A highly selective chemodosimeter for the rapid detection of Hg 2+ ions in aqueous media

Article abstract of DOI:10.1016/j.tetlet.2012.03.040

A novel S,S′-diallyl carbohydrazonodithioate derivative 3 of rhodamine B hydrazone was developed as a chemodosimeter for selective detection of mercury ions based on Hg²⁺ promoted cyclization. The allyl groups of 3 play a key role in the bindin

Full text of DOI:10.1016/j.tetlet.2012.03.040

Tetrahedron Letters 53 (2012) 2571–2574
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A highly selective chemodosimeter for the rapid detection of Hg2+ ions
in aqueous media
⇑
Ambadas B. Rode, Jinkwon Kim, Sang-Ho Kim, Gajendra Gupta, In Seok Hong
Department of Chemistry, College of Natural Science, Kongju National University, 182 Shinkwan-dong, Gongju, Chungnam 314-701, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
A novel S,S0-diallyl carbohydrazonodithioate derivative 3 of rhodamine B hydrazone was developed as a
chemodosimeter for selective detection of mercury ions based on Hg2+ promoted cyclization. The allyl
groups of 3 play a key role in the binding and selection of Hg2+ ions. The probe responds selectively to
Hg2+ over various other competitive cations with marked chromo- and fluorogenic changes. The forma-
tion of stable oxadiazole derivative 8 was a strong driving force for this high selectivity. Practically, this
probe is more promising because of the remarkable high selectivity, faster response, low detection limit,
and aqueous solubility of 3.
Article history:
Received 13 January 2012
Revised 22 February 2012
Accepted 12 March 2012
Available online 15 March 2012
Keywords:
Chemodosimeter
Selective detection
Mercury ions
Ó 2012 Elsevier Ltd. All rights reserved.
Diallyl carbohydrazonodithioate derivative
Fluorescence
Introduction
Result and discussions
Recently, considerable attention has been focused on fluores-
cent chemosensors for selective and rapid detection of toxic heavy
metal ions. The Hg2+ ion is an especially important target due to its
high affinity to the thiol group in proteins, causing many health
problems.1 Several fluorescent chemosensors have been reported
for selective detection of Hg2+ ions.2–4 Fluorescent chemodosime-
ters have become a focus of recent research compared to well-
developed fluorescent sensors.5 This alternative approach involves
the use of highly selective and specific chemical reaction between
the dosimeter molecules and the target.
Mercury ions have a strong ability to bind to sulfur atoms, and
they can also bind to a double bond as a Lewis acid. Initially, based
on these binding abilities of Hg2+, we tried to synthesize an allyl
dithiocarbazate derivative 2 of rhodamine B as shown in Scheme 1.
The reaction was carried out by a one-step three-component cou-
pling reaction with rhodamine B hydrazide 1, carbon disulfide, and
allyl bromide in the presence of cesium carbonate (Cs2CO3) and
Several fluorescent chemodosimeters have been employed for
the selective detection of Hg2+ ions based on the strong thiophilic
nature of Hg2+ ion.6 However, several significant challenges still ex-
ist, such as elevated temperatures, long reaction time, the need for
excess quantities of Hg2+, and cross sensitivities toward other less
thiophilic metal ions, such as Ag+ and Pb2+. Accordingly, there is a
need for new optimal chemodosimeters for Hg2+ detection, which
must have fast response time at ambient temperature and the abil-
ity to detect Hg2+ selectively at parts per billion levels in aqueous
media.
N
O
N
N
O
N
S
CS2, Cs2CO3
TBAB
S
N
N
NH2
N
H
2
Br
O
O
1
CS2, Cs2CO3
CS2, Cs2CO3
TBAB
TBAB
CH3I
Br
N
O
N
N
O
N
In this Letter, we report a rhodamine B derivative containing an
S,S0-diallyl carbohydrazonodithioate group as a simple and novel
chemodosimeter for Hg2+ ion, which can give a highly selective
and rapid spectroscopic response to mercury ions.
S
S
N
N
N
N
S
S
O
4
O
3
⇑
Corresponding author. Tel.: +82 41 850 8498; fax: +82 41 856 8613.
E-mail address: ishong@kongju.ac.kr (I.S. Hong).
Scheme 1. Synthetic route of rhodamine B derivatives 3 and 4.
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.03.040

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A. B. Rode et al. / Tetrahedron Letters 53 (2012) 2571–2574
tetrabutylammonium bromide (TBAB). However, the S,S0-diallyl
carbohydrazonodithioate derivative 3 was formed dominantly in-
stead of mono alkylated derivative 2. Even though the equivalent
of allyl bromide was adjusted to 0.5 equiv of rhodamine B hydra-
zide, mono-alkylated product was still not detected. That might
be due to the highly nucleophilic character of sulfur atom.
The presence of two allyl groups in 3 was confirmed by 1H NMR,
13C NMR, and HR-Mass. To clarify the exact structure of 3, single
crystals of compound 3 were grown from acetone/petroleum ether
as white needles. The crystal structure of 3 clearly showed two
allyl groups bound to the sulfur atoms, the double bond character
of the C29–N4 bond and five-membered spiro-lactam ring (Fig. 4a).
Additionally, as a control compound, the S,S0-dimethyl carbohydr-
azonodithioate derivative 4 was prepared by the same method
using a methyl iodide to examine the role of double bond. Both
compounds 3 and 4 displayed a colorless solution and emitted
no fluorescence. When compound 3 was mixed with mercury ions,
the color of solution was immediately changed to pink, and the
solution emitted the strong fluorescence. Interestingly, the solu-
tion of 4 incubated with Hg2+ did not change color and did not emit
any fluorescence.
two methyl groups, did not show any absorbance and fluorescence
response toward Hg2+ ions.
To assess the specificity of this chemodosimeter, various ions,
including heavy metal ions, were examined in parallel under the
same condition. As shown in Figure 2a and b, the reaction of 3 with
Hg2+ produces both strong fluorescence and absorbance responses;
whereas other metal ions do not show this behavior.7 Therefore, it
can be concluded that 3 displays an extremely high selectivity for
Hg2+ ion only against the other metal ions examined. Tae et al. also
reported a similar rhodamine-based probe,2e which can selectively
detect mercury ions. However, in addition to Hg2+, Tae’s probe
showed some sensitivity toward other less thiophilic cations, for
example, Ag+ and Zn2+. Our probe doesnot show any sensitivities
toward other 16 metal cations showed in Figure 2 except Hg2+. This
unique property enables Hg2+ to be directly detected by the naked
eye. However, dimethyl derivative 4 did not show any color change
in the presence of mercury ions (Fig. 2c).
Furthermore, the time dependence response of 3 to Hg2+ ions
revealed that the reaction of 3 with one equivalent Hg2+ started
immediately, as there was a sudden change in fluorescence inten-
sity, and completed within 61 min. The fluorescence intensity was
saturated after 10 min.8
Figure 1 shows the spectral variation of 3 upon gradual addition
of mercury ions. As expected, 3 itself displays a colorless solution
and emits no fluorescence, indicating that it predominantly exists
in spirocyclic form. With increasing concentrations of the Hg2+
ions, a new emissive peak centered at 576.5 nm appeared with
increasing fluorescence intensity (Fig. 1a).
Next, 1H NMR titration of 3 with Hg2+ was conducted to eluci-
date the binding mode. As shown in Figure 3, new sets of peaks ap-
peared after the addition of Hg2+. The olefinic protons and allylic
protons of two allyl groups displayed new peaks in the downfield,
which suggested that Hg2+ initially bound to the allyl group of 3.
Moreover, 1H NMR titration of 4 with mercury ions showed no
change of any chemical shifts (Fig. 3d), which is consistent with the
results of no fluorescence response toward Hg2+ and other various
Figure 1b shows the absorbance titrations, which were carried
out using 20 l
M of 3 with varied concentration of Hg2+. There
was also a new absorption band centered at 570 nm which ap-
peared with increasing absorbance intensity and, was consistent
with the fluorescence spectra results. The increase in absorption
and fluorescence intensity after addition of more than one equiva-
lent of Hg2+ suggests that there is no 1:1 stoichiometry between 3
and Hg2+ ions. Moreover, S,S0-dimethyl carbohydrazonodithioate
derivative 4, in which the allyl groups were replaced with the
Figure 2. (a) Fluorescence response of 3 (5
(kem = 576.5 nm, kex = 530 nm). (b) Absorbance (570 nm) of 3 (20
metal ions species (20
M). Metal ions examined; K+, Na+, Li+, Ca2+, Mg2+, Ba2+, Zn2+
Cd2+, Co2+, Cr3+, Cu2+, Fe2+, Hg2+, Sr2+, Ni2+, Pb2+, and Ag+. (c) Color changes after
addition of Hg2+ to probe 3 and 4 ([probe] = [Hg2+] = 20
M).
l
M) with
5
l
M of all metal ions
Figure 1. (a) Fluorescence (kex = 530 nm) titration spectra of 3 (1
l
M) with [Hg2+
(water/ethanol:80/20(v/v)). (b) UV–vis
l
M with Hg2+ from 0, 20, 39.2, 57.7, 75.5,
]
lM) with various
from 0, 0.4, 1.0, 1.4, 2.0, and 2.4
lM
l
,
absorption titration spectra of 3 (20
92.6, 109.1, 125, and 140.4
lM.
l

A. B. Rode et al. / Tetrahedron Letters 53 (2012) 2571–2574
2573
Figure 4. (a) Crystal structure of 3 (b) Crystal structure of 8 with displacement
atomic ellipsoids drawn at the 30% probability level. All hydrogen atoms are
omitted for clarity.
Figure 3b shows the peaks of free 3 as well as those of Hg2+
-
bound 5/6/7. This means that there are equilibriums between 3
and mercury ions. As shown in Scheme 2, the mercury-bound
derivative 5 was quickly converted to the spiro-lactam ring opened
6, which emitted the strong fluorescence. Then, intramolecular
cyclization of 6 generated intermediate 7, which was slowly trans-
formed to the stable oxadiazole derivative 8. The lack of further in-
crease of fluorescence after initial emission and gradual increase of
fluorescence in increasing concentration of Hg2+ ions strongly indi-
cate there were fast equilibriums between 5, 6 and 7. The equilib-
riums between 3, 5, 6 and 7 were further confirmed by treatment
of KI,3e which caused immediate disappearance of the color and the
fluorescence. The color and fluorescence of the solution were re-
stored after treatment of the excess amounts of Hg2+ ions (data
were not shown.)
Finally, a stable cyclic 2-allylthio-1,3,4-oxadiazole derivative 8
was formed through removal of S-allyl-Hg+ group. The structure
of the stable 2-allylthio-1,3,4-oxadiazole 8 was also confirmed by
X-ray crystallography analysis.10 Figure 4b clearly showed the for-
mation of an oxdiazole ring with opened spirolactam ring and no
additional bound mercury ions. To the best of our knowledge, this
is the first case reporting the crystal structure of 1,3,4-oxadiazole
based rhodamine B derivative.
Figure 3. 1H NMR titration of 3 and 4 with Hg2+ ions (DMSO-d6). (a) 3 only (b) 3
with 1 equiv of Hg2+ (c) 4 only (d) 4 with 1 equiv of Hg2+. Upper dashes indicate
newly appeared peaks after addition of mercury ions.
metal ions. These results suggest that the allyl groups in 3 play a
key role in the initial Hg2+ binding. An early study by Shin et al.
showed Hg2+ initially binds to oxygen and sulfur and promotes
cyclization of thiosemicarbazide to 1,3,4-oxadiazole.9 However,
in our case, the fact that allyl groups in 3 play a key role in the ini-
tial binding is further confirmed by 1H NMR titration of 4 with
mercury ions, which showed no change of any chemical shifts.
Unlike compound 4, there were significant changes in the NMR
signals of compound 3, in both the xanthene hydrogens and N,N-
diethyl groups. Downfield shifts of both the methylene and methyl
signals in N,N-diethyl group of 3 clearly suggest that Hg2+ induced
the formation of delocalized xanthene moiety of the rhodamine B.
Most noticeably, there was broadening and downfield shifts of
xanthene protons around 6.4 ppm. We conclude that this broaden-
ing is due to slow exchange between the complexed spirolactam
ring opened form and free 3.
For practical applicability, the proper pH condition of this new
chemodosimeter was also evaluated. The ring opening of free
rhodamine B derivative 3 took place spontaneously under acid

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A. B. Rode et al. / Tetrahedron Letters 53 (2012) 2571–2574
Scheme 2. Proposed mechanisms for the production of 2-allythiol-1,3,4-oxadiazole derivative of rhodamine B.
conditions (pH <5) because of the strong protonation. When the pH
of the solution was over 5, no significant ring opening of 3 was ob-
served. However, in the presence of the Hg2+ ions, there was an
obvious fluorescence OFF–ON change between pH 5 and 9.8 Thus,
chemodosimeter 3 can detect Hg2+ ions over a wide pH range from
5 to 9. This property of chemodosimeter 3 suggests that no buffer
solutions are required for the detection of Hg2+ ion, which is con-
venient for practical application.
References and notes
1. (a) Von, B. R. J. Appl. Toxicol. 1995, 15, 483; (b) Harris, H. H.; Pickering, I. J.;
George, G. N. Science 2003, 301, 1203; (c) Nolan, E. M.; Lippard, S. J. Chem. Rev.
2008, 108, 3443.
2. (a) Ono, A.; Togashi, H. Angew. Chem., Int. Ed. 2004, 43, 4300; (b) Nolan, E. M.;
Lippard, S. J. J. Am. Chem. Soc. 2003, 125, 14270; (c) Descalzo, A. B.; Martínez-
Mánez, R.; Radeglia, R.; Rurack, K.; Soto, J. J. Am. Chem. Soc. 2003, 125, 3418; (d)
Hennrich, G.; Walther, W.; Resch-Genger, U.; Sonnenschein, H. Inorg. Chem.
2001, 40, 641; (e) Hennrich, G.; Sonnenschein, H.; Resch-Genger, U. J. Am. Chem.
Soc. 1999, 121, 5073; (f) Huang, J.; Xu, Y.; Qian, X. J. Org. Chem. 2009, 74, 2167.
3. (a) Huang, W.; Song, C.; He, C.; Lv, G.; Hu, X.; Zhu, X.; Duan, C. Inorg. Chem.
2009, 48, 5061; (b) Huang, W.; Zhu, X.; Wua, D.; He, C.; Hu, X.; Duan, C. Dalton
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H.; Su, B.-Y.; Lan, Z.; Xu, J.-G. Chem. Commun. 2008, 16, 1859; (f) Yang, H.; Zhou,
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H.; Swamy, K. M. K.; Kim, S. K.; Kim, S. H.; Lee, S.; Yoon, J. Tetrahedron Lett. 2007,
48, 5966.
Moreover, to assess the possibility of detecting Hg2+ at a low
concentration, fluorescence titrations were conducted with
15 lM of 3. The fluorescence intensity was found to increase with
the Hg2+ concentration in the range from 4 to 61 ppb.8 From this
titration experiment, the detection limit of this chemodosimeter
system was estimated to be about 4 ppb, which is comparable to
those of some previously reported highly sensitive sensors.
4. (a) Zhang, G.; Zhang, D.; Yin, S.; Yang, X.; Shuai, Z.; Zhu, D. Chem. Commun.
2005, 2161; (b) Park, S. M.; Kim, M. H.; Choe, J. I.; No, K. T.; Chang, S. K. J. Org.
Chem. 2007, 72, 3550; (c) Lee, M. H.; Wu, J.-S.; Lee, J. W.; Jung, J. H.; Kim, J. S.
Org. Lett. 2007, 9, 2501; (d) Zheng, H.; Qian, Z. H.; Xu, L.; Yuan, F. F.; Lan, L. D.;
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J. Am. Chem. Soc. 2005, 127, 16030; (f) Palomares, E.; Vilar, R.; Durrant, J. R.
Chem. Commun. 2004, 262.
Conclusion
In summary, we devised a ratiometric fluorescent probe 3 for
mercury species based on Hg2+ promoted cyclization. We showed
that the allyl groups of 3 play a key role in the binding and selec-
tion of mercury ions. The good features of this system, such as
remarkably high selectivity toward Hg2+ ions over miscellaneous
competitive cations, quick response (61 min), aqueous solubility,
the limit of quantification (about 4 ppb), and a wide pH range from
5 to 9, make it promising to determine Hg2+ ions in aqueous solu-
tion for practical analysis.
5. Liu, B.; Tian, H. Chem. Commun. 2005, 25, 3156. and references therein.
6. (a) Chae, M. Y.; Czarnik, A. W. J. Am. Chem. Soc. 1992, 114, 9704; (b) Dujols, V.;
Ford, F.; Czarnik, A. W. J. Am. Chem. Soc. 1997, 119, 7386; (c) Yang, Y.-K.; Yook,
K.-J.; Tae, J. J. Am. Chem. Soc. 2005, 127, 16760; (d) Liu, B.; Tian, H. Chem.
Commun. 2005, 3156; (e) Ros-Lis, J.; Marcos, M. D.; Martinez-Manez, R.; Rurack,
K.; Soto, J. Angew. Chem., Int. Ed. 2005, 44, 4405; (f) Wu, J. S.; Hwang, I. C.; Kim,
S. K.; Kim, J. S. Org. Lett. 2007, 9, 907.
7. As a reviewer suggested, the reactivity of 3 toward Pd2+ and Pt2+ was examined
to check the formation of allyl-metal complex. Pt2+ ions showed no activity to
bind to 3. However, the solution of 3 and Pd2+ showed color change and
emitted strong fluorescence similar to Hg2+ ions. This supports further
formation of allyl–metal complex.
Acknowledgments
8. See Supplementary data.
This work was supported by the Basic Science Research Pro-
gram through the National Research Foundation of Korea (NRF)
funded by the Ministry of Education, Science and Technology
(2009-0071513). J.K. acknowledges financial support from the Pri-
ority Research Center Program (2009-009825) through the Na-
tional Research Foundation (NRF) of Korea.
9. Ko, S. K.; Yang, Y. K.; Tae, J.; Shin, I. J. Am. Chem. Soc. 2006, 128, 14150.
10. Crystallographic data (excluding structure factors) for structures 3 and 8 in this
Letter have been deposited with the Cambridge crystallographic data centre as
supplementary publications Nos. CCDC-860194 and 860195, respectively.
Copies of the data can be obtained, free of charge, on application to CCDC, 12
Union Road, Cambridge CB2 1EZ, UK, [fax: +44 (0)1223 336033 or email:
deposit@ccdc.cam.ac.uk].
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2012.
03.040.