Highly selective recognition of fluoride anion through direct deprotonation of intramolecularly hydrogen-bonded phenolic hydroxyl groups

Article abstract of DOI:10.1016/j.tetlet.2013.07.021

A novel chemosensor for fluoride anion has been developed. This sensor, constructed by merging six phenolyl units into a hexaazatriphenylene (HAT) core, could recognize F^- visually and spectroscopically with high selectivity over other anions,

Full text of DOI:10.1016/j.tetlet.2013.07.021

Accepted Manuscript
Highly selective recognition of fluoride anion through direct deprotonation of
intramolecularly hydrogenbonded phenolic hydroxyl groups
Xiang Zhang, Jie Fu, Tian-Guang Zhan, Liyan Dai, Yingqi Chen, Xin Zhao
PII:
S0040-4039(13)01160-X
DOI:
http://dx.doi.org/10.1016/j.tetlet.2013.07.021
TETL 43219
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
3 May 2013
23 June 2013
3 July 2013
Please cite this article as: Zhang, X., Fu, J., Zhan, T-G., Dai, L., Chen, Y., Zhao, X., Highly selective recognition
of fluoride anion through direct deprotonation of intramolecularly hydrogenbonded phenolic hydroxyl groups,
Tetrahedron Letters (2013), doi: http://dx.doi.org/10.1016/j.tetlet.2013.07.021
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Highly selective recognition of fluoride anion
through direct deprotonation of intra-
molecularly hydrogenbonded phenolic
hydroxyl groups
Leave this area blank for abstract info.
Xiang Zhang, Jie Fu, Tian-Guang Zhan,
Liyan Dai,* Yingqi Chen, Xin Zhao*

1
Tetrahedron Letters
journal homepage: www.elsevier.com
Highly selective recognition of fluoride anion through direct deprotonation of
intramolecularly hydrogenbonded phenolic hydroxyl groups
Xiang Zhanga, Jie Fub, Tian-Guang Zhanb, Liyan Daia, Yingqi Chena, Xin Zhao b
aDepartment of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China
bShanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A novel chemosensor for fluoride anion has been developed. This sensor, constructed by
merging six phenolyl units into a hexaazatriphenylene (HAT) core, could recognize F visually
and spectroscopically with high selectivity over other anions, which was demonstrated by
naked-eye experiment and UVvis absorption spectroscopy study.
Available online
2013 Elsevier Ltd. All rights reserved.
Keywords:
Recognition
Fluoride
Phenol
Deprotonation
Hexaazatriphenylene
Chemosensors capable of selectively and efficiently detecting
fluoride anion have gained considerable attention in the past
decades because of the duplicitous effects of fluoride anion in
biological systems.1 While it exhibits beneficial effect on dental
care and has been widely adopted in the treatment of
osteoporosis,2 excessive fluoride ions intake may lead to
fluorosis, urolithiasis, and even cancer.3 In this context, a vast
number of fluoride anion sensors with various chemical
structures have been developed and different working models
that utilize the changes of color (naked-eye), UVvis absorption,
fluorescence emission, or electrochemical property have been
established. Among the various fluoride anion sensors developed
in the past decades, the use of NH unit, including urea/thiourea4,
pyrrole/indole5, and amide6, to bind fluoride anion via hydrogen-
bonding interaction, has been extensively studied and well
documented. In contrast, very little attention has been paid to
hydroxyl-based system,7 although hydroxyl group can also be
excellent hydrogen-bonding donor and its proton even exhibits
more acidity compared to the proton of NH unit. The reason
might be attributed to low recognition selectivity of OH when it
binds to anions through hydrogenbonding. Herein we report a
hexaazatriphenylene (HAT)-phenol hybrid chemosensor (1)
which displays a high degree of F discrimination both in organic
solvent and aqueous mixture by direct deprotonation of phenolic
OHs. The high selectivity was revealed to originate from the
formation of intramolecular hydrogen bonds between the
phenolic OHs and nitrogen atoms of HAT core. As a result, the
intermolecular hydrogen bonds between OH units and anions
should be weakened dramatically (or even prevented) and only
deprotonation of OHs by F could occur.
The synthesis of sensor 1 is shown in Scheme 1. 2,2'-
Dihydroxy-benzoin (3) was firstly obtained in 52% yield through
benzoic condensation of salicylaldehyde (2) and then 3 was
oxidized to generate diketone 4 in 81% yield. Refluxing a
mixture of 4 and hexamine 58 in glacial acid afforded 1 in 26%
yield (see Supplementary materials for details).
Single crystals of 1 suitable for X-ray crystallographic
analysis were grown by slowly diffusing petroleum ether into a
solution of 1 in acetone. 9 As shown in Figure 1, the six phenolic
OH groups are intramolecularly hydrogen-bonded with the
nitrogen atoms of HAT core. The distances between these
formation of
———
 Liyan Dai. Tel.: 0086-571-87952693; fax: 0086-571-87952693; e-mail: dailiyan@zju.edu.cn.
 Xin Zhao. Tel.: 0086-21-54925023; fax: 0086-21-64166128; e-mail: xzhao@mail.sioc.ac.cn.

2
Tetrahedron Letters
Figure 2. Photo of the solutions of 1 (5×10-4 M in DMSO) before and after
the addition of F (5 equiv) and other anions (100 equiv), respectively.
a
1.2
Scheme 1. Synthesis of compound 1.
0.8
0.4
0.0
300
350
400
450
500
Wavelength (nm)
b
1.2
0.9
0.6
0.3
0.0
-
- -
none, Cl , Br , I , NO
3
-
H PO
2
4
-
-
4
-
ClO and HSO
4
Figure 1. The crystal structure of 1.
AcO
hydrogen atoms and nitrogen atoms are in the range of 1.942.14
Å, notably shorter than the sum of their van der Waals radii
(d0=2.65 Å, d/d0=0.730.81). Such short bond lengths suggest
that these intramolecular hydrogen bonds are quite strong and
thus might prevent the OH units from forming intermolecular
hydrogen bond with external hydrogen-bonding acceptors such
as anions. Furthermore, it is also found that all the phenolyl units
twisted out of the HAT plane, as a result of the steric effect
between the hydrogen atoms of the adjacent phenolyl units.
-
F
250
300
350
400
450
500
550
Wavelength (nm)
Figure 3. (a) UV–vis spectral of sensor 1 (2.5×10-5 M in DMSO) upon the
addition of 0, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 30, and 50 equiv of F, and (b)
UV–vis spectral of sensor 1 (2.5×10-5 M in DMSO) upon the addition of 50
equiv of different anions.
Naked-eye experiment was first carried out in DMSO. As
depicted in Figure 2, distinctive color change of the solution of 1
from pale yellow to reddish orange was observed upon the
addition of 5 equiv of tetra-n-butylammonium fluoride (TBAF).
In sharp contrast, no obvious color change could be detected by
naked-eye even in the presence of up to 100 equiv of AcO,
NO3 , ClO4 , AcO, and H2PO4 in DMSO, respectively. Upon
the addition of 50 equiv of F into a DMSO solution of 1, its
absorbance at 377 nm declined dramatically from 0.98 to 0.18
(Figure 3b). In contrast, for the other anions, even for AcO, and






H2PO4 , Cl, Br, I, NO3 , ClO4 , and HSO4 , demonstrating a

high selectivity of 1 towards F over other anions. Such
H2PO4 from which fluoride is hard to be discriminated, the
spectral changes of 1 were quite small when they were
introduced into the solution of 1 respectively. The dramatic
difference clearly indicates a high sensing selectivity of 1
towards F over other anions.
significant color change facilitates its application as
a
colorimetric sensor for F.
It was found that compound 1 was fluorescence silent, which
might be attributed to the charge transfer between electron-
deficient HAT core and electron-rich phenol units. Fluorescence
emission could not be turned on upon the addition of anions.
Therefore, the recognition behavior of 1 was further investigated
using UVvis spectroscopy. The solution of 1 in DMSO
exhibited a maximum absorption peak at 377 nm. Upon
incremental introduction of F in the form of TBAF salt, this
peak decreased gradually and concomitant increases of an
absorption band in the range of 250-325 nm was observed
(Figure 3a). Moreover, gradual increase of absorption in the
range of 430-500 nm was also simultaneously observed. All these
results clearly indicated that fluoride anions interacted with
sensor 1, resulting in the dramatic UV-vis absorption change of
the sensor.
It was reported that recognition of F in aqueous phase is
extremely difficult because of the strong hydration of fluoride
anion by water molecules,1 In order to explore the recognition
capability of 1 in aqueous mixture, UV-vis titration of 1 with F
in a DMSOH2O (9:1, v/v) binary solvent was also recorded. As
exhibited in Figure 4a, progressive addition of F into a solution
of 1 in DMSOH2O (9:1, v/v) leads to quite similar spectra
change as that observed in DMSO, suggesting similar interacting
pattern between 1 and F in DMSO with or without the presence
of water. Similarly, while the introduction of F resulted in
considerable UVvis absorption change of 1 in DMSOH2O
(9:1, v/v), its absorption band exhibited almost no change upon
the addition of even 1000 equiv of the other anion tested above
(Figure 4b), indicating the excellent selectivity towards F was
still kept in the presence of water.
The selectivity of 1 towards different anions was then
investigated by treating 1 with excessive F, Cl, Br, I, HSO4 ,


3
a
1.0
0.8
0.6
0.4
0.2
0.0
300
350
400
450
500
Wavelength (nm)
b
1.0
0.8
0.6
0.4
0.2
0.0
-
-
-
-
,
none, Cl , Br , I , NO
Figure 5. Partial 1H NMR spectra (400 MHz) of 1 upon the addition of F in
DMSO-d6 at 25 oC.
3
-
-
-
AcO , H PO , ClO
2
4
4
-
4
and HSO
assumption was supported by a control experiment using Cl, an
anion that was reported capable of forming hydrogen bond with
free phenolic OH.12 The chemical shift of the hydroxyl proton of
1 displayed almost no change upon the addition of 10 equiv of
Cl, suggesting no detectable hydrogen-bonding exists between
chloride anion and the hydroxyl units (Figure S2, Supplementary
-
F
Information). Other basic anions such as CO3 and HCO3 were
2
250
300
350
400
450
500
550
also examined. Upon the addition of 50 equiv of them, decline of
absorbance of 1 at 377 nm was also observed. However, the
decreasing extents caused by CO32 and HCO3 were not as large
as that by F−, indicating that 1 still exhibited selectivity towards
F. Neutral basic species such as n-butylamine was also tested.
Upon the addition of n-butylamine, the absorption spectrum of 1
just exhibited very small change, indicating an excellent
selectivity between F and neutral basic species (Figure S3,
Supplementary Information).
Wavelength (nm)
Figure 4. (a) UV–vis spectral of sensor 1 (2.5×10-5 M in DMSOH2O (9:1,
v/v)) upon the addition of 0, 10, 30, 60, 100, 150, 200, 300, 400, 500, 700 and
1000 equiv of F, and (b) UV–vis absorption changes of 1 (2.5×10-5 M in
DMSOH2O (9:1, v/v)) upon the addition of 1000 equiv of different anions.
To further probe the recognition mechanism between F and
sensor 1, 1H NMR dilution and titration experiments were
1
performed. H NMR dilution experiment in DMSO-d6 (0.110
In summary, we have developed a novel chemosensor for
highly selective recognition of fluoride anion. Thanks to the high
acidity of the phenolic OH units and the strong intramolecular
hydrogen bonds formed between them and HAT core, the
formation of intermolecular hydrogen-bonding between the OHs
and anions was blocked and thus only direct deprotonation of
OHs by F could occur, which led to a high selectivity to fluoride
over other anions. While most fluoride sensors have mainly been
constructed by employing NH unit as hydrogen-bonding donor to
bond F, this work demonstrates that the use of OH could also be
a promising way to construct sensors for F detection. One
advantage of the use of phenolic OH is that the deprotonation of
hydroxyl unit usually results in multiplex responses of the
sensors due to the generation of phenolic anion. Taking this
advantage, more phenolic OH-based F sensors are anticipated in
the near future.
mM) revealed that no concentration-dependent shifts of the
signals of 1 were observed in the whole concentration range
examined, suggesting that no dimerization or other higher order
aggregation of 1 existed under the experimental condition. Upon
the addition of F (0.25 equiv), the signal of phenolic OH protons
broadened first and then disappeared completely when only 0.5
equiv of F was added. The protons of the aromatic rings
consistently displayed continuous upfield-shifts with the increase
of the concentration of fluoride. Furthermore, a signal (16.1 ppm)
corresponding to HF2 appeared when 10 equiv of fluoride was
introduced (Figure 5, inset).10 These phenomena strongly
suggested that deprotonation of phenolic OH by F occurred once
fluoride was introduced. This result is different from the
examples reported in the previous literatures,4b,11 which usually
involve a two-stepwise mechanism, this is, formation of
hydrogen bond between NH(or OH) and F first and then
deprotonation of the NH (or OH) by excessive F. In this case,
there was no hydrogen-bonding step but direct deprontonation.
This should be attributed to the strong intramolecular hydrogen-
bonding interaction in sensor 1 which prevents its phenolic OHs
from forming stable intermolecular hydrogen bond with fluoride
anion. As a result, direct deprotonation of OHs by F occurs due
to its high basicity. The deprotonation of hydroxyl groups was
Acknowledgments
We thank NSFC (No. 21172249) for financial support.
Supplementary data
1
Supplementary data associated with this article can be found,
in the online version, at***.
further ascertained by H NMR titration experiment of 1 with
OH, a strong Brønsted base instead of a hydrogen-bonding
acceptor, which showed similar 1H NMR spectra change as that
of F (Figure S1, Supplementary Information). For the other
anions, their basicities are not high enough to deprotonize the
OHs. Since the formation of intermolecular hydrogen bonds with
1 is blocked, the interaction between them and 1 should be very
weak, which leads the high selectivity to fluoride anion. This
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