The pH-influenced PET processes between pyronine and different heterocycles

Area of Science:

• Supramolecular Chemistry
• Fluorescent Probes
• Chemical Sensing

Background:

• Development of responsive fluorescent probes is crucial for chemical sensing and biomedical imaging.
• Rosamine derivatives offer a versatile scaffold for designing novel optical sensors.
• Understanding structure-property relationships is key to optimizing probe performance.

Purpose of the Study:

• To design and synthesize novel OFF-ON and ON-OFF type pH probes based on rosamine.
• To investigate the influence of heterocyclic substituents on probe response and photophysical properties.
• To evaluate the potential biomedical applications of the developed probes, including cellular imaging.

Main Methods:

• Synthesis of rosamine-based compounds with varying heterocyclic linkers (indole, imidazole, quinolinyl).
• Characterization of photophysical properties, including fluorescence emission and pH-dependent response.
• Computational analysis using time-dependent density functional theory (TD-DFT) to elucidate pH-dependent PET mechanisms.
• Confocal fluorescence imaging to assess probe performance in biological systems.

Main Results:

• Probe 1a (indole-pyronine) exhibited an OFF-ON pH response with a pK_a of 1.41 and a 15-fold fluorescence increase.
• Probes 1c-d (quinolinyl-pyronine) displayed monotonous ON-OFF pH responses (pK_a 3.26 and 2.62) with significant fluorescence quenching (263- and 46-fold).
• Electron donating abilities of heterocycles correlated with photoinduced electron transfer (PET) processes and pH sensitivity.
• Probe 1d demonstrated lysosome targeting ability with appropriate pK_a and good biocompatibility.

Conclusions:

• The study successfully designed rosamine-based pH probes with tunable OFF-ON and ON-OFF fluorescence responses.
• Modulation of heterocyclic substituents effectively controlled probe sensitivity and response mechanisms via PET.
• Probe 1d shows promise for lysosome-specific imaging in biomedical applications due to its favorable properties.