Indolequinone-rhodol conjugate as a fluorescent probe for hypoxic cells: enzymatic activation and fluorescence properties

Abstract

Hypoxia is an important feature of many diseases such as malignant solid tumors, inflammatory diseases and cardiac ischemia. We herein focused on the development of a novel hypoxia-sensitive fluorescent probe, IQ-R, consisting of an indolequinone unit and a rhodol fluorophore. IQ-R has good solubility in water and longer wavelength for absorption and emission, which are favorable for cellular bioimaging. While the fluorescence of rhodol in the IQ-R conjugate was quenched by the function of intramolecular indolequinone unit, it was restored under hypoxic conditions through the enzymatic one-electron reduction of IQ-R by NADPH:cytochrome P450 reductase to release the nonconjugated free rhodol. When administered to A549 cells, IQ-R was activated and reduced by endogenous reductase preferentially under hypoxic conditions, thereby visualizing hypoxic cancer cells by robust fluorescence.

Iridium(III) Anthraquinone Complexes as Two‐Photon Phosphorescence Probes for Mitochondria Imaging and Tracking under Hypoxia

“…To determine the potential of probes for imaging hypoxia in tumor cells, A549 cells were selected because they are known to express reductase . First, to evaluate the potential toxicity of the probes to the cells, a standard 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay was performed under normoxia and hypoxia conditions.…”

New 3‐(Heteroaryl)‐2‐iminocoumarin‐based Borate Complexes: Synthesis, Photophysical Properties, and Rational Functionalization for Biosensing/Biolabeling Applications

“…The photophysicalp roperties of these novel 3-(heteroaryl)-2-iminocoumarin-basedb orate complexes were evaluated in differento rganic solvents (CH 2 Cl 2 ,D MSO,T HF,a nd toluene) and, for those exhibiting significant solubility in water (1,3,6,8, and 9), also in phosphate-buffered saline (PBS, pH 7.5), which mimics physiological conditions. These spectroscopicd ata are gatheredi nT able1,a nd the corresponding electronic absorption, excitation,a nd emission spectra are availablei nt he Supporting Information (see also Figure 1f or illustrative examples).…”

“…In order to consider the use of such "Boricos" as valuable reportersi nbiological and/or bioanalytical applications that involveb iosensing and biolabeling operations, it is essentialt oi mpartt heir fluorescents caf-folds with fluorogenic reactivity (e.g.,t hrough the introduction of ap henol moiety acting as an effective fluorescence switch), water solubility,a nd bioconjugation ability (Scheme 1). This would potentially enablet he development of novel biocompatible fluorogenic dyes with superior performances to those currentlya vailablew ithin the class of "smart" fluorescent phenols [6] (i.e.,7 -hydroxycoumarins, (naphtho)fluoresceins, [7] and rhodols [8] ). To achievet his ambitious goal, we have planned the synthesis of "Borico" derivatives from 3-(heteroaryl)-7-hydroxy-2-iminocoumarin ligandsu sing the two-step method (i.e.,t ransimination ands ubsequent boron complexation) reportedb ys ome of us.…”

“…In addition to these photophysical measurements, the pK a values of the phenolm oieties of three representative "7-hydroxy-Borico" dyes 1, 2,a nd 7 weree valuated as6 . 8,6.0, and 7.9, respectively,b ym onitoring their fluorescencee missions as af unctiono ft he environmental pH (see the Supporting Information). These results suggest that, under physiological conditions, the emissive phenolate forms of "7-hydroxy-Borico" dyes 1 and 2 are predominant, whereas their N-aryl analogues are fully deprotonated only in more basic aqueous media.…”

Ruthenium(II) anthraquinone complexes as two-photon luminescent probes for cycling hypoxia imaging in vivo

“…1). It was reported that NADPH catalyzes the reduction of quinone derivatives under hypoxic condition but not under normoxic condition [36,37]. Then the luminescence intensity rapidly decreased to the initial level after exposure to air (Fig.…”