Colorimetric chemosensor for multiple targets, Cu²⁺, CN⁻ and S²⁻

Abstract

A simple and easily synthesized colorimetric chemosensor 1, (E)-2-(((2-((2,4-dinitrophenyl)amino)phenyl)imino)methyl)phenol, was designed and synthesized for the detection of Cu²⁺, CN⁻ and S²⁻. Receptor 1 showed a highly selective colorimetric response to copper(II) ions by changing its color from pale yellow to orange immediately without any interference from other metal ions. Also, the sensitivity of UV-vis based assay (8.77 μM) for Cu²⁺ is below the World Health Organization (WHO) guidelines for drinking water (31.5 μM). In addition, chemosensor 1 could be used to quantify Cu²⁺ in water samples and the sensing mechanism of the 1–Cu²⁺ complex was explained by theoretical calculations. The 1–Cu²⁺ complex could be reversible simply through treatment with an appropriate reagent such as EDTA. Moreover, with the “naked eye” 1 could sense cyanide and sulfide by color changes from pale yellow to pale pink and deep pink, respectively, in aqueous solution. Furthermore, sensor 1 can detect both CN⁻ (0.28 μM) and S²⁻ (10.7 μM) below the given guidelines (WHO: 1.9 μM for CN⁻ and Environmental Protection Agency: 7.8 mM for S²⁻).

---

1. Introduction

The development of selective and sensitive chemosensors for the detection of metal ions and anions has received considerable attention because of their important roles in medicine, living systems and ecosystems.^1–3 Among the different types of chemosensors, sensors based on colorimetric determination of anions and metal ions have many advantages because of their convenience, low cost, and rapid tracking of analytes.^4,5 Therefore, colorimetric sensors are recently getting popular due to their capability to detect analytes by the naked eye without utilizing any expensive instruments.^6–11

Among the various metal ions, copper serves as an indispensable cofactor by composing the active part in a large variety of enzymes, including cytochrome c oxidase, superoxide dismutase and tyrosinase.^12–15 Thus, steady ingestion of copper is necessary for our good health.¹⁶ However, unregulated overloading of copper can induce several diseases including Parkinson's, Alzheimer's and prion diseases.^17–21 On the other hand, Cu²⁺ is a major environmental pollutant due to its widespread use. Therefore, World Health Organization (WHO) has prescribed the safe limit of copper in drinking water at 2 ppm (31.5 μM).²² Thus, the development of chemosensors for the detection and monitoring of Cu²⁺, with high sensitivity, low detection limit and quick response, is of great importance.²³

The development of molecular sensors for anions has been a subject of great research interest, because anions play important roles in a wide range of environmental, clinical, chemical, and biological applications.^24–32 Among the various anions, cyanide with a wide use in our life is most concerned, because it is one of the most rapidly acting and powerful poisons. Its toxicity results from its disposition to bind to the iron in cytochrome c oxidase, interfering with electron transport and resulting in hypoxia.^33–45 Cyanide could be absorbed through the lungs, gastrointestinal tract and skin, leading to vomiting, convulsion, loss of consciousness, and eventual death.^46–48 Despite its toxicity, its application in various fields as raw material for synthetic fibers, resins, herbicides, and the gold extraction process is inevitable,^49–51 which releases cyanide into the environment as a toxic contaminant. Thus, there is a need for an effective sensing system to monitor cyanide concentration from contaminant sources.

Sulfide is an extensive environmental pollutant generally released from the paper, petrochemical and leather industries.⁵² In consequence, sulfide as a toxic traditional pollutant can be widely found in water not only due to industrial processes but also thanks to microbial reduction of sulfate by anaerobic bacteria or from sulfur-containing amino acids in meat proteins. The protonated forms, HS⁻ or H₂S, are even more toxic than sulfide itself.⁵³ It can damage the human nerve and respiratory systems, causing people to lose consciousness or even die at very low concentrations (ppm levels).⁵⁴ However, in biological systems, H₂S is usually afforded from L-cysteine in reactions catalyzed by enzymes such as cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfur transferase (3MST), as well as from nonenzymatic processes.⁵⁵ Following nitric oxide (NO) and carbon monoxide (CO), H₂S has been regarded to be the third gasotransmitter to regulate cardiovascular, neuroma, immune, endocrine, and gastro-intestinal systems.^56–58 Several studies have shown that H₂S participates in many physiological processes, such as angiogenesis, vasodilation, regulation of inflammation, neuromodulation and apoptosis.^59–62 In addition, it has also proved that abnormal H₂S production is linked to human diseases such as Alzheimer's disease, Down's syndrome, hypertension, and liver cirrhosis.^63–66 Therefore, the quantitative detection of H₂S is of great significance for both environmental and biological systems.⁶⁷

Herein, we report on a new Schiff base chemosensor 1, based on the combination of a dinitrobenzene and a phenol group (Scheme 1). Chemosensor 1 detected Cu²⁺ by color change from pale yellow to orange, CN⁻ from pale yellow to pale pink, and S²⁻ from pale yellow to deep pink in aqueous solution. The detection mechanisms were proposed for Cu²⁺ with intra-molecular charge transfer (ICT) and for S²⁻ and CN⁻ with the deprotonation process.

Scheme 1 Synthetic procedure of 1.

2. Experimental

2.1. Materials and instrumentation

All the solvents and reagents (analytical grade and spectroscopic grade) were obtained from Sigma-Aldrich and used as received. ¹H NMR and ¹³C NMR spectra were recorded on a Varian 400 and 100 MHz spectrometer. Chemical shifts (δ) were reported in ppm, relative to tetramethylsilane Si(CH₃)₄. Absorption spectra were recorded at room temperature using a Perkin Elmer model Lambda 25 UV/vis spectrometer. Electrospray ionization mass spectra (ESI-mass) were collected on a Thermo Finnigan (San Jose, CA, USA) LCQTM Advantage MAX quadrupole ion trap instrument.

2.2. Synthesis of N1-(2,4-dinitrophenyl)benzene-1,2-diamine

1-Fluoro-2,4-dinitrobenzene (0.17 g, 1 mmol) and benzene-1,2-diamine (0.11 g, 1 mmol) were dissolved in 5 mL of acetonitrile. Then, this solution was stirred for 4 h at room temperature. The red powder produced was filtered, washed using methanol and diethyl ether, and air-dried. Yield: 90%. ¹H NMR (400 MHz, DMSO-d₆) δ 9.74 (s, 1H), 8.91 (d, 1H), 8.23 (d, 1H), 7.12 (m, 2H), 6.83 (d, 1H), 6.64 (t, 2H), 5.28 (s, 2H). ¹³C NMR (100 MHz, DMSO-d₆) δ 148.28, 145.30, 136.26, 131.46, 130.09, 129.23, 128.72, 123.54, 121.53, 117.15, 116.76, 116.15 ppm.

2.3. Synthesis of 1

N1-(2,4-Dinitrophenyl)benzene-1,2-diamine (0.27 g, 1 mmol) and salicylaldehyde (0.11 mL, 1.1 mmol) were dissolved in 5 mL of methanol. Then, three drops of phosphoric acid were added into the reaction mixture, which was stirred for 1 h at room temperature. The pale yellow powder produced was filtered, washed using iced-methanol, and air dried. Yield: 80%. ¹H NMR (400 MHz, DMSO-d₆) δ 12.33 (s, 1H), 10.26 (s, 1H), 8.99 (s, 1H), 8.91 (s, 1H), 8.20 (d, 1H), 7.65 (d, 2H), 7.53 (d, 2H), 7.48 (d, 1H), 7.37 (t, 1H), 6.96 (m, 2H), 6.86 (d, 1H). ¹³C NMR (100 MHz, DMSO-d₆) δ 163.74, 159.96, 146.43, 144.21, 136.28, 133.53, 132.15, 131.54, 130.86, 129.69, 128.48, 127.80, 127.09, 123.13, 119.56, 119.33, 119.04, 116.97, 116.48 ppm. ESI-MS m/z [M − H⁺]⁻: calcd, 377.09; found, 377.33. Anal. calcd for C₁₉H₁₄N₄O₅ (378.10): C, 62.01; H, 4.19; N, 14.06%. Found: C, 62.13; H, 3.84; N, 14.07%.

2.4. UV-vis titration measurement of 1 with Cu²⁺

Receptor 1 (3.78 mg, 0.01 mmol) was dissolved in dimethyl sulfoxide (DMSO, 1 mL) and 6 μL of the receptor 1 (10 mM) was diluted to 2.994 mL of bis–tris buffer/DMSO (1/1, v/v) to make the final concentration of 20 μM. Cu(NO₃)₂·2.5H₂O (2.4 mg, 0.01 mmol) was dissolved in DMSO (1 mL). 0–180 μL of the Cu(NO₃)₂ solution (10 mM) was transferred to the receptor 1 solution (20 μM) prepared above. After mixing them for a few seconds, UV-vis spectra were taken at room temperature.

2.5. Job plot measurement of 1 with Cu²⁺

Receptor 1 (3.78 mg, 0.01 mmol) was dissolved in DMSO (1 mL) and 300 μL of the receptor 1 (10 mM) was diluted to 29.7 mL of bis–tris buffer/DMSO (1 : 1, v/v) to make the final concentration of 100 μM. Cu(NO₃)₂·2.5H₂O (2.4 mg, 0.01 mmol) was dissolved in DMSO (1 mL) and 300 μL of the copper solution (10 mM) was diluted to 29.7 mL of bis–tris buffer/DMSO (1 : 1, v/v) to make the final concentration of 100 μM. 4.5, 4.0, 3.5, 3.0, 2.5, 2.0, 1.5, 1.0, and 0.5 mL of the 1 solution were taken and transferred to vials. 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, and 4.5 mL of the copper solution were added to solutions of 1 prepared above. Each vial had a total volume of 5 mL. After shaking the vials for a few seconds, UV-vis spectra were taken at room temperature.

2.6. Competition of 1 toward various metal ions

Receptor 1 (3.78 mg, 0.01 mmol) was dissolved in DMSO (1 mL) and 6 μL of this solution (10 mM) was diluted with 2.994 mL of bis–tris buffer/DMSO (1 : 1, v/v) to make the final concentration of 20 μM. MNO₃ (M = Na, K; 0.01 mmol), M(NO₃)₂ (M = Mn, Co, Ni, Cu, Zn, Cd, Mg, Ca, Pb; 0.01 mmol), M(ClO₄)₂ (M = Fe; 0.01 mmol) and M(NO₃)₃ (M = Al, Fe, Cr, Ga, In; 0.01 mmol) were separately dissolved in bis–tris buffer (1 mL). 48 μL of each metal solution (10 mM) was taken and added into 3 mL of each receptor 1 (20 μM) prepared above to make 8 equiv. Then, 48 μL of the Cu(NO₃)₂ solution (10 mM) was added into the mixed solution of each metal ion and receptor 1 to make 8 equiv. After mixing them for a few seconds, UV-vis spectra were taken at room temperature.

2.7. UV-vis titration measurements of 1 with anions

For CN⁻; receptor 1 (3.78 mg, 0.01 mmol) was dissolved in DMSO (1 mL) and 3 μL of the receptor 1 (10 mM) was diluted to 2.997 mL of bis–tris buffer/DMSO (1/9, v/v) to make the final concentration of 10 μM. Tetraethylammonium cyanide (16.56 mg, 0.1 mmol) was dissolved in bis–tris buffer (1 mL). 0–84 μL of the CN⁻ solution (100 mM) was transferred to the receptor 1 solution (10 μM) prepared above. After mixing them for a few seconds, UV-vis spectra were taken at room temperature.

For S²⁻; receptor 1 (3.78 mg, 0.01 mmol) was dissolved in DMSO (1 mL) and 3 μL of the receptor 1 (10 mM) was diluted to 2.997 mL of bis–tris buffer/DMSO (1/9, v/v) to make the final concentration of 10 μM. Sodium sulfide nonahydrate (24.01 mg, 0.1 mmol) was dissolved in bis–tris buffer (1 mL). 0–27 μL of the S²⁻ solution (100 mM) was transferred to the receptor 1 solution (10 μM) prepared above. After mixing them for a few seconds, UV-vis spectra were taken at room temperature.

2.8. Job plot measurements of 1 with anions

For CN⁻; receptor 1 (3.78 mg, 0.01 mmol) was dissolved in DMSO (1 mL) and 300 μL of the receptor 1 (10 mM) was diluted to 29.7 mL of bis–tris buffer/DMSO (1 : 9, v/v) to make the final concentration of 100 μM. Tetraethylammonium cyanide (16.56 mg, 0.1 mmol) was dissolved in bis–tris buffer (1 mL) and 30 μL of the tetraethylammonium cyanide solution (100 mM) was diluted to 29.97 mL of bis–tris buffer/DMSO (1 : 9, v/v) to make the final concentration of 100 μM. 4.5, 4.0, 3.5, 3.0, 2.5, 2.0, 1.5, 1.0, and 0.5 mL of the 1 solution were taken and transferred to vials. 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, and 4.5 mL of the tetraethylammonium cyanide solution were added to solutions of 1 prepared above. Each vial had a total volume of 5 mL. After shaking the vials for a few seconds, UV-vis spectra were taken at room temperature.

For S²⁻; receptor 1 (3.78 mg, 0.01 mmol) was dissolved in DMSO (1 mL) and 300 μL of the receptor 1 (10 mM) was diluted to 29.7 mL of bis–tris buffer/DMSO (1 : 9, v/v) to make the final concentration of 100 μM. Sodium sulfide nonahydrate (24.01 mg, 0.1 mmol) was dissolved in bis–tris buffer (1 mL) and 30 μL of the sodium sulfide nonahydrate solution (100 mM) was diluted to 29.97 mL of bis–tris buffer/DMSO (1 : 9, v/v) to make the final concentration of 100 μM. 4.5, 4.0, 3.5, 3.0, 2.5, 2.0, 1.5, 1.0, and 0.5 mL of the 1 solution were taken and transferred to vials. 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, and 4.5 mL of the sodium sulfide nonahydrate solution were added to solutions of 1 prepared above. Each vial had a total volume of 5 mL. After shaking the vials for a few seconds, UV-vis spectra were taken at room temperature.

2.9. Competition of 1 toward various anions

For CN⁻; receptor 1 (3.78 mg, 0.01 mmol) was dissolved in DMSO (1 mL) and 3 μL of this solution (10 mM) was diluted with 2.997 mL of bis–tris buffer/DMSO (1 : 9, v/v) to make the final concentration of 10 μM. Tetraethylammonium salts of F⁻, Cl⁻, Br⁻ and I⁻, and tetrabutylammonium salts of OAc⁻, PO₄³⁻, N₃⁻, SCN⁻ and BzO⁻ (0.1 mmol), and sodium salts of SCN⁻, N₃⁻, SO₄²⁻ and S²⁻ (0.1 mmol) were separately dissolved in bis–tris buffer (1 mL). 78 μL of each anion solution (100 mM) was taken and added into 3 mL of each receptor 1 (10 μM) prepared above to make 260 equiv. Then, 78 μL of the tetraethylammonium cyanide solution (100 mM) was added into the mixed solution of each anion and receptor 1 to make 260 equiv. After mixing them for a few seconds, UV-vis spectra were taken at room temperature.

For S²⁻; receptor 1 (3.78 mg, 0.01 mmol) was dissolved in DMSO (1 mL) and 3 μL of this solution (10 mM) was diluted with 2.997 mL of bis–tris buffer/DMSO (1 : 9, v/v) to make the final concentration of 10 μM. Tetraethylammonium salts of F⁻, Cl⁻, Br⁻ and I⁻, and tetrabutylammonium salts of OAc⁻, PO₄³⁻, N₃⁻, SCN⁻ and BzO⁻ (0.1 mmol), and sodium salts of SCN⁻, N₃⁻, SO₄²⁻ and S²⁻ were separately dissolved in bis–tris buffer (1 mL). 26.4 μL of each anion solution (100 mM) was taken and added into 3 mL of each receptor 1 (10 μM) prepared above to make 88 equiv. Then, 26.4 μL of the sodium sulfide nonahydrate solution (100 mM) were added into the mixed solution of each anion and receptor 1 to make 88 equiv. After mixing them for a few seconds, UV-vis spectra were taken at room temperature.

2.10. ¹H NMR titrations of 1 with anions

For CN⁻; five NMR tubes of 1 (3.78 mg, 0.01 mmol) dissolved in DMSO-d₆ were prepared, and then five different equiv. (0, 0.1, 0.5 and 1 equiv.) of tetraethylammonium cyanide dissolved in DMSO-d₆ were added to 1 solution separately. After shaking them for a minute, their ¹H NMR spectra were taken.

For S²⁻; four NMR tubes of 1 (3.78 mg, 0.01 mmol) dissolved in DMSO-d₆ were prepared, and then four different equiv. (0, 0.5, 1, 5 and 10 equiv.) of sodium sulfide nonahydrate dissolved in D₂O were added to 1 solution separately. After shaking them for a minute, their ¹H NMR spectra were taken.

2.11. Determination of Cu²⁺ in water samples

UV-vis spectral measurements of water samples containing Cu²⁺ were carried out by adding 6 μL of 1 mM stock solution of 1 and 0.60 mL of 50 mmol L⁻¹ bis–tris buffer stock solution to 2.394 mL sample solutions. After well mixed, the solutions were allowed to stand at 25 °C for 2 min before the test.

2.12. Theoretical calculation methods of 1 with Cu²⁺

All theoretical calculations were performed by DFT/TD-DFT method with the hybrid exchange-correlation functional B3LYP^68,69 applying the 6-31G**^70,71 basis set for the main group elements, whereas the Lanl2DZ effective core potential (ECP)^72–74 was employed for Cu. The energy-minimized structures of 1 and 1–Cu²⁺ complex were obtained in various geometric forms. In vibrational frequency calculations, there was no imaginary frequency for the optimized geometries of 1 and 1–Cu²⁺ complex, suggesting that these geometries represented local minima. For all calculations, the solvent effect of water was considered by using the Cossi and Barone's CPCM (conductor-like polarizable continuum model).^75,76 In order to investigate the transition energies for the optimized structures of 1 and 1–Cu²⁺ complex, we calculated the lowest 25 singlet–singlet transitions using their ground state geometry (S₀) with TD-DFT (B3LYP) method. The GaussSum 2.1 was used to calculate the contribution of molecular orbital in electronic transitions.⁷⁷ All the calculations were performed with Gaussian 03 suite.⁷⁸

3. Results and discussion

The receptor 1 was synthesized by coupling N1-(2,4-dinitrophenyl)benzene-1,2-diamine with salicylaldehyde in methanol (Scheme 1). The precursor N1-(2,4-dinitrophenyl)benzene-1,2-diamine was obtained by substitution reaction of 1-fluoro-2,4-dinitrobenzene and benzene-1,2-diamine in acetonitrile. Receptor 1 and the precursor N1-(2,4-dinitrophenyl)benzene-1,2-diamine were characterized by ¹H NMR, ¹³C NMR, ESI-mass spectrometry and elemental analysis.

3.1. Spectroscopic studies of 1 toward Cu²⁺

To examine the colorimetric properties of 1, the UV-vis absorption was measured with various metal ions (Na⁺, K⁺, Mg²⁺, Ca²⁺, Al³⁺, Ga³⁺, In³⁺, Cr³⁺, Mn²⁺, Fe²⁺, Fe³⁺, Co²⁺, Ni²⁺, Cu²⁺, Zn²⁺ Cd²⁺, Hg²⁺, Ag⁺ and Pb²⁺) in bis–tris buffer/DMSO (1 : 1, v/v, 10 mM, pH 7.0). Upon the addition of 8 equiv. of each metal ion, only Cu²⁺ induced a distinct spectral change at 412 nm, while other metal ions showed either no or small changes in the absorption spectra relative to the free receptor 1 (Fig. 1a). For example, Fe²⁺ and Fe³⁺ showed a small red-shift. In consistency with the absorption spectrum, the solution color of 1 changed from pale yellow to orange with copper ion (Fig. 1b), indicating that the receptor 1 could serve as a potential candidate of colorimetric chemosensor for Cu²⁺.

Fig. 1 (a) Absorption spectral change of 1 (20 μM) in the presence of 8 equiv. of various metal ions in a mixture of bis–tris buffer/DMSO (1 : 1, v/v). (b) Color change of receptor 1 (20 μM) in the presence of 8 equiv. of various metal ions in a mixture of bis–tris buffer/DMSO (1 : 1, v/v).

The binding properties of 1 with Cu²⁺ were studied by UV-vis titration experiments. On treatment with Cu²⁺ to solution of 1, the absorption band at 348 nm significantly decreased, and a new band at 412 nm gradually reached a maximum at 8 equiv. of Cu²⁺ (Fig. 2). An isosbestic point was observed at 381 nm, indicating that only one product was generated from 1 upon binding to Cu²⁺. The Job plot analysis⁷⁹ showed a 1 : 1 stoichiometry of Cu²⁺ to 1 (Fig. S1†). To further examine the binding mode between 1 and Cu²⁺, a positive-ion ESI-mass experiment was carried out. The positive-ion mass spectrum of 1 with 1 equiv. of Cu²⁺ showed the formation of the [1²⁻ + Cu²⁺ + DMSO + H⁺] complex [m/z 517.93, calcd m/z 518.03] (Fig. S2†).

Fig. 2 Absorption spectral changes of 1 (20 μM) in the presence of different concentrations of Cu²⁺ (from 0 to 9 equiv.) at room temperature.

The sensing mechanism of Cu²⁺ by 1 could be explained by intra-molecular charge transfer (ICT). Kaur et al. suggested that the ICT mechanism referred to the push–pull effect of the electron-donating and electron-withdrawing groups.⁸⁰ That is, the red shift indicates that the energy gap of ICT band decreases, upon binding Cu²⁺ ion to the electron-withdrawing moieties. Likewise, we assume that the red shift of 1–Cu²⁺ complex might be induced by binding of Cu²⁺ ion to the electron withdrawing groups such as the imine and the aniline with the nitro moiety. Therefore, the change of ICT band might be responsible for the color change from pale yellow to orange.

Based on the UV-vis titration of 1 with Cu²⁺, the association constant (K) of 1 with Cu²⁺ was calculated by using Benesi–Hildebrand equation (Fig. S3†).⁸¹ The K value was determined to be 2.7 × 10³ M⁻¹, which is within the range of those (10³ to 10¹²) reported for Cu²⁺ sensing chemosensors.^82–84 The detection limit^85,86 of receptor 1 for Cu²⁺ ions on the basis of 3σ/K was found to be 8.77 μM (Fig. S4†), which is lower than the WHO guideline (31.5 μM) for Cu²⁺ in drinking water.²² Therefore, receptor 1 can serve as a good indicator for monitoring Cu²⁺ ions in aqueous solution.

To further check the practical applicability of receptor 1 as a Cu²⁺ selective sensor, the competition experiments were conducted (Fig. 3). Upon treatment with 8 equiv. of Cu²⁺ in the presence of the same concentration of other metal ions, there were no obvious interferences for the detection of Cu²⁺. In cases of Fe²⁺ and Fe³⁺, somewhat higher absorbance at 412 nm was observed, due to their original absorbance (compare Fig. 3 with Fig. 1). Thus, 1 could be used as a selective colorimetric sensor for Cu²⁺ in the presence of most competing metal ions.

Fig. 3 (a) Competitive selectivity of 1 (20 μM) towards Cu²⁺ (8 equiv.) in the presence of other metal ions (8 equiv.) in a mixture of bis–tris buffer/DMSO (1 : 1, v/v). (b) Colorimetric competitive experiment of 1 (20 μM) in the presence of Cu²⁺ (8 equiv.) and other metal ions (8 equiv.) in a mixture of bis–tris buffer/DMSO (1 : 1, v/v).

We investigated the effect of pH on the absorption response of receptor 1 to Cu²⁺ ion in a series of solutions with pH values ranging from 2 to 12 (Fig. S5†). The color of the 1–Cu²⁺ complex remained in the orange color between pH 6 and 10. These results indicated that Cu²⁺ could be clearly detected by the naked eye or UV-vis absorption measurements using 1 over the pH range of 6–10.

To examine the reversibility of sensor 1 toward Cu²⁺, ethylenediaminetetraacetic acid (EDTA, 1 equiv.) was added to the complexed solution of sensor 1 and Cu²⁺. As shown in Fig. 4, the absorbance at 412 nm disappeared immediately. Upon addition of Cu²⁺ again, the absorbance was recovered. The absorbance changes were almost reversible even after several cycles with the sequentially alternative addition of Cu²⁺ and EDTA. These results indicated that sensor 1 could be recyclable simply through treatment with a proper reagent such as EDTA. Such reversibility and regeneration could be important for the fabrication of chemosensors to detect Cu²⁺.

Fig. 4 (a) UV-vis spectral changes of 1 (20 mM) after the sequential addition of Cu²⁺ and EDTA in bis–tris buffer/DMSO (v/v, 1 : 9). (b) Reversible changes in absorbance of 1 (20 mM) at 412 nm after the sequential addition of Cu²⁺ and EDTA; 1 (1), 2 (1 + Cu²⁺), 3 (1 + Cu²⁺ + EDTA), 4 (1 + Cu²⁺ + EDTA + Cu²⁺).

In order to examine the practical application of the chemosensor 1 in environmental samples, the chemosensor 1 was applied for the determination of Cu²⁺ in aqueous environment samples, using the calibration curve of 1 toward Cu²⁺ (Fig. S6†). Drinking water samples were chosen (Table 1) and showed a suitable recovery and R.S.D. values. These results suggested that the chemosensor 1 was suitable for the determination of Cu²⁺ concentration.

Table 1 Determination of Cu(II) in water samples^a

Sample	Cu(II) added (μmol L^−1)	Cu(II) found (μmol L^−1)	Recovery (%)	R.S.D. (n = 3) (%)
a Conditions: [1] = 10 μmol L^−1 in 10 mM bis–tris buffer/DMSO solution (1 : 1, pH 7.0).
Drinking water	0.00	0.00	—	—
	10.00	10.75	107.5	7.9

---

To clearly demonstrate the sensing mechanisms of 1 toward Cu²⁺, theoretical calculations were performed with the 1 : 1 stoichiometry (Cu²⁺ : receptor), based on Job plot and ESI-mass spectrometry analysis. To get the energy-minimized structures of 1 and 1–Cu²⁺ complex, their geometric optimizations were performed by DFT/B3LYP level (main group atom: 6-31G** and Cu: Lanl2DZ/ECP). The significant structural properties of the energy-minimized structures were shown in Fig. 5. The energy-minimized structure of 1 has a bent structure with the dihedral angles of −65.983° (1C, 2N, 3C, 4C) and −28.185 (3C, 4C, 5N, 6C), and the hydrogen bonds are observed in 3N–5H and 9O–10H (Fig. 5a). 1–Cu²⁺ complex exhibits a square planar structure with the dihedral angles of 8.833° (9O, 2N, 5N, 6O), −28.185 (3C, 4C, 5N, 6C) and −150.565 (1C, 2N, 3C, 4C), and Cu²⁺ is coordinated with 9O, 2N, 5N and 7O atoms of 1 (Fig. 5b). We also investigated the absorption to the singlet excited states of 1 and 1–Cu²⁺ complex via TDDFT calculations. In case of 1, the third lowest excited state was considered to be responsible for the yellow color of 1, which was determined to HOMO−1 → LUMO and HOMO → LUMO+1 transitions (403.53 nm, Fig. S7†). The major composition, HOMO−1 → LUMO, indicated ICT transition from the three benzene rings to two nitro groups. For 1–Cu²⁺ complex, the 14th lowest excited state was considered to be responsible for orange color of 1–Cu²⁺ complex, which was determined to HOMO → LUMO+1 (α) and HOMO → LUMO+2 (β) transitions (438.86 nm, Fig. S8†). The transitions were almost similar to the HOMO−1 → LUMO transition of 1 (Fig. S9†). These results indicated that the chelation of Cu²⁺ with 1 stabilized the energy of ICT transition, which induced the different color change of 1 in the presence of Cu²⁺.

Fig. 5 The energy-minimized structures of (a) 1 and (b) 1–Cu²⁺ complex.

Based on Job plot, ESI-mass spectrometry analysis and theoretical calculations, we propose that the oxygen atom of the hydroxyl group, the nitrogen atom of the imine group, the nitrogen atom of amine group, and the oxygen atom of the nitro group in 1 might bind to Cu²⁺ (Scheme 2).

Scheme 2 Proposed structure of 1–Cu²⁺ complex.

3.2. Spectroscopic studies of 1 toward CN⁻ and S²⁻

The colorimetric sensing abilities of 1 toward various anions were also investigated in a mixture of bis–tris buffer/DMSO (1 : 9, v/v) upon addition of tetraethylammonium (TEA) salts of CN⁻, F⁻, Cl⁻, Br⁻, and I⁻, and tetrabutylammonium (TBA) salts of OAc⁻, H₂PO₄⁻, N₃⁻, SCN⁻ and BzO⁻, and sodium salts of NO₂⁻, HSO₄⁻ and S²⁻. Upon the addition of 260 equiv. of each anion, the 1 showed almost no change in absorption peak in the presence of F⁻, Cl⁻, Br⁻, I⁻, OAc⁻, H₂PO₄⁻, N₃⁻, SCN⁻, BzO⁻, NO₂⁻ and HSO₄⁻ (Fig. 6a). By contrast, CN⁻ and S²⁻ showed distinct spectral changes. Consistent with the changes in their UV-vis spectra, CN⁻ and S²⁻ showed color changes from yellow to pale pink and to deep pink, respectively, while other anions had no change in color (Fig. 6b). Additionally, a cross-validation study of the 1–Cu²⁺ complex toward cyanide and sulfide ion was conducted (Fig. S10†). The addition of S²⁻ to the complexed solution of sensor 1 and Cu²⁺ changed its color from yellow to dark yellow, confirming existence of both Cu²⁺ and S²⁻. However, the addition of CN⁻ to 1–Cu²⁺ solution changed its color from yellow to colorless. Therefore, the existence of both Cu²⁺ and CN⁻ could not be discernible with 1.

Fig. 6 (a) Absorption spectral change of 1 (10 μM) in the presence of 260 equiv. of various anions in a mixture of bis–tris buffer/DMSO (1 : 9, v/v). (b) Color change of receptor 1 (10 μM) in the presence of 260 equiv. of various anions in a mixture of bis–tris buffer/DMSO (1 : 9, v/v).

First of all, the binding properties of 1 with CN⁻ were studied by UV-vis titration experiments (Fig. 7a). Once one looks carefully into Fig. 7a, there is the two-step change of the absorption bands. The first change is that the absorbance at 350 nm decreased gradually, while a new absorbance at 500 nm increased with a clear isosbestic point at 398 nm (Fig. 7b). The second change is that the absorbance at 350 nm continuously decreased, and the broad band in the range of 425–525 nm gradually increased with a well-defined isosbestic point at 418 nm (Fig. 7c). Based on this two-step UV-vis process, we proposed that, in the first step, the NH and OH of 1 might form hydrogen bonding with CN⁻, and in the second step, the hydroxyl group be completely deprotonated by CN⁻ (Scheme 3). The negative charge of 1⁻ generated from the deprotonation would lead to the red shift, resulting in the pale pink color. Therefore, the bathochromic shift of the absorption band led us to propose the transition of intra-molecular charge transfer (ICT) band through the deprotonation of the chemosensor 1 by the cyanide, based on Bhattacharya's proposal.^87–89

Fig. 7 (a) Absorption spectral changes of 1 (10 μM) in the presence of different concentrations of CN⁻ (from 0 to 280 equiv.) at room temperature. (b) Absorption spectral changes of 1 (10 μM), extracted from the range of 0–100 equiv. of CN⁻ in (a). (c) Absorption spectral changes of 1 (10 μM), extracted from the range of 110–280 equiv. of CN⁻ in (a).

Scheme 3 Proposed sensing mechanism of 1 for cyanide.

To further prove the sensing mechanism between 1 and CN⁻, the interaction between 1 and OH⁻ was also investigated (Fig. S11†). UV-vis spectral change of 1 upon addition of 10 equiv. of OH⁻ was similar to that of 1 obtained from the addition of CN⁻, which indicated the deprotonation between 1 and CN⁻. The formation of 1⁻ generated from the deprotonation was further supported by ESI-mass spectrometry analysis (Fig. S12†). The positive-ion mass spectrum of 1 upon addition of CN⁻ showed the formation of the 1⁻ + 2TEA [m/z; 636.93, calcd; 637.41]. The Job plot⁷⁴ showed a 1 : 1 stoichiometry between 1 and CN⁻ (Fig. S13†).

Based on the UV-vis titration of 1 with CN⁻, the association constant (K) of 1 with CN⁻ was calculated by using non-linear fitting analysis (Fig. S14†). The K value was determined to be 4.2 × 10³. This value is within the range of those (1.0 to 1.0 × 10⁵) reported for CN⁻ chemosensors.^90–93 The detection limit (3σ/K) of receptor 1 for the analysis of CN⁻ was calculated to be 0.28 μM (Fig. S15†).⁸⁰ The value is 6 times lower than the WHO guideline (1.9 μM) for CN⁻ in drinking water.⁸¹ Hence, receptor 1 could be used as a good detector for monitoring CN⁻ ion in drinking water.

The preferential selectivity of 1 as a naked eye chemosensor for the detection of CN⁻ was studied in the presence of various competing anions. For competition studies, receptor 1 was treated with 260 equiv. of CN⁻ in the presence of 260 equiv. of other anions (Fig. 8). There was no interference in the detection of CN⁻ in the presence F⁻, OAc⁻, Cl⁻, Br⁻, I⁻, PO₄³⁻, N₃⁻, SCN⁻, BzO⁻, NO₂⁻ and SO₄²⁻, except S²⁻. Thus, 1 could be used as a selective colorimetric sensor for CN⁻ in the presence of the competing anions.

Fig. 8 (a) Competitive selectivity of 1 (10 μM) towards CN⁻ (260 equiv.) in the presence of other anions (260 equiv.) in a mixture of bis–tris buffer/DMSO (1 : 9, v/v). (b) Colorimetric competitive experiment of 1 (10 μM) in the presence of CN⁻ (260 equiv.) and other anions (260 equiv.) in a mixture of bis–tris buffer/DMSO (1 : 9, v/v).

To further understand the nature of interaction between sensor 1 and the cyanide, ¹H NMR study was initiated (Fig. S16†). Upon addition of 0.2 equiv. of TEA(CN) as the cyanide source, two singlets at 12.39 ppm (–OH₁) and 10.31 ppm (–NH₁₁) almost disappeared. This result might be attributed to possible double hydrogen bonding of the Y-shaped ion causing stronger binding.⁹⁴ On excess addition of CN⁻ to 1 solution, the two singlets at 12.39 ppm (–OH₁) and 10.31 ppm (–NH₁₁) completely disappeared. At the same time, all aromatic protons shifted to upfield, which suggests that the negative charge generated from the deprotonation of 1 by CN⁻ was delocalized over the whole receptor molecule. Therefore, these results could support the proposal that the sensing mechanism of 1 for cyanide occurs by the deprotonation pathway. Based on UV-vis titration, Job plot, ESI-mass spectrometry analysis and ¹H NMR study, we propose that receptor 1 senses CN⁻ by the deprotonation process, as shown in Scheme 3.

The effect of pH on the absorption response of receptor 1 to CN⁻ was investigated in a series of solutions with pH values ranging from 2 to 12 (Fig. S17†). The color of the 1–CN⁻ species remained in the pale pink color between pH 7 and 11. These results indicated that CN⁻ could be clearly detected by the naked eye or UV-vis absorption measurements using 1 over the pH range of 7.0–11.0.

Next, the binding properties of 1 with S²⁻ were also studied by UV-vis titration experiments (Fig. S18†). If one looks carefully into the UV-vis titration, there is the three-step change of the absorption bands. The first change is up to 60 equiv. of S²⁻ that the absorbance at 348 nm decreased gradually, while a new absorbance at 500 nm increased with a clear isosbestic point at 385 nm (Fig. S18b†). The second change is up to 75 equiv. of S²⁻ that the absorbance at 348 nm continuously deceased, and at the same time, a new band at 425 nm increased with a well-define isosbestic point at 390 nm (Fig. S18c†). The third change is up to 88 equiv. of S²⁻ that the absorbance at 348 nm slightly deceased, and a new band at 412 nm showed a slight increase with the isosbestic point at 373 nm (Fig. S18d†). Based on this three-step UV-vis process, we proposed that, in the first step, the NH and OH of 1 might form hydrogen bonding with S²⁻, and in the second step, the hydroxyl group be completely deprotonated by S²⁻, and in the third step, the amine group be completely deprotonated by S²⁻ (see Scheme 4). The deep pink color of the solution observed upon addition of sulfide to receptor 1 might be attributed to the intramolecular charge transfer (ICT) transition from the deprotonation of the chemosensor 1 by the sulfide, based on Bhattacharya's proposal.^83–85 To further prove the sensing mechanism between 1 and S²⁻, the interaction between 1 and OH⁻ was also investigated (Fig. S19†). UV-vis spectral change of 1 upon addition of 14 equiv. of OH⁻ was nearly identical to that of 1 obtained from the addition of S²⁻.

Scheme 4 Proposed sensing mechanism of 1 for sulfide.

The Job plot⁷⁴ indicated a 1 : 1 stoichiometric ratio between the S²⁻ and 1 (Fig. S20†). Moreover, the negative-ion mass spectrum of 1 with 1 equiv. of S²⁻ showed the formation of the 1⁻ + NaCl + H₂O complex [m/z 453.33, calcd m/z 453.06] (Fig. S21†).

To further explain the proposed sensing mechanism between the receptor 1 and S²⁻, ¹H NMR titrations of 1 were performed by the addition of S²⁻ (Fig. 9). Upon addition of 0.2 equiv. of S²⁻, two singlets at 12.39 (–OH₁) and 10.31 ppm (–NH₁₁) disappeared. This result might be due to possible double hydrogen bonding of the Y-shaped ion causing stronger binding.⁹⁴ Upon further addition of S²⁻, all aromatic protons shifted to upfield, which was much larger than that observed with CN⁻. These results suggest that both protons of 1 in the presence of an excess of S²⁻ might undergo the deprotonation to generate 1²⁻ species. Therefore, the double negative charges developed from deprotonation of 1 by excess S²⁻ were delocalized through the whole receptor molecule and then, all protons showed large upfield-shift. Based on the UV-vis titration, Job plot, ESI-mass analysis and ¹H NMR titrations, we proposed the sensing mechanism of S²⁻ by 1, as shown in Scheme 4.

Fig. 9 ¹H NMR titration of receptor 1 with S²⁻.

Based on the UV-vis titration data, the binding constant for 1 with S²⁻ was estimated to be 1.2 × 10³ M⁻¹ from Benesi–Hildebrand equation (Fig. S22†).⁸¹ The detection limit⁸⁵ (3σ/K) of receptor 1 as a colorimetric sensor for the analysis of S²⁻ ion was found to be 10.7 μM (Fig. S23†). The value is 80 times lower than a Secondary Maximum Contaminant Level (SMCL) set for odor in drinking water as established by the EPA (7.8 mM).⁹⁵ Hence, receptor 1 could be used as a good detector for monitoring S²⁻ ion in drinking water.

The preferential selectivity of 1 as a naked eye chemosensor for the detection of S²⁻ was studied in the presence of various competing anions. For competition studies, receptor 1 was treated with 88 equiv. of S²⁻ in the presence of 88 equiv. of other anions, as shown in Fig. 10. There was no interference in the detection of S²⁻ in the presence F⁻, OAc⁻, Cl⁻, Br⁻, I⁻, PO₄³⁻, N₃⁻, SCN⁻, BzO⁻, SO₄²⁻, NO₂⁻ and CN⁻. Just in a case, if S²⁻ and CN⁻ species are present simultaneously, only S²⁻ could be detected by 1. That is, S²⁻ species interacts with 1 much more strongly than CN⁻ one. Thus, 1 could be used as an excellent selective colorimetric sensor for S²⁻ in the presence of the competing anions.

Fig. 10 (a) Competitive selectivity of 1 (10 μM) towards S²⁻ (88 equiv.) in the presence of other anions (88 equiv.) in a mixture of bis–tris buffer/DMSO (1 : 9, v/v). (b) Colorimetric competitive experiment of 1 (10 μM) in the presence of S⁻ (88 equiv.) and other anions (88 equiv.) in a mixture of bis–tris buffer/DMSO (1 : 9, v/v).

The effect of pH on the absorption response of receptor 1 to S²⁻ was studied in a series of solutions with pH values ranging from 2 to 12 (Fig. S24†). The color of the 1–S²⁻ species remained in the deep pink color between pH 7 and 11. These results indicated that S²⁻ could be clearly detected by the naked eye or UV-vis absorption measurements using 1 over the pH range of 7.0–11.0.

To study the reversible behaviors of 1 toward CN⁻ and S²⁻, Al³⁺ was added to the each solution of 1–CN⁻ and 1–S²⁻. For CN⁻, the absorbance at 500 nm disappeared immediately (Fig. S25†). Upon addition of CN⁻ again, the absorbance was recovered. The absorbance changes were almost reversible with the sequentially alternative addition of CN⁻ and Al³⁺. In case of S²⁻, the absorbance at 427 nm also disappeared immediately (Fig. S26†). Upon addition of S²⁻ again, the absorbance was also recovered, and the absorbance changes were reversible even for several cycles.

4. Conclusion

We have developed an outstanding colorimetric chemosensor 1, based on the combination of (E)-2-(((2-((2,4-dinitrophenyl)amino)phenyl)imino)methyl)phenol moiety and salycilaldehyde, capable of recognizing the multiple targets, Cu²⁺, CN⁻, and S²⁻, in aqueous solution. The receptor 1 displayed a highly selective and sensitive colorimetric recognition toward Cu²⁺ by a color change from pale yellow to orange, and enabled the analysis of Cu²⁺ ions with a sensitivity limit of 8.77 μM, which was below the WHO acceptable limit (31.5 μM) in drinking water. In addition, the chemosensor 1 could be used to quantify Cu²⁺ in water samples and the sensing mechanism of 1–Cu²⁺ complex was explained by theoretical calculations. Moreover, 1 can detect CN⁻ with a color change from pale yellow to pale pink. The detection limit for CN⁻ was found to be 0.28 μM, which was lower than the WHO acceptable limit (1.9 μM) in drinking water. Moreover, 1 has the ability to detect S²⁻ with a color change form pale yellow to deep pink, and showed a very low sensitivity limit of 10.7 μM, much lower than the EPA acceptable limit (7.8 mM) in drinking water. On the basis of the results, we believe that receptor 1 will offer an important guidance to the development of single receptors for recognizing both cations and anions.

Acknowledgements

Financial support from Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2014R1A2A1A11051794 and NRF-2015R1A2A2A09001301) are gratefully acknowledged. We thank Nano-Inorganic Laboratory, Department of Nano & Bio chemistry, Kookmin University to access the Gaussian 03 program packages.

References

1. A. P. de Silva, H. Q. N. Gunaratne, T. Gunnlaugsson, A. J. M. Huxley, C. P. MCCoy, J. T. Rademacher and T. E. Rice, Chem. Rev., 1997, 97, 1515–1566.
2. B. Valeur and I. Leray, Coord. Chem. Rev., 2000, 205, 3–40.
3. G. R. You, G. J. Park, J. J. Lee and C. Kim, Dalton Trans., 2015, 44, 9120–9129.
4. P. D. Beer and P. A. Gale, Angew. Chem., Int. Ed., 2001, 40, 486–516.
5. S. K. Sahoo, D. Sharma, R. K. Bera, G. Crisponi and J. F. Callan, Chem. Soc. Rev., 2012, 41, 7195–7227.
6. P. Anzenbacher Jr, A. C. Try, H. Miyaj, K. Jursikova, V. M. Lynch, M. Marquez and J. L. Sessler, J. Am. Chem. Soc., 2000, 122, 10268–10272.
7. H. Miyaji and J. L. Sessler, Angew. Chem., Int. Ed., 2001, 40, 154–157.
8. H. Miyaji, W. Sato and J. L. Sessler, Angew. Chem., Int. Ed., 2000, 39, 1777–1780.
9. S. Xu, K. Chen and H. Tian, J. Mater. Chem., 2005, 15, 2676–2680.
10. M. S. Han and D. H. Kim, Tetrahedron, 2004, 60, 11251–11257.
11. S. H. Li, C. W. Yu and J. G. Xu, Chem. Commun., 2005, 450–452.
12. R. McRae, P. Bagchi, S. Sumalekshmy and C. J. Fahrni, Chem. Rev., 2009, 109, 4780–4827.
13. K. J. Barnham, C. L. Masters and A. L. Bush, Drug Discovery, 2004, 3, 205–214.
14. J. Li, Y. Zeng, Q. Hu, X. Yu, J. Guo and Z. Pan, Dalton Trans., 2012, 41, 3623–3626.
15. H. Kim, Y. J. Na, E. J. Song, K. B. Kim, J. M. Bae and C. Kim, RSC Adv., 2014, 4, 22463–22469.
16. Y. K. Jang, U. C. Nama, H. L. Kwon, I. H. Hwang and C. Kim, Dyes Pigm., 2013, 99, 6–13.
17. Y. F. Tan, N. O'Toole, N. L. Taylor and A. H. Millar, Plant Physiol., 2010, 152, 747–761.
18. V. Desai and S. G. Kaler, Am. J. Clin. Nutr., 2008, 88, 855–858.
19. C. N. Hancock, L. H. Stockwin, B. Han, R. D. Divelbiss, J. H. Jun, S. V. Malhotra, M. G. Hollingshead and D. L. Newton, Free Radicals Biol. Med., 2011, 50, 110–121.
20. J. Y. Noh, G. J. Park, Y. J. Na, H. Y. Jo, S. A. Lee and C. Kim, Dalton Trans., 2014, 43, 5652–5656.
21. K. B. Kim, H. Kim, E. J. Song, S. Kim, I. Noh and C. Kim, Dalton Trans., 2013, 42, 16569–16577.
22. WHO, Guidelines for Drinking Water Quality, WHO guidelines values for chemicals that are of health significance in drinking water, Geneva, 3rd edn, 2008.
23. R. Krämer, Angew. Chem., Int. Ed., 1998, 37, 772–773.
24. D. Chen, R. J. Letcher, L. T. Gauthier, S. G. Chu, R. McCrindle and D. Potter, Environ. Sci. Technol., 2011, 45, 9523–9530.
25. Q. Wang, Y. Xie, Y. Ding, X. Li and W. Zhu, Chem. Commun., 2010, 46, 3669–3671.
26. Y. Ding, T. Li, W. Zhu and Y. Xie, Org. Biomol. Chem., 2012, 10, 4201–4207.
27. C. R. Wang and Q. B. Lu, J. Am. Chem. Soc., 2010, 132, 14710–14713.
28. Y. Kim, H. Kwak, S. J. Lee, J. S. Lee, H. J. Kwon, S. H. Nam, K. Lee and C. Kim, Tetrahedron, 2006, 62, 9635–9640.
29. J. J. Park, Y. Kim, C. Kim and J. Kang, Tetrahedron Lett., 2011, 52, 2759–2763.
30. J. Kang, Y. J. Lee, S. K. Lee, J. H. Lee, J. H. Lee, J. J. Park, Y. Kim, S. J. Kim and C. Kim, Supramol. Chem., 2010, 22, 267–273.
31. E. J. Song, H. Kim, I. H. Hwang, K. B. Kim, A. R. Kim, I. Noh and C. Kim, Sens. Actuators, B, 2014, 195, 36–43.
32. J. Kang, J. H. Lee, Y. H. Kim, S. K. Lee, E. Y. Kim, H. G. Lee and C. Kim, J. Inclusion Phenom. Macrocyclic Chem., 2011, 70, 29–35.
33. B. Vennesland, E. E. Comm, C. J. Knownles, J. Westly and F. Wissing, Cyanide in Biology, Academic Press, London, 1981.
34. J. Y. Noh, I. H. Hwang, H. Kim, E. J. Song, K. B. Kim and C. Kim, Bull. Korean Chem. Soc., 2013, 34, 1985–1989.
35. G. J. Park, I. H. Hwang, E. J. Song, H. Kim and C. Kim, Tetrahedron, 2014, 70, 2822–2828.
36. L. Tang, P. Zhou, K. Zhong and S. Hou, Sens. Actuators, B, 2013, 182, 439–445.
37. R. Yang, W. Wu, W. Wang, Z. Li and J. Qin, Macromol. Chem. Phys., 2010, 211, 18–26.
38. B. Chen, Y. Ding, X. Li, W. Zhu, J. P. Hill, K. Arigac and Y. Xie, Chem. Commun., 2013, 49, 10136–10138.
39. Y. Xie, Y. Ding, X. Li, C. Wang, J. P. Hill, K. Ariga, W. Zhanga and W. Zhu, Chem. Commun., 2012, 48, 11513–11515.
40. X. Chen, S. Nam, G. Kim, N. Song, Y. Jeong, I. Shin, S. K. Kim, J. Kim, S. Park and J. Yoon, Chem. Commun., 2010, 46, 8953–8955.
41. Y. Qua, B. Jin, Y. Liu, Y. Wub, L. Yang, J. Wua and J. Hua, Tetrahedron Lett., 2013, 54, 4942–4944.
42. S. Sumiya, T. Doi, Y. Shiraishi and T. Hirai, Tetrahedron, 2012, 68, 690–696.
43. V. K. Gupta, A. K. Singh and N. Gupta, Sens. Actuators, B, 2014, 204, 125–135.
44. S. S. Razi, R. Ali, P. Srivastava and A. Misra, Tetrahedron Lett., 2014, 55, 2936–2941.
45. M. Kumar, R. Kumar and V. Bhalla, Tetrahedron Lett., 2013, 54, 1524–1527.
46. K. W. Kulig, Cyanide Toxicity, U. S. Department of Health and Human Services, Atlanta, GA, 1991.
47. S. L. Baskin and T. G. Brewer, in Medical Aspects of Chemical and Biological Warfare, ed. F. R. Sidell, E. T. Takafuji and D. R. Franz, TMM Publications, Washington, DC, 1997, pp. 271–286.
48. C. Baird and M. Cann, Environmental Chemistry, Freeman, New York, 2005.
49. G. C. Miller and C. A. Pritsos, Cyanide, social, industrial and economic aspects, the Proceedings of the TMS Annual Meeting, 2001, pp. 73–81.
50. S. A. Lee, G. R. You, Y. W. Choi, H. Y. Jo, A. R. Kim, I. Noh, S. Kim, Y. Kim and C. Kim, Dalton Trans., 2014, 43, 6650–6659.
51. C. Young, L. Tidwell and C. Anderson, Cyanide: Social, Industrial and Economic Aspects: Minerals, Metals, and Materials Society, Warrendale, 2001.
52. J. M. Liu, X. X. Wang, F. M. Li, L. P. Lin, W. L. Cai, X. Lin, L. H. Zhang, Z. M. Li and S. Q. Lin, Anal. Chim. Acta, 2011, 708, 130.
53. L. R. Goodwin, D. Francom, F. P. Dieken, J. D. Taylor, M. W. Warenycia, R. J. Reiffenstein and G. Dowling, J. Anal. Toxicol., 1989, 13, 105.
54. K. Yao, D. Caruntu, Z. M. Zeng, J. J. Chen, C. J. O'Connor and W. L. Zhou, J. Phys. Chem. C, 2009, 113, 14812–14817.
55. C. R. Liu, W. Chen, W. Shi, B. Peng, Y. Zhao, H. M. Ma and M. Xian, J. Am. Chem. Soc., 2014, 136, 7257–7260.
56. C. Y. Liu, H. F. Wu, B. J. Han, B. C. Zhu and X. L. Zhang, Dyes Pigm., 2014, 110, 214–218.
57. B. D. Paul and S. H. Snyder, Nat. Rev. Mol. Cell Biol., 2012, 13, 499–507.
58. J. M. Fukuto, S. J. Carrington, D. J. Tantillo, J. G. Harrison, L. J. Ignarro, B. A. Freeman, A. Chen and D. A. Wink, Chem. Res. Toxicol., 2012, 25, 769–793.
59. A. Papapetropoulos, A. Pyriochou, Z. Altaany, G. D. Yang, A. Marazioti, Z. M. Zhou, M. G. Jeschke, L. K. Branski, D. N. Herndon, R. Wang and C. Szabo, Proc. Natl. Acad. Sci. U. S. A., 2009, 106, 21972–21977.
60. G. D. Yang, L. Y. Wu, B. Jiang, W. Yang, J. S. Qi, K. Cao, Q. H. Meng, A. K. Mustafa, W. T. Mu, S. M. Zhang, S. H. Snyder and R. Wang, Science, 2008, 322, 587–590.
61. G. D. Yang, L. Y. Wu and R. Wang, FASEB J., 2006, 20, 553–555.
62. L. Li, M. Bhatia and P. K. Moore, Curr. Opin. Pharmacol., 2006, 6, 125–129.
63. K. Eto, M. Ogasawara, K. Umemura, Y. Nagai and H. Kimura, J. Neurosci., 2002, 22(9), 3386–3391.
64. K. Etoa, T. Asadab, K. Arimab, T. Makifuchic and H. Kimura, Biochem. Biophys. Res. Commun., 2002, 293, 1485–1488.
65. P. Kamoun, M. C. Belardinelli, A. Chabli, K. Lallouchi and B. Chadefaux-Vekemans, Am. J. Med. Genet., Part A, 2003, 116, 310–311.
66. S. Fiorucci, E. Antonelli, A. Mencarelli, S. Orlandi, B. Renga, G. Rizzo, E. Distrutti, V. Shah and A. Morelli, Hepatology, 2005, 42, 539–548.
67. S. K. Bae, C. H. Heo, D. J. Choi, D. Sen, E. H. Joe, B. R. Cho and H. M. Kim, J. Am. Chem. Soc., 2013, 135, 9915–9923.
68. A. D. Becke, J. Chem. Phys., 1993, 98, 5648–5652.
69. C. Lee, W. Yang and R. G. Parr, Phys. Rev. B: Condens. Matter Mater. Phys., 1988, 37, 785–789.
70. P. C. Hariharan and J. A. Pople, Theor. Chim. Acta, 1973, 28, 213–222.
71. M. M. Francl, W. J. Petro, W. J. Hehre, J. S. Binkley, M. S. Gordon, D. F. DeFrees and J. A. Pople, J. Chem. Phys., 1982, 77, 3654–3665.
72. P. J. Hay and W. R. Wadt, J. Chem. Phys., 1985, 82, 270–283.
73. P. J. Hay and W. R. Wadt, J. Chem. Phys., 1985, 82, 284–298.
74. P. J. Hay and W. R. Wadt, J. Chem. Phys., 1985, 82, 299–310.
75. V. Barone and M. Cossi, J. Phys. Chem. A, 1998, 102, 1995–2001.
76. M. Cossi and V. Barone, J. Chem. Phys., 2001, 115, 4708–4717.
77. N. M. O'Boyle and A. L. Tenderholt, J. Comput. Chem., 2008, 29, 839–845.
78. M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, J. A. Montgomery Jr, T. Vreven, K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratchian, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth, P. Salvador, J. J. Dannenberg, V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M. C. Strain, O. Farkas, D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul, S. Clifford, J. Cioslowski, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara, M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W. Wong, C. Gonzalez and J. A. Pople, Gaussian 03, Revision D.01, Gaussian, Inc., Wallingford, CT, 2004.
79. P. Job, Ann. Chim., 1928, 9, 113–203.
80. P. Kaur, D. Sareen and K. Singh, Talanta, 2011, 83, 1695–1700.
81. H. A. Benesi and J. H. Hildebrand, J. Am. Chem. Soc., 1949, 71, 2703–2707.
82. G. R. You, G. J. Park, J. J. Lee and C. Kim, Dalton Trans., 2015, 44, 9120–9129.
83. S. A. Lee, J. J. Lee, J. W. Shin, K. S. Min and C. Kim, Dyes Pigm., 2015, 116, 131–138.
84. Y. J. Na, Y. W. Choi, J. Y. Yun, K. M. Park, P. S. Chang and C. Kim, Spectrochim. Acta, Part A, 2015, 136, 1649–1657.
85. Y. K. Tsui, S. Devaraj and Y. P. Yen, Sens. Actuators, B, 2012, 161, 510–519.
86. J. E. Huheey, E. A. Keiter and R. L. Keiter, Inorganic Chemistry: Principles of Structure and Reactivity, 4th edn, Harper Collins College Publishers, New York, 1993.
87. N. Kumari, S. Jha and S. Bhattacharya, J. Org. Chem., 2011, 76, 8215–8222.
88. L. Li, F. Liu and H. Li, Spectrochim. Acta, Part A, 2011, 79, 1688–1692.
89. P. Xie, F. Guo, S. Yang, D. Yao, G. Yang and L. Xie, J. Fluoresc., 2013, 013, 1316–1320.
90. W. Gong, Q. Zhang, L. Shang, B. Gao and G. Ning, Sens. Actuators, B, 2013, 177, 322–326.
91. Y. M. Hijji, B. Barare and Y. Zhang, Sens. Actuators, B, 2012, 169, 106–112.
92. H. Tavallali, G. Deilamy-Rad, A. Parhami and S. Kiyani, Spectrochim. Acta, Part A, 2014, 121, 139–146.
93. D. Kim, Y. Chung, M. Jun and K. H. Ahn, J. Org. Chem., 2009, 74, 4849–4854.
94. V. Amendola, L. Fabbrizzi, L. Mosca and F. P. Schmidtchen, Chem.–Eur. J., 2011, 17, 5972–5981.
95. EPA, The Guidelines for the Health Risk Assessment of Chemical Mixtures, U. S., 1986.

---

Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c5ra27553a

---