Evaluation of borinic acids as new, fast hydrogen peroxide–responsive triggers

• Published in: Proceedings of the National Academy of Sciences - PNAS 2021-12, Vol.118 (50), p.1-7
• Main Authors: Gatin-Fraudet, Blaise, Ottenwelter, Roxane, Le Saux, Thomas, Norsikian, Stéphanie, Pucher, Mathilde, Lombès, Thomas, Baron, Aurélie, Durand, Philippe, Doisneau, Gilles, Bourdreux, Yann, Iorga, Bogdan I., Erard, Marie, Jullien, Ludovic, Guianvarc’h, Dominique, Urban, Dominique, Vauzeilles, Boris
• Format: Article
• Language: English
• Subjects: Chemical Sciences; Coumarin; Fluorescent indicators; Hydrogen peroxide; Other; Oxidation; Physical Sciences; Response time
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2107503118

Hydrogen peroxide (H₂O₂) is responsible for numerous damages when overproduced, and its detection is crucial for a better understanding of H₂O₂-mediated signaling in physiological and pathological processes. For this purpose, various “off–on” small fluorescent probes relying on a boronate trigger have been prepared, and this design has also been involved in the development of H₂O₂-activated prodrugs or theranostic tools. However, this design suffers from slow kinetics, preventing activation by H₂O₂ with a short response time. Therefore, faster H₂O₂-reactive groups are awaited. To address this issue, we have successfully developed and characterized a prototypic borinic-based fluorescent probe containing a coumarin scaffold. We determined its in vitro kinetic constants toward H₂O₂-promoted oxidation. We measured 1.9 × 10⁴ M−1 s−1 as a second-order rate constant, which is 10,000-fold faster than its well-established boronic counterpart (1.8 M−1 s−1). This improved reactivity was also effective in a cellular context, rendering borinic acids an advantageous trigger for H₂O₂-mediated release of effectors such as fluorescent moieties.