A novel amidepyridinium-based tripodal fluorescent chemosensor for phosphate ion via binding-induced excimer formation

Article abstract of DOI:10.1016/j.tetlet.2008.07.078

A new tripodal fluorescent chemosensor 1 having amidepyridinium moiety as the key binding site and anthracene moiety as the sensing subunit was synthesized. In competitive polar organic solvent, this chemosensor 1 displayed high selectivity toward H₂

Full text of DOI:10.1016/j.tetlet.2008.07.078

Tetrahedron Letters 49 (2008) 5655–5657
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Tetrahedron Letters
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A novel amidepyridinium-based tripodal fluorescent chemosensor
for phosphate ion via binding-induced excimer formation
b,
Wei-tao Gong a, , Kazuhisa Hiratani
*
*
a Division of Advanced Science and Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan
b Department of Applied Chemistry, Utsunomiya University, 7-1-2, Youtou, Utsunomiya 321-8585, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A new tripodal fluorescent chemosensor 1 having amidepyridinium moiety as the key binding site and
Received 4 June 2008
Revised 7 July 2008
Accepted 14 July 2008
Available online 17 July 2008
anthracene moiety as the sensing subunit was synthesized. In competitive polar organic solvent, this
chemosensor 1 displayed high selectivity toward H2PO4 by formation of binding-induced excimer
emission.
À
Ó 2008 Elsevier Ltd. All rights reserved.
The binding and sensing of anionic species by artificial recep-
tors is an expanding area of supramolecular chemistry.1,2 In this
sense, development and precise arrangement of cooperative bind-
ing motifs in the cavity of artificial hosts are of special importance,
however extreme challenge, for efficient anion recognition. Among
these binding motifs for anions, hydrogen bonds are the most
widely employed due to their directional nature, which possess
the capability to differentiate anionic species with different geo-
metries.1 During the past two decades, the hydrogen donating
properties of NH groups, such as neutral amine, amide, urea, pyr-
role, and indole, as well as the charged ammonium, guanidinium,
and imidazolium-based anion receptors have been well estab-
lished.1g In contrast, amidepyridinium-based anion receptors, and
especially sensors which combine the hydrogen donating proper-
ties of neutral amide group and acidic C–H at the pyridinium ring,
is surprisingly less investigated, although pyridinium-based anion
hosts had been reported by Steed and his coworkers recently.3
On the other hand, the overall receptor topology has a profound
effect on anion binding.4 In comparison to those rigid cyclic struc-
tures, flexible podand receptors remain challenging and are poten-
tially significant, since they frequently display rapid complexation/
decomplexation kinetics and undergo significant conformational
change on binding. Those properties form the basis of molecular
switches or switchable sensing devices.5,3b
The preparation of tripodal chemosensor 1 was achieved in an
acceptable yield by refluxing of symmetrical amide derivative 2
with 9-chloromethylanthracene in dry CH3CN for 48 h and then
anion exchange with NH4PF6. The detailed synthetic route is
shown in Scheme 1.6,7
The structure of chemosensor 1 was fully characterized with H1
NMR, MS, and elemental analysis.6,7 In order to provide some
i, ii
O
C
C
O
O
C
NH
CO OH
CO OH
HN
NH
CO OH
N
N
N
2
O
C
O
C
C
O
NH
iii, iv
NH
HN
Intrigued by these, herein, we introduce a new tripodal fluores-
cent chemosensor 1, which bears 3-amidepyridinium as the key
binding motif and anthracene moiety as the sensing subunit. Under
the cooperative multi-interactions of amide and acidic ÀCH
N+
N+
N+
-
3P F6
À
groups, 1 displayed highly fluorescent selectivity toward H2PO4
than other inorganic anions, such as FÀ, ClÀ, BrÀ, IÀ, HSO4 , and
À
AcOÀ by formation of unique excimer emission in competitive
polar organic solvents.
1
Scheme 1. Synthetic route to chemosensor 1. Reagents and condition: (i): excess
SOCl2, 70 °C, 8 h; (ii) 3-fold 3-aminopyridine, dry THF; (iii) 3-fold 9-chlorometh-
ylanthracene, dry CH3CN, reflux, 48 h; (iv) mixed solvent of DMF and H2O, excess
NH4PF6.
* Corresponding authors.
E-mail address: weitaogong@hotmail.com (W. Gong).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.07.078

5656
W. Gong, K. Hiratani / Tetrahedron Letters 49 (2008) 5655–5657
degree of preorganization into a conical conformation with all
three binding sites and sensing arms co-aligned, cis-cyclohexane
1,3,5-tricarboxylic acid was used herein as the starting material.
To the best of our knowledge, this is the first case using cis-cyclo-
hexyl group as the central core of tripodal receptor for anion sens-
ing compared to the well-establised podands having hexa-
substituted benzene as the core.8,3f
It was predicted that the arrangement of multiple anthracene
groups in the chemosensor 1 might report the anion binding by
appearance of some unique optical phenomena. As the potential
anion-dependent conformational change of host would induce
the possible association between those multiple anthracene moie-
ties to form excimer emission, giving rise to selective anion
sensing.
With this in mind, the investigation on optical-response of
chemosensor 1 toward various anions was first carried out by
using fluorescent spectroscopy in polar organic solvent (9:1
CH3CN–EtOH). By excitation of anthracene fluorophore at
368 nm, 1 alone displayed typical monomer emission of anthra-
cene fluorescence consisting of three sharp bands at 387, 413,
and 436 nm, as well as a shoulder at 466 nm. The relative weakly
fluorescent intensity of 1 was ascribed to the quenching effect of
PET process from the anthracene moieties to the charged pyridin-
ium ring.3f No evidence of excimer emission was shown in fluores-
cence spectrum of 1, which basically excluded the inter- or
intramolecular association between anthracene moieties under
the investigated conditions. This phenomenon indicated the pres-
ence of a certain favorable conformation of 1 to keep the relatively
remote distance between those anthracene moieties.
À
lM) upon addition of H2PO4 in
Figure 2. Changes in fluorescence spectra of 1 (50
9:1 CH3CN–EtOH solution with excitation at 368 nm.
remarkably enhanced broad band (at 505 nm) corresponded to
the excimer emission between anthracenes was observed simulta-
À
neously. This result demonstrated that the binding of H2PO4
pulled the separated anthracene moieties closer indicating the
occurrence of binding-induced conformational change of tripodal
chemosensor 1.
Absorption spectra of chemosensor 1 in the presence and
absence of the aforementioned anions were also measured to sup-
port those variations of fluorescence spectra. As shown in Figure 3,
the absorption bands of anthracene moieties were hardly affected
by FÀ, ClÀ, Br-, IÀ, HSO4À, and AcO, which indicate the insulating
role of the –CH2– group via minimizing the ground state inter-
actions between anthracene moieties and binding sites. On the
Figure 1 displays the changes in fluorescence of chemosensor 1
upon addition of various inorganic anions, such as FÀ, ClÀ, BrÀ, IÀ,
À
À
HSO4À, AcO , and H2PO4 having tetra-n-butyl ammonium as the
counter cation. It is worth noting from Figure 1 that only upon
À
addition of H2PO4 induced a marked change of fluorescent emis-
À
sion of 1, and in contrast, other anions showed negligible effect.
This result demonstrated that chemosensor 1 exhibited high selec-
other hand, addition of H2PO4 induced the apparent bathochro-
mic shift of the absorption bands of anthracene. This result implied
À
À
tivity toward H2PO4 in such competitive polar organic solvent by
not only the presence of strong interactions between H2PO4 and
changing its fluorescent properties. Fluorescent titration experi-
ments pointed to 1:1 stoichiometry between 1 and H2PO4À, which
is shown in Figure 2. Furthermore, the binding constant was calcu-
lated from this titration curve to give lgK to be 4.28.
binding sites of chemosensor 1 but also the formation of some
interaction and association between anthracenes at the ground
states.9,2c Therefore, the appearance of the new fluorescence band
at longer wavelength region in Figure 1 must be attributed to the
excimer fluorescence between anthracenes.
Just as shown in Figures 1 and 2, upon addition of H2PO4À, a
small increasing intensity of monomer fluorescence of chemosen-
sor 1 was found due to the inhibition of the photo-induced electron
transfer (PET) process from anthracene fluorophore to pyridinium
moiety. More significantly, together with this PET process, a
À
In order to know more about the interactions between H2PO4
and chemosensor 1, 1H NMR investigation was also performed and
the results are shown in Figure 4. Because the addition of more
À
than 0.5 equiv H2PO4 resulted in gradually precipitation during
the 1H NMR titration and made the spectra rather unclear, just
Figure 1. Changes in fluorescence spectra of 1 (50
l
M) upon addition of various
Figure 3. Changes of absorption spectra of 1 (50 lM) upon addition of various
anions in 9:1 CH3CN–EtOH solution with excitation at 368 nm.
anions in 9:1 CH3CN–EtOH solution.

W. Gong, K. Hiratani / Tetrahedron Letters 49 (2008) 5655–5657
5657
References and notes
1. For anion recognition, see reviews: (a) Schmidtchen, F. P.; Berger, M. Chem. Rev.
1997, 97, 1609; (b) Bianchi, A.; Bowman-James, K.; Carcia-Espana, E. Eds.;
Wiley-VCH: New York, 1997.; (c) Beer, P. D.; Gale, P. A. Angew. Chem., Int. Ed.
2001, 40, 486; (d) Gale, P. A. Coord. Chem. Rev. 2003, 240, 1; (e) Katayev, E. A.;
Ustynyuk, Y. A.; Sessler, J. L. Coord. Chem. Rev. 2006, 250, 3004; (f) Schmidtchen,
F. P. Coord. Chem. Rev. 2006, 250, 2918; (g) Gale, P. A. Acc. Chem. Res. 2006, 39,
465; (h) Yoon, J.; Kim, S. K.; Singh, N. J.; Kim, K. S. Chem. Soc. Rev. 2006, 35, 355;
(i) Gale, P. A.; Garcia-Garrido, S. E.; Garric, J. Chem. Soc. Rev. 2008, 37, 151.
2. For anion sensing: (a) Martinez-Manez, R.; Sancenon, F. Chem. Rev. 2003, 103,
4419; (b) Kameta, N.; Hiratani, K. Chem. Commun. 2005, 725; (c) Kameta, N.;
Hiratani, K. Tetrahedron Lett. 2006, 47, 4947; (d) Gunnlaugsson, T.; Glynn, M.;
Tocci, G. M.; Kruger, P. E.; Pfeffer, F. M. Coord. Chem. Rev. 2006, 250, 3094; (e) Xu,
Z.-C.; Kim, S.; Lee, K.-H.; Yoon, J. Tetrahedron Lett. 2007, 48, 3797; (f) Dahan, A.;
Ashkenazi, T.; Kuznetsov, V.; Makievski, S.; Drug, E.; Fadeev, L.; Bramson, M.;
Schokoroy, S.; Rozenshine-Kemelmakher, E.; Gozin, M. J. Org. Chem. 2007, 72,
2289; (g) Luxami, V.; Kumar, S. Tetrahedron Lett. 2007, 48, 3083; (h) dos Santos,
M. G.; Cidalia, P. B.; Fernandez, S. E.; Plush, J.; Leonard, P.; Gunnlaugsson, T.
Chem. Commun. 2007, 3389; (i) Kumar, M.; Babu, J. N.; Bhalla, V.; Athwal, N. S.
Supramolecular Chem. 2007, 19, 511; (j) Chen, C.-Y.; Lin, T.-P.; Lin, C.-K.; Chen,
S.-C.; Tseng, M.-C.; Wen, Y.-S.; Sun, S.-S. J. Org. Chem. 2008, 73, 900.
Figure 4. Partial 1H NMR spectra of 1 in the absence (lower) and the presence
(upper) of 0.5 equiv H2PO4 in DMSO-d6. Black stars denote the all protons of
anthracene moieties and black triangle show all protons of pyridinium rings.
À
3. (a) Abouderbala, L. O.; Belcher, W. J.; Boutelle, M. G.; Cragg, P. J.; Dhaliwal, J.;
Fabre, M.; Steed, J. W.; Turner, D. R.; Wallace, K. J. Chem. Commun. 2002, 358; (b)
Wallace, K. J.; Belcher, W. J.; Turner, D. R.; Syed, K. F.; Steed, J. W. J. Am. Chem.
Soc. 2003, 125, 9699; (c) Belcher, W. J.; Fabre, M.; Farhan, T.; Steed, J. W. Org.
Biomol. Chem. 2006, 4, 781; (d) Turner, D. R.; Paterson, M. J.; Steed, J. W. J. Org.
Chem. 2006, 71, 1598; (e) Turner, D. R.; Paterson, M. J.; Steed, J. W. Chem.
Commun. 2008, 1395; (f) Filby, M. H.; Dickson, S. J.; Zaccheroni, N.; Prodi, L.;
Bonacchi, S.; Montalti, M.; Paterson, M. J.; Humphries, T. D.; Chiorboli, C.; Steed,
J. W. J. Am. Chem. Soc. 2008, 130, 4105; (g) Ghosh, K.; Masanta, G.;
Chattopadhyay, A. P. Tetrahedron Lett. 2007, 48, 6129; h(h) Ghosh, K.; Sarkar,
A. R.; Masanta, G. Tetrahedron Lett. 2007, 48, 8725; (i) Ghosh, K.; Masanta, G.
Tetrahedron Lett. 2008, 49, 2592.
À
Figure 5. Fluorescent response to H2PO4 via formation of excimer emission.
4. (a) Choi, K.; Hamilton, A. D. Coord. Chem. Rev. 2003, 240, 101; (b) Chmielewski,
M. J.; Jurczak, J. Chem. Eur. J. 2005, 11, 6080; (c) Bowman-James, K. Acc. Chem.
Res. 2005, 38, 671; (d) Korendovych, I. V.; Cho, M.; Butler, P. L.; Staples, R. J.;
Rybak-Akimova, E. V. Org. Lett. 2006, 8, 3171.
À
the effect of adding 0.5 equiv H2PO4 was recorded. It was clear
5. Abouderbala, L. O.; Belcher, W. J.; Boutelle, M. G.; Cragg, P. J.; Steed, J. W.; Turner,
D. R.; Wallace, K. J. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 5001.
that the amide proton (from 11.55 to 12.86, 1.3 ppm shifted) and
hydrogen proton at the
a-position of pyridinium ring (from 9.25
6. Procedure for synthesis of compound 2: First, cis-cyclohexane 1,3,5-tricarboxylic
acid was reacted with thionyl chloride at 70 °C for 8 h to give the corresponding
acid chloride. After drying of 1 h under reduced pressure, this acid chloride was
used directly to the next reaction. Then, a solution containing 3-aminopyridine
(0.282 g, 3 mmol) and Et3N (1.01, 10 mmol) in dry THF (25 mL) was prepared
and cooled by ice-water bath. The aforementioned acid chloride (1 mmol) also
in dry THF (15 mL) was added dropwise into the above solution within about
20 min, and the stirring was continued for overnight under room temperature.
Then, the precipitated white solid was filtered, washed several times with
distilled water, and dried under reduced pressure. Without further purification,
it was conformed that this white solid was the target compound 2 (74%).
For compound2: 1H NMR (DMSO-d6, 500 MHz) 1.37 (m, cyclohexyl, 3H), 2.09 (m,
cyclohexyl, 3H), 2.58 (m, cyclohexyl, 3H), 7.33 (dd, pyridine, 3H), 8.04 (d,
J = 8.5 Hz, pyridine, 3H), 8.24 (d, J = 4 Hz, pyridine,3H), 8.73 (s, pyridine, 3H),
10.10 (br, ÀNH, 3H). ESI-MS (cationic mode), 445.2 (M+H); Elemental Anal.
Calcd for C24H24N6O3: C, 64.85; H, 5.44; N, 18.91. Found: C, 64.82; H, 5.53; N,
18.76. (18.91).
7. Procedure for synthesis of chemosensor 1: A mixture of compound 2 (0.444 g,
1 mmol) with 9-chloromethylanthracene (0.68 g, 3 mmol) in dry CH3CN was
refluxed for 48 h, and gradually yellow precipitate was formed. After cooling to
room temperature, the precipitate was filtered off and washed several times
with cold CH3CN. After recrystallization using EtOH, pure chemosensor 1 as
chloride salt was obtained in 46% yield. Then, the chloride salt (100 mg) was
dissolved in 1 ml DMF. During dropwise addition of saturated aqueous NH4PF6
to 9.60 ppm, 0.35 ppm shifted) displayed a remarkable downfield
shift upon addition of 0.5 equiv H2PO4 in DMSO-d6 solution, indi-
À
cating the presence of hydrogen bonding interactions between NH,
À
acidic CH and H2PO4 ion. On the other hand, other hydrogen pro-
tons at the pyridinium ring shifted to upfield implying the partic-
ipation of electrostatic interaction of charged pyridinium ring in
binding H2PO4À. In this context, the cooperative function of mul-
ti-interactions within the binding cavity gave rise to the excellent
À
binding and sensing properties of chemosensor 1 toward H2PO4
in competitive polar organic solvents. Furthermore, all protons of
anthracene moieties were slightly shifted to higher magnetic field.
À
This result suggested that the binding of H2PO4 via cooperation of
multi-interactions induced the reduction of the distance between
plural anthracene moieties and correspondingly the formation of
excimer (Fig. 1).
Based on above results, the proposed binding process of recep-
À
tor 1 toward H2PO4 is shown in Figure 5. Before complexation
with H2PO4À, anthracene moieties are separated each other remote
enough to emit only monomer fluorescence. This relative remote
distance between them is induced by its favorable conformation,
which might be controlled by the six-membered intramolecular
hydrogen bonding between carbonyl group and acidic CH at the
solution (2 ml),
a light yellow precipitate was formed. After washing the
precipitate several times with distilled water, the desired chemosensor 1 was
obtained in 88% yield.
For chemosensor 1: 1H NMR (DMSO-d6, 500 MHz) 1.32 (m, cyclohexyl, 3H), 1.94
(m, cyclohexyl, 3H), 2.53 (m, cyclohexyl, 3H), 6.95 (s, –CH2–, 2H), 7.67 (m,
anthracene, 12H), 8.02 (m, pyridinium, 3H), 8.26 (d, J = 8, anthracene, 6H), 8.39
(d, J = 8, anthracene, 6H), 8.57 (d, J = 9.5, pyridinium, 3H), 8.69 (d, J = 9.5,
pyridinium, 3H), 8.94 (s, anthracene, 3H), 9.25 (s, pyridinium, 3H), 11.55 (br,
–NH, 3H). ESI-MS (cationic mode), 1015.8 (MÀ3PF6ÀÀ2H+); Elemental Anal.
Calcd for C69H57f18N6O3P3: C, 57.03; H, 3.95; N, 5.78. Found: C, 57.21; H, 3.87; N,
5.66.
À
pyridinium ring. However, when H2PO4 was introduced, the
anion-dependent comformational change accomplished by cooper-
ative multi-interactions induced the cavity in receptor 1 selective
À
only for H2PO4 complexation. As a result, the anthracene moieties
come closer and overlap some extent to form the excimer emission
of them, which emitted strong green fluorescence.
8. a Amendola, V.; Boiocchi, M.; Fabbrizzi, L.; Palchetti, A. Chem. Eur. J. 2005, 11,
5648; b Wright, A. T.; Anslyn, E. V. Chem. Soc. Rev. 2006, 35, 14; c Wiskur, S. L.;
Floriano, P. N.; Anslyn, E. V.; McDevitt, J. T. Angew. Chem., Int. Ed. 2003, 42, 2070;
d Schmuck, C.; Schwegmann, M. J. Am. Chem. Soc. 2005, 127, 3373.
9. (a) Fages, F.; Desvergne, J.-P.; Laurent, H. B. J. Org. Chem. 1994, 59, 5264; (b)
Silver, A. P. D.; Gunaratne, H. Q. N.; Gunnlaugsson, T.; Huxley, A. J. M.; Mccoy, C.
P.; Rademacher, J. T.; Rice, T. E. Chem. Rev. 1997, 97, 1515; (c) Molard, Y.;
Bassani, D. M.; Desvergne, J. P.; Horton, P. N.; Hursthouse, M. B.; Tucker, J. H. R.
Angew. Chem., Int. Ed. 2005, 44, 1072; (d) Cho, H. K.; Lee, D. H.; Hong, J.-In Chem.
Commun. 2005, 1690.
In conclusion, a new tripodal fluorescent chemosensor 1 based
À
on amidepyridinium binding motif for selective H2PO4 sensing
À
was developed. The excellent H2PO4 binding is attributed to the
cooperation of multi-interactions, such as hydrogen bonding, elec-
trostatic interactions, as well as the dynamic conformational
change via formation of unique binding-induced excimer.