Crystal structure and Hirshfeld surface analysis of 3-eth-oxy-1-ethyl-6-nitro-quinoxalin-2(1H)-one.

The asymmetric unit of the title compound, C12H13N3O4, consists of two mol-ecules differing to a small degree in their conformations. In the crystal, layers of mol-ecules are connected by weak C-H⋯O hydrogen bonds and slipped π-stacking inter-actions. These layers lie parallel to (10) and are stacked along the normal to that plane. Hirshfeld surface analysis indicates that the most important contributions for the crystal packing arise from H⋯H (43.5%) and H⋯O/O⋯H (30.8%) contacts. The density functional theory (DFT) optimized structure of the title compound at the B3LYP/ 6-311 G(d,p) level agrees well with the experimentally determined mol-ecular structure in the solid state.

Synthesis, structure and Hirshfeld surface analysis of 1,3-bis-[(1-octyl-1H-1,2,3-triazol-4-yl)meth-yl]-1H-benzo[d]imidazol-2(3H)-one.

The title mol-ecule, C29H44N8O, adopts a conformation resembling a two-bladed fan with the octyl chains largely in fully extended conformations. In the crystal, C-H⋯O hydrogen bonds form chains of mol-ecules extending along the b-axis direction, which are linked by weak C-H⋯N hydrogen bonds and C-H⋯π inter-actions to generate a three-dimensional network. A Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H⋯H (68.3%), H⋯N/N⋯H (15.7%) and H⋯C/C⋯H (10.4%) inter-actions.

Crystal structure determination, Hirshfeld surface, crystal void, inter-molecular inter-action energy analyses, as well as DFT and energy framework calculations of 2-(4-oxo-4,5-di-hydro-1H-pyra-zolo[3,4-d]pyrimidin-1-yl)acetic acid.

In the title mol-ecule, C7H6N4O3, the bicyclic ring system is planar with the carb-oxy-methyl group inclined by 81.05 (5)° to this plane. In the crystal, corrugated layers parallel to (010) are generated by N-H⋯O, O-H⋯N and C-H⋯O hydrogen-bonding inter-actions. The layers are associated through C-H⋯π(ring) inter-actions. A Hirshfeld surface analysis indicates that the most important contributions to the crystal packing are from H⋯O/O⋯H (34.8%), H⋯N/N⋯H (19.3%) and H⋯H (18.1%) inter-actions. The volume of the crystal voids and the percentage of free space were calculated to be 176.30 Å3 and 10.94%, showing that there is no large cavity in the crystal packing. Computational methods revealed O-H⋯N, N-H⋯O and C-H⋯O hydrogen-bonding energies of 76.3, 55.2, 32.8 and 19.1 kJ mol-1, respectively. Evaluations of the electrostatic, dispersion and total energy frameworks indicate that the stabilization is dominated via dispersion energy contributions. Moreover, the optimized mol-ecular structure, using density functional theory (DFT) at the B3LYP/6-311G(d,p) level, was compared with the experimentally determined one. The HOMO-LUMO energy gap was determined and the mol-ecular electrostatic potential (MEP) surface was calculated at the B3LYP/6-31G level to predict sites for electrophilic and nucleophilic attacks.

Crystal structure, Hirshfeld surface analysis and DFT calculations of (E)-3-[1-(2-hy-droxy-phenyl-anilino)ethyl-idene]-6-methyl-pyran-2,4-dione.

The asymmetric unit of the title compound, C14H13NO4, contains three independent mol-ecules, which differ slightly in conformation. Each contains an intra-molecular N-H⋯O hydrogen bond. In the crystal, O-H⋯O hydrogen bonds form chains of mol-ecules, which are linked into corrugated sheets parallel to (03) plane by C-H⋯O hydrogen bonds together with π inter-actions between the carbonyl groups and the 2-hy-droxy-phenyl rings. The layers are linked by further C-H⋯O hydrogen bonds. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H⋯H (49.0%), H⋯O/O⋯H (28.3%) and H⋯C/C⋯H (10.9%) inter-actions. van der Waals inter-actions are the dominant inter-actions in the crystal packing. Moreover, density functional theory (DFT) optimized structures at the B3LYP/ 6-311 G(d,p) level are compared with the experimentally determined mol-ecular structure in the solid state. The HOMO-LUMO behavior was elucidated to determine the energy gap of 4.53 eV.

Crystal structure, Hirshfeld surface analysis and inter-action energy calculation of 4-(furan-2-yl)-2-(6-methyl-2,4-dioxo-pyran-3-yl-idene)-2,3,4,5-tetra-hydro-1H-1,5-benzodiazepine.

The title compound {systematic name: (S,E)-3-[4-(furan-2-yl)-2,3,4,5-tetra-hydro-1H-benzo[b][1,4]diazepin-2-yl-idene]-6-methyl-2H-pyran-2,4(3H)-dione}, C19H16N2O4, is constructed from a benzodiazepine ring system linked to furan and pendant di-hydro-pyran rings, where the benzene and furan rings are oriented at a dihedral angle of 48.7 (2)°. The pyran ring is modestly non-planar [largest deviation of 0.029 (4) Šfrom the least-squares plane] while the tetra-hydro-diazepine ring adopts a boat conformation. The rotational orientation of the pendant di-hydro-pyran ring is partially determined by an intra-molecular N-HDiazp⋯ODhydp (Diazp = diazepine and Dhydp = di-hydro-pyran) hydrogen bond. In the crystal, layers of mol-ecules parallel to the bc plane are formed by N-HDiazp⋯ODhydp hydrogen bonds and slipped π-π stacking inter-actions. The layers are connected by additional slipped π-π stacking inter-actions. A Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H⋯H (46.8%), H⋯O/O⋯H (23.5%) and H⋯C/C⋯H (15.8%) inter-actions, indicating that van der Waals inter-actions are the dominant forces in the crystal packing. Computational chemistry indicates that in the crystal the N-H⋯O hydrogen-bond energy is 57.5 kJ mol-1.

Synthesis and Identification of Novel Potential Molecules Against COVID-19 Main Protease Through Structure-Guided Virtual Screening Approach.

The novel coronavirus disease that arises in the end of 2019 (COVID-19) in Wuhan, China, has rapidly spread over the globe and was considered as a world pandemic. Currently, various antiviral therapies or vaccines are available, and many researches are ongoing for further treatments. Targeting the coronavirus' main protease (key enzyme: 3CLpro) is growing in importance in anti-SARS-CoV-2 drug discovery process. The present study aims at predicting the antiviral activity of two novel compounds using in silico approaches that might become potential leads against SARS-CoV-2. The 3D structures of the new compounds are elucidated by single-crystal X-ray techniques. The interactions between different units of 4 and 5 were emphasized by analyzing their corresponding Hirshfeld surfaces and ESP plots. NBO and FMO analyses were investigated as well. Molecular docking combined with molecular dynamics simulations (MDs) was performed to investigate the binding modes and molecular interactions of 4 and 5 with the amino acids of coronavirus main protease (6LU7) protein. The best docking scores were obtained for both ligands through the major binding interactions via hydrogen/hydrophobic bonds with the key amino acids in the active site: HIS41, CYS145, MET49, MET165, HIS172, and GLU166 amino acids. A MD simulation study was also performed for 100 ns to validate the stability behavior of the main protease 3CLpro-ligand complexes. The MD simulation study successfully confirmed the stability of the ligands in the binding site as potent anti-SARS-CoV-2 (COVID-19) inhibitors. Additionally, MMPBSA energy of both docked complexes was determined as a validation assay of docking and MD simulations to validate compound conformation and interaction stability with 3CLpro. The synthesized compounds might be helpful in the fight against COVID-19 prior to biological activity confirmation in vitro and in vivo.

Crystal structure and Hirshfeld surface analysis of 2-(2-oxo-3-phenyl-1,2,3,8a-tetra-hydro-quinoxalin-1-yl)ethyl acetate.

In the title mol-ecule, C18H16N2O3, the di-hydro-quinoxaline moiety, with the exception of the N atom is essentially planar with the inner part of the methyl-propano-ate group (CH2-CH2-O) nearly perpendicular to it. In the crystal, inversion dimers formed by C-H⋯O hydrogen bonds are connected into oblique stacks by π-stacking and C-H⋯π(ring) inter-actions.

A newly synthesized 6-methyl-7H,8H,9H-[1,2,4]triazolo[4,3-b][1,2,4]triazepin-8-one for potential inhibitor of adenosine A1 receptor: a combined experimental and computational studies.

6-Methyl-7H,8H,9H-[1,2,4]triazolo[4,3-b][1,2,4]triazepin-8-onehas been synthesized, characterized by spectroscopic techniques (FT-IR, 1H and 13C NMR) and finally the structure was confirmed by single crystal X-ray diffraction studies. In the title molecule, C6H7N5O, the 7-membered ring adopts a bowl-like conformation. In the crystal, the molecules form stacks along the c-axis direction through offset π-stacking interactions between the 5-membered rings and C-H···N hydrogen bonds. The stacks are associated via a combination of N-H···N, C-H···O and C-H···N hydrogen bonds. Further, the Hirshfeld surface analysis reveals the nature of molecular interactions and the fingerprint plot provides information about the percentage contribution from each individual molecular contact to the surface. In addition, due to its biological interest the target molecule adenosine A1 receptor was found based on Structural Activity Relationship (SAR) analysis and, further, subjected into molecular docking and molecular dynamics analysis to understand the binding interaction and stability of the molecule in adenosine A1 receptor system. Furthermore, the Density Functional Theory (DFT) calculations were carried for free compound and the compound in active site (single point DFT), to know the internal stability.Communicated by Ramaswamy H. Sarma.

Crystal structure, computational study and Hirshfeld surface analysis of ethyl (2S,3R)-3-(3-amino-1H-1,2,4-triazol-1-yl)-2-hy-droxy-3-phenyl-propano-ate.

In the title mol-ecule, C13H16N4O3, the mean planes of the phenyl and triazole rings are nearly perpendicular to one another as a result of the intra-molecular C-H⋯O and C-H⋯π(ring) inter-actions. In the crystal, layers parallel to (101) are generated by O-H⋯N, N-H⋯O and N-H⋯N hydrogen bonds. The layers are connected by inversion-related pairs of C-H⋯O hydrogen bonds. The experimental mol-ecular structure is close to the gas-phase geometry-optimized structure calculated by DFT methods. Hirshfeld surface analysis indicates that the most important inter-action involving hydrogen in the title compound is the H⋯H contact. The contribution of the H⋯O, H⋯N, and H⋯H contacts are 13.6, 16.1, and 54.6%, respectively.

Crystal structure, Hirshfeld surface analysis and inter-action energy and DFT studies of (2Z)-4-benzyl-2-(2,4-di-chloro-benzyl-idene)-2H-1,4-benzo-thia-zin-3(4H)-one.

The title compound, C22H15Cl2NOS, contains 1,4-benzo-thia-zine and 2,4-di--chloro-benzyl-idene units, where the di-hydro-thia-zine ring adopts a screw-boat conformation. In the crystal, inter-molecular C-HBnz⋯OThz (Bnz = benzene and Thz = thia-zine) hydrogen bonds form corrugated chains extending along the b-axis direction which are connected into layers parallel to the bc plane by inter-molecular C-HMethy⋯SThz (Methy = methyl-ene) hydrogen bonds, en-closing R 4 4(22) ring motifs. Offset π-stacking inter-actions between 2,4-di--chloro-phenyl rings [centroid-centroid = 3.7701 (8) Å] and π-inter-actions which are associated by C-HBnz⋯π(ring) and C-HDchlphy⋯π(ring) (Dchlphy = 2,4-di-chloro-phen-yl) inter-actions may be effective in the stabilization of the crystal structure. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H⋯H (29.1%), H⋯C/C⋯H (27.5%), H⋯Cl/Cl⋯H (20.6%) and O⋯H/H⋯O (7.0%) inter-actions. Hydrogen-bonding and van der Waals inter-actions are the dominant inter-actions in the crystal packing. Computational chemistry indicates that in the crystal, the C-HBnz⋯OThz and C-HMethy⋯SThz hydrogen-bond energies are 55.0 and 27.1 kJ mol-1, respectively. Density functional theory (DFT) optimized structures at the B3LYP/6-311G(d,p) level are compared with the experimentally determined mol-ecular structure in the solid state. The HOMO-LUMO behaviour was elucidated to determine the energy gap.

Crystal structure, Hirshfeld surface analysis and inter-action energy and DFT studies of methyl 4-[3,6-bis-(pyridin-2-yl)pyridazin-4-yl]benzoate.

The title com-pound, C22H16N4O2, contains two pyridine rings and one meth-oxy-carbonyl-phenyl group attached to a pyridazine ring which deviates very slightly from planarity. In the crystal, ribbons consisting of inversion-related chains of mol-ecules extending along the a-axis direction are formed by C-HMthy⋯OCarbx (Mthy = methyl and Carbx = carboxyl-ate) hydrogen bonds. The ribbons are connected into layers parallel to the bc plane by C-HBnz⋯π(ring) (Bnz = benzene) inter-actions. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H⋯H (39.7%), H⋯C/C⋯H (27.5%), H⋯N/N⋯H (15.5%) and O⋯H/H⋯O (11.1%) inter-actions. Hydrogen-bonding and van der Waals inter-actions are the dominant inter-actions in the crystal packing. Computational chemistry indicates that in the crystal, C-HMthy⋯OCarbx hydrogen-bond energies are 62.0 and 34.3 kJ mol-1, respectively. Density functional theory (DFT) optimized structures at the B3LYP/6-311G(d,p) level are com-pared with the experimentally determined mol-ecular structure in the solid state. The HOMO-LUMO behaviour was elucidated to determine the energy gap.

Crystal structure, Hirshfeld surface analysis and DFT study of (2Z)-2-(2,4-di-chloro-benzyl-idene)-4-[2-(2-oxo-1,3-oxazolidin-3-yl)eth-yl]-3,4-di-hydro-2H-1,4-benzo-thia-zin-3-one.

The title compound, C20H16Cl2N2O3S, is built up from a di-hydro-benzo-thia-zine moiety linked by -CH- and -C2H4- units to 2,4-di-chloro-phenyl and 2-oxo-1,3-oxazolidine substituents, where the oxazole ring and the heterocyclic portion of the di-hydro-benzo-thia-zine unit adopt envelope and flattened-boat conformations, respectively. The 2-carbon link to the oxazole ring is nearly perpendicular to the mean plane of the di-hydro-benzo-thia-zine unit. In the crystal, the mol-ecules form stacks extending along the normal to (104) with the aromatic rings from neighbouring stacks inter-calating to form an overall layer structure. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H⋯H (28.4%), H⋯Cl/Cl⋯H (19.3%), H⋯O/O⋯H (17.0%), H⋯C/C⋯H (14.5%) and C⋯C (8.2%) inter-actions. Weak hydrogen-bonding and van der Waals inter-actions are the dominant inter-actions in the crystal packing. Density functional theory (DFT) optimized structures at the B3LYP/ 6-311 G(d,p) level are compared with the experimentally determined mol-ecular structure in the solid state. The HOMO-LUMO behaviour was elucidated to determine the energy gap.

Synthesis, crystal structure, DFT calculations and Hirshfeld surface analysis of 2-(1-decyl-2-oxo-indolin-3-yl-idene)propanedi-nitrile.

In the title mol-ecule, C21H25N3O, the 1-decyl substituents are in an extended conformation and inter-calate in the crystal packing to form hydro-phobic bands. The packing is further organized by π-π-stacking inter-actions between pyrrole and phenyl rings [centroid-centroid distance = 3.6178 (11) Å] and a C=O⋯π(pyrrole) inter-action [3.447 (2) Å]. Hirshfeld surface analysis indicates that the H⋯N/N⋯H inter-actions make the highest contribution (17.4%) to the crystal packing.

Crystal structure and Hirshfeld surface analysis of 3,4-dihydro-2-(2,4-dioxo-6-methylpyran-3-ylidene)-4-(4-pyridin-4-yl)-1,5-benzodiazepine.

The title compound, C20H17N3O3 [systematic name: 2-(6-methyl-2,4-dioxo-pyran-3-yl-idene)-4-(pyridin-4-yl)-2,3,4,5-tetra-hydro-1H-1,5-benzodiazepine], is built up from a benzodiazepine ring system linked to pyridyl and pendant di-hydro-pyran rings, where the benzene and pyridyl rings are oriented at a dihedral angle of 43.36 (6)°. The pendant di-hydro-pyran ring is rotationally disordered in a 90.899 (3):0.101 (3) ratio with the orientation of each component largely determined by intra-molecular N-HDiazp⋯ODhydp (Diazp = diazepine and Dhydp = di-hydro-pyran) hydrogen bonds. In the crystal, mol-ecules are linked via pairs of weak inter-molecular N-HDiazp⋯ODhydp hydrogen bonds, forming inversion-related dimers with R 2 2(26) ring motifs. The dimers are further connected along the b-axis direction by π-π stacking inter-actions between the pendant di-hydro-pyran and pyridyl rings with centroid-centroid distances of 3.833 (3) Šand a dihedral angle of 14.51 (2)°. Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H⋯H (50.1%), H⋯C/C⋯H (17.7%), H⋯O/O⋯H (16.8%), C⋯C (7.7%) and H⋯N/N⋯H (5.3%) inter-actions. Hydrogen-bonding and van der Waals inter-actions are the dominant inter-actions in the crystal packing.

Dichlorido(3,5,5'-trimethyl-1,3'-bi-1H-pyrazole-κN,N)copper(II).

In the title complex, [CuCl(2)(C(9)H(12)N(4))], the Cu(II) atom exhibits a distorted square-planar coordination geometry involving two chloride ions and two N-atom donors from the bipyrazole ligand. The chelate ring including the Cu(II) atom is essentially planar, with a maximum deviation of 0.0181 (17) Šfor one of the coordinated N atoms. This plane forms a dihedral angle of 30.75 (6)° with the CuCl(2) plane. In the crystal, each pair of adjacent mol-ecules is linked into a centrosymmetric dimer by N-H⋯Cl hydrogen bonds. The crystal structure is stabilized by inter-molecular C-H⋯N and C-H⋯Cl hydrogen bonds and weak slipped π-π stacking inter-actions between symmetry-related mol-ecules, with an inter-planar separation of 3.439 (19) Šand a centroid-centroid distance of 3.581 (19) Å.

Chloridobis[2-(1,5-dimethyl-1H-pyrazol-3-yl-κN)-1-methyl-1H-imidazole-κN]copper(II) chloride methanol hemisolvate tetra-hydrate.

In the title compound, [CuCl(C(9)H(12)N(4))(2)]Cl·0.5CH(3)OH·4H(2)O, the Cu(II) ion adopts a distorted trigonal-bipyramidal coordination arising from two bidentate ligands and a Cl(-) anion. The two heterocyclic ligands are planar with dihedral angles of 3.4 (1) and 0.7 (1)° between the pyrazole and imidazole rings. In the crystal, water mol-ecules and uncoordinated chloride anions form an O-H⋯Cl and O-H⋯O hydrogen-bonded sheet parallel to (100) which lies between two layers of complex mol-ecules. The packing is further stabilized by C-H⋯Cl and C-H⋯O hydrogen bonds. The methanol solvent mol-ecule is disordered across a centre of inversion.