Colorimetric test kit for Cu2+ detection

Article abstract of DOI:10.1021/ol802117p

(Chemical Equation Presented) A coumarin-based colorimetric chemosensor 1 was designed and synthesized. It exhibits good sensitivity and selectivity for the copper cation over other cations such as Zn²⁺, Cd²⁺, Pb²⁺, Co^2-, Fe²⁺, Ni²⁺, Ag ^-, and alkali and alkaline earth metal cations both in aqueous solution and on paper-made test kits. The change in color is very easily observed by the naked eye in the presence of Cu²⁺ cation, whereas other metal cations do not induce such a change. The quantitative detection of Cu²⁺ was preliminarily examined.

Full text of DOI:10.1021/ol802117p

ORGANIC
LETTERS
Colorimetric Test Kit for Cu2+ Detection
2008
Vol. 10, No. 21
5015-5018
Ruilong Sheng,† Pengfei Wang,*,† Yunhua Gao,† Yan Wu,† Weimin Liu,†
Jingjin Ma,† Huaping Li,*,‡ and Shikang Wu†
Laboratory of Organic Optoelectronic Functional Materials and Molecular
Engineering, Technical Institute of Physics and Chemistry, the Chinese Academy of
Sciences, Beijing, 100190, China, and Center for Polymers and Organic Solids,
Departments of Materials, Chemistry & Biochemistry, UniVersity of California, Santa
Barbara, California 93106
wangpf@mail.ipc.ac.cn; hli@chem.ucsb.edu
Received September 10, 2008
ABSTRACT
A coumarin-based colorimetric chemosensor 1 was designed and synthesized. It exhibits good sensitivity and selectivity for the copper cation
over other cations such as Zn2+, Cd2+, Pb2+, Co2+, Fe2+, Ni2+, Ag+, and alkali and alkaline earth metal cations both in aqueous solution and
on paper-made test kits. The change in color is very easily observed by the naked eye in the presence of Cu2+ cation, whereas other metal
cations do not induce such a change. The quantitative detection of Cu2+ was preliminarily examined.
The development of sensitive chromogenic chemosensors has
been receiving much attention in recent years because of the
potential application in clinical biochemistry and the envi-
ronment. A number of chemosensors have been developed
for selective recognition of different species on the basis of
different host-guest interactions, such as hydrogen-bonding,
electrostatic force, metal-ligand coordination, hydrophobic
and van de Waals force interactions, etc.1 Most of these
chemosensors have been employed in solution by means of
spectroscopic instrumentation.2 This will significantly restrict
the practical applications of these chemosensors. For simplic-
ity, convenience and low cost, the fabrication of small
molecular chemosensors into colorimetric test kits is highly
demanding. For example, the current concern regarding
children’s toys requires the development of test kits for toxic
metals such as lead. On the other hand, copper is a widely
used industrial metal, and its cation is toxic at high
concentration3 and is involved in brain diseases such as
Alzheimer’s, Parkinson’s, and Prion at a trace amount.4 Even
though some colorimetric/fluorescent chemosensors have
been developed for the detection of Cu2+ so far,5 the sensing
methods for fast detection of Cu2+ in aqueous solution,
especially using colorimetric sensors without resorting to
instruments, are relatively rare.5a,b,f In this Letter, a simple
colorimetric test kit based on a coumarin Schiff base
derivative, chemosensor 1, was fabricated for the qualitative
and quantitative detection of Cu2+ in aqueous solution.
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† Chinese Academy of Sciences.
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E.; Kozlowski, H.; Valensin, D.; Valensin, G. Chem. ReV. 2006, 106, 1995.
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119, 7386. (b) Gunnlaugsson, T.; Leonard, J. P.; Murray, N. S. Org. Lett.
2004, 6, 1557. (c) Wu, Q.; Anslyn, E. V. J. Am. Chem. Soc. 2004, 126,
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1612. (e) Zheng, L.; Miller, E. W.; Pralle, A.; Isacoff, E. Y.; Chang, C. J.
J. Am. Chem. Soc. 2006, 128, 10. (f) Martinez, R.; Zapata, F.; Caballero,
A.; Espinosa, A.; Tarraga, A.; Molina, P. Org. Lett. 2006, 8, 3235. (g) Zhang,
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‡ University of California, Santa Barbara.
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10.1021/ol802117p CCC: $40.75
Published on Web 10/15/2008
2008 American Chemical Society

Coumarin and its derivatives are excellent chromogenic and
fluorogenic dyes that are widely utilized as reporters in
chemosensors.6 In this work, we designed and synthesized a
coumarin derivative as a new colorimetric chemosensor 1
(Scheme 1), in which 7-di(ethoxy-carbonylmethyl)amino cou-
marin serves as chromophore core. Diaminomaleonitrile was
coupled with coumarin at the 3-position carbonyl to form Schiff
base derivative. An intramolecular charge transfer (ICT) is thus
enhanced as a result of the extended π-conjugation and the
stronger electron-withdrawing ability of the nitrile group. The
extended ICT usually exhibits high sensitivity to external
perturbations such as the polarity of solution and the electric
field in its vicinity, often showing as remarkable color changes.7
The formed imine and the rest of the amine groups in
chemosensor 1 act as chelating sites of metallic cations, in
particular, transition and post-transition metal cations.
Scheme 1.
Synthesis of Chemosensor 1a
Figure 1. (a) Solutions of 1 upon addition of different metal ions.
(b) Absorption changes of 1 in H2O/DMSO (v/v ) 60/40) (1.0 ×
10-5 M) upon addition of 1 equiv of different perchlorate salts (1.0
× 10-5 M). (c) Optical density of 1 at 535 nm upon the addition
of different cations.
a For synthetic protocols and compound characterization see Supporting
Information.
Chemosensor 1 was synthesized with 3-aminophenol as a
starting material (shown in Scheme 1). N-Alkylation of 3-ami-
nophenol with ethyl bromoacetate or ethyl chloroacetate was
catalyzed by ammonium dihydrogen phosphate in acetonitrile
to produce 2 (yield 70%). Compound 2 was esterified with
propiolic acid to form ester 3 by DCC/DMAP coupling reaction
(yield 30%). The intramolecular ring closure of ester 3 was
catalyzed by 0.1 equiv of tetrakis(triphenyl phosphine)palla-
dium(0) (Pd(PPh3)4) in TFA at room temperature to yield
coumarin 4 with a yield of 40%.8 Coumarin aldehyde 5 was
obtained from the classic Vilsmeier reaction9 of coumarin 4
and POCl3 in DMF (yield 40%). The final condensation of
coumarin aldehyde 5 and diamino maleonitrile in ethanol gave
rise to chemosensor 1 (yield 70%). Detailed procedures and
characterizations are reported in Supporting Information.
Chemosensor 1 is soluble in a mixture solvent of H2O and
DMSO, further diluted for analyte detection in aqueous solution.
The yellow solution of 1 is stable within a pH range of 7-10
(Figure S1, Supporting Information) in H2O/DMSO (v/v ) 60/
40). A strong and broad absorption band from 380 to 530 nm
peaked at 460 nm (ε ) 4.2 × 104 M-1 cm-1) was observed.
By comparison to that of coumarin aldehyde 5, the absorbance
of 1 shifts to the red with a similar molar absorption coefficient,
reflecting the enhanced intramolecular charge transfer due to
the extended π-conjugation and strong electron-withdrawing
ability of nitriles after the formation of Schiff base between
coumarin aldehyde 5 and diaminmaleonitrile. The responses
of 1 in H2O/DMSO (v/v ) 60/40) to a series of individual
metallic cations were investigated. As shown in Figure 1a,
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Org. Lett., Vol. 10, No. 21, 2008

solutions of 1 upon the addition of 1 equiv of Ag+, Fe3+, Fe2+,
Co2+, Ni2+, Zn2+, Cd2+, Cu2+, Hg2+, Pb2+, Ca2+, and Mg2+
display distinguishing red color with Cu2+ compared with those
with other cations, indicating the sensitivity and selectivity of
1 to Cu2+ over other cations. Their corresponding UV-vis
absorption spectra are depicted in Figure 1b.
From the instrumental read-outs, the spectral responses
of 1 to different cations can be classified into three types.
For type 1 cations such as Zn2+, Cd2+, Pb2+, Ag+, Fe3+, Fe2+,
Co2+, Ni2+, Ca2+, and Mg2+, the spectral changes of aqueous
solutions of 1 were negligible before and after these cations
were added. Hg2+ is the type 2 cation, which induced the
slightly red-shifted absorbance of 1 solution with decreased
molar absorption coefficient. The UV-vis absorption spec-
trum of 1 solution shifted to the red about 70 nm when
combined with Cu2+, the type 3 cation. For comparison, their
optical densities at 535 nm upon the addition of these cations
to 1 solution are charted in Figure 1c. The differential optical
responses of a solution of 1 to these cations indicate that
the interactions between 1 and these cations increase from
type 1 to type 2 and, in turn, to type 3 (Figure 1b).
Figure 3.
1H NMR spectra of chemosensor 1 upon addition of 0.3,
1.0, and 2.0 equiv of Cu2+ in D2O/d6-DMSO (v/v ) 60/40).
Figure 2b gives a 1:1 stoichiometric ratio between 1 and
Cu2+ for the newly formed species, corroborated by MALDI-
TOF mass spectroscopy in which a maximum peak is found
at m/z ) 513.8 for [1 + Cu2+ - H+]+ (calcd 513.9) (Figure
S2, Supporting Information). On the basis of 1:1 stoichiom-
etery, the stability constant of the complex between 1 and
Cu2+ was estimated to be 6.6 × 105 M-1 (r2 ) 0.998) by
using nonlinear curve fitting (Figure S3, Supporting Informa-
tion).10 The plot of optical density change (A/A0) at 535 nm
against added concentrations of Cu2+ shows that the limit
of detection is about 1.2 × 10-6 M (Figure S4, Supporting
Information).
The 1H NMR titration spectra of 1 solution with Cu2+ D2O
solution illustrate its characteristically structural changes
upon interactions with Cu2+. As shown in Figure 3, the
proton chemical shifts of the coumarin ring are shifted
slightly upfield; more obviously, the integral of a new peak
at 7.9 ppm assigned to aminyl increased from 0.31 to 0.96
in reference to those of coumarin protons when the added
Cu2+ was increased from 0.3 to 2 equiv. These NMR results
suggest that Cu2+ depronated the amine to form Cu-N
bonding, and coordinated with the imino of the Schiff base
and 2-carbonyl of the coumarin core. This picture was
confirmed by X-ray single crystal structures of metal
complexes involving analogous ligands in the literature.11
These results also elicit the complex stability constant in a
1:1 binding model between 1 and Cu2+, which is different
from those Cu2+ complexes with bisdentate ligands in an
1:2 stoichiometry.12 The large red-shifted UV-vis absor-
bance of 1 solution upon the addition of Cu2+ is thus
rationalized to result from the extended ICT in such a
push-pull Cu(II) Schiff base complex.
Figure 2. (a) Titration curves of chemosensor 1 in H2O/DMSO
(v/v ) 60/40) (2.0 × 10-5 M) upon addition of Cu2+ at 0, 0.4, 0.8,
1.2, 1.6, 2.0, 2.4, 2.8, 3.2, 3.6, 4.0, 4.4, and 4.8 × 10-5 M. (b)
Job’s plot of the complex formed by 1 and Cu2+
.
The selectivity of 1 (1.0 × 10-5 M) to Cu2+ (1.0 × 10-5
M) was further demonstrated in the presence of 3 equiv of
To elicit the interactions between 1 and Cu2+, UV-vis
absorption spectral variation of 1 (2.0 × 10-5 M) in H2O/
DMSO solution was titrated with Cu2+ from 0 to 4.8 × 10-5
M. As shown in Figure 2a, the maximum absorbance at 460
nm gradually decreased, and concomitantly a rising new
absorbance that peaked at 535 nm appeared. An isosbestic
point is clearly observed at 480 nm, indicating the formation
of a new complex between 1 and Cu2+. The Job’s plot in
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Wiley-VCH: New York, 2001; p 341.
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Org. Lett., Vol. 10, No. 21, 2008
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M, 5.0 × 10-4 M, 1.0 × 10-3 M and show that the
discernible concentration of Cu2+ can be as low as 1.0 ×
10-4 M.
Figure 4
.
Optical density of 1 (1.0 × 10-5 M) at 535 nm with
addition of Cu2+ (1.0 × 10-5 M) in the presence of 3 equiv of
Figure 5.
Photographs of the test kits with 1 for detecting Cu2+
other metal cations.
ion in aqueous solution with different concentrations. Left to right:
0, 1.0 × 10-4 M, 5.0 × 10-4 M, 5.0 × 10-3 M.
other cations. As shown in Figure 4, the optical density of 1
and Cu2+ at 535 nm was not affected in the presence of other
cations such as Ca2+, Zn2+, Cd2+, Pb2+, Co2+, Fe2+, Ni2+,
and Ag+. These results are significantly different from other
Cu(II) sensors5 that are usually affected by Co2+, Zn2+, Cd2+,
and Ni2+. However, the optical density of 1 decreased about
10% when Hg2+ was added. In the presence of Fe3+, the
optical intensity of 1 decreased about 70%. The interference
of Hg2+ and Fe3+ on the optical response of 1 to Cu2+ might
be due to the competitive coordination13 of these metals with
aminomaleonitrile moitey.
To investigate the practical application of chemosensor
1, test strips were prepared by immersing filter papers into
a THF solution of 1 (0.1 M) and then drying in air. The test
strips containing 1 were utilized to sense different cations.
To these cation solutions, different test kits were immersed
for 10 s. After several drops of ethanol (to dissolve 1) were
added, the obvious color change was observed only with
Cu2+ solution. Also, these test strips were applied for sensing
different Cu2+ concentrations, exhibiting colorimetric changes
differentiable by naked eyes. As depicted in Figure 5, the
red color of the test strips intensified from 0, to 1.0 × 10-4
In summary, a new colorimetric chemosensor 1 was
designed and synthesized by coupling coumarin aldehyde 5
with diaminomaleonitrile to form Schiff base structure with
the enhanced intramolecular charge transfer. The sensitivity
and selectivity of 1 to Cu2+ over other metal cations in
aqueous solution were demonstrated via its optical response,
ascribed to the formation of the push-pull Cu(II) Schiff base
complex. Based on the colorimetric response of 1 to Cu2+,
test strips containing 1 were fabricated, which also exhibits
a good sensitivity and selectivity to Cu2+ as in solution. The
quantitative detection of Cu2+ using these test strips was
attempted.
Acknowledgment. This work was supported by NNSF
of China (no. 20673132), the Croucher Foundation of Hong
Kong, the Chinese Academy of Sciences “hundred talents
program”, the National Basic Research Program of China
(no. 2006CB933000) and the 111 Project (B07012).
SupportingInformationAvailable:Synthesisofchemosen-
sor 1 and Figures S1-S4. This material is available free of
charge via the Internet at http://pubs.acs.org.
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2007, 9, 4567.
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