A Novel Adamantane-Dioxetane-Based Chemiluminescent Probe for Highly Selective and Sensitive Bioimaging of Hydrogen Peroxide In Vitro and In Vivo

Abstract

Hydrogen peroxide (H₂O₂) is an important intracellular reactive oxygen species that participates in a variety of life activities as a second messenger, especially as a pro-inflammation marker. Chemiluminescence is currently an ideal chemical tool for detecting biological substances, with the advantages of excellent signal-to-noise ratio and free autofluorescence interference, which is a cutting-edge science and technology for life sciences research. Herein, we report the design and evaluation of a novel chemiluminescent probe embedding a pentafluorobenzenesulfonyl ester group as a recognition moiety in a dioxetane skeleton. The results of imaging in living cells indicate that probe 4 (in 5 proposed probes) possesses high sensitivity, good selectivity, and the lowest limit of detection toward exogenous and endogenous H₂O₂ (LOD = 0.511 nM) compared with all the reported probes. It especially demonstrates excellent recognition performance in distinguishing between ONOO^– and H₂O₂. Additionally, probe 4 shows low cytotoxicity and good biocompatibility, which performs highly specific and accurate imaging in the acute colitis mouse model. Taken together, this work reports a chemiluminescent probe for real-time monitoring of H₂O₂ dynamics in vitro and in vivo, which presents a reliable chemical tool for biosensing and disease diagnosis.