Synthesis, characterization, antiproliferative activity, docking, and molecular dynamics simulation of new 1,3-dihydro-2H-benzimidazol-2-one derivatives.

Cancer is a global public health problem that affects millions each year. Novel anticancer drug candidates are in need to treat various cancers and to overcome the resistance that exists against drugs in use. Benzimidazole derivatives have been reported as anticancer agents. These lead us to synthesize similar benzimidazole derivatives and investigate their anticancer activity. In this study, six new 1,3-dihydro-2H-benzimidazol-2-one-based molecules (2a-f) were synthesized. The structures of these molecules were verified by spectroscopic methods. The antiproliferative activities of molecules 2a-f were screened against a panel of human cancer cell lines, including the liver, colon, lung, and breast. The molecules were also tested towards normal human lung cell line to determine their selectivity. The results demonstrated that compound 2d had the highest cytotoxic effect compared to compounds 2a-c, 2e, and 2f against DLD-1 and MDA-MB-231 cell lines. The binding potential of the relatively active compound, 2d, with three targets was investigated through molecular docking. The stability of target-compound complexes procured from the docking was explored through molecular dynamics (MD) simulation. The docking and MD simulation studies revealed that compound 2d had the highest potential to bind to GALR3 among the targets. Furthermore, the computational pharmacokinetic study demonstrated that the synthesized compounds had drug-like properties.Communicated by Ramaswamy H. Sarma.

Density functional modeling, and molecular docking with SARS-CoV-2 spike protein (Wuhan) and omicron S protein (variant) studies of new heterocyclic compounds including a pyrazoline nucleus.

Nowadays, different vaccines and antiviral drugs have been developed and their effectiveness has been proven against SARS-CoV-2. Pyrazoline derivatives are biologically active molecules and exhibit broad-spectrum biological activity properties. In this scope, four new molecules (4a-d) including a pyrazoline core were synthesized in order to predict their antiviral properties theoretically. Compounds 4a-d were purified by the crystallization method. The structures of 4a-d were completely characterized by NMR, IR, and elemental analysis. The molecular structures of the compounds in the ground state have been optimized using density functional theory with the B3LYP/6-31++G(d,p) level. The quantum chemical parameters were predicted by density functional theory calculations. Moreover, the molecular docking studies of 4a-d with SARS-CoV-2 Spike protein (Wuhan) and omicron S protein (variant) were presented to investigate and predict potential interactions. The binding sites, binding types and energies, bond distances of the non-covalent interactions and calculated inhibition constants (calc. Ki) as a consequence of molecular docking for 4a-d were presented in this study. Furthermore, the stability of the protein-4a complex obtained from the docking was investigated through molecular dynamics simulation.Communicated by Ramaswamy H. Sarma.

Palladium N-Heterocyclic Carbene Complexes: Synthesis from Benzimidazolium Salts and Catalytic Activity in Carbon-carbon Bond-forming Reactions.

Detailed and generalized protocols are presented for the synthesis and subsequent purification of four palladium N-heterocyclic carbene complexes from benzimidazolium salts. Detailed and generalized protocols are also presented for testing the catalytic activity of such complexes in arylation and Suzuki-Miyaura cross-coupling reactions. Representative results are shown for the catalytic activity of the four complexes in arylation and Suzuki-Miyaura type reactions. For each of the reactions investigated, at least one of the four complexes successfully catalyzed the reaction, qualifying them as promising candidates for catalysis of many carbon-carbon bond-forming reactions. The protocols presented are general enough to be adapted for the synthesis, purification and catalytic activity testing of new palladium N-heterocyclic carbene complexes.

Crystal structure and computational studies of (3Z)-4-benzoyl-3-[(2,4-di-nitro-phen-yl)hydrazinyl-idene]-5-phenyl-furan-2(3H)-one.

In the mol-ecular structure of the title compound, C23H14N4O7, the furan, di-nitro-phenyl and phenyl rings are almost in the same plane (r.m.s. deviation = 0.127 Å), with the benzoyl ring inclined by a dihedral angle of 56.4 (1)° to the three-ring system. A bifurcated intra-molecular N-H⋯(O,O) hydrogen bond is present. In the crystal, adjacent mol-ecules are linked by C-H⋯O hydrogen bonds into chains parallel to [001]. A π-π stacking inter-action between the benzoyl and di-nitro-phenyl moieties contributes to the crystal packing. Theoretical calculations using DFT(B3YLP) methods were used to confirm the mol-ecular structure.

N-Methylphthalimide-substituted benzimidazolium salts and PEPPSI Pd-NHC complexes: synthesis, characterization and catalytic activity in carbon-carbon bond-forming reactions.

A series of novel benzimidazolium salts (1-4) and their pyridine enhanced precatalyst preparation stabilization and initiation (PEPPSI) themed palladium N-heterocyclic carbene complexes [PdCl2(NHC)(Py)] (5-8), where NHC = 1-(N-methylphthalimide)-3-alkylbenzimidazolin-2-ylidene and Py = 3-chloropyridine, were synthesized and characterized by means of (1)H and (13)C{(1)H} NMR, UV-vis (for 5-8), ESI-FTICR-MS (for 2, 4, 6-8) and FTIR spectroscopic methods and elemental analysis. The synthesized compounds were tested in Suzuki-Miyaura cross-coupling (for 1-8) and arylation (for 5-8) reactions. As catalysts, they demonstrated a highly efficient route for the formation of asymmetric biaryl compounds even though they were used in very low loading. For example, all compounds displayed good catalytic activity for the C-C bond formation of 4-tert-butylphenylboronic acid with 4-chlorotoluene.

Crystal structure of 1,3-bis-(4-methyl-benz-yl)-1H-1,3-benzimidazol-3-ium bromide monohydrate.

In the title hydrated symetrically substituted 1,3-bis-(4-methyl-benz-yl)benzimidazolium salt, C23H23N2 (+)·Br(-)·H2O, the dihedral angles between the benzimidazole ring system (r.m.s. deviation = 0.003 Å) and the pendant benzene rings are 73.18 (16) and 77.52 (16)°. Both benzene rings lie to the same side of the benzimidazole ring system, giving the cation an overall U-shape. In the crystal, the cation is linked to the water mol-ecule by a short C-H⋯O hydrogen bond and the water mol-ecule forms O-H⋯Br hydrogen bonds. Together, these inter-actions lead to [010] chains. The packing is consolidated by C-H⋯Br hydrogen bonds and aromatic π-π stacking inter-actions [centroid-centroid distances = 3.5401 (17) and 3.8815 (18) Å], generating a three-dimensional network.

Synthesis, spectroscopic (FT-IR/NMR) characterization, X-ray structure and DFT studies on (E)-2-(1-phenylethylidene) hydrazinecarboximidamide nitrate hemimethanol.

The title molecular salt, (E)-2-(1-phenylethylidene) hydrazinecarboximidamide nitrate hemimethanol C9H13N4(+)·NO3(-)·0.5CH4O, was synthesized and characterized by elemental analysis, FT-IR and NMT spectroscopies, and single-crystal X-ray diffraction technique. Quantum chemical calculations were performed to study the molecular and spectroscopic properties of the title compound, and the results were compared with the experimental findings. The calculated results show that the optimized geometry can well reproduce the crystal structure parameters, and the theoretical vibrational frequencies and GIAO (1)H and (13)CNMR chemical shifts show good agreement with experimental values. The dipole moment, linear polarizability and first hyperpolarizability values were also computed. The linear polarizabilities and first hyper polarizabilities of the studied molecule indicate that the compound is a good candidate of nonlinear optical materials. On the basis of the thermodynamic properties of the title compound at different temperatures have been calculated, revealing the correlations between standard heat capacities (C) standard entropies (S), and standard enthalpy changes (H) and temperatures.

Vibrational and theoretical analysis of pentyl-4-benzoyl-1-[2,4-dinitrophenyl]-5-phenyl-1H-pyrazole-3-carboxylate.

Infrared spectrum of the compound, pentyl-4-benzoyl-1-[2,4-dinitrophenyl]-5-phenyl-1H-pyrazole-3-carboxylate (PBDPPC) has been measured. Conformational search through relaxed scan has been carried out to find the most stable conformational isomer. After the full geometry optimization for the most stable conformer using B3LYP and BLYP hybrid functionals of Density Functional Theory (DFT), vibrational normal modes have been calculated at the same theoretical levels. Potential Energy Distribution (PED) of each normal mode has been calculated by means of VEDA4 to obtain contributions of internal coordinates to the normal modes. Natural Bond Orbital (NBO) analysis has been performed to get insights into the possible hydrogen bonding sites for all the conformational isomers.