Specific recognition of β-cyclodextrin by a tetraphenylethene luminogen through a cooperative boronic acid/diol interaction

Article abstract of DOI:10.1002/chem.201102613

An unexpected recognition of β-cyclodextrin (CD) from α- and γ-CDs was achieved. The emission from a diboronic acid-containing tetraphenylethene (TPEDB) was amplified upon addition of β-CD, whereas there was almost no response for α-, and γ-CDs. TPEDB is

Full text of DOI:10.1002/chem.201102613

DOI: 10.1002/chem.201102613
Specific Recognition of b-Cyclodextrin by a Tetraphenylethene Luminogen
through a Cooperative Boronic Acid/Diol Interaction
Yi Liu,[a] Anjun Qin,*[a] Xiujuan Chen,[a] Xiao Yuan Shen,[a] Li Tong,[a] Rongrong Hu,[b]
Jing Zhi Sun,*[a] and Ben Zhong Tang*[a, b]
Cyclodextrins (CDs) are cyclic oligosaccharides composed
of six (a), seven (b), eight (g), or more glucopyranoside
units. CDs have been one of the most extensively studied
hosts and widely applied across multiple fields including
supramolecular chemistry,[1–3] and pharmaceutical[4] and bio-
medical science.[5,6] In such fields, the host–guest interaction
between the hydrophobic cavity of CDs, and guest mole-
cules with proper shape and size, nearly dominates the
entire self-assembly process . Besides offering a hydrophilic
environment, the multiple hydroxyl groups on the rim of
CDs could function as reactive sites for covalent modifica-
tion. Can these hydroxyl groups be involved in the host–
guest interaction process? Or is there a third interaction ex-
isted between CDs and recognized molecules? Exploring
and establishing such an interaction will surely contribute to
fundamental supramolecular chemistry, bring innovation to
the molecular recognition applications, and also help to un-
derstand the cooperative interactions in sophisticated bio-
logical-recognition events.
Enlightened by the reversible reaction between boronic
acid and diols that forms cyclic esters in aqueous media,[7]
and the boron-based recognition of monosaccharide[8] and
oligosaccharide[9] that features dynamic covalent interac-
tions,[10] we are interested in exploring whether such dynam-
ic interactions can be applied to establishing an alternative
binding type for CDs. Although there are a few reports on
the combination of monoboronic acid derivatives with CDs,
the rather weak binding affinity between them prevents the
interaction from playing the key role.[11]
Our success in developing a “light-up” biosensor for d-
glucose (Glu)[12] by a diboronic acid-containing tetrapheny-
lethene moiety (TPEDB) prompted us to investigate the
possible interaction between TPEDB and CDs. As shown in
Figure 1A, the fluorescence (FL) of TPEDB in carbonate
buffer solution remained nearly unchanged at a molar ratio
of less than 1 for TPEDB/b-CD, which is progressively in-
tensified with the addition of b-CD. The highest FL intensity
was recorded in the molar ratio of TPEDB/b-CD of 500,
which was 10.4 times stronger than that of TPEDB. To our
surprise, the increment of FL intensities of TPEDB in car-
bonate buffer solution was very small upon addition of ana-
logues of b-CD, that is, a-CD and g-CD (Figure 1B and the
Supporting Information; S1).
We then tried to understand and explain such unexpected
specific recognition of b-CD from a- and g-CDs experimen-
tally and theoretically. We first supposed that the oligomeri-
zation (model 1 in Figure 2), which is well applied in the ex-
planation of the specific detection of d-Glu by TPEDB, is
the cause for this phenomenon. But this mechanism was
firstly excluded because the condensation reaction between
TPEDB and CDs is difficult to form due to the low affinity
of boronic acid to trans diols in CDs. Furthermore, there
would not be such remarkable difference when TPEDB in-
teracted with a-, b-, and g-CDs due to their structural simi-
larity. Therefore, other mechanism(s) are responsible for the
specific recognition of b-CD by TPEDB.
CDs are well known as host materials in supramolecular
chemistry. Is the host–guest interaction responsible for the
specific recognition of b-CD by TPEDB (see model 2 in
Figure 2)? To verify our conjecture, three water-soluble tet-
raphenylethene (TPE) derivatives 1–3 (structures shown in
Figure 3) were designed and successfully synthesized (see
the Supporting Information; scheme S1).[13] The experimen-
tal results showed that addition of CDs to the aqueous solu-
tions of these water-soluble TPEs caused a slight emission
enhancement (Figure 3, and the Supporting Information;
S2–S5). We thus concluded that the recognition is unlikely
to be caused solely by the host–guest interaction, and the
boronic acid groups are essential for the specific recogni-
tion.
[a] Y. Liu, Prof. A. Qin, X. Chen, X. Y. Shen, L. Tong, Prof. J. Z. Sun,
Prof. B. Z. Tang
MoE Key Laboratory of Macromolecule Synthesis
and Functionalization
Department of Polymer Science and Engineering
Zhejiang University, Hangzhou 310027 (P.R. China)
Fax : (+852)2358-1594
E-mail: qinaj@zju.edu.cn
sunjz@zju.edu.cn
tangbenz@ust.hk
[b] R. Hu, Prof. B. Z. Tang
Department of Chemistry
Institute of Molecular Functional Materials
The Hong Kong University of Science & Technology
Clear Water Bay, Kowloon, Hong Kong (P.R China)
A further question is rationally raised as to whether the
two boronic acid groups are necessary for such recognition.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201102613.
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COMMUNICATION
Figure 2. Supposed interaction of TPEDB and b-CD.
Figure 1. A) FL spectra of TPEDB (10 mm) in carbonate buffer (0.2m,
pH 10.5) containing 0.5 vol% DMSO in the presence of different amount
of b-CD. B) Variation in the FL intensity (I) of TPEDB (10 mm) with
*
their peaked values as a function of the concentration of CDs; a-CD ( ),
~
*
b-CD ( ), and g-CD ( ). I0 presents the intensity in absence of CDs.
Figure 3. FL responses of water-soluble TPE derivatives (10 mm) in car-
bonate buffer (0.2m, pH 10.5) containing 0.5 vol% DMSO to CDs
(5.0 mm). Inset: chemical structures of TPE derivatives of 1–3, and
TPEMB; FL response of TPEMB (10 mm) in carbonate buffer containing
20 vol% DMSO to CDs (5.0 mm).
Inset: chemical structure of TPEDB.
To answer this question, and to further uncover the underly-
ing recognition mechanism, monoboronic acid-functional-
ized TPE (TPEMB) was prepared (see the Supporting Infor-
mation; Scheme S1).[12] The emission behavior of TPEMB
was similar to compounds 1–3 when CDs were added into
its aqueous solution (Figure 3, see the Supporting Informa-
tion; S6 and S7), ruling out the dual recognition mechanism
including the cavity of CDs (host–guest interaction) and
monoboronic acid reaction with diols (model 3 in Figure 2),
which is used to interpret the findings of borate-CDs com-
plex-based chiral separation of diol enantiomers by capillary
electrophoresis.[14] It is further concluded that the two bor-
onic acid groups are prerequisite for the specific recognition
of b-CD.
To collect additional information about the specific inter-
action mechanism between TPEDB and b-CD, an induced
circular dichroism (ICD) technique was used. It is well
known that CDs are chiral hosts and capable of inducing the
circular dichroism signals of bound achiral guests, although
they have no signals in the detectable wavelength of the
equipment. Furthermore, a general relationship between the
sign, intensity of the ICD signal, and the spatial arrange-
ment of guest molecules and CDs has been well document-
ed.[15] Delightfully, TPEDB possesses different ICD respons-
es upon addition of CDs, which enabled us to distinguish
their mutual interactions.
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A. Qin, J. Zhi Sun, B. Zhong Tang et al.
As shown in Figure 4A, a negative ICD signal of TPEDB
was recorded when b-CD was added, suggesting that there
is interaction between its phenyl rings and the b-CD cavity.
firmed that the two boronic acid groups on TPEDB play a
critical role in the interaction between TPEDB and b-CD.
The FL and ICD responses of TPEs are consistent on b-
and g-CDs but different on a-CD, shedding light on the
binding model of TPEDB and CDs. As a classical polyaryl-
vinyl propeller, TPEs are racemic mixtures of two rapidly
interconverting enantiomers of M- and P helicities with op-
posite arrangement of phenyl rotors.[16] The absences of ICD
signal of TPEs upon addition of a-CD could be due to the
understanding that the interaction of a-CD with both con-
formations of TPEs is identical, and thus balances the posi-
tive and negative circular dichroism signals.[17] Meanwhile,
the a-CD could interact with one phenyl ring on the TPEs
regardless of helicity, which would partially restrict the rota-
tion of this phenyl ring but leave three phenyl rings freely
rotated, resulting in a weak FL according to the restriction
of intramolecular rotation (RIR) mechanism[18] of aggrega-
tion-induced emission.[19] g-CD, however, possesses a rela-
tively larger cavity than a- and b-CDs. Thus, it could proba-
bly interact with two phenyl rings of TPEs simultaneously
and be able to enrich one enantiomer conformation by
enantioselective complexation. Furthermore, such an inter-
action would also boost the emission of TPEs by confining
the rotation of the phenyl rings in a larger degree than that
of a-CD, resulting in a relatively higher ICD signal and
stronger FL.
The strong FL intensity and high ellipticity value of
TPEDB upon addition of b-CD are extraordinary. The inter-
action mechanism between them should be different from
that of TPEs with other two CDs. On the bases of above re-
sults, we speculate that TPEDB may be anchored on the
outside edge of b-CD through the host–guest-aided coopera-
tive boronic acid/diols dynamic covalent-binding interaction
in the aqueous solution with a pH of 10.5 (model 4 in
Figure 2, the Supporting Information, Scheme S2).[8,9] The
phenyl rings on TPEDB could probably first interact with
the b-CD aided by the host–guest interaction, and then the
diboronic acids react with the adjacent two hydroxyl groups
on the alternative glucoside units to form cyclic boronate,
although the diols possess trans configuration with dihedral
angles of near 618. Furthermore, the overall interaction
strength will be amplified through the binding cooperativi-
ty.[20] When the TPEDB is fixed on the b-CD by the boro-
nate bonds, the intramolecular rotations of its phenyl rings
will be restricted, which will activate the RIR process and
open up the radiative decay channel. The ICD signal will
also be intensified by the bonding interaction at the same
time, probably due to fixing of one enantiomer with the aid
of host–guest interactions.
Figure 4. A) ICD spectra of TPEDB (10 mm) in carbonate buffer (0.2m,
pH 10.5) containing 0.5 vol% DMSO in the presence of different amount
of b-CD. B) Variation in the ellipticity values (q) with CD concentra-
~
*
*
tions; a-CD ( ), b-CD ( ), and g-CD ( ).
Moreover, the signal became progressively stronger with
each addition of b-CD. However, almost no ICD signals of
TPEDB were observed upon addition of a-CD, but a small-
er negative signal of TPEDB was recorded for g-CD, which
was gradually intensified until reaching the plateau at a g-
CD concentration of 50 mm (Figure 4B and the Supporting
Information; S8). For comparison, the ICD signals of 1–3,
and TPEMB upon addition of CDs were also measured (see
the Supporting Information, Figure S9). Similar phenomena
(like the ICD signals of TPEDB upon addition of a- and g-
CDs) were observed but rather weaker negative ICD signals
of TPEs were induced by b-CD. These results further con-
To ascertain the binding sites of TPEDB on the b-CD, we
optimized the geometry of the former and analyzed the
crystal structure of the latter. According to the optimized
geometry of TPEDB (see the Supporting Information; Fig-
ure S10), the distance between two oxygen atoms in separat-
ed boronic acids is 13.98 and 10.08 ꢁ for the trans- and cis
isomers, respectively. The average distances of the pairs of
2,3-diols on separated glucosides measured from the crystal
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Specific Recognition of b-Cyclodextrin
COMMUNICATION
structure of b-CD are 5.43, 9.73, and 12.15 ꢁ, respectively.[21]
The diols with the distance of 9.73 ꢁ, which lie in the alter-
nate glucosides of b-CD are well matched to react with the
boronic acids of the cis-TPEDB. In contrast, the distance
mismatch of 2,3-diols in the alternate glucosides of a- and g-
CDs for diboronic acids of TPEDB is probably responsible
for the failure of forming the host–guest interaction-aided
boronic acid/diol dynamic covalent bond.
The optimized structure of the 1:1 complex formed by
TPEDB with a cis conformation and b-CD suggests that the
TPE moiety is tilted above the entrance of the nanocavity
of b-CD, and blocks the attack from another TPEDB on the
wider rim of the b-CD (see the Supporting Information, Fig-
ure S11). Therefore, the formation of the 2:1 complex was
disfavored. Furthermore, the non-linear regression analysis
of the fluorescence changes of TPEDB versus concentration
of b-CD also indicates the formation of the 1:1 stoichiomet-
ric complex between TPEDB and b-CD with an overall
binding constant (K) of 686mÀ1 (assuming that TPEDB con-
sists of an equal molar ratio of the cis- and trans isomer;[22]
see the Supporting Information, Figure S12).[23]
Since the diols on b-CD possess a trans configuration, the
boronic acid/diols reaction is a dynamic process with a low
binding constant.[9c] The addition of more reactive and favor-
able cis diols, such as monosaccharide, to the system of
TPEDB and b-CD will destruct the boronate bonds and
form a new compound of TPEDB and monosaccharide.
The FL intensity of the system decreased upon addition
of the monosaccharide of d-Glu, d-mannose (Man), d-galac-
tose (Gal), or d-fructose (Fru; Figure 5A and the Support-
ing Information; S13). This result indicates that the diboron-
ic acids on the TPEDB are more likely to react with the cis
diols on the monosaccharide than the trans-2,3-diols on the
b-CD. When the boronic acids on TPEDB with a concentra-
tion of 10 mm are bound by the diols on the monosacchar-
ides, the phenyl rings of the resultant compounds could
rotate more freely, which may activate the non-radiative
decay and lead to the emission decrease. The FL attenuation
rates follow the order of Fru>Gal>Man>Glu, which is
consistent with the binding constants (Ka) of saccharide with
phenylboronic acids (Ka, sugar/MÀ1 =160 for Fru, 15 for Gal,
13 for Man, and 4.6 for Glu).[24] The ICD of TPEDB and b-
CD also disappeared after the addition of d-Fru. (see the
Supporting Information, Figure S14), further suggesting the
destruction of the system. Addition of Fru to the systems of
TPEDB and a-CD or g-CD has increased the FL slightly,
confirming our speculation that boronic acid/diol-binding
does not contribute to the boosted emission in these systems
(see the Supporting Information, Figure S15). The slight in-
crement of FL could probably be attributed to increased vis-
cosity of the media after the addition of sugar.
Figure 5. A) Variation in the FL intensity (I) of the mixture of TPEDB
(10 mm) and b-CD (5.0 mm) at 452 nm as a function of the concentration
of monosaccharide in a carbonate buffer containing 0.5 vol% DMSO
(pH 10.5). I0 is the intensity in absence of a monosaccharide, Glu=d-glu-
~
*
*
cose ( ), Man=d-mannose ( ), Gal=d-galactose ( ), Fru=d-fructose
~
(
). B) Variation in the FL intensity (I) of the mixture of TPEDB
(10 mm) and b-CD (5.0 mm) at 452 nm as a function of the concentration
of guest molecular in a carbonate buffer containing 0.5 vol% DMSO
(pH 10.5). I0 is the intensity in absence of a guest molecular. dl-Phe=
*
*
dl-phenylalanine ( ), l-Phe=l-phenylalanine ( ), t-Ca=trans-cinnamic
~
~
acid ( ), Ada=1-adamantecarboxylic acid ( ).
binding constants between guests and b-CD enables the
former to enter the hydrophobic cavity of b-CD, which will
destruct or prohibit the formation of the 1:1 emissive com-
plex of TPEDB and b-CD.[26] A similar attenuated ICD
signal was also observed when Ada was mixed into the solu-
tion of TEPDB and b-CD (see the Supporting Information,
Figure S18).
In summary, we have systematically investigated the inter-
actions between TPEDB and CDs and developed a concep-
tually new binding model for b-CD based on host–guest in-
teraction-aided boronic acid/diol-binding. The two boronic
Furthermore, the emission of the system of TPEDB and
b-CD also decreased upon addition of guest molecules with
high complexation constants, such as dl-phenylalanine (dl-
Phe), l-phenylalanine (l-Phe), trans-cinnamic acid (t-Ca),
and 1-adamantecarboxylic acid (Ada), regardless of the ad-
dition sequence (Figure 5B, S16, and S17).[25] The higher
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A. Qin, J. Zhi Sun, B. Zhong Tang et al.
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acids on TPEDB could cooperatively bind to two pairs of al-
ternative diols on a b-CD, in which the FL was intensified
due to the RIR process. Thus, specific recognition of b-CD
was realized from a- and g-CDs due to the fit-distance-
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rims. Meanwhile, the interaction was proven to be a dynam-
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Acknowledgements
This work is partially supported by the National Science Foundation of
China (20974028, 20974098, 50873086, and 21074113), the Natural Sci-
ence Foundation of Zhejiang Province (Z4110056), the Ministry of Sci-
ence and Technology of China (2009CB623605), the Research Grants
Council of Hong Kong (603509, HKUST2/CRF/10), and the University
Grants Committee of Hong Kong (AoE/P-03/08). The authors thank Dr.
C. M Deng and Professor Z. Shuai for theoretical calculations. B.Z.T. is
grateful for the support from the Cao Guangbiao Foundation of Zhejiang
University.
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Keywords: cooperative effects · cyclodextrins · host–guest
systems · molecular recognition · tetraphenylethene
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Received: August 22, 2011
Published online: December 1, 2011
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