A novel OFF-ON-OFF fluorescence probe based on coumarin for Al3+ and F− detection and bioimaging in living cells (2023)

A new pyrazole derived Schiff base (E)-N'-(2,3-dihydroxybenzylidene)-1-phenyl-5-(thiophen-2-yl)-1H-pyrazole-3-carbohydrazide (W) was devised and synthesized, which exerted a splendid sensitivity and selectivity fluorescence “turn-on” for Al³⁺, accompanied by a solution color changed to bright green. The complex W[Al³⁺] could be applied as a sequential sensor to Fe³⁺. The lowest detection limits of W for detecting Al³⁺ and Fe³⁺ ions were 9.42×10^-9 M and 2.1×10^-8 M singly. The stoichiometric ratio of W to both Al³⁺ and Fe³⁺ was determined to be 1:2 by Job’s Plot, ¹H NMR and mass spectrometry titration as well as theoretical arithmetic. Additionally, W was triumphantly applied to detecting Al³⁺ and Fe³⁺ in running water.

Herein, we report a new phenolphthalein appended Schiff base (PASB) as reversible fluorescent sensor for the detection of pyrophosphate (PPi) ions through the metal displacement mechanism. PASB showed sensing exclusively toward Al³⁺ ions in DMF/H₂O (v/v=1/4, pH 5.5) solution, which resulted in a significant fluorescence enhancement at 540nm. The 1: 2 binding stoichiometry for the complex formation between PASB and Al³⁺ was confirmed by Job’s plot and mass spectroscopic studies. Moreover, a solution of the in situ formed PASB–Al³⁺ complex displayed a high selectivity to PPi. The addition of PPi to PASB-Al³⁺ ensemble significantly quenched its fluorescence. Thus, a dual response was established based on “Off–On–Off” strategy for detection of both Al³⁺ and PPi. The detection limit is 5.86nM and 26nM for Al³⁺ and PPi, respectively. On this basis, we use PASB to detect Al³⁺ in food samples. Furthermore, PASB was successfully applicable to detect Al³⁺ and PPi for intracellular imaging in Human liver cancer cells.

A new highly selective and sensitive probe 2-hydroxy-1-formylnaphthalene trihydroxybenzoyl hydrazone (1) was designed and synthesized for sequential detection of Al³⁺ and F⁻ ions with “OFF-ON-OFF” fluorescent signals. This probe 1 displays high selectivity towards Al³⁺ among 17 metal cations, the resultant complex [1-Al³⁺] formed by the coordination of 1 with Al³⁺ can be recognized as a sequential probe for sensing F⁻. Moreover, the formation of this 1-Al³⁺ complex with a 1:1 stoichiometry leads to a significant fluorescence enhancement at 505nm with high selectivity, for that 1 shows “turn-on” fluorescence response to Al³⁺ with negligible interferences from other various metal cations, and the resultant sequential probe 1-Al³⁺ complex exhibits the nearly complete quenching of emission intensity with successive addition of F⁻, which is only specific for F⁻, without being hampered by the existence of other various anions. The lowest limit of detection (LOD) values of 1 and 1-Al³⁺ complex for separately sensing Al³⁺ and F⁻ ions are determined to be 2.55×10⁻⁸ M and 1.48×10⁻⁷ M, respectively. In addition, 1 can severe as a highly selective probe towards Al³⁺ and F⁻ ionsby the “naked-eye” detection, for the solution color easily changing from colorless to yellow-green with the introduction of Al³⁺ and further to colorless upon subsequent addition of F⁻.

The hydrazone sensor (1) derived from pyrazine-2-carbohydrazide and 1-phenyl-3-methyl-4-benzoyl-5-pyrazolone (PMBP) was applied to the fluorescent “turn-on” detection of Al³⁺ in semi-aqueous solutions. The strongly emissive 1+Al³⁺ complex could identify F⁻ among other tested anions. The detection limits of sensor 1 for Al³⁺ and F⁻ were 0.18 and 0.20μM, respectively, which are both much lower than the corresponding values recommended by the World Health Organization, namely, 7.41 and 79μM. Several spectral methods, including single crystal X-ray analysis for the crystal structures of the Cu²⁺ and Ni²⁺ complexes of sensor 1, as well as the density-functional theory method, were used to elucidate the binding mode between the sensor and Al³⁺. 1 can also be used for a selective sensor to continuously monitor Al³⁺ and F⁻ in living cells.

A novel acylhydrazone coumarin fluorescent chemosensor C⁴ for detection of Ni²⁺ was designed and synthesized. The experimental results revealed a low detection limit of 2.1×10⁻¹¹ M with high selectivity and excellent sensitivity towards Ni²⁺. C⁴ showed a good linear relationship with the concentration of Ni²⁺ from 1.3×10⁻⁶ to 1.6μM. Moreover, a stable complex was formed between C⁴ and with Ni²⁺ and the binding ratio was proved to be 2: 1 by Job’s plot and mass spectrum. The sensing ability of C⁴ towards Ni²⁺ was attributed to parity-forbidden transition according to fluorescence titrations and DFT calculations. The detection of Ni²⁺ in water samples illustrated C⁴ could be successfully applied for the detection of Ni²⁺ in real environmental samples. What’s more, the fluorescence microscopy images of Hela cells demonstrated the high potential of the novel biosensor for the investigation of biological processes involving Ni²⁺, as well.

Pyrans constitute an important class of 6-member heterocycles with one oxygen atom. This article outlines applications of pyrans and their benzo derivatives for the time period 2008–18. Together with benzo derivatives, pyrans form a wide variety of scaffolds for pharmaceutical applications with many approved drugs, promising candidates in clinical trials and recently isolated bioactive natural products. In the last decade, cyclodextrins and carbohydrate-based polymers have been investigated for innovative biomedical applications. Pyran dyes have also emerged as promising photoredox catalysts and key components in solar cells and sensors. Finally, applications of pyrans as catalysts and “chiral pool” reagents in chemical synthesis are summarized.

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, Volume 214, 2019, pp. 7-13

A new Schiff base derivative fluorescence-colorimetric chemosensor 2-hydroxy-5-[(2-hydroxy-1-naphthyl)methylideneamino]benzoic acid (H₃L), has been designed and synthesized. H₃L displayed high selectivity and sensitivity for detecting Cr³⁺, Cu²⁺, Fe³⁺ and Al³⁺ ions in DMF/H₂O (v/v = 1/1) solution. When Cr³⁺, Cu²⁺ or Fe³⁺ ions were added, the solution of H₃L in DMF/H₂O exhibited different color changes. While with the addition of Fe³⁺ or Al³⁺ ions, the solution of H₃L in DMF/H₂O displayed different fluorescence responses. The bonding modes and bonding ratios of H₃L and metal ions were explored by the Job's plot, ¹H NMR titration, and electrospray ionization mass spectrometry (ESI-MS). The detection limits of H₃L with Cr³⁺, Cu²⁺, Fe³⁺and Al³⁺ ions were 3.37 × 10⁻⁷ M, 4.65 × 10⁻⁷ M, 3.58 × 10⁻⁷ M and 4.89 × 10⁻⁷ M, respectively.

Sensors and Actuators B: Chemical, Volume 253, 2017, pp. 317-325

A novel coumarin based azo-phenol ligand (H₂L) has been synthesized and characterized by several spectroscopic techniques. An almost 16 fold enhancement of emission intensity has been observed upon gradual addition of Mg²⁺ to H₂L in DMSO:H₂O (1:5v/v) medium while it has no significant effect in emission intensity even in presence of other metal ions. The emission intensity of L-Mg²⁺ complex has almost quenched on gradual addition of F⁻ to it. The limit of detection for both Mg²⁺ and F⁻ are of 10⁻⁸M order, hence the newly developed chemosensor is highly efficient in detecting Mg²⁺ and F⁻ in very minute levels. The chemosensor can even detect Mg²⁺ in the intracellular region of human lung cancer cells (A549 cells).

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, Volume 218, 2019, pp. 359-365

A novel coumarin-derived Schiff base fluorescence probe (CTB) has been successfully designed and synthesized through exploiting tris-(2-aminothyl)-amine moiety as a recognition unit for the highly selective and sensitive detection of Cd²⁺. It is based on CN isomerization and the photo-induced electron transfer (PET) mechanism. The investigation into the sensing processes showed that CTB exhibited an excellent selectivity for Cd²⁺. The sensitivity exceeded that of other competing metal ions, and had a high sensitivity, a detection limit of 1.16 × 10⁻⁷ M with the association constants of 1.37 × 10¹¹ M⁻². The experiments including Job's plot, UV–Vis titration, ¹H NMR titration and ESI-MS spectrum established that the probe CTB binds to Cd²⁺ in a 1:2 ratio. Further studies also demonstrated that probe CTB can be successfully applied to the fluorescence imaging of Cd²⁺ in HepG-2 cells.

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, Volume 193, 2018, pp. 415-421

In this paper, a simple naphthalene-based derivative (HL) has been designed and synthesized as a Al³⁺-selective fluorescent chemosensor based on the PET mechanism. HL exhibited high selectivity and sensitivity towards Al³⁺ over other commonly coexisting metal ions in ethanol with a detection limit of 2.72nM. The 1:1 binding stoichiometry of the complex (HL-Al³⁺) was determined from the Job's plot based on fluorescence titrations and the ESI-MS spectrum data. Moreover, the binding site of HL with Al³⁺ was assured by the ¹H NMR titration experiment. The binding constant (Ka) of the complex (HL-Al³⁺) was calculated to be 5.06×10⁴M⁻¹ according to the Benesi-Hildebrand equation. In addition, the recognizing process of HL towards Al³⁺ was chemically reversible by adding Na₂EDTA. Importantly, HL could directly and rapidly detect aluminum ion through the filter paper without resorting to additional instrumental analysis.

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, Volume 201, 2018, pp. 216-222

A fluorescence probe based on thiosemicarbazide has been synthesized and well characterized by ¹H NMR, ¹³C NMR, Elemental analysis, Electrospray ionization mass spectra. The probe 1 functions as a multitarget ion sensor, detect biologically and ecologically important Cd²⁺, PO₄³⁻ and Cr³⁺. Meanwhile, probe 1 displays selectivity for Cd²⁺ over other metal ions and anions in DMF by emission spectrum. Interestingly, probe 1 has been explored to recognize PO₄³⁻ in CH₃OH-H₂O (v:v = 1:9). The binding stoichiometry of probe 1 with Cd²⁺ and PO₄³⁻ are 2:1 and 1:1, respectively, which are confirmed by Electrospray ionization mass spectra. Probe 1 is selective, sensitive and reversibility/reusability to Cd²⁺ and PO₄³⁻ with the detection limit as low as 0.035 μM and 0.011 μM respectively. Besides, the designed probe 1 has shown potential applications in the area of photo-printing.

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, Volume 204, 2018, pp. 777-782

Fluorion are pivotal anions in biology because they play an important role in dental care, treating osteoporosis, preventing tooth decay and promoting the healthy growth of bone. Studies have shown that high levels of fluoride will lead to the inactivation of the mitochondria. Therefore, it is urgent to develop a method to detect the fluoride anions in the mitochondria. Herein, we have developed a novel mitochondrial-target fluorescent probe for detecting F⁻ in living cells. The probe exhibited excellent sensitivity and high selectivity for F⁻ over the other relative species. With changing fluoride ions, the fluorescence spectrum of the probe changed significantly with a large turn-on fluorescence signal. Cell imaging indicated that the probe can penetrate viable cell membranes and rapidly detects and images fluorion over other anions in the mitochondria.