Synthesis and characterization of tetradentate Schiff base complexes: Investigating substituent effects on spectral properties and biomolecular interactions

This work reports the synthesis of four tetradentate Schiff base ligands— H 2 L X ; where X = Cl ( N,N ′-bis(5-chloro-2-hydroxybenzylidene)-2,2-dimethylpropane-1,3-diamine), Br ( N,N ′-bis(5-bromo-2-hydroxybenzylidene)-2,2-dimethylpropane-1,3-diamine), Me ( N,N ′-bis(5-methyl-2-hydroxybenzylidene)-2,2-dimethylpropane-1,3-diamine), and OMe ( N,N ′-bis(5-methoxy-2-hydroxybenzylidene)-2,2-dimethylpropane-1,3-diamine)—prepared by the reaction of 5-substituted salicylaldehydes and 2,2-dimethyl-1,3-propanediamine, and their subsequent Ni(II) and Cu(II) complexes. The structural characterization of all new compounds was confirmed by elemental (CHN) analysis, FT-IR, and 1 H NMR spectroscopy. Geometry optimization was performed using the B3LYP functional; the LanL2DZ basis set was applied for Cu and Ni, and 6-31G(d) for all other elements. This work focuses on the key interactions of the ligands and their Ni/Cu complexes with DNA and BSA. The results indicate that H 2 L Me and its Ni complex predominantly bind within the DNA minor groove, whereas the Cu complex favors major-groove interaction. H 2 L Me forms three key hydrogen bonds with the nucleotide bases (≈2.92–3.12 Å), while also interacting through a hydrogen bond (≈3.34 Å) with amino-acid residues within the active sites of BSA. These results offer a practical model for advancing Schiff-base ligand chemistry toward metallodrug development by enabling controlled biomolecular interactions that may improve efficacy and safety. • Four Schiff bases and their Ni and Cu complexes were synthesized and characterized. • The shift in C N and C O stretches corresponds to the change in bond lengths due to complexation. • Molecular docking demonstrated strong binding to DNA and BSA. • Free ligands form specific H-bonds and hydrophobic interactions with BSA.