Synthesis of novel bis(β-cyclodextrin)s and metallobridged bis(β-cyclodextrin)s with 2,2′-diselenobis(benzoyl) tethers and their molecular multiple recognition with model substrates

Article abstract of DOI:10.1021/jo025919a

To investigate quantitatively the cooperative binding ability of β-cyclodextrin dimers, a series of bridged bis(β-cyclodextrin)s with 2,2′-diselenobis(benzoyl) spacer connected by different lengths of oligo(ethylenediamine)s (2-5) and their platinum(IV) complexes (6-9) have been synthesized and their inclusion complexation behavior with selected substrates, such as Acridine Red, Neutral Red, Brilliant Green, Rhodamine B, ammonium 8-anilino-l-naphthalenesulfonate, and 6-p-toluidino-2-naphthalenesulfonic acid, were investigated by means of ultraviolet, fluorescence, fluorescence lifetime, circular dichroism, and 2D-NMR spectroscopy. The spectral titrations have been performed in aqueous phosphate buffer solution (pH 7.20) at 25 °C to give the complex stability constants (Ks) and Gibbs free energy changes (-ΔG°) for the inclusion complexation of hosts 2-9 with organic dyes and other thermodynamic parameters (ΔH° and TΔS°) for the inclusion complexation of 2-5 with fluorescent dyes ANS and TNS. The results obtained indicate that β-cyclodextrin dimers 2-5 can coordinate with one or two platinum(IV) ions to form 1:1 or 1:2 stoichiometry metallobridged bis(β-cyclodextrin)s. As compared with parent β-cyclodextrin (1) and bis(β-cyclodextrin)s 2-5, metallobridged bis(β-cyclodextrin)s 6-9 can further switch the original molecular binding ability through the coordinating metal to orientate two β-cyclodextrin cavities and an additional binding site upon the inclusion complexation with model substrates, giving the enhanced binding constants Ks for both ANS and TNS. The tether length between two cyclodextrin units plays a crucial role in the molecular recognition with guest dyes. The binding constants for TNS decrease linearly with an increase in the tether length of dimeric β-cyclodextrins. The Gibbs free energy change (-ΔG°) for the unit increment per ethylene is 0.32 kJ.mol-¹ for TNS. Thermodynamically, the higher complex stabilities of both ANS and TNS upon the inclusion complexation with 2-5 are mainly contributed to the favorable enthalpic gain (-ΔH°) by the cooperative binding of one guest molecule in the closely located two β-cyclodextrin cavities as compared with parent β-cyclodextrin. The molecular binding ability and selectivity of organic dyes by hosts 1-9 are discussed from the viewpoints of the multiple recognition mechanism and the size/shape-fitting relationship between host and guest.

Full text of DOI:10.1021/jo025919a

Syn th esis of Novel Bis(â-Cyclod extr in )s a n d Meta llobr id ged
Bis(â-Cyclod extr in )s w ith 2,2′-Diselen obis(ben zoyl) Teth er s a n d
Th eir Molecu la r Mu ltip le Recogn ition w ith Mod el Su bstr a tes
Yu Liu,* Li Li, Heng-Yi Zhang, and Yun Song
Department of Chemistry, State Key Laboratory of Elemento-Organic Chemistry,
Nankai University, Tianjin 300071, China
yuliu@public.tpt.tj.cn
Received May 9, 2002
To investigate quantitatively the cooperative binding ability of â-cyclodextrin dimers, a series of
bridged bis(â-cyclodextrin)s with 2,2′-diselenobis(benzoyl) spacer connected by different lengths of
oligo(ethylenediamine)s (2-5) and their platinum(IV) complexes (6-9) have been synthesized and
their inclusion complexation behavior with selected substrates, such as Acridine Red, Neutral Red,
Brilliant Green, Rhodamine B, ammonium 8-anilino-1-naphthalenesulfonate, and 6-p-toluidino-2-
naphthalenesulfonic acid, were investigated by means of ultraviolet, fluorescence, fluorescence
lifetime, circular dichroism, and 2D-NMR spectroscopy. The spectral titrations have been performed
in aqueous phosphate buffer solution (pH 7.20) at 25 °C to give the complex stability constants
S
(K ) and Gibbs free energy changes (-∆G°) for the inclusion complexation of hosts 2-9 with organic
dyes and other thermodynamic parameters (∆H° and T∆S°) for the inclusion complexation of 2-5
with fluorescent dyes ANS and TNS. The results obtained indicate that â-cyclodextrin dimers 2-5
can coordinate with one or two platinum(IV) ions to form 1:1 or 1:2 stoichiometry metallobridged
bis(â-cyclodextrin)s. As compared with parent â-cyclodextrin (1) and bis(â-cyclodextrin)s 2-5,
metallobridged bis(â-cyclodextrin)s 6-9 can further switch the original molecular binding ability
through the coordinating metal to orientate two â-cyclodextrin cavities and an additional binding
site upon the inclusion complexation with model substrates, giving the enhanced binding constants
S
K for both ANS and TNS. The tether length between two cyclodextrin units plays a crucial role in
the molecular recognition with guest dyes. The binding constants for TNS decrease linearly with
an increase in the tether length of dimeric â-cyclodextrins. The Gibbs free energy change (-∆G°)
-
1
for the unit increment per ethylene is 0.32 kJ ‚mol for TNS. Thermodynamically, the higher
complex stabilities of both ANS and TNS upon the inclusion complexation with 2-5 are mainly
contributed to the favorable enthalpic gain (-∆H°) by the cooperative binding of one guest molecule
in the closely located two â-cyclodextrin cavities as compared with parent â-cyclodextrin. The
molecular binding ability and selectivity of organic dyes by hosts 1-9 are discussed from the
viewpoints of the multiple recognition mechanism and the size/shape-fitting relationship between
host and guest.
In tr od u ction
erative binding of one guest molecule in the closely
located two cyclodextrin cavities. Hence, a variety of
dimeric cyclodextrins with a considerable structural
diversity have been designed and synthesized to under-
stand the recognition process controlled by the simulta-
neous operation of several weak interactions and also to
gain insights into the factors and mechanism governing
â-Cyclodextrin is a toroidally shaped polysaccharide
made up of seven D-glucose monomers linked by r-1,4-
glucose bonds. Its exterior, bristling with hydroxy groups,
is fairly polar, whereas the interior of the cavity is
nonpolar. These structural features enable â-cyclodextrin
to accommodate bicyclic aliphatic and aromatic com-
pounds to form host-guest or supramolecular complexes
in aqueous solutions.1 As compared with parent â-cy-
clodextrin, the bridged bis(â-cyclodextrin)s tethered by
some simple functional groups can enhance the original
molecular binding ability and selectivity through coop-
the inclusion complexation behavior of bridged cyclodex-
trin dimers.4
-10
Recently, some functional organosele-
-3
(4) Harada, A.; Furue, M.; Nozakura, S. Polym. J . 1980, 12, 29.
(5) Breslow, R.; Greenspoon, N.; Guo, T.; Zarzychi, R. J . Am. Chem.
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(
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3536.
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3
*
To whom correspondence should be addressed. Tel: +86-22-
3503625. Fax: +86-22-2350-4853.
1) Saenger, W. Angew. Chem. 1980, 92, 343; Angew. Chem., Int.
Ed. Engl. 1980, 19, 344.
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Engl. 1994, 33, 803.
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2
(
Chem. 1994, 59, 5149.
(
(9) J iang, T.; Lawrence, D. S. J . Am. Chem. Soc. 1995, 117, 1857.
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(
1
0.1021/jo025919a CCC: $25.00 © 2003 American Chemical Society
Published on Web 12/06/2002
J . Org. Chem. 2003, 68, 527-536
527

Liu et al.
CHART 1
nium bridged bis(â-cyclodextrin)s have been applied
successfully to enzyme-mimetic chemistry and nano-
structure supramolecular assembly.11,12 Therefore, the
molecular recognition studies on bridged bis(â-cyclodex-
trin)s are one of the crucial topics in supramolecular
chemistry and biochemistry.1
inclusion complexation behavior of a series of novel
synthesized bis(â-cyclodextrin)s linked by 2,2′-diseleno-
bis(benzoyl) tether with the selective dye molecules
(Chart 1) and their complexation thermodynamics with
guest dyes such as ANS and TNS (Chart 2). It is of our
special interest to elucidate the molecular recognition
behavior of guest dyes by organoselenium-bridged bis-
3,14
We have recently demonstrated that the organosele-
nium- and oligoethylenediamine-bridged bis(â-cyclodex-
trin)s can form more stable complexes with some fluo-
rescent dyes than native â-cyclodextrin through the
cooperative binding, and their metal complexes show yet
(â-cyclodextrin)s with ligated platinum ions. The results
obtained indicate that the oligo(ethylenediamine) tethers
incorporated in the organoselenium â-cyclodextrin dimers
not only adjust the linker length between the two
cyclodextrin moieties but also ligate to metal ions, which
enables us to modify and potentially switch the original
molecular binding ability through the metal ligation.
1
5-17
stronger abilities to bind to guest molecules.
These
results will promote our understanding of the multiple
recognition and the induced-fit interaction hypothesis
proposed for the binding of specific substrates by biologi-
cal receptors. Unfortunately, the thermodynamics and
the role of linker length in molecular recognition have
rarely been investigated so far upon the inclusion com-
Resu lts a n d Discu ssion
Syn th esis. As illustrated in Scheme 1, organosele-
nium-bridged bis(â-cyclodextrin) 2 was synthesized in
plexation with organoselenium-bridged bis(â-cyclodex-
1
9% yield from 2,2′-diselenobis(benzoic acid) and â-cy-
trin)s.1
8,19
In the present study, we wish to report the
clodextrin according to our recently reported proce-
dures,20 while oligo(ethylenediamino)-tethered organose-
lenium-bridged bis(â-cyclodextrin)s 3-5 were prepared
in satisfactory yields starting from 6-O-monotosyl-â-
cyclodextrin, which was converted to mono[6-oligo(eth-
ylenediamino)-6-deoxy]-â-cyclodextrins according to pro-
cedures similar to those described for 2. And then,
metallobridged bis(â-cyclodextrin)s 6-9 were prepared
from oligo(ethylenediamino)-tethered organoselenium-
(11) (a) Liu, J .-Q.; Gao, S.-J .; Luo, G.-M.; Yan, G.-L.; Shen, J .-C.
Biochem. Biophys. Res. Commun. 1998, 247, 397. (b) Ma, X.-Y.; Wu,
Y.-H.; Ding, L.; Zhao, D.-Q.; Ni, J .-Z.; Liu, Y. Chem. J . Chine. University
1
2
999, 20, 1163. (c) Liu, Y.; Li, B.; Li, L.; Zhang, H.-Y. Helv. Chim. Acta
002, 85, 9.
(12) (a) Liu, Y.; You, C.-C.; Zhang, H.-Y.; Kang, S.-Z.; Zhu, C.-F.;
Wang, C. Nano Lett. 2001, 1, 613. (b) Liu, Y.; Li, L.; Fan, Z.; Zhang,
H.-Y.; Wu, X.; Guan, X.-D.; Liu, S.-X. Nano Lett. 2002, 2, 257.
(13) Szejtli, J . Osa, T. In Comprehensive Supramolecular Chemistry;
Atwood, J . L., Davies, J . E. D., MacNicol, D. D., V o¨ gtle, F., Eds;
Elsevier: Oxford, U.K., 1996; Vol. 3.
(
(
14) Breslow, R.; Halfon, S.; Zhang, B. Tetrahedron 1995, 51, 377.
15) Liu, Y.; You, C.-C.; Chen, Y.; Wada, T.; Inoue, Y. J . Org. Chem.
(18) Rekharsky, M. V.; Mayhew, M. P.; Goldgerg, R. N.; Ross, P.
D.; Yamashoji, Y.; Inoue, Y. J . Phys. Chem. A 1997, 101, 87.
(19) Inoue, Y.; Liu, Y.; Tong, L.-H.; Shen, B.-J .; J in, D.-S. J . Am.
Chem. Soc. 1993, 115, 10637.
(20) Liu, Y.; Li, B.; You, C.-C.; Wada, T.; Inoue, Y. J . Org. Chem.
2001, 66, 225.
1
999, 64, 7781.
16) Liu, Y.; Li, B.; Wada, T.; Inoue, Y. Supramol. Chem. 1999, 10,
79.
(
2
(
17) Liu, Y.; You, C.-C.; Li, B. Chem. Eur. J . 2001, 7, 1281.
5
28 J . Org. Chem., Vol. 68, No. 2, 2003

Synthesis of Novel Bis(â-cyclodextrin)s
CHART 2
SCHEME 1
F IGUR E 1. J ob plots of (a) the 2/Pt(IV) system ([2] +
-
4
-3
[
(
Pt(IV)] ) 5.0 × 10 mol‚dm ) and (b) the 4/Pt(IV) system
-4 -3
[4] + [Pt(IV)] ) 5.0 × 10 mol‚dm ).
spectral property for probing chirality21,22 and has been
widely employed to elucidate the absolute conformation
of achiral compound enclosed in chiral cavity. Therefore,
circular dichroism spectra are a convenient method for
investigating the conformations of chromophoric tethers
attached to two cyclodextrin units.1
6,20
In this work, the
CD spectra of 2-5 were taken at a low concentration of
-
4
1
× 10 in aqueous buffer solution at pH 7.20 in order
to investigate the initial conformation of â-cyclodextrin
dimers with a chromophoric organoselenium tether.
As shown in Figure 2, the substantially different CD
spectra of organoselenium bridged bis(â-cyclodextrin)s
2
-5 indicate that there exists significant, but different,
degrees of interaction between the aromatic tether and
the two chiral cavities of â-cyclodextrin dimer. In our
recent investigation,20 the CD spectrum of dimeric host
bridged bis(â-cyclodextrin)s 2-5, respectively, by the
4
coordination reaction with PtCl in aqueous solution. The
2
in aqueous solution shows two negative Cotton effect
complex formation of the metallobis(â-cyclodextrin)s was
peaks at 233 nm (∆ꢀ ) -4.03) and 266 nm (∆ꢀ ) -0.32)
and a weak positive peak at 325 nm (∆ꢀ ) 0.35). The
bridged bis(â-cyclodextrin)s 3-5, possessing similar teth-
ers appended to â-cyclodextrin, display very similar
patterns on the circular dichroism spectra, but they give
the opposite Cotton effects to 2, i.e., a positive Cotton
validated by the elemental analysis data, IR spectra, and
H NMR spectra, and the conductivity measurements
showed that the complex stoichiometry was 1:1 for both
1
2
1
-Pt(IV) (6) and 3-Pt(IV) (7) complexes, while it was
:2 for both 4-Pt(IV) (8) and 5-Pt(IV) (9), respectively.
A representative J ob plot for the 1:1 and 1:2 complexation
of bis(â-cyclodextrin)s 2 and 4 with Pt(IV) is shown in
Figure 1.
Cir cu la r Dich r oism Sp ectr a of â-Cyclod extr in
Dim er s 2-5. Circular dichroism (CD) is an essential
(
21) Nakanishi, K.; Berova, N.; Woody, R. W. Circular Dichroism:
Principles and Applications; VCH: New York, 1994.
22) Rodger, A.; Nord e´ n, B. Circular Dichroism and Linear Dichro-
ism; Oxford University Press: New York, 1997.
(
J . Org. Chem, Vol. 68, No. 2, 2003 529

Liu et al.
TABLE 1. F lu or escen ce Lifetim e (τ) a n d Rela tive
Qu a n tu m Yield (Φ) of ANS in th e P r esen ce a n d Absen ce
of Na tu r a l â-Cyclod extr in a n d Bis(â-cyclod extr in )s 1-5 in
Aqu eou s Bu ffer Solu tion (p H 7.20) a t 25.0 °C
ANS/µM host equiv τS/ns ΦS/% τL/ns ΦL/%
ø2
ref
1
00
1
50
1
1
1
1
0
none
none
0.4 100
0.4 100
1.42
1.46
a
b
a
b
c
c
a
a
5
2
0
1
1
2
3
4
5
40
10
20
20
20
20
0.5
1.5
0.6
1.2
2.0
2.4
96.5
67.6
88.1
75.2 10.1
61.8 10.3
62.6
3.1
3.2
7.4
3.5 1.00
32.4 1.24
11.9 1.04
24.8 1.46
38.2 1.47
0
0
0
0
9.95 37.4 1.36
a
This work. In the presence of host, the fluorescence decay was
not single but double exponential with short and long lifetimes,
b
indicated by subscripts S and L, respectively. Reference 15.
c
Reference 20.
-4
F IGURE 2. Circular dichroism spectra of hosts 2-5 (1 × 10
-
3
mol dm ) in aqueous solution at 25 °C.
The short and long fluorescence lifetimes (τ
S
L
and τ )
and relative quantum yields (Φ) observed for ANS in the
presence of â-cyclodextrin or bis(â-cyclodextrin) 2-5 are
summarized in Table 1. From the data listed in Table 1,
we can see that ANS itself exhibits a very short lifetime
of 0.4 ns in aqueous solution but two lifetimes of 0.5 and
effect peak at 232 nm (∆ꢀ ) 27.6) with a shoulder at 260
nm (∆ꢀ ) 8.64) and a weak negative peak at 318 nm (∆ꢀ
)
- 1.43) for 3, two moderate positive Cotton effect peaks
at 242 nm (∆ꢀ ) 6.40) and at 261.4 nm (∆ꢀ ) 7.57) for 4,
and at 234.8 nm (∆ꢀ ) 2.0) and at 264.8 nm (∆ꢀ ) 3.61)
3
.1 ns in the presence of â-cyclodextrin. The two decay
for 5, respectively. On the basis of the Kajtar’s sector rule
and Harata’s results,23,24 we deduce that the benzene ring
lifetimes indicates that the ANS molecule is located in
two distinctly different environments, one of which is
polar and the other is nonpolar. The shorter lifetime is
consistent with the initial lifetime, while the elongated
lifetime of 3.12 ns in the presence of â-cyclodextrin clearly
indicates that the environment around the ANS molecule
is more hydrophobic than that in the bulk water. J udging
in the tether of 2 does not penetrate deeply into the cavity
of â-cyclodextrin but is shallowly self-included in the
cavity. However, it is difficult to be self-included into the
cavity for the benzene ring in 3-5 tethered by longer
1
linkers. Consequently, the transition moments of the L
a
1
and L bands for 3-5 become perpendicular to the axis
b
from the different lifetime (τ
S
L
and τ ) observed for ANS
of â-cyclodextrin, affording two positive Cotton effects.
The negative Cotton effect at 318 nm indicates that the
transition dipole moment of the Se-Se bond in host 3 is
inferred to be parallel to the host axis while the transition
dipole moment of Se-Se bonds in hosts 4 and 5 is
deduced to be perpendicular to the axis of host, since
there are no negative Cotton effects at corresponding
bands. On the other hand, the 2D-NOESY spectrum of
in the presence of bis(â-cyclodextrin)s (2-5), we infer that
the short- and long-lived fluorescing species are assigned
to free and included ANS, respectively. It is noted that,
although the short lifetimes (τ
as native and bis(â-cyclodextrin)s, the distinctly different
long lifetimes (τ ) are obtained for native (3.2 ns) and
S
) are practically the same
L
bis(â-cyclodextrin)s (7.4-10.3 ns), reflecting the critical
difference in microenvironmental hydrophobicity of the
host cavity. Interestingly, despite possessing various
tether lengths, the host compounds 3-5 give only slightly
2
host compound 4 in D O (see Supporting Information)
shows no signal of correlation between the protons of the
bridged chain and H-3 and H-5 of â-cyclodextrin. This
result indicates that the bridged chain is not located
inside cyclodextrin cavities and corresponds with the
circular dichroism spectrum analysis.
different τ
has a shorter τ
L
(10.1 ( 0.2 ns), while the host compound 2
(7.4 ns). As we demonstrated in previous
L
reports,17 the shorter lifetime upon inclusion complex-
ation with bis(â-cyclodextrin)s is ascribed to the interac-
tion of the anilino moiety of ANS with the â-cyclodextrin
cavity, and the much longer lifetime (10.1 ( 0.2 ns) is
attributed to the naphthalene group of ANS partly
penetrating into an adjacent â-cyclodextrin cavity of the
dimers. Therefore, the self-inclusion of the benzene ring
for host compound 2 is unfavorable for inclusion com-
F lu or escen ce Lifetim e. It is well-documented that
the inclusion complexation of fluorescent dyes by cyclo-
dextrin hosts not only induces the fluorescence enhance-
ment and peak shift16 but also leads to significantly
elongated fluorescence lifetimes in the hydrophobic en-
2
5
vironment, as demonstrated by Bright and Reins-
borough.26 In this study, we measured the lifetime of
plexation with ANS, giving the τ shorter than bis(â-
L
ANS in aqueous buffer solution (pH 7.20) in the pres-
ence and absence of â-cyclodextrin 1 and bis(â-cyclodex-
trin)s 2-5 in order to assess the microenvironmental
polarity around the included ANS and to understand the
inclusion complexation behavior of bridged bis(â-cyclo-
dextrin)s.
cyclodextrin)s 3-5. This hydrophobic difference between
parent â-cyclodextrin and bridged bis(â-cyclodextrin)s
will subsequently result in the dramatically different
stability of the complex upon inclusion complexation with
guest molecules.
Sp ectr a l Titr a tion s. In the fluorescence spectral
titration experiments, the original fluorescence intensi-
ties of guest molecules were relatively weak, especially
for ANS and TNS, but the stepwise addition of a known
amount of host compound caused significant successive
enhancement in fluorescence intensity with appreciable
(23) Kajtar, M.; Horvath-Toro, C.; Kuthi, E.; Szejtli, J . Acta Chim.
Acad. Sci. Hung. 1982, 110, 327.
(24) Harata, K.; Uedaira, H. Bull. Chem. Soc. J pn. 1975, 48, 375.
(25) Bright, F. V.; Catena, G. C. Anal. Chem. 1989, 61, 905.
(26) J abe, D. J .; Verrall, R. E.; Paley, R.; Reinsborough, U. C. J .
Phys. Chem. 1988, 92, 3582.
5
30 J . Org. Chem., Vol. 68, No. 2, 2003

Synthesis of Novel Bis(â-cyclodextrin)s
F IGURE 3. UV-vis spectral changes of Brilliant Green (19
µM) and the nonlinear least-squares analysis (inset) of the
differential intensity (∆A) to calculate the complex stability
F IGURE 4. Continuous variation plot of the 4/AR system
-
5
-3
([bis(â-cyclodextrin) unit] + [AR] ) 2.0 × 10 mol dm ).
constant (K ) upon addition of 4 (0-250 µM from a to j) in
S
from the analysis of the sequential changes of fluores-
cence intensity (∆F) at various host concentration, using
a nonlinear least-squares method according to the curve-
fitting eq 230
aqueous buffer solution.
hypsochromic shifts. The hypsochromic shift of fluores-
cence peak for AR was relatively small as compared with
NR, RhB, ANS, and TNS. These phenomena suggested
that the fluorophore experienced a less polar environment
and the inclusion complex was formed by adding host
compound. On the other hand, the bridged bis(â-cyclo-
dextrin)s 3-5 with long spacers would quench the
fluorescence of RhB, which is consistent with the case of
â-cyclodextrin or modified â-cyclodextrins.27 It is unex-
pected that the bis(â-cyclodextrin) 2 tethered by a shorter
linker effectively enhanced the original fluorescence
intensity of RhB. These results indicated that the func-
tional tether of bridged bis(â-cyclodextrin)s not only
influenced the host-guest binding ability but also changed
the fluorescence behavior of guest molecule to some
extent. Actually, the enhanced fluorescence intensity of
RhB upon associating with 2 is attributed to the inclusion
complexation of the fluorescent acid form of RhB in the
pseudocavity formed by the dicarboxylate linker between
two â-cyclodextrin units,28 while the hosts 3-5 tethered
by the longer spacers prefer to bind with the colorless
lactonic form of RhB through hydrogen-bonding, thus
resulting in the quenched fluorescence of RhB.
∆
F ) {R([H] + [G] + 1/K ) (
0 0 S
2
2
2
R ([H] + [G] + 1/K ) - 4R [H] [G] }/2 (2)
x
0
0
S
0
0
where [G]
0
0
and [H] refer to the total concentrations of
the guest and host, and R is the proportionality coef-
ficient, which may be taken as a sensitivity factor for the
fluorescence change. For each host examined, the plot of
∆
0
F as a function of [H] gave an excellent fit; the
experimental data do not show any significant deviations
from the theoretical curve in each case. In the repeated
measurements, the K values were reproducible within
S
an error of (5%. Furthermore, the stoichiometry of the
host-guest inclusion complexation was determined by
the continuous variation method. A representative J ob
plot is given in Figure 4, showing the 1:1 stoichiometry
for the inclusion complexation of 4 with AR. The K
S
values obtained are listed in Table 2, along with the free
energy change of complex formation (-∆G°). The complex
stability constants (K
S
) are also plotted against the host
examined in Figure 7.
To further investigate the molecular binding ability
and selectivity, the binding constants of bis(â-cyclodex-
trin)s with Brilliant Green (BG) were determined by
means of ultraviolet spectroscopy. As can been seen from
Figure 3, the absorption maximum of BG is considerably
decreased upon increasing the concentration of bis(â-
cyclodextrin)s 4, indicating the inclusion complex formed
between 4 and BG.
If a 1:1 stoichiometry is assumed, where the two
â-cyclodextrin moieties in 2-5 are treated as a host unit,
the inclusion complexation of a guest (G) with a host (H)
is express by eq 1.
Bin d in g Mod el. To infer the binding model of the
organoselenium-bridged bis(â-cyclodextrin)s with guest
dyes, we recorded the 300-MHz NOESY spectrum of RhB
2
(5.0 mM in D O) in the presence of 1 equiv of 4. As shown
in Figure 5, the NOESY spectrum displays clear NOE
cross-peaks between the H-3 and H-5 of â-cyclodextrin
and the methyl protons of diethylamino groups in RhB
(
peaks A) as well as those between the H-3 and H-5 and
the aromatic protons of diethylaminophenyl in RhB
peaks B). Furthermore, the cross-peaks C were observed
(
between the aromatic protons of linker in 4 and the
aromatic protons of the benzoate moiety in RhB. These
results indicate that the cooperative interaction exists
KS
H + G y
\
z H‚‚‚G
(1)
(28) Liu, Y.; Chen, Y.; Liu, S.-X.; Guan, X.-D.; Wada, T.; Inoue, Y.
)29 can be obtained
Org. Lett. 2001, 3, 1657.
The effective stability constant (K
S
(29) Becker, H. C.; Norden, B. J . Am. Chem. Soc. 1997, 119, 5798.
30) Liu, Y.; Han, B.-H.; Sun, S.-X.; Wada, T.; Inoue, Y. J . Org.
(
(27) Liu, Y.; You, C.-C. J . Phys. Org. Chem. 2001, 14, 11.
Chem. 1999, 64, 1487.
J . Org. Chem, Vol. 68, No. 2, 2003 531

Liu et al.
TABLE 2. Com p lex Sta bility Con sta n t (KS) a n d Gibbs
F r ee En er gy Ch a n ge (-∆G°) for th e In clu sion
Com p lexa tion of Dye Molecu les w ith â-Cyclod extr in 1
a n d Bis(â-cyclod extr in )s 2-9 in Aqu eou s Bu ffer Solu tion
(
p H 7.20) a t 25.0 °C
KS(X)/ log
-∆G°
a
(kJ ‚mol 1) methodsb ref
-
host guest
KS
KS(1)
KS
1
2
3
4
5
AR
NR
BG
RhB
ANS
TNS
AR
NR
BG
RhB 11870
ANS 1200
TNS 13770
AR
NR
BG
RhB
ANS
TNS 12900
AR
2089 ≡1
480 ≡1
2187 ≡1
4240 ≡1
103 ≡1
3670 ≡1
3.32
2.68
3.34
3.63
2.01
3.56
18.90
15.30
19.10
20.70
11.49
20.35
20.10
19.24
19.90
23.26
17.59
23.66
19.30
19.88
23.50
21.39
17.90
23.46
20.80
18.62
22.70
21.14
19.46
22.89
25.10
19.46
21.20
20.85
18.24
22.77
20.06
24.63
20.79
26.83
21.49
25.05
19.37
23.89
FL
FL
UV
FL
FL
FL
FL
FL
UV
FL
FL
FL
FL
FL
UV
FL
FL
FL
FL
FL
UV
FL
FL
FL
FL
FL
UV
FL
FL
FL
FL
FL
FL
FL
FL
FL
FL
FL
c
d
e
c
f
f
3320
2350
3060
1.6 3.52
4.9 3.37
1.4 3.49
2.8 4.07
11.7 3.08
3.8 4.14
1.2 3.39
6.3 3.48
6.1 4.12
1.3 3.75
13.3 3.14
3.5 4.11
2.1 3.63
3.8 3.26
4.3 3.98
1.2 3.70
25.0 3.41
2.8 4.01
11.9 4.39
5.4 3.41
2.4 3.71
1.1 3.65
15.2 3.20
2.7 3.99
31.7 3.51
5.6 4.32
42.1 3.64
13.7 4.70
56.5 3.76
6.7 4.39
d
d
e
d
d
d
d
d
e
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
2440
3040
13300
5590
1370
4320
1830
9500
5060
2570
NR
BG
RhB
ANS
TNS 10220
AR
NR
1
F IGURE 5. H-NOESY spectrum (300 MHz) of a mixture of
24800
2570
5150
4500
1570
9740
3270
-3
4
with RhB ([4] ) [RhB] ) 5.0 × 10 M) in D
2
O at 298 K
with a mixing time of 600 ms.
BG
RhB
ANS
TNS
ANS
TNS 20700
ANS 4390
TNS 50200
ANS 5820
TNS 24500
ANS 2480
TNS 15330
6
7
8
9
24
3.39
4.2 4.18
a
Relative selectivity for each dye, where host X ) 1-9. b CD,
c
circular dichroism; UV, ultraviolet/visible; FL, fluorescence. Ref-
erence 36. This work. Reference 20. f Reference 15.
d
e
between 4 and RhB. It is well-known that the extensive
aggregation of RhB exist in the higher concentration
region.31 We investigated the fluorescence spectra of
concentrated RhB in the presence of â-cyclodextrin and
compound 4 to confirm the binding model of the inclusion
complexation of RhB with compound 4 in the 2D-NMR
experiment. The results obtained indicate that the fluo-
rescence intensity of RhB was dramatically quenched in
the higher concentration region and shows two separate
fluorescence peaks at 575 and 640 nm, respectively,
belonging to the free and aggregated RhB deduced by the
excitation spectrum of two emission peaks individually.
When â-cyclodextrin was added to the concentrated RhB
solution, the fluorescence intensity of RhB was signifi-
cantly enhanced, being greater at longer wavelength than
at shorter wavelength. Therefore, it is considered that
the dissociation of RhB dimers, upon addition of â-cyclo-
dextrin to concentrated RhB solution, is attributed to the
binding of the monomer to the â-cyclodextrin cavity
F IGURE 6. Fluorescence spectral changes of RhB (5.0 mM)
upon addition of 4 (the concentration of host 4: 0-6.7 mM
from a to k).
maintaining a low concentration of free RhB in solution.
Similar phenomena were observed when compound 4 was
added to the concentrated RhB solution (Figure 6), which
would confirm that the monomer of RhB is included in 4
at the higher concentration, and the 2D-NMR spectrum
under the experimental conditions used also reflects the
reality of the binding model upon inclusion complexation
with bridged bis(â-cyclodextrin)s.
Bin d in g Ability of Br id ged Bis(â-cyclod extr in )s
-5. Studies on molecular multiple recognition by the
2
cyclodextrin dimers indicated that the functional bridged
chain spacer between two cyclodextrin units plays a
crucial role in determining the inclusion complex sta-
(31) Politzer, I. R.; Crago, K. T.; Hampton, T.; J oseph, J .; Boyer, J .
H.; Shah, M. Chem. Phys. Lett. 1989, 159, 258.
5
32 J . Org. Chem., Vol. 68, No. 2, 2003

Synthesis of Novel Bis(â-cyclodextrin)s
bility,1
5-17,32-35
since the conformation, length, flexibility,
and additional coordination site of the functional group
tether may control how the dual cyclodextrin cavities
adjust their orientation and conformation to cooperatively
binding one guest molecule through the simultaneous
operation of several weak forces such as ion-dipole,
dipole-dipole, dipole-induced dipole, van der Waals,
electrostatic, hydrogen bonding, and hydrophobic interac-
tions according to the size/shape-fit concept between
host and guest. As can be seen from Table 2, guest dyes
AR and NR, possessing a similar heterocycle anthracene
moiety, gave entirely different binding constants upon
inclusion complexation with native â-cyclodextrin (1),
S
displaying K values of 2089 and 480 for the AR and NR,
respectively.36 This result seems reasonable, since ex-
amination with CPK (Corey-Pauling-Koltum) molecule
models indicates that AR, which has small substituent,
can be well-embedded in the cavity of â-cyclodextrin in
the longitudinal direction, while NR can partly penetrate
into the cyclodextrin cavity to form a weaker inclusion
complex due to the steric hindrance. As compared with
parent 1, bridged bis(â-cyclodextrin)s 2-5 form much
more stable inclusion complexes with AR and NR through
cooperative binding by two â-cyclodextrin units, display-
ing a binding affinity sequence of AR > NR, except for
host compound 3. It is significantly noted that the
enhanced molecular binding abilities of host 5 are much
greater for AR than that for NR, thus exhibiting a
remarkably high AR/NR molecular selectivity of 10. The
stability sequence of inclusion complexation of bridged
bis(â-cyclodextrin)s for AR does not coincide with that
for NR, which depends on how bridged bis(â-cyclodex-
trin)s with flexible/rigid tether fit to the size/shape of
guest molecules. As compared with the linear AR and
NR molecules, the triangular BG and the T-shaped RhB
guest molecules seem unable to fully enjoy cooperative
binding of the two â-CD moieties upon inclusion com-
plexation with bis(â-cyclodextrin)s 2-5. As can be seen
from Figure 7, the enhanced molecular binding ability
S
F IGURE 7. Complex stability constants (K ) for the inclusion
complexation of hosts 1-9 with guest molecules in aqueous
solution.
can control the molecular recognition behavior of bis(â-
cyclodextrin)s to some extent. As can be seen from Table
2
and Figure 7, the importance of tether length in
molecular recognition is more clearly demonstrated by
comparing the host selectivity sequence obtained for six
guest dyes. The K values for the inclusion complexation
S
of six dyes by host compounds 1-5 decrease in following
the order:
AR 5 > 4 > 2 > 3 > 1
NR 3 > 5 > 2 > 4> 1
BG 3 > 4 > 5 > 2 > 1
RhB 2 > 3 > 4 > 5 > 1
ANS 4 > 5 > 3 > 2 > 1
TNS 2 > 3 > 4 > 5 > 1
(1.1-2.8) is a relatively flat pattern for inclusion com-
plexation of RhB with 2-5. However, closed examination
of molecular binding ability toward the BG/RhB pair
demonstrates that the tether length between two â-cy-
clodextrin units can change the original molecular se-
lectivity. The natural â-cyclodextrin 1 and the short-
tethered 2 showed relatively good molecular selectivity
up to 1.9 and 3.9, respectively, for the RhB/BG pair, but
the moderate-tethered 3 and long-tethered 4 and 5
exhibited inverted molecular selectivity, giving the gen-
eral BG/RhB selectivity of 2.4, 1.9, 1.1, respectively. It is
also noted that the inclusion complex stability of bis(â-
cyclodextrin)s 2-5 with linear guest TNS is higher than
that of ANS, but the enhanced molecular binding ability
for TNS is less than for ANS, showing weak molecular
selectivity for the TNS/ANS pair. These results indicate
that the tether length between two â-cyclodextrin units
The complex stability order may be attributed to the
distance and contacting surface area between host bis-
(â-cyclodextrin)s and guest dyes. Typically, the distance
between the two cavities in host 2 is too short to
appropriately accommodate the triangular BG but is
better for the T-shaped guests, giving the higher binding
constant for RhB. Further investigation indicated that
the Gibbs free energy change (-∆G°) decreases linearly
with an increasing number of ethylene units in the tether
(N ) for the inclusion complexation of bis(â-cyclodextrin)s
E
2-5 with TNS. Using previously reported17 and present
data, the Gibbs free energy changes (-∆G°) for the
inclusion complexation with TNS were plotted against
the number of ethylene units in the tether, giving good
linear relationships. As shown in Figure 8, the free
energy changes (-∆G°) decrease linearly and afford the
(
32) Venema, F.; Rowan, A. E.; Nolte, R. J . M. J . Am. Chem. Soc.
1
996, 118, 257.
(
(
33) Breslow, R.; Zhang, B. J . Am. Chem. Soc. 1996, 118, 8495.
34) Haskard, C. A.; Easton, C. J .; May, B. L.; Lincoln, S. F. J . Phys.
Chem. 1996, 100, 14457.
35) Chiu, S.-H.; Myles, D. C.; Garrell, R. L.; Stoddart, J . F. J . Org.
Chem. 2000, 65, 2792.
36) Liu, Y.; Chen, Y.; Li, B.; Wada, T.; Inoue, Y. Chem. Eur. J . 2001,
, 2528.
unit decrement of complex stability per ethylene (-d∆G°/
(
-1
dN ) as 0.44 kJ ‚mol for oligo(ethylenediamino)-bridged
E
-
1
bis(â-cyclodextrin)s and 0.32 kJ ‚mol
possible explanation for the unit decrement of complex
for 2-5. One
(
7
J . Org. Chem, Vol. 68, No. 2, 2003 533

Liu et al.
TABLE 3. Th er m od yn a m ic P a r a m eter s for 1:1 In clu sion
Com p lexa tion of Gu est Molecu les w ith â-Cyclod extr in 1
a n d Bis(â-cyclod extr in )s 2-5 in Aqu eou s Solu tion a t
2
5 °C
host guest -∆G°/kJ ‚mol- -∆H°/kJ ‚mol-1 T∆S°/kJ ‚mol-1 ref
1
1
2
3
4
5
ANS
TNS
ANS
TNS
ANS
TNS
ANS
TNS
ANS
TNS
11.7
19.0
17.6
23.7
17.9
23.5
19.5
22.9
18.2
22.8
6.9
4.0
4.8
15.0
4.9
11.9
26.9
4.6
7.7
1.4
7.9
0.8
a
b
c
c
c
c
c
c
c
c
22.5
11.8
45.0
18.9
11.8
24.3
26.1
22.0
a
Reference 25. b Reference 26. c This work.
6
-9 can afford much more stable inclusion complexes
with model substrates, attributed to the cooperative
association of two tethered hydrophobic cavities with
model substrates, the conformation fixed by metal liga-
tion, as well as the additional electrostatic and/or electron-
transfer interaction between ligated metal and accom-
modated guest molecule. As a result of cooperative
binding, the binding constant of bis(â-cyclodextrin) 4 with
ANS is higher than that of native â-cyclodextrin by a
factor of 25, while that of the corresponding metallo-
bridged bis(â-cyclodextrin) 8 is greater by a factor of 56.5.
This result may point to a mechanism concerning mo-
lecular multiple recognition behavior; i.e. two hydropho-
bic binding sites (cyclodextrin cavities) and one (or two)
metal coordination center(s) in metallobridge bis(â-cy-
clodextrin)s jointly contribute to the cooperative binding
toward model substrates. By comparing the enhancement
effect for each guest, we can see that the highest
enhancement given by metallobridged bis(â-cyclodex-
trin)s for each guest dye (with the observed enhancement
factors shown in the parentheses) is with 8 (×56.5) for
ANS and with 7 (×13.7) for TNS, respectively. From a
comparison of the enhancement factor, we may conclude
that the bent guest ANS is able to fully enjoy the
cooperative binding of metallobridged bis(â-cyclodextrin)s
compared to the linear guests TNS.
F IGURE 8. Plot of Gibbs free energy changes (-∆G°) versus
the ethylene number in the tether for the inclusion complex-
ation of dimeric â-cyclodextrins 2-5 (b) and oligo(ethylene-
diamino)-bridged bis(â-cyclodextrin)s (O) with TNS.
stability per ethylene unit of the latter is that the
flexibility of 2-5 linked by rigid polyamine tether is lower
than that of the bridged bis(â-cyclodextrin)s linked by
olig(ethylendiamine) groups, and then the unit decrement
of complex stability per ethylene of former is higher than
that of latter. However, careful examination also noted
an interesting odd-even effect from the straight lines
drawn in Figure 8; i.e. the points for one and three
ethylenes are systematically higher and that for two
lower than the line. We do not have direct evidence yet
whether this effect may be contributing to the relative
orientation of cyclodextrin units.
Bin d in g Ability of Meta llobr id ged Bis(â-cyclo-
d extr in )s 6-9. To further extend the original binding
ability of modified cyclodextrin, much work has been
devoted to the design and syntheses of cyclodextrin
derivatives possessing a coordinated metal center. In-
deed, metal ions were introduced to the functional groups
of a cyclodextrin tether, giving a variety of metallobridged
cyclodextrins, which can alter not only the original
binding ability of cyclodextrin derivatives but also the
Th er m od yn a m ic P a r a m eter s. Using the common
dyes ANS and TNS as guest molecules, fluorometric
titrations have been performed at several temperatures
ranging from 25.0 to 40.0 °C to calculate the complex
molecular selectivity.3
7-40
As can be seen from Chart 1
and Table 2, the coordination of Pt(IV) to functional
tethers 2-5 gave a series of metallobridged bis(â-cyclo-
dextrin)s 6-9, but bis(â-cyclodextrin)s with shorter teth-
ers (2 and 3) ligated one metal ion and the bis(â-
cyclodextrin)s with longer tethers (4 and 5) ligated two
metal ions, therefore showing significantly different
molecular binding ability for ANS and TNS. This result
seems reasonable, since the N and Se atoms in long-
tethered 4 and 5 can be jointly ligated to Pt(IV), giving
the metallobridged bis(â-cyclodextrin)s with two Pt(IV).
Compared to the parent â-cyclodextrin 1 and dimeric
â-cyclodextrins 2-5, metallobridged bis(â-cyclodextrin)s
S
stability constants K and the Gibbs free energy changes
(∆G°) at different temperatures for inclusion complex-
ation of organoselenium-bridged bis(â-cyclodextrin)s 2-5.
The enthalpic and entropic changes (∆H° and ∆S°) of the
inclusion complexes formation are obtained from the
S
temperature dependence of the equilibrium constant K .
The thermodynamic parameters obtained for each inclu-
sion complexation of bridged bis(â-cyclodextrin) with
selective guest dyes are listed in Table 3. To compare and
discuss the molecular binding behavior of parent â-cy-
clodextrin 1 and bridged bis(â-cyclodextrin)s 2-5 pos-
sessing different length spacers from the thermodynamic
point of view, the thermodynamic quantities Gibbs free
energy (-∆G°), enthalpy (-∆H°), and entropy changes
(T∆S°) for the inclusion complexation with ANS and TNS
are plotted against the hosts 1-5 in Figure 9.
(
37) Schneider, H. J .; Xiao, F. J . Chem. Soc., Perkin. Trans 2. 1992,
87.
38) Haskard, C. A.; Easton, C. J .; May, B. L.; Lincon, S. F. Inorg.
Chem. 1996, 35, 1059.
39) Impellizzeri, G.; Maccarrone, G.; Rizzarelli, E.; Vecchio, G.;
3
(
(
Corradini, R.; Marchelli, R. Angew. Chem. 1991, 103, 1363; Angew.
Chem., Int. Ed. Engl. 1991, 30, 1348.
As can be recognized more easily from Figure 9, the
inclusion reactions of bridged bis(â-cyclodextrin)s 2-5
(40) Corradini, R.; Dossena, A.; Galaverna, G.; Marchelli, R.; Pa-
nagia, A.; Sartor, G. J . Org. Chem. 1997, 62, 6283.
5
34 J . Org. Chem., Vol. 68, No. 2, 2003

Synthesis of Novel Bis(â-cyclodextrin)s
that the bent guest (ANS) is only poorly accommodated
in the cavity of 1 and therefore the contribution of the
second cavity in 2-5 is much more pronounced to give
an enhancement of binding ability. The association
process, which leads to the loss of conformational free-
dom, is inherently accompanied by entropic loss. There-
fore, it is not difficult to understand the favorable
enthalpic gain (-∆H°) and large entropic loss (T∆S°) or
less positive entropic gain (T∆S°) upon inclusion com-
plexation with bridged bis(â-cyclodextrin)s. The stronger
binding of TNS for 2-5 than that for 1 is achieved by
the exothermic enthalpy changes. Thermodynamically,
it may be concluded that the general trend of the
enthalpy-driven inclusion complexation for bridged bis-
(
â-cyclodextrin)s 2-5 in both cases of ANS and TNS may
be ascribed to the cooperative binding mechanism of
F IGURE 9. Gibbs free energy (-∆G°), enthalpy (-∆H°), and
entropy changes (T∆S°) for the inclusion complexation of TNS
bridged bis(â-cyclodextrin)s.
(
a) and ANS (b) with â-cyclodextrin and bis(â-cyclodextrin)s
2
-5 in aqueous buffer solution (pH 7.20) at 25 °C.
Con clu sion
In conclusion, bridged bis(â-cyclodextrin)s 2-5 teth-
ered by organoselenium bridges significantly extend the
original molecular binding ability of parent â-cyclodex-
trin, and the complex stability constants for the selected
guests are larger than native â-cyclodextrin by factors
from 1.2 to 56.5 through the cooperative interaction.
Furthermore, the complex stability also depends greatly
on the tether length of bis(â-cyclodextrin)s and the size/
shape of guest. In particular, the coordination of plati-
num(IV) ion to the tether not only orientates two â-cy-
clodextrin cavities to fit the shape of guest molecule, but
the coordinated Pt also acts an additional site of guest
recognition through coordination and/or electrostatic
interaction. As an important result, a further enhanced
molecular binding ability could be observed for metallo-
bis(â-cyclodextrin)s 6-9. Thermodynamically, the inclu-
sion complexation of 2-5 with ANS and TNS is mainly
enthalpy driven with a negative or positive entropic
contribution. These results further confirm that van der
Waals and hydrophobic interaction jointly contribute to
the stability of the host-guest inclusion complex.
with ANS and TNS are all exothermic and give the larger
negative enthalpic gain (-∆H°) with positive or negative
entropic changes (T∆S°), indicating that the inclusion
complexes formation is mainly driven by enthalpy.
However, the largest enthalpic gain (-∆H°) does not
immediately imply the highest complex stability and is
often canceled by larger entropic loss, as is the case with
bis(â-cyclodextrin) 3 and ANS. It is noted that both ANS
and TNS possess a phenyl or naphthyl moiety, but the
complexation entropic term of TNS is favorable to that
of ANS. Typically, the inclusion complexation of native
â-cyclodextrin 1 with TNS shows the entropic driving
process, indicating that entropic gain upon extensive
desolvation will offset the entropy loss. At the same time,
van der Waals or hydrophobic interaction (-∆H° ) 11.8
kJ ‚mol ) and desolvation (T∆S° ) 11.9 kJ ‚mol-1) play
-1
almost the same role for 2, contributing to the Gibbs free
energy (-∆G°). One possible explanation for the entropic
gain (T∆S°) of inclusion complexation with TNS is that
the linear TNS allows a more ordered solvent shell, which
is broken up upon binding, leading to the favorable
entropy term. In view of the structural features of ANS
compared with those of TNS, it would appear that an
equatorial approach is sterically hindered. The relatively
Exp er im en ta l Section
In str u m en ts. NMR spectra were performed at 300 MHz.
Fluorescence lifetimes were determined by the time-correlated
single-photon-counting method with a time resolution of 0.5
ns. A self-oscillating discharge lamp filled with hydrogen gas
was employed as the pulsed light source, and the excitation
light was made monochromatic by a 10 cm monochromator.
The emission from the sample was passed through an ap-
propriate filter placed before the detector unit in order to
eliminate scattered excitation light. Maximum counts of up
to 10 000 were collected for each measurement. The ac-
cumulated signals were then processed and the lifetime
determined by deconvolution with nonlinear least-squares fit.
Mater ials. Acridine Red (AR), Neutral Red (NR), Rhodamine
B (RhB), Brilliant Green (BG), ammonium 8-anilino-1-naph-
thalenesulfonate (ANS), and sodium 6-p-toluidino-2-naphtha-
lenesulfonic acid (TNS) were commercially available. All
chemicals were reagent grade and were used without further
purification, unless noted otherwise. â-Cyclodextrin (1) of
reagent grade was recrystallized twice from water and dried
in vacuo at 95 °C for 24 h prior to use. N,N-Dimethylforma-
mide (DMF) was dried over calcium hydride for 2 days and
then distilled under a reduced pressure prior to use. 6,6′-[2,2′-
Diselenobis(benzoyloxyl)]-bridged bis(â-cyclodextrin) (2) and
S
low K values appear to support this observation. In the
case of ANS, we see that the axial approach is sterically
allowed, and this is most likely the mode of complex-
ation.25 In this case desolvation and van der Waals or
hydrophobic interaction jointly contribute to the Gibbs
free energy (-∆G°).
Differing from the binding behavior of the parent
â-cyclodextrin, the bridged bis(â-cyclodextrin)s 2-5 can
increase the interaction between the hosts and the guest
dyes through the cooperative binding of one guest mol-
ecule in the closely located two â-cyclodextrin cavities.
Therefore, the inclusion complexation of 2-5 with guest
dyes as compared with 1 gives the stronger van der
Waals and hydrophobic interaction and leads to the
higher enthalpy changes (-∆H°), which immediately
contribute to the complex stability. As shown in Figure
9
, the enhanced binding of ANS by 2-5 accompanies a
further increase in the originally favorable enthalpic gain
-∆H°) or by a strengthening of the van der Waals or
hydrophobic interaction. The reasonable explanation is
(
J . Org. Chem, Vol. 68, No. 2, 2003 535

Liu et al.
1
6
,6′-[2,2′-diselen obis[2-(ben zoyla m in o)et h ylen ea m in o]]-
bridged bis(â-cyclodextrin) (3) were prepared according to the
8.1 (m,8H). IR (KBr) ν/cm- 3302.2, 2931.5, 1708.7, 1690.5,
1663.5, 1636.4, 1586.2, 1409.7, 1298.5, 1152.1, 1078.0, 1028.6,
942.4, 855.8, 750.9, 705.7, 578.4. UV/vis (water): λmax (ꢀ) )
2
0
recently reported procedures. Disodium hydrogen phosphate
and sodium dihydrogen phosphate were dissolved in distilled,
deionized water to make a 0.10 M phosphate buffer solution
of pH 7.20, which was used in the spectral measurements.
Syn t h esis of 6,6′-[2,2′-Diselen ob is(b en zoyla m in o-3-
a za p en tyla m in o)]-Br id ged Bis(â-cyclod extr in ) 4. Mono-
317.0 nm (7900 mol dm3 cm ). Anal. Calcd for C98
-
1
-1
146 72
H O -
Se
2
‚PtCl
Bis(â-cyclod extr in )-P t(IV) Com p lex 7. Bis(â-cyclodex-
trin) complex 7 was prepared according to procedures similar
4
‚8H
2
O: C, 37.79; H, 5.24. Found: C, 38.03; H, 5.13.
1
2
to those for the synthesis of 6 in 70% yield. H NMR (D O,
[
6-(5-amino-3-azapentylamino)-6-deoxy]-â-cyclodextrin (1 mmol)
TMS) 3.2-3.7 (m, 84H), 4.8-4.9 (m, 14H), 7.3-8.0 (m, 8H).
was dissolved in DMF (30 mL) and then treated with 1 equiv
-1
IR (KBr) ν/cm 3298.1, 2929.8, 1649.6, 1592.1, 1412.6, 1367.4,
of DCC, 1-hydroxybenzotriazole hydrate (HOBT), and 2,2′-
1
7
331.5, 1258.2, 1152.8, 1078.2, 1028.8, 943.8, 856.6, 753.7,
4
1
diselenobis(benzoic acid) (0.5 mmol). The mixture was stirred
for 12 h in an ice bath and another 18 h at room temperature,
and then allowed to stand for 3 days until no more precipita-
tion deposited. The precipitate was removed by filtration and
the filtrate was evaporated to dryness under reduced pressure.
The residue was dissolved in a minimum amount of hot water
and then poured into 150 mL of acetone. The precipitate
formed was collected by filtration. This procedure was repeated
several times. The crude product thus obtained was purified
on a column of Sephadex G-25 with water as eluent. After the
residue was dried in vacuo, a pure sample was obtained in
-1
3
05.1. UV/vis (water): λmax (ꢀ) ) 317.0 nm (9900 mol dm
-1
cm ). Anal. Calcd for C102
H
158
O
70
N
4
Se
2
‚PtCl
4
2
‚8H O: C, 38.29;
H, 5.48; N, 1.75. Found: C, 37.95; H, 5.40; N, 1.93.
Bis(â-cyclod extr in )-P t(IV) com p lex 8. Bis(â-cyclodex-
trin) complex 8 was prepared according to procedures similar
to those for the synthesis of 6 in 65% yield. H NMR (D
1
2
O,
TMS) 3.2-3.7 (m, 84H), 4.9-5.2 (m, 14H), 7.2-8.0 (m, 8H).
-1
IR (KBr) ν/cm 3294.7, 2928.7, 1699.0, 1650.3, 1591.1, 1558.8,
1
8
540.6, 1418.7, 1364.1, 1337.7, 1152.3, 1078.1, 1029.6, 943.8,
54.4, 751.6, 705.0. UV/vis (water): λmax (ꢀ) ) 288 nm (14 200
mol dm3 cm ). Anal. Calcd for C106
-
1
-1
H
O
N
Se
‚2PtCl ‚
168
70
6
2
4
1
5% yield as a light yellow solid. MS (MALDI-TOF): m/z 2843
1
10H
N, 2.19.
2
O: C, 34.80; H, 5.18; N, 2.29. Found: C, 34.91; H, 4.99;
[
M + K]+. H NMR (D
2
O, TMS): 2.7-3.1 (m, 16H), 3.3-3.8
-
1
(m, 84H), 4.8 (m, 14H), 7.1-7.9 (m, 8H). IR (KBr) ν/cm
3
1
7
300.6, 2928.0, 1659.0, 1630.1, 1586.5, 1548.7, 1533.9, 1500.0,
Bis(â-cyclod extr in )-P t(IV) com p lex 9. Bis(â-cyclodex-
trin) complex 9 was prepared according to procedures similar
to those in the synthesis of 6 in 62% yield. H NMR (D
429.7, 1367.0, 1152.6, 1078.8, 1031.4, 943.5, 855.6, 752.8,
04.7. UV/vis (water): λmax (ꢀ) ) 308.5 nm (5900 mol dm3
-
1
1
2
O, TMS)
-
1
cm ). Anal. Calcd for C106
.20; N, 2.90. Found: C, 44.04; H, 6.07; N, 3.12.
Syn t h esis of 6,6′-[2,2′-Diselen obis(ben zoyla m in o-3,6-
H
168
O
70
N
6
Se
2
‚5H
2
O:‚C, 43.99; H,
3.3-3.7 (m, 84H), 4.9-5.2 (m, 14H), 7.2-8.0 (m, 8H). IR (KBr)
-
1
6
ν/cm 3310.1, 2928.6, 1649.8, 1589.9, 1558.7, 1418.3, 1366.3,
1335.4, 1300.7, 1152.5, 1078.4, 1030.3, 943.8, 855.5, 751.6. UV/
Vis (water): λmax (ꢀ) ) 295 nm (9900 mol dm3 cm ). Anal.
-
1
-1
d ia za octyla m in o)]-Br id ged Bis(â-cyclod extr in ) 5. Bis(â-
cyclodextrin) 5 was prepared in 12% yield from 2,2′-diselenobis-
Calcd for C110
H
176
O
70
N
8
Se
2
‚2PtCl
4
2
‚8H O: C, 35.63; H, 5.27, N
4
1
(benzoic acid) and mono[6-(8-amino-3,6-diazaoctylamino)-6-
3.02. Found: C 35.79, H 5.35, N 2.68.
deoxy]-â-cyclodextrin according to a procedure similar to that
+
1
described above. MS (MALDI-TOF): m/z 2930 [M + K] . H
NMR (D
Ack n ow led gm en t. This work was supported by
Natural Science Foundation (No. 29992590-8 and
9972029) of China, Tianjin Natural Science Foundation
No.013613511), and the Foundation of Ministry of
2
O, TMS): 2.5-2.9 (m, 24H), 3.1-3.9 (m, 84H), 4.8
1
-
(
1
1
m, 14H), 7.1-7.9 (m, 8H). IR (KBr) ν/cm 3302.0, 2928.2,
2
(
659.6, 1640.3, 1629.5, 1586.9, 1548.8, 1534.1, 1429.6, 1366.3,
331.5, 1152.9, 1079.0, 1032.1, 943.3, 856.1, 752.5, 704.7. UV/
-
1
3
-1
vis (water): λmax (ꢀ) ) 310.0 nm (6000 mol dm cm ). Anal.
Calcd for C110 Se O: C, 43.03; H, 6.50; N, 3.65.
Found: C, 42.91; H, 6.40; N, 4.06.
Education, which are gratefully acknowledged.
H
178
O
70
N
8
2
‚10H
2
Su p p or tin g In for m a tion Ava ila ble: 2D NOESY spec-
Bis(â-cyclod extr in )-P t(IV) Com p lex 6. The complex 6
trum of host compound 4 in D
2
O; the method for calculating
was synthesized by the reaction of bis(â-cyclodextrin) 2 with
the thermodynamic parameters and stability constants (K
S
)
4
PtCl in aqueous solution. The complex obtained was purified
for 1:1 inclusion complexation of ANS and TNS with â-cyclo-
by column chromatography over Sephadex G-25 with distilled,
dextrin 1 and bis(â-cyclodextrin)s 2-5; and typical plots of log
deionized water to give a pure sample in isolated yields of 70%.
K versus 1/T for the fluorometric titrations of 2-5 with TNS.
S
1
H NMR (D O, TMS) 3.2-3.8 (m, 80H), 4.8-5.2(m, 14H), 7.5-
2
This material is available free of charge via the Internet at
http://pubs.acs.org.
(41) Kamigata, N.; Iizuka, H.; Izuoka, A.; Kobayashi, M. Bull. Chem.
Soc. J pn. 1986, 59, 2179.
J O025919A
5
36 J . Org. Chem., Vol. 68, No. 2, 2003