Chemical tuning of photoswitchable azobenzenes: a photopharmacological case study using nicotinic transmission

• Lorenzo Sansalone,
• Jun Zhao,
• Matthew T. Richers and
• Graham C. R. Ellis-Davies

Beilstein J. Org. Chem. 2019, 15, 2812–2821, doi:10.3762/bjoc.15.274

• properties of the tetrafluoroazobenzene (4FAB) scaffold. Ultraviolet light switching and rapid thermal relaxation of the metastable cis configuration are the main drawbacks associated with standard AB-based switches. We designed our photoprobes to take advantage of the excellent thermodynamic stability of

• . Keywords: acetylcholine receptors; bidirectional; photoswitchable drug; tetrafluoroazobenzene; visible light; Introduction Starting in 1937, azobenzenes (ABs) have attracted much attention because they undergo a photoreversible chemical transformation of the thermodynamically favored trans configuration

• neurotransmitters. We have synthesized a photoswitchable tetrafluoroazobenzene (4FAB) agonist of nicotinic acetylcholine receptors that is biologically inert at sub-millimolar levels in the cis AB configuration. Photoswitching of the chromophore on neurons with violet light rapidly activates inward currents. We