Fig. 1
From: Rationally designed azobenzene photoswitches for efficient two-photon neuronal excitation

Strategy toward optimized azobenzene photoswitches for the two-photon (2P) excitation of light-gated glutamate receptors (LiGluR). a Operating mode of MAG-type photoswitchable tethered ligands (PTLs) on LiGluR, which are composed of three covalently tethered units: a glutamate ligand, an azobenzene core, and a maleimide group that binds to a cysteine residue genetically engineered in the receptor. Ultraviolet-visible (one-photon; 1P) or near-infrared (2P) light excitation induces glutamate recognition and channel opening via trans → cis isomerization, which results in ion flow across the membrane. This process is reverted by illumination with visible light excitation (1P) or thermal back-isomerization of the cis state of the switch. b Structures of the azobenzene cores of MAG, MAG0, MAG2P, and MAG460 PTLs proposed for the photoswitching of LiGluR under 1P and 2P excitation conditions. c Structures of PTLs \({\bf{MAG}}_{{\bf{2P}}}^{{\bf{slow}}}\) and \({\bf{MAG}}_{{\bf{2P}}_ - {\bf{F}}}^{{\bf{slow}}}\)