Unveiling Volcano-Type Trends in SOCT-ISC Photosensitization: Energy Gap Law-Guided Strategy for Efficient...

Area of Science:

• Materials Science
• Photochemistry
• Organic Chemistry

Background:

• High-performance photosensitizers are crucial for photodynamic therapy.
• Understanding excited-state dynamics is key to designing effective heavy-atom-free photosensitizers.
• Cyanine dyes offer a promising scaffold for photosensitizer development.

Purpose of the Study:

• To investigate the excited-state dynamics of cyanine-based photosensitizers functionalized at the C2 position.
• To establish a rational design strategy for optimizing photosensitizer performance.
• To explore the relationship between photo-induced electron transfer and singlet oxygen generation.

Main Methods:

• Synthesis of cyanine-based compounds with varying C2 substituents.
• Femtosecond transient spectroscopy to probe excited-state dynamics.
• Quantum chemical calculations to elucidate electronic structure and energy levels.
• In vitro and in vivo evaluation of photodynamic anticancer efficacy.

Main Results:

• A 'volcano-type' relationship was observed between photo-induced electron transfer efficiency and singlet oxygen quantum yield.
• The charge-separated (CS) state energy was identified as a critical factor controlling the balance between intersystem crossing and charge recombination.
• The optimized compound, TCy-Pyr, demonstrated superior in vitro and in vivo anticancer efficacy and aggregation-induced targeting.

Conclusions:

• The study elucidates the excited-state dynamics governing spin-orbit charge transfer intersystem crossing (SOCT-ISC) in cyanine photosensitizers.
• A rational design strategy based on CS-state energy modulation was established for developing high-performance photosensitizers.
• TCy-Pyr represents a promising candidate for photodynamic therapy due to its enhanced efficacy and tumor-targeting capabilities.