Singlet Excited State-Dominated Intracellular Unnatural Photocatalytic Reaction

Abstract

Intracellular unnatural photocatalysis has recently emerged as a promising approach for applications including proximity labeling and photobiocatalysis. However, most reported intracellular photocatalytic reactions rely on long-lived triplet excited states, whose sensitization often generates reactive oxygen species (ROS), causing irreversible photodamage and oxidative stress in cells. Herein, we report the use of perylene and its derivatives, which exhibit near-unity fluorescence quantum yields, as photocatalysts for the development of intracellular photocatalytic reactions mediated predominantly by singlet excited states. These compounds efficiently mediate the photoreduction of azides in various media, including organic solvents, cell culture media, and mammalian cells, enabling cascade formation of indole derivatives. Moreover, incorporation of an azide moiety into the perylene scaffold allows light irradiation alone to induce intramolecular azide reduction by the perylene unit, resulting in intramolecular cyclization and formation of a perylene-fused indole structure. Exploiting this transformation, we demonstrate photoactivatable super-resolution fluorescence imaging in living cells. This study establishes a singlet-state-mediated photocatalytic reaction for intracellular unnatural photocatalysis, providing a powerful tool for cellular manipulation with high spatiotemporal precision.