Selective detection of fluoride via amplified donor-acceptor interaction of 6H-indolo[2,3-b]quinoline

Article abstract of DOI:10.1016/j.saa.2018.11.064

In this report, 6H-indolo[2,3-b]quinoline (hereafter 2a) was synthesized and employed as an optical chemosensor for fluoride. The sensitivity of 2a towards fluoride was established from the change in both the absorption and emission signals. The various i

Full text of DOI:10.1016/j.saa.2018.11.064

Accepted Manuscript
Selective detection of fluoride via amplified donor-acceptor
interaction of 6H-indolo[2,3-b]quinoline
Rupa Pegu, Gopal Pandit, Ankur Kanti Guha, Sajal Kumar Das,
Sanjay Pratihar
PII:
DOI:
Reference:
S1386-1425(18)31061-8
https://doi.org/10.1016/j.saa.2018.11.064
SAA 16628
Spectrochimica Acta Part A: Molecular and Biomolecular
Spectroscopy
To appear in:
Received date: 7 May 2018
Revised date:
Accepted
date:
27 November 2018
29 November 2018
Please cite this article as: Rupa Pegu, Gopal Pandit, Ankur Kanti Guha, Sajal Kumar Das,
Sanjay Pratihar , Selective detection of fluoride via amplified donor-acceptor interaction
of 6H-indolo[2,3-b]quinoline. Saa (2018), https://doi.org/10.1016/j.saa.2018.11.064
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journal homepage: www.elsevier.com
Selective detection of Fluoride via amplified Donor-Acceptor interaction
of 6H-indolo[2,3-b]quinoline
Rupa Pegu,[a] Gopal Pandit,[a] Ankur Kanti Guha,[b] Sajal Kumar Das,*[a] and Sanjay
Pratihar*[a]
aDepartment of Chemical Sciences, Tezpur University, Assam-784028, India, E-mail: spratihar29@gmail.com or spratihar@tezu.ernet.in
and sajalkd@tezu.ernet.in
bDepartment of Chemistry, Cotton College State University, Panbazar, Guwahati, Assam-781001, India
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
In this report, 6H-indolo[2,3-b]quinoline (hereafter 2a) was synthesized and
employed as an optical chemosensor for fluoride. The sensitivity of 2a towards
fluoride was established from the change in both the absorption and emission
signals. The various in-situ 1H NMR, UV-Vis, and density functional studies
indicate that the 1:2 binding interaction between 2a and fluoride followed by
deprotonation to its corresponding di-anion (2a2–), which in turn boosted the donor-
acceptor interaction between indole and quinoline moiety in 2a2– via expansion of
torrision angle by 10.2˚ as compared to 2a. Consequently the significant changes in
both the absorption and emission signal of 2a allow us to detect and estimate the
concentration of fluoride up to 0.2 µM fluoride from the mixture of different
anions.
Available online
Keywords:
Sensor
Donor
Acceptor
6H-indolo[2,3-b]quinoline
Fluoride
2009 Elsevier Ltd. All rights reserved.
1. Introduction
The sensing and recognition of fluoride has grown into an area of great interest in supramolecular and biological
chemistry because of its applications in many areas.1 Fluoride is well known for its important application in dental care and
in the treatment of osteoporosis.2 However excess fluoride can cause bone fluorosis, immune system disruption, thyroid
disorder, kidney damage, and even cancer.3 Furthermore, high intake of fluoride in plants may inhibit photosynthetic
capacities and hence affect biomass productivity.4 Thus, there is a growing interest on the development of optical chemo
sensor, where the interaction with an anion leads to a change in the absorbance (color) or fluorescence properties of the
receptor, for selective detection and estimation of fluoride from a mixture of other anions and are the most widely studied
class of anion sensor.5 To date, there are a number of ways in which optical anion sensing can be achieved. One frequently
used strategy is to functionalize an anion binding group with a chromophoric or fluorophoric group capable of signaling the
binding event into corresponding change in absorbance or emission signal.6 The signaling unit is either directly attached to
the receptor or separated from the receptor through a short covalent linker. In both the cases, formations of a supramolecular
anion−receptor complex through noncovalent interactions lead to a change in the absorbance or emission properties of the
signaling unit. 7,8 “Chemodosimeters” are another type of discrete optical sensors, in which anion reacts with the sensor (or
9
catalyzes a reaction) to create a new molecule with different optical properties. In most of the cases, the principle of the
sensing methods rely either on strong interactions between Lewis-acidic boron or silicon with fluoride (Fig. 1), or hydrogen
bonding and other types of interactions involving fluoride as a participant or a disrupter (Fig. 1).10 Towards this, Gabbai
and co-workers developed colorometric fluoride sensor based on; (i) B-F interaction in highly delocalized aryl

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substituents containing boron compounds, (ii) charge transfer (CT) or intramolecular charge transfer (ICT) process in
fluoride binding to triarylboranes with extended π-conjugation, and (iii) metal-to-ligand charge transfer (MLCT)
absorption bands from the interaction between fluoride and boron center of borylated ligands in transition metal
11
complexes (Fig. 1). On the other hand, in most of the silicon based sensor, electrofugal tert-butyldiphenylsilane
(TBDPS) group has been attached with chromogenic fragment. The interaction of fluoride with Lewis acidic silicon
promotes the cleavage of Si-O bond, which undergo dramatic changes in the UV−vis absorption properties of the
chromogenic unit, corresponding to a change in color (Fig. 1). 12
Fig. 1. Sensor based on “chemodosimeters”. Sensing through strong interactions between Lewis-acidic boron and fluoride (Type I). Sensor
based on fluoride promoted cleavage of Si-O bond (Type II). Sensor based on fluoride induced deprotonation (Type 3).
There is another type of sensors, in which strongest hydrogen bonding interaction between N-H fragment(s) of
amides, sulfonamides, pyrroles, indoles, ureas and fluoride has been utilized for the deprotonation of N-H to generate
the corresponding anionic molecule.13 The extra charge brought through deprotonation caused a change in the dipole
associated to the charge-transfer transition, which ultimately modifies absorption and emission signal of the molecule
(Fig. 1). Owing this strategy, various class of molecule containing indole moieties viz. tris(indolyl) methanes,14 bis(indolyl)
methanes,15 hydrazone based indoles,16 indole-linked quinolone derivative,17 oxidized bis(indolyl) methanes,18 bisindole
diazine,19 BODIPY-indole conjugate20 DNP derivative of bis(indolyl) methane21 etc. with varying degrees of affinity and
selectivity towards fluoride have been developed. In the present work, we wanted to utilize the 6H-indolo[2,3-
b]quinoline (2a) as chemosensor for the detection of anions. The donor acceptor interaction between indole and
quinoline moiety of 2a is expected to be modified after the interaction with anions as both the moieties are not in the
same plane. In fact, strongest hydrogen bonding interaction between N-H of indoles and fluoride followed by
deprotonation resulted the formation of di-anion (2a2–). The extra charge in 2a2– caused more delocalization between
indole and quinoline via expansion of torrision angle by 10.2˚ in 2a2– as compared to 2a. Thus, the fluoride induced
boosted interaction modifies the absorption and emission signal of 2a and has been utilized for the selective detection
of fluoride in presence of other anions.
2.
Experimental Section
2.1.
Synthesis of 6H-indolo[2,3-b]quinoline (2a)
In a 10 mL round bottom flask equipped with a magnetic bar and refluxed condensor, was charged with Fe(ox)–Fe3O4 (0.05
mmol) in water (3 mL) stirred vigorously for 5 min in open air. [25] After that, 2-nitro benzaldehyde (1 mmol) and Indole
(2.2 mmol) was added to it and placed into a constant temperature bath and refluxed at 110 C for 6 h under vigorous
stirring. After completion of the reaction, the product was extracted with ethylacetate (20 mL×3) and washed with water (10
mL×3), brine (10 mL) and dried over anhydrous Na2SO4. After removing the solvent the crude residue was used as it is for
next step. A solution of 1a (1 mmol) and SnCl2. 2H2O (5 mmol) in methanol (4 mL) was refluxed for 3 h. The solution was
allowed to cool at room temperature and was then poured into ice. After that, 5% aqueous NaHCO3 solution was added to it
to make the solution slightly basic (pH ≈ 8). After that, ethylacetate (50 mL) was added to the reaction mixture and filtered
through a bed of Celite. The organic layer was washed with water (50 mL), brine (50 mL) and dried over anhydrous Na2SO4

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and evaporated to dryness under reduced pressure. The residue was purified by silica gel column chromatography using
1
hexane/ethyl acetate to afford pure 2a. Yield = 58% IR (KBr): 3333, 3427, 3030, 2280, 1708 cm-1. H NMR 400 MHz
(DMSO): δ (ppm) 7.05 (t, 1H, J=8 Hz), 7.10 (d, 1H, J=12 Hz), 7.17-7.25 (m, 2H), 7.42 (t, 1H, J=7.6 Hz), 7.49-7.53 (m, 2H),
7.59-7.63 (m, 2H), 7.83 (s, 1H), 7.92 (d, 1H, J=8 Hz), 8.22 (d,1H, J=8 Hz), 8.34 (d, 1H, J=8 Hz), 10.82 (s, 1H, N-H), 11.75
(s, 1H, N-H) 13C NMR 109.2 MHz (DMSO): 107.8, 112.4, 112.6, 119.7, 119.9, 120.1, 120.6, 121.6, 121.8, 122.2, 124.7,
126.0, 126.3, 127.1, 127.3, 129.7, 129.8, 132.0, 137.8, 144.5, 144.6, 145.7.
2.2.
Computational Details
The molecules were fully optimized without any geometry constraints at Becke, three-parameter, Lee-Yang-Parr (B3LYP)
level of theory using 6-311+G** basic set. 22 Frequency calculations have also been performed at the same level of theory to
characterize the nature of the stationary states. All geometries were found to be local minimum with real frequencies. The
fluorescence spectra of 2a and 2a-F- were computed within the TD-DFT framework using B3LYP/6-311+G** level of
theory in solution phase (using DMSO as the solvent with dielectric constant 46.7). For solvent phase calculations,
polarizable continuum model (PCM) has been used.23 All calculations were performed using Gaussian09 suite of program.24
3.
Results and Discussion
The Fe(ox)-Fe3O4 promoted condensation reaction between 2-nitro benzaldehyde and 2 equivalent of corresponding
indole leads to the bis(indollyl)methane (1a) in 82% yield.25 The corresponding 6H-indolo[ 2,3-b]quinoline moiety
was synthesized via following a reported SnCl2 mediated intramolecular cyclization of 1a via C–N bond formation by
Kundu and co workers (Scheme 1).26
Scheme 1. Synthetic route of 6H-indolo[2,3-b]quinoline.
3.1.
UV-vis and DFT study
The compound 2a showed three peaks at 222, 312, and 422 nm with extinction coefficients (, mol-1Lcm-1) of 5×104,
4×103, and 3.22×103 in dimethyl sulfoxide (DMSO). Upon gradual addition of tetrabutyl ammonium fluoride (TBAF)
to DMSO solution of compound 2a (50 µM), the absorbance at 422 nm increases, while a new band centered at 485
nm is gradually appears due to the interaction between 2a and fluoride (Fig. 2). However the absorbance at 422 nm
reaches maximum after the addition of 5 equivalent fluorides. Further addition of fluoride leads to an increases in the
absorbance at 484 nm band with decrease in the absorbance for band at 422 nm.27 The new band at 484 nm may be
attributed due to the association or association-dissociation equilibrium between two different type of N–H of 2a and
fluoride. This phenomenon can occur either stepwise or single step. Initially, to get an idea about the binding
stoichiometry between fluoride and compound 2a, Job’s plot experiment with a fixed fluoride and 2a concentration of
100 µM was done by using UV-vis study. The binding stoichiometry between compound 2a and fluoride was found to
be 1:2. So, two chemically different N–H present in compound 2a interacting with two different fluoride. The
calculated binding constant from the corresponding absorbance change upon gradual addition of fluoride to 2a was
found to be 5.0 ×103 M-2 using Bensi-Hildenberg equation.28 So, fluoride promoted H-bonded interaction or
interaction followed by deprotonation between 2a and fluoride is responsible for the corresponding colour change. To

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check this, [Bu4N]OH was added in the DMSO solution of compound 2a, which brought the same colour and spectral
changes of 2a as those observed with fluoride anions. The strong base [Bu4N]OH will definitely leads to
deprotonation in compound 2a by abstracting two N–H proton. Further, to check the reversibility of the process, protic
solvent such as; methanol or water was added in brown colour solution of 2a after treated with fluoride or [Bu4N]OH.
In both the cases, brown colour solutions turned into light yellow and revert back to its original absorption spectra,
which indicate that the proton dissociation–association process is reversible in nature. To clarify the change in
absorption spectrum after the interaction of fluoride, geometry of 2a, 2a-2F– and its di-anion (2a2–) were optimized at
B3LYP/6-311+G** level of theory and their HOMO-LUMO energy gap were determined.
Fig. 2. The changes in UV-vis spectra of 2a recorded in DMSO (50 M) after gradual addition of fluoride (a) and Job’s plot for compound
2a with a fixed concentration of 2a and fluoride of 100 M (b).
In compound 2a, HOMO primarily resides on both indole and quinoline moiety and LUMO localized majorly on the
quinoline moiety (Fig. 3). The 1:2 hydrogen bonding interaction between two different N–H protons and fluoride
promotes a negative charge transfer around indole and quinoline moieties, resulting decrease in HOMO-LUMO
energy gap in 2a-2F–, which further decrease in dianion (2a2–) and shows corresponding transition at 485 nm (Fig. 2-
3).
Fig. 3. Calculated HOMO LUMO energy gap of 2a, 2a-2F-, and 2a2–
3.1.
NMR study
Further, to get an idea about the binding phenomenon of compound 2a with fluoride, 1H NMR titration of compound
2a was done with gradual addition of fluoride in DMSO-d6. After addition of 0.5 equivalent of TBAF salt to
compound 2a leads to complete disappearance of both the N–H proton of quinoline and indole moiety, which indicate
very fast H-bonded association-dissociation equilibrium because of highly acidic quinoline and indole N–H proton
(Fig. 4). Although complete disappearance of both the N–H proton was observed at lower equivalent of TBAF, but no

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generation of corresponding peak for [HF2]– was observed at lower equivalent of TBAF.29 However, addition of 20
equivalent of fluoride resulted a new triplet peak at 16.1, indicates the formation of [HF2]– via the abstraction of both
the indole and quinoline N–H proton of 2a (Fig. 4).30 Further 19F NMR of 2a in DMSO-d6 after the addition of 20
equivalent of fluoride shows a signal at -146.1 ppm corresponding to [HF2]– due to the deprotonantion of 2a. On the
other hand gradual addition of TABF to DMSO-d6 solution of 2a results down field shift of Hc proton of indole
moiety as well as up-field shift of both Hd and He proton. Both the up-field and down-field shift of corresponding ring
proton increases with increasing amount of TBAF, which suggest the delocalization of electron around the molecule
increases with subsequent generation of di-anion of 2a. The down-field shift of indole C–H (Hc) proton and up-field
shift of quinoline C–H proton indicates that the negative charge brought after the abstraction of indole N–H results the
flow of electron from indole to quinoline moiety, which is responsible for change in both absorption and emission
signal of 2a after the interaction with fluoride.31 Further to check the donor-acceptor interaction between indole and
quinoline moiety, both the structure 2a and its di-anion 2a2– were optimized in DMSO solvent at B3LYP/6-311+G**
level of theory. In compound 2a, the torrision angle between indole and quinoline moiety was found to be 108.6˚,
which suggest the possible donor-acceptor interaction between indole and quinoline moiety of 2a. However expansion
of torrision angle by 10.2˚ in di-anion (2a2–) is likely to be indicative of more planarity between indole and quinoline
moiety, which is also indicative of more electron flow from indole to quinoline moiety after deprotonation (Fig. 5).
The more electron donation from indole to quinoline moiety in 2a2– is also likely to be responsible for corresponding
lower HOMO-LUMO energy gap and subsequent red shift of the existing band in 2a to low energy band at 485 nm in
2a2–.
1
Fig. 4. H NMR spectra of compound 2a in DMSO-d6 upon gradual addition of TBAF; change of the N–H proton (a) and change of other
protons (b).

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Fig. 5. Calculated torrision angle between indole and quinoline moiety in 2a and 2a2–
3.1.
Emission study
The fluorescence emission spectra of 2a consist of one band with maxima at 490 nm corresponding to the neutral species
upon photo irradiation at 420 nm. Upon gradual addition of TBAF in DMSO solution of 2a, a significant enhancement of the
existing 490 nm band was observed due to the interaction between fluoride and two N–H of 2a. On the other hand, after
addition of TBAF to DMSO solution of 2a, a new band appears at 535 nm upon photo irradiation at 485 nm, which is found
to be absent in 2a (Fig. 6). To get a theoretical insight of the corresponding transition, the fluorescence spectra of 2a and 2a-
F– were computed within the TD-DFT framework using B3LYP/6-311+G** level of theory32 in polarizable continuum
model (PCM) using DMSO solvent33 using Gaussian09 suite of program.34 The calculated fluorescence bands are in very
good agreement with the experimental one (Fig. 6-7). For compound 2a, the calculations showed two bands; one intense
band at 486 nm (oscillator strength, f = 0.029) and the other at 472 nm (oscillator strength, f = 0.010). The band at 486 nm
was assigned to the transition from HOMO to LUMO, while the transition at 472 nm is assigned to the transition from
HOMO-1 to LUMO. The fluorescence band for fluoride bonded structure (2a-F–) was also calculated at same level of theory
in DMSO. The calculation revealed one band at 536 nm (f = 0.012) for HOMO to LUMO and another at 482 nm (f = 0.054)
for HOMO-1 to LUMO transition (Fig. 7). The assigned calculated band positions as well as its oscillator strength are found
to be in good correlation with experimentally observed result.

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Fig. 6. The changes in emission spectra of 2a recorded in DMSO (5 M) after gradual addition of fluoride upon photoirradiation at 420 nm
(a) and at 485 nm (b).
Fig. 7. TD-DFT calculated fluorescence spectra of compounds 2a and 2a-F–.
3.1.
Selectivity in presence of other anions
To verify the anion specificity, UV-vis monitoring of 2a was performed with other tetrabutylammonium salts (TBA-
X: X= Cl, Br, I, CH3COO, BF4, PF6, SbF6, H2PO4, PO4, HF2, and HSO4) in DMSO. Under identical experimental
condition, no appearance of peak at 485 nm was observed with other anions in spite of their presence in large excess
compared to fluoride. However, in most of the anions, a decrease in intensity of 422 nm peak was observed in most of
the cases.35 The generation of new peak at 490 nm is also observed in a mixture of different anions containing
fluoride, which shows the selectivity of 2a towards fluoride in presence of other anions (Fig. 8).

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Fig. 8. The change in UV-vis spectra of 2a (in 50 µM DMSO solution) after the addition of different anions (50 µM) (a); change of
absorbance at 485 nm after the addition of different anions (b).
Further selectivity of compound 2a was tested from emission study. Room temperature emission spectrum of 2a
solution in DMSO shows a single and structured band peaking around 490 nm upon photoirradiation at 420 nm, which
is ascribed to the neutral species. The enhancement in intensity of 490 nm peak was found to be observed upon
gradual addition of fluoride. On the contrary, nearly no detectable fluorescence enhancement was observed upon
addition of large excess of other tetrabutylammonium salts (TBA-X: X= Cl, Br, I, CH3COO, BF4, PF6, SbF6, and
HSO4). Gratifyingly, a distinct difference in fluorescence enhancement of the existing 490 nm peak of compound 2a
could also able to detect variable concentration of fluoride in presence of different anions (Fig. 9).
Fig. 9. The change in emission spectra of 2a (in 5 µM DMSO solution) after the addition of different anions (100 µM), mix. a and mix. b
represent two different mixture of eight different anion (10 µM) with 5 and 10 µM of fluoride respectively (a); and change of fluorescence
intensity at 490 nm after the addition of different anions (b).
4.
Conclusions

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In summary, 6H-indolo[2,3-b]quinoline (2a) was synthesized and applied as a selective chemosensor for fluoride via
color changes as well as change in both the absorption and emission signals. The observed evidences from in-situ 1H
NMR, UV-Vis, emission and density functional studies suggest that torrision angle between indole and quinoline
moiety in 2a is likely to be enhanced during the fluoride induced deprotonation of 2a, which is amplifying the donor-
acceptor interaction between indole and quinoline moiety and is responsible for the spectroscopic change in 2a. The
selective detection of fluoride in presence of other anions using both the absorbance and emission signal is also found
to be suitable with 2a and allow us to detect and estimate the concentration of fluoride up to 0.2 µM.
Acknowledgments
The financial support to this work by DST-New Delhi (Grant No. IFA-12-CH-39) and Indian National Science
Academy (INSA) for providing fellowship to SP is gratefully acknowledged.
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23
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Vreven, K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani,
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revision D.02, Gaussian, Inc.: Pittsburgh, PA, 2009.

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The decrease in absorbance may be due to the lowering in concentration of corresponding anion of 2a, which is
due to the aggregated assembly between the anion of 2a and the corresponding tetrabutyl ammonium (TBA) cation of added
TBAF.
28
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29
The fluoride induced hydrogen bonding interaction with N-H proton of indole of 2a facilitate the rapid
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equivalent of TBAF.
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31
1
During the H NMR titration, we observed the following; (i) intensity of the shifted peaks were lower, (ii) some
unidentified peaks. This may be due to the lowering in concentration of the corresponding di-anion (2a2-), which may be due
to the less solubility of 2a2- or aggregated assembly between the 2a2-and the corresponding tetrabutylammonium (TBA)
cation of added TBAF.
32
J. P. Perdew, K. Burke, M. Ernzerhof, Generalized gradient approximation made simple, Phys. Rev. Lett., 77
(1996) 3865.
33
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distributions of the solvent, Chem. Rev. , 94 (1994) 2027-2094.
34
M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, J. A. Montgomery Jr, T.
Vreven, K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani,
N. Rega, G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y.
Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratchian, 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, P. Y. Ayala, K. Morokuma, G.
A. Voth, P. J. Salvador, J. Dannenberg, V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M. C. Strain, O. Farkas, D. K.
Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul, S. Clifford, J. Cioslowski, B. B.
Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A.
Nanayakkara, M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W. Wong, C. Gonzalez, J. A. Pople, Gaussian 03,
revision D.02, Gaussian, Inc.: Pittsburgh, PA, 2009.
35
The selectivity of 2a towards fluoride in presence of other anions in aqueous medium was checked after the
addition of aqueous solution of mixture of 10 different anions to DMSO solution of 2a (DMSO : H2O = 9:1, 2.7 : 0.3 mL).
However we did not observe any change in the absorbance spectra of 2a. The presence of water inhibits the formation of di-
anion via inhibiting the fluoride induced deprotonation process.

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Graphical abstract

ACCEPTED MANUSCRIPT
Highlights
6H-indolo[2,3-b]quinoline (2a) was synthesized and applied as a selective chemosensor for fluoride, in which
torrision angle between indole and quinoline moiety in 2a is likely to be enhanced during the fluoride induced
deprotonation of 2a, which is amplifying the donor-acceptor interaction between indole and quinoline moiety
and is responsible for the spectroscopic change in 2a.

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