Synthesis and Photochemical Properties of Fluorescent Metabolites Generated from Fluorinated Benzoylmenadiones in Living Cells.
Fiche publication
Date publication
juin 2023
Journal
The Journal of organic chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DAVIOUD-CHARVET Elisabeth , Dr SPECHT Alexandre, Dr ELHABIRI Mourad
Tous les auteurs :
Trometer N, Cichocki B, Chevalier Q, Pécourneau J, Strub JM, Hemmerlin A, Specht A, Davioud-Charvet E, Elhabiri M
Lien Pubmed
Résumé
This work describes the reactivity and properties of fluorinated derivatives ( and ) of plasmodione () and its metabolite, the plasmodione oxide (). Introduction of a fluorine atom on the 2-methyl group markedly alters the redox properties of the 1,4-naphthoquinone electrophore, making the compound highly oxidizing and particularly photoreactive. A fruitful set of analytical methods (electrochemistry, absorption and emission spectrophotometry, and HRMS-ESI) have been used to highlight the products resulting from UV photoirradiation in the absence or presence of selected nucleophiles. With and in the absence of nucleophile, photoreduction generates a highly reactive -quinone methide (-QM) capable of leading to the formation of a homodimer. In the presence of thiol nucleophiles such as β-mercaptoethanol, which was used as a model, -QMs are continuously regenerated in sequential photoredox reactions generating mono- or disulfanylation products as well as various unreported sulfanyl products. Besides, these photoreduced adducts derived from are characterized by a bright yellowish emission due to an excited-state intramolecular proton transfer (ESIPT) process between the dihydronapthoquinone and benzoyl units. In order to evidence the possibility of an intramolecular coupling of the -QM intermediate, a synthetic route to the corresponding anthrones is described. Tautomerization of the targeted anthrones occurs and affords highly fluorescent stable hydroxyl-anthraquinones. Although probable to explain the intense visible fluorescence emission also observed in tobacco BY-2 cells used as a cellular model, these coupling products have never been observed during the photochemical reactions performed in this study. Our data suggest that the observed ESIPT-induced fluorescence most likely corresponds to the generation of alkylated products through reduction species, as demonstrated with the β-mercaptoethanol model. In conclusion, thus acts as a novel (pro)-fluorescent probe for monitoring redox processes and protein alkylation in living cells.
Référence
J Org Chem. 2023 06 2;: