Turn on ESPT: Novel salicylaldehyde based sensor for biological important fluoride sensing

Article abstract of DOI:10.1016/j.jphotobiol.2014.05.004

A novel and simple salicylaldehyde based anion fluorescent sensor 1 has been designed, which can selectively sense fluoride by 'turn on' excited-state intermolecular proton transfer (ESPT). The binding constant and the stoichiometry were obtained by non-linear least-square analysis of the titration curves.

Full text of DOI:10.1016/j.jphotobiol.2014.05.004

Accepted Manuscript
Turn on ESPT: novel salicylaldehyde based sensor for biological important flu-
oride sensing
Kai Liu, Xiaojun Zhao, Qingxiang Liu, Jianzhong Huo, Huifang Fu, Ying Wang
PII:
S1011-1344(14)00146-8
DOI:
http://dx.doi.org/10.1016/j.jphotobiol.2014.05.004
JPB 9741
Reference:
Journal of Photochemistry and Photobiology B: Bi-
ology
To appear in:
Received Date:
Revised Date:
Accepted Date:
20 March 2014
26 April 2014
5 May 2014
Please cite this article as: K. Liu, X. Zhao, Q. Liu, J. Huo, H. Fu, Y. Wang, Turn on ESPT: novel salicylaldehyde
based sensor for biological important fluoride sensing, Journal of Photochemistry and Photobiology B: Biology
(2014), doi: http://dx.doi.org/10.1016/j.jphotobiol.2014.05.004
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Graphic Abstract
1

Turn on ESPT: novel salicylaldehyde based sensor for biological important
fluoride sensing
Kai Liu*,a , Xiaojun Zhaob, Qingxiang Liub, Jianzhong Huoa, Huifang Fua, Ying Wangb
aKey Laboratory of Inorganic-Organic hybrid Functional Material Chemistry, Ministry of Education,
Tianjin Normal University, Tianjin, 300387, China
bTianjin Key Laboratory of Structure and Performance for Functional Molecule, College of
Chemistry, Tianjin Normal University, Tianjin, 300387, China
*Corresponding author. Tel.: +86-22-23766515; Fax: +86-22-23766532
E-mail: hxxylk@mail.tjnu.edu.cn
2

Abstract
A novel and simple salicylaldehyde based anion fluorescent sensor 1 has been designed, which can
selectively sense fluoride by ‘turn on’ excited-state intermolecular proton transfer ( ESPT ). The
binding constant and the stoichiometry were obtained by non-linear least-square analysis of the titration
curves.
Keywords: anion recognition, fluorescent sensor, ESPT, deprotonation
3

1. Introduction
Recently, much attention has been paid on the anion recognition [1-4], and considerable efforts have
been devoted to design and synthesis of functionalized receptors for the development of potential anion
chemosensors [1-4]. Of particular interest concerning anion sensing is the fluoride ion, due to its well-
established role in treatment of osteoporosis and dental care [5, 6]. To data, although several sensing
systems for fluoride have been reported [7, 8], most of them are fluorescent ‘turn-off’ sensor. Generally,
fluorescence enhancement is favorable to the sensitivity in the sensing process, compared to those
displaying fluorescence quenching, because the false results, derived from other quenchers, maybe
reported by fluorescent ‘turn off’ sensor in practical samples [9].
Furthermore, numerous signal mechanisms [4], such as intramolecular charge transfer (ICT),
photoinduced electron transfer (PET), excimer/exiplex, metal-to-ligand charge transfer, competitive
binding, fluorescence resonance energy transfer (FRET), have been developed to design anion
fluorescent sensors. However, excited-state intra/intermolecular proton transfer (ESPT), as a well-
documented signal mechanism [10-12], has scarcely been used in anion recognition and sensing [13-
17]. In fact, ESPT occurs in the excited state through an intramolecular hydrogen bonded ring [10-12],
in which proton/hydrogen is transferred to an electronegative atom. And ESPT molecules are employed
extensively in photostabilizers, lasers, optical devices and information processing.
Hydrogen bonds were used extensively in the design of charge-neutral anion receptors, especially
for NH group [1, 2], such as amide, urea, thiourea, sul-fonamide, pyrrole and indole. However, only
few anion sensors involved the OH groups to obtain the anion binding and sensing [1, 2]. In addition,
the OH acidity of receptor maybe dramatically improved upon photoexcitation [13-17], and thus the
ESPT channel could be open by anion binding [10, 13].
On the basis of the above-mentioned background, herein we designed and synthesized a new
compound 1 containing OH group. Sensor 1 exhibited the high selectivity for the biologically
important F− , and ‘turn-on’ ESPT was suggested to be the signal mechanism.
2. Experimental
2.1 Materials and equipments
4

Commercially available 3-(dimethylamino)phenol and quinolin-8-amine were purchased from
Aladdin, China. Other reagents for synthesis were used without further purification. All anions in the
form of tetrabutylammonium salts were obtained from Sinopharm Chemical Reagent Co. Ltd., stored
in a desiccator under vacuum. Acetonitrile for spectroscopy was obtained from the J&K Scientific LTD.
Absorption spectra were recorded on a Shimadzu UV2550 spectrophotometer. Fuorescence spectra
1
were carried out on Shimadzu RF-5301PC spectrofluorometer. H NMR was determined in DMSO-d6
on a Bruker 400 MHz spectrometer using TMS as internal standard. High resolution mass spectrum
was performed on an Agilent 1200 time-of-flight mass spectrometer. C, H, N elemental analyses were
made on Elementar Vario-III elemental analyzer.
Scheme 1
2.2 Synthesis of receptor 1
4-(Dimethylamino)salicylaldehyde was prepared by the reported procedure [18] with little
modification. To a dry DMF solution ( 21.0 ml ) containing 3-(dimethylamino)phenol ( 3.10 g, 22.6
mmol ) was added POCl3 ( 4.0 ml, 43.2 mmol ) at 0 ℃. The mixture was stirred for 10 min, and further
stirred for 30 min at room temperature. Then the resulting mixture was stirred overnight at 80 ℃. After
cooling, the reaction mixture poured into ice-cold water. The solution was neutralized using saturated
Na2CO3, and the formed precipitate was filtered off, washed several times with water and dried under
1
vacuum. m.p. 80.1-81.2 °C [19]; H NMR ( 400 MHz, CDCl3 ) : δ 3.09 ( s, 6H, CH3 ), 6.10 -7.29 ( m,
3H, Ar-H ), 9.53 ( s, 1H, OH ), 11.61 ( s, 1H, CHO ).
Quinolin-8-amine ( 0.36 g, 2.5 mmol ) and compound 2 ( 0.41 g, 2.5 mmol ) were mixed in dry
methanol ( 25 ml ). The mixture was refluxed for 3 h under N2. Then the methanol was evaporated and
the residue was purified by silica gel column chromatography ( ethyl acetate/ n-hexane = 1:3 ) to give
1
sensor 1 in 65.2% yield as green-brown solid. H NMR ( 400 MHz, DMSO-d6 ): δ 3.02 ( s, 6H,
CH3 ), 5.96 -6.37 ( m, 3H, Ar-H ), 7.30-8.82 ( m, 6H), 9.12 ( s, 1H, CH=N ), 13.97 ( s, 1H, OH); ESI-
MS: 292.1417 (M+H+); Anal. calcd. for C18H17N3O: C, 74.18; H, 5.89; N, 14.39; O, 5.54.
3. Results and discussion
3.1 UV-VIS spectral response of sensor 1
5

Fig. 1
To establish the anion binding and sensing affinities of sensor 1, spectrophotometric titration
experiments have been performed by adding a standard solution of various anions ( F−, Cl−, Br−, I−,
−
−
H2PO4 , HSO4 , NO3− and AcO−, tetrabutylammonium salts, TBA ) to CH3CN solution of sensor 1 at
room temperature. As shown in Fig. 1, sensor 1 itself displayed two maximum absorption bands at ∼
220 nm and ∼ 391 nm, which can be assigned to n-π* and π-π* transition [19] favored by the planar
orientation enforced by intramolecular hydrogen bonding ( Scheme 2 ) [7, 13, 20], respectively. Upon
addition of < 1.0 equiv. F− to the solution of sensor 1, the peak at ∼220 nm and ∼ 391 nm decreased
insignificant. And with further increasing amount of F−, two peaks fell gradually and vanished, at the
same time, the new peaks at ∼ 240 nm, ∼ 328 nm and∼ 431 nm occurred. Considering the strong
−
basicity of F− [21] and high stability of [HF2] complex [7, 13], these spectral changes were
presumably ascribed to the first hydrogen bond interaction between sensor 1 and F− [1], and
subsequently, the deprotonation of OH at the sensor 1 [7, 13, 21]. This suggested the formation of
negatively charged PhO− of sensor 1, which resulted in the substantial increase on charge density of
sensor 1 [1], and the enhancement in push-pull effect of intramolecular charge-transfer in the ground
state [1]. To substantiate the assumption, titration of sensor 1 with TBAOH, which can deprotonate the
OH [1, 21], was carried out. The newly generated bands matched well with those induced by TBAF.
This indicated the occurrence of deprotonation in the titration of sensor 1 with TBAF [7, 13].
Fig. 2
Fig. 3
On performing the similar titration of sensor 1 with TBAHSO4, as displayed in Fig. 2, the absorption
band at ∼ 391 nm gradually decreased and disappeared with the formation of the absorption band at ∼
435 nm and ∼ 455 nm. These spectral changes were attributed to protonation of C=N moiety of sensor
−
1, due to the strong acidity of HSO4 ( pKa = 1.99 in aqueous solution ). Furthermore, the clear
isosbestic poin at ∼ 406 nm was observed, which indicated the formation of single component during
−
the titration process. Analogous titrations were also carried out for Cl−, Br−, I−, H2PO4 , NO3− and AcO−
with tetrabutylammonium as counter cation. In these cases, as shown in Fig. 3, no obvious spectral
changes were found, which indicated the weak interaction between sensor 1 and the above-mentioned
anions.
3.2 Fluorescence response of sensor 1
6

Fig. 4
−
−
To get insight into the binding nature of sensor 1 for various anions ( F−, Cl−, Br−, I−, H2PO4 , HSO4 ,
NO3− and AcO− ), fluorescence titration was conducted in CH3CN with excitation at 310 nm. Free
sensor 1 displayed an emission maximum at 415 nm with a low intensity, suggesting that sensor 1
existed in enol form of Schiff base [20, 22]. This conformation cannot undergo ESPT [23, 24].
Moreover, absorption study showed that strong bases e.g. F− and OH− can remove the OH proton to
form the corresponding anion in the ground state. Therefore, the F− titration was expected to induce the
distinct fluorescence spectral changes of sensor 1. Fig. 4 displayed the fluorescence response of sensor
1 for F−. Upon addition of less than 1.0 equiv. TBAF to sensor 1 in CH3CN, the changes were
negligible, which was in good agreement with the results of UV-VIS titration. This suggested that F−
first formed hydrogen-bond complex with sensor 1. Furthermore, the acidity of phenolic proton was
dramatically enhanced upon photoexcitation [13-17]. Therefore, subsequent fluoride-triggered
deprotonation of phenolic OH would occur, and ESPT channel might be opened upon fluoride binding
[13-17]. Further spectral behaviors confirmed the aforementioned expectation. New and blue-shifted
emission band at 394 nm appeared, enhanced dramatically and reached its limiting value after the
addition of about 35.0 equiv. F−. Fluoride-triggered deprotonation produced the corresponding
phenoxide anion displayed ‘turn-on’ fluorescence signal.
Fig. 5
−
Studies of interaction with other anions ( Cl−, Br−, I−, H2PO4−, HSO4 , NO3− and AcO−) were also
carried out by spectrofluorimetric titrations. As seen from Fig. 5, an insignificant change in the
fluorescence of sensor 1 was found, which indicated that sensor 1 was fluorescent selective
chemosensor for F− in CH3CN.
3.3 H NMR spectra study
Considering the stronger interaction between sensor 1 and F−, their interaction was explored by 1H
NMR titration technique to ascertain the binding site of sensor 1 with anion. As displayed from Fig. 6,
free sensor 1 exhibited the sharp signal at 13.97 ppm, which were assigned to OH. The occurrence of
OH signal in the far downfield region revealed the existence of Ph-OH…N=C intramolecular hydrogen
bond assembly of sensor 1 itself [20, 22], as shown in Scheme 2. With increasing F− concentration, the
phenolic OH proton was broadened, underwent a continuous downfield shift, and disappeared
7

completely. Additionally, the new signal at 16 ppm, which pertained to [HF2]− complex [7, 13],
occurred. These observations clearly indicated the destruction of original intramolecular hydrogen-
bonding interaction, and the formation of intermolecular hydrogen-bonding interaction between sensor
1 and F−, and the subsequent proton transition [1, 7, 13-17] from the phenolic OH to F−. This also
confirmed our previous expectation. Furthermore, in the process, the upfield shift of the CH signal on
phenyl group and quinolyl moiety, as well as the imine CH=N proton, were observed, due to the
shielding effect of negative electron delocalization on the π -conjugated framework.
Fig. 6
Scheme 2
Fig. 7
3.4 Determination of the association constants
To further test the binding strength between host and guest, association constants (K) were
calculated by non-linear least-square analysis of the titration curves according to the following relation
for 1:1 complexation.
1

∆X = B C +CG +



2
2




1
1



eq. 1
−
CH + CG +
− 4CH C

H






G 
K
K





where △X is the difference value between the absorbance of the whole system and the absorbance of
free host, B is a floating parameter in the analysis, CH and CG are the concentration of host and guest,
respectively. As seen from Fig. 7, the plot of A versus CG displayed satisfactory non-linear
−
relationship and for F− ( R =0.994 ) and HSO4 ( R =0.973 ), respectively. These indicated the
−
formation of 1:1 complexation between sensor 1 and guest ( F− and HSO4 ). The binding constants
were 4.13×104 M-1 and 1.41×104 M-1 for F− and HSO4−, respectively. The K values ( 2.45×106 M-1,
R=0.991 ) for F−, calculated from fluorescent titration, was bigger than that obtained from UV-VIS
titration. This further confirmed the enhancement of phenolic OH acidity upon the photoexcitation [13-
17, 25].
Conclusions
8

In summary, we presented the photophysical properties of a novel and simple fluorescent sensor 1,
which displayed highly selective ‘turn-on’ affinity for biological important F− over other anions
examined. Fluoride-driven ESPT may be responsible for the spectral behaviors.
Acknowledgements
This work was supported by the Tianjin Science & Technology Development Fund Planning Project
for Colleges and Universities ( No. 20120507 ), National Science Foundation of Tianjin ( No.
13JCQNJC06000 ) and Innovation Project of the Undergraduate ( No. 2013116 ).
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10

Captions
Fig. 1. Changes in UV-VIS absorption spectra for sensor 1 ( 4.0×10-5 mol/l ) upon addition of TBAF
( 0-60.0 equiv.).
Fig. 2. Changes in UV-VIS absorption spectra for sensor 1 ( 4.0×10-5 mol/l ) upon addition of
TBAHSO4 ( 0-50.0 equiv.).
Fig. 3. Changes in UV-VIS absorption spectra for sensor 1 ( 4.0×10-5 mol/l ) upon addition of 45.0
equiv. of various anions.
Fig. 4. Changes in the fluorescence spectra of sensor 1 ( 4.0×10-7 mol/l ) upon addition of TBAF ( 0-
35.0 equiv. ).
Fig.5. Emission spectral changes of sensor 1 ( 4.0×10-7 mol/l ) upon addition of 35.0 equiv. of anions in
CH3CN.
Fig. 6. Partial 1H NMR titration spectra of sensor 1 with the addition of a) 0, b) 0.5, c) 1.0, d) 2.0 equiv.
F− in DMSO-d6.
Fig.7. Non-linear plot according to eq. 1, assuming 1:1 stoichiometry for association between sensor 1
and F− and HSO4−, respectively, a) UV-VIS titration results induced by F−, b) UV-VIS titration results
−
induced by HSO4 , c) spectrofluorimetric titration results induced by F−.
Scheme 1. Synthesis of sensor 1.
Scheme 2 Proposed binding mode of sensor 1 with F−.
11

1.6
1.2
0.8
0.4
0.0
200
300
400
500
Wavelength (nm)
Fig. 1
2.0
1.5
1.0
0.5
0.0
200
300
400
500
Wavelength ( nm )
Fig. 2
12

1.6
1.2
0.8
0.4
0.0
-
- -
-
None, Cl , Br , I , H2PO4 ,
-
-
NO , AcO
3
-
HSO4
-
F
200
300
400
500
Wavelength (nm)
Fig. 3
800
600
400
200
0
400
450
500
550
Wavelength (nm)
Fig. 4
13

800
600
400
200
0
-
F
-
- -
-
None, Cl , Br , I , H2PO4 ,
-
-
-
HSO4 , NO3 , AcO
400
500
600
Wavelength (nm)
Fig. 5
d)
16.316.216.116.0
c)
b)
a)
15
14
13
12
11
10
ppm
9
8
7
6
Fig. 6
14

1.5
1.0
0.5
0.0
0.24
0.18
0.12
0.06
0.00
b)
a)
0.0000 0.0002 0.0004 0.0006 0.0008
-
0.0000 0.0005 0.0010 0.0015 0.0020
[HSO4 ] (mol/l)
-
[F ] (mol/l)
450
300
150
0
c)
0.000000 0.000003 0.000006 0.000009
[F ] (mol/l)
-
Fig. 7
15

NH2
CHO
N
HO
OH
N
DMF+POCl3
OH
2
N
N
N
NMe2
EtOH, Reflux
1
Scheme 1
Scheme 2
16

Highlights
Turn on ESPT: novel salicylaldehyde based sensor for biological important
fluoride sensing
Kai Liu*,a , Xiaojun Zhaob, Qingxiang Liub, Jianzhong Huoa, Huifang Fua, Ying Wangb
► New salicylaldehyde based fluorescent sensor 1 was designed.
► Sensor 1 displayed ‘turn on’ fluorescence for biologically important fluoride ion.
► ESPT was responsible for the fluoride-induced fluorescence enhancement.
17