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

Hydrogen peroxide (HO) is responsible for numerous damages when overproduced, and its detection is crucial for a better understanding of HO-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 HO-activated prodrugs or theranostic tools. However, this design suffers from slow kinetics, preventing activation by HO with a short response time. Therefore, faster HO-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 HO-promoted oxidation. We measured 1.9 × 10 m⋅s as a second-order rate constant, which is 10,000-fold faster than its well-established boronic counterpart (1.8 m⋅s). This improved reactivity was also effective in a cellular context, rendering borinic acids an advantageous trigger for HO-mediated release of effectors such as fluorescent moieties.