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Alkaline phosphatase (ALP)-induced

The development of enzyme-activatable photosensitizers and their combination with conventional chemodrugs for antitumor therapy are of great interest. In this work, we reported a strategy of constructing activatable photosensitizers by interfering with the intramolecular charge transfer (ICT) state of an orthogonal boron dipyrromethene (BODIPY) chromophore. By conjugating a cathepsin B substrate peptide with a photosensitizer, BDP-BDP-NH

Photolabile groups offer promising tools to study biological processes with high spatial and temporal control. In the investigation, we designed and prepared several new glycine amide derivatives of Sanger's reagent and demonstrated that they serve as a new class of photocages for Zn2+ and an acetylcholinesterase (AChE) inhibitor. We showed that the mechanism for photocleavage of these substances involves initial light-driven cyclization between the 2,4-dinitrophenyl and glycine methylene groups to form acyl benzimidazole N-oxides, which undergo secondary photoinduced decarboxylation in association with rupture of an amide bond. The cleavage reactions proceed with modest to high quantum yields. We demonstrated that these derivatives can be used in targeted intracellular delivery of Zn2+, fluorescent imaging by light-triggered Zn2+ release, and regulation of biological processes including the enzymatic activity of carbonic anhydrase (CA), negative regulation of N-methyl-d-aspartate receptors (NMDARs), and pulse rate of cardiomyocytes. The successful proof-of-concept examples described above open a new avenue for using Sanger's reagent-based glycine amides as photocages for the exploration of complex cellular functions and signaling pathways.

In this work, we reported a di-nuclear Cu(II) complex bearing double guanidinium arms for sensing pyrophosphate (PPi) with high selectivity and sensitivity. Using pyrocatechol violet (PV) and esculetine as colorimetric and fluorescent indicators respectively, the copper complex-indicator ensemble exhibited remarkable colorimetric and fluorescent changes upon addition of PPi in the aqueous solution. Comparing to the di-nuclear Cu(II) complex without guanidinium arms, the introduction of positively-charged guanidinium groups lead to 2.6 × 104-fold enhancement on the binding affinity toward pyrophosphate (PPi). The ensemble containing copper complex and PV was further used to monitor the hydrolysis of PPi catalyzed by pyrophosphatase (PPase).

New chiral bisboronic receptors based on pyrene-excimer were synthesized and applied for the determination of absolute configuration and enantiomeric composition of tartaric acid. The distinction was visualized by portable UV lamp in certain concentration range. There were three ways for the sensors to enantioselectively recognize tartaric acid, including the fluorescence spectrum, UV–vis spectrum, and CD spectrum. The enantiomeric excess of tartaric acid was measured quantitatively by using fluorescence analytical technique. Compared with the previous chiral boronic acid sensors, sensor 1 showed weaker background fluorescence and excellent chiral recognition ability of D/ l -tartaric acid throughout the whole pH range.

Phospholipase D (PLD), as an enzyme that catalyses the hydrolysis of L-α-phosphatidylcholine to produce phosphatidic acid, plays an important role in regulating biological processes. In this work, polydiacetylenes (PDAs) bearing imidazolium as head group are reported for the efficient detection of PLD activity. Owing to the strong interaction between negatively charged phosphatidic acid and positively charged imidazolium moieties of PDAs, the PDAs were found to produce a colour transition from blue to red, and an increase in fluorescence. No obvious changes to PDAs were observed when PLD was absent in the reaction, or when the activity of PLD was inhibited by halopemide. The colour and fluorescence changes of PDAs are attributed to the generation of phosphatidic acid in the PLD-catalysed reaction. Furthermore, a paper sensor based on PDAs was constructed and exhibited convenient and sensitive detection of PLD activity.

A fluorescent probe is constructed to quickly and accurately detect bisulfite. The detection mechanism was considered to operate via the bisulfite, causing deprotonation of amido bond of 8-aminoquinoline derivative leading to fluorescence enhancement. The probe has a good selectivity for bisulfite over the other competitive substances such as F−, Cl−, Br−, I−, C2O42−, NO2−, ClO4−, OAc−, PO43−, CO32−, HCO3−, HS−, HSO4−, SCN−, SO42−, S2O32−, Cys, Hcy and GSH. There is a good linear relationship between fluorescence intensity and the concentration of bisulfite in the range of 0–200 μM. The limit of detection was calculated to be 0.61 μM. Furthermore, the probe has also been successfully used for imaging bisulfite in living cells.

This paper describes the design and synthesis of a benzothiazole-based fluorescent probe (H1) for zinc and cadmium ion detection and discrimination, using cysteine as an auxiliary reagent. Among the various metal ions tested, zinc and cadmium ions induced blue-shifted emissions of probe H1 from 573 nm to 520 nm and 540 nm, respectively. The addition of cysteine caused the emission of H1-Cd2+ to red-shift back to 573 nm. In contrast, the emission of H1-Zn2+ with the addition of cysteine only decreased without any red-shift of wavelength. Furthermore, confocal laser scanning micrographs of HeLa cells demonstrated satisfactory cell permeability of H1 and selectivity toward zinc and cadmium ions in living cells. Test strip experiments suggest that probe H1 can recognise zinc and cadmium ions together by a remarkable fluorescence change, thus providing a convenient method for tracking zinc and cadmium ions in biological systems.

l -Arginine ( l -Arg) and l -lysine ( l -Lys) are both essential amino acids and paly significant roles in human beings and other living organisms. Therefore, it is necessary to develop the feasible methods with high selectivity and sensitivity for the detection of l -Arg and l -Lys. Herein, aminopyrene modified diacetylene monomer (PCDA-PY) was prepared and incorporated into diacetylene monomer (PCDA) to form polydiacetylene (PDA) vesicles. With the assist of Mg2+, PDAs system underwent colorimetric and fluorescent changes upon the addition of l -Arg or l -Lys. The introduction of Mg2+ and pyrene moiety makes PDAs system more sensitive toward l -Arg or l -Lys. Furthermore, an “OR AND” logic gate was constructed based on the optical changes of PDAs system with the three elements including Mg2+, l -Arg and l -Lys.

In the present study, a mitochondria-targeted fluorescent probe FL based on fluorescein derivative for hypochlorite sensing was designed and synthesized. The probe FL showed highly selective to HOCl among various reactive oxygen/nitrogen species. With the increasing amount of HOCl from 0 to 50 μM, a linear correlation between the fluorescence intensity of FL at 530 nm and the concentration of HOCl was found. The detection limit is calculated to be 0.068 μM. Furthermore, the probe demonstrated a perfect mitochondria targetable ability and it was successfully applied to image mitochondrial HOCl in living HeLa cells. The success of subcellular imaging indicated that the mitochondria-targetable probe FL might be further used to investigate biological functions and pathological roles of HOCl at organelle levels.

Aluminum is the third (after O and Si) most abundant metal in the earth’s crust and associates with neurological diseases when abnormal level of Al3+ occurs in nervous center. Developing highly sensitive and selective methods for Al3+ detection is of significant interest. In this work, we developed an excited state intramolecular proton transfer (ESIPT) and aggregation-induced emission (AIE) active fluorescent probe for ratiometric detection of Al3+ in aqueous medium and living cells. The BTZ-SF can detect Al3+ with high selectivity and a good linear relationship (R2 = 0.9911) between fluorescence intensity ratio (I476 nm/I568 nm) and Al3+ concentration (0–100 μM). In addition, the detection limit was calculated as low as 2.2 μM. The single crystal structure of BTZ-SF–Al clearly exhibited the interaction between BTZ-SF and Al3+ with a hexa-coordinated structure. Furthermore, confocal fluorescence images of HeLa cell indicated that BTZ-SF could be used for monitoring Al3+ in living cells. Finally, a test s...

Hypochlorous acid (HOCl) plays a vital role in many physiological and pathological processes as one of reactive oxygen species (ROS). Developing highly sensitive and selective methods for HOCl detection is of significant interest. In this work, we developed a benzothiazole based probe 1 for ratiometric fluorescence detection of hypochlorite in living cells. The probe can detect HOCl with high selectivity, fast response (within 30 s) as well as low detection limit (0.18 mmol/L). Fluorescence co-localization studies demonstrated that probe 1 was a mitochondria-targeted fluorescent probe. Furthermore, confocal fluorescence images of HeLa cell indicated that probe 1 could be used for monitoring intracellular HOCl in living cells. Finally, test strips experiment suggests that the probe 1 can detect the hypochlorous acid in tap water accompanied by remarkable color change.

Photolabile groups offer promising tools to study biological processes with high spatial and temporal control. In the investigation, we designed and prepared several new glycine amide derivatives of Sanger's reagent and demonstrated that they serve as a new class of photocages for Zn2+ and an acetylcholinesterase (AChE) inhibitor. We showed that the mechanism for photocleavage of these substances involves initial light-driven cyclization between the 2,4-dinitrophenyl and glycine methylene groups to form acyl benzimidazole N-oxides, which undergo secondary photoinduced decarboxylation in association with rupture of an amide bond. The cleavage reactions proceed with modest to high quantum yields. We demonstrated that these derivatives can be used in targeted intracellular delivery of Zn2+, fluorescent imaging by light-triggered Zn2+ release, and regulation of biological processes including the enzymatic activity of carbonic anhydrase (CA), negative regulation of N-methyl-d-aspartate receptors (NMDARs), and pulse rate of cardiomyocytes. The successful proof-of-concept examples described above open a new avenue for using Sanger's reagent-based glycine amides as photocages for the exploration of complex cellular functions and signaling pathways.

In this paper, we designed and synthesized three benzothiazole-based fluorescent probes L1, L2, and L3 for zinc ion detection. Among various metal ions, only the zinc ion exhibited fluorescence enhancement at 475 nm accompanied by the blue-shift emission wavelength in HEPES buffer solution containing probes. Through titration experiment, the detection limit of L1 for zinc ion sensing was calculated to be as low as 7 nM, which showed a high sensitivity. Furthermore, the confocal laser scanning micrographs of HeLa cells demonstrate good cell permeability of probe L1 and selective detection of zinc ion in living cells. The L1–Zn2+ complex was further used for pyrophosphate (PPi) sensing in HEPES buffer solution, the limit of detection was calculated to be as low as 60 nM. L1–Zn2+ can monitor the enzyme catalyzed degradation process of PPi, thus providing a meaningful way for tracking of zinc ion and pyrophosphate in biological systems.

Highly sensitive and selective fluorescent probes 1 and 2 for detection of palladium ions (Pd2+) were synthesized based on excited-state intramolecular proton transfer process (ESIPT) using 2-(2′-hydroxy-)benzothiazole moiety. Different metal ions were used to optimize their sensitivity and selectivity but best results were obtained with Pd2+. Probe 1 produced green fluorescence with Stokes shift of about 163 nm upon addition of Pd2+, whereas probe 2 displayed red fluorescence with a large Stokes shift of about 217 nm under similar conditions. The detection limits of 1 and 2 to Pd2+ were found to be 285 nM and 14.6 nM, respectively. Mechanistic aspects of probes 1 and 2 were discussed to account for the optical changes leading to the strong ESIPT fluorescence in very short duration. Furthermore, the portable test strips were also prepared by direct deposition of the probe molecules onto the filter paper to detect the lowest possible ppm levels of Pd2+.

Developing highly sensitive and selective methods for HOCl/OCl– detection is of significant interest. In this work, two fluorescent probes based on mono- and bis-formylated fluorescein, FN-1 and FN-2, were developed. The probes exhibit rapid response and high selectivity to HOCl/OCl– over other reactive oxygen species (ROS)/reactive nitrogen species (RNS). Furthermore, a good linearity between the fluorescent intensity at 529 nm and the concentration of HOCl/OCl– in the range 0–10 μM were presented. The probes FN-1 and FN-2 showed detection limits as low as 0.21 and 0.23 μM, respectively. The confocal laser scanning micrographs of HeLa cells confirmed cell permeability of the two probes and their abilities to detect HOCl/OCl– in living cells. Compared to compound FN-1, FN-2 has lower background fluorescence and a higher speed of the reaction with HOCl/OCl– which made it a better option for the detection of HOCl/OCl– in aqueous solution.

A new dinuclear-copper(II) complex ( Cu-L 2 ) with two ammonium arms based on bis-2-((pyridin-2-ylmethylamino)methyl)phenol as the coordinated unit was synthesized. The complex exhibited high affinity with pyrophosphate (PPi) in aqueous solution. Using pyrocatechol violet (PV) as a colorimetric indicator, the indicator displacement assay (IDA) was carried out to determine the binding constant between the complex and PPi. A ca. 784-fold enhancement was founded when compared Cu-L 2 to ammonium-free counterpart ( Cu-L 1 ) . The new dinuclear complex was successfully used to monitor the hydrolysis of PPi catalyzed by pyrophosphatase (PPase). Furthermore, by employing esculetine as a fluorescent indicator, the complex was also used to detect PPi released during polymerase chain reaction (PCR).

Zinc is of great importance to humans and other biological systems. For example, too high or low levels of zinc(II) ions (Zn2+) can result in various human disease states, and poor handling of Zn2+ leads to environmental pollution. Owing to the important roles played by this metal, many convenient, low-cost and easy-to-operate fluorescence probes for Zn2+ detection have been developed. Chief among these are fluorescence-based sensors that have high sensitivities and selectivities. In this review, we describe the fluorescence probes for Zn2+ which have been prepared and assessed in the time period since 2015. The presentation is organized according to different fluorophore families, including quinoline, naphthalene, coumarin, rhodamine, naphthalimide, pyrene, fluorescein, phenol derivatives, as well as several other fluorophores. The discussion of each probe concentrates mainly on its mode of action.

Traditional fluorescent sensors for simultaneous detection of metal ions require the use of specially designed fluorescent probes. In this manuscript, we have employed a new strategy for the design of a sensor for simultaneous detection of metal ions that is based on a fluorescent probe encapsulated hydrogel matrix. An investigation designed to assess this strategy led to the development of a novel dual fluorescent encapsulated hydrogel microsphere sensor for sensitive and simultaneous detection of Al3+ and Hg2+. The hyperbranched poly (poly (ethylene glycol) diacrylate) (HB-PEGDA) and thiolated sodium alginate (SA-SH) composite hydrogel microspheres used to construct the sensor, which contain two fluorescent probes encapsulated in a highly dense manner, were prepared by using a self-assembly method in conjunction with a microfluidic device. The functionalized hydrogel microspheres were shown to exhibit high selectivity for Al3+ and Hg2+ among various metal ions with a detection limit of 70 nM and 120 nM, respectively. In addition, the hydrogel microspheres can be readily separated from test samples and utilized for repeated use by removing Al3+ and Hg2+ by addition of a solution containing EDTA and KI. Compared with previously devised sensors, the new HB-PEGDA/SA-SH composite hydrogel microspheres containing two encapsulated fluorescent probes are readily prepared and effective for simultaneous detection of two different metal ions.

In this paper, highly sensitive and selective fluorescent probe 1 for GSH is designed and synthesized based on modulation of the excited-state intramolecular proton transfer (ESIPT) process of 2-(2′-hydroxy-3′-ethoxyphenyl)benzothiazole. Upon introducing GSH in neutral solution containing CTAB micelles, dinitrophenyl, the protecting group of the probe, is removed via the nucleophilic substitution, thereby retrieving the ESIPT process of 2-(2′-hydroxy-3′-ethoxyphenyl)benzothiazole, which results in a fluorescence enhancement at 485 nm. Additionally, the fluorescence intensity of the probe is linearly proportional to GSH concentration ranging from 0 to 100 μM and the obtained detection limit is as low as 0.81 μM. The enhanced selectivity toward GSH over Cys and Hcy is also attributed to one more carboxyl group in GSH. Importantly, the probe is successfully utilized for monitoring GSH in living HeLa cells.

Fluoride plays an important role in our daily life as it associates with a variety of biological and pathological processes. Hence, an analytic method that can detect fluoride ions under physiological conditions with high sensitivity and specificity, and fast response, is needed. Herein, we introduced a dioxetane-based chemiluminescent probe, CL-F, specifically designed for the detection of fluoride ions in physiological environment. The probe CL-F emitted strong green chemiluminescent light within 1 min when incubating with fluoride ions specifically. The linear range for sensing fluoride ions and limit of detection were determined to be 0–30 μM and 0.91 μM, respectively. The probe CL-F was then successfully applied in quantifying fluoride ions in toothpaste and in vivo imaging in living mice, demonstrating CL-F as a promising tool for sensing fluoride ion in vitro and in vivo.

Using cyanine dye-coupling 2-pyridylmethyl chelating unit as fluorescent probe, we successfully developed an indicator of copper clock reaction to monitor the process of cysteine (Cys) oxidation. During the monitoring assay, the fluorescent changes reflected three sequential reaction and binding behaviors including oxidation of Cys, oxidation of Cu(I) and binding between Cu(II) and the oxidation product cystine (Cys-Cys). Because the different kinetic trajectories were obtained when used Cys, GSH and Hcy as the substrates, respectively, a new strategy for distinguishing Cys from GSH and Hcy was further developed using the cyanine dye-coupling Cu(II) complex.

Enzymes are a class of macromolecules that function as highly efficient and specific biological catalysts requiring only mild reaction conditions. Enzymes are essential to maintaining life activities, including promoting metabolism and homeostasis, and participating in a variety of physiological functions. Accordingly, enzymatic levels and activity are closely related to the health of the organism, where enzymatic dysfunctions often lead to corresponding diseases in the host. Due to this, diagnosis of certain diseases is based on the levels and activity of certain enzymes. Therefore, rapid real-time and accurate detection of enzymes in situ are important for diagnosis, monitoring, clinical treatment and pathological studies of disease. Fluorescent probes have unique advantages in terms of detecting enzymes, including being simple to use in highly sensitive and selective real-time rapid in-situ noninvasive and highly spatial resolution visual imaging. However, fluorescent probes are most commonly used to detect oxidoreductases, transferases and hydrolases due to the processes and types of enzyme reactions. This paper summarizes the application of fluorescent probes to detect these three types of enzymes over the past five years. In addition, we introduce the mechanisms underlying detection of these enzymes by their corresponding probes.

Reactive oxygen (ROS) and nitrogen (RNS) species cause oxidative and nitrosative stresses, respectively. These stresses are implicated not only in diverse physiological processes but also in various pathological processes, including cancer and neurodegenerative disorders. In addition, some ROS and RNS in the environment are pollutants that threaten human health. As a consequence of these effects, sensitive methods, which can be employed to selectively monitor ROS and RNS in live cells, tissues and organisms as well as in environmental samples, are needed so that their biological roles can be understood and their concentrations in environmental samples can be determined. In this review, fluorescent, luminescent and colorimetric ROS and RNS probes, which have been developed since 2011, are comprehensively discussed.