Singlet Oxygen Production (Amplification) upon Activation of an Otherwise Dormant Photosensitizer with ROS (Singlet Oxygen)

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

Ottawa

Conferencia; 98th Canadian Chemistry Conference and Exhibition (CSC); 2015

Canadian Society for Chemistry

Singlet oxygen (1O2) is areactive oxygen species whose cytotoxic properties are exploited inphotodynamic therapy towards control of cell proliferation. Here we show thedesign of a dormant 1O2 photosensitizer that is readilyactivated upon its reaction with ROS, enabling the controlled delivery of 1O2specifically in cells/tissues where metabolic imbalance leads to a large ROSproduction. The new compound is based on a two segment photosensitizer-trapmolecule where the photosensitizer segment consists of a Br substituted BODIPYdye. The trap segment in turn consists of the chromanol ring of a-tocopherol, the most potent lipidsoluble antioxidant. Photoinduced electron transfer from the chromanol segmentis shown to effectively deactivate the photosensitizer activity. Oxidation ofthe trap segment with ROS restores the ability of the photosensitizer segmentto produce 1O2. Steady-state and time-resolvedabsorption, fluorescence, phosphorescence (1O2 emission)and photoxidation product studies show that enhancements of ca. 40-fold in 1O2production are achieved in going from dormant to active species. The juxtaposedantioxidant-prooxidant antagonistic chemical activities of the two segmentcompound combined with the ROS induced activation of the otherwise dormant pro-oxidantsegment provide a new paradigm of chemical activity.