Reactive Oxygen Species Mediated Activation of a Dormant Singlet Oxygen Photosensitizer: From Autocatalytic Singlet Oxygen Amplification to Chemicontrolled Photodynamic Therapy

Here we show the design, preparation, and characterization of a dormant singlet oxygen (O-1(2)) photo sensitizer that is activated upon its reaction with reactive oxygen species (ROS), including O-1(2) itself, in what constitutes an autocatalytic process. The compound is based on a two segment photosensitizer-trap molecule where the photo sensitizer segment consists of a Br-substituted boron-dipyrromethene (BODIPY) dye. The trap segment consists of the chromanol ring of alpha-tocopherol, the most potent naturally occurring lipid soluble antioxidant. Time-resolved absorption, fluorescence, and O-1(2) phosphorescence studies together with fluorescence and O-1(2) phosphorescence emission quantum yields collected on Br2B-PMHC and related bromo and iodo-substituted BODIPY dyes show that the trap segment provides a total of three layers of intramolecular suppression of O-1(2) production. Oxidation of the trap segment with ROS restores the sensitizing properties of the photosensitizer segment resulting in similar to 40-fold enhancement in O-1(2) production. The juxtaposed antioxidant (chromanol) and prooxidant (Br-BODIPY) antagonistic chemical activities of the two-segment compound enable the autocatalytic, and in general ROS-mediated, activation of O-1(2) sensitization providing a chemical cue for the spatiotemporal control of O-1(2).The usefulness of this approach to selectively photoactivate the production of singlet oxygen in ROS stressed vs regular cells was successfully tested via the photodynamic inactivation of a ROS stressed Gram negative Escherichia coli strain.