Spectrophotometric study of selective binding behaviors of dye molecules by pyridine-and bipyridine-modified ?2-cyclodextrin derivatives with a functional tether in aqueous solution

Article abstract of DOI:10.1021/jp046363t

Four ?2-cyclodextrin (?2-CD) derivatives bearing pyridine or bipyridine linkers, i.e., mono[6-(3-pyridinecarboxamide)ethyleneamino-6-deoxy]-?2-CD(2), mono[6-(4-pyridinecarboxamide)ethyleneamino-6-deoxy]-?2-CD (3), N,Na?2-bis(2-aminoethyl)-2,2a?2-bipyridine-4, 4a?2-dicarboxamide-bridged bis(6-amino-6-deoxy-?2-CD) (4), N,Na?2-bis(2-aminoethyl)-2,2a?2-bipyridine-3, 3a?2-dicarboxamide-bridged bis(6-amino-6-deoxy-?2-CD) (5), and their copper-(II) complexes (6 and 7) were selected as molecular receptors to explore the conformation-function relationship of oligo(?2-CD)s. The original conformations of hosts 4-7 and their inclusion complexation behaviors with some guest molecules, i.e., ammonium 8-anilino-1-naphthalenesulfonate (ANS), sodium 6-(p-toludino)-2-naphthalenesulfonate (TNS), and rhodamine B (RhB), were comprehensively investigated by means of UV-vis, 2D NMR, and fluorescence spectroscopy. The results indicated that these oligo(?2-CD)s, especially bis(?2-CD) 5 and its copper(II) complex 7, exhibited the significantly enhanced binding abilities toward guest molecules as compared with native ?2-CD. Typically, hosts 5 and 7 efficiently enhanced the original binding ability of native ?2-CD toward ANS by a factor of 38-42 times. These increased binding abilities of oligomeric hosts were discussed from the viewpoint of the size/shape-fit and multipoint recognition between host and guest.

Full text of DOI:10.1021/jp046363t

J. Phys. Chem. B 2004, 108, 19541-19549
19541
Spectrophotometric Study of Selective Binding Behaviors of Dye Molecules by Pyridine-
and Bipyridine-Modified â-Cyclodextrin Derivatives with a Functional Tether in Aqueous
Solution
Yu Liu,* Xue-Qing Li, Yong Chen, and Xu-Dong Guan
Department of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Nankai UniVersity,
Tianjin 300071, P. R. China
ReceiVed: August 12, 2004; In Final Form: September 24, 2004
Four â-cyclodextrin (â-CD) derivatives bearing pyridine or bipyridine linkers, i.e., mono[6-(3-pyridinecar-
boxamide)ethyleneamino-6-deoxy]-â-CD (2), mono[6-(4-pyridinecarboxamide)ethyleneamino-6-deoxy]-â-CD
(3), N,N′-bis(2-aminoethyl)-2,2′-bipyridine-4,4′-dicarboxamide-bridged bis(6-amino-6-deoxy-â-CD) (4), N,N′-
bis(2-aminoethyl)-2,2′-bipyridine-3,3′-dicarboxamide-bridged bis(6-amino-6-deoxy-â-CD) (5), and their copper-
(II) complexes (6 and 7) were selected as molecular receptors to explore the conformation-function relationship
of oligo(â-CD)s. The original conformations of hosts 4-7 and their inclusion complexation behaviors with
some guest molecules, i.e., ammonium 8-anilino-1-naphthalenesulfonate (ANS), sodium 6-(p-toludino)-2-
naphthalenesulfonate (TNS), and rhodamine B (RhB), were comprehensively investigated by means of UV-
vis, 2D NMR, and fluorescence spectroscopy. The results indicated that these oligo(â-CD)s, especially bis(â-
CD) 5 and its copper(II) complex 7, exhibited the significantly enhanced binding abilities toward guest
molecules as compared with native â-CD. Typically, hosts 5 and 7 efficiently enhanced the original binding
ability of native â-CD toward ANS by a factor of 38-42 times. These increased binding abilities of oligomeric
hosts were discussed from the viewpoint of the size/shape-fit and multipoint recognition between host and
guest.
Introduction
the linker group can significantly alter the conformation and
binding behavior of the resultant bis(â-CD)s. Although this
concept is drawn from a rather limited variation of bis(â-CD)
species, we ensure that it should be extended more generally to
a wide variety of synthetic receptors. Therefore, we wish to
report contrastive studies on the conformation and binding
behavior of bis(â-CD)s with 2,2′-bipyridine-4,4′-dicarboxamide
and 2,2′-bipyridine-3,3′-dicarboxamide linkers as well as their
copper(II) complexes (Chart 1). It is our special interest to
explore how the bridge group affects the cooperative binding
of bis(â-CD)s and further understand the factors governing the
molecular multiple recognition mechanism.
It is well known that cyclodextrins (R-, â-, and γ-CDs) are
a class of cyclic oligosaccharides with six to eight D-glucose
units linked by R-1,4-glucose bonds which can accommodate
various guest molecules in their truncated cone-shaped hydro-
phobic cavity either in aqueous solution or in the solid state.1-3
Possessing dual hydrophobic cavities in a close vicinity and a
nucleophilic or electrophilic linker with a good structural variety
in a single molecule, bridged CD dimers can greatly enhance
the original binding ability and molecular selectivity of parent
CD through the potential cooperative binding of two adjacent
CD units4-12 and therefore be successfully employed in several
areas of science and technology as an excellent model system
mimicking substrate-specific interaction of enzymes.13,14 More-
over, there is another advantage for CD dimers upon inclusion
complexation with model substrates. That is, besides the
cooperative sandwich binding of two CD cavities with sub-
strates, the linker groups can also provide the additional binding
interactions toward substrates through several noncovalent
interactions such as van der Waals, hydrophobic, hydrogen-
bond, electrostatic, or electron-transfer interactions. To under-
stand the role of linker group in the molecular recognition, a
number of functional groups, such as alkanedioates,15,16 disul-
fides,17,18 bipyridines,19,20 and imidazole,21,22 have been selected
as the linkers between two CD units. We recently reported the
molecular recognition behaviors of a series of azacyclodextrins,23
especially the bis(â-CD)s with 2,2′-bipyridine-4,4′-dicarboxylic
bridges.24 In this work, we find that fine-tuning the structure of
Results and Discussion
Synthesis. As illustrated in Scheme 1, bipyridine-bridged bis-
(â-CD) 5 is synthesized in a yield of 20% by the reaction of
2,2′-bipyridine-3,3′-dicarboxylic dichloride with mono[6-(2-
aminoethyleneamino)-6-deoxy]-â-CD, while two mono-modi-
fied â-CDs, i.e., mono[6-(3-pyridinecarboxamide)ethylene-
amino-6-deoxy]-â-CD (2) and mono[6-(4-pyridinecarbox amide)-
ethyleneamino-6-deoxy]-â-CD (3), are synthesized in relatively
high yields (56% for 2, 50% for 3) as reference compounds.
The further reactions of bis(â-CD) 5 with copper(II) perchlorate
give the copper(II) complex 7 in a moderate yield (40%). In
our previous report,23 we demonstrated that coordination of bis-
(â-CD) 4 with copper(II) perchlorate displays a 2:3 stoichiom-
etry, which indicates that besides each bis(â-CD) unit associating
with one copper(II) ion, two bis(â-CD) components participate
in the binding of the third copper(II) ion. However, when
altering the 2,2′-bipyridine-4,4′-dicarboxamide linker in bis(â-
CD) 4 to the 2,2′-bipyridine-3,3′-dicarboxamide group, the
* To whom correspondence should be addressed. Phone: +86-022-
23503625. Fax: +86-022-23503625. E-mail: yuliu@public.tpt.tj.cn.
10.1021/jp046363t CCC: $27.50 © 2004 American Chemical Society
Published on Web 11/17/2004

19542 J. Phys. Chem. B, Vol. 108, No. 50, 2004
Liu et al.
CHART 1
resultant bis(â-CD) 5 will adopt a different coordination
stoichiometry with copper(II) ion. Figure 1 shows a representa-
Unfortunately, our repeated attempts to prepare single crystals
of â-CD dimers and their metal complexes were unsuccessful.
Therefore, to reveal the reason for the different coordination
stoichiometry of bis(â-CD)s 4 and 5 with copper(II) ion, we
perform a molecular modeling study with the CAChe 3.2
program (Oxford Molecular Co., 1999) and obtain the energy-
optimized structures of bis(â-CD)s 4 and 5. The initial geometry
of â-CD used in these calculations is taken from the crystal
structure described in the literature,25 and the energy of these
structures is minimized using the MM2 force field. Although
the computed structures may not taken as direct evidence of
the actual structures, these computed models can still provide
some useful information about the possible geometries of bis-
(â-CD)s.26 As shown in Figure 2, the bipyridine group in bis-
(â-CD) 4 is coplanar and exists in a cis conformation. Further
investigations with a Corey-Pauling-Koltun (CPK) molecular
model demonstrate that three copper(II) ions in metallooligo-
(â-CD) 6 adopt two types of four-coordinate geometry upon
coordination with bipyridine dicarboxamide bridge (Chart 1).
That is, the copper(II) ion located between two bis(â-CD)
components (Cu1) adopts a tetrahedral geometry upon coordina-
tion with two bipyridine groups, while either of the other two
copper(II) ions (Cu2 and Cu3) adopts a planar geometry when
coordinated with four -NH- fragments in the linker group.
These two factors jointly result in a perpendicular conformation
of metallooligo(â-CD) 6 as shown in Chart 1. However, bis-
(â-CD) 5 is found to adopt a trans conformation as shown in
Figure 2, which may be attributed to the steric hindrance
between two carbonyl groups at the 3,3′-positions of bipyridine.
Figure 1. Job’s plot of 5/Cu(II) ([5] + [Cu2+] ) 1 × 10-4 mol dm-3
system by UV-vis spectra.
)
tive spectrophotometric titration curve to determine the coor-
dination stoichiometry of 5 with copper(II) ion. As can be seen
in Figure 1, the Job’s plot for the 5/Cu(II) system displays a
maximum at 0.67 which corresponds to a 2:1 5/Cu(II) stoichi-
ometry. This result indicates that although possessing four
-NH- fragments and one bipyridine group in each bis(â-CD)
5, two bis(â-CD)s 5 can only coordinate with one copper(II)
ion. This 2:1 stoichiometry for 5/Cu(II) complex is also verified
by elemental analysis.
Conformation. It is well known that elucidation of the crystal
structure is one of the most convincing methods of unequivo-
cally illustrating the geometrical structure of CD derivatives.

Study of Selective Binding Behaviors
J. Phys. Chem. B, Vol. 108, No. 50, 2004 19543
SCHEME 1
Figure 3. UV-vis spectra of bis(â-CD)s 4 and 5 in aqueous solution
at 25 °C ([4] ) [5] ) 0.9 × 10-4 mol‚dm-3).
carbon-carbon bond, the absorption intensities of these two
bands will quench, accompanied by hypsochromic shifts of the
absorption maximums, and sometimes only one absorption band
can be observed. As illustrated in Figure 3, bis(â-CD) 4 shows
two absorption bands at 241 (ꢀ ) 191 510 mol-1 dm-3 cm-1
)
and 294 nm (ꢀ ) 10 130 mol-1 dm-3 cm-1), respectively,
assigned to absorptions of the coplanar bipyridine chromophore.
However, bis(â-CD) 5 only gives one absorption band at 270
nm (ꢀ ) 9710 mol-1 dm-3 cm-1). This phenomenon further
verifies the twist of the bipyridine group in bis(â-CD) 5.
Interestingly, the absorption intensity of bis(â-CD) 4 at 294
nm obviously increases (ꢀ from 10 130 to 12 770 mol-1 dm-3
cm-1) after coordination with copper(II) ion, accompanying a
significant bathochromic shift (20 nm) of the absorption peak.
Moreover, the other absorption peak of 4 at 241 nm changes to
a shoulder after coordination with copper(II) ion, as illustrated
in Figure 4a. These phenomena, together with the 2:3 coordina-
tion stoichiometry determined by the Job’s plot, may indicate
a relatively strong metal-ligand coordination involving two bis-
(â-CD)s and three copper(II) ions as shown in Chart 1. However,
the UV spectrum of metallooligo(â-CD) 7 is quite similar to
that of its precursor 5 (Figure 4b), except a slight increase of
the absorption intensity at 270 nm (ꢀ from 9710 to 10 150 dm-3
cm-1), which indicates that the bipyridine units in 7 still remain
in the the trans conformation. These results will be greatly
helpful to understand their binding mode with guest molecules.
Fluorescence Titrations. For a more qualitative assessment
of the inclusion complexation behavior of bis(â-CD)s and their
copper(II) complexes, the spectral titrations of hosts 1-7 with
ammonium 8-anilino-1-naphthalenesulfonic acid (ANS), sodium
6-(p-toludino)-2-naphthalenesulfonate (TNS), and rhodamine B
(RhB) are performed at 25 °C in aqueous solution by fluores-
cence spectroscopy. Figure 5 shows the typical spectral changes
of ANS with the gradual addition of host 5. The relative
fluorescence intensity of ANS gradually enhances with an
increase of the concentration of 5. Because ANS barely
fluoresces in aqueous solution but emits a strong fluorescence
in nonpolar environment, the spectral changes observed indicate
that the aromatic group of ANS is embedded into the hydro-
phobic â-CD cavities, forming a host-guest inclusion complex.
Further study indicates that the pH value of the solution does
not change significantly during the experimental procedure.
These results lead us to deduce that the binding behavior is
dependent on the individual structural features of host and guest.
The stoichiometry for the inclusion complexation of hosts
4-7 with guest molecules is determined through the Job’s
experiments by fluorescence spectroscopy. By treating each bis-
(â-CD) unit in hosts 4-7 as a host unit, all of the Job’s plots
show maxima at a molecular fraction of bis(â-CD) of 0.5, which
In this conformation two pyridine rings in the linker group are
not coplanar but twist to each other with a dihedral angle of
about 30° and two ethylenediamino chains adopt a “tilt-out”
Figure 2. MM2-optimized structure of bis(â-CD)s 4 and 5 (â-CD
cavities are omitted).
conformation relative to the bipyridine group. Therefore, these
two ethylenediamino chains are too distant to enable coordina-
tion with copper(II) ion, which consequently results in the 2:1
5/Cu(II) coordination stoichiometry.
Another piece of evidence for the different conformations of
bis(â-CD)s 4 and 5 comes from the UV spectra. Generally, the
UV spectra of bipyridine and its derivatives have a great
relationship with their conformations.27 A coplanar bipyridine
chromophore usually shows two absorption bands in the
ultraviolet region. If two pyridine units twist along the central

19544 J. Phys. Chem. B, Vol. 108, No. 50, 2004
Liu et al.
Figure 4. UV-vis spectra of (a) 4 and 6 ([4] ) [6] ) 0.9 × 10-4 mol‚dm-3) and (b) 5 and 7 ([5] ) [7] ) 0.9 × 10-4 mol‚dm-3).
TABLE 1: Stability Constants (KS) and Gibbs Free Energy
Changes (-∆G°) for the Inclusion Complexation of Guest
Dyes with Hosts 1-7 in Aqueous Solution at 25 °C
host guest λex/nm
KS/M-1
log KS -∆G°/kJ mol-1 ref
1
2
3
4
5
6
7
ANS
TNS
RhB
ANS
TNS
RhB
ANS
TNS
RhB
ANS
TNS
RhB
ANS
TNS
RhB
ANS
TNS
RhB
ANS
TNS
RhB
350
350
520
350
350
520
350
350
520
350
350
520
350
350
520
350
350
520
350
350
520
112
2.05
3.56
3.69
2.58
3.66
3.50
2.45
3.53
3.41
2.82
3.88
4.06
3.67
4.12
3.80
3.59
4.24
4.16
3.63
4.01
4.13
11.70
20.30
21.07
14.74
20.9
a
a
a
b
b
b
b
b
b
a
a
a
b
b
b
a
a
a
b
b
b
3590
4900
383
4590
3160
281
3410
2560
665
7610
11 360
4650
13 100
6360
3900
17 300
14 300
4230
10 170
13 500
19.98
13.98
20.16
19.45
16.11
22.16
23.15
20.93
23.50
21.71
20.50
24.19
23.72
20.70
22.87
23.58
Figure 5. Fluorescence spectral changes of ANS (1.0 × 10-5
mol‚dm-3) and the nonlinear least-squares analysis (inset) of the
differential intensity (∆F) to calculate the complex stability constant
(Ks) upon addition of 5 (0-375 × 10-6 mol‚dm-3 from a to m) in
aqueous solution.
indicates 1:1 inclusion complexation stoichiometry between a
host unit and a guest molecule. Moreover, the Job’s experiments
for inclusion complexation of mono-modified â-cyclodextrins
2 and 3 with guest molecules are also performed under
comparable conditions to give 1:1 stoichiometry.
a Reference 24c. b This work.
Validating the 1:1 stoichiometry, where each bis(â-cyclo-
dextrin) moiety in 4-7 is treated as a host unit, inclusion
complexation of a guest (Dye) with a host can be expressed by
the following equation
molecular n:n binding mode (Figure 6d). To estimate the actual
binding mode of bis(â-CD) 5 with guest molecule, we perform
2D NMR experiments to investigate the structure of the host-
guest inclusion complex since two protons closely located in
space can induce an NOE correlation between the relevant
protons in the NOESY or ROESY spectrum. In a preliminary
experiment the ROESY spectra of hosts 4 and 5 show no NOE
correlations between the protons of 2,2′-bipyridine-dicarboxa-
mide linker (aromatic protons and ethylene protons) and the
interior protons of â-CD (H-3 and H-5), indicating that the linker
group of bis(â-CD) is not self-included in the â-CD cavity. By
comparing the ROESY spectra of 4 and 5 we can see that the
ROESY spectrum of 4 is more complicated than that of 5 in
the aromatic region (Figure 7). This phenomenon should be
reasonable because the cis conformation of 4 enables close
distances among the bipyridine protons and thus results in more
complicated NOE signals. Unfortunately, the conformational
features of hosts 6 and 7 are unable to be estimated by 2D NMR
due to the paramagnetic disturbance of copper(II).
Ks
dye + host y\z dye‚host
Therefore, the effective stability constant (KS)23 could be
calculated from analysis of the sequential changes in fluores-
cence intensity (∆F) at varying host concentrations by using a
nonlinear least-squares method according to the curve-fitting
equation.28 Figure 5 (inset) illustrates a typical curve-fitting plot
for titration of ANS with host 5, which shows excellent fits
between the experimental and calculated data. In repeated
measurements the Ks values are reproducible within an error of
(5%. The Ks values obtained are listed in Table 1 along with
the Gibbs free energy changes (-∆G°).
Binding Mode. We demonstrated that the cis conformer 4
adopts a cooperative sandwich binding mode upon inclusion
complexation with guest molecule,23 where two side groups of
the guest molecule are embedded into the hydrophobic cavities
from the primary side of â-CD to form a sandwich inclusion
complex, as illustrated in Figure 6a. However, for the trans
conformer 5, the CPK model studies give three possible binding
modes, i.e., the intermolecular 2:2 binding mode (Figure 6b),
the intramolecular 1:1 binding mode (Figure 6c), and the inter-
Moreover, the ROESY spectrum of an equimolar mixture of
host 5 with T-shaped guest RhB (Figure 8) displays the clear
NOE correlations between the H-3 and H-5 protons of â-CD
and the methyl protons of diethylamino groups in RhB (peaks
b) as well as the NOE correlations between the H-5 protons of
â-CD and the aromatic protons of diethylaminophenyl group

Study of Selective Binding Behaviors
J. Phys. Chem. B, Vol. 108, No. 50, 2004 19545
Figure 6. Possible binding modes of bis(â-CD)s 4 and 5 with guest molecule.
Figure 7. Partial ROESY spectra of bis(â-CD)s 4 (left) and 5 (right) in D2O with a mixing time of 200 ms at 298 K.
in RhB (peaks a). Further examination of the intensities of these
correlations indicates that the correlations between the H-5
protons of â-CD and the methyl protons of diethylamino groups
in RhB are stronger than those between the H-3 protons of â-CD

19546 J. Phys. Chem. B, Vol. 108, No. 50, 2004
Liu et al.
Figure 8. ROESY spectrum of a mixture of host 5 and RhB ([5] ) [RhB] )3.0 × 10-3 mol‚dm-3) in D2O with a mixing time of 200 ms at
298 K.
and the methyl protons of diethylamino groups in RhB. Since
both the H-3 and H-5 protons are located at the interior of the
â-CD cavity and the H-5 protons are located near the primary
side (narrow side) of the cavity but the H-3 protons near the
secondary side (wide side) of cavity, these NOE correlations
indicate that the diethylaminophenyl group of RhB is accom-
modated in the â-CD cavities from the primary side. This result
excludes the possibility of an intermolecular n:n binding mode,
where the guest molecule is included hypothetically in the â-CD
cavities from the secondary side. Moreover, Figure 8 does not
display the NOE correlations between the protons of the
diethylaminophenyl group in RhB and the protons of the linker
group in 5, which excludes the possibility of the intramolecular
1:1 binding mode. According to this binding mode, one side
group of the guest molecule should be located near the linker
group of the host bis(â-CD) and give the corresponding NOE
correlations. Therefore, we can deduce that bis(â-CD) 5 actually
adopts an intermolecular 2:2 binding mode upon complexation
with guest RhB, where two diethyldiaminophenyl groups of RhB
are cooperatively included by two â-CD cavities from the
primary side.
The intermolecular 2:2 binding mode is also verified by the
ROESY spectrum of the 5/ANS system. The simple reason for
choosing ANS as the guest molecule to examine the binding
geometry of bis(â-CD) is that ANS possesses two different
aromatic fragments, i.e., phenyl and naphthyl groups, and their
chemical shifts can be easily recognized in the 1H NMR
spectrum. As can be seen from Figure 9, the ROESY spectrum
of an equimolar mixture of host 5 and ANS displays NOE
correlations between the Ha protons of the phenyl group in ANS
and the H-3/H-5 protons of â-CD (peaks a), the NOE correla-
tions between the Hb protons of the phenyl group in ANS and
the H-3 protons of â-CD (peaks b), as well as the NOE
correlations between the Hc protons of the naphthyl group in
ANS and the H-3/H-5 protons of â-CD (peaks c). These results
indicate that the phenyl and naphthyl groups of ANS are
separately included by two â-CD cavities from the primary side.
From the above 2D NMR results, together with the 1:1 host-
guest inclusion complexation stoichiometry obtained from the
Job’s experiments for each bis(â-CD) unit, we can also confirm
that bis(â-CD) 5 adopts an intermolecular 2:2 binding mode
upon complexation with ANS.
On the basis of the conformations of metallooligo(â-CD)s 6
and 7, the CPK model studies give their possible binding modes
with guest molecules. As illustrated in Figure 10a, two bipy-
ridine units in 6 are perpendicular to each other and each bis-
(â-CD) unit adopts a sandwich binding mode upon inclusion
complexation with a guest molecule. However, metallooligo-
(â-CD) 7 adopts a double-helical conformation (Figure 10b),
where two bipyridine units are nearly parallel to each other,
and each bis(â-CD) unit provides a â-CD cavity to form the
sandwich inclusion complex with a guest molecule. It is
noteworthy that the bipyridine dicarboxamide bridge in these
dual hosts acts as both a connector between two â-CD cavities
and a versatile coordinating site for metal ions. Moreover, the
copper(II) ion(s) introduced in the bridge not only adjusts and
orients the â-CD cavities and the linker group to fit the size/
shape of guest molecule, but also acts as an additional guest
binding site(s) through the electrostatic and/or electron-transfer
interactions with the accommodated guest molecules. These
advantages, together with the cooperative binding of two â-CD
cavities with one guest molecule, will significantly enhance the
original binding ability of parent cyclodextrin, which will be
discussed below.

Study of Selective Binding Behaviors
J. Phys. Chem. B, Vol. 108, No. 50, 2004 19547
Figure 9. ROESY spectrum of a mixture of host 5 and ANS ([5] ) [ANS] ) 3.0 × 10-3 mol‚dm-3) in D2O with a mixing time of 200 ms at
298 K.
However, bis(â-CD)s 4 and 5 and their copper(II) complexes 6
and 7 significantly enhance the original binding ability of parent
â-CD toward guest molecules by a factor of 1.3-42. This result
may be attributed to a multiple recognition behavior of these
oligomeric hosts toward guest molecules. In addition to the
cooperative binding of one guest molecule by two â-CD cavities,
the linker group located near the accommodated guest also
provides some additional interactions with guest molecule. These
factors jointly contribute to the stronger host-guest association
achieved by oligo(â-CD)s in comparison to monomeric hosts.
Moreover, as can be readily recognized from Table 1, the Ks
values for inclusion complexation of hosts 4-7 with guest
molecules increase in the following order
4: ANS < TNS < RhB
5: ANS < RhB < TNS
6: ANS < RhB < TNS
7: ANS < TNS < RhB
Figure 10. Schematic binding modes of metallooligo(â-CD)s 6
and 7.
We can see that the linear guest molecule TNS and the T-shaped
guest RhB are better bound by oligo(â-CD)s than the bent guest
ANS. This may be attributed to the fact that longitudinal
incorporation of linear or T-shaped guest molecule with oligo-
(â-CD) fits better into the geometrical requirement than the bent
guest, which consequently gives the strong van der Waals and
hydrophobic interactions between host and guest. On the other
hand, although both TNS and ANS possess a phenyl and
naphthyl group, the former forms a more stable complex with
oligomeric â-CD than the latter, which may be also attributed
to the size-fit relationship between host and guest. The CPK
Molecular Binding Ability. It is demonstrated that native
and simple modified â-CDs afford the limited binding ability
with guest molecule due to the relatively weak host-guest
hydrophobic interactions. However, â-CD dimers and their metal
complexes can greatly enhance the original binding ability of
parent â-CD through the cooperative binding of two adjacent
cavities and the potential multiple recognition ability. As can
be seen from Table 1, the Ks values for inclusion complexa-
tion of mono-modified â-CDs 2 and 3 with guest molecules
are only 0.5-3.4 times as high as those for native â-CD.

19548 J. Phys. Chem. B, Vol. 108, No. 50, 2004
Liu et al.
model studies show that the naphthyl group in ANS cannot
penetrate deeply into the â-CD cavity owing to steric hindrance.
Therefore, among the guest molecules used, the weakest binding
ability for ANS by oligo(â-cyclodextrin)s should be reasonable.
In addition, by comparing the enhancement effects for each
guest, we can see that the oligo(â-CD) which gives the highest
enhancement for each guest dye (with the observed enhancement
factors shown in the parentheses) is 5 (×42) for ANS, 6 (×4.8)
for TNS, and 6 (×2.9) for RhB, respectively. From a comparison
of these enhancement factors, we can conclude that the bent
guest ANS, rather than linear guest TNS and T-shaped guest
RhB, is able to more fully exploit the cooperative multiple
binding of oligo(â-CD) with the binding ability exhibiting more
than 40-fold enhancement. Close examination of the binding
abilities of hosts 4-7 toward ANS shows that the cis conformer
4 only increases the original binding ability of â-CD toward
ANS by a factor of 6, but its copper(II) complex 6 enhances
this value to 38. This may be attributed to the additional binding
interactions provided by the coordinated copper(II) ions.
However, the trans conformer 5 and its cooper(II) complex 7
show the significantly enhanced binding ability toward ANS
up to 38-42 times higher than that of â-CD. This result can be
explained by the double-helical binding mode of hosts 5 and 7,
which results in a shorter distance between two â-CD cavities
and thus improves the host-guest size fit.
25 °C on a JASCO FP-750 spectrometer equipped with a
constant-temperature water bath, with excitation and emission
slits of 5 nm for all the fluorescent dyes. The excitation
wavelengths for ANS, TNS, and RhB were 350, 350, and 520
nm, respectively.
Synthesis of Mono[6-(3-pyridinecarboxamide)ethylene-
amino-6-deoxy]-â-CD (2). Dicyclohexylcarbodiimide (DCC,
0.49 g, 2 mmol) and nicotinic acid (0.3 g, 2 mmol) were
dissolved in dry DMF (30 mL), and mono[6-(2-aminoethyl-
eneamino)-6-deoxy]-â-CD (2.35 g, 2 mmol) was added to this
solution at 0 °C under nitrogen atmosphere. After stirring the
reaction mixture for 18 h in an ice bath and another 24 h at
room temperature, the insoluble matter was removed by filtration
and the filtrate evaporated under reduced pressure to dryness.
The residue was dissolved in water, and then acetone was added
to the solution to give a pale precipitate. The crude product
obtained was purified by column chromatography over Sephadex
G-25 with distilled deionized water as the eluent to give a pure
1
sample as a yellow solid. Yield: 1.5 g, 1.1 mmol, 56%. H
NMR (600 MHz, D2O, TMS): δ 2.6-3.0 (m, 4H), 3.1-4.0
(m, 42H), 4.8-5.0 (m, 7H), 7.2-7.4 (m, 1H), 8.0-8.1 (m, 1H),
8.3-8.6 (m, 1H), 8.7-8.8 (m, 1H). IR (KBr) νmax/cm-1: 3372,
3351, 3071, 2926, 2151, 1603, 1558, 1425, 1371, 1245, 1155,
1079, 1035, 943, 848, 758, 704, 654, 608, 580, 528, 426. Anal.
Calcd for C50H78O35N3‚3H2O: C, 44.98; H, 6.34; N, 3.15.
Found: C, 44.82; H, 6.53; N, 3.15. UV-vis (water): λmax/nm
(ꢀ/M-1 cm-1) 262 (3800 mol-1 dm-3 cm-1).
Conclusion
In summary, a series of â-CD derivatives bearing pyridine
and bipyridine linkers as well as their copper(II) complexes are
synthesized in moderate to high yields. Comparative studies on
the conformations and binding behaviors of these hosts indicate
that cis-bis(â-CD) 4 and trans-bis(â-CD) 5 as well as their
copper(II) complexes 6 and 7 exhibit different inclusion
complexation geometry upon association with guest molecules,
which consequently leads to the obvious difference in the
binding abilities of these â-CD derivatives, giving relatively
strong binding with linear and T-shaped guests and a significant
enhancement effect on the binding ability toward bent guest as
compared with native and monomeric â-CD. The present results
provide a convenient and powerful method for controlling the
conformation of synthetic receptors in aqueous solution, which
will be useful for the design and synthesis of new supramo-
lecular systems.
Synthesis of Mono[6-(4-pyridinecarboxamide)ethylene-
amino-6-deoxy]-â-CD (3). Compound 3 was prepared in 50%
yield from isonicotinic acid and mono[6-(2-aminoethylene-
amino)-6-deoxy]-â-CD as a slight-yellow solid according to
procedures similar to those employed in the synthesis of 2. 1H
NMR (600 MHz, D2O, TMS): δ 2.6-3.0 (m, 4H), 3.2-3.8
(m, 42H), 4.8-4.9 (m, 7H), 7.5-7.6 (m, 2H), 8.4-8.5 (m, 2H).
IR (KBr) νmax/cm-1: 3358, 3049, 2085, 1603, 1547, 1452, 1371,
1301, 1243, 1206, 1155, 1079, 1034, 944, 849, 756, 708, 677,
658, 613, 581, 531, 449, 432. Anal. Calcd for C50H78O35N3‚
8H2O: C, 42.14; H, 6.65; N, 2.95. Found: C, 42.20; H, 6.53;
N, 3.02. UV-vis (water): λmax/nm (ꢀ/M-1 cm-1) 266 (2060
mol-1 dm-3 cm-1).
Synthesis of N,N′-Bis(2-aminoethyl)-2,2′-bipyridine-3,3′-
dicarboxamide-Bridged Bis(6-amino-6-deoxy-â-CD) (5). 2,2′-
Bipyridine-3,3′-dicarboxylic dichloride (0.28 g, 1.0 mmol) was
dissolved in dry pyridine (20 mL) containing DCC (0.7 g, 3.4
mmol). Dry mono[6-(2-aminoethyleneamino)-6-deoxy]-â-CD
(4.1 g, 3.0 mmol) in DMF (30 mL) was added to this solution
at room temperature under nitrogen atmosphere, and the resultant
mixture was stirred for 24 h in an ice bath. The solution was
allowed to warm and stirred for an additional 2 days at room
temperature until no more precipitate was deposited. Then the
precipitate was removed by filtration, and the filtrate was
evaporated under reduced pressure to dryness. The residue was
dissolved in water, and then acetone was added to the solution
to give a reddish precipitate. The crude product obtained after
drying was purified by column chromatography over Sephadex
G-25 with distilled deionized water as the eluent to give a pure
Experimental Section
General. Ammonium 8-anilino-1-naphthalenesulfonate (ANS),
sodium 6-(p-toludino)-2-naphthalenesulfonate (TNS), and
Rhodamine B (RhB) were purchased from Wako. All chemicals
were reagent grade and used without further purification unless
noted otherwise. â-CD of reagent grade (Shanghai Reagent
Works) was recrystallized twice from water and dried in vacuo
for 12 h at 100 °C. N,N-Dimethylformamide (DMF) was dried
over calcium hydride for 2 days and distilled under reduced
pressure prior to use. Pyridine was refluxed over calcium hydride
for 8 h and distilled prior to use. Mono[6-(2-aminoethylene-
amino)-6-deoxy]-â-CD, N,N′-bis(2- aminoethyl)-2,2′-bipyridine-
4,4′-dicarboxamide-bridged bis(6-amino-6-deoxy-â-CD) (4), and
its copper(II) complex 6 were prepared according to our previous
report.23,24 Elemental analyses were performed on a Perkin-
Elmer-2400C instrument. NMR spectra were obtained on a
Bruker AV600 instrument. UV-vis spectra were recorded in a
conventional quartz cell (10 × 10 × 45 mm) at 25 °C on a
Shimadzu UV2401 spectrometer. Fluorescence spectra were
measured in a conventional quartz cell (10 × 10 × 45 mm) at
1
sample as a yellow solid. Yield: 0.8 g, 0.3 mmol, 30%. H
NMR (600 MHz, D2O, TMS): δ 2.6-4.2 (m, 92H), 4.7-5.0
(m, 14H), 7.3-7.6 (m, 2H), 7.8-8.1 (m, 2H), 8.3-8.6 (m, 2H).
IR (KBr): νmax/cm-1 3330, 2929, 1647, 1560, 1418.4, 1330,
1154, 1079, 1032, 944, 845, 755, 705, 580. Anal. Calcd for
C
100H156O70N6‚8H2O: C, 44.38; H, 6.41; N, 3.11. Found: C,
44.24; H, 6.40; N, 3.25. UV-vis (water): λmax/nm (ꢀ/M-1 cm-1
)
270 (9710 mol-1 dm-3 cm-1).

Study of Selective Binding Behaviors
J. Phys. Chem. B, Vol. 108, No. 50, 2004 19549
(10) Brilirakis, N.; Henry, B.; Berthault, P.; Venema, F.; Nolte, R. J.
M. Tetrahedron 1998, 54, 3523.
(11) (a) Liu, Y.; You, C.-C.; Chen, Y.; Wada, T.; Inoue, Y. J. Org.
Chem. 1999, 64, 7781. (b) Liu, Y.; Li, B.; You, C.-C.; Wada, T.; Inoue, Y.
J. Org. Chem. 2001, 66, 225.
(12) Park, J. W.; Song, H. E.; Lee, S. Y. J. Phys. Chem. B 2002, 106,
5177.
(13) (a) Breslow, R.; Zhang, B. J. Am. Chem. Soc. 1992, 114, 5882. (b)
Zhang, B.; Breslow, R. J. Am. Chem. Soc. 1997, 119, 1676. (c) Breslow,
R.; Dong, S. D. Chem. ReV. 1998, 98, 1997. (d) Breslow, R.; Zhang, B. J.
Am. Chem. Soc. 1994, 116, 7893.
(14) (a) Spies, M. A.; Schowen, R. L. J. Am. Chem. Soc. 2002, 124,
14049. (b) Liu, J.-Q.; Luo, G.-M.; Ren, X.-J.; Mu, Y.; Bai, Y.; Shen, J.-C.
Biochim. Biophys. Acta 2000, 222. (c) Ren, X.-J.; Liu, J.-Q.; Luo, G.-M.;
Zhang, Y.; Luo, Y.-M.; Yan, G.-L.; Shen, J.-C. Bioconjugate Chem. 2000,
11, 682.
(15) Harada, A.; Furue, M.; Nozakura, S. Polym. J. 1980, 12, 29.
(16) Breslow, R.; Greenspoon, N.; Guo, T.; Zarzycki, R. J. Am. Chem.
Soc. 1989, 111, 8296.
Synthesis of Bis(â-CD)-copper(II) Complex 7. Bis(â-
cyclodextrin) 5 was added portionwise to a dilute aqueous
solution of slightly excess copper(II) perchlorate in an ice/water
bath. Several drops of chloroform were further added, and the
resultant solution was kept at 5 °C for 2 days. Then the
precipitate formed was collected by filtration, washed succes-
sively with a small amount of ethanol and diethyl ether, and
then dried in vacuo to give bis(â-cyclodextrin)-Cu(II) complex
7 as a green solid in 40% yield. IR (KBr): νmax/cm-1 3322,
2930, 1652, 1610, 1421, 1364, 1301, 1154, 1080, 1032, 944,
845, 757, 705, 580, 526, 430, 410. Anal. Calcd for C100H156O70N6‚
0.5Cu(ClO4)2‚8H2O: C, 42.33; H, 6.11; N, 2.96. Found: C,
42.61; H, 6.02; N, 2.89. UV-vis (water): λmax/nm (ꢀ/M-1 cm-1
)
270 (10 110 mol-1 dm-3 cm-1).
Acknowledgment. This work was supported by NNSFC
(90306009 and 20272028), the Special Fund for Doctoral
Program from the Ministry of Education of China (No.
20010055001), and the Natural Science Fund of Tianjin
(043604411), which are gratefully acknowledged.
(17) Breslow, R.; Chung, S. J. Am. Chem. Soc. 1990, 112, 9659.
(18) Okabe, Y.; Yamamura, H.; Obe, K.; Ohta, K.; Kawai, M.; Fujita,
K. J. Chem. Soc., Chem. Commun. 1995, 581.
(19) Deschenaux, R.; Ruch, T.; Deschenaux, P.-F.; Juris, A.; Ziessel,
R. HelV. Chim. Acta 1995, 78, 619.
(20) Nelissen, H. F. M.; Schut, A. F. J.; Venema, F.; Feiters, M. C.;
Nolte, R. J. M. Chem. Commun. 2000, 577.
References and Notes
(21) Breslow, R.; Halfon, S. Proc. Natl. Acad. Sci. U.S.A. 1992, 89,
6916.
(22) Luo, M.-M.; Xie, R.-G.; Yuan, D.-Q.; Lu, W.; Xia, P.-F.; Zhao,
H.-M. Chin. J. Chem. 1999, 17, 384.
(23) (a) Liu, Y.; Han, B.-H.; Chen, Y.-T. J. Phys. Chem. B 2002, 106,
4678. (b) Liu, Y.; Yang, Y.-W.; Cao, R.; Song, S.-H.; Zhang, H.-Y.; Wang,
L.-H. J. Phys. Chem. B 2003, 107, 14130. (c) Liu, Y.; Zhao, Y.-L.; Zhang,
H.-Y.; Fan, Z.; Wen, G.-D.; Ding, F. J. Phys. Chem. B 2004, 108, 8836.
(24) (a) Liu, Y.; Chen, Y.; Li, B.; Wada, T.; Inoue, Y. Chem. Eur. J.
2001, 7, 2528. (b) Liu, Y.; Chen, Y.; Liu, S.-X.; Guan, X.-D.; Wada, T.;
Inoue, Y. Org. Lett. 2001, 3, 1657. (c) Liu, Y.; Chen, Y.; Li, L.; Zhang,
H.-Y.; Liu, S.-X.; Guan, X.-D. J. Org. Chem. 2001, 66, 8518.
(25) Betzel, C.; Saenger, W.; Hingerty, B. E.; Brown, G. M. J. Am.
Chem. Soc. 1984, 106, 7545.
(1) Saenger, W. Angew. Chem., Int. Ed. Engl. 1980, 19, 344.
(2) Wenz, G. Angew. Chem., Int. Ed. Engl. 1994, 33, 803.
(3) Szejtli, J. Chem. ReV. 1998, 98, 1743.
(4) (a) Breslow, R.; Greenspoon, N.; Guo, T.; Zarzycki, R. J. Am.
Chem. Soc. 1989, 111, 8296. (b) Zhang, B.; Breslow, R. J. Am. Chem. Soc.
1993, 115, 9353. (c) Breslow, R.; Yang, Z.; Ching, R. J. Am. Chem. Soc.
1998, 120, 3536. (d) Breslow, R.; Chung, S. J. Am. Chem. Soc. 1990, 112,
9659.
(5) French, R. R.; Wirz, J.; Woggen, W.-D. HelV. Chim. Acta 1998,
81, 1521.
(6) Breslow, R.; Halfon, S.; Zhang, B. Tetrahedron 1995, 51, 377.
(7) Ishimaru, Y.; Masuda, T.; Iida, T. Tetrahedron Lett. 1997, 38, 3743.
(8) (a) Jiang, T.; Sukumaran, D. K.; Soni, S. D.; Lawrence, D. S. J.
Org. Chem. 1994, 59, 5149. (b) Jiang, T.; Lawrence, D. S. J. Am. Chem.
Soc. 1995, 117, 1857.
(26) Yang, J.; Breslow, R. Angew. Chem., Int. Ed. 2000, 39, 2692.
(27) Nakamoto, K. J. Phys. Chem. 1960, 64, 1420.
(9) Maletic, M.; Wennemers, H.; McDonald, Q. D.; Breslow, R.; Still,
W. C. Angew. Chem., Int. Ed. Engl. 1996, 35, 1490.
(28) Liu, Y.; Han, B.-H.; Sun, S.-X.; Wada, T.; Inoue, Y. J. Org. Chem.
1999, 64, 1487.