Naked eye sensing of anions using thiourea based chemosensors with real time application

Article abstract of DOI:10.1016/j.tetlet.2013.08.005

Novel chromogenic sensors with thiourea moiety as receptor unit were synthesized and characterized using IR and NMR spectroscopic techniques. The receptors 1 and 2 bearing hydrogen bonding site demonstrate visually striking color change, UV-vis, and fluor

Full text of DOI:10.1016/j.tetlet.2013.08.005

Accepted Manuscript
Naked eye sensing of anions using thiourea based chemosensors with real time
application
G. Vinithra, S. Suganya, S. Velmathi
PII:
S0040-4039(13)01342-7
DOI:
http://dx.doi.org/10.1016/j.tetlet.2013.08.005
TETL 43362
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
18 June 2013
29 July 2013
1 August 2013
Please cite this article as: Vinithra, G., Suganya, S., Velmathi, S., Naked eye sensing of anions using thiourea based
chemosensors with real time application, Tetrahedron Letters (2013), doi: http://dx.doi.org/10.1016/j.tetlet.
2013.08.005
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G.Vinithra, S.Suganya and S.Velmathi*

1
Tetrahedron Letters
journal homepage: www.elsevier.com
Naked eye sensing of anions using thiourea based chemosensors with real time
application
G.Vinithra, S.Suganya and S.Velmathi*
Department of Chemistry, Organic and Polymer Synthesis Laboratory, National Institute of Technology, Tiruchirappalli-620 015, INDIA
* velmathis@nitt.edu, svelmathi@hotmail.com.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Novel chromogenic sensors with thiourea moiety as receptor unit were synthesized and
characterized using IR and NMR spectroscopic techniques. The receptors 1 and 2 bearing
hydrogen bonding site demonstrate visually striking colour change, UV-Vis, and fluorescence
-
-
responses for F-, AcO- and OH- over other anions such as Cl-, Br-, H2PO4 and HSO4 . Both the
Available online
receptors 1 and 2 demonstrate detection limit at micro molar level. Further insight to the nature
of interaction between receptors and anions was studied using H NMR titration experiment. In
particular, the fluoride of tooth paste and mouthwash in water phase can be detected by receptor
2.
1
Keywords:
Azo linked thiourea
F- and AcO- ions
Naked eye sensing
Real sample analysis
Fluorescence quenching
2009 Elsevier Ltd. All rights reserved.
Chemosensors provide a powerful method for
studying
large number of anion receptors containing the thiourea subunits
have been designed, synthesized and tested for anion recognition
and sensing during the past decades20. But simple thiourea does
not act as a visual sensor, in order to make them do so some
signaling unit or chromophore bearing group which imparts
colour change has to be tailored with thiourea moiety on either
side. Sensitivity at lower equivalent can be achieved only by
integrating thiourea moiety with bulkier group which in turn
require multistep synthesis which is very cumbersome.14,21-22
Thiourea moiety linked with simple signaling unit are also
known,23-25 however sensitivity and selectivity is achieved only
at higher equivalent. Accordingly development of simple, small,
synthetic molecule which is sensitive enough to anions at lower
amount is still a challenge. Here we have introduced thiourea
based chemosensor prepared in a one- pot synthesis method,
which can be efficiently used for sensing anions at low
concentration and further use in real sample analysis.
molecular recognition and thus they have wide application in
biological, environmental, clinical as well as industrial, chemical
processes.1-3 The development of chromogenic receptors for
anion sensing is a relatively new area of research in
supramolecular chemistry.4-5 Indeed, designing a colorimetric
anion sensor is a challenging one as it allows ‗naked eye‘
detection without the aid of sophisticated probes. Fluoride is
attracting huge interest, as it is a biologically important anion
that shows beneficial effect in human physiology such as
prevention of dental caries, treatment of osteoporosis6 etc.
Similarly acetate also plays a major role in daily life because
carboxylates are critical components in numerous metabolic
processes7 and is present in living system as acetyl coenzyme
and also used as a food additive. Initially, anion recognition was
mainly achieved by using charged host molecules, such as
protonated polyamines or azamacrocycles8 guanadinium9 or
transition metal or lanthanide ion based complexes10. More
recently, neutral receptors such as amides,11 carbamides12, urea
and thioureas13, amidoureas14 as well as pyrroles15, indoles16,
calixpyrroles17 and catechols18 have been employed as
recognition moieties for anions. The use of such versatile
synthetic functionalities has enabled the design and construction
of more refined anion receptors, which facilitates a more
effective targeting approach to anion sensing using arrays of
hydrogen bonding sites, where both the selectivity and the
sensitivity of the recognition process can be achieved19. The
motive of choosing sensor studies with receptor possessing
thiourea as binding site is to establish the fact that small
synthetic molecule could act as efficient chemosensors.
Moreover, thiourea moiety is often chosen as anion binding site
as it is a good hydrogen bond donor and forms quite stable
The chromogenic receptors 1 and 2 were prepared by simple
two-step, one- pot synthesis method and the structure was
confirmed using FTIR and NMR spectroscopy. The formation of
thiourea was confirmed from the singlet peak formed in the
1
region 12.8 and 9.4 ppm in H NMR spectrum and a band at
3394 cm-1 in IR spectrum. (For details see supporting
information).
H
H
R
N
N
N
S
O
N
R-H Receptor 1
R- NO2 Receptor 2
Figure 1. Structure of 1 and 2
complexes with anions like fluoride and acetate. Therefore, a
———
* Corresponding author. Tel.: +91-431-2503640; 91-09486067404; Fax: +91-431-2500133; E-mail: velmathis@nitt.edu

2
Tetrahedron
found to be 9.58x103, 1.96x103 and 3.02x103 respectively. The
binding constant of receptor 1 is higher than that of receptor 2,
and this indicates that nitro group in receptor 2 does not show
any influence on binding constant. Job‘s plot study revealed that
receptor 1 and 2 forms complex in the ratio 1:1 with respective
anions. Detection limits were calculated using the absorbance
obtained on incremental addition of individual anions with fixed
concentration of receptors at 2.5 x 10-5 M (Table 1).
Detection limit ( in M)
Receptor
F-
AcO-
OH-
-
1
2
5.36x10-7
2.94 x 10-5
3.43x10-6
6.58 x 10-6
5.92 x10-7
Figure 2. Color changes of receptor 1 (top) receptor 2
(bottom) in ACN (2.5 x 10-5 M) before and after the addition of
four equivalents of respective anions.
Table 1. Detection limit of various anions with receptor 1 and 2
This shows that the receptors are sensitive enough to monitor
quantity of F-, AcO- and OH- in micro molar level.
To inquest the recognition behavior of the receptors, naked
eye detection experiment was carried out by addition of
acetonitrile (ACN) solution of 1.5x10-3 M of various anions such
The emission properties of these receptors were explored to
establish if the changes in absorbance spectra could be observed
through the emission spectra, Figure 4 shows the fluorescence
spectra recorded from solutions of receptor 1 and 2 (2.5 x 10-5
M) in ACN in the presence and absence of various anions. The
free receptor 1 exhibited a band centered at 412nm (λex = 360nm)
on introducing only four equivalents of F- and AcO- ions, which
resulted in the noticeable quenching of the fluorescence
emission. In the case of receptor 2 fluorescence band with
emission maxima at 416nm quenched dramatically on addition of
F-,AcO- and OH-. The quenching is endorsed to photo induced
electron transfer (PET) mechanism27. The excited state of the
fluorophore was not quenched by electron transfer from the
receptor (thiourea group) to the fluorophore (azophenyl group),
prior to the receptor–anion interactions. However, upon
interaction with anions, electron transfer from the electron-rich
thiourea moiety bonded with the anion to the electron deficient
azophenyl signaling unit became more feasible. Upon further
addition of F- and AcO- the deprotonated species, which was
more electron-rich than the hydrogen-bonded complex with
anion, activated the PET process more efficiently and supported
more quenching. The possible mechanism is shown in Scheme 2
(supporting information). The quenching constant was calculated
from the measurement of fluorescence intensity of the receptors
both in presence and absence of F-, AcO- and OH- ions. (Table
-
-
as F-, Cl-, Br-, AcO-, HSO4 , H2PO4 , OH- (tetrabutyl ammonium
was used as the counter cation) to the solution of receptors (2.5x
10-5 M). The dramatic color change of receptor 1 from pale
yellow to intense yellow upon the addition of F- and AcO- ion
solution was clearly observed visually even on addition of four
equivalents. Similar color changes were also observed upon
introducing F-, AcO- and OH- to ACN solution of receptor 2.
Both the receptors were found to be insensitive to large excess
addition of other anions (Figure 2). The color change clearly
suggests the formation of anion complexes of receptors via
hydrogen bonding. The color change is more visible to receptor 2
than receptor 1, which specifies the presence of NO2 group as
chromogenic signaling subunit26.
The anion binding ability of receptors (2.5 x 10-5 M) in ACN
with tetrabutyl ammonium salts of various anions (1.5 x 10-3 M)
were investigated using UV-Vis titration experiment. The
electronic spectra in the absence of anions was dominated by two
bands, one at 283nm (receptor 1) and 289nm (receptor 2) which
is assigned to the excitation of π electron in the aromatic system
and another band at 350nm. Upon addition of only F- and AcO-
ions to receptor 1 resulted in the intensity of the absorbance band
at 283 nm decrease gradually with concomitant increase with red
shift in the absorbance band at 350nm(Figure 3).
2).
500
0.7
0.6
350
R1
.
R2
0.6
-
R1+F
-
400
300
200
100
0
300
250
200
150
100
50
R2+F
-
R1+Cl
0.5
-
R2+Cl
-
R1+Br
0.4
0.4
-
-
R2+ Br
-
R1+AcO
-
200l F
-
-
4
R2+ AcO
200l AcO
R1+H PO
2
0.3
0.2
0.1
-
R2+H PO
2
-
4
R1+HSO
4
-
0.2
0.0
R2+HSO
4
-
R1+OH
-
-
-
R2+OH
0l F
0l AcO
250 300 350 400 450 500 550
Wavelength(nm)
.
250 300 350 400 450 500 550
Wavelength(nm)
0
400
450
500
550
400 450 500 550 600 650
Wavelength(nm)
1.4
1.25
1.00
0.75
0.50
0.25
0.00
Wavelength(nm)
1.2
1.0
0.8
0.6
0.4
0.2
0.0
150l AcO-
0l AcO-
-
Figure 4. The fluorescence change of receptor 1 (left) and 2
(right) (2.5 x 10-5 M in ACN) upon addition of four equivalents
of respective anions (1.5 x10-3M in ACN).
200l F
-
0l F
Quenching constant
Receptor
F-
AcO-
OH-
-
250 300 350 400 450 500
Wavelength(nm)
225
300
Wavelength(nm)
375
450
1
2
6.1x103
2.120x103
Figure 3. The UV-Vis absorption spectrum of receptor 1
(top) 2 (bottom) (2.5 x 10-5 M in ACN, 3ml ) on incremental
addition of F-(left) and AcO-(right).
1.5941x104
2.4503x104
2.379x103
Table 2. Quenching constant of various anions with receptors 1
and 2
The binding constant of the anion complexes of receptor 1
and 2 were calculated using Benesi- Hildebrand (B-H) plot from
the variation in the absorbance in the region around 390-420nm.
The binding constants for F- and AcO- complexes of receptor 1
were determined to be 1.22x104 and 2.59x104 respectively,
whereas for F-, AcO- and OH- complexes of receptor 2 were
To get the insight into the binding mode of receptor 2 with F− and
AcO- ,1H NMR titration experiments were then performed in
DMSO-d6. It was found that the intensity of thiourea N–H signal
at 12.5 and 12 ppm broadens on addition till one equivalent and
disappears entirely on further addition and slight shielding in the

3
aromatic protons is also observed. These observations indicate
that the deprotonation process of thiourea N–H segments is
involved in the receptor‘s interaction with F−/AcO- through
hydrogen bonding (Figure 5). With the output of all the
spectroscopic titrations, mechanism was proposed behind the
anion sensing nature of both receptors 1, 2 (Figure 6).
of anions in real-life owing to the simplicity in the synthesis
and sensitivity towards analytes.
Acknowledgments
Authors express their thanks to DRDO (ERIP/ER/1006004/M/01/1333
dated 23-05-2011) for financial assistance in the form of a major sponsored
project
References and notes
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F.M.; Coord. Chem.Rev. 2006, 250, 3094–3177.
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1
Figure 5. Stack plot of the H NMR (300 MHz, DMSO-d6)
2006, 250, 3004–3037.
spectra of receptor 2 upon addition of 0.5, 1, 1.5 and 2
equivalents of F- (A) and AcO- (B).
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Plenum Press: New York, 1991; p 59l. (b) Kleerekoper, M.;
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2815.
X=F/OAc
Figure 6. Proposed mechanism of receptors 1, 2 with F-/AcO-
ions.
Commercially available toothpaste and mouthwash which
contain fluoride was used to investigate the efficiency of receptor
2 as real time sensor. 100mg of tooth paste was made into
solution with 5ml H2O and used for colorimetric analysis28 and
mouth wash was used as such. To our surprise on adding only
50l of toothpaste solution and mouthwash into the receptor 2
resulted in an excellent colour change (Figure 7), which was
further proved from the quenching of fluorescence and changes
in absorption spectrum (supporting information).
19. Gale, P.A.; Coord. Chem. Rev. 2001, 213, 79–128.
20. Shao, J.; Lin, H.; Lin, H. K.; Talanta. 2008, 75, 1015–1020.
21. Huang, W.; Su, H.; Li, J.; Lin, H.; Spectrochimica Acta., 2010,
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Ill Lee,Y.; Microchem J., 2013, 106, 27–33.
Figure 7. Colorimetric changes of receptor 2 with toothpaste (A)
and mouthwash (B).
Mostly, thiourea based receptors consisting of electron
withdrawing substituents such as –NO2, -Cl, -Br, are used as
anion sensor to enhance the acidity of NH unit.29 The additional
importance of azo group is that it can give positive response even
in the absence of any electron withdrawing substituent since azo
phenyl itself can act as signaling unit and enhance the acidity of
thiourea moiety. The newly developed small and azo linked thio
urea compounds fortunately showed positive response in the real
sample analysis.
28. Mahapatra, A.K.; Manna, S.K.; Sahoo, P.; Talanta. 2011, 85,
2673– 2680.
29. (a) Kim, D. W.; Kim, J.; Hwang, J.; Park, J. K.; Kim, J. S.; Bull.
Korean Chem. Soc. 2012, 33, 1159-1164. (b) Odago, M. O.;
Colabello, D. M.; Lees, A. J.; Tetrahedron. 2010, 66, 7465-7471
(c) Jose, D. A.; Kumar, D. K.; Kar, P.; Verma S.; Ghosh A.;
Ganguly, B.; Ghosh, H. N.; Das, A. Tetrahedron, 2007, 63.
12007-12014. (d) Kim, K. S.; Kang, S. Y.; Yeo, H. M.; Nam, K.
C.; Bull. Korean Chem. Soc. 2007, 28, 1815-1817.
To sum up, we have presented new colorimetric
chemosensors 1-2, which allow ―naked-eye‖ detection in a
straightforward and inexpensive manner. Further the anion
recognition via hydrogen-bonding interactions was easily
monitored by anion-complexation induced changes in UV–Vis
fluorescence and NMR spectroscopic studies. In particular, the
sensor has detected successfully fluoride of toothpaste and mouth
wash and is expected to provide useful opportunities in detection

4
Tetrahedron
Supplementary Material
General materials, methods, details for UV-Vis and fluorescent
titrations spectroscopic data are available.