Amplification of Singlet Oxygen Production upon Activation of an Otherwise Dormant Sensitizer with Singlet Oxygen

ANDRES M. DURANTINI; GONZALO COSA

Montreal

Congreso; McGill­CIHR Drug Development Training Program DDTP Retreat; 2014

McGill University

Singlet oxygen (1O2) is a reactive oxygen species(ROS) whose cytotoxic properties are exploited in photodynamic therapy (PDT)towards control of cell proliferation. It is formed following lightillumination of photosensitizers enabling spatiotemporal control on the productionof this ROS species. Major interest lies in monitoring the evolution of singletoxygen in live cells towards measuring efficacy of new PDT drugs as well as tomap the locations of generation of 1O2. Here we willdescribe proof of concepts results where we show that the probe H2B-PMHC,a fluorogenic antioxidant (a tocopherol analogue) designed in our laboratory,may act as a singlet oxygen marker. Previous reports showing that tocopherolscavenges 1O2 were promising in this regard. We show thatupon reaction with 1O2 an endoperoxide is formed whichdeactivates an intramolecular quenching in H2B-PMHC leading to a60-fold emission enhancement. We next demonstrate the ability to activatethrough a similar chemical reaction, the sensitization of singlet oxygen inotherwise dormant singlet oxygen sensitizers, analogues of H2B-PMHCthat bear heavy atoms favoring 1O2 sensitization overfluorescence emission. The new analogues, much like H2B-PMHC, arequenched intramolecularly. Upon ROS scavenging and deactivation of theintramolecular quenching pathway, the photoexcited compounds undergointersystem crossing and sensitize singlet oxygen. Our results from laser flashphotolysis, steady-state fluorescence, time-resolved fluorescence and singletoxygen phosphorescence studies on the newly synthetized BODIPY dyes (Figure 1)demonstrate that in particular Br2B-PMHC is a great ROS-activatedsinglet oxygen photosensitizer that may prove a suitable compound to usetowards controlling cell proliferation in tissues characterized by largeproduction of ROS such as cancer cells.