Iridium(III)-based minor groove binding complexes as DNA photocleavage agents

Area of Science:

• Coordination Chemistry
• Bioinorganic Chemistry
• Photochemistry

Background:

• Quaterpyridyl (qtpy) ligands form transition metal complexes known for DNA binding.
• Iridium(III) complexes offer unique photophysical properties for potential applications.

Purpose of the Study:

• Synthesize and characterize new tricationic iridium(III)-qtpy complexes.
• Investigate their DNA binding interactions and photonuclease activity.

Main Methods:

• Synthesis of iridium(III) complexes with qtpy ligand.
• Spectroscopic studies (UV-Vis, fluorescence) to assess DNA interaction.
• DNA binding assays (fluorescence quenching, affinity measurements).
• Molecular dynamics simulations.
• Plasmid DNA cleavage assays under photoirradiation.

Main Results:

• Novel water-soluble tricationic iridium(III)-qtpy complexes ([Ir(bpy)2(qtpy)]3+ and [Ir(phen)2(qtpy)]3+) were synthesized.
• Complexes exhibit high-energy excited states quenched by duplex DNA and mononucleotides.
• Strong preference for duplex DNA binding over quadruplex DNA, with higher affinity than Ru(II) analogues.
• Molecular dynamics confirm minor groove binding via the qtpy ligand.
• Complex 1 acts as a synthetic photonuclease, cleaving plasmid DNA upon photoirradiation.

Conclusions:

• Tricationic iridium(III)-qtpy complexes are effective DNA minor groove binders with high affinity for duplex DNA.
• These complexes possess photonuclease activity, demonstrating potential for targeted DNA cleavage applications.