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 1O2 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 1O2 photosensitization. Therefore, 1O2 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 1O2 or cumyloxyl radical as typical ROS, have been examined to reveal that oxidation by the cumyloxyl radical is more effective than that by 1O2.

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

Pirillo J.;Mazzone G.;Russo N.
2018

Abstract

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 1O2 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 1O2 photosensitization. Therefore, 1O2 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 1O2 or cumyloxyl radical as typical ROS, have been examined to reveal that oxidation by the cumyloxyl radical is more effective than that by 1O2.
density functional calculations; oxidation; photochemistry; reaction mechanisms; sensitizers
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11770/298873
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