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Peroxynitrite (ONOO-) plays crucial roles in a variety of physiological and pathological processes in living systems, and therefore, real-time and in situ imaging of ONOO- is of great significance to in-depth study its biological roles. Herein, we have developed PET-ESIPT-based fluorescent probes (BCN and BCN-A) for the detection of ONOO- in living cells, zebrafishes and brain tissues. BCN was a highly sensitive ONOO- probe in which the fluorescence property of the fluorophore was simultaneously controlled by PET and ESIPT mechanisms, and transformed to BCN-A via acetylation. Especially, BCN showed large Stokes shift in response to ONOO-, and displayed high selectivity to ONOO-. BCN-A employed the acetate group to switch off ESIPT process of the fluorophore and improve the membrane permeability. In living cells, BCN-A released an ONOO--responsive probe (BCN) by the hydrolysis of esterase, and then detected ONOO-. Biological imaging demonstrated that although both metformin and rotenone are mitochondrial complex I inhibitors, metformin can increase the generation of ONOO- while rotenone had no significant influence on the generation of ONOO- in living cells and zebrafishes. Moreover, the amygdala and perirhinal/entorhinal cortex in the brain of depressive mouse both showed increasing fluorescence intensity relative to those of normal mouse, which suggested that the LPS-induced depressive disorder could result in the generation of ONOO- in the two brain areas of mouse. We expect that the probes (BCN and BCN-A) could extensively serve as the powerful molecular tools to investigate the biological roles of ONOO- for the in-depth study of drug mechanism and depressive disorder. [Display omitted] • Using cyanobenzene dicarbonyl unit as response site for ONOO-. • PET-ESIPT-based response mechanism to ONOO-. • Imaging of metformin-induced ONOO- in living cells and zebrafishes. • Detection of ONOO- level changes in brain depressive mice. [ABSTRACT FROM AUTHOR]

Peroxynitrite (ONOO-) plays crucial roles in a variety of physiological and pathological processes in living systems, and therefore, real-time and in situ imaging of ONOO- is of great significance to in-depth study its biological roles. Herein, we have developed PET-ESIPT-based fluorescent probes (BCN and BCN-A) for the detection of ONOO- in living cells, zebrafishes and brain tissues. BCN was a highly sensitive ONOO- probe in which the fluorescence property of the fluorophore was simultaneously controlled by PET and ESIPT mechanisms, and transformed to BCN-A via acetylation. Especially, BCN showed large Stokes shift in response to ONOO-, and displayed high selectivity to ONOO-. BCN-A employed the acetate group to switch off ESIPT process of the fluorophore and improve the membrane permeability. In living cells, BCN-A released an ONOO--responsive probe (BCN) by the hydrolysis of esterase, and then detected ONOO-. Biological imaging demonstrated that although both metformin and rotenone are mitochondrial complex I inhibitors, metformin can increase the generation of ONOO- while rotenone had no significant influence on the generation of ONOO- in living cells and zebrafishes. Moreover, the amygdala and perirhinal/entorhinal cortex in the brain of depressive mouse both showed increasing fluorescence intensity relative to those of normal mouse, which suggested that the LPS-induced depressive disorder could result in the generation of ONOO- in the two brain areas of mouse. We expect that the probes (BCN and BCN-A) could extensively serve as the powerful molecular tools to investigate the biological roles of ONOO- for the in-depth study of drug mechanism and depressive disorder. [Display omitted] • Using cyanobenzene dicarbonyl unit as response site for ONOO-. • PET-ESIPT-based response mechanism to ONOO-. • Imaging of metformin-induced ONOO- in living cells and zebrafishes. • Detection of ONOO- level changes in brain depressive mice. [ABSTRACT FROM AUTHOR]