Instigating the in vitro antidiabetic activity of new tridentate Schiff base ligand appended M(II) complexes: From synthesis, structural characterization, quantum computational calculations to molecular docking, and molecular dynamics simulation studies

In search of novel medications that could be effective in preventing and treating diabetes, four new [Co(L)(H2O)(3)] (2), [Ni(L)(H2O)(3)] (3), [Cu(L)(H2O)] (4) and [Zn(L)(H2O)] (5) complexes were synthesized from 4-Chloro-2-(((3-mercapto-5-[pyridin-4-yl]-4H-1,2,4-triazol-4-yl)imino)methyl)phenol ligand (H2L), which is obtained by the condensation of 5-chlorosalicylaldehyde with 4-amino-5-(pyridin-4-yl)-4H-1,2,4-triazole-3-thiol in 1:1 ratio. The Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR) (H-1 and C-13), elemental analyses, UV-visible, electron spin resonance (ESR), thermogravimetric analysis (TGA), scanning electron microscopy, energy dispersive X-ray analysis (EDAX), and X-ray diffraction (XRD) studies were used to successfully characterize the compounds. The ligand act in a tridentate manner and coordinates to the metal ions through N-azomethine, O-phenolic and S-thiol functionalities. On the premise of their spectral and physico-analytical data; octahedral geometry for complex 2 and 3, while square planar and tetrahedral geometry for complex 4 and 5 was proposed. Theoretical calculations of the synthesized compounds have been performed by using density functional theory (DFT)/B3LYP method and parameters such as HOMO-LUMO energy values and MESP were calculated. In vitro examinations against alpha-amylase and alpha-glucosidase reveal promising results for the compounds. Nickel (II) complex (3) against alpha-amylase and zinc (II) complex (5) against alpha-glucosidase were found to be good inhibitors. Molecular docking experiments against the receptors 1BSI and 5ZCC were done to support the observation and considerable binding energies and interactions were observed. Additionally, a 100-ns molecular dynamics simulation (MDS) was done to assess the stability of the complex structures generated during in silico research, and it showed a stable conformation and binding pattern for the compounds.