From Porphyrins to Versatile Photostable Bacteriochlorins: Triplet-State-Driven Design of Perfluorinated Photosensitizers.

Perfluorinated tetrapyrrolic photosensitizers offer a promising platform for photodynamic therapy, yet establishing clear relationships between molecular structure, excited-state behavior, and therapeutic efficacy remains a major challenge. We report a systematic study of porphyrin and bacteriochlorin derivatives designed to elucidate how structural modifications govern photophysical properties and biological performance. Comprehensive spectroscopic analyses, including measurements of triplet-state lifetimes in both solution and micellar formulations, revealed that metalation and macrocycle reduction critically modulate excited-state deactivation pathways and intersystem crossing efficiencies. These effects translate directly into differences in the photodynamic activity. The lead bacteriochlorin exhibits high photostability and prolonged intratumoral retention, together with a pronounced shift toward type I photochemistry, enabling efficient photodynamic activity under hypoxic conditions and resulting in sustained tumor control in long-term in vivo studies. This work identifies triplet-state dynamics as a key design parameter linking molecular architecture to biological response and provides a rational basis for the development of next-generation photosensitizers.