A Fluorescent coumarinylalkyne probe for the selective detection of mercury(II) ion in water

Article abstract of DOI:10.1016/j.tetlet.2009.06.017

A coumarin-based alkyne was developed as a fluorescent chemodosimeter for the selective detection of mercuric ion. It showed a high selectivity and sensitivity to mercury(II) ion over other metal ions in water.

Full text of DOI:10.1016/j.tetlet.2009.06.017

Tetrahedron Letters 50 (2009) 4766–4768
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A Fluorescent coumarinylalkyne probe for the selective detection
of mercury(II) ion in water
Dong-Nam Lee, Gun-Joong Kim, Hae-Jo Kim *
Department of Chemistry, Kyonggi University, Suwon 443-760, 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 coumarin-based alkyne was developed as a fluorescent chemodosimeter for the selective detection of
Received 13 May 2009
Revised 4 June 2009
Accepted 5 June 2009
Available online 9 June 2009
mercuric ion. It showed a high selectivity and sensitivity to mercury(II) ion over other metal ions in
water.
Ó 2009 Elsevier Ltd. All rights reserved.
Fluorescent sensors for heavy metals such as mercury, cadmium
and lead are of growing interest due to their bioaccumulation, bio-
magnification, and persistence in the environment. Especially mer-
methylsilylacetylene in the presence of catalytic amount of
PdCl (PPh and CuI. Desilylation of the intermediate with tetra-
butyl-ammonium fluoride afforded the desired product 1 as a yel-
low solid in 28% yield over 3 steps.
2
3 2
)
1
cury ion detection by optical probes is a rapidly growing area.
Bacteria-mediated organomercury accumulates in higher organ-
Chemical reaction of 1 with water in the presence of mercuric
ion was monitored by H NMR spectroscopy. Upon the addition
of aqueous mercury(II) ion to 1 in DMSO-d , the acetylenic proton
6
2
1
isms and has been implicated as a cause of prenatal brain damage,
various cognitive and motion disorders,3 or Minamata disease.
Therefore, it is of considerable importance to sense the lethal mer-
cury ion with a cost-effective, facile, and biologically applicable
detection method.
4
Et N
O
O
Br2
Et2N
O
O
2
Over the past years, researchers have tried to develop efficient,
selective, and sensitive mercury ion probes based on fluorescent
AcOH
Br
5
small molecules. Most of them, however, were operating in an ex-
6
cess or at least an equivalent amount of mercury ion. To the best
1
) cat. CuI
Et2N
O
O
of our knowledge, there are only a few fluorescent probes known,
which modulate the fluorescence intensities significantly in the
presence of catalytic or substoichiometric amounts of mercuric
PdCl2(PPh3)2
H
TMS
2) Bu NF
4
H
7
1
ions. Koide and co-workers recently developed a fluorescent
7
c
chemodosimeter for mercuric ion using a fluorescein alkyne.
Scheme 1. The synthesis of probe 1.
Herein, we report a luminescent probe operating in the presence
of substoichiometric amounts of mercuric ions based on a fluores-
cent coumarin-derived alkyne.
It is well known as Kucherov reaction that alkynes reacts with
water in the presence of catalytic amount of mercury(II) ion to give
an enol, which tautomerizes to ketone.7 To visually sense a mer-
curic ion in water, a coumarin-derived alkyne (1) was prepared as a
fluorescent chemodosimeter according to the modified literature
,8
9
procedure (Scheme 1). It was expected that the coumarin unit
would operate as a signaling unit whereas the acetylene as a reac-
tion unit. Treatment of 7-diethylamino-coumarin with bromine in
acetic acid gave rise to the 3-bromo-7-diethylamino-coumarin. An
acetylene functional group of 1 was introduced through the Sono-
gashira reaction of 3-bromo-7-diethylaminocoumarin with tri-
Figure 1. Partial 1H NMR spectra of 1 (20 mM in DMSO-d
of HgCl (5.0 equiv) at 25 °C. (a) 1, (b) after 6.8 min, (c) after 1.4 h, treated with
NaOH (10 equiv).
6
2
/D O) upon the addition
*
Corresponding author. Tel.: +82 31 249 9633; fax: +82 31 241 9635.
E-mail address: haejkim@kgu.ac.kr (H.-J. Kim).
2
0
040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.06.017

D.-N. Lee et al. / Tetrahedron Letters 50 (2009) 4766–4768
4767
0
0
0
.6
.4
.2
0
0
0
0
.6
.4
.2
0
4
4
25nm
71nm
0
50
100
min
150
200
250
350
450
nm
550
650
Figure 4. Fluorescence microscopic images of 1 (30
of various metals (each in 5.0 equiv except 0.5 equiv of Hg ). Scale bar 50 lm.
l
M, PBS pH 7.4) in the presence
Figure 2. Time-dependent UV–vis spectral change upon the addition of 0.5 equiv of
Hg to 1 (30 lM, pH 7.4 PBS buffer).
2+
2+
Fig. S3) or a fluorescence microscope (kex band 450–480 nm, kem
00 nm). The obvious fluorescence decrease was prominently ob-
served only for mercury ion. Most other metal ions did not show
any significant fluorescence changes but almost the same intensity
as 1 itself (Fig. 4).
at 4.24 ppm disappeared while another simple set of aromatic pro-
tons were appearing (Fig. 1), which was consistent with the 3-acyl-
5
7
-diethylamino-coumarin (Ref) (Fig. S1 in Supplementary data).
The chemical reaction was also confirmed by UV–vis spectroscopy
Fig. 2). Absorbance of 1 at k 425 nm decreased while the absor-
(
The conversion of an acetylene to ketone is well known to pro-
ceed in the presence of catalytic amounts of mercury ions in
bance at k 471 nm was increasing with a pseudoisosbestic point
at k 450 nm upon the addition of mercury(II) ion in PBS buffer
8
water. Motivated by the catalytic role of mercuric ions in the reac-
(
pH 7.4). A bathochromic shift was observed as the acetylene func-
tion, we tried to determine the limit of mercury ion concentration
tionality was converted to the more electron-withdrawing car-
bonyl group. The chemical conversion is so fast that the reaction
enough to cause a detectable fluorescence change of 1. The concen-
2
+
tration of Hg ion was decreased from 5.0
1.2 l
l
M to 1.0 nM. As low as
M of mercuric ions, [Hg ]/[1] = 0.6, has completely quenched
the fluorescence of 1 (2.0 M) in water (PBS pH 7.4) (Fig. 5).
is complete within 1 h at 25 °C under a high dilution condition of
2
+
reactants and substoichiometric amount of Hg2 ([1] = 30
+
lM,
l
2
Hg(OAc) = 0.5 equiv, Fig. 2 inset).
According to the sensitivity curve, less than 0.24 ppm of mercuric
ions is enough to monitor the complete quenching of the fluores-
cence of 1. This indicates probe 1 can be utilized not only to the
The fluorescence intensity of 1 at kem 488 nm decreased com-
2+
pletely upon the addition of 0.5 equiv of Hg ion to 1 (30 lM) in
water (PBS buffer at pH 7.4),10 whereas no significant changes
were observed in the presence of other metal ions in excess such
2
+
qualitative analysis of Hg ions using a UV lamp or a fluorescence
microscope but also to the quantitative analysis of micromolar
+
+
2+
2+
2+
3+
2+
2+
3+
2+
2+
2+
as Na , K , Mg , Ca , Ba , Al , Mn , Fe , Fe , Co , Ni , Cu ,
2
+
2
+
+
2+
concentration of Hg ions in water to enable an application for
Zn , and Ag ions (5.0 equiv each). In contrast to Hg ion, other
heavy metal ions such as Pb and Cd ions do not induce any
detectable fluorescence changes either (Fig. 3). Selectivity factor,
1
1
2
+
2+
assaying fish for safe human consumption.
From the observed results, we propose the fluorescence sensing
mechanism of 1, which is specific to mercury(II) ion. Mercuric ion
catalyzes the conversion reaction from an alkyne to ketone in
water (Fig. 6). Mecury(II)-promoted hydration of 1 through an
enol-keto tautomerization may lead to the stable keto product
defined as F
3 while the factor for other metals was less than 2.0, which are
comparable to probe 1. Of note is the observed selectivity for
0
/F, for mercuric ion was calculated to be more than
1
2
+
2+
2+
Hg over Cu and Pb , major competitors in real-life field
samples.
(Ref). The fluorescence intensity of 1 decrease as the reaction pro-
ceeds due to the possible transition of the coumarin HOMO elec-
tron to the carbonyl orbital in LUMO upon the excitation of
Competitive experiments in the presence of excess of other
metals (5.0 equiv) also corroborated the mercuric ion (0.5 equiv)
selectivity of 1 (Fig. S2).
The fluorescence response of the chemodosimeter was also
detectable by the naked eye using a UV lamp (kex 365 nm,
1
2
coumarin chromophore.
In summary, we have developed a novel fluorescent chemodos-
imeter, based on a fluorescent coumarin-derived alkyne. The al-
kyne probe reacted with water in the presence of mercuric ion
and displayed a sensitive fluorescence response to substoichiomet-
180
120
60
0
0
1
2
3
4
5
6
-
6
Figure 3. Metal ion selectivity of 1 (30
metals (each in 5.0 equiv except 0.5 equiv of Hg ), where kex at 425 nm and kem at
88 nm.
l
M, PBS pH 7.4) in the presence of various
[Hg(II)]/10 M
2
+
4
Figure 5. Mercuric ion sensitivity of 1 (2.0 lM, PBS pH 7.4).

4
768
D.-N. Lee et al. / Tetrahedron Letters 50 (2009) 4766–4768
Et2N
O
O
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O
O
X
H
H
H
O
1
Ref (X = H) or (Hg)
Flu-ON
Flu-OFF
Hg2+
H+
Et2N
O
O
O
Et2N
O
O
H2O H+
Hg2+
Hg+
H
H
H
3.
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Figure 6. A proposed mechanism.
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Acknowledgments
Support of this work by a grant from the Korea Research Foun-
dation (Grant No. KRF-2008-313-C00508) is gratefully
acknowledged.
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Supplementary data (experimental procedure and selected
spectral data (NMR, MS, fluorescence spectra) for 1) associated
with this article can be found, in the online version, at
doi:10.1016/j.tetlet.2009.06.017.
1
0. Though the mercury-mediated hydration of an alkyne is well known to occur
in an acidic solution, the fluorescence intensity of 1 was very weak in the acidic
condition and its change was negligible upon the addition of Hg(II) to 1.
Significant fluorescence changes could be observed at the pH range between 7
and 9 (Fig. S4).
1
1. U.S. EPA, Regulatory Impact Analysis of the Clean Air Mercury Rule: EPA-452/R-
05-003, 2005.
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