Two benzothiadiazole-based fluorescent sensors for selective detection of Cu2+ and OH– ions

Journal Pre-Proof Two benzothiadiazole-based fluorescent sensors for selective detection of Cu2+ and OH – ions Xue-Mei Tian, Shu-Li Yao, Jie Wu, Haomiao Xie, Teng-Fei Zheng, Xiu-Juan Jiang, Yongquan Wu, Jiangang Mao, Sui-Jun Liu PII: DOI: Reference:

S0277-5387(19)30527-3 https://doi.org/10.1016/j.poly.2019.08.002 POLY 14097

To appear in:

Polyhedron

Received Date: Revised Date: Accepted Date:

23 April 2019 31 July 2019 1 August 2019

Please cite this article as: X-M. Tian, S-L. Yao, J. Wu, H. Xie, T-F. Zheng, X-J. Jiang, Y. Wu, J. Mao, S-J. Liu, Two benzothiadiazole-based fluorescent sensors for selective detection of Cu2+ and OH – ions, Polyhedron (2019), doi: https://doi.org/10.1016/j.poly.2019.08.002

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Two benzothiadiazole-based fluorescent sensors for selective detection of Cu2+ and OH– ions

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Xue-Mei Tian,a Shu-Li Yao,a Jie Wu,b Haomiao Xie,c Teng-Fei Zheng,*a Xiu-Juan

aSchool

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Jiang,a Yongquan Wu,*b Jiangang Mao,a Sui-Jun Liu*a

of Chemistry and Chemical Engineering, Jiangxi University of Science and

Technology, Ganzhou 341000, Jiangxi Province, P.R. China

of Chemistry and Chemical Engineering, Gannan Normal University, Ganzhou 341000,

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bSchool

cDepartment

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Jiangxi Province, P.R. China

of Chemistry, Texas A&M University, College Station, Texas 77840, United States

(S.-J. Liu) E-mail: [email protected]

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(Y.-Q. Wu) E-mail: [email protected]

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(T.-F. Zheng) E-mail: [email protected]

To Polyhedron (Regular Paper)

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Abstract Two

benzothiadiazole-based

compounds,

namely

4,7-di(1H-imidazol-1-yl)benzo-

[2,1,3]thiadiazole (1) and 4,7-di(1H-pyrazol-1-yl)benzo-[2,1,3]thiadiazole (2), have been

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synthesized via Cu-catalyzed cross-coupling reaction, which can be used to detect Cu2+ and OH–

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by fluorescence quenching with high selectivity and sensitivity, respectively. The detection limits

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were determined to be 0.11 μM for Cu2+ and 55 μM for OH–. Furthermore, two compounds have

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cell permeability and 1 could be used for Cu2+ detection in living cells.

1. Introduction

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Keywords: Copper(II); Hydroxide; Fluorescence sensors; In vivo imaging

The design and synthesis of sensors for the detection of metal ions and anions are the main

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topics owning to their vital roles in environmental and chemical areas [1-6]. Copper is one of the essential elements in many biological systems [7-8]. While overloading Cu2+ could result in the

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degeneration of nervous system, such as Parkinson, hypo-glycemia, Menkes, Alzheimer and Wilson [9-10]. The safe limit of copper in drinking water set by the U.S. Environmental Protection Agency (EPA) is 20 μM [11].

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Reliable sensors for monitoring of hydroxide ion concentrations are also in urgent need [12-13].

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Among the most produced chemicals, hydroxide is widely used in many industrial processes [14]. Even though it is quite useful, some negative effects could not be ignored. High pH values may affect enzymatic activity in soil and cause soil environmental degradation [15]. In addition, getting in touch with high levels of hydroxide for a long time can lead to various physiological and biochemical problems involving irritation in mucous membranes and respiratory paralysis [16]. Considering that Cu2+ and OH- ions have the potential impacts on human health and environment, it is essential to develop highly sensitive and selective sensors for detecting and estimating trace levels of Cu2+ and OH- ions.

JOURNAL PRE-PROOF Unlike other analytical techniques, fluorescence analysis exhibits many merits such as rapid response, high sensitivity and simplicity [17-19]. Some organic dye molecules have been demonstrated to selectively detect Cu2+ ion through fluorescence quenching or fluorescence enhancement processes [20-21]. However, they rarely display sensitivity toward Cu2+ at the nanomolar level and corresponding bioimaging studies in living cells (Tables S1 and S2, SI) [22].

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Up to now, there are seldom reports regarding the detection of OH- [14,23]. Therefore, the

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development of fluorescence sensors for selective detection of Cu2+ and OH- has gained much

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attention from chemists [24-26].

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The classical design of fluorescent sensor consists of fluorophores and receptor units, which are either intrinsically attached or extrinsically separated by spacer [27]. Benzothiadiazole derivatives

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possess visible optical and electronic properties [28-29], and are expected to be used as electron

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acceptor in molecular optoelectronic device due to the strong electron-withdrawing capacity and high electron affinity [30]. As well as other common fluorophores, benzothiadiazole derivatives

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have also been used as a fluorophore in the detection of ions [31], however, the example of sensing hydroxide are still very rare. As part of our continuing investigations on the synthesis and

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properties of fluorescent sensors [32-34], two BTD derivatives, 4,7-di(1H-imidazol-1-yl)benzo[2,1,3]thiadiazole (1) and 4,7-di(1H-pyrazol-1-yl)benzo-[2,1,3]thiadiazole (2) have been

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synthesized (Scheme 1). The two compounds show high selectivity and sensitivity for detecting

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Cu2+ and OH– by naked-eye and fluorescence sensing, respectively. Furthermore, compound 1 shows the detection ability for Cu2+ in living cells.

2. Experimental 2.1. Materials and general methods With the exception of compounds 1 and 2, all solvents and materials were of reagent grade and used by purchased without further purification. Compounds 1 and 2 were synthesized according to

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the procedures of reported literatures [35-36]. The solid and liquid luminescence spectra were obtained by using a F4600 (Hitachi) luminescence spectrophotometer. The UV–Vis spectra were recorded on a UV–2500 spectrophotometer. Thermogravimetric analysis (TGA) was carried out

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on a NETZSCH STA2500 (TG/DTA), ranging from room temperature (RT) to 700 °C under a

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nitrogen atmosphere with a heating rate of 10 °C min−1 and employing an empty Al2O3 crucible as

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reference. The infrared spectra (IR) were measured in the range of 400–4000 cm−1 on a Bruker

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ALPHA FT-IR spectrometer by using KBr pellets. Elemental analyses of C, H, and N were conducted on Perkin-Elmer 240C analyzer. 1H NMR spectra were obtained on 400 MHz NMR

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spectrometers (Bruker Avance 400). The chemical shifts were referenced to signals at 7.26 ppm.

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High-resolution mass spectra (HRMS) were acquired by using Agilent 6520 Q-TOF LC/MS with electrospray ionization (ESI) source.

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2.2. Synthesis of 1 and 2

Synthesis of 4,7-di(1H-imidazol-1-yl)benzo-[2,1,3]thiadiazole (1): The synthetic route of 1 is

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shown in scheme 1. A mixture of 4,7-dibromo[2,1,3]benzothiadiazole (2.94 g, 10 mmol), imidazole (2.315 g, 34 mmol), K2CO3 (5.53 g, 40 mmol), 1,10-phenanthroline (phen, 0.432 g, 2.4

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mmol) and CuI (0.34 g, 1.8 mmol) was dissolved in 150 mL DMF with a 250 mL flask and

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refluxed under N2 atmosphere for 72 h. After being cooled down to room temperature, 400 mL distilled water were added to receive precipitation. Then, the precipitation was extracted three times with CH2Cl2 (100 mL) and the dark green crude product was collected. After the solvent was removed by evaporation and the crude product was further purified by column chromatography with V(CH2Cl2)/V(CH3OH) = 16:1 as eluent, yellow solid (0.93 g) was successfully obtained with a yield of 31.6% based on 4,7-dibromo[2,1,3]benzothiadiazole.

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Compound 1 crystallizes in the monoclinic C2/c space group. IR spectrum (cm−1): 3134w, 1608w, 1517s, 1478m, 1317m, 1253m, 1104m, 1078w, 1014w, 881w, 826w, 754w. 1H NMR (CDCl3): δ 8.45 (s, 2H), 7.71 (d, J = 16.1 Hz, 4H), 7.33 (s, 2H). Anal. Calcd for C12H12N6O2S (%): C, 47.36;

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H, 3.97; N, 27.62. Found (%): C, 47.84; H, 3.48; N, 29.33. HRMS (ESI): Calcd for C12H8N6SH

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[M+H]+ 269.0609, found: 269.0609.

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Synthesis of 4,7-di(1H-pyrazol-1-yl)benzo-[2,1,3]thiadiazole (2): The synthetic route of 2 is

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shown in scheme 1. A mixture of 4,7-dibromo[2,1,3]benzothiadiazole (2.94 g, 10 mmol), pyrazole (1.63 g, 24 mmol), K2CO3 (5.53 g, 40 mmol), phen (0.432 g, 2.4 mmol) and CuI (0.34 g, 1.8

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mmol) in 150 mL DMF was dissolved in a 250 mL flask and refluxed under N2 atmosphere for 72

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h. After being cooled down to room temperature, 100 mL H2O was added and the mixture was extracted three times with CH2Cl2 (100 mL), then the organic phase was further dried with

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anhydrous MgSO4 and filtered. The solvent was removed by rotary evaporation to leave tawny crude product. After the following column chromatography by using hexane: ethyl acetate (6:1) as

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eluent, yellow solid was isolated in 37% yield based on 4,7-dibromo[2,1,3]benzothiadiazole. Compound 2 crystallizes in the orthorhombic P21212 space group. IR spectrum (cm−1): 3852m,

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1610w, 1527s, 1397s, 1083m, 1048m, 966m, 850m, 755s. 1H NMR (400 MHz, CDCl3) δ 9.07 (dd,

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J = 2.6, 0.5 Hz, 2H), 8.32 (s, 2H), 7.82 (d, J = 1.4 Hz, 2H), 6.58 (dd, J = 2.5, 1.8 Hz, 2H). Anal. Calcd for C12H8N6S (%): C, 53.72; H, 3.00; N, 31.32. Found (%): C, 54.00; H, 3.75; N, 33.39. HRMS (ESI): Calcd for C12H8N6SH [M+H]+ 269.0609, found: 269.0605. (Insert Scheme 1) 2.3. Crystallographic data and structure refinements.

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The single-crystal X-ray diffraction data were obtained by using a Bruker D8 QUEST diffractometer with Mo-Kα radiation ( = 0.71073 Å) by  scan mode [37]. The structures of two compounds were solved by using the direct method and were refined by full-matrix least-squares

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methods with the SHELX 2017/1 [38-39]. The non-hydrogen atoms of the organic ligands were

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located in successive difference Fourier syntheses and refined with anisotropic thermal parameters

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on F2. The hydrogen atoms of ligands were generated theoretically at the specific atoms and

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refined isotropically with fixed thermal factors. The summary of the crystal data collection and structure refinement parameters for 1 and 2 are provided in table 1.

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(Insert Table 1)

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2.4. General procedure for spectroscopic measurements.

The stock solution of 1 (0.1 mM) for analysis of metal ions was prepared by using DMF as the

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solvent. The solutions of different testing species were prepared from metal ions (0.2 M) of Li+, Na+, K+, Mg2+, Ca2+, Al3+, Cr3+, Fe3+, Co2+, Ni2+, Cu2+, Zn2+, Ag+ and Cd2+ in DMF. The

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selectivity experiments were carried out by addition of different metal ions (15 equiv.). The fluorescence competition experiments were conducted with the addition of other metal ions (15

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equiv.) to the solution of [1+Cu2+] system. Fluorescence titration experiments were performed

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upon addition of 0.01 M Cu2+ solutions (0 equiv. to 4 equiv.) to the solution of 1 (0.05 mM). For all the measurement, the excitation wavelength was 466 nm and both the excitation and emission slit widths were 10 nm. The UV–Vis absorption experiments were conducted with addition of different metal ions (15 equiv.). The UV–Vis titration experiments were investigated by addition of 0.01 M Cu2+ solutions (0 equiv. to 4 equiv.) to the solution of 1 (0.05 mM). The concentration of 2 in fluorescence examination was also 0.1 mM with DMF as the solvent.

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The solutions of different anions (HPO42–, HCO3–, H2PO4–, SO42–, CO32–, F–, Cl–, Br–, I–, AcO–, NO3–, OCN–, SCN–, WO4–, and OH–) with 0.2 M were prepared in distilled water. The selectivity experiments were carried out by addition of different anions (20 equiv.). The fluorescence titration

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experiments were performed by adding 0.1 M OH– (0 equiv. to 50 equiv.) into the solution of 2

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(0.05 mM). As for all the measurement, the excitation wavelength was 469 nm and the slit widths

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of both the excitation and emission were 5 nm. The UV-Vis absorption experiments were

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conducted by adding different anions (20 equiv.). The UV-Vis titration experiments were

(0.05 mM).

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2.5. Procedures for cell imaging.

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investigated with the addition of 0.1 M OH– solutions (0 equiv. to 60 equiv.) to the solution of 2

The vitro experiments were performed using MCF-7 cells. First of all, before the experiments,

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20 μL 0.01 mM solution of 1 were cultured in 1980 μL RPMI1640 medium. Then, the MCF-7 cells were incubated with 1 solution in an atmosphere of 5% CO2 at 37 °C for 1h. After incubation,

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the cells were washed three times with PBS buffer to remove excess solution of 1. Finally, the incubated cells were mounted onto a glass slide for fluorescence images. The cells were incubated

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with Cu2+ (6 equiv.) and 1 under the same conditions. The experimental procedure of 2 is

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analogous with 1.

3. Results and discussion 3.1. Structural Comparison Compounds 1 and 2 crystallize in the monoclinic C2/c and orthorhombic P21212 space groups, respectively. Their structures are shown in Fig. 1. Both 1 and 2 are benzothiadiazole-based compounds, and the diversity of structures is mainly ascribed to the distinct sites of nitrogen

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atoms. Interestingly, benzothiadiazole ring and imidazole (or pyrazole) ring in both 1 and 2 are not in the same plane. At room temperature, the emission spectra of compounds 1 and 2 were investigated. As shown in Fig. S2 (SI), compounds 1 and 2 in solid state give strong emission

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band with the maximum at 575 and 550 nm upon excitation at 468 nm, respectively. Two

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compounds were characterized by IR, 1H NMR, element analysis, and mass spectroscopy (Fig.

3.2. Luminescence sensing properties

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(Insert Fig. 1)

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S3-S5, SI).

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Due to their strong binding affinity with the imidazole group in 1 and the electron-withdrawing

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capacity of BTD, the metal ions and anion sensing properties of 1 have been investigated. The results suggested that no appreciable changes in the emission spectra were observed for all of the

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tested anions (Fig. S7, SI), and the fluorescence intensities of 1 exhibit a remarkable change upon the interaction with Cu2+. The interaction of 1 with different metal ions (Li+, Na+, K+, Mg2+, Ca2+,

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Al3+, Cr3+, Fe3+, Co2+, Ni2+, Cu2+, Zn2+, Ag+ and Cd2+) were systematically studied by fluorescence and UV-Vis spectra. With the excitation wavelength at 466 nm, compound 1 (0.1 mM) shows a

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strong emission peak at about 538 nm. As shown in Fig. 2a, in the process of adding 15 equiv. of

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metal ions into 1 such as Li+, Na+, Ca2+, Mg2+ and K+, no obvious change of the fluorescence intensity was observed, while the addition of Cd2+, Zn2+, Cr3+, Al3+, Co2+, Ni2+, Ag+ and Fe3+ causes a weak reduction of the fluorescence intensity. Notably, the addition of Cu2+ leads to a dramatic quenching in the solution system of 1 (Fig. S8, SI), and the fluorescence image of 1 with Cu2+ ion displays the visual color change when excited by UV lamp at 365 nm, which indicates the naked eye recognition of Cu2+ (Fig. 2b). Thus 1 may be promising for Cu2+ detection.

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To study the influence of other metal ions in Cu2+ sensing of 1, the fluorescence competition experiments were conducted by adding 15 equiv. of other cations into the solution of [1+Cu2+] system. The fluorescence intensities of mixed solutions decreased significantly and their relative

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intensities reach the similar value of the solution, which only included 1 and Cu2+ (Fig. 2c). The

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experimental results indicate that the existence of other competitive metal ions has no obvious

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interference on the determination of Cu2+, and 1 has high fluorescence selectivity for Cu2+.

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The sensitivity of 1 toward Cu2+ was investigated by the titration experiments at the excitation wavelength of 466 nm (Fig. S9, SI). The fluorescence intensity of 1 at 538 nm gradually decreases

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upon the addition of Cu2+ and reached to the minimum value after the addition of 4 equiv. of Cu2+.

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In addition, the detection limit calculated with 3σ/k (k: the slope, σ: the standard error) was about 0.11 μM (Fig. S10, SI). The results demonstrate that 1 has good sensitivity and selectivity toward

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Cu2+ cation.

Besides high sensitivity and selectivity, the real-time detection of Cu2+ via using a fluorescent

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chemosensor is another important factor, and thus response time was determined by monitoring changes in fluorescence intensities at 538 nm (Fig. S11, SI). These results indicate 1 has fast

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response time. The chemical reversibility test of the binding of 1 with Cu2+ was studied by adding

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CO32- to 1-Cu2+ system (Fig. S12, SI). To study the binding property of 1 toward Cu2+, the UV-Vis spectroscopic experiments and

absorption titration experiments were conducted (Fig. S13-S14, SI). The UV-Vis absorption spectra of 1 exhibit obvious changes upon addition of Cu2+, and the intensity of absorption peak increases at 388 nm. No significant changes of absorption spectra were observed upon addition of other metal ions under the same condition. The UV-Vis titration experiments of 1 with Cu2+ reveal

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that the intensity of the absorption peaks at 310, 320 and 388 nm gradually increases. Blue shifts are also observed for the absorption peaks at 388 nm. It is reasonable to speculate their strong binding affinity with the imidazole group in 1 and the electrons from imidazole species were

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transferred to the empty d-orbital of Cu2+ to quench the fluorescence [40,41]. These results

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confirm the existence of interaction between 1 and Cu2+ [42-45]. Job's plot is applied to determine

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the stoichiometry between 1 and Cu2+ in DMF solution, with keeping the total concentration of

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Cu2+ and 1 at 1 mM, and changing the mole fraction of Cu2+ (from 0 to 0.9). The Job's plot (Fig. S15, SI) indicates that the stoichiometric ratio of 1 and Cu2+ appears to be 1:1 [17]. The possible

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coordination fashion between 1 and Cu2+ is shown in Fig. S16a (SI). (Insert Fig. 2)

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In the same way, the metal ions and anion sensing properties of 2 have been investigated. As shown in Fig. S17-S18 (SI), the presence of OH– displayed fluorescence quenching, while the fluorescence intensity of 2 toward metal ions could not show obvious change. The selectivity of 2

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was investigated upon addition of 20 equiv. of different anions (HPO42–, HCO3–, H2PO4–, SO42–, CO32–, F–, Cl–, Br–, I–, AcO–, NO3–, OCN–, SCN–, WO4– and OH–) at the excitation wavelength of

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469 nm. The presence of OH– results in a significant fluorescence quenching at 550 nm (Fig. 3a). On the contrary, the addition of other anions leads to comparative fluorescence intensities of blank

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(Fig. S18, SI). The fluorescence image indicates that 2 can naked eye recognize OH– based on the

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visual color change excited by 365 nm UV lamp (Fig. 3b). These results suggest that compound 2 could be served as a potential selective fluorescence sensor for OH–. To further evaluate the selectivity of 2 toward OH–, the competition experiments were performed upon addition of 20 equiv. of other different anions into the solution of 2 containing OH–. The results indicate that the presence of other anions (except H2PO4–) does not interfere the detection ability of 2 toward OH– (Fig. 3c). The addition of H2PO4– could partially not quench the fluorescence may be due to the interaction of H2PO4– with OH–. The experimental results indicate that compound 2 has a pronounced selectivity for OH–.

JOURNAL PRE-PROOF The sensitivity of 2 with OH– was studied by fluorescence titration experiments. As the concentration of OH– increasing, the fluorescence intensity at 550 nm gradually decreases and finally reaches the minimum value upon addition of 50 equiv. OH– (Fig. S19, SI). The detection limit calculated by 3σ/k is 55 μM (Fig. S20, SI). Fluorescence response depending on the time was further measured. The fluorescence intensities of 2 with OH– were continuously recorded. After

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13 s, the fluorescence intensity decreased significantly (Fig. S21, SI), suggesting that 2 exhibits

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fast response time.

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To further study the binding mode between 2 and OH–, the UV-Vis spectroscopic experiment

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and absorption titration experiment with OH– were carried out. Compound 2 has a main absorption peak at 413 nm in DMF solution (Fig. S22, SI). After addition of 20 equiv. of OH–, the intensity of the main absorption peak significantly decreases at 413 nm. In the presence of 0-60

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equiv. of OH–, the intensity of the absorption peaks at 320 nm gradually increases and almost

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reaches the maximum upon addition of 60 equiv. of OH–. At the same time, the intensity of the absorption peaks gradually decreases at 270 nm and 413 nm (Fig. S23, SI). The absorption bands form two isosbestic points at 290 nm and 380 nm. The observed blue shift could be attributed to

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the electron transfer and hydrogen bonding interaction between 2 and hydrated OH− (Fig. S16b, SI) [46-47]. The stoichiometry ration of 2 and OH– in DMF solution is determined by Job's plot

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(Fig. S24, SI), with keeping the total concentration of OH– and 2 at 1 mM. The stoichiometric ratio of 2 and OH– is determined as 2:3. (Insert Fig. 3)

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3.3. Imaging experiments in living cells.

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To further investigate their sensing properties for biological applications, fluorescence imaging

experiments were accomplished by using MCF-7 cells under vitro experimental conditions. MCF7 cells were incubated with 0.01 mM of 1 for 1 h, exhibiting strong fluorescence (Fig. 4b and 4c). When the cells were incubated with Cu2+ and 1 under the same condition, the fluorescence intensity of 1 in cells decreased with the same trend observed in DMF solution (Fig. 4e and 4f).

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The cellular imaging experiments indicate that 1 has cell permeability and detection ability for Cu2+ in living cells. The fluorescence imaging experiments of 2 in living cells were also carried out (Fig. 5). The

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cell fluorescence images display strong green fluorescence (Fig. 5b and 5c), which demonstrates

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that 2 has cell permeability. Considering the interaction of CO2 with OH– during the cell

(Insert Fig. 4)

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(Insert Fig. 5)

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incubation, the experiments of fluorescence imaging to detect OH– of 2 were not performed.

The toxicity analysis of 1 and 2 were determined by the MTT assay to establish the safer doses

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of the sensor for the bioimaging experiments (Fig. 6a and Fig. 6b). The results indicate that the cytotoxicity of these two compounds is relatively low at a cell imaging concentration of 10 μM.

4. Conclusions

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(Insert Fig. 6)

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In summary, two compounds based on benzothiadiazole moieties have been successfully

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developed for the detection of Cu2+ and OH– ions. Compounds 1 and 2 exhibit “turn-off” fluorescent responding to Cu2+ and OH– with the detection limits of 0.11 μM and 55 μM,

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respectively. Furthermore, fluorescence images of 1 and 2 in MCF-7 cells confirm their cell

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permeability and 1 could be used as fluorescence probe for monitoring Cu2+ in living cells. Appendix A. Supplementary data CCDC 1888349 and 1888350 contain the supplementary crystallographic data for 1 and 2.

These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html, or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (+44) 1223-336-033; or e-mail: [email protected].

Acknowledgements

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This work was financially supported by the National Natural Science Foundation of China (21501077), the China Postdoctoral Science Foundation (2016M592107), the Natural Science Foundation of Jiangxi Province (20161ACB21013, 20161BAB203089 and 20171BCB23066), the

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Project of Jiangxi Provincial Department of Education (No. GJJ170497), and the Program for

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Qingjiang Excellent Young Talents, JXUST.

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[26] Y. Xie, S.G. Ning, Y. Zhang, Z.L. Tang, S.W. Zhang, R.R. Tang, Dyes Pigm. 150 (2018) 36-

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[28] X. Han, W.X. Gong, Y. Tong, D.H. Wei, Y.Y. Wang, J. Ding, H.W. Hou, Y.L. Song, Dyes Pigment. 137 (2017) 135-142. (2010) 13453-13461.

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[29] M. Shen, J. Rodríguez-López, J. Huang, Q. Liu, X.H. Zhu, A.J. Bard, J. Am. Chem. Soc. 132 [30] R.Y.Y. Lin, C.P. Lee, Y.C. Chen, J.D. Peng, T.C. Chu, H.H. Chou, H.M. Yang, J.T. Lin, K.C. Ho, Chem. Commun. 48 (2012) 12071-12073.

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[31] F.Z. Chen, J. Zhang, W.B. Qu, X.X. Zhong, H. Liu, J. Ren, H.P. He, X.H. Zhang, S.F. Wang, Sens. Actuators B: Chem. 266 (2018) 528-533.

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[32] S.L. Yao, T.F. Zheng, X.M. Tian, S.J. Liu, C. Cao, Z.H. Zhu, Y.Q. Chen, J.L. Chen, H.R. Wen, CrystEngComm 20 (2018) 5822-5832. [33] S.L. Yao, S.J. Liu, C. Cao, X.M. Tian, M.N. Bao, T.F. Zheng, J. Solid State Chem. 269 (2019)

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Huang, H.R. Wen, Inorg. Chem. 58 (2019) 3578-3581. [35] X. Zhang, J. X. Chen, H. G. Zheng, Inorg. Chem. Commun. 69 (2016) 4-6. [36] Y.B. Fu, F. Qiu, F. Zhang, Y.Y. Mai, Y.C. Wang, S.B. Fu, R.Z. Tang, X.D. Tang, X.L. Feng, Chem. Commun. 51 (2015) 5298-5301. [37] G.M. Sheldrick, SADABS, Program for empirical absorption correction of area detector data. university of göttingen: Germany. 1996. [38] G.M. Sheldrick, Crystal structure refinement with SHELXL. Acta Cryst. C71 (2015) 3-8.

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[39] G.M. Sheldrick, SHELXT - Integrated Space-Group and Crystal-Structure Determination. Acta Cryst. A71 (2015) 3-8. [40] A. Uslu, S.O. Tümay, A. Şenocak, F. Yuksel, E. Özcan, S. Yeşilot, Dalton Trans. 46 (2017) 9140-9156. [41] M.M. Zhang, X.W. Si, D.H. Jiang, X.L. Yang, Y. Lu, Y.H. Shen, Colloid. Polym. Sci. 295

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(2017) 2383-2393. [42] P. Wang, J. Wu, Spectrochim. Acta A Mol. Biomol. Spectrosc. 208 (2019) 140-149.

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[43] F.N. Moghadam, M. Amirnasr, S. Meghdadi, K. Eskandari, A. Buchholz, W. Plass,

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Spectrochim. Acta A Mol. Biomol. Spectrosc. 207 (2019) 6-15.

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D. Chellappa, Coord. Chem. Rev. 357 (2018) 50-104.

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[46] A.K. Singh, G. Pandey, K. Singh, A. Kumar, M. Trivedi, V. Singh, Dalton Trans. 47 (2018) [47] C.N. Carroll, O.B. Berryman, C.A. JohnsonII, L.N. Zakharov, M.M. Haley, D.W. Johnson,

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Chem. Commun. (2009) 2520-2522.

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Captions to Scheme and Figures

Scheme 1. Synthetic routes of compounds 1 and 2.

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Fig. 1. Crystal structures of compounds 1 (a) and 2 (b)

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Fig. 2. Fluorescence spectra (a) and fluorescence images (b) of 1 (0.1 mM) in DMF solution in the presence of different metal ions (15 equiv.) upon the excitation at 466 nm; (c)

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Competitive experiments of 1 (0.1 mM) in DMF solution in the presence of Cu2+ and the

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same concentration of different metal ions upon the excitation at 466 nm.

Fig. 3. Fluorescence spectra (a) and fluorescence images (b) of 2 (0.1 mM) in DMF solution in the presence of different anions (20 equiv.) upon an excitation at 469 nm; (c) Competitive

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experiments of 2 (0.1 mM) in DMF solution in the presence of 20 equiv. of OH– and the same

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concentration of different anions upon an excitation at 469 nm.

Fig. 4. Bright-field transmission images (a, d), fluorescence images (b, e), and merged image (c, f): (a and b) MCF-7 cells were incubated with 1 (0.01 mM) in a RPMI1640 medium for 1 h; (d

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and e) MCF-7 cells are incubated with Cu2+ (0.06 mM) and 1 in a RPMI1640 medium for 1 h.

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Fig. 5. Bright-field transmission images (a), fluorescence images (b), and merged image (c): (a

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and b) MCF-7 cells were incubated with 2 (0.01 mM) in a RPMI1640 medium for 1 h.

Fig. 6. MTT assay to determine the cytotoxic effect of compounds 1 (a) and 2 (b) on MCF-7 cells.

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Table 1. Crystal data and structure refinements for 1 and 2 1.2H2O

C12H8N6S

Mr

304.34

268.30

crystal system

monoclinic

orthorhombic

space group

C2/c

P21212

a[Å]

17.9559(13)

13.240(7)

b[Å]

11.1157(8)

18.38(1)

c[Å]

7.2787(5)

α [°]

90

β [°]

113.519(2)

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90 90 90

1332.09(16)

1141.9(11)

1.518

1.561

4

4

632

552

μ[mm-1]

0.26

0.28

Collected reflections

9070

3417

Unique reflections

1185

2124

Rint

0.026

0.042

Ra /wRb [I >2σ(I)]

0.0325/0.0792

0.0483 / 0.0931

R1a/wR2b (all data)

0.0399/0.0840

0.0687 / 0.1009

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F(000)

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4.692(3)

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Dcalc [g cm-3]

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V[Å3]

GOF on F2 aR

1.08

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C12H12N6O2S

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molecular formula

γ [°]

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2

1.04

= Σ(||F0| – |FC||)/Σ|F0|. bwR2 = [Σw(|F0|2 – |FC|2)2/(Σw|F0|2)2]1/2

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Scheme 1. Synthetic routes of compounds 1 and 2.

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(a)

(b)

Fig. 1

(a)

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(b)

(c)

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Fig. 2

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(a)

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(b)

(c) Fig. 3

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Fig. 4

Fig. 5

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(a)

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(b)

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Fig. 6

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Two benzothiadiazole-based fluorescent sensors for selective detection of copper(II) and hydroxide

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Xue-Mei Tian, Shu-Li Yao, Jie Wu, Haomiao Xie, Teng-Fei Zheng,* Xiu-Juan Jiang, Yongquan Wu,* Jiangang Mao, Sui-Jun Liu*

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Two benzothiadiazole-based fluorescent sensors for selective detection

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of copper(II) and hydroxide

Xue-Mei Tian, Shu-Li Yao, Jie Wu, Haomiao Xie, Teng-Fei Zheng,* Xiu-Juan Jiang, Yongquan Wu,* Jiangang Mao, Sui-Jun Liu*

Two benzothiadiazole-based compounds exhibit high selectivity and sensitivity to detect Cu2+ and OH– ions, respectively, and 1 could be used as fluorescence probe for monitoring Cu2+ in living cells.

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