The development of chromogenic and fluorogenic sensors for anions is well-established field in supramolecular chemistry because of their roles in chemical and biological processes ^[1]. Among inorganic anions,F^- ions are usually used for the prevention of dental caries and treatment of osteoporosis ^{[2, 3, 4, 5]}. Over-intake of fluoride can cause fluorosis and lead to nephrotoxic changes and urolithiasis in humans ^{[6, 7]}. Therefore,the interest in developing of novel chemosensors for the selective detection of fluoride ions has grown in the last few years.

The conventional approaches for fluoride sensing are mainly based on the fluoride ionic electrode,fluoride-hydrogen bonding or deprotonation ^{[8, 9]}. Recently,the most popular strategy is to utilize the high affinity of fluoride to silica for the construction of sensors with Si-O,or Si-C bonds ^{[6, 10, 11, 12, 13]}. The approaches involve the direct linkage of a Si-O protected fragment to chromophore/fluorophore,or the insertion of a conjugated system between a Si-O group and chromophore/fluorophore followed by a unique F^--triggered cascade reaction. The reported mechanism is mainly to release the F^--silica-protected group and the signal subunit with delocalized oxygen negative charge. However,realization of novel chromogenic and fluorogenic sensors for fluoride ions is still a challenge,especially with respect to different mechanisms,novel chromophore with high sensitivity.

Recently,aryl phthalate esters were reported as self-immolative linkers for potential fluoride sensors. The fluoride-sensitive self-immolative linker,such as 2-(trimethylsilyl)ethyl ether group,was explored by conjugating the phthalic anhydride with the fluorescent dyes 7-hydroxycoumarin (previous probe,Fig. 1) ^[14]. To improve the sensitivity and operational ability of the above systems,the more sensitive fluorophore containing electronwithdrawing group (such as CF₃ group) should be used to design the sensor. In this study,using the novel the fluorescent dyes 7-hydroxy-4-trifluoromethyl coumarin,we developed a new probe 3 to investigate the potential signal changes (Fig. 1).

Fig. 1

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Fig. 1.(a) UV–visible spectra of compound 3 (20 mmol/L) in presence of 20 equiv. of various anion in CH3CN solution; (b) color changes of receptor compound 3 in CH3CN solution upon addition of various anions; (c) UV–visible spectra of compound 3 in presence of various anion in CH3CN solution. The red bars represent the absorbance enhancement at 434 nm of 3 in the presence of 20 equiv. of the anion of interest after addition of 20 equiv. of fluoride ions and (d) UV–visible spectral changes of 3 (20 mmol/L) in CH3CN upon the titration with TBAF (0 to 20 equiv.)

NMR spectra were recorded on Bruker AVANCE III 500 MHz and chemical shifts were reported in parts per million (ppm,d) downfield from internal standard Me₄Si (TMS). HRMS were recorded on solanX 70 FT-MS spectrometer with methanol and water (v/v = 1:1) as solvent. IR were recorded on Bruker VERTEX70. Flash chromatography was carried out on silica gel (200- 300 mesh). The intermediate 1 and 2 was synthesized as described in the literature (Figs. S1 and S2 in the Supporting information) ^{[14, 15, 16]}.

Synthesis of probe 3 (Scheme 1): 2-(Trimethylsilyl) ethyl hydrogen phthalate (1,1.29 g,4.83 mmol) ^{[14, 15]},7-hydroxy- 4-(trifluoromethyl)-coumarin (2,1.11 g,4.83 mmol) ^[16],and 4-dimethylaminopyridine (0.65 g,5.3 mmol) were dissolved in a mixture of anhydrous methylene chloride (15 mL) and anhydrous DMF (9 mL). N,N-Dicyclohexylcarbodiimide was quickly added to the reaction mixture,which was stirred under Nc overnight. Dicyclohexyl urea was filtered off,and the filtrate was diluted in 10 mL of methylene chloride. The solution was washed with brine and then dried over anhydrous Na₂SO₄. The crude product was collected by evaporation under reduced pressure and then purified by flash chromatography on silica gel (PE/EA = 30:1) to yield 3 (0.92 g,45%) as a white solid. Compounds 3 were characterized by ¹H NMR,¹³C NMR and ESI-HRMS analyses (Figs. S3-S5 in Supporting information). ¹H NMR (500 MHz,CDCl₃): δ 7.93-7.87 (m,1H),7.87-7.78 (m,2H),7.69-7.62 (m,2H),7.45 (d,1H,J = 2.5 Hz),7.38 (dd,1H,J = 9.0,2.5 Hz),6.80 (s,1H),4.46-4.37 (m,2H),1.12-1.08 (m,2H),0.05 (s,9H); ¹³C NMR (100 MHz,CDCl₃): δ 166.71,165.75,158.51,1=.11,154.29,131.84,131.69,131.56,131.39,129.37,128.96,126.35,118.99,111.10,64.40,17.37,
-1.53; ESI-HRMS (m/z): Calcd. for [C₂₃H₂₁F₃O₆Si + Na] 501.09572 ([M + Na]⁺),found 501.09485.

Scheme 1

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Scheme 1.Synthesis of probe 3.

Fig. 1

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Fig. 1.The designed probe 3.

All UV-vis spectroscopy were recorded after the addition of tetrabutylammonium salts in CH₃CN,while keeping the ligand concentration constant (5 × 10^-3 mol/L) on a SHIMADZU UV-1800 spectrophotometer ^[17]. The solutions of the anions were prepared from the tetrabutylammonium salts of anions (F^-,Cl^-,Br^-,I^-,ClO₄ ^-,NO₃ ^-,AcO^-,H₂PO₄ ^-,BF₄ ^-,HSO₄ ^-).

Fig. 2

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Fig. 2.(a) UV–visible spectra of compound 3 (20 mmol/L) in presence of 20 equiv. of various anion in CH3CN solution; (b) color changes of receptor compound 3 in CH3CN solution upon addition of various anions; (c) UV–visible spectra of compound 3 in presence of various anion in CH3CN solution. The red bars represent the absorbance enhancement at 434 nm of 3 in the presence of 20 equiv. of the anion of interest after addition of 20 equiv. of fluoride ions and (d) UV–visible spectral changes of 3 (20 μmol/L) in CH3CN upon the titration with TBAF (0 to 20 equiv.)

Fig. 3

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Fig. 3.(a) Fluorescence spectra of compound 3 (20 mmol/L) in presence of 20 equiv. of various anion in CH3CN solution; (b) fluorescence changes of receptor compound 3 in CH3CN solution upon addition of various anions; (c) fluorescence spectra of compound 3 in presence of various anion in CH3CN solution. The red bars represent the fluorescence intensity enhancement at 504 nm of 3 in the presence of 20 equiv. of the anion of interest after addition of 20 equiv. of TBAF; (d) fluorescence spectral changes of 3 (20 μmol/L) (λex = 350 nm) in CH3CN upon the titration with TBAF (0 to 20 equiv.). Inset: Changes in intensity of 504 nm of compound 3 as a function of [F-].

All fluorescence spectroscopy were recorded after the addition of tetrabutylammonium salts in CH₃CN,while keeping the ligand concentration constant (5 × 10^-3 mol/L),on a Hitachi F-4600 spectrofluorometer. The solutions of the anions were prepared from the tetrabutylammonium salts of anions.

For ¹H NMR titrations,probe 3 was dissolved in DMSO-d6,which was mixed with different equiv. of fluoride ions in NMR tubes. The spectra were performed at 298 K ^[18].

First,the chromogenic behavior of probe 3 in acetonitrile was investigated upon the addition of different anions (Fig. 2a) ^[9]. When tetrabutylammonium fluoride (TBAF) was added,a new redshifted peak at 434 nm was observed in the UV-visible spectrum of probe 3. This can be attributed to complete fluoride deprotection as a consequence of the release of chromenolate anion ^[16]. An instantaneous colorimetric change from colorless to yellow (Fig. 2b,top,naked-eye detection) was observed. However,the addition of other anions such as Cl^-,Br^-,I^-,ClO₄ ^-,NO₃ ^-,AcO^-,H₂PO₄ ^-,BF₄ ^-,HSO₄ ^- ions (as their tetrabutylammonium salts) did not lead to any color change (Fig. 2b,bottom,naked-eye detection),indicating the highly selective nature of probe 3 for fluoride ions. This excellent selectivity was further highlighted by the interference experiments (Fig. 2c),in which a consistent turn-on color response was observed upon the addition of 20 equiv. of F^- ions to the solutions of 3 containing equal concentrations of potentially competing anions. Next,the addition of increasing concentrations of fluoride ions resulted in a dramatic color change from colorless to yellow,because of a gradual growth in the absorbance peak at 252 nm and 434 nm and the simultaneous decrease of new peaks at 282 nm and 314 nm with two clear isosbestic points at 265 and 348 nm in acetonitrile (Fig. 2d).

Most remarkable changes were observed in the fluorescence titration studies ^[19]. Upon the addition of fluoride ions,the fluorescence emission intensity of probe 3 increased drastically at 504 nm (red-shift 50 nm than the previous probe) ^[14],from nonfluorescent to blue green fluorescent (Fig. 3b,top) and was saturated with 20 equiv. of fluoride ions in acetonitrile (Fig. 3a) ^[20]. However,the addition of others anions such as Cl^-,Br^-,I^-,ClO₄ ^-,NO₃ ^-,AcO^-,H₂PO₄ ^-,BF₄ ^-,HSO₄ ^- ions (as their tetrabutylammonium salts) did not lead to any change in the emission intensity (Fig. 3b,bottom),further indicating that probe 3 shows highly selectivity for fluoride ions over other anions ^[21]. Further,the excellent selectivity of probe 3 was confirmed by competition experiments (Fig. 3c),in which a consistent turn-on fluorescence response was observed upon the addition of fluoride ions to the sample solutions of 3 containing equal concentrations of potentially competing anions. The fluorescence detection limit of probe 3 was determined to be 0.19 μmol/L (Fig. S6 in Supporting information).

To test the potential mechanism involving the fluoride deprotonation as a consequence of the release of chromenolate anion,¹H NMR titrations were further performed in DMSO-d6 (Fig. 4) ^{[14, 22, 24]}. The addition of increasing concentrations of F^- ions resulted in a significant upfield shift of the coumarin group signal (Ha-d shift to Ha'-d'). Moreover,when the concentration of F^- was increased gradually (up to 9.0 equiv.),the new set of H'_e and H'_f signal of phthalic acid also be founded. It was confirmed that the mechanism should be fluoride-induced self-immolative linker cleavage followed by releasing the potential phthalic acid and the optical coumarin containing CF₃-group.

Fig. 4

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Fig. 4.1H NMR titration spectra of 3 in DMSO-d6 (4.18 × 10-3 mol/L) upon addition of Fluoride ions (as tetrabutylammonium salts in DMSO-d6) at 298 K, from the bottom to top: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 9.0 equiv.

Moreover,in order to evaluate the practical application of probe 3,a test paper was prepared by immersing a filter paper into a CH₃CN solution of probe 3 (5.0 × 10^-4 mol/L) and the test paper was then dried in air ^[23]. When the test strips coated with probe 3 were immersed into the solution of F^- in CH₃CN (5 × 10^-2 mol/L),the obvious color change from colorless to blue green was observed under the 365 nm UV-lamp (Fig. 5).

Fig. 5

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Fig. 5.Photographs of test strips of probe 3 (5.0 × 10-4 mol/L) exposed to fluoride ions (5 × 10-2 mol/L).

In summary,a new chromogenic and fluorescent probe 3 based on fluoride-sensitive self-immolative linker was developed as a consequence of the release of chromenolate anion. This probe 3 displayed drastic changes in the UV-visible absorption and fluorescence emission intensities selectively for fluoride ions in acetonitrile. The strategy based on fluoride-sensitive self-immolative linker has great potential for sensor design. Further studies on the development of this novel strategy by introducing novel fluorophores are in progress.

We are grateful for financial support from National Natural Science Foundation of China (No. 21202099),the Science Foundation of Shanghai Institute of Technology (No. YJ2011-75) and the Opening Fund of Shanghai Key Laboratory of Chemical Biology (No. SKLCB-2014-01).