A non-symmetric pillar[5]arene-based selective anion receptor for fluoride

Article abstract of DOI:10.1039/c2cc00125j

A novel non-symmetric pillar[5]arene-based anion receptor containing multiple triazole anion-binding sites was designed and synthesized. It has high affinity and selectivity for the fluoride anion.

Full text of DOI:10.1039/c2cc00125j

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COMMUNICATION
A non-symmetric pillar[5]arene-based selective anion receptor for fluoridew
Guocan Yu,a Zibin Zhang,a Chengyou Han,a Min Xue,a Qizhong Zhou*b and Feihe Huang*a
Received 7th January 2012, Accepted 30th January 2012
DOI: 10.1039/c2cc00125j
A novel non-symmetric pillar[5]arene-based anion receptor containing
multiple triazole anion-binding sites was designed and synthesized.
It has high affinity and selectivity for the fluoride anion.
along the CH–H-bond a large (5 D) dipole whose positive end
points toward the H atom.8b Third, the naphthalene groups can be
used as the fluorescent chromophores.
By condensation of 1 and paraformaldehyde with boron
trifluoride diethyl etherate [BF3ÁO(C2H5)2] as
a catalyst,
Anions are associated with many biological, environmental,
chemical, and pathological processes.1 In recent years, a great
number of artificial compounds that are able to bind anions with
high affinity and/or selectivity have been reported.2 These receptors
are often constructed from a combination of strong hydrogen-
bonding donors,3 positively charged moieties,4a and Lewis acid
metal ions.4b Among anions, the fluoride anion (FÀ) is of particular
interest owing to its important role in dental care and clinical
treatment of osteoporosis.5 Excess FÀ in the body can result in
gastric and kidney disorders, dental and skeletal fluorosis,
urolithiasis, or even death.6 Fluoride is the smallest anion with a
high charge density and a hard Lewis basic nature, which result in
its unusual chemical properties. Therefore, to design and synthesize
novel receptors for FÀ with high affinity and selectivity is a
challenging mission for chemists.
pillar[5]arene 2 was prepared. Compound 3, which was obtained
by treatment of 2-bromomethyl naphthalene with sodium azide
in acetone/water (10 : 1) at 50 1C, reacted with 2 in the presence of
CuSO4Á5H2O and sodium ascorbate in DMF at 90 1C to afford
four constitutional isomers 4a, 4b, 4c and 4d (Scheme 1a and
ESIw),7h among which only the spectrum of 4a was analyzable.
The overlap of peaks in the spectra of the other isomers makes it
impossible to assign these spectra. Given the rigid pillar structure
and size of the pillar[5]arene cavity, five triazole rings on one side
of 4a may interact with anions via hydrogen bonding interactions
cooperatively9 (Scheme 1b). Therefore, we thought that this
fluorescent pillar[5]arene should be a good receptor for a special
anion with high affinity and high selectivity, enabled by the size
of the rigid pillar[5]arene cavity.
Pillar[5]arenes7 are a new type of macrocyclic hosts. Their
repeating units are connected by methylene bridges at the para-
positions, forming a unique pillar architecture, which is different
from the basket-shaped structure of the meta-bridged calixarenes.
The unique structure and easy functionalization of pillar[5]arenes
afford them outstanding ability to selectively bind different kinds
of guests and provide a useful platform for the construction of
various receptors with different functions. However, although the
complexation of pillar[5]arenes to cationic and neutral guests has
been well studied, the binding of pillar[5]arenes to inorganic
anions has not been explored yet.7 Herein we want to report the
design and preparation of a novel non-symmetric pillar[5]arene
and its application in anion-binding. This non-symmetric
pillar[5]arene is composed of the following three parts. First, the
non-symmetric pillar[5]arene-based framework provides a rigid
platform to connect binding sites for anions. Second, the triazole
rings, which can be easily obtained through click chemistry, are
sensitive to anions8 because the electronegativities of the three
nitrogen atoms combine to polarize the CH bond, and the lone
pairs of electrons on the nitrogen atoms act to establish and orient
To determine the binding constants of 4a to halide anions,
fluorescence titration experiments were carried out with the
concentration of 4a kept constant at 1.50 Â 10À4 M and that
of tetrabutylammonium halides (TBAX) varied from 0 to
9.00 Â 10À4 M at 25 1C. Addition of the fluoride anion to a
solution of 4a in acetone resulted in a substantial decrease in
the intensity of the emission band at 381 nm (Fig. S7, ESIw).
a Department of Chemistry, Zhejiang University, Hangzhou 310027,
P. R. China. E-mail: fhuang@zju.edu.cn; Fax: +86 571 8795 3189;
Tel: +86 571 8795 3189
b Department of Chemistry, Taizhou University, Taizhou 317000,
P. R. China. E-mail: qizhongchou@tzc.edu.cn
w Electronic supplementary information (ESI) available: Synthetic
procedures and characterizations. For ESI see DOI: 10.1039/c2cc00125j
Scheme 1 (a) Synthesis of fluorescent non-symmetric pillar[5]arene
4a; (b) binding of the fluoride anion by multiple triazole groups of 4a;
(c) chemical structure of model compound 5.
c
2958 Chem. Commun., 2012, 48, 2958–2960
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Titration with the other halide anions only reduced the
corresponding intensity a little even after the addition of
6 equiv of ClÀ, BrÀ, or IÀ. The association constants for FÀ,
ClÀ, BrÀ, and IÀ with 4a were calculated to be (1.25 Æ 0.08) Â
FÀ led to specific changes in the 1H NMR spectrum
(no characteristic peaks related to HF2À), the peak related to
triazole protons H1 shifted downfield significantly, from
8.165 ppm to 9.556 ppm (Dd = +1.391 ppm), which was caused
by the formation of C–HÁ Á ÁFÀ hydrogen bonds between triazole
protons on the pillar[5]arene host and the anion guest. Corres-
pondingly, the signals related to protons H11a and H11b shifted
upfield and coalesced into one peak, while there were almost no
chemical shift changes for H11a and H11b when 4a complexed
with ClÀ, BrÀ, and IÀ. Meanwhile, when 4a complexed with FÀ,
chemical shifts of protons on naphthalene rings of the host
changed dramatically (Fig 1e). In addition, upfield shifts were
observed for protons H10 (Dd = À0.394, À0.108, À0.086
and À0.023 ppm for FÀ, ClÀ, BrÀ and IÀ, respectively). These
differences in chemical shift changes between the fluoride anion
and the other three halide anions were caused by the particularity
of the fluoride anion. The electronegativity and basicity of the
fluoride anion are the strongest and its size is the smallest among
the halide anions. When 4a binds a fluoride anion, the C–HÁ Á ÁFÀ
hydrogen bond forms easily and the repeating units rotate
around the methylene bridge, so five triazole rings at one side
of the pillar[5]arene are inclined to converge and interact with the
FÀ while the pillar architecture of 4a changes into a conical
104 MÀ1, 858 Æ 73 MÀ1, 614 Æ 51 MÀ1 and 284 Æ 19 MÀ1
,
respectively, by using the Stern–Volmer equation.10 It is found
that the pillar[5]arene formed 1 : 1 complexes with all of the four
halide anions. The measured binding constant between 4a and FÀ
was the highest. It was almost 15-fold to that of ClÀ and about
20-fold and 44-fold to those of BrÀ and IÀ, respectively. These
data show that the binding strength between 4a and FÀ is the
strongest, and along with the reduction of halide anions’ electro-
negativity, the association constants of complexation between 4a
and the halide anions decrease gradually. It should be noted that a
gradual enhancement of fluorescence intensity was observed when
trace amount of water was progressively injected into the solution.
This phenomenon was caused by the reduction of hydrogen
bonding between 4a and the halide anions.
The interactions between triazole hydrogen atoms of 4a and the
fluoride anion were further confirmed by using model compound
5 (Scheme 1c), which contains only one triazole unit. Upon the
addition of excess FÀ, the triazole hydrogen signal shifted down-
field slightly (Dd = +0.096 ppm) (Fig. S18, ESIw). The Ka value
was estimated by a fluorescence titration experiment to be 38 Æ
2 MÀ1. The quenching of fluorescence observed in the emission
spectrum of 5 was not notable, indicating the weak binding ability
of 5 with FÀ. The association constant of FÀ with 4a is far higher
than that of FÀ with 5. Triazole units on one side of 4a wrapped
up the FÀ simultaneously as a result of multiple hydrogen bond
interactions, which led to the high Ka value. The much higher
binding constant of 4a and FÀ emphasizes the important
geometric characteristic of the pillar[5]arene structure.
1
structure. From comparison of H NMR spectra we find that
receptor 4a has selectivity towards FÀ over ClÀ, BrÀ, and IÀ.
1H NMR titration experiments in acetone-d6 were carried out
to pinpoint the anion receptor sites and fully explore the inter-
action modes between the halide anions and 4a. Fig. S19 (ESIw)
shows the 1H NMR spectral changes of 4a upon the addition of
FÀ, ClÀ, BrÀ, and IÀ. For all of the halide complexes, chemical
shifts of the triazole protons H1 and the protons H6 and H9 on
naphthyl rings all underwent downfield shifts, which indicated the
formation of C–HÁ Á ÁXÀ hydrogen bonding interaction. The rest
of the aromatic protons and H10 on the methylene bridge showed
upfield shifts, which can be ascribed to the anion-induced
through-bond shielding effect and the p–p stacking interactions
between the naphthyl rings that take place as 4a wraps around
the anion. All of the proton resonances shifted more for FÀ than
for ClÀ, BrÀ, and IÀ. In addition, the peaks of 4a became broad
during the addition of FÀ, indicating that the kinetics of the
complexation were on the same time scale as the 1H NMR
experiment, consistent with the stronger anion binding.
The binding of 4a to halide anions was also studied through
1H NMR spectra with TBAX as anion source. Fig. 1 illustrates
1H NMR chemical shift changes of 4a with the addition of
different halide anions. Upon the addition of ClÀ, BrÀ and IÀ,
the signal related to the triazole protons H1 shifted downfield
(Dd = +0.449, +0.337 and +0.100 ppm, respectively).
Compared with ClÀ, BrÀ and IÀ, the complexation of 4a with
In order to explore other evidence for the C–HÁ Á ÁFÀ interactions
in solution, 19F NMR spectra were carried out. Fig. S20 (ESIw)
shows the 19F NMR spectra of 4a upon the addition of FÀ, the
resonance of free FÀ appeared at À128.16 ppm. However, in the
mixture of 4a and FÀ (1 : 1), the singlet of free FÀ disappeared.
A possible reason for this is that the FÀ is located in the cavity of 4a
and shielded by its electron-rich cyclic structure after the formation
of an inclusion complex between 4a and FÀ.7c,e Another reason is
the host-induced broadening effect.7e
The phenomenon that the conformation of 4a changed from the
pillar architecture into the conical structure when 4a interacted with
FÀ was further validated by NOESY NMR spectroscopy. The
NOESY spectrum (Fig. S21, ESIw) of the uncomplexed 4a shows
no correlation between the protons on the naphthyl rings, indicating
that the interproton distances between each other are large. When
FÀ was included into the cavity of 4a and formed C–HÁ Á ÁFÀ
hydrogen bonds, the NOE cross peaks (A, B, C, D in Fig. 2)
Fig. 1 Partial 1H NMR spectra (400 MHz, acetone-d6, 298 K): (a) 4a
(1.00 mM); (b) 4a (1.00 mM) and 4 equiv. of TBAI; (c) 4a (1.00 mM)
and 4 equiv. of TBABr; (d) 4a (1.00 mM) and 4 equiv. of TBACl; (e) 4a
(1.00 mM) and 4 equiv. of TBAF.
c
This journal is The Royal Society of Chemistry 2012
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between naphthyl rings were observed. The associated changes
(Fig. S22, ESIw) in through-space interactions arose from the
conformation change in 4a upon the formation of C–HÁ Á ÁFÀ
hydrogen bonding interactions and indicated that the distances
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were investigated. The addition of CF3COOÀ, NO3À, HSO4
,
À
CH3COOÀ, ClO4À, and H2PO4À produced only a nominal change
in the fluorescence spectrum of 4a due to their low affinities
towards 4a. The corresponding association constants were far
lower than that of 4a and FÀ (Table S1, ESIw). As for PF6À, it
could not get into the cavity and interact with 4a due to its large
size. No chemical shift changes were observed in 1H NMR spectra
after adding 4 equiv. of TBAPF6 into the solution of 4a (Fig. S24,
ESIw). Compared with a wide range of anions, the strength of the
binding between 4a and FÀ is remarkable (Fig. S25, ESIw).
In conclusion, a novel fluorescent non-symmetric pillar[5]arene-
based receptor 4a with high selectivity and affinity towards the
fluoride anion has been synthesized. Due to the unique geometric
structure of 4a, multiple C–HÁ Á ÁFÀ hydrogen-bonding inter-
actions between 4a and the fluoride anion formed and greatly
improved their affinity. This novel pillar[5]arene-based neutral
anion receptor enriches the structural diversity of anion binding
chemistry, and can be further used in the fabrication of sensing
devices for the fluoride anion.
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This work was supported by the National Natural Science
Foundation of China (20834004, 91027006, 21172166), the
Fundamental Research Funds for the Central Universities
(2010QNA3008), National Basic Research Program
(2009CB930104), and Zhejiang Provincial Natural Science
Foundation of China (R4100009, Y4100783). Thanks to
Mr. Xiaopeng Chen for his assistance with molecular modelling.
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