Fluorescein‐Containing Superoxide Probes with a Modular Copper‐Based Trigger

Abstract

Fluorescein‐derived superoxide probes featuring a copper(II) complex that can be activated by superoxide to initiate ether bond cleavage and uncage a fluorescein reporter for imaging in live cells are described. Compared to other superoxide sensing moieties, this bond cleavage strategy can be modularly adapted to fluorescent reporters with different properties without compromising the superoxide reactivity and selectivity. A green‐emitting probe and its lysosome‐targeting analogue have been successfully developed. Both probes are sensitive with more than 30‐fold fluorescence enhancement towards superoxide and are highly selective with no significant response towards other reactive oxygen species. A structure–activity relationship study of the copper‐based superoxide trigger showed that the secondary coordination environment of the copper(II) center is important for the superoxide reactivity and selectivity. The probes have been applied in imaging changes in intracellular superoxide level in live HeLa and HEK293T cells upon menadione stimulation and also in a cellular inflammation model in RAW 264.7 cells.

Probe and dye design through copper-mediated reactions of N-arylhydroxylamines

“…6 The detection is based on coordination assisted ether bond cleavage, and similar reactions have been extensively applied in copper ion probe design in recent years. 2 a ,7 For example, most recently, Yi Liu et al proposed a TPA modified near infrared (NIR) dye that enables in vivo sensing of Cu + . 7 a Some types of urea bonds are breakable under catalysis by copper ions.…”

Intraperitoneal Injection of Cyanine-Based Nanomicelles for Enhanced Near-Infrared Fluorescence Imaging and Surgical Navigation in Abdominal Tumors

“…New types of fluorescent dyes, including cyanine, − squaraine, ,− coumarin, − rhodamine, − and fluorescein, − have recently attracted extensive attention and continue to be developed, presenting new opportunities and challenges for fluorescence-guided surgery. Among these dyes, cyanine dyes are considered as one of the most efficient NIR fluorophores due to their higher molar/mass extinction coefficient and higher fluorescence quantum yield.…”

Superoxide targeted “turn-on” fluorescence sensing enabled by a diselenide based quinoline probe and its in vitro anticancer activity in cancer cells

“…24,25 As we know, many fluorophore derivatives such as BODIPY, fluorescein, dibenzothiazoline and cyclohexene have been synthesized for detection of superoxide ions; however, there is only one report on quinoline based derivatives. [26][27][28][29][30] Also, there are many reports on organoselenium containing fluorescent probes for the detection of superoxide and their utility for live cell imaging. 31 The comparative study of selenium containing superoxide sensing probes is given in Table 1.…”