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(A) The fluorescence intensity of HMN (10 μM) at (A1) 485 nm, (A2) 546 nm, and (A3) 609 nm in the presence of (1) no interfering species, (2) Ala, (3) Arg, (4) Asp, (5) Glu, (6) Ile, (7) Phe, (8) Ser, (9) Thr, (10) Trp, (11) Val, (12) His, (13) VC, (14) AcO⁻, (15) Br⁻, (16) Cl⁻, (17) NO3⁻, (18) NO2⁻, (19) N3⁻, (20) SO3²⁻, (21) S2O3²⁻, (22) Cu⁺, (23) Ca²⁺, (24) Fe²⁺, (25) Fe³⁺, (26) Zn²⁺, (27) HClO, (28) O2⁻, (29) H2O2, (30) TBHP, (31) NO, (32) Cys, (33) Hcy, (34) GSH, (35) H2S(LC), and (36) H2S(HC) in PBS (25 mM, pH 7.4, containing 20% acetonitrile). Concentrations were 1 mM for (2)–(30), 0.55 mM for (32) and (33), 0.65 mM for (34), 0.5 mM for (35), and 5.0 mM for (36). (B) The fluorescence intensity of HMN (10 μM) at (B1) 485 nm, (B2) 546 nm, and (B3) 609 nm in the presence or absence of biothiols at different pH values ranging 4.0–10.0 in PBS (25 mM, containing 20% acetonitrile). Concentrations were 0.55 mM for Cys/Hcy, 0.65 mM for GSH, 0.5 mM for H2S(LC), and 5.0 mM H2S(HC). Excitation at 410 nm for (A1/B1), 470 nm for (A2/B2), and 550 nm for (A3/B3). H2S(LC) and H2S(HC) denote H2S at low and high concentrations, respectively
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Biothiols, which have a close connection of generation and metabolism pathways among of them, are essential reactive sulfur species (RSS) in the cells and play vital roles in human physiology. However, biothiols possess highly similar chemical structures and properties, resulting in an enormous challenge of simultaneously discriminating them from e...
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... They harbor similar chemical properties owing to their similar chemical structures, but play different roles in some physiological events. Apart from being the biosynthesis precursors of GSH and sulfur-containing proteins [4], Cys also participates in maintaining the biological conformation of protein, and mediates the body's intestinal function, lipid metabolism and other processes [5][6][7]. It is worth noting that Cys is tightly related to the occurrence and development of various diseases. ...
Cysteine (Cys), one of the important participants in protecting cells from oxidative stress, is closely associated with the occurrence and development of various diseases. Moreover, cell viscosity as a pivotal microenvironmental parameter has recently attracted increasing attention due to its dominant role in governing intracellular signal transduction and diffusion of reactive metabolites. Thus, simultaneous detection of Cys and viscosity is imperative for investigating their pathophysiological functions and cross-link. Herein we present a mitochondria-targetable dual-channel fluorescence probe ABDSP by grafting the acrylate modified pyridinium unit to dimethylaminobenzene. Whilst the probe is a seemingly simple, it could simultaneously discriminate Cys and viscosity in a fashion of distinguishable signals. Furthermore, the probe was successfully employed for visualizing mitochondrial Cys and viscosity, and probe into their cross-link during acetaminophen-induced hepatotoxicity.
... A typical pK a of aromatic thiols is ∼6.5, and ∼8.5 for aliphatic thiols. 564,565 Fluorescence-based assays can be applied for thiol detection and quantification, in addition to chromatography, UV/vis spectroscopy, potentiometry, and mass spectrometry. 566−568 Many of the fluorescence assays use the nucleophilicity of the thiols in reactions such as the Michael addition, cleavage of benzenesulfonamides and benzenesulfonates, cyclization with an aldehydes, cleavage of (O-, S-, Se-)phenyl ethers, cleavage of disulfides, or make use of the high affinity of thiols toward metals. ...
... 584 He et al. enhanced this idea and were the first that expanded the functionality with the probe HMN 219, that simultaneously distinguished between Cys/Hcy, GSH, and hydrogen sulfide (Figure 68). 565 S-Phenyl ethers and Se-phenyl ethers can also be used as leaving groups. The bond length of the carbon-heteroatom bond increases from oxyethers over thioethers to selenoethers, with a concomitant decrease in stability. ...
... The most stable bond (oxyethers) also makes the reaction rate of O-phenyl etherbased probes generally slow. 575,585,586 However, rates can be increased by adding electron-withdrawing groups at the aromatic ring, for example, in nitrophenyl-O-ethers. 565,586 In 2015, Kim et al. developed probe 220 for the selective and fast detection of GSH under physiological conditions. A phenylselenide linked to a coumarin probe was used as a leaving group. ...
Many successful stories in enzyme engineering are based on the creation of randomized diversity in large mutant libraries, containing millions to billions of enzyme variants. Methods that enabled their evaluation with high throughput are dominated by spectroscopic techniques due to their high speed and sensitivity. A large proportion of studies relies on fluorogenic substrates that mimic the chemical properties of the target or coupled enzymatic assays with an optical read-out that assesses the desired catalytic efficiency indirectly. The most reliable hits, however, are achieved by screening for conversions of the starting material to the desired product. For this purpose, functional group assays offer a general approach to achieve a fast, optical read-out. They use the chemoselectivity, differences in electronic and steric properties of various functional groups, to reduce the number of false-positive results and the analytical noise stemming from enzymatic background activities. This review summarizes the developments and use of functional group probes for chemoselective derivatizations, with a clear focus on screening for enzymatic activity in protein engineering.
... However, these probes are generally used for the monitoring of total biothiols or one of them. The probe that can be used for detecting and discriminating biothiols has rarely been explored, [16,[21][22][23] which remains the challenge for the rational design of functional molecular probes. ...
Small molecular biothiols, cysteine (Cys), homocysteine (Hcy) and glutathione (GSH), play important roles in organisms, and their concentration levels are indicative of some human diseases. Herein we report an organic dye‐conjugated β‐diketonate‐Eu³⁺ complex, [Eu(NBD‐keto)3(DPBT)] (NBD‐keto: 7‐nitro‐2,1,3‐benzoxadiazole (NBD)‐conjugated to 1,1,1,2,2‐pentafluoro‐5‐phenyl‐3,5‐pentanedionate through a “O” ether bond; DPBT: 2‐(N,N‐diethylanilin‐4‐yl)‐4,6‐bis(3,5‐dimethylpyrazol‐1‐yl)‐1,3,5‐triazine), which acts as a unique luminescent probe for detecting and discriminating biothiols. [Eu(NBD‐keto)3(DPBT)] itself is not luminescent due to intramolecular interactions between NBD and β‐diketonate‐Eu³⁺ moieties. Upon reaction with biothiols, the β‐diketonate‐Eu³⁺ complex [Eu(keto)3(DPBT)] is generated, which emits long‐lived red emission at 610 nm. Meanwhile, three biothiol‐substituted NBD derivatives that exhibit different luminescence behaviors, green emissive (short‐lived) NBD‐NR (R=Cys or Hcy) at 540 nm and non‐luminescent NBD‐SR (R=GSH), are also generated. These luminescence response behaviors allow time‐gated and steady‐state luminescence modes to be combined for detecting total biothiols and discriminating GSH and Cys/Hcy. Using this probe, the quantitative detection and discrimination of GSH and Cys/Hcy in lysis solutions of HeLa cells were realized, which revealed the potential of the probe for biomedical applications.
... Under the circumstances, plenty of fluorescent probes, such as fluorescent proteins, organic dyes, and inorganic nanoparticles (NPs), have been elaborately manipulated and exhibited tremendous utility in the field of bioimaging [11][12][13]. Among the above-mentioned fluorescent materials, inorganic NPs such as quantum dots or up-conversion NPs bring about inevitable biocompatibility concerns given their undefined purity and are hard to degrade, which severely restrains the clinical translations compared to organic small molecules [14]. ...
... A series of NIR AIEgens were synthesized to serve as fluorescent vectors by Tang et al. [86]. As illustrated in Figure 7a, the loose nucleic acid would be condensed into positively charged nanoparticles in the presence of aneN 3 [12], and then internalized into the cell. Owing to the electrostatic interaction between the negatively charged endosomal membrane and the positively charged vector/DNA complexes, the genetic cargo and AIEgens would be released. ...
Near-infrared (NIR) fluorescence materials have exhibited formidable power in the field of biomedicine, benefiting from their merits of low autofluorescence background, reduced photon scattering, and deeper penetration depth. Fluorophores possessing planar conformation may confront the shortcomings of aggregation-caused quenching effects at the aggregate level. Fortunately, the concept of aggregation-induced emission (AIE) thoroughly reverses this dilemma. AIE bioconjugates referring to the combination of luminogens showing an AIE nature with biomolecules possessing specific functionalities are generated via the covalent conjugation between AIEgens and functional biological species, covering carbohydrates, peptides, proteins, DNA, and so on. This perfect integration breeds unique superiorities containing high brightness, good water solubility, versatile functionalities, and prominent biosafety. In this review, we summarize the recent progresses of NIR-emissive AIE bioconjugates focusing on their design principles and biomedical applications. Furthermore, a brief prospect of the challenges and opportunities of AIE bioconjugates for a wide range of biomedical applications is presented.
... Monitoring the dynamics of H 2 S in vivo provides a better understanding of basic physiological and pathological mechanisms. Based on the nucleophilic and reducing capacity of H 2 S, the sensing strategies include nucleophilic addition reaction (probe 20), H 2 S-induced thiolysis (probe 21), the reduction of azide group (probe 22), etc. [88][89][90]. As a vital biomarker, GSH plays a key role in maintaining physiological homeostasis. ...
NIR-II imaging is developed rapidly for noninvasive deep tissue inspection with high spatio-temporal resolution, taking advantage of diminished autofluorescence and light attenuation. Activatable NIR-II fluorescence probes are widely developed to report pathological changes with accurate targeting, among which organic fluorescent probes achieve significant progress. Furthermore, the activatable NIR-II fluorescent probes exhibited appealing characteristics like tunable physicochemical and optical properties, easy processability, and excellent biocompatibility. In the present review, we highlight the advances of activatable NIR-II fluorescence probes in design, synthesis and applications for imaging pathological changes like reactive oxygen species (ROS), reactive nitrogen species (RNS), reactive sulfur species (RSS), pH, hypoxia, viscosity as well as abnormally expressed enzymes. This non-invasive optical imaging modality shows a promising prospect in targeting the pathological site and is envisioned for potential clinical translation.
... Different NBD receptors can be employed to develop multi-reactable probes to differentiate different biothiols. [204][205][206][207][208][209][210][211] For example, Yi, Sun, and coworkers installed the NBD amine motif and the NBD thioether/ether motif onto one coumarin fluorophore to construct dual-reactable probes 112 and 113 (Fig. 22). 204 Both probes demonstrate almost no background fluorescence due to dual-quenching effects from the both NBD moieties, but show a strong blue fluorescence of coumarin upon reaction with H 2 S. The fluorescence enhancement of probe 112, however, is low (o3 fold) in the presence of Cys/Hcy/GSH, which may be due to slower thiolysis of the NBD thioether moiety. ...
... In 2017, Lin and coworkers developed hybrid fluorescent dyad 117, which contains a hydroxyphenyl benzothiazole merocyanine (HBTMC) fluorophore connected to an NBD ether for triple-channel imaging. 208 As shown in Fig. 26, the HBTMC moiety serves as a recognition unit for H 2 S, and the NBD ether moiety is the recognition unit for Cys/Hcy. Probe 117 is non-fluorescent, which is likely due to the protected hydroxyl NBD chromophore and associated quenching of the HBTMC moiety by the NBD group. ...
... enhancement at 546 nm and 609 nm, respectively; treatment with GSH induced a 33.6-fold enhancement at 609 nm; and treatment with H 2 S induced a 52.7-fold enhancement at 485 nm. 208 Further DFT studies reveal that the response emission of probe 117 to biothiols is regulated by the PET and ICT effects, and HBTMC-SH has a larger energy difference between the lowest unoccupied molecular orbital (LUMO) and highest occupied molecular orbital (HOMO) than that of HBTMC. In addition, upon addition of high, non-physiologically relevant concentrations of H 2 S (5 mM) to the mixture of 117 and Cys/Hcy, both the green and red emissions gradually bleach, with the appearance of a signal in the blue channel. ...
... Azoles scaffolds have been associated with biological activities such as antitumor, antihypertensive, anti-histaminic, and antimicrobial activities ( Figure 1) (Aiello et al., 2008;Boyer et al., 2011;Daletos et al., 2014;He et al., 2017;Johnson et al., 2008;Ko et al., 2001;Leventhal et al., 2006;Mishra et al., 2019;Oksuzoglu et al., 2008;Sun et al., 2004;Wang et al., 2014). The synthesis of benzoxazoles has been studied extensively via different pathways, including (a) cyclization of 2-aminophenols with β-diketones (Mayo et al., 2014;Miao et al., 2019), carboxylic acids (Dev et al., 2016;Yuan et al., 2018), aldehydes (Layek et al., 2020;Matloubi Moghaddam et al., 2006;Sirgamalla et al., 2020), acyl chloride Zheng et al., 2019), isocyanides (Akbay et al., 2003), alcohols (Doan et al., 2019;Kaldhi et al., 2019), (b) oxidative intramolecular C-O coupling, (c) C-H arylation reaction, and (d) oxidative cyclization of phenolic Schiff base (Chang et al., 2002). ...
We have developed the green method for the synthesis of benzoxazoles and benzothiazoles with moderate to good yields using imidazolium chlorozincate (II) ionic liquid supported into Fe3O4 nanoparticles ([email protected]) under solvent-free sonication. The reaction was performed under mild conditions and only produced water as a sole byproduct. The reactions under solvent-free sonication showed advantages of faster reaction rate (30 min) and high yields of the products (up to 90%). Moreover, the [email protected] material was easily separated from the reaction mixture and can be recycled for five consecutive runs with a slight decrease in its catalytic performance (from 82 to 73%).
... The geometry optimization of ground states was computed with density functional theory (DFT) at the B3LYP/6-31 G* * levels. The HOMO and LUMO were employed to study the PET mechanism by complying with reference (He et al., 2017). Scheme 1. Illustration of the rational design of 1 based on Cd 2+ and H 2 L. ...
The abuse of antibiotics has triggered the rise of drug-resistance bacteria, which has seriously threatened public health globally. As a result, carrying out efficient and accurate antibiotic and bacteria identification are quite significant but challenge. Herein, an unprecedented Cd-MOF-based sensor, [CdL]n [1, H2L = 4-(2-methyl-1H-benzo[d]imidazol-1-yl) isophthalic acid] with multiple fluorescence response behaviour towards antibiotics and bacteria was developed. Single-crystal X-ray diffraction revealed that 1 is a mesomeric 2D bilayer, which is comprised of two opposite chiral mono-layers, each assembled by left-handed or right-handed helixes. More interestingly, 1 represented multiplex detection capability towards antibiotics and bacteria through two detection behaviors: toward nitro-antibiotics and chlortetracycline (CTC) via fluorescent quenching, while toward Staphylococcus albus (S. albus) via fluorescent enhancement. Remarkably, 1 showed a low limit of detection (LOD, 47 CFU/mL) accompanied with specificity in the detection of S. albus compared to other bacteria, such as Staphylococcus aureus, Acinetobacter baumannii, Klebsiella pneumonia, Pseudomonas aeruginosa and Escherichia coli. In addition, the LOD could reach to ppm level for nitro-antibiotics and CTC. Moreover, the practical application of 1 was further reinforced through the detection of nitro-antibiotics and CTC, as well as S. albus in fetal calf serum and river water.
... Biothiols play key roles in physiological and pathological processes [1][2][3][4]. Cys, glutathione (GSH) and homocysteine (Hcy) are the most common thiols in the body [5][6][7]. Cys is an essential amino acid in organism, which is transformed from methionine in vivo and participates in protein synthesis and cell redox process [8][9][10][11]. Abnormal levels of intracellular Cys can result in skin lesions [12,13], liver injury [14][15][16][17][18], cardiovascular disease and neurodegenerative disease [19,20]. ...
Cysteine (Cys) is an essential amino acid in organism, which is transformed from methionine in vivo and participates in protein synthesis and cell redox process. Therefore, the detection of Cys is of great significance. In this work, a novel fluorescent probe, (E)-3-(2-chloroquinolin-3-yl)-1-(pyren-3-yl) prop-2-en-1-one (PAQ) was designed and synthesized to specifically detect Cys. The response mechanism of the reaction between PAQ and Cys was due to the addition reaction of Cys to α,β-unsaturated ketone of PAQ. Interestingly, the addition of Cys induced significant fluorescence intensity enhancement at 462 nm. PAQ exhibited favorable sensing properties towards Cys such as the low limit of detection (0.27 μM) and fast response speed (2 min). In addition, PAQ displayed high selectivity and anti-interference ability toward Cys among various analytes. Notably, PAQ has been successfully used to image exogenous and endogenous Cys in HeLa cells.
... Due to the strong electron-withdrawing ability of nitro group on NBD moiety, the PET process in compound 1 could be prohibited, resulting in no emission [45]. Interaction of compound 1 with Cys/Hcy may break the ether bond based on aromatic thiolysis of NBD, releasing the fluorophore 1-(benzo[d]thiazol-2-yl)naphthalen-2-ol (compound 2) with the excited-state intramolecular proton transfer (ESIPT) properties and NBD-S-Cys/NBD-S-Hcy, followed by amino-substituted NBD chromophores NBD-N-Cys/NBD-N-Hcy after sequential nucleophilic substitution and intramolecular rearrangement, which will lead to fluorescence 'turn-on' in blue and green spectral region, respectively, upon exciting with different wavelengths. ...
... The response rate of 1 toward Cys, H 2 S n was faster than Hcy, GSH. The nucleophilicities of the biothiols could be attributed to different response rates [45]. The lowest pK a value of H 2 S 2 (pK a = 5.0) among these analytes rendered H 2 S 2 highly nucleophilic as a thiolate anion (HS 2 − ) under neutral condition [46]. ...
Biothiols of cysteine (Cys), homocysteine (Hcy), glutathione (GSH) and hydrogen polysulfides (H2Sn, n > 1) play vital roles in physiological and pathological processes. In this manuscript, a fluorescent probe (compound 1) for simultaneous detection and discrimination of Cys/Hcy, GSH and H2Sn was developed, employing fluorophore of 1-(benzo[d]thiazol-2-yl)naphthalen-2-oxy linked with 7-nitrobenzo-2-oxa-1,3-diazole (NBD) as a response unit and a quencher. Compound 1 exhibited different ratiometric colorimetric responses toward GSH at 430 nm and 375 nm from Cys/Hcy at 480 nm and 375 nm, while it displayed a different colorimetric response at 561 nm toward H2Sn. Meanwhile it could act as a naked-eye probe toward GSH, Cys/Hcy and H2Sn with corresponding solution color of light yellow, orange and purple, respectively. Upon excitation at 370 nm, compound 1 responded to all these biothiols with 'turn-on' blue fluorescence, whereas upon excitation at 470 nm, it could respond to Cys/Hcy with 'turn-on' green fluorescence. Data of mass spectra, lifetimes and ¹H NMR spectra interpreted the aromatic nucleophilic substitutions of compound 1 by GSH, Cys/Hcy and H2Sn to produce fluorophore1-(benzo[d]thiazol-2-yl)naphthalen-2-ol (compound 2) and corresponding NBD derivatives which could be discriminated through their absorption and fluorescence signals as well as solution colors. Furthermore, compound 1 was applied to image Cys/Hcy and H2Sn/GSH in 786-O cells.
