Clickable Pyclen-Based Luminescent Lanthanide Complexes: Application to Two-Photon Microscopy

Area of Science:

• Coordination Chemistry
• Bioconjugation Chemistry
• Bioimaging and Biosensing

Background:

• Lanthanide luminescent bioprobes are crucial for advanced biological imaging and sensing.
• Functionalization of biomolecules using click chemistry offers a straightforward route to smart luminescent tools.
• Developing novel probes with enhanced photophysical properties and efficient cellular uptake is essential.

Purpose of the Study:

• To synthesize and characterize novel lanthanide complexes with a reactive alkyne group for click chemistry functionalization.
• To evaluate the photophysical properties, specifically two-photon absorption and emission, of the synthesized europium (Eu³⁺) and samarium (Sm³⁺) complexes.
• To demonstrate the utility of these complexes as bioprobes for live-cell imaging via conjugation to cell-penetrating peptides.

Main Methods:

• Synthesis of pyclen-based lanthanide complexes featuring a terminal alkyne group and a 4-(4-alkylthiophenyl)picolinate sensitizer.
• Copper-catalyzed azide-alkyne cycloaddition (click chemistry) for conjugating lanthanide complexes to azide-functionalized cell-penetrating peptides.
• Two-photon microscopy imaging of live HeLa cells using the synthesized lanthanide-peptide conjugates.

Main Results:

• The synthesized Eu³⁺ and Sm³⁺ complexes exhibited excellent two-photon absorption and emission properties.
• Conjugation to cell-penetrating peptides via click chemistry did not significantly alter the luminescence properties of the complexes.
• Efficient delivery and detection of Eu³⁺ luminescence in live HeLa cells at low concentrations (50 nM), and high-quality imaging with the Sm³⁺ complex were achieved.

Conclusions:

• The developed lanthanide complexes are versatile building blocks for creating smart luminescent bioprobes.
• Click chemistry provides an efficient method for conjugating these probes to biomolecules for biological applications.
• These novel bioprobes demonstrate significant potential for advanced live-cell imaging and sensing applications.