Sensing and Bioimaging of the Gaseous Signaling Molecule Hydrogen Sulfide by Near-Infrared Fluorescent Probes (original) (raw)
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A ratiometric, near-infrared (NIR), fluorescence and colorimetric probe DNPOCy for hydrogen sulfide (H2S) has been developed. The chemical basis for the operation of the probe is thiolysis of a dinitrophenyl ether, which liberates a cyanine dye chromophore. The probe exhibits a rapid response and high sensitivity to H2S in pure aqueous media, in the near infrared optical widow. DNPOCy is highly selective for H2S over other biologically relevant species including biothiols. This probe can be conveniently used for monitoring H2S without the interference from pH dependent effects of physiological media. The practical utility of probe was demonstrated by its application to the detection of H2S in live cells.
An activatable ratiometric near-infrared fluorescent probe for hydrogen sulfide imaging in vivo
Science China Chemistry, 2020
Ratiometric fluorescent probes hold great promise for in vivo imaging; however, stimuli-activatable ratiometric probes with fluorescence emissions in near-infrared (NIR) region are still very few. Herein, we report a hydrogen sulfide (H 2 S)-activatable ratiometric NIR fluorescent probe (1-SPN) by integrating a H 2 S-responsive NIR fluorescent probe 1 into a H 2 S-inert poly[2,6-(4,4-bis-(2-ethylhexyl)-4H-cyclopenta[2,1-b;3,4-b′]dithiophene)-alt-4,7(2,1,3-benzothiadiazole)] (PCPDTBT)-based NIR semiconducting polymer nanoparticle (SPN). 1-SPN shows "always on" PCPDTBT fluorescence at 830 nm and weak probe 1 fluorescence at 725 nm under excitation at 680 nm. The ratio of NIR fluorescence intensities between 725 and 830 nm (I 725 /I 830) is small. Upon interaction with H 2 S, the fluorescence at 725 nm is rapidly switched on, resulting in a large enhancement of I 725 / I 830 , which is allowed for sensitive visualization and quantification of H 2 S concentrations in living cells. Taking advantage of enhanced tissue penetration depth of NIR fluorescence, 1-SPN is also applied for real-time ratiometric fluorescence imaging of hepatic and tumor H 2 S in living mice. This study demonstrates that activatable ratiometric NIR fluorescent probes hold great potential for in vivo imaging. ratiometric probe, activatable probe, near-infrared fluorescence, molecular imaging, H 2 S
Proceedings of the National Academy of Sciences
Hydrogen sulfide (H2S) is a reactive small molecule generated in the body that can be beneficial or toxic owing to its potent redox activity. In living systems, disentangling the pathways responsible for H2S production and their physiological and pathological consequences remains a challenge in part due to a lack of methods for monitoring changes in endogenous H2S fluxes. The development of fluorescent probes with appropriate selectivity and sensitivity for monitoring production of H2S at biologically relevant signaling levels offers opportunities to explore its roles in a variety of systems. Here we report the design, synthesis, and application of a family of azide-based fluorescent H2S indicators, Sulfidefluor-4, Sulfidefluor-5 acetoxymethyl ester, and Sulfidefluor-7 acetoxymethyl ester, which offer the unique capability to image H2S generated at physiological signaling levels. These probes are optimized for cellular imaging and feature enhanced sensitivity and cellular retention ...
A Fast-Response Red Shifted Fluorescent Probe for Detection of H2S in Living Cells
Molecules
Near-infrared (NIR) fluorescent probes are attractive tools for bioimaging applications because of their low auto-fluorescence interference, minimal damage to living samples, and deep tissue penetration. H2S is a gaseous signaling molecule that is involved in redox homeostasis and numerous biological processes in vivo. To this end, we have developed a new red shifted fluorescent probe 1 to detect physiological H2S in live cells. The probe 1 is based on a rhodamine derivative as the red shifted fluorophore and the thiolysis of 7-nitro 1,2,3-benzoxadiazole (NBD) amine as the H2S receptor. The probe 1 displays fast fluorescent enhancement at 660 nm (about 10-fold turn-ons, k2 = 29.8 M−1s−1) after reacting with H2S in buffer (pH 7.4), and the fluorescence quantum yield of the activated red shifted product can reach 0.29. The probe 1 also exhibits high selectivity and sensitivity towards H2S. Moreover, 1 is cell-membrane-permeable and mitochondria-targeting, and can be used for imaging o...
Hydrogen sulfide (H 2 S) is a reactive small molecule generated in the body that can be beneficial or toxic owing to its potent redox activity. In living systems, disentangling the pathways responsible for H 2 S production and their physiological and pathological consequences remains a challenge in part due to a lack of methods for monitoring changes in endogenous H 2 S fluxes. The development of fluorescent probes with appropriate selectivity and sensitivity for monitoring production of H 2 S at biologically relevant signaling levels offers opportunities to explore its roles in a variety of systems. Here we report the design, synthesis, and application of a family of azide-based fluorescent H 2 S indicators, Sulfidefluor-4, Sulfidefluor-5 acetoxymethyl ester, and Sulfidefluor-7 acetoxymethyl ester, which offer the unique capability to image H 2 S generated at physiological signaling levels. These probes are optimized for cellular imaging and feature enhanced sensitivity and cellular retention compared with our previously reported molecules. In particular, Sulfidefluor-7 acetoxymethyl ester allows for direct, real-time visualization of endogenous H 2 S produced in live human umbilical vein endothelial cells upon stimulation with vascular endothelial growth factor (VEGF). Moreover, we show that H 2 S production is dependent on NADPH oxidase-derived hydrogen peroxide (H 2 O 2 ), which attenuates VEGF receptor 2 phosphorylation and establishes a link for H 2 S/H 2 O 2 crosstalk.
Analytical Chemistry, 2015
Hydrogen sulfide has emerged as an exciting endogenous gasotransmitter in addition to nitric oxide and carbon dioxide. Noninvasive detection methods for hydrogen sulfide thus become indispensable tools for studying its diverse roles in biological systems. Accordingly, fluorescent probes for hydrogen sulfide have received great attention in recent years. A practically useful fluorescent probe for bioimaging of hydrogen sulfide should be selective, sensitive, fast-responsive, biocompatible, observable in the biological optical window, and capable of deep-tissue imaging. These sensing properties, however, are extremely difficult to achieve at the same time. Disclosed here is the two-photon fluorescent probe that meets all of these criteria. The probe belongs to a Michael acceptor system, which raised a serious selectivity issue over the competing biothiols such as cysteine and glutathione. We have addressed the selectivity issue by optimizing the electronic and steric interactions between biothiols and the probe, in addition to achieving very high sensitivity, fast-response, and biocompatibility. Also, the sensing mechanism suggested in the literature was revised. The probe thus enables us to image the endogenously produced hydrogen sulfide with negligible interference from other biothiols in live cells. The excellent sensing properties of the probe combined with its capability of bioimaging thus make it a practically useful tool for further studying biological roles of hydrogen sulfide.
Molecules
Hydrogen sulfide (H2S) is an essential signaling gas within the cell, and its endogenous levels are correlated with various health diseases such as Alzheimer’s disease, diabetes, Down’s syndrome, and cardiovascular disease. Because it plays such diverse biological functions, being able to detect H2S quickly and accurately in vivo is an area of heightened scientific interest. Using probes that fluoresce in the near-infrared (NIR) region is an effective and convenient method of detecting H2S. This approach allows for compounds of high sensitivity and selectivity to be developed while minimizing cytotoxicity. Herein, we report a review on the synthesis, mechanisms, optical properties, and selected biomedical applications of H2S sensors.
The Analyst, 2015
We have developed a novel colorimetric and ratiometric fluorescence probe for the selective and sensitive monitoring of hydrogen sulfide based on a dicyanoisophorone platform. An excellent linear relationship of fluorescence intensity ratio (I637/I558) (R(2) = 0.9867) versus hydrogen sulfide concentration in the range of 1-12 μM was obtained. This probe exhibited a remarkable fluorescence response to hydrogen sulfide over other physiological thiols or biological species, which fluoresces in the red region with a large Stokes shift (172 nm). This probe was successfully utilized to monitor H2S under in vitro physiological conditions and for imaging H2S in living cells and living zebrafish in vivo.
Analytica Chimica Acta, 2019
Gasotransmitter hydrogen sulfide (H 2 S), produced enzymatically in body, has important functions in biological signaling and metabolic processes. An abnormal level of H 2 S expression is associated with different diseases, therefore, development of novel bioanalytical methods for rapid and effective detection of H 2 S in biological conditions is of great importance. In this work, we report the development of a new responsive nanosensor for ratiometric luminescence detection of H 2 S in aqueous solution and live cells. The nanosensor (Ru@FITC-MSN) was prepared by immobilizing a luminescent ruthenium(II) (Ru(II)) complex into a fluorescein isothiocyanate (FITC) conjugated water-dispersible mesoporous silica nanoparticle (MSN), showing dual emission bands at 520 nm (FITC) and 600 nm (Ru complex). The red luminescence of the formed Ru@FITC-MSN was quenched in the presence of Cu 2þ. The in-situ generated RueCu@FITC-MSN responded to H 2 S rapidly and selectively, showing a linear ratiometric luminescence change in FITC and Ru(II) channels with the H 2 S concentration (0.5e4 mM). Limit of detection (LoD) and limit of quantification (LoQ) were determined to be 0.36 and 1.21 mM. Followed by investigation of cellular uptake processes, the utility of the nanosensor for ratiometric imaging of H 2 S in live cells and its capability to monitor H 2 S levels in inflammatory breast cancer cells were then demonstrated. This study provides a powerful approach for detection of highly reactive and unstable H 2 S biomolecules in live systems.