Synthesis and Photochemical Properties of Fluorescent Metabolites Generated from Fluorinated Benzoylmenadiones in Living Cells

Nathan Trometer (1) , Bogdan Cichocki (2) , Quentin Chevalier (3) , Jérémy Pécourneau (4) , Jean-Marc Strub (5) , Andréa Hemmerlin (3) , Alexandre Specht (6) , Elisabeth Davioud-Charvet (1) , Mourad Elhabiri (7, 1)

1 LIMA - Laboratoire d'innovation moléculaire et applications
2 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
3 IBMP - Institut de Biologie Moléculaire des Plantes
4 L2CM - Laboratoire Lorrain de Chimie Moléculaire
5 LSMBO - Laboratoire de Spectrométrie de Masse BioOrganique [Strasbourg]
6 CAMB - Conception et application de molécules bioactives
7 ECPM - École Européene de Chimie, Polymères et Matériaux de Strasbourg

This work describes the reactivity and properties of fluorinated derivatives (F-PD and F-PDO) of plasmodione (PD) and its metabolite, the plasmodione oxide (PDO). 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 F-PDO and in the absence of nucleophile, photoreduction generates a highly reactive ortho-quinone methide (o-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, o-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 F-PDO 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 o-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, F-PDO thus acts as a novel (pro)-fluorescent probe for monitoring redox processes and protein alkylation in living cells.

Mots clés: Anthraquinone; ESIPT; Menadione; nucleophile; o-quinone methide; photoactivation

Domaines: Chimie organique

Nathan Trometer, Bogdan Cichocki, Quentin Chevalier, Jérémy Pécourneau, Jean-Marc Strub, et al.. Synthesis and Photochemical Properties of Fluorescent Metabolites Generated from Fluorinated Benzoylmenadiones in Living Cells. Journal of Organic Chemistry, 2023, ⟨10.1021/acs.joc.3c00620⟩. ⟨hal-04157610⟩