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

Abstract

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.