Shi Tang

A novel furfural derivative–indolium conjugated colorimetric and fluorescent probe, called 

, has been synthesized via the aldol reaction of 5-(

-nitrophenyl) furfural and 1-ethyl-2,3,3-trimethyl-3H-indol-1-ium iodide, and its response to cyanide in a DMSO/H

O (1:1, v/v) solution was measured using colorimetric and fluorescence analysis. This 

 probe showed a significant solution color and fluorescence change in response to cyanide, even in the presence of other anions, such as F

. In UV-vis and fluorescence spectrometry analysis, a large blue shift (83 nm), color bleaching, and fluorescence quenching were observed upon addition of cyanide anion (CN

). A significant color change was detected by visual observation. Additionally, the limit of detection of the L1 probe toward CN

 mol/L. This result was attributable to an intramolecular charge transfer (ICT) in the probe. The ICT progress was then terminated, along with the color change and fluorescence quenching, as the indol C=N underwent a nucleophilic attack of CN

 detection mechanism of the probe was confirmed by 

H NMR, mass spectrometry (MS), and density functional theory (DFT) measurements.

In recent years, more attention has been paid to the design and preparation of small-molecule fluorescent probes to detect and recognize anions in the area of optical materials (1–5). Among many anions, cyanide anion (CN

) is important as a result of its special characteristics (6,7). CN

 is widely used in organic synthesis, metallurgical engineering, electroplating technology, and other fields (8–10). The increased used of CN

 in industry has also led to increased cyanide contamination in the environment (11,12). Cyanide is one of the most highly toxic compounds and it can cause harm to living organisms, decreasing oxidative metabolism utilization of oxygen; Fe

, leading to the phenomenon of oxygen deficiency (13–15). As a result, it is essential to develop new detection methods to trace CN

Titration, electrochemistry, and spectroscopy have been widely used to detect CN

 (12,16–18). Spectroscopic methods in particular have attracted increasing attention for this purpose, because of their higher selectivity, higher efficiency, easier operation, and lower cost compared to the other methods (19–21). It has been reported that a variety of colorimetric and fluorescent probes exhibit alteration of absorbance or fluorescence upon interaction with CN

, because of reactions that lead to cyanide addition on many functional groups, such as thiazole (15,22), aldehyde (23), Schiff base (18, 24–28), dicyano-vinyl (19, 29–32), and imidazole.

In this work, we synthesized a furfural derivative–indolium conjugate, called 

, for use as a cyanide probe. The conjugate is based on 5-(

-nitrophenyl) furfural and 1-ethyl-2,3,3-trimethyl-3H-indol-1-ium iodide in a DMSO/H

O (1:1, v/v, Tris-HCl buffer, pH 7.2) solution (scheme 1). The limit of detection (LOD) of the 

 mol/L, far surpassing the World health Organization (WHO) standard (1.9 × 10

, based on a deprotonation process that the indolium C=N group of the L1 probe underwent during the nucleophilic attack of CN

, retards conjugation between the furfural derivative and the indolium compound, resulting in color and spectroscopic changes. The solution color faded gradually, and the fluorescence quenched slowly, with the dropwise addition of cyanide and the probe readily responded to the cyanide concentration even in the presence of other anions, such as F

All reagents and solvents were analytical grade, and used as obtained from commercial sources without further purification. Ultrapure water was used throughout the experiments. Tetrabutylammonium salt of anions (CN

) were purchased from Sigma-Aldrich. Sodium salts (S

C NMR spectra were obtained using a 500 MHz instrument and TMS was used as an internal standard. A Shimadzu UV-2550 spectrometer was used to produce UV-vis spectra. Fluorescence spectra were obtained using a Shimadzu RF-5301 fluorescence spectrophotometer.

A schematic illustration of the steps in the synthesis of the 

 probe is shown in Scheme 2. First, 5-(p-nitrophenyl) furfural (M1) and 1-ethyl-2,3,3-trimethyl-3H- indol-1-ium iodide (M2) were prepared as described in previous work (34,35). Then, 5-(p-nitrophenyl) furfural (2mM) and 1-ethyl-2,3,3-trimethyl-3H-indol-1-ium iodide (2 mM) were mixed in absolute ethanol (20 mL). Piperidine was added to the solution as a catalyst. The mixture was stirred and refluxed at 80 °C for 12 h. After the above reaction, the solution was cooled to ambient temperature immediately; after removing the solvent and following purification, a dark red powder, which is the L1 probe, was obtained. The 

H NMR spectra data for the various synthesized materials is given in Table I.

Theoretical Approach to the structure of the L1 Probe and L1-CN

The Gaussian 09 program was performed in order to compute a theoretical structure for the probe. The optimization of the molecular configurations of 

-CN in the ground and excited states were carried out using DFT with the b3lyp methodology involving 6-31G (d) basis sets.

 probe was prepared to have a strong electron-withdrawing benzpyrole derivative and an electron donating fur-aldehyde derivative, which are connected through an ethylene bridge, and then form a typical "D-π-A" conjugation system with intramolecular charge transfer (ICT) properties. Evaluation of the structure of the L1 probe was achieved by analysis of 

C NMR, and MS spectra. Detailed characterization of the intermediates (

) are provided in the supporting information from Table I. The selective behavior of the 

 probe toward anions was tested with UV-vis absorption spectroscopy and fluorescence spectroscopy in a DMSO:H

O (1:1, v/v, 0.01 M Tris-HCl buffer, pH 7.2) solution. The UV-vis absorption spectral response of the 

 probe was tested with aqueous solutions of the salts of all common anions analytes, including CN

 probe displays a strong absorption peak, with a maximum at 475 nm (Figure 1a). The addition of 50 equivalents of other anions did not cause any significant absorption band changes at 392 nm with a gradually increasing concentration of CN

 probe displays a strongly fluorescence peak at 565 nm (Figure 1b). Upon increasing the concentration of CN

, the fluorescence peak disappears, and other anions did not cause significant fluorescence changes.

To obtain more information about the response of 

, we carried out UV-vis and fluorescence titration experiments. As the concentration of CN

 was gradually increased, the UV-vis absorption at 392 nm increased, while the absorption gradually decreased at 475 nm (Figure 2a). It is noteworthy that the blue shift of the absorption wavelength, consistent with an evident color change from yellow to lime, demonstrates that 

 in a manner that is visible to the naked eye. The absorption intensities at 475 nm decreased linearly with an increasing CN

 concentration from 0.0 to 25 μM (R = 0.995), and the achieved detection limit was 3.65× 10

 probe could be used as an effective sensor for monitoring trace amounts of CN

 based on colorimetric and fluorescence analysis.

UV-vis and fluorescence spectroscopy were used to evaluate the selectivity of 

 over other anions. The addition of 50 equivalents of CN- and other anions, including F-, Cl-, Br-, I-, Ac-, SO

 did not lead to observable changes in absorption at 475 nm or the intensity of emission at 565 nm (Figure 3); the color change and fluorescence quenching of 

 remained apparent, and little interference from other anions was noted.

To examine the possible mechanism of the 

H NMR titration, MS, and DFT methods were carried out. For the 

H NMR chemical shift of the vinylic proton Ha and Hb on L1 was at 7.97 ppm and 7.91 ppm. The–N–CH

 of the Hc protons was at 4.76 ppm. After CN- was added into the L1, all 1H NMR signals shifted upfield. The peaks belonging to the vinylic protons Ha and Hb exhibited an upfield shift from 7.97 and 7.91 ppm to 6.75 and 6.48 ppm upon adding 1 equivalent of CN

. Additionally, the signals in accordance with –N–CH2– (Hc protons) presented an upfield shift from 4.76 to 3.17 ppm (Figure 4c). Further, MS analysis was carried out. The 

 peak was at 387.32 m/z (Figure 4b). The peak of the additive product 

-CN was at 414.36 m/z (Figure 4a). The additive product L1-CN was characterized upon adding 1 equivalent of CN

 underwent the cyanide nucleophilic addition reaction that cleanly converted the -C=N group.

To validate the suggested mechanism of L1 detection of CN

, DFT calculations were made at the b3lyp /6-31G(d) level of theory. In Figure 5, the optimized ground-state (S0) structures, the highest occupied molecular orbitals (HOMO), and lowest unoccupied molecular orbitals (LUMO) of L1 and L1-CN are shown. Important differences between 

-CN can be seen. Both the HOMO and LUMO of 

 disperse over the whole molecule, demonstrating good delocalization of the electron cloud density and the active ICT processes. Upon the nucleophilic addition of CN-, the conjugation is interrupted, the ICT process is blocked, and the HOMO and LUMO of the 

-CN additive product are focused on the furfural derivative and indolium. Also, the HOMO-LUMO energy gap of 

 was calculated to be 2.65 eV, much lower than that of 

-CN (2.89 eV). This building-up energy gap is responsible for the blue shift of the UV–vis of 

. The experimental phenomenon was well in line with the theoretical results. Therefore, we can summarily conclude that 

In summary, we have reported an effective technique for the construction of a highly selective furfural derivative–indolium probe, called 

 through color change and through UV-vis and fluorescence spectroscopic data. Visual observation revealed that the solution color changed from yellow to lime. Also, the color change was followed by yellow fluorescence quenching. The mechanism for detection of CN

 probe was characterized as a nucleophilic addition reaction, as determined by 

, even in the presence of other anions, and has a low limit of detection (LOD) of 3.65 × 10

 probe is an effective and convenient sensor for recognizing cyanide in complicated wastewater systems.

This study was supported by the scientific research foundation of Hainan University (KYQD[ZR]1917) and the Hainan Provincial Natural Science Foundation of China (319QN165).

(1) X. Chen, T. Pradhan, F. Wang, J.S. Kim, and J. Yoon, 

(6) L. G. Nandi, C. R. Nicoleti, I. C. Bellettini, and V. G. Machado, 

(7) X. Huang, X. Gu, G. Zhang, and D. Zhang, 

(8) L. Peng, M. Wang, G. Zhang, D. Zhang, and D. Zhu, 

(9) D.S. Kim, Y.-M. Chung, M. Jun, and K. H. Ahn, 

(10) Z. Xu, X. Chen, H. N. Kim, and J. Yoon, 

(11) H. Tavallali, G. Deilamy-Rad, A. Parhami, and N. Hasanli, 

(12) S. Liu, M. Yang, Y. Liu, H. Chen, and H. Li, 

(14) F. Wang, L. Wang, X. Chen, and J. Yoon, 

(16) G. Ding, H. Zhou, J. Xu, and X. Lu, 

(17) J.P. Anzenbacher, D.S. Tyson, K. Jursíková, and F.N. Castellano, 

(18) P.X. Pei, J.H. Hu, C. Long, and P.W. Ni, 

(19) L. Yang, X. Li, J. Yang, Y. Qu, and J. Hua, 

(21) X. Lou, L. Qiang, J. Qin, and Z. Li, 

(25) W.T. Gong, Q.L. Zhang, L. Shang, B. Gao, and G.L. Ning, 

(31) W.C. Lin, S.K.Fang, J.W. Hu, H.Y. Tsai, and K. Y. Chen, 

(34) Q. Lin, Y.P. Fu, P. Chen, T.B. Wei, Y.M. Zhang, 

 are with the Key Laboratory of Tropical Biological Resources of the Ministry Education, at the School of Life and Pharmaceutical Sciences, at Hainan University, in Haikou, in the People's Republic of China. Direct correspondence to: lijunjian1020@163.com

Shi Tang

Articles

A Furfural Derivative–Indolium Conjugated Colorimetric and Fluorescent Probe for Cyanide Detection