Novel amide-based macrocyclic Co(ii) complexes: correlating structural, computational, and biological properties through DFT and docking

Abstract

A series of Co(II) complexes incorporating functionalized macrocyclic scaffolds, designated as [Co(N₄O₄MacL₁)Cl₂]–[Co(N₄O₄MacL₃)Cl₂], were synthesized using three structurally related macrocyclic ligands (N₄O₄MacL₁–N₄O₄MacL₃), each featuring an amide-based tetradentate donor framework. The complexes were comprehensively characterized by elemental analysis, FTIR spectroscopy, magnetic susceptibility measurements, UV-visible spectroscopy, ¹H and ¹³C NMR spectroscopy, and powder X-ray diffraction. Spectroscopic and analytical findings confirm that the ligands act as monoanionic tetradentate donors, coordinating through nitrogen and oxygen donor sites. The magnetic and electronic spectral data support an octahedral coordination geometry around the Co(II) center in all complexes. Thermal stability and kinetic parameters were assessed through thermogravimetric analysis, employing the Coats-Redfern and Flynn-Wall-Ozawa (FWO) models to determine activation energies and thermodynamic parameters. Moreover, density functional theory (DFT) calculations provided insights into optimized geometries, bond parameters, and frontier molecular orbital characteristics, which corroborate the experimental observations. The biological activities of the ligands and their Co(II) complexes were evaluated through in vitro antimicrobial assays against fungal strains A. niger and C. albicans, and bacterial strains B. subtilis, S. aureus, E. coli, and S. typhi. Additionally, antioxidant activity assessed by the DPPH free-radical scavenging assay revealed that [Co(N₄O₄MacL₃)Cl₂] demonstrated the highest radical-quenching efficiency. Among the complexes studied, [Co(N₄O₄MacL₂)Cl₂] displayed the most promising antimicrobial activity with minimal cytotoxic effects. Molecular docking studies further validated the biological results, indicating favourable interactions of the complexes with relevant biomolecular targets. Overall, these findings highlight the therapeutic potential of amide-containing macrocyclic ligands and their cobalt(II) complexes as promising candidates for antimicrobial applications, selective cytotoxic behaviour, and effective antioxidant activity.