Supramolecular crown ether probe/γ-cyclodextrin complex sensors for alkali metal ion recognition in water

Article abstract of DOI:10.1246/bcsj.75.1527

Crown ether probes C3-12C4 and C3-18C6, in which the pyrenyl moieties as fluorophore and benzo-12-crown-4 or benzo-18-crown-6 acting as ion recognition sites are connected by a trimethylene spacer, have been synthesized. Their supramolecular function for alkali metal ion sensing in water is compared with that of the previously designed C3-15C5/γ-CyD complex sensor. The C3-12C4, C3-15C5, and C3-18C6 are found to selectively form 2:1 complexes with Na⁺, K⁺, and Cs⁺, respectively, in the presence of γ-CyD and to exhibit pyrene dimer emission in water. These results demonstrate that the selectivity of the crown ether probe/γ-CyD complexes can be tuned by simply altering their crown ether ring size. The apparent 2:1 binding constants of the probes with alkali metal ions are determined at the optimum γ-CyD concentrations for each probe. For C3-12C4/γ-CyD complex, the accurate binding constant could not be obtained due to the relatively large deviation for the response. However, the fitting curve reveals that the binding constant is about 10⁷ M^-2. The 2:1 binding constants of the C3-15C5/γ-CyD complex for K⁺ and C3-18C6/γ-CyD complex for Cs⁺ are (3.8 ± 1.3) x 10⁹ M^-2 and (5.8 ± 4.6) x 10⁷ M^-2, respectively. These values are considerably larger than those of the corresponding benzocrown ethers in organic solvents. In the suparamolecular sensing system, the dimer formation of the probes inside the γ-CyD is selectively promoted by alkali metal ion binding in water. This is a novel sensing mechanism in which the dynamic molecular recognition events are successfully utilized for ion sensing in water.

Full text of DOI:10.1246/bcsj.75.1527

Bull. Chem.
Soc. Jpn.
75
7
© 2002 The Chemical Society of Japan
Bull. Chem. Soc. Jpn., 75, 1527–1532 (2002) 1527
The Chemical
Society of Ja-
pan
The Chemical
Society of Ja-
γ
Supramolecular Crown Ether Probe/ -Cyclodextrin Complex Sensors
for Alkali Metal Ion Recognition in Water
pan
AI
7
Supramolecular Crown Ether Probe/γ-CyD Sensors
A. Yamauchi et al.
15
Akiyo Yamauchi, Takashi Hayashita,* Ayako Kato, and Norio Teramae*
2002
1527
1532
BCSJA8
0009-2673
01454
12
21
2001
3
Department of Chemistry, Graduate School of Science, Tohoku University, Aoba-ku, Sendai 980-8578
(Received December 21, 2001)
Crown ether probes C3-12C4 and C3-18C6, in which the pyrenyl moieties as fluorophore and benzo-12-crown-4
or benzo-18-crown-6 acting as ion recognition sites are connected by a trimethylene spacer, have been synthesized.
Their supramolecular function for alkali metal ion sensing in water is compared with that of the previously designed C3-
15C5/γ-CyD complex sensor. The C3-12C4, C3-15C5, and C3-18C6 are found to selectively form 2:1 complexes with
Na+, K+, and Cs+, respectively, in the presence of γ-CyD and to exhibit pyrene dimer emission in water. These results
demonstrate that the selectivity of the crown ether probe/γ-CyD complexes can be tuned by simply altering their crown
ether ring size. The apparent 2:1 binding constants of the probes with alkali metal ions are determined at the optimum γ-
CyD concentrations for each probe. For C3-12C4/γ-CyD complex, the accurate binding constant could not be obtained
due to the relatively large deviation for the response. However, the fitting curve reveals that the binding constant is about
107 M−2. The 2:1 binding constants of the C3-15C5/γ-CyD complex for K+ and C3-18C6/γ-CyD complex for Cs+ are
(3.8 1.3)×109 M−2 and (5.8 4.6)×107 M−2, respectively. These values are considerably larger than those of the cor-
responding benzocrown ethers in organic solvents. In the suparamolecular sensing system, the dimer formation of the
probes inside the γ-CyD is selectively promoted by alkali metal ion binding in water. This is a novel sensing mechanism
in which the dynamic molecular recognition events are successfully utilized for ion sensing in water.
14
2002
2.12
5.7.4
Supramolecular chemistry concerns the novel structure and
properties of a molecular assembly constructed by multiple
weak non-covalent interactions such as hydrogen bonds, aro-
matic π-stacking, and van der Waals interactions.1 The coop-
eration of individual interactions of supramolecular complexes
is expected to induce a novel function which differs from that
found in simple molecules. In addition to designs of various
supramolecular structures,2 unique supramolecular sensors
have been extensively developed for ion and molecule recogni-
tion.3 The advantages of supramolecular sensors are: 1) feasi-
bility of controlling dynamic molecular recognition events, 2)
enhancement of binding efficiency and selectivity by the coop-
eration of individual interactions, 3) better synthetic facility
compared to conventional receptors in which several function-
al groups are covalently connected, and 4) diversity of compo-
nent combinations.
Chart 1. Formula.
Cyclodextrins (CyDs) are attractive molecules for construc-
tion of supramolecular complex structures because of the wa-
ter-soluble CyDs possess nanosize hydrophobic cavities that
enable them to incorporate various organic molecules in wa-
ter.4 We recently used a benzo-15-crown-5 probe (C3-15C5)/
γ-CyD complex to selectively sense potassium ion in water
(Chart 1). Dimerization of C3-15C5 inside the γ-CyD pro-
vides a highly selective binding site for the potassium ion (Fig.
1).5,6 In general, control of metal-crown ether interaction in
water is quite difficult due to the fact that the metal ions are
strongly hydrated. However our finding demonstrates that the
recognition selectivity of crown ether probe/γ-CyD complexes
in water can be tuned by simply altering their crown ether ring
sizes. Thus the selectivity of crown ether probe/γ-CyD com-
Fig. 1. Possible structure of 2:1:1 complex of C3-15C5
with K+ and γ-CyD.
plex sensors can be shifted to smaller size ions by reducing the
ring size from 15C5 to 12C4. Similarly, selective recognition
for larger metal ions is expected by expanding the ring size to
18C6. To verify this prediction, crown ether probes C3-12C4
and C3-18C6 possessing benzo-12-crown-4 (B12C4) and ben-
zo-18-crown-6 (B18C6) moieties are newly designed and their

1528 Bull. Chem. Soc. Jpn., 75, No. 7 (2002)
Supramolecular Crown Ether Probe/γ-CyD Sensors
amide (C3-18C6). This compound was synthesized from the
corresponding benzocrown ether in a similar manner to that de-
scribed for C3-12C4. 4ꢀ-Nitrobenzo-18-crown-6 was purified by
recrystallization from ethanol-hexane to give the product as pale
yellow crystals (3.3 g, 74%). 1H NMR (CDCl3, 270 MHz) δ 7.87
(dd, J = 8.0 Hz, 2.6 Hz, 1H, ArH), 7.72 (d, J = 2.6 Hz, 1H, ArH),
6.86 (d, J = 8.0 Hz, 1H, ArH), 4.14–4.30 (m, 4H, CH2), 3.91–4.01
(m, 4H, CH2), 3.62–3.91 (m, 12H, CH2). 4ꢀ-Aminobenzo-18-
crown-6: brown viscous liquid. 1H NMR (CDCl3, 270 MHz) δ
6.68 (d, J = 8.2 Hz, 1H, ArH), 6.26 (d, J = 2.6 Hz, 1H, ArH), 6.19
(dd, J = 8.2 Hz, 2.6 Hz, 1H, ArH), 4.01–4.12 (m, 4H, CH2), 3.78–
3.93 (m, 4H, CH2), 3.60–3.76 (m, 12H, CH2). C3-18C6 was puri-
fied by chromatography on silica gel with CH2Cl2–MeOH–EtOAc
(10/0.2/0.5) and CH2Cl2–MeOH (9/1) as eluent, and by recrystal-
lization from CH2Cl2–MeOH to give the product as white solid
(50 mg, 6%) . 1H NMR (DMSO-d6, 270 MHz) δ 9.75 (s, 1H,
NH), 7.95–8.42 (m, 9H, pyrenyl), 7.27 (d, J = 2.4 Hz, 1H, ArH),
7.07 (dd, J = 8.4 Hz, 2.4 Hz, 1H, ArH), 6.86 (d, J = 8.4 Hz, 1H,
ArH), 3.95–4.06 (m, 4H, CH2), 3.67–3.79 (m, 4H, CH2), 3.47–
3.66 (m, 12H, CH2), 2.02–2.19 (m, 2H, CH2). Anal. Calcd for
C36H39NO7•0.2H2O: C, 71.91; H, 6.60; N, 2.33%. Found: C,
71.91; H, 6.58; N, 2.44%.
supramolecular function for alkali metal ion sensing in water is
compared with that of the previously designed C3-15C5/γ-
CyD complex sensor.
Experimental
Apparatus. UV-vis absorption spectra were recorded on a
Hitachi U-3000 spectrophotometer with 5-cm quartz cells. The
absorption spectra of each sample were obtained by subtraction of
the spectra of γ-CyD solution containing 1% acetonitrile (MeCN)
in the absence of probe. Fluorescence spectra were obtained on a
JASCO FP-770 spectrofluorometer using excitation and emission
bandwidths of 5 and 1.5 nm, respectively. These spectra were col-
lected at 298 0.5 K under an aerated condition. 1H NMR spec-
tra were obtained using a JEOL-GSX270 (270 MHz; JEOL
DATUM).
Reagents. Water was doubly distilled and deionized by a
Milli-Q Labo system (Millipore) before use. Acetonitrile (fluores-
cence reagent, Nakalai Tesque) was used as-received. All other
chemicals were commercially available and were used without
further purification unless otherwise stated.
Synthesis of N-(2,3,5,6,8,9-Hexahydro-1,4,7,10-benzotetra-
oxacyclododecin-12-yl)-4-(1-pyrenyl)butyramide (C3-12C4).
3.46 g (0.015 mol) of benzo-12-crown-4 were dissolved in chloro-
form (110 cm3) containing acetic acid (110 cm3). Then 70% nitric
acid (32 cm3, 0.50 mol) was carefully added dropwise. After stir-
ring for 6 h at room temperature, the chloroform layer was re-
moved using a separatory funnel, and then it was washed with wa-
ter and 5% aqueous Na2CO3. The chloroform layer was dried
(MgSO4) and the solvent was removed in vacuo. The resulting
residue was purified by recrystallization from ethanol to give 4ꢀ-
nitrobenzo-12-crown-4 (3.77 g, 93%). 1H NMR (CDCl3, 270
MHz) δ 7.91 (dd, J = 8.9 Hz, 3.2 Hz, 1H, ArH), 7.86 (d, J = 3.2
Hz, 1H, ArH), 6.96 (d, J = 8.9 Hz, 1H, ArH), 4.21–4.30 (m, 4H,
CH2), 3.80–3.92 (m, 4H, CH2), 3.73–3.79 (m, 4H, CH2). 4ꢀ-Nitro-
benzo-12-crown-4 (1.0 g, 0.0037 mol) was dissolved in 100 cm3
THF containing 10% Pd/C (0.3 g) and hydrazine monohydrate (16
cm3, 1.0 mol). The mixture was stirred under reflux condition for
1 h. The reaction mixture was filtrated through a glass filter, and
the filtrate was evaporated to give 4ꢀ-aminobenzo-12-crown-4 as
yellow gelatinous solid. 1H NMR (CDCl3, 270 MHz) δ 6.82 (d, J
= 9.9 Hz, 1H, ArH), 6.30 (d, J = 2.4 Hz, 1H, ArH), 6.23 (dd, J =
9.9 Hz, 2.4 Hz, 1H, ArH), 4.09–4.16 (m, 4H, CH2), 3.75–3.91 (m,
8H, CH2), 3.33–3.58 (s, Br, 2H, NH2). 4ꢀ-Aminobenzo-12-crown-
4 (0.66 g, 0.0028 mol) and 1-pyrenebutyric acid (0.66 g, 0.0023
mol) were dissolved in CH2Cl2 (340 cm3). Then, 1-(3-dimethyl-
aminopropyl)-3-ethylcarbodiimide hydrochloride (0.50 g, 0.0026
mol) dissolved in CH2Cl2 (50 cm3) was added. The mixture was
kept in an ice-water bath for 2 h while being stirred. This was fol-
lowed by stirring for 46 h at room temperature. The residue ob-
tained after removal of the solvent was purified by chromatogra-
phy on silica gel with CH2Cl2–MeOH (9/1) and CH2Cl2–MeOH–
EtOAc (10/0.5/0.5) as eluent, and by recrystallization from
CH2Cl2–MeOH to give the product as white solid (0.17 g, 14%).
1H NMR (DMSO-d6, 270 MHz) δ 9.81 (s, 1H, NH), 7.94–8.44 (m,
9H, pyrenyl), 7.34 (d, J = 2.4 Hz, 1H, ArH), 7.10 (dd, J = 8.6 Hz,
2.4 Hz, 1H, ArH), 6.94 (d, J = 8.6 Hz, 1H, ArH), 3.94–4.07 (m,
4H, CH2), 3.56–3.74 (m, 8H, CH2), 2.00–2.15 (m, 2H, CH2).
Anal. Calcd for C32H31NO5: C, 75.42; H, 6.13; N, 2.75%. Found:
C, 75.15; H, 5.81; N, 2.70%.
Results and Discussion
Synthesis of C3-12C4 and C3-18C6 Probes.
The C3-
12C4 and C3-18C6 probes were prepared in three steps from
the commercially available benzocrown ethers. The benzo-
crown ethers were first nitrated in chloroform/acetic acid solu-
tion containing nitric acid, followed by reduction to 4ꢀ-amino-
benzocrown ethers in THF of hydrazine monohydrate with
10% Pd/C. The C3-12C4 and C3-18C6 probes were obtained
by condensing the 4ꢀ-aminobenzocrown ethers with 1-pyrene
butylic acid in CH2Cl2 containing 1-(3-dimethylaminopropyl)-
3-ethylcarbodiimide hydrochloride. The products were puri-
fied by chromatography on silica gel followed by recrystalliza-
tion from CH2Cl2/methanol. The structures of C3-12C4 and
1
C3-18C6 probes were fully confirmed by H NMR and com-
bustion analysis.
γ
Sensing Properties of Crown Ether Probe/ -CyD Com-
plexes. Since the solubility of crown ether probes in water
was very low, the probes were first dissolved in acetonitrile as
stock solution. The sample solutions of probe/γ-CyD com-
plexes in water containing 1% acetonitrile were prepared by
diluting the stock solution with water containing γ-CyD and
the corresponding chloride salts. In this procedure, a consis-
tent concentration of probe solutions was obtained. In our pre-
liminary study, an increase of acetonitrile content in the sam-
ple solution was found to diminish the response function of
C3-15C5/γ-CyD complex. Thus fluorescence measurements
were carried out for the probe/γ-CyD complexes in water con-
taining 1% acetonitrile. The concentration of probe was fixed
to 0.50 µM (1 M = 1 mol dm−3). Figure 2 shows the fluores-
cence spectra of crown ether probe/γ-CyD complex sensors in
water containing 0.10 M TMACl or alkali metal chlorides.
Without γ-CyD, only weak fluorescences are noted when the
solution contains 0.10 M TMACl (condition 1). In contrast,
significant fluorescence emissions appear in the presence of
5.0 mM γ-CyD (condition 2). This appearance of fluorescence
indicates that crown ether probes form inclusion complexes
with γ-CyD.7 For C3-12C4/γ-CyD complex, the broad emis-
Synthesis of N-(2,3,5,6,8,9,11,12,14,15-Decahydro-1,4,7,10,
13,16-benzohexaoxacyclooctadecin-18-yl)-4-(1-pyrenyl)butyr-

A. Yamauchi et al.
Bull. Chem. Soc. Jpn., 75, No. 7 (2002) 1529
complex exhibits no spectral change in the presence of 0.10 M
TMACl or NaCl. However, upon addition of 0.10 M KCl, the
broad featureless band with an emission maximum at 470 nm
(dimer emission) is strongly intensified and there is quenching
of the monomer emission. The fluorescence spectra of C3-
18C6 probe are also shown in Fig. 2c. For C3-18C6/γ-CyD
complex, the broad emission band at around 470 nm intensifies
with concomitant decrease in the intensity of the monomer flu-
orescence only in the presence of 0.10 M CsCl. Similar to the
C3-15C5/γ-CyD and the C3-12C4/γ-CyD complexes, the ab-
sorption spectrum of C3-18C6/γ-CyD complex exhibits a re-
duction in the resolution and intensity of absorption in the
presence of Cs+, which indicates that the dimer formation is
promoted inside the γ-CyD cavity.
Figure 3 shows plots of the ratio of the dimer emission to
that of the monomer emission (ID/IM) vs the ionic radius of al-
kali metal cations. The selectivity of the crown ether probe/γ-
CyD complexes is consistent with the extraction selectivity of
bis-crown ethers.11 Thus C3-12C4, C3-15C5, and C3-18C6
probes form 2:1 complexes with Na+, K+, and Cs+, respec-
tively, inside the γ-CyD cavity and exhibit selective dimer
emission in water. These results clearly demonstrate that the
selectivity of the crown ether probe/γ-CyD complex sensor is
tunable by regulating the crown ether ring size of the probes.
γ
Binding Constants of Crown Ether Probe/ -CyD Com-
plexes. When one wants to determine the binding constants
of probe/γ-CyD complexes, the increase in dimer emission
with the alkali metal ion binding must be recorded under prop-
er experimental conditions. As shown in Fig. 4, the fluores-
cence intensity ratio (ID/IM) is strongly dependent on γ-CyD
concentration. Thus the concentration of γ-CyD should be op-
timized for each probe. The binding constant of the C3-15C5/
γ-CyD complex for K+ is determined in the presence of 5 mM
5,6
Fig. 2. Fluorescence spectra of probes ([probe] = 0.50 µM
in 99% water/1% MeCN (v/v)) with added species. (a)
C3-12C4 excited at 331.0 nm, (b) C3-15C5 excited at
330.5 nm and (c) C3-18C6 excited at 329.0 nm. (1) [γ-
CyD] = 0 mM and 0.10 M TMACl. (2) [γ-CyD] = 5.0
mM and 0.10 M TMACl. (3) [γ-CyD] = 5.0 mM and 0.10
M NaCl. (4) [γ-CyD] = 5.0 mM and 0.10 M KCl. (5) [γ-
CyD] = 5.0 mM and 0.10 M CsCl.
γ-CyD,
because the increase in the intensity ratio, ID/IM,
shows the maximum at 5 mM of γ-CyD concentration (Fig.
4b). The C3-12C4 probe exhibits the response maximum for
Na+ binding when the γ-CyD concentration is ca. 15 mM
(Fig. 4a). On the other hand, the increase in ID/IM of C3-18C6
for Cs+ binding is maximized when the concentration of γ-
CyD is 5-10 mM (Fig. 4c). Thus, the binding constant for al-
kali metal ions is determined in the presence of 15 mM γ-CyD
for C3-12C4, and 5 mM γ-CyD for C3-18C6, respectively.
Figure 5a shows the fluorescence spectra of C3-12C4/γ-
CyD complex upon addition of Na+. With increasing Na+
concentration, the intensity of monomer emission decreases,
while that of the dimer emission increases. Figure 5b plots the
intensity ratio (ID/IM) as a function of Na+ concentration. On
the assumption that the change in fluorescence is induced only
by 2:1 complex formation between the probe (L) and the met-
al ion (M+), the fluorescence ratio (ID/IM) can be expressed by
the following equations:12
sion band at around 470 nm is clearly seen even in the absence
of metal ions (Fig. 2a). The excitation spectrum monitored at
470 nm does not fit with that recorded at 377 nm. Thus the
broad emission band is assigned to the pyrene dimer emission
formed in the ground state.8 The C3-12C4/γ-CyD complex
shows no obvious spectral change upon addition of 0.10 M
KCl instead of 0.10 M TMACl. However, in the presence of
0.10 M NaCl, the dimer emission is intensified with quenching
of the monomer emission (condition 3 in Fig. 2a). The UV-vis
spectrum of the C3-12C4/γ-CyD complex in the presence of
Na+ shows a reduction in the resolution and intensity of ab-
sorption, which indicates the ground state interaction between
two pyrenyl moieties.9,10 These absorption and excitation
spectral changes demonstrate that the dimer formation of C3-
12C4 is promoted inside the γ-CyD cavity in the presence of
Na+. Figure 2b shows the fluorescence spectra of C3-15C5
probe reported in previous papers.5,6 The C3-15C5/γ-CyD
φfD φcD
φfM φfM
4
+
−1+ 1+8K[M+][L]0
(
)
ID
(1)
(2)
=
φcM
φfM
IM
4+
−1+ 1+8K[M+][L]0
(
)
+
[ML2
]
K =
[M+][L]2

1530 Bull. Chem. Soc. Jpn., 75, No. 7 (2002)
Supramolecular Crown Ether Probe/γ-CyD Sensors
Fig. 4. Fluorescence intensity ratio, ID/IM, of (a) C3-12C4,
(b) C3-15C5, and (c) C3-18C6 with 0.10 M (ꢀ) TMACl
and 0.10 M (ꢁ) MCl as a function of γ-CyD concentration.
[probe] = 0.50 µM in 99% water/1% MeCN (v/v). The
guest cation and emission wavelengths for the dimer/
monomer fluorescence are (a) Na+, 480/377 nm, (b) K+,
470/378 nm, and (c) Cs+, 470/377 nm, respectively.
Fig. 3. Dependence of fluorescence intensity ratio, ID/IM, of
(a) C3-12C4, (b) C3-15C5, and (c) C3-18C6 on the ionic
radius of alkali metal ions. [probe] = 0.50 µM in 99%
water/1% MeCN (v/v). [γ-CyD] = 5.0 mM. [MCl] =
0.10 M (M+ = Li+, Na+, K+, Rb+, Cs+). The emission
wavelengths for the dimer/monomer fluorescence are (a)
480/377 nm, (b) 470/378 nm, and (c) 470/377 nm, respec-
tively.
rate K value could not be determined from the nonlinear least-
square fitting with Eq. 1. However, the fitting curve reveals
that the K value is about 107 M−2. In this system, the response
for K+ is very small. Thus, high Na+ selectivity is obtained.
Figure 6a shows the fluorescence spectra of C3-18C6/γ-
CyD complex upon addition of Cs+. With an increase in Cs+
concentration, the dimer emission intensity of the C3-18C6/γ-
CyD complex increases and that of monomer emission de-
creases. Figure 6b represents the dependence of the intensity
ratio (ID/IM) upon the concentrations of alkali metal cations.
The points in Fig. 6b are fitted well with Eq. 1 (solid line) in
the presence of Cs+. The binding constant calculated by the
where [L]0 is the initial concentration of the probe, and φfD and
φfM are the fluorescence quantum yields for the probe at the
emission wavelength for the dimer fluorescence and that for
the monomer fluorescence, respectively. Similarly, φcD and
non-linear program is (5.8
4.6) × 107 M−2. For Cs+ ion
φ
cM are those for the 2:1 complex at dimer and monomer emis-
sensing with C3-18C6/γ-CyD complex, the detection limit es-
timated from 3σ of the deviation of blank fluorescence ratio
(ID/IM) is 1.4 × 10−4 M. In this system, the response for Na+
is negligible. Although there are a few examples of Cs+ selec-
tive indicators, they have been utilized only in organic media.13
sion wavelengths, respectively. The value of φfD/φfM can be de-
termined from the intensity ratio (ID/IM) when [M+] = 0 M.
Although the experiments were repeated three times, the de-
viations of points in Fig. 5b were relatively large, and an accu-

A. Yamauchi et al.
Bull. Chem. Soc. Jpn., 75, No. 7 (2002) 1531
Fig. 5. (a) Fluorescence spectra of C3-12C4. [C3-12C4] =
0.50 µM in 99% water/1% MeCN (v/v); [γ-CyD] = 15
mM. Excitation wavelength: 331.0 nm. (b) Dependence
of ID/IM on the concentration of (ꢁ) Na+ and (ꢀ) K+. The
emission wavelengths for the dimer/monomer fluorescence
are 480/377 nm.
Fig. 6. (a) Fluorescence spectra of C3-18C6. [C3-18C6] =
0.50 µM in 99% water/1% MeCN (v/v). [γ-CyD] = 5.0
mM. Excitation wavelength: 329.0 nm. (b) Dependence
of ID/IM on the concentration of (ꢁ) Cs+ and (ꢀ) Na+.
The emission wavelengths for the dimer/monomer fluores-
cence are 470/377 nm.
Table 1. 2:1 Binding Constants of the Probes with Alkali
Metal Ions
ing constant of the C3-12C4/γ-CyD complex for Na+ is much
smaller than that of the C3-15C5/γ-CyD complex for K+.
This may be attributed to a weak binding ability of B12C4
with Na+ in water. The sensitivity of C3-18C6/γ-CyD com-
plex for Cs+ is also lower than that of the C3-15C5/γ-CyD
complex for K+. For β-CyD complex, the C3-15C5 exhibits
no response by the addition of K+, indicating that the cavity
size of β-CyD is too small to incorporate the probe dimer.
Similarly the inclusion behavior of probes into γ-CyD strongly
depends on the probe structure.6,14 Since the apparent binding
constant includes the equilibrium constants of the inclusion
complexes with γ-CyD, the binding constant of the probe/γ-
CyD complex with an alkali metal cation can not be directly
compared among different ring sizes of crown ether probes.
However, the present results clearly demonstrate that the su-
pramolecular crown ether probe/γ-CyD complexes provide a
selective alkali metal ion recognition system in water.
K/M−2
Benzocrown ether in
Probe
Ion In γ-CyD aqueous soln.
organic soln.11
3.2 × 104(a)
1.4 × 106(b)
1.9 × 106(c)
C3-12C4 Na+
C3-15C5 K+
C3-18C6 Cs+
~107
(3.8 1.3) × 109
(5.8 4.6) × 107
(a) B12C4 for Na+ in MeCN, (b) B15C5 for K+ in MeOH,
(c) B18C6 for Cs+ in MeOH.
Thus the C3-18C6/γ-CyD complex would be a promising can-
didate to be used for the in situ monitoring of Cs+ in water.
The apparent binding constants of the probe/γ-CyD com-
plexes with alkali metal ions are summarized in Table 1. For
all probe/γ-CyD complexes, the binding constants are consid-
erably larger than those of the benzocrown ethers in organic
solvent.11 These abnormally high binding constants in water
reveal the characteristic supramolecular function of the probe/
γ-CyD complex sensors. It is evident that the dimer formation
of the probe inside γ-CyD is selectively promoted by alkali
metal ion binding in water. This is a novel sensing mechanism
in which the dynamic molecular recognition events are suc-
cessfully utilized for ion sensing in water. The apparent bind-
Conslusions
This study demonstrated that the selectivity of crown ether
probe/γ-CyD complex sensors for alkali metal ions was tun-
able by simply varying the crown ether ring size of probes.
Thus C3-12C4, C3-15C5, and C3-18C6 selctively responded
to Na+, K+, and Cs+, respectively, by forming 2:1 complexes
with target alkali metal ions inside the γ-CyD in water. For the

1532 Bull. Chem. Soc. Jpn., 75, No. 7 (2002)
Supramolecular Crown Ether Probe/γ-CyD Sensors
Umemoto, M. Yoshizawa, N. Fujita, T. Kusukawa, and K.
Biradha, Chem. Commun., 2001, 509. c) “Molecular Catenanes,
Rotaxanes and Knots,” ed by J.-P. Sauvage and C. Dietrich-
Buchecker, VCH, Weinheim (1999). d) S. A. Nepogodiev and J.
F. Stoddart, Chem. Rev., 98, 1959 (1998).
C3-12C4/γ-CyD complex, the accurate binding constant could
not be determined because of the relatively large deviation for
the response. However, the fitting curve revealed that the K
value was about 107 M−2. The 2:1 binding constant of B12C4
with Na+ in acetonitrile was 3.2 × 104 M−2. The high K value
of the C3-12C4/γ-CyD complex suggested that the formation
of 2:1 complex between C3-12C4 and Na+ was facilitated by
γ-CyD. The apparent binding constants of the C3-15C5/γ-
CyD complex for K+ and C3-18C6/γ-CyD complex for Cs+
3
For examples: a) R. R. Shah and N. L. Abbott, Science,
293, 1296 (2001). b) Y. Kim, R. C. Johnson, and J. T. Hupp, Nano
Lett., 1, 165 (2001). c) B. Colonna and L. Echegoyen, Chem.
Commun., 2001, 1104. d) S. L. Wiskur and E. V. Anslyn, J. Am.
Chem. Soc., 123 10109 (2001). e) J. Li and Y. Lu, J. Am. Chem.
Soc., 122, 10466 (2000). f) T. Hayashita, T. Onodera, R. Kato, S.
Nishizawa, and N. Teramae, Chem. Commun., 2000, 755. g)
W.-S. Xia, R. H. Schmehl, and C.-J. Li, Chem. Commun., 2000,
695. h) R. K. Castellano, S. L. Craig, C. Nuckolls, and J. R.
Rebek, J. Am. Chem. Soc., 122, 7876 (2000). i) S. Nishizawa,
Y. Kato, and N. Teramae, J. Am. Chem. Soc., 121, 9463 (1999).
were (3.8
1.3) × 109 M−2 and (5.8
4.6) × 107 M−2.
These values were also higher than the 2:1 binding constants
of B15C5 for K+ (1.4 × 106 M−2) and B18C6 for Cs+ (1.9 ×
106 M−2) in methanol. In both systems, response for Na+ was
negligible. Thus, selective sensing of K+ by C3-15C5/γ-CyD
complex and Cs+ by C3-18C6/γ-CyD complex in water was
feasible. Although an optimum structure of crown ether
probes has not been clarified, the novel supramolecular func-
tion of these crown ether probe/γ-CyD complexes would be
useful for the monitoring of alkali metal ions in clinical and
environmental aqueous samples in combination with autoana-
lyzer systems.15
4
J. Szejtli and T. Osa, “Comprehensive Supramolecular
Chemistry,” Pargamon/Elsevier, Oxford (1996), Vol. 3.
A. Yamauchi, T. Hayashita, S. Nishizawa, M. Watanabe,
and N. Teramae, J. Am. Chem. Soc., 121, 2319 (1999).
A. Yamauchi, T. Hayashita, A. Kato, S. Nishizawa, M.
Watanabe, and N. Teramae, Anal. Chem., 72, 5841 (2000).
5
6
The present results showed that the function of the probe/
CyD complexes could be tuned by proper design of the iono-
phores and applied to various lipophilic chromo- and fluoro-
ionophores. We have recently reported that the supramolecular
boronic acid fluorophore/β-CyD complex can selectively sense
sugars in water.16,17 We expect that these supramolecular com-
plex systems will create a novel analytical methodology for the
development of more sophisticated sensing systems for ion
and molecule recognitions in water.
7
8
9
S. Li and W. C. Purdy, Chem. Rev., 92, 1457 (1992).
F. M. Winnik, Chem. Rev., 93, 587 (1993).
A. Ueno, I. Suzuki, and T. Osa, J. Am. Chem. Soc., 111,
6391 (1989).
10 a) W. G. Herkstroeter, P. A. Martic, and S. Farid, J. Chem.
Soc., Perkin Trans. 2, 1984, 1453. b) T. Yorozu, M. Hoshino, and
M. Imamura, J. Phys. Chem., 86, 4426 (1982).
11 R. M. Izatt, K. Pawlak, J. S. Bradshaw, and R. L. Bruening,
Chem. Rev., 91, 1721 (1991).
12 G. Grynkiewicz, M. Poenie, and R. Y. Tsien, J. Biol.
Chem., 260, 3440 (1985).
This research was supported by a Grant-in-Aid for Scientific
Research (12440208,14340230) from the Ministry of Educa-
tion, Culture, Science, Sports and Technolgy, and by a Grant-
in-Aid for JSPS Fellows from Japan Society for the Promotion
of Science.
13 a) H.-F. Ji, G. M. Brown, and R. Dabestani, Chem. Com-
mun., 1999, 609. b) H.-F. Ji, R. Dabestani, G. M. Brown, and R.
A. Sachleben, Chem. Commun., 2000, 833. c) W.-S. Xia, R. H.
Schmehl, and C.-J. Li, Chem. Commun., 2000, 695.
14 N. Yoshida, H. Yamaguchi, T. Iwao, and M. Higashi, J.
Chem. Soc., Perkin Trans. 2, 1999, 379.
15 E. Chapoteau, B. P. Czech, W. Zazulak, and A. Kumar,
Clin. Chem., 38, 1654 (1992).
References
16 a) A.-J. Tong, A. Yamauchi, T. Hayashita, Z.-Y. Zhang, B.
D. Smith, and N. Teramae, Anal. Chem., 73, 1530 (2001). b) T.
Hayashita, A. Yamauchi, A. Kato, A.-J. Tong, B. D. Smith, and N.
Teramae, Bunseki Kagaku, 50, 355 (2001).
1
a) J.-M. Lehn, “Supramolecular Chemistry: Concepts and
Perspectives,” VCH, Weinheim (1995). b) D. S. Lawrence, T.
Jiang, and M. Levett, Chem. Rev., 95, 2229 (1995).
2
For comprehensive reviews: a) B. J. Holliday and C. A.
Mirkin, Angew. Chem. Int. Ed., 40, 2022 (2001). b) M. Fujita, K.