Synthesis, Characterization, and Therapeutic Potential of Novel Schiff Base Metal Complexes: Nickel(II) and Copper(II) Complexes Based 2‐[(2‐Chloroquinolin‐3‐yl)methylidene]aminobenzenethiol (CQAT)

ABSTRACT This research focused on the design and comprehensive characterization of two novel transition metal complexes derived from the symmetrical Schiff base 2‐[(2‐chloroquinolin‐3‐yl)methylidene]aminobenzenethiol (CQAT), coordinated with nickel(II) (NiCQAT) and copper(II) (CuCQAT) ions. The structural elucidation of these complexes was achieved through a range of advanced analytical techniques. Thermal analysis revealed the stability and decomposition patterns of the complexes, supporting the identification of their coordination geometries. The collective data indicated that both NiCQAT and CuCQAT complexes adopt octahedral coordination, with the specific formulas [Ni(CQAT) 2 (H 2 O) 2 ] and [Cu(CQAT) 2 (H 2 O) 2 ], respectively. To complement the experimental findings, density functional theory (DFT) calculations were employed. These theoretical calculations confirmed the proposed molecular structures and provided detailed insights into key quantum chemical parameters, such as HOMO–LUMO energies, molecular orbitals, and electronic distributions, which are crucial for understanding the complexes' reactivity and stability. Furthermore, extensive in vitro biological evaluations were conducted to assess the anti‐inflammatory and antioxidant properties of the synthesized complexes. These assays demonstrated that both NiCQAT and CuCQAT exhibited significantly enhanced bioactivity compared to the free CQAT ligand, suggesting a synergistic effect of metal coordination on the ligand's biological efficacy. To further explore the mode of action, molecular docking studies were performed targeting two key proteins—human cyclooxygenase‐2 (PDB ID: 5IKT) and human peroxiredoxin 2 (PDB ID: 5IJT). The docking simulations provided valuable insights into the binding affinities, interaction energies, and key amino acid residues involved in the binding process, offering a molecular‐level understanding of their potential biological mechanisms. The findings from these multidisciplinary studies highlight the therapeutic potential of CQAT and its nickel and copper complexes, positioning them as promising candidates for further development in the field of medicinal chemistry.