Reversible molecular switch of acridine red by triarylpyridine-modified cyclodextrin

Article abstract of DOI:10.1021/ol3031473

A novel molecular switch based on the supramolecular complex of 2,4,6-triarylpyridine modified β-cyclodextrin and acridine red was successfully constructed in aqueous solution, displaying the controlled photophysical behaviors by the effect of supramolecular positive cooperativity and fluorescence resonance energy-transfer process.

Full text of DOI:10.1021/ol3031473

ORGANIC
LETTERS
2013
Vol. 15, No. 1
124–127
Reversible Molecular Switch of Acridine
Red by Triarylpyridine-Modified
Cyclodextrin
Ying-Ming Zhang,† Min Han,†,‡ Hong-Zhong Chen,† Yan Zhang,† and Yu Liu*,†
Department of Chemistry, State Key Laboratory of Elemento-Organic Chemistry,
Nankai University, Tianjin 300071, People’s Republic of China, and Traditional Chinese
Medicine Research & Development Institute of Tasly Academy, Tianjin Tasly Group Co., Ltd.,
Tianjin 300410, People’s Republic of China
yuliu@nankai.edu.cn
Received November 15, 2012
ABSTRACT
A novel molecular switch based on the supramolecular complex of 2,4,6-triarylpyridine modified β-cyclodextrin and acridine red was successfully
constructed in aqueous solution, displaying the controlled photophysical behaviors by the effect of supramolecular positive cooperativity and
fluorescence resonance energy-transfer process.
Stimuli-responsive supramolecular systems have stimu-
lated considerable interest toward the construction of
highly functional materials, mainly due to their immense
advantages to achieve reversible and precise control of the
photophysical properties and electronic communications
in diverse nanoarchitectures through the cooperative con-
tribution of noncovalent forces.1 Among various compo-
nents that are commonly involved in the molecular recogni-
tion and self-assembly, macrocyclic synthetic receptors as
building blocks offer an alternative and even a more
powerful strategy in the field of stimuli-responsive supra-
molecular systems.2ꢀ6 Of which, cyclodextrins (CDs) as a
class of cyclic oligosaccharides represent the superior
candidates to construct the dynamically assembled nano-
machines. However, the inventive developments of their
reversible switching process with associated change in the
spectroscopic behaviors still deserve our careful attention.
Recently, Harada et al. have designed a [2]rotaxane com-
prising β-CD and oligothiophene units, implementing a
ꢀ
(2) Badjic, J. D.; Balzani, V.; Credi, A.; Silvi, S.; Stoddart, J. F.
† Nankai University.
Science 2004, 303, 1845–1849.
‡ Tianjin Tasly Group Co., Ltd.
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Nature 1994, 369, 133–137. (b) Silvi, S.; Venturi, M.; Credi, A. J. Mater.
Chem. 2009, 19, 2279–2294.
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M. W.; Botros, Y. Y.; Stoddart, J. F. Chem. Sci. 2011, 2, 204–210.
(b) Yang, Y.-W. Med. Chem. Commun. 2011, 2, 1033–1049.
(5) (a) Sobczuk, A. A.; Tsuchiya, Y.; Shiraki, T.; Tamaru, S-i.;
Shinkai, S. Chem.;Eur. J. 2012, 18, 2832–2838. (b) Zhang, M.; Xu,
D.; Yan, X.; Chen, J.; Dong, S.; Zheng, B.; Huang, F. Angew. Chem., Int.
Ed. 2012, 51, 7011–7015.
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H.-J.; Jang, W.-D. J. Mater. Chem. 2010, 20, 211–222. (c) Liu, K. L.;
Zhang, Z.; Li, J. Soft Matter 2011, 7, 11290–11297. (d) Whittell, G. R.;
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1621–1636. (g) Wang, C.; Wang, Z.; Zhang, X. Acc. Chem. Res. 2012, 45,
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r
10.1021/ol3031473
Published on Web 12/12/2012
2012 American Chemical Society

tunable intermolecular energy transfer process from the
excited [2]rotaxane to the sexithiophene derivative.7
Stoddart et al. have successfully elucidated a bistable [2]-
rotaxane in which the redox-responsive movements of
R-CD toward tetrathiafulvalene and triazole moieties were
efficiently achieved under the control of external inputs.8
We have previously demonstrated a twisted intramole-
cular charge transfer (TICT) sensor for the magnesium ion
(Mg2þ) based on triarylpyridineꢀcrown ether conjugate.9
These findings inspired us to hypothesize that a reversibly
photophysical process may take place from the triaryl-
pyridine moiety as a donor molecule to some appro-
priate guests as acceptor molecules. In the present work,
one of the most commonly employed xanthene dyes,10
acridine red (AR), was chosen as guest molecule to com-
prehensively study the cooperative noncovalent inter-
actions in the host-enhanced molecular switch, taking
both the binding affinity of β-CD with AR and the
spectral complementarity of triarylpyridine and AR
into account.
Figure 1. Emission spectral changes of 1 (5.0 ꢁ 10ꢀ5 M) upon
addition of 0ꢀ150 equiv of HClO4 in aqueous solution at 25 °C
(λex = 335 nm). Inset: visible emission of 1 in the absence (I) and
presence (II) of HClO4.
It is well-established that the 2,4,6-triarylpyridine signal-
ing unit is an attractive chromophore featuring visible
emission from a locally excited state and a charge transfer
state induced by the coordination of an ion to pyridyl
nitrogen.12 Therefore, the quantitative investigation of intra-
molecular charge transfer (ICT) property of compound 1 in
the presence of perchloric acid was examined by means
of the absorption and fluorescence spectroscopy titration.
As shown in Figure S5 (Supporting Information) with
the stepwise addition of HClO4 to a solution of 1, the
absorption peak of 1 at 270 nm gradually declined while
the absorption peak at 333 nm increased in proportion,
accompanied by an isosbestic point at 304 nm. In addi-
tion, the protonation of nitrogen atoms on triarylpyridine
moiety led to a significant bathochromic shift from 363
to 440 nm with an enhancement of emission intensity
(Figure 1). Obviously, these new absorption and emission
bands in the long-wavelength region originate from the
ICT process from the phenoxyl to pyridyl moiety.9 It was
noteworthy that this ICT process could be readily distin-
guished by not only spectroscopic experiments but also the
naked eye upon irradiation with 365 nm light. That is, 1
(5.0 ꢁ 10ꢀ5 M) alone exhibited no obvious fluorescence
but gave a strong blue fluorescence in the presence of
HClO4 (Figure 1, inset photos). Furthermore, as shown in
Figure S6 (Supporting Information), deprotonation of
Scheme 1. Synthetic Routes of Compound 1 and Molecular
Structure of Acridine Red (AR)
The synthetic route of 2,4,6-triarylpyridine modified
β-CD (1) and molecular structure of AR were described
in Scheme 1. 4-(4,6-Diphenylpyridin-2-yl)phenol (3) was
prepared from 4-hydroxybenzaldehyde and acetophenone
according to the reported literature.11 Next, mono[6-O-(p-
toluenesulfonyl)]-β-CD (2) reacted with the intermediate 3
under basic conditions to afford compound 1 in 60% yield
(Figures S1ꢀS3, Supporting Information). Benefiting from
the CD unit as solubilizer, host compound 1 showed a
satisfactory water solubility up to 0.2 M (i.e., 250.2 mg/mL).
The good solubility of 1 was ascribed to the partial inclusion
of triarylpyridine moiety into the cavity of CD in water
(Figure S4, Supporting Information).
1 Hþ system with NaOH could restore the original emis-
3
sion of 1, which facilitates the proton-triggered reversible
molecular switch by the addition of acid and base as
described below.
(7) Sakamoto, K.; Takashima, Y.; Hamada, N.; Ichida, H.; Yamaguchi,
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(9) Liu, Y.; Han, M.; Zhang, H.-Y.; Yang, L.-X.; Jiang, W. Org. Lett.
2008, 10, 2873–2876.
Subsequently, the photophysical behaviors accompanied
by the formation of a supramolecular complex between 1
and AR were further verified by fluorescence spectral
titration. As seen in Figure S7 (Supporting Information),
(10) Dsouza, R. N.; Pischel, U.; Nau, W. M. Chem. Rev. 2011, 111,
7941–7980.
(11) (a) Katritzky, A. R.; Schwarz, O. A.; Abdel Rahman, A. E.;
Leahy, D. E. J. Heterocycl. Chem. 1984, 21, 1673–1677. (b) Karkia, R.;
Thapaa, P.; Kanga, M. J.; Jeonga, T. C.; Namb, J. M.; Kimb, H.-L.;
Nac, Y.; Chod, W.-J.; Kwonb, Y.; Leea, E.-S. Bioorg. Med. Chem. 2010,
18, 3066–3077.
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1536–1538. (b) Fang, A. G.; Mello, J. V.; Finney, N. S. Org. Lett. 2003, 5,
967–970. (c) Mello, J. V.; Finney, N. S. J. Am. Chem. Soc. 2005, 127,
10124–10125.
Org. Lett., Vol. 15, No. 1, 2013
125

of donor through long-range dipoleꢀdipole interaction.
As seen in Figure S11 (Supporting Information), no obvi-
ous spectral overlap could be observed between the fluo-
rescence emission band of 1 and absorption band of AR,
whereas there was appreciable overlap in the case of 1 Hþ
3
and dye molecule. Therefore, it is anticipated that the
1 Hþ/AR complex could exhibit the through-space energy
transfer behaviors.
3
Figure 2. Emission spectral changes of AR upon addition of 1 in
the presence of HClO4 at 25 °C ([AR] = 5.0 ꢁ 10ꢀ6 M, [HClO4] =
6.0 ꢁ 10ꢀ2 M, [1] = 0ꢀ6.0 ꢁ 10ꢀ4 M, respectively, from a to l).
Inset: The nonlinear least-squares analysis of the differential
spectral changes (ΔF) at 557 nm to calculate the stability constant
(KS) of 1 and AR (λex = 520 nm).
when excited at 520 nm to avoid any absorption of 1 and
1 Hþ, the fluorescence intensity of AR was significantly
3
enhanced upon stepwise addition of 1 in the neutral
solution, indicating that the guest molecule AR was en-
capsulated into the hydrophobic cavity of CD. According
to the 1:1 binding stoichiometry in the supramolecular com-
plex between native β-CD and AR,13 the binding constant
(KS) in 1/AR system was calculated to be 8.39 ꢁ 103 Mꢀ1
(Figure S7, Supporting Information, inset) by analyzing the
sequential changes in fluorescence intensity (ΔF) of AR at
varying concentrations of 1 by a nonlinear least-squares
curve-fitting method. Moreover, using the similar fluores-
cence titration method, the KS value between 1 and AR
under acidic conditions was calculated to be 2.29 ꢁ 104 Mꢀ1
(Figure 2). Comparatively, lacking the 2,4,6-triarylpyridine
moiety, the binding abilities of β-CD/AR complexes
in neutral and acidic conditions were only 2.93 ꢁ 103 and
3.74 ꢁ 103 Mꢀ1, respectively (Figures S8 and S9, Support-
ing Information). Considering that the fluorescence emis-
sion of AR was not sensitive to the addition of HClO4
under our experimental conditions (Figure S10, Support-
ing Information), the significant enhancement in complex
Figure 3. Emission spectral changes of 1/AR complex upon
addition of HClO4 in aqueous solution at 25 °C ([1] = [AR] =
5.0 ꢁ 10ꢀ5 M, [HClO4] = 0ꢀ15.0 ꢁ 10ꢀ4 M, respectively, from a
to j, λex = 335 nm). Inset: visible emission of 1/AR complex in the
absence (I) and presence (II) of HClO4.
The fluorescence emission spectra of 1 Hþ/AR complex
3
(1:1, 5.0 ꢁ 10ꢀ5 M) with increasing amounts of HClO4 are
shown in Figure 3. Through a calculation based on the
binding constant between 1 Hþ and AR as well as the
3
concentrations of host and guest, more than 40% of 1 Hþ
3
could be convertedto1 Hþ/AR complex under our experi-
3
mental conditions. When excited at 335 nm that corre-
sponded to the absorption band of triarylpyridine moiety,
the emission of 1 at 363 nm was gradually decreased upon
addition of HClO4, and the CT emissionof1 Hþ at 440 nm
3
and AR emission at 564 nm were synchronously increased
(Figure 3, inset photos). In addition, the excitation spec-
trum of 1 Hþ/AR complex was recorded by monitoring
3
formation constants of 1/AR and 1 Hþ/AR systems is
contributed to the supramolecular cooperative contribu-
tions of protonated triarylpyridine substituent and β-CD
cavity toward guest molecules.
It is well-documented that some criteria must be re-
quired to achieve a more effective fluorescence resonance
energy transfer (FRET) process.7,14 That is, the donor and
acceptor chromophores should be located in close proxi-
mity, and the absorption spectrum of acceptor should
sufficiently fall into the fluorescence emission spectrum
the emission wavelength at 620 nm, in which the signals
assigned to the absorptions of AR in the range from 430
to 580 nm and a strong band assigned to the absorptions
3
qof 1 Hþ around 350 nm appeared, giving further evi-
3
dence for the energy transfer process (Figure S12, Support-
ing Information). Applying the absolute fluorescence
quantum yield (ΦF) of 1 Hþ in the absence (0.157) and
presence (0.113) of AR, the energy transfer efficiency (E)
3
in 1:1 1 Hþ/AR complex was calculated as 28.2%.15
3
These phenomena clearly indicate that the protonation of
triarylpyridine moiety may cause the charge transfer from
(13) (a) Liu, Y.; Han, B.-H.; Chen, Y.-T. J. Org. Chem. 2000, 65,
6227–6230. (b) Liu, Y.; Chen, Y. Acc. Chem. Res. 2006, 39, 681–691.
(14) (a) Papagni, A.; Del Buttero, P.; Moret, M.; Sassella, A.;
Miozzo, L.; Ridolfi, G. Chem. Mater. 2003, 15, 5010–5018. (b) Fabricio,
(15) Maligaspe, E.; Kumpulainen, T.; Lemmetyinen, H.; Tkachenko,
N. V.; Subbaiyan, N. K.; Zandler, M. E.; D’Souza, F. J. Phys. Chem. A
2010, 114, 268–277.
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A.-L.; Cosultchi, A.; Perez, E. Energy Fuels 2005, 19, 477–484.
126
Org. Lett., Vol. 15, No. 1, 2013

phenoxyl to pyridyl moiety followed by a FRET from the
excited 1 Hþ as donor to the included AR dye as acceptor.
To confirm the assumption of FRET mechanism in the
3
Scheme 2. Schematic Illustration of the AcidꢀBase-Modulated
Molecular Switch
formation of 1 Hþ/AR complex, some control experi-
3
ments were carried out. The emission spectra of 1 Hþ
3
upon addition of AR in different molar ratios are shown in
Figure S13 (Supporting Information). The CT emission of
1 Hþ at440 nmwas decreased, whereas the fluorescenceof
3
emission AR at 564 nm was accordingly increased, un-
doubtedly demonstrating the energy transfer process from
1 Hþ to AR in aqueous solution. Moreover, although the
3
emission intensity of AR in the presence of 1 Hþ was
3
0.5 times higher upon excitation at 525 nm, the one was
2.3 times higher upon excitation at 335 nm at the same
concentrations (Figures S14 and S15,Supporting Infor-
mation). Therefore, we can deduce that the effect of
supramolecular positive cooperativity and intermolec-
zular FRET process jointly contribute to the proton-
triggered fluorescence enhancement of dye molecule in
1 Hþ/AR complex.
3
Among the various external stimuli, it has been proven
that pH change is a simple and accessible strategy to
efficiently modulate the multicomponent assemblies in a
precisely controlled manner. In our case, when NaOH was
compared with the corresponding native β-CD. Further-
more, an efficient molecular switch based on 1/AR supra-
molecular complex has been represented. As investigated by
fluorescence titrations, it is demonstrated that fluorescent
enhancement in the supramolecular system could be modu-
lated in a reversible way by adopting a proton-controlled
binding and release strategy. We also envision that the
triarylpyridine/AR couple as a new donor/acceptor system
may find potential application in the biological system and
construction of new molecule-based optical devices.
added to the solution of 1 Hþ/AR, the fluorescence emis-
3
sion at 363 nm of 1 was restored, suggesting that the
triarylpyridine unit existed in neutral state. Meanwhile,
the cooperative binding in hostꢀguest complex and FRET
process from 1 Hþ to AR were completely suppressed.
3
In addition, the enhancement of AR emission could be
regenerated along with the reproduction of CT emission at
440 nm whenadding anotherportion ofHClO4 tothe same
solution (Figure S16, Supporting Information). The rever-
sibility can be repeated for several cycles (Figure S16,
Supporting Information, inset). Consequently, a noncova-
lently connected conjugate of triarylpyridine-grafted CD
and dye molecule based on the effect of positive supramo-
lecular cooperativity and FRET mechanism was success-
fully constructed and the photophysical communications
between donor and acceptor sites could be reversibly
governed by adding acid and base in series. The schematic
illustration of this reversible switching process via the
acidꢀbase input is illustrated in Scheme 2.
Acknowledgment. This work is financially supported by
the 973 Program (2011CB932502), NNSFC (No. 20932004
and 21102075), the Specialized Research Fund for the
Doctoral Program of Higher Education (20110031120014),
and the National Science and Technology Major Pro-
jects “Major new drugs innovation and development”
(2010ZX09401-406).
Supporting Information Available. General experimen-
tal procedures and characterization data for 1, as well as
the fluorescence titrations in control experiments. This
information is available free of charge via the Internet at
http://pubs.acs.org.
In conclusion, a newly synthesized β-CD derivative bear-
ing a 2,4,6-triarylpyridine moiety (1) is found to form a
stable supramolecular complex with AR, pronouncedly
increasing about 1 order of magnitude in KS value as
The authors declare no competing financial interest.
Org. Lett., Vol. 15, No. 1, 2013
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