Synthesis of Novel Tritopic Hydrazone Ligands: Spectroscopy, Biological Activity, DFT, and Molecular Docking Studies

Abstract

Polytopic organic ligands with hydrazone moiety are at the forefront of new drug research among many others due to their unique and versatile functionality and ease of strategic ligand design. Quantum chemical calculations of these polyfunctional ligands can be carried out in silico to determine the thermodynamic parameters. In this study two new tritopic dihydrazide ligands, N’2, N’6-bis[(1E)-1-(thiophen-2-yl) ethylidene] pyridine-2, 6-dicarbohydrazide (L1) and N’2, N’6-bis[(1E)-1-(1H-pyrrol-2-yl) ethylidene] pyridine-2, 6-dicarbohydrazide (L2) were successfully prepared by the condensation reaction of pyridine-2, 6-dicarboxylic hydrazide with 2-acetylthiophene and 2-acetylpyrrole. The FT-IR, 1H, and 13C NMR, as well as mass spectra of both L1 and L2, were recorded and analyzed. Quantum chemical calculations were performed at the DFT/B3LYP/cc-pvdz/6-311+ G (d, p) level of theory to study the molecular geometry, vibrational frequencies, and thermodynamic properties including changes of ∆H, ∆S, and ∆G for both the ligands. The optimized vibrational frequency and (1H and 13C) NMR obtained by B3LYP/cc-pvdz/6-311 + G (d, p) showed good agreement with experimental FT-IR and NMR data. Frontier molecular orbital (FMO) calculations were also conducted to find the HOMO, LUMO, and HOMO–LUMO gaps of the two synthesized compounds. To investigate the biological activities of the ligands, L1 and L2 were tested using in vitro bioassays against some Gram-negative and Gram-positive bacteria and fungus strains. In addition, molecular docking was used to study the molecular behavior of L1 and L2 against tyrosinase from Bacillus megaterium. The outcomes revealed that both L1 and L2 can suppress microbial growth of bacteria and fungi with variable potency. The antibacterial activity results demonstrated the compound L2 to be potentially effective against Bacillus megaterium with inhibition zones of 12 mm while the molecular docking study showed the binding energies for L1 and L2 to be −7.7 and −8.8 kcal mol−1, respectively, with tyrosinase from Bacillus megaterium.‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬

Molecular Docking, HOMO-LUMO, Quantum Chemical Computation and Bioactivity Analysis of vic-Dioxim Derivatives Bearing Hydrazone Group Ligand and Their NiII and CuII Complexes

“…In our study, [Cu(L 2 H)2] had the lowest η and the highest σ value when compared to other compounds. Besides, a high ω value corresponds to having a good electrophile property for a molecule (Rupa et al, 2022) where [Cu(L 2 H)2] had the highest ω value in our study. Thus [Cu(L 2 H)2] had a potent and sufficient electrophile ability (acceptor) among other compounds.…”

Green synthesis of ZnO nanoparticles usingCocos nuciferaleaf extract: Characterization, antimicrobial, antioxidant, and photocatalytic activity

“…Antimicrobial screening of ZnO NPs (50 μL dose used & concentration was 150 μg disc −1 ) was assessed against various bacterial and fungal strains. Three gram (+ve) bacterial strains such as Staphylococcus aureus (cars-2), Bacillus megaterium ( BTCC-18 ), and Bacillus cereus (carsgp-1) as well as two fungal strains, for instance, Aspergillus niger (carsm-3) and Trichoderma harzianum (carsm-2) ) were used in agar well diffusion method alike to our previous report [67]. Mueller–Hinton Agar (HiMedia, India) was used to form agar medium to culture bacteria and potato dextrose agar medium (HiMedia, India) was used to culture fungal strains.…”

“…Mueller–Hinton Agar (HiMedia, India) was used to form agar medium to culture bacteria and potato dextrose agar medium (HiMedia, India) was used to culture fungal strains. Ceftriaxone (10 μL) for bacterial strains and amphotericin-B (10 μL dose and 50 μg disc −1 ) for fungal strains were used as standards [67]. After placing the sample in a culture medium, the discs were incubated for 24 h at 37 °C for bacteria and 48 h at 26 °C for fungi in the incubator.…”

Investigation of Major Flavonoids from Artemisia argyi as a Potential COVID-19 Drug: Molecular Docking and DFT Calculations

“…The high lying HOMO, less Eg, and good HOMO separation indicate that charge transfer is possible with a greater binding affinity than would be expected. Recently, studying FMOs theory has become increasingly important to investigate the structure-activity relationships of small structural drugs [34][35][36]. As flavonoids 1-6 are all highly conjugated systems, the HOMOs and LUMOs distributions are all mainly located in the aromatic systems with poor separations except compound 5 and compound 6.…”