A highly selective and synthetically facile aqueous-phase cyanide probe

Article abstract of DOI:10.1016/j.tetlet.2008.08.115

Disperse Orange 3 (4-(4-nitrophenylazo)aniline)-based chemosensor 1 has been prepared. This structurally simple receptor displays great selectivity for the cyanide anion over other common inorganic anions in aqueous environment and can detect cyanide in water sample at micromolar concentrations.

Full text of DOI:10.1016/j.tetlet.2008.08.115

Tetrahedron Letters 49 (2008) 6521–6524
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Tetrahedron Letters
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A highly selective and synthetically facile aqueous-phase cyanide probe
*
Hao-Tao Niu, Xueliang Jiang, Jiaqi He, Jin-Pei Cheng
Department of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Disperse Orange 3 (4-(4-nitrophenylazo)aniline)-based chemosensor 1 has been prepared. This structur-
ally simple receptor displays great selectivity for the cyanide anion over other common inorganic anions
in aqueous environment and can detect cyanide in water sample at micromolar concentrations.
Ó 2008 Elsevier Ltd. All rights reserved.
Received 15 June 2008
Revised 28 August 2008
Accepted 29 August 2008
Available online 11 September 2008
Keywords:
Cyanide detection
Anion recognition
It is well known that anions play an important role in the field
of biology, medicine, catalysis, and environment.1,2 In recent years,
the development of chemosensors capable of selectively recogniz-
ing and sensing anions appears to be particularly attractive. There
is an increasing attention toward the development of colorimetric
probes which have the advantage of showing easily observable
color changes in the presence of target guests.
considerations in mind, we now introduce a simple yet effective
colorimetric sensor 1 (Scheme 1), which utilizes an azo dye as a
chromophore and a trifluoroacetyl group as an electrophile. It is
well known that cyanide anion is a strong nucleophilic reagent,
and the nucleophilic attack to the carbon atom of an electron-defi-
cient carbonyl group can achieve the so-called ‘naked eye’ detec-
tion of cyanide anion in aqueous environment.
Recently, considerable attention has been paid to the sensing of
cyanide anion for many reasons. Cyanide is one of the most toxic
anions and harmful to environment or human health. For example,
it is lethal to humans at concentrations of 0.5–3.5 mg per kg of
body weight.3 Recent studies have shown that the lethal cyanide
Compound 1 was synthesized in a single step starting from
commercially available precursor Disperse Orange 3 (4-(4-nitroph-
enylazo)aniline) (Scheme 1).16 This compound and trifluoroacetic
anhydride were stirred in nitrobenzene overnight. Then the mix-
ture was filtered and the filter cake was crystallized by acetonitrile
to obtain the target compound 1 in moderate yield (70%). The
structure of 1 was confirmed by 1H NMR, 13C NMR, and HRMS data.
concentration in the blood of fire victims is 23–26 l
M.4 The bind-
ing of cyanide to cytochrome oxidase reduces the activity of this
enzyme and inhibits oxygen utilization by cells.5 But cyanide can-
not be discarded for its wide application in the production of or-
ganic chemicals and polymers, such as nitriles, nylon, and acrylic
plastics.6 In addition, it is critical to the gold-extraction process.7
To date, several strategies have been developed to detect
cyanide anion, including the formation of cyanide complexes with
transition metals,8 boron derivatives,9 CdSe quantum dots,10
nucleophilic addition reactions to carbonyl group,11 displacement
approach,12 hydrogen-bonding interaction,13 deprotonation pro-
cess,14 and luminescence lifetime measurement.15 Many receptors
for cyanide reported so far have several limitations such as poor
selectivity over fluoride or acetate, use in specific reaction
conditions or utilization of expensive instruments, and compli-
cated synthesis. In addition, many of them are reported to work
only in organic media, so the search for effective sensing systems
in aqueous environment is still a great challenge. With these
As
a first step, the interaction mechanism between the
compound 1 and cyanide was investigated. 1H NMR titration
experiments were carried out by addition of Bu4CN to the acetoni-
trile-d3 solution of 1 ( Fig. 1). With the increasing addition of
NO2
NO2
N
(CF3CO)2O
PhNO2, RT
N
N
N
HN
O
NH2
CF3
* Corresponding author.
E-mail address: chengip@most.cn (J.-P. Cheng).
Scheme 1. Synthetic procedure of compound 1.
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.08.115

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H.-T. Niu et al. / Tetrahedron Letters 49 (2008) 6521–6524
cyanide, all the aromatic protons exhibited an upfield shift to dif-
ferent extent, which is compatible with the proposed switching
mechanism (Scheme 2).
In order to gain systematic knowledge on the effect of water on
the binding affinity and selectivity for cyanide, we chose water–
acetonitrile mixtures as solvents (0%, 2.5%, 5.0 %, 7.5%, and 10.0%
water, respectively) and 1À2 anions of present interest, namelÀy,
CNÀ, FÀ, AcOÀ, H2PO4À, Cl , BrÀ, IÀ, HSO4À, NO3À, ClO4À, SCN ,
À
and N3 as their tetrabutylammonium salts were added to the
solution of 1, respectively. Figure 2 shows the color changes and
the corresponding absorption spectra upon addition of different
anions in CH3CN. It can be seen that the color changed from color-
less to orange/yellow in the presence of CNÀ, FÀ, AcOÀ, H2PO4À, and
HSO4À. Only addition of 1 equiv of the five kinds of anions induced
distinct spectra changes (Fig. 2b), while other anions such as ClÀ,
À
BrÀ, IÀ, ClO4À, SCN , and N3 did not induce any color changes,
À
Figure 1. Plots of 1H NMR spectra of 1 on addition of Bu4CN in acetonitrile-d3.
even in large excess.
Though obvious interaction was observed on addition of CNÀ in
CH3CN, the selectivity for CNÀ is rather poor due to the interfer-
ence of FÀ, AcOÀ, H2PO4À, and HSO4À. When 2.5% water in
water–acetonitrile mixture was chosen as solvent, only CNÀ, FÀ,
and AcOÀ showed obvious interaction with the sensor 1. The color
changed to deep yellow upon addition of CNÀ, and pale yellow
upon addition of FÀ and AcOÀ. It is not surprising considering the
solvent effect. Namely, anions such as FÀ, AcOÀ, H2PO4À, and
HSO4À should interact with water through hydrogen-bonding lead-
ing to a large decrease in their nucleophilicity. While cyanide has
weaker hydrogen-bonding ability and stronger nucleophilicity
toward the carbonyl group12 (see Fig. 3).
NO2
NO2
CN-
N
N
N
N
N
H
HN
O
CF3
CN
O-
CF3
Our thought was confirmed with further water increase. 5.0%
vol of water resulted in selective CNÀ response (Fig. 4). Addition
of other anions tested had minor influence on both the color and
Scheme 2. Structure of the probe 1 and its proposed mechanism upon the addition
of cyanide.
Figure 2. (a) The correspondiÀngÀcolor changes and (Àb) absorptiÀon spectra when compound 1 (25
l
M) was treated with various anions (vials from the left: 1 only, CNÀ, FÀ,
AcOÀ, H2PO4À, HSO4À, ClÀ, Br , I , NO3À, ClO4À, SCN , N3À; CN , FÀ, AcOÀ, H2PO4À, HSO4À, NO3À: 1 equiv; ClÀ, BrÀ, IÀ, ClO4À, SCNÀ, N3À: 50 equiv) in CH3CN.
Figure 3. (a) The cÀorrespoÀnding color changesÀand (b) absorption spectra when compound 1 (25
l
ÀM) was treated with variouÀs anions (vials from the left: 1 only, CNÀ, FÀ, AcOÀ,
H2PO4À, HSO4À, Cl , BrÀ, I , NO3À, ClO4À, SCN , N3À; CNÀ, FÀ, AcOÀ, H2PO4À, HSO4À: 1 equiv; Cl , BrÀ, IÀ, NO3À, ClO4À, SCN , N3À: 50 equiv) in CH3CN–H2O (97.5:2.5, v:v).

H.-T. Niu et al. / Tetrahedron Letters 49 (2008) 6521–6524
6523
Figure 4. (a) The correspondÀing color changes andÀ(b) absorption spectra when compound 1 (25
l
M) was treated with various anions (vials from the left: 1 only, CNÀ, FÀ,
AcOÀ, H2PO4À, HSO4À, ClÀ, Br , IÀ, NO3À, ClO4À, SCN , N3À; CNÀ, FÀ, AcOÀ: 2 equiv; H2PO4À, HSO4À, ClÀ, BrÀ, IÀ, NO3À, ClO4À, SCNÀ, N3À: 100 equiv) in CH3CN–H2O (95:5, v:v).
the absorption spectra of the solution of 1. 5% vol of water is en-
ough to avoid completely the interference of FÀ and AcOÀ. When
7.5% vol or 10.0% vol of water was used as solvent, the selectivity
of CNÀ to FÀ and AcOÀ became higher, even when F- and AcOÀ were
in large excess (Figs. S17 and S18).
To quantitatively study the binding affinity of 1 toward the an-
ions in pure acetonitrile and in water–acetonitrile mixtures, four
kinds of anions CNÀ, FÀ, AcOÀ, and H2PO4 were chosen. UV–vis
À
titration experiments were done by addition of aliquots of various
anions to the solution of 1. The association constants17 are col-
lected in Table 1. We can see that in pure CH3CN, 1 interacts
strongly with the four kinds of anions (K > 104). With the increase
of the proportion of water, the binding constants for FÀ, and AcOÀ,
À
H2PO4 are sharply reduced. While that for cyanide remains rela-
tively high. The results are in agreement with the above qualitative
analysis.
Both the selectivity and sensitivity are important for a sensor.
As stated above, sensor 1 can recognize cyanide with high selectiv-
ity when the proportion of water is more than 5%. To determine the
Figure 5. The corresponding detection limit of 1 in pure water for cyanide in the
sensitivity of sensor 1 in practical application, the detection limit in
presence of different proportion of water in acetonitrile–water mixtures.
water–acetonitrile (Fig. S19) mixtures and in corresponding pure
water was calculated (Fig. 5). We can see from Figure 5 that when
the proportion of water in water–acetonitrile is between 2.5% and
Acknowledgments
5.5%, the detection limit in corresponding pure water is most high,
even below 5 lM. This means sensor 1 can detect cyanide in
This project was supported by the Major State Basic Research
Development Program of China (Grant No. G2007CB808000) and
the Natural Science Foundation of China (NSFC No. 20702038).
pure water sample at very low concentration, which makes sensor
1 a powerful tool for the detection of cyanide in practical
application.
In summary, we have developed a Disperse Orange 3-based
chemosensor for the ‘naked-eye’ detection of cyanide in aqueous
environment with high selectivity and sensitivity. Our method is
safe, fast, simple to use and allows the detection of cyanide in pure
Supplementary data
Experimental details, UV–vis titration spectra, colorimetric
studies, and detection limit studies are available. Supplementary
data associated with this article can be found, in the online version,
at doi:10.1016/j.tetlet.2008.08.115.
water at a very low concentration (below 5 lM).
Table 1
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—
—
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