The synthesis of Benzoazines on the base of o-Bromomethylbenzophenone derivatives

Convenient and efficient methods for the preparation of novel phthalazine and pyrazino[1,2-b]isoquinoline derivatives are reported that utilized the reaction of [2-(bromomethyl)phenyl](4-chlorophenyl)methanone with 1,2-dinucleophiles. The crystal structure for 11-(4-Chlorophenyl)-1-oxo-1,2-dihydropyrazino[1,2-b]isoquinolin-5-ium bromide is also described

Bis{μ2-2-[(2-hy­droxy­eth­yl)(meth­yl)amino]­ethano­lato}bis­(μ3-N-methyl-2,2′-aza­nediyldiethano­lato)tetra­kis­(thio­cyan­atato-κN)dichromium(III)dimanganese(II) dimethyl­formamide tetra­solvate

The heterometallic title complex, [Cr2Mn2(C5H11NO2)2(C5H12NO2)2(NCS)4]·4C3H7NO, was prepared using manganese powder, Reineckes salt, ammonium thio­cyanate and a non-aqueous solution of N-methyl­diethano­lamine in air. The centrosymmetric mol­ecular structure of the complex is based on a tetra­nuclear {Mn2Cr2(μ-O)6} core. The tetra­nuclear complex mol­ecule and the two uncoordinated dimethyl­formamide mol­ecules are linked by O—H⋯O hydrogen bonds, while the two other mol­ecules of dimethyl­formamide do not participate in hydrogen bonding

Ethyl 1,6-dimethyl-2-oxo-4-(quinolin-4-yl)-1,2,3,4-tetra­hydro­pyrimidine-5-carboxyl­ate

In the title compound, C18H19N3O3, the tetra­hydro­pyrimidone ring adopts a distorted boat conformation. In the crystal structure, inter­molecular N—H⋯O hydrogen bonds link the mol­ecules into centrosymmetric dimers, which are further linked via inter­molecular C—H⋯π inter­actions. In addition, an intra­molecular C—H⋯O hydrogen bond occurs

A community effort in SARS-CoV-2 drug discovery.

peer reviewedThe COVID-19 pandemic continues to pose a substantial threat to human lives and is likely to do so for years to come. Despite the availability of vaccines, searching for efficient small-molecule drugs that are widely available, including in low- and middle-income countries, is an ongoing challenge. In this work, we report the results of an open science community effort, the "Billion molecules against Covid-19 challenge", to identify small-molecule inhibitors against SARS-CoV-2 or relevant human receptors. Participating teams used a wide variety of computational methods to screen a minimum of 1 billion virtual molecules against 6 protein targets. Overall, 31 teams participated, and they suggested a total of 639,024 molecules, which were subsequently ranked to find 'consensus compounds'. The organizing team coordinated with various contract research organizations (CROs) and collaborating institutions to synthesize and test 878 compounds for biological activity against proteases (Nsp5, Nsp3, TMPRSS2), nucleocapsid N, RdRP (only the Nsp12 domain), and (alpha) spike protein S. Overall, 27 compounds with weak inhibition/binding were experimentally identified by binding-, cleavage-, and/or viral suppression assays and are presented here. Open science approaches such as the one presented here contribute to the knowledge base of future drug discovery efforts in finding better SARS-CoV-2 treatments.R-AGR-3826 - COVID19-14715687-CovScreen (01/06/2020 - 31/01/2021) - GLAAB Enric

Crystal structure of 4-tert-butyl-2-{2-[N-(3,3-dimethyl-2-oxobutyl)-N-isopropylcarbamoyl]phenyl}-1-isopropyl-1H-imidazol-3-ium perchlorate

In the title salt, C26H40N3O2+·ClO4−, the positive charge of the organic cation is delocalized between the two N atoms of the imidazole ring. The C...;N bond distances are 1.338 (2) and 1.327 (3) Å. The substituents on the benzene ring are rotated almost orthogonal with respect to this ring due to the presence of the bulky isopropyl substituents. The dihedral angle between the benzene and imidazole rings is 75.15 (12)°. Three of the O atoms of the anion are disordered over two sets of sites due to rotation around one of the O—Cl bonds. The ratio of the refined occupancies is 0.591 (14):0.409 (14). In the crystal, the cation and perchlorate anion are bound by an N—H...O hydrogen bond. In addition, the cation–anion pairs are linked into layers parallel to (001) by multiple weak C—H...O hydrogen bonds

Teaching a Neural Network to Attach and Detach Electrons from Molecules

Physics-inspired Artificial Intelligence (AI) is at the forefront of methods development in molecular modeling and computational chemistry. In particular, interatomic potentials derived with Machine Learning algorithms such as Deep Neural Networks (DNNs), achieve the accuracy of high-fidelity quantum mechanical (QM) methods in areas traditionally dominated by empirical force fields and allow performing massive simulations. The applicability domain of DNN potentials is usually limited by the type of training data. As such, transferable models are aimed to be extensible in the description of chemical and conformational diversity of organic molecules. However, most DNN potentials, such as the AIMNet model we proposed previously, were parametrized for neutral molecules or closed-shell ions due to architectural limitations. In this work, we extend machine learning framework toward open-shell anions and cations. We introduce AIMNet-NSE (Neural Spin Equilibration) architecture, which being properly trained, could predict atomic and molecular properties for an arbitrary combination of molecular charge and spin multiplicity. This model explores a new dimension of transferability by adding the charge-spin space. The AIMNet-NSE model is capable of reproducing reference QM energies for cations, neutrals, and anions with errors of about 2-3 kcal/mol, compared to the reference QM simulations. The spin-charges have errors ~0.01 electrons for small organic molecules containing nine chemical elements {H, C, N, O, F, Si, P, S and Cl}. The AIMNet-NSE model allows to fully bypass QM calculations and derive the ionization potential, electron affinity, and conceptual Density Functional Theory quantities like electronegativity, hardness, and condensed Fukui functions with a speed up to 104 molecules per second on a single modern GPU. We show that these descriptors, along with learned atomic representations, could be used to model chemical reactivity through an example of regioselectivity in electrophilic aromatic substitution reactions.</p