Functionalized imidazolium and benzimidazolium salts as paraoxonase 1 inhibitors: Synthesis, characterization and molecular docking studies.

Paraoxonase (PON) is a key enzyme in metabolism of living organisms and decreased activity of PON1 was acknowledged as a risk for atherosclerosis and organophosphate toxicity. The present study describes the synthesis, characterization, PON1 inhibitory properties and molecular docking studies of functionalized imidazolium and benzimidazolium salts (1a-5g). The structures of all compounds were elucidated by IR, NMR, elemental analysis and structures of compounds 2b and 2c were characterized by single-crystal X-ray diffraction. Compound 1c, a coumarin substituted imidazolium salt showed the best inhibitory effect on the activity of PON1 with good IC50 value (6.37 µM). Kinetic investigation was evaluated for this compound and results showed that this compound is competitive inhibitor of PON1 with Ki value of 2.39 µM. Molecular docking studies were also performed for most active compound 1c and one of least active compound 2c in order to determine the probable binding model into active site of PON1 and validation of the experimental results.

(E)-4-Hy-droxy-N'-(2-hy-droxy-5-iodo-benzyl-idene)benzohydrazide methanol monosolvate.

In the title compound, C(14)H(11)IN(2)O(3)·CH(4)O, the dihedral angle between the benzene rings is 33.2 (3)°. The mol-ecule displays trans and anti conformations about the C=N and N-N bonds, respectively. There is an intra-molecular O-H⋯N(azomethine) hydrogen bond. Inter-molecular N-H⋯O and O-H⋯O hydrogen bonds consolidate mol-ecules into a three-dimensional architecture.

(E,E)-N'-{4-[(2-Benzoyl-hydrazin-1-yl-idene)meth-yl]benzyl-idene}benzo-hydrazide.

In the title compound, C(22)H(18)N(4)O(2), the mol-ecules lie across an inversion centre. The dihedral angle between the mean planes of the central and terminal benzene rings is 66.03 (2)°. The mol-ecule displays trans and anti conformations about the C=N and N-N bonds, respectively. In the crystal, N-H⋯O hydrogen bonds, with the O atoms of C=O groups acting as acceptors, link the mol-ecules into a chain along [101].

3-Amino-4-[4-(dimethyl-amino)-phen-yl]-4,5-dihydro-1,2,5-thia-diazole 1,1-dioxide.

The title compound, C(10)H(14)N(4)O(2)S, exists in the amine tautomeric form. The dihedral angle between the benzene and thia-diazo-lidine rings is 66.54 (19)°. In the crystal, mol-ecules are linked by N-H⋯O and N-H⋯N hydrogen bonds into a layer parallel to the ac plane. The layers are further linked by C-H⋯O hydrogen bonds.

(E)-N'-(2-Hy-droxy-benzyl-idene)furan-2-carbohydrazide.

In the title compound, C(12)H(10)N(2)O(3), the dihedral angle between the benzene ring and the furan ring is 16.12 (13)°. The conformation is stabilized by an intra-molecular O-H⋯N hydrogen bond. Inter-molecular N-H⋯O hydrogen bonds with the keto group as acceptor lead to strands along [001]. The mol-ecule displays a trans configuration with respect to the C=N and N-N bonds.

1-(4-Chloro-3-fluoro-phen-yl)-2-[(3-phenyl-isoquinolin-1-yl)sulfan-yl]ethanone.

In the title compound, C(23)H(15)ClFNOS, the isoquinoline system and the 4-chloro-3-fluoro-phenyl ring are aligned at 80.4 (1)°. The dihedral angle between the isoquinoline system and the pendant (unsubstituted) phenyl ring is 19.91 (1)°.

3-(4-Methoxy-phen-yl)-1H-isochromen-1-one.

The asymmetric unit of the title compound, C(16)H(12)O(3), contains two crystallographically independent mol-ecules. The isochromene ring system is planar (maximum deviation 0.024 Å) and is oriented at dihedral angles of 2.63 (3) and 0.79 (3)° with respect to the methoxy-benzene rings in the two independent mol-ecules.

Direct and solvent-assisted keto-enol tautomerism and hydrogen-bonding interactions in 4-(m-chlorobenzylamino)-3-phenyl-4,5-dihydro-1H-1,2,4-triazol-5-one: a quantum-chemical study.

The tautomeric equilibrium of the title triazole compound was computationally analyzed at the B3LYP/6-311++G(d,p) and MP2/6-311++G(d,p) levels of theory. The solvent effect was considered for three solvents (chloroform, methanol, and water). Two distinct mechanisms were applied: a direct intramolecular transfer using the polarizable continuum model (PCM) and a solvent-assisted mechanism. The calculations indicated that the keto form is more stable in all cases. It was found that the barrier heights for the tautomerization reaction are very high, indicating a relatively disfavored process. Although the barrier heights for solvent-assisted reactions are significantly lower than those for the unassisted tautomerization reaction, implying the importance of the superior catalytic effect of the solvents, monosolvation was not found to be sufficient for the reaction to occur. Finally, the two intermolecular hydrogen-bonding interactions in the crystal structure were investigated in the gas phase; according to the calculated energies and structural parameters, the order of stability is N3-H3···O1 > N1-H1···O1.

N-(4-nitrobenzoyl)-N'-(1,5-dimethyl-3-oxo-2-phenyl-1H-3(2H)-pyrazolyl)-thiourea hydrate: synthesis, spectroscopic characterization, X-ray structure and DFT studies.

The title molecule (C19H17N5O4S·H2O) was synthesized and characterized by IR-NMR spectroscopy, MS and single-crystal X-ray diffraction. The molecular geometry, vibrational frequencies and gauge-independent atomic orbital (GIAO) 1H and 13C NMR chemical shift values of the compound in the ground state have been calculated by using the density functional theory (DFT) method with 6-31G(d) basis set, and compared with the experimental data. All the assignments of the theoretical frequencies were performed by potential energy distributions using VEDA 4 program. The calculated results show that the optimized geometries can well reproduce the crystal structural parameters, and the theoretical vibrational frequencies and 1H and 13C NMR chemical shift values show good agreement with experimental data. To determine conformational flexibility, the molecular energy profile of the title compound was obtained with respect to the selected torsion angle, which was varied from -180° to +180° in steps of 10°. Besides, molecular electrostatic potential (MEP), frontier molecular orbitals (FMO) analysis and thermodynamic properties of the compound were investigated by theoretical calculations.