Molecular taekwondo. 2. A new calix[4]azacrown bearing two different binding sites as a new fluorescent ionophore

Article abstract of DOI:10.1021/jo020538i

Synthesis and binding studies of a new calixarene-based fluoroionophore were made. Calix[4]azacrown having an anthracenyl unit displayed large chelation-enhanced fluorescence effects with Cs⁺, Rb⁺, and K⁺ over other metal ion tested. Interesting molecular taekwondo processes between Cs⁺-Cu²⁺ and Cs⁺-Ag⁺ pairs were monitored via fluorescent changes.

Full text of DOI:10.1021/jo020538i

Molecu la r Ta ek w on d o. 2. A New
Ca lix[4]a za cr ow n Bea r in g Tw o Differ en t
Bin d in g Sites a s a New F lu or escen t
Ion op h or e
J ong Seung Kim,*,† Kwan Ho Noh,† Seoung Ho Lee,†
Sung Kuk Kim,† Sook Kyung Kim,‡ and J uyoung Yoon*,§
Department of Chemistry, Konyang University,
Nonsan 320-711, Korea, Department of New Materials
Chemistry, Silla University, Pusan 617-736, Korea, and
Department of Chemistry, Ewha Womans University,
Seoul 120-750, Korea
jongskim@konyang.ac.kr; jyoon@ewha.ac.kr
Received August 12, 2002
F IGURE 1. Structure of compounds 1-3.
Abstr a ct: Synthesis and binding studies of a new calix-
arene-based fluoroionophore were made. Calix[4]azacrown
having an anthracenyl unit displayed large chelation-
enhanced fluorescence effects with Cs+, Rb+, and K+ over
other metal ion tested. Interesting “molecular taekwondo”
processes between Cs+-Cu2+ and Cs+-Ag+ pairs were moni-
tored via fluorescent changes.
Calixarenes with appropriate appended groups are
good candidates because they have been shown to be
highly specific ligands, and their potential applications
as sensing agents have received increasing interest.1,2 On
the other hand, fluoroionophores chemically communicate
ion concentrations and are the subject of substantial
investigation for metal ion analysis.3 In fact, several
calixarene-based fluorescent sensors have already been
designed.4-7
Recently, we have synthesized new pyrene-armed
calix[4]azacrowns as new fluorescent ionophores (Figure
1).8 When metal ion is bound to either 1 or 2, the metal
ion itself can choose its better binding partner between
the two different binding sites, such as crown ether and
F IGURE 2. CHEF effects of compound 4 (6.0 µM) with metal
ions (100 equiv, 600 µM) in ethanol-dichloromethane (9:1, v/v)
at 450 nm.
azacrown ligand. Furthermore, when K+ ion was added
to a solution containing 2 and Ag+, we observed a
fluorescence quenching effect as the amount of K+ ion
increases. For example, complexation of K+ into the
crown ether site induced the decomplexation of Ag+ from
the azacrown site. We named this interesting “coming-
in and kicking-out” process as a “molecular taekwondo”
process.8
In a continuation of this work, we report herein the
synthesis and binding studies of a new calix[4]arene
derivative 4 containing two binding sites such as a crown
ether and an azacrown ether. In this system, the selective
binding properties toward metal ions and “molecular
taekwondo” processes between Cs+-Cu2+ and Cs+-Ag+
pairs were easily monitored via fluorescence change.
Our synthesis began with 25,27-bis(5-chloro-3-oxa-
pentyloxy)calix[4]arene (5), which was prepared following
the published procedure.9 Under a nitrogen atmosphere,
treatment of 5 with p-toluenesulfonamide and Cs2CO3 in
DMF led to calix[4]monoazacrown p-toluenesulfonate (6)
in 28% yield (Scheme 1). Calix[4]monoazacrown-5 (7) was
obtained in 70% yield after tosyl group was removed
using sodium amalgam. Finally, treatment of 7 with
* Corresponding authors.
† Konyang University.
‡ Silla University.
§ Ewha Womans University.
(1) Bo¨hmer, V. Angew. Chem., Int. Ed. Engl. 1995, 34, 713.
(2) Kim, J . S.; Shon, O. J .; Ko, J . W.; Cho, M. H.; Yu, I. Y.; Vicens,
J . J . Org. Chem. 2000, 65, 2386. (b) Kim, J . S.; Lee, W. K.; No, K.;
Asfari, Z.; Vicens, J . Tetrahedron Lett. 2000, 41(18), 3345. (c) Kim, J .
S.; Shon, O. J .; Sim, W.; Kim, S. K.; Cho, M. H.; Kim, J . G.; Suh, I. H.;
Kim, D. W. J . Chem. Soc., Perkin Trans. 1 2001, 31. (d) Kim, J . S.;
Thuery, P.; Nierlich, M.; Rim, J . A.; Yang, S. H.; Lee, J . K.; Vicens, J .
Bull. Kor. Chem. Soc. 2001, 22(3), 321.
(3) Chemosensors of Ion and Molecule Recognition; Desvergne, J .
P., Czarnik, A. W., Eds.; NATO ASI series; Kluwer Academic: Dor-
drecht, 1997. (b) de Silva, A. P.; Gunaratne, H. Q.; Gunnlaugsson, N.
T. A.; Huxley, T. M.; McCoy, C. P.; Rademacher, J . T.; Rice, T. E. Chem.
Rev. 1997, 97, 1515.
(4) Aoki, I.; Sakaki, T.; Shinkai, S. J . Chem. Soc., Chem. Commun.
1992, 730.
(5) J in, T.; Ichikawa, K.; Koyama, T. J . Chem. Soc., Chem. Commun.
1992, 499.
(6) J i, H.-F.; Brown, G. M.; Dabestani, R. Chem. Commun. 1999,
609. (b) J i, H.-F.; Dabestani, R.; Brown, G. M.; Sachleben, R. A. Chem.
Commun. 2000, 833. (c) J i, H.-F.; Dabestani, R.; Brown, G. M.; Hettich,
R. L. J . Chem. Soc., Perkins Trans. 2 2001, 585.
(7) Leray, I.; O’Reilly, F.; Habib J iwan, J .-L.; Soumillion, J .-Ph.;
Valeur, B. Chem. Commun. 1999, 795.
(8) Kim, J . S.; Shon, O. J .; Rim, J . A.; Kim, S. K.; Yoon J . J . Org.
Chem. 2002, 67, 2348.
(9) Kim, J . S.; Lee, W. K.; No, K.; Asfari, Z.; Vicens, J . Tetrahedron
Lett. 2000, 41, 3345.
10.1021/jo020538i CCC: $25.00 © 2003 American Chemical Society
Published on Web 12/07/2002
J . Org. Chem. 2003, 68, 597-600
597

SCHEME 1. Syn th esis of Com p ou n d 4
1,2-bis(5-chloro-3-oxa-1-pentyloxy)-4-(10-cyano-9-anthryl-
is partially quenched by photoinduced electron transfer
(PET) from the dialkoxybenzene moiety of the crown ring
to the excited singlet state of 9-cyanoanthracene.6 Upon
complexation, only in the crown ether binding site, the
oxygen lone pairs no longer participate in PET, causing
the CHEF effect. From the fluorescence titration experi-
ment, the association constants for Cs+ ion was estimated
to be 9.8 × 105 M-1 in EtOH-CH2Cl2 (9:1, v/v).10
methyl)benzene (8)6c gave compound 4 in 30% yield.
The perchlorate salts of Ca2+, Cd2+, Co2+, Cs+, Cu2+
,
Hg2+, K+, Li+, Mg2+, Mn2+, Na+, Pb2+, Rb+, Sr2+, and Zn2+
were used to evaluate metal ion binding ability.10 Using
these metal ions (600 µM, 100 equiv), 4 (6.0 µM)
displayed large chelation-enhanced fluorescence (CHEF)
effects with Cs+, Rb+, and K+ in EtOH-CH2Cl2 (9:1, v/v)
(Figure 2). Io is the fluorescence intensity in the absence
of metal ion, and I is the intensity when 100 equiv of
each metal ion was added. As illustrated in Dabestani’s
recent papers, in the absence of metal ions, fluorescence
As illustrated in our previous report,8 1 displayed large
CHEF effects upon the complexation with Cu2+, K+, Pb2+
,
and Rb+. On the other hand, 2 displayed similar CHEF
effects with Ag+, Co2+, Cu2+,and Pb2+. Unlike 1, 2 did
F IGURE 3. (a) Fluorescent emission spectra of 4 upon the addition of various amount of Cs+ in ethanol-dichloromethane (9:1,
v/v) and (b) fluorescent emission spectra of titrations of compound 4 (6 µM)‚Cs+ (10 equiv) upon the addition of various amount
of Cu2+ in ethanol-dichloromethane (9:1, v/v).
598 J . Org. Chem., Vol. 68, No. 2, 2003

regarding the “molecular syringe” process in 1,3-alternate
calix[4]azacrowns, Kim et al. recently reported12 intra-
molecular Ag+ ion tunneling through the π-basic calix-
tube in 3 (Figure 1). Upon the addition of trifluoroacetic
acid to a solution of 3 and Ag+, Ag+ ion tunneling from
the azacrown site to the crown ether site was observed
1
using a dynamic H NMR technique. In our case, these
processes can be easily monitored via fluorescent changes
as well. These phenomena were also reproduced in 4.
When 1 equiv of Cu2+ or Ag+ was added to the solution
of 4 (6 µM) in dichloroethane-ethanol (1:1, v/v), there
was not any change in fluorescenct emission. Addition
of trifluoroacetic acid to a solution containing only 4 did
not induce any enhancement of its fluorescence emission
intensity, either. On the other hand, the addition of
trifluoroacetic acid (1.0 equiv) to these solution of either
4‚Cu2+ or 4‚Ag+ induced the CHEF effects, indicating
that Cu2+ or Ag+ ions are located in the crown ether site
by the electrostatic repulsion between metal ion and
quaternary ammonium ion.
In conclusion, we report a synthesis and binding study
of a new calixarene-based fluoroionophore. Among the
metal ions examined, 4 displayed large CHEF effects
with Cs+, Rb+, and K+. Also, interesting “molecular
taekwondo” processes between Cs+-Cu2+ and Cs+-Ag+
pairs in 4 were easily monitored via fluorescent changes
and productively compared with those of Ag+-K+ and
Cu2+-K+ pairs in 2. Furthermore, intramolecular metal
ion tunnelings through π-basic calixtube upon the addi-
tion of trifluoroacetic acid were also easily monitored via
fluorescent changes. Introduction of a second fluorophore
on the azacrown ether site is under investigation.
F IGURE 4. Fluorescence emission spectra of compound 2 (6
µM)‚Ag+(10 equiv) upon the addition of CF3COOH (1 equiv)
in ethanol-dichloromethane (v/v, 9:1).
not show any CHEF effect with K+ and Rb+. When metal
ion is bound to 2, K+ showed a better binding affinity
with the crown ether moiety of 2, and therefore, no CHEF
effect has been observed. Productively compared, 4
showed large CHEF effects only with Cs+, Rb+, and K+,
which are located in the crown ether site. Since we
introduced a fluorophore in the crown ether site of 4, the
“molecular taekwondo” process was confirmed again in
an opposite mode compared to 2. Upon the addition of
Cs+ to 4, the CHEF effect was observed due to the
inhibition of the PET mechanism (Figure 3). This CHEF
effect also confirms that Cs+ is in the crown ether site.
When Cu2+ ion was added to a solution containing 4 (6
µM) and Cs+(10 equiv), we observed a fluorescence
quenching effect as the amount of Cu2+ ion increases
(Figure 3). Complexation of Cu2+ into the azacrown ether
site induced the decomplexation of Cs+ from the crown
ether site. However, we could only observe partial de-
complexations of Cs+ from the crown ether site of 4 under
our experimental condition. The above observation was
repeated using the Cs+-Ag+ pair.
Exp er im en ta l Section
Syn th esis. Ca lix[4]m on oa za cr ow n p-tolu en su lfon a te (6).
Under nitrogen, a mixture of p-toluenesulfonamide (0.53 g, 5.15
mmol), Cs2CO3 (3.25 g, 23.5 mmol), and DMF (100 mL) was
heated to 80 °C for 30 min. 25,27-Bis(5-chloro-3-oxapentyloxy)-
calix[4]arene (5) (5.00 g, 7.85 mmol) dissolved in DMF (20 mL)
was added dropwise over a period of 3 h. After refluxing for 24
h, the mixture was dissolved in CH2Cl2 (100 mL) and treated
with 10% aqueous NaHCO3 (100 mL). The organic layer was
washed with water (100 mL) and dried over anhydrous MgSO4
and filtered. Column chromatography using ethyl acetate as an
eluent on silica gel gave 6 as a pale brownish solid in 28%
yield: mp 298-301 °C; FAB MS m/z (M+) calcd 735.9, found
736.2. Anal. Calcd for C43H45NO8S: C, 70.12; H, 6.11. Found:
C, 70.15; H, 6.09.
Ca lix[4]m on oa za cr ow n -5 (7). Under nitrogen, to solution
of 1,4-dioxane (100 mL) and methanol (20 mL) were carefully
added calix[4]monoazacrown p-toluensulfonate (1.0 g, 1.35
mmol), sodium hydrogen phosphate (0.42 g, 2.97 mmol), and 6%
Na(Hg) amalgam (3.9 g, 67.5 mmol). The reaction mixture was
refluxed for 2 days at 80 °C. After cooling to room temperature,
the solvent was evaporated in vacuo. CH2Cl2 (50 mL) and water
(50 mL) were added, and the organic layer was separated. The
CH2Cl2 layer was washed twice with 10% aqueous Na2HPO4
followed by drying over anhydrous MgSO4. After filtration of
magnesium sulfate, removal of the solvent in vacuo gave 7 as a
white solid in 70% yield: mp 181-183 °C; FAB MS m/z (M+)
calcd 581.7, found 582.3. Anal. Calcd for C36H39NO6: C, 74.26;
H, 6.70. Found: C, 74.29; H, 6.75.
Furthermore, when 1 equiv of trifluoroacetic acid was
added into a solution of 2 and Ag+ (10 equiv), fluorescence
emission intensity was further enhanced due to the
protonation of benzylic amine (Figure 4). Interestingly,
during this process, Ag+ moved to the crown ether moiety
by intramolecular tunneling through the calix-tube.
Following the couple of reports from Shinkai group11
(10) The association constant was obtained using the computer
program ENZFITTER, available from Elsevier-BIOSOFT, 68 Hills
Road, Cambridge CB2 1LA, United Kingdom.
1,3-Alter n a te 25,27-[4-(10-Cya n o-9-a n th r ylm eth yl)-1,2-
ph en ylen ebis(5-dioxy-3-oxa-1-pen tyloxy)]calix[4]azacr own -
(11) Ikeda, A.; Shinkai, S. J . Am. Chem. Soc. 1994, 116, 3102. (b)
Koh, K. N.; Araki, K.; Shinkai, S.; Asfari, Z. Vicens, J . Tetrahedron
Lett. 1995, 36, 6095.
(12) Kim, J . S.; Yang, S. H.; Rim, J . A.; Kim, J . Y.; Vicens, J .;
Shinkai, S. Tetrahedron Lett. 2001, 42, 8047.
J . Org. Chem, Vol. 68, No. 2, 2003 599

5 (4). Under nitrogen, a mixture of calix[4]monoazacrown-5 (7)
(0.4 g, 0.68 mmol), NaI (0.26 g, 1.73 mmol), Cs2CO3 (3.59 g, 11.0
mmol), and 1,2-bis(5-chloro-3-oxa-1-pentyloxy)-4-(10-cyano-9-
anthrylmethyl)benzene (8) (0.41 g, 0.76 mmol) in dry CH3CN
(100 mL) was refluxed for 2 days. After cooling to room
temperature, the solvent was evaporated in vacuo. CH2Cl2 (50
mL) and water (50 mL) were added, and the organic layer was
separated. The CH2Cl2 layer was washed twice with 10%
aqueous NaCl solution followed by drying over anhydrous
MgSO4. After filtration of magnesium sulfate, removal of the
solvent in vacuo gave 4 as a yellow solid (30%), which was
recrystallized from diethyl ether (30 mL): mp 217-220 °C; FAB
MS m/z (M+) calcd 1047.2, found 1047.3. Anal. Calcd for
C66H66N2O10: C, 75.63; H, 6.30. Found: C, 75.59; H, 6.35.
Gen er a l P r oced u r e for F lu or escen t Stu d y.
measurements, excitation was at 390 nm; excitation and emis-
sion slit widths were both 3 nm.
Fluorescence titration experiments were performed using 6
µM of 4 and various amounts of cesium perchlorate in ethanol
and dichloromethane (9:1, v/v). After calculating the concentra-
tions of the complex form of 4 and free 4 from the fluorescence
titration experiments, the association constant was obtained
using the computer program ENZFITTER.10
Ack n ow led gm en t. This research was supported by
a Grant from the Korea Science and Engineering
Foundation (KOSEF-R01-2000-000-00047-0). We also
gratefully thank KBSI in Daejeon for the instrumenta-
tion support (1H and 13C NMR and mass spectrometer).
1
Stock solutions (1.00 mM) of those metal perchlorate salts
were prepared using ethanol. A stock solution of 4 was prepared
in dichloromethane (0.06 mM). Test solutions were prepared by
placing 400 µL of the probe stock solution into a test tube, adding
an appropriate aliquot of each metal stock, and diluting the
solution to 4 mL with ethanol and dichloromethane. For all
Su p p or tin g In for m a tion Ava ila ble: Additional H and
13C NMR and IR data (Data S1-S3) for 4, 6, and 7, respec-
tively. This material is available free of charge via the Internet
at http://pubs.acs.org.
J O020538I
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