Fluorescence sensing of Cu2+ within a pseudo 18-crown-6 cavity

Article abstract of DOI:10.1016/j.tetlet.2009.08.011

We report herein a pseudo-crown based fluorescent receptor (1) for the selective detection of Cu²⁺ cation. Receptor 1 can detect Cu²⁺ even in 5 μM level in acetonitrile-water (9:1 v/v). Compound 1 is very effective for the detection of Cu²⁺ amongst the series of metal ions studied (Li⁺, Na⁺, K⁺, Ca²⁺, Mg²⁺, Ba²⁺, Pb²⁺, Fe³⁺, Co²⁺, Ni²⁺, Cu²⁺, Zn²⁺, Cd²⁺, Hg²⁺ and Mn²⁺).

Full text of DOI:10.1016/j.tetlet.2009.08.011

Tetrahedron Letters 50 (2009) 5910–5913
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Fluorescence sensing of Cu2+ within a pseudo 18-crown-6 cavity
*
Shyamaprosad Goswami , Rinku Chakrabarty
Department of Chemistry, Bengal Engg. and Science University, Shibpur, Howrah 711 103, India
a r t i c l e i n f o
a b s t r a c t
We report herein a pseudo-crown based fluorescent receptor (1) for the selective detection of Cu2+ cation.
Article history:
Receptor 1 can detect Cu2+ even in 5
lM level in acetonitrile–water (9:1 v/v). Compound 1 is very effec-
Received 8 July 2009
Revised 4 August 2009
Accepted 7 August 2009
Available online 12 August 2009
tive for the detection of Cu2+ amongst the series of metal ions studied (Li+, Na+, K+, Ca2+, Mg2+, Ba2+, Pb2+
Fe3+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, Hg2+ and Mn2+).
,
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Fluorescent sensor
Copper(II) recognition
Pseudo 18-crown-6 cavity
Excimer formation
Amongst the soft transition metal ions, Cu2+ is the third in
abundance (after Fe2+ and Zn2+). It is one of the essential heavy me-
tal ions in human body and plays an important role in various bio-
logical systems.1 Selective chemosensors, designed and
synthesized for in vitro and in vivo purposes have now been of con-
siderable interest and among them, sensing of Cu2+ ion constitutes
a very active area of research.2 Chemosensors are molecular-sized
or larger devices that interact with analytes reversibly and in real
time.3 Although in recent times many signal types have been avail-
able, fluorescence proffers high sensitivity. Therefore this mode of
signal transduction has been widely used for the detection of a
number of transition metal ions. Among the sensors targeted to-
wards the detection and estimation of metal ions, Cu2+ has got con-
siderable attention.4,5 Detection of specific metal ion with high
specificity under physiologically relevant conditions is an impor-
tant area in designing fluorescent chemosensors for applications
in clinical biology. Due to its widespread use, Cu2+ is a pollutant
in high concentration and is associated with brain diseases such
as Alzheimer’s, Parkinson’s and Prion at a trace amount.6 The tox-
icity of Cu2+ for human body is, however, low compared to other
heavy metals but certain microorganisms are affected7 by even
submicro-molar concentration of Cu2+
.
O
O
O
O
O
O
Cu2+
O
O
O
O
O
Me
O
Me
Cu(ClO4)2
Me Me
O
O
O
O
NH
HN
NH
HN
Receptor 1 + Cu2+
Receptor 1
Scheme 1. Receptor 1 and its complexation with Cu2+ cation.
* Corresponding author. Tel.: +91 33 2668 2961 3; fax: +91 33 2668 2916.
E-mail address: spgoswamical@yahoo.com (S. Goswami).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.08.011

S. Goswami, R. Chakrabarty / Tetrahedron Letters 50 (2009) 5910–5913
5911
2.5
(i)
Isosbestic point
OH
O
O
OH
TsO
O
O
OTs
at
324 nm
A
2.0
1.5
1.0
0.5
0.0
OH
O
O
O
O
OMe
(ii)
A
OMe MeO
+
CHO
(iii)
CHO
CHO
A'
O
O
O
O
1a
OMe
MeO
A'
200
250
300
350
400
450
COOH
COOH
wavelength (nm)
B
Li+
K+
Na+
Ca2+
Herein we report a receptor with pseudo 18-crown-6 cavity
(receptor 1) which selectively binds Cu2+ even in 5
M level concen-
Cu2+
0.2
l
Mg2+
Pb2+
Co2+
Cu2+
Cd2+
Mn2+
Ba2+
tration which can be detected by fluorescence method. Here naph-
thalene moiety is part of the main skeleton of the fluoroionophore
and is positioned in a particular manner so that, due to the binding
of metal ion they can come closer and hence aromatic stacking is
possible (Scheme 1). The two naphthalene units will provide a
hydrophobic environment and thus the receptor offers a high ‘com-
plex stability’. Again the benzene rings directly attached to the ether
Fe3+
Ni2+
Zn2+
Hg2+
0.1
0.0
moiety can participate in cation-p interactions and thus can increase
the sensitivity towards the metal ions. 18-Crown-6 has long been
known for selective binding of K+ ions. Many applications have also
been known using this property.8 But here the pseudo crown moiety
(receptor 1) shows high selectivity towards Cu2+ over K+.
1b
The synthesis of receptor 1 is described in Scheme 2. The syn-
thesis begins with tris-ethyleneglycol which was converted to
ditosylate, A. This, when reacted with vanillin, K2CO3 and dry ace-
tone using a phase transfer catalyst (TBAB) produced the expected
dialdehyde (A0) which on oxidation afforded the dicarboxylic acid
B. The corresponding acid chloride C on coupling with 1-naphthyl-
amine yielded the desired receptor 1 which was purified by pre-
parative TLC using 2% MeOH in CHCl3.
0
4
8
12
16
[G]/[H]
Figure 1. (1a) UV spectra of receptor 1 after addition of Cu2+; (1b) UV-binding curve
of receptor 1 (where change of absorbance is plotted against ratio of concentrations
of host and guest).
shows selective fluorescence quenching with Cu2+ and may be
used for its quantitative estimation.
In preliminary fluorescence studies, the receptor 1 having naph-
thalene moiety as fluorophore (5 lM) in acetonitrile–water (9:1 v/
v) in presence of metal ions viz. Ni2+, Zn2+ and Pb2+ shows fluores-
cence quenching with Cu2+ (small quenching takes place in case of
Fe3+), and other metal ions do not affect so much the fluorescence
of 1. Also the presence of alkali and alkaline earth metals do not af-
fect the fluorescence of 1 even in larger amounts. Therefore 1
Cu2+
Li+
Na+
K+
Ca2+
Mg2+
Pb2+
Co2+
Cu2+
Cd2+
Hg2+
Mn2+
Ba2+
Fe3+
Ni2+
Zn2+
O
O
O
O
O
O
O
O
OMe MeO
OMe MeO
0.02
0.00
(iv)
COCl
COCl
COOH
COOH
C
B
NH2
(v)
C
+
Receptor 1
0.0
0.2
0.4
0.6
0.8
1.0
Xh
Scheme 2. Reagents and conditions: (i) Et3N, p-TsCl, 12 h; (ii) K2CO3, TBAB, dry
acetone, rt, 24 h; (iii) aq KMnO4, 3 h; (iv) oxalyl chloride, dry CH2Cl2, dry DMF (cat.
amount), N2-atmosphere, 3 h; (v) dry CH2Cl2, NEt3, rt, 12 h.
Figure 2. Job’s plot of receptor 1 by UV method, where Xh stands for mol fraction of
host and I indicates the change of absorbance.
D

5912
S. Goswami, R. Chakrabarty / Tetrahedron Letters 50 (2009) 5910–5913
The cation binding properties of 1 were investigated by observ-
guest is taking place via electrostatic interactions between the
receptor 1 and Cu2+. The complex formation affects the electronic
properties of the fluorophore resulting in a change with a subse-
quent new charge transfer interactions between the receptor 1
ing the changes in their fluorescence emission (in case of 1) and
absorption spectra in acetonitrile–water (9:1 v/v). UV–vis experi-
ments were carried out in CH3CN–H2O (9:1 v/v) solvent. The titra-
tion of
1
(c = 1.2 ꢀ 10ꢁ5 M), which exhibits
a
broad strong
and Cu2+
.
absorption band at 294 nm due to the naphthalene moiety, was
carried out with perchlorate salts of cations such as Li+, Na+, K+,
Ca2+, Mg2+, Ba2+, Pb2+, Fe3+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, Mn2+ and
Hg2+. Upon addition of perchlorate salts of cations, a continuous
decrease of absorbance is observed. The value of association con-
stant (Ka) determined by the UV–vis method is found to be
8.96 ꢀ 105 (see Supplementary material). An isosbestic point is ob-
served at ꢂ324 nm, indicating the formation of a new complex be-
tween 1 and Cu2+ (Fig. 1a). When an isosbestic point is constructed
by the superposition of the absorption spectra of two species by
using the absorbance and keeping the same molar concentration
for both species, the isosbestic point corresponds to a wavelength
at which these spectra cross each other. The isosbestic point indi-
cates that in spite of addition of increasing amount of guest (Cu2+),
for the particular concentration of the host (receptor 1) only one
complex is formed and as a result one common absorbance point
is observed here. Complex formation between the host and the
The stoichiometry of the complexes was confirmed from the
break in the titration curve (Fig. 1b). The break at 1:1 confirms
the binding mode. Job’s plot of the cations also supports the 1:1
binding mode (Fig. 2).
The fluorescence titration of fluorophore containing receptor 1
in acetonitrile with Cu2+ exhibited a remarkable decrease of fluo-
rescence intensity at 348 nm (value of binding constant is
2.09 ꢀ 105) (see Supplementary material) with a simultaneous
growth of new peak at 403 nm (Dk = 55 nm resulting ultimately
ꢂ45% fluorescence quenching in total (Fig. 4a) that is, ‘switching-
off’ due to the formation of strong cation–host complexations
which lock the cavity. Their corresponding fluorescence spectra
are depicted in Figure 3. The fluorescence intensity is also deter-
mined in case of Fe3+. But no significant change of fluorescence
intensity was observed in case of other metal cations. From the
instrumental read-out it can be concluded that the response of 1
50
a
30
Cu2+
40
30
20
10
0
Li
Na
Ca
Ba
Fe
Ni
Zn
Hg
K
Mg
Pb
Co
Cu
Cd
Mn
20
10
a
0
2
4
6
8
10
12
concentration of Cu2+
400
500
600
Wavelength (nm)
2
1
0
b
Li+
Na+
K+
Cu2+
1.6
1.2
Ca2+
Mg2+
Ba2+
Pb2+
Fe3+
Co2+
b
Ni2+
Cu2+
Zn2+
Cd2+
Hg2+
Mn2+
-2
0
2
4
6
8
10
12
Figure 4. (a) The plot of quantum yield of receptor 1 and 1-Cu2+ complex versus
concentration of Cu2+; (b) fluorescence response of receptor 1 towards metal ion
[G]
Figure 3. Fluorescence spectra of receptor 1 after addition of (a) 1 equiv of metal
ions; (b) fluorescence binding constant curve of receptor 1, where [G] refers to the
concentration of guest solutions added and Io stands for initial intensity and I stands
for final intensity.
upon addition of 5 lM solutions of individual metal ions. Inset shows the response
towards Cu2+ ꢂ10ꢁ7 M plus co-existing metal ion at ꢂ10ꢁ5 M. [Here in Fig. b, the
ratio of change of absorbance to the initial absorbance was plotted with the
concentration of the guest molecules added.]

S. Goswami, R. Chakrabarty / Tetrahedron Letters 50 (2009) 5910–5913
5913
5
4
3
2
1
0
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to Cu2+ is highest and for other cations it remains almost the same
(Fig. 4b). Florescence spectrum of 1 was also recorded using aceto-
nitrile as a solvent and we found similar results. Here we also
noted the high selectivity of receptor 1 towards Cu2+
.
In case of Cu2+ an additional peak at 403 nm along with mono-
mer emission at 348 nm was noticed due to an excimer formation
(Fig. 3a). The excimer emission resulted from the intramolecular,
rather than intermolecularly, as indicated by the dilution experi-
ment at different concentrations in which the intensities of the ra-
tio of excimer to monomer changed gradually (Fig. 5).
The MMX studies9 of receptor 1 and its different mode of com-
plexation with cations are very interesting with respect to the
experimental findings. Receptor 1 forms a tight complex with
Cu2+ compared to the other cations like K+ (Fig. S2).
The interactions of host–guest complexations and their differ-
ent modes of binding have been studied using MMX calculations.
The stabilization energy (Table 1) is further lowered by complexa-
tion with Cu2+. This calculation also fulfills the objective of stronger
and better binding of host with the guest cations studied.
In summary, pseudo-crown based fluorescent receptor 1 has
been designed and synthesized. The highest sensitivity and selec-
tivity of 1 towards Cu2+ over other metal cations (Li+, Na+, K+,
Ca2+, Mg2+, Ba2+, Pb2+, Fe3+, Co2+, Ni2+, Zn2+, Cd2+ and Hg2+) as their
perchlorate salts were demonstrated via its fluorescence response.
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Acknowledgements
We wish to express our appreciation to CSIR and DST, Govt. of
India for financial support. R.C. thanks CSIR, Govt. of India for a Se-
nior Research Fellowship.
Supplementary data
Supplementary data (1H, 13C and mass spectra of receptor 1,
general procedure for preparation, fluorescence spectra and table
of binding constants) associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2009.08.011.
9. The optimization of structures was carried out using MMX (PCMODEL Serena
Software 1993). Molecular modeling was performed using standard constants
and the dielectric constants were maintained at 1.5.