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Conditional Singlet Oxygen Generation through a Bioorthogonal DNA‐targeted Tetrazine Reaction
Author(s) -
Linden Greta,
Zhang Lei,
Pieck Fabian,
Linne Uwe,
Kosenkov Dmitri,
Tonner Ralf,
Vázquez Olalla
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201907093
Subject(s) - bioorthogonal chemistry , singlet oxygen , tetrazine , photosensitizer , photodynamic therapy , chemistry , combinatorial chemistry , intracellular , bodipy , photochemistry , biophysics , biochemistry , oxygen , fluorescence , click chemistry , biology , physics , organic chemistry , quantum mechanics
We report the use of bioorthogonal reactions as an original strategy in photodynamic therapy to achieve conditional phototoxicity and specific subcellular localization simultaneously. Our novel halogenated BODIPY‐tetrazine probes only become efficient photosensitizers (Φ Δ ≈0.50) through an intracellular inverse‐electron‐demand Diels–Alder reaction with a suitable dienophile. Ab initio computations reveal an activation‐dependent change in decay channels that controls 1 O 2 generation. Our bioorthogonal approach also enables spatial control. As a proof‐of‐concept, we demonstrate the feasibility of the selective activation of our dormant photosensitizer in cellular nuclei, causing cancer cell death upon irradiation. Thus, our dual biorthogonal, activatable photosensitizers open new venues to combat current limitations of photodynamic therapy.