Synthesis, Spectroscopic Characterization, Antibacterial Activity, and Computational Studies of Novel Pyridazinone Derivatives.

In this work, a novel series of pyridazinone derivatives (3-17) were synthesized and characterized by NMR (1H and 13C), FT-IR spectroscopies, and ESI-MS methods. All synthesized compounds were screened for their antibacterial activities against Staphylococcus aureus (Methicillin-resistant), Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa, and Acinetobacter baumannii. Among the series, compounds 7 and 13 were found to be active against S. aureus (MRSA), P. aeruginosa, and A. baumannii with the lowest MIC value range of 3.74-8.92 µM. Afterwards, DFT calculations of B3LYP/6-31++G(d,p) level were carried out to investigate geometry structures, frontier molecular orbital, molecular electrostatic potential maps, and gap energies of the synthesized compounds. In addition, the activities of these compounds against various bacterial proteins were compared with molecular-docking calculations. Finally, ADMET studies were performed to investigate the possibility of using of the target compounds as drugs.

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 mol-ecular docking study of diethyl 2,2'-({[(1E,1'E)-(hydrazine-1,2-diyl-idene)bis-(methanylyl-idene)]bis-(4,1-phenyl-ene)}bis-(-oxy))di-acetate.

The title Schiff base, C22H24N2O6, adopts an E configuration. The mol-ecule is planar, the mean planes of the phenyl ring system (r.m.s deviation = 0.0059 Å) forms a dihedral angle of 0.96 (4)° with the mean plane of the phenyl ring moiety (r.m.s deviation = 0.0076 Å). In the crystal, mol-ecules are linked by weak inter-molecular C-H⋯O and C-H⋯N hydrogen bonds into chains extending along the c-axis and b-axis directions, respectively. A mol-ecular docking study between the title mol-ecule and 5-HT2C, which is a G protein receptor and ligand-gated ion channels found in nervous systems (PDB ID: 6BQH) was executed. The experiment shows that it is a good potential agent because of its affinity and ability to stick to the active sites of the receptor.

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.

Polymorphism of 2-(5-benzyl-6-oxo-3-phenyl-1,6-di-hydro-pyridazin-1-yl)acetic acid with two monoclinic modifications: crystal structures and Hirshfeld surface analyses.

Two polymorphs of the title compound, C19H16N2O3, were obtained from ethano-lic (polymorph I) and methano-lic solutions (polymorph II), respectively. Both polymorphs crystallize in the monoclinic system with four formula units per cell and a complete mol-ecule in the asymmetric unit. The main difference between the mol-ecules of (I) and (II) is the reversed position of the hy-droxy group of the carb-oxy-lic function. All other conformational features are found to be similar in the two mol-ecules. The different orientation of the OH group results in different hydrogen-bonding schemes in the crystal structures of (I) and (II). Whereas in (I) inter-molecular O-H⋯O hydrogen bonds with the pyridazinone carbonyl O atom as acceptor generate chains with a C(7) motif extending parallel to the b-axis direction, in the crystal of (II) pairs of inversion-related O-H⋯O hydrogen bonds with an R 2 2(8) ring motif between two carb-oxy-lic functions are found. The inter-molecular inter-actions in both crystal structures were analysed using Hirshfeld surface analysis and two-dimensional fingerprint plots.

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, Hirshfeld surface analysis and DFT studies of 2-[5-(4-methyl-benz-yl)-6-oxo-3-phenyl-1,6-di-hydro-pyridazin-1-yl]acetic acid.

The title pyridazinone derivative, C20H18N2O3, is not planar. The phenyl ring and the pyridazine ring are inclined to each other by 10.55 (12)°, whereas the 4-methyl-benzyl ring is nearly orthogonal to the pyridazine ring, with a dihedral angle of 72.97 (10)°. In the crystal, mol-ecules are linked by pairs of O-H⋯O hydrogen bonds, forming inversion dimers with an R 2 2(14) ring motif. The dimers are linked by C-H⋯O hydrogen bonds, generating ribbons propagating along the c-axis direction. The inter-molecular inter-actions were additionally investigated using Hirshfeld surface analysis and two-dimensional fingerprint plots. They revealed that the most significant contributions to the crystal packing are from H⋯H (48.4%), H⋯O/O⋯H (21.8%) and H⋯C/C⋯H (20.4%) contacts. Mol-ecular orbital calculations providing electron-density plots of HOMO and LUMO mol-ecular orbitals and mol-ecular electrostatic potentials (MEP) were also computed, both with the DFT/B3LYP/6-311 G++(d,p) basis set.

Crystal structures and Hirshfeld surface analyses of 4-benzyl-6-phenyl-4,5-di-hydro-pyridazin-3(2H)-one and methyl 2-[5-(2,6-di-chloro-benz-yl)-6-oxo-3-phenyl-1,4,5,6-tetra-hydropyridazin-1-yl]acetate.

The asymmetric units of the title compounds both contain one nonplanar mol-ecule. In 4-benzyl-6-phenyl-4,5-di-hydro-pyridazin-3(2H)-one, C17H14N2O, (I), the phenyl and pyridazine rings are twisted with respect to each other, making a dihedral angle of 46.69 (9)°; the phenyl ring of the benzyl group is nearly perpendicular to the plane of the pyridazine ring, the dihedral angle being 78.31 (10)°. In methyl 2-[5-(2,6-di-chloro-benz-yl)-6-oxo-3-phenyl-1,4,5,6-tetra-hydropyridazin-1-yl]acetate, C20H16Cl2N2O3, (II), the phenyl and pyridazine rings are twisted with respect to each other, making a dihedral angle of 21.76 (18)°, whereas the phenyl ring of the di-chloro-benzyl group is inclined to the pyridazine ring by 79.61 (19)°. In the crystal structure of (I), pairs of N-H⋯O hydrogen bonds link the mol-ecules into inversion dimers with an R 2 2(8) ring motif. In the crystal structure of (II), C-H⋯O hydrogen bonds generate dimers with R 1 2(7), R 2 2(16) and R 2 2(18) ring motifs. The Hirshfeld surface analyses of compound (I) suggests that the most significant contributions to the crystal packing are by H⋯H (48.2%), C⋯H/H⋯C (29.9%) and O⋯H/H⋯O (8.9%) contacts. For compound (II), H⋯H (34.4%), C⋯H/H⋯C (21.3%) and O⋯H/H⋯O (16.5%) inter-actions are the most important contributions.

Crystal structure and Hirshfeld surface analysis of (E)-6-(4-hy-droxy-3-meth-oxy-styr-yl)-4,5-di-hydro-pyridazin-3(2H)-one.

In the title com-pound, C13H14N2O3, the dihydropyridazine ring (r.m.s. deviation = 0.166 Å) has a screw-boat conformation. The dihedral angle between its mean plane and the benzene ring is 0.77 (12)°. In the crystal, inter-molecular O-H⋯O hydrogen bonds generate C(5) chains and N-H⋯O hydrogen bonds produce R 2 2(8) motifs. These types of inter-actions lead to the formation of layers parallel to (12). The three-dimensional network is achieved by C-H⋯O inter-actions, including R 2 4(8) motifs. Inter-molecular inter-actions were additionally investigated using Hirshfeld surface analysis and two-dimensional fingerprint plots. The most significant contributions to the crystal packing are by H⋯H (43.3%), H⋯C/C⋯H (19.3%), H⋯O/H⋯O (22.6%), C⋯N/N⋯C (3.0%) and H⋯N/N⋯H (5.8%) contacts. C-H⋯π inter-actions and aromatic π-π stacking inter-actions are not observed.

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.

Crystal structure and Hirshfeld surface analysis of ethyl 2-[5-(3-chloro-benz-yl)-6-oxo-3-phenyl-1,6-di-hydro-pyridazin-1-yl]acetate.

The title pyridazinone derivative, C21H19ClN2O3, is not planar. The unsubstituted phenyl ring and the pyridazine ring are inclined to each other, making a dihedral angle of 17.41 (13)° whereas the Cl-substituted phenyl ring is nearly orthogonal to the pyridazine ring [88.19 (13)°]. In the crystal, C-H⋯O hydrogen bonds generate dimers with R 2 2(10) and R 2 2(24) ring motifs which are linked by C-H⋯O inter-actions, forming chains extending parallel to the c-axis direction. The inter-molecular inter-actions were investigated using Hirshfeld surface analysis and two-dimensional fingerprint plots, revealing that the most significant contributions to the crystal packing are from H⋯H (44.5%), C⋯H/H⋯C (18.5%), H⋯O/H⋯O (15.6%), Cl⋯H/H⋯Cl (10.6%) and C⋯C (2.8%) contacts.

Crystal structure and the DFT and MEP study of 4-benzyl-2-[2-(4-fluoro-phen-yl)-2-oxoeth-yl]-6-phenyl-pyridazin-3(2H)-one.

The title pyridazin-3(2H)-one derivative, C25H19FN2O2, crystallizes with two independent mol-ecules (A and B) in the asymmetric unit. In mol-ecule A, the 4-fluoro-phenyl ring, the benzyl ring and the phenyl ring are inclined to the central pyridazine ring by 86.54 (11), 3.70 (9) and 84.857 (13)°, respectively. In mol-ecule B, the corresponding dihedral angles are 86.80 (9), 10.47 (8) and 82.01 (10)°, respectively. In the crystal, the A mol-ecules are linked by pairs of C-H⋯F hydrogen bonds, forming inversion dimers with an R 2 2(28) ring motif. The dimers are linked by C-H⋯O hydrogen bonds and a C-H⋯π inter-action, forming columns stacking along the a-axis direction. The B mol-ecules are linked to each other in a similar manner and form columns separating the columns of A mol-ecules.

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

The asymmetric unit of the title compound, C17H12Cl2N2O, contains one independent mol-ecule. The mol-ecule is not planar, the phenyl and pyridazine rings are twisted with respect to each other, making a dihedral angle of 29.96 (2)° and the di-chloro-phenyl ring is nearly perpendicular to the pyridazine ring, with a dihedral angle of 82.38 (11)°. In the crystal, pairs of N-H⋯O hydrogen bonds link the mol-ecules to form inversion 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 inter-molecular inter-actions were investigated using Hirshfeld surface analysis and two-dimensional fingerprint plots, and the mol-ecular electrostatic potential surface was also analysed. The Hirshfeld surface analysis of the title compound suggests that the most significant contributions to the crystal packing are by H⋯H (31.4%), Cl⋯H/H⋯Cl (19.9%) and C⋯H/H⋯C (19%) contacts.