Efficient indole-based receptor for Cu2+ ion

Article abstract of DOI:10.2174/157017811799304340

A new fluorescent sensor 1 was designed and synthesized through the condensation of indole-3-aldehyde and N-(2-hydroxyethyl)ethylenediamine. It exhibits good sensitivity and selectivity for the copper cation over other cations such as K⁺, Na⁺, Ca²⁺, Cr²⁺, Mg²⁺, Zn²⁺, Al³⁺ and Fe³⁺. The fluorescence intensity of the sensor was decreased with increasing the concentration of Cu²⁺. The analysis of the Benesi-Hildebrand equation indicated the formation 1:1 complex of 1 and Cu²⁺ with association constant K_ass=3.34×10⁵M.

Full text of DOI:10.2174/157017811799304340

648
Letters in Organic Chemistry, 2011, 8, 648-651
Efficient Indole-Based Receptor for Cu2+ Ion
Huamei Geng, Na Liu, Xin Tian, Rong Li* and Jiantai Ma*
College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, P. R. China
Received August 17, 2010: Revised July 16, 2011: Accepted September 05, 2011
Abstract: A new fluorescent sensor 1 was designed and synthesized through the condensation of indole-3-aldehyde and
N-(2-hydroxyethyl)ethylenediamine. It exhibits good sensitivity and selectivity for the copper cation over other cations
such as K+, Na+, Ca2+, Cr2+, Mg2+, Zn2+, Al3+ and Fe3+. The fluorescence intensity of the sensor was decreased with
increasing the concentration of Cu2+. The analysis of the Benesi-Hildebrand equation indicated the formation 1:1 complex
of 1 and Cu2+ with association constant Kass=3.34ꢀ105M.
Keywords: Indole-3-aldehyde, N-(2-hydroxyethyl)ethylenediamine, copper sensor.
INTRODUCTION
EXPERIMENTAL
Synthesis of Sensor 1
Cations play a fundamental and important role in a wide
range of chemical, biological, medical and environmental
processes. Design and development of efficient cation probes
capable of sensing the targeted cations with highly
selectively, have therefore attracted a great deal of attention
[1]. Among all the cations, Cu2+ is one of the most important
environmental pollutants and an essential trace element in
various biological systems [2], therefore, designing an
efficient sensor for Cu2+ is necessary. Due to high detection
sensitivity and simplicity, fluorescence signaling is one of
the first choices [3]. And designing fluorescence sensor for
copper ion has drawn worldwide attention recently. Chen et
al. reported a Cu2+ sensor based on gold nanoparticles with a
detection limit of 3.6ꢁM [4]. Huang and co-workers
synthesized a colorimetric sensor for Cu2+ in aqueous
solution based on metal ion-induced deprotonation [5]. Dr.
Frigoli prepared a cascade FRET-mediated ratiometric
sensor for Cu2+ ions based on dual fluorescent ligand-coated
polymer nanoparticles [6].
Indole-3-carboxaldehyde (0.75 g, 5.1 mmol) dissolved in
ethanol (50ml) was added dropwise to N-(2-
Hydroxyethyl)ethylenedramine (1.1 g, 5.0 mmol), after the
mixture was stirred for 24 h. Then over 4-fold excess of
NaBH4 (0.76 g, 20.1 mmol) was added and the solution was
stirred for 5 h. The residue was treated with 50 ml of water
and extracted with CH2Cl2. The organic phase was dried
with anhydrous sodium sulfate and the solvent evaporated to
obtain a yellow oil, which was purified by silica gel column
chromatography using ethyl acetate/MeOH (v/v: 4:1). Yield:
45%. 1H-NMR (300 MHz, CDCl3) ꢂ(ppm): 9.99 (s, 1H,
ArNH), 7.60 (d, 1H, J=7.8, ArCH), 6.93-7.28 (m, 4H,
ArCH), 3.89 (s, 1H, OH), 3.53 (s, 2H, CH2), 3.35(s, 2H,
CH2), 2.70 (d, 2H, J=4.2, CH2), 2.62-2.59(m, 4H, CH2)
2.07(s, 2H, NH); MS ESI([M+1]): 234.1, calcd for:
C13H19N3O.
All the reactions in the experimental procedure were
carried out under nitrogen atmosphere at room temperature.
Phenanthroline [7], dansyl [3a], anthracene [8] have been
investigated as fluorescence molecular chemosensor for
Cu2+, they display good sensitivity and selectivity to Cu2+.
While, indole as fluorophoric group does not seem to be so
widespread, though its biological ubiquity forming part of
the amino acid tryptophane is of very high quantum yield
[9]. Moreover, the indole ring-metal binding in biological
systems has been recently identified [10], when combined
with fluorescence spectroscopy, indole derivatives are
potential fluorescent chemosensors [9]. In this letter, a
simple fluorescence probe based on an indole derivative,
chemosensor 1 was reported for the qualitative and quanti-
tative detection of Cu2+ in ethanol solution. Fluorescence
characterization showed that the chemosensor exhibited
excellent selectivity and sensitivity to Cu2+. This may be
helpful for constructing new metal sensing chemical sensors.
Stock solutions (1 mM) of the perchlorate salts of K+,
Na+, Ca2+, Cr2+, Mg2+, Zn2+, Al3+, Fe3+ and Cu2+ ions in water
were prepared. Stock solutions of the sensor 1 (10 mM) were
prepared in ethanol solution. Test solutions were prepared by
placing 20 ꢁL of the probe stock solution in a test tube,
adding an appropriate aliquot of each stock metal salt and
diluting the resulting solution to 2 mL with ethanol solution.
For all measurements, fluorescence spectra were obtained by
excitation at 285 nm.
RESULTS AND DISCUSSION
Sensor
1 (Scheme 1) was synthesized by N-(2-
hydroxyethyl)ethylenediamine and indole-3-aldehyde which
was prepared by the literature method [11], followed by
reduction with NaBH4. The structure of compound 1 was
characterized by 1H NMR and MS.
*Address correspondence to these authors at the College of Chemistry and
Chemical Engineering, Lanzhou University, Lanzhou, 730000, P. R. China;
Tel: 86-931-8912577; Fax: 86-931-8912596;
Chemosensor 1 is soluble in ethanol solution. The
perchlorate salts of K+, Na+, Ca2+, Cr2+, Mg2+, Zn2+, Al3+,
Fe3+ and Cu2+ ions were used to evaluate the selectivity of
E-mails: majiantai@lzu.edu.cn, liyirong@lzu.edu.cn
1875-6255/11 $58.00+.00
© 2011 Bentham Science Publishers

Efficient Indole-Based Receptor for Cu2+ Ion
Letters in Organic Chemistry, 2011, Vol. 8, No. 9
649
N
O
H
N
H
N
H
N
NH2(CH2)2NH(CH2)2OH
POCl3
H
N
OH
CHO
N
H
N
NaBH4
H
N
OH
N
H
Sensor 1
Scheme 1. Synthesis of sensor 1.
either an electron transfer or an electronic energy transfer
involving the transition metal and the excited fluorophore as
observed in other Cu2+-recognition sensors [13]. In Fig. (3)
and Table 2, the fluorescence intensity ratio F/F0 shows a
hyperbolic decrease with the concentration of Cu2+ (0-1
equiv) up to a mole ratio.
The sensor 1 associates with Cu2+ in 1:1 stoichiometry,
this is confirmed by the Benesi-Hildebrand analysis. When
assuming a 1:1 association between sensor 1 and Cu2+, the
Benesi-Hildebrand equation is given as follows [14]:
1
1
1
=
[
+1]
F ꢀ F
0
Fꢁ
ꢀ F
0
K
ass[Cu2+ ]
Fig. (1). Ralative fluorescence intensity of sensor 1 (10 μM) in the
presence of varions ions (10 μM). ꢀex=285 nm. ꢀem=349 nm.
F0 is the fluorescence intensity of 1, Fꢂ is the intensity
measured with excess amount of Cu2+, F is the intensity
Table 1. Ralative Fluorescence Intensity of Sensor 1 (10 μM) in the Presence of Varions Ions (10 μM). ꢀex=285 nm, ꢀem=349 nm
Free
Ca2+
Mg2+
Zn2+
Cr2+
Al3+
K+
Na+
Fe3+
Cu2+
F/F0
1
0.77
0.87
1.18
0.85
1.1
0.91
0.87
0.69
0.33
metal ion binding properties of 1. As shown in Fig. (1) and
Table 1, upon addition of 1 equiv of Zn2+ and Al3+, the
fluorescence intensity of 1 has increased. K+, Na+, Ca2+, Cr2+
and Mg2+ had no influence on the fluorescence intensity of 1.
While the fluorescence was a little quenched with Fe3+,
which also existed in most copper ion fluorescence probes.
measured with Cu2+, Kass is the association constant (M-1),
and [Cu2+] is the concentration of Cu2+ added (M). As shown
However, compared with other cations, Cu2+ has
a
significantly fluorescence quenching effect with sensor 1, the
fluorescence intensity quenched to 33%, which indicated the
selectivity and sensitivity of 1 to Cu2+ over other cations.
To evaluate the feasibility of a fluorescence sensor for
Cu2+, the sensitivity is one of the key elements. In
fluorescence emission, free sensor 1 exhibits ꢀmaxem at 349
nm upon excitation at 285 nm in ethanol solution (Fig. 2).
Upon addition of increasing Cu2+, a remarkable 11 nm blue-
shift from 349 to 338 nm of fluorescence emission and
obvious decrease in fluorescence intensity ratio F/F0 changed
from 1 to 0.11(Fig. 3). The detection limit for Cu2+ is
established at 10-7 M under current experimental conditions.
The blue-shift attributes to the intra-ligand ꢁ-ꢁ* transitions of
the indole groups [12]. The reason of fluorescence
quenching of sensor 1 is probably due to the occurrence of
Fig. (2). Fluorescence intensity of sensor 1(10 μm) with increasing
concentration of Cu2+（0 μM，0.04 μM, 0.18 μM，0.68 μM, 1.18
μM, 4.88 μM, 8.88 μM）in ethnol solution. ꢀex=285 nm, ꢀem=349
nm.

650 Letters in Organic Chemistry, 2011, Vol. 8, No. 9
Geng et al.
Fig. (4). Benesi-Hilderbrand plot of sensor 1 with Cu2+. ꢂex=285
nm, ꢂem=349 nm.
Fig. (3). Ralative fluorescence intensity of sensor 1(10 μm) at
different concentration of Cu2+. ꢂex=285 nm, ꢂem=349 nm.
of the interfering metal ions. As a result, the sensor 1 shows
a high selectivity to Cu2+ ion.
in Fig. (4), plot of 1/ (F-F0) against 1/ [Cu2+] shows a liner
relationship, indicating that 1 actually associates with Cu2+ in
1:1 stoichiometry. The association constant Kass, between 1
and one Cu2+, is determined from the ratio of intercept/slope
to be 3.34ꢀ105 M (r2=0.998).
The association of sensor 1 and Cu2+ ion makes the
formation of the host-guest complex through the interaction
between the N atoms of sensor 1 and Cu2+. As it is well
known, Cu2+ ion is a paramagnetic ion with an empty d shell,
it always desires a square planar geometry when it is
In conclusion, we developed
a highly selective
fluorescent sensor 1 for Cu2+ using the indole group as the
receptors. The sensor forms a stable 1:1 complex with Cu2+
and has high association constant (Kass). Therefore, it shows
much better selectivity over some other metal ions and
responds to Cu2+ by quenching fluorescence intensity in the
1ꢀ10-7 to 1ꢀ10-5 M range. We expect that sensor 1 will
possesses practical applications in cellular Cu2+ imaging and
other Cu2+ detection field.
Table 2. Ralative Fluorescence Intensity of Sensor 1(10 μm) at Different Concentration of Cu2+. ꢀex=285 nm, ꢀem=349 nm
Cu2+
F/F0
Cu2+
F/F0
0
0.02
0.96
1.88
0.65
0.04
0.93
4.88
0.38
0.06
0.91
5.88
0.34
0.08
0.87
8.88
0.21
0.18
0.85
9.88
0.19
0.28
0.82
0.48
0.79
0.68
0.79
1
0.88
0.77
10.88
0.17
20.88
0.11
coordinated [15]. So, the fluorescence intensity decreased
suggesting that Cu2+ formed a complex with the three
nitrogen atoms and one oxygen of the sensor 1 and strongly
quenched the emission intensity.
To explore practical applicability of 1 as a Cu2+-selective
fluorescent chemosensor, competition experiments were also
performed in the presence of Cu2+ at 10 ꢁM mixed with 10
ꢁM background metal cations such as K+, Na+, Ca2+, Cr2+,
Mg2+, Zn2+, Fe3+(Fig. 5). The fluorescence intensity ratio
F/F0 of solution containing both background metal cations
and Cu2+ showed no obvious variation comparing with that
only containing Cu2+ (Table 3). The strong formation
constant of Cu2+ ion determines the selectivity, and thus the
strong coordination of Cu2+ ion in the square planar
environment with sensor 1 is not perturbed by the presence
Fig. (5). Ralative fluorescence intensity of sensor 1(10 μM)
containing Cu2+ (1 equiv) and the background ions (1 equiv).
ꢂex=285 nm, ꢂem=349 nm.
Table 3. Ralative Fluorescence Intensity of Sensor 1(10 μM) Containing Cu2+ (1 equiv) and the Background Ions (1 equiv). ꢀex=285
nm, ꢀem=349 nm
Ca2++Cu2+
Zn2++Cu2+
Cr2++Cu2+
K++Cu2+
Na++Cu2+
Fe3++Cu2+
Cu2++mix
Cu2+
F/F0
0.41
0.25
0.43
0.4
0.41
0.37
0.41
0.33

Efficient Indole-Based Receptor for Cu2+ Ion
Letters in Organic Chemistry, 2011, Vol. 8, No. 9
651
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