A novel triple-mode fluorescent pH probe from monomer emission to aggregation-induced emission

Abstract

A tetraphenylethylene (TPE)-based pH fluorescent probe was synthesised, which could selectively monitor pH variation in THF–H₂O (2 : 8, v/v) solution in wide-range pH (1.99–11.64) values. It displayed a monomer emission under acidic condition, but exhibited ratiometric fluorescence under neutral condition and aggregation-induced emission (AIE) under basic condition subsequently.

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The measurement of pH plays an important role in variety of systems, especially in living organisms such as cell growth, cell adhesion, chemo taxis and ionic transition.^1,2 Many methods for detecting pH value have been applied to date, for instance, potentiometric,³ nuclear magnetic resonance (NMR),⁴ absorbance spectroscopy and acid–base indicator titration. Among the fluorophores developed, the utilization of fluorescent probe to detect pH attracts increasing attention due to its excellent properties compared to the traditional measurements such as better sensitivity and selectivity, noninvasiveness and high signal-to-noise ratio.^5,6 Fluorescence-based techniques, such as BODIPY,⁷ chromenoquinoline,⁸ rhodamine,^6,9 transition metal complex¹⁰ fluorescein,¹¹ naphthalimide¹² and quantum dots,¹³ are becoming more and more popular for the measurement of intracellular pH and cell imaging.^2,14 Moreover, sol–gel¹⁵ and nanoparticles¹⁶ based pH probes have also been developed.

By contrast to those fluorescent probes with absolute intensity at only one peak, the fluorescence intensity at two wavelengths (ratiometric fluorescent probes)¹⁷ and calculation of their ratio gives more inspiration for the design of pH probes. Normal organic dyes experience small stokes shifts, which may lead to self-quenching and the excitation backscattering effects may cause detection errors. Because of these disadvantages, the designing of ratiometric fluorescent probes are utilized to reduce these bad influences of such factors.¹⁸

Most traditional fluorophores are usually constructed based on aromatic molecular motifs, which may experience strong molecular interaction in concentrated solutions and solid aggregates, resulting in a decrease in fluorescence intensity. In order to avoid the aggregation-caused quenching (ACQ) effect in practical applications, aggregation-induced emission (AIE) based system was reported by Tang and co-workers in 2001.¹⁹ AIE effect is a general property that is caused by the restriction of intramolecular rotation (RIR) in the aggregates. The development of fluorescent probes, solid-state emitters and other functional materials based on AIE effect has encouraged many researchers these years.²⁰ With an excellent AIE effect, tetraphenylethylene (TPE)-based fluorescent probes have been widely designed and synthesized.^21,22 Moreover, most of the fluorescent probes for pH detection were based on the mechanism of protonation and deprotonation of molecules. The working principle of AIE-based pH sensing process is the dissolution (disaggregation) and aggregation of an AIE luminogen in different pH environments.^22,23 Inspired by this mechanism, fluorescent pH probes based on AIEE can be readily designed. AIE systems with monomer emission are widely available. As reported, bridged TPE units with phenyl rings locked display monomer emission in both solution and crystalline states as a result of the RIR mechanism.²⁴ With the change in the degree of polarity of solvent, molecules consisted by hydrophilic and hydrophobic moieties also exhibit monomer emission and AIE at the same time.²⁵ Recently, Zheng et al. reported that the TPE derivatives with hydrophilic and flexible chains around the TPE core or bridged TPE structure reduce its hydrophobic force as it can make the compound more compatible with water and restrict the rotation of the phenyl rings to display the enhancement of monomer emission and the decrease of aggregate-induced due to the encapsulation in the cavity of γ-cyclodextrin or the bridged TPE unit.²⁶

Herein, we report a new amphiphilic molecule fluorescent probe 1 constructed on TPE, which acts as a hydrophobic moiety, linked with two potential hydrophilic moieties containing secondary amines for wide-range pH detection. Probe 1 showed triple-mode fluorescent responses from monomer emission to aggregation-induced emission over the pH range 1.99 to 11.64 in THF–H₂O (2 : 8, v/v) solution based on the solvation and AIEE mechanisms. The selectivity experiment over metal cations showed that the TPE-based pH probe exhibited high selectivity under complex conditions.

The target probe molecule 1 and intermediary compound 3 were synthesized in a facile route as shown in Scheme 1. Compound 3 was reduced from 2^21a under reflux in methanol with the presence of triphenylphosphine (PPh₃). Compound 1 was obtained from 3 and p-ethoxybenzaldehyde in toluene under reflux, and then reduced by sodium borohydride (NaBH₄) at room temperature in THF–methanol. The chemical structures of the new compounds were fully characterized by ¹H NMR, ¹³C NMR, FTIR and MS.

Scheme 1 Synthesis of probe 1.

Probe 1, as a potential AIE-active compound, was soluble in some common organic solvents, such as chloroform, acetonitrile, tetrahydrofuran (THF), and N,N-dimethylformamide (DMF), but was insoluble in water. Herein, the AIE behavior of probe 1 was investigated in aqueous THF solution (10 μM) with different THF–water ratios. As shown in Fig. 1, when the water fraction in dilute THF solution was increased from 0% to 80%, probe 1 indeed behaved as a weak fluorescence emitter, only with the monomer emission at 377 nm. Moreover, the fluorescence intensity increased as the water fraction ratio increased. When it is molecularly dissolved in a good solvent almost there was no fluorescence as expected. As the water fraction increased to 1 : 8.5, a new band at 483 nm was expected to be observed for probe 1 as a result of the aggregation at a high water fraction solution. When the water fraction reached to 90%, a strong AIE band was observed. The fluorescence changes of probe 1 in aqueous THF solution (10 μM) with different THF–water ratio under UV light (365 nm) were also carried out (Fig. S2, ESI†). When the water fraction in dilute THF solution was increased from 0% to 70%, probe 1 showed almost no fluorescence as expected. An enhancement of the fluorescence of probe 1 can be observed as the water fraction in THF–water mixture exceeded 80%. The fluorescence enhancement of probe 1 was attributed to the formation of nanoaggregates suggesting that probe 1 was AIE-active. As a conclusion, based on the above information on AIE behavior of probe 1, the UV-vis and fluorescence experiments were carried out in THF–H₂O (2 : 8, v/v) aqueous solution. The UV-vis absorption titration spectra of probe 1 (10 μM) to pH was carried out in a solution of THF–H₂O (2 : 8, v/v) as shown in Fig. S14–16 (ESI†). When the pH value changed from 2.08 to 8.09, there were minimal changes at two wavelengths of 277 nm and 328 nm, respectively. However, in the strong alkaline condition (pH = 9.94–11.84), there was no change at 328 nm, while there was a clear enhancement at 277 nm.

Fig. 1 Fluorescence spectra (λ_ex = 305 nm) of probe 1 (10 μM) in a THF–H₂O binary solvent mixture.

Next, the fluorescence properties of probe 1 (10 μM) were investigated as it displayed a strong fluorescence at 377 nm when excited at 305 nm in THF–H₂O (2 : 8, v/v). The standard pH titrations on probe 1 were obtained in a solution of THF–H₂O (2 : 8, v/v). In the fluorescence spectrum (Fig. 2), probe 1 exhibited an emission band at 377 nm under an acidic condition. As the pH value increased from 1.99 to 7.02, the fluorescent intensity of probe 1 at 377 nm linearly decreased. Furthermore, the fluorescent quantum yield of probe 1 under acidic condition was 10.9%. Upon the addition of base to the solution of probe 1 (10 μM) in THF–H₂O (2 : 8, v/v), varying the pH of the media from 7.02 to 8.50, a gradual decrease in intensity of emission band at 377 nm was observed along with the appearance of a new band at 483 nm in a ratiometric manner (Fig. 3). The calculations of fluorescence intensity ratios of the two emission band at 483 nm and 377 nm (I_{483 nm}/I_{377 nm}) within the range of pH from 7.02 to 8.50 (Fig. S6 and S7, ESI†) established that aggregates of probe 1 served as dual-emission ratiometric probe for pH detection. Actually, this ratiometric emission taking place allowed us to correct the pH sensitivity. As the pH continuously changed from 8.50 to 11.64, the fluorescence intensity increased at 483 nm (Fig. 4) as a result of aggregation of probe 1 under alkaline condition and the fluorescence quantum yield was calculated to be 6.7%. These fluorescence changes can also be easily observed with naked eyes upon the addition of both acid and base into the solution of probe 1 (10 μM) in THF–H₂O (2 : 8, v/v) under UV light (365 nm) (Fig. S13, ESI†). A strong fluorescence emission of probe 1 can be observed in an alkaline solution while fluorescence was quenched in an acidic solution. In other words, according to fluorescence emission measurements, probe 1 behaved as a typical pH-induced “off–on” type fluorescence molecular switch for base.

Fig. 2 Fluorescence responses to the probe 1 (10 μM) to different pH: 1.99, 2.01, 2.55, 2.98, 3.60, 4.00, 4.77, 5.08, 5.62, 6.58 and 7.02 in THF–H₂O (2 : 8, v/v) (λ_ex = 305 nm). Inset: linear relationship of fluorescence intensity at 377 nm and varying pH values from 1.99 to 7.02.

Fig. 3 Fluorescence responses of the probe 1 (10 μM) to different pH: 7.02, 7.24, 7.59, 7.85, 8.03, 8.43 and 8.50 in THF–H₂O (2 : 8, v/v) (λ_ex = 305 nm). Inset (1): linear relationship of fluorescence intensity at 377 nm (black line) and 483 nm (red line) to pH; inset (2): ratio metric calibration curve of I_{483 nm}/I_{377 nm} (intensity at 483 nm vs. intensity at 377 nm).

Fig. 4 Fluorescence responses of the probe 1 (10 μM) to different pH: 8.50, 8.94, 9.57, 10.11, 10.51, 10.74, 11.13 and 11.64 in THF–H₂O (2 : 8, v/v) (λ_ex = 305 nm). Inset: linear relationship of fluorescence intensity at 483 nm to pH.

It was well known that TPE-based fluorescent probes with monomer emission cannot be widely observed. Bridged TPE and TPE core with hydrophilic moieties could exhibit monomer emission with the appearance of AIE at the same time. Probe 1 showed monomer emission under acidic condition and exhibited dual-emission wavelength, both monomer emission and AIE under neutral condition. In order to have a better understanding of the mechanism of probe 1, the fluorescence tests were investigated in water and THF solutions. No changes of both intensity and wavelength of fluorescence spectrum in a solution of THF were found with the addition of both acid and base (Fig. S17, ESI†). Moreover, only a weak monomer emission at 377 nm was exhibited. Furthermore, when probe 1 was dissolved in water, only AIE can be obtained. It exhibited fluorescence quenching with the addition of acid but there were no changes under alkaline condition (Fig. S18 and S19, ESI†). It indicates that both THF and water fraction played important roles to the dual-emission properties of probe 1. Probe 1 contains a hydrophobic moiety and two potential hydrophilic moieties as an amphiphilic molecule. The hydrophobic segments gather in the core and the hydrophilic blocks are in contact with water to form the shell. Moreover, the hydrophilic and hydrophobic segments are connected by noncovalent interactions. Most important, the double hydrophilic segments in probe 1 surrounded with water molecules which act as the cave molecule-loaded nanocapsules for TPE core staying without assembled, meanwhile, TPE moiety as a hydrophobic segment was surrounded by organic solvent. Therefore, the restriction of the free rotation of the phenyl rings in TPE occurred to give the TPE monomer emission. In conclusion, due to the two chains stretched into water and the TPE moiety restricted in the THF, the phenyl rings also could not rotate freely, which resulted in the appearance of monomer emission at 377 nm. The molecular arrangement became more defined at higher water content. When the probe 1 was dissolved in a low water fraction ratio medium (<80%), monomer emission was enhanced with the increasing water ratio. This was caused by the decrease in the cavity, provided by THF. However, when the water fraction ratio reached to 85% and more, the cavity was not enough for TPE core stay, resulting in an aggregated emission at 483 nm. Moreover, as the water fraction ratio was increased the aggregated-induced emission was enhanced and the monomer emission quenched meanwhile.

In order to get more evidence for the mechanism, the ¹H NMR spectra changes of probe 1 in d₈-THF–D₂O to acid and base were performed (Fig. 5). When probe 1 was dissolved in neutral and base condition because of the aggregation formed by N–H⋯N hydrogen bonding, the H_a and H_b were under different chemical environment, resulting in a doublet at 4.23 ppm. As the base was added into the mixture, the hydrophilicity decreased and compound 1 aggregated and stacked. Probe 1 cannot be dissolved well in high D₂O fraction solution, resulting in a disappearance of the signals of H_t, the protons of TPE core, H_a and H_b. However, when acid was added into the solution of probe 1, the amino parts transferred into salts and it can be well dissolved in D₂O, the doublet was changed into singlet and shifted to 4.28 ppm due to the breakup of intermolecular hydrogen bond. The protons of phenyl rings in the chain moieties were stretched into D₂O without stacked with TPE core, which caused the signal appearance of H_c and H_d as two doublet (7.21, 7.19 and 6.86, 6.84 ppm).

Fig. 5 Changes of ¹H NMR spectra of probe 1 in d₈-THF–D₂O. (a) With the addition of 4 equiv. CF₃COOH; (b) with the addition of 4 equiv. NaOH; (c) without any addition.

The size and morphology of the microstructure formed by compound 1 under different conditions in THF aqueous solution were analyzed by TEM and are shown in Fig. 6. When probe 1 was under acidic condition, TEM images indicated the spherical morphology with a diameter of about 2 μm, convincingly indicating that the fluorescent emission was caused by the amphiphile and the solvent effect. When base was added into the solution of probe 1, the TEM image confirmed the formation of large size self-assembled linearly crystalline TPE nanowires with a diameter of about 200–450 nm due to the hydrogen bonding induced J-aggregation. This resulted in the enhancement and red-shift photoluminescence in comparison with those of TPE spherical aggregates.

Fig. 6 TEM image of compound 1 with the addition of (a) acid; (b) base in THF–H₂O mixture.

Sensing mechanisms based on the transformation from vesicles to aggregation, which lead to the triple-mode fluorescence behaviors with the response from acid to base conditions was proposed, as shown in Fig. 7. When probe 1 was under an acidic condition, its amine groups were transformed into ammonium salts, which could be well dissolved in high water fraction solution. As a result, there were no emissions of aggregate states at 483 nm. These ammonium salts of probe 1 could be well dissolved in high water fraction solution. The two potential hydrophilic moieties became more dissolvable in the mixture solution and the two chains were surrounded by water molecules. However, the TPE core was hydrophobic moiety, the THF molecules surround the TPE core. This hydrophobic solvophobic interaction caused monomer emission. A spherical core was formed by the amphiphilic and solvophobic interaction. The probe 1 with chains stretched into water fraction and the TPE remained in the THF fraction, resulting in the restriction of the phenyl rings rotating freely, which is similar to the encapsulation in the cavity of γ-cyclodextrin,^26a This fraction of THF acted as a cavity for TPE core staying unassembled. Furthermore, the N-atoms were positively charged, the atoms with the same charge would be repelled between two molecules. Additionally, attributed to the deprotonation of amine groups, the electron-donating ability of N-atoms were recovered, and the photoinduced electron transfer (PET) process would be more efficient, which resulted in fluorescence quenching at the 377 nm band of monomer emission of probe 1 as the pH value increased from 1.99 to 7.02. However, when base was added into the solution of probe 1 in THF–H₂O media, the molecules of probe 1 were transformed back to the amine form. The decrease in the hydrophilicity induced the molecules to aggregate in the aqueous medium, resulting in TPE core assembled and staked with a new emission band at 483 nm. The deprotonation of probe 1 induced the intermolecular hydrogen bonding, resulting in the formation of J-aggregation of probe 1. The fluorescence wave shifted from 377 nm to 483 nm. This 106 nm red-shift was caused by monomer emission to AIE. When the pH changed from 7.02 to 8.50, the monomer emission quenched, and hence the AIEE in a ratiometric manner. It acted as a ratiometric fluorescent probe for pH. As the base was continuously added, and the pH value changed from 8.50 to 11.64, a significant AIEE exhibited. However, there were no significant changes of monomer emission at 377 nm.

Fig. 7 Mechanism of pH response of probe 1.

On account of that the amine groups can bind with many metal ions in solution, the selectivity experiments of probe 1 to H⁺ over metal ions, including Na⁺, K⁺, Ca²⁺, Mg²⁺, Mn²⁺, Al³⁺, Zn²⁺, Fe³⁺, Pb²⁺, Cu²⁺, Hg²⁺, Ag⁺, Li⁺, Co²⁺, Cd²⁺, Ba²⁺, Ni²⁺ and Cr³⁺ were also further investigated in THF aqueous (THF–H₂O = 2 : 8, v/v). As shown in Fig. 8 and S11 (ESI†), no changes in the fluorescence properties were observed for probe 1 upon the addition of all the metal ions both in the fluorescence emission intensity and wavelengths. Upon that, with high selectivity to proton, the pH-responsive behavior of probe 1 could not be interfered by metal ions in a complex environment.

Fig. 8 Ratios of fluorescence intensity at 377 nm of probe 1 (10 μM) in the presence of various metal ions (4 equiv.) in aqueous solution of THF–H₂O (2 : 8, v/v).

In summary, we have described the synthesis and photophysical properties of a novel TPE-based triple-mode fluorescent probe for pH 1 detection in a wide range of pH value from 1.99 to 11.64 in a high water fraction solution of THF–H₂O (2 : 8, v/v) media. When probe 1 was dissolved in acidic condition (pH value changed from 1.99 to 7.02), only the fluorescence quenching of monomer emission was observed at 377 nm. However, when the probe 1 was under an alkaline condition, it exhibited a new fluorescence band at 483 nm due to AIE effect. As the pH value increased from 7.02 to 8.50, the fluorescence intensity decreased at 377 nm and increased at 483 nm in a ratiometric manner. As the pH value continuously increased from 8.50 to 11.64, a significant AIEE at band of 483 nm was observed. Moreover, it also displayed an excellent selectivity to various metal cations. This new finding provided a new method to the utilization of fluorescence with AIE effect to detect pH as expected. All results demonstrated that the TPE-based pH fluorescent probe has great potential in practical application and it also gives an excellent model for pH fluorescent probe designing. What is the most important, a new fluorescence sensing mechanism for pH based on the transformation from vesicles to aggregation of TPE derivative was proposed.

Acknowledgements

This project was funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

Notes and references

1. (a) H. R. Kermis, Y. Kostov, P. Harms and G. Rao, Biotechnol. Prog., 2002, 18, 1047; (b) B. Tang, F. Yu, P. Li, L. Tong, X. Duan, T. Xie and X. Wang, J. Am. Chem. Soc., 2009, 131, 3016; (c) M. Tantama, Y. P. Hung and G. Yellen, J. Am. Chem. Soc., 2011, 133, 10034; (d) X. Chen, T. Pradhan, F. Wang, J. S. Kim and J. Yoon, Chem. Rev., 2012, 112, 1910; (e) G. T. Hanson, T. B. McAnaney, E. S. Park, M. E. P. Rendell, D. K. Yarbrough, S. Chu, L. Xi, S. G. Boxer, M. H. Montrose and S. J. Remington, Biochemistry, 2002, 41, 15477; (f) D. G. Pijanowska, A. Baraniecka, R. Wiater, G. Ginalska, J. Łobarzewski and W. Torbicz, Sens. Actuators, B, 2001, 78, 263; (g) P. Vermathen, A. A. Capizzano and A. A. Maudsley, Magn. Reson. Med., 2000, 43, 665.
2. (a) Y. Urano, D. Asanuma, Y. Hama, Y. Koyama, T. Barrett, M. Kamiya, T. Nagano, T. Watanabe, A. Hasegawa, P. L. Choyke and H. Kobayashi, Nat. Med., 2009, 15, 104; (b) P. Li, H. Xiao, Y. Cheng, W. Zhang, F. Huang, W. Zhang, H. Wang and B. Tang, Chem. Commun., 2014, 50, 7184.
3. E. G. Webb and R. C. Alkire, J. Electrochem. Soc., 2002, 149, B280.
4. A. A. Sehgal, L. Duma, G. Bodenhausen and P. Pelupessy, Chem.–Eur. J., 2014, 20, 6332.
5. (a) S. Brasselet and W. E. Moerner, Single Mol., 2000, 1, 17; (b) C. Sun, P. Wang, L. Li, G. Zhou, X. Zong, B. Hu, R. Zhang, J. Cai, J. Chen and M. Ji, Appl. Biochem. Biotechnol., 2014, 172, 1036.
6. W. L. Czaplyski, G. E. Purnell, C. A. Roberts, R. M. Allred and E. J. Harbron, Org. Biomol. Chem., 2014, 12, 526.
7. (a) J. Han, A. Loudet, R. Barhoumi, R. C. Burghardt and K. Burgess, J. Am. Chem. Soc., 2009, 131, 1642; (b) N. Boens, V. Leen and W. Dehaen, Chem. Soc. Rev., 2012, 41, 1130.
8. W. Huang, W. Lin and X. Guan, Tetrahedron Lett., 2014, 55, 116.
9. (a) N. I. Georgiev, A. M. Asiri, K. A. Alamry, A. Y. Obaid and V. B. Bojinov, J. Photochem. Photobiol., A, 2014, 277, 62; (b) L. Liu, P. Guo, L. Chai, Q. Shi, B. Xu, J. Yuan, X. Wang, X. Shi and W. Zhang, Sens. Actuators, B, 2014, 194, 498.
10. S. Z. Topal, E. Onal, A. G. Gurek and C. Hirel, Dalton Trans., 2013, 42, 11528.
11. (a) X. L. Guan and Z. X. Su, Polym. Adv. Technol., 2008, 19, 385; (b) M. J. Doughty, Ophthalmic Physiol. Optic., 2010, 30, 167; (c) G. Ghini, C. Trono, A. Giannetti, G. L. Puleo, L. Luconi, J. Amadou, G. Giambastiani and F. Baldini, Sens. Actuators, B, 2013, 179, 163.
12. N. V. Marinova, N. I. Georgiev and V. B. Bojinov, J. Photochem. Photobiol., A, 2011, 222, 132.
13. T. Kurabayashi, N. Funaki, T. Fukuda, S. Akiyama and M. Suzuki, Anal. Sci., 2014, 30, 545.
14. (a) D. K. Rana, S. Dhar and S. C. Bhattacharya, Phys. Chem. Chem. Phys., 2014, 16, 5933; (b) H. S. Lv, S. Y. Huang, Y. Xu, X. Dai, J. Y. Miao and B. X. Zhao, Bioorg. Med. Chem. Lett., 2014, 24, 535; (c) R. Sanders, A. Draaijer, H. C. Gerritsem, P. M. Houpt and Y. K. Levine, Anal. Biochem., 1995, 227, 302.
15. (a) S. A. Grant and R. S. Glass, Sens. Actuators, B, 1997, 45, 35; (b) D. Wencel, B. D. MacCraith and C. McDonagh, Sens. Actuators, B, 2009, 139, 208.
16. B. Korzeniowska, R. Woolley, J. DeCourcey, D. Wencel, C. E. Loscher and C. McDonagh, J. Biomed. Nanotechnol., 2014, 10, 1336.
17. (a) J. Fan, C. Lin, H. Li, P. Zhan, J. Wang, S. Cui, M. Hu, G. Cheng and X. Peng, Dyes Pigm., 2013, 99, 620; (b) C. G. Niu, X. Q. Gui, G. M. Zeng and X. Z. Yuan, Analyst, 2005, 130, 1551; (c) H. Sun, A. M. Scharff-Poulsen, H. Gu and K. Almdal, Chem. Mater., 2006, 18, 3381.
18. J. Fan, M. Hu, P. Zhan and X. Peng, Chem. Soc. Rev., 2013, 42, 29.
19. (a) J. Luo, Z. Xie, J. W. Y. Lam, L. Cheng, H. Chen, C. Qiu, H. S. Kwok, X. Zhan, Y. Liu, D. Zhu and B. Z. Tang, Chem. Commun., 2001, 1740; (b) Y. Hong, J. W. Lam and B. Z. Tang, Chem. Soc. Rev., 2011, 40, 5361.
20. (a) C. Gao, G. Gao, J. Lan and J. You, Chem. Commun., 2014, 50, 5623; (b) X. G. Hou, Y. Wu, H. T. Cao, H. Z. Sun, H. B. Li, G. G. Shan and Z. M. Su, Chem. Commun., 2014, 50, 6031; (c) P. Wang, X. Yan and F. Huang, Chem. Commun., 2014, 50, 5017; (d) K. Li, Z. Zhu, P. Cai, R. Liu, N. Tomczak, D. Ding, J. Liu, W. Qin, Z. Zhao, Y. Hu, X. Chen, B. Z. Tang and B. Liu, Chem. Mater., 2013, 25, 4181; (e) G.-L. Fu and C.-H. Zhao, Tetrahedron, 2013, 69, 1700; (f) D. Ding, K. Li, B. Liu and B. Z. Tang, Acc. Chem. Res., 2013, 46, 2441; (g) Z. Zhao, B. Chen, J. Geng, Z. Chang, L. Aparicio-Ixta, H. Nie, C. C. Goh, L. G. Ng, A. Qin, G. Ramos-Ortiz, B. Liu and B. Z. Tang, Part. Part. Syst. Charact., 2014, 31, 481.
21. (a) J.-H. Ye, L. Duan, C. Yan, W. Zhang and W. He, Tetrahedron Lett., 2012, 53, 593; (b) J.-H. Ye, J. Liu, Z. Wang, Y. Bai, W. Zhang and W. He, Tetrahedron Lett., 2014, 55, 3688; (c) S. Zhang, J. Yan, A. Qin, J. Sun and B. Z. Tang, Sci. China: Chem., 2013, 56, 1253; (d) S. Chen, J. Liu, Y. Liu, H. Su, Y. Hong, C. K. W. Jim, R. T. K. Kwok, N. Zhao, W. Qin, J. W. Y. Lam, K. S. Wong and B. Z. Tang, Chem. Sci., 2012, 3, 1804; (e) S. Chen, Y. Hong, Y. Liu, J. Liu, C. W. Leung, M. Li, R. T. Kwok, E. Zhao, J. W. Lam, Y. Yu and B. Z. Tang, J. Am. Chem. Soc., 2013, 135, 4926.
22. Y. Dong, J. W. Y. Lam, A. Qin, Z. Li, J. Liu, J. Sun, Y. Dong and B. Z. Tang, Chem. Phys. Lett., 2007, 446, 124.
23. Y. Hong, J. W. Lam and B. Z. Tang, Chem. Commun., 2009, 4332.
24. (a) B.-P. Jiang, D.-S. Guo, Y.-C. Liu, K.-P. Wang and Y. Liu, ACS Nano, 2014, 8, 1609; (b) J. Shi, N. Chang, C. Li, J. Mei, C. Deng, X. Luo, Z. Liu, Z. Bo, Y. Q. Dong and B. Z. Tang, Chem. Commun., 2012, 48, 10675.
25. S. Kohmoto, R. Tsuyuki, Y. Hara, A. Kaji, M. Takahashi and K. Kishikawa, Chem. Commun., 2011, 47, 9158.
26. (a) S. Song, H.-F. Zheng, D.-M. Li, J.-H. Wang, H.-T. Feng, Z.-H. Zhu, Y.-C. Chen and Y.-S. Zheng, Org. Lett., 2014, 16, 2170; (b) J.-H. Wang, H.-T. Feng, J. Luo and Y.-S. Zheng, J. Org. Chem., 2014, 79, 5746.

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c4ra15240a

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