Mitochondria Targeting with Luminescent Rhenium(I) Complexes.

Area of Science:

• Organometallic Chemistry
• Bioinorganic Chemistry
• Cellular Imaging

Background:

• Rhenium(I) tricarbonyl complexes with 1,10-phenanthroline (phen) are known for their luminescent properties.
• Developing targeted probes for cellular organelles like mitochondria is crucial for biological research.
• Understanding the mechanism of action for novel imaging agents is essential for their application.

Purpose of the Study:

• To synthesize and characterize new neutral fac-[Re(CO)₃(phen)L] compounds.
• To evaluate these compounds as luminescent probes for staining living cancer cells, specifically targeting mitochondria.
• To elucidate the mechanism behind the observed mitochondrial accumulation.

Main Methods:

• One-pot synthesis of fac-[Re(CO)₃(phen)L] compounds.
• Characterization using IR, UV-Vis, NMR spectroscopy, mass spectrometry, and X-ray crystallography.
• Confocal microscopy for cellular imaging and localization studies.
• In vitro studies to verify ligand dissociation from the rhenium center.

Main Results:

• Two new neutral fac-[Re(CO)₃(phen)L] compounds (1, 2) were successfully synthesized and characterized.
• Both compounds exhibited orange luminescence and were used to stain HeLa cancer cells.
• Confocal microscopy confirmed accumulation of the dyes within the mitochondria of cancer cells.
• A ferrocene-containing derivative (3) showed similar mitochondrial accumulation, and its mechanism involved ligand dissociation to form a luminescent fac-[Re(CO)₃(phen)]⁺ core.
• Ligand release from the Re center was confirmed in vitro.

Conclusions:

• The synthesized rhenium compounds effectively stain mitochondria in living cancer cells.
• Mitochondrial accumulation is driven by a dissociation mechanism, where luminescent fac-[Re(CO)₃(phen)]⁺ species form and interact with cellular components.
• These findings highlight a rare dissociation-driven mechanism with significant potential for biological applications and organelle-specific imaging.