A simple quinoxaline-based highly sensitive colorimetric and ratiometric sensor, selective for nickel and effective in very high dilution

Article abstract of DOI:10.1016/j.tetlet.2013.07.051

A new quinoxaline based receptor (HQNM) has been designed and synthesized which shows a remarkable color change from colorless to yellow on specific binding with nickel. The cation recognition property of the receptor is monitored by the UV-vis and ¹H NMR titrations. It is observed that the receptor shows a specific selectivity toward nickel over other interfering cations. Thus, a significant bathochromic shift in UV-vis spectrum with a sharp yellow color in 'naked-eye' makes the receptor suitable for the easy detection of nickel ion.

Full text of DOI:10.1016/j.tetlet.2013.07.051

Tetrahedron Letters 54 (2013) 5075–5077
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A simple quinoxaline-based highly sensitive colorimetric and
ratiometric sensor, selective for nickel and effective in very high
dilution
a
a
b
a
Shyamaprosad Goswami a, , Shampa Chakraborty , Sima Paul , Sandipan Halder , Annada C. Maity
⇑
a Department of Chemistry, Bengal Engineering and Science University, Shibpur, Howrah 711103, West Bengal, India
b Department of Chemistry, Indian Institute of Technology, Kanpur 208016, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A new quinoxaline based receptor (HQNM) has been designed and synthesized which shows a remark-
able color change from colorless to yellow on specific binding with nickel. The cation recognition prop-
erty of the receptor is monitored by the UV–vis and 1H NMR titrations. It is observed that the receptor
shows a specific selectivity toward nickel over other interfering cations. Thus, a significant bathochromic
shift in UV–vis spectrum with a sharp yellow color in ‘naked-eye’ makes the receptor suitable for the easy
detection of nickel ion.
Received 9 May 2013
Revised 4 July 2013
Accepted 7 July 2013
Available online 15 July 2013
Keywords:
Ó 2013 Elsevier Ltd. All rights reserved.
Metal ion sensor
Nickel ion Sensor
Quinoxaline
Ion recognition
Ratiometric
Cations play an important role in the field of supramolecular
chemistry. In this communication, we are discussing the design
and synthesis of a simple highly sensitive sensor for nickel. Nickel
is used in various industrial applications for example, in Ni–Cd bat-
teries, electroplating, rods for arc welding, pigments for paints,
ceramics, surgical and dental prostheses, catalysts for hydrogena-
tion, and as magnetic tapes of computers. Enzymes of some micro-
organisms and plants contain nickel as an active site, which makes
the metal an essential nutrient for them. Number of methods, such
as atomic absorption spectrometry (AAS), flame atomic absorption
spectrometry-electro thermal atomization (AAS-ETA),1,2 ICP-AES,
and flame photometry3 can be used for the determination of nickel.
On the other hand, it is also a toxic metal and known to cause
pneumonitis, asthma, and cancer of lungs and also cause disorder
of respiratory and central nervous system.4–9
In this Letter, we report a designed Schiff’s [1] base between the
phenyl hydrazine compound (X) and quinoxaline aldehyde10–13
and its cation binding properties were investigated by means of
UV–visible, and by ‘naked-eye’ and 1H NMR titration. The amine
was synthesized between p-nitro benzoate ester and hydrazine hy-
drate in dry methanol medium under refluxing condition by the re-
ported procedure.14a The target deep yellow imine receptor HQNM
was formed in one step by the facile Schiff’s base condensation
reaction of quinoxaline aldehyde with the yellowish amine (X) in
methanol medium (Scheme 1) and was produced in 80% yield after
recrystallization from methanol. Its molecular structure and purity
were established from different spectroscopic studies like 1H NMR,
LCMS, and FT-IR.
The binding behavior of receptor (HQNM) with different cations
was studied in CH3CN–HEPES buffer (9:1, v/v, pH 7.4) solvent. The
titration was carried out in CH3CN–HEPES buffer (9:1, v/v, pH 7.4)
at 1 Â 10À5 M concentration of receptor HQNM upon the addition
of incremental amounts from 0–200 ll of nickel chloride solution
(2 Â 10À4 M).
The UV–visible spectrum of the receptor (HQNM) is character-
ized by two bands centered at 340 and 442 nm (Fig. 1). As shown
in Figure 1, upon gradual increasing the nickel ion concentration,
the band at 340 nm gradually weakens and a new band appears
at 442 nm with an isosbestic point at 370 nm, indicating the
NH2
O
NH
CHO
N
N
N
N
O
Dry MeOH
r.t, 8h
N
+
N
H
NO2
NO2
HQNM
X
⇑
Corresponding author. Fax: +91 3326682916.
E-mail address: spgoswamical@yahoo.com (S. Goswami).
Scheme 1. Synthesis of the receptor (HQNM).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.07.051

5076
S. Goswami et al. / Tetrahedron Letters 54 (2013) 5075–5077
O2N
0.35
0.30
0.25
0.20
0.15
0.10
0.05
0.00
N
340nm
N
H
N
N
O
N
N
442nm
O
NH
NH
, MeOH
Ni
O
NiCl2.6H2O
r.t, 12 h
N
4
N
N
N
NO2
5
NO2
370nm
Scheme 2. Probable host-guest binding mode in solution phase.
0.8
0.6
0.4
0.2
0.0
250 300 350 400 450 500 550 600
wavelength(nm)
Figure 1. UV–vis absorption spectra of HQNM (1 Â 10À5 M) in CH3CN–HEPES buffer
(9:1, v/v, pH 7.4) upon titration with nickel chloride (NiCl2Á6H2O, 0.8 equiv). The
arrows show changes due to the increasing concentration of Ni2+. Inset, binding
isotherms were recorded at 250 and 600 nm with Ni2+. The solid line is global least-
squares fit to the experimental data.
formation of a new complex between the receptor (HQNM) and the
nickel cation (Fig. 1) which is also responsible for the generation of
yellow color after the addition of nickel chloride into the solution
of the receptor. Figure 1 actually indicates the change of absor-
bance with the concentration of nickel. Furthermore the sensing
ability of HQNM with nickel at different pH was investigated. At
lower pH range, the sensor HQNM has no response to nickel in
absorption spectroscopy due to protonation and at pH 7.4 the sen-
sibility of the receptor HQNM toward nickel is maximum and at
higher pH the absorbance diminishes (Supplementary data) which
may be due to the fact that the receptor HQNM is unstable at high-
er pH. This indicates that the probe may be suitable for bio-appli-
cations at the physiological pH. The free probe is highly stable
under the assay conditions. Since HQNM has an acidic hydrogen
moiety, it would act as a weak acid in acetonitrile solution. The
pKa of HQNM was determined by pH-dependent UV–vis spectral
changes. Supplementary Fig. S2 shows plots of absorbance at
340 nm as a function of pH. This sigmoidal plot allowed us to
determine the pKa value of HQNM to be 5.14.
Figure 2. (A À A0)/A0 ratios of receptor HQNM (1 Â 10À5 M) after the addition of
0.8 equiv of each of the various cations (2 Â 10À4 M) in acetonitrile. Inset: color
changes of receptor HQNM (1 Â 10À5 M) upon the addition of 0.8 equiv of each of
the different guest cations (2 Â 10À4 M).
significant influence. The color changes are most probably due to
the formation of hydrogen bonds or deprotonation of the –NH
group of receptor HQNM on the addition of nickel ion which is
shown in Scheme 2. To further explore the binding mechanism,
Job’s plot of the UV–vis titrations of Ni2+ ion with a total volume
of 2 ml was revealed. A maximum absorption was observed when
the molar fraction reached 0.67, which is indicative of a 2:1 stoichi-
ometric complexation between HQNM and Ni2+ ion for the newly
formed species. The ESI mass spectrum of a mixture of HQNM
and NiCl2.6H2O also revealed the formation of a 2:1 ligand–metal
complex through the metal coordination interaction, with a major
signal at m/z = 700.0.[possibly for (2 M+Ni)+ ions]. From the IR data
the phenomenon is also well explained by the decreasing broad-
ness of the –NH peak at 3372 cmÀ1 due to the insertion of nickel
metal in HQNM (Supplementary data).
From the UV–visible titration data it is revealed that minimum
1.47 lM of nickel can be detected by using 10 lM of receptor
HQNM using the equation DL = K Â Sb1/S, where K = 3, Sb1 is the
standard deviation of the blank solution and S is the slope of the
calibration curve14b(Supplementary data).
These hydrogen bonds or de-protonations affect the electronic
properties of the chromophore which results in a change of color
from colorless to yellow along with a new charge-transfer interac-
tion between the nickel bound –NH moieties and the electron defi-
cient nitro group.15,16 Furthermore, the strong hydrogen-bonding
After addition of 0.8 equiv of nickel chloride, it reaches a satura-
tion level. Titrations were also carried out with various cations like
Na+, K+, Cr2+, Mn2+, Cd2+, Fe2+, Fe3+, Co2+, Cu2+, Zn2+ etc as their tetra
butyl ammonium salts. Interestingly there is no obvious change
observed in the UV spectrum except with cobalt ion, which shows
slight interference (Supplementary data). There is appearance of a
small new peak at 448 nm which indicates that the receptor
(HQNM) has a slight response to cobalt ion due to the same size
of ionic radius of the two cations. The cavity of HQNM binds selec-
tively to nickel over cobalt possibly because of the size of the nickel
cation which better fits in the core of the cavity as created by the
quinoxaline moiety and the hydrazone part (Scheme 2) forming a
stable six-membered ring.
Figure 2 actually shows the selectivity for nickel over the other
cations as shown by the sky blue bar. The slight interference of co-
balt is shown by the yellow bar but it cannot be detected by naked
eye which is shown in the inset. From the experimental data, it can
be concluded that the receptor HQNM possesses high selectivity
and sensitivity toward nickel in acetonitrile-HEPES buffer (9:1, v/
v, pH 7.4) medium. The other cations except cobalt had no practical
interaction between receptor HQNM and nickel could enhance
p
0.020
0.015
0.010
0.005
0.000
0.0
0.2
0.4
0.6
0.8
1.0
Xh
Figure 3. Job’s plot diagram of receptor HQNM for Ni2+ (where Xh is the mole
fraction of host and I indicates the change of the absorbance).
D

S. Goswami et al. / Tetrahedron Letters 54 (2013) 5075–5077
5077
The selectivity of the receptor may be due to enhanced acidity
of the amide NHb of hydrazone. The selectivity here is greatly influ-
enced based on charge-charge interactions, and the involvement of
both N–H. . ..Ni bonds. The unique binding motif can find a greater
utility in the development of new cation receptors/sensors with
enhanced binding affinity and substrate specificity, which is
actively being investigated.
In conclusion, herein we report a new receptor which selec-
tively recognizes nickel cation over other interfering cations in
CH3CN–HEPES buffer (9:1, v/v, pH 7.4) solution. Its bold color
changes only after addition of nickel ion makes it an excellent
sensor for detecting nickel cation by ‘naked-eye’.
Acknowledgements
Authors thank the DST (SR/S1/0C-58/2010) (Govt. of India) and
UGC (for a fellowship to S.P.) for financial support and S.C. thanks
TCG Life Sciences Ltd (Chembiotek), Kolkata and Mr. S. Munshi of
their department for spectral help.
Supplementary data
Figure 4. Partial 1H NMR spectra (400 MHz) of HQNM in DMSO-d6 at 25 °C and
corresponding changes after the gradual addition of different equivalents of nickel
chloride from .(a) HQNM (b) HQNM+0.2 equiv Ni2+ (c) HQNM+0.5 equiv Ni2+ (d)
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2013.07.
051.
HQNM+0.8 equiv Ni2+ (e) HQNM+1.0 equiv Ni2+
.
delocalization, which was expected to reduce the energy of the
p⁄ transition and therefore accounts for the appearance of a
References and notes
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yellow color.17 A well-defined isosbestic point at 370 nm emerged
during the spectral titrations, which indicated the formation of the
stable complex with a certain stoichiometric ratio between the
receptor and the cation resulting in a new ICT (internal charge
transfer) band that appeared at 442 nm. The 2:1 stoichiometry
for the host–guest complexation was elaborated by the profile of
the intensities of the decreasing band centered at 340 nm and
increasing band at 442 nm which was also confirmed by Job’s plot
analysis (Fig. 3). The binding constant of HQNM with nickel is
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proton of hydrazide undergoes an upfield shift from
d
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