- Email: [email protected]
Development of a boron-dipyrromethene-Cu2+ ensemble based colorimetric probe toward hydrogen sulfide in aqueous media
Tetrahedron Letters 52 (2011) 5000–5003
Contents lists available at ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
Development of a boron-dipyrromethene-Cu2+ ensemble based colorimetric probe toward hydrogen sulfide in aqueous media Xianfeng Gu a,b, Chunhua Liu a, Yi-Chun Zhu c,⇑, Yi-Zhun Zhu a,⇑ a
School of Pharmacy, Fudan University, Shanghai 201203, China State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China c Department of Physiology and Pathophysiology, Shanghai College of Medicine, Fudan University, Shanghai 200021, China b
a r t i c l e
i n f o
Article history: Received 11 May 2011 Revised 22 June 2011 Accepted 1 July 2011 Available online 13 July 2011 Keywords: Boron-dipyrromethene Colorimetric probe Hydrogen sulfide Gasotransmitter Biological sensor
a b s t r a c t A boron-dipyrromethene-Cu2+ ensemble based colorimetric probe for detection of hydrogen sulfide in aqueous media is reported. Complex 1–Cu(II) is able to selectively sense hydrogen sulfide over other anions and thiols followed by the release of compound 1 to give a remarkable change of UV absorption in aqueous solution (HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid) buffer, 50 mM, pH 7.4, 5% DMSO). Ó 2011 Published by Elsevier Ltd.
Hydrogen sulfide (H2S), once considered solely as a toxic gas, is now recognized as an important biological mediator. In 1996, Abe and Kimura first published their results about the role of hydrogen sulfide in human neuromodulation, which had become a research prelude on the biological signaling function of hydrogen sulfide.1 Since then, research has unfolded on all aspects of the biological functions of hydrogen sulfide, such as cardioprotective,2 neuroprotective,3 and gastroprotective effects,4 the regulation of insulin release5 and anti-inflammatory effects,6 which make it known that hydrogen sulfide also plays an important, probably even pivotal, role in human and biological systems. As research progressed, hydrogen sulfide has been identified as the third gasotransmitter together with nitric oxide (NO) and carbon monoxide (CO). All of them (NO, CO, and H2S) exert a series of biological effects on various biological targets, resulting in either cytotoxic or cytoprotective responses. However, many details on how these gasotransmitters perform their biological roles are still unknown. So the development of water-soluble, bio-compatible and selective probes capable of detecting these gasotransmitters has become a topical objective for chemists and biologists. Sensors for detecting gaseous hydrogen sulfide have been reported, but with poor selectivity over other related anions and sulfur derivatives.7 In fact, hydrogen sulfide in the biosystem usually exists in physiological fluids. However, only a few sensors reported ⇑ Corresponding authors. E-mail addresses: [email protected] (X. Gu), [email protected] (Y.-Z. Zhu). 0040-4039/$ - see front matter Ó 2011 Published by Elsevier Ltd. doi:10.1016/j.tetlet.2011.07.004
so far were able to detect hydrogen sulfide in aqueous media.8 As is well known, hydrogen sulfide, in aqueous media, is essentially present under both its protonated H2S and deprotonated HS forms, (in water, pKa = 6.76 at 37 °C). Therefore, the detection of hydrogen sulfide in aqueous system could be achieved by sensing anion of HS. It is well known that coordination chemistry is widely applied in cation detecting.9 In recent years, the complex of dye and metal(s) has also been designed for sensing anions, as the metal(s) coordinated could strongly interact with anionic analytes to attain recognizing purpose.10 Recently, it was reported that copper complex sensitively senses thiols, such as cysteine and glutatione, over other amino acids in aqueous media.11 Based on these results, we designed a boron-dipyrromethene-Cu2+ ensemble based colorimetric sensor for detecting hydrogen sulfide in aqueous media (Fig. 1). It is known that quinoline and 2,20 -dipicolylamine are widely applied in copper recognition.9,12 Therefore we incorporated these two moieties to boron-dipyrromethene (Bodipy) dye, and expected that it could form a Bodipy-Cu2+ ensemble based sensor to recognize hydrogen sulfide in aqueous solution. As expected, compound 113 can form a 1:1 complex with Cu2+ in HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid) buffer (50 mM, pH 7.4, containing 5% DMSO), identified by UV–vis and mass spectra. The optical features of compound 1 are characteristics of the Bodipy platform. The main absorption band of compound 1, attributed to the 0–0 vibrational band of a strong S0–S1 transition, is centered at 569 nm in HEPES buffer. Upon gradual addition of copper chloride to a solution of 1 in HEPES buffer, a
X. Gu et al. / Tetrahedron Letters 52 (2011) 5000–5003
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Figure 1. The chemical structure of 1 and 1–Cu2+ ensemble.
decrease in the absorption band at 569 nm and a concomitant increase of a new band at 520 nm was observed, with a distinct isosbestic point at 528 nm, which is consistent with the presence of only two species, free ligand, and Cu2+–ligand complex. Concomitantly, the color of the solution turned from pink to orange. The intensity of absorption at 520 nm reaches the maximum value when 1.0 equiv of Cu2+ was added. The titration profile shows that the absorption at 569 nm descends almost linearly until a ligandto-metal ratio of 1:1 is reached (Fig. 2). Further addition of Cu2+ does not affect the absorption spectrum, suggesting a 1:1 stoichiometry for the Cu2+ complex. The binding constant was determined to be 0.5 105 using Benesi–Hildebrand plots (Fig. 3). The 1:1 binding model of Cu2+ and 1 can be further confirmed by mass spectra. The ESI mass spectrum of complex 1–Cu(II) has a major peak with m/z of 739.3 ([1–Cu(II)]+), which corresponds to 1:1 complex (Fig. S1). Based on the results of titration experiments and mass spectrum of 1–Cu2+ complex, the boron-dipyrromethene-Cu2+ ensemble based sensor was prepared by mixing equal equivalents of compound 1 and copper chloride in the solution of HEPES buffer (50 mM, pH 7.4, containing 5% DMSO). To sense hydrogen sulfide in aqueous system, hydrogen sulfide solution was prepared according to the literature method8 (dissolving NaHS in HEPES buffer solution (50 mM, pH 7.4)). The characteristic absorption of 1– Cu2+ complex, attributed to the 0–0 vibrational band of a strong S0–S1 transition, is centered at 520 nm in HEPES buffer (50 mM, pH 7.4, containing 5% DMSO). Gradual addition of hydrogen sulfide to a solution of 1–Cu2+ in HEPES buffer, a decrease in the absorption band at 520 nm and a concomitant increase of a new band
Figure 2. The absorption spectra of compound 1 (5 106 M) in the presence of different concentrations of copper chloride (0, 0.1, 0.2, 0.4, 0.6, 0.8, 1.0, 1.2, 1.4 equiv) in HEPES buffer (50 mM, pH 7.4, containing 5% DMSO). Inset is the titration profile according to the absorbance at 569 nm.
Figure 3. Benesi–Hildebrand plot of 1 (5 lM in HEPES buffer, 50 mM, pH 7.4, containing 5% DMSO, 569 nm) in the presence of Cu2+ for 1:1 stoichiometry between 1 and Cu2+.
at 569 nm were observed, with a distinct isosbestic point at 535 nm. Concomitantly, the color of the solution turned from orange to pink. Notably, upon addition of hydrogen sulfide, a pronounced enhancement at 569 nm was noted even after 10 s, indicative of a fast reaction of 1–Cu2+ with HS ( Fig. S3). The absorption band at 569 nm is the characteristic absorption of compound 1 which is red-shifted by 50 nm compared to that of complex of 1–Cu2+. The intensity of absorption at 569 nm reaches maximum value when 2.0 equiv of hydrogen sulfide solution was added. As shown in Figure S4, a linear relationship is observed between the absorbance change and HS amount at lower concentration than 6 lM. The detection limit for HS was determined as 1.67 107 M under the experimental conditions. Moreover, the change in absorption profile was quite large. The ratio of the absorbance at 520 and 569 nm showed sigmoid dependence on the NaHS concentration, with a 34-fold ratiometric enhancement (Fig. 4). This indicates the capability of 1–Cu2+ ensemble for detecting HS by absorption colorimetry and ratiometry. The UV–vis spectra of 1–Cu2+ + NaHS system, obtained by interaction of 1–Cu2+ with 3 equiv of NaHS, are characteristics of compound 1. Therefore, the sensing mechanism can be proposed that HS selectively interacted with copper metal in 1–Cu2+ ensemble to release compound 1. Mass analysis was further performed to confirm the production of 1 in the reaction. The ESI mass spectrum of 1–Cu2+ + NaHS system gave peaks of [M+H]+ at m/z = 678.4 and [M+Na]+ at 700.3, respectively, identical to that of compound 1 (Fig. S2). The selectivity of boron-dipyrromethene-Cu2+ ensemble-based sensor toward hydrogen sulfide over relevant anions has also been evaluated by measuring the changes in the UV–vis spectra upon addition of excess amount of various anions. The unique absorption change with appearance of the characteristic absorption of compound 1 was observed only by the addition of hydrogen sulfide solution, which can be ascribed to release of compound 1 in the reaction. On the other hand, no dramatic change in the UV spectra was observed for the addition of other anions such as F, Cl, Br, I , SO4 2 , SO3 2 , NO3 , HCO3 , H2 PO4 , N3 , NO2 , SCN and CN (Fig. 5a). Likewise, 1–Cu2+ turned from orange to pink upon HS addition in HEPES buffer (50 mM pH 7.4, containing 5% DMSO) but other anions did not induce color changes (Fig. 5b). These results indicate the excellent selectivity of boron-dipyrrometheneCu2+ ensemble based sensor toward hydrogen sulfide over the other competitive anions.
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Figure 4. (a) The absorption spectra of 1–Cu2+ complex (5 106 M) in the presence of different concentrations of NaHS (0, 0.4, 0.8, 1.2, 1.6, 2.0, 2.4, 3.0 equiv) in HEPES buffer (50 mM pH 7.4, containing 5% DMSO). (b) Ratio of absorbance at 569 nm and absorbance at 520 nm as a function of Cu2+ concentration. Inset: Color of solutions of 1–Cu2+ in the absence and presence of NaHS.
The selectivity of boron-dipyrromethene-Cu2+ ensemble-based sensor toward hydrogen sulfide against other thiols like cysteine and glutathione (GSH) has also been evaluated by measuring the changes in the UV–vis spectra upon addition of excess amount of various thiols. The unique absorption change with the appearance of the characteristic absorption of compound 1 was observed only by the addition of hydrogen sulfide solution. Whereas, slight change in the UV spectra was observed for the addition of cysteine, and no dramatic change in the UV spectra was observed for the addition of GSH (Fig. S5). These results indicate the excellent selectivity of boron-dipyrromethene-Cu2+ ensemble based sensor toward hydrogen sulfide against other thiols. In summary, we have developed a novel boron-dipyrrometheneCu2+ ensemble based sensor for detecting hydrogen sulfide in aqueous media. It displays a 50 nm red-shift of the absorption and a dramatic color change from orange to pink upon addition of hydrogen sulfide solution. Moreover, the change in absorption profile was quite large. The ratio of the absorbance at 569 and 520 nm showed a 34-fold ratiometric enhancement. This indicates the capability of 1–Cu2+ ensemble for detecting HS by absorption colorimetry and ratiometry. In addition, boron-dipyrromethene-Cu2+ ensemble
Figure 5. (a) Comparison of UV absorption spectra of 1–Cu2+ in HEPES buffer (50 mM pH 7.4, containing 5% DMSO) after the addition of 10 equiv of various anions (a: F, b: Cl, c: Br, d: I, e: SO4 2 , f: NO3 , g: NO2 , h: N3 , i: AcO, j: HCO3 , k: SO3 2 , l: H2 PO4 , m: HS, n: SCN, o: CN). (b) Color change of 1–Cu2+ in HEPES buffer (50 mM pH 7.4, containing 5% DMSO) after the addition of 10 equiv of various anions (a: F, b: Cl, c: Br, d: I, e: SO4 2 , f: NO3 , g: NO2 , h: N3 , i: AcO, j: HCO3 , k: SO3 2 , l: H2 PO4 , m: HS, n: SCN, o: CN).
based sensor showed excellent selectivity toward hydrogen sulfide over the other competitive anions and thiols. Acknowledgments We gratefully acknowledge Yulin Zhang for providing us dyes generously, and the financial support by the National Science
X. Gu et al. / Tetrahedron Letters 52 (2011) 5000–5003
Foundation of China (No. 21002013), New Teacher Foundation from Ministry of Education in China (No. 20090071120), Foundation of State Key Laboratory of Natural and Biomimetic Drugs (K20100106), National Basic Research Program of China (973 Program) (No. 2010CB912600), STCSM (No. 10431903200). Supplementary data Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.tetlet.2011.07.004. References and notes 1. Abe, K.; Kimura, H. J. Neurosci. 1996, 16, 1066–1071. 2. (a) Lefer, D. J. Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 17907–17908; (b) Wang, Q.; Liu, H. R.; Mu, Q.; Rose, P.; Zhu, Y. Z. J. Cardiovasc. Pharmacol. 2009, 54, 139–146; (c) Wang, Q.; Wang, X. L.; Liu, H. R.; Rose, P.; Zhu, Y. Z. Antioxid. Redox. Signal 2010, 12, 1155–1165; (d) Wang, X.; Wang, Q.; Guo, W.; Zhu, Y. Z. Biosci. Rep. 2010.; (e) Yang, G.; Wu, L.; Bryan, S.; Khaper, N.; Mani, S.; Wang, R. Cardiovasc. Res. 2010, 86, 487–495; (f) Yang, G.; Wu, L.; Jiang, B.; Yang, W.; Qi, J.; Cao, K.; Meng, Q.; Mustafa, A. K.; Mu, W.; Zhang, S.; Snyder, S. H.; Wang, R. Science 2008, 322, 587–590. 3. (a) Gong, Q. H.; Pan, L. L.; Liu, X. H.; Wang, Q.; Huang, H.; Zhu, Y. Z. Amino Acids 2010.; (b) Gong, Q. H.; Wang, Q.; Pan, L. L.; Liu, X. H.; Huang, H.; Zhu, Y. Z. Pharmacol. Biochem. Behav. 2010, 96, 52–58; (c) Gong, Q. H.; Wang, Q.; Pan, L. L.; Liu, X. H.; Xin, H.; Zhu, Y. Z. Brain. Behav. Immun. 2010.; (d) Hu, L. F.; Lu, M.; Tiong, C. X.; Dawe, G. S.; Hu, G.; Bian, J. S. Aging Cell 2010, 9, 135–146; (e) Kimura, H.; Nagai, Y.; Umemura, K.; Kimura, Y. Antioxid. Redox. Signal 2005, 7, 795–803; (f) Lee, M.; Schwab, C.; Yu, S.; McGeer, E.; McGeer, P. L. Neurobiol. Aging 2009, 30, 1523–1534.
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4. Medeiros, J. V.; Bezerra, V. H.; Gomes, A. S.; Barbosa, A. L.; Lima-Junior, R. C.; Soares, P. M.; Brito, G. A.; Ribeiro, R. A.; Cunha, F. Q.; Souza, M. H. J. Pharmacol. Exp. Ther. 2009, 330, 764–770. 5. Wu, L.; Yang, W.; Jia, X.; Yang, G.; Duridanova, D.; Cao, K.; Wang, R. Lab. Invest. 2009, 89, 59–67. 6. Sivarajah, A.; Collino, M.; Yasin, M.; Benetti, E.; Gallicchio, M.; Mazzon, E.; Cuzzocrea, S.; Fantozzi, R.; Thiemermann, C. Shock 2009, 31, 267–274. 7. Cardoso, A. A.; Liu, H.; Dasgupta, P. K. Talanta 1997, 44, 1099–1106. 8. Galardon, E.; Tomas, A.; Roussel, P.; Artaud, I. Dalton T 2009, 42, 9126–9130. 9. Ballesteros, E.; Moreno, D.; Gomez, T.; Rodriguez, T.; Rojo, J.; Garcia-Valverde, M.; Torroba, T. Org. Lett. 2009, 11, 1269–1272. 10. (a) Guo, Z. Q.; Zhu, W. H.; Tian, H. Macromolecules 2010, 43, 739–744; (b) Kim, S. K.; Lee, D. H.; Hong, J. I.; Yoon, J. Accounts Chem. Res. 2009, 42, 23–31; (c) Lou, X. D.; Zhang, Y.; Li, Q. Q.; Qin, J. G.; Li, Z. Chem. Commun. 2011, 47, 3189–3191; (d) Martinez-Manez, R.; Sancenon, F. Chem. Rev. 2003, 103, 4419–4476; (e) Moragues, M. E.; Martinez-Manez, R.; Sancenon, F. Chem. Soc. Rev. 2011, 40, 2593–2643. 11. (a) Jung, H. S.; Han, J. H.; Habata, Y.; Kang, C.; Kim, J. S. Chem. Commun. 2011, 47, 5142–5144; (b) Zhao, C. C.; Zhou, Y.; Lin, Q. N.; Zhu, L. Y.; Feng, P.; Zhang, Y. L.; Cao, J. A. J. Phys. Chem. B 2011, 115(4), 642–647. 12. (a) Lim, M. H.; Wong, B. A.; Pitcock, W. H.; Mokshagundam, D.; Baik, M. H.; Lippard, S. J. J. Am. Chem. Soc. 2006, 128, 14364–14373; (b) Lim, M. H.; Xu, D.; Lippard, S. J. Nat. Chem. Biol 2006, 2, 375–380. 13. Characterization of compound 1. 1H NMR (400 MHz, CDCl3) d 8.65–8.62 (d, 1H), 8.49 (d, 2H), 8.06–8.02 (m, 1H), 7.70 (s, 1H), 7.68 (s, 1H), 7.64–7.58 (m, 2H), 7.41–7.27 (m, 7H), 7.10 (t, 2H), 7.04 (d, 1H), 6.53 (d, 1H), 6.39 (s, 1H), 4.85 (s, 4H), 4.14 (s, 2H), 2.62 (s, 3H), 2.36 (q, 2H), 1.38 (s, 3H), 1.01 (t, 3H); 13C NMR(100 MHz, CDCl3) d 159.1, 158.5, 154.0, 149.1, 146.7, 144.5, 138.2, 137.9, 137.1, 136.7, 135.9, 134.7, 133.2, 131.4, 130.6, 130.4, 129.4, 128.7, 128.5, 128.10, 127.7, 124.3, 122.9, 122.1, 121.2, 114.3, 105.7, 58.6, 41.0, 17.2, 14.6, 12.8, 11.8; HRMS (ESI) calcd for C41H39N7BF2: 678.3328. Found: 678.3338 [M+H]+.
Contents lists available at ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
Development of a boron-dipyrromethene-Cu2+ ensemble based colorimetric probe toward hydrogen sulfide in aqueous media Xianfeng Gu a,b, Chunhua Liu a, Yi-Chun Zhu c,⇑, Yi-Zhun Zhu a,⇑ a
School of Pharmacy, Fudan University, Shanghai 201203, China State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China c Department of Physiology and Pathophysiology, Shanghai College of Medicine, Fudan University, Shanghai 200021, China b
a r t i c l e
i n f o
Article history: Received 11 May 2011 Revised 22 June 2011 Accepted 1 July 2011 Available online 13 July 2011 Keywords: Boron-dipyrromethene Colorimetric probe Hydrogen sulfide Gasotransmitter Biological sensor
a b s t r a c t A boron-dipyrromethene-Cu2+ ensemble based colorimetric probe for detection of hydrogen sulfide in aqueous media is reported. Complex 1–Cu(II) is able to selectively sense hydrogen sulfide over other anions and thiols followed by the release of compound 1 to give a remarkable change of UV absorption in aqueous solution (HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid) buffer, 50 mM, pH 7.4, 5% DMSO). Ó 2011 Published by Elsevier Ltd.
Hydrogen sulfide (H2S), once considered solely as a toxic gas, is now recognized as an important biological mediator. In 1996, Abe and Kimura first published their results about the role of hydrogen sulfide in human neuromodulation, which had become a research prelude on the biological signaling function of hydrogen sulfide.1 Since then, research has unfolded on all aspects of the biological functions of hydrogen sulfide, such as cardioprotective,2 neuroprotective,3 and gastroprotective effects,4 the regulation of insulin release5 and anti-inflammatory effects,6 which make it known that hydrogen sulfide also plays an important, probably even pivotal, role in human and biological systems. As research progressed, hydrogen sulfide has been identified as the third gasotransmitter together with nitric oxide (NO) and carbon monoxide (CO). All of them (NO, CO, and H2S) exert a series of biological effects on various biological targets, resulting in either cytotoxic or cytoprotective responses. However, many details on how these gasotransmitters perform their biological roles are still unknown. So the development of water-soluble, bio-compatible and selective probes capable of detecting these gasotransmitters has become a topical objective for chemists and biologists. Sensors for detecting gaseous hydrogen sulfide have been reported, but with poor selectivity over other related anions and sulfur derivatives.7 In fact, hydrogen sulfide in the biosystem usually exists in physiological fluids. However, only a few sensors reported ⇑ Corresponding authors. E-mail addresses: [email protected] (X. Gu), [email protected] (Y.-Z. Zhu). 0040-4039/$ - see front matter Ó 2011 Published by Elsevier Ltd. doi:10.1016/j.tetlet.2011.07.004
so far were able to detect hydrogen sulfide in aqueous media.8 As is well known, hydrogen sulfide, in aqueous media, is essentially present under both its protonated H2S and deprotonated HS forms, (in water, pKa = 6.76 at 37 °C). Therefore, the detection of hydrogen sulfide in aqueous system could be achieved by sensing anion of HS. It is well known that coordination chemistry is widely applied in cation detecting.9 In recent years, the complex of dye and metal(s) has also been designed for sensing anions, as the metal(s) coordinated could strongly interact with anionic analytes to attain recognizing purpose.10 Recently, it was reported that copper complex sensitively senses thiols, such as cysteine and glutatione, over other amino acids in aqueous media.11 Based on these results, we designed a boron-dipyrromethene-Cu2+ ensemble based colorimetric sensor for detecting hydrogen sulfide in aqueous media (Fig. 1). It is known that quinoline and 2,20 -dipicolylamine are widely applied in copper recognition.9,12 Therefore we incorporated these two moieties to boron-dipyrromethene (Bodipy) dye, and expected that it could form a Bodipy-Cu2+ ensemble based sensor to recognize hydrogen sulfide in aqueous solution. As expected, compound 113 can form a 1:1 complex with Cu2+ in HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid) buffer (50 mM, pH 7.4, containing 5% DMSO), identified by UV–vis and mass spectra. The optical features of compound 1 are characteristics of the Bodipy platform. The main absorption band of compound 1, attributed to the 0–0 vibrational band of a strong S0–S1 transition, is centered at 569 nm in HEPES buffer. Upon gradual addition of copper chloride to a solution of 1 in HEPES buffer, a
X. Gu et al. / Tetrahedron Letters 52 (2011) 5000–5003
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Figure 1. The chemical structure of 1 and 1–Cu2+ ensemble.
decrease in the absorption band at 569 nm and a concomitant increase of a new band at 520 nm was observed, with a distinct isosbestic point at 528 nm, which is consistent with the presence of only two species, free ligand, and Cu2+–ligand complex. Concomitantly, the color of the solution turned from pink to orange. The intensity of absorption at 520 nm reaches the maximum value when 1.0 equiv of Cu2+ was added. The titration profile shows that the absorption at 569 nm descends almost linearly until a ligandto-metal ratio of 1:1 is reached (Fig. 2). Further addition of Cu2+ does not affect the absorption spectrum, suggesting a 1:1 stoichiometry for the Cu2+ complex. The binding constant was determined to be 0.5 105 using Benesi–Hildebrand plots (Fig. 3). The 1:1 binding model of Cu2+ and 1 can be further confirmed by mass spectra. The ESI mass spectrum of complex 1–Cu(II) has a major peak with m/z of 739.3 ([1–Cu(II)]+), which corresponds to 1:1 complex (Fig. S1). Based on the results of titration experiments and mass spectrum of 1–Cu2+ complex, the boron-dipyrromethene-Cu2+ ensemble based sensor was prepared by mixing equal equivalents of compound 1 and copper chloride in the solution of HEPES buffer (50 mM, pH 7.4, containing 5% DMSO). To sense hydrogen sulfide in aqueous system, hydrogen sulfide solution was prepared according to the literature method8 (dissolving NaHS in HEPES buffer solution (50 mM, pH 7.4)). The characteristic absorption of 1– Cu2+ complex, attributed to the 0–0 vibrational band of a strong S0–S1 transition, is centered at 520 nm in HEPES buffer (50 mM, pH 7.4, containing 5% DMSO). Gradual addition of hydrogen sulfide to a solution of 1–Cu2+ in HEPES buffer, a decrease in the absorption band at 520 nm and a concomitant increase of a new band
Figure 2. The absorption spectra of compound 1 (5 106 M) in the presence of different concentrations of copper chloride (0, 0.1, 0.2, 0.4, 0.6, 0.8, 1.0, 1.2, 1.4 equiv) in HEPES buffer (50 mM, pH 7.4, containing 5% DMSO). Inset is the titration profile according to the absorbance at 569 nm.
Figure 3. Benesi–Hildebrand plot of 1 (5 lM in HEPES buffer, 50 mM, pH 7.4, containing 5% DMSO, 569 nm) in the presence of Cu2+ for 1:1 stoichiometry between 1 and Cu2+.
at 569 nm were observed, with a distinct isosbestic point at 535 nm. Concomitantly, the color of the solution turned from orange to pink. Notably, upon addition of hydrogen sulfide, a pronounced enhancement at 569 nm was noted even after 10 s, indicative of a fast reaction of 1–Cu2+ with HS ( Fig. S3). The absorption band at 569 nm is the characteristic absorption of compound 1 which is red-shifted by 50 nm compared to that of complex of 1–Cu2+. The intensity of absorption at 569 nm reaches maximum value when 2.0 equiv of hydrogen sulfide solution was added. As shown in Figure S4, a linear relationship is observed between the absorbance change and HS amount at lower concentration than 6 lM. The detection limit for HS was determined as 1.67 107 M under the experimental conditions. Moreover, the change in absorption profile was quite large. The ratio of the absorbance at 520 and 569 nm showed sigmoid dependence on the NaHS concentration, with a 34-fold ratiometric enhancement (Fig. 4). This indicates the capability of 1–Cu2+ ensemble for detecting HS by absorption colorimetry and ratiometry. The UV–vis spectra of 1–Cu2+ + NaHS system, obtained by interaction of 1–Cu2+ with 3 equiv of NaHS, are characteristics of compound 1. Therefore, the sensing mechanism can be proposed that HS selectively interacted with copper metal in 1–Cu2+ ensemble to release compound 1. Mass analysis was further performed to confirm the production of 1 in the reaction. The ESI mass spectrum of 1–Cu2+ + NaHS system gave peaks of [M+H]+ at m/z = 678.4 and [M+Na]+ at 700.3, respectively, identical to that of compound 1 (Fig. S2). The selectivity of boron-dipyrromethene-Cu2+ ensemble-based sensor toward hydrogen sulfide over relevant anions has also been evaluated by measuring the changes in the UV–vis spectra upon addition of excess amount of various anions. The unique absorption change with appearance of the characteristic absorption of compound 1 was observed only by the addition of hydrogen sulfide solution, which can be ascribed to release of compound 1 in the reaction. On the other hand, no dramatic change in the UV spectra was observed for the addition of other anions such as F, Cl, Br, I , SO4 2 , SO3 2 , NO3 , HCO3 , H2 PO4 , N3 , NO2 , SCN and CN (Fig. 5a). Likewise, 1–Cu2+ turned from orange to pink upon HS addition in HEPES buffer (50 mM pH 7.4, containing 5% DMSO) but other anions did not induce color changes (Fig. 5b). These results indicate the excellent selectivity of boron-dipyrrometheneCu2+ ensemble based sensor toward hydrogen sulfide over the other competitive anions.
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Figure 4. (a) The absorption spectra of 1–Cu2+ complex (5 106 M) in the presence of different concentrations of NaHS (0, 0.4, 0.8, 1.2, 1.6, 2.0, 2.4, 3.0 equiv) in HEPES buffer (50 mM pH 7.4, containing 5% DMSO). (b) Ratio of absorbance at 569 nm and absorbance at 520 nm as a function of Cu2+ concentration. Inset: Color of solutions of 1–Cu2+ in the absence and presence of NaHS.
The selectivity of boron-dipyrromethene-Cu2+ ensemble-based sensor toward hydrogen sulfide against other thiols like cysteine and glutathione (GSH) has also been evaluated by measuring the changes in the UV–vis spectra upon addition of excess amount of various thiols. The unique absorption change with the appearance of the characteristic absorption of compound 1 was observed only by the addition of hydrogen sulfide solution. Whereas, slight change in the UV spectra was observed for the addition of cysteine, and no dramatic change in the UV spectra was observed for the addition of GSH (Fig. S5). These results indicate the excellent selectivity of boron-dipyrromethene-Cu2+ ensemble based sensor toward hydrogen sulfide against other thiols. In summary, we have developed a novel boron-dipyrrometheneCu2+ ensemble based sensor for detecting hydrogen sulfide in aqueous media. It displays a 50 nm red-shift of the absorption and a dramatic color change from orange to pink upon addition of hydrogen sulfide solution. Moreover, the change in absorption profile was quite large. The ratio of the absorbance at 569 and 520 nm showed a 34-fold ratiometric enhancement. This indicates the capability of 1–Cu2+ ensemble for detecting HS by absorption colorimetry and ratiometry. In addition, boron-dipyrromethene-Cu2+ ensemble
Figure 5. (a) Comparison of UV absorption spectra of 1–Cu2+ in HEPES buffer (50 mM pH 7.4, containing 5% DMSO) after the addition of 10 equiv of various anions (a: F, b: Cl, c: Br, d: I, e: SO4 2 , f: NO3 , g: NO2 , h: N3 , i: AcO, j: HCO3 , k: SO3 2 , l: H2 PO4 , m: HS, n: SCN, o: CN). (b) Color change of 1–Cu2+ in HEPES buffer (50 mM pH 7.4, containing 5% DMSO) after the addition of 10 equiv of various anions (a: F, b: Cl, c: Br, d: I, e: SO4 2 , f: NO3 , g: NO2 , h: N3 , i: AcO, j: HCO3 , k: SO3 2 , l: H2 PO4 , m: HS, n: SCN, o: CN).
based sensor showed excellent selectivity toward hydrogen sulfide over the other competitive anions and thiols. Acknowledgments We gratefully acknowledge Yulin Zhang for providing us dyes generously, and the financial support by the National Science
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Foundation of China (No. 21002013), New Teacher Foundation from Ministry of Education in China (No. 20090071120), Foundation of State Key Laboratory of Natural and Biomimetic Drugs (K20100106), National Basic Research Program of China (973 Program) (No. 2010CB912600), STCSM (No. 10431903200). Supplementary data Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.tetlet.2011.07.004. References and notes 1. Abe, K.; Kimura, H. J. Neurosci. 1996, 16, 1066–1071. 2. (a) Lefer, D. J. Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 17907–17908; (b) Wang, Q.; Liu, H. R.; Mu, Q.; Rose, P.; Zhu, Y. Z. J. Cardiovasc. Pharmacol. 2009, 54, 139–146; (c) Wang, Q.; Wang, X. L.; Liu, H. R.; Rose, P.; Zhu, Y. Z. Antioxid. Redox. Signal 2010, 12, 1155–1165; (d) Wang, X.; Wang, Q.; Guo, W.; Zhu, Y. Z. Biosci. Rep. 2010.; (e) Yang, G.; Wu, L.; Bryan, S.; Khaper, N.; Mani, S.; Wang, R. Cardiovasc. Res. 2010, 86, 487–495; (f) Yang, G.; Wu, L.; Jiang, B.; Yang, W.; Qi, J.; Cao, K.; Meng, Q.; Mustafa, A. K.; Mu, W.; Zhang, S.; Snyder, S. H.; Wang, R. Science 2008, 322, 587–590. 3. (a) Gong, Q. H.; Pan, L. L.; Liu, X. H.; Wang, Q.; Huang, H.; Zhu, Y. Z. Amino Acids 2010.; (b) Gong, Q. H.; Wang, Q.; Pan, L. L.; Liu, X. H.; Huang, H.; Zhu, Y. Z. Pharmacol. Biochem. Behav. 2010, 96, 52–58; (c) Gong, Q. H.; Wang, Q.; Pan, L. L.; Liu, X. H.; Xin, H.; Zhu, Y. Z. Brain. Behav. Immun. 2010.; (d) Hu, L. F.; Lu, M.; Tiong, C. X.; Dawe, G. S.; Hu, G.; Bian, J. S. Aging Cell 2010, 9, 135–146; (e) Kimura, H.; Nagai, Y.; Umemura, K.; Kimura, Y. Antioxid. Redox. Signal 2005, 7, 795–803; (f) Lee, M.; Schwab, C.; Yu, S.; McGeer, E.; McGeer, P. L. Neurobiol. Aging 2009, 30, 1523–1534.
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