Optical Control of Invertebrate nAChR and Behaviors with Dithienylethene-Imidacloprid

Photopharmacology involving azobenzene or dithienylethene has changed established methods of studying receptor functions, allowing for increasing the spatiotemporal resolution. There are no photopharmacological tools available for the invertebrate nicotinic acetylcholine receptor (nAChR). Here, we report a photochromic ligand, dithienylethene-imidacloprid (DitIMI), using a dithienylethene photoswitch embedded in the nAChR agonist imidacloprid. It was found that DitIMI displayed good photochromism and fluorescence switching behaviors upon irradiation with UV/vis light in aqueous solution. We demonstrated that open-DitIMI has low spontaneous in vitro and in vivo activity but can be photoisomerized to a highly active closed-form. Surprisingly, the photoswitchable DitIMI showed a large difference in insecticidal activity between the open and closed forms, in which the insecticidal activity against Aphis craccivora of the ring-closed isomers for DitIMI was 355 times that of the corresponding ring-open isomers. This photoisomerization can further be translated to photomodulation of neuron membrane potential and behavioral responses of living mosquito larvae and American cockroaches. The photomanipulation of nACh neurotransmission opens new avenues to understanding inhibitory circuits in intact animals.