New color chemosensors for cyanide based on water soluble azo dyes

Article abstract of DOI:10.1016/j.tetlet.2010.08.098

Cyanide detection in pure water is important for many applications. We present a novel type of chemodosimeter azo dye developed on the basis of the benzophenone as the electrophilic receptor of the cyanide anion and a saccharidic moiety to render the dye

Full text of DOI:10.1016/j.tetlet.2010.08.098

Tetrahedron Letters 51 (2010) 5810–5814
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Tetrahedron Letters
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New color chemosensors for cyanide based on water soluble azo dyes
⇑
Jalal Isaad , Anne Perwuelz
Laboratoire de Génie et Matériaux Textiles (GEMTEX), UPRES EA 2461, Ecole Nationale Supérieure des Arts et Industries Textiles (ENSAIT), 2 Allée Louise et Victor
Champier, BP 30329, 59056 Roubaix Cedex 01, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 7 May 2010
Revised 4 August 2010
Accepted 31 August 2010
Available online 8 September 2010
Cyanide detection in pure water is important for many applications. We present a novel type of chemod-
osimeter azo dye developed on the basis of the benzophenone as the electrophilic receptor of the cyanide
anion and a saccharidic moiety to render the dye water soluble. This chemodosimeter is found to be
highly selective and tunable toward only cyanide in pure water.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Cyanide
Water solubility
Chemosensing
Carbohydrate
Azo dye
1. Introduction
detection techniques.16 Methods based on anion-induced changes
of the optical properties (either absorption or emission) of recep-
A few decades ago, there was a general feeling that nature could
effectively handle hazardous substances. Although nowadays hu-
man beings are more concerned for their sensitive natural environ-
ment, pollution is still a problem. Experts estimate that the
industrial processes introduce up to a million different pollutants
into the atmosphere and the aquatic ecosystem.1
tors are especially attractive. Recent examples which use this ap-
proach involve the use of large chemosensors based on Ru(II)-
containing pyrrolylquinoxalines,17 Zn(II) complexes of porphyrin
derivatives,18 boronic acid groups,19 trifluoroacetophenone deriva-
tives,20 and Re(I) polypyridyl complexes,21 among others.22 How-
ever some of these systems need to be carried out in organic
solvents or a mixture of organic solvents and water, which limits
their applicability for the analyses of ‘real’ samples that are often
in aqueous solution.
Recently, a new category of water soluble dyes was developed
as dyeing agents in water.23 The water solubility was obtained
by the glycoconjugation of the starting organic dyes with lactose
or with its monosaccharidic components, glucose or galactose,
which is the most important characteristic that we aim to transfer
to (or improve in) the organic cyanide chemodosimeters.
From this perspective, we report herein the synthesis of new
water soluble glycoconjugated azo dyes based on benzophenone
as the cyanide receptor, and their ability to selectively detect cya-
nide in pure water.
Cyanides are categorized within these substances, which are
considered one of the most lethal poisons known.2–11 The absorp-
tion is the mechanism of toxicity for cyanide which occurs through
the lungs, gastrointestinal track, and skin. Cyanide is highly toxic
due to the inhibition of the oxygen utilization by cells, binding
with ferric iron in cytochrome oxidase and blocking the oxidative
process of cells. The tissues with the highest oxygen requirements
(brain, heart, and lungs) are the most affected by acute poisoning.
Even though cyanide poisoning is not common, it can occur
because of smoke inhalation from residential and industrial fires
and among people who work in the metal, mining, electroplating,
jewellery manufacture, and X-ray film recovery trades.1–15 Numer-
ous chemical and physiochemical methods for the detection and
determination of cyanides, such as potentiometry, chromatogra-
phy, spectrophotometry, flow injection, and electrochemical anal-
yses are used,1–14 but only potentiometric determination has
been reported as offering continuous cyanide monitoring.15
Several methods have previously been developed to detect
cyanide by using a wide diversity of experimental protocols and
2. Results and discussion
Our approach to a new type of cyanide chemodosimeters is de-
picted in Figure 1.
A latent chromogenic moiety with a carbonyl group (–COR) may
comprise a new type of chemodosimeters for cyanide because cya-
nide has strong affinity toward the carbonyl group and thus attack
cyanide of the carbonyl group and may trigger the ‘latent’ chromo-
⇑
Corresponding author. Tel.: +33 0320258936; fax: +33 0320272597.
E-mail address: jalal.isaad@ensait.fr (J. Isaad).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.08.098

J. Isaad, A. Perwuelz / Tetrahedron Letters 51 (2010) 5810–5814
5811
O
R
HO
R
Compound 4 was characterized by spectroscopic and analytical
techniques such as the 1H and 13C NMR spectra. The integration
and multiplicity in the 1H NMR spectra were indicative of the pres-
CN
CN-
ence of both aromatic and glucidic rings in 4. The resonance in 13
C
NMR spectra of the samples at 193.2 ppm was assigned to the car-
bonyl carbon of the benzophenone unit.
Dye
R = Ph
Dye
2.1. UV–vis spectra studies
Figure 1. A schematic diagram for the displacement approach to new
chemodosimeters.
UV–vis absorption spectra of the newly generated glyco-conju-
gated dyes are crucial because the modified dyes should display
the same color as the starting materials to ensure that the chromo-
phore is not affected by the glycoconjugation process. As in the
case of dye obtained by the attachment of glucide to a phenolic hy-
droxyl group of dye 1, the UV–vis spectra of the starting dye 1 and
the glycoconjugated dyes 4 in DMSO are shown in Table 1. The re-
sults reported in Table 1 show that kmax does not exhibit any sig-
nificant shift after the glycoconjugation with the glucide units.
Furthermore, molar extinction coefficient values can be considered
constant.
genic moiety into an ‘active’ state. To evaluate this mechanism, we
focused our attention to the electrophilic character of the carbonyl
group of the benzophenone which can be introduced as an electro-
phile for the anion in an azo dye functional group as a chromophore.
Scheme 1 represents the synthesis of an azo dye 1 possessing a
benzophenone unit. The synthesis was carried out by treating the
commercial 4-aminophenol with sodium nitrite in acidic medium
at 0 °C to form the corresponding diazonium salt, followed by
treating with the benzophenone.
The azoic dye 1 was not soluble in water, insensitive to warm-
ing, stirring, powdering, and microwaving. All attempts to solubi-
lize it led to two-phase systems, with the water phase almost
completely clear and colorless. To render the dyes 1 water-soluble,
we attempted to glycoconjugate it with saccharidic moiety. For
this purpose, the protected ethereal lactose 2e was prepared from
2.2. Studies of the anion-dye interaction in solution
As a first step, the chromogenic sensing ability of 1 was studied
in DMSO in the presence of six different anions namely, FÀ, ClÀ,
CH3COOÀ, H2PO4À, SCNÀ, and CNÀ. Figure 2 shows that only the
addition of one equivalent of FÀ and CNÀ induced distinct spectra
a,D-lactose 2 depending on the procedure reported in the literature
(Scheme 2).22 Next, the oxygen atom of the hydroxyl group in dye
1 was linked to the carbon of the bromine atom of the protected
sugar 2e in the presence of KOH as the strong inorganic base and
18-crown-6 as the phase transfer agent. We used non-anhydrous
THF as the solvent due to its help in dissolving KOH without affect-
ing the yield by competing with the crown ether.
changes, while other anions such ClÀ, CH3COOÀ, H2PO4 and SCNÀ
À
did not induce any color changes even in large excess.
The 1H NMR spectrum of the initial anion-free solution of dye 1
showed four multiplets between d = 8.15 ppm and d = 7.06 ppm,
which correspond to the protons of the three aromatic rings, and
one singlet at d = 5.31 ppm which corresponds to the protons of
the aromatic alcohols: by adding the cyanide and the fluoride to
this solution, a new singlet appeared at d = 3.77 ppm. Therefore,
the results of 1H NMR prove that the exchange color is due to
the formation of the cyanohydrin and fluorohydrin during the
nucleophilic attack of cyanide and fluoride anions toward the car-
bonyl group of dye 1 (Fig. 3).
The final step was the deprotection of this last compound using
TFA, which results in the isolation of the water soluble chemodos-
imeter 4 in good yield (Scheme 3).
O
In spite of the interesting reactivity of dye 1 found in DMSO, it
shows poor selectivity, with respect to FÀ. To take benefit of the
favorable features of 1 as a chemodosimeter, and to improve its
selectivity towards CNÀ, we tested the reactivity of the glycoconju-
gated form of 1 (dye 4) in pure water to investigate the anion
nucleophility and the sensing response.
O
NH2
a
N
N
OH
The anion sensing properties of the glycoconjugated dyes 4
4-aminophenol
were studied in solution by using water as the solvent. An intense
*
absorption band for the
p?p transition of 4-glycoconjugated
OH
1
azophenyl chromophore appears at kmax = 356 nm, while it is very
weak at kmax = 455 nm for 4. The anions selected for these studies
were FÀ, ClÀ, BrÀ CH3COOÀ, H2PO4À, SCNÀ, and CNÀ. A solution of 4
Scheme 1. Synthetic process of compound 1. Reagents and conditions: (a) NaNO2,
HCl 37%, H2O, 0 °C to rt, 12 h.
Br
O
O
O
OR1
O
O
O
OH
O
OH
O
O
HO
HO
a
e
O
O
O
O
O
O
O
O
OR2
MeO
O
HO
O
OH
OH
MeO
OH
2
MeO
O
MeO
O
2a : R1 = H R2 = H
2b
2e
a
b
c
: R1 = MIP R2 = H
2c : R1 = MIP R2 = CH3
2d
: R1 = H R2 = CH3
Scheme 2. Conversion of lactose 2 into the 4-bromo butyl-protected lactose 2e. Reagents and conditions: (a) DMP, TsOH, 80 °C, 5 h (b) DMP, TsOH, 80 °C, 1.5 h (c) MeI, NaH,
DMF, 0 °C to rt, 2 h (d) H2O/MeOH (1:10), 1.5 h, 80 °C (e) 1,4-dibromo butane, KOH, 18 crown 6, THF, rt, 12 h.

5812
J. Isaad, A. Perwuelz / Tetrahedron Letters 51 (2010) 5810–5814
O
O
Br
O
N
N
O
N
N
O
O
O
O
N
O
O
O
a
b
O
N
+
O
O
O
O
O
( )
4
2e
O
(
)
4
O
O
O
O
O
OH
OH
HO
HO
O
1
O
O
O
O
O
3,
O
HO
OH
O
OH
OH
4
O
O
Scheme 3. Glycoconjugation of chemodosimeter 1. Reagents and conditions: (a) KOH, 18-crown-6, THF, rt, 12 h (b) TFA, rt, 3 h.
Table 1
Spectoscopic data for the dyes 1 and 4
OH
OH
O
Dyes
kmax (nm)
log (e )
(max)/MÀ1 cmÀ1
NC
F
1
4
356
356
4.0170
4.0100
CN-
F-
N
DMSO
N
DMSO
N
N
N
N
in water (0.5 mM) was treated at room temperature with a con-
stant amount of the different anions (one equivalent added as tet-
rabutylammonium salts). As showed in the Figure 4, the addition of
CNÀ only causes a change in the UV–vs absorption spectrum of dye
4. The intensity of the absorption bands increases by emerging a
new band at 455 nm. This was perceived by naked-eye observa-
tion: a color change from colorless to yellow was only observed
upon addition of cyanide (Fig. 4).
OH
456 nm
OH
456 nm
OH
355 nm
Figure 3. Hosts and a plausible sensing mechanism of cyanide and fluoride.
are relatively few examples of colorimetric probes for cyanide24
compared to the number of chromogenic chemosensors for certain
anions such as fluoride or carboxylates.24 However, because of its
wide use and serious toxicity, the development of new chemosen-
sors for cyanide in water offers many interests25 such as rapid and
screening applications. In this field, chromogenic optical probes
will play an important role.
To analyze quantitatively the changes observed in water by
adding CNÀ increasingly, a series of titrations using UV–vs spec-
troscopy will be carried out on dye 4. An example of the titration
curves obtained upon the addition of increasing amounts of cya-
nide to dye 4 is illustrated in Figure 5. The changes observed in
the absorption spectrum of 4 show that two species are present
in the solution, where their proportions depend on the amount
of cyanide added. In the absence of anion, compound 4 in water
has a kmax value of 356 nm. Upon addition of cyanide, the new
It is known that the nucleophilic character of different species is
solvent-dependent. In fact, the protic solvents decrease the anion’s
nucleophilicity by hydrogen bonding to the nucleophile one pair
(solvation effects).
A suitable solvent induces the selectivity
enhancement by using water; which means a solvent of special
importance, since it is a suitable media for testing chromo- sensing
probes for anions of environmental interest. In pure DMSO solu-
tion, dye 1 react with the anions CNÀ and FÀ, but in water, the gly-
coconjugated form of 1 (dye 4) react selectively with CNÀ by the
changing of the solution color from colorless to yellow as in the
case of the dye 1 in DMSO.
This selective response to cyanide is an attractive feature. Since
the cyanide is a highly toxic anion, it is still in use widely in differ-
ent applications, that is, electroplating, mining, metallurgy, etc.
Moreover, cyanide can also be present in certain foods such as cas-
sava roots, pits of certain fruits and bitter almonds. Actually, there
Figure 2. Absorption spectra and color change when dye 1 (0.5 mM) was treated with various analytes (vials from the left:, ClÀ, CH3COOÀ, H2PO4À, SCNÀ, FÀ and CNÀ as Bu4N+
salts) in DMSO.

J. Isaad, A. Perwuelz / Tetrahedron Letters 51 (2010) 5810–5814
5813
Figure 4. Absorption spectra and color changes when dye 7 (0.5 mM) was treated with various analytes (vials from the left:, ClÀ, BrÀ CH3COOÀ, H2PO4À, SCNÀ, FÀ and CNÀ as
Bu4N+ salts) in water.
level due to the selective reaction of this anion with selected ben-
zophenone glycoconjugated azo dye. It is a simple method, and it
allows a selective detection of very low cyanide concentration by
the naked eye.
0.8
A356
A455
0.7
Dye 4
0.6
0.5
0.4
0.3
0.2
0.1
0
Acknowledgements
This work is financially supported by GEMTEX Laboratory—
France. We thank Doctor Ayham Alruhban very much for the help-
ful and valuable comments on the text.
Supplementary data
0
2
4
6
M
8
10
[CN-]/ 10-5
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.08.098.
Figure 5. Absorption changes of 4 upon the addition of increasing amounts of
cyanide using a 2 Â 10À5 M solution of 4 in pure water.
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3. Conclusion
In summary, we have reported the use of water soluble azo dye
as probes for the detection of selected anions. In particular, a selec-
tive chromo detection of cyanide was reached in water to the ppm

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