Heterosubstituted Derivatives of PtPFPP for O₂ Sensing and Cell Analysis: Structure-Activity Relationships

Area of Science:

• Biochemistry
• Biophysics
• Materials Science

Background:

• Phosphorescent probes are valuable tools for molecular oxygen (O2) sensing and bioimaging.
• Existing probe options are limited, necessitating the development of new molecular probes.
• Platinum(II)-porphyrin complexes offer promising photophysical properties for probe development.

Purpose of the Study:

• To synthesize and characterize novel heterosubstituted phosphorescent bioprobes based on the Pt(II)-tetrakis(pentafluorophenyl)porphyrin (PtPFPP) dye.
• To tune the cell permeability of these probes for targeted intracellular or extracellular applications.
• To establish structure-activity relationships for PtPFPP-based bioprobes.

Main Methods:

• Synthesis of PtPFPP derivatives via click modification of para-fluorine atoms with various thiols (e.g., thio-glucose, PEG, cysteamine).
• Characterization of spectral properties and cell-penetrating ability using time-resolved fluorescence and PLIM imaging in mammalian cell cultures.
• Evaluation of probe cytotoxicity under experimental conditions.

Main Results:

• Successfully synthesized a family of heterosubstituted PtPFPP bioprobes with tunable cell permeability.
• Tri- and tetra-PEGylated probes exhibited low cell internalization, suitable for extracellular sensing.
• Cysteamine-conjugated probes demonstrated efficient intracellular penetration.
• No significant cytotoxicity was observed for the developed probes.

Conclusions:

• The new PtPFPP derivatives provide a versatile platform for developing targeted phosphorescent bioprobes.
• The ability to control cell permeability enhances their utility in diverse bioimaging and sensing applications.
• These probes offer a promising alternative to existing limited options for O2 sensing and bioimaging.