Crystal structure, Hirshfeld surface analysis and DFT study of (5E,5'E,6Z,6'Z)-6,6'-[ethane-1,2-diyl-bis(aza-nylyl-idene)]bis-{5-[2-(4-fluoro-phen-yl)hydra-zono]-3,3-di-methyl-cyclo-hexa-none} 2.5-hydrate.

The title compound, C30H34F2N6O2·2.5H2O, was obtained by condensation of 2-[2-(4-fluoro-phen-yl)hydrazono]-5,5-di-methyl-cyclo-hexan-1,3-dione with ethyl-enedi-amine in ethanol and crystallized as a 1:2.5 hydrate in space group C2/c. The two independent mol-ecules, with approximate crystallographic C 2 symmetries, have different conformations and packing environments, are stabilized by intra-molecular N-H⋯N hydrogen bonds and linked by O-H⋯O hydrogen bonds involving the water mol-ecules. A Hirshfeld surface analysis showed that H⋯H contacts make by far the largest (48-50%) contribution to the crystal packing. From DFT calculations, the LUMO-HOMO energy gap of the mol-ecule is 0.827 eV.

Synthesis, crystal structure, DFT, Hirshfeld surface analysis, energy framework, docking and molecular dynamic simulations of (E)-4-(4-methylbenzyl)-6-styrylpyridazin-3(2H)-one as anticancer agent.

In this work, a novel crystal, (E)-4-(4-methylbenzyl)-6-styrylpyridazin-3(2H)-one (E-BSP) was synthesized via Knoevenagel condensation of benzaldehyde and (E)-6-(4-methoxystyryl)-4,5-dihydropyridazin-3(2H)-one. The molecular structure of E-BSP was confirmed by using FT-IR, 1H-NMR, 13C-NMR, UV-vis, ESI-MS, TGA/DTA thermal analyses and single crystal X-ray diffraction. The DFT/B3LYP methods with the 6-311++G(d,p) basis set were used to determine the vibrational modes over the optimized structure. Potential energy distribution (PED) and the VEDA 4 software were used to establish the theoretical mode assignments. The same approach was used to compute the energies of frontier molecular orbitals (HOMO-LUMO), global reactivity descriptors, and molecular electrostatic potential (MEP). Additionally, experimental and computed UV spectral parameters were determined in methanol and the obtained outputs were supported by FMO analysis. Molecular docking and molecular dynamics (MD) simulation analyses of the E-BSP against six proteins obtained from different cancer pathways were carried out. The proteins include; epidermal growth factor receptor (EGFR), Estrogen receptor (ERα), Mammalian target of rapamycin (mTOR), Progesterone receptor (PR) (Breast cancer), Human cyclin-dependent kinase 2 (CDK2) (Colorectal cancer), and Survivin (Squamous cell carcinoma/Non-small cell lung cancer). The results of the analyses showed that the compound had less binding energies ranging between -6.30 to -9.09 kcal/mol and formed stable complexes at the substrate-binding site of the proteins after the 50 ns MD simulation. Therefore, E-BSP was considered a potential inhibitor of different cancer pathways and should be used for the treatment of cancer after experimental validation and clinical trial.Communicated by Ramaswamy H. Sarma.

Crystal structure and Hirshfeld surface analysis of 2,4,6-tri-amino-pyrimidine-1,3-diium dinitrate.

The title compound, C4H9N5 2+·2NO3 -, crystallizes in the monoclinic crystal system, space group P21/c. The asymmetric unit, which comprises a diprotonated tri-amino-pyrimidine dication and two nitrate anions, has an almost planar geometry with a dihedral angle of 0.92 (4)° between the mean plane of the cation and that defined by both anions. In the crystal, hydrogen-bonding inter-actions between the 2,4,6-tri-amino-pyrimidine cation and the nitrate anions lead to a one-dimensional supra-molecular network with weak anionic inter-actions forming a three-dimensional network. These inter-actions were investigated using Hirshfeld surface analysis, which indicates that the most important contributions for the packing arrangement are from O⋯H/H⋯O (53.2%), N⋯H/H⋯N (12.5%) and C⋯H/H⋯C (9.6%) inter-actions. Energy framework analysis showed that of the components of the framework energies, electrostatic repulsion (E rep) is dominant.

Synthesis of 3-Methoxy-6- [(2, 4, 6-trimethyl-phenylamino)-methyl]-phenol Schiff base characterized by spectral, in-silco and in-vitro studies.

The structure of the title compound (I) (C17H19NO2)2 the Schiff base, {3-Methoxy-6-[(2,4,6-trimethyl-phenylamino)-methyl]-phenol} was characterized by 1H, 13C NMR, UV-VIS and IR spectroscopic techniques. The crystal structure was determined by X-ray analysis. The compound (I) was crystallized in the Monoclinic space group P21/c, with a = 25.9845 (12), b = 7.3318 (4), c = 16.3543 (8) Å, ß = 100.713(°) (4), and Z = 8. The intermolecular interactions of the compound (I) was analyzed using Hirshfeld surface and Fingerprint analysis. Based on the crystal-void calculation, the volume of the void and surface area of the Schiff base compound (I) was described. The frontier molecular orbital energy gap reveals charge transfer interactions involving donors and acceptors. The invitro studies on antibacterial property of the title compound shows best MIC value for Staphylococcus aureus and the compound effect on MTT assay on A549 lung cancer cell line. The molecular docking result shows that the compound has good molecular-level interaction with anticancer drug target having good interactions with active site residues. The non-covalent interactions in the protein-ligand complex were well established from NCI analysis.

Crystal structure and Hirshfeld surface analysis of dimethyl 3,3'-{[(1E,2E)-ethane-1,2-diyl-idene]bis(aza-nylyl-idene)}bis-(4-methyl-benzoate).

The title Schiff base compound, C20H20N2O4, synthesized by the condensation reaction of methyl 3-amino-4-methyl-benzoat and glyoxal in ethanol, crystallizes in the the monoclinic space group P21/n. The mol-ecule is Z-shaped with the C-N-C-C torsion angle being 47.58 (18)°. In the crystal, pairs of mol-ecules are linked via C-H⋯N hydrogen bonds, forming centrosymetric dimers with an R 2 2(8) ring motif; this connectivity leads to the formation of columns running along the a-axis direction. Hirshfeld surface analysis and two-dimensional fingerprint plots were used to explore the inter-molecular inter-actions and revealed that the most significant contributions to the crystal packing are from H⋯H (49.4%), H⋯O/O⋯H (19.0%) and H⋯C/C⋯H (17.5%) contacts. Energy frameworks were constructed through different inter-molecular inter-action energies to investigate the stability of the compound. The net inter-action energies for the title compound were found to be electrostatic (E ele = -48.4 kJ mol-1), polarization (E pol = -9.7 kJ mol-1), dispersion (E dis = -186.9 kJ mol-1) and repulsion (E rep = 94.9 kJ mol-1) with a total inter-action energy, E tot, of -162.4 kJ mol-1.

Crystal structure of (E)-3-({6-[2-(4-chloro-phen-yl)ethen-yl]-3-oxo-2,3-di-hydro-pyridazin-4-yl}meth-yl)pyridin-1-ium chloride dihydrate.

In the title compound, C18H15ClN3O+·Cl-·2H2O, three intra-mol-ecular hydrogen bonds are observed, N-H⋯O, O-H⋯Cl and O-H⋯O. In the crystal, mol-ecules are connected by C-H⋯Cl and N-H⋯O hydrogen bonds. Strong C-H⋯Cl, N-H⋯O, O-H⋯Cl and O-H⋯O hydrogen-bonding inter-actions are implied by the Hirshfeld surface analysis, which indicate that H⋯H contacts make the largest contribution to the overall crystal packing at 33.0%.

Crystal structure and Hirshfeld surface analysis of 6-((E)-2-{4-[2-(4-chloro-phen-yl)-2-oxoeth-oxy]phen-yl}ethen-yl)-4,5-di-hydro-pyridazin-3(2H)-one.

The pyridazine ring in the title compound, C20H17ClN2O3, adopts a screw-boat conformation. The whole mol-ecule is flattened, the dihedral angles subtended by the least-squares plane of the central aromatic ring with those of the terminal benzene and pyridazine rings being 15.18 (19) and 11.23 (19)°, respectively. In the crystal, the mol-ecules are linked by pairs of N-H⋯O bonds into centrosymmetric dimers and by C-H⋯π contacts into columns. The results of the Hirshfeld surface analysis show that the most prominent inter-actions are H⋯H, accounting for 36.5% of overall crystal packing, and H⋯O/O⋯H (18.6% contribution) contacts.

Crystal structure and Hirshfeld surface analysis of 4-(2,6-di-chloro-benz-yl)-6-[(E)-2-phenyl-ethen-yl]pyridazin-3(2H)-one.

The title pyridazinone derivative, C19H14Cl2N2O, an important pharmacophore with a wide variety of biological applications is not planar, the chloro-phenyl and pyridazinone rings being almost perpendicular, subtending a dihedral angle of 85.73 (11)°. The phenyl ring of the styryl group is coplanar with the pyridazinone ring [1.47 (12)°]. In the crystal, N-H⋯O hydrogen bonds form inversion dimers with an R 2 2(8) ring motif and C-H⋯Cl hydrogen bonds also occur. The roles of the inter-molecular inter-actions in the crystal packing were clarified using Hirshfeld surface analysis, and two-dimensional fingerprint plots indicate that the most important contributions to the crystal packing are from H⋯H (37.9%), C⋯H/H⋯C (18.7%), Cl⋯H/ H⋯Cl (16.4%) and Cl⋯C/C⋯Cl (6.7%) contacts.

Synthesis, spectroscopy, crystal structure, TGA/DTA study, DFT and molecular docking investigations of (E)-4-(4-methylbenzyl)-6-styrylpyridazin-3(2H)-one.

In this study, we present the synthesis of novel pyridazin-3(2H)-one derivative namely (E)-4-(4-methylbenzyl)-6-styrylpyridazin-3(2H)-one (MBSP). The chemical structure of MBSP was characterized using spectroscopic techniques such as FT-IR, 1H NMR, 13C NMR, UV-Vis, ESI-MS, and finally, the structure was confirmed by single X-ray diffraction studies. The DFT calculation was performed to compare the gas-phase geometry of the title compound to the solid-phase structure of the title compound. Furthermore, a comparative study between theoretical UV-Vis, IR, 1H- and 13C NMR spectra of the studied compound and experimental ones have been carried out. The thermal behavior and stability of the compound were analyzed by using TGA and DTA techniques which revealed that the compound is thermostable up to its melting point. Finally, the in silico docking and ADME studies are performed to investigate whether MBSP is a potential therapeutic for COVID-19.

Crystal structure, Hirshfeld surface analysis and DFT studies of (E)-4-methyl-2-{[(2-methyl-3-nitro-phen-yl)imino]-meth-yl}phenol.

The title compound, C15H14N2O3, was prepared by condensation of 2-hy-droxy-5-methyl-benzaldehyde and 2-methyl-3-nitro-phenyl-amine in ethanol. The configuration of the C=N bond is E. An intra-molecular O-H⋯N hydrogen bond is present, forming an S(6) ring motif and inducing the phenol ring and the Schiff base to be nearly coplanar [C-C-N-C torsion angle of 178.53 (13)°]. In the crystal, mol-ecules are linked by C-H⋯O inter-actions, forming chains along the b-axis direction. The Hirshfeld surface analysis indicates that the most important contributions to the crystal packing are from H⋯H (37.2%), C⋯H (30.7%) and O⋯H (24.9%) inter-actions. The gas phase density functional theory (DFT) optimized structure at the B3LYP/ 6-311 G(d,p) level is compared to the experimentally determined mol-ecular structure in the solid state. The HOMO-LUMO behaviour was elucidated to determine the energy gap.

Synthesis, crystal structure and Hirshfeld surface analysis of 1,7-dimethyl-5a,6,11a,12-tetra-hydro-benzo[b]benzo[5,6][1,4]oxazino[2,3-e][1,4]oxazine.

Mol-ecules of the title compound, C16H16N2O2, occupy special positions on the twofold rotation axes. The heterocyclic ring adopts a slightly twisted envelope conformation with one of the two junction carbon atoms as the flap. The mean planes through the two halves of the mol-ecule form a dihedral angle of 72.01 (2)°. In the crystal, mol-ecules are linked by pairs of C-H⋯O and N-H⋯C contacts into layers parallel to (100). H⋯H contacts make the largest contribution to the Hirshfeld surface (58.9%).

Crystal structure, Hirshfeld surface analysis and DFT studies of 2-[(2-hy-droxy-5-methyl-benzyl-idene)amino]-benzo-nitrile.

The title compound, C15H12N2O, was synthesized by condensation reaction of 2-hy-droxy-5-methyl-benzaldehyde and 2-amino-benzo-nitrile, and crystallizes in the ortho-rhom-bic space group Pbca. The phenol ring is inclined to the benzo-nitrile ring by 25.65 (3)°. The configuration about the C=N bond is E, stabilized by a strong intra-molecular O-H⋯N hydrogen bond that forms an S(6) ring motif. In the crystal, C-H⋯O and C-H⋯N inter-actions lead to the formation of sheets perpendicular to the a axis. C-H⋯π inter-actions, forming polymeric chains along the a-axis direction, connect these sheets into a three-dimensional network. A Hirshfeld surface analysis indicates that the most important contributions for the packing arrangement are from H⋯H and C⋯H/H⋯C inter-actions. The density functional theory (DFT) optimized structure at the B3LYP/6-311 G(d,p) level is compared with the experimentally determined mol-ecular structure and the HOMO-LUMO energy gap is given.

Crystal structure, Hirshfeld surface analysis and DFT studies of (E)-2-{[(3-chloro-4-methyl-phen-yl)imino]-meth-yl}-4-methyl-phenol.

The title compound, C15H14ClNO, was synthesized by condensation reaction of 2-hy-droxy-5-methyl-benzaldehyde and 3-chloro-4-methyl-aniline, and crystallizes in the monoclinic space group P21/c. The 3-chloro-benzene ring is inclined to the phenol ring by 9.38 (11)°. The configuration about the C=N bond is E and an intra-molecular O-H⋯N hydrogen bond forms an S(6) ring motif. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the packing arrangement are from H⋯H (43.8%) and C⋯H/H⋯C (26.7%) inter-actions. The density functional theory (DFT) optimized structure at the B3LYP/ 6-311 G(d,p) level is compared with the experimentally determined mol-ecular structure and the HOMO-LUMO energy gap is provided.

Crystal structure, Hirshfeld surface analysis and DFT studies of 4-methyl-2-({[4-(tri-fluoro-meth-yl)phen-yl]imino}-meth-yl)phenol.

The title compound, C15H12F3NO, crystallizes with one mol-ecule in the asymmetric unit. The configuration of the C=N bond is E and there is an intra-molecular O-H⋯N hydrogen bond present, forming an S(6) ring motif. The dihedral angle between the mean planes of the phenol and the 4-tri-fluoro-methyl-phenyl rings is 44.77 (3)°. In the crystal, mol-ecules are linked by C-H⋯O inter-actions, forming polymeric chains extending along the a-axis direction. The Hirshfeld surface analysis indicates that the most important contributions to the crystal packing are from C⋯H/H⋯C (29.2%), H⋯H (28.6%), F⋯H/H⋯F (25.6%), O⋯H/H⋯O (5.7%) and F⋯F (4.6%) inter-actions. The density functional theory (DFT) optimized structure at the B3LYP/6-311 G(d,p) level is compared with the experimentally determined mol-ecular structure in the solid state. The HOMO-LUMO behaviour was elucidated to determine the energy gap. The crystal studied was refined as an inversion twin.

Synthesis, crystal structures and Hirshfeld surface analysis of 1,4-dibenzyl-6-methyl-1,4-di-hydro-quinoxaline-2,3-dione.

The title quinoxaline mol-ecule, C23H20N2O2, is not planar, the dihedral angle angle between the mean planes of the benzene rings being 72.54 (15)°. In the crystal, mol-ecules are connected into chains extending parallel to (10) by weak C-H⋯O hydrogen bonds. Weak C-H⋯π inter-actions link the chains, forming a three-dimensional network structure. Hirshfeld surface analysis revealed that the most important contributions for the crystal packing are from H⋯H (48.7%), H⋯C/C⋯H (32.0%), H⋯O/O⋯H (15.4%), C⋯C (1.9%), H⋯N/N⋯H (1.1%) contacts.

Crystal structure and Hirshfeld surface analysis of 2-{[(4-iodo-phen-yl)imino]-meth-yl}-4-nitro-phenol.

The title compound, C13H9IN2O3, was synthesized by a condensation reaction between 2-hy-droxy-5-nitro-benzaldehyde and 4-iodo-aniline, and crystallizes in the ortho-rhom-bic space group Pna21. The 4-iodo-benzene ring is inclined to the phenol ring by a dihedral angle of 39.1 (2)°. The configuration about the C=N double bond is E. The crystal structure features C-H⋯O hydrogen-bonding inter-actions. A Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the packing arrangement are O⋯H/H⋯O (26.9%) and H⋯H (22.0%) inter-actions.

Crystal structure, Hirshfeld surface analysis and DFT studies of 6-[(E)-2-(thio-phen-2-yl)ethenyl]-4,5-di-hydro-pyridazin-3(2H)-one.

In the title compound, C10H10N2OS, the five atoms of the thio-phene ring are essentially coplanar (r.m.s. deviation = 0.0037 Å) and the pyridazine ring is non-planar. In the crystal, pairs of N-H⋯O hydrogen bonds link the mol-ecules into dimers with an R 2 2(8) ring motif. The dimers are linked by C-H⋯O inter-actions, forming layers parallel to the bc plane. The theoretical geometric parameters are in good agreement with XRD results. The inter-molecular inter-actions were investigated using a Hirshfeld surface analysis and two-dimensional fingerprint plots. The Hirshfeld surface analysis of the title compound suggests that the most significant contributions to the crystal packing are by H⋯H (39.7%), C⋯H/H⋯C (17.3%) and O⋯H/H⋯O (16.8%) contacts.

Crystal structure and Hirshfeld surface analysis of 4-(4-methyl-benz-yl)-6-phenyl-pyridazin-3(2H)-one.

In this paper, we describe the synthesis of a new di-hydro-2H-pyridazin-3-one derivative. The mol-ecule, C18H16N2O, is not planar; the benzene and pyridazine rings are twisted with respect to each other, making a dihedral angle of 11.47 (2)°, and the toluene ring is nearly perpendicular to the pyridazine ring, with a dihedral angle of 89.624 (1)°. The mol-ecular conformation is stabilized by weak intra-molecular C-H⋯N contacts. In the crystal, pairs of N-H⋯O hydrogen bonds link the mol-ecules into inversion dimers with an R 2 2(8) ring motif. The inter-molecular inter-actions were investigated using Hirshfeld surface analysis and two-dimensional (2D) fingerprint plots, revealing that the most important contributions for the crystal packing are from H⋯H (56.6%), H⋯C/C⋯H (22.6%), O⋯H/H⋯O (10.0%) and N⋯C/C⋯N (3.5%) inter-actions.