Azobenzene-diamides as Photopharmacological Ligands for Insect Ryanodine Receptor.

Photoresponsive ligands are powerful tool compounds for studying receptor function with spatiotemporal resolution. However, to the best of our knowledge, such a ligand is not available for the ryanodine receptor (RyR). Herein, we present a photochromic ligand (PCL) for insect RyR by decorating chlorantraniliprole (CHL) with photoswitchable azobenzene (AB). We demonstrated that one potent ligand, named ABCHL13, shows light-induced reversible trans-cis isomerization and 3.5-fold insecticidal activity decrease toward oriental armyworm ( Mythimna separata ) after UV-light irradiation, that is, trans -ABCH13 has higher activity than the cis -ABCH13. ABCHL13 enables optical control over intracellular Ca ²⁺ release in dorsal unpaired median (DUM) neurons of M. separata and American cockroach ( Periplaneta americana ) and cardiac function of P. americana . Our results provide a first photopharmacological toolkit that is applicable to light-dependent regulation of RyR and heart beating.