Naked eye detection of fluoride and pyrophosphate with an anion receptor utilizing anthracene and nitrophenyl group as signaling group

Article abstract of DOI:10.1016/j.tetlet.2011.03.092

New chromogenic receptor 2 utilizing anthracene and nitrophenyl group as signaling group was designed and synthesized. The receptor 2 utilizes amide N-H, amine N-H, and 9-anthracenyl hydrogen to bind anions. The receptor 2 binds anions through hydrogen bo

Full text of DOI:10.1016/j.tetlet.2011.03.092

Tetrahedron Letters 52 (2011) 2759–2763
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Naked eye detection of fluoride and pyrophosphate with an anion receptor
utilizing anthracene and nitrophenyl group as signaling group
Jin Joo Park a, Young-Hee Kim a, Cheal Kim b, , Jongmin Kang a,
⇑
⇑
a Department of Chemistry, Institute for Chemical Biology, Sejong University, Seoul 143-747, Republic of Korea
b Department of Fine Chemistry, and Eco-Product and Materials Education Center, Seoul National University of Technology, Seoul 139-743, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
New chromogenic receptor 2 utilizing anthracene and nitrophenyl group as signaling group was designed
Received 15 February 2011
Revised 15 March 2011
Accepted 20 March 2011
Available online 7 April 2011
and synthesized. The receptor 2 utilizes amide N–H, amine N–H, and 9-anthracenyl hydrogen to
À
bind anions. The receptor 2 binds anions through hydrogen bonds with a selectivity of CH3CO2
>
À
À
À
À
H2PO4 > C6H5CO2 > HSO4 > ClO4 > NO3À. In addition, the receptor 2 proved to be an efficient naked
eye detector for fluoride and pyrophosphate.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Chromogenic anion receptor
Naked eye anion receptor
NO2
The recognition and sensing of anions have become the focus of
considerable attention because anions play an important role in
biological, medical, environmental, and chemical sciences.1 In this
regard, colorimetric anion sensing and fluorometric anion sensing
have drawn particular attention. Many chemical sensors follow
the approach of the covalent attachment of signaling subunits
and binding sites.2 Chromogenic or fluorogenic groups that are
covalently linked to the receptor moiety as signaling subunits
and multiple hydrogen-bonding interactions as binding sites have
been frequently utilized. Hydrogen-bonding sites as binding sites
typically used in chromogenic or fluorogenic chemsensors are ur-
eas,3 thioureas,4 calix[4]pyrroles,5 amines,6 and amides.7 Among
the binding units mentioned above, amide and amines are the
most biologically relevant groups.
Previously, we reported on a novel colorimetric receptor 1,
which has a nitrophenyl group and a quinoline group as chromo-
genic signaling subunits.8 In this receptor, both amide and amine
groups are incorporated so that anions can make strong multiple
interactions with the hydrogen atoms of these groups through
hydrogen bonds, and the receptor 1 showed selectivity for fluoride
and cyanide ions.
O
NH
NH
N
1
As an extension of our work, we have designed a new receptor
2. The new receptor 2 has two amide hydrogens and two amine
hydrogens anchored at 1,8-position of anthracene. The receptor 2
was found to be a selective receptor for acetate and dihydrogen
phosphate and good naked eye detector for fluoride and pyrophos-
phate. Their binding phenomena could be monitored by UV–vis
spectra, fluorescence spectra, and 1H NMR.
The receptor 2 was synthesized from the reaction between 1,8-
diaminoanthracene9 and 2-bromo-(4-nitrophenyl)acetamide un-
der presence of sodium bicarbonate in 46% yields (Scheme 1).10
Because of low solubility of the receptor 2, we studied the bind-
ing phenomena in DMSO. The receptor 2 displayed strong absorp-
tion bands at 331 nm in DMSO. Figure 1a shows the family of
spectra obtained over the course of the titration of solution 2 with
⇑
Corresponding authors. Tel.: +82 2 3408 3213; fax: +82 2 462 9954 (J.K.).
E-mail addresses: chealkim@snut.ac.kr (C. Kim), kangjm@sejong.ac.kr (J. Kang).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.03.092

2760
J. J. Park et al. / Tetrahedron Letters 52 (2011) 2759–2763
NH2
NH2
O
+
2
Br
HN
NO2
O
NH HN
NO2
NO2
NaHCO3 / H2O
46%
NH HN
O
2
Scheme 1. The synthetic procedure for the anion receptor 2.
a
0.6
b
Host
Host
2eq.
4eq.
6eq.
2eq.
60
50
40
30
20
10
0
4eq.
6eq.
0.5
0.4
0.3
0.2
0.1
0
8eq.
10eq.
12eq.
14eq.
16eq.
20eq.
25eq.
30eq.
40eq.
50eq.
60eq.
70eq.
80eq.
100eq.
8eq.
10eq.
15eq.
20eq.
25eq.
30eq.
40eq.
50eq.
70eq.
100eq.
250
350
450
350
450
550
Figure 1. Family of UV–vis spectra (a) and fluorescence spectra (b) recorded over the course of titration of 20 lM DMSO solutions of the receptor 2 with the standard solution
tetrabutylammonium acetate.
tetrabutylammonium acetate in DMSO. As acetate ions were added
to the 20 M solution of 2, kmax showed bathochromic shift and
The stoichiometry between the receptor 2 and acetate was
determined by Job plot using 1H NMR, which showed evident 1:1
stoichiometry (Fig. 2).
l
clear isosbestic point at 346 nm. The presence of the sharp isos-
bestic point indicates that only two species were present at equi-
librium over the course of the titration experiment. In addition,
the receptor 2 displayed strong fluorescence emission in DMSO
as shown in Figure 1b. The excitation and emission wavelength
were 331 and 440 nm, respectively. The intensity of emission
A Benesi–Hildebrand plot11 by use of change at 331 nm in UV–
vis spectrum and 440 nm in fluorescence spectrum gave the asso-
ciation constants. The association constants calculated were
4.5 Â 103 MÀ1 from UV–vis titration and 4.8 Â 103 MÀ1 from fluo-
rescence titration, respectively.
spectrum from 20
l
M solution of the receptor 2 gradually in-
This phenomenon could be confirmed by a 1H NMR titration. In
DMSO-d6, both amide N–H hydrogen peak and amine N–H hydro-
gen peak of receptor 2 showed downfield shifts upon addition of
acetate ion. For example, the amide peak of the receptor 2
appearing at 10.8 ppm showed downfield shift until 11.0 ppm with
slight broadening and amine peak of the receptor 2 appearing at
creased as the concentration of tetrabutylammonium acetate salts
was increased (2–100 equiv), which also indicates the association
between the receptor 2 and acetate.
Dihydrogen
phosphate
6
5
4
3
2
1
0
Acetate
Table 1
The association constants (MÀ1) of the receptor 2 with various anions in DMSO
Anion
2
UV (Ka)
UV (Keq
)
Fluorescence (Ka)
NMR (Ka)
FÀ
HP2O7
CH3CO2
C6H5CO2
H2PO4
HSO4
7.0 Â 102
5.0 Â 102
3À
À
4.5 Â 103
1.7 Â 102
3.6 Â 103
9.6 Â 10
5.3 Â 10
2.0 Â 10
4.8 Â 103
1.0 Â 102
3.5 Â 103
8.0 Â 10
6.6 Â 10
2.9 Â 10
5.2 Â 103
1.2 Â 102
3.0 Â 103
À
À
À
0
0.2
0.4
0.6
0.8
1
[H]/{[H]+[G]}
À
ClO4À
Figure 2. The Job plots of 2 with tetrabutylammonium acetate and tetrabutylam-
NO3
monium dihydrogen phosphate using 1H NMR.

J. J. Park et al. / Tetrahedron Letters 52 (2011) 2759–2763
2761
Figure 3. 1H NMR spectra of 2 mM of 2 with increased amounts of tetrabutylammonium acetate (0–2.5 equiv) in DMSO-d6.
6.8 ppm showed downfield shift until 7.00 ppm, indicating that
both amide and amine participate in the binding event through
hydrogen bonds. In addition, 9-H of the anthracene moiety appear-
ing at 9.09 ppm showed downfileld shift until 9.13 ppm, indicating
that 9-H of anthracene moiety also participates in hydrogen bond-
ing with acetate (Fig. 3).
Many examples of receptors in which aromatic hydrogens par-
ticipate in hydrogen bonding with anions have been reported.12
For titration, amide N–H peak was used. Analysis of chemical shift
utilizing EQNMR13 gave the association constant of 5.2 Â 103 MÀ1
,
which is similar to the values obtained from UV–vis and fluores-
cence titrations.
a
b
Host
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
Host
0.7
5eq.
5eq.
10eq.
0.6
0.5
0.4
0.3
0.2
0.1
0
15eq.
10eq.
20eq.
30eq.
50eq.
70eq.
100eq.
150eq.
200eq.
250eq.
300eq.
400eq.
20eq.
25eq.
30eq.
35eq.
40eq.
50eq.
70eq.
100eq.
130eq.
160eq.
200eq.
250eq.
300eq.
400eq.
250
350
450
550
250
350
450
550
c
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
Host
1.0eq.
4.0eq.
7.0eq.
10eq.
20eq.
30eq.
40eq.
50eq.
250
350
450
550
Figure 4. Family of UV–vis spectra recorded over the course of titration of 20
lM DMSO solutions of the receptors 2 with the standard solution tetrabutylammonium fluoride
(a), tetrabutylammonium pyrophosphate (b) and tetrabutylammonium hydroxide (c).

2762
J. J. Park et al. / Tetrahedron Letters 52 (2011) 2759–2763
Figure 5. 1H NMR spectra of 2 mM of 2 with increased amounts of tetrabutylammonium fluoride (0–1.5 equiv) in DMSO-d6.
Figure 6. The color changes of the receptor 2 when 20 lM DMSO solutions of receptor was treated with 40 equiv of various anions.
With tetrabutylammonium dihydrogen phosphate, a similar
phenomenon was observed. In UV–vis titration, kmax of 2 showed
bathochromic shift, spectra showed the clear isosbestic point at
360 nm and Job plot showed 1:1 stoichiometry again. In addition,
amide N–H hydrogen, amine N–H hydrogen and 9-H of the anthra-
cene moiety showed downfield shifts again. From these experi-
ments, association constants for dihydrogen phosphate were
calculated as 3.6 Â 103 and 3.0 Â 103 MÀ1 from the UV–vis and
1H NMR titrations, respectively.
10.8 ppm completely disappeared with 1.5 equiv of fluoride ion (
Fig. 5).
Figure 6 shows the color change of the solutions of the receptors
2 upon additions of various anions in DMSO. It can be seen that the
color changes from pale yellow to brilliant yellow in the presence
of fluoride and pyrophospahte with naked eye. It is interesting that
the receptor 2 can differentiate pyrophosphate from phosphate
with naked eye. Other anions did not induce any color changes
even with excess amounts.
We also investigated association constants of other anions. The
results are summarized in Table 1. The receptor 2 interacts with
most of anions through hydrogen bonds at the concentration we
investigated except halides. Halides seem to be too small to be
accommodated in the large cavity of the receptor 2. In DMSO solu-
tion, even 1 (receptor): 2 (halides) binding did not occur. However,
with fluoride and pyrophosphate, the receptor 2 was deprotonated.
When excess of fluoride or pyrophosphate was added, the kmax of 2
moved from 331 nm to 446 nm. The deprotonation of the com-
pound 2 was confirmed through the titration experiments with tet-
rabutylammonium hydroxide ion ( Fig. 4). A Benesi–Hildebrand
plot by use of absorption intensity change at 446 nm gave deproto-
nation equilibrium constants for the receptor 2. From the experi-
ments, the equilibrium constants of the receptor 2 for fluoride
and pyrophosphate were calculated as 7.0 Â 102 and 5.0 Â 102,
respectively. The deprotonation phenomenon was also confirmed
by 1H NMR. For example, the amide N–H peak appearing at
In summary, we have developed a new anion receptor 2 utiliz-
ing anthracene and nitrophenyl group as signaling group. The
receptor 2 utilizes amide N–H, amine N–H, and 9-anthracenyl
hydrogen to bind anions. Through deprotonation, the receptor 2
can detect fluoride and pyrophosphate with naked eye. In addition,
the receptor 2 can bind anions through hydrogen bonds with a
À
À
À
À
À
selectivity of CH3CO2 > H2PO4 > C6H5CO2 > HSO4 > ClO4
>
NO3À. Probably due to its large cavity, the receptor 2 does not have
affinity to halides at all.
Acknowledgments
This research was supported by Basic Science Research Program
through the National Research Foundation of Korea (NRF) funded
by the Ministry of Education, Science and Technology (2010-
0021333).

J. J. Park et al. / Tetrahedron Letters 52 (2011) 2759–2763
2763
4545; (d) Bühlmann, P.; Nishizawa, S.; Xiao, K. P.; Umezawa, Y. Tetrahedron
1997, 53, 1647; (e) Benito, J. M.; Gómez-García, M.; Blanco, J. L. J.; Mellet, C. O.;
Fernández, J. M. G. J. Org. Chem. 2001, 66, 1366; (f) Dryfe, R. A. W.; Hill, S. S.;
Davis, A. P.; Joos, J.-B.; Roberts, E. P. L. Org. Biomol. Chem. 2004, 2, 2716; (g) Fan,
E.; Van Arman, S. A.; Kincaid, S.; Hamilton, A. D. J. Am. Chem. Soc. 1993, 115, 369.
5. (a) Panda, P. K.; Lee, C.-H. J. Org. Chem. 2005, 70, 3148; (b) Sessler, J. L.; Davis, J.
M. Acc. Chem. Res. 2001, 34, 989.
The Converging Research Center Program through the National
Research Foundation of Korea (NRF) funded by the Ministry of Edu-
cation, Science and Technology (2009-0082832).
We acknowledge Dr. Kun Cho from the mass spectrometry lab
of Korea Basic Science Institute for MS analysis.
6. Wichmann, K.; Antonioli, B.; Söhnel, T.; Wenzel, M.; Gloe, K.; Price, J. R.; Lindoy,
L. F.; Blake, A. J.; Schröder, M. Coord. Chem. Rev. 2006, 250, 2987.
Supplementary data
7. (a) Chmielewski, M. J.; Jurczak, J. Chem. Eur. J. 2005, 11, 6080; (b) Bao, X.; Zhou,
Y. Sens. Actuators, B: Chem. 2010, 147, 434; (c) Kang, S. O.; Linares, J. M.; Powell,
D.; VanderVelde, D.; Bowman-James, K. J. Am. Chem. Soc. 2003, 125, 10152; (d)
Kondo, S.-i.; Hiraoka, Y.; Kurumatani, N.; Yano, Y. Chem. Commun. 2005, 1720;
(e) Xie, H.; Yi, S.; Wu, S. J. Chem. Soc., Perkin Trans. 2 1999, 12, 2751; (f) Sessler, J.
L.; An, D.; Cho, W.-S.; Lynch, V.; Marquez, M. Chem. Eur. J. 2005, 11, 2001; (g)
Chellappan, K.; Singh, N. J.; Hwang, I.-C.; Lee, J. W.; Kim, K. S. Angew. Chem., Int.
Ed. 2005, 44, 2899; (h) Nishiyabu, R.; Anzenbacher, P., Jr. J. Am. Chem. Soc. 2005,
127, 8270.
Supplementary data (NMR, UV, fluorescence spectra) associated
with this article can be found, in the online version, at doi:10.1016/
j.tetlet.2011.03.092.
References and notes
8. Kang, J.; Jang, S. P.; Kim, Y.-H.; Lee, J. H.; Park, E. B.; Lee, H. G.; Kim, J. H.; Kim, Y.;
Kim, S.-J.; Kim, C. Tetrahedron Lett. 2010, 51, 6658.
9. Miao, R.; Zheng, Q.-Y.; Chen, C.-F.; Huang, Z.-T. Tetrahedron Lett. 2005, 46, 2155.
1. (a) Xu, Z.; Kim, S. K.; Yoon, J. Chem. Soc. Rev. 2010, 39, 1448; (b) Haugland, R. P. The
Handbook. A Guide to Fluorescent Probes and Labeling Technologies, 10th ed.;
Molecular Probes Inc.: Eugene, OR, 2005; (c)Anion Sensing; Stibor, I., Ed.;
Springer-Verlag: Berlin, 2005; (d) Lhoták, P. Top. Curr. Chem. 2005, 255, 65; (e)
Matthews, S. E.; Beer, P. D. Supramol. Chem. 2005, 17, 411; (f) Martinez-Manez, R.;
Sancenon, F. Chem. Rev. 2003, 103, 4419; (g) Beer, P. D.; Gale, P. A. Angew. Chem.,
Int. Ed. 2001, 40, 486; (h) Haryley, J. H.; James, T. D.; Ward, C. J. J. Chem. Soc., Perkin
Trans. 1 2000, 19, 3155; (i) de Silva, A. P.; Nimal Gunaratne, H. Q.; Gunnlaugsson,
T.; Huxley, A. J. M.; McCoy, C. P.; Rademacher, J. T.; Rice, T. E. Chem. Rev. 1997, 97,
1515; (j)Fluorescent Chemosensors for Ion and Molecule Recognition; Czarnik, A.
W., Ed.; American Chemical Society Books: Washington, DC, 1993.
10. Synthesis of compound 2: To
a solution of 200 mg (0.96 mmol) of 1,8-
diaminonanthracene in 40 mL of water was added 160 mg (1.92 mmol) of
sodium bicarbonate and the mixture was refluxed for an hour. Then, 2-bromo-
N-(4-nitrophenyl)acetamide (497 mg, 1.92 mmol) was added slowly and
vigorous agitation was maintained for 3 h. The mixture was then cooled and
filtered, and the solid was washed by water. Dried solid was recrystallized in
acetone. The precipitated solid was filtered from the acetone. Washing the
solid with clean acetone gave green-brown solid product 2 (251 mg) in 46%
yield. 1H NMR (500 MHz, DMSO-d6) d 10.9 (s, 2H), 9.1 (s, 1H), 8.3 (s, 1H), 8.2 (d,
J = 9 Hz, 4H), 7.9 (d, J = 8.5 Hz, 4H) 7.3 (m, 4H), 6.9 (s, 2H), 6.4 (d, J = 7 Hz, 2H),
4.3 (s, 4H). 13C NMR (500 MHz, DMSO-d6) d 170.4, 145.0, 143.8, 142.3, 132.1,
126.6, 125.5, 125.0, 121.8, 119.0, 116.1, 114.4, 100.64, 47.54 HRMS (ESI): calcd
for C30H24N6O6 + H m/e 565.1836; found, 565.1830.
2. (a) Kwon, J. Y.; Jang, Y. J.; Kim, S. K.; Lee, K.-H.; Kim, J. S.; Yoon, J. J. Org. Chem.
2004, 69, 5155; (b) Kim, S. K.; Singh, N. J.; Kim, S. J.; Kim, H. G.; Kim, J. K.; Lee, J.
W.; Kim, K. S.; Yoon, J. Org. Lett. 2003, 5, 2083.
3. (a) Thangadurai, T. D.; Singh, N. J.; Hwang, I.-C.; Lee, J. W.; Chandran, R. P.; Kim,
K. S. J. Org. Chem. 2007, 72, 5461; (b) Boiocchi, M.; Boca, L. D.; Gomez, D. E.;
Fabbrizzi, L.; Licchelli, M.; Monzani, E. J. Am. Chem. Soc. 2004, 126, 16507; (c)
Werner, F.; Schneider, H.-J. Helv. Chim. Acta 2000, 83, 465; (d) Snellink-Ruel, B.
H. M.; Antonisse, M. M. G.; Engbersen, J. F. J.; Timmerman, P.; Reinhoudt, D. N.
Eur. J. Org. Chem. 2000, 165; (e) Jun, E. J.; Swamy, K. M. K.; Bang, H.; Kim, S.-J.;
Yoon, J. Tetrahedron Lett. 2006, 47, 3103; (f) Ayling, A. J.; Perez-Payan, M. N.;
Davis, A. P. J. Am. Chem. Soc. 2001, 123, 12716.
4. (a) Gunnlaugsson, T.; Davis, A. P.; Hussey, G. M.; Tierney, J.; Glynn, M. Org.
Biomol. Chem. 2004, 2, 1856; (b) Gunnlaugsson, T.; Davis, A. P.; O’Brien, J. E.;
Glynn, M. Org. Biomol. Chem. 2005, 3, 48; (c) Kim, S. K.; Singh, N. J.; Kim, S. J.;
Swamy, K. M. K.; Kim, S. H.; Lee, K. H.; Kim, K. S.; Yoon, J. Tetrahedron 2005, 61,
11. Benesi, H. A.; Hildebrand, J. H. J. Am. Chem. Soc. 1949, 71, 2703.
12. (a) Jeong, K.-S.; Cho, Y. L. Tetrahedron Lett. 1997, 38, 3279; (b) Gale, P. A.;
Hursthouse, M. B.; Light, M. E.; Sessler, J. L.; Warriner, C. N.; Zimmerman, R. S.
Tetrahedron Lett. 2001, 42, 6759; (c) 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; (d) Yoon, D.-W.; Hwang, H.; Lee, C.-H. Angew. Chem., Int.
Ed. 2002, 41, 1757; (e) Kwon, J. Y.; Jang, Y. J.; Kim, S. K.; Lee, K.-H.; Kim, J. S.;
Yoon, J. J. Org. Chem. 2004, 69, 5155; (f) In, S.; Cho, S. J.; Lee, K. H.; Kang, J. Org.
Lett. 2005, 7, 3993.
13. Hynes, M. J. J. Chem. Soc., Dalton Trans. 1993, 311.