Diphenylether based derivatives as Fe(iii) chemosensors: Spectrofluorimetry, electrochemical and theoretical studies

Article abstract of DOI:10.1039/c5ra00969c

4-(2,4-Dinitrophenoxy)-3-methoxybenzaldehyde (DPE-I) and (4-(2,4-dinitrophenoxy)-3-methoxyphenyl)methanol (DPE-II) were synthesized with high yield and characterized by spectroscopic techniques. The complexation behaviours of DPE-I and DPE-II for various

Full text of DOI:10.1039/c5ra00969c

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Diphenylether based derivatives as Fe (III) chemosensors:
Spectrofluorimetry, Electrochemical and Theoretical studies
Rashmi Sharma, Manmohan Chhibber*, Susheel K Mittal
Thapar University, Patiala, India-147004.
E-mail:mchhibber@thapar.edu
Abstract
4-(2,4-dinitrophenoxy)-3-methoxybenzaldehyde (DPE-I) and (4-(2,4-dinitrophenoxy)-3-
methoxyphenyl)methanol (DPE-II) were synthesized with high yield and characterized by
spectroscopic techniques. The complexation behaviours of DPE-I and DPE-II for various
cationic species (Na+, K+, Mg2+, Cu2+, Ba2+, Cr3+, Fe3+, Co2+, Ni2+, Zn2+, Cd2+, and Pb2+) in
HEPES buffered CH3CN: H2O system were investigated and compared by spectroscopic and
voltammetric techniques. Both receptors showed high degree of selectivity for Fe3+ over
other cations. Receptors showed 1:1 complexation with Fe3+. DPE-I showed fluorescence
quenching on complexation with Fe3+ ion at 350nm due to PET (photon induced transfer)
mechanism between Fe3+ and the large π electron conjugate system of ligand, while DPE-II
displayed emission band at 314 nm which underwent fluorescence quenching selectively on
gradual addition of Fe3+ at 314nm and simultaneously a new band at 424 nm emerged with
isobestic point at 355 nm which increases with increase in Fe3+ conc. Electrochemically,
DPE-I due to presence of electron withdrawing (aldehydic group) facilitates reduction of
nitro group on benzene ring of the molecule so, peak potentials of the two curves obtained for
DPE-I appear at -1.16 V (Epc1) and -1.39 V (Epc2) respectively, while in DPE-II (methanolic
group) due to its electron donating character makes the reduction of nitro group a little
difficult due to which peak potentials occur at higher potential as compared to DPE-I i.e. at -
1.30 V (Epc1) and -1.43 V(Epc2) respectively.
Introduction
Synthesizing sensitive and selective chemosensor for specific metal detection is an interesting
topic due to challenges in molecular design and their applications in a number of research
fields [1–4]. Ionophores with functional groups like carboxylate [5,6], sulfonate [7,8],
phosphonate [9–11], carbohydrate [12,13] and ammonium [14–16] can selectively trap
metals ions. However, none of the attempts has been made to use diphenylether based

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receptor having (R-O-R) ethereal linkage for metal detection. This is our first report using
diphenylether based receptors for detection of iron.
Iron plays a significant role in many biochemical processes [17, 18] and is an important metal
ion for most organisms. Fe3+ acts as a cofactor in many enzymatic reactions involved in the
mitochondrial respiratory chain, and both its deficiency and excess can induce a variety of
diseases [18–20]. A surplus of iron induces oxidative damage, rendering the intracellular
scavenging of iron a major therapeutic target [21]. Therefore, methods of ferric ion detection
have received a great deal of study. However, in spite of the important role of Fe3+ in
chemical and biological processes, selective and sensitive chemosensors for Fe3+ are still rare.
In the past few years, several analytical techniques for the determination of trace amounts of
Fe3+ have been reported, including atomic absorption spectrometry (AAS) [22], inductively
coupled plasma-atomic emission spectrometry (ICP-AES) [23], inductively coupled plasma-
mass spectrometry (ICP-MS) [24], electrochemical methods [25, 26] etc. Although these
methods offer good limits of detection and wide linear ranges, most of these require the use
of expensive and sophisticated instrumentation and complicated pretreatment procedures, not
inappropriate for on-line or in-field monitoring. Owing to their advantages of simple
equipment, rapid response, high sensitivity and easy operation, fluorescent approaches have
been developed for the determination of Fe3+. Currently, there have been a lot of
developments in the field of Fe3+ chemosensors which have been used as fluorescent probes
[27–41]. A comparative study of the chemosensors for Fe3+ has been shown in Table S1 [42,
7, 3, 43 and 44]. However, many of these probes exhibit either one or two of the following
features that limit their practical applications. Firstly, most of the reported Fe3+ probes cannot
work in aqueous media due to their hydrophobicity and low binding affinity. Secondly, most
of these have interference problems caused by other transition metal cations such as Cu2+,
Co2+, Al3+ or Hg2+. Therefore, searching for highly selective chemosensors for Fe3+ in
aqueous solutions is of great importance.
With purely organic hosts, appropriate geometry can sometimes be a problem for a proper
host–guest interaction. On the other hand, metal ions can profitably orient the ligands in right
conformations so that their hydrogen bond donor groups can converge towards an external
guest. So, in this report, we have developed widespread diphenylether based chemosensors
which get oriented in proper conformation to best fit the Fe3+ and hence can be used in
various fields of analysis, as it can be used as a fluorescent chemosensor as well as

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electrochemical chemosensor. In this manuscript, complexation behavior of DPE-1 and
DPE-II with various cations (Na+, K+, Cr3+, Fe3+, Co2+, Ni2+, Cu2+, Zn2+, Ba2+, Hg2+,Cd2+ and
Pb2+) were investigated in aqueous media by spectrophotometric and voltammetric methods
and the binding mode was further studied by using Gauss View 4.1.2 software.
Material and instrumental methods
Reagents and measurements
All reagents were purchased from commercial suppliers and used without further purification.
Acetonitrile was distilled and was stored on molecular sieves before use. TLC analyses were
performed on silica gel plates and column chromatography was conducted over silica gel
1
(mesh 100–120). H NMR spectra were recorded using JEOL A1 spectrometer operating at
400 MHz. 13C NMR sepctra was recorded at 100 MHz. All chemical shifts are reported in
ppm relative to the TMS as an internal reference. UV-Vis studies were carried out on a
Analytic Jena machine using slit width of 1.0 cm and matched quartz cells. Fluorescence
spectra were determined on a Perkin Elmer LS-55 fluorescence spectrometer.
Electrochemical measurements were carried out on Gamry Potentiostat/Galvanostat/ZRA
Interface 1000. Solvents (acetonitrile, dichloromethane, dimethyl formamide) used in the
spectrophotometric and electrochemical experiments were of HPLC grade (Sd Fine, India)
and used as obtained. For cation interaction investigation, nitrate (Loba Chemie, India) and
perchlorate salts (Sigma Aldrich) of the metal were used. Tetrabutylammonium
hexaflouorophosphate (Sigma Aldrich) was used as a supporting electrolyte in all the
voltammetric experiments. The working electrode was a glassy carbon electrode (CH
Instruments, USA, 2 mm diameter). Platinum electrode was used as a counter electrode. All
the potentials were reported against Ag/Ag+ reference electrode. The Ag/Ag+ electrode
contained an internal solution of 0.01M AgNO3 and 0.1M TBAPF6 in solvents like
acetonitrile, dimethyl formamide and dichloromethane. The working GC electrode was
polished with alumina followed by washing with water and solvent before each cyclic
voltammogram. The electrochemical measurements were carried out at a temperature of 25.0º
1º C. In all experiments, the test solutions were de-aerated by a stream of N2 gas purging
through the solution for at least 4-5 minutes.
Further, theoretical studies were performed by using Gauss View 4.1.2 software to know the
binding mode of selective metal ion. For metal ion titrations, the solutions were prepared in

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CH3CN:H2O (9:1, v/v) containing 10 mM HEPES buffer. Stock solution of DPE-I and DPE-
II (10-3 M) were prepared in CH3CN.
Synthesis
Compounds were synthesized as shown in Scheme 1 according to methods described in the
literature [45]. Synthesized compounds were confirmed for their purity by melting point,
1
TLC, H and 13C NMR spectroscopy which was in accordance with the previously reported
literature (Figure S1 and S2).
Preparation of metal-ligand complexes
The binding ability studies of DPE-I and DPE-II were carried out with different metal ions
viz. Na+, K+, Cr3+, Fe3+, Co2+, Ni2+, Cu2+, Zn2+, Ba2+, Hg2+,Cd2+ and Pb2+ using spectroscopic
and voltammetric experiments. DPE-I and DPE-II were taken in ACN: H2O (9:1) medium.
The solvent medium was prepared by taking 10mM of HEPES buffer to maintain pH = 7.
Ligands DPE-I and DPE-II were taken in 20µM amounts to which 50 equivalents of each
metal was added separately to prepare the metal-ligand complex solutions at 25 ºC. Those
solutions of each metal with ligands were subjected to different studies on
spectrophotometry, spectroflorimetry and voltammetry. Each study was conducted within 5
minutes of preparation of each metal-ligand complex.
OH
F
K2CO3
NO2
OCH3
OCH3
O2N
O
+
18-C-6, DMF
O2N
CHO
CHO
NO2
DPE-I
NO2
OCH3
NO2
OCH3
NaBH4
MeOH
O
O
O2N
CHO
O2N
CH2OH
DPE-II
Scheme 1. Synthesis procedure of DPE-I and DPE-II compounds.

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Results and discussion
UV-Vis studies
The UV-Vis spectroscopic studies of receptors DPE-I and DPE-II (20 µM) were investigated
in HEPES buffered CH3CN:H2O (9:1; v/v) solvent system at pH 7.0 0.1 because the pure
CH3CN solvent developed turbidity with receptors. DPE-I showed an absorption band at 240
nm while DPE-II showed an absorption band at 280 nm due to n→π* transition. On the
addition of different metal ions, viz. Na+, K+, Cr3+, Fe3+, Co2+, Ni2+, Cu2+, Zn2+, Ba2+,
Hg2+,Cd2+ and Pb2+ to solutions of DPE-I and DPE-II, no significant changes in their
respective UV-Vis spectra were observed except in the case of Fe3+ ions as shown in Figure
S3. In order to evaluate the complete structural behaviour of DPE-I and DPE-II towards Fe3+,
titrations of DPE-I and DPE-II were performed with different concentrations of the metal ion.
On the addition of 17 equivalents of Fe3+ to the solution of DPE I (Figure 1a), the absorption
band at 240 nm gets flattened. A new band appears at 385 nm at 18 equivalents of Fe3+. On
further addition of iron solution there was an increase in absorption intensity at 385 nm which
attains a saturation point after 46 equivalents. Similarly, for DPE-II, the absorption band at
280 nm gets flattened on the addition of 11 equivalents of Fe3+, and a new band appears at
360 nm at 14.5 equivalents. On further addition of iron solution there was an increase in the
absorption intensity of the band at 360 nm which attains a saturation point after 26.5
equivalents of Fe3+ as shown in Figure 1b. The absorption ratio at (240nm/385nm) two
wavelengths varied from 0.03987 to 1.34262, indicating 33.67 fold absorption ratio changes
for DPE-I while for DPE-II absorption ratio at two wavelengths (280nm/360nm) varied from
0.07597 to 0.96272, indicating 12.67 fold absorption ratio changes. Appearance of new bands
at 385 nm and 360 nm, respectively for DPE-I and DPE-II on addition of Fe3+ (17
equivalents) indicate formation of the corresponding complexes. Further addition of Fe3+ ions
resulting in increase in absorbance is due to the increase in concentration of the resulting
metal-ligand complexes.
Thus, these chemo sensors can be used to estimate a wide range of Fe3+ ions ratio metrically
between concentrations of 2 × 10-5 to 1 × 10-3 M and 2 × 10-5 to 6 × 10-4 M for DPE-I and
DPE-II respectively, as shown in Figures 2a and 2b. The lower detection limit and stability
constants for the complexes are shown in Table-1.

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Table 1
Stability constants and some parameters of the DPE –I and DPE-II in the presence of Fe3+ in
HEPES buffered CH3CN:H20 system
Complex
Coefficient of
regression (R2)
0.999
Stability constant
Detection limit
DPE-I+Fe3+
DPE-II+Fe3+
1.3 × 103 M-1
3.0 × 103 M-1
4.23 × 10-4 M
2.93 × 10-4 M
0.998
Figure 1 Absorption spectra of (a) DPE- I (20 µM) and (b) DPE- II (20 µM) at pH 7.0 0.1
(10 mM HEPES in CH3CN: H2O 9: 1, v: v) upon complexation with increasing
concentration of Fe3+ ions
Figure 2 Ratiometric response of different concentrations of Fe3+ ions on (a) DPE-I (20 µM)
and (b) DPE-II (20 µM) at pH 7.0 0.1 (10 mM HEPES in CH3CN: H2O 9: 1, v: v).
To study practical applicability of DPE-I and DPE-II, competitive experiments were carried
out in the presence of 10 equivalents of Fe3+ ions mixed with 50 equivalents of each of the
different metal ions. No significant variations in the absorption spectra were observed in the

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presence of a number of interfering metal ions like Na+, K+, Cr3+, Fe3+, Ni2+, Cu2+, Zn2+, Ba2+,
and Pb2+. Similar behaviour was observed for DPE-I and DPE-II compounds (Figure 3a, 3b).
Figure 3 Black bars represent selectivity of (a) DPE-I and (b) DPE-II upon addition of
different metal ions at pH 7.0 0.1 (10 mM HEPES in CH3CN: H2O 9: 1, v: v) and red bars
show the competitive selectivity of ligands in the presence of interfering metal ions
Emission properties of receptors
To obtain an insight into the fluorescent properties of the receptor, DPE-I was excited at 240
nm and displayed emission band at 350 nm. Further, complexation with different metal ions
such as Na+, K+, Cr3+, Fe3+, Co2+, Ni2+, Cu2+, Zn2+, Ba2+, Hg2+,Cd2+ and Pb2+ in CH3CN: H20
(9:1, v/v) were studied, which underwent fluorescence quenching selectively on addition of
Fe3+, whereas other metal ions did not show any significant change. While DPE-II was
excited at 280 nm which displayed emission band at 314 nm which underwent fluorescence
quenching selectively on gradual addition of Fe3+. Simultaneous to the quenching process a
new band at 424 nm emerged with isobestic point at 355 nm. The emission at 424 nm
increases with increase in Fe3+ conc., whereas other metal ions did not show any significant
change. In order to evaluate the complete structural behaviour of DPE-I and DPE-II towards
Fe3+, the fluorescence titrations of DPE-I and DPE-II were performed at different
concentrations of metal ions as shown in Figure 4a and 4b.

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Figure 4 (a) Fluorescence spectra of (a) DPE-I and (b) DPE-II (20 µM) at pH 7.0 0.1 (10
mM HEPES in CH3CN: H2O 9: 1, v: v), upon complexation with increasing concentration of
Fe3+ ions
Ratiometric behaviour of DPE-I and DPE-II in presence of different Fe3+ concentrations is
shown in Figure S4. In the fluorescence titration of DPE I with Fe3+ ions, the plot of Io/ I (I 0
and I, fluorescence intensity of DPE I without and with Fe3+ ions) vs. Fe (III) concentration
was not a straight line. This indicated that the fluorescence quenching of DPE I by Fe3+ ions
did not obey the Stern–Volmer quenching equation (I0/I = 1 + K [Fe]). Therefore, the
fluorescence quenching is a static quenching. The disappearance in fluorescence intensity of
DPE-I on interaction with Fe3+ may be explained by the favourable photo induced electron
transfer (PET) mechanism between ligand and Fe3+ [46] while such mechanism was not
supported for DPE-II. PET mechanism is observed in DPE-I as the lone pairs on oxygen of –
CHO are engaged through conjugation with Fe3+. In case of DPE-II, the lone pairs on oxygen
of –OH not being conjugated with the benzene ring are available for excitation resulting in
emission band at 424 nm and no PET mechanism is observed.
The linear ratiometric response (I424/I314) in case of DPE-II, with increasing concentration of
Fe3+ also makes it a unique probe for it. Presence of isobestic point at 355 nm proves that one
intermediate is formed before complete complexation which is also highly fluorescent and
fluorescent intensity at 424 nm goes on increasing upto 50 equivalents of Fe3+ ions due to
complex formed between DPE-II and Fe3+. The Fe3+ ions are likely to bind to the ligands via
O-atoms of the nitro and methoxy groups. The PET process occurs due to the transfer of
electron density from ligand to the metal ion. The higher the charge density a cation
possesses (the charge density of Fe3+ is 6.09) [47], the stronger the electronic affinity it
provides. So, it is reasonable to be used to achieve PET processes between Fe3+ and the large
π
electron conjugate system of ligand. Moreover, from theoretical studies it is observed that
the DPE-I is a good electron donor, which displays an ability to coordinate Fe3+ ions, so that
there can be a reasonable charge transfer between DPE-I and the Fe3+ ions.
The non-linear regression analysis of fluorescence data for Fe-DPE I complex showed the
formation of 1:1 complex with association constant 5.1×103 M-1 while DPE-II showed better
association constant of 7×103 M-1. To elicit the interactions between Fe3+ and DPE-I and
DPE-II respectively, the binding stoichiometry was determined by the Job’s plot [48, 49].
The Job’s function FJob is calculated according to the equation FJob = (1 - X) F0 - F. The plot

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of the fluorescence versus the mole fraction of the added Fe3+ (Figures 5a and 5b,) shows two
parts that can be fitted by straight lines. The lines intersect at X equal to 0.5. These results
reveal the formation of a 1:1 complex formulated as DPE-I –Fe3+ and DPE-II –Fe3+,
respectively.
Figure 5 Job's plot of (a) DPE-I and Fe3+ (b) DPE-II and Fe3＋ which indicated the
stoichiometry of L-Fe3＋ complex is 1:1
Electrochemical measurements
Electrochemical properties of DPE-I and DPE-II were investigated by CV and DPV. The
cyclic voltammograms for DPE-I and DPE-II in CH3CN:H2O (9:1, v/v) solution containing
0.1 M TBAPF6 as the supporting electrolyte are shown in Figures 6a and 6b.
Electrochemical behaviour of DPE-I and DPE-II
Synthesis of DPE-I and DPE-II containing electron donating and electron withdrawing
substituents, respectively was done to check their remote substituent effect on the electronic
environment around the ethereal oxygen of the diphenylether group. These compounds are
identified as DPE-I (containing –CHO group meta to methoxy group on benzene ring) and
DPE-II (containing –CH2OH group meta to methoxy group on benzene ring). It is
hypothicated that the aldehydic group should facilitate reduction of nitro group on benzene
ring of the molecule, while methanolic group, due to its electron donating character, should
make the reduction of nitro group, a little difficult. Peak potentials of the two curves obtained
for DPE-I appear at -1.16 V (Epc1) and -1.39 V (Epc2), respectively, whereas corresponding
peaks for DPE-II are observed at -1.30 V (Epc1) and -1.43 V(Epc2), respectively (Figures 6a
and 6b). Corresponding peak currents for the respective peak potentials are shown in Table 2.

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Figure 6 Cyclic and differential pulse voltammograms of (a) DPE-I (b) DPE-II (5 ×10-4M)
at pH 7.0 0.1 (10 mM HEPES in CH3CN : H2O 9 : 1, v : v) using 0.1M TBAPF6
as supporting electrolyte, scan rate 20 mV s-1 and GC as working electrode.
Modulation amplitude for DPV: 50mVsec-1
Table 2 Peak potential (V) and peak current (µA) values for DPE-I and DPE-II (5 ×10-4M),
scan rate 100mV/sec
Peak potentials
(V)
Cathodic peak currents
(µA)
Compound
Epc1
-1.16
-1.30
Epc2
-1.39
-1.43
ipc1
-45.7
-62.6
ipc2
-37.4
-76.5
DPE-I
DPE-II
Effect of scan rate
In order to understand nature of the electrode processes taking place for DPE-I and DPE-II,
peak currents of cathodic waves were plotted against square root of scan rate (Figure 7). A
linear relation between peak current and square root of scan rate shows that Fick’s law of
diffusion is obeyed and the charge transport is diffusion based process. For DPE-II
with
increase in scan rate from 20 mV s-1 to 100 mV s-1, two separate reduction peaks at -1.30 V
and -1.43 V merge to form a single broad reduction peak. It indicated that at higher scan rates
the two different reduction processes were observed as a single step, while for DPE-I both the

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reduction steps were observed as separate peaks even at 200 mV s-1 or higher scan rates. This
observation is also supported by the DPV curves (Figure S5).
Figure 7 Plots of peak current and square root of scan rate for DPE-I and DPE-II
Effect of concentration of the electroactive compound
Electrochemical study of the compounds DPE-I and DPE-II was done to know the effect of
different concentrations on their respective CV behaviors. Results are shown in Figure S6.
With increase in concentration of each of DPE-I and DPE-II, a corresponding increase in the
respective peak currents was observed along with a cathodic shift in the peak potential. This
is due to the reason that increase in concentration of redox substances makes the velocity of
mass diffusion rapid and hence the electrode processes become more controlled by the
electrode reactions. Calibrations for concentration of analyte species and cathodic peak
currents were plotted and observed coefficients of regression varied within range 0.98-0.99,
as shown in Figure 8.
Figure 8 Calibration curves between concentrations of receptors and peak current for DPE-I
and DPE-II

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Effect of solvent
Receptors DPE-I and DPE-II were studied for their voltammetry in different solvent systems
like dicholormethane (DCM), acetonitrile (ACN) and N, N-dimethylforamide (DMF). In
addition, mixed solvent systems of ACN: H20 (9:1, v/v) and DMF: H20 (9:1, v/v) were also
taken for the study anticipating some interactions of water with substituents –CHO in DPE-I
and –CH2OH in DPE-II. Cyclic voltammetric and differential pulse voltammetric graphs for
DPE-I and DPE-II in different solvent media are shown in Figure S7.
DPV peaks for both the compounds in all solvent systems are identified in Table 3. It is
interesting to note that DPE-I shows only one reduction peak while DPE-II shows three
reduction peaks in ACN solvent system. These can be explained as below:
In receptor DPE-I there are three prominent functional groups like –CHO, -OCH3 and –NO2
which can be responsible for the cathodic current peaks. Amongst these three groups, because
of its electron withdrawing inductive effect nitro is the most probable candidate for reduction
and hence shows a peak at lowest value of applied potential i.e. -1.36V. The absence of peaks
in DPE-I (-1.68V) and DPE-II (-1.85V) is due to replacement of carbonyl bearing functional
group –CHO in DPE-I with –CH2OH in DPE-II. This change in functional group infact easies
out electron withdrawing tendency of ethereal oxygen para to –CHO group, hence the
absence of cathodic peak at -1.68V. The cathodic peak at -1.68V in DPE-II is probably due to
methoxy group as the peak at -1.85V in DPE-II disappears with change in solvent system
from ACN to ACN: H2O (9:1, v/v) system due to interaction of -OCH3 group indicating its
involvement with H2O through hydrogen bonding. Moreover, the absence of corresponding
peak (-1.85V) in DPE-I in both ACN and its mixture with water can also be justified due to
poor reduction potential of –CHO (in DPE-I) as compared to –CH2OH (in DPE-II). The

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absence of Epc3 in ACN: H2O solvent system is clear indication of hydrogen bonding of
CH2OH group with water as shown below:
NO2
OCH3
O
H
O
O
O2N
C
H2
H
H
Hydrogen bonding of -CH2OH group of DPE-II with water molecule
In solvent media like DCM, the main observation as compared with ACN solvent system is
with regard to shift in all peaks of DPE-I and DPE-II to lower potential values. This
important shift is due to low dipole moment of DCM (1.60 D) as compared to ACN (3.92 D)
and DMF (3.86 D). Hence, polarity of the solvent does influence reduction potentials of
target molecules. It is further noticed that the reduction potentials of DPE-I and DPE-II are
almost similar due to similar dipole moments of ACN and DMF solvents.
Table 3 Peak potentials (V) for DPE-I and DPE-II (5 ×10-4M) in different solvent systems
Dipole
moment
(D)
DPE-I
DPE-II
Epc2 (V)
Solvent
Epc1 (V) Epc2 (V) Epc3 (V)
Epc1 (V)
Epc3 (V)
ACN
DMF
3.92
3.86
1.60
-1.36
-1.25
-1.23
-1.16
-----
-1.48
-1.47
-1.39
----
-1.87
-1.750
----
-1.32
-1.348,
-1.290
-1.30
-1.68
-1.70
-1.62
-1.43
-1.85
-1.89
-1.82
----
DCM
ACN:H20
Metal-Ligand complexation studies

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Voltammetric studies of the synthesized diphenylether based compounds were performed to
study their tendency to complex with transition metal ions so that these can be projected as
ionophores suitable for heavy metal detection by simple voltammetric methods. DPE-I and
DPE-II were studied for their tendency for complexation with Fe3+ ions. Voltammograms
were drawn for both DPE-I and DPE-II with and without Fe3+ ions. Significant decrease in
current magnitude of Ep1 and Ep2 from 45.7 µA to 9.7 µA and 37.4 µA to 11.0 µA
respectively, for DPE-I prompted us to study complexation on a quantitative way as shown in
Figure 9. Incremental amounts of Fe3+ were added to 2.5 µmoles of DPE-I and the resulting
current magnitude are given in Table 4. Similar experiments were carried out on DPE-II
compound. It can be seen from Table 3 that with addition of increasing concentration of Fe3+,
a linear fall in cathodic peak current is observed till metal ions ratio with the ligand is reached
1:1 (Figure 10). Further addition of the metal ions did not bring any further change in current
magnitude. Exactly similar trend in current magnitude was observed for DPE-II. Hence,
DPE-I and DPE-II can be projected as ionophores for Fe3+ metal detection. Calibration curves
for the detection of Fe3+ using DPE-I and DPE-II are shown in Figure 10. The proposed
method is valid for the detection of Fe3+ species in the concentration range 0-2.5 µmoles.
Presence of other metal ions (Na+, K+, Cr3+, Fe3+, Co2+, Ni2+, Cu2+, Zn2+, Ba2+, Hg2+,Cd2+ and
Pb2+) have also been studied and results indicate selectivity for Fe3+ ions only.

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Figure 9 Cyclic and differential pulse voltammaograms of Ligands (DPE-I and DPE-II) upon
increment addition of metal (µM Fe3+) at pH 7.0 0.1 (10 mM HEPES in CH3CN:
H2O 9: 1, v: v), 0.1M TBAPF6
Figure 10 Calibration curves showing response of metal (Fe3+) addition to ligands (a) DPE-I
and (b) DPE-II
Table 4 Peak current values for DPE-I and DPE-II with and without Fe3+ ion
DPE-I
DPE-II
Ligand ‘L’
(DPE-I
ip2
ip1
∆ip2
∆ip1
ip2
ip1
∆ip2
∆ip1
/DPE-II)
(-1.39V)
(-1.16V)
(-1.39V)
(-1.16V)
(-1.43V)
(-1.30V)
(-1.43V)
(-1.30V)
µA
µA
µA
µA
µA
µA
µA
µA
Without
metal
-37.43 -45.67
---
---
-76.51 -62.59
---
---
(2.5µmoles)
L +Fe3+
(0.5µmoles)
L +Fe3+
(1.0µmoles)
L +Fe3+
(1.5µmoles)
L +Fe3+
-32.64 -40.79
-24.08 -30.01
-20.05 -23.75
-14.56 -14.85
-11.01 -10.71
-11.01 -9.73
-4.79
-13.35
-17.38
-22.87
-26.42
-26.42
-4.88
-53.79 -40.82 -22.72
-21.77
-29.03
-37.98
-46.60
-46.69
-46.69
-15.66 -38.29 -33.56 -38.22
-21.92 -27.77 -24.61 -48.74
-31.07 -13.03 -15.99 -63.48
-34.96 -13.02 -15.90 -63.49
-35.94 -13.02 -15.90 -63.49
(2.5µmoles)
L +Fe3+
(2.8µmoles)
L +Fe3+
(3.5µmoles)

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Interference studies
Selectivity of DPE-I and DPE-II was confirmed further by interference studies with various
interfering metal ions added in excess to the target metal ion. Voltammetric study was done
to study the effect of the presence of other ions on the response of DPE-I and DPE-II for Fe3+
ions. Both the derivatives responded selectively to Fe3+ ions even in the presence of other
metal ions (Table 5) as indicated from the quenching of the electroactive nature of ligands
(DPE-I and DPE-II) i.e. large decrease in peak currents. After complexation with the metal
ions, the receptors donot remain electroactive due to non-availability of lone pair of electrons
on the heteroatoms.
Table 5 Peak potential (V) values for DPE-I and DPE-II alone and with different metal ions
Metal
studied
Ligand
Na+
DPE-I
DPE-II
Ep2 (V) Ep1 (V) Ep2 (V)
Ep1 (V)
-1.16
-1.20
-1.14
-1.15
-1.01
--
-1.39
-1.36
-1.38
-1.39
-1.22
--
-1.30
-1.31
-1.23
-1.27
-1.21
--
-1.43
-1.45
-1.41
-1.41
-1.42
--
K+
Mg2+
Cr3+
Fe3+
Co2+
Cu2+
Zn2+
-1.14
-1.16
-1.10
-1.16
-1.36
-1.36
-1.35
-1.39
-1.30
-1.28
-1.32
-1.29
-1.42
-1.42
-1.44
-1.38
Ba2+
Theoretical Studies
The computational study was carried out by using Density Functional Theory (DFT) in an
attempt to better understand the nature of receptors and their interaction with metal ion. The
B3LYP function was employed for calculations with 6-31G basis set on Gaussian 03W
programmer except for Fe3+, for which LanL2DZ was used [50-53]. The receptors DPE-1 and
DPE-II have three dimensional structure forming a pseudo cavity between ethereal oxygen,
nitrogen of nitro group and oxygen of methoxy group and B3LYP/6-31G basis set was
employed for their optimization (Figure 11a, 11b). However, DPE I-Fe3+ and DPE II-Fe3+
were optimized by using B3LYP/6-31G and LanL2DZ basis set for Fe3+ (Figure 11c, 11d).
Optimized structures revealed the possible mode of complexation in which ether group, due
to its flexible nature gets rotated and forms best fit metal-ligand coordination sites between
Fe3+ and the receptors. On coordination with Fe3+, there is an increase in the stability of the

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whole system which was confirmed from the value of energy optimization (Table 6). The gap
between HOMO-LUMO is less for DPE I-Fe3+ and DPE II-Fe3+ as compared to receptor
DPE-1 and DPE-II alone, as depicted in Figure 12. Further, the HOMO-LUMO of the DPE-
I+Fe3+ and DPE-II+Fe3+ showed that LUMO is main contributor in electronic transition [50,
51].
Binding energies obtained from theoretical studies (as shown in Table S2) have proved that
energy values of DPE molecules decrease with the addition of Fe3+. Energy for DPE-I
decreases from -1175 a.u to -1298 a.u while for DPE-II energy decrease found was from -
1177 a.u to -1299 a.u. Hence, leading to the formation of the stable complexes. Energy
decrease in case of DPE-II is slightly more than that of DPE-I proving DPE-II to be more
stable than DPE-I.
(a) DPE-I
(b) DPE-II
(c) DPE-I+Fe3+
(d) DPE-II+Fe3+
Figure 11 The DFT optimized structures of receptors DPE-I and DPE-II and their
complexes with Fe3+calculated at the B3LYP/6-31G/LanL2DZ level respectively.
The red, blue, gray, and purple spheres refer to O, N, C, and Fe, respectively

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Table 6 Energy values (in a.u) of HOMO, LUMO and LUMO+1 for DPE-I and DPE-II and
their complexes with Fe3+
Energy in a.u
Receptor
EHOMO
0.256
0.487
0.236
0.488
ELUMO ELUMO+1
Egap1
0.143
0.019
0.143
0.021
Egap2
0.149
0.052
0.149
0.035
0.113
0.468
0.093
0.467
0.107
0.435
0.087
0.453
DPE-I
DPE-I+Fe3+
DPE-II
DPE-II+Fe3+

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LUMO DPE-I
LUMO DPE-I+Fe3+
0.143 a.u
0.019 a.u
HOMO DPE-I
HOMO DPE-I+Fe3+
LUMO DPE-II
LUMO DPE-II+Fe3+
0.143 a.u
0.021 a.u
HOMO DPE-II
HOMO DPE-II+Fe3+
Figure 12 The HOMO-LUMO gap of: receptors DPE-I and DPE-II and their Fe3+ complexes
calculated at the B3LYP/6-31G/LANL2DZ level respectively.

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Real Life sampling
In order to test the analytical applicability of the proposed voltammetric method, the
chemosensors were used for the determination of iron in pharmaceutical samples (Feriron)
and water samples (tap water and mineral water) and some synthetic samples.
Pharmaceutical sample was prepared by dissolving one tablet of Feriron in 10 mL HCl and
heated to dryness. After that, the sample was dissolved in 10 mL distillated water, filtered and
transferred to a 25 mL standard flask and this volume was completed with distillated water.
Each synthetic sample was spiked with the addition of 1 mL of 10-2 M standard metal ion
solution, keeping the total volume of the sample equal to 100 mL. Complexometric method
was also used for the determination of iron contents in these samples. The results of the
voltammetric sensors obtained are presented in Table 7 and compared with those obtained by
using complexation with EDTA. The sensors are found to be in satisfactory agreement with
those obtained from the complexometric method. These observations and results have
confirmed that present chemosensors can be used for practical analysis.
Table 7 Determination of Fe (III) in real samples using complexometric method and
proposed chemosensors
Total Iron Found (
ꢀ
g·ml–1 or g·kg–1)
Sample
Name
Adjusted pH
Chemosensor Complexometric
(DPE-1)
Chemosensor
(DPE-II)
Complexometric
method
method
Feriron
3.5
3.5
3.5
3.5
3.5
10.7 0.02
11.1 0.03
12.5 0.02
6.59 0.07
4.89 0.06
12.79 0.05
16.89 0.05
12.2 0.01
7.1 0.02
4.9 0.02
12.7 0.01
16.9 0.04
Tap
6.1 0.08
5.3 0.01
6.4 0.06
5.1 0.01
11.4 0.03
15.5 0.04
Water
Mineral
Water
RS-1
RS-2
11.53 0.03
15.39 0.02
Shows the standard deviation (n=3).

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Acknowledgments
We thank BRNS, BARC Mumbai for financial assistance vide research grant no.
2012/37C/5/BRNS/621 and we also thank SAI Labs, Thapar University, Patiala for NMR
studies.
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