A novel α-ketoamide reactivity-based two-photon fluorogenic probe for visualizing peroxynitrite in Parkinson’s disease models

Peroxynitrite (ONOO[Formula: see text] contributes to oxidative stress and neurodegeneration in Parkinson’s disease (PD). Developing a peroxynitrite probe would enable in situ visualization of the overwhelming ONOO − flux and understanding of the ONOO − stress-induced neuropathology of PD. Herein, a novel [Formula: see text]-ketoamide-based fluorogenic probe ( DFlu) was designed for ONOO − monitoring in multiple PD models. The results demonstrated that DFlu exhibits a fluorescence turn-on response to ONOO − with high specificity and sensitivity. The efficacy of DFlu for intracellular ONOO − imaging was demonstrated systematically. The results showed that DFlu can successfully visualize endogenous and exogenous ONOO − in cells derived from chemical and biochemical routes. More importantly, the two-photon excitation ability of DFlu has been well demonstrated by monitoring exogenous/endogenous ONOO − production and scavenging in live zebrafish PD models. This work provides a reliable and promising [Formula: see text]-ketoamide-based optical tool for identifying variations of ONOO − in PD models.