Effect of lanthanide complex structure on cell viability and association.

Area of Science:

• Coordination Chemistry
• Biophysical Chemistry
• Luminescent Probes

Background:

• Lanthanide complexes are valuable luminescent probes.
• Modulating hydrophobicity and charge is crucial for optimizing probe performance.
• Understanding cell interactions is key for in vivo applications.

Purpose of the Study:

• To systematically investigate the impact of hydrophobicity and charge on lanthanide complex cell viability and association.
• To synthesize and characterize a series of terbium-DOTA complexes with varied antenna and pendant arm modifications.
• To evaluate the potential of these complexes as responsive luminescent probes for extracellular detection.

Main Methods:

• Synthesis of terbium-DOTA complexes with diverse sensitizing antennas and carboxyamide pendant arms.
• In vitro assessment of cell viability using standard assays.
• Quantification of cellular association via ICP-MS and fluorescence microscopy.

Main Results:

• Complexes generally exhibited high cell viability (ED50 > 300 μM), with only minor reduction by hexyl substitution.
• Hydrophobic moieties did not enhance cellular association compared to hydrophilic amino acid derivatives.
• The hydrophilic 2-methoxyisophthalamide antenna was found to disfavor cellular association.

Conclusions:

• The studied terbium-DOTA complexes demonstrate excellent cell viability, making them attractive for biological applications.
• Cellular association is not directly correlated with hydrophobicity, suggesting complex interplay with probe structure.
• The findings support the development of responsive luminescent probes based on this scaffold for extracellular analyte detection.