Synergistic Energy-Harvesting Coumarin Photocages Enabling Lysosomal pH Rescue

Light-triggered molecular tools releasing bioactive actuators with high spatial and temporal control have prompted significant advances in optobiology. Such probes however require high levels of photosensitivity at biocompatible wavelengths to trigger a biological response safely and efficiently. Here, we propose synergistic, multi-chromophoric, water-soluble systems in which quadrupolar antennas sensitize a coumarinyl photocage, delivering a carboxylic acid payload upon one-photon (visible) or two-photon excitation in the biological transparency near-infrared (NIR) window. Strikingly, the molecular design promotes a 50 % increase in photo-cleavage quantum yield, leading to record photosensitivity for NIR-triggered release of acetic acid. We further demonstrated that these molecular tools efficiently rescue impaired lysosomal pH in a genetic cellular model of Parkinson’s disease. These photoactivated tools are therefore promising candidates for the phototherapeutic management of neurodegenerative diseases