Benzimidazole-Based Tripodal
Receptor: Highly Selective Fluorescent
Chemosensor for Iodide in Aqueous
Solution
Narinder Singh† and Doo Ok Jang*,†,‡
Department of Chemistry, Yonsei UniVersity, Wonju 220-710, Korea, and Center for
BioactiVe Molecular Hybrids, Yonsei UniVersity, Seoul 120-749, Korea
dojang@yonsei.ac.kr
Received March 10, 2007
ABSTRACT
We synthesized a novel tripodal fluorescent receptor bearing benzimidazole motifs as recognition sites in the pods of the receptor. The
recognition behavior of the receptor toward various anions was evaluated in CH3CN/H2O (9:1, v/v) solution. The receptor showed changes in
fluorescent intensity only with I-, but it showed no significant changes on addition of other anions such as F-, Cl-, Br-, HSO4-, NO3-,
CH3COO-, and H2PO4-.
The design and synthesis of receptors capable of sensing
anions selectively have provided important tools of detecting
biologically and environmentally important analysts.1 Iodide
plays an important role in several biological activities such
as neurological activity and thyroid function. Hence the
iodide content of urine and milk is often required for
nutritional, metabolic, and epidemiological studies of thyroid
disorder.2 Moreover, elemental iodine has been frequently
used in many areas of chemistry for synthesizing valuable
molecules such as drugs and dyes. Therefore, developing
receptors that can bind iodide selectively is strongly desired.
Spectroscopic or electrochemical tools have been used to
observe anion binding to a receptor, and the fluorescent
sensing of anions has drawn much attention for its high
sensitivity and selectivity.3 Nevertheless, there are few reports
on the fluorescent recognition of iodide,4 and in-depth
research has not been done on the estimation of iodide in
† Department of Chemistry, Yonsei University.
‡ Bioactive Molecular Hybrids, Yonsei University.
(1) (a) Katayev, E. A.; Ustynyuk, Y. A.; Sessler, J. L. Coord. Chem.
ReV. 2006, 250, 3004-3047. (b) Schmidtchen, F. P. Coord. Chem. ReV.
2006, 250, 2918-2928. (c) Gale, P. A. Acc. Chem. Res. 2006, 39, 465-
475. (d) Amendola, V.; Esteban-Go´mez, D.; Fabbrizzi, L.; Licchelli, M.
Acc. Chem. Res. 2006, 39, 343-353. (e) Yoon, J.; Kim, S. K.; Singh, N.
J.; Kim, K. S. Chem. Soc. ReV. 2006, 35, 355-360. (f) Bowman-James, K.
Acc. Chem. Res. 2005, 38, 671-678. (g) Gale, P. A. Coord. Chem. ReV.
2003, 240, 167-189. (h) Sessler, J. L.; Camiolo, S.; Gale, P. A. Coord.
Chem. ReV. 2003, 240, 17-55.
(2) (a) Haldimann, M.; Zimmerli, B.; Als, C.; Gerber, H. Clin. Chem.
1998, 44, 817-824 and refs therein. (b) Aumont, G.; Tressol, J.-C. Analyst
1986, 3, 841-843. (c) Jalali, F.; Rajabi, M. J.; Bahrami, G.; Shamsipur,
M. Anal. Sci. 2005, 21, 1533-1535.
(3) (a) Gunnlaugsson, T.; Glynn, M.; Tocci, G. M.; Kruger, P. E.; Pfeffer,
F. M. Coord. Chem. ReV. 2006, 250, 3094-3117. (b) Martı´nez-Ma´n˜ez, R.;
Sanceno´n, F. Chem. ReV. 2003, 103, 4419-4476. (c) Desvergne, J. P.;
Czarnik, A. W. Chemosensors of Ion and Molecule Recognition; Kluwer:
Dordrecht, 1997. (d) De Silva, A. P.; Gunaratne, H. Q. N.; Gunnlaugsson,
T.; Huxley, A. J. M.; McCoy, C. P.; Rademacher, J. T.; Rice, T. E. Chem.
Rev. 1997, 97, 1515. (e) Fluorescent Chemosensors for Ion and Molecule
Recognition; Czarnik, A. W., Ed.; American Chemical Society: Washington,
D.C., 1992.
ORGANIC
LETTERS
2007
Vol. 9, No. 10
1991-1994
10.1021/ol070592r CCC: $37.00 © 2007 American Chemical Society
Published on Web 04/18/2007
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the presence of other anions, i.e., selective estimation of
iodide.
As part of our ongoing studies on simple and easy-to-
make receptors for anion recognition,5 here we present the
synthesis and anion binding studies of a new flexible tripodal
receptor containing three benzimidazole groups as recogni-
tion sites for iodide. To date, there have been no reports in
which a benzimidazole-based tripodal receptor is used for
recognition of any anions.
The strategy for the design of the receptor is based upon
two ideas. First, N-H bonds in the receptor aligned in
parallel may effectively make a complex with an anion.
Second, the flexibility of the receptor would allow encap-
sulation of large anions such as iodide.
The receptor 2 was prepared by applying the condensation
reaction of tripodal aldehyde 1 with 2-aminobenzimidazole
in a THF and MeOH solvent mixture in the presence of a
catalytic amount of toluenesulfonic acid (Scheme 1).6 Upon
completion of the reaction, the imine linkages of the product
were reduced with NaBH4.
The receptor 2 displayed a maximum at 495 nm in its
fluorescence spectrum that was recorded with its 10 íM
concentration in CH3CN/H2O (9:1, v/v) at neutral pH
(HEPES buffer) when excited at 346 nm. The changes in
fluorescence intensity of 2 upon addition of a particular anion
are shown in Figure 1, and the fluorescence ratio (Io - I)/Io
is displayed in Figure 2. As can be seen from Figures 1 and
2, it is clear that there was marked quenching upon addition
of iodide, and no significant quenching was observed upon
addition of any F-, Cl-, Br-, HSO4-, NO3-, CH3COO-, and
H2PO4-.
The preference for iodide suggests that the flexible
pods in 2 are more compatible to the size of iodide than to
the size of other anions. The higher binding of F- among
halides on the basis of its basicity has been known, and
anions tend to bind in the order of F- > Cl- > Br- > I-.7
However, there are many examples where other halides (with
the exception of F-) bind predominantly because of the
complementary size of the pseudocavity formed by the
receptor binding sites.8 Thus, we think that it is better to
encapsulate the iodide according to its size, not according
to its basicity.
(4) For some examples of molecular recognition of iodide: (a) Rodriguez-
Docampo, Z.; Pascu, S. I.; Kubik, S.; Otto, S. J. Am. Chem. Soc. 2006,
128, 11206-11210. (b) Kim, H.; Kang, J. Tetrahedron Lett. 2005, 46,
5443-5445. (c) Ariga, K.; Kunitake, T.; Furuta, H. J. Chem. Soc., Perkin
Trans. 2 1996, 667-672.
(5) (a) Kang, J.; Kim, H. S.; Jang, D. O. Tetrahedron Lett. 2005, 46,
6079-6082. (b) Kim, H. S.; Moon, K. S.; Jang, D. O. Supramol. Chem.
2006, 18, 97-101.
(6) Chand, D. K.; Ragunathan, K. G.; Mak, T. C. W.; Baradwaj, P. K.
J. Org. Chem. 1996, 61, 1169-1171.
Scheme 1. Synthesis of Receptor 2
Figure 1. Changes in fluorescence intensity of 2 (10 íM) upon
addition of 5.0 equiv of a particular tetrabutylammonium anion salt
in CH3CN/H2O (9:1, v/v) (10 mM HEPES buffer, pH ) 7.0) with
excitation at 346 nm.
Figure 2. Fluorescence ratio (Io - I/Io) of 2 (10 íM) at 495 nm
upon addition of 5.0 equiv of a particular tetrabutylammonium anion
salt in HEPES buffered (10 mM, pH ) 7.0) CH3CN/H2O (9:1, v/v).
1992 Org. Lett., Vol. 9, No. 10, 2007
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连接
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HEPES:(N-(2-Hydroxyethyl)piperazine-N′-(2-ethanesulfonic acid))缓冲体系
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To confirm our point and to rule out the possibility of
heavy atomic effects due to iodide, we designed another
compound 3 (Scheme 2), which resembles the single pod of
receptor 2. We selected a 30 íM concentration of compound
3 (a 30 íM concentration of 3 has approximately the same
number of binding sites as that of a 10 íM concentration of
2) and then studied the quenching activity by iodide. No
significant changes in the fluorescence intensity were
observed in the typical experiment. This proved that although
2 and 3 have the same type of binding sites only an
appropriate size of the pseudocavity of 2 can bind iodide,
and iodide is believed to be bound cooperatively in the cavity
of 2.
To learn more about the properties of 2 as a receptor for
iodide, fluorescence titration was carried out. The fluores-
cence intensity of a 10 íM solution of 2 decreased as the
concentration of tetrabutylammonium iodide salt increased
as shown in Figure 3. The receptor 2 exhibited a high
sensitivity toward iodide, quenching 75% of its fluorescence
intensity with 3.0 equiv of iodide. The association constant
Ka of 2 for iodide was calculated on the basis of Benesi-
Hildebrand plot,9 and it was found to be 2.2 � 105 M-1.
The Stern-Volmer plot (plot of Io/I vs concentration of
guest) is a straight line. This confirmed the formation of one
type of complex between 2 and iodide.10 The stoichiometry
of the complex formed was determined by Job’s plot,11 and
it was found to be 1:1. There were no significant changes in
the fluorescence intensity of 2 upon addition of F-, Cl-, Br-,
HSO4-, NO3-, CH3COO-, and H2PO4-. This shows that the
receptor 2 is highly selective in its response to iodide in
comparison to other anions. Thus, the receptor 2 can be used
for selective recognition of iodide, and it can detect iodide
up to a low concentration of 2.1 íM.12
The system was further extended to estimate the iodide
in the presence of other anions, which may interfere in
estimation (Figure 4). Experiments were performed to
measure the fluorescence intensity in a series of solutions
containing the receptor 2, different amounts of iodide, and
other anions having a concentration 10 times greater than
the concentration of iodide in CH3CN/H2O (9:1, v/v).
The fluorescence titration of 2 for iodide in aqueous
solution was carried out in the presence of F-, Cl-, Br-,
HSO4-, NO3-, CH3COO-, and H2PO2-. The fluorescence
intensity was almost identical to that obtained in the absence
(7) (a) Amendola, V.; Esteban-Gomez, D.; Fabbrizzi, L.; Licchelli, M.
Acc. Chem. Res. 2006, 39, 343-353. (b) Bowman-James, K. Inorg. Chem.
2003, 42, 1397-1399. (c) Inoue, Y.; Kanbara, T.; Yamamoto, T. Tetra-
hedron Lett. 2003, 44, 5167-5169. (d) Hossain, A.; Kang, S. O.; Powell,
D.; Stephen, D.; Arungundram, S. S.; Saunders, C. H. Tetrahedron Lett.
2002, 43, 7785-7788. (e) Cotero´n, J. M.; Kacket, F.; Schneider, H. J. J.
Org. Chem. 1996, 61, 1429-1435. (f) Gale, P. A.; Sessler, J. L.; Kra´l, V.;
Lynch, V. J. Am. Chem. Soc. 1996, 118, 5140-5141. (g) Beer, P. D.; Gale,
P. A.; Dusan, H. Tetrahedron Lett. 1995, 36, 767-770. (h) Scheerder, J.;
Fochi, M.; Engbersen, J.; Reinhoudt, D. N. J. Org. Chem. 1994, 59, 7815-
7820.
(8) (a) Kang, J.; Kim, J. Tetrahedron Lett. 2005, 46, 1759-1762. (b)
Stastny, V.; Lhotak, P.; Michlova, V.; Stilbor, I.; Sykora, J. Tetrahedron
2002, 58, 7207-7211. (c) Tuntulani, T.; Thavornyutikarn, P.; Poompradub,
S.; Jaiboon, N.; Tuangpornvisuti, V.; Chaichit, N.; Asfari, Z.; Vicens, J.
Tetrahedron 2002, 58, 10277-10285. (d) Choi, K.; Hamilton, A. D. J. Am.
Chem. Soc. 2001, 123, 2456-2457. (e) Andrievsky, A.; Ahius, F.; Sessler,
J. L.; Vo¨gtle, F.; Gudat, D.; Moini, M. J. Am. Chem. Soc. 1998, 120, 9712-
9713. (f) Davis, A. P.; Perry, J. P.; Williams, R. P. J. Am. Chem. Soc.
1997, 119, 1793-1794.
(9) Benesi, H.; Hildebrand, H. J. Am. Chem. Soc. 1949, 71, 2703-2707.
(10) Keizer, J. J. Am. Chem. Soc. 1983, 105, 1494-1498.
(11) Job, P. Ann. Chim. 1928, 9, 113-203.
(12) Shortreed, M.; Kopelman, R.; Kuhn, M.; Hoyland, B. Anal. Chem.
1996, 68, 1414-1418.
Scheme 2. Structure of 3
Figure 3. Fluorescence spectra changes of 2 (10 íM) upon addition
of tetrabutylammonium iodide (0-50 íM) in HEPES buffered (10
mM, pH ) 7.0) CH3CN/H2O (9:1, v/v).
Figure 4. Estimation of I- in the presence of F-, Cl-, Br-, HSO4-,
NO3-, CH3COO-, and H2PO4- in HEPES buffered (10 mM, pH
) 7.0) CH3CN/H2O (9:1, v/v).
Org. Lett., Vol. 9, No. 10, 2007 1993
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Iodide:Other anions=1:10
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同一的
of anions with the exception of H2PO2-. H2PO4- caused a
small interference when the sample contained a very small
amount of iodide (up to 4 íM), whereas other anions did
not cause any interference in the estimation of iodide.
Finally, an 1H NMR titration experiment was performed
to understand the character of the receptor-anion interac-
tions. The series of 1H NMR spectra of receptor 2 upon
addition of increasing amounts of tetrabutylammonium iodide
in DMSO-d6 are shown in Figure 5. Upon addition of 0.5
equiv of iodide salt, the signal of N-H at the benzylic
position split into two signals. The benzylic N-H signal of
pure receptor 2 at 6.60 ppm shifted to 6.48 ppm upon
addition of 1 equiv of iodide salt. This is a significant shift
in the benzylic N-H signal of receptor 2 which shows that
this binding site plays a vital role in the binding mode of
iodide.
In conclusion, we have synthesized an easy-to-make
neutral tripodal fluorescent anion receptor 2 based upon
benzimidazole moieties and investigated its binding proper-
ties toward iodide. It showed an extremely high selectivity
for iodide over a wide range of anions. The receptor acts as
a selective sensor for iodide even in the presence of other
ions in 10% aqueous CH3CN without any interference.
Acknowledgment. This work was supported by the
Center for Bioactive Molecular Hybrids at Yonsei University.
Supporting Information Available: Synthesis, charac-
terization data, experimental procedures, NMR spectra, and
fluorescence data. This material is available free of charge
via the Internet at http://pubs.acs.org.
OL070592R
Figure 5. Plot of 1H NMR spectra of receptor 2 on addition of
tetrabutylammonium iodide in DMSO-d6.
1994 Org. Lett., Vol. 9, No. 10, 2007
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直到
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裂分
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重要的
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模式
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研究