A sugar-aza-crown ether-based fluorescent sensor for Hg2+ and Cu2+

Carbohydrate Research 344 (2009) 2236–2239

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A sugar-aza-crown ether-based fluorescent sensor for Hg2+ and Cu2+ Yu-Chi Hsieh a, Jiun-Ly Chir b, Hsiu-Han Wu a, Po-Sheng Chang a, An-Tai Wu a,* a b

Department of Chemistry, National Changhua University of Education, Changhua 50058, Taiwan Biotechnology Center in Southern Taiwan, Academia Sinica, Tainan County 744, Taiwan

a r t i c l e

i n f o

Article history: Received 21 July 2009 Received in revised form 12 August 2009 Accepted 22 August 2009 Available online 27 August 2009 Keywords: Fluorescent sensor Sugar-aza-crown ether Fluorescence Anthracene

a b s t r a c t A fluorescent sensor, 5, based upon the sugar-aza-crown ether structure with two anthracenetriazolymethyl groups was prepared and its fluoroionophoric properties toward transition metal ions were investigated. In methanol, the sensor exhibits highly selective recognition of Cu2+ and Hg2+ ions among a series of tested metal ions. The association constant for 5
Cu2+ and 5
Hg2+ in methanol was calculated to be 4.0  105 M 1 and 1.1  105 M 1, respectively. The detection limits for the sensing of Cu2+ and Hg2+ ions were 1.39  10 6 M and 1.39  10 5 M, respectively. Ó 2009 Elsevier Ltd. All rights reserved.

Cyclic sugar amino acids (SAAs)1–7 have recently attracted attention for their features as structurally rigid molecular scaffolds and interior cavities of precise dimensions. These characteristics may allow SAAs to mimic cyclodextrins (CDs) and allow them to be used in the formation of inclusion complexes8–12 with guests for molecular recognition processes.2–4 Such artificial recognition of ions and molecules may lead to the development of new fluorescent sensors. The design and synthesis of new fluorescent sensors for the efficient detection of trace metal ions is one of the most important research topics in environmental chemistry and biology. Derivatives of SAA, sugar-aza-crowns ethers (SAC), which can be obtained by converting the amide in cyclic SAAs into an amine13 or by a one-pot reductive amination of a C-ribosyl azido aldehyde,14 provides a potential molecular framework for the design of selective fluorescent sensors. For example, modified pyranoidbased SACs with bispyrenyl were synthesized to form a new fluorescent molecular sensor for Cu2+.15 Therefore, modified SACs with appropriate appended fluorescent sensor would be good candidates for cation probes. However, until the present, few SAC fluorescent sensors have been found in the literature. With regard to the fluorescence responses of fluorescent sensors, anthracene and pyrene have emerged as the most effective functional groups for fluorescence signaling.16–18 In pioneering work, Czarnik and co-workers19 reported that an azacrown-appended anthracene acts as a fluorescent Hg2+- and Cu2+-selective sensor. In addition, Chang’s group reported a disubstituted dimethylcyclam derivative having two anthracene groups,20 which * Corresponding author. Fax: +886 4 7211 190. E-mail address: [email protected] (A.-T. Wu). 0008-6215/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.carres.2009.08.027

was a highly Hg2+- and Cu2+-selective fluorescent sensor. Herein, we report a fluorescent sensor, 5, with a furanoid-based SAC and two triazole moieties as the binding sites, and two anthracene moieties as the signaling units. The designed fluorescent sensor exhibits a highly selective and efficient fluorescence behavior for Cu2+ and Hg2+ ions in methanol. The synthesis of fluorescent sensor 5 is outlined in Scheme 1. SAC ether 4 was easily obtained from C-ribosyl azido aldehyde following the reported protocol.14 The reaction of 9-(azidomethyl)anthracene 1 with propargyl alcohol under ‘click’ conditions21,22 afforded the 1,2,3-triazole alcohol 2 in 87% yield. Treatment of 2 with thionyl chloride afforded chloromethyl1,2,3-triazole 3 in 91% yield. Subsequently, the fluorescent sensor 5 was prepared in 73% yield by the reaction of the SAC ether 4 with chloromethyl-1,2,3-triazole 3 using K2CO3 as a base in the presence of KI and n-Bu4NI at reflux in acetonitrile.23 We examined the effect of different solvents (dichloromethane, methanol, and acetonitrile) on the fluorescence spectrum of 5. The fluorescence intensity showed a dependence on the polarity of the solvent, with more polar solvents having a greater influence (Fig. 1). The spectrum of 5 (1.35  10 5 M) is composed of a triple emission with peaks around 395, 415, and 440 nm, which are independent of the nature of solvent, upon excitation at 367 nm. Therefore, we decided to investigate the metal complexation properties in methanol. The chemosensing properties of 5 were investigated by measuring fluorescence responses in methanol upon excitation at 367 nm. The binding ability of 5 toward metal ions was examined by comparing the fluorescence intensities of the solutions before and after the addition of 100 equiv of 11 metal ions as their perchlorate salts: Li+, Na+, K+, Ca2+, Mg2+, Hg2+, Co2+, Ni2+, Cu2+, Zn2+, and Pb2+ (Fig. 2).

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N3

HO

Cl

N N N

OH

SOCl2 CH2Cl2

Cu, CuSO4 EtOH

1

N N N

3

2

N H

O

O

O

O

O

3 N N N N N N

K2CO3, KI, t-BuNI

O

H N

CH3CN

NO

4 O

NO

O

O

5

O

Scheme 1. Synthesis of fluorescent sensor 5.

40

50

40

5 in CH2Cl2 30

20

10

0 380

400

420

440

460

480

500

520

Fluorescence Intensity (a.u.)

Fluorescence Intensity (a.u.)

5, Pb, Mg, Ca, Zn, K, Li, Na 5 in MeOH 5 in CH3CN

30

Co, Ni 20

0 380

540

Wavelength (nm) Figure 1. Fluorescence spectra of 5 in different solvents.

We found that the fluorescence of 5 was quenched by Co2+, Ni2+, Hg , and Cu2+ ions. Of these ions, Hg2+ and Cu2+ most effectively quenched the fluorescence intensity (82% inhibition for Hg2+ and 92% inhibition for Cu2+, Fig. 3). Furthermore, complexation experiments were also done by absorption measurements. As the concentration of the metal ion increased, no influence was observed on the absorbance peak (367 nm) of 5. To investigate the properties of sensor 5 further, we performed fluorescence titrations of 5 with Cu2+ or Hg2+ ion in methanolic solution. Fluorescent sensor 5 shows a gradual decrease in fluorescence as the concentration of Hg2+ or Cu2+ ion increased from 1.39  10 6 M to 2.78  10 4 M (Fig. 4). From the fluorescence titration profiles, the association constant (Ka) for 5
Cu2+ and 5
Hg2+ in methanol was calculated to be 4.0  105 M 1 and 1.1  105 M 2, respectively, by a Stern–Volmer plot. However, there is a less discrimination between Hg2+ (Ka = 4.0  105 M 2) and Cu2+ (Ka = 1.1  105 M 1) metal ions. These binding constants are similar to those of 9-(trpnmethy)anthracene toward Hg2+ and Cu2+, reported by Czarnik and co-workers.19 Therefore, the fluorescence quenching mechanism with Hg2+ and Cu2+ may be the same. The quenching effect of fluorescence may be attributed to a reverse PET24–26 mechanism involving electron donating from the excited

Hg Cu

10

400

420

440

460

480

500

520

540

Wavelength (nm) Figure 2. Fluorescence spectra of 5 upon addition of ClO4 salts of Li+, Na+, K+, Ca2+, Mg2+, Hg2+, Co2+, Ni2+, Zn2+, Cu2+, and Pb2+ (100 equiv) in MeOH. kex = 367 nm.

2+

0

(I-I0)/I0(415nm)*100%

Pb

Cu

Li

Ni

Co

Ca

Na

K

Hg

Mg

Zn

-20

-40

-60

-80

-100 Figure 3. Fluorescence intensity changes ((I I0)/I0  100%) of 5 (1.35  10 with various metal ions (1.35  10 3 M) in MeOH at 415 nm. kex = 367 nm.

5

M)

anthracene units to the triazole groups. That is, the anthracene units behave as an excited electron donor and the metal ion bound triazole groups behave as an electron acceptor.

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40 0

-15 -20 -25 -30 0

20

5

10 2+

15

20

[Cu ]/[5]

10

2

R =0.9971

8

(I0-I) (415nm) *Χ

I - I0

Fluorescence Intensity (a.u.)

0 eq. 0.1 eq. 0.2 eq. 0.3 eq. 0.4 eq. 0.5 eq. 0.6 eq. 0.7 eq. 0.8 eq. 0.9 eq. 1 eq. 2 eq. 10 eq. 20 eq.

-10

30

10

2+

5 + Cu

-5

6 4 2 0 0.0

0 380

400

420

440

460

480

500

520

0.2

0.4

0.6

0.8

1.0

Χ = [5] / {[5] + [Cu2+]}

540

Wavelength (nm) 8

5 + Hg

0

0 eq. 1.1 eq. 1.2 eq. 1.3 eq. 1.4 eq. 1.5 eq. 1.6 eq. 1.7 eq. 1.8 eq. 1.9 eq. 2 eq. 2.5 eq. 3 eq. 4 eq. 6 eq. 8 eq. 10 eq.

I - I0

Fluorescence Intensity (a.u.)

-5

30

-10 -15 -20 -25 -30 0

20

5

10 2+

15

20

[Hg ] / [5]

10

0 380

400

420

2 R =0.9612

2+

5

440

460

480

500

520

540

Wavelength (nm)

6

(I0-I) (415nm) *Χ

40

4

2

0 0.0

0.2

0.4

0.6

0.8

1.0

Χ = [5] / {[5] + [Hg2+]} Figure 5. Job plot of (a) a 1:1 complex of 5 with Cu(ClO4)2 and (b) a 1:2 complex of 5 with Hg(ClO4)2.

Figure 4. Fluorescence spectra of 5 in MeOH upon addition of increasing concentrations (a) Cu(ClO4)2 and (b) Hg(ClO4)2. kex = 367 nm.

The insets of Figure 4a and b show the decrease of fluorescence intensity as a function of [Cu2+]/[5] and [Hg2+]/[5], respectively. These curves directly point to 1:1 and 1:2 stoichiometry for 5
Cu2+ and 5
Hg2+, respectively. Additional support for the 1:1 and 1:2 stoichiometry of 5
Cu2+ and 5
Hg2+ was provided by a Job plot27 (Fig. 5). A maximum fluorescence change was observed when the molar fraction of the sensor [5] versus [5] + [Cu2+] was 0.5 (Fig. 5a), which indicated that a 1:1 adduct was formed with 5. Figure 5b shows the Job plot for the complex 5
Hg2+, the maximum appears at 0.3, which indicated that a 1:2 adduct was formed between 5. By using the previously mentioned fluorescence titration results, the detection limits of 5 for the analysis of Cu2+ and Hg2+ ions were determined as 1.39  10 6 M and 1.39  10 5 M, respectively. To understand better the complexation behavior of 5 with Cu2+ and Hg2+ ions, 1H NMR experiments were carried out in deuterated methanol. Because Cu2+ is a paramagnetic ion, not suitable for NMR experiments, we investigated the complexation of 5 with Hg2+. Figure 6 displays the chemical shifts of receptor 5 upon the addition of Hg2+ ion. In the presence of 2.0 equiv of Hg2+ ion, the proton in the triazole–CH2–anthracene was downfield shifted by 0.02 ppm. In addition, the protons in the triazole and anthracene ring were downfield shifted, suggesting that a significant conformational change of the SAC ring occurs as a consequence of Hg2+ complexation.

Figure 6. Partial 1H NMR spectra of 5 (5.20  10 presence of 2.0 equiv of Hg(ClO4)2 in MeOD.

3

M) in the (a) absence and (b)

In conclusion, a new fluorescent sensor, 5, was designed and synthesized by coupling a SAC ether and two anthracenetriazolymethyl moieties. The sensor shows higher selectivity for Hg2+ and Cu2+ ions over the other metal ions investigated. Upon addition of Hg2+ or Cu2+ ion into the solution of 5, the fluorescence intensity was quenched, probably with the complexation events being signaled by the control of the reverse PET.

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1. Experimental 1.1. General methods All reagents were obtained from commercial suppliers and were used without further purification. Dichloromethane was distilled over CaH2. Methanol was distilled over magnesium and iodine. Analytical thin-layer chromatography was performed using Silica Gel 60 F254 plates (Merck). The 1H and 13C NMR spectra were recorded with Bruker AM 300 (300 MHz) spectrometers. Chemical shifts are expressed in ppm with residual CHCl3 as reference. Low- and high-resolution mass spectra were recorded under fast atom bombardment (FAB) conditions. UV–vis spectra were recorded by using HP-8453 spectrophotometer with a diode array detector, and the resolution was set at 1 nm. Fluorescence spectra were recorded on a Cary Eclipse Fluorescence spectrophotometer. 1.2. (1-((Anthracen-10-yl)methyl)-1H-1,2,3-triazol-4yl)methanol (2) To a solution of 1 (2.94 g, 12.61 mmol) and propargyl alcohol (1.12 mL, 18.92 mmol) in 30 mL of ethanol were added copper turnings (0.32 g) and saturated copper sulfate solution (6.87 mL), and the reaction mixture was stirred in microwave for 30 min at 90 °C. After completion of the reaction, the reaction mixture was filtered through Celite. The Celite pad was washed with CHCl3 and filtrates were concentrated. The residue was purified by column chromatography (hexane/EtOAc 5:1) to give 2 (3.17 g, 87%) as a yellow solid. Mp 173 °C; Rf = 0.15 (1:1 hexane/EtOAc); 1H NMR (300 MHz, CDCl3) d 8.56 (s, 1H), 8.27 (d, J = 9.0 Hz, 2H), 8.06 (d, J = 8.4 Hz, 2H), 7.54 (m, 4H), 7.09 (s, 1H), 6.51 (s, 2H), 4.56 (s, 2H); 13C NMR (75 MHz, CDCl3) d 131.42, 130.76, 129.95, 129.50, 127.74, 125.43, 123.49, 122.86, 121.30, 56.40, 46.45; HRMS (FAB): calcd for C18H16N3O [M]+, m/z 290.1293, found m/z 290.1285. 1.3. 1-((Anthracen-10-yl)methyl)-4-(chloromethyl)-1H-1,2,3triazole (3) To a solution of 2 (3.17 g, 10.96 mmol) in dry CH2Cl2 (40 mL) was added SOCl2 (1.19 mL, 16.44 mmol) at 0 °C. The mixture was stirred for 1 h, then the mixture was concentrated, and purified by chromatography (hexane/EtOAc 8:1) to give 3 (3.06 g, 91%) as a yellow solid. Mp 170 °C; Rf = 0.72 (hexane/EtOAc 1:1); 1H NMR (300 MHz, CDCl3) d 8.53 (s, 1H), 8.23 (d, J = 9.0 Hz, 2H), 8.04 (d, J = 8.4 Hz, 2H), 7.54 (m, 4H), 7.11 (s, 1H), 6.45 (s, 2H), 4.48 (s, 2H); 13C NMR (75 MHz, CDCl3) d 144.52, 131.30, 130.64, 129.93, 129.59, 129.43, 127.70, 125.46, 125.37, 123.28, 122.72, 122.11, 46.39, 35.96; HRMS (FAB): calcd for C18H14ClN3 [M]+, m/z 307.0876, found m/z 307.0875. 1.4. Fluorescent sensor (5) To a solution of SAC 4 (0.14 g, 0.35 mmol) in acetonitrile were added compound 3 (2.5 equiv, 0.28 g), n-BuNI (1 equiv, 0.13 g), KI (5 equiv, 0.29 g), and K2CO3 (4.0 equiv, 0.19 g). After the solution stirred overnight under reflux, the mixture was concentrated, and then dissolved in CH2Cl2–H2O containing a drop of NaOH (1 M). The solution was extracted by CH2Cl2, filtered, concentrated,

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and purified by chromatography (EtOAc/MeOH 3:1) to give 5 (0.24 g, 73%) as a yellow solid. Mp 191 °C (decomp); Rf = 0.1 (EtOAc/MeOH 1:1); 1H NMR (300 MHz, CDCl3) d 8.40 (s, 2H), 8.25 (d, J = 8.7 Hz, 4H), 7.92 (d, J = 8.4 Hz, 3H), 7.55 (t, J = 8.7 Hz, 4H), 7.43 (t, J = 8.4 Hz, 4H), 7.03 (s, 2H), 6.47 (s, 4H), 4.03 (d, J = 8.7 Hz, 4H), 3.95 (dd, J = 6.3, 2.4 Hz, 2H), 3.66 (d, J = 13.2 Hz, 2H), 3.47-3.35 (m, 6H), 2.24–2.20 (m, 6H), 2.09–1.99 (m, 7H), 1.43 (s, 3H), 1.27 (s, 3H), 1.27 (s, 6H), 1.16 (s, 6H); 13C NMR (75 MHz,CDCl3) d 131.3, 130.7, 129.8, 129.4, 127.6, 125.3, 123.8, 123.0, 122.1, 112.9, 83.2, 81.7, 80.5, 76.6, 76.1, 55.2, 50.0, 48.7, 46.4, 26.3, 26.1, 24.9; HRMS (FAB): calcd for C56H61N8O6 [M+H]+, m/z 941.4714, found m/z 941.4730. Acknowledgment We thank the National Science Council of Taiwan for financial support. Supplementary data Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.carres.2009.08.027. References 1. Fuchs, E. F.; Lehmann, J. Carbohydr. Res. 1976, 49, 267–273. 2. Suhara, Y.; Hildreth, J. E. K.; Ichikawa, Y. Tetrahedron Lett. 1996, 37, 1575–1578. 3. Suhara, Y.; Ichikawa, M.; Hildreth, J. E. K.; Ichikawa, Y. Tetrahedron Lett. 1996, 37, 2549–2552. 4. Wessel, H. P.; Mitchell, C.; Lobato, C. M.; Schmid, G. Angew. Chem., Int. Ed. Engl. 1995, 34, 2712–2713. } ller, C.; Kitas, E.; Wessel, H. P. J. Chem. Soc., Chem. Commun. 1995, 23, 2425– 5. Mu 2426. 6. Szabo, L.; Smith, B. L.; McReynolds, K. D.; Parrill, A. L.; Morris, E. R.; Gervay, J. J. Org. Chem. 1998, 63, 1074–1078. 7. Locardi, E.; Stöckle, M.; Gruner, S.; Kessler, H. J. Am. Chem. Soc. 2001, 123, 8189– 8196. } diger, V. Chem. Rev. 1998, 98, 1755–1785. 8. Schneider, H.-J.; Hacket, F.; Ru 9. Rekharsky, M. V.; Inoue, Y. Chem. Rev. 1998, 98, 1875–1917. 10. Uekama, K.; Hirayama, F.; Irie, T. Chem. Rev. 1998, 98, 2045–2076. 11. Loftsson, T.; Brewster, M. E. J. Pharm. Sci. 1996, 85, 1017–1169. 12. Szejtli, J. Chem. Rev. 1998, 98, 1743–1753. 13. Ménand, M.; Blais, J. C.; Hamon, L.; Valéry, J. M.; Xie, J. J. Org. Chem. 2005, 70, 4423–4430. 14. Hsieh, Y. C.; Chir, J. L.; Zou, W.; Wu, A. T. Carbohydr. Res. 2009, 344, 1020–1023. 15. Xie, J.; Ménand, M.; Maisonneuve, S.; Métivier, R. J. Org. Chem. 2007, 72, 5980– 5985. 16. Akkaya, E. U.; Huston, M. E.; Czarnik, A. W. J. Am. Chem. Soc. 1990, 112, 3590– 3593. 17. Huston, M. E.; Engleman, C.; Czarnik, A. W. J. Am. Chem. Soc. 1990, 112, 7054– 7056. 18. Shiraishi, Y.; Tokitoh, Y.; Nishimura, G.; Hirai, T. Org. Lett. 2005, 7, 2611–2614. 19. Yoon, J.; Ohler, N. E.; Vance, D. H.; Aumiller, W. D.; Czarnik, A. W. Tetrahedron Lett. 1997, 38, 3845–3848. 20. Youn, N. J.; Chang, S.-K. Tetrahedron Lett. 2005, 46, 125–129. 21. Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int. Ed. 2001, 40, 2001– 2004. 22. Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. Angew. Chem., Int. Ed. 2002, 41, 2596–2599. 23. Calvet, S.; David, O.; Vanucci-Bacqué, C.; Fargeau-Bellasoued, M.-C.; Lohmmet, G. Tetrahedron 2003, 59, 6333–6339. 24. Ojida, A.; Mito-oka, Y.; Inoue, M.-A.; Hamachi, I. J. Am. Chem. Soc. 2002, 124, 6256–6258. 25. de Silva, A. P.; Gunaratne, H. Q. N.; Lynch, P. L. M. J. Chem. Soc., Perkin Trans. 2 1995, 685–690. 26. Choi, M.; Kim, M.; Lee, K. D.; Han, K.-N.; Yoon, I.-A.; Chung, H.-J.; Yoon, J. Org. Lett. 2001, 3, 3455–3457. 27. Connors, K. A. Binding Constants; Wiley: New York, 1987.