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We report gas-phase reactions of free Co n (CO) m + (n = 3-11, m = 0-2) with H2, expecting a catalytic reaction of coadsorbed CO and H2 on Co n +. Preadsorption of CO molecules is found to promote H2 adsorption, in particular, on Co n (CO)+ (n = 5, 8-10). Density functional theory (DFT) calculations reveal that the reactivity is governed by the molecular-orbital energy of Co n +, which is tuned by preadsorbed CO molecules. Collision-induced-dissociation experiments performed on Co n COH2+ (n = 8-10) imply that at least some of the CO and H2 molecules are bound together on Co n +.Disturbance of the thyroid hormone homeostasis has been associated with adverse health effects such as goiters and impaired mental development in humans and thyroid tumors in rats. In vitro and in silico methods for predicting the effects of small molecules on thyroid hormone homeostasis are currently being explored as alternatives to animal experiments, but are still in an early stage of development. The aim of this work was the development of a battery of in silico models for a set of targets involved in molecular initiating events of thyroid hormone homeostasis deiodinases 1, 2, and 3, thyroid peroxidase (TPO), thyroid hormone receptor (TR), sodium/iodide symporter, thyrotropin-releasing hormone receptor, and thyroid-stimulating hormone receptor. The training data sets were compiled from the ToxCast database and related scientific literature. Classical statistical approaches as well as several machine learning methods (including random forest, support vector machine, and neural networks) were explored in combination with three data balancing techniques. The models were trained on molecular descriptors and fingerprints and evaluated on holdout data. Furthermore, multi-task neural networks combining several end points were investigated as a possible way to improve the performance of models for which the experimental data available for model training are limited. Classifiers for TPO and TR performed particularly well, with F1 scores of 0.83 and 0.81 on the holdout data set, respectively. Models for the other studied targets yielded F1 scores of up to 0.77. An in-depth analysis of the reliability of predictions was performed for the most relevant models. All data sets used in this work for model development and validation are available in the Supporting Information.We report herein the discovery of a class of potent small-molecule inhibitors of anaplastic lymphoma kinase (ALK) containing a fused indoloquinoline scaffold. The most promising compound CJ-2360 has an IC50 value of 2.2 nM against wild-type ALK and low-nanomolar potency against several clinically reported ALK mutants. This compound is capable of achieving complete tumor regression in the ALK-positive KARPAS-299 xenograft model with oral administration in mice. CJ-2360 represents a promising ALK inhibitor for advanced preclinical development.Owing to excellent metallic conductivity, hydrophilic surfaces, and surface redox properties, a two-dimensional (2D) metal carbide of Ti3C2T x -MXene could serve as a promising pseudocapacitive electrode material for energy storage devices. Meanwhile, the 2D reduced graphene oxide (rGO) combining with the hierarchical cubic spinel nickel-cobalt bimetal oxide (NiCo2O4) nanospikes could control ion diffusion for charge storage, thereby facilitating the improvement of the energy density of a supercapacitor. As per the strategy, the pseudocapacitive 2D Ti3C2T x was loaded on a flexible acid-treated carbon fiber (ACF) backbone to prepare a Ti3C2T x /ACF negative electrode by a convenient drop-casting method. Meanwhile, 2D rGO was deposited on ACF by a simple dip-dry process, which was further decorated by the spinel NiCo2O4 nanospikes using a hydrothermal method to obtain a NiCo2O4@rGO/ACF positive electrode. The fabricated Ti3C2Tx/ACF electrode exhibited an excellent specific capacitance of 246.9 F/g (197.5 mF/cm to step up the energy density of a supercapacitor.The intramolecular 1H NMR dipole-dipole relaxation of molecular fluids has traditionally been interpreted within the Bloembergen-Purcell-Pound (BPP) theory of NMR intramolecular relaxation. The BPP theory draws upon Debye's theory for describing the rotational diffusion of the 1H-1H pair and predicts a monoexponential decay of the 1H-1H dipole-dipole autocorrelation function between distinct spin pairs. Using molecular dynamics (MD) simulations, we show that for both n-heptane and water this is not the case. In particular, the autocorrelation function of individual 1H-1H intramolecular pairs itself evinces a rich stretched-exponential behavior, implying a distribution in rotational correlation times. However, for the high-symmetry molecule neopentane, the individual 1H-1H intramolecular pairs do conform to the BPP description, suggesting an important role of molecular symmetry in aiding agreement with the BPP model. The intermolecular autocorrelation functions for n-heptane, water, and neopentane also do not admit a monoexponential behavior of individual 1H-1H intermolecular pairs at distinct initial separations. We suggest expanding the autocorrelation function in terms of modes, provisionally termed molecular modes, that do have an exponential relaxation behavior. With care, the resulting Fredholm integral equation of the first kind can be inverted to recover the probability distribution of the molecular modes. [https://www.selleckchem.com/products/odm208.html Opevesostat] The advantages and limitations of this approach are noted.The identification of crystalline drug polymorphs using terahertz vibrational spectroscopy is a powerful approach for the nondestructive and noninvasive characterization of solid-state pharmaceuticals. However, a complete understanding of the terahertz spectra of molecular solids is challenging to obtain because of the complex nature of the low-frequency vibrational motions found in the sub-3 THz (sub-100 cm-1) range. Unambiguous assignments of the observed spectral features can be achieved through quantum mechanical solid-state simulations of crystal structures and lattice vibrations utilizing the periodic boundary condition approach. The terahertz spectra of two polymorphs of enalapril maleate are presented here to demonstrate that even large pharmaceuticals can be successfully modeled using solid-state density functional theory, including cocrystalline solids comprised of multiple distinct species. These simulations enable spectral assignments to be made, but also provide insights into the conformational and cohesion energies that contribute to the polymorph stabilities.