Pro-luciferin probes containing (2-diphenylphosphino)benzoate and 2-thiolo-2-methylpropionate moieties: Synthesis, characterization, and reactivity toward nitroxyl. (February 2023)

• Record Type: Journal Article
• Authors: Szala, Marcin; Modrzejewska, Julia; Grzelakowska, Aleksandra; Kolińska, Jolanta; Michalski, Radosław; Artelska, Angelika; Sikora, Adam; Podsiadły, Radosław
• Is Part Of: Dyes and pigments. Volume 210(2023)
• Publication Date: 2023-02
• Subjects: Fluorogenic probes -- Luciferin derivatives -- Nitroxyl -- Hypochlorous acid -- Reactive oxygen and nitrogen species; Dyes and dyeing -- Periodicals; Pigments -- Periodicals; 667.2
• DOI: 10.1016/j.dyepig.2022.110996
• Languages: English
• ISSNs: 0143-7208

Abstract

Abstract: Multiple studies have shown that the generation of the reactive oxygen and nitrogen species (RONS) can promote a tumor formation via a redox-signaling mechanism. RONS in vivo are usually detected by fluorogenic probes. In this study, we report synthesis of four new firefly luciferin-based probes with two different reactive groups for nitroxyl recognition, either (2-diphenylphosphino)benzoate or 2-thiolo-2-methylpropionate moiety. We have also compared the reactivity and selectivity of these probes relative to nitroxyl, hypochlorous acid and another analytes. All studied probes "turn on" fluorescence in the reaction with nitroxyl due to release of the methyl ester of luciferin, that can be used for the bioluminescence imaging of nitroxyl in luciferase-transfected cells. In the reaction with hypochlorous acid, stable nonfluorescent products are formed. The use of various analytical techniques allowed the determination of the stoichiometry of the reaction between the probes and nitroxyl, and confirmed the structures of the resulting products. Graphical abstract: Image 1 Highlights: Firefly luciferin-based probe for detection of nitroxyl. 2-(Diphenylphosphino)benzoic acid (DPPB) and 2-mercapto-2-methylpropionic acid (DMMP) were used as HNO-selective group. HNO reacts with the 2-mercapto-2-methylpropionic acid moiety stoichiometrically and turns on emission. The probes show high sensitivity and remarkable fluorescent turn on enhancement. Reactivity of HNO toward thiols is the main limitation of the synthesized probes.