Introduction

Fluoride is a trace element present in our bodies, which helps to care tooth, build dental enamel and prevent osteoporosis [1,2,3,4,5]. However, even at low concentration, long-term consumption causes bone fluoridation, decreased thyroid activity, bone disease, and adversely affecting the immune system [6,7,8,9,10]. In addition, fluoride is widely applied in industries such as pesticide production containing fluoride and production of steel, aluminum and ceramics. By this industrial spread, fluoride is increasing irreversible pollution to the environment [11,12,13,14]. Thus, monitoring and sensing fluoride are of great importance to health care and environment.

So far, fluoride detection techniques can be classified into several types, such as electrode methods, 19F NMR analysis, fluorescence or colorimetric detection [15,16,17,18,19,20]. Among the various approaches, the most attractive is the colorimetric sensor that can detect fluoride via color changes visually without relying on expensive device use. In addition, colorimetric sensors have diverse advantages like low cost, easy method, quick response, and great selectivity [21,22,23,24,25,26].

Fluoride interacts with NH or OH groups through strong hydrogen bonds [27]. Therefore, a variety of colorimetric chemosensors which include NH or OH groups, have been designed to sense fluoride [28,29,30,31,32,33,34]. Julolidine moiety having an OH group is well known as a chromophore and great proton donor [35,36,37,38,39,40]. Pyridazine moiety acts as an electron withdrawing group and is also used in various biochemical and physicochemical applications [41]. Therefore, we predicted that the combination of the pyridazine group and the julolidine one may show deformation of energy transition via hydrogen bond interactions and unique sensing properties to fluoride.

Herein, we illustrate a novel reversible chemosensor PDJ, which was produced in one step by coupling 3-chloro-6-hydrazinylpyridazine with 8-hydroxyjulolidine-9-carboxaldehyde. PDJ could sense F– by a color variation from colorless to yellow through the naked eye, show reversible reaction, and be reused by TFA (trifluoroacetic acid). Binding pattern and sensing mechanism of PDJ to F– were presented by Job plot, 1H NMR titration, ESI-mass spectral analyses and calculations.

Experiments

General Information

With a Varian spectrometer, 1H and 13C NMR data were afforded. Absorption and ESI-MS data were given with a Perkin Elmer spectrometer and a ACQUITY QDa, respectively.

Synthesis of PDJ ((E)-9-((2-(6-chloropyridazin-3-yl)hydrazono)methyl)-2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinolin-8-ol)

3-Chloro-6-hydrazinylpyridazine (0.9x10-3 mol, 0.133 g) and 8-hydroxyjulolidine-9-carboxaldehyde (1.2x10-3 mol, 0.272 g) were dissolved in methanol (5.0 mL). The mixture was stirred for 8 h after a few drops of CH3COOH were added. The yellowish-brown powder formed. Then, it was rinsed with CH3OH, filtered and dried (yield: 32%). 1H NMR: 11.32 (s, 1H), 10.77 (s, 1H), 8.08 (s, 1H), 7.60 (d, J =9.3 Hz, 1H), 7.21 (d, J =9.5 Hz, 1H), 6.71 (s, 1H), 3.15 (m, 4H), 2.60 (m, 4H), 1.85 (m, 4H). 13C NMR: 157.1(1C), 153.4(1C), 146.7(1C), 146.5(1C), 144.7(1C), 129.8(1C), 127.5(1C), 115.3(1C), 112.6(1C), 106.4(2C), 49.2(1C), 48.8(1C), 26.7(1C), 21.5(1C), 20.7(1C), 20.3(1C). ESI-MS for [PDJ + H+], calcd, 344.13 (m/z); found, 344.34.

UV–vis Titration

A PDJ stock (5.0x10–3 M) was provided in 1,000 μL of DMSO. 12 μL of PDJ (5.0x10–3 M) was diluted with 2.986 mL of CH3CN to produce 2.0x10–5 M. TEAF (tetraethylammonium fluoride, 1x10–4 mol) was dissolved in CH3CN (1,000 μL) and 3.0 - 33.0 μL of the F– (1x10–1 M) was added to 2.0x10–5 M of PDJ. UV-vis spectra were measured after 8 s.

Job Plot

Solutions having PDJ (100 μM) and TEAF (100 μM) were made. Amounts of PDJ and F– kept steady (3,000 μL) and acetonitrile as solvent was employed. UV-vis spectra were measured after 8 s. Job plot was drawn by plotting against the molar fraction of fluoride under the constant total concentration (100 μM). A is the absorbance of PDJ after addition of F–, and A0 is the absorbance of the free PDJ at 414 nm.

Competitive Test

A PDJ stock (5.0x10-3 M) was provided in 1,000 μL of DMSO. In cells containing 3,000 μL of CH3CN, 27 μL of other anion stocks (I−, NO2−, Br−, SCN−, OAc−, Cl−, H2PO4−, N3−, BzO−, CN− and S2−; 100 mM) was diluted to produce 45 equiv. 27 μL of TEAF (1x10-1 M) was added to each cell. 12 μL (5.0x10-3 M) of PDJ was added to the cell. UV-vis spectra were measured after 8 s.

1H NMR Titration

Five NMR tubes containing PDJ (4.8 mg, 1.4x10-5 mol) dissolved in DMSO-d6 (1,400 μL) were provided. Five varied equivalents (0, 0.5, 1, 2 and 5) of TEAF dissolved in DMSO-d6 were put into five NMR tubes. 1H NMR spectra were measured after 8 s.

Reversible UV–vis Titration

A PDJ stock (5.0x10–3 M) was provided in 1,000 μL of DMSO and a F- stock (100 mM) was provided in CH3CN (1 mL). 12 μL of PDJ (5x10–3 M) and 27 μL of F– were diluted with 2.961 mL of CH3CN. Then, 1.2 – 18.0 μL of TFA (5x10–2 M) were added to a mixture of PDJ and F–. UV-vis spectra were measured after 8 s.

Theoretical Studies

To apprehend geometry structures and energy transition states of PDJ and PDJ with F–, calculations were worked through Gaussian 16 program [42]. We used B3LYP and DFT calculations for geometry optimization, and applied the 6-31G(d,p) basis set to all atoms [43,44,45,46]. Imaginary frequencies were not displayed for optimized patterns of PDJ and PDJ with F–, indicating that the optimized geometry signified local minima. To consider the solvent interaction to PDJ, IEFPCM model was applied in all DFT calculations [47]. PDJ was placed into a small cavity surrounded by a dielectric continuum of given solvent CH3CN (ε = 35.688). Based on the optimized patterns of PDJ and PDJ with F–, TD-DFT calculations were performed and twenty of UV-vis transition states were investigated.

Results and Discussion

PDJ was synthesized by the coupling reaction between 3-chloro-6-hydrazinylpyridazine and 8-hydroxyjulolidine-9-carboxaldehyde (Scheme 1). PDJ was affirmed by 1H NMR, 13C NMR and ESI-MS (Figs. S1, S2 and S3).

Scheme 1
scheme 1

Synthetic route of PDJ

Full size image

Colorimetric Response of PDJ to F−

Colorimetric probing capabilities of receptor PDJ with varied anions in CH3CN were studied with UV-vis spectroscopy (Fig.1a). On addition of anions (45 equiv), PDJ exhibited little variation in absorption spectra except CN– and F–. The addition of CN– to PDJ displayed that the absorbance at 414 nm increased slightly. However, its solution color did not change. In contrast, the addition of F– to PDJ displayed that the absorbance at 414 nm remarkably increased and its solution color varied from colorless to yellow (Fig. 1b). This outcome suggested that PDJ can be a clearly selective colorimetric receptor for F–.

Fig. 1
figure 1

(a) Absorbance variation of PDJ (2×10–5 M) with varied anions (45 equiv). (b) Colorimetric response of PDJ (2×10–5 M) upon addition of varied anions (45 equiv)

Full size image

Binding characters of PDJ with fluoride were investigated through UV-vis titration (Fig. 2). On the addition of F–, the absorbance at 372 nm consistently decreased and that at 414 nm increased constantly with a saturation at 45 equiv of F–. Complete isosbestic point emerged at 388 nm, meaning that a species was formed from the interaction of PDJ and F–. The bathochromic shift drove us to presume the transition of intramolecular charge transfer (ICT) band via deprotonation of PDJ by F– [48].

Fig. 2
figure 2

Absorbance variations of PDJ (2×10–5 M) with increment of F−

Full size image

Job plot was executed to comprehend the binding stoichiometry of PDJ and F– (Fig. S4). When the ratio ([F–]/([PDJ]+[F–])) was 0.5, the value of A-A0 at 424 nm was the largest, suggesting that PDJ reacted with F– through a 1:1 ratio. Binding constant of PDJ with F– was afforded to be 8.9×10 M–1 (R2 = 0.9914) with Li’s equation (Fig. S5) [49]. Detection limit of PDJ for F– was calculated 12.1 μM using 3σ/K (Fig. 3), which is low compared to those of colorimetric F– sensors (Table S1) [50].

Fig. 3
figure 3

Determination of the detection limit of PDJ (2×10–5 M) for F− on the basis of the calibration curve

Full size image

A competing test was applied to extend the sensing ability of PDJ (Fig. 4a). S2- inhibited naked-eye sensing of F- by PDJ. The rest of the anions interfered little with absorbance (10 – 40%) at 414 nm. However, there was no problem observing color changes with the naked eye (Fig. 4b). These outcomes signified that PDJ may work as a clearly colorimetric sensor for fluoride with varied competing anions.

Fig. 4
figure 4

(a) Competitive selectivity of PDJ (2×10–5 M) to F− (45 equiv) with various anions (45 equiv). (b) Colorimetric response of PDJ (2×10–5 M) to F− (45 equiv) with other anions (45 equiv)

Full size image

The 1H NMR titration further demonstrated the reaction between PDJ and fluoride (Fig. 5). The OH proton (H5) and the NH proton (H3) of PDJ were displayed, respectively, as a singlet at 11.3 ppm and 10.8 ppm. With addition of half equiv of F–, the H3 disappeared and the H5 was reduced owing to H-bonding between fluoride and H3 and H5. With addition of one equiv of F–, the H5 also disappeared. With excess addition of F– to PDJ, a new triplet peak at 16.2 ppm was displayed, signifying the generation of FHF– species through deprotonation of H5 in PDJ by F–. This presumed that the negative charge formed from the deprotonation of a hydroxyl group of PDJ by fluoride might be delocalized through the benzene ring and Schiff base. Deprotonation of H5 in PDJ by F– was further affirmed by an ESI-MS test (Fig. S6). Negative-ion data of PDJ with F– displayed the number of 342.19 (m/z), assignable to [PDJ – H+]– (calcd; 342.11). Based on Job plot, 1H NMR titrations and ESI-MS, the appropriate probing process of F– by PDJ was suggested in Scheme 2.

Fig. 5
figure 5

1H NMR titration of PDJ with F−

Full size image
Scheme 2
scheme 2

Proposed probing mechanism of PDJ for F−

Full size image

To examine the reversibility of PDJ to F–, TFA was put to the solution of PDJ and F–. (Fig. 6). Upon addition of TFA, absorbance at 414 nm constantly decreased and that at 372 nm continually increased. The last UV-visible spectrum was same as that of PDJ. On addition of F– again, the absorbance of 372 and 414 nm was returned. The variations of absorbance were reversible even in third cycles with the subsequently alternating addition of F– and TFA (Fig. S7). These results suggested that PDJ can be easily recycled through treatment with appropriate reagents like TFA.

Fig. 6
figure 6

Absorbance variations of PDJ (2×10–5 M) with increment of TFA

Full size image

Theoretical Calculations

With reference to the outcomes of ESI-MS and Job plot, optimized structures of PDJ and PDJ with F– were investigated (Fig. 7). Dihedral angle of PDJ was 179.632° and exhibited a planer structure (Fig. 7a). Dihedral angle of PDJ with F– was –2.246° and also showed a planer structure (Fig. 7b).

Fig. 7
figure 7

Energy-optimized patterns of (a) PDJ and (b) PDJ with F−

Full size image

Based on energy-optimized patterns of PDJ and PDJ with F–, TD-DFT calculations were performed. For PDJ, the big absorption band occurred from the HOMO → LUMO+1 (372.37 nm, Fig. S8), indicating that ICT occurred from the julolidine to the pyridazine. For PDJ with F–, absorption band relevance with red-shift stemmed from HOMO → LUMO+1 transition (415.96 nm, Fig. S9) and exhibited π → π* transition. In the category of the major excited states of PDJ and PDJ-F–, their molecular orbitals and transition energies are shown in Fig. S10. With addition of F– to PDJ, the decrease of HOMO to LUMO+1 energy gap would be caused by the deprotonation of –OH proton and hydrogen bonding of –NH proton, which subsequently results in bathochromic shift. In addition, the red-shift recorded in the UV-visible experiment was well consistent with the calculated results. Based on diverse spectroscopic analyses and calculations, we envisioned the plausible detection process of PDJ to F– (Scheme 2).

Conclusion

We synthesized a reversible colorimetric chemosensor PDJ for detecting F–. PDJ exhibited selectivity only to F– by responding colorless to yellow. The limit of detection for F– was 12.1 μM. Especially, PDJ can detect F– with little interference in other anions except for S2–. Moreover, PDJ can be simply recycled through treatment with appropriate reagents such as TFA. The binding character and sensing process of PDJ with F– were demonstrated by Job plot, 1H NMR titration, DFT calculation and ESI-MS. We believe that a new reversible sensor PDJ may contribute to designing a useful fluoride probe.