Fluorogenic Strain-Promoted Alkyne-Diazo Cycloadditions

Frédéric Friscourt, Christoph J. Fahrni, Geert Jan Boons*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    Abstract

    Fluorogenic reactions, in which non- or weakly fluorescent reagents produce highly fluorescent products, are attractive for detecting a broad range of compounds in the fields of bioconjugation and material sciences. Herein, we report that a dibenzocyclooctyne derivative modified with a cyclopropenone moiety (Fl-DIBO) can undergo fast strain-promoted cycloaddition reactions under catalyst-free conditions with azides, nitrones, nitrile oxides, as well as mono- and disubstituted diazo-derivatives. Although the reaction with nitrile oxides, nitrones, and disubstituted diazo compounds gave cycloadducts with low quantum yield, monosubstituted diazo reagents produced 1H-pyrazole derivatives that exhibited an approximately 160-fold fluorescence enhancement over Fl-DIBO combined with a greater than 10 000-fold increase in brightness. Concluding from quantum chemical calculations, fluorescence quenching of 3H-pyrazoles, which are formed by reaction with disubstituted diazo-derivatives, is likely due to the presence of energetically low-lying (n,π∗) states. The fluorogenic probe Fl-DIBO was successfully employed for the labeling of diazo-tagged proteins without detectable background signal. Diazo-derivatives are emerging as attractive reporters for the labeling of biomolecules, and the studies presented herein demonstrate that Fl-DIBO can be employed for visualizing such biomolecules without the need for probe washout.

    Original languageEnglish
    Pages (from-to)13996-14001
    Number of pages6
    JournalChemistry - A European Journal
    Volume21
    Issue number40
    DOIs
    Publication statusPublished - 1 Sept 2015

    Keywords

    • bioorthogonal
    • click chemistry
    • cycloaddition
    • cyclooctyne
    • fluorogenic probes

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