Dual-Responsive Near-Infrared BODIPY-Based Fluorescent Probe for the Detection of F- and HClO in Organisms.

Fluoride anions (F-) play a crucial role in human physiological processes. However, excessive intake of F- would affect oxygen metabolism and promote the generation of oxygen-free radicals. Hence, it is essential to develop a precise and efficient fluorescent probe for visualizing F--induced oxidative stress. In this work, we developed the first bifunctional BODIPY-based fluorescent probe dfBDP with p-tert-butyldimethylsilanolate benzyl thioether as the sensing site for the detection of F- and HClO via two distinct reactions, the self-immolative removal and the thioether oxidation, which generate the sensing products with two nonoverlap fluorescence bands: 800-1200 and 500-750 nm, respectively. The probe dfBDP displays rapid response, high specificity, and sensitivity for the detection of F- (LOD, 316.2 nM) and HClO (LOD, 33.9 nM) in vitro. Cellular imaging reveals a correlation between F--induced oxidative stress and the upregulation of HClO. Finally, probe dfBDP was employed to detect F- and HClO in mice under the stimulation of F-. The experimental results display that the level of HClO elevates in the liver of mice.

Visible-light-promoted difluoroamidated oxindole synthesis via electron donor-acceptor complexes.

A method involving a metal-free visible-light-promoted synthesis was developed for the construction of difluoroalkylated oxindoles with N-phenylacrylamides and bromodifluoroacetamides as starting materials in the presence of N,N,N',N'-tetramethylethylenediamine (TMEDA). Twenty-four examples of the photochemical reaction were successfully performed, with good yields (44-99%) and excellent substrate adaptability. Mechanistic studies showed that the visible-light-promoted reaction involved a radical addition to N-phenylacrylamide, intramolecular cyclization, dehydrogenation, and rearomatization. The difluoroacetamide radical was produced as a result of electron transfer to bromodifluoroacetamides from the electron donor TMEDA in their electron-donor-acceptor (EDA) complexes under visible light irradiation. This protocol is a promising photochemical method due to its advantages of mild conditions, simple operation, wide substrate scope and high yields. And the obtained products may have great potential in the field of medicine.

A BODIPY-based fluorescent probe for simultaneous detection of H2O2 and viscosity during the pyroptosis process.

A dual functional BODIPY fluorescent probe was developed for simultaneous detection of H2O2 and viscosity, by collecting fluorescence from 800-1100 nm and 550-750 nm, respectively. Bioimaging based on the probe shows that H2O2 accumulates and cytoplasmic viscosity increases during the palmitic acid (PA)-induced pyroptosis process.

A fluorescent probe generating in situ the reactive species for rapid and selective detection of mustard gas.

Sulfur mustard (SM) is an important chemical warfare agent (CWA) and has been used frequently in various conflicts. It is important to develop a facile, rapid, sensitive and selective detection method for SM. In this work, we constructed a novel fluorescent probe PCS capable of generating active sensing species for rapid and selective detection of SM and its simulant CEES (2-chloroethyl ethyl sulfide). PCS exhibits excellent chemical and photostability and can generate reactive species in situ for rapid (within 90 s, at 60 °C) and selective detection of SM and CEES in solution with high sensitivity (∼nM level). Moreover, PCS could enable the detection of mustards in situ. A test strip with PCS and KOH was prepared and realized the sensitive and selective detection of CEES in the gas phase. In addition, the PCS probe can realize facile and rapid detection of CEES-contaminated surfaces by spraying its sensing system (ethanol solution containing PCS and KOH). The sensing mechanism was well demonstrated through the separation and characterization of the sensing product.

Bifunctional Fluorescent Probes for the Detection of Mustard Gas and Phosgene.

Mustard gas [sulfur mustard (SM)] and phosgene are the most frequently used chemical warfare agents (CWAs), which pose a serious threat to human health and national security, and their rapid and accurate detection is essential to respond to terrorist attacks and industrial accidents. Herein, we developed a fluorescent probe with o-hydroxythioketone as two sensing sites, AQso, which can detect and distinguish mustard gas and phosgene. The dual-sensing-site probe AQso reacts with mustard gas to form a cyclic product with high sensitivity [limit of detection (LOD) = 70 nM] and is highly selective to SM over phosgene, SM analogues, active alkylhalides, acylhalides, and nerve agent mimics, in ethanol solutions. When encountering phosgene, AQso rapidly converts to cyclic carbonate, which is sensitive (LOD = 14 nM) and highly selective. Their sensing mechanisms of AQso to mustard gas and phosgene were well demonstrated by separation and characterization of the sensing products. Furthermore, a facile test strip with the probe was prepared to distinguish 2-chloroethyl ethyl sulfide (CEES) and phosgene in the gas phase by different fluorescence colors and response rates. Not using the complicated instrument, the qualitative and quantitative detection of CEES or phosgene can be achieved only by measuring the red-green-blue (RGB) channel intensity of the test strip after being exposed to CEES or phosgene gas by the smartphone with an RGB color application.

Real-time, sensitive and simultaneous detection of GSH and Cys/Hcy by 8-substituted phenylselenium BODIPYs: a structure-activity relationship.

Real-time and sensitive detection of biothiols is the key to biomedical research and clinical diagnosis. It is necessary to develop a highly sensitive and selective fluorescent probe for the detection of biothiols. In this paper, we have developed a series of meso-arylselenium BODIPY probes for the rapid and sensitive detection of biothiols and the dual-channel discrimination of GSH and Cys/Hcy. A structure-activity relationship was established from five p-substituted phenylselenium (R = NO2, F, H, OCH3 or N(CH2CH2)2O) BODIPYs. Compared with most reported fluorescent probes, such as meso-BODIPY sulfur ethers, these probes display much lower LODs (∼nM levels) and more rapid responses, which are ascribed to the higher fluorescence efficiencies of the sensing products (Φf = 0.48 for GSH, 0.18 for Cys and 0.14 for Hcy) and the introduction of arylselenium, which is more active than arylthiol. Among them, the best sensing performance is that of probe 2a (R = NO2); therefore, a structure-activity relationship of these fluorescent probes was also obtained. The excellent sensing performance was further revealed in the detection of GSH and Cys/Hcy in live cells.

A coumarin-based fluorescent probe with 4-phenylselenium as the active site for multi-channel discrimination of biothiols.

Biological mercaptans, also known as biothiols, play their own roles in a number of important physiological processes, and the abnormal levels of biothiols are closely associated with a variety of diseases. Therefore, the selective detection of biothiols in biological systems is crucial for understanding their roles in physiological processes and the early diagnosis of diseases. In this article, we developed a coumarin-based fluorescent probe (CouSePh) with 4-phenylselenium as the active site for the discriminative detection of all three biothiols. By introducing 4-phenylselenium as the active group, the probe CouSePh exhibits a rapid and sensitive response to three biothiols. For all three biothiols, the first-step sensing reaction is the nucleophilic substitution of 4-phenylselenium by the thiol group of biothiols, and they subsequently undergo three distinct intramolecular reactions to form three sensing products with different fluorescence emissions. The sensing mechanisms of the three biothiols have been demonstrated by spectral measurements and the analysis of high resolution mass spectrometry as well as the separation and characterization of the sensing product. Furthermore, by two-channel fluorescence imaging, probe CouSePh has been successfully applied in the discriminative detection of endogenous biothiols in living cells.

Visible Light-Driven Decarboxylative Alkylation of Aldehydes via Electron Donor-Acceptor Complexes of Active Esters.

There are some synthesis methods from widely available aldehydes to the corresponding ketones, however, they involved in multistep reactions with Grignard's reagents or transition metal catalysts. In this paper, we have developed photocatalyst-free and visible light-driven decarboxylative alkylation of pyridinaldehydes. The photochemical reactions are initiated via photoinduced single electron transfer from triethylamine to N-hydroxyphthalimide esters in electron donor-acceptor complexes. This photochemical method can achieve to translate 15 pyridinaldehydes and 11 2-quinolinaldehydes to the corresponding ketones. Furthermore, this strategy can also achieve two other transformations, disulfanes to aryl sulfides and a styrene sulfone to the alkyl-substituted alkene.

An 8-arylselenium BODIPY fluorescent probe for rapid and sensitive discrimination of biothiols in living cells.

By introducing 8-arylselenium as the active group, a BODIPY fluorescent probe ASeBD was constructed for rapid and sensitive detection and dual-channel discrimination of GSH and Cys/Hcy in solution and in living cells, and its mechanism was demonstrated.

Regioselective benzoyloxylative dearomatization of naphthols by benzoyl peroxide under catalyst-free conditions.

A direct regioselective benzoyloxylative dearomatization of both α- and ß-naphthols by benzoyl peroxide under an air atmosphere, and radical inhibitor- and catalyst-free conditions at room temperature is described. The methodology provides a new efficient strategy for the construction of α-ketol derivatives bearing an oxo-quaternary carbon center from naphthols with good to excellent yields.

Visible-Light-Mediated Alkylation of Thiophenols via Electron Donor-Acceptor Complexes Formed between Two Reactants.

A metal-free, photocatalyst-free, photochemical system was developed for the direct alkylation of thiophenols via electron donor-acceptor (EDA) complexes (KEDA = 145 M-1) between two reactants, N-hydroxyphthalimide esters as acceptors and thiophenol anions as donors, in the presence of a tertiary amine. The EDA complexes in the reaction system have a broad range of visible-light absorption (400-650 nm) and can trigger the reaction effectively under sunlight.

Rapid and Effective Reaction of 2-Methylpyridin-N-oxides with Triphosgene via a [3,3]-Sigmatropic Rearrangement: Mechanism and Applications.

A facile and effective synthesis of 2-chloromethylpyridines was developed by a one-pot reaction of 2-alkylpyridin-N-oxides and triphosgene at room temperature. As starting materials, N-oxides of 2-alkylpyridine derivatives, including 2-alkylpyridines, 2-methyl quinolines, and phenanthroline, can react rapidly with triphosgene in the presence of triethylamine, affording 2-chloromethylpyridines in good to excellent yields (52-95%). Using the 2-methylquinoline substrate for the mechanistic study, it has been well demonstrated that the chlorination reaction undergoes a [3,3]-sigmatropic rearrangement, which can be observed as a reversible process by monitoring the intermediates. Moreover, the chlorination reaction can be used to construct a rapid and sensitive fluorescent probe for the detection of phosgene.

Quinoline-2-thione-based fluorescent probes for selective and sensitive detections of mustard gas and its analogues.

Sulfur mustard (SM, also called as mustard gas (HD)) is a persistent and highly toxic gas used as chemical weapon in wars and military conflicts. Moreover, owing to its simple structure and easy synthesis, it is the most likely chemical agent used by terrorists. For this reason, it is vital important to develop a facile, rapid and reliable detection system for SM. In this paper, we have developed four quinoline-2-thiones as fluorescent probes, 2a-2d, for the detection of SM and its analogues, half sulfur mustard (CEES) and a nitrogen mustard NH1. In the presence of KOH, these quinoline-2-thiones deprotonated to quinoline-2-thiophenol anions, which react with SM and its analogues rapidly to form quinoline-2-thiethers with highly efficient fluorescence, giving turn-on fluorescence response. The sensing products with CEES were isolated and fully characterized, thereby, the sensing mechanism was firmly established. The fluorescent probes with 4-trifluoromethyl group, 2b and 2d, exhibit rapid response to SM, CEES and NH1 (within 1 min at 60 °C for CEES and NH1), high sensitivity (limit of detection, 50 nM for SM and 20 nM for NH1) and high selectivity. Furthermore, polymer film test strips were fabricated with probe-embedded poly(ethylene oxide) for the detection of CEES vapor. These test strips displayed a rapid response (<4 min) to gaseous CEES with high sensitivity (0.2 ppm) and high selectivity. These results show that fluorescent probes 2b and 2d have a good application prospect in the field detection of mustard gas.

Sensitive and selective detections of mustard gas and its analogues by 4-mercaptocoumarins as fluorescent chemosensors in both solutions and gas phase.

Mustard gas has been used as a chemical warfare agent for a century, and is the most likely chemical weapon used in wars or by terrorists. Thus, it is important to develop a facile, rapid and highly selective method for the detection of mustard gas. In this paper, two fluorescent probe molecules, 4-mercaptocoumarins, have been developed for rapid and sensitive detections of SM and its analogues (CEES and NH1) in both solutions and gas phase. The sensing reaction is a nucleophilic addition at three-membered hetercyclic sulfonium/ammonium formed from SM, CEES/NH1 in ethanol. Two fluorescent probes (4-mercaptocoumarins, ArSH) in ethanol deprotonate to form thiophenol anions (ArS-) resulting from their low pKa values (3.2-3.4), and the nucleophilic addition of the anion ArS- generates the corresponding thioethers, giving a turn-on fluorescence response. The thiophenol anion can fast sense SM, CEES and NH1 (within 1-4 min) with high sensitivity (~nM level) at 60 °C, and high selectivity through adding a tertiary amine, and two probes exhibit excellent chemical and photostability in detection systems. Furthermore, a facile test strip with the sensor was fabricated for the detection of CEES vapor with rapid response (3 min), high sensitivity (9 ppb) and high selectivity.

Sensitive and Visual Detection of Phosgene by a TICT-Based BODIPY Dye with 8-(o-Hydroxy)aniline as the Active Site.

Phosgene and its substitutes (diphosgene and triphosgene) are widely utilized as chemical industrial materials and chemical warfare agents and pose a threat to public health and environmental safety due to their extreme toxicity. Research efforts have been directed to develop selective and sensitive detection methods for phosgene and its substitutes. In this paper, we have prepared two BODIPY-based fluorescent probes, o-Pah and o-Pha, which are two isomers with different active sites, ortho-aminohydroxy (3',4' or 4',3') phenyls at meso position of BODIPY, and compared their sensing performance toward triphosgene. The probe with o-(4'-amino-3'-hydroxyl), o-Pha, exhibits better sensing performance over the o-(3'-amino-4'-hydroxyl), o-Pah, for instance, a lower limit of detection (LOD) (0.34 nm vs. 1.2 nm), and more rapid response (10 s vs. 200 s). Furthermore, based on the above comparative studies, a red-fluorescence probe o-Phae has been constructed through extending 3,5-conjugation of o-Pha. The probe o-Phae displays rapid response (60 s), high sensitivity to triphosgene (LOD=0.88 nm), and high selectivity for triphosgene over relevant analytes including nitric oxide. Finally, a facile test strip for phosgene was fabricated by immobilizing o-Phae in a polyethylene oxide membrane for sensitive (<2 ppm) and selective detection of phosgene in the gas phase.

Phenothiazine and semi-cyanine based colorimetric and fluorescent probes for detection of sulfites in solutions and in living cells.

Four hemicyanine probes for selectively detecting sulfites (HSO3 -/SO3 2-) have been constructed by the condensation reaction of 7-substituted (CN, Br, H and OH) phenothiazine aldehyde with 1-ethyl-2,3,3-trimethylindolium iodide. All four probes show a fast and sensitive response to HSO3 -/SO3 2- via a Michael addition, with a detection limit lower than 40 nM based on monitoring their UV/vis absorption changes. Although all four probes display an increase in fluorescence when responding to HSO3 -/SO3 2-, the increment is larger for the probe with an electron-withdrawing group than the probe with an electron-donating group, except for Br. Thus, among four probes the 7-cyano probe (PI-CN) possesses the largest fluorescent response to HSO3 -/SO3 2-, and the lowest detection limit (7.5 nM). More expediently and easily, a film and a test paper with PI-CN have been prepared to detect HSO3 -/SO3 2- in a sample aqueous solution selectively. Finally, the detection of HSO3 -/SO3 2- by PI-CN in biological environments has been demonstrated by cell imaging.

Rapid and sensitive detection of nitric oxide by a BODIPY-based fluorescent probe in live cells: glutathione effects.

Nitric oxide (NO) is an important signaling molecule involved in various physiological and pathological processes. The effects of NO depend on its concentration, and the spatial and temporal constraints of the cell microenvironment. Meanwhile, NO can react with some biomolecules such as biothiols, leading to a short biological lifetime. Thus, it is very crucial to establish a real-time visualization method for monitoring NO levels. In this work, we have developed a fluorescent probe, RBA, for NO, with a 3-extended BODIPY as a fluorophore and a secondary amine as the active site. The probe RBA can quickly sense NO (∼10 s) in aerobic solutions to generate a fluorescent N-nitrosamine (RBA-NO, Φf = 0.87) due to blocking of the photoinduced electron transfer (PET) process from the secondary amine to the BODIPY core. This sensing reaction displays high sensitivity (LOD = 10 nM) and high selectivity for NO over relevant analytes except some reducing reagents including biothiols, and a remarkable interference effect is observed ascribed to a competitive reaction with biothiols. Furthermore, the exo- and endogenous detection of NO in live cells and zebra fish was achieved, and it was demonstrated that glutathione (GSH) weakens drastically the fluorescence response by cell-imaging experiments. These results imply that the colorimetric and fluorescence response of the chemosensor for NO depends on the levels of both NO and GSH in environments.

A rapid-response and ratiometric fluorescent probe for nitric oxide: From the mitochondria to the nucleus in live cells.

Nitric oxide (NO) is a very important signal molecule implicated in numerous physiological and pathological processes, and its detection is the key to understand these processes. For this reason, various fluorescent probes have been developed for detection analysis of NO. However, few rapid-response (<1 min) and ratiometric fluorescent probe are reported for real-time detection of short-time NO in biological systems. In this work, we report a rapid-response (within several seconds) and ratiometric fluorescent probe, RatioTr, which displays selective and sensitive detection of NO in solutions, and detections of exo- and endogenous NO in live RAW 264.7 cells. Unexpectedly, the probe RatioTr and its sensing product (p-Nus) display different cellular localizations, the mitochondria and the nucleus, which were demonstrated by co-stained experiments. The sensing process of RatioTr toward NO from mitochondria to nucleus was observed in live cells by confocal fluorescence images. Furthermore, the subcellular localizations were demonstrated by measurements of pKa and interaction of p-Nus and DNA. In the presence of a natural DNA, calf thymus DNA, RatioTr is more sensitive to NO (LOD = 2.8 nM). Therefore, due to the nucleus localization together with a high fluorescence efficiency in the nucleus, p-Nus is a good candidate of cell-permeant nucleic acid stain or a fluorescent probe for the nucleus.

Synthesis of Oxadiazolones with Hydrazides: The Mechanism and the Sensing Application as Sensitive, Rapid, and Visual Fluorescent Sensors for Phosgene.

The reaction of hydrazides with triphosgene in the presence of triethylamine is a facile method to construct various oxadiazolones. Utilizing this reaction, a new class of colorimetric and fluorogenic phosgene chemosensors were developed with the BODIPY as fluorophore, five BODIPY-based hydrazides, which exhibited highly effective reactions with phosgene. The mechanism was updated. Finally, the test paper with a hydrazide was fabricated for facile, selective, and visual detection of phosgene gas.

BODIPY-based selenides as fluorescent probes for rapid, sensitive and mitochondria-specific detection of hypochlorous acid.

Hypochlorous acid (HClO) is a powerful microbicidal agent in the innate immue system; however, abnormal HClO levels can cause tissue damage and many diseases. Thus, it is vitally important to develop facile, rapid and accurate analytical methods for the detection of HClO/ClO-in vitro and in vivo. In this work, we have constructed three meso-substituted BODIPY selenides with different hydrocarbyl groups (ethyl for BSe-Et, benzyl for BSe-Bz and phenyl for BSe-Ph) as fluorescent probes for the detection of HClO/ClO-. All three non-fluorescent probes can sense HClO/ClO- to form fluorescent selenoxides by blocking the photo-induced electron transfer process. Their sensing properties display a clear relationship with the structure of the hydrocarbyl. The sensing reactivity is heavily dependent on the electron-donating ability of hydrocarbyls, with the order of the response time as BSe-Et (2 s) < BSe-Bz (5 s) ≪ BSe-Ph (>100 s). Both BSe-Et and BSe-Bz afford a large fluorescence response and very low detection limits (0.3 nM and 0.8 nM), and BSe-Bz displays a higher selectivity over BSe-Et. Finally, as a representative, BSe-Bz was successfully applied to the detection of exo- and endogenous HClO in living cells, and demonstrated to be a mitochondria-localized fluorescent probe.