Theoretical Insights into the Switching Off/On of 1 O2 Photosensitization in Chemicontrolled Photodynamic Therapy.

Density Functional Theory and time-dependent (TD) DFT calculations were carried out for recently reported 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-based photosensitizers (PSs) that could be activated by reactive oxygen species (ROS) to generate 1 O2 specifically in target tissues. To assess the applicability of the compounds as activatable PSs (a-PSs) in photodynamic therapy, absorption wavelengths; singlet-triplet energy gaps; and spin-orbit matrix elements for the radiationless transition, Sn →Tm , were investigated. A TD-DFT qualitative analysis indicated that only a Br-substituted BODIPY derivative with the chromanol ring of α-tocopherol linked by methylene functioned as an a-PS. The chromanol ring promotes photoinduced electron transfer to the BODIPY unit that reduces the probability of intersystem crossing and triplet-state population, and can turn off 1 O2 photosensitization. Therefore, 1 O2 photosensitization can be switched on only in target cells in which the chromanol ring is oxidized by ROS. The oxidation reaction pathways of the most promising derivative, by either 1 O2 or cumyloxyl radical as typical ROS, have been examined to reveal that oxidation by the cumyloxyl radical is more effective than that by 1 O2 .