The interest in the photochromism and functional applications of donor-acceptor Stenhouse adducts (DASAs) soared in recent years owing to their outstanding advantages and flexible design. However, their low solubility and irreversible conversion in aqueous solutions hampered exploring DASAs for biology and medicine. It is notably unknown whether the barbiturate electron acceptor group retains the pharmacological activity of drugs such as phenobarbital, which targets γ-aminobutyric acid (GABA)-type A receptors (GABAARs) in the brain. Here, we have developed the model compound DASA-barbital based on a scaffold of red-switching second-generation DASAs, and we demonstrate that it is active in GABAARs and alters the neuronal firing rate in a physiological medium at neutral pH. DASA-barbital can also be reversibly photoswitched in acidic aqueous solutions using cyclodextrin, an approved ingredient of drug formulations. These findings clarify the path toward the biological applications of DASAs and to exploit the versatility displayed in polymers and materials science.

Donor–Acceptor Stenhouse Adduct Displaying Reversible Photoswitching in Water and Neuronal Activity / R. Castagna, G. Maleeva, D. Pirovano, C. Matera, P. Gorostiza. - In: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY. - ISSN 0002-7863. - (2022), pp. 1-8. [Epub ahead of print] [10.1021/jacs.2c04920]

Donor–Acceptor Stenhouse Adduct Displaying Reversible Photoswitching in Water and Neuronal Activity

C. Matera
Penultimo
;
2022

Abstract

The interest in the photochromism and functional applications of donor-acceptor Stenhouse adducts (DASAs) soared in recent years owing to their outstanding advantages and flexible design. However, their low solubility and irreversible conversion in aqueous solutions hampered exploring DASAs for biology and medicine. It is notably unknown whether the barbiturate electron acceptor group retains the pharmacological activity of drugs such as phenobarbital, which targets γ-aminobutyric acid (GABA)-type A receptors (GABAARs) in the brain. Here, we have developed the model compound DASA-barbital based on a scaffold of red-switching second-generation DASAs, and we demonstrate that it is active in GABAARs and alters the neuronal firing rate in a physiological medium at neutral pH. DASA-barbital can also be reversibly photoswitched in acidic aqueous solutions using cyclodextrin, an approved ingredient of drug formulations. These findings clarify the path toward the biological applications of DASAs and to exploit the versatility displayed in polymers and materials science.
donor–acceptor stenhouse adduct; DASA; photoswitch; photopharmacology; neuronal activity; neurobiology; optopharmacology; barbiturates; barbital; phenobarbital; photochromism; GABA; GABA receptor
Settore CHIM/08 - Chimica Farmaceutica
Settore BIO/14 - Farmacologia
Settore CHIM/06 - Chimica Organica
17-ago-2022
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/936526
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