Bis-1,2,4-triazol derivatives: Synthesis, characterization, DFT, antileishmanial activity and molecular docking study.

In this study, triazol derivatives, 4,4'-(((1E, 1E')-1,2-phenylenebis (methanylyidene)) bis (azanylidene)) bis (5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (2), 4,4'-(((1E, 1E')-1,3-phenylenebis (methanylyidene)) bis (azanylidene)) bis (5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (3) and 4,4'-(((1E, 1E')-1,4-phenylene bis (methanyl yidene)) bis (azanylidene)) bis (5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (4) were synthesized from the reaction of 4-amino-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one and phthalaldehyde/isophthalaldehyde/terephthalaldehyde, respectively. Compounds 2-4 were characterized by Fourier transform infrared (FTIR), proton and carbon-13 nuclear magnetic resonance (1H- and 13C- NMR) spectroscopic methods. Theoretical study for compounds 2-4 were carried out by DFT/B3LYP/6-311++G(d,p). Structural and spectroscopic parameters were determined theoreticaly and compared with experimental ones. Also, the molecular electrostatic potential (MEP) maps of compounds were obtained. Leishmanicidal activity of compounds 2-4 against to Leishmania infantum was determined by microdilution broth method containing alamar blue. As a result of the study, compounds 2-4 were found to be effective against the specie of Leishmania. Molecular docking analysis against Trypanothione Reductase (TRe) with compound 2 was carried out to see the necessary interactions responsible for antileishmanial activity. The docking calculations of compound 2 supported the antileishmanial activity exhibiting high inhibition constant.Communicated by Ramaswamy H. Sarma.

3-(5-(1H-imidazol-1-yl) pent-1-en-1-yl)-9-ethyl-9H-carbazole: synthesis, characterization (IR, NMR), DFT, antimicrobial-antioxidant activities and docking study.

3-(5-(1H-imidazol-1-yl) pent-1-en-1-yl)-9-ethyl-9H-carbazole called as compound 1 was synthesized and characterized by proton and carbon-13 nuclear magnetic resonance (1H- and 13C- NMR) and Fourier transform infrared (FTIR) spectroscopic methods. Density Functional Theory/Becke, 3-parameter (DFT/B3LYP), for compound 1 were performed with 6-311++G(d,p) method. Optimized geometry, frontier molecular orbitals (HOMO; highest occupied molecular orbital; LUMO: lowest unoccupied molecular orbital), IR and NMR parameters of compound 1 were obtained. The evaluations reveal that the calculation results support the experimental results. In addition, the antimicrobial (a microwell dilution method) and antioxidant activities (2,2-Diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS) ferric ion reducing antioxidant power (FRAP) of compound 1 were evaluated. According to the results obtained, it showed higher antimicrobial activity (Minimal inhibition concentration (MIC): 78.12 µg/mL) against B. subtilis subsp. Spizizenii. Morever, molecular docking studies were carried out to investigate the interactions of an antimicrobial agent on some important enzymes played important roles in nucleic acid (Deoxyribo nucleic acid (DNA) synthesis, cell wall synthesis, protein synthesis, and metabolism etc. The compound 1 was strongly bound to tyrosyl-tRNA synthetase enzyme (binding energy: -11.18 and Ki: 6.37 nM) and Beta-Ketoacyl-Acp Synthase III enzyme (binding energy: -10.29 and Ki: 28.47 nM).Communicated by Ramaswamy H. Sarma.

New chalcone derivative, ethyl 2-(4-(3-(benzo[b]thiophen-2-yl)acryloyl)phenoxy)acetate: synthesis, characterization, DFT study, enzyme inhibition activities and docking study.

Chalcone derivative, ethyl 2-(4-(3-(benzo[b]thiophen-2yl)acryloyl)phenoxy)acetate (I), was synthesized. Compound I was characterized by proton and carbon-13 nuclear magnetic resonance (1H- and 13C- NMR), fourier transform infrared (FTIR) and mass (LC-ESI-MS/MS) spectroscopic methods. Density Functional Theory (DFT) calculations for compound I were performed at B3LYP/6-311++G(d,p) level. Optimized geometry, frontier molecular orbitals (HOMO; highest occupied molecular orbital; LUMO: lowest unoccupied molecular orbital), IR and NMR parameters of compound I were obtained. The evaluations reveal that the calculation results support the experimental results. The inhibition effects of compound I on cholinesterases and GST enzyme were investigated. Ki and inhibition concentration (IC50) values were calculated separately. Ki values of compound I were found for GST 14.19 ± 2.15, for AChE 11.13 ± 1.22 and for BChE 8.74 ± 0.76 recpectively. The docking analysis of compound I supported the enzym inhibition activity exhibiting high inhibition constant and binding energy for three receptors. Compound I is strongly bound to AChE, huBChE and Glutathione S-transferase with binding energies -11.24, -8.56 and -10.39 kcal/mol, respectively.Communicated by Ramaswamy H. Sarma.

The new Schiff base 4-[(4-Hydroxy-3-fluoro-5-methoxy-benzylidene)amino]-1,5-dimethyl-2-phenyl-1,2-dihydro-pyrazol-3-one: experimental, DFT calculational studies and in vitro antimicrobial activity.

The synthesized Schiff base, 4-[(4-Hydroxy-3-fluoro-5-methoxy-benzylidene)amino]-1,5-dimethyl-2-phenyl-1,2-dihydro-pyrazol-3-one (I), has been characterized by (13)C NMR, (1)H NMR, 2D NMR ((1)H-(1)H COSY and (13)C APT), FT-IR, UV-vis and X-ray single-crystal techniques. Molecular geometry of the compound I in the ground state, vibrational frequencies and chemical shift values have been calculated by using the density functional method (DFT) with 6-311++G(d,p) basis set. The obtained results indicate that optimized geometry can well reflect the crystal structural parameters. The differences between experimental and calculated results of FT-IR and NMR have supported the existence of intermolecular (O-H⋯O type) and intramolecular (C-H⋯O type) hydrogen bonds in the crystal structure. Molecular electrostatic potential (MEP), frontier molecular orbital analysis (HOMO-LUMO) and electronic absorption spectra were carried out at B3LYP/6-311G++(d,p). HOMO-LUMO electronic transition of 3.92eV is due to contribution of the bands the n→π∗. The antimicrobial activity of the compound I was determined against the selected 11 bacteria and 8 fungi by microdilution broth assay with Alamar Blue. In vitro studies showed that the compound I has no antifungal effect for selected fungal isolates. However, the compound I shows remarkable antibacterial effect for the bacteria; Streptococcus pneumoniae, Haemophilus influenzae and Enterococcus faecalis.

Experimental and theoretical investigation of the molecular and electronic structure of 3-ethoxy-4-isopropylaminocyclobut-3-ene-1,2-dione.

The title compound, 3-ethoxy-4-isopropylaminocyclobut-3-ene-1,2-dione (EIAC) has been synthesized and characterized by NMR, FT-IR, UV-vis spectroscopy and single-crystal X-ray diffraction. The (1)H NMR spectra were recorded at 300 K and 315 K in CDCl(3) to determine syn/anti conformers of the compound EIAC. Density functional theory (DFT) calculations, optimized geometrical parameters, vibrational frequencies and chemical shift values of syn/anti conformer in CDCl(3) have been performed at B3LYP/6-311G(d) level, and compared with the experimental data. The values provided with the calculations support the experimental data of the compound EIAC. The presence of NH⋯O type intermolecular H bond can be perceived from the difference between experimental calculations and results of FT-IR and NMR calculations. In addition, B3LYP/6-311G(d) basis set has been used to calculate the molecular electrostatic potential, frontier molecular orbitals and electronic absorption spectra. HOMO-LUMO electronic transition of 5.12 eV is derived from the contribution of the bands n→σ(*) or π→π(*). FT-IR, NMR and X-ray spectral results and additionally DFT calculations exhibit that the compound EIAC exists in keto-enamine tautomeric form. The experimental (1)H NMR spectra recorded at 300 K and 315 K and theoretical (1)H NMR data indicate that the compound EIAC is in syn conformer.

Experimental (13C NMR, 1H NMR, FT-IR, single-crystal X-ray diffraction) and DFT studies on 3,4-bis(isoproylamino)cyclobut-3-ene-1,2-dione.

In this work, 3,4-bis(isoproylamino)cyclobut-3-ene-1,2-dione C(10)H(16)N(2)O(2) (I), was synthesized and characterized by (13)C NMR, (1)H NMR, FT-IR, UV-vis spectroscopy and single-crystal X-ray diffraction. DFT method with 6-31G(d,p) basis set has been used to calculate the optimized geometrical parameters, atomic charges, vibrational frequencies and chemical shift values. The calculated vibrational frequencies and chemical shift values are compared with experimental FT-IR and NMR spectra. The results of the calculation shows good agreement between experimental and calculated values of the compound I. The existence of N-H⋯O type intermolecular ve C-H⋯O type intramolecular hydrogen bonds can be deduced from differences between experimental and calculated results of FT-IR and NMR. In addition, the molecular electrostatic potential map and frontier molecular orbitals and electronic absorption spectra were performed at B3LYP/6-31G(d,p) level of theory. HOMO-LUMO electronic transition of 4.90 eV are derived from the contribution of the bands π→π* and n→π* The spectral results obtained from FT-IR, NMR and X-ray of I revealed that the compound I is in predominantly enamine tautomeric form, which was supported by DFT calculations.

2-Benzoylmethyl-4-[(2-benzylidene-ethylidene)amino]-5-(2-thienylmethyl)-2H-1,2,4-triazol-3(4H)-one.

In the mol-ecule of the title compound, C(24)H(20)N(4)O(2)S, the dihedral angle between the triazole and thio-phene rings is 66.80 (4)° and the dihedral angle between the two benzene rings is 63.37 (4)°. An intra-molecular C-H⋯O inter-action results in the formation of a six-membered ring. A π⋯π contact between the benzene rings, [centroid-centroid distance = 3.918 (2) Å] may stabilize the structure. Weak C-H⋯π inter-actions are also present. The S, C and H atoms of the thiophene ring are disordered over two positions and were refined with occupancies of 0.654 (3) and 0.346 (3).