Specific naked eye sensing of cyanide by chromogenic host: Studies on the effect of solvents

Article abstract of DOI:10.1016/j.tetlet.2012.12.053

We have synthesized receptor 1, which showed high selectivity toward CN^- over other competitive anions in protic solvents. In addition, it distinguished CN^- from other anions by color changes. Furthermore, its detection limit is far

Full text of DOI:10.1016/j.tetlet.2012.12.053

Tetrahedron Letters 54 (2013) 1015–1019
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Tetrahedron Letters
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Specific naked eye sensing of cyanide by chromogenic host: studies on the
effect of solvents
Jongmin Kang a, , Eun Joo Song b, Hyun Kim b, Young-Hee Kim a, Youngmee Kim c, Sung-Jin Kim c,
⇑
Cheal Kim b,
⇑
a Department of Chemistry, Sejong University, Seoul 143-747, Republic of Korea
b Department of Fine Chemistry, Seoul National University of Science & Technology, Seoul 139-743, Republic of Korea
c Department of Chemistry and Nano Science, Ewha Womans University, Seoul 120-750, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
We have synthesized receptor 1, which showed high selectivity toward CNÀ over other competitive
anions in protic solvents. In addition, it distinguished CNÀ from other anions by color changes. Further-
more, its detection limit is far below the WHO guidelines of drinking water. However, in aprotic solvents
such as acetonitrile, the unique selectivity for CNÀ disappeared, and the nonselective color change was
observed for strongly basic anions such as FÀ, AcOÀ, and H2PO4À. These results suggest that receptor 1
interacts with cyanide with different mechanisms depending on solvents. The interaction mechanisms
between 1 and cyanide in protic and aprotic solvents were investigated.
Article history:
Received 7 November 2012
Revised 10 December 2012
Accepted 14 December 2012
Available online 21 December 2012
Keywords:
Cyanide sensing
Naked eye sensing
Colorimetric sensing
Solvents effects
Ó 2012 Elsevier Ltd. All rights reserved.
Chemodosimetric approach
There have been considerable efforts to develop efficient artifi-
cial receptors for anion recognition and sensing as anions play a
major role in biological, medical, environmental, and chemical sci-
ences.1 In recent years, artificial receptors specific for cyanide have
been of particular interest2 due to the extreme toxicity of cyanide
in physiological systems3 and environment.4 Despite its toxicity,
cyanide is still widely used in gold mining, electroplating, polymer
production such as nitriles, nylon, and acrylic plastics.5 Among var-
ious cyanide sensing strategies, optical sensors which allow selec-
tive naked eye detection of cyanide are attractive. Cyanide anion
receptors based on hydrogen bonding usually showed limitations
such as poor selectivity over fluoride or acetate.6 In addition, many
of them are reported to work only in aprotic organic media. There-
fore the search for effective cyanide sensing systems in aqueous
environments or protic solvents is still a great challenge. For the
recognition of cyanide in aqueous or protic solvents, many
researchers adopted a chemodosimetric approach. This reaction
based recognition takes advantage of the good nucleophilicity of
the cyanide ion.7 It is well known that the cyanide anion is a strong
nucleophilic reagent, and the nucleophilic attack to the carbon
atom of an electron-deficient carbonyl group can achieve naked
eye detection of the cyanide anion in protic solvents. With these
considerations in mind, we introduce an effective colorimetric sen-
sor 1, which utilizes a nitrophenyl group as a chromophore and a
thiourea group as an electrophile.
Preparation of receptor 1 is depicted in Scheme 1. Reaction of 4-
nitrophenyl isothiocyanate with bis(2-pyridylmethyl)amine in
dichloromethane afforded 1 in 85% yields. 1 was characterized by
1H NMR, elemental analysis, and LRMS. The structure of 1 was fur-
ther confirmed by single crystal X-ray diffraction and is shown in
Figure 1.
The chromogenic sensing ability of 1 was studied first in etha-
nol in the presence of seven different anions such as CNÀ, FÀ, ClÀ,
BrÀ, IÀ, CH3COOÀ, H2PO4À. Figure 2a shows that only the addition
of CNÀ induced distinct spectral changes while other anions such
as FÀ, ClÀ, BrÀ, IÀ, CH3COOÀ, H2PO4 did not induce any spectral
À
changes. In addition, the solution color changed from colorless to
yellow only with cyanide (Fig. 2b). Cyanide has a strong thiocar-
bonyl carbon affinity, which results in the addition reaction of
CNÀ to the thiocarbonyl carbon. Subsequent proton transfer of
thiourea hydrogen to the developing alkylsulfide anion of 1 pro-
duces an anionic state of 1, which enhances the charge-transfer
interactions between the electron-rich and electron-deficient moi-
eties resulting in a visible color change (Scheme 2).
⇑
Corresponding authors. Tel.: +82 2 3408 3213; fax: +82 2 462 9954 (J.K.); tel.:
+82 2 970 6693; fax: +82 2 973 9149 (C.K.).
Titration of receptor 1 with cyanide in ethanol was performed
for the quantitative study. In pure ethanol, receptor 1 displayed a
E-mail addresses: kangjm@sejong.ac.kr (J. Kang), chealkim@snut.ac.kr (C. Kim).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.12.053

1016
J. Kang et al. / Tetrahedron Letters 54 (2013) 1015–1019
NO2
S
N
N
H
N
NO2
N
N
N
N
+
H
SCN
CH2Cl2
85%
1
Scheme 1. The synthetic procedure for receptor 1.
strong absorption band at 337 nm, which is caused by the
combination of a nitrophenyl group and a thiourea group. Figure 3
shows the family of spectra obtained over the course of the titra-
tion of solution 1 with tetraethylammonium cyanide in ethanol.
As cyanide ions were added to the 40 lM solution of 1, the inten-
sity of the absorption peak at 337 nm gradually decreased, while
the intensity of the peak at 424 nm began to increase until it
reached a limiting value. The presence of the sharp isosbestic point
at 376 nm indicates that only two species were present at equilib-
rium over the course of the titration experiment. By plotting the
changes of 1 in the absorbance at 424 nm as a function of CNÀ con-
centration, a sigmoidal curve was obtained and is shown in the in-
set of Figure 3. To corroborate the 1:1 ratio between 1 and CNÀ,
Job’s plot analysis was executed. The measured absorbance varia-
tion at 424 nm (A = AabsÀAi) reaches to a maximum when the mo-
lar fraction of ([1]/[CNÀ] + [1]) is 0.5, confirming the 1:1
stoichiometry (Fig. 4). A Benesi–Hildebrand plot by the use of
change at 424 nm in UV–vis spectrum gave the association con-
Figure 1. Crystal structure of
ellipsoids are shown at the 50% probability level.
1 along with the atom labeling. Displacement
stant of 2.5 ( 0.2) Â 103 MÀ1
.
Colorimetric and absorption detection limits of 1 for CNÀ ion
were tested. A plot of (AÀA0) versus the cyanide concentration in
ethanol solution gave a linear relationship (Fig. 5). The detection
limit calculated on the basis of 3
below the WHO guidelines of drinking water (1.9
r
/K8 is 0.19
l
M. This value is far
l
M),9 which
makes receptor 1 a powerful tool for the detection of the cyanide
ion.
We also investigated the interaction mechanism between the
receptor 1 and cyanide in aprotic solvents to compare with interac-
tion mechanism in protic solvents. Figure 6 shows the family of
spectra obtained over the course of the titration of solution 1 with
tetraethylammonium cyanide in acetonitrile. As cyanide ions were
added to the 40 lM solution of 1, kmax of 1 moved from 343 to
434 nm and the spectra showed the clear isosbestic point at
370 nm. The presence of the sharp isosbestic point also indicates
that only two species were present at equilibrium over the course
of the titraÀtion experiment. Other basic anions such as FÀ, AcOÀ,
and H2PO4 showed almost the same phenomena. These results
indicate that only direct deprotonation occurs with basic anions
in acetonitrile. Therefore, in acetonitrile, the selectivity for CNÀ is
rather poor as basic anions such as FÀ, AcOÀ, and H2PO4À were de-
tected by a simple deprotonation mechanism (Fig. 7a). All of these
basic anions showed color change in acetonitrile while only CNÀ
showed color change in protic solvents such as ethanol (Fig. 7b).
The interaction between 1 and cyanide was further studied
through 1H NMR in CD3OD. Upon the addition of the CNÀ to the
receptor 1, most of the aromatic peaks were shifted upfield except
H5 and H6 (Fig. 8). Especially, pronounced upfield shifts were ob-
served for H1 and H2. These large upfield shifts could be explained
from the proposed sensing mechanism shown in Scheme 2. After
the addition reaction of CNÀ to thiocarbonyl carbon and subse-
quent proton transfer of thiourea hydrogen, alkylsulfide anion
formed. Then, delocalization of the electron to the nitroaromatic
ring increased the electron density in the aromatic ring, which re-
sults in large upfield shifts of H1 and H2. The formation of a cyanide
adduct was further confirmed by mass spectroscopy. The electro-
spray ionization mass spectrum of the cyanide adduct showed a
Figure 2. UV–vis spectra of 1 (40 lM) upon the addition of various anions (5 equiv)
in ethanol (a) and color changes of solution of 1 in the presence of various anions
(50 equiv) in ethanol (b).

J. Kang et al. / Tetrahedron Letters 54 (2013) 1015–1019
1017
NO2
NO2
S-
S
N
NC
CN-
ethanol
N
N
N
N
N
N
H
H
N
O-
NO2
N
+
O-
SH
SH
N
NC
N
NC
N
N
N
N
-
N
N
Scheme 2. The proposed sensing mechanism of 1 for cyanide in ethanol.
Figure 5. Absorption intensity of 1 versus CNÀ concentrations [1] = 40
lM.
Figure 3. Family of UV–vis spectra recorded over the course of titration of 40
ethanol solution of the receptor 1 with tetraethylammonium cyanide.
lM
Figure 6. Family of UV–vis spectra recorded over the course of titration of 40
acetonitrile solution of the receptor 1 with tetraethylammonium cyanide.
lM
Figure 4. Job plots of receptor 1 and cyanide in ethanol.

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J. Kang et al. / Tetrahedron Letters 54 (2013) 1015–1019
Figure 9. ESI-mass spectrum of 1 (0.1 mM) upon the addition of tetraethylammo-
nium cyanide (0.1 mM) in ethanol.
nism in CD3CN is somewhat different from the interaction
mechanism in CD3OD. The delocalized electron comes from the di-
rect deprotonation from urea N–H (Scheme 3). These different
interaction mechanisms depending on the type of solvent were
in accord with results of UV–vis titration and colorimetric
experiments.
In conclusion, we have synthesized a new receptor 1, which
showed high selectivity toward the CNÀ ion over other competitive
anions in protic solvents such as ethanol. In addition, it distin-
guished CNÀ from other anions by color changes. Furthermore,
its detection limit is far below the WHO guidelines of drinking
water. However, in aprotic solvents such as acetonitrile, poor selec-
tivity for cyanide was observed due to unselective deprotonation
by strongly basic anions. These results suggest that receptor 1
interacts with cyanide with different mechanisms depending on
the solvents. While direct deprotonation occurred in acetonitrile,
the nucleophilic attack of CNÀ to the thioncarbonyl group occurred
first in protic solvents such as ethanol and methanol. It is known
that the nucleophilicity of the chemical species is solvent-depen-
dent. The protic solvents decrease the anion’s nucleophilicity by
hydrogen bonding to the nucleophile. Anions such as FÀ, AcOÀ,
and H2PO4À interact with protic solvents through hydrogen-bond-
ing leading to a large decrease in their nucleophilicity. However,
CNÀ has weaker hydrogen-bonding ability and stronger nucleophi-
licity toward the carbonyl group. Therefore, the colorimetric sensor
1 allows a selective detection of very low CNÀ concentration by the
naked eye in protic solvents.
Figure 7. UV–vis spectra of 1 (40 lM) upon the addition of various anions (5 equiv)
in acetonitrile (a) and color changes of solution of 1 in the presence of various
anions (50 equiv) in acetonitrile (b).
molecular mass of 440.80, which corresponds to the formula of
[1 + CN + 2H2O] (Fig. 9). However, 1H NMR titration experiments
carried out in CD3CN showed different interaction mechanisms.
Upon the addition of 0.5 equiv of the CNÀ to the receptor 1, the
N–H peak appearing at 12.36 ppm disappeared completely, which
indicates immediate deprotonation of the NH in the aprotic sol-
vent. In addition, pronounced upfield shifts of the aromatic protons
H1 and H2 were observed again as in the case of CD3OD (Fig. 10).
These upfield shifts also resulted from the delocalization of elec-
trons to the nitroaromatic ring. However, the interaction mecha-
Figure 8. 1H NMR spectra of 2 mM of 1 upon successive addition of tetraethylammonium cyanide in CD3OD. The shifts of H1 and H2 peaks are designated by dotted lines.

J. Kang et al. / Tetrahedron Letters 54 (2013) 1015–1019
1019
Figure 10. 1H NMR spectra of 2 mM of 1 upon successive addition of tetraethylammonium cyanide in CD3CN. The shifts of H1 and H2 peaks are designated by dotted lines.
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This research was supported by Basic Science Research Program
through the National Research Foundation of Korea (NRF) funded
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Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2012.12.
053.
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