Schiff Base Fluorescent Probe Research Articles

Sensitive Detection and Cell Imaging of Ca2+ Based on a "Turn-On" Schiff Base Fluorescent Probe.

Ca2+ ion as a second messenger in signaling pathway plays many vital roles in many biological phenomena. Thus, it is of significance for developing effective probes to detect Ca2+ ion specifically. Herein, a new Schiff base fluorescent probe FPH, fluorescein monoaldehyde (2-aminomethylpyridine) hydrazone, was designed and synthesized to identify Ca2+ in DMSO aqueous solution. The probe FPH revealed significant responses to Ca2+ with a fluorescence enhancement at 540 nm, exhibiting an evident fluorescence change from ultraweak luminescence to bright green. Otherwise, the FPH displayed a good linear range of 0.67 × 10-6 to 3.33 × 10-6 mol/L with a lower detection limit at 7.02 × 10-8 mol/L. The probe FPH were further successfully utilized to detect Ca2+ in living cells by an increased bright green fluorescence.

A Novel AIE-Active Salicylaldehyde-Schiff Base Probe with Carbazole Group for Al3+ Detection in Aqueous Solution.

A donor-acceptor Schiff-base fluorescent probe BKS with chelation enhanced fluorescence (CHEF) mechanism was designed and synthesized via benzophenone(Acceptor), salicylaldehyde and carbazole(Donor) for Al3+ detection, which exhibited typical aggregation-induced emission (AIE) characteristic. BKS probe could provide outstanding selectivity to Al3+ with a prominent fluorescence "turn-on" at 545nm in a wide pH range from 2 to 11. By the Job's plot, the binding stoichiometry ratio of probe BKS to Al3+ was determined 1:1. The proposed strategy offered a very low limit of detection at 1.486 µM in THF/H2O(V/V = 1:4, HEPBS = 10 mM, pH = 7.40),which was significantly lower than the standard of WHO (Huang et al., Microchem J 151:104195, 2019)-(Yongjie Ding et al., Spectrochim Acta Mol Biomol Spectrosc 167:59-65, 2021) guidelines for drinking water. BKS probe could provide a wider linear detection range of 50 to 500 µM. Furthermore, the probe could hardly be interfered by other examined metal ions. The analysis of Al3+ in real water samples with appropriate recovery (100.72 to 102.85) with a relative standard deviation less than 2.82% indicated the accuracy and precision of BKS probe and the great potential in the environmental monitoring of Al3+.

A Julolidine Aldehyde Dansyl Hydrazine Schiff Base as Fluorescence Chemosensor for Zn2+ ions Recognition and its Application.

The Schiff base fluorescent probe (Dz-Jul), containing julolidine aldehyde and dansyl hydrazine, was derived using a simple condensation. This chemosensor showed high selectivity towards Zn2+ and quick response (170s) in DMSO/H2O solutions (8/2, v/v, pH 7.2 buffer). A fluorometric titration determined that Dz-Jul-Zn2+ has a binding ratio of 1:1, and the association constant (Ka) is 1.03 × 105M-1. The Dz-Jul detection limit of Zn2+ ions was 15nM, much lower than the WHO standard (76.0nM). DFT, ESI mass, and FTIR spectral demonstrated a plausible complexation mode between Dz-Jul and Zn2+ ions. In actual water samples, Zn2+ has been detected with good detection performance using Dz-Jul. Additionally, Dz-Jul-coated test strips allowed for rapid and qualitative monitoring of Zn2+ ions in a visible manner.

Porphyrin-based Schiff base fluorescent probe: Mercuric ion recognition by naked eye colorimetric analysis and application of test strip detection

(E)-4,4′,4″-(20-(4-(2-(2-hydroxybenzylidene)hydrazine-1-carbonyl)phenyl)porphyrin-5,10,15-triyl)tris(1-methylpyridin-1-ium) (named as Por-SA) was synthesized and developed as a fluorescent chemosensor for recognition towards Hg2+ ions in organic-semi aqueous DMSO(Dimethyl sulfoxide)/H2O (8:2, v/v) solution with high selectivity. The sensing ability of water-soluble Por-SA ligands to detect various cations was investigated in aqueous solutions via colorimetric and spectrophotometric methods. Hg2+ can be identified by naked eye colorimetric analysis, and the color of the solution changes from pink to green under daylight, the fluorescence of solution is significantly quenched under 365 nm UV lamp. The probe coordination mode to Hg2+ by probe was further evaluated by the means of density functional theory calculation (DFT), 1HNMR spectroscopy and Job's plot. Furthermore, the probe Por-SA can recognize Hg2+ with a low limit of detection of 17.3 μM. Probe Por-SA is successfully utilised for detecting the changes of Hg2+ ions in test paper strips. Therefore, Por-SA has the potential to become a universal tool for detecting target metal ions in the environmental and biological fields.

Medium-dependent selectivity for Cu2+ and glutathione by a near-infrared fluorescent probe

A novel near-infrared Schiff base fluorescent probe was synthesized. The probe displayed medium-dependent selectivity and could specifically recognize Cu2+ in EtOH/H2O (9:1, v/v) while respond to glutathione (GSH) in THF/H2O (9:1, v/v). Addition of Cu2+ to the probe solution caused obvious fluorescence quenching and color change. The detection limit was calculated to be 37 nM. The probe could specifically detect GSH through fluorescence turn-on in THF/H2O (9:1, v/v) medium based on GSH-induced hydrolysis of the probe, with the detection limit as low as 20 nM. The sensing mechanism of the probe was verified by spectral analysis and density functional theory (DFT) calculations. Application of the probe to real water samples analysis and bioimaging was achieved.

Synthesis and Application of 1,8-Naphthalimide Derivatives Fluorescent Probe for Sequential Recognition of Cu2+ and H2PO4.

A naphthalimide Schiff base fluorescent probe (BSS) was designed and synthesized from 4-bromo-1,8-naphthalic anhydride, and its structure was characterized by 1HNMR, 13CNMR, FTIR, and MS. Fluorescence emission spectra showed that probe BSS could realize the "turn-off" detection of Cu2+ in acetonitrile solution, detection process with strong specificity and excellent anti-interference of other metal ions. In the fluorescence titration experiments, fluorescence intensity of BSS showed a good linear relationship with the Cu2+ concentration (0-10 µmol/L), and the detection limit was up to 7.0 × 10- 8 mol/L. Meanwhile, BSS and Cu2+ could form a 1:1 complex (BSS-Cu2+) during the reaction process. Under the same detection conditions, complex BSS-Cu2+ had specific fluorescence recovery properties for H2PO4- and the whole process was not only fast (6s) but also free of interference from other anions, with a detection limit was as low as 5.7 × 10- 8 mol/L. In addition, complex BSS-Cu2+ could be successfully applied to the detection of H2PO4- in actual water samples, which with excellent application prospects.

A Highly Efficient and Selective Glycine Based Schiff Base Fluorescent Probe for Dual Sensing of Zn(II) and Cu(II) and its Antibacterial Activity and BSA Interaction Studies

AbstractA mesogenic glycine based Schiff base compound of the type, (E)‐methyl 2‐((2‐hydroxy‐4‐(tetradecyloxy)benzylidene)amino)acetate (HL) has been successfully synthesized and characterized using analytical and spectroscopic techniques. The Schiff base compound was evaluated for chemosensor activity towards different metal ions using fluorescence spectroscopy. The experiment reveals highly efficient and selective “turn‐on” and “turn‐off” responses of the fluorescence intensity towards zinc(II) and copper(II), respectively, in presence of other metal ions. The binding constant and the stoichiometry ratio were determined using Benesi‐Hildebrand equation giving 1 : 1 stoichiometry. The limits of detection for both the metal ions were estimated from the fluorescence titration experiments. The reversibility nature of the Schiff base probe was also studied using EDTA as chelating ligand. The compound, HL exhibits two INHIBIT logic gates with chemical inputs (i) Zn2+ (IN1) and Cu2+ (IN2) and (ii) Zn2+ (IN1) and EDTA (IN2). An IMPLICATION logic gate was also obtained when Cu2+ (IN1) and EDTA (IN2) serve as chemical inputs. The compound was found to exhibit potent antibacterial activity and efficient binding interaction with BSA. Molecular docking studies were carried out in order to ascertain the degree of interaction and the nature of binding of the compound with the proteins.

Al3+ induced hydrolysis of anthraquinone-based Schiff base fluorescent probe for determination PPi ions and bioimaging

Herein, a novel anthraquinone derivative appended fluorescent probe (HAD), has been developed as a reversible probe for detection of aluminium ions (Al3+) and pyrophosphate (PPi) in buffer medium. The probe displays fluorescence “turn-on” response towards Al3+ with high specificity. The activation of the chelation-enhanced fluorescence (CHEF) effect occurs as a consequence of the formation of a complex via coordination with Al3+, which was due to the imine bond is dynamic and reversible and further causing subsequent cleavage of the -C=N bond in the presence of Al3+. This complex significantly amplifies the fluorescence response. Additionally, according to the Job's plot and high-resolution mass spectrometry (HRMS) measurements, the binding stoichiometry of HAD and Al3+ ions is 1:2. Moreover, Density functional theory (DFT) investigations further elucidate the binding mechanism. The original spectrum is restored after the addition of PPi, which is due to the formation of more stable Al3+-PPi complex. The specific determination of Al3+ and PPi with the detecting limit of 47.6 nM and 73.7 nM (S/N = 3), respectively. Due to its exceptional biocompatibility, the probe has facilitated the development of Al3+ and PPi imaging in vitro and in vivo, thereby showcasing its remarkable capabilities in the realm of environmental and biological analysis.

Chelation-enhanced fluorescence-enabled coumarin-hydrazone Schiff bases for the detection of Al3+ ions and its real-time applications

We designed a simple coumarin-hydrazone-based Schiff base fluorescent probe, namely 7-(diethylamino)-N'-(2,4-dihydroxybenzylidene)-2-oxo-2H-chromene-3-carbohydrazide (L), which was successfully synthesized and utilized for selective detection of Al3+ ion via fluorescence ‘turn-on’ method. The Probe L could detect Al3+ by a sharp increment in fluorescence intensity (∼15 times) in a semi-aqueous DMSO medium. The detection limit of L towards Al3+ was calculated to be 50 nM, and the former undergoes a 1:1 stoichiometry binding with a higher binding constant of ∼ 2.14 × 104 M−1. Probe L detects Al3+ by the well-known chelation-enhanced fluorescence (CHEF) mechanism and inhibits C = N isomerization by fluorescence time-resolved measurement. Experimental results from FT-IR, NMR, and ESI mass spectrometry confirm the interaction mechanism between probe L and Al3+ ions, further supported by DFT calculations. In addition, the probe L fabricated paper strips could detect Al3+ in the naked eye under UV light.

A sensitive “turn-on” Schiff-base fluorescent probe for the selective detection of Fe3+ and bio-imaging

A novel Schiff-base fluorescent probe, 4-(N-(2- hydroxyl-1-naphthalymethylimino)-ethylamino) −7-nitro-1,2,3-benzoxadiazole (HENB) was synthesized and utilized for spectral sensing of Fe3+ ions at neutral pH. The binding of Fe3+ to HENB in C2H5OH-HEPES buffer (1:1 v/ v, 25 mM, pH 7.2) resulted in a pronounced emission enhancement at 530 nm, which is possibly due to the inhibition of photo-induced electron transfer (PET) process as well as the chelation enhanced fluorescence (CHEF) effect. HENB shows good selectivity and sensitivity toward Fe3+ with the detection limit as low as 4.51 nM. Test strips made of HENB was used for rapid “naked-eye” detection of Fe3+ ions in aqueous medium. Moreover, HENB was successfully applied in fluorescence imaging of exogenous and endogenous Fe3+ in live Hela cells as well as zebrafish. Importantly, HENB is capable of effectively monitoring the variations of Fe3+ in living cells during ferroptosis process.

Anthraquinone-based Schiff base fluorescent probe for the sequential sensing of Al3+ and pyrophosphate in a near-perfect aqueous solution and bioimaging

A new anthraquinone derivative fluorescent probe (DPHA) was designed and synthesized for sequentially detecting aluminum ions and pyrophosphate (PPi) in a near-perfect aqueous medium with 0.4 % DMSO as a co-solvent. The DPHA probe displayed “turn-on” fluorescence sensing of Al3+ at 575 nm, overcoming the interference of the other common cations through an apparent color variation from purple to light pink. Anthraquinone-derived conjugated skeleton and Schiff base-mediated multiple binding sites were responsible for the sensitive fluorescence response and selective recognition, respectively, thus producing a chelation-enhanced fluorescence effect. Furthermore, Job's plot analysis and high-resolution mass spectrometry (HRMS) studies supported the formation of a 1:1 ligand/metal complex for Al3+. The plausible binding mechanism was recognized by both experimentally and theoretically. The succeeding addition of PPi regenerated the original spectrum of DPHA and thus the strong affinity of Al3+ to PPi. The in-situ formed DPHA-Al3+ complex for selective identification of PPi by electrostatic interaction by drawing out Al3+ and releasing the DPHA probe. Except for specific recognition of Al3+ and PPi with corresponding low detection limits of 42.2 nM and 65.2 nM (S/N = 3). Owing to its good biocompatibility, DPHA also applied as a visual probe for monitoring Al3+ ions and PPi in living cells and zebrafish, demonstrating its outstanding potential in biological work.

A new turn-on fluorescent probe for fast detection of diabetic biomarker beta-hydroxybutyrate in vitro

Beta-hydroxybutyrate (β-HB) serve as a valuable diagnostic biomarker for Diabetic Ketoacidosis (DKA). Here, a new Schiff base fluorescent probe T was designed and synthesized to detect β-HB level in aqueous solution in vitro. The probe T can detect β-HB sensitively and selectively in DMF solution (5.0 × 10−5 M) among other interfering species (cations, anions, amino acids, biomarkers). The detection limit of probe T for β-HB was calculated to be 0.154 μM. These results demonstrate that the probe T may provide a convenient method for rapid detection of β-HB to diagnose diabetic ketoacidosis.

A “turn-on” Schiff base fluorescent probe for recognizing Zn2+ and its application in indictor and imaging of zebrafish

A novel fluorescent probe was designed and synthesized by using benzothiazole ring as fluorophore to specifically recognize Zn2+ in aqueous solution. In methanol and aqueous mixed solution, the probe had a significant fluorescence enhancement response to zinc ions and indicated high selectivity and sensitivity. Through fluorescence titration, 1H NMR titration, Job’s plot, HRMS data and DFT calculation, the binding ratio of the probe to Zn2+ was 2: 1, and the detection limit was 2.85 × 10-8 M. The probe was further applied to actual water sample to detect Zn2+, and the medium-speed filter paper was combined with probe solution to make an indicator to detect Zn2+ more conveniently and quickly. More importantly, the probe could detect Zn2+ in zebrafish from the results of fluorescence imaging, which proved that the probe had a broader prospect in biological field.

Highly selective fluorescent probe in aqueous solution based on coumarin Schiff base for detecting Cu2+ and specific biosensing of glutathione in mitochondria

The concentration change of overexpressed mitochondrial glutathione (mGSH) in cancer cells can effectively induce cell apoptosis, therefore the development of mGSH -activated turn-on fluorescent probe for cancer cells is extremely beneficial for chemotherapy research. Herein, coumarin Schiff base fluorescent probe N'-((7-(diethylamino)-2-oxo-2H-chromen-3-yl) methylene) picolinohydrazide (NCMP) was prepared, which exhibited selective fluorescence quenching upon the addition of Cu2+. The conjugate NCMP-Cu2+ complex could be used to selectively detect GSH, presenting an “ON-OFF-ON” fluorescence response pattern. The detection limits were 1.98×10-8 M for Cu2+ and 8.20×10-8 M for GSH, respectively. The binding mode of Cu2+ ion with NCMP was ascertained by Job plot, ESI-MS, FT-IR and DFT methods. Probes NCMP-Cu2+ was almost non-toxic, which could be employed for selective fluorescence imaging of GSH in zebrafish and mitochondria of living cells. Consequently, this developed sensor platform has potential application value for future cancer research and biomedical diagnostics.

A tetraphenylethene-based Schiff base AIEgen with a large Stokes shift as probe for highly sensitive and selective detection of aqueous Cu2+ ions and its application in cell imaging

In this work, an AIE-active tetraphenylethene-based Schiff base fluorescent probe 3 with a large Stokes shift (247 nm) was designed and synthesized. It was found that the aggregated probe 3 exhibited very high selectivity and anti-interference ability for Cu2+ in PBS buffer (70% fw) through a fluorescence “turn–off” strategy. Job’s plot and NMR analysis indicated the two phenolic hydroxyl groups of the benzene ring and the N atom (-CH=N-) on probe 3 interacted with Cu2+ ions in a 1:1 stoichiometric ratio. A comprehensive analysis of the Stern–Volmer and binding constant indicated a rather strong interaction between probe 3 and Cu2+ ions. Probe 3 illustrated excellent sensitivity toward Cu2+ under ppb level (4.5 nM) and achieved more than 95% recovery in river, lake and tap water toward estimation of Cu2+ ions in the analytical applications. Moreover, probe 3 was able to realize bioimaging of HepG2 cells and be quenched by intracellular Cu2+ ions, making it promising as a sensitive Cu2+ sensor for organisms.

A coumarin hydrazide Schiff base fluorescent probe for sensitively sensing Al3+ in living cells

A coumarin-based Schiff base fluorescence probe 1, which could specifically recognize Al3+ with high anti-interference was developed. After the addition of Al3+, the reaction reaches the platform in about 30 min with a fluorescent detection limit 0.12 μM. The coordination reaction between the carbonyl group, hydroxyl group, –NC- of probe 1 and Al3+ limits the molecular twist and fluorescence quenching effect from photoinduced electron transfer and then induces the increase of red fluorescence. The detection for Al3+ by the probe shows good repeatability in alternating Al3+ and EDTA. The probe was also applied to the successful monitoring Al3+ in living cells and real water sample.

Selective detection of BF3 in living cells and environmental water samples using Schiff-base fluorescent probe

A new pyrazole naphthalene-based Schiff base (3c) as a colorimetric and turn-on fluorescent sensor for rapid detection of BF3 was developed. Ligand 3c showed a significant fast response and superior selectivity for BF3 with significant color change by naked eye over other competitive species. Sensor probe 3c showed low detection limit (LOD) of 2.46 nM, which was far lower than the previous reports. Based on the Job’s plot, the binding association ratio of 3c with BF3 was found to be 1:1. The sensing mechanism of 3c with BF3 based on the intramolecular charge transfer (ICT) was confirmed by FTIR, 1H NMR titration, ESI mass spectra, and DFT calculation. Moreover, the sensing probe 3c was found to be reversible with the addition of triethylamine (NEt3), which revealed that 3c could behave as a good candidate for BF3 and NEt3 controlled “ON-OFF-ON” mode. Most importantly, probe 3c has been successfully applied to quantitatively detect BF3 species in various water samples, and using low-cost test paper strips as well as living cells.

A new naphthalimide-picolinohydrazide derived fluorescent “turn-on” probe for hypersensitive detection of Al3+ ions and applications of real water analysis and bio-imaging

The development of high-selective chemosensors for trace Al3+ detection in the ecosystem is crucially importance due to its detrimental effects. In this work, a simple Schiff-base fluorescent probe NPP derived from naphthalimide and picolinohydrazide was rationally designed and prepared for efficient detection of Al3+. NPP exhibited prominent sensing behaviors toward Al3+ with low detection limit (LOD) (39 nM), rapid response time (1 min), strong binding affinity (4.02 × 104), good anti–interference characteristics and visual detection. Binding ratio of NPP-Al3+ complex was determined to be 1:1 by Job’s plot analysis. In addition, the chelation mechanism of NPP with Al3+ ions was proposed and substantiated by the density functional theory (DFT) and time-dependent density functional theory (TD-DFT), IR spectrum and 1H NMR titration experiments. Furthermore, this “signal-on” probe NPP was efficiently utilized as a promising indicator for Al3+ detection in environmental and biological samples.

Highly selective fluorescent detection platform based on isoquinoline Schiff base ligand monitors glutathione in biological systems

Aberrant levels of intracellular glutathione (GSH) have been held responsible for various disease and pathological processes, and existing evidence underscores the significance of GSH detection in biological systems. The recognition, discrimination, and precise detection of GSH in the cellular matrix and living organisms can revolutionize our understanding of the physiological and pathological processes of GSH. Herein, we reported a new isoquinoline Schiff base fluorescence probe, N'-((7-(diethylamino)-2-oxo-2H-chromene)methylene) isoquinoline-3-carbohydrazide (NCMC), which can selectively recognize GSH by its ensemble complex NCMC-Cu2+ with a low nanomolar level detection limit (4.16 × 10−8 M) in the aqueous environment. Moreover, the binding behavior and “ON-OFF-ON” fluorescence probing pattern were illustrated in detail by UV–vis titration, ESI-MS spectroscopy, and density functional theory calculations. Notably, the nontoxic NCMC-Cu2+ ensemble platform showed great potential for detecting GSH distribution in cells and zebrafish larvae, and can also be applied in differentiating endogenous GSH in both cancer cells and normal cells, which may represent a promising GSH fluorescence probe in bioimaging and disease diagnosis.

A novel naphthalimide-based “turn-on” fluorescent chemosensor for highly selective detection of Zn2+

A novel Schiff base fluorescent probe (E)-N'-((2-butyl-6-hydroxy-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-5-yl)methylene)furan-2-carbohydrazide (NFP) was prepared via a simple condensation strategy. NFP displayed high selectivity and rapid response (30 s) toward Zn2+ along with a remarkable fluorescence enhancement in DMSO/H2O solution (9/1, v/v, pH 7.4, HEPES buffer, 0.2 mM). Limit of detection (LOD) of NFP for Zinc ions was determined to be 39 nM, which was much lower than the WHO standard (76.0 μM). Binding ratio of NFP with Zn2+ ions was calculated to be 1:1 using job's plot analysis and the association constant (Ka) of NFP–Zn2+ was 1.18 × 105 M−1 on the basis of fluorometric titration. The plausible complexation mode of NFP with Zn2+ ions was demonstrated by the density functional theory (DFT), 1H NMR titration and IR spectrum. The good detection performance of NFP for Zn2+ was successfully reconfirmed by the detection of Zn2+ in real water samples. Furthermore, NFP-coated test strips were easily prepared and used for quickly and qualitatively monitoring Zn2+ ions in a visible manner.