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 (kISC) and the quantum yield of 1O2 generation (& phi;& UDelta;). We present a case study for designing heavy-atomfree PSs (R-SB) via a combination of experimental and theoretical investigations. Electron-donating groups were introduced to the thiophene-fused BODIPY core. The measured & phi;& UDelta; increased as the calculated kISC 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-atomfree 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.