Two quenching groups are better than one: A robust strategy for constructing HOCl fluorescent probe with minimized background fluorescence and ultra-high sensitivity and its application of HOCl imaging in living cells and tissues

Abstract

We report herein fluorescent probes equipped with dual-quenching groups exhibiting superior sensitivity than probes with mono-quenching groups. Importantly, with this strategy, the probe with dual-quenching groups react with HOCl through two distinct reaction mechanisms, which reduce the plausible side reactions with other competing analytes and enhance the probe’s selectivity. As a proof-of-concept study, we designed and synthesized a probe with dual-quenching groups DQ-HOCl to detect HOCl, which is one of the most important ROS and linked with a number of diseases. In addition, two control probes with mono-quenching groups, MQ-HOCl-1 and MQ-HOCl-2, were also synthesized for comparison purpose. Fluorescent assays demonstrated that DQ-HOCl indeed shows ultra-high sensitivity and selectivity compared with probes with mono-quenching groups. Furthermore, the probe has been successfully utilized to imaging exogenous/endogenous HOCl in living cells. Moreover, DQ-HOCl was applied to visualize HOCl in kidney tissues from rat due to the increased penetration depth and lower tissue autofluorescence from the nature of two-photon probes.

Ke Cheng

PhD

My research interests lie at the surface of chemistry and biology, where I am deeply passionate about applying innovative chemistry to advance fields such as chemoproteomics, drug discovery, nanomedicine, and theranostics. My aim is to provide robust methodologies for mapping biological interactomes, accelerating drug development, and expanding therapeutic opportunities.