A Ratiometric Fluorescent Sensor for Cd2+ Based on Internal ... - MDPI

Download PDF
5 downloads 0 Views 3MB Size Report
Comment
Nov 2, 2017 - Hongzhi Yang 1, Aixia Han 1,2,*, Xiaomei Yang 2 and Ling Zang 2,*. 1 ... development, particularly when compared to those with spectral response in high energy blue or UV region. ... purple solid (0.45 g), yield 49%.
sensors Article

A Ratiometric Fluorescent Sensor for Cd2+ Based on Internal Charge Transfer Dandan Cheng 1,† , Xingliang Liu 1,† , Yadian Xie 1 , Haitang Lv 1 , Zhaoqian Wang 1 , Hongzhi Yang 1 , Aixia Han 1,2, *, Xiaomei Yang 2 and Ling Zang 2, * 1

2

* †

Chemical Engineering College, Qinghai University, Xining 810016, China; [email protected] (D.C.); [email protected] (X.L.); [email protected] (Y.X.); [email protected] (H.L.); [email protected] (Z.W.); [email protected] (H.Y.) Department of Materials Science and Engineering, University of Utah, Salt Lake City, UT 84108, USA; [email protected] Correspondence: [email protected] (A.H.); [email protected] (L.Z.); Tel.: +86-971-5310-427 (A.H.); +1-801-587-1551 (L.Z.) These authors contributed equally to this work.

Received: 9 October 2017; Accepted: 31 October 2017; Published: 2 November 2017

Abstract: This work reports on a novel fluorescent sensor 1 for Cd2+ ion based on the fluorophore of tetramethyl substituted bis(difluoroboron)-1,2-bis[(1H-pyrrol-2-yl)methylene]hydrazine (Me4 BOPHY), which is modified with an electron donor moiety of N,N-bis(pyridin-2-ylmethyl)benzenamine. Sensor 1 has absorption and emission in visible region, at 550 nm and 675 nm, respectively. The long wavelength spectral response makes it easier to fabricate the fluorescence detector. The sensor mechanism is based on the tunable internal charge transfer (ICT) transition of molecule 1. Binding of Cd2+ ion quenches the ICT transition, but turns on the π − π transition of the fluorophore, thus enabling ratiometric fluorescence sensing. The limit of detection (LOD) was projected down to 0.77 ppb, which is far below the safety value (3 ppb) set for drinking water by World Health Organization. The sensor also demonstrates a high selectivity towards Cd2+ in comparison to other interferent metal ions. Keywords: ratiometric fluorescent sensor; Me4 BOPHY; Cd2+ ion; ICT

1. Introduction Cadmium represents a highly toxic industrial and environmental pollutant, and it is classified as a human carcinogen. Exposure to cadmium may cause cancer mutation of some organs, such as lung, endometria, prostate, kidney, etc. [1]. World Health Organization (WHO) underlines drinking water value for cadmium as 3 ppb [2]. So, detection of cadmium at trace level remains an important task, for which cadmium ion (Cd2+ ) usually remains as the target for chemical sensors to monitor the cadmium pollution in water environment. Current methods for Cd2+ detection include UV-Vis spectrometry [3], atomic absorption spectrometry (AAS) [4], inductively coupled plasma atomic emission spectroscopy (ICP-AES) [5], and fluorescent sensors [6–16]. Among these, fluorescent sensors are uniquely compelling due to their high sensitivity, good selectivity [6–16], and capability for ratiometric sensing to further improve the detection sensitivity [17–20]. However, many fluorescence sensors for Cd2+ ion reported thus far have some technical drawbacks, for example, a poor limit of detection (LOD) [7,8,18], complicated synthesis of sensor molecules [6], solvent toxicity [7], and a hardly controlled fluorescence change [14]. In order to develop high performance fluorescent sensors, the fluorophore must be designed with both high quantum efficiency and chemical tunability in response to metal binding [21,22]. Borondipyrromethene (BODIPY) has long been studied as an outstanding organoboron fluorophore and been used in the development of fluorescent Sensors 2017, 17, 2517; doi:10.3390/s17112517

www.mdpi.com/journal/sensors

several from our lab (F-BOPHY1-3) [36], which all showed high efficiency of fluorescence. We noticed that there have been only two BOPHY fluorescent sensors reported so far, which were used for detecting Cu2+ and H+, respectively [37,38]. In this paper, we report on synthesis of a novel fluorescent sensor 1 for Cd2+ (Scheme 1) based on a BOPHY fluorophore substituted by tetramethyl group (Me4BOPHY), in conjugation through a vinyl link with an electron donor moiety Sensors 2017, 17, 2517 2 of 10 N,N-bis(pyridin-2-ylmethyl)benzenamine (BPA). BPA is also a strong chelator to Cd2+ ion, thus affording high sensing sensitivity. Pristine sensor 1 exhibits a significant internal charge transfer sensors for many metal Me4BOPHY ions [23–27],and including Cd2+ [28,29]. and In 2014, a novelextending organoboron (ICT) transition between BPA, with an ion absorption fluorescence into 2+ compound bis(difluoroboron)-1,2-bis[(1H-pyrrol-2-yl)methylene]hydrazine (BOPHY) (Scheme 1) was long wavelength, 550 nm and 675 nm, respectively. When chelated with Cd the electron-donating reported has distinctive absorption and emissionand features that sensor power of [30–32]. BPA willBOPHY be reduced, thus quenching the ICT transition turning onare thesuited π − π for transition development, particularly when compared to those with spectral response in high blue orofUV of the fluorophore, which combined the results in blue-shift of the absorption andenergy fluorescence 1. region. Many BOPHY derivatives have ever since synthesized [33–35], including several from our lab Such dramatic spectral change can be used to develop efficient fluorescence sensor for Cd2+ (F-BOPHY1-3) [36], which all showed high efficiency of fluorescence. detection, particularly through the ratiometric fluorescence modulation [39–43].

Scheme 1. Molecule Molecule structures structures of of bis(difluoroboron)-1,2-bis[(1H-pyrrol-2-yl)methylene]hydrazine bis(difluoroboron)-1,2-bis[(1H-pyrrol-2-yl)methylene]hydrazine Scheme 1. (BOPHY), substituted BOPHY BOPHY (Me (Me44BOPHY) (BOPHY), tetramethyl tetramethyl substituted BOPHY) and and sensor sensor 1. 1.

2. Experimental Methods We noticed that there have been only two BOPHY fluorescent sensors reported so far, which were used for detecting Cu2+ and H+ , respectively [37,38]. In this paper, we report on synthesis 2.1. Materials and Instrumentation of a novel fluorescent sensor 1 for Cd2+ (Scheme 1) based on a BOPHY fluorophore substituted All of the solvents and chemicals were purchased through in analytical grade andwith wereanused as received. by tetramethyl group (Me4BOPHY), in conjugation a vinyl link electron donor 2+ ion, Column chromatography used 300–400 mesh silica (BPA). gels. Ultrapure water was produced a Milli-Q moiety N,N-bis(pyridin-2-ylmethyl)benzenamine BPA is also a strong chelator by to Cd Direct 16 system Millipore. UV-VisPristine absorption spectra were gained oninternal a Shimadzu thus affording highofsensing sensitivity. sensor 1 exhibits a significant chargeUV-2550 transfer spectrophotometer (Shimadzu, Kyoto, Japan). Fluorescence spectra were obtained on a Cary Eclipse (ICT) transition between Me4BOPHY and BPA, with an absorption and fluorescence extending into 1 13 2+ fluorescence spectrophotometer Agilent. H When and chelated C NMR with spectra recorded with a long wavelength, 550 nm and 675from nm, respectively. Cd were the electron-donating Mercury instrument at 400 andquenching 100 MHz the by ICT using DMSO-dand 6 as turning the solvents. were power of plus BPA will be reduced, thus transition on theMS π −spectra π transition recorded on a MALDI-TOF MS Performance (Shimadzu, Japan). of the fluorophore, which combined the results in blue-shift of the absorption and fluorescence of 1. Such dramatic spectral change can be used to develop efficient fluorescence sensor for Cd2+ detection, 2.2. Molecularthrough Synthesis particularly the ratiometric fluorescence modulation [39–43].

Compound 2 [30] and 3 [29] were synthesized according to literatures, while 1 was synthesized 2. Experimental Methods as illustrated in Figure 1. Dry toluene used in synthesis was distilled over sodium and benzophenone. mixture of 2 (0.50 g, 1.48 mmol), 3 (0.45 g, 1.48 mmol), and p-toluenesulfonicacid 2.1. Materials andAInstrumentation (1 g, 5.81 mmol) was dissolved in dry toluene (50 mL), followed by the addition of 1 mL piperidine All of the werestirring purchased in h analytical and were used as received. as catalyst. Thesolvents mixtureand waschemicals refluxed with for 12 under angrade atmosphere of nitrogen, during Column chromatography 300–400 meshchanged silica gels. Ultrapure watertowas by ato Milli-Q which time the color of theused reaction mixture from pale yellow red.produced After cooling room Direct 16 system of Millipore. UV-Vis absorption spectra were gained on a Shimadzu UV-2550 temperature, the mixture was poured into H2O (100 mL) and extracted with CH2Cl2. After solvent spectrophotometer (Shimadzu, Kyoto, Japan). Fluorescence spectra were obtained on a Cary Eclipse fluorescence spectrophotometer from Agilent. 1 H- and 13 C-NMR spectra were recorded with a Mercury plus instrument at 400 and 100 MHz by using DMSO-d6 as the solvents. MS spectra were recorded on a MALDI-TOF MS Performance (Shimadzu, Japan). 2.2. Molecular Synthesis Compound 2 [30] and 3 [29] were synthesized according to literatures, while 1 was synthesized as illustrated in Figure 1. Dry toluene used in synthesis was distilled over sodium and benzophenone. A mixture of 2 (0.50 g, 1.48 mmol), 3 (0.45 g, 1.48 mmol), and p-toluenesulfonicacid (1 g, 5.81 mmol) was dissolved in dry toluene (50 mL), followed by the addition of 1 mL piperidine as catalyst. The mixture

Sensors 2017, 17, 2517

3 of 10

was refluxed with stirring for 12 h under an atmosphere of nitrogen, during which time the color of the reaction mixture changed from pale yellow to red. After cooling to room temperature, the mixture3 of was Sensors 2017, 17, 2517 10 poured into H2 O (100 mL) and extracted with CH2 Cl2 . After solvent removal, the crude product was purified by (silicaby gel,column CH2 Cl2chromatography /petroleum ether,(silica v/v =gel, 2/1),CH producing a dark removal, thecolumn crude chromatography product was purified 2Cl2/petroleum 1 H-NMR (400 MHz, DMSO-d ) δ = 8.61–8.60 1 purple solid (0.45 g), yield 49%. (m, 2H), 7.92 (s, 1H), 7.84 6 49%. H NMR (400 MHz, DMSO-d ether, v/v = 2/1), producing a dark purple solid (0.45 g), yield 6) 7.65–7.62 J =7.84 5.6 Hz, 2H), 7.65–7.62 7.25 (d, J =(m, 5.22H), Hz, J7.38 = 5.2(d, Hz, δ(s,=1H), 8.61–8.60 (m, (m, 2H),2H), 7.927.38 (s, (d, 1H), (s, 1H), J =2H), 5.6 7.20–7.18 Hz, 2H), (m, 7.252H), (d, (d,Hz, J = J2.8 Hz,Hz, 2H), 6.727.20-7.18 (d, J = 6.0 Hz, 2H), 6.68 1H), 4.87 2.48 2H), (s, 3H), J7.17 = 5.2 = 5.2 2H), (m, 2H), 7.17 (d,(s,J 1H), = 2.8 6.16 Hz, (s, 2H), 6.72 (d,(s, J =4H), 6.0 Hz, 6.682.32 (s, 13 (s, 3H), 2.31 3H).4.87 (Figure S1, Supplementary Materials). C-NMR (100(Figure MHz, DMSO-d 6 ) δ = 157.67, 1H), 6.16 (s,(s, 1H), (s, 4H), 2.48 (s, 3H), 2.32 (s, 3H), 2.31 (s, 3H). S1, Supplementary 13C 149.40, 150.75, 150.07, 148.72, 140.24, 139.84,6) 136.69, 136.49, 133.39, 132.27, 128.63,148.72, 124.96,140.24, 124.08,139.84, 122.98, Materials). NMR (100 MHz, DMSO-d δ = 157.67, 150.75, 150.07, 149.40, 121.81, 120.34, 117.88, 114.17, 113.24, 112.24, 56.83, 13.66, 10.73, 10.65. (Figure S2, Supplementary 136.69, 136.49, 133.39, 132.27, 128.63, 124.96, 124.08, 122.98, 121.81, 120.34, 117.88, 114.17, 113.24, Materials). MALDI-TOFMS: m/z calculated forSupplementary C33 H31 B2 F4 N7 : Materials). 623.28; found: 623.47. (Figurem/z S3, 112.24, 56.83, 13.66, 10.73, 10.65. (Figure S2, MALDI-TOFMS: Supplementary Materials). calculated for C33H31B2F4N7: 623.28; found: 623.47. (Figure S3, Supplementary Materials).

Figure 1. The of 1. 1 Figure 1. The synthesis synthesis route route of

2.3. 2.3. Sample Sample Preparation Preparation and and Spectral Spectral Measurements Measurements 2+, A was prepared prepared in in acetonitrile. acetonitrile. Metal Metal ion ion solutions solutions of of Cd Cd2+ A stock stock solution solution (0.5 (0.5 mM) mM) of of sensor sensor 1 1 was , 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+ , Mn , Pb , Cu , Co , Mg , Ca , Ba , Fe , and Hg were prepared by dissolving the Zn 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+ Zn , Mn , Pb , Cu , Co , Mg , Ca , Ba , Fe , and Hg were prepared by dissolving the corresponding nitratesalts salts in acetonitrile. Thesesolutions stock solutions were diluted to needed corresponding nitrate in acetonitrile. These stock were diluted to needed concentrations concentrations for UV-Vis sensor and testing. UV-Visspectra and fluorescent spectra were measured underBriefly, room for sensor testing. fluorescent were measured under room temperature. temperature. Briefly, 2.5 mL solution of 1 (2 μM) was put into a 1 cm quartz cuvette, followed by 2.5 mL solution of 1 (2 µM) was put into a 1 cm quartz cuvette, followed by addition of different addition of different concentrations of metal ion. The series of concentrations of metal ions were thus concentrations of metal ion. The series of concentrations of metal ions were thus added and were added andfor were forand thefluorescence absorption and fluorescence spectra. Since of added volume the measured themeasured absorption spectra. Since added volume the metal ionof stock metal ion stock solution was small (up to 8 μL), the concentration of sensor 1 would remain almost solution was small (up to 8 µL), the concentration of sensor 1 would remain almost unchanged. unchanged. For fluorescence spectra measurement, excitationwas wavelength 410widths nm and For fluorescence spectra measurement, the excitationthe wavelength set at 410was nmset andatslit at slit widthsnm. at 5 nm/10 nm. 5 nm/10 2+ 2+

3. 3. Results Results and and Discussion Discussion 2+ 3.1. 3.1. Spectral Spectral Change Change of of 11 Upon Upon Titration Titration with Cd2+

As As shown shown in in Figure Figure 2, the absorption absorption spectrum spectrum of of pristine pristine 11 has has two pronounced pronounced peaks peaks around 505 505 nm and 550 nm. These These two two absorption absorption peaks peaks are are significantly significantly red-shifted red-shifted in comparison comparison with those of Me 4 BOPHY, which has the corresponding two peaks at 444 nm and 467 nm. Such spectral those of 4 BOPHY, which has the corresponding two peaks at redshift due to ICT the electronic ICT electronic transition, as previously in other electron redshift isisdue to the transition, as previously observed inobserved other electron donor-acceptor donor-acceptor [29].1 In 1 theMe fluorophore Me 4BOPHY is in full conjugation with molecules [29]. molecules In molecule themolecule fluorophore BOPHY is in full conjugation with the aniline 4 the aniline group of BPA through the vinyl bridge (Scheme 1), thus facilitating the ICT transition. group of BPA through the vinyl bridge (Scheme 1), thus facilitating the ICT transition. Upon titration 2+ ion,with Upon titration Cd2+ ion, the at 550 nm gradually decreased, accompanied by a rising with Cd the absorption at absorption 550 nm gradually decreased, accompanied by a rising blue-shifted blue-shifted absorption at 475 nm. An isosbestic point was 520 clearly seen around absorption peak centered peak at 475centered nm. An isosbestic point was clearly seen around nm, indicating the 2+-bound 2+ 520 nm, indicating the stoichiometric conversion of molecule 1 from unbound to the Cd stoichiometric conversion of molecule 1 from unbound to the Cd -bound state. As the concentration state. As the concentration of Cd2+ increased, the color of the solution turned from red to bright yellow, consistent the absorption spectral change shown in Figure 2. The observed spectral change is due to the binding of Cd2+ at the BPA chelator (Scheme 2), which in turn reduces the electron-donating capability of the aniline moiety. As a result, the ICT transition of molecule 1 is

Sensors 2017, 17, 2517

4 of 10

of Cd2+ increased, the color of the solution turned from red to bright yellow, consistent the absorption spectral change shown in Figure 2. The observed spectral change is due to the binding of Cd2+ at the BPA chelator 2), which in turn reduces the electron-donating capability of the aniline moiety. Sensors 2017, 17, (Scheme 2517 4 of 10 Sensors 2017, 17, 2517 4 of 10 As a result, the ICT transition of molecule 1 is diminished. Indeed, as molecule 1 is fully chelated, diminished. as becomes moleculemostly 1 is fully chelated,of the spectrum becomes mostly the absorptionIndeed, spectrum characteristic the πabsorption − π transition of the Me part, 4 BOPHY diminished. Indeed, as molecule 1 is fully chelated, the absorption spectrum becomes mostly centered around 475π nm 2). of the Me4BOPHY part, centered around 475 nm (Figure 2). − (Figure π transition characteristic of the characteristic of the π − π transition of the Me4BOPHY part, centered around 475 nm (Figure 2).

Figure 2. UV-vis absorption spectral change recorded for an acetonitrile solution of sensor 1 (2 μM) Figure 2. 2. UV-vis UV-vis absorption absorption spectral spectral change change recorded recorded for for an an acetonitrile acetonitrile solution solutionof of sensor sensor 11 (2 (2 μM) µM) Figure 2+ ion. upon the titration of Cd 2+ upon the the titration titration of of Cd Cd2+ ion. ion. upon

Scheme 2. Sensing mechanism of 1 towards Cd2+. 2+. Scheme 2. 2. Sensing Sensing mechanism mechanism of of 11 towards towards Cd Cd2+ Scheme .

The same series of titration of Figure 2 was also monitored for fluorescence spectral change, as The same series of titration of Figure 2 was also monitored for fluorescence spectral change, as shown Figure 3a. The unbound 1 hasalso an emission band centered at 675 nm, which is Theinsame series of titration of molecule Figure 2 was monitored for fluorescence spectral change, shown in Figure 3a. The unbound molecule 1 has an emission band centered at 675 nm, which is significantly red-shifted in unbound comparison to the 1two bands (485 nm and nm) which that are as shown in Figure 3a. The molecule hasemission an emission band centered at 518 675 nm, is significantly red-shifted in comparison to the two emission bands (485 nm and 518 nm) that are typically observed for the fluorophoretoofthe tetramethyl substituted BOPHY The strong significantly red-shifted in comparison two emission bands (485 nm and(Me 5184BOPHY). nm) that are typically typically observed for the fluorophore of tetramethyl substituted BOPHY (Me4BOPHY). The strong redshift isfor mainly a result ofof the ICT transition (Scheme 2), which turn is caused by the BPA observed the fluorophore tetramethyl substituted BOPHY (Me4inBOPHY). The strong redshift redshift is mainly a result of the ICT transition (Scheme 2), which in turn is caused by the BPA 2+ substitution. Upon binding with the (Scheme Cd ion,2),the emission was blue-shifted to 570 nm, is mainly a result of the ICT transition which in turnpeak is caused by the BPA substitution. substitution. Upon binding with the Cd2+ ion, the emission peak was blue-shifted to 570 nm, implying that with the ICT as discussed above. The fluorescence quantum Upon binding thetransition Cd2+ ion, is thediminished, emission peak was blue-shifted to 570 nm, implying that theyield ICT implying that the ICT transition is diminished, as discussed above. The fluorescence quantum yield of pristineis1diminished, determinedas asdiscussed 7.6% by using B in acetonitrile as a standard = 0.89, λex = transition above.Rhodamine The fluorescence quantum yield of pristine(φ1F determined of pristine 1 determined as 7.6% by using Rhodamine B in acetonitrile as a standard (φF = 0.89, λex = 4957.6% nm).byBy comparing the total fluorescenceasintensity and(ϕthe absorbance at the same excitation as using Rhodamine B in acetonitrile a standard = 0.89, λ = 495 nm). By comparing ex F 495 nm). By comparing the total fluorescence intensity and the absorbance at the same excitation wavelength 495 nm between unbound and Cd2+at-bound state of 1, thewavelength fluorescence495 quantum yield the total fluorescence intensitythe and the absorbance the same excitation nm between wavelength 495 nm between the unbound and Cd2+-bound state of 1, the fluorescence quantum yield 2+ 2+ 2+ of Cd -boundand 1 can estimated The spectral changeyield shown in Figure 3a1enables the unbound Cd be-bound statetoofbe 1, 44.2%. the fluorescence quantum of Cd -bound can be of Cd2+-bound 1 can be estimated to be 44.2%. The spectral change shown in Figure 3a enables ratiometric sensing by plotting the ratio of fluorescent intensity at 570 nm and 730 nm (F570/F730) as ratiometric sensing by plotting the ratio of2+fluorescent intensity at 570 nm and 730 nm (F570/F730) as a function of the concentration of Cd (relative to that of 1), as shown in Figure 3b. An a function of the concentration of Cd2+ (relative to that of 1), as shown in Figure 3b. An2+ approximately linear relationship was obtained, allowing for determining the concentration of Cd approximately linear relationship was obtained, allowing for determining the concentration of Cd2+ using this linear calibration. The limit of detection (LOD) can be projected by taking three times the using this linear calibration. The limit of detection (LOD) can be projected by taking three times the standard deviation of measurement as the detectable signal, that is, 0.3 in this study. Using the slope

Sensors 2017, 17, 2517

5 of 10

estimated to be 44.2%. The spectral change shown in Figure 3a enables ratiometric sensing by plotting the ratio of fluorescent intensity at 570 nm and 730 nm (F570/F730) as a function of the concentration of Cd2+ (relative to that of 1), as shown in Figure 3b. An approximately linear relationship was obtained, allowing for determining the concentration of Cd2+ using this linear calibration. The limit of detection (LOD) can be projected by taking three times the standard deviation of measurement as the detectable signal, that is, 0.3 in this study. Using the slope of the linear fitting of Figure 3b, we5 of can Sensors 2017, 17, 2517 10 determine the LOD to be 6.9 nM, or 0.77 ppb, which is far below the safety value set for drinking below by theWHO safety(3 value setindicating for drinking water feasibility by WHO (3ofppb), strong of using water ppb), a strong usingindicating sensor 1 a for tracefeasibility level detection of 2+ 2+ sensor 1 for trace level detection ofon Cdthe. fluorescence The ratiometric sensing, relying on theand fluorescence Cd . The ratiometric sensing, relying measurement of both bound unbound measurement ofpotentially both bound and unbound state of of 1, signal could by potentially the robustness of state of 1, could improve the robustness cancelingimprove the interference from the 2+ signal by canceling the interference from the environment. By comparing with other fluorescence environment. By comparing with other fluorescence sensors for Cd reported in literature (Table 1), sensors1 developed for Cd2+ reported in literature 1), sensor 1 developed in this study has many sensor in this study has many(Table advantages over other Cd2+ sensors. 2+ advantages over other Cd sensors.

Figure 3. 3. (a) (a)Fluorescence Fluorescencespectral spectral change recorded an acetonitrile solution of sensor 1 (2upon μM) Figure change recorded for for an acetonitrile solution of sensor 1 (2 µM) 2+ ion; (b) The ratio of fluorescence intensity (F570/F730) measured for the same upon titration of Cd 2+ titration of Cd ion; (b) The ratio of fluorescence intensity (F570/F730) measured for the same solutions 2+ (relative to that of 1), solutions nm asofathe function of the concentration of to Cdthat at 570 nm at and570 730nm nmand as a730 function concentration of Cd2+ (relative of 1), showing linear showing linear fitting as indicated in the plot. fitting as indicated in the plot. Table1.1.The Thecomparison comparisonofof11with withother otherCd Cd2+2+ sensors sensors in in literature. literature Table Refs. LOD (mol L−1) −1 Refs. [7] LOD (mol 1.97 × 10L−7 ) [8] 2.76××10 10−−77 [7] 1.97 1.76××10 10−−77 [8] [18] 2.76 [18] [29] Not 1.76 available × 10−7 [29]This work Not6.9 available × 10−9 This work 6.9 × 10−9

Wavelength of Emission Solvent Used Wavelength of Emission Used 456 nm CH2Cl2/CHSolvent 3CN (1/9) 500 456 nm nm H22O CH Cl2 /CH3 CN (1/9) 495 nm/558 nm HEPES H2 O 500 nm 495 nm HEPES (9/1) 597nm/558 nm CH3COCH3/H2O 597 nm CH COCH3 /H2 O (9/1) 570 nm/730 nm CH33CN 570 nm/730 nm CH3 CN

3.2. Sensing Mechanism and Job’s Plot 3.2. Sensing Mechanism and Job’s Plot As illustrated in Scheme 2, the sensing mechanism of 1 relies on switching the fluorescence As illustrated in to Scheme 2, the mechanism of 1 relies switching the fluorescence from from ICT transition local π − π sensing transition at the BOPHY site.onThe BPA chelator affords strong 2+ ICT transition localion, π −and π transition at thethe BOPHY site.donating The BPApower chelator strong binding to binding to thetoCd this weakens electron of affords the aniline moiety, thus the Cd2+ ion,the andICT thistransition. weakens the donating power of the aniline moiety, thus diminishing Theelectron tridentate chelation of BPA forms 1:1 complex withdiminishing Cd2+ ion, as 2+ ion, as also reported the transition. BPA forms 1:1 complex alsoICT reported in The othertridentate studies chelation wherein of the same chelator was with usedCd [29]. The 1:1 chelation in other studieswas wherein the same chelator was used [29]. The 1:1 chelation stoichiometry was also stoichiometry also confirmed in this study through a Job’s plot approach [44], as shown in confirmed in thisplot study a Job’s plot [44], shown in Figure Job’s plotbetween is commonly Figure 4. Job’s is through commonly used to approach determine theasstoichiometry of a4. complex two 2+ ion) used to determine the total stoichiometry of a complexofbetween species, which 1the total species, for which the molar concentrations the two two species (herefor molecule and Cdmolar 2+ concentrations of thewhile two species (here molecule 1 and Cdareion) are kept constant, while their relative are kept constant, their relative concentrations varied. A measured variable (here the concentrations are varied. A measured variable (here the fluorescence intensity ratio, F570/F730) that is fluorescence intensity ratio, F570/F730) that is dependent on the complex formation can be plotted as dependent onthe themolar complex formation can be plotted as a The function of the molar of the binding a function of fractions of the binding species. maximum of the fractions plot corresponds to the stoichiometry of the complex formed. In this study, the total concentration of molecule 1 and Cd2+ ion was fixed at 2 μM, and the molar ratio of the two species was changed from 1:9 to 9:1, and the fluorescence intensity ratio F570/F730 was measured under the same conditions. Clearly, as shown in Figure 4, the maximum of the plot corresponds to a 1:1 complex between 1 and Cd2+.

Sensors 2017, 17, 2517

6 of 10

species. The maximum of the plot corresponds to the stoichiometry of the complex formed. In this study, the total concentration of molecule 1 and Cd2+ ion was fixed at 2 µM, and the molar ratio of the two species was changed from 1:9 to 9:1, and the fluorescence intensity ratio F570/F730 was measured under the same conditions. Clearly, as shown in Figure 4, the maximum of the plot corresponds to aSensors 1:1 complex between 1 and Cd2+ . 2017, 17, 2517 6 of 10

2+ in acetonitrile, with the total concentration of Figure 4. 4. Job’s Job’s plot plot of of the the binding binding between between 11 and and Cd Cd2+ Figure in acetonitrile, with the total concentration of the two two species species fixed fixed at at 22 µM. μM. the

3.3. Sensing Selectivity 3.3. Sensing Selectivity The high selectivity of 1 towards Cd2+ ion was examined by comparative experiments, which The high selectivity of 1 towards Cd2+ ion was examined by comparative experiments, which were were conducted by repeating the same fluorescence measurements shown in Figure 3 but in the conducted by repeating the same fluorescence measurements shown in Figure 3 but in the presence presence of 10 other common metal ions, Mn2+, Pb2+, Cu2+, Co2+, Mg2+, Ca2+, Ba2+, Fe2+, Hg2+, and Zn2+. of 10 other common metal ions, Mn2+ , Pb2+ , Cu2+ , Co2+ , Mg2+ , Ca2+ , Ba2+ , Fe2+ , Hg2+ , and Zn2+ . In contrast to the efficient spectral change observed for Cd2+ (far left bar in the figure), all of the other In contrast to the efficient spectral change observed for Cd2+ (far left bar in the figure), all of the metal ions (except for Zn2+) demonstrated almost no spectral change, as indicated by the low values other metal ions (except for Zn2+ ) demonstrated almost no spectral change, as indicated by the low of F570/F730 measured under the same experimental conditions (Figure 5a). However, upon the values of F570/F730 measured under the same experimental conditions (Figure 5a). However, upon the addition of Cd2+ ion at the same concentration, all of the 10 solutions containing the different metal addition of Cd2+ ion at the same concentration, all of the 10 solutions containing the different metal ions showed dramatic fluorescence change at the same degree as that observed for the solution of ions showed dramatic fluorescence change at the same degree as that observed for the solution of 1 + Cd2+. This observation indicates good sensing selectivity for molecule 1 towards Cd2+, which in 1 + Cd2+ . This observation indicates good sensing selectivity for molecule 1 towards Cd2+ , which in turn is largely due to the strong chelation, as illustrated in Scheme 2. The mild fluorescence response turn is largely due to the strong chelation, as illustrated in Scheme 2. The mild fluorescence response observed for Zn2+ ion is not surprised considering the similar coordination property between Zn2+ observed for Zn2+ ion is not surprised considering the similar coordination property between Zn2+ and Cd2+. However, due to the weaker electron affinity of Zn2+ ion (with standard reduction potential and Cd2+ . However, due to the weaker electron affinity of Zn2+ ion (with standard reduction potential of −0.7 V, as compared to that of Cd2+, −0.4 V), the binding with Zn2+ cannot block the ICT transition of −0.7 V, as compared to that of Cd2+ , −0.4 V), the binding with Zn2+ cannot block the ICT transition as effectively as Cd2+. Indeed, as shown in Figure 5b, under the same concentration the solution of as effectively as Cd2+ . Indeed, as shown in Figure 5b, under the same concentration the solution of 1 + Cd2+ exhibited a dramatic fluorescence color change (consistent with the spectral measurement 1 + Cd2+ exhibited a dramatic fluorescence color change (consistent with the spectral measurement shown Figure 3), whereas the solution of 1 + Zn2+ remained about the same color as the solution of 1. shown Figure 3), whereas the solution of 1 + Zn2+ remained about the same color as the solution of 1. Such dramatic difference in color change provides additional feature to distinguish Cd2+ from other Such dramatic difference in color change provides additional feature to distinguish Cd2+ from other metal ions when using 1 as sensor. metal ions when using 1 as sensor.

d Figure 5. (a) Fluorescence intensity ratio (F570/F730) measured for sensor 1 in acetonitrile (2 μM) in

of −0.7 V, as compared to that of Cd2+, −0.4 V), the binding with Zn2+ cannot block the ICT transition as effectively as Cd2+. Indeed, as shown in Figure 5b, under the same concentration the solution of 1 + Cd2+ exhibited a dramatic fluorescence color change (consistent with the spectral measurement shown Figure 3), whereas the solution of 1 + Zn2+ remained about the same color as the solution of 1. Such dramatic difference in color change provides additional feature to distinguish Cd2+ from other Sensors 2017, 17, 2517 7 of 10 metal ions when using 1 as sensor.

Sensors 2017, 17, 2517

7 of 10

3.4. Fast Sensor Response The sensor 1 could rapidly detect Cd2+ ion, as shown in Figure 6. When we put 2 μM Cd2+ into 2 μM sensor 1dsolution, the fluorescence intensity ratio (F570/F730) of sensor 1 quickly increased and reached a stable value within 1 min. This is a good trait for fast and real-time determination. Figure intensity ratio (F570/F730) measured forfor sensor 1 in acetonitrile (2(2 μM) inin Figure5.5.(a)(a)Fluorescence Fluorescence intensity ratio (F570/F730) measured sensor 1 in acetonitrile µM) In addition to the high sensitivity and selectivity observed above, sensor 1 also demonstrated a the absence ofof metal ions (black), and inin the presence ofofvarious metal ions (2(2μM), the absence metal ions (black), and the presence various metal ions µM),(blue), (blue),followed followed fast response, consistent 2+with the strong chelation with Cd2+. As shown in Figure 6, the ratiometric byby addition into each of of thethe eleven solutions (red); (b)(b) Photographs taken forfor the 2 μM additionofof2 2μM µMCd Cd2+ into each eleven solutions (red); Photographs taken the 2 µM 2+ ion. Due to the fluorescence response of 1 was finished in one min upon addition 2+ 2+ 2+. 2+of 1:1 Cd solution ofof 1,1, inincomparison and CdCd solution comparisontotothe theones onescontaining containing2 2μM µMofofZn Zn and . experimental operation limit, we could not monitor the sensor response in any faster time scale, though the real response time of 1 seems to be in seconds or even faster. This fast fluorescence 3.4. Fast Sensor Response response makes sensor 1 ideal for real-time monitoring, particularly for in-field detection. Also 2+ into The sensor 1 could 6rapidly Cd2+ ion, as shown in 1, Figure 6. When we put 2 µM Cd indicated from Figure is the detect high photostability sensor wherein the fluorescence of 1 was 2 µM sensor the binding fluorescence ratio of sensor 1 quickly and measured ten1 solution, times after withintensity Cd2+ ion, but(F570/F730) no significant change in theincreased fluorescence reached awas stable value within 1 min. This is a good trait for fast and real-time determination. intensity observed.

Figure 6. Time Timecourse course of fluorescence the fluorescence intensity ratio (F570/F730) change measured on an Figure 6. of the intensity ratio (F570/F730) change measured on an acetonitrile 2+ ion (2 μM). 2+ acetonitrile solution of sensor 1 (2 μM) upon addition of Cd solution of sensor 1 (2 µM) upon addition of Cd ion (2 µM).

4. Conclusions In addition to the high sensitivity and selectivity observed above, sensor 1 also demonstrated 2+ . As shown 2+ the report consistent on a novelwith fluorescence 1 for theCd selective detection of Cd6, ion ratiometric with LOD a fastWe response, the strongsensor chelation with in Figure 2+ 4BOPHY down to 0.77 ppb. The sensor molecule is based a fluorophore of Meof fluorescence response of 1 was finished in oneonmin upon addition 1:1 Cdin conjugation ion. Due towith the 2+ an electron donor group, namely BPA, which also affords strong binding with Cd . The electron experimental operation limit, we could not monitor the sensor response in any faster time scale, donor-acceptor conjugation enables long wavelength, desired forresponse sensor though the real response time of 1 seemsICT to befluorescence in seconds orateven faster. This fast fluorescence development. with the Cd2+ ion, particularly the fluorescence is switched from Also ICT transition be makes sensor 1Upon idealbinding for real-time monitoring, for in-field detection. indicated to from the π − π transition, which dominated by the Me4BOPHY fluorophore, which is located in much shorter wavelength region. Such dramatic fluorescence change enables ratiometric sensing by measuring the relative emission intensity at the two wavelengths as a function of the concentration of Cd2+ ion, thus allowing for quantitative detection of Cd2+. High selectivity towards Cd2+ was also evidenced for the sensor as examined with ten other common metal ions.

Sensors 2017, 17, 2517

8 of 10

Figure 6 is the high photostability sensor 1, wherein the fluorescence of 1 was measured ten times after binding with Cd2+ ion, but no significant change in the fluorescence intensity was observed. 4. Conclusions We report on a novel fluorescence sensor 1 for the selective detection of Cd2+ ion with LOD down to 0.77 ppb. The sensor molecule is based on a fluorophore of Me4 BOPHY in conjugation with an electron donor group, namely BPA, which also affords strong binding with Cd2+ . The electron donor-acceptor conjugation enables ICT fluorescence at long wavelength, desired for sensor development. Upon binding with the Cd2+ ion, the fluorescence is switched from ICT transition to be the π − π transition, which dominated by the Me4 BOPHY fluorophore, which is located in much shorter wavelength region. Such dramatic fluorescence change enables ratiometric sensing by measuring the relative emission intensity at the two wavelengths as a function of the concentration of Cd2+ ion, thus allowing for quantitative detection of Cd2+ . High selectivity towards Cd2+ was also evidenced for the sensor as examined with ten other common metal ions. Supplementary Materials: The Supplementary Materials are available online at http://www.mdpi.com/14248220/17/11/2517/s1. Acknowledgments: This work was financially supported by the Qinghai Science & Technology Department of China (Grant No. 2016-HZ-806), the National Natural Science Foundation of China (Grant No. 21362027), the China Scholarship Council (CSC) and the Qinghai University (Grant No. 2015-QGY-5). Author Contributions: Dandan Cheng carried out the majority of experiments and wrote the article; Xingliang Liu designed and synthesized sensor 1; Yadian Xie did part of the experiments under the help of Dandan Cheng; Haitang Lv measured the fluorescent spectra; Zhaoqian Wang was responsible for UV spectra measuriment; Hongzhi Yang did part of synthesis experiments; Aixia Han was responsible for the whole work; Xiaomei Yang helped on data analysis and manuscript editing; Ling Zang helped supervising the research design. Conflicts of Interest: The authors declare no conflict of interest.

References 1. 2. 3.

4. 5.

6. 7. 8. 9. 10.

Huff, J.; Lunn, R.M.; Waalkes, M.P.; Tomatis, L.; Infante, P.F. Cadmium-induced Cancers in Animals and in Humans. Int. J. Occup. Environ. Health 2007, 13, 202–212. [CrossRef] [PubMed] World Health Organization. Available online: http://www.who.int/water_sanitation_health/publications/ drinking-water-quality-guidelines-4-including-1st-addendum/en/ (accessed on 1 November 2017). Wen, X.D.; Yang, Q.L.; Yan, Z.D.; Deng, Q.W. Determination of cadmium and copper in water and food samples by dispersive liquid–liquid microextraction combined with UV–vis spectrophotometry. Microchem. J. 2011, 97, 249–254. [CrossRef] Manzoori, J.L.; Bavili-Tabrizi, A. Cloud point preconcentration and flame atomic absorption spectrometric determination of Cd and Pb in human hair. Anal. Chim. Acta 2002, 470, 215–221. [CrossRef] Rao, K.S.; Balaji, T.; Rao, T.P.; Babu, Y.; Naidu, G.R.K. Determination of iron, cobalt, nickel, manganese, zinc, copper, cadmium and lead in human hair by inductively coupled plasma-atomic emission spectrometry. Spectrochim. Acta Part B 2002, 57, 1333–1338. Xue, L.; Liu, C.; Jiang, H. Highly Sensitive and Selective Fluorescent Sensor for Distinguishing Cadmium from Zinc Ions in Aqueous Media. Org. Lett. 2009, 11, 1655–1658. [CrossRef] [PubMed] Zhao, Q.; Li, R.F.; Xing, S.K.; Liu, X.M.; Hu, T.L.; Bu, X.H. A Highly Selective On/Off Fluorescence Sensor for Cadmium(II). Inorg. Chem. 2011, 50, 10041–10046. [CrossRef] [PubMed] Gunnlaugsson, T.; Lee, T.C.; Parkesh, R. Highly selective fluorescent chemosensors for cadmium in water. Tetrahedron 2004, 60, 11239–11249. [CrossRef] Zhang, X.X.; Wang, R.J.; Fan, C.B.; Liu, G.; Pu, S.Z. A highly selective fluorescent sensor for Cd2+ based on a new diarylethene with a 1,8-naphthyridine unit. Dyes Pigments 2017, 139, 208–217. [CrossRef] Khani, R.; Ghiamati, E.; Boroujerdi, R.; Rezaeifard, A.; Zaryabi, M.H. A new and highly selective turn-on fluorescent sensor with fast response time for the monitoring of cadmium ions in cosmetic, and health product samples. Spectrochim. Acta Part A 2016, 163, 120–126. [CrossRef] [PubMed]

Sensors 2017, 17, 2517

11. 12.

13. 14.

15.

16.

17.

18.

19.

20. 21. 22. 23. 24. 25.

26.

27. 28.

29. 30. 31.

9 of 10

Chao, D.B. Highly selective detection of Zn2+ and Cd2+ with a simple amino-terpyridine compound in solution and solid state. J. Chem. Sci. 2016, 128, 133–139. [CrossRef] Zhou, X.Y.; Li, P.X.; Shi, Z.H.; Tang, X.L.; Chen, C.Y.; Liu, W.S. A Highly Selective Fluorescent Sensor for Distinguishing Cadmium from Zinc Ions Based on a Quinoline Platform. Inorg. Chem. 2012, 51, 9226–9231. [CrossRef] [PubMed] Goswami, P.; Das, D.K. A New Highly Sensitive and Selective Fluorescent Cadmium Sensor. J. Fluoresc. 2012, 22, 391–395. [CrossRef] [PubMed] Zhou, Y.; Xiao, Y.; Qian, X.H. A highly selective Cd2+ sensor of naphthyridine: fluorescent enhancement and red-shift by the synergistic action of forming binuclear complex. Tetrahedron Lett. 2008, 49, 3380–3384. [CrossRef] Mameli, M.; Aragoni, M.C.; Arca, M.; Caltagirone, C.; Demartin, F.; Farruggia, G.; De Filippo, G.; Devillanova, F.A.; Garau, A.; Isaia, F.; et al. A Selective, Nontoxic, OFF–ON Fluorescent Molecular Sensor Based on 8-Hydroxyquinoline for Probing Cd2+ in Living Cells. Chem. Eur. J. 2010, 16, 919–930. [CrossRef] [PubMed] Liu, Y.; Qiao, Q.L.; Zhao, M.; Yin, W.T.; Miao, L.; Wang, L.Q.; Xu, Z.C. Cd2+ -triggered amide tautomerization produces a highly Cd2+ -selective fluorescent sensor across a wide pH range. Dyes Pigments 2016, 133, 339–344. [CrossRef] Lu, C.L.; Xu, Z.C.; Cui, J.N.; Zhang, R.; Qian, X.H. Ratiometric and Highly Selective Fluorescent Sensor for Cadmium under Physiological pH Range: A New Strategy to Discriminate Cadmium from Zinc. J. Org. Chem. 2007, 72, 3554–3557. [CrossRef] [PubMed] Xue, L.; Li, G.P.; Liu, Q.; Wang, H.H.; Liu, C.; Ding, X.L.; He, S.G.; Jiang, H. Ratiometric Fluorescent Sensor Based on Inhibition of Resonance for Detection of Cadmium in Aqueous Solution and Living Cells. Inorg. Chem. 2011, 50, 3680–3690. [CrossRef] [PubMed] Taki, M.; Desaki, M.; Ojida, A.; Iyoshi, S.; Hirayama, T.; Hamachi, I.; Yamamoto, Y. Fluorescence Imaging of Intracellular Cadmium Using a Dual-Excitation Ratiometric Chemosensor. J. Am. Chem. Soc. 2008, 130, 12564–12565. [CrossRef] [PubMed] Chiu, T.Y.; Chen, P.H.; Chang, C.L.; Yang, D.M. Live-Cell Dynamic Sensing of Cd2+ with a FRET-Based Indicator. PLoS ONE 2013, 8, e65853. [CrossRef] [PubMed] Wang, C.; Huang, H.L.; Bunes, B.R.; Wu, N.; Xu, M.; Yang, X.M.; Yu, L.; Zang, L. Trace Detection of RDX, HMX and PETN Explosives Using a Fluorescence Spot Sensor. Sci. Rep. 2016, 6, 25015. [CrossRef] [PubMed] Xu, M.; Han, J.M.; Wang, C.; Yang, X.M.; Pei, J.; Zang, L. Fluorescence Ratiometric Sensor for Trace Vapor Detection of Hydrogen Peroxide. ACS Appl. Mater. Interfaces 2014, 6, 8708–8714. [CrossRef] [PubMed] Kamiya, M.; Johnsson, K. Localizable and Highly Sensitive Calcium Indicator Based on a BODIPY Fluorophore. Anal. Chem. 2010, 82, 6472–6479. [CrossRef] [PubMed] Atilgan, S.; Kutuk, I.; Ozdemir, T. A near IR distyryl BODIPY-based ratiometric fluorescent chemosensor for Hg(II). Tetrahedron Lett. 2010, 51, 892–894. [CrossRef] Qi, X.; Jun, E.J.; Xu, L.; Kim, S.J.; Joong Hong, J.S.; Yoon, Y.J.; Yoon, J. New BODIPY Derivatives as OFF−ON Fluorescent Chemosensor and Fluorescent Chemodosimeter for Cu2+ : Cooperative Selectivity Enhancement toward Cu2+ . J. Org. Chem. 2006, 71, 2881–2884. [CrossRef] [PubMed] Wu, Y.K.; Peng, X.J.; Guo, B.C.; Fan, J.L.; Zhang, Z.C.; Wang, J.Y.; Cui, A.J.; Gao, Y.L. Boron dipyrromethene fluorophore based fluorescence sensor for the selective imaging of Zn (II) in living cells. Org. Biomol. Chem. 2005, 3, 1387–1392. [CrossRef] [PubMed] Liu, J.; Wu, K.; Li, S.; Song, T.; Han, Y.F.; Li, X. A highly sensitive and selective fluorescent chemosensor for Pb2+ ions in an aqueous solution. Dalton Trans. 2013, 42, 3854–3859. [CrossRef] [PubMed] Cheng, T.Y.; Xu, Y.F.; Zhang, S.Y.; Zhu, W.P.; Qian, X.H.; Duan, L.P. A Highly Sensitive and Selective OFF-ON Fluorescent Sensor for Cadmium in Aqueous Solution and Living Cell. J. Am. Chem. Soc. 2008, 130, 16160–16161. [CrossRef] [PubMed] Peng, X.J.; Du, J.J.; Fan, J.L.; Wang, J.Y.; Wu, Y.K.; Zhao, J.Z.; Sun, S.G.; Xu, T. A Selective Fluorescent Sensor for Imaging Cd2+ in Living Cells. J. Am. Chem. Soc. 2007, 129, 1500–1501. [CrossRef] [PubMed] Tamgho, I.S.; Hasheminasab, A.; Engle, J.T.; Nemykin, V.N.; Ziegler, C.J. A new highly fluorescent and symmetric pyrrole–BF2 chromophore: BOPHY. J. Am. Chem. Soc. 2014, 136, 5623–5626. [CrossRef] [PubMed] Yu, C.J.; Jiao, L.J.; Zhang, P.; Feng, Z.Y.; Cheng, C.; Wei, Y.; Mu, X.L.; Hao, E.H. Highly fluorescent BF2 complexes of hydrazine–Schiff base linked bispyrrole. Org. Lett. 2014, 16, 3048–3051. [CrossRef] [PubMed]

Sensors 2017, 17, 2517

32. 33.

34. 35.

36.

37. 38.

39. 40. 41.

42.

43. 44.

10 of 10

Huaulmé, Q.; Mirloup, A.; Retailleau, P.; Ziessel, R. Synthesis of highly functionalized BOPHY chromophores displaying large stokes shifts. Org. Lett. 2015, 17, 2246–2249. [CrossRef] [PubMed] Rhoda, H.M.; Chanawanno, K.; King, A.J.; Zatsikha, Y.V.; Ziegler, C.J.; Nemykin, V.N. Unusually Strong Long Distance Metal-Metal Coupling in Bis (ferrocene) Containing BOPHY: An Introduction to Organometallic BOPHYs. Chem. Eur. J. 2015, 21, 18043–18046. [CrossRef] [PubMed] Wang, L.; Tamgho, I.S.; Crandall, L.; Rack, J.; Ziegler, C. Ultrafast dynamics of a new class of highly fluorescent boron difluoride dyes. Phys. Chem. Chem. Phys. 2015, 17, 2349–2351. [CrossRef] [PubMed] Sekhar, A.R.; Sariki, S.K.; Reddy, R.V.R.; Bisai, A.; Sahu, P.K.; Tomar, R.S.; Sankar, J. Zwitterionic BODIPYs with large stokes shift: Small molecular biomarkers for live cells. Chem. Commun. 2017, 53, 1096–1099. [CrossRef] [PubMed] Zhou, L.; Xu, D.F.; Gao, H.Z.; Zhang, C.; Ni, F.F.; Zhao, W.Q.; Cheng, D.D.; Liu, X.L.; Han, A.X. β-Furan-Fused bis (Difluoroboron)-1,2-bis ((1H-pyrrol-2-yl) methylene) hydrazine Fluorescent Dyes in the Visible Deep-Red Region. J. Org. Chem. 2016, 81, 7439–7447. [CrossRef] [PubMed] Li, Y.X.; Zhou, H.P.; Yin, S.H.; Jiang, H.; Niu, N.; Huang, H.; Shahzad, S.A.; Yu, C. A BOPHY probe for the fluorescence turn-on detection of Cu2+ . Sens. Actuators B 2016, 235, 33–38. [CrossRef] Jiang, X.D.; Su, Y.J.; Yue, S.; Li, C.; Yu, H.F.; Zhang, H.; Sun, C.L.; Xiao, L.J. Synthesis of mono-(p-dimethylamino)styryl-containing BOPHY dye for a turn-on pH sensor. RSC Adv. 2015, 5, 16735–16739. [CrossRef] Xu, Z.C.; Xiao, Y.; Qian, X.H.; Cui, J.N.; Cui, D.W. Ratiometric and selective fluorescent sensor for CuII based on internal charge transfer (ICT). Org. Lett. 2005, 7, 889–892. [CrossRef] [PubMed] Wang, J.B.; Qian, X.H.; Cui, J.N. Detecting Hg2+ ions with an ICT fluorescent sensor molecule: Remarkable emission spectra shift and unique selectivity. J. Org. Chem. 2006, 71, 4308–4311. [CrossRef] [PubMed] Bozdemir, O.A.; Guliyev, R.; Buyukcakir, O.; Selcuk, S.; Kolemen, S.; Gulseren, G.; Nalbantoglu, T.; Boyaci, H.; Akkaya, E.U. Selective manipulation of ICT and PET processes in styryl-bodipy derivatives: Applications in molecular logic and fluorescence sensing of metal ions. J. Am. Chem. Soc. 2010, 132, 8029–8036. [CrossRef] [PubMed] Srikun, D.; Miller, E.W.; Domaille, D.W.; Chang, C.J. An ICT-based approach to ratiometric fluorescence imaging of hydrogen peroxide produced in living cells. J. Am. Chem. Soc. 2008, 130, 4596–4597. [CrossRef] [PubMed] Thiagarajan, V.; Ramamurthy, P.; Thirumalai, D.; Ramakrishnan, V.T. A novel colorimetric and fluorescent chemosensor for anions involving PET and ICT pathways. Org. Lett. 2005, 7, 657–660. [CrossRef] [PubMed] Zhao, W.Q.; Liu, X.L.; Lv, H.T.; Fu, H.; Yang, Y.; Huang, Z.P.; Han, A.X. A phenothiazine–rhodamine ratiometric fluorescent probe for Hg2+ based on FRET and ICT. Tetrahedron Lett. 2015, 56, 4293–4298. [CrossRef] © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).