Spectroscopic, theoretical and computational investigations of novel benzo[b]thiophene based ligand and its M(II) complexes: As high portentous antimicrobial and antioxidant agents

Abstract

The reaction of 3-chlorobenzo[b]thiophene-2-carbohydrazide with 4-(diethylamino) salicylaldehyde gave the new ligand; 3-chloro-N'-(4-(diethylamino)-2-hydroxybenzylidene)-benzo[b]thiophene-2-carbohydrazide. The Cu(II), Co(II), Ni(II), and Zn(II) complexes have been successfully prepared. The ligand and the complexes were characterized by analytical, FT-IR, ¹H NMR, mass, UV-visible spectroscopy, molar conductivity, and magnetic susceptibility measurements. The FT-IR spectral data showed that the ligand adopted a tridentate fashion when binding with the metal ions via the nitrogen atoms of the imine (C = N), carboxyl (C = O), and phenolic oxygen (O-H) donor atoms. Density Functional Theory (DFT) estimations for the ligand at the DFT/B3LYP level via 6-31G⁺⁺ (d, p) replicate the structure and geometry. Finally, HOMO and LUMO analyses were used for the charge transfer interface of the structure. Furthermore, molecular docking and ADME calculations were also performed to correlate and interpret the experimental results. The antimicrobial activity study illustrated enhancement in the activity of the free ligand upon complex formation, and the Cu(II) complex (MIC 25 µg mL^-1) may be considered a promising antibacterial agent, and the Ni(II) and Zn(II) complexes (MIC 25 µg mL^-1) as promising antifungal agents. Also, synthesized Cu(II) and Zn(II) metal complexes (MIC 3.125 µg mL^-1) showed promising anti-TB activity against M. tuberculosis. Further, benzo[b]thiophene-based ligand and its metal complexes were evaluated for in vitro antioxidant activity, and in silico docking studies were carried out against Cytochrome c Peroxidase (PDB ID: 2X08).

Keywords: ADME-Tox; Antimicrobial; Antioxidant; Benzo[b]thiophene; DFT; Transition metal complexes.