Integrating cyclic voltammetry, fluorescence, and docking to elucidate DNA-Schiff-base ligand interactions

Schiff-base ligands are versatile coordination compounds with notable biological and electrochemical importance and understanding their interactions with DNA is essential for exploring their potential pharmacological and sensing applications. This study investigates the binding mechanisms between twelve structurally distinct Schiff-base ligands and calf thymus DNA (ct-DNA), emphasizing the influence of electronic and steric factors on binding affinity. Fluorescence spectroscopy, cyclic voltammetry (CV), and molecular docking were combined to evaluate binding constants, quenching behavior, and molecular interactions. Fluorescence titrations revealed moderate-to-strong binding affinities (K_b = 2.07-9.61 × 10³ M^-1) with predominantly static quenching. Ligands containing planar aromatic systems and electron-withdrawing substituents exhibited stronger binding, whereas bulky or methoxy-substituted analogues showed weaker interactions. These observations were further supported by CV studies, showing decreased redox currents accompanied by potential shifts upon formation of DNA-ligand complex. Molecular docking supported the experimental findings, highlighting hydrogen bonding, π-π stacking, and hydrophobic interactions as dominant stabilizing forces. Overall, the integrated spectroscopic, electrochemical, and computational analyses demonstrate a clear structure-activity relationship, establishing that ligand planarity and electronic properties are key determinants of DNA-binding strength and illustrating the potential of cyclic voltammetry as a complementary tool for studying biomolecular interactions.