Fluorescent Detection of Hypochlorous Acid from Turn‐On to FRET‐Based Ratiometry by a HOCl‐Mediated Cyclization Reaction

Abstract

Hypochlorous acid (HOCl), a reactive oxygen species (ROS), plays a significant biological role in living systems. However, abnormal levels of HOCl are implicated in many inflammation-associated diseases. Therefore, the detection of HOCl is of great importance. In this work, we describe the HOCl-promoted cyclization of rhodamine-thiosemicarbazides to rhodamine-oxadiazoles, which is then exploited as a novel design strategy for the development of a new fluorescence turn-on HOCl probe 2. On the basis of the fluorescence resonance energy transfer (FRET) signaling mechanism, 2 was further converted into 1a and 1b, which represent the first paradigm of FRET-based ratiometric fluorescent HOCl probes. The outstanding features of 1a and 1b include well-resolved emission peaks, high sensitivity, high selectivity, good functionality at physiological pH, rapid response, low cytotoxicity, and good cell-membrane permeability. Furthermore, these excellent attributes enable us to demonstrate, for the first time, the ratiometric imaging of endogenously produced HOCl in living cells by using these novel ratiometric probes. We expect that 1a and 1b will be useful molecular tools for studies of HOCl biology. In addition, the HOCl-promoted cyclization reaction of rhodamine-thiosemicarbazides to rhodamine-oxadiazoles should be widely applicable for the development of different types of fluorescent HOCl probes.

A specific fluorescence probe for hypochlorous acid based on rhodamin101 thiosemicarbazides and its application for living cells imaging

“…Inspired by Lin's work [11] , in this paper, we described a novel HOCl-amplified fluorescent probe based on HOCl-promoted cyclization of rhodamine 101 thiosemicarbazide to rhodamine 101 oxadiazoles reaction mechanism with high selectivity and its application in cell imaging.…”

Using photochemistry to understand and control the production of reactive oxygen species in biological environments

“…7). [62][63][64][65][66][67][68][69][70] In the overall turn on, the probes are made of a donor molecule linked to a suitable acceptor molecule, which does not exhibit fluorescence (Fig. 7a).…”

Hypochlorous Acid - Analytical Methods and Antimicrobial Activity

“…Beside this, a method has also been developed using three water-soluble dihydrofluorescein-ether probes for the detection of HOCl via oxidation; these probes were applied to determine accumulated hypochlorous acid in organelles in a zebra fish model [19]. HOCl has also been detected by a HOCl-promoted cyclization reaction based on fluorescence resonance energy transfer (FRET) signaling mechanism; the authors claimed that their study shed light on the development of new fluorescent HOCl probes [20]. Kim et al [21] developed a boron-dipyrromethene (BODIPY)-based probe for the selective detection of HOCl in living cells.…”