SO2 Derivatives Research Articles

A synergetic FRET/ICT platform-based fluorescence probe for ratiometric imaging of bisulfite in lipid droplets

A deep-red emission and lipid droplets-targeted fluorescence probe (named ZFPy) for effective bioimaging of bisulfite was developed from flavone moiety and benzoindole derivative based on intramolecular charge transfer (ICT) and Förster resonance energy transfer (FRET) platform. ZFPy displayed promising fluorescence parameters including bright deep red fluorescence (615 nm), large Stokes shift (205 nm), extended emission window gap (140 nm), high absolute fluorescence quantum yield (4.1%) and stable emission signal output. In addition, ZFPy realized ratiometric fluorescence monitoring for SO2 derivatives with low detection limit (30 nM), preferable linearity, high sensitivity and selectivity. Interestingly, dual fluorophores (i.e. the donor moiety and 1,1,2,3-tetra-substituent-1H-benzo[e]indol-3-ium iodide moiety) released the same emission band about 475 nm to enhance the emission signal when ZFPy reacted with SO2 derivatives, to the best of our knowledge, this is the first synergetic FRET/ICT platform for fluorescence probe, which might effectively offer ZFPy a high sensitivity and low detection limit in the detection of SO2 derivatives. More importantly, ZFPy could image exogenous and endogenous SO2 derivatives in living HeLa, HepG2 and L-O2 cells with good biocompatibility and photostability. ZFPy also preferred to load on lipid droplets with high Pearson’s coefficient (0.95).

Accurately monitoring of sulfur dioxide derivatives in agricultural crop leaf tissues by a novel sensing system

Accurately monitor SO2 derivatives in agricultural crop leaf tissues is imperative, but it is still limited. A fluorescent sensing system with the characteristic of ratiometric near-infrared (NIR) fluorescence response to analyte is conducive to applying in agricultural crop leaf tissues. Herein, we rationally constructed 7-diethyl-amino-aza-coumarin conjugated quinolinium hybrid, CQ-1, as the first fluorescent sensing system to monitor SO2 derivatives in ratiometric NIR response manner in agricultural crop leaf tissues. CQ-1 exhibited specific and sensitive ratiometric NIR response to SO2 derivatives, with detection limits calculated to be 0.016 μM. Moreover, the fluorescence ratios (I516/I714) of the CQ-1 displayed linear relationship with the concentrations of introduced SO2 derivatives from 0 to 300 μM. Fluorescence imaging experiments revealed that CQ-1 was able to detect pre-treated SO2 derivatives in agricultural crop leaf tissues. Significantly, quantitative detection of SO2 derivatives in leaf tissues which were assimilated by stomata from SO2 polluted air was successfully conducted. The sensing system developed herein will be used as an effective tool to accurately monitor the subtle changes of SO2 derivative level in various agricultural crops.

Sulfur dioxide derivatives produce antidepressant- and anxiolytic-like effects in mice

Sulfur dioxide (SO2) can be endogenously generated from sulfur-containing amino acids in animals and humans. Increasing evidence shows that endogenous SO2 may act as a gaseous molecule to participate in many physiological and pathological processes. However, the role of SO2 and its derivatives in the central nervous system remains poorly understood. The present study explored the protective effects of exogenous SO2 derivatives (Na2SO3:NaHSO3, 3:1 M/M) on cellular injury in vitro by using the cell proliferation assay (MTS), cell counting kit 8 assay (CCK-8), and cyto-flow assay in the corticosterone (CORT)-induced PC12 cell injury model. We also examined the antidepressant and anxiolytic effects of SO2 derivatives on the chronic mild stress (CMS)-induced depression mouse model by using the open field test, novelty suppressed feeding test, forced swimming test, tail suspension test, and sucrose preference test. In the MTS and CCK-8 assays, we found that preexposure of SO2 derivatives significantly blocked CORT-induced decrease of cellular survival without causing any negative effects. Results from the cyto-flow assay indicated that treatment with SO2 derivatives could reverse CORT-induced early and late apoptosis of PC12 cells. Systemic treatment with SO2 derivatives produced markedly antidepressant- and anxiolytic-like activities in mice under normal condition and rapidly reversed CMS-induced depressive- and anxiety-like behaviors. In conclusion, these findings indicate that exogenous SO2 derivatives show protective properties against the detrimental effects of stress and exert antidepressant- and anxiolytic-like actions. The present study suggests that exogenous SO2 derivatives are potential therapeutic agents for the treatment of depression, anxiety, and other stress-related diseases.

A mitochondria-targeted ratiometric fluorescence probe for detection of SO2 derivatives in living cells

In this report, a mitochondria-targeted probe based on an efficient platform constructed by pyridinium-coumarin and 2-dicyanomethylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran (TCF) with high selectivity and sensitivity toward SO2 derivatives was presented. As far as we know, pyridinium-coumarin is first used as a donor moiety to construct a FRET system. Compared with our previous work, it showed better solubility, higher biocompatibility and faster response speed. It also presented low detection limit (80.5 nM), excellent energy transfer efficiency (98.2%) and low cytotoxicity. Moreover, the probe could detect exogenous and endogenous bisulfite in living cells as well as in mitochondria successfully.

Fluorescent Probe for Simultaneous Discrimination of GSH, Cys, and SO2 Derivatives.

Biothiols and SO2 derivatives, as essential reactive sulfur species (RSS), play vital roles in various physiological processes and have a close network of generation and metabolic pathways among them. To clarify their complex correlations, fluorescent probes to simultaneously detect GSH, Cys, and SO2 derivatives are highly desirable. Herein, we develop the first fluorescent probe (BO-HEM) to simultaneously discriminate GSH, Cys, and SO2 derivatives. The fluorescent probe is designed by integration of hemicyanine and BODIPY fluorophores through an ether bond. The ether bond of the probe is rapidly replaced by thiolates through nucleophilic aromatic substitution (SNAr) to generate hemicyanine with NIR fluorescence and sulfur-BODIPY. The amino groups of Cys but not GSH then further replace the thiolate to form amino-BODIPY. As for SO32-, nucleophilic addition to the double bond of BO-HEM generates adduct O-BODIPY with green fluorescence. To further improve the sensing performance, the nanoprobe with increased reactivity and biocompatibility is constructed by encapsulation of BO-HEM into the polymeric micelle. More importantly, by taking advantage of the hydrophilicity of the reaction products, the spectral discrimination was further enhanced to avoid signal interference. The nanoprobe is applied to discriminate biothiols and SO2 derivatives in living cells through three-color fluorescence imaging.

A new FRET-based ratiometric fluorescent probe for the detection of SO2 derivatives in mitochondria of living cells

We developed a new mitochondria-targeted ratiometric fluorescent probe (named PPA) for SO2 derivatives (HSO3−/SO32−) with a large (pseudo) Stokes shift (209 nm) based on FRET platform in which water-soluble (E)-4-(4-(dimethylamino)styryl)-1-alkylpyridin-1-ium was chosen as acceptor moiety and phenothiazine oxide as donor moiety. Probe PPA showed specific response toward HSO3−/SO32− over H2S, GSH, Cys and Hcy. The recognition group underwent a nucleophilic addition reaction with HSO3−/SO32− to give rise to clear dual-emission signal changes in enhanced blue channel and subdued red channel under a single wavelength excitation. Moreover, probe PPA was successfully used for the detection of endogenous HSO3−/SO32− and bioimaging of mitochondria-targeted in living cells.

Decreased endogenous nitric oxide contributes to sulfur dioxide derivative-alleviated cadmium toxicity in foxtail millet roots

Cadmium (Cd) is an environmental pollutant that is highly toxic to animals and plants. Although sulfur dioxide (SO2) has recently been considered as a novel bio-regulator, whether and how SO2 regulates Cd-induced phytotoxicity in plant roots is largely unknown. In this study, SO2 derivatives (Na2SO3/NaHSO3, M/M = 3:1) were used to investigate the beneficial roles and detailed mechanisms of SO2 in the alleviation of Cd-induced root growth suppression in foxtail millet seedlings. Our results showed that exogenously applied SO2 derivatives (0.5 mM) reversed Cd inhibition of root elongation. Cd-induced endogenous nitric oxide (NO) production downregulated the enzyme activities of superoxide dismutase (SOD) and peroxidase (POD), as well as corresponding transcript levels, and increased the expression of genes involved in Cd uptake (SiNRAMP1, SiNRAMP6, SiIRT1, and SiIRT2) in foxtail millet roots. Upon Cd exposure, SO2 derivative application reduced NO generation by inhibiting nitrate reductase (NR) and nitric oxide synthase (NOS) activities, thus resulting in increased activities of SOD and POD and suppressed Cd uptake-related gene expression, which in turn reduced reactive oxygen species (ROS) accumulation and decreased Cd content in the roots. This study suggested a beneficial role of SO2 derivatives in protecting foxtail millet roots against Cd toxicity by decreasing endogenous NO; this might be applicable to enhancing crop tolerance to Cd pollutants.

A highly sensitive and fast responsive fluorescent probe for SO2 derivatives and its application in living cell imaging

A new fluorescence probe 1 for sulfur dioxide derivatives has been developed which acts through nucleophilic addition of the derivatives and shows high stability, specificity, and sensitivity. In the presence of SO2 derivatives, the fluorescence intensity of probe 1 significantly decreases within a short time period of 40 s, along with a low detection limit of 0.32 µM. Fluorescence imaging capability of probe 1 was also investigated, showing clear detection of SO2 derivatives in living cells. The results indicate that this probe has a great potential for the detection of SO2 derivatives in broad biological and relevant samples.

A novel mitochondrial-targeted two-photon fluorescent probe for ultrafast monitoring of SO2 derivatives and its applications

SO2 derivatives maintain a certain balance and play an important role in many metabolic processes. However, excessive ingestion of them can lead to serious complications of various diseases. Therefore, a rapid and precision detection of SO2 derivatives with high selectivity and sensitivity would be an advance for their bio-analytic studies. Accordingly, a novel deep red and two-photon fluorescent SO2 derivatives probe (DRQ) was developed here for the first time. The probe showed fast ratio response rate (within 5 s), excellent sensitivity (the detection limit is 103 nM for red channel and 17 nM for green channel), and outstanding selectivity toward SO2 derivatives in 10 mM PBS buffer. Moreover, the ratiometric probe DRQ displays a 99 nm blue-shift in emission upon addition of SO2 derivatives. Intriguingly, the probe can be made into test papers for real-time monitoring of SO2 derivatives. Moreover, it can be also applied for visual ratio imaging of SO2 derivatives in cellular mitochondria and zebrafish under two-photon absorption (green channel) and one-photon absorption (red channel).

A novel mitochondria-targetted near-infrared fluorescent probe for selective and colorimetric detection of sulfite and its application in vitro and vivo

Overdoses of SO2 and its derivatives (SO32−/HSO3−) in food or organisms are harmful to health. To detect SO32−/HSO3−, a novel NIR fluorescent probe 1, based upon the intramolecular charge transfer (ICT) mechanism, was developed. This probe was easily synthesized, and gave noticeable colorimetric and linear fluorescence changes at 690 nm after reaction with sulfite from 3.13 to 200 µM. Moreover, probe 1 displayed high sensitivity (LOD = 0.46 µM), excellent selectivity (among 13 kinds of anions and 3 kinds of biothiols) and quick response (within 30 min) towards SO32−/HSO3−. The SO32−/HSO3− sensing mechanism was confirmed as the Michael addition reaction. Furthermore, the probe showed wide applications for measuring SO32−/HSO3− in real samples, including sugar, tap water, wine and traditional Chinese medicine. The probe could also be used to detect SO32−/HSO3− in mitochondria of HepG2 cells and zebrafish, which suggested potential application for monitoring SO2 derivatives in clinical diagnostics.

A FRET-based supramolecular nanoprobe with switch on red fluorescence to detect SO2 derivatives in living cells.

SO2, an important gasotransmitter, plays significant roles in human physiological activities. The reported probes for the detection of SO2 derivatives are mostly based on the quenching or blue-shift of fluorescence, leading to interference from the background signal. Herein, we develop a novel FRET-based nanoprobe that shows turn-on fluorescence at 615 nm in the presence of SO32-/HSO3-. The nanoprobe consists of N,O,B-chelated dipyrromethene (BDP) as the energy donor, and hemicyanine derivatives of HEM-CO-Ph with a responsive site to SO32-/HSO3- as the energy acceptor. Initially, the fluorescence of BDP is quenched by HEM-CO-Ph due to the efficient FRET process. In the presence of sulfites, the nucleophilic addition interrupts the conjugation of HEM-CO-Ph and results in a 200 nm blue-shift of the absorption, leading to the suppression of the FRET process and recovery of the red fluorescence of BDP. The nanoprobe shows fast response to SO32-/HSO3- with high selectivity, great biocompatibility and cellular uptake. It is the first supramolecular nanoprobe for the detection of SO32-/HSO3- by using intermolecular energy transfer, ingeniously turning the nanoprobe from "OFF" state to "ON" state. The nanoprobe is applied to monitor exogenous and endogenous SO2 derivatives in the mitochondria of living cells.

A near-infrared fluorescent probe for ratiometric sensing of SO2 in cells and zebrafish.

Developing suitable molecular tools for monitoring SO2 and its derivatives in living organisms is attractive due to their importance for human health. Herein, the first near-infrared fluorescent probe Mito-HN with aggregation-induced emission enhancement (AIEE) characteristics for ratiometric sensing of SO2 derivatives in vitro, in cells, and in zebrafish was designed and synthesized. By connecting the electron-donating naphthopyran and electron-withdrawing hemicyanine via the alkenyl group, this probe displays a near-infrared fluorescence emission and notable solid-state luminescence with AIEE features. Based on the specific 1,4-addition reaction of HSO3-/SO32- with the C[double bond, length as m-dash]C double bond of Mito-HN, this probe can specifically sense HSO3- in real time with an excellent near-infrared ratiometric fluorescence effect, a low detection limit of 0.17 μM, and a fast response time of less than 30 s. Cell imaging and zebrafish imaging results demonstrate that Mito-HN can ratiometrically not only sense endogenous SO2 derivatives in mitochondria but also monitor SO2 in living organisms. We anticipate that Mito-HN could be applied for the diagnosis of SO2-related diseases in the future.

A novel mitochondria-targeted ratiometric fluorescent probe for endogenous sulfur dioxide derivatives as a cancer-detecting tool.

A new mitochondria-targeted fluorescent probe RBC, constructed using a coumarin moiety which was selected as the donor and a benzothiazole derivative as the acceptor, for SO2 derivatives (HSO3-/SO32-) was presented. The probe designed on a new FRET platform showed high selectivity and a low detection limit. Importantly, the probe could respond to HSO3-/SO32- within 35 s. Furthermore, the probe could target mitochondria and was successfully used for fluorescence imaging of endogenous bisulfite in HepG2 with low cytotoxicity, which significantly assisted in cancer diagnosis.

Mitochondria-targeted polydopamine nanoprobes for visualizing endogenous sulfur dioxide derivatives in a rat epilepsy model.

Epilepsy is the fourth most common neurological disorder, and aberrantly elevated sulfur dioxide derivatives (SO32-/HSO3-) are thought to underlie the hippocampal neuronal apoptosis in epilepsy. We have designed and synthesized a mitochondria-targeted polydopamine nanoprobe for visualizing endogenous SO32-/HSO3- by the nucleophilic addition reaction. The nanoprobe was used for imaging SO2 derivatives both in the mitochondria of cultured cells and zebrafish, and successfully applied in the hippocampus of a rat model of epilepsy. The PDAD nanoprobe could be of great value for the elucidation of mechanisms of abnormal SO32-/HSO3- involved in diseases such as epilepsy.

A mitochondria-targeted fluorescent probe for the detection of endogenous SO2 derivatives in living cells

A unique fluorescent probe (ZACA) for the monitoring of SO2 derivatives was developed from coumarin and benzoindoles based on FRET and ICT. ZACA exhibited an active emission signal, large Stokes shift, wide emission window distance, and high photostability. It also possessed many advantages in the ratiometric detection of HSO3-/SO32- including low detection limit and high selectivity and sensitivity. Importantly, ZACA was successfully applied in the ratiometric detection of endogenous HSO3-/SO32- in living cells with excellent cellular imaging capability (1 μM) and mitochondria-targeting ability (co-localization coefficient: 0.91).

A novel mitochondrial targeting fluorescent probe for ratiometric imaging SO2 derivatives in living cells

As an important endogenous signaling molecule, SO2 plays a key role in many physiological processes. However, excessive intake of SO2 and its derivatives lead to serious health complications of various diseases. In order to study the role of SO2 and its derivatives in the biological environment, it is of great significance to develop new and effective monitoring methods. Here, a new red emission fluorescent probe (TNPI) based on pyrazoline and hemicyanine dyes for the high selective detection of SO2 derivatives was developed. The probe TNPI showed some advantages such as long emission wavelength (640 nm), obvious color and fluorescence changes after reaction with SO2 derivatives, high selectivity and sensitivity toward SO2 derivatives (detection limit = 80 nM), and large fluorescence emission shift (160 nm) and signal ratio change (from 0.45–445, about 989 times). Intriguingly, the probe was successfully exploited for the fluorescence imaging of SO2 derivatives in the mitochondria of living cells with low cytotoxicity.

New carbazole fluorescent sensor for ultrasensitive and ratiometric sensing of SO2 derivatives and hydrazine

The probe CBTA is a novel bifunctional fluorescent probe that can detect bisulfite and hydrazine hydrate in a rational manner. And probe CBTA could specifically detect bisulfite and hydrazine hydrate among different analytes. Moreover, the response time of probe CBTA to SO2 derivatives and hydrazine is extremely short, and the detection limits for bisulfite and hydrazine are as low as 5.6 nmol and 39 nmol. Cellular experiments also indicated that the probe CBTA was low in cytotoxicity and could be applied to cellular fluorescence imaging. Therefore, the probe CBTA could provide an efficient means for detecting SO2 derivatives and hydrazine in vitro.

Ratiometric sensing of sulfite/bisulfite ions and its applications in food samples and living cells

Two novel ratiometric fluorescence probes based on diformyl phenol appended indolium dye (DFIN) and diformyl bisphenol appended indolium dye (BPIN) were designed and synthesized. The probes DFIN and BPIN exhibited high selectivity towards SO2 derivatives with fast response time (100 and 120 s). The detection limit of DFIN and BPIN for sulfite ions were 1.8 nM and 2.1 nM which is lower than the maximum acceptable limit of sulfite ion in food samples by United States Environmental Protection Agency (USEPA). Furthermore, the novel ratiometric fluorescent sensors DFIN and BPIN could be used for recognition of sulfite ions in food samples in addition to living cells.

A Ratiometric and Colorimetric Hemicyanine Fluorescent Probe for Detection of SO2 Derivatives and Its Applications in Bioimaging.

Based upon the intramolecular charge transfer (ICT) mechanism, a novel ratiometric fluorescent probe EB was developed to detect SO32−/HSO3−. The probe displayed both colorimetric and ratiometric responses toward SO32−/HSO3−. It displayed a quick response (within 60 s), good selectivity and high sensitivity (a detection limit of 28 nM) towards SO32−/HSO3−. The SO32−/HSO3− sensing mechanism was confirmed as the Michael addition reaction by ESI-MS. Moreover, the probe could be applied to measure the level of sulfite in real samples, like sugar and chrysanthemum, and it could also be used to detect SO32−/HSO3− in HepG2 cells through confocal fluorescence microscopy, which proved its practical application in clinical diagnosis.

Design of a ratiometric two-photon fluorescent probe for dual-response of mitochondrial SO2 derivatives and viscosity in cells and in vivo

The content of sulfur dioxide (SO2) in mitochondria is related to various physiological and pathological processes. The irregular viscosity in mitochondria would result in mitochondria disorders. In this research, a novel ratiometric two-photon fluorescent probe (MBCB) based on carbazole framework has been strategically designed and synthesized for dual-detection of mitochondrial SO2 derivatives and viscosity. The results show that probe MBCB is capable of responding to SO2 derivatives and viscosity using dual-color imaging. MBCB can not only recognize SO2 derivatives utilizing a ratiometric change of fluorescent intensity (I434 nm/I600 nm), but also shows a high sensitivity and selectivity for monitoring SO2. On the other hand, the fluorescent intensity ratio (I567 nm/I415 nm) of MBCB increased with the increment of viscosity and exhibited a good logarithmic linear relationship between the ratio and viscosity (R2 = 0.99). Satisfactorily, probe MBCB has a good targeting ability to mitochondria and a low cell cytotoxicity, and can be successfully applied to detect HSO3− in living cells and in vivo. Furthermore, the probe can visualize the change of mitochondrial viscosity induced by nystatin.