Divergent Synthesis of Ultrabright and Dendritic Xanthenes for Enhanced Click-Chemistry-Based Bioimaging

Montiel, Luis; Spada, Fabio; Crisp, Antony; Serdjukow, Sascha; Carell, Thomas und Frischmuth, Thomas (2022): Divergent Synthesis of Ultrabright and Dendritic Xanthenes for Enhanced Click-Chemistry-Based Bioimaging. In: Chemistry - A European Journal, Bd. 29, Nr. 5, e202202633

Abstract

Biorthogonal labelling with fluorescent small molecules is an indispensable tool for diagnostic and biomedical applications. In dye-based 5-ethynyl-2 '-deoxyuridine (EdU) cell proliferation assays, augmentation of the fluorescent signal entails an overall enhancement in the sensitivity and quality of the method. To this end, a rapid, divergent synthetic procedure that provides ready-to-click pH-insensitive rhodamine dyes exhibiting outstanding brightness was established. Compared to the shortest available synthesis of related high quantum-yielding rhodamines, two fewer synthetic steps are required. In a head-to-head imaging comparison involving copper(I)-catalyzed azide alkyne cycloaddition reactions with in vitro administered EdU, our new 3,3-difluoroazetidine rhodamine azide outperformed the popular 5-TAMRA-azide, making it among the best available choices when it comes to fluorescent imaging of DNA. In a further exploration of the fluorescence properties of these dyes, a set of bis-MPA dendrons carrying multiple fluorescein or rhodamine units was prepared by branching click chemistry. Fluorescence self-quenching of fluorescein- and rhodamine-functionalized dendrons limited the suitability of the dyes as labels in EdU-based experiments but provided new insights into these effects.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Chemie und Pharmazie > Department für Pharmazie - Zentrum für Pharmaforschung
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie
• ISSN: 0947-6539
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 201269156