Study of DNA/HSA binding by a water-soluble Cu(II) complex with Triazolopyrimidine ligands: Insights from electrochemical impedance spectroscopy analysis

A water-soluble copper(II) complex containing triazolopyrimidine ligands was synthesized and extensively characterized, and its interaction with biologically relevant macromolecules, specifically salmon sperm deoxyribonucleic acid (DNA) and human serum albumin (HSA), was examined using a combined spectroscopic, electrochemical, and nuclear magnetic resonance approach. The analytical techniques employed included ultraviolet-visible absorption spectroscopy, fluorescence spectroscopy, circular dichroism spectroscopy (CD), cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and saturation transfer difference nuclear magnetic resonance (STD NMR). Conventional spectroscopic and electrochemical experiments consistently indicate that the copper complex interacts with deoxyribonucleic acid predominantly through a groove-binding mode rather than intercalation, as reflected by moderate binding constants, limited spectral perturbations, and minor conformational changes. Beyond these observations, this work highlights the potential of electrochemical impedance spectroscopy as a sensitive and largely unexplored complementary tool to probe metal biomacromolecule interactions in solution. Electrochemical impedance spectroscopy measurements reveal that the formation of copper-DNA and copper-HSA adducts modulates charge-transfer and mass-transport processes at the electrode interface, providing dynamic information not directly accessible through standard spectroscopic techniques. The observed trends, including variations in charge-transfer resistance and diffusion behaviour, correlate with binding events and reach saturation at higher macromolecule concentrations, demonstrating the usefulness of this technique as a complementary electrochemical window into metal-biomacromolecule interactions. Overall, these results support the broader implementation of electrochemical impedance spectroscopy in bioinorganic chemistry and offer new insights into the interfacial properties and redox behaviour of biologically relevant copper complexes.