Fluorescent Probe Based on Azobenzene-Cyclopalladium for the Selective Imaging of Endogenous Carbon Monoxide under Hypoxia Conditions

Abstract

Carbon monoxide (CO), a crucial gas message molecule, plays an important role in the regulation of physiological and pathological process. Hypoxia-induced CO is involved in modulating various cellular activities, including signal transduction, proliferation, and apoptosis. However, tracking CO fluctuation in the hypoxic cells is still a challenge due to lack of straightforward, visualized, and noninvasive tools. In this work, based on metal palladium-catalyzed reaction, we present the rational design, synthesis, and biological utility of an azobenzene-cyclopalladium-based fluorescent probe, ACP-2, for CO monitoring. ACP-2 exhibits capacity of detecting CO in aqueous buffer solution and live cells with high sensitivity and specificity. Utilizing ACP-2, we displayed a direct and visual evidence of endogenous CO up-regulation in live cells induced by hypoxia. Moreover, CO up-regulation during oxygen-glucose deprivation/reperfusion (OGD/R) was also imaged and certified by ACP-2.

A Two‐Photon H2O2‐Activated CO Photoreleaser

“…However, the outburst of excessive amounts of ROS, namely oxidative stress, can induce cell damage, ultimately leading to various human diseases . To date, CO has emerged as a promising therapeutic agent against various disease modes associated with oxidative stress Thus, ROS may act as a potential intracellular trigger for precise CO‐releasing. Hydrogen peroxide (H 2 O 2 ) is regarded as a typical factor responsible for cellular oxidative damage as it is one of the key contributors in the redox signaling modulation .…”

“…It was reported in previous work that two compounds were formed in this photolysis reaction. One of the photolysis products, CO, was certified utilizing CO fluorescent probe ACP‐2, which reported by our lab previously (Supporting Information, Figure S10) . As shown in the Supporting Information, Figure S11, fluorescence enhancement of ACP‐2 after irradiation consolidated the releasing of CO. After that, the solution was analyzed by HRMS.…”

Biological signaling by carbon monoxide and carbon monoxide-releasing molecules

“…Interestingly, in the last two months two additional new probes have been added to the series of fluorescent CO detectors available so far. ACP-2 is an azobenzene-cyclopalladium-based fluorescent probe that is constructed with azobenzene-cyclopalladium as the CO recog-nition part combined with boron-dipyrromethene as the fluorophore (56). The second compound, FL-CO-1, is an allyl chloroformate functionalized fluorescein which signals CO and works in combination with PdCl 2 as a trap for CO (30).…”

Small-molecule fluorescent probes for imaging gaseous signaling molecules: current progress and future implications

“…Tang et al developed two uorescent probes 33a and 33b based on azobenzenecyclopalladium for imaging of endogenous CO under hypoxic conditions (probes 33). 50 Compared with probe 33a, probe 33b displayed more advantages including better sensitivity, faster response time and higher uorescence enhancement. Encouraged by these merits, probe 33b was used to directly visualize the intracellular CO upregulation under hypoxic stress and oxygen-glucose deprivation/reperfusion (OGD/R) conditions for the rst time.…”