Spectrochemical and theoretical approaches for acylhydrazone-based fluoride sensors

Article abstract of DOI:10.1007/s11164-018-3609-4

Abstract: Acylhydrazone derivatives N′-[1-(2-fluorophenyl)ethylidene]pyridine-3-carbohydrazide (R1) and N′-[2-fluorobenzylidene]benzohydrazide (R2) were synthesized from their corresponding hydrazides and characterized by spectroscopic methods. The respon

Full text of DOI:10.1007/s11164-018-3609-4

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-018-3609-4
Spectrochemical and theoretical approaches
for acylhydrazone‑based fuoride sensors
Jemini Jose, et al. [full author details at the end of the article]
Received: 6 July 2018 / Accepted: 24 September 2018
© Springer Nature B.V. 2018
Abstract
Acylhydrazone derivatives N′-[1-(2-fuorophenyl)ethylidene]pyridine-3-carbohy-
drazide (R1) and N′-[2-fuorobenzylidene]benzohydrazide (R2) were synthesized
from their corresponding hydrazides and characterized by spectroscopic methods.
The response of these acylhydrazones towards diferent anions was studied by col-
orimetric and spectrofuorometric methods in acetonitrile. The receptors exhibited
a specifc response towards fuoride ion. The binding afnity of the receptors with
fuoride anion was studied by fuorescence spectroscopic techniques and ab initio
density functional theory calculations with Becker’s three-parameter Lee–Yang–Par
(B3LYP) exchange functional with 6-311G basis set.
Graphical abstract
2.0
Ligand
Acetate
Bromide
1.5
1.0
0.5
0.0
Chloride
Fluoride
Iodide
Posphate
275 300 325 350 375 400 425 450 475 500
wavelength(nm)
F
F
O
F-
O
N
N
N
N
H
R
N
R
N
H
F
R=H, CH3
Keywords Acylhydrazones · TD-DFT · Ab initio · Fluoride sensing · Anion
recognition
Vol.:(0123456789)
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J. Jose et al.
Introduction
We discuss the fuoride sensing ability of acylhydrazones N′-[1-(2-fuorophenyl)
ethylidene]pyridine-3-carbohydrazide (R1) and N′-[2-fuorobenzylidene]benzo-
hydrazide (R2) in acetonitrile. Optical and electrochemical sensing of biochemi-
cally and environmentally important species has emerged as a focus of attention
for research into sensor design in the contemporary era [1–4]. In particular, the
progress of fuoride ion chemosensors is of great importance, due to its advanta-
geous impacts on human physiology [5, 6]. Among inorganic anions, the fuoride
ion plays a special role in bone growth, tooth care, and related metabolic activities.
Additionally, fuoride is an efective component in drugs and fabrication of nuclear
weapons [7–9]. Although fuorine intake is fast, it is discharged slowly. Excess fuo-
ride consumption results in acute fuorosis and is identifed as one of the poten-
tial threats faced by many people living in India. Mining as well as other related
activities result in unnatural concentrations of fuoride along with other anions.
This subject is very important in the present environmental scenario too. Lessened
rainfall and global warming will increase the atmospheric temperature, raising the
concentration of fuoride ion in surface water. Being very small in size and highly
electronegative, detection of fuoride in protic solvents when present in minute con-
centrations has always been a challenge, as has its removal. As a result of its signif-
cance, detection of fuoride using an efectively synthesized receptor and negligible
instrumental help is greatly favored for efective applications. For this reason, col-
orimetric chemosensors have attracted immense interest in recent years [10–12].
Functional groups which have been explored as good receptors for fuoride
ions include amides, pyrrole, urea/thiourea, imidazolium, phenylhydrazone, etc.
[13–17]. However, the majority of these sufer from interference from other anions.
Hydrazones are widely used in analytical chemistry as a selective metal-extract-
ing agent, as well as in spectroscopic determination of certain transition metals.
They have been the subject of extensive investigation due to their versatile chelat-
ing behavior, in particular those derived from pyridoxal phosphate and isonicotinic
acid. Their potential hydrogen-donor ability also supports the sensing behavior of
hydrazone compounds. In this connection, we synthesized two acylhydrazones and
studied their fuoride sensing ability using experimental and theoretical approaches.
Results and discussion
The structural formula of compounds R1, R2 is shown in Fig. 1.
Fig. 1 Structural formula of
receptors R1, R2
F
F
O
O
N
N
NH
NH
N
Receptor 1
Receptor 2
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Spectrochemical and theoretical approaches for…
Good-quality crystals were separated from methanolic medium, and the crys-
tal structures reported in Acta E [18–20]. Characteristic infrared (IR) stretching
frequencies of imine-containing chelating groups in receptors R1, R2 appeared
at 1538 and 1558 cm−1, respectively. The 1H nuclear magnetic resonance
(NMR) spectrum of R1 showed two singlets at δ 10.95 and δ 2.36 ppm, attrib-
uted to N–H protons and methyl protons, respectively. For R2, subsequent NH
1
protons appeared at δ 10.05 and singlet hydrogen at 9.03 ppm in the H NMR
spectrum.
Colorimetric analysis and UV–Vis spectral analysis
The interaction of receptors R1, R2 with various anions such as fuoride, chlo-
ride, iodide, bromide, dihydrogen phosphate, and acetate ions was investigated
in acetonitrile by colorimetric analysis. Appreciable color changes from color-
less to yellow were observed for the receptors on addition of fuoride anion,
while other anions failed to cause color changes. This inability to cause any sig-
nifcant color change in the receptor solutions indicates no recognition of these
anions except fuoride. This is well supported by ultraviolet–visible (UV–Vis)
analysis. The spectral profles in Figs. 2 and 3 show absorption peaks at 281 and
293 nm, attributable to π → π* transitions for R1 and R2, respectively. Com-
pounds R1 and R2 showed absorption at 308 and 306 nm, respectively, assigned
to n → π* transition. Signifcant variation in the absorption spectra was identi-
fed with fuoride ion, because of complexation between the host and guest mol-
ecules. Moreover, receptor R2 exhibited a new peak for acetate ion with less
3
R1
R1+Fluoride
2
1
0
300
350
400
450
500
550
600
Wavelength (nm)
Fig. 2 Absorption spectra of N′-[(1E)-1-(2-fuorophenyl)ethylidene]pyridine-3-carbohydrazide (R1) with
fuoride ion
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J. Jose et al.
2.0
1.5
1.0
0.5
0.0
R2
Acetate
Bromide
Chloride
Fluoride
Iodide
Posphate
275 300 325 350 375 400 425 450 475 500
Wavelength(nm)
Fig. 3 Absorption spectra of N′-[(E)-2-fuorobenzylidene]benzohydrazide (R2) with diferent TBA ani-
ons
intensity at 375 nm. Slight variation in color was observed for R2 when mixing
with acetate too.
To determine the anion sensing ability of the compounds with fuoride and ace-
tate at 298 K, titrations were carried out in acetonitrile and monitored using UV–Vis
spectroscopy. The experiment was performed by preparing 5 × 10−5 mol L−1 solu-
tion of compounds R1 and R2 in acetonitrile, followed by addition of tetrabutyl-
ammonium ions at diferent concentrations. As the amount of fuoride ion in the
UV–Vis titrations was increased, the receptors showed an intensity decrease and a
2.0
0 eq
1.0 eq
1.5 eq
1.5
2.0 eq
2.5 eq
3.0 eq
3.5 eq
4.0 eq
4.5 eq
5.0 eq
1.0
0.5
0.0
225 250 275 300 325 350 375 400 425 450 475
wavelength(nm)
Fig. 4 Absorption spectra of N′-[(1E)-1-(2-fuorophenyl)ethylidene]pyridine-3-carbohydrazide (R1)
[5 × 10−5 M] with diferent equivalents of fuoride ion
1 3

Spectrochemical and theoretical approaches for…
0 eq
1 eq
2.0
1.5
1.0
0.5
0.0
1.5 eq
2.0 eq
2.5 eq
3.0 eq
3.5 eq
4.0 eq
4,5 eq
250
300
350
400
450
wavelength(nm)
Fig. 5 Absorption spectra of N′-[(E)-2-fuorobenzylidene]benzohydrazide [5 × 10−5 M] (R2) with difer-
ent equivalents of fuoride ion
small bathochromic shift in the absorption band corresponding to n → π* transi-
tions, plus subsequent formation of a new band at 368 and 377 nm, respectively.
Both the new transition band and relative intensity of the receptor with respect to the
band upon addition of fuoride depended on the receptor used, as shown in Figs. 4
and 5.
Fluorescence spectral studies
The fuorescence spectrum of both receptors R1, R2 was monitored in acetonitrile.
The excitation wavelength was optimized and chosen as 398 and 375 nm for R1 and
R2, respectively. When 0–5 equivalent of tetrabutylammonium fuoride was added to
the solution of receptors R1, R2, a concomitant increase of the fuorescence intensity
was observed. The fuorescence spectral profles are shown in Figs. 6 and 7.
Fig. 6 Emission spectra of
N′-[(1E)-1-(2-fuorophenyl)
ethylidene]pyridine-3-carbohy-
drazide (R1, 100 μM) at 398 nm
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J. Jose et al.
Fig. 7 Emission spectra of
N′-[(E)-2-fuorobenzylidene]
benzohydrazide (R2, 100 μM)
in acetonitrile at 375 nm
Addition of fuoride anion induced a slight red-shifted emission band at 438
(R1) and 450 nm (R2). These are clear indications that the so-called fuorescence
enhancement results from removal of the n → π* transitions which normally mask
the π → π* transition that is mainly responsible for the emission behavior. Hence,
the recognition of a molecule does not simply absorb color but also involves seri-
ous electronic reorganization within the molecule, appreciably afecting the high-
est occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital
(LUMO) interactions. In the same conditions, no signifcant spectral changes were
observed on addition of 5 equivalents of other tetrabutylammonium anion salts.
Computational details
UV–Vis and fuorescence spectral studies confrmed selective sensing of fuo-
ride ion by the receptors. To investigate the chemosensing mechanism of R1, R2
toward F− ions, computational calculations using ab initio density functional theory
(DFT) for the structural properties of the receptors and their complexes with F− ion
were carried out. DFT calculations with Becker’s three-parameter Lee–Yang–Par
(B3LYP) exchange functional with 6-311G basis set were carried out for geometry
optimization. The optimized ground-state structures of R1, R2 and their fuoride
complexes are shown in Fig. 8. The energy gap between the HOMO and LUMO
molecular orbitals of R1, R2, and their fuoride complexes are shown in Fig. 9.
The bond parameters of the optimized structures of the receptors are presented in
Table 1. Selected experimental and theoretical parameters for R1, R2 are presented
in Table 2. The results show that the experimental and theoretical values are in good
agreement with recent contributions in the feld [18–22].
The N9–H19 and C10–O bond distances of R1 in ground state were found to
be 1.01 and 1.22 Å respectively, being increased in the R1–F complex. This bond
length elongation can be ascribed to N9–H19 bond breakage and generation of a
single bond between C10–O, while C7–N8 and N8–N9 had approximately equiva-
lent values in R1 and R1–F. The theoretical bond distances of N10–H and N10–C11
were 1.00 and 1.38 Å, respectively, for R2. The increase of these distances in R2–F
can be attributed to bond elongation due to addition of fuorine. The shortening of
the N8–N9 and N9–N10 bond distances after addition of fuorine also supports the
sensing ability of the acylhydrazones. The calculated F–H values of R1–F and R2–F
1 3

Spectrochemical and theoretical approaches for…
Fig. 8 Optimized ground-state geometry of R1, R2, R1–F, and R2–F
Fig. 9 Energy gap between HOMO and LUMO orbitals of R1, R1–F, R2, and R2–F
1 3

J. Jose et al.
Table 1 Bond characters of R1,
R2, R1–F, and R2–F at ground
state
R1
R1–F
R2
R2–F
C4–C7
C7–N8
N8–N9
N9–H19
C10–O
1.48
1.28
1.39
1.01
1.22
C8–H12
C8–N9
N9–N10
N10–H
1.08 1.09
1.29 1.28
1.37 1.29
1.00 1.69
1.380 1.43
1.22 1.22
1.29
1.37
1.35
1.25
N10–C11
C10–N9–N8
122.93 119.06 C11–O
N8–N9–C10–O 14.805 1.897 O–C11–N10–N9 2.37 17.45
F–H 1.02 F–H 0.96
–
–
were 1.02 and 0.96 Å, respectively, close to the value for a fuorine–hydrogen single
bond. Therefore, a plausible mechanism for the addition of fuorine in R1, R2 is
shown in Fig. 10.
Conclusions
Two acylhydrazone receptors R1, R2 were synthesized in good yield via condensa-
tion reaction. Both receptors R1, R2 exhibited higher sensitive for fuoride anion
with a prominent color change observable to the naked eye. They were found to
provide anion recognition through H-bonding interactions. The sensing ability
and binding afnity of both receptors towards fuoride were examined using spec-
troscopic techniques and ab initio DFT calculations, revealing high sensitivity for
and selectivity towards fuoride even in a biologically competing solvent such as
acetonitrile.
Experimental section
Materials and methods
2-Fluoroacetophenone, 2-fuorobenzaldehyde, nicotinic acid hydrazide, benzoic acid
hydrazide (Fluka), and tetra-n-butylammonium salts (Aldrich) were of analytical
grade and stored in vacuum desiccators containing self-indicating silica gel, being
used without further purifcation. All solvents were purifed prior to use.
1H NMR spectra of the samples were recorded on a Bruker Avance 500
(500 MHz) spectrometer in CDCl3 at 298 K with tetramethylsilane (TMS) as inter-
nal standard. FT-IR spectra were measured on a PerkinElmer FT-IR spectrometer
using KBr pellets. UV–Vis and fuorescence spectra were recorded in 1-cm-path-
length quartz cell on a PG Instrument T90+ spectrophotometer and JASCO FP-8300
spectrofuorophotometer, respectively.
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Spectrochemical and theoretical approaches for…
1 3

J. Jose et al.
F
F
O
O
F-
N
N
N
H
N
R
R
N
N
H
F
R=H, CH3
Fig. 10 Suggested mechanism of sensing
Synthesis of acylhydrazone compounds R1, R2
The receptors were prepared by adapting the reported procedure [23–25]. Metha-
nolic dispersion of nicotinic acid hydrazide and benzoic acid hydrazide (0.137 g,
1 mmol) were added, respectively, with 2-fuoroacetophenone and 2-fuorobenzalde-
hyde (0.138 g, 1 mmol) in methanol. After addition of glacial acetic acid, the reac-
tion mixture was refuxed for 6 h. The crystallized product was fltered of, washed
with a minimum quantity of methanol, and dried over P4O10 in vacuo. The receptors
were characterized by IR and 1H-NMR spectroscopy.
N’‑[1‑(2‑Fluorophenyl)ethylidene]pyridine‑3‑carbohydrazide
(R1) Colorless,
C14H12FN3O, yield 80 %, melting point 166–168 °C. IR data (KBr, cm−1): 3212,
1
3037, 2835, 1659, 1612, 1538, and 1494. H NMR (400 MHz, CDCl3, δ, ppm.):
10.95 (s, 1H), 7.26–8.03 (m, 8H), 2.36 (s, 3H).
N′‑[2‑Fluorobenzylidene]benzohydrazide (R2) Colorless, C13H10FN3O, yield 76 %,
melting point 195–197 °C. IR (KBr, υ in cm−1): 3216, 3069, 2835, 1642, 1614,
1
1558, 1493. H NMR (400 MHz, CDCl3, δ, ppm.): 10.05 (s, 1H), 7.26–8.00 (m,
9H), 9.03 (s, 1H).
UV–visible and fuorescence titrations
Stock solutions of R1, R2 were prepared in acetonitrile. TBA salt (F−, Cl−,
Br−, I−, ClO4−, H2PO4−, and AcO−) solutions were prepared at concentration of
1 × 10−5 mol L−1 in acetonitrile. Diferent equivalents of tetrabutylammonium salts
(F−, Cl−, Br−, I−, ClO−4 , H2PO−4 , and AcO−) were added to the receptors, and their
corresponding UV–visible and fuorescence spectra were recorded at 298 K.
Computational methods
All calculations were performed using Gaussian 09 software. Hybrid density func-
tional theory (DFT) calculations were carried out using the B3LYP method with
6-31G+(d, p) basis set to optimize the ground-state geometry of the receptors and
receptor–fuoride complexes [26, 27]. The 6-31G(d, p) basis set is moderate and
suitable for such large organic compounds, being a proper basis set for ionic com-
pounds. To investigate the solvent efect of dimethylsulfoxide (DMSO, dielectric
1 3

Spectrochemical and theoretical approaches for…
constant 46.826), polarized continuum model (PCM) calculations were performed
throughout the steps.
Acknowledgements P.B.S. is grateful for fnancial support from CHRIST (Deemed to be University),
Bengaluru.
References
1. Y. Zhou, Z. Xu, J. Yoon, Chem. Soc. Rev. 40, 2222 (2011)
2. H.N. Kim, W.X. Ren, J.S. Kim, J. Yoon, Chem. Soc. Rev. 41, 3210 (2012)
3. Y. Zhou, J. Yoon, Chem. Soc. Rev. 41, 52 (2012)
4. J. Jose, R. Datta, P.B. Sreeja, Orient. J. Chem. 33, 1438 (2017)
5. H.T. Chifotides, B.L. Schottel, K.R. Dunbar, Acc. Chem. Res. 46, 894 (2013)
6. V. Baelum, S. Pongpaisal, W. Pithpornchaiyakul, S. Pisuithanakan, R. Teanpaisan, P.N. Papapanou,
G. Dahlen, O. Fejerskov, Acta Odontol. Scand. 60, 80 (2002)
7. S. Purser, P.R. Moore, D.O. Hagan, S. Purser, P.R. Moore, Chem. Soc. Rev. 37, 320 (2008)
8. A. Strunecka, P. Connett, J. Appl. Biomed. 2, 141 (2004)
9. H. Rosenberg, J.C. Mosteller, W. Air, W.A.F. Base, O.F.W. Spray, Ind. Eng. Chem. 45, 2283 (1953)
10. Z. Liang, W. Limin, Z. Guanjun, Y. Jianjun, C. Xiaofei, T. Mingshuang, W. Yue, Chin. J. Chem. 30,
2823 (2012)
11. Y. Qu, J. Hua, H. Tian, Chem. Soc. Rev. 39, 3007 (2010)
12. D.A. Jose, D.K. Kumar, B. Ganguly, A. Das, Org. Lett. 6, 3445 (2004)
13. P.D. Beer, P.A. Gale, Angew. Chem. Int. Ed. 40, 486 (2001)
14. P.A. Gale, Coordin. Chem. Rev. 240, 191 (2003)
15. V. Amendola, D. Esteban-go, Ä. Mez, L. Fabbrizzi, M. Licchelli, C. Generale, Acc. Chem. Res. 39,
343 (2006)
16. P.A. Gale, R. Quesada, Coord. Chem. Rev. 250, 3219 (2006)
17. V.K. Gupta, R.N. Goyal, R.A. Sharma, Talanta 76, 859 (2008)
18. P.B. Sreeja, M. Sithambaresan, N. Aiswarya, M.R.P. Kurup, Acta Crystallogr. E 70, o115 (2014)
19. P.B. Sreeja, M. Sithambaresan, N. Aiswarya, M.R.P. Kurup, Acta Crystallogr. E 70, o532 (2014)
20. P.B. Sreeja, M. Sithambaresan, N. Aiswarya, M.R.P. Kurup, Acta Crystallogr. E 69, o1828 (2013)
21. A. Saeed, S. Ashraf, J.M. White, D.B. Soria, C.A. Franca, M.F. Erben, Spectrochim. Acta Part A
150, 409 (2015)
22. I. Arshad, J. Yameen, A. Saeed, J. White, F. Albericio, Crystals 7, 19 (2017)
23. P.B. Sreeja, A. Sreekanth, C.R. Nayar, M.R.P. Kurup, A. Usman, I.A. Razak, S. Chantrapromma,
H.K. Fun, J. Mol. Struct. 645, 221 (2003)
24. P.B. Sreeja, M.R.P. Kurup, A. Kishore, C. Jasmin, Polyhedron 23, 575 (2004)
25. P.B. Sreeja, M.R.P. Kurup, Spectrochim. Acta Part A 61, 331 (2005)
26. T. Yanai, D.P. Tew, N.C. Handy, Chem. Phys. Lett. 393, 51 (2008)
27. I. Yilmaz, A. Cukurovali, Dyes Pigm. 83, 211 (2009)
Afliations
Jemini Jose1 · A. Sreekanth2 · Athira M. John1 · Sabeel M. Basheer2 ·
P. B. Sreeja1
*
P. B. Sreeja
sreeja.pb@christuniversity.in
1
2
Department of Chemistry, CHRIST (Deemed to be University), Hosur Road, Bangalore 560029,
India
Department of Chemistry, National Institute of Technology, Tiruchirappalli 620015, India
1 3