Singlet Oxygen Formation vs Photodissociation for Light-Responsive Protic Ruthenium Anticancer Compounds: The...

Area of Science:

• Coordination Chemistry
• Photochemistry
• Chemical Biology

Background:

• Ruthenium complexes with protic diimine ligands exhibit photocytotoxicity against cancer cells upon blue light irradiation.
• Previous studies suggested photodissociation as the mechanism, but recent findings point to singlet oxygen formation.
• The electronic properties of the ligands, particularly their protonation state, are crucial for this activity.

Purpose of the Study:

• To investigate the mechanism of photocytotoxicity of ruthenium complexes with protic diimine ligands.
• To correlate the protonation state of the ligands with the formation of reactive oxygen species and photocytotoxicity.
• To elucidate the electronic factors governing singlet oxygen generation and photodissociation.

Main Methods:

• Synthesis and characterization of ruthenium complexes with 6,6'-dihydroxybipyridine ligands.
• Cellular studies including treatment with complexes, blue light irradiation, and assessment of reactive oxygen species (ROS) and apoptosis.
• Spectroscopic techniques (luminescence) and theoretical calculations (TD-DFT) to study electronic properties and energy states.

Main Results:

• Complex 3 shows low EC50 values against breast cancer cells upon blue light irradiation.
• Cellular studies confirm the formation of singlet oxygen (¹O₂) and apoptosis indicators upon treatment with complex 3 and blue light.
• Deprotonation of the diimine ligands (to O⁻) significantly enhances ¹O₂ quantum yields (ϕΔ) and shifts the accessible excited states, favoring ¹O₂ formation over photodissociation.

Conclusions:

• The photocytotoxicity of these ruthenium complexes is primarily mediated by singlet oxygen formation.
• Deprotonation of the 6,6'-dihydroxybipyridine ligand to its anionic form is critical for efficient ¹O₂ generation and enhanced photocytotoxicity under physiological conditions.
• The study highlights the importance of ligand protonation state in tuning the photophysical and photobiological properties of ruthenium-based anticancer agents.