Regulating ¹O₂ generation from heavy-atom-free triplet photosensitizers based on thiophene-fused BODIPY

Triplet photosensitizers (PSs) used in photodynamic therapy (PDT) exhibit a strong relationship between the intersystem crossing (ISC) and generation of singlet oxygen (¹O₂). However, the effective design of PS molecules, particularly, heavy-atom-free PS, remains challenging due to limited understanding of the correlation between ISC rate (k_ISC) and the quantum yield of ¹O₂ generation (Φ_Δ). We present a case study for designing heavy-atom-free PSs (R–SB) via a combination of experimental and theoretical investigations. Electron-donating groups were introduced to the thiophene-fused BODIPY core. The measured Φ_Δ increased as the calculated k_ISC increased. The remarkable agreement between the experimental and theoretical findings improved our understanding of the ISC process in R–SB structures and established a framework for the potential future molecular design of heavy-atom-free PSs based on the BODIPY core. Among the various R–SB structures synthesized, carbazolyl benzene (Cbz) -SB exhibited fluorescence emission and was the most effective for ¹O₂ generation. Cbz-SB was further utilized for mitochondria-targeted fluorescence bioimaging and the PDT of HeLa cells, demonstrating its potential applicability in the respective areas.