of α relaxation. From this, we estimate the effective elastic modulus of amorphous materials and capture the effects of conformation on the relaxation process. Remarkably, our theoretical results agree well with experiments.Polymerized ionic liquids (PolyILs) are promising candidates for a broad range of technologies. However, the relatively low conductivity of PolyILs at room temperature has strongly limited their applications. In this work, we provide new insights into the roles of various microscopic parameters controlling ion transport in these polymers, which are crucial for their rational design and practical applications. Using broadband dielectric spectroscopy and neutron and light scattering techniques, we found a clear connection between the activation energy for conductivity, fast dynamics, and high-frequency shear modulus in PolyILs at their glass transition temperature (Tg). In particular, our analysis reveals a correlation between conductivity and the amplitude of fast picosecond fluctuations at Tg, suggesting the possible involvement of fast dynamics in lowering the energy barrier for ion conductivity. We also demonstrate that both the activation energy for ion transport and the amplitude of the fast fluctuations depend on the high-frequency shear moduli of PolyILs, thus identifying a practically important parameter for tuning conductivity. The parameters recognized in this work and their connection to the ionic conductivity of PolyILs set the stage for a deeper understanding of the mechanism of ion transport in PolyILs in the glassy state.Polystyrene beads are often used as test particles in aerosol science. Here, a contact-less technique is reported for determining the refractive index of a solid aerosol particle as a function of wavelength and temperature (20-234 °C) simultaneously. Polystyrene beads with a diameter of 2 μm were optically trapped in air in the central orifice of a ceramic heating element, and Mie spectroscopy was used to determine the radius and refractive index (to precisions of 0.8 nm and 0.0014) of eight beads as a function of heating and cooling. Refractive index, n, as a function of wavelength, λ (0.480-0.650 μm), and temperature, T, in centigrade, was found to be n = 1.5753 – (1.7336 × 10-4)T + (9.733 × 10-3)λ-2 in the temperature range 20 less then T less then 100 °C and n = 1.5877 – (2.9739 × 10-4)T + (9.733 × 10-3)λ-2 in the temperature range 100 less then T less then 234 °C. The technique represents a step change in measuring the refractive index of materials across an extended range of temperature and wavelength in an absolute manner and with high precision.