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

ANDRES M. DURANTINI; LANA E. GREENE; RICHARD LINCOLN; SOL R. MARTÍNEZ; GONZALO COSA

Santiado de Chile

Conferencia; 25th I-APS Conference; 2016

Here we show the design, preparation, andcharacterization of a dormant singlet oxygen (1O2) photosensitizerthat is activated upon its reaction with reactive oxygen species (ROS), including1O2 itself, in what constitutes an autocatalytic process.The compound is based on a two segment photosensitizer-trap molecule where the photosensitizer segmentconsists of a Br-substituted borondipyrromethene (BODIPY) dye. The trap segmentconsists of the chromanol ring of α-tocopherol, the most potent naturally occurring lipidsoluble antioxidant. Time-resolved absorption, fluorescence, and 1O2phosphorescence studies together with fluorescence and 1O2phosphorescence emission quantum yields collected on Br2B-PMHC and related bromo and iodo-substitutedBODIPY dyes show that the trap segment provides a total of three layers ofintramolecular suppression of 1O2 production. Oxidationof the trap segment with ROS restores the sensitizing properties of thephotosensitizer segment resulting in ∼40-foldenhancement in 1O2 production. The juxtaposed antioxidant(chromanol) and prooxidant (Br-BODIPY) antagonistic chemical activities of thetwo-segment compound enable the autocatalytic, and in general ROS-mediated,activation of 1O2 sensitization providing a chemical cuefor the spatiotemporal control of 1O2. The usefulness ofthis approach to selectively photoactivate the production of singlet oxygen inROS stressed vs regular cells was successfully tested via the photodynamicinactivation of a ROS stressed Gram negative Escherichia coli strain.