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X. Cao et al. / Tetrahedron Letters 55 (2014) 2029–2032
afford tetraiodo-calix[4]arene 2 in 90% yield.17 Compound 2,
PdC12(PPh3)2 and CuI were stirred in Et3N and DMF under a N2
atmosphere, and 1-ethynylnaphthalene was then added. The
mixture was stirred at 100 °C for 14 h. The evaporated crude prod-
uct was then purified by column chromatography to give a white
powder C4N4 in 84% yield. The structure of C4N4 was character-
ized by MALDI-TOF-MS (Fig. S3), NMR spectra, and microanalysis
(Figs. S1 and S2). The compound was confirmed by the presence
of two doublets (3.36–3.40 and 4.96–5.00 ppm) for the bridging
methylene groups in the 1H NMR spectra.18
The fluorescence spectrum of C4N4 (kex = 300 nm) in CH3CN
exhibited a characteristic emission band at 378 nm. The molecular
recognition behavior of the C4N4 was studied with respect to
nitrobenzenes derivatives 3a–h by fluorescence spectroscopy.
Figure 1 shows the fluorescence response of C4N4 with eight
equivalents of the nitrobenzenes derivatives (3a–h), including
o-nitrophenol, m-nitrophenol, p-nitrophenol, 2,4,6-trinitrophenol,
nitrobenzene, 1,3-dinitrobenzene, 2,6-dinitrotoluene, and 2,4,
6-trinitrotoluene. Interestingly, p-nitrophenol caused the most sig-
nificant quench of C4N4, but the other nitrobenzene derivatives
had very little effect on fluorescence. This shows that fluorescence
quenching by p-nitrophenol was not only due to the quenching of
the nitro group, but also due to the host–guest interaction by
matching size.
In order to investigate the binding constant and stoichiometry
between host and guest, the fluorescence spectra of C4N4
(1 Â 10À5 M) at increasing concentrations of 3c are depicted in Fig-
ure 2. It was found that while no shift in the fluorescence maxi-
mum was observed, the fluorescence intensity of C4N4 decreased
with increasing concentrations of 3c. The association constant of
C4N4 for 3c was evaluated using the Benesi–Hildebrand equation
and was found to be 10.06 Â 103 MÀ1 (Fig. 2).19 Meanwhile, in
the Job plot, the maximum fluorescence change was observed
when the molar fraction of C4N4 to 3c was 0.5, implying that a
1:1 inclusion complex has been formed (Fig. S6).20 An important
Figure 2. Fluorescence spectra titration of C4N4 (1 Â 10À5 M) with various
equivalents of 3c in CH3CN (0, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45,
48, 51, 54, 57, 60 equiv, kex = 300 nm). Inset: Benesi-Hildebrand analysis of the
fluorescence changes for the complexation between C4N4 and 3c (kex = 300 nm).
With increasing concentrations of 3c, the fluorescence intensities of C4N4 gradually
decreased.
feature of C4N4 is the high binding affinity toward 3c over other
nitrobenzenes. Based on fluorescence titration experiments
between C4N4 and other nitrobenzenes derivatives, including
o-nitrophenol and m-nitrophenol, their association constants (Ka)
were determined as shown in Table 1 (Figs. S4 and S5). The Ka of
the 3c inclusion complex was far higher indicating C4N4 binds
selectively to 3c.
The 1H NMR spectra of mixtures of C4N4 and 3c were investi-
gated as depicted in Figure 3. The signals from the aromatic ring
protons of 3c slight shifted downfield (Ha, 0.013 ppm; Hb,
0.024 ppm; Scheme S2). This phenomenon may be due to
p–p
stacking interactions between 3c and C4N4.21 Because of the reci-
procity, the inclusion complex of C4N4 with 3c through the host
and guest inclusion induces a strong fluorescence quenching due
to a well-defined electron transfer. Moreover, 3c is an electron-
poor molecule, with low electron density and caused shielding to
reduce. As a result, the aromatic ring of 3c is in a relatively high
magnetic field position and caused the downfield shifting of Ha
and Hb. Characteristic changes in the infrared absorption (IR) can
also be seen (Fig. S7). The vibration localized in the benzene ring
of the calixarene cavity moves from 1530 cmÀ1 to 1550 cmÀ1
while the other peaks do not change significantly, indicating that
interaction occurs between C4N4 and 3c.
To understand the match between C4N4 and 3c, computational
,
a p–p
calculations were carried out at the B3LYP/6-31G level using
Gaussian 03.22 The results from the molecular mechanics calcula-
tion were generally consistent with the 1H NMR and fluorometric
experimental results. Figure S8 shows the optimized structure of
the host–guest complex (Tables S1 and S2). Compound 3c was par-
tially located inside the deep, electron-rich cavity of C4N4. The p–p
stacking interactions between the benzene ring of 3c and alkynyl
group of C4N4 (d1 = 4.0 Å, d2 = 4.1 Å) are also shown in Figure S8.
Meanwhile, molecular orbitals (MOs) were calculated for C4N4
and C4N4 ꢀ 3c, also using the B3LYP/6-31G level (Fig. 4). In C4N4
and C4N4 ꢀ 3c, HOMOs are both majorly localized on the
naphthalene ring and alkynyl group. The LUMOs of C4N4 are
Figure 1. (a) The structures of the guests. (b) Fluorescence intensity changes for
C4N4 (1 Â 10À5 M) in CH3CN upon addition of 3a–h (8 Â 10À5 M). (c) [((I0 À I)/I0)].
(kex = 300 nm). I0 is the fluorescent emission intensity of the host, and I is the
fluorescent intensity after adding 3a–h. The C4N4 as a fluorescence probe system
Table 1
The complex constants between C4N4 and other nitrophenol isomers
3a
3b
3c
Ka (103)
0.34
3.21
10.06
for isomeric nitrophenol, as selective binding of p-nitrophenol, results in
significant change in the fluorescence intensity.
a