A new fluorogenic chemodosimetric system for mercury ion recognition

Article abstract of DOI:10.1016/j.tetlet.2010.08.088

A new probe system for fluorogenic sensing of mercury ions has been designed and synthesized. It is the first intermolecular reaction-based fluorogenic chemodosimetric probe system for Hg(II) ion recognition. High and low concentrations of mercury ions gave different fluorescence responses that could easily be distinguished by the naked eye. This unique system allows detection of the concentration and presence of the mercury ion.

Full text of DOI:10.1016/j.tetlet.2010.08.088

Tetrahedron Letters 51 (2010) 5784–5786
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A new fluorogenic chemodosimetric system for mercury ion recognition
⇑
Wen Xiu Ren, Sankarprasad Bhuniya, Jun Feng Zhang, Young Hoon Lee, Suk Joong Lee, Jong Seung Kim
Department of Chemistry, Korea University, Seoul 136-701, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
A new probe system for fluorogenic sensing of mercury ions has been designed and synthesized. It is the
first intermolecular reaction-based fluorogenic chemodosimetric probe system for Hg(II) ion recognition.
High and low concentrations of mercury ions gave different fluorescence responses that could easily be
distinguished by the naked eye. This unique system allows detection of the concentration and presence of
the mercury ion.
Received 6 August 2010
Accepted 30 August 2010
Available online 16 September 2010
Keywords:
Ó 2010 Elsevier Ltd. All rights reserved.
Chemodosimetric
Fluorescence
Mercury
Copper
Chromogenic
The detection and quantification of heavy- and transition-metal
(HTM) ions have drawn current interest because of their detrimen-
tal effect on the living species and their adverse impact on the
environment.1
Upon addition of Hg2+ ions to a mixture of 1 and o-PDA (both
non-fluorescence),8 it catalyzed desulfurization (Fig. S1) and pro-
moted the formation of the unstable spiroheterocyclic intermedi-
ate 2, which subsequently was converted to
3 through an
Mercury, one of the most toxic HTM elements, represents a ma-
jor source of toxicity for microorganisms and environments, even
at low concentrations. When consumed by humans, mercury can
trigger several serious disorders, including sensory, motor, and
neurological damage.2 In the past few decades, many sophisticated
analytical tools have been developed to detect mercury ions,3 espe-
cially fluorescent chemosensors,4 in view of their high sensitivity.
More recently, the chemodosimetric approach has attracted much
attention given its great simplicity, sensitivity, selectivity, and irre-
versibility.5 Most methods are designed on mercury-promoted
desulfurization reactions;5c–h as a consequence, it increases the
fluorescent intensity originating mainly from the functional group
interconversion. Our major interest is the introduction of this well-
known desulfurization technique towards chemodosimetric sen-
sors for Hg2+ with the fabrication of a fluorescent dye triggered
by an intermolecular chemical reaction.
intramolecular rearrangement.9 Although the formation of 3 is
well supported with spectroscopic data that correlates with
authentic data, the corresponding mechanism remains unclear.
Compound 3 is a classic dye, with strong green fluorescence, that
is widely used as a basic skeleton in the design of new organic pig-
ments, laser dyes, textile dyes, and polymer fibers.10
UV irradiation of a mixture of 1, o-PDA, and Hg2+ in CH3CN could
accelerate the reaction rate. For example, upon the irradiation with
a handheld UV lamp (365 nm) for 5 min,11 the fluorescence inten-
sity at 492 nm dramatically increased by approximately 19-fold
(compared with the intensity without irradiation at 1.5 h)
(Fig. S3). In addition, the molar ratio of 1 and o-PDA can also influ-
ence the reaction rate. To optimize the system, various molar ratios
Herein, we have designed and synthesized a novel probe system
utilizing mercury-promoted desulfurization reactions as outlined
in Scheme 1. The 6,10-dithiaspiro-acenaphthene quinone (1) was
prepared in high yield (89%) and further catalyzed with o-phenyl-
enediamine (o-PDA) to form 3 in the presence of Hg2+ ions and as a
consequence amplified the fluorescent signal.6 To the best of our
knowledge, this is the first intermolecular reaction-based ‘turn
on’ fluorescent sensing approach for Hg2+ ions.
⇑
Corresponding author. Tel.: +82 2 3290 3143; fax: +82 2 3290 3121.
E-mail address: jongskim@korea.ac.kr (J.S. Kim).
Scheme 1. Synthesis of ligand 1 and proposed reaction mechanism.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.08.088

W. X. Ren et al. / Tetrahedron Letters 51 (2010) 5784–5786
5785
of 1 and o-PDA were tested with a fixed concentration of 20
l
M of
other competitive metal ions was investigated as illustrated in Fig-
Hg2+ ion in CH3CN (Fig. S4). The system containing 1 (20
o-PDA (3.0 equiv) gave the best results.
l
M) and
ure 2. Some transition and post transition metal ions like Ag+, Co2+
,
and Zn2+ slightly reduced the fluorescence intensity because of
their complexation ability with o-PDA (Fig. S10).
The UV–vis absorption behavior of the probe system toward
representative metal ions was investigated by treatment with
physiologically important alkali, alkaline earth, and transition-
metal perchlorates in CH3CN, as presented in Figure 3. Upon inter-
action with various metal ions, significant changes in absorption
As shown in Figure 1, the fluorescence titration profile of 1 and
o-PDA (3.0 equiv) versus Hg2+ demonstrated that the concentration
of Hg2+ could impact emission intensity and emission wavelength.
In the presence of a low concentration of Hg2+ ions (0–1.4 equiv),
the fluorescence emission at 492 nm (same with 3) and emission
intensity were enhanced with gradually increased Hg2+ ions. Upon
further addition of Hg2+ ions (>1.4 equiv), the emission band at
492 nm gradually decreased and concomitantly blue shifted to
454 nm. This may be caused by either: (1) interaction of Hg2+ with
3 and/or; (2) the decrease in concentration of free o-PDA in a solu-
tion of excess Hg2+ ion due to ligation of o-PDA to Hg2+, which dis-
rupts the formation of 3 and consequently decreases emission
intensity (Fig. S5). To rationalize this change in the presence of ex-
cess Hg2+ ions, we examined spectral changes upon the gradual
addition of Hg2+ to a solution of 3 (Fig. S6). There was a strong
emission at 492 nm of 3 that gradually blue shifted and reached
spectra were immediately observed, particularly with Cu2+
,
because Cu2+ can easily interact with o-PDA and produce a
CuPDAx(ClO4)2 (x = 1 or 2) complex in solution, resulting in a con-
comitantly chromogenic change from colorless to brown.12
It is to be noted that due to the strong interactions between
Cu2+ with o-PDA, the existence of high concentrations of Cu2+ can
kmax = 454 nm in a 150 l
M concentration of Hg2+, with a significant
increased emission intensity due to internal charge transfer (ICT).
NMR titration experiments were performed to verify the coordina-
tion mechanism between 3 and Hg2+. Comparison of the 1H NMR
spectra of 3 before and after the addition of Hg2+ revealed that
all the proton signals were shifted downfield (Fig. S7). These
changes were likely due to metal ion complexation, in which
Hg2+ was bound to an imidazole nitrogen in 3.10a,c Furthermore,
complexation of Hg2+ with 3 was weaker than with o-PDA
(Fig. S8). Thus, control of the emission intensity and wavelength
of a sample is possible by controlling the concentration of o-PDA.
This Hg2+ concentration dependence of fluorescent spectral
changes implied that this unique system allows detecting the pres-
ence and concentration of the Hg2+ ion.
To understand the role of other metals ions in this chemical
transformation, identical experiments were carried out with other
Figure 2. Fluorescence enhancement (I À I0)/I0 of the probe system (1 (20 lM) and
o-PDA (3.0 equiv)) in CH3CN, kmax = 492 nm. (Front line) upon the addition of
different metal ions (10 equiv, except Cu2+ (5.0 equiv)) and Hg2+ (1.0 equiv); (back
line) competitive selectivity of the sensor system toward Hg2+ ions (1.0 equiv) in
the presence of other metal ions (10 equiv, except Cu2+ (1.0 equiv)), kex = 380 nm.
heavy, alkaline, and alkaline earth metals, such as Ag+, Ba2+, Ca2+
,
Cd2+, Co2+, Cu2+, Cs2+, K+, Li+, Mg2+, Na+, Rb+, and Sr2+; however,
these ions did not influence any fluorescence changes, even at very
high concentrations. Only the addition of Fe2+, Pb2+, and Zn2+ gave
relatively slight fluorescence enhancements (Fig. S9).
From a practical application point of view, the interference from
other metal ions should be taken into account; hence, the fluores-
cence change in this Hg2+ ion-catalyzed reaction in the presence of
Figure 1. Fluorescence response of the probe system (1 (20
lM) and o-PDA
Figure 3. (a) The color response of the probe system upon the addition of different
(3.0 equiv)) upon addition of the Hg2+ ion (0–100
l
M) in CH3CN, kex = 380 nm.
metal ions. (b) UV–vis spectra of 1 (20 lM) and o-PDA (3.0 equiv) in the presence of
Inset: fluorescence images in the absence of the Hg2+ ion (left); in the presence of
the Hg2+ ion (low concentration, middle; high concentration, right).
different metal ions (Ag+, Ba2+, Ca2+, Cd2+, Co2+, Cu2+, Cs2+, Fe2+, K+, Li+, Mg2+, Na+,
Pb2+, Rb+, Sr2+, Zn2+ (10 equiv); Hg2+ (1.0 equiv)) in CH3CN.

5786
W. X. Ren et al. / Tetrahedron Letters 51 (2010) 5784–5786
5. (a) Cho, D.-G.; Sessler, J. L. Chem. Soc. Rev. 2009, 38, 1647; (b) Lee, D.-N.; Kim,
G.-J.; Kim, H.-J. Tetrahedron Lett. 2009, 50, 4766; (c) Kim, J. H.; Kim, H. J.; Kim, S.
H.; Lee, J. H.; Do, H. J.; Kim, H.-J.; Lee, J. H.; Kim, J. S. Tetrahedron Lett. 2009, 50,
5958; (d) Santra, M.; Ryu, D.; Chatterjee, A.; Ko, S.-K.; Shin, I.; Ahn, K. H. Chem.
Commun. 2009, 2115; (e) Choi, M. J.; Kim, Y. H.; Namgoong, J. E.; Chang, S.-K.
Chem. Commun. 2009, 3560; (f) Jiang, W.; Wang, W. Chem. Commun. 2009,
3913; (g) Lee, M. H.; Lee, S. W.; Kim, S. H.; Kang, C. H.; Kim, J. S. Org. Lett. 2009,
11, 2101; (h) Namgoong, J. E.; Jeon, H. L.; Kim, Y. H.; Choi, M. G.; Chang, S.-K.
Tetrahedron Lett. 2010, 51, 167.
interfere with the formation of 3 and consequently quench fluores-
cence. Further addition of o-PDA can recover its strong signal,
allowing Hg2+ interactions (Fig. S11).
In summary, we developed a Hg2+-catalyzed intermolecular
reaction-based probe system which demonstrated high selectivity
for Hg2+. This is a new and unconventional chemodosimeter strat-
egy to detect Hg2+ ions, even in the presence of other competitive
metal ions.
6. General: Compound 1 was synthesized according to a literature process7. All
reagents and solvents for syntheses were of commercial grade and used
without further purification. All reactions were performed under a highly pure
nitrogen or argon atmosphere. Synthesized products were purified by column
chromatography on silica gel (100–200 mesh). All fluorescence and UV–vis
absorption spectra were recorded with RF-5301PC and S-3100
spectrophotometers, respectively. NMR and mass spectra were recorded with
a Varian instrument (300 MHz) and HRMS mass spectra.
Acknowledgment
This work was supported by the Creative Research Initiative
program (No. 2010-0000728) of the National Research Foundation
of Korea.
Preparation of benzo[de]-benzo[4,5]imidazo[2,1-a]isoquinolin-7-one (3). Mixture
of
1
(0.027 g, 0.1 mmol), o-PDA (32 mg, 0.3 mmol), and Hg(ClO4)2ÁxH2O
(0.060 g, 0.14 mmol) in CH3CN (3.0 mL) were stirred under UV irradiation at
365 nm for 5 min. After the reaction was finished, the mixture was filtered and
the solvent removed in vacuo. The reaction mixture was purified by column
chromatography with methylene chloride to give pure 3 (10.2 mg, 38%) as a
yellowish green solid. MP = 192–193 °C. 1H NMR (300 MHz, CDCl3): d 7.46–
7.49 (m, 2H), 7.76–7.83 (m, 2H), 7.86–7.90 (m, 1H), 8.12 (d, J = 8.6 Hz, 1H), 8.21
(d, J = 8.2 Hz, 1H), 8.54–8.57 (m, 1H), 8.75–8.83 (m, 1H). HRMS (FAB): calcd for
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.08.088.
C
18H11N2O [M+H]+ 271.0871; found 271.0871.
References and notes
7. Almog, J.; Stepanov, N.; Dubnikova, F. Tetrahedron Lett. 2008, 49, 1870.
8. Both compound 1 and o-PDA showed non-fluorescence no matter with or
without Hg2+ ion even after 5 min UV irradiation.
9. (a) Garner, R.; Garner, G. V.; Suschitzky, H. J. Chem. Soc. C 1970, 825; (b) Davis,
R.; Tamaoki, N. Org. Lett. 2005, 7, 1461.
10. (a) Galunov, N. Z.; Krasovitskii, B. M.; Lyubenko, O. N.; Yermolenko, I. G.;
Patsenker, L. D.; Doroshenko, A. O. J. Lumin. 2003, 102, 119; (b) Tamuly, C.;
Barooah, N.; Laskar, M.; Sarma, R. J.; Baruah, J. B. Supramol. Chem. 2006, 18, 605;
(c) Hu, J. W.; Zhang, G. H.; Shih, H.-H.; Jiang, X. Q.; Sun, P. P.; Cheng, C.-H. J.
Organomet. Chem. 2008, 693, 2798; (d) Podsiadly, R.; Kolinska, J.; Sokolowska, J.
Color. Technol. 2008, 124, 79; (e) Kolinska, J.; Podsiadly, R.; Sokolowska, J. Color.
Technol. 2008, 124, 341.
11. All of the samples irradiated by handhold UV lamp (365 nm, 5 min) have been
kept for 5 min before fluorescence measurement to stabilize the fluorescence
intensity (Fig. S2).
12. (a) Chiswell, B.; Lions, F.; Morris, B. S. Inorg. Chem. 1964, 3, 110; (b) Marks, D. R.;
Phillips, D. J.; Redfern, J. P. J. Chem. Soc. A 1967, 1464; (c) Duff, E. J. J. Chem. Soc. A
1968, 434; (d) Duff, E. J. J. Chem. Soc. A 1968, 836; (e) Marks, D. R.; Phillips, D. J.;
Redfern, J. P. J. Chem. Soc. A 1968, 2013; (f) Gross, R.; Kaim, W. Inorg. Chem.
1987, 26, 3596; (g) Chao, M.-S.; Chung, C.-S. Inorg. Chem. 1987, 26, 3600; (h)
Mizuno, M.; Funahashi, S.; Nakasuka, N.; Tanaka, M. Inorg. Chem. 1991, 30,
1550.
1. (a) Harris, Z. L.; Gitlin, J. D. Am. J. Clin. Nutr. 1996, 63, 836S; (b) Scheinberg, I. H.;
Sternlieb, I. Am. J. Clin. Nutr. 1996, 63, 842S; (c) Nendza, M.; Herbst, T.; Kussatz,
C.; Gies, A. Chemosphere 1997, 35, 1875; (d) Boening, D. W. Chemosphere 2000,
40, 1335.
2. (a) ATSDR Toxicological Profile for Mercury; U.S. Department of Health and
Human Services: Atlanta, GA, 1999; (b) Campbell, L. M.; Dixon, D. G.; Hecky, R.
E. J. Toxicol. Environ. Health 2003, 6, 325; (c) ATSDR ToxProfiles: Mercury; U.S.
Department of Health and Human Services: Atlanta, GA, 2005.
3. (a) Díez, S.; Bayona, J. M. J. Chromatogr., A 2002, 963, 345; (b) Cizdziel, J. V.;
Gerstenberger, S. Talanta 2004, 64, 918; (c) Jitaru, P.; Adams, F. C. J. Chromatogr.,
A 2004, 1055, 197; (d) Li, Y.; Chen, C.; Li, B.; Sun, J.; Wang, J.; Gao, Y.; Zhao, Y.;
Chai, Z. J. Anal. At. Spectrom. 2006, 21, 94.
4. (a)Fluorescent Chemosensors for Ion and Molecule Recognition; Czarnik, A. W.,
Ed.; American Chemical Society: Washington, DC, 1993; p 1; (b) 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; (c) Zhao, Y.; Lim, Z.;
He, C.; Wu, H.; Duan, C. Inorg. Chem. 2006, 45, 10013; (d) Peng, X.; Du, J.; Fan, J.;
Wang, J.; Wu, Y.; Zhao, J.; Sun, S.; Xu, T. J. Am. Chem. Soc. 2007, 129, 1500; (e)
Dai, Z.; Canary, J. W. New J. Chem. 2007, 31, 1708; (f) Nolan, E. M.; Lippard, S. J.
Chem. Rev. 2008, 108, 3443; (g) Taki, M.; Desaki, M.; Ojida, A.; Iyoshi, S.;
Hirayama, T.; Hamachi, I.; Yamamoto, Y. J. Am. Chem. Soc. 2008, 130, 12564; (h)
Cheng, T.; Xu, Y.; Zhang, S.; Zhu, W.; Quian, X.; Duan, L. J. Am. Chem. Soc. 2008,
130, 16160; (i) Nolan, E. M.; Lippard, S. J. Acc. Chem. Res. 2009, 42, 193.