Synthesis and spectroscopic investigation of a novel sensitive and selective fluorescent chemosensor for Ag+ based on a BINOL–glucose derivative

Based on a versatile 2,2′-binaphthol (BINOL) backbone, a novel BINOL–glucose derivative fluorescent sensor was synthesized using a click reaction. The fluorescence responses of the BINOL–glucose derivative (S,β-d)-1 conclude that it can be used as a specific fluorescent chemical sensor for Ag+ in the presence of a large number of competing metal ions without any obvious interference from other metal ions. Mass spectrometric and NMR spectroscopic data were used to study the mechanism, and implied the formation of a 1 + 1 complex between BINOL–glucose 1 and Ag+. Both the oxygen atoms of S-BINOL and two nitrogen atoms of triazole were involved in coordinating the silver ion.


Introduction
It is very important to discover and design new highly selective uorescent sensors that can detect heavy metal ions, which may cause serious harm to human health and the living environment. Among the important heavy metals, silver has been paid more attention because of its adverse effects on biological harmony and the environment, due to its ability to easily bind to mercapto groups in proteins and inactivate respiratory enzymes. 1,2 It is very difficult to identify silver ions from other heavy metal ions because of the moderate coordination ability of Ag + . However, almost all uorescent sensors containing triazole experience interference from other transition metals, especially from mercury ions when attempting to identify silver ions, [3][4][5][6][7][8] which leads to the limitation of the use of specic uorescent sensors for silver ions. Only a few uorescent sensors 9-13 that can detect Ag + have been reported in recent years. So, it is still a challenge to design an effective chemical method to target only Ag + .
Moreover, sugar is a hot research topic due to its natural existence, good biocompatibility and structural diversity without being toxic. Furthermore, its good water solubility is considered to be a very ideal feature for using it as a component in uorescent chemical sensors. In recent years, triazole modied functional sugar derivatives have attracted continuous interest in research [31][32][33][34] and various sugar-based uorescent chemosensors have been synthesized using click reactions. In this way, a novel BINOL-glucose derivative uorescent sensor was synthesized through the Cu-catalyzed 1,3-dipolar cycloaddition [35][36][37][38][39][40] of an alkyne and azole. The synthesis was based on a versatile (S)-BINOL backbone, and the (S)-BINOL and two triazole units were used to represent the uorophore and recognition group, respectively. The synthesized sensor could then be used as a specic uorescent chemical sensor for Ag + in the presence of a large number of competing cations, as anticipated.

Materials and methods
All the solvents were of analytical purity, and the materials were obtained from commercial suppliers or prepared by our laboratory, with no further purication of the commercially suppled chemicals before use. If not otherwise specied, the solvents used in the optical spectroscopic studies were of spectroscopic purity. Various metal ion solutions (0.1 M) were prepared from their respective nitrates in distilled-deionized water, except for K + , Hg 2+ , Mn 2+ , and Ba 2+ , which were made from their chloride salts. AgNO 3 was used as the Ag + source unless otherwise stated. 1 H nuclear magnetic resonance (NMR) and 13 C NMR were measured on a Bruker AM-400WB spectrometer using tetramethylsilane (TMS) as an internal standard and CDCl 3 or CD 3 OD as solvents. All UV-Vis absorptions were recorded on an Agilent 8453 UV-Vis spectrometer. Fluorescence emission spectra were obtained using a Hitachi F-4500 uorescence spectrometer at 298 K, unless otherwise stated. Electrospray ionization mass spectrometric (ESI-MS) data were recorded using a Thermo Fisher LCQ. Melting points were measured on a WRS-1B melting point apparatus. Optical rotation was carried out using a Rudolph AUTOPOL IV automatic polarimeter.
Synthesis of (S,b-D)-2 S-2,2 0 -Bis(prop-2-yn-1-yloxy)-1,1 0 -binaphthalene (0.63 g, 1.75 mmol) and 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl azide (1.4 g, 3.67 mmol) were added to 50 mL of tetrahydrofuran (THF) with stirring at 273 K under an argon atmosphere and the mixture was stirred for ve minutes. Sodium ascorbate (0.69 g, 3.48 mmol) and CuSO 4 $5H 2 O (0.44 g, 1.76 mmol) were added to the mixture and the temperature slowly rose to room temperature, aer which it was stirred for 12 h under Ar 2 . Aer the reaction was completed, the mixture was poured into ice water. The mixture was extracted three times with EtOAc and then the organic layer was washed with brine and dried over anhydrous MgSO 4 . Aer evaporation of the organic solvent, the crude product was puried directly by column chromatography on silica (petroleum ether :  13

Synthesis of (S,b-D)-1
A mixture of (S,b-D)-2 (1.3 g, 1.17 mmol), NaOH (0.47 g, 11.7 mmol), and methanol (100 mL) was stirred at room temperature for 12 h. Aer the reaction was completed, the solvent was removed under reduced pressure to obtain the crude product. The product was puried directly by ash column chromatography on silica gel using dichloromethane and methanol in a ratio of 2 : 1 (v/v) as the eluent to give the desired product 1 (0.75 g, 82.8%) as a white solid:[a] 25 D -54 (c 0.07, CH 3 OH). 1

Fluorescence and UV-visible measurements
A stock solution of (S,b-D)-1 (2.0 Â 10 À5 mol L À1 ) prepared in methanol and stock solutions of the metal ions (0.1 mol L À1 M in H 2 O) were freshly prepared before testing each performance. For each uorescence quenching measurement, varying equivalents of Ag + stock solution were added to the sensor solutions in a 5 mL volumetric ask at 298 K. The competition experiments involved mixing of each metal ion solution with a stock solution of Ag + of the same concentration (2.0 Â 10 À5 mol L À1 ). The Job plot for the complexation of (S,b-D)-1 with Ag + was obtained by recording the uorescence response of (S,b-D)-1 with different ratios of Ag + . A 2.0 mM stock solution of (S,b-D)-1 dissolved in methanol and a 2.0 mM AgNO 3 in H 2 O were freshly prepared for each measurement.

Results and discussion
The BINOL-glucose derivative uorescent sensor was synthesized using "click chemistry", as shown in Scheme 1. According to the previous literature, the dipropargyl 3 (ref. 41) derivative of (S)-BINOL was prepared (Scheme 1). The reaction of dipropargyl 3 and azide-functionalized glucose 4 was carried out in THF at room temperature in the presence of sodium ascorbate and copper(II) sulfate to afford BINOL-glucose derivative 2 in moderate yield aer a simple purication process. The new uorescent sensor 1 was obtained when 2 was hydrolyzed in methanol, in 83% yield. The structures of the desired compounds were determined from 1 H NMR, 13 C NMR, and ESI-MS measurements. different solutions using uorescence spectroscopy. First, the uorescence measurements of (S,b-D)-1 were carried out in CH 3 OH ([(S,b-D)-1] ¼ 20 mM). As shown in Fig. 1, only the addition of Ag + ions to a solution of (S,b-D)-1 could result in an almost complete quenching of the uorescence, however, other metal ions induced no obvious change in the uorescence response. When the uorescence selectivity experiments of (S,b-D)-1 were tested in THF solution (as shown in Fig. S8 †), no signicant difference in the uorescence response was found. The discrimination between the different metal ions showed a sensitive dependence on the solvent. So, all of the uorescence measurements of (S,b-D)-1 were investigated in methanol solution, in which (S,b-D)-1 was found to be highly selective and sensitive towards Ag + . An unexpected quenching of the uorescence of the excimer emission upon addition of Ag + ions to a solution of 1 may be due to PET (photoinduced electron transfer). In other words, the metal ions combined with electron acceptor triazole units and the glucose units behaved as a PET donor. This means that the two triazole units of (S,b-D)-1 form a selective and effective metal ion binding site.

Metal ion competition studies
For an effective cation probe, the key factor is the ability to detect a specic metal ion in the presence of different metal ions. Fig. 2 shows the results of competition experiments we conducted in which we tested the ability of the probe to selectively detect one metal ion over other metal ions. The addition of 5.0 equiv. of Ag + combined with 5.0 equiv. of the other metal ions in methanol solutions of (S,b-D)-1, respectively, were used in the competitive experiments. The quenching ratio of the I F /I 0 value at 375 nm (where I 0 represents the uorescence intensity of only (S,b-D)-1 and I F represents the uorescence intensity upon the addition of a mixture of competitive metal ions and Ag + ) for the majority of the competitive metal ions was almost 0.17. No signicant interference was observed in the presence of the various competitive metal ions. This indicated that the BINOL-glucose sensor could be used to detect Ag + in the presence of various competitive ions without any obvious interference from the other metal ions. Based on the uorescence results, we found that the BINOL-glucose derivative has high selectivity and sensitivity to Ag + and therefore can be used as an Ag + sensor.
The binding tests of (S,b-D)-1 towards Ag + were also studied upon the addition of different amounts of Ag + to (S,b-D)-1 in CH 3 OH, using UV-Vis absorption spectroscopy. As shown in Fig. 3, the maximum absorption wavelength of (S,b-D)-1 was found to be around 229 nm upon the addition of 0 to 3 equivalent of Ag + . However, there was found to be a slight change in the UV-Vis absorption spectrum of (S,b-D)-1 in the presence of various concentrations of Ag + , where the absorbance at 210 nm was observed to begin to increase, which may indicate the formation of a (S,b-D)-1-Ag + complex. It is a pity that the slight absorbance intensity shi did not induce any obvious color change. The interaction between the host and guest was evaluated using uorescence spectroscopy. From Fig. 3, it can be seen that (S,b-D)-1 has three absorption peaks at 229 nm, 290 nm and 335 nm. The maximum absorption wavelength l max of (S,b-D)-1 was around 229 nm with weak uorescence emission. However, the absorption at 290 nm was observed to have a stronger uorescence intensity (see Fig. S9 †), and so, l ex ¼ 290 nm. Fig. 1 Fluorescence spectra of 1 (2 Â 10 À5 mol L À1 in CH 3 OH) upon the addition of K + , Ag + , Ba 2+ , Cd 2+ , Mg 2+ , Ca 2+ , Cr 3+ , Al 3+ , Co 2+ , Cu 2+ , Ni 2+ , Mn 2+ , Zn 2+ , Hg 2+ , Mn 2+ , Sn 2+ , Pb 2+ , and Sr 2+ ions (5 equiv.).  As shown in Fig. 4, the uorescence spectra of (S,b-D)-1 upon adding different equivalents of Ag + were used to determine the nature of the complex formed between (S,b-D)-1 and Ag + . When the amount of Ag + used was above 3 equiv., the intensity of the uorescence emission underwent a strong change. We assumed that the stoichiometry ratio of (S,b-D)-1-Ag + complex is 1 : 1, so the association constant K of (S,b-D)-1 with Ag + was found to be 2.4 Â 10 6 M À1 (R ¼ 0.997) from the Lineweaver-Burk plot of 1/ (F 0 À F) versus 1/[Ag + ]. As shown in Fig. 5, the maximum uorescence quenching of (S,b-D)-1 provided by Ag + takes place at a ratio of 1 : 1. Based on the uorescence analyses, the BINOLglucose compound and Ag + were proposed to form a 1 + 1 complex. The Job plot for the complex provided further direct evidence that the (S,b-D)-1-Ag + complex stoichiometry ratio was 1 : 1. Respectively, the detection limit (LOD) of (S,b-D)-1 to Ag + was assessed to be 1.57 Â 10 À9 mol L À1 using the following equation: LOD ¼ 3s/s, where s represents the standard deviation of the (S,b-D)-1 solution and s represents the slope between the uorescence intensity versus the Ag + concentration (Fig. S11 †). Further evidence for the 1 : 1 complex stoichiometry ratio was obtained from ESI-MS spectra data (see Fig. S7, ESI data †). The peak at m/z ¼ 881.1 (calcd 881) was found to correspond to [1-Ag + + H + ], which supports our assumption there is strong binding between (S,b-D)-1 and Ag + .
The 1 H NMR experiments were carried out in CD 3 OD to nd out further detailed information on the binding of Ag + with (S,b-D)-1. As shown in Fig. 6, different equiv. (from 0 to 1 equiv.) of Ag + were added to a solution of (S,b-D)-1 and resulted in an obvious downshi in the chemical shis, however, the shis tended to saturation when the amount of Ag + was beyond 1 equiv. The H a nuclear magnetic peaks of the -OCH 2linking triazole groups are split into two sets of signals; a group of displacement peaks migrate Dd 0.11 ppm downeld from 5.05 ppm to 5.16 ppm, while another group of displacement peaks shi up eld by 0.09 ppm, from 5.05 ppm to 4.96 ppm. These changes demonstrate that Ag + is selectively bound to the BINOL-glucose sensor through the oxygen atoms on the BINOL. The H c peak of the glucose linked to the triazole groups exhibited a smaller chemical shi from 5.31 ppm to 5.54 ppm. In particular, the H b peak of the triazole rings was observed to undergo an obvious downshi of Dd ¼ 0.97 ppm from 7.26 ppm to 8.23 ppm. From the above data, we concluded that both of the oxygen atoms of the BINOL and the nitrogen atoms on the triazole of (S,b-D)-1 were involved in the formation of a tetrahedral complex with a silver ion at the center. The results obtained from uorescence and NMR spectroscopic and mass spectrometric analyses were also used to conrm the recognition between the BINOL-glucose compound and Ag + in a 1 + 1 complex.

Conclusions
In summary, through a four step reaction, a novel highly selective and sensitive BINOL-glucose derivative uorescent sensor (S,b-D)-1 that can detect Ag + was synthesized with an overall yield of 30%. (S,b-D)-1 was observed to function as an Ag + specic uorescent sensor, as it showed high sensitivity and specicity in the experiments. The highly selective uorescence turn-off behavior was caused by the formation of a 1 + 1 binding   5 The Job plot of a 1 : 1 complex of (S,b-D)-1 with Ag + on the basis of the fluorescence signal. X represents the molar fraction of Ag + . The total concentration of (S,b-D)-1 and Ag + was found to be 2.0 Â 10 À5 M. complex between BINOL-glucose 1 and Ag + without any interference from various different metal ions. The uorescence quenching was ascribed to both the triazole nitrogen atoms and the oxygen atoms of (S,b-D)-1 involved in the coordination with Ag + . These results show the possibility of preparing highly selective uorescent sensors based on the versatile BINOL backbone for the detection of various metal ions.

Conflicts of interest
There are no conicts to declare.