Interaction of Chiral Photoactive Complexes with DNA

Chiral photoactive metal complexes combine stereoselective molecular recognition with tunable excited-state reactivity; two desirable properties for the design of photosensitizers for photodynamic therapy (PDT). Helical supramolecular assemblies and enantiopure monometallic complexes generate stereochemically defined molecular surfaces that interact enantioselectively with DNA. Such recognition can strengthen complex-DNA association, thereby enhancing ROS-mediated DNA damage upon irradiation. Whereas DNA binding governs molecular recognition and localization, the electronic properties of the metal center control the photochemical pathway. Ru(II) complexes typically possess long-lived MLCT states that sensitize singlet oxygen through Type II mechanisms. In contrast, Fe(II) complexes undergo ultrafast relaxation to MC states, limiting singlet-oxygen sensitization and their development for PDT. Nevertheless, our results demonstrate that Fe(II) complexes can damage DNA through Type I pathways. Chiral Fe(II) complexes based on phenanthroline-imine ligands combine selective DNA binding with absorption beyond 600 nm, providing a versatile platform for developing selective, visible-light-activated photosensitizers based on earth-abundant metals.