Azocalix[4]arene strapped calix[4]pyrrole: A confirmable fluoride sensor

Article abstract of DOI:10.1021/ol301684r

A new chromogenic fluoride sensor based on 1,3-di-p-nitrophenylazocalix[4] arene-calix[4]pyrrole (1) was designed and synthesized. The color of the solution of probe 1 changed upon the addition of any F^-, CH ₃CO₂^-, PhCO₂^-, and H ₂PO₄^- ions. However, from these ions the highly specific sensing of F^- is achieved by the addition of Ca ²⁺ which leads to a color change from light sky blue (of 1·F^-) back to the original light orange color of 1.

Full text of DOI:10.1021/ol301684r

ORGANIC
LETTERS
2012
Vol. 14, No. 16
4050–4053
Azocalix[4]arene Strapped Calix[4]pyrrole:
A Confirmable Fluoride Sensor
Preecha Thiampanya, Nongnuj Muangsin, and Buncha Pulpoka*
Supramolecular Chemistry Research Unit and Organic Synthesis Research Unit,
Department of Chemistry, Faculty of Science, Chulalongkorn University,
254 Phayathai Road, Bangkok 10330, Thailand
buncha.p@chula.ac.th
Received April 26, 2012
ABSTRACT
A new chromogenic fluoride sensor based on 1,3-di-p-nitrophenylazocalix[4]arene-calix[4]pyrrole (1) was designed and synthesized. The color of the
solution of probe 1 changed upon the addition of any Fꢀ, CH3CO2ꢀ, PhCO2ꢀ, and H2PO4ꢀ ions. However, from these ions the highly specific sensing
of Fꢀ is achieved by the addition of Ca2þ which leads to a color change from light sky blue (of 1 Fꢀ) back to the original light orange color of 1.
3
Fluoride (Fꢀ) plays an important role in human life, and
the deficiency or overexposure of the amount of Fꢀ causes
osteoporosis and poor dental health.1 Many design and
synthesesof highlysensitive and selective chemosensorsfor
Fꢀ have been reported,2 but there is still a need for further
development. Presently, chromogenic anion sensors have
received increasing attention and have become promising
candidates for sensing probes, especially for Fꢀ, because it
allows detection of the species of interest with the naked
eye.3 Many frameworks have been developed,3 such as
porphyrin,3a calix[4]pyrrole,4 and calix[4]arene,5 but the
chromogenic azo-calix[4]arene has become a preferred
candidate for a sensing probe because of its particular
preorganized framework that promptly accommodates
ions or neutral molecules.5a,6 Azo-calix[4]arene’s selective
sensing property can be monitored by a change in the
UVꢀvis spectra and, more practically, by the visible
change in their solution colors. Although many chromo-
genic sensors based on calix[4]arene have been developed
for sensing specific cations and other molecules, calixarene-
based chromogenic sensors for anions have rarely been
ꢀ
(1) For example: (a) Gunnlaugsson, T.; Glynn, M.; Tocci (nee Hussey),
G. M.Kruger, P. E.; Pfeffer, F. M. Coord. Chem. Rev. 2006, 250, 3094.
(b) Yeo, H. M.; Ryu, B. J.; Nam, K. C. Org. Lett. 2008, 10, 2931.
(c) Upadhyay, K. K.; Mishra, R. K.; Kumar, V.; Chowdhury, P. K. R.
Talanta 2010, 82, 312.
(2) For example: (a) Jung, H. S.; Kim, H. J.; Vincens, J.; Kim, J. S.
Tetrahedron Lett. 2009, 50, 983. (b) Kwon, J. Y.; Jang, Y. J.; Kim, S. K.;
Lee, H.-K.; Kim, J. S.; Yoon, J. J. Org. Chem. 2004, 69, 5155. (c) Lee,
M. H.; Gabbaı, F. P. Inorg. Chem. 2007, 46, 8132. (d) Guha, S.; Saha, S.
J. Am. Chem. Soc. 2010, 132, 17674. (e) He, X.-M.; Yam, V. W.-W Org.
Lett. 2011, 13, 2172. (f) Zhang, J. F.; Lim, C. S.; Bhuniya, S.; Cho, B. R.;
Kim, J. S. Org. Lett. 2011, 13, 1190.
ꢀ
(4) For example: (a) Farinha, A. S. F.; Tome, A. C.; Cavaleiro,
J. A. S. Tetrahedron 2010, 66, 7595. (b) Yoo, J.; Kim, M.-S.; Hong, S.-J.;
Sessler, J. L.; Lee, C.-H. J. Org. Chem. 2009, 74, 1065.
(5) For example: (a) Chang, K.-C.; Su, I.-H.; Wang, Y.-Y.; Chung,
W.-S. Eur. J. Org. Chem. 2010, 4700. (b) Quinlan, E.; Matthews, S. E.;
Gunnlaugsson, T. J. Org. Chem. 2007, 72, 7497. (c) Kim, H. J.; Kim,
S. K.; Lee, J. Y.; Kim, J. S. J. Org. Chem. 2006, 71, 6611.
(3) (a) Suksai, C.; Tuntulani, T. Chem. Soc. Rev. 2003, 32, 192.
€
(b) Dix, J. P.; Vogtle, F. Chem. Ber. 1981, 114, 638. (c) Kim, J. Y.; Kim,
G.;Kim, C. R.;Lee, S. H.; Lee, J. H.;Kim, J. S. J. Org. Chem. 2003, 68, 1933.
(d) Chen, C. F.; Chen, Q. Y. New J. Chem. 2006, 30, 143. (e) Kaewtong,
C.; Noiseephum, J.; Uppa, Y.; Wanno, B.; Morakot, N.; Morakot, N.;
Tuntulani, T.; Pulpoka, B. New J. Chem. 2010, 34, 1104.
(6) For example: (a) Menon, S. K.; Modi, N. R.; Patel, B.; Patel,
€
€
€
M. B. Talanta 2011, 83, 1329. (b) Karakus, O. O.; Deligoz, H.
J. Macromol. Sci. A 2010, 47, 1111.
r
10.1021/ol301684r
Published on Web 08/06/2012
2012 American Chemical Society

reported. More particularly, calix[4]arene strapped calix-
[4]pyrroles show a greater enhancement in terms of both
anion binding affinities and modulating the inherent anion
selectivity. Moreover, previous reports have shown that
calix[4]-crown strapped calix[4]pyrroles display a highly
specific ion-pair sensing property, such as that for CsF.7
However, most anion receptors that bind Fꢀ ions do so
along with other anions, such as acetate, benzoate, or
dihydrogen phosphate ions (H2PO4ꢀ). Some of those
receptors are chromogenic sensors, but their color changes
upon binding of the Fꢀ ion are quite similar to those upon
binding of acetate, benzoate or H2PO4ꢀ ions. This led us to
develop a chromogenic sensor for Fꢀ ion detection based
on calix[4]arene-calix[4]pyrrole.
Scheme 1. Synthetic Pathway of Chromogenic Sensor 1
Here, we report the synthesis of a new design of chromo-
genic sensor, 1,3-di-p-nitrophenylazocalix[4]arene-calix-
[4]pyrrole (1), that serves as a confirmable and reversible
Fꢀ sensor. The molecule sensor 1 contains an azobenzene
moiety serving as a sensing unit as well as enhancing the anion
binding by increasing the H-bonding ability of the calix-
[4]arene platform, while the calix[4]pyrrole acts as an anion
binding unit. The investigation of its affinity toward various
anions was accomplished by UVꢀvis spectroscopy and its
visible solution color changes.
The synthesis of 1 was carried out as shown in Scheme 1.
The synthesis starts by the condensation of 2-(8-tosyl-
triethyleneglycol)acetophenone (2) with calix[4]arene using
K2CO3 as a base in acetonitrile to provide 1,3-calix-
[4]diacetophenone (3) (85% yield). Subsequently, the diazo-
coupling reaction of 3 with p-nitrobenzene-diazoniumtetra-
fluoroborate in the presence of pyridine in tetrahydrofuran
(THF) gave chromogenic 1,3-di-p-nitrophenylazocalix[4]-
diacetophenone (4) (24% yield). According to the 1H
NMR spectra of 3 and 4, the phenolic OH signal shifted
from 7.26 to 8.70 ppm, which implies that the azo-p-
nitrophenyl group not only can serve as a chromophore
but also increases the H-bonding ability of the phenolic
OH anion-binding site. Treating 4 with pyrrole in a
presence of a catalytic amount of trifluoroacetic acid gave
1,3-calix[4]arene-bisdipyrroethane (5) in 39% yield. This
key precursor (5) was then condensed with dry acetone in
the presence of a catalytic amount of BF3 OEt2 at rt to
3
provide the desired chromogenic sensor 1 in 13% yield.
The cone conformation of compounds 1, 3, 4, and 5 was
confirmed by the AB pattern of doublets at around 4.4
and 3.5 ppm (J = 13 Hz) for the methylenic protons
(ArCH2Ar) on the 1H NMR spectra and a singlet at 31 ppm
for methylene bridge carbons on the 13C NMR spectra.
Upon allowing a dichloromethane/methanol solution of
compound 4 to undergo slow evaporation at a temperature
of4 °C, single crystals suitable for X-ray analysis were obtained.
The ORTEP drawing (Figure 1) confirms that 4adopts a pinch
cone conformation. The p-nitrophenylazo moiety aligned ap-
proximately planar to the phenolic unit of the calix[4]arene
framework allowing electron transfer by resonance.
Figure 1. ORTEP drawing of 4. Displacement ellipsoids are
scaled to the 50% probability level.
The chromogenic behavior of 1 was revealed by UVꢀvis
analysis (Figure 2). The UVꢀvis absorptions of 1 were
investigated upon the addition of 6 equiv of tetra-n-butyl-
ammonium (TBA) salts of Fꢀ, Clꢀ, Brꢀ, Iꢀ, CH3CO2
,
ꢀ
PhCOOꢀ, NO3ꢀ, PF6ꢀ, ClO4ꢀ, and H2PO4ꢀ into a solu-
tion of 1. Free 1 exhibited one absorption band at 395 nm.
The addition of the above anion based salts in the ligand
solutiongavea bathochromic shift, from 395 nm toaround
(7) (a) Kim, S. K.; Sessler, J. L.; Gross, D. E.; Lee, C.-H.; Kim, J. S.;
Lynch, V. M.; Delmau, L. H.; Hay, B. P. J. Am. Chem. Soc. 2010, 132,
5827. (b) Sessler, J. L.; Kim, S. K.; Gross, D. E.; Lee, C.-H.; Kim, J. S.;
Lynch, V. M. J. Am. Chem. Soc. 2008, 130, 13162.
ꢀ
600 nm, only with Fꢀ, CH3CO2ꢀ, PhCO2ꢀ, and H2PO4
,
Org. Lett., Vol. 14, No. 16, 2012
4051

while Clꢀ, Brꢀ, Iꢀ, NO3ꢀ, PF6ꢀ, and ClO4ꢀ did not effect
ligand color. The magnitude of these bathoꢀchromic shifꢀts
is in the order Fꢀ > CH3CO2 > PhCO2 > H2PO4
,
ꢀ
with significant color changes from light orange to light
sky blue, blue, light pink, and light yellow being observed,
respectively (inset in Figure 2).
Figure 3. UVꢀvis titration of 1 (0.02 mM) in CH3CN upon
addition of Fꢀ (0ꢀ6 equiv). (Inset) Plot of absorbance at 396 nm
as a function of [Fꢀ].
Figure 2. Wavelength changes of 1 upon the addition of various
anions. Condition: 1 (0.02 mM)/CH3CN; TBA salts (6 equiv)/
CH3CN; (inset) color change of 1 (A = Ligand 1, B = 1 þ Fꢀ,
C = 1 þ CH3CO2ꢀ, D = 1 þ PhCO2ꢀ, E = 1 þ H2PO4ꢀ).
Table 1. Stability Constants (log β) of the 1:1 Complexes of 1
with the Indicated Anions in MeCN, as Evaluated by UVꢀvis
Titration (t = 25 °C, I = 0.01 M Bu4NPF6)
anions
Fꢀ
log β
3.07 (0.08), 11.09 (0.07)a
2.55 (0.02)
The spectroscopic changes can be explained by a charge
transfer from the donor oxygen of the azophenol unit
to the acceptor substituent (ꢀNO2) of the chromophore.
After complexation of 1 with anions, the excited state
would be more strongly stabilized by anion binding,
resulting in a bathochromic shift ofthe absorption maxima
as well as in color changes.4 Thus, 1 could enable colori-
ꢀ
H2PO4
acetate
4.81 (0.06)
benzoate
5.64 (0.09)
a 2:1 complex (A2L).
1
S17 show the H NMR spectra of 1 (3.58 mM) with
different amounts of TBAF in acetonitrile-D3 and revealed
that the phenolic protons of the azocalix[4]arene moieties
at 8.80 ppm disappeared when only 0.1 equiv of Fꢀ was
added into a solution of 1 along with displacement of
the Hc proton signal from 7.82 to 7.72 ppm. This indicates
that the phenolic protons of 1 were strongly reactive with
Fꢀ, as previously reported.4 Moreover, protons Ha and
Hb of the nitrobenzene units shifted upfield from 8.28 and
7.88 ppm to 8.26 and 7.80 ppm, respectively, which implies
that the electron was pushed from the phenolic unit by the
Fꢀ ion.
metric differentiation of Fꢀ, acetate, benzoate and H2PO4
ꢀ
anions possessing different sizes and shapes.8
In order to investigate the stoichiometry and stability con-
stants between 1 and anions (as TBA salts), UVꢀvis titration
was performed using 0.02 mM 1 in CH3CN. The absorption
peak at 600 nm increased with increasing concentrations of Fꢀ
added (Figure 3). The stoichiometry of the 1 F‑complex was
3
determined by the mole ratio plot (inset in Figure 3) and using
the SIRKO program,9 which clearly showed that at least
two species of complexes (1:1 and 2:1 (anion/ligand) with log
β = 3.07 and 11.09, respectively) existed. The association
constants of 1:1 complexes of 1 with acetate, benzoate, and
H2PO4ꢀ are summarized in Table 1. The specific order of the
binding affinities is as follows: benzoate > acetate > Fꢀ >
H2PO4ꢀ. The preference of 1 to bind benzoate over the
other anions studied may be due to a preorganization of 1
to accommodate benzoate, which is confirmed by1H NMR
titration study (Figures 5 and S19).
In addition, the Hd and He signals shifted upfield from
around 6.86ꢀ6.72 and 7.02 ppm to 6.66 and 6.85 ppm,
respectively, which indicated that the azocalix[4]arene plat-
form rearranged to accommodate the Fꢀ ion. The pyrrolic
NH peak shifted downfield from 8.04 to 8.09 ppm at
0.1 equiv, and disappearedat 0.2 equiv, of addedFꢀ anions,
which was in contrast to the case of the β-pyrrolic protons.
Thissuggeststhat the calix[4]pyrrole unit participated in Fꢀ
binding by H-bonding and also that the phenolic OH and
thepyrrolicNH of probe1served as anion binding sites and
enhanced the binding ability to detect anions.
In order to understand the binding mode of 1 with Fꢀ
ions, 1H NMR titrations were carried out. Figures 4 and
(8) Lee, D. H.; Lee, H. Y.; Lee, K. H.; Hong, J.-I. Chem. Commun.
2001, 1188.
(9) Nishizawa, S.; Kato, R.; Hayashita, T.; Teramae, N. Anal. Sci.
1998, 14, 595.
However, 1H NMR titration revealed a different manner
of complexation of benzoate by probe 1 (Figure 5).
4052
Org. Lett., Vol. 14, No. 16, 2012

Figure 4. 1H NMR spectra of compound 1 (3.58 mM) in MeCN
in the presence of different amounts of TBAF.
Figure 5. 1H NMR spectra of compound 1 (3.58 mM) in CD3CN
in the presence of different amounts of benzoate ions.
The phenolic OH signal at 8.80 ppm became a broad peak
and then dissapeared when only 0.1 and 0.2 equiv of
benzoate were added into the solution of 1, respectively,
without displacement of the Ha and Hb signals. This
implies that electron push did not occur. The NH peak
gradually shifted downfield from 8.16 to 8.65 ppm while
the pyrrolic signals were displaced upfield from 5.80 and
5.61 ppm to 5.75 and 5.57 ppm, respectively, upon the
addition of the benzoate salt solution. This suggests that
receptor 1 bound the benzoate ion by H-bonding from
the ꢀNH and ꢀOH groups of the calix[4]pyrrole and azocalix-
[4]arene, respectively. Moreover, these 1H NMR titration
studies also showed that probe 1 preorganized prior to
binding benzoate over Fꢀ, since there were fewer peak shifts
of 1. The acetateꢀreceptor 1 interaction was in between that
for the Fꢀ and benzoate complexes with 1. The 1H NMR
titration studies also demonstrate that the complexation
mode of receptor 1 with Fꢀ, acetate, and benzoate was
endocomplexation with different magnitudes of interactions
with phenol and calix[4]pyrrole units.
Figure 6. Reversibility of Fꢀ coordination by 1 due to the
addition of Ca(NO3)2 solution.
The decomplexation of the 1 Fꢀ complex occurred
3
and chromogenically that probe 1 could discriminate
between Fꢀ, acetate, benzoate and H2PO4, which possess
different sizes and shapes, with binding affinities in the
order benzoate > acetate > Fꢀ > H2PO4ꢀ. The detection
of Fꢀ can be confirmed by the addition of CaNO3 solution
upon the addition of Ca2þ (2 equiv) into the solution of
1 with Fꢀ (6 equiv) in CH3CN. The UVꢀvis spectrum and
color change showed that the addition of Ca2þ to the
solution of 1 Fꢀ results in a revival of the absorption
3
spectra of free receptor 1 (Figure 6). This finding suggests
that ion pair complexation did not occur but that the Fꢀ
ion was stripped out by Ca2þ to form the CaF2 salt.
into the solution of 1 Fꢀ.
3
Acknowledgment. The authors gratefully acknowledge
the 90th Anniversary of Chulalongkorn University Fund
(Rathchadaphiseksomphot Endowment Fund) and the
Thailand Research Fund (RSA/06/2545 and RTA
5380003) for financial support.
Contrastingly, the ion pair complexes, 1 CH3CO2 Ca2þ
ꢀ
3
3
and 1 PhCO2 Ca2þ, formed after addition of 2 equiv
of Ca(NO3)2 into 1 CH3CO2ꢀ and 1 PhCO2ꢀ complexes
(Figures S23 and S24).
‑
3
3
3
3
In summary, a chromogenic anion sensor 1 was success-
fully synthesized. The integration of an azobenzene unit
onto the calix[4]arene framework enhanced the anion
binding ability of the phenolic OH group of the calix-
[4]arene by the electron pull from the phenolic groups to
the nitrobenzene units and provided naked-eye detection
ability for anions. It was demonstrated spectroscopically
Supporting Information Available. Experimental pro-
cedures and spectroscopic data for all new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
The authors declare no competing financial interest.
Org. Lett., Vol. 14, No. 16, 2012
4053