Highly sensitive and selective reversible sensor for the detection of Cr3+

Article abstract of DOI:10.1016/j.tetlet.2009.08.025

A new fluorescent sensor capable of sensing Cr³⁺ has been synthesized. Complexing with Cr³⁺ triggers the formation of a highly fluorescent ring-open form which is pink in color. The sensor shows extremely high fluorescence enhancemen

Full text of DOI:10.1016/j.tetlet.2009.08.025

Tetrahedron Letters 50 (2009) 6407–6410
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Tetrahedron Letters
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Highly sensitive and selective reversible sensor for the detection of Cr3+
*
Aruna J. Weerasinghe, Carla Schmiesing, Ekkehard Sinn
Department of Chemistry, Western Michigan University, Kalamazoo, MI 49008, USA
a r t i c l e i n f o
a b s t r a c t
A new fluorescent sensor capable of sensing Cr3+ has been synthesized. Complexing with Cr3+ triggers the
formation of a highly fluorescent ring-open form which is pink in color. The sensor shows extremely high
fluorescence enhancement upon complexation with Cr3+ and it can be used as a ‘naked eye’ sensor. Bind-
ing of Cr3+ was found to be reversible as the pink color disappears with excess EDTA.
Ó 2009 Elsevier Ltd. All rights reserved.
Article history:
Received 27 July 2009
Revised 13 August 2009
Accepted 15 August 2009
Available online 20 August 2009
Keywords:
Chromium
Rhodamine B
Sensor
Fluorescent
Trivalent chromium, Cr3+, is an important metal for human and
animal biology as it is involved in several biochemical processes at
the cellular level.1 Chromium deficiency can increase the risk fac-
tors associated with diabetes and cardiovascular diseases.2 In addi-
Recently, Mao et al. developed a rhodamine-6G-based turn-on
sensor for Cr3+ 12
Another chemosensor was reported by Zhou
.
et al. based on rhodamine B for the detection of Cr3+ in living
cells.13 Our sensor shows extremely high sensitivity compared to
the above-mentioned Cr3+ sensors attributed to the very high asso-
ciation constants for the binding of Cr3+-(vide infra). The sensitivity
of our sensors matches that of the powerful Hg2+ sensor developed
by Zhan et al.10a
tion, chromium is
a known environmental pollutant that
accumulates due to agricultural and industrial activities.3 There-
fore, great importance is attached to developing selective chemo-
sensors for chromium. Due to its simplicity, selective fluorimetric
detection of Cr3+ has great advantages over other detection tech-
niques such as electrochemical4 and potentiometric.5 Trivalent
chromium is one of the most effective fluorescent quenchers
known due to its paramagnetic nature which also makes it difficult
to develop a turn-on sensor. In the recent past, several attempts
have been made to develop chemosensors to detect paramagnetic
species.6
We report compound 1 as a new fluorescent sensor for Cr3+
.
Sensor 1 shows very good sensitivity as well as selectivity for
Cr3+. Both nitrate and perchlorate salts of chromium yielded essen-
tially the same result. The one metal which showed interference
was Hg2+, for which the nitrate salt showed emission enhancement
while the perchlorate did not.
As shown in Scheme 1, the rhodamine B derivative 1 was pre-
pared in 81% yield by reacting 29a with thiophene-2-furanaldehyde
in an equal molar ratio in ethanol.14 The structure was confirmed
using 1H NMR, 13C NMR, mass spectra, and X-ray crystallography
(Supplementary data). Single crystal was grown from CH3CN solu-
tion and the crystallographic data confirmed the presence of the
spirolactam form of the structure (Fig. 1).
Compound 1 was designed to bind metal ions via the carbonyl
O, inamine N, and thiophene S as donors. All the spectroscopic
studies were performed in acetonitrile in which sensor 1 formed
a colorless solution that was stable for more than one week. The
solution of compound 1 was very weakly fluorescent in the ab-
sence of any analyte due to the predominant ring-closed spirolac-
tone. This was further confirmed by the 13C NMR signal at d 66.26
corresponding to C-1 (Fig. 1). The absorption spectra showed no
peak above 400 nm but upon the addition of Cr3+, a new peak
appeared at 559 nm with a shoulder at 520 nm (Supplementary
Rhodamine B is extensively used as a chemosensor due to its
remarkable properties such as a high absorption coefficient, high
fluorescent quantum yield, and excitation and emission within vis-
ible wavelengths.7 In addition, the equilibrium between the
nonfluorescent spirocyclic form and the highly fluorescent ring-
open form provides a better model for the development of
turn-on sensors. Recently, several rhodamine B-based turn-on
fluorescent sensors have been developed for metal ions.8 Several
successful attempts have been made to develop selective fluores-
cent sensors based on rhodamine B for Cu2+ 9
, , , and
Pb2+ 8 Hg2+ 10
In all these sensors, the mechanism involves the formation
Fe3+ 11
.
of a ring-open form from the spirolactam form upon the binding of
the cation, resulting in fluorescence enhancement (550–600 nm).
* Corresponding author. Tel.: +1 269 387 2832; fax: +1 269 387 2909.
E-mail addresses: ekk.sinn@wmich.edu, esinn@mst.edu (E. Sinn).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.08.025

6408
A. J. Weerasinghe et al. / Tetrahedron Letters 50 (2009) 6407–6410
O
COOH
HCl
NH2 NH2
N
NH2
N
O
N
N
O
2
N
OHC
S
O
Ethanol / Reflux / 12 h
S
N
N
N
O
1
N
Scheme 1. Synthetic pathway of 1.
2.0
2.0
1.5
1.0
0.5
0.0
1.5
1.0
0.5
0.0
0
2
4
6
8
10 12 14
-6
M
[Cr3+] / 10
550
600
650
700
Wavelength, nm
Figure 2. Fluorescence changes of 1 (10
l
M) with Cr3+ (0–13
lM) in CH3CN.
Figure 1. X-ray crystal structure of 1.
peaked at 583 nm, while that with Zn2+ peaked at 576 nm, indicat-
ing a hypsochromic shift of 7 nm compared with that with Cr3+
data). Meanwhile the solution turned pink instantaneously as a re-
sult of the ring-open structure formation caused by Cr3+ binding.
Job’s plot indicated a 1:1 binding stoichiometry between sensor
.
The hypsochromic shift w.r.t Cr3+ is 10 nm for Pb2+ where the fluo-
rescence intensity peaked at 573 nm. All these observations indi-
cate that sensor 1 has high sensitivity and selectivity towards
Cr3+ over other metal ions tested. Furthermore, the prominent col-
or change allows Cr3+ to be detected by the naked eye (Fig. 5).
Similar to most rhodamine-based spirolactam chemosensors,
the binding of Cr3+ must be due to the ring-opening mechanism.
Chromium can chelate with carbonyl oxygen, inamine nitrogen,
and thiophene sulfur. The other three coordination sites can be
occupied by nitrate ligands. Furthermore, the sensing mechanism
is found to be reversible as the pink color of the complex disap-
pears with the addition of excess EDTA.
and Cr3+ with association constant15 2.0 Â 104 MÀ1
.
The fluorescence spectrum of 1 showed a peak at 583 nm upon
the addition of Cr3+ corresponding to the delocalization in the xan-
thene moiety of rhodamine. There was a significant emission
intensity enhancement (>1200-fold) with 1.0 equiv of Cr3+
(Fig. 2), which indicates that compound 1 is an excellent turn-on
sensor for Cr3+
.
It is very important to have a high selectivity for a good sensor
system. We tested our sensor with possible interferences including
nitrate salts of Na+, K+, Ni2+, Zn2+, Cd2+, Hg2+, and Pb2+ and chloride
salts of Ca2+, Mn2+, Fe3+, Co2+, and Cu2+ (Fig. 3). Sensor 1 showed a
certain emission enhancement with Hg2+ (<600-fold), while Zn2+
and Pb2+ showed very weak responses (Fig. 4). The association con-
stant (K) was determined using Benesi–Hildebrand method16 to be
1.0 Â 104 MÀ1. The fluorescent enhancement of sensor 1 with Cr3+
In conclusion, we have synthesized in a very high yield the new
fluorescent chemosensor 1 which is very stable in CH3CN for more
than one week. Sensor 1 showed high sensitivity and selectivity to-
wards Cr3+ over other interference cations except Hg2+, which
showed a significant but smaller effect. We were able to use the

A. J. Weerasinghe et al. / Tetrahedron Letters 50 (2009) 6407–6410
6409
2.0
1.5
1.0
0.5
0.0
Cr3+
Hg2+
Free 1, Na+,K+,Ca2+,Mn2+
Fe3+,Co2+,Ni2+,Cu2+,Cd2+
Zn2+
Pb2+
550
600
650
700
Wavelength, nm
Figure 3. Fluorescence changes of 1 (10
l
M) with Na+, K+, Ca2+, Cr3+, Mn2+, Fe3+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, Hg2+, and Pb2+ (10
lM) in CH3CN (excitation at 510 nm).
Acknowledgments
1200
1000
800
600
400
200
0
The authors wish to acknowledge the financial support under
U.S Army Grant No. WS911QY-07-1-0003. The authors would also
like to thank Dr. Andre Venter for the help given in obtaining ESI
mass spectra.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2009.08.025.
References and notes
1. (a) Sarkar, M.; Banthia, S.; Samanta, A. Tetrahedron Lett. 2006, 47, 7575; (b)
Latva, S.; Jokiniemi, J.; Peraniemi, S.; Ahlgren, M. J. Anal. At. Spectrom. 2003, 18,
84; (c) Huang, K.; Yang, H.; Zhou, Z.; Yu, M.; Li, F.; Gao, X.; Yi, T.; Huang, C. Org.
Lett. 2008, 10, 2557.
2. Singh, A. K.; Gupta, V. K.; Gupta, B. Anal. Chim. Acta 2007, 585, 171.
3. Zayed, M.; Norman, T. Plant Soil 2003, 249, 139.
Cr Hg Zn Pb Cd Ni Fe Cu Co Mn
Metal Ions
K
Na Ca
4. Singh, A. K.; Singh, R.; Saxena, P. Sensors 2004, 4, 187.
5. Hassan, S. S. M.; EL-Shahawi, M. S.; Othman, A. M.; Mosaad, M. A. Anal. Sci.
2005, 21, 673.
Figure 4. Fluorescence intensity of 1 (10 lM) at 583 nm with metal ions (10 lM) in
CH3CN (excitation at 510 nm).
6. (a) Ghosh, P.; Bharadwaj, P. K.; Mandal, S.; Ghosh, S. J. Am. Chem. Soc. 1996,
118, 1553; (b) Royzen, M.; Dai, Z.; Canary, W. J. J. Am. Chem. Soc. 2005, 127,
1612; (c) Rurack, K.; Kollmannsberger, M.; Resch-Genger, U.; Daub, J. J. Am.
Chem. Soc. 2000, 122, 968; (d) Banthia, S.; Samanta, A. J. Phys. Chem. B 2006,
110, 6437; (e) Prodi, L.; Bolletta, F.; Montalti, M.; Zaccheroni, N. Coord. Chem.
Rev. 2000, 205, 59; (f) Sankaran, N. B.; Banthia, S.; Das, A.; Samanta, A. New J.
Chem. 2002, 26, 1529; (g) Ramachandram, B.; Samanta, A. Chem. Commun.
1997, 1037.
7. Yang, Y. K.; Yook, K. J.; Tae, J. J. Am. Chem. Soc. 2005, 127,
16760.
8. Kwon, J. Y.; Jang, Y. J.; Lee, Y. J.; Kim, K. M.; Seo, M. S.; Nam, W.; Yoon, J. J. Am.
Chem. Soc. 2005, 127, 10107.
9. (a) Xiang, Y.; Tong, A.; Jin, P.; Ju, Y. Org. Lett. 2006, 8, 2863; (b) Dujols, V.; Ford,
F.; Czarnik, A. W. J. Am. Chem. Soc. 1997, 119, 7386.
10. (a) Zhan, X. Q.; Qian, Z. H.; Zheng, H.; Su, B. Y.; Lan, Z.; Xu, J. G. Chem. Commun.
2008, 1859; (b) Huang, J.; Xu, Y.; Qian, X. J. Org. Chem. 2009, 74, 2167; (c) Wu, J.
S.; Hwang, I. C.; Kim, K. S.; Kim, J. S. Org. Lett. 2007, 9, 907; (d) Zheng, H.; Qian,
Z. H.; Xu, L.; Yuan, F. F.; Lan, L. D.; Xu, J. G. Org. Lett. 2006, 8, 859; (e) Lee, M. L.;
Wu, J. S.; Lee, J. W.; Jung, J. H.; Kim, J. S. Org. Lett. 2007, 9, 2501; (f) Ko, S. K.;
Yang, Y. K.; Tae, J.; Shin, I. J. Am. Chem. Soc. 2006, 128, 14150; (g) yang, H.; Zhou,
Z. G.; Huang, K. W.; Yu, M. X.; Li, F. Y.; Yi, T.; Huang, C. H. Org. Lett. 2007, 9,
4729.
Figure 5. A photograph of compound 1 (10
from left to right: 1 free, Na+, K+, Ca2+, Cr3+, Mn2+, Fe3+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+
Hg2+, and Pb2+
lM) with different metal ions (6 lM),
,
.
ring-opening mechanism of the new rhodamine B derivatives to
develop a new sensor for Cr3+. Our future work will focus on devel-
oping sensors for toxic metals using the same mechanism em-
ployed in this work.
11. (a) Xiang, Y.; Tong, A. Org. Lett. 2006, 8, 1549; (b) Zhang, M.; Gao, Y.; Li, M.; Yu,
M.; Li, F.; Li, L.; Zhu, M.; Zhang, J.; Yi, T.; Huang, C. Tetrahedron Lett. 2007, 48,
3709.
12. Mao, J.; Wang, L.; Dou, W.; Tang, X.; Yan, Y.; Liu, W. Org. Lett. 2007, 9, 4567.

6410
A. J. Weerasinghe et al. / Tetrahedron Letters 50 (2009) 6407–6410
13. Zhou, Z.; Yu, M.; Yang, H.; Huang, K.; Li, F.; Yi, T.; Huang, C. Chem. Commun.
2008, 3387.
(1H, dd, J = 6.2 Hz, 1.4 Hz), 7.22 (1H, d, J = 5.1 Hz), 7.47 (2H, m), 7.96 (1H, dd,
J = 6.2 Hz, 1.4 Hz), 8.90 (1H, s). 13C NMR (100 MHz, CDCl3): d 12.71, 44.41,
66.26, 97.98, 106.17, 108.00, 123.37, 123.98, 127.04, 127.88, 128.07, 128.39,
129.47, 129.74, 133.31, 141.42, 142.25, 148.99, 151.44, 153.40, 164.69. ESI MS:
551.33 [M+1]+.
14. Preparation of 1:
A solution of 2 (0.5 g, 1.1 mmol) and thiophene-2-
carboxaldehyde (0.16 g, 1.4 mmol) in 25 ml of ethanol was refluxed for 12 h.
The mixture was allowed to cool down to room temperature and the red
crystals formed were separated by filtration, washed with ethanol, and dried in
air (0.49 g), yield 81%. 1H NMR (400 MHz, CDCl3): 1.14 (12H, t, J = 6.9 Hz), 3.31
(8H, q, J = 6.9 Hz), 6.23 (2H, dd, J = 8.8 Hz, 2.6 Hz), 6.43 (2H d, J = 2.2 Hz), 6.50
(2H, d, J = 8.8 Hz), 6.90 (1H, dd, J = 4.9 Hz, 3.7 Hz), 7.06 (1H, d, J = 2.9 Hz), 7.12
15. Connors, K. A. Binding Constants-The Measurement of Molecular Complex
Stability; John Wiley & Sons: New York, 1987.
16. Benesi, H.; Hildebrand, J. J. Am. Chem. Soc. 1949, 71, 2703.