N2O2 Schiff-Base nickel(II) and iron(III) template complexes of 2-hydroxy-5-ethoxyacetophenone S-methylthiosemicarbazone: Synthesis, characterization, DFT calculations, molecular docking, and antioxidant activity

Two new complexes, [Ni (L)] (1) and [Fe (L)Cl] (2), were synthesized through template condensation of 2-hydroxy-5-ethoxyacetophenone S-methylthiosemicarbazone (H2L1) with 2-hydroxy-4-methoxybenzaldehyde in the presence of nickel(II) and iron(III) ions. The complexes were characterized using elemental analysis, magnetic measurements, FT-IR, UV–Vis, ESI-MS and 1H NMR spectra. In order to gain further insights into their structural features, Density Functional Theory (DFT) calculations were employed to optimize the geometries and predict vibrational frequencies of the complexes, providing valuable insights into their structural stability and bonding interactions. The frontier molecular orbital (HOMO and LUMO) analyses were conducted for the optimized geometries to evaluate the electronic properties and chemical reactivity. The computational results confirmed the proposed square-planar geometry for (1) and square-pyramidal geometry for (2). TD-DFT analyses predicted the theoretical UV–Vis spectra and compared with experimental spectra. Molecular docking analyses were performed with EGFR (PDB ID: 4HJO) and B-DNA (PDB ID: 1BNA). Binding parameters and ADME analyses were also conducted. The antioxidant capacity of the compounds were examined using the CUPRAC (cupric reducing antioxidant capacity) method, and their radical scavenging activity was determined by the DPPH (1,1-Diphenyl-2-picrylhydrazyl) assay. [Ni(L)] exhibited higher antioxidant activity compared to [Fe(L)Cl] and the ligand (H2L1) in the CUPRAC assay. © 2025 Elsevier B.V.