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

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

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

AMER CHEMICAL SOC

Lugar: Washington; Año: 2016

0002-7863

Here we show the design, preparation, andcharacterization of a dormant singlet oxygen (1O2) photosensitizerthat is activated upon its reaction with reactiveoxygen species (ROS), including 1O2 itself, in what constitutesan autocatalytic process. The compound is based on a twosegment photosensitizer−trap molecule where the photosensitizersegment consists of a Br-substituted borondipyrromethene(BODIPY) dye. The trap segment consistsof the chromanol ring of α-tocopherol, the most potentnaturally occurring lipid soluble antioxidant. Time-resolvedabsorption, fluorescence, and 1O2 phosphorescence studiestogether with fluorescence and 1O2 phosphorescence emission quantum yields collected on Br2B−PMHC and related bromo andiodo-substituted BODIPY dyes show that the trap segment provides a total of three layers of intramolecular suppression of 1O2production. Oxidation of the trap segment with ROS restores the sensitizing properties of the photosensitizer segment resultingin ∼40-fold enhancement in 1O2 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, activationof 1O2 sensitization providing a chemical cue for the spatiotemporal control of 1O2.The usefulness of this approach to selectivelyphotoactivate the production of singlet oxygen in ROS stressed vs regular cells was successfully tested via the photodynamicinactivation of a ROS stressed Gram negative Escherichia coli strain.