New Visible-Light-Sensitive Dicyanocoumarin- and COUPY-Based Caging Groups with Improved Photolytic Efficiency

Photolabile protecting groups (PPGs), also known as caging groups, are valuable tools in photopharmacology. They enable precise control over the release of bioactive compounds from the corresponding caged compounds at a precisely controlled time and place using light of specific wavelengths. This study introduces a novel approach to fine-tuning the photophysical and photochemical properties of visible-light-sensitive dicyanocoumarin- and COUPY-based caging groups by incorporating a phenyl group in a position adjacent to the photolabile bond. Our photoactivation studies with visible light demonstrated that this structural modification slightly improved the photolytic efficiency of both dicyanocoumarin- and COUPY-caged model compounds compared to their methyl-substituted or unsubstituted counterparts. Furthermore, COUPY PPGs were efficiently photoactivated with red light (620 nm) and successfully used to cage two antitumor drugs, chlorambucil and 4-phenylbutyric acid. These findings highlight the potential of phenyl-containing caging groups based on dicyanocoumarin and COUPY scaffolds as versatile platforms for developing new light-activated tools for photopharmacology applications.