A donor-acceptor Stenhouse adduct active in neuronal GABAARs and photoswitchable in water

(PO 8) Donor-acceptor Stenhouse adducts are a rapidly emerging class of photochromic compounds whose conformation can be efficiently switched using visible and nearinfrared light. Over the last year, the switching mechanism of DASA has been extensively studied. However, the use of these compounds in water has been hampered by a spontaneous and irreversible conversion to a non photoactive form. The difficulty of using DASAs in water is even more disappointing since they are native red absorbing photoswitching, quality that is widely appreciated in the field of photopharmacology. This field combines a pharmacological approach with the use of light to enable spatio-temporal control of biological processes and drug action. To date, photopharmacology has been extensively used to manipulate biological activity at the cellular level by targeting ion channels, G protein-coupled receptors, enzymes and protein–protein interactions [1,2]. In order to reduce phototoxicity of light used in photopharmacology, low-energy light (i.e. red light) should be used (less scattering in tissue and deeper penetration in the body) and red-absorbing photodrugs need to be designed. To this end, here, we present the molecular design of a novel γ-aminobutyric acid type A receptors (GABAARs) ligand derivative based on the DASA scaffold that displays photochromic properties with red light and is active in neuronal GABAARs [3]. References 1. Eli, S.; Castagna, R.; Mapelli, M.; Parisini, E. Front. Mol. Biosci. 2022, 9, 841777. 2. Castagna, R.; Kolarski, D.; Cuttoli, R. D.-d.; Maleeva, G. J. Mol. Neurosci. 2022, 72, 1433. 3. Castagna, R.; Maleeva, G.; Pirovano, D.; Matera, C.; Gorostiza, P. chemRxiv 2022. doi:10.26434/ chemrxiv-2022-0ps7t