Imatinib intermediate as a two in one dual channel sensor for the recognition of Cu2+ and I- ions in aqueous media and its practical applications

Article abstract of DOI:10.1039/c4dt01516a

An imatinib intermediate, 6-methyl-N-[4-(pyridin-3-yl)pyrimidin-2-yl] benzene-1,3-diaminepyridopyrimidotoluidine (PPT-1), was developed for the colorimetric sensing of Cu²⁺ ions in aqueous solution. With Cu ²⁺, the receptor PPT-1 showed a highly selective naked-eye detectable color change from colorless to red over the seventy other tested cations. The colorimetric sensing ability of PPT-1 was successfully utilized in the preparation of test strips and supported silica for the real samples analysis to detect Cu²⁺ ions from 100% aqueous environment. Moreover, the iodide-sensing ability of receptor PPT-1 was explored among the ten examined anions.

Full text of DOI:10.1039/c4dt01516a

Dalton
Transactions
View Article Online
View Journal | View Issue
PAPER
Imatinib intermediate as a two in one dual channel
sensor for the recognition of Cu2+ and I− ions in
aqueous media and its practical applications†
Cite this: Dalton Trans., 2014, 43,
13299
Samadhan R. Patil,a Jitendra P. Nandre,a Devising Jadhav,a Shilpa Bothra,b
S. K. Sahoo,b Manisha Devi,c Chullikkattil P. Pradeep,c Pramod P. Mahulikar*a and
Umesh D. Patil*a
An imatinib intermediate, 6-methyl-N-[4-(pyridin-3-yl)pyrimidin-2-yl]benzene-1,3-diaminepyridopyrimido-
toluidine (PPT-1), was developed for the colorimetric sensing of Cu2+ ions in aqueous solution. With
Cu2+, the receptor PPT-1 showed a highly selective naked-eye detectable color change from colorless to
red over the seventy other tested cations. The colorimetric sensing ability of PPT-1 was successfully uti-
lized in the preparation of test strips and supported silica for the real samples analysis to detect Cu2+ ions
from 100% aqueous environment. Moreover, the iodide-sensing ability of receptor PPT-1 was explored
among the ten examined anions.
Received 23rd May 2014,
Accepted 7th July 2014
DOI: 10.1039/c4dt01516a
www.rsc.org/dalton
sclerosis,
lipid
metabolism
and
inflammatory
Introduction
disorders.7,8,11–13 Therefore, there is a need to develop newer
Copper, the third most abundant transition element in technologies and methods for the qualitative and quantitative
humans, plays an important role in various physiological pro- detection of copper. In the past literatures, different analytical
cesses such as hemoglobin biosynthesis, bone development, methods are developed for the detection of Cu2+, namely,
dopamine production, and nerve function regulation.1–4 Simi- inductively coupled plasma detectors, quantum-dot-based
larly, Cu2+ ions play critical role as catalytic cofactors for a assay, fluorescence anisotropy, surface-plasmon resonance
variety of metalloenzymes such as copper–zinc superoxide dis- detector, and electrochemical and fluorescent sensors14,15
mutases, lysyloxidase, cytochrome c oxidase, and tyrosinase.5–8 These technologies can detect Cu2+ ion selectively with high
Apart from the biotic significances, copper is extensively used sensitivity but need highly sophisticated expensive instrumen-
in various industrial, pharmaceuticals and agricultural pur- tation. Although fluorescent sensor can have better sensitivity
poses such as for making alloys, electrical wires, machine and selectivity with fast response, literature reports tell that
parts, batteries and fertilizers.9 Under normal condition, the the same is not well suited particularly for paramagnetic
average concentration of copper in the blood should not cations like Cu2+ due to their ability to act as fluorescent
exceed 100–150 µg dL−1, because an increased concentration quencher, which rendered low signal output. Therefore, fluo-
of copper by any means in the body can cause improper cellu- rescent sensors are sometimes less advantageous for the recog-
lar functions and progression of various diseases.10 Excess nition of Cu2+, and they give false spectrometric response.16,17
accumulation of copper in humans because of the widespread Alternatively, the absorption-based colorimetric chemosensor
utilization leads to serious detrimental effects, including neu- can be explored because of the distinct visual color change
rodegenerative diseases such as Alzheimer’s disease, Menkes with analyte due to charge transfer band for easy detection by
disease, Wilson’s disease, prion disease, amyotrophic naked-eye.
On the other hand, considerable research has been focused
on the selective recognition of anions in water for monitoring
aSchool of Chemical Sciences, North Maharashtra University, P. B. No. 80,
environmental pollution, medicinal diagnostic and the analy-
Jalgaon - 425 001, M.S., India. E-mail: mahulikarpp@rediffmail.com,
sis of biological samples.18 Among the various biologically
udpatil.nmu@gmail.com; Fax: +91-0257-2258403; Tel: +91-0257-2258431
bDepartment of Applied Chemistry, S. V. National Institute Technology,
important anions, iodide plays imperative roles in several bio-
Surat-395 007, Gujrat, India
logical activities such as thyroid gland function and neuro-
logical activity. In addition, elemental iodine has been used to
cSchool of Basic Sciences, Indian Institute of Technology, Mandi, Kamand-175005,
Himachal Pradesh, India
†Electronic supplementary information (ESI) available. See DOI: 10.1039/
synthesize drugs, fine chemicals, and dyes that can be applied
in the chemistry, biology and food disciplines.19,20 Radioactive
c4dt01516a
This journal is © The Royal Society of Chemistry 2014
Dalton Trans., 2014, 43, 13299–13306 | 13299

View Article Online
Paper
Dalton Transactions
isotope of iodine is used in medicines and also in analytical solving an accurately weighed PPT-1 in CH3CN, and then diluted to
chemistry. The iodide content of urine and milk is often 3 × 10−5 mol L−1 with CH3CN–H2O (40 : 60) mixed solvent.
required to provide information for nutritional, metabolic and
The 1H and 13C-NMR spectra were recorded on a Bruker
epidemiological studies of thyroid disorder.21,22 Due to the 400 MHz Avance II multinuclear probe NMR spectrometer at
important roles played by iodide in day to day life, there is also ambient temperature in CDCl3 with TMS as internal standard
a need for developing simple analytical method to detect and the chemical shifts were reported in ppm. The electron
iodide in aqueous system. Similar to cations, several methods spray mass spectra were recorded on a Q-TOP micromass
in literatures are available for iodide detection such as ICP-MS, (LCMS) mass spectrometer. The IR spectra were recorded on a
capillary electrophoresis and iodide-selective electrode.23,24 Perkin Elmer spectrophotometer as KBr discs and the IR
Recently, fluorescent sensors have been extensively developed bands are expressed in frequency (cm−1). Absorption spectra
with high sensitivity and selectivity for the detection of were recorded on a Perkin Elmer U 3900 Co, USA UV/Visible
iodide.25–28 However, very few colorimetric chemosensors are double beam spectrophotometer. The purity of the compound
available for the detection of iodide in aqueous system.28–30 and progress of the reaction were monitored by means of thin
Thus, there is a significant demand for the expansion of syn- layer chromatography (TLC). Pre-coated silica gel 60 F254
thetic receptors capable of selectively recognizing iodide over (Merck) on alumina plate (7 × 3 cm) was used and visualized
the other important anions in aqueous system.
by using either iodine or short UV/Visible lamp. Melting
Recently, the design and synthesis of imatinib (a derivative points, which are uncorrected, were recorded on the celsius
of 2-phenylamino-pyrimidine) derivatives has increased scale by open capillary method.
immensely due to their anticancer applications. Imatinib is
Synthesis of N-(5-amino-2-methylphenyl)-4-(3-pyridinyl)-2-
one of the largest selling anticancer drugs and tyrosine kinase pyrimidineamine (PPT-1). The receptor PPT-1 was synthesized
inhibitor and is used mostly for the treatment of chronic by adopting the known literature procedure31,37 as shown in
myeloid leukemia and gastrointestinal stromal tumors.31,32 Scheme 1. A 100 mL three-necked, round-bottomed flask
Imatinib is synthesized by a multistep synthetic pathway and equipped with a mechanical stirrer, reflux condenser, and
its synthesis goes through a series of intermediates. To date, thermometer socket was charged with N-(2-methyl-5-nitro-
there has been no report on the utilization of imatinib inter- phenyl)-4-(pyridin-3-yl)pyrimidin-2-amine (3, 0.307 g, 1 mmol)
mediates as a chemosensor. Moreover, several chemosensors [ESI†], hydrazine mono hydrate (0.154 g of 65% solution in
for recognition of Cu2+ or iodide are reported, but very few of water, 2 mmol), FeCl3 (2.1 mg, 0.013 mmol), active carbon
them are able to recognize Cu2+ and I− simultaneously in (0.02 g) and water (40 mL). The reaction mass was heated to
aqueous system (Table S1†). Herein, as a part of our ongoing about 80 °C for 6–8 h, and the reaction progress was
efforts in the field of sensing33–36 and to address the above monitored by TLC. After completion of reaction, the reaction
stated problems, we have successfully developed an imatinib mixture was cooled to room temperature. Insoluble materials
intermediate (PPT-1) for the highly selective and sensitive col- were filtered off, and the filtrate was extracted with ethyl
orimetric sensing of Cu2+ and iodide ions from 100% aqueous acetate (10 mL × 5). The combined organic layers were washed
solution. Furthermore, the receptor PPT-1 was successfully with brine and dried over anhydrous Na2SO4. The solvent was
utilized in the development of test strips and supported silica removed under reduced pressure in vacuo to obtained the
for the detection of Cu2+ ions.
product as yellow crystals (yield: 80%); m.p. 140–142 °C;
IR (cm−1) [KBr]: 3360–33 050, 2940, 2860, 1633, 1602; mass
Experimental
Materials and instrumentation
Unless otherwise stated, all the chemicals used for the syn-
thesis of PPT-1 were of AR grade and were purchased either
from S. D. Fine Chemicals or Sigma Aldrich depending on
their availability. All the solvents were of spectroscopic grade
and were used without further treatment. The aqueous stock
solutions of cations and anions of concentration 1 × 10−2
mol L−1 were prepared from their corresponding salt, i.e.
AgClO4, Al(ClO4)3·9H2O, Ba(ClO4)2, Ca(NO3)2·4H2O, Cd(ClO4)2·
H2O, Co(ClO4)2·6H2O, Cr(ClO4)3·6H2O, Fe(ClO4)2·xH2O, HgCl2,
LiBr, Mg(ClO4)2, Mn(ClO4)2·H2O, Ni(ClO4)2·6H2O, Fe(ClO4)3·H2O,
Pb(ClO4)2·3H2O, Zn(ClO4)2·6H2O, Cu(ClO4)2·6H2O, (n-Bu)4NOAc,
(n-Bu)4NBr, (n-Bu)4NCl, (n-Bu)4NClO4, (n-Bu)4NCN, (n-Bu)4NF·xH2O,
(n-Bu)4NH2PO4, (n-Bu)4NHSO4, (n-Bu)4NNO3, and (n-Bu)4NI. The
Scheme 1 Synthesis of imatinib intermediate i.e. 6-methyl-N1-(4-
stock solution of PPT-1 (1 × 10−3 mol L−1) was prepared by dis- (pyridin-3-yl)pyrimidin-2-yl)benzene-1,3-diamine (PPT-1).
13300 | Dalton Trans., 2014, 43, 13299–13306
This journal is © The Royal Society of Chemistry 2014

View Article Online
Dalton Transactions
Paper
[ESI, 70 eV] m/z (%): 279 (26), 278 (65); 1H-NMR (400 MHz, from 240 nm) and a broad peak with maxima at 358 nm
CDCl3, δ ppm): 2.07 (3H, bs, CH3), 4.87 (2H, s, NH2), 6.33–6.35 (a red-shift of 53 nm from 305 nm) appeared. The spectral
(1H, dd, J = 4 Hz, ArH), 6.79–6.80 (1H, d, J = 4 Hz, ArH), shifts accompanied with the color change clearly delineated
6.86–6.88 (1H, d, J = 8 Hz, ArH), 7.36–7.38 (1H, d, J = 12 Hz, the formation of a complex species between PPT-1 and Cu2+.
ArH), 7.53–7.56 (1H, dd, J = 4 Hz, ArH), 8.40–8.43 (1H, m, However, other cations (Ag+, Al3+, Ba2+, Ca2+, Cd2+, Co2+, Cr3+,
ArH), 8.46–8.48 (1H, d, J = 8 Hz, ArH), 8.69–8.71 (2H, m, ArH), Cu2+, Fe2+, Fe3+, Li+, Mg2+, Mn2+, Ni2+, Pb2+, Zr2+, Zn2+ and
9.25 (1H, s, NH); 13C-NMR (100 MHz, CDCl3, δ ppm): 17.1, Hg2+) showed no remarkable changes between 330 and
99.8, 103.6, 106.2, 118.3, 121.4, 129.8, 131.2, 134.6, 142.2, 400 nm. Furthermore, the competitive experiments inferred
144.3, 146.9, 147.2, 155.6, 160.8, 169.7. Anal. calcd for that the selective recognition of Cu2+ ions was slightly or not
C16H15N5: C, 69.29; H, 5.45; N, 25.25. Found: C, 69.42; H, 5.43; influenced in the presence of various interfering cations in
N, 25.14 (Fig. S1 and S2†).
100% aqueous medium (Fig. S3†).
The UV-Vis absorption titration of PPT-1 with Cu2+ was
performed to determine the various analytical parameters
such as binding ability, stoichiometry, and detection limit.
The changes in UV-Vis spectrum of PPT-1 upon successive
incremental addition of Cu2+ ions is shown in Fig. 3. Upon
addition of 1–5 equivalents of Cu2+ ions to PPT-1, the absor-
bance peaks at 223 nm and 358 nm were increased sharply
which may be attributed to the interaction of Cu2+ ions with
PPT-1. Furthermore, to determine the stoichiometry of the
formed complex between PPT-1 and Cu2+, Job’s plot (Fig. S4†)
and mole ratio plot (Fig. S5†) methods were employed and the
1 : 1 stoichiometry was found for the PPT-1·Cu2+ complex
formed in solution. To confirm the mechanism of binding of
Cu2+ with PPT-1, we carried out 1H-NMR titrations exper-
iments, in which spectra were recorded by adding incremental
amounts of copper perchlorate (0, 0.2, 0.5, 1.0 equiv.) to the
solution of PPT-1 in CDCl3. Addition of paramagnetic Cu2+
affects the NMR resonance frequency of protons, which are
close to the binding sites of the ligand. It was found that the
peak corresponding to –NH2 protons at δ = 3.641 ppm dis-
appears immediately on addition of 0.2 equivalents of Cu2+.
Furthermore, additions of Cu2+ results in overall broadening
of all the peaks of the compound (Fig. S6†). The disappearance
of peak due to –NH2 proton on addition of 0.2 equivalents of
Cu2+ confirms the deprotonation and binding of PPT-1 with
copper. The broadening of peaks on addition of more
amounts of copper is expected due to the paramagnetic nature
of Cu2+. A more direct evidence for the formation of 1 : 1
complex of PPT-1 with Cu2+ is obtained from the HR-MS analy-
sis of a mixture of PPT-1 and copper perchlorate in acetonitrile
(Fig. S7†). A MS peak observed at 414.6850 (calc. = 414.0388)
corresponds to [(PPT-1-2H + Cu)·2H2O + K + H]. Furthermore,
the binding or association constant for the complexation of
PPT-1 and Cu2+ was obtained from Benesi–Hildebrand plot
Computational study
The structural optimization of PPT-1 and its host–guest com-
plexes with the Cu2+ and I− was performed using the computer
program Gaussian 09W38 by applying the density functional
theory (DFT) method. All the DFT calculations were performed
in the gas phase with a hybrid functional B3LYP (Becke’s three
parameter hybrid functional using the LYP correlation func-
tional) using the basis sets 6-31G(d,p) for C, H, N atoms and
LANL2DZ for Cu, I atoms.
Results and discussion
Sensing of Cu2+ by PPT-1
The selective and sensitive detection of Cu2+ ions in water can
be seen from the observed color change of PPT-1 solution
from colorless to dark red (Fig. 1). To perform these naked-eye
experiments, 5 equivalents of various cations (30 µL, 1 ×
10−2 M, in H2O) including Cu2+ ions were added to the solu-
tion of PPT-1 (2 mL, 3 × 10−5 M) in CH3CN–H2O (40 : 60, v/v).
No significant color change was observed with other cations,
which reflects the ability of PPT-1 to recognize Cu2+ ions selec-
tively from aqueous solutions.
The UV-Vis absorption spectra were recorded to gain more
insight into the chemosensing mechanism and binding behav-
ior of PPT-1 towards different metal cations (Fig. 2). The recep-
tor PPT-1 exhibited three peaks at 240, 270 and 305 nm in
CH3CN–H2O (40 : 60, v/v). The peaks at 240 nm and 270 nm
were assigned due to the π→π* electronic transition whereas
the maxima at 305 nm appeared due to the n→σ* or n→π*
transition. Upon addition of Cu2+ ions (30 µL, 1 × 10−2, in
H2O) to the PPT-1 solution (2 mL, 3 × 10−5 M) in CH3CN–H2O
(40 : 60, v/v), two new peaks at 223 nm (a blue-shift of 17 nm
Fig. 1 Naked-eye detection of Cu2+ ion by PPT-1 in the presence of other metal cations under visible or sunlight.
This journal is © The Royal Society of Chemistry 2014
Dalton Trans., 2014, 43, 13299–13306 | 13301

View Article Online
Paper
Dalton Transactions
Fig. 2 Absorption spectra of PPT-1 (3 × 10−5 M) in CH3CN–H2O (40 : 60, v/v) upon addition of 5 equivalents of various metal cations (1 × 10−2 M,
in H2O).
Fig. 3 UV-Vis absorption titration spectra of PPT-1 (3 × 10−5 M) in
CH3CN–H2O (40 : 60) with the addition of 1–5 equivalents of Cu2+ ions
(1 × 10−3 M, in H2O).
Fig. 4 Benesi–Hildebrand plot of 1/[ΔA] against 1/[Cu2+].
analysis by using the absorption titration experiments based
on 1 : 1 binding model (Fig. 4), and it was found to be 5171 M−1
.
The limit of detection (LOD) and limit of quantification
(LOQ) of the receptor PPT-1 was calculated for Cu2+ ions.
To calculate the relative standard deviation, the absorption
measurements of ten blank samples were taken. The cali-
bration curves (absorbance vs. [Cu2+]) were plotted (Fig. S8†),
and then the obtained slope was used to calculate LOD and
LOQ values. According to the IUPAC definition, the LOD and
LOQ was calculated using the standard relationship i.e. LOD =
(3.3 × standard deviation)/slope and LOQ = (10 × standard devi-
ation)/slope. The calculated LOD and LOQ values of PPT-1 for
Cu2+ ions are 0.54 µM and 1.6 µM, respectively. These observed
LOD and LOQ limits are far superior to the allowed limit of
Cu2+ for human beings.
Fig. 5 Practical application of PPT-1 for detection of Cu2+ by test
strip method.
The desired test strips were prepared by soaking small strips of
cellulose paper (Whatman) in the solution of PPT-1 (1 × 10−2
M) in acetonitrile and dried in air. When the strip was dipped
in aqueous solution of Cu2+ (1 × 10−3 M), the colorless strips
sharply turned into dark brown color (Fig. 5 and ESI video†).
Analytical applications of PPT-1
In order to ensure the analytical applicability for the detection
of Cu2+, PPT-1 loaded test strips and silica gel were prepared.
13302 | Dalton Trans., 2014, 43, 13299–13306
This journal is © The Royal Society of Chemistry 2014

View Article Online
Dalton Transactions
Paper
Fig. 6 Practical application of PPT-1 for detection of Cu2+ by silica
support method.
Fig. 8 UV-Vis spectral titration of PPT-1 (3 × 10−5 M) in CH3CN–H2O
(40 : 60) upon incremental addition of 1–5 equivalents of iodide
(1 × 10−3 M, in H2O). Inset: Mole ratio plot/change in absorption spectra
(ΔA) as a function of mole equivalents of I− ions.
The rapid color change of the test strip in solution clearly
inferred the practical application of PPT-1 for the qualitative
detection of Cu2+ in aqueous medium.
addition of I− ions to the solution of PPT-1, a new intense
absorption band at 232 nm was observed. Furthermore, the
selective and sensitive detection of I− in the presence of other
competing anions from aqueous solutions was also free from
the interference of the other anions (Fig. S8†). The above
results clearly indicate that the receptor PPT-1 recognizes
I− selectively over other anions.
Moreover, the qualitative recognition of Cu2+ by PPT-1 was
worked on a solid support (Fig. 6 and ESI video†). The silica
gel (60–120 mesh, 10 g, colorless) was first treated with PPT-1
(in methanol, 50 mL, 1 × 10−2 M), and then dried to get a sig-
nificantly faint yellow color silica gel loaded with the receptor
on the surface. When it was treated with 10 mL aqueous solu-
tion of Cu2+ (A = 1 × 10−3 M, B = 1 × 10−4 M, D = 1 × 10−5 M,
E = 1 × 10−6 M), the faint yellow color promptly turned to a
dark brown color (ESI video†), whereas in bottle ‘C’, the
untreated silica was added into the aqueous solution of Cu2+
ions (1 × 10−2 M). The prompt color change of the solid silica
gel was observed only in the presence of silica loaded with
PPT-1, which clearly inferred the practical application of PPT-1
for the qualitative detection of Cu2+ in aqueous medium.
The recognition profile and mode of binding of PPT-1 with
I− was illustrated by performing the absorption titration exper-
iments. Upon continuous addition of I− (1 × 10−3 M, in H2O)
from 1–5 equivalents to the solution of PPT-1 in CH3CN–H2O
(40 : 60, v/v), the intensity of the band at 232 nm was success-
fully enhanced due to the formation of pseudo cavity of comp-
lementary size by PPT-1 to make electrostatic and/or hydrogen
bonding with I− (Fig. 8). To confirm the mechanism of
binding of PPT-1 with I−, we carried out 1H-NMR titration
experiments, in which spectra were recorded by adding varying
equivalents of tetrabutylammonium iodide (0, 0.2, 1.0, 4.0,
6.0) to the solution of PPT-1 in CDCl3. It was found that the
peak corresponding to –NH2 protons at δ = 3.641 ppm under-
goes broadening accompanied by a small shift to δ =
3.651 ppm (Fig. S10†). The broadening of the peak suggests
that the I− sensing is mainly due to hydrogen bonding. To
confirm the stoichiometry of binding, we carried out HR-MS
studies on acetonitrile solutions of PPT-1 in presence of I−
anions. Observation of a MS peak at 980.6509 (calc. 980.4284),
corresponding to the species [2(PPT-1) + I + TBA + K + H2O],
confirms the 2 : 1 binding stoichiometry (Fig. S11†). To get
further comprehension concerning the binding stoichiometry,
Job’s plot and mole ratio plot methods were employed. The
Job’s plot (Fig. S12†) and mole ratio plot (Fig. 8, inset) clearly
delineated the formation of host–guest complex between
PPT-1 and iodide in 2 : 1 binding stoichiometry. The associ-
ation constant or binding constant for the complexation of
PPT-1·I− was calculated from Benesi–Hildebrand plot (Fig. 9)
and was found to be 5687 M−1. This high value of binding con-
stant designates the strong binding interactions between
PPT-1 and I−. In order to check the applicability of receptor
Sensing of I− by PPT-1
The binding profiles of PPT-1 toward various anions were
investigated by UV-Vis absorption spectroscopy. Except I−, the
introduction of various anions of concentration 1 × 10−2 M in
water did not cause any significant change in the absorption
profile of PPT-1 in CH3CN–H2O (40 : 60, v/v) (Fig. 7). Upon
Fig. 7 UV-Vis spectral changes of PPT-1 (3 × 10−5 M) in CH3CN–H2O
(40 : 60) upon addition of 5 equivalents of TBA salts of different anions
(1 × 10−2 M, in H2O).
This journal is © The Royal Society of Chemistry 2014
Dalton Trans., 2014, 43, 13299–13306 | 13303

View Article Online
Paper
Dalton Transactions
lowered respectively by −322.91 kcal mol−1 and −9.49 kcal mol−1
,
which indicates the formation of stable complexes. The recep-
tor PPT-1 organized itself by a slight molecular twist to encap-
sulate Cu2+ preferably through the pyridine-N and amine-N
atoms. Since the ICT band in PPT-1 originates from the elec-
tron donation from HOMO, localized on the pyrimidine,
amino and sp2-nitrogen substituents to the LUMO, localized
on the pyridine ring (Fig. 11), the considerable perturbation in
this band on the addition of Cu2+ can be ascribed to the stabil-
ization of LUMO and a consequent decrease in the energy gap
between HOMO and LUMO. The lowering of energy gap
resulted in the observed bathochromic or red-shift of 53 nm in
the ICT band and consequently the perceptible change in
color from colorless to dark red. On the other hand, the
protons at the amine groups (–NH2 and –NH–) can act as both
hydrogen bond donor and acceptor, which makes an interest-
ing combination for the recognition of iodide anion. The ana-
lysis of the molecular electrostatic potential (MEP) map of
PPT-1 (Fig. 10b) also indicates that the two most positive
regions shown in blue color are located above the amine
protons. On interaction with iodide ion, molecular-twist was
observed in the PPT-1 molecules, which created a pseudo cavity
of complementary size to encapsulate iodide ion through
multiple weak intermolecular hydrogen bonds. Furthermore,
the HOMO and LUMO diagrams of PPT-1 and (PPT-1)2·I− indi-
cate the internal charge transfer occurred during the iodide rec-
ognition between the receptor and iodide ions (Fig. 11).
Fig. 9 Benesi–Hildebrand plot of 1/[ΔA] against 1/[I−] for binding constant.
PPT-1, we have calculated the detection limit and quantifi-
cation limit for I− ions. From the straight line regression
obtained by the graph plotted between absorbance vs. concen-
tration of I− ions (Fig. S13†), the estimated limit of detection
(LOD) and limit of quantification (LOQ) for I− was found to be
0.22 µM and 6.7 µM, respectively.
Theoretical results
The structural optimization of the receptor PPT-1 and its
PPT-1·Cu2+/I− complexes along with the intermolecular charge
transfer (ICT) process that occurred during the encapsulation
of analytes (Cu2+ and I−) by PPT-1 was investigated in the gas
phase by applying the exchange-correlation function B3LYP,
and the basis sets 6-31G(d,p) (for C, H and N atoms) and
LANL2DZ (for Cu and I atoms). The optimized structure of the
receptor PPT-1 and its PPT-1·Cu2+/I− complexes was shown in
Conclusion
Fig. 10. On complexation of PPT-1 with Cu2+ and I−, the calcu- In summary, we have successfully developed an imatinib inter-
lated interaction energy (Eint = Ecomplex − Ereceptor − ECu2+ ) was mediate PPT-1 as a chemosensor for the recognition of Cu2+
/I−
Fig. 10 DFT computed optimized structure of the receptor (a) PPT-1 with its (b) molecular electrostatic potential (MEP), (c) PPT-1·Cu2+ and
(d) (PPT-1)2·I in the gas phase.
13304 | Dalton Trans., 2014, 43, 13299–13306
This journal is © The Royal Society of Chemistry 2014

View Article Online
Dalton Transactions
Paper
Fig. 11 DFT computed LUMO and HOMO diagrams of (a) receptor PPT-1, (c) alpha and (b) beta orbitals of PPT-1·Cu2+, and (d) (PPT-1)2·I in the
gas phase.
and I− from 100% aqueous media with high selectivity and
sensitivity.
5 Handbook of metalloproteins, ed. A. Messerschmidt,
R. Huber, T. Poulos and K. Weighardt, John Wiley & Sons,
Chichester, 2001, vol. 2, pp. 1149–1413.
6 K. D. Karlin, Science, 1993, 261, 701–708.
7 B. Halliwell and J. M. C. Gutteridge, Biochem. J., 1984, 219,
1–14.
8 M. C. Linderand and M. Hazegh-Azam, Am. J. Clin. Nutr.,
1996, 63, 797S–811S.
9 A. K. Jain, R. K. Singh, S. Jain and J. Raisoni, Transition
Met. Chem., 2008, 33, 243–249.
The recognition of Cu2+ was confirmed by remarkable color
change from colorless to dark red with the appearance of a
new charge transfer band. The remarkable colorimetric
sensing of PPT-1 confirmed a 1 : 1 (PPT-1·Cu2+) binding model
with the detection limit down to 0.54 µM. Moreover, PPT-1 can
be applied to detect Cu2+ in the aqueous media by naked-eye
using test strip and silica support methods, whereas, the
iodide ions did not bring any color change of PPT-1, but
resulted a remarkable spectroscopic response by giving a new 10 W. T. Tak and S. C. Yoon, Korean J. Nephrol., 2001, 20, 863–
intense peak in the absorption spectrum at 232 nm. With 871.
PPT-1, the iodide ions can be detected up to 0.22 µM in 11 K. J. Barnham, C. L. Masters and A. I. Bush, Nat. Rev. Drug
aqueous solution. The good selectivity of chemosensor PPT-1 Discovery, 2004, 3, 205–214.
for the detection of Cu2+ and I− from pure aqueous medium 12 E. Gaggelli, H. Kozlowski, D. Valensinand and G. Valensin,
can open new doors for many practical applications in chemi-
cal, environmental and biological systems.
Chem. Rev., 2006, 106, 1995–2044.
13 E. Madsen and J. D. Gitlin, Annu. Rev. Neurosci., 2007, 30,
317–337.
14 N. Shao, J. Y. Jin, H. Wang, Y. Zhang, R. H. Yang and
W. H. Chan, Anal. Chem., 2008, 80, 3466–3475.
15 L. Zhang, L. Shangand and S. Dong, Electrochem. Commun.,
2008, 10, 1452–1454.
Acknowledgements
16 L. Yang, Q. Song, K. Damit-Og and H. Cao, Sens. Actuators,
B, 2013, 176, 181–185.
17 C. Yu, L. Chen, J. Zhang, J. Li, P. Liu, W. Wang and B. Yan,
Talanta, 2011, 85, 1627–1633.
18 M. E. Moragues, R. Martinez-Manez and F. Sancenón,
Chem. Soc. Rev., 2011, 40, 2593–2643.
SRP is thankful to DST, New Delhi, India, for financial assist-
ant under INSPIRE fellowship scheme and Dr UDP is grateful
for the financial support from the DST, New Delhi, India,
under FAST TRACK scheme for Young Scientists (Reg. no.
CS-088/2013).
19 M. Vetrichelvan, R. Nagarajan and S. Valiyaveettil, Macro-
molecules, 2006, 39, 8303–8310.
20 H. Kim and J. Kang, Tetrahedron Lett., 2005, 46, 5443–5445.
21 M. Haldimann, B. Zimmerli, C. Als and H. Gerber, Clin.
Chem., 1998, 44, 817–824, and references therein.
22 F. Jalali, M. J. Rajabi, G. Bahrami and M. Shamsipur, Anal.
Sci., 2005, 21, 1533–1537.
Notes and references
1 E. Gaggelli, H. Kozlowski, D. Valensin and G. Valensin,
Chem. Rev., 2006, 106, 1995–2044.
2 E. D. Harris, J. Trace Elem. Exp. Med., 2001, 14, 207–210.
3 C. Andreini, L. Banci, I. Bertini and A. Rosato, J. Proteome
Res., 2008, 7, 209–216.
23 S. Chandra, K. S. Lokesh and H. Lang, Sens. Actuators, B,
2009, 137, 350–356.
24 K. Ito, T. Ichihara, H. Zhuo, K. Kumamoto, A. R. Timerbaev
and T. Hirokawa, Anal. Chim. Acta, 2003, 497, 67–74.
4 E. L. Que, D. W. Domaille and C. J. Chang, Chem. Rev.,
2008, 108, 1517–1549.
This journal is © The Royal Society of Chemistry 2014
Dalton Trans., 2014, 43, 13299–13306 | 13305

View Article Online
Paper
Dalton Transactions
25 N. Singh, H. J. Jung and D. O. Jang, Tetrahedron Lett., 2009, 36 A. K. Gupta, A. Dhir and C. P. Pradeep, Dalton Trans., 2013,
50, 71–74.
42, 12819–12823.
26 K. Ghosh and T. Sen, Tetrahedron Lett., 2008, 49, 7204–7208.
27 K. R. Rathikrishnan, V. K. Indirapriyadharshini,
37 K. A. Kalesh, D. S. B. Sim, J. Wang, K. Liu, Q. Lin and
S. Q. Yao, Chem. Commun., 2010, 46, 1118–1120.
S. Ramakrishna and R. Murugan, Tetrahedron, 2011, 67, 38 H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman,
4025–4030.
G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson,
H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian,
A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg,
M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa,
M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai,
T. Vreven, J. A. Montgomery Jr., J. E. Peralta, F. Ogliaro,
M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin,
V. N. Staroverov, R. Kobayashi, J. Normand,
K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar,
J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene,
J. E. Knox, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo,
R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin,
R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin,
K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador,
J. J. Dannenberg, S. Dapprich, A. D. Daniels, Ö. Farkas,
J. B. Foresman, J. V. Ortiz, J. Cioslowskiand and D. J. Fox,
GAUSSIAN 09 (Revision A.1), Gaussian, Inc., Wallingford,
CT, 2009.
28 Y. Zhao, L. Yao, M. Zhang and Y. Ma, Talanta, 2012, 97,
343–348.
29 K. Ghosh and I. Saha, Supramol. Chem., 2010, 22, 311–317.
30 J.-H. Choi, I.-H. Ahn, J. L. Sessler and D.-G. Cho, Supramol.
Chem., 2011, 23, 283–286.
31 Y.-F. Liu, C.-L. Wang, Y.-J. Bai, N. Han, J.-P. Jiao and
X.-L. Qi, Org. Process Res. Dev., 2008, 12, 490–495.
32 H. Liu, W. Xia, Y. Luo and W. Lu, Monatsh. Chem., 2010,
141, 907–911.
33 J. Nandre, S. Patil, V. Patil, F. Yu, L. Chen, S. Sahoo,
T. Prior, C. Redshawd, P. Mahulikar and U. Patil, Biosens.
Bioelectron., 2014, 61, 612–617.
34 A. S. Kuwar, U. A. Fegade, K. C. Tayade, U. D. Patil,
H. Puschmann, V. V. Gite, D. S. Dalal and R. S. Bendre,
J. Fluoresc., 2013, 23, 859–864.
35 S. K. Sahoo, D. Sharma, R. K. Bera, G. Crisponi and
J. F. Callan, Chem. Soc. Rev., 2012, 41, 7195–7227.
13306 | Dalton Trans., 2014, 43, 13299–13306
This journal is © The Royal Society of Chemistry 2014