Colorimetric ‘naked eye’ sensor for fluoride ion based on isatin hydrazones via hydrogen bond formation: Design, synthesis and characterization ascertained by Nuclear Magnetic Resonance, Ultraviolet–Visible, Computational and Electrochemical studies

Article abstract of DOI:10.1016/j.inoche.2020.108216

A new colorimetric sensor ‘R-IND’ based on isatin hydrazones have been designed and synthesized by simple Schiff base reaction. The anion sensing properties of R-IND were examined, characterized by common spectroscopic techniques such as Fourier Transform-Infrared (FT-IR), Ultraviolet–Visible (UV–Visible), Proton and Carbon Nuclear Magnetic Resonance (¹H & ¹³C NMR), Electrospray Ionization Mass Spectroscopy (ESI-MS) and electrochemical studies. The sensor R-IND bearing ortho hydroxy group and amine group acting as binding sites. The sensor R-IND exhibited sensitive and selective sensing towards F^? ion over the other competitive anions like Cl^?, I^?, Br^?, H₂PO₄^?, AcO^?, CN^–, NO₃^–, ClO₄^? and HSO₄^? in 100% Aetonitrile and 20% aqua Acetonitrile media. The bathochromic shift of 222 nm and 228 nm was observed in UV–Vis spectra with a color change from pale yellow to purple which is due to the complex formation between R-IND and F^? ion through hydrogen bond formation. This was further accounted by ¹H NMR titration. The Job's plot reveals 1:2 stoichiometry between the host-guest complex. Binding and association constants were found to be 1.72 × 10⁹ M^?1, 2.82 × 10⁹ M^?1 and 6.0 × 10⁵ M^?1, 2.0 × 10⁶ M^?1 in 100% ACN and 20% aqua ACN respectively. The detection limit of sensor R-IND was turned out to be 0.45 and 0.41 ppm for F^? ion in organic and aqua organic medium which is lesser than World Health Organization (WHO) permission level (1 ppm). The characteristic potential difference of 1.069 V has been observed for R-IND+F^? complex in the electrochemical study. Finally, economically viable paper-based colorimetric test strips of R-IND were developed to detect the F^? ions in 100% aqueous solution.

Full text of DOI:10.1016/j.inoche.2020.108216

InorganicChemistryCommunications121(2020)108216
Contents lists available at ScienceDirect
Inorganic Chemistry Communications
journal homepage: www.elsevier.com/locate/inoche
Short communication
Colorimetric ‘naked eye’ sensor for fluoride ion based on isatin hydrazones
via hydrogen bond formation: Design, synthesis and characterization
ascertained by Nuclear Magnetic Resonance, Ultraviolet–Visible,
Computational and Electrochemical studies
⁎
B.U. Gauthamaa, B. Narayanaa, , B.K. Sarojinib, J.G. Manjunathac, N.K. Suresha
a Department of Studies in Chemistry, Mangalore University, Mangalagangothri 574199, Karnataka, India
b Department of Industrial Chemistry, Mangalore University, Mangalagangothri 574199, India
c Department of Chemistry, FMKMC Constituent College of Mangalore University, Madikeri 571201, Karnataka, India
G R A P H I C A L A B S T R A C T
A R T I C L E I N F O
A B S T R A C T
Keywords:
A new colorimetric sensor ‘R-IND’ based on isatin hydrazones have been designed and synthesized by simple
Schiff base reaction. The anion sensing properties of R-IND were examined, characterized by common spec-
troscopic techniques such as Fourier Transform-Infrared (FT-IR), Ultraviolet–Visible (UV–Visible), Proton and
Carbon Nuclear Magnetic Resonance (1H & 13C NMR), Electrospray Ionization Mass Spectroscopy (ESI-MS) and
electrochemical studies. The sensor R-IND bearing ortho hydroxy group and amine group acting as binding sites.
The sensor R-IND exhibited sensitive and selective sensing towards F− ion over the other competitive anions like
Colorimetric
Electrochemical
Fluoride
Sensing
Hydrogen bond formation
Cl−, I−, Br−, H2PO4−, AcO−, CN–, NO3–, ClO4 and HSO4 in 100% Aetonitrile and 20% aqua Acetonitrile
media. The bathochromic shift of 222 nm and 228 nm was observed in UV–Vis spectra with a color change from
pale yellow to purple which is due to the complex formation between R-IND and F− ion through hydrogen bond
formation. This was further accounted by 1H NMR titration. The Job’s plot reveals 1:2 stoichiometry between the
host-guest complex. Binding and association constants were found to be 1.72 × 109 M−1, 2.82 × 109 M−1 and
6.0 × 105 M−1, 2.0 × 106 M−1 in 100% ACN and 20% aqua ACN respectively. The detection limit of sensor R-
IND was turned out to be 0.45 and 0.41 ppm for F− ion in organic and aqua organic medium which is lesser than
World Health Organization (WHO) permission level (1 ppm). The characteristic potential difference of 1.069 V
has been observed for R-IND+F− complex in the electrochemical study. Finally, economically viable paper-
based colorimetric test strips of R-IND were developed to detect the F− ions in 100% aqueous solution.
−
−
⁎ Corresponding author.
https://doi.org/10.1016/j.inoche.2020.108216
Received 13 August 2020; Received in revised form 31 August 2020; Accepted 31 August 2020
Availableonline02September2020
1387-7003/©2020ElsevierB.V.Allrightsreserved.

B.U. Gauthama, et al.
InorganicChemistryCommunications121(2020)108216
1. Introduction
2.2. UV–Visible experiments of the sensor R-IND with anions
The sensing and recognition of various anions are being a hot topic
in the field of supramolecular chemistry due to its important roles
played in the areas of biological, chemical, environmental areas [1–6].
Normally sensing of anions is quite difficult on comparing with cations,
due to their size, shape, and low stability constants [7]. Many sensors
have been developed for the sensing of anions based on the electrostatic
interaction and hydrogen bonding [8–10].
The UV–Visible titration experiment was carried out to check the
response of sensor R-IND towards various anions. The sensor R-IND of
2 × 10−5 M concentration and Tetrabutylammonium (TBA) salts
(TBAX where X = F−, Cl−, I−, Br−, H2PO4−, AcO−, CN–, NO3–, ClO4
−
and HSO4−) of 1.0 × 10−2 M were prepared in 100% ACN and 20%
aqua ACN media. The UV–Visible titrations were carried out by adding
the different equivalent of anions to the 2 ml solution of sensor R-IND in
cuvette through micropipette and the absorption spectra obtained was
recorded between the range of 200–700 nm.
Among the various anions, fluoride is the one having distinctive
chemical and biological properties and huge applications in daily life.
Fluoride ions having high charge density, electronegativity, small ionic
size, and hard Lewis base nature. Many dental problems in humans like
osteoporosis can be cured by the vital role played by fluoride ions [11].
According to WHO, F− intake above 2 mg/L in drinking water may lead
to serious health problems like bone cancer, thyroid disorder and bone
fragility [12,13]. In the case of flora, excess F− leads to a decrease in
growth and yield and consequently affect the surrounding fauna. Be-
sides, F− is being used in microelectronic sensors, computer chip pro-
duction and television screens [14].
2.3. NMR titrations
To further confirm the formation of a complex between the sensor
and fluoride ion, the NMR titration experiment was performed by
taking R-IND in DMSO‑d6 with the addition of 0.5, 1.0, and 1.5
equivalent of F− ion. Chemical shift changes in R-IND NMR spectra
were examined before and after the addition of F− ion.
There are several reported techniques for the detection of anions
which include mass spectroscopy [15], ion chromatography [16], flow
injection distillation method [17], electrochemistry [18] and colori-
metry [19]. The development of colorimetric anion sensors/chemo-
sensors is necessary, because of its visual detection which can give
qualitative and quantitative information, cost-effective and no major
instrument required. Chemosensors interacts with anions through hy-
drogen bonding, electrostatic and coordinate interactions or sometimes
combination of these type. Considerable chemosensors are reported
containing amines [20], urea [21], imidazole [22], imines [23],
thiourea [24], phenol [25], pyrrole [26] and hydrazones [27] which
detects via formation of hydrogen bond. The present study involves the
formation of Schiff bases through a reaction between hydrazones of
isatin and aromatic aldehyde containing ortho hydroxyl group.
Synthesis of F− sensor (Z)-3-(((E)-5-bromo-2-hydroxybenzylidene)
hydrazono)indolin-2-one (R-IND) was attempted through the formation
of isatin hydrazones in the first step and condensation of this with an
aromatic aldehyde in the second step. The Sensor R-IND can detect F−
in 100% ACN and 20% aqua ACN medium without the interference of
other anions through the formation of hydrogen bonding between the
hydroxy and amine group of the R-IND and F− ion and it was further
supported by UV–Vis, NMR titration and electrochemical techniques. A
density functional study was also carried out for its computational
support.
2.4. Electrochemical studies
All electrochemical measurements were performed by the use of a
CH Instrument 6038 potentiostat. A conventional three-electrode
system was employed that included a saturated calomel electrode, a
platinum wire, and glassy carbon electrode as the reference, auxiliary
and working electrode. The measurements were conducted by immer-
sing the three-electrode system into a 50 ml electrochemical cell con-
taining supporting electrolyte solution and the analyte. All of the
measurements were performed at room temperature. The synthesized
R-IND (2 × 10−5 M) was prepared by dissolution in acetonitrile.
Sodium dihydrogen phosphate and disodium hydrogen phosphate were
obtained from Himedia. 0.1 M phosphate buffer solution was employed
as a supporting electrolyte and was prepared by mixing 0.1 M sodium
dihydrogen phosphate and disodium hydrogen phosphate
2.5. Computational studies
Hybrid exchange-correlation function B3LYP with 6-311G basic set
in the Maestro-MS program was used for the DFT calculations for the
evaluation of F− ion interaction with sensor R-IND with ACN solvent
phase.
2.6. Test strips
To evaluate the practical application of R-IND for the determination
of fluoride ion, test strips of R-IND was developed by immersing filter
papers into the ACN solution of R-IND (2 × 10−3 M) and later dried at
35 °C. After infiltration treatment with the aqueous solution of the
anion of known concentration and drying, the test strips were observed
under the naked eye and UV lamp.
2. Experimental
2.1. Materials and methods
All reagents and solvents, all the anions received as tetra-
butylammonium salts from Merck (India) and SD Fine Chem Pvt.
Limited (India) and used as such without purification. All UV–Visible
spectra were carried out in 100% ACN and 20% aqua ACN, NMR
spectra of the samples were taken using a JEOL (400 MHz), where
tetramethylsilane (TMS) was used as the internal standard and
DMSO‑d6 as the solvent. Resonance multiplicities were explained as s
(singlet), d (doublet), t (triplet), and m (multiplet). SHIMADZU FT-IR-
Prestige 21 spectrophotometer used to record FT-IR spectra using the
attenuated transmission method with the frequency range of
400–4000 cm−1. Mass spectra were analyzed on a Waters Micromass Q-
Tofmicro spectrometer with an ESI source. Spectroquant pharo300
Spectrometer was used to record UV–Vis spectra with standard 3.5 ml
quartz cells with 1 cm path length. The progress of the reaction was
monitored by TLC. The melting point was recorded on Raga melting-
point apparatus in open capillaries42.
3. Results and discussion
3.1. Synthesis and characterization of sensor R-IND
The design and synthesis of R-IND are expressed in Scheme 1. In
typical, by simple condensation reaction between isatin (0.50 g,
0.003 mmol) and hydrazine hydrate (0.2 g, 0.004 mmol) in the pre-
sence of methanol as solvent under reflux for 6 h. Soon after, the formed
precipitate was filtered through Whatman No. 41 filter paper and wa-
shed several times with cold methanol to yield an intermediate com-
pound. The completion of the reaction was monitored by TLC. The R-
IND was obtained by the reaction of the intermediate compound with 5-
bromosalicylaldehyde in the presence of ethanol as solvent at 78–80 °C
for 6 h [28]. The obtained solid was washed several times with cold
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B.U. Gauthama, et al.
InorganicChemistryCommunications121(2020)108216
H2N
shown in the Fig. 1 a. This shift in the absorption band induced by the
F− ion, which is also called a bathochromic shift or redshift. The
bathochromic shift of 222 nm can be attributed to the formation of the
hydrogen bond between the hydroxy and amine group of host moiety
(R-IND) and the guest F− ion leading to the formation of a host-guest
complex. The UV–Vis titration experiment has shown a clear isosbestic
point at 454 nm which further supports the strong interaction of R-IND
with the F− ion. Further, the formation of the complex resulting in a
visible color change from pale yellow to purple color (Fig. 2. a) gives a
promising proof for the anion sensing. With very little sensing time and
no major equipment required, R-IND is fairly suitable for the colori-
metric sensing of F− ion in the organic medium [29].
N
O
i
NH2NH2.H2O
O
O
ii
N
N
H
H
i) methanol, ii) refluxed for 6 hr
Br
H2N
O
N
N
N
i
OH
O
O
HO
To assess the F− sensing ability of R-IND in a water-based medium,
experiments were carried out in 20% aqua and 50% aqua ACN medium.
As shown in Fig. 1. b, at 20% aqua ACN medium the obtained ab-
sorption maxima in the absence (328 nm) and presence (556 nm) of F−
ion does not show many changes on comparing with the organic
medium which suggests that water molecule does not interrupt in the
sensing of F− ion. However, the color obtained in the sensing is lighter
than the pure ACN medium (Fig. 2. b). It is to be noted that, R-IND was
not able to sense the F− ion at 50% aqua ACN. This may be due to the
loss in the basicity of F− ion caused by solvation with the water mo-
lecule [30].
ii
N
N
Br
H
H
R-IND
i) ethanol, ii) refluxed for 6 hr
Scheme 1. Route for the synthesis of sensor R-IND.
ethanol. The reaction completion was monitored by TLC.
Melting point = 168–170 °C, 1H NMR (400 MHz, DMSO‑d6),
δ(ppm): 6.89–6.91 (d, 1H, ArH), 6.97–6.99 (d, 1H, ArH), 7.06–7.10 (t,
1H, ArH), 7.43–7.47 (m, 1H, ArH), 7.57–7.60 (m, 1H, ArH), 7.63–7.65
(d, 1H, ArH), 7.90–7.91 (d, 1H, ArH) 8.96 (s, 1H), 11.01 (S, NH), 11.90
(S, OH) (Fig-S1). 13C NMR (100 MHz, DMSO‑d6), δ (ppm): 110.13,
110.91, 119.41, 119.58, 119.74, 122.38, 122.68, 134.07, 134.45,
136.14, 144.75, 150.85, 158.77, 159.33, 164.36 (Fig-S2). LCMS
(ESIMS) m/z: [M−H]− Calculated for C15H10BrN3O2 is 343.00, Found:
343.95 (Fig-S3). FT-IR (KBr) ν (cm−1) = 3346, 3138, 2336, 2091,
1655, 1533, 1181, 938, 700, 500 (Fig-S4). Yield = 80%.
3.3. Selective detection of F- ion by R-IND
The sensor should have excellent selectivity towards anions of in-
terest in the presence of various competitive anions to become an
outstanding chemical sensor. Therefore the selective sensing ability of
R-IND towards F− ions were examined with the participation of various
anions such as Cl−, Br−, H2PO4−, AcO−, CN–, NO3–, ClO4− and HSO4
−
3.2. UV–Visible titration in 100% ACN and 20% aqua ACN medium
as shown in Fig. 3. One can observe from Fig. 3. that the UV–Vis spectra
were not altered much in the presence of other common anions. These
results were proved that the R-IND is suitable for the detection of F−
ion in the presence of other common anions.
The anion recognition properties of the R-IND were investigated by
examining variation in the UV–Vis spectra upon addition of different
anions of its Tetrabutylammonium (TBA) salts such as (F−, Cl−, I−
,
Br−, H2PO4−, AcO−, CN–, NO3–, ClO4 and HSO4−) in organic and
organo-aqueous solvents such as ACN and 20% aqua ACN mixtures
respectively. As observed in Fig. 1. a, the anion free ACN solution of R-
IND has shown an intense absorption band at 328 nm. Upon in-
troduction of F− ion of certain equivalents, the strong absorption band
at 328 nm was shifted to the higher wavelength of 550 nm, whereas the
addition of other anions did not alter the absorption peak indicating
that other than F− ion does not affect the UV–Vis spectra of R-IND as
−
3.4. Determination of stoichiometry, binding constant, limit of detection
(LOD) and limit of quantification (LOQ)
The binding stoichiometry between F− ion and R-IND were studied
by UV–Vis titration experiments in 100% ACN and 20% aqua ACN
medium. The large bathochromic shift of 228 nm was observed for
UV–Vis spectra of R-IND upon incremental addition of F− ion which is
Fig. 1. UV–Vis spectra of sensor R-IND (2.0 × 10−5 M) in a. 100% ACN b. 20% aqua ACN upon the addition of 0.0–2.0 equivalent and 0.0–1.8 equivalent of
tetrabutylammonium salt of F− ions.
3

B.U. Gauthama, et al.
InorganicChemistryCommunications121(2020)108216
Fig. 2. The visual color change of sensor R-IND (a. 2.0 × 10−5 M in 100% ACN) after the addition of 2.0 equivalent and R-IND (b. 2.0 × 10−5 M in 20% aqua ACN)
after the addition of 1.8 equivalent of different anions as TBAF salts (1 × 10−2 M).
Fig. 3. Changes in the UV–Vis spectra of sensor R-IND (2.0 × 10−5 M) in 100% ACN and 20% aqua ACN upon addition of 2.0 equivalent (a) and 1.8 equivalent (b) of
different TBA salts of anions (1.0 × 10−2 M).
Fig. 4. Job’s plot for complexation of R-IND with F− ions determined by UV–Visible experiments in a. 100% ACN medium and b. 20% aqua ACN medium.
4

B.U. Gauthama, et al.
InorganicChemistryCommunications121(2020)108216
Fig. 5. B–H plot for the titration of R-IND with F− ion in a.100% ACN medium and b. 20% aqua ACN medium.
Fig. 6. Calibration curve for the determination of detection limit of R-IND with F− ions in a. 100% ACN medium and b. 20% aqua ACN medium.
Table 1
Statistical details related to sensor R-IND (2.0 × 10−5 M) in 100% ACN and 20% aqua ACN medium in the presence of F− ions (1 × 10−2 M) of known
concentration.
Medium of detection
Absorption band without F− ion (nm)
Absorption band with F− ion (nm)
Redshift/ Bathochromic shift (nm)
Visible color change
100% ACN
328
328
550
556
222
228
Pale yellow -purple
Pale yellow- purple
20% aqua ACN
Table 2
attraction between the host-guest complexes is measured in terms of
binding constant and the association constant. Further, with the help of
Benesi–Hildebrand (B-H) plot the binding constant, association con-
stant was calculated and the B-H plot was shown in Fig. 5 [31]. The
binding and association constant of the R-IND+F− complex in 100%
ACN and 20% aqua ACN were found to be 1.72 × 109 M−1, 6.0 × 105
M−1 and 2.82 × 109 M−1, 2.0 × 106 M−1 respectively. The detection
limit of R-IND for the detection of F− ion was obtained by calculating
standard deviation and linear fitting values. By plotting changes in
absorbance as a function of F− concentration as in Fig. 6, the detection
limit and quantification limit of R-IND for F− ion were found to be
0.45 ppm and 1.35 ppm in 100% ACN respectively, whereas in 20%
aqua ACN medium, it was found to be 0.41 ppm and 1.25 ppm re-
spectively. The results were tabulated in Tables 1 and 2. The statistical
Statistical data of sensor R-IND upon sensing F− ions.
R-IND+F−
Binding constant
Asociation
LOD in
ppm
LOQ in
ppm
complex
(M−1
)
constant (M−1
)
100% ACN
1.72 × 109
6.0 × 105
0.45
0.41
1.35
1.25
20% aqua ACN
2.82 × 109
2.0 × 106
responsible for the change of color from pale yellow to purple and
noticeable to the naked eye. The Job’s plot was established to make out
the binding stoichiometry between F− ion and R-IND is expressed in
Fig. 4. The results revealed that absorption was maximum when the F−
ion mole fraction was reached around 0.4, which concludes 1:2 binding
stoichiometry between the host R-IND and guest F− ion. The affinity of
5

B.U. Gauthama, et al.
InorganicChemistryCommunications121(2020)108216
Table 3
Comparison of the detection limit, binding constant and the solvent used for the detection of F− ion by various chemosensors.
Sensors
Detection limit
Solvent
Binding constants (M−1
)
Reference
Amino-Naphthoquinone
Benzilidine hydrazines
Peptide triazole
0.4 µM
0.4 ppm
0.72 µM
0.31 µM
–
DMF
10 × 10−4
7.9 × 10−4
1.25 × 10−3
7.59 × 10−5
2 × 10−5
[13a]
DMSO:HEPES buffer
CHCl3
[32]
[33]
Phenoxy aniline
PBS buffer: DMSO
ACN:H2O
[31a]
Coumarin-Salicylidene
Isatin hydrazones
[34]
0.45 ppm
ACN: H2O
2.82 × 109
Present method
Fig. 7. 1HNMR titration of sensor R-IND in a DMSO‑d6 solvent with stepwise addition of (0–2 eq.) of F− ion as Tetrabutylammonium salts.
Scheme 2. Plausible interactions of R-IND with
fluoride ion.
comparison of present work with reported work was listed in Table 3
and clearly suggests that R-IND binds with F− ions superiorly on
comparing with other reported methods.
interaction of the OH and NH protons in the R-IND with F− ions might
be due to internal charge transfer, which accounted for the long bath-
ochromic shift and the generation of purple color (Scheme 2).
3.5. 1H NMR titration of R-IND
3.6. Study of sensing of F− ion by R-IND at different pH range
Further investigation has been carried out in support of sensing of
F− ion by R-IND, 1H NMR titration experiments have been carried out
in DMSO‑d6 solvent. The results of the investigation were presented in
Fig. 7. The peak at 11.907 ppm was attributed to OH proton of the
aldehyde moiety was disappeared whereas the peak intensity at
11.016 ppm was assigned to NH proton of the indole moiety was re-
duced upon the addition of 0.5 equivalent of F− ion. This dis-
appearance of the OH peak confirms the deprotonation of OH hydrogen
in the aldehyde binding site. The upfield shift of aromatic protons gives
us further evidence for the deprotonation. On further addition of F−
ions of 1.0 and 2.0 equivalent, NH peak was disappeared followed by
further upfield shift of aromatic protons indicating the deprotonation of
NH proton of the indole binding site [35]. Therefore, such strong
One of the most key factors for the detection of fluoride ions in real
sample applications is an acceptable wide pH range. The effect of
change in pH on the spectral responses and color of free R-IND and R-
IND+F− was examined over the pH range of 4.0–9.0. As can be seen
from Fig. 8, free R-IND does not exhibit a significant change in its ab-
sorbance and color at 328 nm within a range of pH values (between pH
4.0 and 9.0). For R-IND+F− complex, absorbance intensity varied over
the pH range to some extent with the highest absorption intensity at
biological pH ie pH 7.0 as shown in Fig. 7 [36]. These results show that
R-IND can be used as a colorimetric sensor to detect fluoride ions in
biological systems and industrial samples.
6

B.U. Gauthama, et al.
InorganicChemistryCommunications121(2020)108216
Table 4
Statistical data obtained by Differential Pulse Voltammetry study.
Ions
Epa (V)
Ipa (µA)
R-IND
1.079
1.069
1.078
1.076
1.080
1.074
1.077
1.076
1.079
1.077
1.078
4.801
5.220
5.581
5.790
5.569
5.545
5.531
5.546
5.551
5.563
5.531
R-IND+F−
R-IND+Cl−
R-IND+I−
R-IND+NO2
R-IND+NO3
–
–
−
R-IND+ClO4
R-IND+OH–
R-IND+CN–
R-IND+AcO−
R-IND+Br−
3.7. Electrochemical studies
Differential pulse voltammetry (DPV) study was carried out to sense
the F− ion using ACN as a solvent at a glassy carbon electrode. The
formation of the hydrogen bond complex has been accounted for by
DPV study (Fig. 9. c) with the variation in the potential of R-IND+F−
complex on comparing with the other anions and the results have been
given in the Table 4. From the result, it is evident that R-IND+F−
Fig. 8. The absorption changes of free R-IND and R-IDN+F− in 20% aqua ACN
solution at different pH.
Fig. 9. a. Effect of concentration of F− ion on peak current. b. The electrochemical response of R-IND at different scan rates. c. DPV of R-IND and other listed anions.
7

B.U. Gauthama, et al.
InorganicChemistryCommunications121(2020)108216
Fig. 10. The HOMO-LUMO gap of receptor R-IND and R-IND+F− complex calculated at the B3LYP/6-311 G level using Maestro-MS software.
0.30
current obtained by the use of differential pulse voltammogram in
0.1 M PBS at pH 6.5 using a scan rate 0.05 V/s at glassy carbon elec-
trode is depicted in Fig. 9. a [38]. The peak current increased with the
0.25
F− ion concentration across the ranges from 1 to 7 µM. The plot of the
peak current as a function of the concentration of F− ion provided
0.20
linear relationship with the regression equation of Ipa
(A) = 6.89 × 10−6 + 0.216 C (M) and a correlation coefficient of 0.99
R-IND
Toothpaste
Mouth wash
(Fig. 9. a. inset). These results give us satisfactory evidence to utilize R-
IND as an electrochemical sensor for the detection of F− anion.
0.15
0.10
0.05
0.00
3.8. Computational study of R-IND with fluoride ion
The selectivity of R-IND towards F− ion can be further assisted by
density functional theory calculations (DFT) using Maestro-MS software
with the B3LYP/6-311G basis set (Fig. 10). The information about the
extent of the feasibility of sensing of F− ion by using R-IND can be
obtained by energy level difference between HOMO-LUMO of free R-
IND and R-IND+F− complex. From Fig. 10, it is observed that HOMO
was distributed across the molecule whereas LUMO was dispersed more
in the area of Schiff base in free R-IND. After forming a complex with
fluoride ion HOMO and LUMO layers were distributed around the
whole molecule and in the aldehyde moiety respectively. In an account
of the large bathochromic shift of 222 nm in absorption spectra, the
energy gap between the HOMO and LUMO in R-IND+F− complex has
been reduced to 2.0253 eV from 6.0448 eV [39]. Thus R-IND can be
used as an excellent probe for the colorimetric sensing of F− ions.
300
375
450
525
600
675
Wavelength (nm)
Fig. 11. Detection of F− ion in some commercial products like mouth wash and
toothpaste using R-IND in 20% aqua ACN medium.
complex shows a predominant difference in current and potential
comparing with free R-IND and R-IND+other ions.
3.7.1. Electrochemical response at various scan rates
The synthesized R-IND of 10 µM in a suitable solvent was subjected
to a linear sweep voltammetry study at a glassy carbon electrode in
0.1 M phosphate buffer solution of pH 6.5. Fig. 9. b. shows the linear
sweep voltammogram of R-IND at different scan rates from 0.100 to
0.250 V/s. It was observed that as the scan rate increased peak current
also increased linearly with the regression equation of Ipa
(μA) = 4.66 + 50.42 v (V/s) (Fig. 9. b. inset) and a correlation coef-
ficient of 0.99. This relationship indicates that the electrode reaction
involves an adsorption-controlled process [37].
3.9. Real sample analysis
On further study, the experiments have been carried out to detect
F− ion in some real samples like some oral hygiene products (tooth-
paste and mouth wash). In brief, the mouth wash and toothpaste were
weighed about 10 mg and dissolved in 5 ml of distilled water. Later a
drop from the solution was added to the R-IND of 2 × 10−5 M 20%
aqua ACN solution. The change in the solution color of R-IND
+(toothpaste/mouth wash) was noticeable and observed under UV
light to obtain Absorption spectra as depicted in Fig. 11. The absorption
spectra have a similar bathochromic shift (like Fig. 1) which is again
3.7.2. Effect of concentration of F− on peak current
The relationship between the concentration of F− ion and peak
8

B.U. Gauthama, et al.
InorganicChemistryCommunications121(2020)108216
Fig. 12. Schematic representation of the preparation of test strips and color changes of R-IND upon the addition of different concentrations of fluoride ions. The
sensor showed color and spectra change upon addition of.
due to the formation hydrogen bond between R-IND and F− ion.
Declaration of Competing Interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influ-
ence the work reported in this paper.
3.10. Test strips for the detection of fluoride ion in 100% aqueous solutions
Despite many benefits of colorimetric sensing of some important
ions, the method can be inadequate in some circumstances due to bit
lengthy experimental procedures (analyte preconcentration, etc..).
Thus, the technology with low cost, simple, in-field detection of an
analyte of interest has some interest and is necessary too. With this
regard, Whatman 41 filter paper was immersed in an R-IND solution in
ACN and dried under hot air drier. Later, the dried pale yellow colored
strip was dipped into F− solution of different concentrations (Fig. 12)
and the immediate color change can be attributed to the formation of
hydrogen-bonded R-IND+F− complex.
Acknowledgment
The authors gratefully acknowledge BSR one time grant to Prof. B.
Narayan for purchase of chemicals. Authors thank DST-PURSE, and
NMR Facility Mangalore University for helping in the characterization
and also thank the Department of Chemistry FMKMC College, Madikeri,
Mangalore University Constituent College for the electrochemical
study.
Appendix A. Supplementary data
4. Conclusion
Supplementary data to this article can be found online at https://
doi.org/10.1016/j.inoche.2020.108216.
In conclusion, a fast, inexpensive and simple to use isatin based
sensor for the sensing of F− ions has been developed in 100% ACN and
20% aqua ACN media with good sensitivity as well as selectivity. The
Sensor R-IND exhibited color change only upon the addition of F− ions
with the significant red shift in UV–Vis spectra among the other com-
References
[1] R. Martinez-Manez, F. Sancenon, Fluorogenic and chromogenic chemosensors and
reagents for anions, Chem. Rev. 103 (2003) 4419–4476.
petitive anions like Cl−, I−, Br−, H2PO4−, AcO−, CN–, NO3–, ClO4
−
[2] C.N. Carroll, J.J. Naleway, M.M. Haley, D.W. Johnson, Arylethynyl receptors for
neutral molecules and anions: emerging applications in cellular imaging, Chem.
Soc. Rev. 39 (2010) 3875–3888.
and HSO4−. The hydrogen bond formation between the hydroxyl,
amine group of the R-IND and F− ion is responsible for the complex
formation which was further accounted by 1H NMR titration experi-
ments. The electrochemical study reveals that the electrode reaction
involves an adsorption-controlled process and a distinguishable oxida-
tion peak at 1.069 V was observed in the presence of F− ion. The Job’s
plot reveals 1:2 stoichiometry between host-guest. The binding constant
was calculated by B-H plot, found to be 1.72 × 109 & 2.82 × 109 M−1
which is quite higher than similar reported methods, theoretically
supported by DFT studies. Further, association constant, LOD and LOQ
were calculated. Finally, most feasible test strips were developed to
determine F− ion in 100% water which can be witnessed through the
naked eye.
[3] M. Wenzel, J.R. Hiscock, P.A. Gale, Anion receptor chemistry: highlights from 2010,
Chem. Soc. Rev. 41 (2012) 480–520.
[4] P.A. Gale, Anion receptor chemistry: highlights from 2008 and 2009, Chem. Soc.
Rev. 39 (2010) 3746–3771.
[5] Y.M. Hijji, B. Barare, A.P. Kennedy, R. Butcher, Synthesis and photophysical
characterization of a Schiff base as anion sensor, Sens. Actuators, B 136 (2009)
297–302.
[6] J.W. Steed, Coordination and organometallic compounds as anion receptors and
sensors, Chem. Soc. Rev. 38 (2009) 506–519.
[7] P.D. Beer, P.A. Gale, Anion recognition and sensing: the state of the art and future
perspectives, Angew. Chem. Int. Ed. 40 (2001) 486–516.
[8] C.R. Bondy, S.J. Loeb, Amide based receptors for anions, Coord. Chem. Rev. 240
(2003) 77–99.
[9] K. Choi, A.D. Hamilton, Macrocyclic anion receptors based on directed hydrogen
bonding interactions, Coord. Chem. Rev. 240 (2003) 101–110.
[10] A. Kumar, S.K. Asthana, K.K. Upadhyay, A smart ratiometric red fluorescent che-
modosimeter for fluoride based on anthraquinone nosylate, New J. Chem. 41
(2017) 5098–5104.
[11] S.K. Jha, V.K. Mishra, D.K. Sharma, T. Damodaran, Fluoride in the environment and
its metabolism in humans, Reviews of Environmental Contamination and
Toxicology, vol. 211, Springer, New York, NY, 2011, pp. 121-142.
[12] R.J. Carton, Review of the 2006 united states national research council report:
fluoride in drinking water, Fluoride 39 (2006) 163–172.
CRediT authorship contribution statement
B.U. Gauthama: Conceptualization, Data curation, Investigation,
Methodology, Writing - original draft. B. Narayana: Resources, Project
administration, Writing - review & editing. B.K. Sarojini: Writing -
review & editing. J.G. Manjunatha: Supervision. N.K. Suresh: Data
curation, Methodology.
[13] (a) C. Parthiban, K.P. Elango, Amino-naphthoquinone and its metal chelates for
selective sensing of fluoride ions, Sens. Actuators, B 215 (2015) 544–552;
(b) M. Sabet, M. Salavati-Niasari, O. Amiri, Using different chemical methods for
deposition of CdS on TiO2 surface and investigation of their influences on the dye-
9

B.U. Gauthama, et al.
InorganicChemistryCommunications121(2020)108216
sensitized solar cell performance, Electrochim. Acta 117 (2014) 504–520.
new anthraquinone-based receptors toward fluoride ions, Tetrahedron Lett. 48
[14] (a) S. Sahu, Y. Sikdar, R. Bag, D.K. Maiti, J.P. Cerón-Carrasco, S. Goswami, Visual
detection of fluoride ion based on ICT mechanism, Spectrochim. Acta Part A Mol.
Biomol. Spectrosc. 213 (2019) 354–360;
(2007) 3077–3081.
[23] D.A. Jose, D.K. Kumar, B. Ganguly, A. Das, Urea and thiourea based efficient col-
orimetric sensors for oxyanions, Tetrahedron Lett. 46 (2005) 5343–5346.
[24] X. Zhang, L. Guo, F.Y. Wu, Y.B. Jiang, Development of fluorescent sensing of anions
under excited-state intermolecular proton transfer signaling mechanism, Org. Lett.
5 (2003) 2667–2670.
(b) F. Mohandes, F. Davar, M. Salavati-Niasari, Magnesium oxide nanocrystals via
thermal decomposition of magnesium oxalate, J. Phys. Chem. Solids 71 (2010)
1623–1628.
[15] (a) K. Minakata, H. Nozawa, K. Gonmori, I. Yamagishi, M. Suzuki, K. Hasegawa,
O. Suzuki, Determination of cyanide in blood by electrospray ionization tandem
mass spectrometry after direct injection of dicyanogold, Anal. Bioanal. Chem. 400
(2011) 1945–1951;
[25] R. Sheng, P. Wang, W. Liu, X. Wu, S. Wu, A new colorimetric chemosensor for Hg2+
based on coumarin azine derivative, Sens. Actuators, B 128 (2008) 507–511.
[26] (a) Y.H. Qiao, H. Lin, H.K. Lin, A novel colorimetric sensor for anions recognition
based on disubstituted phenylhydrazone, J. Incl. Phenom. Macrocycl. Chem. 59
(2007) 211–215;
(b) M. Salavati-Niasari, Ship-in-a-bottle synthesis, characterization and catalytic
oxidation of styrene by host (nanopores of zeolite-Y)/guest ([bis (2-hydroxyanil)
acetylacetonato manganese (III)]) nanocomposite materials (HGNM), Microporous
Mesoporous Mater. 95 (2006) 248–256.
(b) S. Hu, J. Song, F. Zhao, X. Meng, G. Wu, Highly sensitive and selective col-
orimetric naked-eye detection of Cu2+ in aqueous medium using a hydrazone
chemosensor, Sens. Actuators, B 215 (2015) 241–248.
[16] (a) O. Destanoğlu, G. Gümüş Yılmaz, R. Apak, Selective determination of free cy-
anide in environmental water matrices by ion chromatography with suppressed
conductivity detection, J. Liq. Chromatogr. Relat. Technol. 38 (2015) 1537–1545;
(b) F. Davar, M. Salavati-Niasari, Synthesis and characterization of spinel-type zinc
aluminate nanoparticles by a modified sol–gel method using new precursor, J.
Alloy. Compd. 509 (2011) 2487–2492.
[27] J. Devi, N. Batra, Synthesis, characterization and antimicrobial activities of mixed
ligand transition metal complexes with isatin monohydrazone Schiff base ligands
and heterocyclic nitrogen base, Spectrochim. Acta Part A Mol. Biomol. Spectrosc.
135 (2015) 710–719.
[28] S.N. Kodlady, B. Narayana, B.K. Sarojini, B.U. Gauthama, Aromatic aldehyde based
chemosensors for fluoride and cyanide detection in organic and aqueous media:
ascertained by characterization, spectroscopic and DFT studies, Inorg. Chim. Acta
494 (2019) 245–255.
[17] (a) J.M. Zhao, H.C. Bi, Y. Li, H.C. Bi, Flow injection on-line distillation method for
determination of cyanide in water, Advanced Materials Research, Trans Tech
Publications Ltd., vol. 1073, 2015, pp. 197-201.
[29] P.M. Reddy, S.R. Hsieh, C.J. Chang, J.Y. Kang, Detection of cyanide ions in aqueous
solutions using cost effective colorimetric sensor, J. Hazard. Mater. 334 (2017)
93–103.
(b) M. Salavati-Niasari, Nanoscale microreactor-encapsulation of 18-membered
decaaza macrocycle nickel (II) complexes, Inorg. Chem. Commun. 8 (2005)
174–177;
[30] (a) G.G.V. Kumar, M.P. Kesavan, G. Sivaraman, J. Rajesh, Colorimetric and NIR
fluorescence receptors for F− ion detection in aqueous condition and its Live cell
imaging, Sens. Actuators, B 255 (2018) 3194–3206;
(c) M. Salavati-Niasari, M.R. Loghman-Estarki, F. Davar, Controllable synthesis of
nanocrystalline CdS with different morphologies by hydrothermal process in the
presence of thioglycolic acid, Chem. Eng. J. 145 (2008) 346–350
[18] (a) M.K. Chahal, M. Sankar, Porphyrin chemodosimeters: synthesis, electro-
chemical redox properties and selective ‘naked-eye’detection of cyanide ions, RSC
Adv. 5 (2015) 99028–99036;
(b) A. Singh, S. Tom, D.R. Trivedi, Aminophenol based colorimetric chemosensor
for naked-eye detection of biologically important fluoride and acetate ions in or-
gano-aqueous medium: effective and simple anion sensors, J. Photochem.
Photobiol., A 353 (2018) 507–520.
(b) M. Salavati-Niasari, Synthesis and characterization of host (nanodimensional
pores of zeolite-Y)–guest [unsaturated 16-membered octaaza–macrocycle manga-
nese (II), cobalt (II), nickel (II), copper (II), and zinc (II) complexes] nanocomposite
materials, Chem. Lett. 34 (2005) 1444–1445;
[31] A. Singh, S.K. Sahoo, D.R. Trivedi, Colorimetric anion sensors based on positional
effect of nitro group for recognition of biologically relevant anions in organic and
aqueous medium, insight real-life application and DFT studies, Spectrochim. Acta
Part A Mol. Biomol. Spectrosc. 188 (2018) 596–610.
(c) M. Salavati-Niasari, D. Ghanbari, M.R. Loghman-Estarki, Star-shaped PbS na-
nocrystals prepared by hydrothermal process in the presence of thioglycolic acid,
Polyhedron 35 (2012) 149–153.
[32] V. Haridas, M.B. Bijesh, S. Dhawan, A. Shandilya, Peptide-triazole hybrid receptors
for anion recognition, Sens. Actuators, B 245 (2017) 903–910.
[33] S.K. Padhan, M.B. Podh, P.K. Sahu, S.N. Sahu, Optical discrimination of fluoride and
cyanide ions by coumarin-salicylidene based chromofluorescent probes in organic
and aqueous medium, Sens. Actuators, B 255 (2018) 1376–1390.
[34] (a) Y. Zhang, S. Jiang, Fluoride-responsive gelator and colorimetric sensor based
on simple and easy-to-prepare cyano-substituted amide, Org. Biomol. Chem. 10
(2012) 6973–6979;
[19] (a) T.B. Wei, G.T. Yan, H. Li, Y.R. Zhu, B.B. Shi, Q. Lin, Y.M. Zhang, A highly
sensitive and selective “turn-on” fluorescence sensor for rapid detection of cyanide
ions in aqueous solution, Supramol. Chem. 28 (2016) 720–726;
(b) Y. Shiraishi, M. Nakamura, N. Hayashi, T. Hirai, Coumarin–spiropyran dyad
with a hydrogenated pyran moiety for rapid, selective, and sensitive fluorometric
detection of cyanide anion, Anal. Chem. 88 (2016) 6805–6811;
(c) F. Wang, L. Wang, X. Chen, J. Yoon, Recent progress in the development of
fluorometric and colorimetric chemosensors for detection of cyanide ions, Chem.
Soc. Rev. 43 (2014) 4312–4324;
(b) E.J. Cho, Y. Lee, H.J. Bae, Y.J. Lee, Novel azo dye-based color chemosensors for
fluoride ions, Spectrochim. Acta Part A Mol. Biomol. Spectrosc. 151 (2015)
655–661;
(c) W. Wei, S.J. Shao, Y. Guo, A fluoride-sensing receptor based on 2, 2′-bis (in-
dolyl) methane by dual-function of colorimetry and fluorescence, Spectrochim. Acta
Part A Mol. Biomol. Spectrosc. 149 (2015) 531–535.
(d) K. Prakash, P.R. Sahoo, S. Kumar, A substituted spiropyran for highly sensitive
and selective colorimetric detection of cyanide ions, Sens. Actuators, B 237 (2016)
856–864;
[35] S.N. Kodlady, B. Narayana, B.K. Sarojini, S.N. Karanth, B.U. Gauthama, A highly
selective chemosensor derived from benzamide hydrazones for the detection of
cyanide ion in organic and organic-aqueous media: design, synthesis, sensing and
computational studies, Supramol. Chem. 32 (2020) 433–444.
(e) J.W. Hu, W.C. Lin, S.Y. Hsiao, Y.H. Wu, H.W. Chen, K.Y. Chen, An indanedione-
based chemodosimeter for selective naked-eye and fluorogenic detection of cya-
nide, Sens. Actuators, B 233 (2016) 510–519;
(f) L.G. Nandi, C.R. Nicoleti, I.C. Bellettini, V.G. Machado, Optical chemosensor for
the detection of cyanide in water based on ethyl (hydroxyethyl) cellulose functio-
nalized with brooker’s merocyanine, Anal. Chem. 86 (2014) 4653–4656;
(g) A. Kumar, S.K. Asthana, K.K. Upadhyay, A smart ratiometric red fluorescent
chemodosimeter for fluoride based on anthraquinone nosylate, New J. Chem. 41
(2017) 5098–5104;
[36] (a) V.C. Diculescu, S. Kumbhat, A.M. Oliveira-Brett, Electrochemical behaviour of
isatin at a glassy carbon electrode, Anal. Chim. Acta 575 (2006) 190–197;
(b) A. Sola, A. Tárraga, P. Molina, The ferrocene-pyrylium dyad as a selective
colorimetric chemodosimeter for the toxic cyanide and hydrogen sulfide anions in
water, Org. Biomol. Chem. 12 (2014) 2547–2551.
[37] (a) R. Manivannan, K.P. Elango, Structure–reactivity correlation in selective col-
orimetric detection of cyanide in solid, organic and aqueous phases using quinone
based chemodosimeters, New J. Chem. 40 (2016) 1554–1563;
(h) S. Ghosh, M.A. Alam, A. Ganguly, N. Guchhait, Amido-Schiff base derivatives
as colorimetric fluoride sensor: effect of nitro substitution on the sensitivity and
color change, Spectrochim. Acta Part A Mol. Biomol. Spectrosc. 149 (2015)
869–874;
(b) A. Maikap, K. Mukherjee, N. Mandal, B. Mondal, A.K. Meikap, Iron (III) oxide
hydroxide based novel electrode for the electrochemical detection of trace level
fluoride present in water, Electrochim. Acta 264 (2018) 150–156;
(c) R. Manivannan, S. Ciattini, L. Chelazzi, K.P. Elango, Benzoquinone–imidazole
hybrids as selective colorimetric sensors for cyanide in aqueous, solid and gas
phases, RSC Adv. 5 (2015) 87341–87351.
(i) A.K. Atta, I.H. Ahn, A.Y. Hong, J. Heo, C.K. Kim, D.G. Cho, Fluoride indicator
that functions in mixed aqueous media: hydrogen bonding effects, Tetrahedron Lett.
53 (2012) 575–578;
(j) A. Kumar, S. Kumar, N. Ahmed, ‘Naked-eye’colorimetric/fluorimetric detection
of F− ions by biologically active 3-((1 H-indol-3-yl) methyl)-4-hydroxy-2 H-
chromen-2-one derivatives, RSC Adv. 6 (2016) 108105–108112;
(k) B. Liu, H. Tian, A ratiometric fluorescent chemosensor for fluoride ions based
on a proton transfer signaling mechanism, J. Mater. Chem. 15 (2005) 2681–2686.
[20] D. Esteban-Gomez, L. Fabbrizzi, M. Licchelli, Why, on interaction of urea-based
receptors with fluoride, beautiful colors develop, J. Org. Chem. 70 (2005)
5717–5720.
[38] (a) D. Mohanasundaram, G.G.V. Kumar, S.K. Kumar, B. Maddiboyina, R.P. Raja,
J. Rajesh, G. Sivaraman, Turn-on fluorescence sensor for selective detection of
fluoride ion and its molecular logic gates behavior, J. Mol. Liq. 113913 (2020);
(b) G. Balamurugan, P. Venkatesan, S.P. Wu, S. Velmathi, Novel ratiometric turn-
on fluorescent probe for selective sensing of cyanide ions, effect of substitution and
bio-imaging studies, RSC Adv. 6 (2016) 24229–24235.
[39] S. Suganya, J.S. Park, S. Velmathi, Visual sensing of aqueous anions by C2-sym-
metric chemosensor and its application in real sample analysis, Sens. Actuators, B
190 (2016) 679–684.
[21] K. Chellappan, N.J. Singh, I.C. Hwang, J.W. Lee, K.S. Kim, A calix [4] imidazolium
[2] pyridine as an anion receptor, Angew. Chem. Int. Ed. 44 (2005) 2899–2903.
[22] S. Devaraj, D. Saravanakumar, M. Kandaswamy, Dual chemosensing properties of
10