Taking Photochromism beyond Visible: Direct One‐Photon NIR Photoswitches Operating in the Biological Window

The success of photopharmacology is inevitably tied to the availability of photoswitches, which can be operated within the biological window (λ=650–1450 nm) to maximize penetration in tissue. A general design strategy has been devised and a dihydropyrene derivative is described here that displays negative T‐type photochromism, allowing for efficient and nearly quantitative (95 %) switching induced by NIR light λ>800 nm. The thermal half‐life of the decolored ring‐open meta‐cyclophanediene isomer ranges from minutes to hours, depending on the solvent polarity and hence serves as a probe of the local environment. Due to the rather subtle geometrical differences between the two isomers, suitably modified NIR photoswitches are potential candidates for switching when bound in the pocket of the biological target, in principle allowing for reversible light‐induced inhibitor deactivation as an alternative approach to externally regulate biological functions.