Sydnone Reporters for Highly Fluorogenic Copper-Free Click Ligations

  • J Org Chem. 2018 Feb 16;83(4):2058-2066. doi: 10.1021/acs.joc.7b03004.
Camille Favre  1  2 ,  Lucie de Cremoux  1  2 ,  Jerome Badaut  2  3 ,  Frédéric Friscourt  1  2
Affiliations
  • 1. Institut Européen de Chimie et Biologie, Université de Bordeaux , 2 rue Robert Escarpit, 33607 Pessac, France.
  • 2. Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, CNRS UMR5287 , Bordeaux, France.
  • 3. Basic Science Department, Loma Linda University , Loma Linda, California 92350, United States.
PMID: 29388773 DOI: 10.1021/acs.joc.7b03004
Abstract

Bioorthogonal fluorescent turn-on reactions are attractive for the sensitive real-time detection of a variety of phenomena including bioconjugation, chemical reactivity, and material assembly. Herein we describe the use of 3,4-disubstituted sydnones, a singular class of mesoionic dipoles, for highly fluorescent turn-on copper-free click cycloadditions with the fluorogenic dibenzocyclooctyne Fl-DIBO. Coherent with time-dependent density functional theory calculations, the pyrazole cycloadducts were found to be highly fluorescent with compelling photophysical properties including excellent fluorescence enhancement (up to 240-fold), high quantum yields (over 45%), and large Stokes shift (over 100 nm). Furthermore, the good stability and reactivity of 4-chlorosydnones with Fl-DIBO allowed us to employ them as chemical reporters for the challenging detection of modified-proteins in complex cellular extracts, with exquisite specificity in no-wash conditions. This novel fluorogenic system significantly expands our chemical biology toolbox and should be beneficial in countless applications.

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