Highly Sensitive Near-Infrared Imaging of Peroxynitrite Fluxes in Inflammation Progress

Abstract

Inflammation is an important protection reaction in living organisms associated with many diseases. Since peroxynitrite (ONOO − ) is engaged in the inflammatory processes, illustrating the key nexus between ONOO − and inflammation is significant. Due to the lack of sensitive ONOO − in vivo detection methods, the research still remains at its infancy. Herein, a highly sensitive NIR fluorescence probe DDAO-PN for in vivo detection of ONOO − in inflammation progress was reported. The probe responded to ONOO − with significant NIR fluorescence enhancement at 657 nm (84-fold) within 30 s in solution. Intracellular imaging of exogenous ONOO − with the probe demonstrated a 68-fold fluorescence increase (F/F 0 ). Impressively, the probe can in vivo detect ONOO − fluxes in LPS-induced rear leg inflammation with a 4.0-fold fluorescence increase and LPS-induced peritonitis with an 8.0-fold fluorescence increase The remarkable fluorescence enhancement and quick response enabled real-time tracking of in vivo ONOO − with a large signal-to-noise (S/N) ratio. These results clearly denoted that DDAO-PN was able to be a NIR fluorescence probe for in vivo detection and high-fidelity imaging of ONOO − with high sensitivity and will boost the research of inflammation-related diseases.

Piperazine-Based Mitochondria-Immobilized pH Fluorescent Probe for Imaging Endogenous ONOO– and Real-Time Tracking of Mitophagy

“…(1.229 g, 85%). 1 Preparation of PMR. A mixture of compound 1 (1.2 g, 2.98 mmol), p-xylylene dichloride (5.15 g, 29.3 mmol), and K 2 CO 3 (0.2 g, 1.45 mmol) in 150 mL of CH 3 CN was refluxed and stirred for 12 h. After cooling the solution to room temperature and concentrating the obtained crude product in a vacuum drying oven to remove the solvent, the obtaining solid was purified by silica gel chromatography with the eluent dichloromethane and methanol (10:1, v/v) to afford solid PMR (0.414 g, 23%).…”

“…A mixture of compound 1 (1.2 g, 2.98 mmol), p-xylylene dichloride (5.15 g, 29.3 mmol), and K 2 CO 3 (0.2 g, 1.45 mmol) in 150 mL of CH 3 CN was refluxed and stirred for 12 h. After cooling the solution to room temperature and concentrating the obtained crude product in a vacuum drying oven to remove the solvent, the obtaining solid was purified by silica gel chromatography with the eluent dichloromethane and methanol (10:1, v/v) to afford solid PMR (0.414 g, 23%). 1 H NMR (600 MHz, DMSO) δ 8.89 (s, 1H), 8.37 (d, J = 7.7 Hz, 2H), 8.17 knowledge, there are only two reports for detecting ONOO − and mitophagy, 33,43 one of which, the viscosity-based fluorescent probe from our research group, is used to simultaneously detect ONOO − and mitophagy, but which relies only on electrostatic attraction and is easily leaked from mitochondria in the process of mitophagy. Therefore, we are committed to the development of mitochondrial-immobilized fluorescent probes with a chloride group for the simultaneous detection of ONOO − and mitophagy.…”

“…ONOO – has attracted extensive attention as an endogenously produced oxidant and contributor to a number of physiological and pathological processes . The particular structure of ONOO – imbues it with a strong oxidizing potential and the overproduction of ONOO – in living cells has been shown to be deleterious and can damage many important biomolecules, such as proteins, DNA, and lipids. − However, the nanomolar concentration and the short half-life of ONOO – has prevented the study of it under physiological condition .…”

Highly sensitive benzothiazole-based chemosensors for detection and bioimaging of peroxynitrite in living cells

“…1a and S14a †), which were due to the ONOO − -promoted deprotection of diphenyl phosphonate group and hydrolysis of benzeneboronic ester. 43,47 Meanwhile, relative uorescent quantum yield(F F ) of BS1 and BS2 varied from 0.05% to 48.9% and from 0.03% to 42.7%, respectively, where the ethanolic solution of anthracene (F F ¼ 27%) was used as a ref. 51.…”

“…[28][29][30][31][32] Recently, much efforts have been devoted to exploiting and designing novel uorescent ONOO − probes with excellent selectivity and sensitivity. From the recent reviews of uorescent chemosensors for ONOO − detection, it could be concluded that these uorescent ONOO − probes were developed based on the strong oxidation, nitration, and nucleophilicity of ONOO − , which usually incorporate some particular reactive moieties into different chromophores, such as alkene, 33,34 N-aminophenol, 35,36 active ketone, [37][38][39] arylboronic esters, [40][41][42][43] organoselenium/organotellurium 44,45 and diphenyl phosphonate unit. 46,47 Taking advantage of these reactive sites, the probes would release their masked uorescence upon attacked by ONOO − , which makes them promising biosensors for ONOO − detection and imaging.…”