A Sensitive and Selective Fluorescent Probe for Cysteine Based on a New Response‐Assisted Electrostatic Attraction Strategy: The Role of Spatial Charge Configuration

Abstract

A new strategy for fast fluorescent detection of cysteine (Cys), based on a response-assisted electrostatic attraction, is demonstrated. By utilizing this strategy, we designed and synthesized three fluorescent probes for the specific detection of Cys under actual physiological conditions. The probe m-CP, a coumarin fluorophore conjugated with a substituted methyl pyridinium group through an unsaturated ketone unit, showed highly selective and sensitive detection for cysteine (Cys) over homocysteine (Hcy) and glutathione (GSH). The kinetic analysis indicated that the sensing process was highly accelerated (a response time less than 1 min) by the response-assisted electrostatic attraction. More importantly, control experiments with isomeric probes first demonstrated that the spatial charge configuration of the probe played an important role in Cys-preferred selectivity and kinetic rate acceleration. Furthermore, the practical utility of the probe m-CP in the fluorescent labeling of Cys residues within proteins was demonstrated. Finally, these probes were employed in living cell imaging with HeLa cells, in which it displayed satisfactory cell permeability and enabled us to distinguish active thiols in the cytoplasm, nucleus, and mitochondria.

Design strategies of fluorescent probes for selective detection among biothiols

“…The isomers of 58, 58 0 were synthesized for evaluating the spatial influence of electrostatic interactions. 94 Cys adducts of 58 0 underwent rapid cyclization to a non-fluorescent thiazepine derivative, presumably due to the destabilization of the zwitterionic form. The results indicated that the proper spatial electrostatic interaction played a significant role in the selectivity and kinetics during the sensing process.…”

Visual Discrimination of Homocysteine from Cysteine through Selective Fluorescent Gel Formation

“…The majority of studies that sought to detect Hcy and Cys have failed in distinguishing these molecules because of their similar spatial arrangement and chemical reactivity . Recently, several studies detected Cys by using chemodosimetric probes through Michael‐type reaction . In contrast to Cys, a few methods enabled the selective discrimination of Hcy.…”

A highly selective and sensitive ON–OFF–ON fluorescence chemosensor for cysteine detection in endoplasmic reticulum

“…As a well-known thiol-containing amino acid in this family, Cys serves as the building block in protein synthesis, detoxification, and metabolism in live organisms Chen et al, 2013;Chen et al 2013;Li et al, 2009;Das et al, 2012). Alterations in the level of cellular Cys has been implicated with neurotoxicity, and the deficiency of Cys may lead to many syndromes, such as a hematopoiesis decrease, slow growth, hair depigmentation, leucocyte loss, psoriasis and so on (Shiu et al, 2011;Yin et al, 2013;Shao et al, 2011;Zhou et al, 2013;Wang et al, 2014).…”