A sugar-aza-crown ether-based fluorescent sensor for Cu2+ and Hg2+ ions

Article abstract of DOI:10.1016/j.carres.2011.03.010

A sugar-aza-crown ether (SAC)-based fluorescent sensor 4 was prepared. It contains a pyrene as the fluorophore and its fluoroionophoric properties toward transition metal ions were investigated. Chemosensor 4 exhibits highly selective recognition toward Cu²⁺ and Hg²⁺ ions among a series of tested metal ions in methanol solution. The association constants for 4Cu ²⁺ and 4Hg²⁺ in methanol solution were calculated to be 7.4 × 10¹ M^-1 and 4.4 × 10³ M ^-1, respectively. Chemosensor 4 formed complexes with the Cu ²⁺ or Hg²⁺ ion at a 1:1 ligand-to-metal ratio with a detection limit of 1.3 × 10^-4 M Cu²⁺ and 1.26 × 10^-5 M Hg²⁺, respectively.

Full text of DOI:10.1016/j.carres.2011.03.010

Carbohydrate Research 346 (2011) 978–981
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Note
2+
2+
A sugar-aza-crown ether-based fluorescent sensor for Cu and Hg ions
⇑
Yu-Chi Hsieh, Jiun-Ly Chir, Shih-Tse Yang, Shau-Jiun Chen, Ching-Han Hu, An-Tai Wu
Department of Chemistry, National Changhua University of Education, Changhua 50058, Taiwan
a r t i c l e i n f o
a b s t r a c t
Article history:
A sugar-aza-crown ether (SAC)-based fluorescent sensor 4 was prepared. It contains a pyrene as the fluo-
rophore and its fluoroionophoric properties toward transition metal ions were investigated. Chemosensor
Received 4 November 2010
Received in revised form 26 February 2011
Accepted 6 March 2011
2+
2+
4
exhibits highly selective recognition toward Cu and Hg ions among a series of tested metal ions in
2+
2+
methanol solution. The association constants for 4ÃCu and 4ÃHg in methanol solution were calculated
Available online 10 March 2011
1
À1
3
À1
2+
to be 7.4 Â 10 M and 4.4 Â 10 M , respectively. Chemosensor 4 formed complexes with the Cu or
2
+
À4
2+
Hg
ion at
a
1:1 ligand-to-metal ratio with
a
detection limit of 1.3 Â 10
M
Cu
and
Keywords:
À5
2+
1.26 Â 10 M Hg , respectively.
Fluorescent sensor
Chemosensor
Pyrene
Ó 2011 Elsevier Ltd. All rights reserved.
+ 15
The design and synthesis of new chemosensors for the efficient
detection of trace metal ions is one of the most important research
topics in environmental chemistry and biology. Among these me-
for Cu2
.
In addition, we have reported that a SAC-based cavitand
2
+
16
as a turn-on type sensor for Cu ion in methanol solution and
SAC-based sensor with two anthracenetriazolymethyl groups exhi-
bit turn-off type fluorescence responses upon interaction with
1
1
7
tal ions, the copper ion is a significant environmental pollutant and
also plays a critical role in various biological processes.2 The mer-
cury ion is also a significant environmental pollutant which is
accumulated in plants, soil, and water. Some prokaryotes convert
this inorganic mercury to methyl mercury, which is a lipophilic
compound that is readily absorbed and poorly excreted. When it
enters the food chain it biomagnifies in higher organisms, espe-
cially in the muscles of large predatory fish, including tuna, sword-
fish, and whales, and when it is subsequently ingested by humans
leads to DNA and nervous system damage.5
–4
2+
2+
Cu and Hg ions in water solution. Herein, we report a SAC-
based structure with two pyrenylmethyl groups as a fluorescent
sensor for metal ions. The designed chemosensor 4 exhibits a
turn-on type response and highly selective fluorescence behavior
2
+
2+
for Cu and Hg ions in methanol solution.
Fluorescent sensor 4 can be easily prepared from 1-pyrene-
methanol 1 in three steps as shown in Scheme 1. 1-Pyrenemetha-
nol 1 was treated with thionyl chloride to obtain 1-chloro-
pyrenemethane 2 (98%). Compound 2 was further coupled with
–9
Fluorescence quenching by heavy metal ions is a well-known
phenomenon and occurs by a number of pathways, which include
2 3 3 4
SAC 3 using K CO as a base in CH CN–KI–n-Bu NI solvent under
1
8
reflux conditions afforded sensor 4 (48%). The structures of 4
were confirmed by NMR spectroscopy and mass spectra (see Sup-
plementary data, Figs. S1–S4).
10–14
spin-orbit coupling, energy transfer, and electron transfer.
Be-
cause Cu and Hg ions have the propensity to quench fluoro-
phore emission, turn-off detection is facile approach for
monitoring these metal ions. For fluorescence detection of Cu
2
+
2+
a
We examined the effect of different solvents (CH
THF, CH CN, and DMSO) on the fluorescence spectrum of 4
(144 M). As shown in Figure 1, the monomer–excimer ratio of 4
2 2
Cl , methanol,
2
+
3
2
+
and Hg ions, enhancement (‘turn-on’) is preferable to fluores-
cence quenching (‘turn-off’) because it lessens the chance of false
positives and is more amenable to multiplexing, the simultaneous
use of several detectors that uniquely respond to different ana-
l
is not affected by the polarity of the solvents, only the monomer
is dominant over the excimer, in which the excimer emission is
quenched completely owing to strong solvation. This indicates that
the two pyrenes of 4 are not present in the parallel conformation.
2
+
2+
lytes. However, to date, few turn-on type Cu and Hg fluorescent
sensors have been found in the literature.1
0,11
Therefore, designing
The fluorescence of 4 (11 lM) revealed three strong emission
2
+
fluorescent sensors that provide a turn-on response following Cu
bands of the pyrene moiety at 377, 396, and 418 nm in methanol.
We examined the chemosensing behavior of the fluorescent sensor
4 by fluorescence measurements in the presence of various metal
ions in methanol by comparing the fluorescence intensities of the
solutions before and after addition of 100 equiv of the following
2
+
or Hg recognition is a considerable challenge. Recently, modified
pyranoid-based SAC (sugar-aza-crown ether) with bispyrenyl moi-
eties was synthesized to form a new fluorescent molecular sensor
+
+
+
2+
2+
1
2 metal ions as their perchlorate salts: Li , Na , K , Ca , Mg ,
2
+
2+
2+
2+
2+
2+
2+
2+
⇑
Corresponding author. Tel.: +886 4 7232105 3542; fax: +886 4 7211 190.
E-mail address: antai@cc.ncue.edu.tw (A.-T. Wu).
Hg , Co , Ni , Pb , Cu , Cd , and Zn . In the presence of Cu
and Hg ions, sensor 4 showed modest and large fluorescence
2
+
0
008-6215/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2011.03.010

Y.-C. Hsieh et al. / Carbohydrate Research 346 (2011) 978–981
979
Cl
OH SOCl2
CH Cl
2
2
9
8%
N
2
O
O
1
K CO , KI
O
O
2
3
O
+
O
t-BuNI, CH CN
3
N
48%
N
H
O
O
O
O
O
O
H
N
3
4
Scheme 1. Synthesis of fluorescent sensor 4.
(
Fig. 3). The fluorescence enhancement can be attributed to the
5
4
3
2
1
00
00
00
00
00
0
2
CH Cl2
photoinduced electron transfer (PET) that occurs upon complexa-
tion of the nitrogen atoms by metal ion. These results suggest that
Cu or Hg ion can be recognized by the two nitrogen atoms of
the linker of 4.
MeOH
THF
2
+
2+
CH CN
3
DMSO
To further investigate the interaction between sensor 4 and me-
2+
tal ions, we performed fluorescence titrations of 4 with Cu and
2
+
2+
2+
Hg ions in methanol. As the concentration for Cu and Hg ions
was gradually increased, the fluorescence intensity of 4 is also in-
creased (Fig. 4). From the fluorescence titration profiles, the associ-
2
+
2+
ation constants for 4ÃCu and 4ÃHg in methanol were calculated
1
3
À1
as 7.4 Â 10 and 4.4 Â 10 M , respectively, by a Stern–Volmer
plot (Figs. S5 and S6). By the Job plot (Fig. S7), a maximum fluores-
cence change was observed when the molar fraction of the sensor
3
50
400
450
500
550
2+
2+
[4] versus [Cu ]+[4] and [4] versus [Hg ]+[4] was 0.5, indicating
Wavelength (nm)
2+
2+
that a 1:1 adduct was formed between 4 and Cu or Hg ion.
By using the above-mentioned fluorescence titration results, the
Figure 1. Fluorescence spectra of 4 (144
l
M) in different solvents.
2
+
2+
detection limits of 4 for the analysis of Cu and Hg ions were
À4
À5
determined as 1.3 Â 10 and 1.26 Â 10 M, respectively. We also
2
+
2+
enhancement, respectively, while the other metal ions had only
small effects (Fig. 2). The enhancement efficiency (I À I
tried to obtain evidence for the proposed Cu and Hg ions in-
duced conformational changes by NMR spectroscopy but failed
due to the extensive broadening of the resonances under the rele-
vant experimental conditions. ESI-MS was conducted using a 1 mM
0
/
I
0
 100%) observed at 377 nm was ꢀ128% and 51% greater than
2+ 2+
the control in the absence of Hg and Cu ions, respectively
solution of 4 in methanol with an excess of Cu(ClO
4
)
2
to give the
2
+
+
2
result of m/z = 927.7 (4+Cu +2H O+1H , Fig. S8), which gave fur-
host
2
-
350
300
250
200
150
100
Pb
2-
Zn
2
-
Cd
Mg
2
-
1
20
00
80
60
2
-
Ni
2
-
Cu
Co
Ca
Hg
1
2
-
2
-
2
-
-
Li
-
Na
-
K
40
50
0
3
20
0
50
400
450
500
Wavelength (nm)
Pb Zn Cd Mg Ni Cu Co Ca Hg Li Na
K
M) upon the addition of Li , Na , K , Ca2+,
+
+
+
Figure 2. Fluorescent spectrum of 4 (11
l
2+
2+
2+
2+
2+
2+
2+
2+
Mg , Hg , Co , Ni , Zn , Cu , Cd , and Pb (100 equiv) in MeOH (excitation at
Figure 3. Fluorescence intensity changes ((I À I
0
)/I
0
 100%) of 4 (11 lM) with
3
43 nm).
various metal ions (11 mM) in MeOH at 377 nm (excitation at 343 nm).

9
80
Y.-C. Hsieh et al. / Carbohydrate Research 346 (2011) 978–981
a
500 eq
350
300
250
200
150
100
500
400
300
200
100
0
I: intensity at 351 nm
0
0
2+
I :intensity at 351 nm for [Hg ]=0 M
5
0
0
0
100
200
300
400
500
2
+
[
Hg ]/[4]
350
400
450
500
Wavelength (nm)
b 3
00
00
00
0
8
7
6
5
4
3
2
0
0
0
0
0
0
0
8
00 eq
Figure 5. Conformation of 4/Hg2+ optimized by density functional theory.
2
1
I: intensity at 343 nm
:intensity at 343 nm for [Cu]=0 M
2+
1
0 eq
I
0
1
. Experimental
0
200
400
600
800
2
+
1.1. General methods
[
Cu ]/[4]
All reagents were obtained from commercial suppliers and were
3 2
used without further purification. CH CN was distilled over CaH .
Analytical thin-layer chromatography was performed using Silica
Gel 60 F254 plates (Merck). The H and C NMR spectra were re-
corded with Bruker AM 300 (300 MHz) spectrometers. Chemical
400
500
1
13
Wavelength (nm)
3
shifts are expressed in ppm with residual CHCl as reference.
Figure 4. (a) Fluorescence spectra of
increasing concentrations of Hg(ClO ; kex = 343 nm. (b) Fluorescence spectra of
(13 M) in MeOH upon addition of increasing concentrations of Cu(ClO
ex = 343 nm.
4 (13 lM) in MeOH upon addition of
Low- and high-resolution mass spectra were recorded under fast
atom bombardment (FAB) conditions. UV–vis spectra were re-
corded by using an HP-8453 spectrophotometer with a diode array
detector, and the resolution was set at 1 nm. Fluorescence spectra
were recorded on a Cary Eclipse Fluorescence spectrophotometer.
Microwave reactions were carried out in a Milestone Start S with
a maximum power of 300 W.
4 2
)
4
k
l
4 2
) ;
ther evidence of the formation of a 1:1 complex between 4 and
2
+
Cu ion.
The selectivity toward Hg2 or Cu2+ ions was further ascertained
+
by the competitive experiment employed with addition of the
2
+
same amount (100 equiv) of competing metal ions to the 4ÃCu
1.2. 2-(Chloromethyl)-3,6-dihydropyrene (2)
2
+
or 4ÃHg mixtures. The fluorescence quenching efficiency of
2
+
2+
Cu and Hg ions was not affected in the presence of surveyed
other interfering metal ions as background (Fig. S9), which means
To a solution of 1-pyrenemethanol 1 (1.52 g, 6.55 mmol) in dry
CH Cl (40 mL) was added SOCl (1.18 mL, 16.32 mmol) at 0 °C.
2 2 2
The mixture was stirred for 1 h, then the mixture was concentrated
to give 2 (1.60 g, 98%) as a green solid; mp 149.9 °C; H NMR
that the ionophore can signal the presence of Cu2 and Hg ions in
+
2+
1
common analytes having various metal ions as background.
2
+
To further investigate the coordinating mode of the 4–Hg
(300 MHz, CDCl
8.10 (d, J = 7.8 Hz, 1H), 8.07–7.964 (m, 4H), 5.29 (s, 2H); C NMR
(75 MHz, CDCl ) d 131.9, 131.1, 130.6, 130.2, 129.1, 128.3, 128.0,
127.6, 127.2, 126.1, 125.6, 125.0, 124.7, 124.6, 122.7, 44.8; HRMS
3
) d 8.34 (d, J = 9.3 Hz, 1H), 8.21–8.15 (m, 3H),
2+
13
complex, computations for 4–Hg were conducted at the B3LYP/
LanL2DZ theory level with the GAUSSIAN 03 package. On the basis
of these calculations of 4–Hg2 complex, we found three stationary
points that could be verified as genuine minima via vibrational fre-
quency analyses. The optimized structure for the most stable iso-
3
+
+
(FAB): calcd for C17
H11Cl (M ), m/z 250.0549, found m/z 250.0551.
2
+
2+
mer of 4–Hg is illustrated in Figure 5. It is clear that the Hg
1.3. Chemosensors 4
ion occupies the coordination center of 4, surrounded by two nitro-
gen atoms of the linker and two oxygen atoms of the ribosyl unit.
The average bond length of Hg–N and Hg–O was estimated as
To a solution of SAC 3 (0.26 g, 0.65 mmol) in acetonitrile were
added compound 2 (2.5 equiv, 0.41 g), t-BuNI (1 equiv, 0.24 g), KI
2
.52 Å and 2.53 Å, respectively.
In conclusion, we synthesized a SAC-based fluorescent sensor 4,
(5 equiv, 0.54 g), and K
was stirred overnight at reflux, the mixture was concentrated,
and then dissolved in CH Cl –H O containing a drop of NaOH
(1 M). The solution was extracted by CH Cl , filtered, concentrated,
2 3
CO (4.0 equiv, 0.36 g). After the solution
which shows recognition toward Cu2 and Hg ions in methanol
+
2+
2
2
2
2+
2+
among 12 metal ions tested. Upon addition of Cu and Hg ions
into a methanol solution of 4, the fluorescence intensity was en-
hanced because of the PET process operating between the amino
group of the SAC ether and the pyrene fluorophore.
2
2
and purified by chromatography (EtOAc–MeOH 1:1 to EtOAc–
MeOH 20:1) to give 4 (0.26 g, 48%) as a yellow solid; mp
1
136.7 °C; R
f
= 0.22 (EtOAc–MeOH 8:1); H NMR (300 MHz, CDCl
3
)

Y.-C. Hsieh et al. / Carbohydrate Research 346 (2011) 978–981
981
d: 8.51 (d, J = 9.3 Hz, 2H), 8.18–7.96 (m,16H), 4.46 (d, J = 13.2 Hz,
2. Sarkar, B. In Metal Ions in Biological Systems; Siegel, H., Siegel, A., Eds.; Marcel
Dekker: New York, 1981; Vol. 12, p 233.
2
3
2
H), 4.39–4.37 (m, 4H), 4.12–4.10 (m, 2H), 4.06–4.02 (m, 2H),
.86–3.85 (m, 2H), 3.12–3.08 (m, 2H), 2.87–2.83 (m, 2H), 2.70–
3
4
.
.
Que, E. L.; Domaille, D. W.; Chang, C. J. Chem. Rev. 2008, 108, 1517–1548.
Pontiki, E.; Hadjipavlou-Litina, D.; Chaviara, A. T.; Bolos, C. A. Bioorg. Med. Chem.
Lett. 2006, 16, 2234–2237.
1
3
.67 (m, 4H), 1.92 (br, 4H), 1.33 (s, 6H), 0.88 (s, 6H); C NMR
) d: 133.0, 131.3, 130.8, 130.7, 129.7, 128.2, 127.4,
5.
Mason, R. P.; Reinfelder, J. R.; Morel, F. M. M. Water, Air, Soil Pollut. 1995, 80,
(
75 MHz, CDCl
3
915–919.
1
7
C
27.1, 125.9, 125.0, 124.8, 124.6, 123.9, 112.7, 83.8, 82.6, 81.9,
6.
Harris, H. H.; Pickering, I. J.; George, G. N. Science 2003, 301, 1203.
7.8, 58.0, 56.2, 52.7, 27.5, 26.2, 24.3. HRMS (FAB): calcd for
7. Kraepiel, A. M. L.; Keller, K.; Chin, H. B.; Malcolm, E. G.; Morel, F. M. M. Environ.
Sci. Technol. 2003, 37, 5551–5558.
+
54
H
54
N
2
O
6
[M+H] , m/z 826.3982, found m/z 827.4058.
8
9
.
.
Burger, J.; Gochfeld, M. Environ. Res. 2004, 96, 239–249.
Kuwabara, J. S.; Arai, Y.; Topping, B. R.; Pickering, I. J.; George, G. N. Environ. Sci.
Technol. 2007, 41, 2745–2749.
Acknowledgment
1
1
1
0. El-Sayed, M. A. Acc. Chem. Res. 1968, 1, 8–16.
1. Koziar, J. C.; Cowan, D. O. Acc. Chem. Res. 1978, 11, 334–341.
2. Svejda, P.; Maki, A. H.; Anderson, R. R. J. Am. Chem. Soc. 1978, 100, 7138–7145.
We thank the National Science Council of Taiwan for financial
support.
13. Masuhara, H.; Shioyama, H.; Saito, T.; Hamada, K.; Yasoshima, S.; Mataga, N. J.
Phys. Chem. 1984, 88, 5868–5873.
1
1
1
1
1
4. Burress, C. N.; Bodine, M. I.; Elbjeirami, O.; Reibenspies, J. H.; Omary, M. A.;
Gabbai, F. P. Inorg. Chem. 2007, 46, 1388–1395.
5. Xie, J.; Ménand, M.; Maisonneuve, S.; Métivier, R. J. Org. Chem. 2007, 72, 5980–
Supplementary data
5
985.
6. Hsieh, Y. C.; Chir, J. L.; Wu, H. H.; Guo, C. Q.; Wu, A. T. Tetrahedron Lett. 2010, 51,
09–111.
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.carres.2011.03.010.
1
7. Chen, Y. B.; Wang, Y. J.; Lin, Y. J.; Hu, C. H.; Chen, S. J.; Chir, J. L.; Wu, A. T.
Carbohydr. Res. 2010, 345, 956–959.
8. Calvet, S.; David, O.; Vanucci-Bacqué, C.; Fargeau-Bellasoued, M.-C.; Lohmmet,
G. Tetrahedron 2003, 59, 6333–6339.
References
1
.
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.