Dual-functional Fluorescent Probe Research Articles

Metal-organic frameworks constructed with base-acid mixed ligands and its potential as dual-functional fluorescent probe toward Fe3+/Al3+ ions

By virtue of mixed ligand strategy (2,5-Bis(1H-pyrazole-4-ylmethylene)-cyclopentanone and 2,5-dihydroxyterephthalic acid / terephthalic acid), four new metal–organic frameworks (MOFs) were fabricated and characterized. When 2,5-dihydroxyterephthalic acid acted as auxiliary ligand, MOFs 1–3 show 1D chain structure. 4 containing auxiliary ligand terephthalic acid (without − OH group) displays a 2D layer structure. Notably, 1 exhibits the significant selectivity toward Fe3+ and Al3+ ions, whereas the fluorescence intensity of 4 changed slightly in the presence of various metal ions, indicating that uncoordinated –OH in 1 plays an important role in sensing process. Moreover, it is revealed that 1 could act as dual-functional fluorescent probe toward Fe3+ and Al3+ with selectivity, sensitivity and reusability, and it could be prepared as fluorescent test papers for rapid on-site detection.

Dual-Functional AIE Fluorescent Probe for Visualization of Lipid Droplets and Photodynamic Therapy of Cancer.

Abnormal lipid droplets (LDs) are known to be intimately bound with the occurrence and development of cancer, allowing LDs to be critical biomarkers for cancers. Aggregation-induced emission luminogens (AIEgens), with efficient reactive oxygen species (ROS) production performance, are prime photosensitizers (PSs) for photodynamic therapy (PDT) with imaging. Therefore, the development of dual-functional fluorescent probes with aggregation-induced emission (AIE) characteristics that enable both simultaneous LD monitoring and imaging-guided PDT is essential for concurrent cancer diagnosis and treatment. Herein, we reported the development of a novel LD-targeting fluorescent probe (TDTI) with AIE performance, which was expected to realize the integration of cancer diagnosis through LD visualization and cancer treatment via PDT. We demonstrated that TDTI, with typical AIE characteristics and excellent photostability, could target LDs with high specificity, which enables the dynamic tracking of LDs in living cells, specific imaging of LDs in zebrafish, and the differentiation of cancer cells from normal cells for cancer diagnosis. Meanwhile, TDTI exhibited fast ROS generation ability (achieving equilibrium within 60 s) under white light irradiation (10 mW/cm2). The cell apoptosis assay revealed that TDTI effectively induced growth inhibition and apoptosis of HeLa cells. Further, the results of PDT in vivo indicated that TDTI had a good antitumor effect on the tumor-bearing mice model. Collectively, these results highlight the potential utility of the dual-functional fluorescent probe TDTI in the integrated diagnosis and treatment of cancer.

A benzothiophene-based fluorescent probe with dual-functional to polarity and cyanide for practical applications in living cells and real water samples

Polarity is a significant intracellular environmental parameter associated with cancer, while cyanide (CN−) is known to be highly toxic to humans. In this work, we designed a dual-functional fluorescent probe (TPABT) for simultaneous detection of polarity and CN−. As a polarity sensor, the probe exhibits NIR emission at 766 nm in 1,4-dioxane (non-polar solvent), whose emission intensity is 71-fold stronger than that in water (polar solvent). Meanwhile, the fluorescence intensity and quantum yield are linearly related to solvent polarity, confirming the polarity response ability of TPABT. For cell polarity detection, low cytotoxicity and polarity sensitivity of probe enable the applications for differentiating cancer cells (HeLa, 4TI) from normal cells (HUV, 3 T3) and monitoring the polarity changes of 4TI cells. As a CN− sensor, TPABT displays a turn-on fluorescence at 640 nm upon the addition of CN−, with advantages of anti-interference, response in aqueous media and low detection limit (22 nM). Additionally, we further explored the practical applications of TPABT for CN− determination in three types of real water samples (drinking water, tap water and lake water) and living cells. Notably, TPABT responses to polarity and CN− in two independent fluorescence channels of 766 and 640 nm, respectively, ensuring the dual functions for polarity and CN− sensing. Consequently, this multi-responsive fluorescent probe TPABT is promising to diagnose polarity-related diseases and detect CN− in real environments.

Dual-Functional Fluorescent Probe in the Diagnosis of Liver Injury and the Evaluation of Drug Therapy with Double Signal Amplification

Dual-Functional Fluorescent Probe in the Diagnosis of Liver Injury and the Evaluation of Drug Therapy with Double Signal Amplification

A Dual Functional Fluorescent Probe Based on Phenothiazine for Detecting Hg2+ and ClO- and its Applications.

For the efficient detection of Hg2+ and ClO-, a double-analyte-responsive fluorescent probe PTB was successfully synthesized by combining N-butyl-3-formyl phenothiazine with hydrazine benzothiazole, and designing a specific reaction site for recognizing two analytes (Hg2+ and ClO-) in a compound. It was shown that probe PTB successfully formed a stable complex with Hg2+ in the coordination ratio of 2:1 by using the strong sulfur affinity of Hg2+, which resulted in a remarkable "turn-off" effect, with a quenching efficiency of 92.5% and four reversible cycles of Hg2+ fluorescence detection. For the fluorescence detection of Hg2+, the response time is fast (≤ 2min) and the detection limit is low (7.8nM), showing extremely high sensitivity, and the performance is obviously better than that of the reported fluorescent probes for detecting Hg2+. In particular, probe PTB has low toxicity and good biocompatibility, and has been successfully used for imaging of Hg2+ in living cells. Moreover, probe PTB uses thioether bond and carbon-nitrogen double bond as reaction sites to detect ClO-, which has large Stokes Shift (149nm), good selectivity, high quenching efficiency (96.5%) and fast time response (about 10s), and successfully detects ClO- in actual water samples. The dual functional fluorescent probe PTB is sensitive for Hg2+ and ClO-. It has been successfully used for making pH fluorescent test paper and imaging detection of exogenous Hg2+ in VSMC cells with low toxicity.

Boron and nitrogen co-doped carbon dots as the dual functional fluorescent probe for Fe3+ and pH detection

Carbon dots doped with boron and nitrogen atoms (B, N-CDs) were designed and prepared by hydrothermal strategy using citric acid, urea and borax as raw materials. The structure and optical properties of B, N-CDs were characterized by various characterization technologies. The results showed that the B, N-CDs exhibited good mono-dispersion, excellent fluorescence stability, and high fluorescence intensity (quantum yield up to 32 %). A dual-functional Fe3+ and pH detection platform based on B, N-CDs was constructed. The Fe3+ sensing method based on B, N-CDs fluorescence quenching showed an excellent linear relationship between 0.044–70 μM (R2 = 0.994), with a detection limit as low as 0.044 μM. Then, this detection method was successfully applied to the high-accuracy detection of Fe3+ in water samples and iron supplement tablets. The study of the quenching mechanism showed that the fluorescence of B, N-CDs was quenched by Fe3+ in two ways: static quenching and dynamic quenching. Moreover, B, N-CDs can also be used as a pH fluorescence sensor in the ranges of pH 2.0–4.8 and 5.2–7.6. The developed sensing system based on B, N-CDs has high selectivity and sensitivity for the detection of Fe3+, and a wide detection range for pH.

Rational construction and evaluation of a dual-functional near-infrared fluorescent probe for the imaging of Amyloid-β and mitochondrial viscosity

Alzheimer's disease is a fatal, incurable, chronic neurodegenerative disease. Diagnosis in its early and even preclinical stages will be beneficial for its prevention and treatment. In the accepted pathological theory, abnormal accumulation of Aβ protein and abnormal mitochondrial function, including changes in mitochondrial viscosity, is closely related to Alzheimer's disease. To date, rare fluorescent probes have been reported that can simultaneously image Aβ plaques and mitochondrial viscosity. Therefore, the development of a dual-functional fluorescent probe for real-time fluorescence imaging of Aβ plaques and mitochondrial viscosity is crucial to discover a novel approach and strategy for the treatment of Alzheimer's disease, and to understand the pathological process and crosstalk between different biomarkers of Alzheimer's disease. Herein, we rationally designed and synthesized a series of fluorescent probes QM-SF-1∼5 with dimethylamino-quinolinium as the skeleton and thiophene as the π bridge to connect the groups with different electron-push/pull capacities. Among them, QM-SF-2 exhibited excellent properties such as large Stokes shift (168 nm), near-infrared emission (689 nm), and high selectivity and sensitivity (limit of detection was 1.07 μM) to Aβ aggregate and mitochondrial viscosity changes, indicating its promising prospects as a dual-functional imaging tool in the pathological study of Alzheimer's disease.

Synthesis and application of a dual-functional fluorescent probe for sequential recognition of Zn2+and glyphosate

A novel fluorescent probe QL was designed and synthesized based on Schiff base by 2-hydrazinobenzothiazole to sequentially recognize Zn2+ and glyphosate. The probe QL was capable to detect Zn2+ in DMSO solution via fluorescence enhancement, and exhibited good selectivity and anti-interference ability. The combination mode was 1:2 between probe QL and Zn2+ according to the method of job’s plot, and the detection limit of probe QL for Zn2+ was found to be 4.51 × 10−8 M, which exhibited excellent sensitivity. Furthermore, the system QL-Zn2+ could detect glyphosate by causing fluorescence quenching response and with a color change from yellow to colorless for naked-eye detection. The detection limit for glyphosate was found to be 4.93 × 10−8 M, which was far below the Standards for Drinking Water Quality (GB5749-2006) acceptable limits (0.7 μg/mL for glyphosate). Notably, the probe QL and its complex QL-Zn2+ have been successfully applied to detect Zn2+ and glyphosate in water, respectively.

A dual functional fluorescent probe based on naphthalimide for detecting Cu2+ and pH and its applications

Cu2+ and pH play a key role in life systems and it is necessary to develop an effective detection method. In view of the significant advantages of the fluorescent probe, we have synthesized a dual functional fluorescent probe NCNB based on naphthalimide for detecting Cu2+ and pH. The probe NCNB is sensitive (LOD = 44.8 nM) and fast for Cu2+ (within 150 s). It can be used not only for qualitative and quantitative detection of Cu2+ in actual water samples, but also for making pH fluorescent test paper with good effect. In addition, the probe NCNB has been successfully used for imaging detection of exogenous Cu2+ in Caco-2 cells with low toxicity.

A dual-functional fluorescent probe based on kaolin nanosheets for the detection and separation of aluminum ions

Aluminum ions (Al3+) are closely related to environmental protection and human health, thus the detection and separation of Al3+ is of great significance. In this study, a dual-functional fluorescent probe for the detection and separation of Al3+ was successfully developed by grafting fluorophore onto kaolin nanosheets. The probe has the characteristics of good dispersion without the involvement of organic solvents, excellent specificity, the low limit of detection (0.55 µM), and fast response time (10 min). And the recovery rates of Al3+ using this probe are in the range from 93.0% to 101.8%, and the corresponding relative standard deviations are in the range from 3.5% to 5.8%. Besides, it also can remove Al3+ in aqueous solution through adsorption, and the removal rates is in the range from 95.1% to 99.3% when the concentration of the probe is 0.4 mg/mL. The probe combines detection and separation functions, overcomes the defect that single-function materials can only be used for detection or separation, which has important significance and good application value.

A dual-functional fluorescent probe for simultaneous visualization and quantification of Au and Pd species in environmental and biological systems

Gold (Au) and palladium (Pd) species have been widely used in synthetic chemistry, biology, and environmental sciences, raising hard-to-ignore health and environment risks due to their potential toxicity. Herein, a novel dual-functional fluorescent probe was rationally designed and developed for simultaneous quantification and visualization of Au3+ and Pd species in the environmental and biological systems. Significant fluorescence enhancement at 484 and 606 nm and color changes were observed upon addition of Au3+ and Pd0 with high sensitivity. The detection limit for Au3+ and Pd0 was as low as 68 nM and 7 nM, respectively. Combined with smartphone chromaticity and dual-channel fluorescence imaging analysis, this probe was successfully applied to the quantification and visualization of Au3+ and Pd species in real water samples. Thus, simultaneous naked-eye visualization and quantification of Au3+ and Pd0 in real water samples was achieved using this probe. The probe was also successfully applied to fluorescence imaging of Au3+ and Pd0 in HeLa cells and zebrafish, promoting the monitor and understanding about gold and palladium species in environmental and biological systems.

Ultra-sensitive detection of hydrogen peroxide and levofloxacin using a dual-functional fluorescent probe

Herein, a flower-shaped fluorescent probe was proposed for hydrogen peroxide (H2O2) and levofloxacin (LVF) sensing based on MoOx QDs@Co/Zn-MOFs with porous structure. Both MoOx QDs and Co/Zn-MOFs exhibited peroxidase-like properties, and the combination of them greatly aroused the synergistic catalytic capabilities between them. In o-Phenylenediamine (OPD)−H2O2 system, MoOx QDs@Co/Zn-MOFs efficiently catalyzed H2O2 to produce •OH and then oxidized OPD to its oxidation product (OxOPD). The OxOPD could not only emit blue fluorescence, but also inhibit the fluorescent intensity of MoOx QDs through fluorescence resonance energy transfer (FRET). Moreover, when introducing LVF into the system, the fluorescent intensities of MoOx QDs increased along with the aggregation of themselves while that of OxOPD remained unchanged, which was explained by the joint behavior of FRET and photo-induced electron transfer (PET) instead of the conventional aggregation-induced emission enhancement (AIEE). With these observation, the proposed probe was employed for H2O2 and LVF determination in biological samples with the limit of detection (LOD) of 32.60 pmol/L and 0.85 μmol/L, respectively, suggesting the method holds great promises for trace H2O2 and LVF monitoring in eco-environment.

Visualizing the Interplay of Lipid Droplets and Protein Aggregates During Aging via a Dual-Functional Fluorescent Probe.

Fluorescence imaging the interplay between lipid droplets (LDs) and protein aggregates (PAs) is extremely valuable for elucidating molecular mechanisms of aging. Here, we describe the first dual-functional fluorescent probe, LW-1, for simultaneously imaging LDs and PAs in distinct fluorescence channels to dissect interplaying roles between LDs and PAs during aging. Notably, based on an intriguing mechanism of hydrogen bonds regulating single bond rotation, LW-1 selectively detected LDs in a red channel. Meanwhile, based on another mechanism of the hydrogen bond regulating intramolecular charge transfer efficiency, probe LW-1 further detected PAs in an NIR channel. Practical applications showed that LW-1 was capable of concurrently detecting LDs and PAs in living cells. Moreover, simultaneously imaging LDs and PAs in intestine tissues of mice at different aging degrees was conducted. The results denoted that the PAs level in the intestine tissue increased dramatically with aging, accompanying the buildup of LDs. Significantly, the interplay between LDs and PAs during aging was observed. These evidences demonstrated that the PAs level was closely related with aging processes in intestine tissues, while LDs were formed correspondingly to interact with PAs, suggesting that excessive PAs can be loaded into LDs and then be removed by lipophagy.

A novel dual-functional fluorescent probe for imaging viscosity and cysteine in living system.

Abnormal changes in intracellular viscosity and cysteine are both associated with several important biological processes such as reversible redox reactions, which play a pivotal role in the process of inflammation. However, it remains unclear how cysteine and viscosity are altered in inflammation. Herein, we firstly report a high-sensitivity and -selectivity near-infrared imaging probe (FCV) for tracking intracellular viscosity and endogenous cysteine. This dual-functional probe displays excellent photostability and large Stokes shifts. FCV exhibits a 54-fold enhancement in fluorescence emission at 560 nm with increasing Cys (λex = 420 nm) and an approximately 63-fold enhancement at 660 nm (λex = 460 nm) with increasing viscosity from 1.0 cP to 952.5 cP. Moreover, FCV reveals the synergistic relationship between viscosity and cysteine in the inflammation model of living cells and zebrafish for the first time. Thus, FCV is a promising vehicle to identify the changes in Cys and viscosity in associated diseases.

A Dual-Functional Fluorescent Probe for Simultaneous Visualization and Quantification of AU and Pd Species in Environmental and Biological Systems

A Dual-Functional Fluorescent Probe for Simultaneous Visualization and Quantification of AU and Pd Species in Environmental and Biological Systems

Two birds with one stone: A novel dual-functional fluorescent probe for simultaneous monitoring and real-time imaging of alkaline pH and viscosity in living cells

Viscosity and pH are two crucial microenvironment parameters, and their abnormal fluctuations at the cellular level can act as key indicators of various diseases diagnosis. Considering that the traditional viscosity/pH meters cannot work in the cellular environment, developing some viscosity/pH-sensitive fluorescent probes is urgently demanded. Herein, a novel dual-functional camphor-based fluorescent probe PN-SP for viscosity and pH detection was constructed based on spiropyran open/closed-ring switching strategy. PN-SP exhibited an intense green emission in response to alkaline pH while a bright red fluorescence was observed in high-viscosity media, which could avoid some problems caused by the use of multiple probes such as cross-talk spectrum and different localizations. The sensing performances of PN-SP were also demonstrated for monitoring viscosity and pH fluctuations in living HeLa cells by means of different emisson channels. Therefore, we believed that this work will provide guidance for designing some dual-functional fluorescent probes.

Dual-Channel Imaging of Amyloid-β Plaques and Peroxynitrite To Illuminate Their Correlations in Alzheimer's Disease Using a Unimolecular Two-Photon Fluorescent Probe.

Alzheimer's disease (AD) involves multiple pathological factors that mutually cooperate and closely contact to form interaction networks for jointly promoting the AD progression. Therefore, the comonitoring of different factors is particularly valuable for elucidating their level dynamics and complex interactions. However, such significant investigations remain a major challenge due to the lack of unimolecular fluorescent probes capable of simultaneous and discriminative visualization of multiple targets. To address this concern, as proof of principle, we rationally designed a unimolecular fluorescent probe to discriminate and simultaneously profile amyloid-β (Aβ) plaques and peroxynitrite (ONOO-), which are both the pronounced AD pathological factors. Herein, a novel ONOO- reaction trigger was installed onto an Aβ plaque binding fluorophore to generate a dual functional fluorescent probe, displaying completely separate spectral responses to Aβ plaques and ONOO- with high selectivity and sensitivity. With this probe, for the first time, we comonitored the distribution and variation of Aβ plaques and ONOO- through two independent fluorescence channels, demonstrating their close apposition and tight correlation during AD course in live cell and mouse models through two-photon imaging mode. Notably, Aβ aggregates induce the neuronal ONOO- generation, which conversely facilitates Aβ aggregation. The two critical events, ONOO- stress and Aβ aggregation, mutually amplify each other through positive feedback mechanisms and jointly promote the AD onset and progression. Furthermore, by coimaging of the level dynamics of Aβ plaques and ONOO-, we found that the cerebral ONOO- is a potential biomarker, which emerges earlier than Aβ plaques in transgenic mouse models. Overall, the dual-channel responsive performance renders this probe as a powerful imaging tool to decipher Aβ plaque-ONOO- interactions, which will facilitate AD-associated molecular pathogenesis elucidation and multitarget drug discovery.

A hydrazone dual-functional fluorescent probe based on carbazole and coumarin groups for the detection of Cu2+ and ClO−: Application in live cell imaging and actual water samples

A new hydrazone derivative LL3 based on carbazole and coumarin was prepared by the condensation of 7-diethylaminocoumarin-3-carbohydrazide with 3-aldehyde-N-butyl carbazole and its structure was characterized using FT-IR, 1H NMR, 13C NMR, MS and elemental analysis techniques. LL3 could be used as a dual-functional fluorescent probe to identify Cu2+ and ClO−. Probe LL3 could recognize Cu2+ and formed a 2:1 complex. Under a 365 nm UV lamp, the color changed from yellowish to blue-green which could be readily distinguished by the naked eye. Meanwhile, under the catalysis of ClO−, the imine bond of probe LL3 was hydrolyzed to obtain carbazolealdehyde, resulting in specific UV-Vis and fluorescence phenomena, so as to realize the detection of ClO−. The recognition mechanism was proved by spectrometric titrations, Job’s plots, FT-IR, 1H NMR, mass spectroscopy (MS) and density functional theory (DFT) calculation analysis. The results of live cell imaging showed that LL3 could be used as a fluorescent probe to detect Cu2+ and ClO− in Hela cells. In addition, the probe LL3 could also be made into a test strip for the detection of Cu2+ in actual water samples.

Design, synthesis and application of a dual-functional fluorescent probe for reactive oxygen species and viscosity.

A fluorescence probe based on cyanine fluorophore was designed and synthesized in this work, which can be used to determine viscosity and reactive oxygen species (e.g., OCl-, ONOO-) at different wavelengths. Under a low viscosity medium, the fluorescence quantum yield of the probe is very low; however, with the increase of the medium viscosity, the probe's emission at 571nm is enhanced by nearly 25-fold due to the inhibition of intramolecular rotations. On the other hand, the probe shows a rapid and linear fluorescence response at 710nm to OCl- or ONOO- within 1min. The different spectral response regions of the probe permit the selective detection of both viscosity and reactive oxygen species. Furthermore, the probe is demonstrated to be cell permeable and capable of detecting the viscosity and the total amount of OCl-/ONOO- in living cells with the help of confocal microscope fluorescence imaging.

A dual-functional fluorescent probe for sequential determination of Cu2+/S2- and its applications in biological systems.

A new acylhydrazine-derived Schiff base fluorescence probe DMI based on "ON-OFF-ON" fluorescence strategy was presented in this paper. Probe DMI could detect Cu2+ selectively and sensitively with dramatic fluorescence quenching in CH3OH-PBS (v/v=3:7) mixed solution. Once the complex DMI-Cu2+ interacted with S2-, 10.67-folds fluorescence increase was induced via a displacement mechanism under the same experimental conditions. The corresponding detection limits for Cu2+ and S2- were calculated to be 1.52×10-8M and 1.79×10-8M, respectively. The structures of DMI and DMI-Cu2+ were systematically characterized by Job's plot analysis, ESI-MS, IR, X-ray diffraction and density functional theory calculations. Furthermore, fluorescence imaging in MCF-7 cells and zebrafish demonstrated the probe DMI could act as a useful tool to monitor and track intracellular Cu2+ and S2-, which was encouraged by remarkable fluorescence performance and low cytotoxicity. Importantly, the complex DMI-Cu2+ could be applied to detect corrupt blood samples, which could estimate the time of death.