Visible near-infrared chemosensor for mercury ion

Article abstract of DOI:10.1021/ol800197t

(Chemical Equation Presented) A visible near-infrared chemosensor (MCy-1) for mercury ions was successfully devised and characterized. A large red-shift (122 nm) of the absorption maximum of MCy-1 was observed. An important feature for the new chemosensor is its high selectivity towards mercury ions over the other competitive species, making the naked-eye detection of mercury ions possible.

Full text of DOI:10.1021/ol800197t

ORGANIC
LETTERS
2008
Vol. 10, No. 7
1481-1484
Visible Near-Infrared Chemosensor for
Mercury Ion
Mei Zhu, Mingjian Yuan, Xiaofeng Liu, Jialiang Xu, Jing Lv, Changshui Huang,
Huibiao Liu, Yuliang Li,* Shu Wang, and Daoben Zhu
Beijing National Laboratory for Molecular Sciences (BNLMS), CAS Key Laboratory of
Organic Solids, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100080,
People’s Republic of China, and Graduate UniVersity of Chinese Academy of Sciences,
Beijing 100080, People’s Republic of China
ylli@iccas.ac.cn
Received November 28, 2007
ABSTRACT
A visible near-infrared chemosensor (MCy-1) for mercury ions was successfully devised and characterized. A large red-shift (122 nm) of the
absorption maximum of MCy-1 was observed. An important feature for the new chemosensor is its high selectivity towards mercury ions over
the other competitive species, making the “naked-eye” detection of mercury ions possible.
The development of selective chemosensors for the detection
of transition- and heavy-metal ions draws particular interest,
as these ions play important roles in living systems and have
an extremely toxic impact on the environment.1 Among them,
mercury(II) (Hg2+) is considered as one of the most toxic
cations for the environment because it is widely distributed
in air, water, and soil.2 Mercury can accumulate in the human
body and affects a wide variety of diseases even in a low
concentration, such as digestive, kidney, and especially
neurological diseases.3 Despites their toxicity, mercury and
mercuric salts are widely used in industrial processes, and a
high percentage of mercury contamination can be attributed
to anthropogenic sources. Recently, considerable efforts have
been made to develop a colorimetric or fluorescent molecular
probe for mercury ions.4 Several chemosensors based on
tricarbocyanine dyes have been reported.5 However, most
of the them are fluorometric sensors and the fluorescent
(3) (a) Grandjean, P.; Weihe, P.; White, R. F.; Debes, F. EnViron. Res.
1998, 77, 165-172. (b) Takeuchi, T.; Morikawa, N.; Matsumoto, H.;
Shiraishi, Y. Acta Neuropathol. 1962, 2, 40-57. (c) Harada, M. Crit. ReV.
Toxicol. 1995, 25, 1-24.
(4) (a) Zhu, X.-J.; Fu, S.-T.; Wong, W.-K.; Guo, J.-P.; Wong, W.-Y.
Angew. Chem., Int. Ed. 2006, 45, 3150-3154. (b) Wu, Z.; Zhang, Y.; Ma,
J. S.; Yang, G. Inorg. Chem. 2006, 45, 3140-3142. (c) Wang, J.; Qian, X.
Org. Lett. 2006, 8, 3721-3724. (d) Nazeeruddin, M. K.; Censo, D. D.;
Humphry-Baker, R.; Gra¨tzel, M. AdV. Funct. Mater. 2006, 16, 189-194.
(e) Praveen, L.; Ganga, V. B.; Thirumalai, R.; Sreeja, T.; Reddy, M. L. P.;
Varma, R. L. Inorg. Chem. 2007, 46, 6277-6282. (f) Wegner, S. V.; Okesli,
A.; Chen, P.; He, C. J. Am. Chem. Soc. 2007, 129, 3474-3475. (g) Kao,
T.-L.; Wang, C.-C.; Pan, Y.-T.; Shiao, Y.-J.; Yen, J.-Y.; Shu, C.-M.; Lee,
G.-H.; Peng, S.-M.; Chung, W.-S. J. Org. Chem. 2005, 70, 2912-2920.
(h) Ha-Thi, M.-H.; Penhoat, M.; Michelet, V.; Leray, I. Org. Lett. 2007, 9,
1133-1136. (i) Ono, A.; Togashi, H. Angew. Chem., Int. Ed. 2004, 43,
4300-4302. (j) Nolan, E. M.; Lippard, S. J. J. Am. Chem. Soc. 2007, 129,
5910-5918.
(1) (a) Czarnik, A. W. Fluorescent Chemosensors for Ion and Molecule
Recognition; American Chemical Society: Washington, DC, 1993. (b) de
Silva, A. P.; Fox, D. B.; Huxley, A. J. M. Coord. Chem. ReV. 2000, 205,
41-47. (c) 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, 1515-1566. (d) He, Q.; Miller, E. W.; Wong, A. P.; Chang, C. J. J.
Am. Chem. Soc. 2006, 128, 9316-9317.
(2) (a) Basu, N.; Scheuhammer, A.; Grochowina, N.; Klenavic, K.; Evans,
D.; O Brien, M.; Chan, M. EnViron. Sci. Technol. 2005, 39, 3585-3591.
(b) Zhang, Z.; Wu, D.; Guo, X.; Qian, X.; Lu, Z.; Zu, Q.; Yang, Y.; Duan,
L.; He, Y.; Feng, Z. Chem. Res. Toxicol. 2005, 18, 1814-1820.
10.1021/ol800197t CCC: $40.75
© 2008 American Chemical Society
Published on Web 03/13/2008

signals must be detected by spectroscopy or under UV light.
Compared to fluorometric sensors, colorimetric sensors have
attracted much attention for allowing so-called “naked-eye”
detection in a straightforward and inexpensive manner,
offering qualitative and quantitative information without
using expensive equipment. Nagano et al. have reported a
zinc ion probe based on tricarbocyanine dyes, which showed
a 44 nm red-shift of the absorption maximum.6 This assay
makes the detection easier and more convenient.
in the methine chain also plays an important role in
maintaining the dyes’ stability.7a To obtain an optimum
response towards Hg2+, we avoided the use of polythia or
polyaza crowns known to bind most thio- or aminophilic
metal ions. The vinyl chlorine on the cyclohexane bridgehead
of compound 1 is reactive and can be replaced by a crown
ether ligand which is a very strong nucleophile.
The ionophoric properties of MCy-1 were investigated by
UV-vis and fluorescent measurements.
Figure 1a shows the absorption spectral changes of MCy-1
as a function of the Hg2+ concentration in methanol at room
As one of the important kinds of near-infrared (NIR) dyes,
heptamethine cyanine dyes7 have been widely used in various
fields and have been employed as fluorescent labels in
fluorescence imaging studies of biological mechanisms. As
we know, the NIR region offers several advantages over the
visible spectral range: (a) it is poorly absorbed by biomol-
ecules, so it can penetrate deeply into tissues; (b) there is
also less auto-fluorescence in this region, and so the
characteristics of the NIR dyes are favorable for in vivo
imaging;8 and (c) there is an intense interest on the
application of NIR probes to detect metal cations and
biological compounds.9
Our work aims to design and construct a new class of NIR
probes with colorimetric assay to specifically detect the
presence of Hg2+ over a wide range of other interfering
cations. To achieve this goal, we report here the design and
synthesis of a novel dye containg dithia-dioxa-monoaza
crown ether moiety10 (MCy-1) that can perform “naked-eye”
detection of Hg2+ ion in the NIR region.
Figure 1. (a) Changes in the UV-vis spectra of MCy-1 (5.16 µM
in methanol) upon titration by Hg(ClO4)2 from 12.4 to 60 µM. (b)
Changes in the UV-vis spectra of MCy-1 (5.16 µM in methanol)
upon addition of mercury ions and subsequent of excess EDTA.
Inset: color change of MCy-1 in the visible region. (A) MCy-1
solution in methanol; (B) and (A) + Hg2+; (C) and (B) + excess
of EDTA.
The synthetic route of MCy-1 is shown in Scheme 1.
temperature. The UV-vis spectrum of MCy-1 in methanol
is characterized by a very intense band centered at 695 nm
(ꢀ ) 86 000 M-1‚cm-1), which is responsible for the blue
color of the solution. The absorption maximum of MCy-1
has about a 88 nm blue-shift in comparison to that of the
parent dye 1.11 This blue-shift was assigned to an efficient
excited-state intramolecular charge transfer (ICT)11 process
from the donor nitrogen atom on the dithia-dioxa-monoaza
macrocycles to the acceptor tricarbocyanine group. The
absorption at 695 nm decreased sharply with the gradual
addition of Hg2+ to the solution of MCy-1. At the same time
a new band centered at 817 nm (ꢀ ) 190 000 M-1‚cm-1)
increased prominently with one isosbestic point at 740 nm.
Such a large red-shift (122 nm) makes the color of the
solution change from blue to almost colorless, and subsequent
addition of an excess of EDTA resulted in recovery of the
original color (Figure 1b).
Scheme 1. Synthesis of Mcy-1
For designing a probe with better photostability, we chose
tricarbocyanine dyes with benzyl groups on the nitrogen
atoms of 3H-indo rings. The rigid chlorocyclohexenyl ring
(5) (a) Ozmen, B.; Akkaya, E. U. Tetrahedron Lett. 2000, 41, 9185-
9188. (b) Tang, B.; Huang, H.; Xu, K.-H.; Tong, L.-L.; Yang, G.-W.; Liu,
X.; An, L.-G. Chem. Commun. 2006, 3609-3611. (c) Sasaki, E.; Kojima,
H.; Nisimatsu, H.; Urano, Y.; Kikuchi, K.; Hirata, Y.; Nagano, T. J. Am.
Chem. Soc. 2005, 127, 3684-3685.
(6) Kiyose, K.; Kojima, H.; Urano, Y.; Nagano, T. J. Am. Chem. Soc.
2006, 128, 6548-6549.
(7) (a) Strekowski, L.; Lipowska, M.; Patonay, G. J. Org. Chem. 1992,
57, 4578-4580. (b) Narayanan, N.; Patonay, G. J. Org. Chem. 1995, 60,
2391-2395. (c) Flanagan, J. H., Jr.; Khan, S. H.; Menchen, S.; Soper, S.
A.; Hammer, R. P. Bioconjugate Chem. 1997, 8, 751-758.
According to the linear Benesi-Hildebrand expression,12
the measured absorbance [1/(A - A0)] at 695 nm varied as
a function of 1/[Hg2+] in a linear relationship (R ) 0.99639),
(8) (a) Leevy, W.; Gammon, S. T.; Jiang, H.; Johnson, J. R.; Maxwell,
D. J.; Jackson, E. N.; Marquez, M.; Worms, D.; Smith, B. D. J. Am. Chem.
Soc. 2006, 128, 16476-16477. (b) Zhang, Z.-R.; Achilefu, S. Org. Lett.
2004, 6, 2067-2070. (c) Li, C.; Greenwood, T. R.; Bhujwalla, Z. M.;
Glunde, K. Org. Lett. 2006, 8, 3623-3626. (d) Kiyose, K.; Kojima, H.;
Urano, Y.; Nagano, T. J. Am. Chem. Soc. 2006, 128, 6548-6549.
(9) (a) Coskun, A.; Yilmaz, M. D.; Akkaya, E. U. Org. Lett. 2007, 9,
607-609. (b) Zhang, Z.; Achilefu, S. Org. Lett. 2004, 6, 2067-2070. (c)
Bouteiller, C.; Clave, G.; Bernardin, A.; Chipon, B.; Massonneau, M.;
Renard, P.-Y.; Romieu, A. Bioconjugate Chem. 2007, 18, 1303-1317.
(10) (a) Descalzo, A. B.; Mart´ınez-Ma´nˇez, R.; Radeglia, R.; Rurack, K.;
Soto, J. J. Am. Chem. Soc. 2003, 125, 3418-3419. (b) Yuan, M. J.; Li, Y.
L.; Li, J. B.; Li, C. H.; Liu, X. F.; Lv, J.; Xu, J. L.; Liu, H. B.; Wang, S.;
Zhu, D. B. Org. Lett. 2007, 9, 2313-2316.
(11) Peng, X.; Song, F.; Lu, E.; Wang, Y.; Zhou, W.; Fan, J.; Gao, Y.
J. Am. Chem. Soc. 2005, 127, 4170-4171.
(12) (a) Benesi, H. A.; Hildebrand, J. H. J. Am. Chem. Soc. 1949, 71,
2703-2707. (b) Barra, M.; Bohne, C.; Scaiano, J. C. J. Am. Chem. Soc.
1990, 112, 8075-8579.
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Org. Lett., Vol. 10, No. 7, 2008

indicating the 1:1 stoichiometry between the Hg2+ ion and
MCy-1 (Figure 2). To confirm the stoichiometry between
the Hg2+ ion and MCy-1, electrospray ionization mass
Figure 3. Partial 1H NMR spectra (400 MHz, DMSO-d6) of MCy-1
before (a) and after (b) addition of 10 equiv of mercury ions.
Figure 2. Benesi-Hilderbrand plot of MCy-1 with Hg2+
.
Na+, K+, Ca2+, and Mg2+. As shown in Figure 4, under
identical conditions to the Hg2+ ion, no significant changes
spectrometry (ESI-MS) spectra analysis was conducted
(see Supporting Information). Mass peaks at m/z 1010.3
and 1210.2 corresponding to [MCy-1 + H]+ and [MCy-1 +
Hg - H]+ are clearly observed, which gave solid evi-
dence for the formation of a 1:1 complex. On the basis
of 1:1 stoichiometry and UV-vis titration data in Fig-
ure 1, the association constant of MCy-1 with Hg2+
ion in MeOH was found to be 4.335 × 104 M-1
(Figure 2).
From the absorption spectra of MCy-1/Hg2+, we can
see that not only was the absorption band at 695 nm red-
shifted but also the developed new band at 817 nm had a
larger molar absorption coefficient than the original one. A
possible reason is that the coordination of the Hg2+ to the
ligand reduces the electron-donating ability of the nitro-
gen atom at the dithia-dioxa-aza macrocycle which was
linked to the tricarbocyanine core; thus, the ICT process is
not possible and the blue-shift in absorption spectra is
suppressed. In other words, the red-shift in absorption spectra
is observed upon Hg2+ binding. More importantly, the Hg2+
sensing and the concomitant absorption changes were clearly
visible to the naked eye, as can be seen in the photograph,
where the blue solution of MCy-1 became almost colorless
Figure 4. (a) Absorbance spectra change of MCy-1 (5.16 µM in
methanol) upon addition of different metal cations (10 equiv). (b)
Absorbance spectra change of MCy-1 (5.16 µM) upon addition of
mixed cations (mix ) Fe3+ + Co2+ + Cu2+ + Zn2+ + Cd2+
+
Pb2+ + Na+ + K+ + Ca2+ + Mg2+); each one is 10 equiv of metal
cations and subsequent addition of 50 equiv of Hg2+ in methanol.
(c) Color change of MCy-1 in the presence of different metal
1
upon titration with Hg2+ ions. H NMR studies provide
further evidence for the interaction between MCy-1 and
Hg2+. Upon the addition of 10 equiv of Hg2+, chemical shift
of protons on the crown ether especially those near the
sulfur atoms broadened and shifted downfield as shown in
Figure 3.
An important feature of a new chemosensor is its
high selectivity towards the Hg2+ over the other com-
petitive species such as Fe3+, Co2+, Cu2+, Zn2+, Cd2+, Pb2+,
cations. From left to right: blank, Hg2+, Fe3+, Co2+, Cu2+, Zn2+
,
Cd2+, Pb2+, Na+, K+, Ca2+, and Mg2+
.
were observed in the UV-vis spectra of MCy-1 upon
addition of Fe3+, Co2+, Cu2+, Zn2+, Cd2+, Pb2+, Li+, Na+,
K+, Ca2+, and Mg2+, respectively. This could probably be
attributed to their low affinity with the receptor MCy-1. The
Org. Lett., Vol. 10, No. 7, 2008
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miscellaneous competitive cations also did not induce any
significant color change of MCy-1. Therefore, MCy-1 can
be considered as an effective colorimetric probe for Hg2+.
Thus, naked-eye detection of Hg2+ becomes possible.
Note that a fluorometric detection of Hg2+ is also possible
for MCy-1. A strong decrease of the fluorescence is observed
upon mercury complexation, which can be explained in terms
of the prevention of the excited-state ICT process from the
donor to the acceptor. To determine the amount of Hg2+ ion
required to induce the complete quenching of fluorescence
from MCy-1, titration experiments were carried out as shown
in Figure 5; when 8 equiv of Hg2+ ion was added, the
physiological conditions, have slight influence on fluores-
cence intensity. Transition-metal ions of Fe3+, Co2+, Cu2+,
Zn2+, and heavy-metal ions of Cd2+ and Pb2+ also did not
induce significant fluorescene change of MCy-1 (Figure 6).
Figure 6. Fluorescence responses of MCy-1 to various metal ions
(including Fe3+, Co2+, Cu2+, Zn2+, Cd2+, Pb2+, Li+, Na+, K+, Ca2+
,
and Mg2+). Excitation was provided at 695 nm, and the emission
was integrated over 705-900 nm. The bars represent the percentage
of fluorescence quenched (1 - I/I0).
In conclusion, we have successfully devised a novel NIR
probe (MCy-1) towards Hg2+ ions. A large red-shift (122
nm) of the absorption maximum of MCy-1 was observed
upon titration with Hg2+ ions followed by a solution color
change from blue to colorless, making the “naked-eye”
detection of Hg2+ ions possible. Importantly, the selectivity
of this system for Hg2+ over other metal ions is extremely
high. This assay offers a method for the detection of Hg2+
that is easier and more convenient for application.
Figure 5. (a) Emission spectra of compound MCy-1 in the pre-
sence of increasing Hg2+ concentration (0, 10, 15, 20, 21, 25, 30,
40 µM) in methanol. Excitation wavelength was 695 nm with
5 nm slit widths. The concentration of the chemosensor was
5.16 µM. (b) Fluorescence intensity of MCy-1 versus Hg2+
concentration.
emission of MCy-1 was almost completely quenched. The
detection limit of the sensor for Hg2+ is about 1.1 × 10-6
M (Figure 5b).
The changes in the fluorescence properties of MCy-1
caused by different metal ions, including Fe3+, Co2+, Cu2+,
Zn2+, Cd2+, Pb2+, Li+, Na+, K+, Ca2+, and Mg2+ were
measured. The fluorescence of MCy-1 quenched markedly
with the addition of Hg2+. Cations such as Li+, Na+, K+,
Ca2+, and Mg2+, which exist at high concentrations under
Acknowledgment. This work was supported by the
National Nature Science Foundation of China (20531060,
20721061) and the National Basic Research 973 Program
of China (Grant No. 2007CB936401 and 2006CB806200).
Supporting Information Available: Synthesis, charac-
terization, binding analysis of MCy-1. This material is
available free of charge via the Internet at http://pubs.acs.org.
OL800197T
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