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

Hydrogen peroxide (H 2 O 2 ) is responsible for numerous damages when overproduced, and its detection is crucial for a better understanding of H 2 O 2 -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 H 2 O 2 -activated prodrugs or theranostic tools. However, this design suffers from slow kinetics, preventing activation by H 2 O 2 with a short response time. Therefore, faster H 2 O 2 -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 H 2 O 2 -promoted oxidation. We measured 1.9 × 10 4 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 H 2 O 2 -mediated release of effectors such as fluorescent moieties.