Design and synthesis of peptide-derived Schiff base Cu(II) and Zn(II) complexes as DNA targeting agents

This work involves the synthesis, characterization, and investigation of novel Cu(II) and Zn(II) metal complexes derived from a peptide-based Schiff base ligand. The characterization of the complexes using various spectroscopic techniques proposed a square planar structure for the Cu(II) complex and a tetrahedral coordination environment for the Zn(II) complex. The interaction of these complexes with Calf Thymus DNA (CT-DNA) was explored using complementary methodologies, UV–visible absorption spectroscopy and viscometry, which determined the binding affinity and provided critical insight into the binding mode (groove binding). Furthermore, density functional theory (DFT) calculations were utilized to establish a structure-activity relationship by analyzing the electronic properties of the complexes. Molecular docking studies were used to predict the precise binding geometry and affinity towards the DNA double helix. Additionally, Swiss-ADME in silico analyses were conducted to evaluate the pharmacokinetic profiles and drug-likeness of these potential metal complexes. This work presents valuable, integrated experimental and computational data of novel peptide-based transition metal complexes that establish a foundation for their exploration as candidates for future biological evaluation.