Controlling binding affinities for anions by a photoswitchable foldamer

Article abstract of DOI:10.1021/ol1014043

A photoswitchable foldamer containing an azobenzene and phenyl-1,2,3-triazole motif was found to show photochemical/dark isomerization in a controllable and reversible manner in both the absence and presence of anions. The transformation in conformation o

Full text of DOI:10.1021/ol1014043

ORGANIC
LETTERS
2010
Vol. 12, No. 16
3630-3633
Controlling Binding Affinities for Anions
by a Photoswitchable Foldamer
Ying Wang,†,‡ Fusheng Bie,†,‡ and Hua Jiang*,†
Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of
Photochemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China,
and Graduate UniVersity of Chinese Academy of Sciences, Beijing, China
hjiang@iccas.ac.cn
Received June 17, 2010
ABSTRACT
A photoswitchable foldamer containing an azobenzene and phenyl-1,2,3-triazole motif was found to show photochemical/dark isomerization in
a controllable and reversible manner in both the absence and presence of anions. The transformation in conformation of the foldamer leads
to changes in binding affinities for anions to a certain extent that depends on the size and the geometrical shape of the anions.
Light-controlled molecular recognition, well-known to ma-
nipulate the conformation of receptors by light to control its
binding affinity for guest molecules, has found many
applications in material sciences and biology.1 In the past
decades, several photoswitchable receptors such as aza-
crowns2 and aza-calixcrowns3 were developed to binding
cations in a controllable manner. Among them, light-induced
changes in molecular geometry were realized through the
photoswitch of azobenzenes,4 which display an extended and
planar conformation in the steady trans form but a compact
and twisted geometry in the cis form during irradiation with
UV light. However, to date, there are few systems that
display a light-controllable binding affinity for anions.5
Previous studies show that the aryl-triazole group can serve
as an effective hydrogen bond donor for anion binding.6
These aryl-triazole-based receptors including macrocycles7
and foldamers7b,8 have been proven to have high affinity and
selectiveness for anions, especially for halide ions. A recent
report demonstrates that the conformational preorganization
of aryl-triazole pentads was also found to have a decisive
effect on the binding affinity for halide ions.9 Taking
(5) Shimasaki, T.; Kato, S.; Ideta, K.; Goto, K.; Shinmyozu, T. J. Org.
Chem. 2007, 72, 1073–1087.
(6) Hua, Y.; Flood, A. H. Chem. Soc. ReV. 2010, 39, 1262–1271.
(7) (a) Li, Y.; Flood, A. H. Angew. Chem., Int. Ed. 2008, 47, 2649–
2652. (b) Li, Y.; Flood, A. H. J. Am. Chem. Soc. 2008, 130, 12111–12122.
(c) Li, Y.; Pink, M.; Karty, J. A.; Flood, A. H. J. Am. Chem. Soc. 2008,
130, 17293–17295.
† Chinese Academy of Sciences.
‡ Graduate University of Chinese Academy of Sciences.
(1) (a) Dugave, C.; Demange, L. Chem. ReV. 2003, 103, 2475–2532.
(b) Renner, C.; Moroder, L. ChemBioChem 2006, 7, 868–878.
(2) Cacciapaglia, R.; Stefano, S. D.; Mandolini, L. J. Am. Chem. Soc.
2003, 125, 2224–2227.
(8) (a) Juwarker, H.; Lenhardt, J. M.; Pham, D. M.; Craig, S. L. Angew.
Chem., Int. Ed. 2008, 47, 3740–3743. (b) Meudtner, R. M.; Hecht, S. Angew.
Chem., Int. Ed. 2008, 47, 4926–4930. (c) Wang, Y.; Li, F.; Han, Y.-M.;
Wang, F.-Y.; Jiang, H. Chem.sEur. J. 2009, 15, 9424–9433. (d) Juwarker,
H.; Lenhardt, J. M.; Castillo, J. C.; Zhao, E.; Krishnamurthy, S.;
Jamiolkowski, R.; Kim, K. H; Craig, S. L. J. Org. Chem. 2009, 74, 8924–
(3) (a) Liu, M.; Yan, X.; Hu, M.; Chen, X.; Zhang, M.; Zheng, B.; Hu,
X.; Shao, S.; Huang, F. Org. Lett. 2010, 12, 2558–2561. (b) Kim, J. S.;
Shon, O. J.; Lee, J. K.; Lee, S. H.; Kim, J. Y.; Park, K.-M.; Lee, S. S. J.
Org. Chem. 2002, 67, 1372–1375.
(4) (a) Pieroni, O.; Fissi, A.; Angelini, N.; Lenci, F. Acc. Chem. Res.
2001, 34, 9–17. (b) Delaire, J. A.; Nakatani, K. Chem. ReV. 2000, 100,
1817–1845.
8934
(9) Lee, S.; Hua, Y.-R.; Park, H.-S.; Flood, A. H. Org. Lett. 2010, 12,
2100–2102
.
.
10.1021/ol1014043  2010 American Chemical Society
Published on Web 07/23/2010

advantage of the strong C-H···anion interaction between the
triazole and the anions and the photoisomerization of
azobenzen, we thus envisioned that plugging the photore-
sponsive azobenzene into the phenyl-triazole oligomers could
provide a photoswitchable foldamer with controllable changes
in binding affinity for anions due to the light-controlled
transition in conformation. We propose (Scheme 1) that while
Scheme 2. Synthesis of Photoswitch 1
Scheme 1. Photoswitch 1 Studied Herein and Proposed
Different Binding Model for Its Two Photoisomers to Anions
1 adopts the trans conformation (1trans), its binding affinities
for anions would be weak as a result of the extended
conformation of the azobenzene core; however, while 1
adopts the cis form (1cis) upon irradiation with UV light, its
binding to the anions would be strengthened as a result of
the spatial preference between the anions and the receptor.
The controllable affinities for anions could thus be achieved
through reversible photoisomerization.
To evaluate this hypothesis, photoswitch 1 (Scheme 1) was
designed to possess two phenyl-1,2,3-triazole units with an
azobenzene moiety at the core. The chain length of 1 was
deliberately chosen to allow folding of the entire chain but
avoid π-stacking within intramolecular strand in the trans
form.10 A water-soluble 2-(2-methoxyethoxy)-ethoxy side
chain was introduced to each phenyl group because it was
proven be conducive to the folding in polar solvents such as
acetone via solvophobic interaction.11
The synthesis of compound 1 is outlined in Scheme 2.
The starting material pentabromophenol 2 was reduced to
give 3. Via a Mitsunobu reaction,12 a water-soluble side chain
was attached to provide 4, one bromo of which was converted
to azide followed by reduction to give 6. Compound 6 was
ethynylated to generate 7 by the Sonogashira reaction with
excess (trimethylsilyl)-acetylene.13 Then, coupling 7 itself
in the presence of CuI afforded azobenzene 8, followed by
removal of the TMS group under a basic conditions to yield
9. Finally, compound 1 was obtained by coupling 8 with 5
through “click chemistry”.14
The photoresponsive properties of 1 were first investigated
by UV-vis spectroscopy in acetone (Figure S1 in Supporting
Information). Upon UV light irradiation, the intensity of the
π-π* transition band at 339 nm shows a sharp descent by
80%, and the intensity of the n-π* transition band at 440
nm slightly increased, indicative of the photoisomerization
of 1 from the trans to the cis state.15 After irradiation of the
above solution with the visible light, 77% intensity of the
absorption at 339 nm was recovered, suggesting that the cis
reversibly switched to the trans. NMR measurements pro-
vided additional information about the photoisomerization
of 1. At a normal state, 1 prefers to exist in the trans form,
and the folding of 1trans was strongly suggested by the
correlations (strong Hd-Hg rather than Hd-He) in 2D
NOESY spectrum (Figure S2 in Supporting Information),
in which the signals were assigned on the basis of 2D NMR
experiments (Figures S3-S6 in Supporting Information).
1trans photoisomerized to 1cis rapidly upon irradiation at 365
nm light, and the ratio of 1trans/1cis was determined to be
18:82 while a photostationary state was achieved. Isomer-
ization caused a typical change in the 1H NMR spectra of 1
(Figure 1):16 the protons He, Hg and especially Hf shift
dramatically to the high field (∆δ ) -0.99 ppm for He,
-1.03 ppm for Hf, and -0.34 ppm for Hg), and the triazole
was also considerably shifted to the upfield (∆δ ) -0.23
ppm). In the NOE spectrum of 1cis (Figure S7 in Supporting
Information), Hd simultaneously has strong correlations with
Hc, Hb, He and Hg. Because of the properties of azobenzene
and the symmetric structure of 1, it is reasonable to speculate
that 1cis adopted a scissor-like conformation in solution
(10) Intramolecular π-stacking would help to stabilize the conforma-
tion of the helix but hinders the isomerization upon irradiation with UV
light.
(11) (a) Prince, R. B.; Saven, J. G.; Wolynes, P. G.; Moore, J. S. J. Am.
Chem. Soc. 1999, 121, 3114–3121. (b) Khan, A.; Kaiser, C.; Hecht, S.
Angew. Chem., Int. Ed. 2006, 45, 1878–1881.
(12) Mitsunobu, O. Synthesis 1981, 1–28.
(13) Sonogashira, K. In Metal-Catalyzed Cross-Coupling Reactions;
Diederich, F., Stang, P. J. , Eds.; Wiley-VCH: Weinheim, 1998; p 203.
(14) (a) Tornoe, C. W.; Christensen, C.; Meldal, M. J. Org. Chem. 2002,
67, 3057–3064. (b) Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew.
Chem., Int. Ed. 2001, 40, 2004–2021.
(15) Khayer, K.; Sander, W. J. Bangladesh Acad. Sci. 2008, 32, 111–
116.
(16) Haberhauer, G.; Kallweit, C. Angew. Chem., Int. Ed. 2010, 49,
2418–2421.
Org. Lett., Vol. 12, No. 16, 2010
3631

stoichiometry was also confirmed by a Job’s plot (Figure
S17 in Supporting Information).
The titrations of other anionic guests with different size
or shape gave shifting patterns similar to those observed in
the case of chloride, and the fitting analyses show a 1:1
binding stoichiometry for 1trans with all of these studied
anions (Figures S18-S29 in Supporting Information). The
binding constants were determined to be 22 M-1 for bromide,
38 M-1 for hydrogen sulfate, 11 M-1 for iodide and 10 M-1
for nitrate ions (Table 1), providing a preference for 1trans to
1
Figure 1
.
Partial H NMR spectra (400 MHz, d6-acetone, 25 °C)
of 1trans and 1cis. [1] ) 2 mM.
Table 1. Association Constants (M-1) of 1trans and 1cis with
Various Anions at Ambient Temperature and Calculated
(Scheme 1). An overall trans conformation was reproduced
when 1cis was kept in the dark for over 10 days at ambient
temperature, indicating a reversible transformation between
1trans and 1cis (Figure S12 in Supporting Information).
Both of the UV-vis spectra of 1trans and 1cis showed little
change upon addition of nBu4N+Cl- up to 40 equiv (Figures
S13 and S14 in Supporting Information), and therefore the
1
Changes in H Chemical Shift (∆δ) of 1,2,3-Triazole Proton Hd
upon Addition of 40 equiv of Anionsa
Ka (M-1
)
∆δ (ppm)
anions (A-)
1trans
1cis
1trans
1cis
Ka, trans/Ka,
cis
Cl-
Br-
I-
NO3
HSO4
70
22
11
10
38
290
87
31
21
66
1.50
1.11
0.51
0.33
0.27
1.75
1.27
0.63
0.42
0.39
4.1
3.9
2.8
2.1
1.7
1
binding properties of 1trans and 1cis were investigated by H
-
NMR spectroscopy. Titration of nBu4N+Cl- to 1trans pro-
duced a considerable shift in signals of Hc, Hd and Hg (Figure
2 and Figure S15 in Supporting Information), indicative that
-
a The association constants were calculated by WinEQNMR.18 The
relative errors for the values are less than 10%.
-
bind the anions in the order of Cl- > HSO4 > Br- > I- ≈
NO3- as a result of the electrostatic nature of the hydrogen-
bonding interaction.19
We next explored the binding properties of 1cis to all of
1
the anions mentioned above. The H NMR spectra of 1cis
show a change totally different from that of 1trans upon the
titrations of nBu4N+Cl- (Figure 3 and Figure S30 in
Figure 2.
Changes in 1H chemical shift for several protons of 1trans
(d6-acetone, 2 mM, 25 °C) upon addition of chloride ions.
these protons, which were supposed to be located at the inner
cavity of the foldamer, participate in hydrogen bonding to
the chloride ion.17 When 40 equiv of chloride was added,
the triazole proton Hd signal dramatically downshifted from
9.28 to 10.79 ppm and signals for Hb and Hg also downshifted
up to ∆δ ) 0.51 and 0.40 ppm, respectively. The titration
curve was fitted well to a 1:1 binding model by using the
EQNMR program18 to generate the binding constant to be
70 M-1 (Figure S16 in Supporting Information), which is
much smaller than that of the oligo(phenyl-1,2,3-triazole)
foldamers8a as a result of the structural disturbance caused
by the introduction of azobenzene into the strand. The 1:1
1
Figure 3
.
Changes in H chemical shift for several protons of 1cis
(d6-acetone, 2 mM, 25 °C) upon addition of chloride ions.
Supporting Information). After 40 equiv of chloride was
added, an obvious downshift of the signals of Hb, He and Hg
(with ∆δ ) 0.49, 0.24, and 0.20 ppm, respectively) can be
(17) Chang, K.-J.; Kang, B. N.; Lee, M. H.; Jeong, K. S. J. Am. Chem.
Soc. 2005, 127, 12214–12215.
(19) Brooks, S. J.; Garc´ıa-Garrido, S. E.; Light, M. E.; Cole, P. A.; Gale,
P. A. Chem.sEur. J. 2007, 13, 3320–3329.
(18) Hynes, M. J. J. Chem. Soc., Dalton Trans. 1993, 311–312.
3632
Org. Lett., Vol. 12, No. 16, 2010

observed, indicating a strong interaction between all of these
protons and the chloride ion. Besides, the triazole showed a
more significant downfield shift (∆δ ) 1.75 ppm) than that
in the case of 1trans. A Job’s plot confirmed a 1:1 binding
stoichiometry for the complexation (Figure S32 in Supporting
Information). These result may suggest that, in the complex,
the two crossed branches of 1cis clamp the chloride in their
interspace. A fit to the chemical shift titration data gave a
binding constant Ka of 290 M-1, which is 4.1-fold greater
than that in the case of 1trans. The enhancement of the binding
affinity may suggest an improvement in spatial complemen-
tarity among the host-guest system.20,21
Titration of the other anions produced similar changes in
1H NMR spectra of 1cis (Figures S33-S44 in Supporting
Information), showing that 1cis binds these anions in the same
manner as to the chloride. The binding constants of 1cis to
these anions were calculated to be 87 M-1 for bromide, 66
M-1 for hydrogen sulfate, 31 M-1 for iodide and 21 M-1
for nitrate (Table 1), indicative of an overall enhancement
in the binding affinity for all of these anions while the
conformation of 1 transformed from the trans to the cis. It
is evident that the enhancement is more sensitive to anions
with small size. For example, while chloride has 4.1-fold
enhancement, bromide and iodide have 3.9- and 2.8-fold,
respectively. This is because the inner cavity of 1cis is
inevitably smaller than that of 1trans. Also, the enhancement
is highly dependent on the geometric shape of the anions.22
Photoisomerization of 1trans produced the largest changes in
binding affinity for the spherical halides, a moderate change
for the trigonal planar nitrate, but the smallest change for
the tetrahedral anions, hydrogen sulfate. Because comple-
mentarity between the receptor and anion is crucial in
selectivity, we speculated that, in the presence of anions,
1cis preferred to form a spherical cavity to hold the anions
(Scheme 1). This may be evidenced by the comparatively
large downshift of Hb in anion titration experiments.
Figure 4. UV-vis spectra of (a) 1trans (30 µM, acetone) in the
presence of 4 equiv of chloride ions. (b) Irradiation with 365 nm
light for 5 min, then (c) irradiation with visible light for 8 min.
The insert figure reflects the changes of the absorbance at 339 nm
upon alternate irradiation with UV and visible light.
S45 in Supporting Information). 1H NMR investigation also
confirmed the reversible isomerization of 1 in the presence
of anions. In the presence of 4 equiv of chloride, exposure
of 1trans to 365 nm light gives 85% of 1trans converted to 1cis
in the photostationary state. However, 1trans was reobtained
when the mixture was further stored in the dark at ambient
temperature for over 14 days (Figure S46 in Supporting
Information). These data hint that the photoswitch still shows
reversible isomerization in the presence of anions.
To summarize, the azobenzene-triazole based photoswit-
chable foldamer presents a controllable change in binding
affinity for anions, which is highly dependent on the size
and shape of the anions. Although the changes in the anion
binding affinity of the present system is not so significant,
this research still provides a useful method to obtain anion
receptors that can totally change their binding behavior to
anions by using light as a trigger, thus providing a potential
application in light-controlled anion transport and separa-
tion.23
Irradiation of 1trans in the presence of 4 equiv of chloride
for 5 min gave a sharp descent on the intensity of band at
339 nm, but 81% of the intensity was recovered after the
solution was further irradiated with the visible light for 8
min (Figure 4). After several cycles of alternate irradiation
with UV and visible lights, 1 still showed very good
recoverability (Figure 4, insert). When the content of chloride
was further increased to 40 equiv, 1 showed properties
identical to those in the case of 4 equiv of chloride (Figure
Acknowledgment. We thank the CAS “Hundred Talents
Program”, the NNSF of China (20772127 and 20972164),
and the National Basic Research Program of China (Grant
No. 2009CB930802) for financial support.
Supporting Information Available: Synthesis of 1.
Titration experiments, 2D NMR spectra, and the Job’s plots.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(20) Sessler, J. L.; Gale, P. A.; Cho, W.-S. Anion Receptor Chemistry;
RSC Publishing: London, 2006
.
(21) (a) Bisson, A. P.; Lynch, V. M.; Monahan, M. K. C.; Anslyn, E. V.
Angew. Chem., Int. Ed. 1997, 36, 2340–2345. (b) Choi, K.; Hamilton, A. D.
J. Am. Chem. Soc. 2003, 125, 10241–10249. (c) Schmuck, C.; Dudaczek,
OL1014043
J. Tedrahedron Lett. 2005, 46, 7101–7105
(22) Beer, P. D.; Gale, P. A. Angew. Chem., Int. Ed. 2001, 40, 486–
516.
.
(23) Elzenga, J. T. M.; Volkenburgh, E. V. Plant Physiol. 1997, 11,
1419–1426.
Org. Lett., Vol. 12, No. 16, 2010
3633