Rational design of highly biocompatible Eu3+ luminescent probes: a combined SOC-NEVPT2 theoretical and experimental study of DNA/protein interactions.

A series of Eu3+ complexes bearing phenanthroline- and dppz-based ligands (dppz = dipyrido[3,2-a:2',3'-c]phenazine) was designed to establish structure-property relationships between ligand structure, photophysical properties, and biological activity. Spectroscopic studies revealed that ligand functionalization strongly modulates antenna efficiency, leading to significant variations in emission intensity, quantum yields, and excited-state lifetimes, while preserving the characteristic Eu3+-centered luminescence. The extended π-conjugation and structural rigidity of the dppz-based systems resulted in competitive photophysical performance by promoting efficient sensitization and reducing vibrational quenching. DNA-binding and BSA quenching assays were used to investigate interactions with biomacromolecules. The results showed that ligand planarity and the nature of the substituents influence both the binding affinity and the interaction mode. Complexes with dppz ligands exhibited π-π interactions compatible with partial intercalation into DNA and considerable protein binding through hydrophobic and electrostatic interactions. Cell viability assays in HeLa cells confirmed ligand design influences the biological response, enabling the identification of systems that balance luminescence efficiency with biocompatibility. These features point to their potential as luminescent probes and bioanalytical platforms. Complementary spin-orbit coupled NEVPT2 (SOC-NEVPT2) calculations provided detailed insight into the electronic structure and excited-state manifold, supporting the experimental trends observed for energy transfer and emission efficiency. Overall, these findings establish clear structure-property relationships and provide useful guidelines for the rational design of Eu3+-based luminescent systems for bioanalytical, sensing, and imaging applications.