Selective and colorimetric fluoride chemosensors containing phenol hydroxyl and 1,3,4-oxadiazole groups

Article abstract of DOI:10.1016/j.tetlet.2012.12.128

Two novel anion sensors, methyl 4-(5-(5-chloro-2-hydroxyphenyl)-1,3,4- oxadiazol-2-yl) benzoate (L1) and methyl 4-(5-(2-hydroxyphenyl)-1,3,4-oxadiazol- 2-yl) benzoate (L2) were reported. Their spectroscopic and colorimetric properties in CH₂Cl₂/CH₃CN (1:2, v/v) solution for F^- sensing were investigated by naked-eye, UV-vis, and fluorescence measurements. Both molecules with coplanar structure possess adjacent phenolic hydroxyl and 1,3,4-oxadiazole units, resulting in a sufficiently strong intramolecular hydrogen bond to hinder the association of most anions, but not F^-, with phenolic hydroxyl hydrogen. They displayed the same color changes from colorless to yellow but different optical shifts upon addition of F^-. Copyright

Full text of DOI:10.1016/j.tetlet.2012.12.128

Tetrahedron Letters 54 (2013) 1348–1351
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Tetrahedron Letters
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Selective and colorimetric fluoride chemosensors containing
phenol hydroxyl and 1,3,4-oxadiazole groups
⇑
Jiantao Ma, Zhe Li, Yanqing Zong, Yi Men , Guowen Xing
Beijing Key Laboratory of Energy Conversion and Storage Materials, College of Chemistry, Beijing Normal University, Beijing 100875, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Two novel anion sensors, methyl 4-(5-(5-chloro-2-hydroxyphenyl)-1,3,4-oxadiazol-2-yl) benzoate (L1)
and methyl 4-(5-(2-hydroxyphenyl)-1,3,4-oxadiazol-2-yl) benzoate (L2) were reported. Their spectro-
scopic and colorimetric properties in CH2Cl2/CH3CN (1:2, v/v) solution for FÀ sensing were investigated
by naked-eye, UV–vis, and fluorescence measurements. Both molecules with coplanar structure possess
adjacent phenolic hydroxyl and 1,3,4-oxadiazole units, resulting in a sufficiently strong intramolecular
hydrogen bond to hinder the association of most anions, but not FÀ, with phenolic hydroxyl hydrogen.
They displayed the same color changes from colorless to yellow but different optical shifts upon addition
of FÀ.
Received 30 September 2012
Revised 7 December 2012
Accepted 14 December 2012
Available online 9 January 2013
Keywords:
Sensor
FÀ
Ó 2013 Elsevier Ltd. All rights reserved.
Oxadiazole
Hydrogen bond
Fluorescence
Inorganic anions are crucial for numerous biochemical and
environmental processes.1 Among the various anions, UV–vis and
fluorescence sensors for fluoride ion have received much attention
due to its duplicitous influence on human health2 and the environ-
ment.3 However, because H2PO4À and CH3COOÀ possess similar ba-
sicity as FÀ and easily form hydrogen bonds, only a few of anion
sensors are capable of distinguishing fluoride ion effectively from
these ions.4 The achievement of specific optical FÀ sensing is still
a challenge.
droxyl and 1,3,4-oxadiazole units, and the resulting intramolecular
hydrogen bond is strong enough to hinder the association of most
anions, but not FÀ, with the phenolic hydroxyl hydrogen. Electron-
withdrawing groups, such as –Cl and –COOCH3, are introduced into
the molecules to tune the acidity and the hydrogen-bond acceptor
abilities of both molecules. Thus, both molecules display highly
selective and colorimetric responses to FÀ; the addition of FÀ cre-
ated distinct color and fluorescence changes that could be ob-
served by the naked-eye and simple instrumentation.
Generally, most fluorescent FÀ sensors consist of two parts: a
receptor and a chromophore. The former is an ion antenna, typi-
cally composed of various better hydrogen-bond donors, such as
phenols, pyrroles, imidazoles, and carbazole-based molecules.5
The latter is capable of converting a test signal into an optical sig-
nal that can be detected by the naked eye and simple instrumenta-
tion. Among fluorescent materials, heterocyclic ring systems,
especially molecules containing 1,3,4-oxadiazole groups, are
attracting a great deal of attention because of their excellent elec-
tron-acceptor abilities, high thermal stability, and high photolumi-
nescence quantum yields. Oxadiazole-based compounds are
promising for highly sensitive ion sensing6 and have also been
studied as electron transporters, emitters for OLED,7 and optical
data storage materials.8
The response of L1 to FÀ was first investigated by UV–vis spec-
troscopy (Fig. 1). Adding FÀ to free L1 in CH2Cl2/CH3CN (1:2, v/v)
gave rise to a dramatic color change from colorless to yellow,
which was accompanied by spectral changes. The shoulder at
294 nm blue shifted to 272 nm, a new broad absorption band
formed at 423 nm, and the band at 327 nm ascribed to the
p–
p⁄
transition of the oxadiazole group decreased in intensity. In the
process, the electron density in L1 was increased by the addition
of FÀ because of the hydrogen bond formation between L1 and
FÀ and subsequent elimination of the proton in the phenolic hydro-
xyl group of L1, which led to an increase in electron delocalization
(Scheme 1). This delocalized
higher than that of L1, resulting in a red shift of the
p
-conjugated bond was energetically
p–
p⁄ transi-
tion9 from 327 to 423 nm. Thus, the hydrogen bond formation
and subsequent deprotonation induced a consistent effect on the
UV–vis absorption of L1. Two isosbestic points were observed at
279 and 352 nm, respectively, despite the reaction having two
steps. The stoichiometry between L1 and FÀ was proved by the
fluorescence job plot (411 nm), in which the maximum value ap-
peared at 0.67, giving a sensor/fluoride stoichiometry of 1:2
We designed and synthesized two novel compounds, L1 and L2
(Scheme 1). Both coplanar molecules possess adjacent phenolic hy-
⇑
Corresponding author.
E-mail address: menyi@bnu.edu.cn (Y. Men).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.12.128

J. Ma et al. / Tetrahedron Letters 54 (2013) 1348–1351
1349
Scheme 1. Sensing behavior of L1 and L2 to FÀ.
Figure 1. UV–vis absorption spectrum changes of L1 (1.0 Â 10À5 mol LÀ1
) in
CH2Cl2/CH3CN (1:2, v/v) upon the addition of FÀ. Inset: the absorbance changes at
327 and 423 nm versus [FÀ]/[L1].
(Fig. S1). The absorbance changes at both 327 and 423 nm as a
function of the [FÀ]/[L1] ratio were shown in the inset of Figure 1.
Calculated after the addition of 3.8 equiv of FÀ, corresponding to
the end of the reaction, the absorbance ratio (A423 nm/A327 nm) in-
creased greatly from 0.011 for free L1 to 3.15 for L1 with FÀ. Impor-
tantly, the corresponding spectral and color changes upon the
addition of other anions, such as BrÀ, IÀ, H2PO4À, and CH3COOÀ,
were quite small (Fig. 2) due to their weak basicity, and the strong
intramolecular hydrogen bond of L1 hindered the association of
these anions with the proton of the phenolic hydroxyl. Thus, L1
can be used as a colorimetric, ratiometric, and highly selective FÀ
sensor.
Figure 3. Emission spectra changes of L1 (1.0 Â 10À5 mol LÀ1) in CH2Cl2/CH3CN
(1:2, v/v) upon the addition of FÀ (0–3.8 equiv) excited at 270 nm. (a) Dotted line
and black arrow: the first fluorescence changes (0–1.9 equiv); (b) Solid line and
black arrows: the second fluorescence changes (1.9–3.8 equiv). Inset: fluorescence
emission color changes of the L1 in the absence (a) and presence (b) of FÀ.
As shown in Figure 3, L1 displayed two-step emission changes
upon FÀ addition. Over the gradual addition of 1.9 equiv of FÀ,
the emission peak at 411 nm decreased (Fig. 3a) simultaneously
with the appearance of
a new blue-shift emission peak at
375 nm, which was attributed to the formation of a hydrogen bond
between L1 and FÀ. Further addition of FÀ led to a gradual increase
in the intensity of the new peak at 375 nm and the appearance of a
new emission peak at 532 nm (Fig. 3b), which was attributed to the
deprotonation of L1. The increasingly negative charge density of
the phenol oxygen atom promoted the intramolecular charge
transfer (ICT)10 from the phenol oxygen anion to the aromatic
rings, which was further enhanced by the –Cl electrophilic group.
The intensity of the peak at 532 nm continued to increase until
the addition of 3.8 equiv of FÀ, after which the peak at 375 nm
Figure 2. UV–vis absorption spectra changes of L1 (1.0 Â 10À5 mol LÀ1) in CH2Cl2/
CH3CN (1:2, v/v) on the addition of [Bu4N]R (R = BrÀ, IÀ, FÀ, H2PO4À, and CH3COOÀ,
3.8 equiv). Inset: relevant color changes of solution.

1350
J. Ma et al. / Tetrahedron Letters 54 (2013) 1348–1351
continued to grow. Consequently, an obvious fluorescence color
change from pale blue to green was observed (Fig. 3, inset), exhib-
iting light-on behavior and colorimetric FÀ sensing. No such spec-
tral changes were detected upon the addition of other anions (BrÀ,
IÀ, H2PO4À, and CH3COOÀ).
The above discussion indicates that the process of L1 sensing FÀ
actually involved a two-step reaction: hydrogen bond formation
and deprotonation. They are attributed to the small radius and
the strong ability of FÀ to form hydrogen bond and to the high sta-
bility of the byproduct, FHFÀ. Interestingly, the addition of 4 equiv
of water changed the solution color from yellow back to colorless
and produced the original absorption spectra. It is clear that the
hydrogen bonding interaction existed between L1 and FÀ and
was then destroyed by the addition of water. To prove the depro-
tonation step, [Bu4N]OH was added, producing the same effect
on the UV–vis and fluorescence emission spectra of L1 as the addi-
tion of FÀ (Fig. S2).
Figure 5. Benesi–Hildebrand plot, determined 1:2 stoichiometry for association
between L1 and FÀ by UV–vis titration results (423 nm).
The sensing mechanism of L1 was further investigated by 1H
NMR titration experiments in DMSO-d6 at room temperature
(Fig. 4). The signal for –OH proton at 10.65 ppm became undetect-
able after the addition of 0.4 equiv of FÀ, which is attributed to the
transformation of the strong hydrogen bonding interaction from –
O–HÁ Á ÁFÀ to –OÀÁ Á ÁH–F (Scheme 1). All other peaks shifted upfield
upon FÀ addition because the increased charge density weakened
the deshielding effect of the electronegative groups. The effect on
the shift of the H3–H5 signals was more than that of the H1 and
creased while that of the new band at 416 nm gradually
increased (Fig. S4), which is similar to the results observed with
L1. The change in the absorbance ratio (A416 nm/A320 nm) for L2,
increasing from 0.003 to 1.621, was lower than that for L1.
However, L2 displayed different two-step emission changes
from that of L1 upon the addition of FÀ (Fig. S5). During the addi-
tion of FÀ from 0 to 7 equiv, the emission peak at 411 nm decreased
following the appearance of a new blue-shifted emission peak at
386 nm with a shoulder at 399 nm. After 7 equiv of FÀ, the peak
intensity at 386 nm increased gradually. Similar to the case of L1,
two emission changes were responsible for this behavior: the
hydrogen bond formation of L2–FÀ and the deprotonation of L2.
In contrast, no new emission peak was observed at longer wave-
lengths, even after the addition of excess FÀ, which is perhaps be-
cause L2 does not contain a withdrawing group in the phenolic
ring, resulting in the negative charge transferring toward the oxa-
diazole ring. The K and detection limit of L2 with FÀ were deter-
H2 signals, producing a large shift (Dd = 0.45, 0.60, and 0.74 ppm
for H3, H4, and H5, respectively, for 3.8 equiv of FÀ). This finding
suggests that the electron density is dispersed along the entire
molecule through the delocalized p-conjugated bond, which favors
the fluorescence emission of the phosphor. The FHFÀ peak was lo-
cated at 16.39 ppm.11
The stoichiometry of L1 and FÀ was also determined by the
Benesi–Hildebrand equation.12 As shown in Figure 5, the value of
1/(AÀA0) is linearly proportional to 1/[FÀ]2 (R = 0.997), which indi-
cated that FÀ interacted with L1 in a 2:1 stoichiometry. This result
is in agreement with that of the job plot and fluorescence titrations
mined to be 1.05 Â 109 L2 molÀ2 and 1.4 Â 10À7 mol LÀ1
,
(Fig. S3). The dissociation constant (K) and detection limit (3r/
slope)13 of L1 toward FÀ were calculated as 2.08 Â 109 L2 molÀ2
respectively. The dissociation constant for the reaction of L1 with
FÀ is double that of L2 and the detection limit is also quite low,
which demonstrate that L1 is a better FÀ sensor.
and 5.6 Â 10À8 mol LÀ1, respectively.
Lacking a –Cl, electron-withdrawing group in the phenolic ring,
L2 also exhibited sensitivity to FÀ. Upon addition of FÀ, the inten-
sities of the absorption bands at 320 and 294 nm gradually de-
In conclusion, we have designed and developed two novel FÀ
sensors, L1 and L2. As the effect of electron-withdrawing substitu-
ents (–Cl), the solution of L1 became yellow and fluorescent green
color upon the addition of FÀ, which can be detected by the naked-
eye and optical spectrum, while the solution of L2 became yellow
without any fluorescent color change. Both compounds could de-
tect FÀ at 0.01 and 0.1 ppm level concentrations, respectively, dis-
playing a high selectivity and quantitative sensitivity for FÀ over
BrÀ, IÀ, H2PO4À, and CH3COOÀ.
Acknowledgments
This work was supported by the Key Technologies R&D Program
for the 12th Five-Year Plan (2012BAJ24B04-3) of the Ministry of
Science and Technology of the People’s Republic of China and by
the Fundamental Research Funds for the Central Universities,
China.
Supplementary data
Supplementary data (experimental and characterization details
for compounds L1 and L2, 1H and 13C NMR spectra, ESI and elemen-
tal analysis, changes in the absorption and emission spectra of L1
upon addition of Bu4NOH, changes in the absorption and emission
spectra of L2 upon addition of FÀ) associated with this article can
Figure 4. Partial 1H NMR titration of L1 in DMSO-d6 in the absence (a) and the
presence of 0.1 equiv; (b) 0.2 equiv; (c) 0.4 equiv; (d) 1.0 equiv; (e) 2.0 equiv; (f)
3.0 equiv; (g) 3.8 equiv; (h) of FÀ.

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