Fluorescent Probe For Hydrogen Sulfide Research Articles

Activity-Based Fluorescent Probes for Hydrogen Sulfide and Related Reactive Sulfur Species.

Hydrogen sulfide (H2S) is not only a well-established toxic gas but also an important small molecule bioregulator in all kingdoms of life. In contemporary biology, H2S is often classified as a "gasotransmitter," meaning that it is an endogenously produced membrane permeable gas that carries out essential cellular processes. Fluorescent probes for H2S and related reactive sulfur species (RSS) detection provide an important cornerstone for investigating the multifaceted roles of these important small molecules in complex biological systems. A now common approach to develop such tools is to develop "activity-based probes" that couple a specific H2S-mediated chemical reaction to a fluorescent output. This Review covers the different types of such probes and also highlights the chemical mechanisms by which each probe type is activated by specific RSS. Common examples include reduction of oxidized nitrogen motifs, disulfide exchange, electrophilic reactions, metal precipitation, and metal coordination. In addition, we also outline complementary activity-based probes for imaging reductant-labile and sulfane sulfur species, including persulfides and polysulfides. For probes highlighted in this Review, we focus on small molecule systems with demonstrated compatibility in cellular systems or related applications. Building from breadth of reported activity-based strategies and application, we also highlight key unmet challenges and future opportunities for advancing activity-based probes for H2S and related RSS.

A Highly Selective Fluorescent Probe for Hydrogen Sulfide and its Application in Living Cell.

A new Near-infrared fluorescent probe for hydrogen sulfide detection was synthesized by employing dicyanoisophorone based fluorescence dye as a fluorophore and methyl 3-(2-(carbonyl)phenyl)-2-cyanoacrylate group as the response unit. The Probe DCI-H2S showed a long emission wavelength (λem = 674nm). Based on the H2S-induced addition-cyclization of deprotecting methyl 3-(2-(carbonyl)phenyl)-2-cyanoacrylate group, the probe DCI-H2S showed high selectivity, sensitivity and response speed toward hydrogen sulfide under room temperature. These numerous advantages of the probe DCI-H2S make it to potentially detect endogenous hydrogen sulfide in living organisms.

Application and Cell Imaging of Turn-On Fluorescent Probe for Hydrogen Sulfide Based on Benzopyran in Food Samples

Application and Cell Imaging of Turn-On Fluorescent Probe for Hydrogen Sulfide Based on Benzopyran in Food Samples

A selective fluorescent probe for hydrogen sulfide from a series of flavone derivatives and intracellular imaging

In this work, through the orthogonal design of two fluorophores and two recognition groups, a series of fluorescent probes were developed from the flavone derivatives for hydrogen sulfide (H2S). The probe FlaN-DN stood out from the primarily screening on the selectivity and response intensities. It could respond to H2S with both the chromogenic and fluorescent signals. Among the recent reported probes for the H2S detection, FlaN-DN indicated the most highlighted advantages including the rapid response (within 200 s) and the high response multiplication (over 100 folds). FlaN-DN was sensitive to the pH condition, thus could be applied to distinguish the cancer micro-environment. Moreover, FlaN-DN suggested practical capabilities including a wide linear range (0–400 μM), a relatively high sensitivity (limit of detection 0.13 μM), and high selectivity towards H2S. As a low cytotoxic probe, FlaN-DN achieved the imaging in living HeLa cells. FlaN-DN could detect the endogenous generation H2S and visualize the dose-dependent responses to the exogenous H2S level. This work provided a typical case of natural-sourced derivatives as functional implements, which might inspire the future investigations.

Dye-embedded NanoMOF as a turn-on fluorescent sensor for selective and sensitive detection of hydrogen sulfide

Developing high-performance fluorescent probes for hydrogen sulfide (H2S) has drawn enormous attention recently. In this paper, we report a stable nanoscale dual-emitting probe RB@UiO-66-NO2 for H2S detection, which was obtained by embedding the red-emitting rhodamine B (RB) in the blue-emitting nitryl-functionalized metal−organic framework (MOF) UiO-66-NO2. The accommodated RB is designed as a reference signal, and the nitro groups on the host skeleton can serve as accessible reactive sites to allow for the selective sensing of H2S by RB@UiO-66-NO2. As a result of H2S's ability to dioxide the nitro group on the ligand and improve the intramolecular charge transfer, RB@UiO-66-NO2 shows enhanced blue fluorescence as well as ratiometric response to H2S. Our investigation shows that RB@UiO-66-NO2 nanoprobe has good stability, fast response (<2 min), distinct color change, and high selectivity and sensitivity (LOD = 5.128 μM) to H2S in the HEPES solution, demonstrating its potential application for H2S detection under various solution conditions.

Synthesis of a Turn-On Fluorescent Probe for Hydrogen Sulfide and Its Application in Red Wine and Living Cells

Synthesis of a Turn-On Fluorescent Probe for Hydrogen Sulfide and Its Application in Red Wine and Living Cells

A new fluorescent probe for hydrogen sulfide based on naphthalimide derivatives and its biological application

• • A novel fluorescent probe SBD for the detection of H 2 S was constructed. • • Probe SBD displayed excellent recognition performance of H 2 S, and its solution color changed from yellow to pink. • • Probe SBD showed good cytocompatibility and could be applied to fluorescence imaging. As a signal transduction molecule in organism, H 2 S plays an important role in many physiological processes. In this paper, a novel H 2 S fluorescent probe SBD was designed based on 1,8-naphthalimide and dinitrobenzenesulfonyl group. In DMSO-PBS solution, probe SBD could recognize H 2 S and change the color of solution from yellow to pink, realizing the naked eye recognition for H 2 S. In addition, probe SBD displayed high fluorescence enhancement rate (45-fold), good selectivity, strong anti-interference ability and the detection limit was as low as 152 nM. Most importantly, probe SBD showed very low cytotoxicity and had been successfully applied to image exogenous H 2 S in living cells.

Near-infrared fluorescent probe for hydrogen sulfide: high-fidelity ferroptosis evaluation in vivo during stroke.

Ferroptosis is closely associated with cancer, neurodegenerative diseases and ischemia-reperfusion injury and the detection of its pathological process is very important for early disease diagnosis. Fluorescence based sensing technologies have become excellent tools due to the real-time detection of cellular physiological or pathological processes. However, to date the detection of ferroptosis using reducing substances as markers has not been achieved since the reducing substances are not only present at extremely low concentrations during ferroptosis but also play a key role in the further development of ferroptosis. Significantly, sensors for reducing substances usually consume reducing substances, instigating a redox imbalance, which further aggravates the progression of ferroptosis. In this work, a H2S triggered and H2S releasing near-infrared fluorescent probe (HL-H2S) was developed for the high-fidelity in situ imaging of ferroptosis. In the imaging process, HL-H2S consumes H2S and releases carbonyl sulfide, which is then catalyzed by carbonic anhydrase to produce H2S. Importantly, this strategy does not intensify ferroptosis since it avoids disruption of the redox homeostasis. Furthermore, using erastin as an inducer for ferroptosis, the observed trends for Fe2+, MDA, and GSH, indicate that the introduction of the HL-H2S probe does not exacerbate ferroptosis. In contrast, ferroptosis progression was significantly promoted when the release of H2S from HL-H2S was inhibited using AZ. These results indicate that the H2S triggered and H2S releasing fluorescent probe did not interfere with the progression of ferroptosis, thus enabling high-fidelity in situ imaging of ferroptosis.

A ratiometric fluorescent probe for hydrogen sulfide in neat aqueous solution and its application in lysosome-targetable cell imaging

Hydrogen sulfide (H2S) has been recently regarded as one of the most important gasotransmitters in the metabolic system, while abnormal H2S concentration is associated with various diseases. Although numerous fluorescent probes have been developed for the detection of cellular H2S, only a few of them can monitor lysosomal H2S with ratiometric fluorescent output. Here, we developed a water-soluble probe 1 toward H2S by introducing 2,4-dinitrophenyl ether into a novel merocyanine-based dye. As expected, H2S induced an obvious red-shift of the probe from 520 nm to 580 nm in neat aqueous solution, and this fluorescent ratiometric response is highly selective and sensitive (with the detection limit of 0.81 nM), rapid (within 10 s), and effective in a wide pH range (2.0–10.0). In particular, the probe was successfully applied for tracing H2S in the lysosomes of living cells and in zebrafish.

Sensing mechanism of a new fluorescent probe for hydrogen sulfide: photoinduced electron transfer and invalidity of excited-state intramolecular proton transfer.

It is of great significance for biological research to develop efficient detection methods of hydrogen sulfide (H2S). When DFAN reacts with H2S, 2,4-dinitrophenyl ether group acting as an electron acceptor generates a hydroxyl-substituted 2,4-dinitrophenyl ether group, resulting in the disappearance of photoinduced electron transfer (PET), and the new formed DFAH can be observed, while being accompanied by a significant fluorescence. In the present study, the PET sensing mechanism of probe DFAN and the excited state intramolecular proton transfer (ESIPT) process of DFAH have been explored in detail based on the density functional theory (DFT) and time-dependent density functional theory (TD-DFT) methods. Our theoretical results show that the fluorescence quenching of DFAN is caused by the PET mechanism, and the result of ESIPT mechanism is not due to the large Stokes shift fluorescence emission of DFAH. We also optimized the geometric structure of the transition state of DFAH. The frontier molecular orbitals and potential barrier show that the ESIPT process does not easy occur easily for DFAH. The enol structure of DFAH is more stable than that of the keto structure. The absence of the PET process resulted in the enol structure emitting strong fluorescence, which is consistent with the single fluorescence in the experiment. Above all, our calculations are sufficient to verify the sensing mechanism of H2S using DFAN.

Recent advances in probe design to detect reactive sulfur species and in the chemical reactions employed for fluorescence switching.

Reactive sulfur species, including hydrogen sulfide, hydropersulfide, and polysulfide, have many roles in biological systems. For example, hydrogen sulfide is involved in the relaxation of vascular smooth muscles and mediation of neurotransmission, while sulfane sulfur, which exists in cysteine persulfide/polysulfide, and glutathione persulfide/polysulfide, is involved in physiological antioxidation and cytoprotection mechanisms. Fluorescence imaging is well suited for real-time monitoring of reactive sulfur species in living cells, and many fluorescent probes for reactive sulfur species have been reported. In such probes, the choice of detection chemistry is extremely important, not only to achieve effective fluorescence switching and high selectivity, but also because the reactions may be applicable to develop other chemical tools, such as reactive sulfur species donors/scavengers. Here, we present an overview of both widely used and recently developed fluorescent probes for reactive sulfur species, focusing especially on the chemical reactions employed in them for fluorescence switching. We also briefly introduce some applications of fluorescent probes for hydrogen sulfide and sulfane sulfur.

A novel quinoline-based colorimetric fluorescent probe for hydrogen sulfide

In this article, a novel fluorescent probe was designed and synthesized based on the quinoline structure for the detection of H2S. After optical evaluation, the probe showed good characteristics, including a fast response, high sensitivity, and good selectivity. More importantly, the probe could be directly observed by the naked eye after responding to H2S and has good application value.

Piperazine appended napthalimide scaffold as turn on fluorescent probe for hydrogen sulfide

The H2S specific fluorescent sensor based on FRET (Forster resonance energy transfer) was designed and synthesized. The probe was synthesized by appending 7-nitro-1, 2,3-benzoxadiazole (NBD) amine to the piperazine coupled napthalimide scaffold. The sulfide induces red color to the probe which was colorless when it is alone. Similarly when illuminate under light the aqueous solution of probe in the presence of sulfide its exhibits strong green fluorescence. The naked eye detectable color as well as fluorescent changes of the probe is highly specific to sulfide no other anions normally present in natural water like fluoride, sulfite and sulfate and biologically relevant species like cysteine, homocysteine and glutathione. The probe exhibits excellent sensitivity towards H2S i.e. linear range of about 1.0–100 µM and LOD of about 0.016 µM. The present sensor system was applied for monitoring H2S in various water samples.

TDDFT study on the photophysical properties of coumarinyl chalcones and sensing mechanism of a derived fluorescent probe for hydrogen sulfide

Coumarin-chalcone hybrids have attracted much attention in recent years due to their important optical properties. Herein, the photophysical properties of a series of coumarinyl chalcones and the sensing mechanism for H2S of a related fluorescent probe CC-DNP were investigated using density functional theory (DFT) and time-dependent density functional theory (TDDFT) methods. The predicted spectral properties agree well with the experimental results, which allowed an assignment of the spectra. Our calculations successfully clarified the experimental observed fluorescence "off-on" effect and the fluorescent quenching mechanism of the probe. The results revealed that the first excited state (S1) of the probe CC-DNP is a dark state with obvious charge transfer from coumarin unit to 2,4-dinitrophenyl (DNP) moiety, which results in the fluorescence quenching via the nonradiative photoinduced electron transfer (PET) process. On the other hand, the excited state S1 in the thiolysis product CC-OH decayed directly to S0, and thus the fluorescence is recovered.

Construction of a novel cell-trappable fluorescent probe for hydrogen sulfide (H2S) and its bio-imaging application.

Fluorescence detection of H2S in living organisms is greatly advantageous because it is nondestructive and can be used for in situ analysis. We have constructed a novel rhodamine analogue dye (Rho630) by extending the conjugated system of rhodamine to create a novel cell-trappable H2S fluorescent probe Rho630-AM-H2S with red light emission. Its application for H2S fluorescence detection in living HeLa cells and zebrafish was investigated. As expected, Rho630-AM-H2S showed a huge fluorescence turn-on response of about 20-fold at 630nm and good selectivity toward H2S in solution. An MTT assay demonstrated that the probe showed negligible cytotoxicity in the concentrations typically used in fluorescence imaging experiments. Cell imaging experiments revealed that compared with compound 4 without cell-trappable unit modification, Rho630-AM-H2S exhibited remarkably enhanced cell penetration ability, as an enormous fluorescence signal increase was observed at the red channel within 5min after Rho630-AM-H2S was incubated with HeLa cells. Finally, the probe Rho630-AM-H2S was used to detect H2S in living HeLa cells and zebrafish with great fluorescence enhancement in the red channel. Graphical abstract.

A highly sensitive fluorescent probe for hydrogen sulfide based on dicyanoisophorone and its imaging in living cells

Due to the importance of hydrogen sulfide (H2S) in physiology and pathology, the development of fluorescence probes for the detection of H2S has attracted extensive attention of researchers. We developed a H2S fluorescence probe (DCN-S) based on dicyanoisopentanone using dithioether and ester groups as the reaction sites. Under the nucleophilic substitution of H2S, disulfide bond of DCN-S was broken. Then the probe changed into dicyanoisophorone derivative and emitted an orange fluorescence band from 530 nm to 700 nm (centred 580 nm). Upon response for H2S, DCN-S exhibited high sensitivity (88 nM detection limit) and large stokes shift (155 nm). Importantly, the probe also was successfully used for endogenous and exogenous imaging of living cells.

Fast response near-infrared fluorescent probe for hydrogen sulfide in natural waters

Rapid and sensitive detection of hydrogen sulfide (H2S) is of great importance for the environmental monitoring. Near-infrared fluorescent probes are recently developed for the sensitive H2S detection thanks to their low background interference, while often hampered by relatively long response time (around 30 min). In this work, we reported a fast response (within 5 min), highly sensitive near-infrared (NIR) fluorescent probe (DCM-OCN) for H2S. The rapid nucleophilic reaction between cyanate moiety and H2S endowed fast response of the NIR probe. The influence of experimental parameters (including CTAB concentration, reaction time, pH value etc.), interference study, and possible mechanism were investigated in detail. The fluorescence increment was linear with H2S concentration in 1–10 μM with a detection limit of 0.28 μM (3σ). The probe was successfully applied to environmental water samples including river water, tap water, lake water, mineral water and artificial wastewater.

Perylenequinone-based "turn on" fluorescent probe for hydrogen sulfide with high sensitivity in living cells.

Hydrogen sulfide (H2S) is a kind of gaseous signal molecule in many physiological processes. In order to detect H2S, a novel "turn on" fluorescent probe 6,12-dihydroxyperylene-1,7-dione (DPD) was designed and synthesized. The probe DPD is fluorescence silence, while the addition of H2S induces an obvious green fluorescence with an obvious color change from dark blue to yellow-green. The probe shows excellent selectivity, fast response (2.5min) and linear curve (0-90μM) in wide effective pH range (4-10). Competition experiments are also revealed in corresponding studies and the detection limit is 3.6μM. The response mechanism is proved to be the reduction of the probe by H2S, which is confirmed by 1H NMR. Furthermore, through the fluorescence turn-on signal toward H2S in Hela cells, probe DPD was successfully applied to monitor H2S in living Hela cells.

A nitroso-based fluorogenic probe for rapid detection of hydrogen sulfide in living cells

A turn-on fluorescent probe for hydrogen sulfide (H2S) employing flavylium derivative as the fluorophore and nitroso group as the recognition unit and was designed and synthesized. The free probe is almost non-fluorescent. Upon addition of H2S to the solution of the probe, its nitroso group was transformed to the corresponding amino group with fast reaction kinetics, affording a dramatic enhancement of fluorescence emission. The fluorescence intensity of the proposed probe at 625 nm showed a good linear with the concentration of NaHS over a range from 0 to 4 μM, with a limit detection of 29 nM (3δ). The proposed probe exhibited high selectivity, excellent sensitivity and rapid response (∼5 min) for H2S. Moreover, this probe was successfully used for fluorescence imaging of exogenous and endogenous H2S in living cells.

Carbon quantum dots-Ag nanoparticle complex as a highly sensitive “turn-on” fluorescent probe for hydrogen sulfide: A DFT/TD-DFT study of electronic transitions and mechanism of sensing

We present an efficient carbon quantum dots (CQDs)-modified silver nanoparticles (AgNPs) (CQDs-AgNPs) as turn-on fluorescence nanoprobe for monitoring hydrogen sulfide (H2S) in brain microdialysate. The fluorescence of the CQDs-AgNPs probe can be selectively and sensitively turned on by H2S due to the formation of AgS bonds between AgNPs and H2S and breaking of the AgN bond between AgNPs and CQDs. Density functional theory (DFT)/time-dependent density functional theory (TD-DFT) investigation were thoroughly conducted on the electronic structures, absorption and emission spectra of CQDs-AgNPs complex as well as the sensing mechanism for hydrogen sulfide. The CQDs-AgNPs fluorescent probe illustrates a wide linear detection range towards H2S from 1 to 1900 nM with the detection limit of ∼0.4 nM. This improved sensitivity, lower limit, along with the high selectivity and fast response toward H2S, makes this CQDs-AgNPs complex successfully monitor H2S basal level in rats without exogenous stimulation, which was calculated to be 3.08 ± 0.10 μM (n = 3). This novel fluorescence probe provides an assay for direct detection of H2S in the cerebral systems and contributes to understand the physiological function and molecular mechanisms of endogenous H2S.