Crystal structure, Hirshfeld surface analysis, crystal voids, inter-action energy calculations and energy frameworks and DFT calculations of ethyl 2-cyano-3-(3-hy-droxy-5-methyl-1H-pyrazol-4-yl)-3-phen-yl-propano-ate.

The title compound, C16H17N3O3, is racemic as it crystallizes in a centrosymmetric space group (P ), although the trans disposition of substituents about the central C-C bond is established. The five- and six-membered rings are oriented at a dihedral angle of 75.88 (8)°. In the crystal, N-H⋯N hydrogen bonds form chains of mol-ecules extending along the c-axis direction that are connected by inversion-related pairs of O-H⋯N into ribbons. The ribbons are linked by C-H⋯π(ring) inter-actions, forming layers parallel to the ab plane. A Hirshfeld surface analysis indicates that the most important contributions for the crystal packing are from H⋯H (45.9%), H⋯N/N⋯H (23.3%), H⋯C/C⋯H (16.2%) and H⋯O/O⋯H (12.3%) inter-actions. Hydrogen bonding and van der Waals inter-actions are the dominant inter-actions in the crystal packing. The volume of the crystal voids and the percentage of free space were calculated to be 100.94 Å3 and 13.20%, showing that there is no large cavity in the crystal packing. Evaluation of the electrostatic, dispersion and total energy frameworks indicates that the stabilization is dominated by the electrostatic energy contributions in the title compound. Moreover, the 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.

Crystal structure, Hirshfeld surface and crystal void analysis, inter-molecular inter-action energies, DFT calculations and energy frameworks of 2H-benzo[b][1,4]thia-zin-3(4H)-one 1,1-dioxide.

In the title mol-ecule, C8H7NO3S, the nitro-gen atom has a planar environment, and the thia-zine ring exhibits a screw-boat conformation. In the crystal, corrugated layers of mol-ecules parallel to the ab plane are formed by N-H⋯O and C-H⋯O hydrogen bonds together with C-H⋯π(ring) and S=O⋯π(ring) inter-actions. The layers are connected by additional C-H⋯O hydrogen bonds and π-stacking inter-actions. Hirshfeld surface analysis indicates that the most important contributions for the crystal packing are from H⋯O/O⋯H (49.4%), H⋯H (23.0%) and H⋯C/C⋯H (14.1%) inter-actions. The volume of the crystal voids and the percentage of free space were calculated as 75.4 Å3 and 9.3%. Density functional theory (DFT) computations revealed N-H⋯O and C-H⋯O hydrogen-bonding energies of 43.3, 34.7 and 34.4 kJ mol-1, respectively. Evaluation of the electrostatic, dispersion and total energy frameworks indicate that the stabilization is dominated via the electrostatic energy contribution. Moreover, the 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.

Synthesis, crystal structure, spectroscopic characterization, DFT calculations, Hirshfeld surface analysis, molecular docking, and molecular dynamics simulation investigations of novel pyrazolopyranopyrimidine derivatives.

A series of new pyrazolopyranopyrimidine derivatives (3-9) were synthesized from 5-amino-2,4-dihydro-3-methyl-4-phenylpyrano-[2,3-c]pyrazole-5-carbonitrile (2) by multicomponent reactions (MCR) involving malononitrile, benzaldehyde, and pyrazolone under refluxing ethanol in the presence of piperidine. Compound (2) was then converted to 2-acetylpyrazolopyranopyrimidine (3) through a reaction with acetic anhydride. The deprotection of 3 using ammonium hydroxide in ethanol, leads to 4. Subsequent chlorination of 4 by phosphorus oxychloride affords 5 which was alkylated using methyl iodide and ethyl bromoacetate in DMF, leading to regioisomers 6-9. The products were characterized by spectroscopic techniques (1H and 13C NMR) and confirmed by single crystal X-ray diffraction (XRD) studies for 2, 5, 6, and 9. Moreover, the geometrical parameters, molecular orbital calculations, and spectral data of 2, 5, 6, and 9 were compared by DFT at the B3LYP/6-311G(d,p) level of theory. There is good agreement between the calculated results and the experimental data. The intermolecular contacts for 2, 5, 6, and 9 were studied by Hirshfeld surface analysis. In addition, the molecular docky study was conducted to investigate the binding patterns of 2, 5, 6, and 9 within the binding site of cyclin-dependent kinase 2 (CDK2) and penicillin-binding protein 1 A. After the docking process, molecular dynamics (MD) simulations for 100 ns were performed on CDK2 and PBP 1 A proteins in the complex with 5.Communicated by Ramaswamy H. Sarma.

Discovery of a new Bcl-2 inhibitor through synthesis, anticancer activity, docking and MD simulations.

A database of 300 compounds was virtually screened and docked against Bcl-2 protein; the stability of the best-formed complex was evaluated through Molecular dynamics, the top ten compounds with the best in-silico complexation affinities were synthesized, and their In-vitro cytotoxic activity was examined. Thiazolidinone (4e) and isoxazoline (4a-d) were evaluated in-silico. For further evaluation and examination, we designed and synthesized from naturally occurring (R)-carvone and characterized it via spectroscopic analysis, as well as tested for their anticancer activities towards human cancer cell lines such as HT-1080 (fibrosarcome cancer), MCF-7 and MDA-MB-231 (breast cancer) and A-549 (lung cancer) by using MTT method with Doxorubicin as standard drug. Among them, compound 4d showed the most promising anticancer activity against HT-1080, A-549, MCF-7, and MDA-MB-231 cell lines with IC50 values of 15.59 ± 3.21 µM; 18.32 ± 2.73 µM; 17.28 ± 0.33 µM and 19.27 ± 2.73 µM respectively.Communicated by Ramaswamy H. Sarma.

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 and Hirshfeld surface analysis study of (E)-1-(4-chloro-phen-yl)-N-(4-ferrocenylphen-yl)methanimine.

The substituted cyclo-penta-dienyl ring in the title mol-ecule, [Fe(C5H5)(C18H13ClN)], is nearly coplanar with the phenyl-1-(4-chloro-phen-yl)methanimine substituent, with dihedral angles between the planes of the phenyl-ene ring and the Cp and 4-(chloro-phen-yl)methanimine units of 7.87 (19) and 9.23 (10)°, respectively. The unsubstituted cyclo-penta-dienyl ring is rotationally disordered, the occupancy ratio for the two orientations refined to a 0.666 (7)/0.334 (7) ratio. In the crystal, the mol-ecules pack in 'bilayers' parallel to the ab plane with the ferrocenyl groups on the outer faces and the substituents directed towards the regions between them. The ferrocenyl groups are linked by C-H⋯π(ring) inter-actions. A Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H⋯H (46.1%), H⋯C/C⋯ H (35.4%) and H⋯Cl/Cl⋯H (13.8%) inter-actions. Thus C-H⋯π(ring) and van der Waals inter-actions are the dominant inter-actions in the crystal packing.

Crystal structure, Hirshfeld surface analysis and inter-action energy calculation of 1-decyl-2,3-di-hydro-1H-benzimidazol-2-one.

The title mol-ecule, C17H26N2O, adopts an L-shaped conformation, with the straight n-decyl chain positioned nearly perpendicular to the di-hydro-benzimidazole moiety. The di-hydro-benzimidazole portion is not quite planar as there is a dihedral angle of 1.20 (6)° between the constituent planes. In the crystal, N-H⋯O hydrogen bonds form inversion dimers, which are connected into the three-dimensional structure by C-H⋯O hydrogen bonds and C-H⋯π(ring) inter-actions. Hirshfeld surface analysis indicates that the most important contributions for the crystal packing are from H⋯H (75.9%), H⋯C/C⋯H (12.5%) and H⋯O/O⋯H (7.0%) inter-actions. Based on computational chemistry using the CE-B3LYP/6-31 G(d,p) energy model, C-H⋯O hydrogen bond energies are -74.9 (for N-H⋯O) and -42.7 (for C-H⋯O) kJ mol-1.