Sensitive fluorescence sensor for nitroaniline isomers based on calix[4]arene bearing naphthyl groups

Article abstract of DOI:10.1016/j.tet.2012.04.076

Novel naphthyl-modified calix[4]arene was synthesized by click chemistry, and exhibited high affinity and selectivity for p-nitroaniline by the fluorescence spectroscopy. However, the sensitivity toward other anilines 3a-e are negligible. The ¹

Full text of DOI:10.1016/j.tet.2012.04.076

Tetrahedron 68 (2012) 5579e5582
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Sensitive fluorescence sensor for nitroaniline isomers based on calix[4]arene
bearing naphthyl groups
,
,
*
Junyan Zhan a b, Xiaolei Zhu a, Fei Fang a, Fajun Miao a, Demei Tian a, Haibing Li a
a Key Laboratory of Pesticide and Chemical Biology of the Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, PR China
b College of Chemistry and Life Science, Guangxi Teachers Education University, Nanning 530001, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Novel naphthyl-modified calix[4]arene was synthesized by click chemistry, and exhibited high affinity
and selectivity for p-nitroaniline by the fluorescence spectroscopy. However, the sensitivity toward other
anilines 3aee are negligible. The 1H NMR, 1H NOESY, MALDI-TOF mass spectroscopy and computational
calculations revealed the formation of hosteguest complex driven by H-bonding and hydrophobic
interactions.
Received 22 February 2012
Received in revised form 7 April 2012
Accepted 20 April 2012
Available online 27 April 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Calix[4]arene
Fluorescence
Nitroaniline isomers
Naphthyl
1. Introduction
this paper, we describe the design and click synthesis of fluorescent
calix[4]arene 2, which showed highly selective recognition toward
The design of molecular recognition structures has attracted
great interest in supramolecular chemistry.1 In this connection,
numerous investigations are now being carried out in both di-
rected synthesis and studies of synthetic receptors and identifi-
cation of the factors that determine interactions of the receptors
with diverse analytes.1b,2 The complexation properties of the host
and guest have been extensively investigated by many means.
Among them, the optical sensors (colorimetric or fluorescence)
are much more popular and powerful tool to sense a variety of
molecular and ionic guests.3 It is noteworthy that design of host
system is also essential for high affinity and selective recognition
of analytes.
Macrocyclic compounds, specifically calixarenes have become
a popular building block for the preparation of new host systems.4
Application of calixarenes as molecular host is based, first of all, on
their ability to bind selectively guest. Calixarenes have the ability to
form supramolecular complexes by electrostatic, donoreacceptor,
p-nitroaniline 3f. Compound 3f is of importance because of its
extremely common use as an intermediate in the synthesis of dyes,
antioxidants, and pharmaceuticals.7
2. Results and discussion
The fluorescent calix[4]arene 2 was synthesized by click chemistry
as shown in Scheme 1. Initially, the reaction of 2,3-naphthalenediol
with 2.2 equiv of 2-azidoethyl 4-methylbenzenesulfonate in CH3CN
and K2CO3 as base gave the desired azide-functionalized naphthol 1 in
high yield (Scheme S1). The reaction of alkynylcalixarene, was reacted
with 1 using CuI as catalyst in toluene at 90 ꢀC to give calix[4]arene 2.8
The structure of the compound was characterized by MALDI-TOF-MS
spectra, elemental analyses, and 1H and 13C NMR studies (Fig. S4). The
cone conformation is proven by two signals for the aromatic protons,
two doublets for the bridging methylene groups, and two singlets for
the tert-butyl groups in the 1H NMR spectra.9
The molecular recognition behavior of the calix[4]arene 2 was
studied toward aniline derivatives 3aef by fluorescence spectros-
copy. Fig. 1 shows the fluorescence response of calix[4]arene 2 to
14 equiv of anilines (3aef), including aniline, o-chloroaniline, p-
chloroaniline, o-nitroaniline, m-nitroaniline, p-nitroaniline. In-
terestingly, p-nitroaniline can significantly quench the fluorescence
of calix[4]arene 2, but other of the aniline derivatives, such as o-
nitroaniline, m-nitroaniline, had very little effect on fluorescence. It
is well known that the nitro-aromatic compounds are a quenching
hydrophobic, and pep stacking interactions of small molecules and
ions with the aromatic system of the macrocyclic cavity. In ongoing
efforts, even though some recognition of neutral organic com-
pounds based on functionalized calixarenes have been reported,5
the fluorescent method to sense molecular was relatively rare.6 In
* Corresponding author. Tel.: þ86 27 67867958; e-mail address: lhbing@
mail.ccnu.edu.cn (H. Li).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.04.076

5580
J. Zhan et al. / Tetrahedron 68 (2012) 5579e5582
(a)
0.012
0.010
0.008
0.006
0.004
0.002
500
O
N
OH
O
OH
400
300
200
100
0
CuI\DIPEA
toluence
N3
N3
O
O
N
N
N
N
O
OH
O
OH
N
1
O
O
0
30000 60000 90000 120000 150000
1/[3f]
2
350
400
Wavelength (nm)
450
500
NH2
NH2
NH2
NH2
NH2
NO2
Cl
(b)
50
40
NO2
Cl
NH2
3a
NO2
3f
3e
3d
3b
3c
NO2
NO2
NO2
NO2
30
20
NO2
3i
NO2
NO2
NO2
3g
3h
3j
3k
Scheme 1. Synthesis of calix[4]arene 2 and the structures of the guest.
0.0
0.2
0.4
0.6
0.8
1.0
75
Control
Molar fraction of 2
500
60
Fig. 2. (a) Fluorescence spectra titration of 2 (5ꢁ10ꢂ6 M) with various equivalents of 3f
in CH3CN (0, 1.5, 3, 4.5, 6, 7.5, 9, 10.5, 12, 13.5, 15, 16.5, 18, 19.5, 22.5 equiv, lex¼295 nm,
Slit¼5). Inset: BenesieHildebrand analysis of the fluorescence changes for the com-
plexation between 2 and 3f (lex¼295 nm, Slit¼5). (b) Job’s plots of 2 toward 3f in
CH3CN solution at an invariant total concentration of 5ꢁ10ꢂ6 M (lex¼295 nm, Slit¼5).
45
400
30
15
300
0
3a 3b 3c 3d 3e 3f 3g 3h 3i 3j 3k
200
complex (Fig. 2b).11 The 1:1 complex of 2 and 3f has been further
revealed based on MALDI mass spectrum (Fig. S1), which exhibited
the peak at m/z 1163.0 (calcd¼1162.4) corresponding to [2þ3fþH]þ.
An important feature of 2 is high binding affinity toward 3f over
other aniline. Based on fluorescence titration experiments between
2 and other anilines derivatives, including o-chloroaniline, p-
chloroaniline, o-nitroaniline, m-nitroaniline (Fig. S2), the associa-
tion constants (Ka) were determined as shown in Table 1. Compared
p-nitroaniline
100
0
350
400
450
500
Wavelength (nm)
Fig. 1. Fluorescence intensity changes for calix[4]arene 2 (5ꢁ10ꢂ6 M) in CH3CN upon
addition of 3aek (5ꢁ10ꢂ5 M). Inset: [((I0ꢂI)/I0)]ꢁ100 (lex¼295 nm, Slit¼5). I0 is the
fluorescent emission intensity of the host, and I is the fluorescent intensity after adding
3aek.
to the Ka, the Ka is highest, which indicated the stronger bind of 2
2e3f
for 3f.
The selectivity of 2 (5.0ꢁ10ꢂ6 M) to p-NAE (5.0ꢁ10ꢂ5 M) was
further demonstrated in the presence of 10 equiv of other com-
petitive species. As shown in Fig. 3, the presence of 3aee and 3gei
does not significantly interfere the 3f selectivity, which suggested
that 2 can be used as a potential chemosensor for 3f.
agent, which can induce the fluorescence quenching. In order to
avoid the effect of the nitro-aromatic group, nitrobenzene, 2,4-
dinitrotoluene, m-dinitrobenzene, 1,4-dinitrobenzene, and 4-
methyl nitrobenzene (3gek) as control guest were used to in-
vestigate the fluorescence response. It was found that the three
nitro-aromatic compounds (3gei) gave little fluorescence change,
which showed that p-nitroaniline induced fluorescence quenching
was not due to the interaction of the nitro-aromatic group.
To seek further more detailed information on the binding
properties of 2 with 3f, the 1H NMR spectra of 2, 3f, mixed 2 with 3f
was investigated as depicted in Fig. 4. The signals of protons on the
aromatic ring of 3f underwent upfield shifting (Ha, 0.063 ppm; Hb,
0.214 ppm). Meanwhile, the proton of NH2 in 3f (Hc) and the proton
of ArOH of calix[4]arene 2 disappeared. This phenomenon may
attribute to H-bonding interactions between NH2 group of 3f and
the phenolic OH of 2.12 Because of the reciprocity, the protons on
the bridging methylene groups of calix[4]arene 2 was upfield
shifted (Hd, 0.017 ppm; He, ꢂ0.002 ppm). The upfield shifts of ar-
omatic ring of 3f and the remarkable shift of Hb (3f) indicated that
the 3f penetrated into the rich-electron cavity of the host calix[4]
arene from the NH2 end of the benzene ring. Overall, the binding of
The fluorescence spectra of 2 (5ꢁ10ꢂ6 M) at increasing con-
centrations of 3f are depicted in Fig. 2a. It was found that while no
shift in the fluorescence maximum was observed, the fluorescence
intensities of 2 gradually decreased with the addition of increasing
concentrations of 3f. The association constant (Ka) of 2 for 3f was
calculated to be 2.06ꢁ104 Mꢂ1 by BenesieHilderbrand equation.10
In the Job plot a maximum fluorescence change was observed
when the molar fraction of 2 versus 3f was 0.5, indicative of a 1:1

J. Zhan et al. / Tetrahedron 68 (2012) 5579e5582
5581
nitroaniline and the aromatic protons of calix[4]arene 2.13 The re-
sult indicated the p-nitroaniline was included in the hydrophobic
cavity of calix[4]arene 2 from the NH2 end. The inclusion complex
form between 2 and 3f through the host and guest inclusion in-
duces a strong fluorescence quenching due to a well-defined
Table 1
The complex constants between 2 and other anilines derivatives
3b
3c
3d
3e
3f
Ka (103)
6.311
6.858
0.445
0.868
20.54
electron transfer process from the fluorophore to the guest.14
A
plausible complexation mode is therefore depicted in Fig. 4.
70
60
50
40
30
20
10
0
500
400
300
200
100
The binding of calix[4]arene 2 and 3f was also examined by
computational calculations at b3lyp/6-31G(d) levels using Gaussian
03.15 The results from molecular mechanics calculation were gen-
erally consistent with the 1H NMR and fluorometric experimental
results. Fig. 5 shows the top view of the optimized structure of the
hosteguest complex. Compound 3f was partially located inside
hydrophobic cavity of the cone calix[4]arene from the NH2 end of
ꢀ
ꢀ
the benzene ring. by two NH/OAr H-bonds (d1¼3.3 A, d2¼3.4 A)
between calixarene hydroxyls and NH2 of 3f.
0
350
400
450
500
Wavelength (nm)
Fig. 3. The fluorescence changes of 2 (5ꢁ10ꢂ6 M) toward 10 equiv 3f in the presence of
10 equiv competitive species. I0 is fluorescence emission intensity at 341 nm for free 2,
and
I is the fluorescent intensity upon addition of competitive species with the
existence of 3f (lex¼295 nm, Slit¼5).
a
b
c
a
b
O2N
NH2
(a)
(b)
c
a
e
d
b
(c)
Fig. 5. The top view on the optimized structure of the inclusion complex of 2 with 3f.
9.0
8.0
7.0
6.0
5.0
4.0
ppm
3. Conclusions
In conclusion, we have synthesized a fluorescent calix[4]arene by
click chemistry, which exhibits high binding affinity and selectivity
toward p-nitroaniline (3f). Job’s plots and MALDI-TOF mass spec-
trum showed a 1:1 stoichiometry complexation between of 2 toward
3f. By a combination of H-bonding and hydrophobic interactions as
revealed by 1H NMR, 1H NOESY, and computational calculations, 2
and 3f complex was formed. The electron-poor aromatic guests were
included in the electron-rich cavity of the host calix[4]arene within
a 1:1 complex mode, which induce the fluorescence quenching. The
reasonable sensor design is an effective strategy to reinforce the
binding affinity and fluorescence modulation.
p-nitroaniline
N
O
H
Fig. 4. The partial 1H NMR spectra (CDCl3, 400 MHz, 298 K) of (a) 3f (8 mM) (b) 2 and
3f (8 mM each) (c) 2 (8 mM); and schematic representation of the possible recognition
process for 2 toward 3f via hosteguest interaction.
3f penetrated into the hydrophobic cavity of calix[4]arene 2 is
driven by H-bonding between NH2 group of guest and the phenolic
OH of host, hydrophobic interactions, and a cavity effect. While
NOESY experiments could be extremely valuable to verify the in-
clusion nature of these complexes, since one can conclude that two
protons are closely located in space. To get further information
about the geometry of the inclusion complexation between the
calixarene and p-nitroaniline, the NOESY spectrum was performed.
As shown in Fig. S3, the NOESY spectrum of an equimolar mixture
of host 2 with p-nitroaniline (8.0 mM each) displays clear NOE
cross-peaks between the Hb protons close to the NH2 end of p-
4. Experimental section
4.1. Instruments
1H NMR and 13C NMR spectra were recorded on Varian Mercury
VX400 instrument at ambient temperature with TMS as the internal
standard. 1H NOESY spectra was recorded on Varian Mercury VX600
instrument at ambient temperature with TMS as the internal stan-
dard. Chemical shifts are expressed in parts per million and J values
are given in hertz. MALDI-TOF-MS were recorded on matrix assisted
laser desorption ionization/time of flight MS. PL spectra were

5582
J. Zhan et al. / Tetrahedron 68 (2012) 5579e5582
recorded on a Cary Eclipse instrument. Computational calculations
were recorded at b3lyp/6-31G(d) levels using Gaussian 03. All
chemicals were A.R. grade and were purified by standard procedures.
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This work was financially supported by the National Natural
Science Foundation of China (21072072, 21102051), Program for
New Century Excellent Talent in University (NCET-10-0428), and the
Innovation Fund Project for Graduate Students of CCNU (2009006).
Supplementary data
Experimental details, MALDI-TOF mass spectrum of 2$p-NAE
complex; fluorescence spectra titration of 2 with 3bee; 1H NOESY
spectrum of a mixture of 2 with the p-nitroaniline 3f; NMR and MS
spectra for compound 2. Supplementary data related to this article
can be found online at doi:10.1016/j.tet.2012.04.076.