Double Thionation of 4‐Dimethylaminophthalimide Leads to the Development of a Highly Effective Photosensitizer

Transforming existing biocompatible fluorophores through thionation presents a compelling strategy to modulate their photodynamic properties while circumventing the limitations associated with heavy atoms, such as metals or halogens. This approach integrates sulfur atoms that enhance intersystem crossing (ISC) to the triplet state via spin-orbit coupling, positioning these photosensitizers as suitable candidates for photodynamic therapy applications. In this study, we investigate the photophysical properties and excited-state dynamics of 4-dimethylaminophthalimide (DMAP) and its thionated derivative, thio-4-dimethylaminophthalimide (SDMAP). DMAP exhibits a fluorescence quantum yield of 17%, demonstrating significant fluorescence emissions. In contrast, SDMAP shows negligible fluorescence due to enhanced ISC within 1.0 ± 0.2 ps, which facilitates the rapid triplet state population, with a lifetime of 3.40 ± 0.05 µs under argon-saturated conditions. Notably, the triplet state of SDMAP generates singlet oxygen with a quantum yield of 0.83 ± 0.05, highlighting its high potential for photodynamic therapy. In comparison, DMAP does not produce singlet oxygen and undergoes radiative and nonradiative decay to the ground state within 5 ± 1 ns. These findings underscore the profound impact of thionation, effectively converting DMAP from a relatively fluorescent molecule into a highly efficient photosensitizer for photocatalysis and deep-tissue photodynamic therapy applications.