Highly reactive (<1 min) ratiometric probe for selective 'naked-eye' detection of cyanide in aqueous media

Article abstract of DOI:10.1016/j.tetlet.2012.12.092

We have designed and synthesized a triphenyl aminebenzothiazole coupled receptor (TBH) that exhibits a selective, sensitive, colorimetric, and ratiometric rapid response toward cyanide anion in aqueous media. The sensing event is explained by spectroscopy along with DFT calculation and CV diagram. Sensor displays a very fast response (<1 min) toward cyanide at room temperature with a 'naked-eye' change over F^- and AcO^- in aqueous media.

Full text of DOI:10.1016/j.tetlet.2012.12.092

Tetrahedron Letters 54 (2013) 1785–1789
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Highly reactive (<1 min) ratiometric probe for selective ‘naked-eye’ detection
of cyanide in aqueous media
⇑
Shyamaprosad Goswami , Abhishek Manna, Sima Paul, Krishnendu Aich, Avijit Kumar Das,
Shampa Chakraborty
Department of Chemistry, Bengal Engineering and Science University, Shibpur, Howrah 711103, West Bengal, India
a r t i c l e i n f o
a b s t r a c t
Article history:
We have designed and synthesized a triphenyl aminebenzothiazole coupled receptor (TBH) that exhibits
a selective, sensitive, colorimetric, and ratiometric rapid response toward cyanide anion in aqueous
media. The sensing event is explained by spectroscopy along with DFT calculation and CV diagram. Sen-
sor displays a very fast response (<1 min) toward cyanide at room temperature with a ‘naked-eye’ change
over FÀ and AcOÀ in aqueous media.
Received 15 September 2012
Revised 19 December 2012
Accepted 22 December 2012
Available online 5 January 2013
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Sensor
Cyanide
Ratiometric
Naked-eye detection
Triphenylamine
Benzothiazole
The development of optical chemosensors for anions of biolog-
ical, environmental, and clinical concerns is currently under active
investigation.1 Among the toxic anions acting as severe environ-
mental pollutants and consequently having adverse health effects,
cyanide is one of the most-concerning anions. It can directly lead to
the death of human beings2 as well as aquatic life,3 even at low
concentration, by binding to a 3 cytochromes, inhibiting the elec-
tron transport chain in mitochondria and by depressing the central
nervous system.4 Due to this, it is lethal to human at concentra-
tions of 0.5–3.5 mg/kg of body weight.5 Despite its toxicity, its
application in various areas as raw materials for synthetic fibers,
resins, herbicides, and the gold extraction process is inevitable,
which release cyanide into the environment as a toxic contami-
nant6,7 and it can lead to serious contamination of the ground
and/or drinking water.8 Thus, there is a need for an efficient sens-
ing system for cyanide to monitor cyanide concentration from con-
taminant sources.
single-electron transfer reaction.12 Recently, nucleophilic addition
of cyanide has also been adopted for sensing cyanide. Based on this
idea, nucleophilic addition of cyanide to oxazine, pyrylium, squara-
ne, trifluoroacetophenone, acyltrazene, acridinium, salicylalde-
hyde, and carboxamide has been reported.13
In spite of these developments, there are still relatively few
examples of selective and sensitive probe for cyanide anion espe-
cially those that display limited inference in the presence of other
anions particularly with FÀ, AcOÀ, and H2PO4À. Moreover, the
receptors based on these approaches have very complex structures.
This requires multiple step synthesis with relatively low overall
yields. As a result, developed chemosensors cannot be prepared
on a large scale. Furthermore, most of the sensors/receptors have
limitations in analytical and bio analytical applications due to poor
sensing of cyanide in aqueous media and most of the chemo
dosimeter type sensors for CNÀ are time consuming, that is, the
neucleophilic attack of cyanide to the sensor is really slow. There-
fore, it is highly desirable to develop sensitive, selective, and easy-
to-prepare chemical sensor for cyanide even in water medium with
a rapid response.
With these considerations in mind, we report here the design
and synthesis of a simple receptor, triphenylamine benzothiazole
hybrid (TBH) that exhibits a selective, sensitive, colorimetric, and
ratiometric response toward cyanide anion in aqueous acetonitrile
solution. Importantly, TBH displays a very fast response (<1 min) to
cyanide at room temperature, and ‘naked-eye’ detection is possible
in the presence of only 1 equiv of cyanide.
In past few years, a variety of colorimetric and fluorescent
probes for cyanide have been reported. One of the common ap-
proaches is utilizing cyanide complexes or addition with Zn2+–por-
phyrin,9a Ru2+–pyridine,9b boronic acid derivatives,9c and CdSe
quantum dots.9d Other strategies were also involved, such as
hydrogen bonding interactions,10 copper–cyanide affinity,11 and
⇑
Corresponding author. Fax: +91 3326682916.
E-mail address: spgoswamical@yahoo.com (S. Goswami).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.12.092

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S. Goswami et al. / Tetrahedron Letters 54 (2013) 1785–1789
O
I
S
N+
CH3
POCl3, DMF
N
N
EtOH
(3)
+
S
Piperidine (cat.)
reflux
N
S
N
MeI, toluene
reflux
CH3
CH3
N+
I
Receptor
(TBH)
CH3
(2)
Scheme 1. Synthesis of the receptor (TBH).
CNÀ and ADP as their potassium salts in solution. In UV–vis absorp-
tion spectrometry, only CNÀ was found to perturb the electronic
behavior of TBH to a significant extent. The absorption spectrum
of TBH (2 Â 10À6 M, in CH3CN/H2O as 1:1) is characterized by an
intense absorption band (a twin band) centered at 507 nm attrib-
uted to intramolecular charge-transfer (ICT) transition, in combi-
0.3
0.2
0.1
0.0
nation with the less intense
p
?
pà transitions at 300 nm. The
ICT band is responsible for the reddish pink color of TBH. Upon
incremental addition of CNÀ solution (2 Â 10À5 M, in HEPES solu-
tion), a complete reduction in the intensity of 507 nm bands
accompanied by ratiometric (isosbestic point at 343 nm) increase
of intensity at 300 nm was observed which achieved saturation
after the addition of 1 equiv solution of CNÀ ions (Figs. 1 and 3).
The visual color change is shown in Figure 2. In emission spectros-
copy there is a negligible change observed in 440 nm range upon
addition of 1 equiv cyanide ion (Supplementary data).
300
400
500
600
Wavelength (nm)
This indicated the minimum required amount of CNÀ which
was used at this point of saturation for the formation of the visual
colorless solution. The large hypsochromic shift in the ICT band re-
sulted in the observed complete bleaching of the original reddish
pink color of the receptor.
Figure 1. UV–vis absorption titration spectra of TBH (c = 2.0 Â 10À6 M) in the
presence of CNÀ (c = 2.0 Â 10À5 M) at pH 7.1 in CH3CN/H2O = 1:1.
The synthesis of the sensor is shown in Scheme 1. The precursor
mono aldehyde of triphenylamine (3) is prepared from the corre-
sponding amine maintaining the Vilsmeier–Haack condition
according to the literature procedure.14 When benzothiazole is
treated with MeI in toluene as a solvent corresponding salt (2) is
obtained. In the presence of piperidine, 2 and 3 are coupled in
absolute ethanol to form the desired receptor (i.e., TBH) in 90%
yield. The purity of TBH was confirmed by 1H NMR, 13C NMR,
and ESI-MS spectra (Supplementary data).
The behavior of TBH toward a variety of anions was explored
with UV–vis absorption spectrometry. The various anions tested
are AcOÀ, ClÀ, BrÀ, IÀ, FÀ, and PhOÀ as their tetra butyl salts; SHÀ,
H2PO4À, PO43À, S2À, N3À, P2O74À, and SCNÀ as their sodium salts;
We envisaged that the observed bleaching of the color in the
presence of CNÀ may arise from the nucleophilic addition reaction
of CNÀ at the benzothiazole ring carbon adjacent to the quaternary
nitrogen atom to give a neutral structure and thus rupturing the
electronic delocalization with the concurrent disappearance of
the low energy band, resulting in the formation of colorless species
(Scheme 2).
This was confirmed by 1H NMR spectra which show the d value
downfield shift (0.61 ppm) from 1.45 to 2.06 ppm of methyl pro-
tons adjacent to quaternary ‘N’ to tertiary ‘N’ (Supplementary
data). From the IR data the phenomenon is also well explained
by the appearance of a new peak at 2250 cmÀ1 due to the insertion
of the cyano group in TBH (Supplementary data). The mass spec-
Figure 2. Visual changes of TBH (c = 2.0 Â 10À6 M) with addition of 1.0 equiv of each anion (c = 2.0 Â 10À5 M) at pH 7.1 in CH3CN/H2O (1:1, V/V).

S. Goswami et al. / Tetrahedron Letters 54 (2013) 1785–1789
1787
5.0
4.5
4.0
3.5
3.0
2.5
2.0
0.00
0.05
0.10
[ CN ] / µM
0.15
0.20
-
Figure 5. Absorption response of TBH with addition of CNÀ (1.0 equiv) (black bar)
in the presence of all other tested anions (5 equiv) (pink bar) at Kmax = 507 nm.
Figure 3. Normalized absorbance (I300/I343) versus [CNÀ]/
gradual addition of cyanide (from the data of Fig. 1).
l
M diagram of TBH with
A507
A300
0.3
S
I
N
CH3
S
N
N+
CH3
CN
CN-
0.2
0.1
0.0
N
Scheme 2.
0
20
40
60
time (sec.)
Figure 6. Time-dependent absorption intensity of TBH at 300 nm (in red) and
507 nm (in black) in the presence of CNÀ (1.0 equiv).
0.3
0.2
0.1
0.0
CN-
performed under a similar experimental condition, no significant
change in the absorption spectrum (Fig. 4) as well as in color of
the solution was noticed (Fig. 2).
ADP
Interestingly, the anions, FÀ and AcOÀ, which have been re-
ported15 to be the most interfering anions in the detection of
CNÀ, also did not affect the sensing process.
TBH +
all other anion
Further, competition experiments have also been performed by
adding CNÀ (1.0 equiv) to the sensor in the presence of commonly
employed interfering anions (5.0 equiv). The selectivity profile dia-
gram (Fig. 5) reveals that cyanide-induced quenching of absor-
bance (Kmax = 507 nm) remains unperturbed and does not get
any interference by the coexisting anions. This indicates that TBH
can be used potentially to quantitatively detect CNÀ concentration
with a high selectivity.
300
400
500
600
Wavelength (nm)
Figure 4. The absorption spectra of TBH (c = 2.0 Â 10À6 M) and TBH with all other
anions (c = 2.0 Â 10À5 M) in CH3CN/H2O (1:1, V/V) at pH 7.1.
We then investigated the time-dependent changes in the
absorption spectra upon incubation of TBH (10 l
M) with CNÀ
(1.0 equiv) for 1 min we see that 1 equiv of cyanide is sufficient
to drive the reaction to completion within 1 min, re-enforcing
the high reactivity feature of the probe (Fig. 6). The calculated
trum (ESI-MS) of the cyano adduct shows the highest peak at m/z
446.0 possibly for (M+CN)+ ions, which also proves a single mono-
nuclear addition of cyanide to the receptor TBH, m/z 418.99 (Sup-
plementary data).
detection limit 0.037 lM (Supplementary data) suggests that the
receptor is very sensitive toward CNÀ ion.
However, when titrations of other anions such as AcOÀ, ClÀ, BrÀ,
IÀ, FÀ, PhOÀ, SHÀ, H2PO4À, PO43À, S2À, N3À, P2O74À, and ADP were
In order to investigate the structural change occurred for the
colorimetric response of TBH–CNÀ, DFT calculations were carried

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S. Goswami et al. / Tetrahedron Letters 54 (2013) 1785–1789
gap (Supplementary data) in the calculated structures also sup-
ports the phenomenon.
In order to see if the results obtained in the solution studies
could be visualized on TLC plate strips so that it can be used as
ready to use ‘dip sticks’, strips coated with TBH were immersed
in the aqueous solutions of KCN in different concentrations and
an instant bleaching of the reddish pink color was observed
(Fig. 8). Development of such dipsticks is useful as instant qualita-
tive information without resorting to the instrumental analysis.
The nucleophilic addition of CNÀ at the methine carbon of TBH
is further supported by the cyclic voltammogram of TBH–CNÀ ad-
duct. The two reversible one-electron reduction processes ob-
served in the cyclic voltammogram of TBH (formally carrying one
positive charge) with E1/2 = À0.19 and À1.13 V versus Hg/HgCl2,
attributed to the reduction processes17 which disappear upon the
addition of CNÀ at the electrophilic methine carbon of the benzo-
thiazole ring (Fig. 9).
In conclusion, we have designed and synthesized a simple
receptor triphenylamine benzothiazole hybrid (TBH) that exhibits
a selective, sensitive, colorimetric, and ratiometric rapid response
toward cyanide anion in aqueous acetonitrile solution. The recog-
nition events of the sensor toward CNÀ are demonstrated nicely
by absorbance spectroscopy and explained by other spectroscopic
data with DFT calculation and CV diagram. From the competition
experiment it is clear that sensor can be used potentially to quan-
titatively detect CN- with a high selectivity over FÀ, AcOÀ, and
other anions. Importantly, TBH displays a very fast response
(<1 min) to cyanide at room temperature, and ‘naked-eye’ detec-
tion is possible in the presence of only 1 equiv of cyanide both in
aqueous solution and in TLC plate strips which are very useful tools
for the detection of cyanide without resorting to the instrumental
analysis.
Figure 7. Optimized structure of TBH (a) and TBH–CN (b).
out for TBH and the TBHÀCN using the DFT/B3LYP/6-31GÃ basis set
(Gaussian 03 program).16 The significant difference in the
-con-
p
junction between TBH and TBH–CN is observed in the optimized
structures of TBH and TBH–CN, shown in Figure 7. It clearly indi-
cates the high degree of conjugation between the two coplanar
aromatic rings, that is, the phenyl ring and the benzothiazole ring
via a ‘C@C’ bond in TBH (Fig. 7a). The hampered conjugation in
TBHÀCN (Fig. 7b) results from the addition of CNÀ at the methine
carbon of the benzothiazole ring which is responsible for observed
hypsochromic shift in the lower wavelength absorbance (ICT) of
TBH on forming the TBHÀCNÀ adduct. The HOMO–LUMO energy
Figure 8. Color changes visualized on TLC plate strips of (a) TBH (c = 2.0 Â 10À3 M) and during addition of KCN at (b) 2.0 Â 10À6 M; (c) 2.0 Â 10À5 M; (d) 2.0 Â 10À4 M and (e)
2.0 Â 10À2 M in CH3CN/H2O = 1:1.4
Figure 9. Cyclic voltammograms of TBH (1 Â 10À3 M, in CH3CN) before (left) and after addition of CNÀ solution (1 Â 10À2 M, in HEPES buffered H2O) (right).

S. Goswami et al. / Tetrahedron Letters 54 (2013) 1785–1789
1789
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Acknowledgments
8. Sun, H.; Zhang, Y. Y.; Si, S. H.; Zhu, D. R.; Fung, Y. S. Sens. Actuators B 2005, 108,
925–932.
We thank the DST and CSIR (Govt. of India) for financial sup-
ports. We also thank Mr. Prasenjit Hazra for CV experiment. A.M.,
K.A., and A.K.D. acknowledge the CSIR, S.P. acknowledges UGC
and S.C. acknowledges DST (SR/S1/OC-58/2010) for providing
fellowship.
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