Thiol–Chromene “Click” Reaction Triggered Self-Immolative for NIR Visualization of Thiol Flux in Physiology and Pathology of Living Cells and Mice

Abstract

Understanding the pathological process of biological systems can greatly improve the prevention and treatment of diseases. The study of pathological processes has now reached the molecular level, and molecular fluorescent probes have become a powerful tool. Chromene, also known as benzo-pyran molecule, is a structural element of natural products with good biological compatibility and was developed as a fluorescent probe. The thiol−chromene "click" nucleophilic pyran ring-opening reaction allows the quick detection of thiol. In this work, the chromene alcohol can function as an efficient self-immolative spacer, which covalently links NIR fluorophore via a carbonyl ester. Due to its favorable characteristics and superior applicability, the self-immolative amplifier NIR-HMPC achieves the specific, rapid, sensitive, NIR fluorescent detection of thiols. Furthermore, the indoles iodized salt in the system can specifically target thiols in mitochondria. Thus, this probe was used to visualize the fluctuations of thiols during oxidative stress and cell apoptosis, cerebral ischemia reperfusion, demonstrating that it is valuable for elucidating pathophysiology process in living organism. This discovery provides an effective means for studying the pathological process of thiol related diseases.

Malononitrile as the ‘double-edged sword’ of passivation-activation regulating two ICT to highly sensitive and accurate ratiometric fluorescent detection for hypochlorous acid in biological system

“…To test the application of biological experiments, we first carried out cytotoxicity experiments according to literature methods [ [46] , [47] , [48] , [49] ]. The results showed that the cells survival rate was more than 85 % (CCK-8 method), indicating that the probe AI had the future to be applied into cells (Fig.…”

PiQSARS: A pipeline for quantitative and statistical analyses of ratiometric fluorescent biosensors

“…Since their discovery, fluorescent probes have been engineered to accurately monitor and quantify in real-time an increasing variety of physiological parameters in living cells such as ion concentration variations [1] , cysteines [2] , pH [3] , enzymatic activity [4] or oxidative stress [5] , [6] , [7] , [8] , but also various cellular compounds [9] , [10] , [11] , [12] . Genetically-encoded fluorescent proteins are of particular interest as they can be addressed to specific organelles, such as the nucleus or the mitochondria, allowing a subcellular resolution [13 , 14] .…”

Fluorescent Probes for Live Cell Thiol Detection

“…In 2020, Yutao Yang et al [137] developed a NIR fluorescent probe (NIR-HMPC, Probe 41, Figure 36) based on a Michael addition reaction followed by self-immolative reaction to selectively detect mitochondrial thiols. This NIR probe made by conjugating hemicyanine dye with a benzopylium was connected with a 7-hydroxymethyl-2,3-dihydro-1H-cyclopent-a[b]chromene-1-one with a carbonyl ester.…”