Thompsonmccray9222

An efficient Cu(I)-catalyzed oxidative cyclization of alkynyl-tethered enynamides for the construction of fused bicyclic cyclopentadiene derivatives is disclosed. The cascade proceeds through alkyne oxidation, carbene/alkyne metathesis, and formal (3 + 2) cycloaddition. Employing aryl-tethered enynamides as starting materials, substituted 2-aminofurans can be exclusively formed.The liquid structures of three alkyl ammonium bromide and urea DESs, ethylammonium bromideurea (11), butylammonium bromideurea (11), and ethylammonium bromide/butylammonium bromideurea (0.50.51), have been studied using small-angle neutron diffraction with H/D substituted sample contrasts. The diffraction data was fit using empirical potential structure refinement (EPSR). An amphiphilic nanostructure was found in all DESs due to cation alkyl chains being solvophobically excluded from charged domains, and due to clustering together. The polar domain was continuous in all three DESs, whereas the apolar domain was continuous for the butylammonium DES and in the mixed DES, but not the ethylammonium DES. This is attributed to solvophobic interactions being weaker for the short ethyl chain. Surprisingly, the urea also forms large clusters in all three DESs. In ethylammonium bromideurea (11), urea-urea orientations are mainly perpendicular, but in butylammonium bromideurea (11) and the mixed system in-plane and perpendicular arrangements are found. The liquid nanostructures found in this work, especially for the ethylammonium DES, are different from those found previously for the corresponding DESs formed using glycerol, revealing that the DES amphiphilic nanostructure is sensitive to the nature of the HBD (hydrogen bond donor).Artificial intelligence and multiobjective optimization represent promising solutions to bridge chemical and biological landscapes by addressing the automated de novo design of compounds as a result of a humanlike creative process. In the present study, we conceived a novel pair-based multiobjective approach implemented in an adapted SMILES generative algorithm based on recurrent neural networks for the automated de novo design of new molecules whose overall features are optimized by finding the best trade-offs among relevant physicochemical properties (MW, logP, HBA, HBD) and additional similarity-based constraints biasing specific biological targets. In this respect, we carried out the de novo design of chemical libraries targeting neuraminidase, acetylcholinesterase, and the main protease of severe acute respiratory syndrome coronavirus 2. Several quality metrics were employed to assess drug-likeness, chemical feasibility, diversity content, and validity. Molecular docking was finally carried out to better evaluate the scoring and posing of the de novo generated molecules with respect to X-ray cognate ligands of the corresponding molecular counterparts. Our results indicate that artificial intelligence and multiobjective optimization allow us to capture the latent links joining chemical and biological aspects, thus providing easy-to-use options for customizable design strategies, which are especially effective for both lead generation and lead optimization. The algorithm is freely downloadable at https//github.com/alberdom88/moo-denovo and all of the data are available as Supporting Information.The enzyme-catalyzed degradation of the biogenic amine serotonin is an essential regulatory mechanism of its level in the human organism. In particular, monoamine oxidase A (MAO A) is an important flavoenzyme involved in the metabolism of monoamine neurotransmitters. Despite extensive research efforts, neither the catalytic nor the inhibition mechanisms of MAO enzymes are currently fully understood. In this article, we present the quantum mechanics/molecular mechanics simulation of the rate-limiting step for the serotonin decomposition, which consists of hydride transfer from the serotonin methylene group to the N5 atom of the flavin moiety. Free-energy profiles of the reaction were computed by the empirical valence bond method. Apart from the enzymatic environment, the reference reaction in the gas phase was also simulated, facilitating the estimation of the catalytic effect of the enzyme. The calculated barrier for the enzyme-catalyzed reaction of 14.82 ± 0.81 kcal mol-1 is in good agreement with the experimental value of 16.0 kcal mol-1, which provides strong evidence for the validity of the proposed hydride-transfer mechanism. Together with additional experimental and computational work, the results presented herein contribute to a deeper understanding of the catalytic mechanism of MAO A and flavoenzymes in general, and in the long run, they should pave the way toward applications in neuropsychiatry.Despite the chemistry of actinide-ligand bonding is continuing and of burgeoning interest, investigations of the chemical bonding of bimetallic complexes involving transuranics remain relatively less, and there are rarely studies on the bonding features between actinide and coinage metals (CM). We present a systematic research on the series of An@Au7 (An = Th to Cm), UCM7 (CM = Cu, Ag, Au), and WAu7 clusters to investigate the unique geometries, electronic structures, and chemical bonding between An 5f6d orbitals and CM ns orbitals, and to find their periodicity across the actinides and within the group of transition metals. momordin-Ic in vitro A unique planar wheel-like structure for An@Au7 clusters with the help of actinide metals encapsulation via spin-orbit coupling, resulting in An(III). Instead, the transition-metal (TM) element W retains its usual six-gold-coordination structure in WAu7, thus forcing the seventh Au out of plane. The An-CM interactions, depending on the ion radii, become stronger with the increase of the atomic number of the actinide metals, as well as the CM. These results show that the presence of actinides in clusters can lead to unique electronic and geometrical structures.In this work, the photochemically and thermally induced isomerization of multiple donor-acceptor Stenhouse adducts (DASAs) of the first, second, and third generation is studied by means of state-of-the-art ab initio electronic structure methods leading to new insight into multiple facets of the reaction mechanism. Importantly, prior to any studies of the reaction mechanism, a set of test calculations demonstrate the suitability of the applied ADC(2) and CC2 methods in the present context. An important aspect in this regard is the availability of electronic energies and gradients under implicit consideration of solvent effects. On the basis of calculated reaction energies and barriers as well as a thorough analysis of the wave function compositions, interesting features of the reaction mechanism are deduced. For example, the closed form of second- and third-generation DASAs can be significantly stabilized by π - π interactions between the donor and acceptor termini when certain structural requirements are fulfilled.