Chromogenic and fluorescent “turn-on” chemodosimeter for fluoride based on F?-sensitive self-immolative linker

Article abstract of DOI:10.1016/j.cclet.2015.11.014

A new chromogenic and fluorescent “turn-on” chemodosimeter 3 was designed and synthesized by using a fluoride-sensitive self-immolative linker, in combination with the fluorescent dyes 7-hydroxy-4-trifluoromethyl coumarin. The chemodosimeter exhibited high selectivity and sensitivity toward fluoride anions through “turn-on” chromogenic and fluorogenic dual modes.

Full text of DOI:10.1016/j.cclet.2015.11.014

Chinese Chemical Letters 27 (2016) 211–214
Contents lists available at ScienceDirect
Chinese Chemical Letters
journal homepage: www.elsevier.com/locate/cclet
Original article
Chromogenic and fluorescent ‘‘turn-on’’ chemodosimeter for fluoride
ꢀ
based on F -sensitive self-immolative linker
Xin-Yu Wang, Feng-Jie Guan, Bin Li, Hua Zhang *, Hong-Wei Wu, Kai Ji, Chuan-Xiang Liu *
School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, China
A R T I C L E I N F O
A B S T R A C T
Article history:
A new chromogenic and fluorescent ‘‘turn-on’’ chemodosimeter 3 was designed and synthesized by
using a fluoride-sensitive self-immolative linker, in combination with the fluorescent dyes 7-hydroxy-4-
trifluoromethyl coumarin. The chemodosimeter exhibited high selectivity and sensitivity toward
fluoride anions through ‘‘turn-on’’ chromogenic and fluorogenic dual modes.
Received 3 August 2015
Received in revised form 8 September 2015
Accepted 19 November 2015
Available online 13 December 2015
ß 2016 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.
Published by Elsevier B.V. All rights reserved.
Keywords:
Colorimetric
Fluorescence
Chemodosimeter
Fluoride ion
Self-immolative
1
. Introduction
The development of chromogenic and fluorogenic sensors for
Recently, aryl phthalate esters were reported as self-immola-
tive linkers for potential fluoride sensors. The fluoride-sensitive
self-immolative linker, such as 2-(trimethylsilyl)ethyl ether group,
was explored by conjugating the phthalic anhydride with the
fluorescent dyes 7-hydroxycoumarin (previous probe, Fig. 1) [14].
To improve the sensitivity and operational ability of the above
systems, the more sensitive fluorophore containing electron-
anions is well-established field in supramolecular chemistry
because of their roles in chemical and biological processes [1].
Among inorganic anions, F ions are usually used for the
prevention of dental caries and treatment of osteoporosis [2–5].
Over-intake of fluoride can cause fluorosis and lead to nephrotoxic
changes and urolithiasis in humans [6,7]. Therefore, the interest in
developing of novel chemosensors for the selective detection of
fluoride ions has grown in the last few years.
ꢀ
3
withdrawing group (such as CF group) should be used to design
the sensor. In this study, using the novel the fluorescent dyes
7-hydroxy-4-trifluoromethyl coumarin, we developed a new
probe 3 to investigate the potential signal changes (Fig. 1).
The conventional approaches for fluoride sensing are mainly
based on the fluoride ionic electrode, fluoride-hydrogen bonding or
deprotonation [8,9]. Recently, the most popular strategy is to
utilize the high affinity of fluoride to silica for the construction of
sensors with Si–O, or Si–C bonds [6,10–13]. The approaches
involve the direct linkage of a Si–O protected fragment to
chromophore/fluorophore, or the insertion of a conjugated system
between a Si–O group and chromophore/fluorophore followed by a
2
. Experimental
NMR spectra were recorded on Bruker AVANCE III 500 MHz and
chemical shifts were reported in parts per million (ppm,
downfield from internal standard Me Si (TMS). HRMS were
recorded on solanX 70 FT-MS spectrometer with methanol and
water (v/v = 1:1) as solvent. IR were recorded on Bruker VERTEX70.
Flash chromatography was carried out on silica gel (200–
d)
4
ꢀ
unique F -triggered cascade reaction. The reported mechanism is
ꢀ
mainly to release the F -silica-protected group and the signal
3
00 mesh). The intermediate 1 and 2 was synthesized as described
in the literature (Figs. S1 and S2 in the Supporting information)
14–16].
Synthesis of probe 3 (Scheme 1): 2-(Trimethylsilyl) ethyl
hydrogen phthalate (1, 1.29 g, 4.83 mmol) [14,15], 7-hydroxy-
-(trifluoromethyl)-coumarin (2, 1.11 g, 4.83 mmol) [16], and
subunit with delocalized oxygen negative charge. However,
realization of novel chromogenic and fluorogenic sensors for
fluoride ions is still a challenge, especially with respect to different
mechanisms, novel chromophore with high sensitivity.
[
4
*
Corresponding authors.
4-dimethylaminopyridine (0.65 g, 5.3 mmol) were dissolved in a
mixture of anhydrous methylene chloride (15 mL) and anhydrous
E-mail addresses: zhanghua@sit.edu.cn (H. Zhang), cxliu@sit.edu.cn (C.-X. Liu).
http://dx.doi.org/10.1016/j.cclet.2015.11.014
001-8417/ß 2016 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.
1

[
(
F
i
g
.
_
1
)
T
D
$
F
I
G
]
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X.-Y. Wang et al. / Chinese Chemical Letters 27 (2016) 211–214
spectrophotometer [17]. The solutions of the anions were prepared
ꢀ
ꢀ
ꢀ
ꢀ
from the tetrabutylammonium salts of anions (F , Cl , Br , I ,
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ClO
4
, NO
3
, AcO , H
2
PO
4
, BF
4
, HSO
4
).
All fluorescence spectroscopy were recorded after the addition
3
of tetrabutylammonium salts in CH CN, while keeping the ligand
concentration constant (5 ꢁ 10ꢀ mol/L), on a Hitachi F-4600
3
spectrofluorometer. The solutions of the anions were prepared
from the tetrabutylammonium salts of anions.
Fig. 1. The designed probe 3.
1
[
(
S
c
h
e
m
e
_
1
)
T
D
$
F
I
G
]
For H NMR titrations, probe 3 was dissolved in DMSO-d
6
,
which was mixed with different equiv. of fluoride ions in NMR
tubes. The spectra were performed at 298 K [18].
3. Results and discussion
First, the chromogenic behavior of probe 3 in acetonitrile was
investigated upon the addition of different anions (Fig. 2a) [9].
When tetrabutylammonium fluoride (TBAF) was added, a new red-
shifted peak at 434 nm was observed in the UV–visible spectrum of
probe 3. This can be attributed to complete fluoride deprotection as
a consequence of the release of chromenolate anion [16]. An
instantaneous colorimetric change from colorless to yellow
(Fig. 2b, top, naked-eye detection) was observed. However, the
Scheme 1. Synthesis of probe 3.
DMF (9 mL). N,N-Dicyclohexylcarbodiimide was quickly added to
the reaction mixture, which was stirred under N overnight.
Dicyclohexyl urea was filtered off, and the filtrate was diluted in
0 mL of methylene chloride. The solution was washed with brine
and then dried over anhydrous Na SO . The crude product was
2
ꢀ ꢀ ꢀ ꢀ ꢀ ꢀ
1
addition of other anions such as Cl , Br , I , ClO , NO3 , AcO ,
4
ꢀ ꢀ ꢀ
2 4
H PO , BF4 , HSO4 ions (as their tetrabutylammonium salts) did
2
4
collected by evaporation under reduced pressure and then purified
by flash chromatography on silica gel (PE/EA = 30:1) to yield 3
not lead to any color change (Fig. 2b, bottom, naked-eye detection),
indicating the highly selective nature of probe 3 for fluoride ions.
This excellent selectivity was further highlighted by the interfer-
ence experiments (Fig. 2c), in which a consistent turn-on color
(
0.92 g, 45%) as a white solid. Compounds 3 were characterized by
1
13
H NMR,
Supporting information). H NMR (500 MHz, CDCl
m, 1H), 7.87–7.78 (m, 2H), 7.69–7.62 (m, 2H), 7.45 (d, 1H,
J = 2.5 Hz), 7.38 (dd, 1H, J = 9.0, 2.5 Hz), 6.80 (s, 1H), 4.46–4.37 (m,
C NMR and ESI-HRMS analyses (Figs. S3–S5 in
1
ꢀ
3
):
d
7.93–7.87
response was observed upon the addition of 20 equiv. of F ions to
(
the solutions of 3 containing equal concentrations of potentially
competing anions. Next, the addition of increasing concentrations
of fluoride ions resulted in a dramatic color change from colorless
to yellow, because of a gradual growth in the absorbance peak at
252 nm and 434 nm and the simultaneous decrease of new peaks
at 282 nm and 314 nm with two clear isosbestic points at 265 and
348 nm in acetonitrile (Fig. 2d).
Most remarkable changes were observed in the fluorescence
titration studies [19]. Upon the addition of fluoride ions, the
fluorescence emission intensity of probe 3 increased drastically
13
2
1
1
3
H), 1.12–1.08 (m, 2H), 0.05 (s, 9H); C NMR (100 MHz, CDCl ): d
66.71, 165.75, 158.51, 155.11, 154.29, 131.84, 131.69, 131.56,
31.39, 129.37, 128.96, 126.35, 118.99, 111.10, 64.40, 17.37,
ꢀ
21 3 6
1.53; ESI-HRMS (m/z): Calcd. for [C23H F O Si + Na] 501.09572
+
(
[M + Na] ), found 501.09485.
All UV–vis spectroscopy were recorded after the addition of
tetrabutylammonium salts in CH CN, while keeping the ligand
concentration constant (5 ꢁ 10 mol/L) on a SHIMADZU UV-1800
3
ꢀ3
[(Fig._2)TD$FIG]
Fig. 2. (a) UV–visible spectra of compound 3 (20
CH CN solution upon addition of various anions; (c) UV–visible spectra of compound 3 in presence of various anion in CH
absorbance enhancement at 434 nm of 3 in the presence of 20 equiv. of the anion of interest after addition of 20 equiv. of fluoride ions and (d) UV–visible spectral changes of
(20 mol/L) in CH CN upon the titration with TBAF (0 to 20 equiv.)
m
mol/L) in presence of 20 equiv. of various anion in CH
3
CN solution; (b) color changes of receptor compound 3 in
3
3
CN solution. The red bars represent the
3
m
3

[
(
F
i
g
.
_
3
)
T
D
$
F
I
G
]
X.-Y. Wang et al. / Chinese Chemical Letters 27 (2016) 211–214
213
Fig. 3. (a) Fluorescence spectra of compound 3 (20
m
mol/L) in presence of 20 equiv. of various anion in CH
3
CN solution; (b) fluorescence changes of receptor compound 3 in
CN solution. The red bars represent the
3
CH CN solution upon addition of various anions; (c) fluorescence spectra of compound 3 in presence of various anion in CH
3
fluorescence intensity enhancement at 504 nm of 3 in the presence of 20 equiv. of the anion of interest after addition of 20 equiv. of TBAF; (d) fluorescence spectral changes of
ꢀ
3
(20
m
mol/L) (
l
ex = 350 nm) in CH
3
CN upon the titration with TBAF (0 to 20 equiv.). Inset: Changes in intensity of 504 nm of compound 3 as a function of [F ].
at 504 nm (red-shift 50 nm than the previous probe) [14], from
nonfluorescent to blue green fluorescent (Fig. 3b, top) and was
saturated with 20 equiv. of fluoride ions in acetonitrile (Fig. 3a)
fluorescence detection limit of probe 3 was determined to be
0.19 mol/L (Fig. S6 in Supporting information).
m
To test the potential mechanism involving the fluoride
ꢀ
ꢀ
ꢀ
[
20]. However, the addition of others anions such as Cl , Br , I ,
deprotonation as a consequence of the release of chromenolate
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
1
ClO
4
, NO
3
, AcO , H
2
PO
4
, BF
4
, HSO
4
ions (as their tetra-
anion, H NMR titrations were further performed in DMSO-d
6
butylammonium salts) did not lead to any change in the
emission intensity (Fig. 3b, bottom), further indicating that
probe 3 shows highly selectivity for fluoride ions over other
anions [21]. Further, the excellent selectivity of probe 3 was
confirmed by competition experiments (Fig. 3c), in which a
consistent turn-on fluorescence response was observed upon the
addition of fluoride ions to the sample solutions of 3 containing
equal concentrations of potentially competing anions. The
(Fig. 4) [14,22,24]. The addition of increasing concentrations of
ꢀ
F
ions resulted in a significant upfield shift of the coumarin group
0
0
signal (Ha-d shift to Ha -d ). Moreover, when the concentration of
ꢀ
0
F
was increased gradually (up to 9.0 equiv.), the new set of H
e
and
0
f
signal of phthalic acid also be founded. It was confirmed that the
H
mechanism should be fluoride-induced self-immolative linker
cleavage followed by releasing the potential phthalic acid and the
3
optical coumarin containing CF -group.
[(Fig._4)TD$FIG]
He
O
Hb'
He'
Hf
Si
Hb
-
-
-O
Hc'
CF
O
O
Hf'
CO
2
2
F-
+
Hc
CF
3
Ha'
CO
O
3
O
Ha
Hd'
O
O
probe 3
Hd
O
He'
Hf'
Hd'
Hc'
Hb'
Ha'
Hc
He+Hf
Ha
Hd Hb
7.50
8
.00
7.00
6.50
6.00
1
(4.18 ꢁ 10ꢀ3 mol/L) upon addition of Fluoride ions (as tetrabutylammonium salts in DMSO-d
Fig. 4. H NMR titration spectra of 3 in DMSO-d
6
6
) at 298 K, from the bottom to
top: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 9.0 equiv.

[
(
F
i
g
.
_
5
)
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[
[
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ꢀ
4
F
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Fig. 5. Photographs of test strips of probe 3 (5.0 ꢁ 10 mol/L) exposed to fluoride
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Moreover, in order to evaluate the practical application of probe
, a test paper was prepared by immersing a filter paper into a
3
CH
CN solution of probe 3 (5.0 ꢁ 10ꢀ4 mol/L) and the test paper
3
was then dried in air [23]. When the test strips coated with probe 3
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ꢀ2
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[
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In summary, a new chromogenic and fluorescent probe 3 based
on fluoride-sensitive self-immolative linker was developed as a
consequence of the release of chromenolate anion. This probe 3
displayed drastic changes in the UV–visible absorption and
fluorescence emission intensities selectively for fluoride ions in
acetonitrile. The strategy based on fluoride-sensitive self-immo-
lative linker has great potential for sensor design. Further studies
on the development of this novel strategy by introducing novel
fluorophores are in progress.
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Acknowledgments
We are grateful for financial support from National Natural
Science Foundation of China (No. 21202099), the Science Founda-
tion of Shanghai Institute of Technology (No. YJ2011-75) and the
Opening Fund of Shanghai Key Laboratory of Chemical Biology (No.
SKLCB-2014-01).
[
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