Fluorescent sensors for amino acid anions based on calix[4]arenes bearing two dansyl groups

Article abstract of DOI:10.1016/j.tetasy.2005.02.032

Two novel types of chiral calix[4]arenes containing hydrazide and dansyl groups were synthesized and examined for their enantioselective recognition abilities by the fluorescence and ¹H NMR spectra in CHCl₃. The results indicate that

Full text of DOI:10.1016/j.tetasy.2005.02.032

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 1527–1534
Fluorescent sensors for amino acid anions based on
calix[4]arenes bearing two dansyl groups
Shun-ying Liu, Yong-bing He,* Guang-yan Qing, Kuo-xi Xu and Hai-juan Qin
Department of Chemistry, Wuhan University, Wuhan, Hubei 470072, China
Received 21 January 2005; accepted 25 February 2005
Available online 23 March 2005
Abstract—Two novel types of chiral calix[4]arenes containing hydrazide and dansyl groups were synthesized and examined for their
enantioselective recognition abilities by the fluorescence and H NMR spectra in CHCl3. The results indicate that both 4a and 4b
1
have excellent enantioselectivities to the N-protected alanine or phenylalanine anions.
ꢀ 2005 Elsevier Ltd. All rights reserved.
1. Introduction
Molecule-based fluorescent sensors are generally com-
posed of a fluorophore and a binding site. By introduc-
ing chirality into the binding site, the resulting
fluorescent sensor can carry out the enantioselective rec-
ognition of chiral molecules. The dansyl group is an
excellent fluorophore9 and hydrazide is valuable as
binding site.10 Only a few samples containing dansyl
groups based on calix[4]arenes for cations have so far
been reported.11
Molecular recognition, and in particular chiral recogni-
tion, is one of the most fundamental and significant
processes in living systems.1 Chiral recognition can
contribute to the understanding of biochemical systems
and offer new perspectives for the development of phar-
maceuticals, enantioselective sensors, catalysts, and
other molecular devices.2
Among the several kinds of host molecule for recogni-
tion, calixarenes offer a number of advantages in terms
of selectivity and efficiency of binding.3 The introduc-
tion of an amino acid could lead to the chirality of the
artificial receptors. Due to the important role played
by amino acid units in several recognition processes of
natural and artificial systems,4 chiral discrimination,5
and stereoselective synthesis, synthetic calix[4]arenes
containing amino acid have been extensively studied.6
To the best of our knowledge, chiral calix[4]arenes act-
ing as enantioselective fluorescent sensors for amino
acid anions have hardly been reported. Herein, we re-
port the synthesis of novel chiral calix[4]arene contain-
ing hydrazide and dansyl groups, and found that these
chiral artificial receptors exhibit excellent enantioselec-
tive recognition toward amino acid anions.
2. Results and discussion
2.1. Synthesis
For the molecular designs of chemosensors, that is, how
to achieve the specific recognition of a certain molecule
and how to transduce the recognition event into a signal
are crucial points. Fluorescent molecular sensors for the
detection of ions or molecules have attracted consider-
able interest because of their high sensitivity and poten-
tial applications in analytical, biological, and clinical
biochemical environments.7 Chiral recognition in lumi-
nescence has been studied over the past two decades.8
The synthetic route of receptors 4a and 4b is shown in
Scheme 1. The intermediates 2a, 2b, 3a, and 3b were
all obtained in high yield (79–93%). Compounds 3a
and 3b were allowed to react with dansyl chloride and
give target molecules 4a and 4b. Receptors 4a and 4b
are easily soluble in common organic solvents, such as
CHCl3, CH3OH, DMSO, and DMF.
*
The stereogenic centers of receptors 4a and 4b disturb
the planar symmetry of the parent rings, which results
Corresponding author. Fax: +86 27 68754076; e-mail: ybhe@whu.
edu.cn
0957-4166/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2005.02.032

1528
S. Liu et al. / Tetrahedron: Asymmetry 16 (2005) 1527–1534
Scheme 1. Synthesis of receptors 4a and 4b.
in more aromatic carbon signals appearing in the 13C
NMR spectra of receptors 4a and 4b. This pattern is
similar to that which has been observed in other chiral
calix[4]arenes.12 The 1H NMR spectra of 4a and 4b
show two sets of AB quartets for the bridging methylene
protons and two sets of singlets for the tert-butyl group.
This indicates that the two receptors are in the cone con-
formation in CHCl3. The 1H NMR spectra of 4a and 4b
also exhibit one set of doublets for the ArOCH2 pro-
tons. This splitting pattern may relate to the introduc-
tion of the chiral moieties in the molecules, as seen in
other chiral calix[4]arenes.12
The fluorescence spectra of receptor 4a were studied
from a solution (5.0 · 10ꢀ5 mol Lꢀ1) of 4a in CHCl3 in
the absence and presence of various enantiomers, D-,
L-Ala, and Phe anions. Upon addition of D- or L-amino
acid anions, the different fluorescent quenching degree
of 4a was observed. The quenching efficiencies of L-ami-
no acid anions were much higher than the D-amino acid
anions. Figures 1 and 2 show fluorescence emission spec-
tra of 4a (at 515 nm) and its L- or D-Ala anions com-
plexes following excitation at 361 nm, respectively. The
graph in the top right corner of Figure 1 illustrates the
fluorescence intensity change of receptor 4a upon addi-
tion of L-Ala anions at 515 nm. Upon addition of L-
Ala anions, the fluorescent intensity of 4a was decreased
gradually with a slight blue shift. While adding D-Ala
anions to the solution of 4a, no blue shift was observed.
The quenching efficiency was 50% by 100 equiv of L-Ala
anions while it was 10% by 100 equiv of D-Ala anions.
The different quenching efficiencies (DIL/DID = 5.0) indi-
cate that receptor 4a has a good enantioselective recog-
nition between L- and D-Ala anions. When upon
addition of 100 equiv of L-Phe anions or D-Phe anions
2.2. Fluorescence spectra
In order to investigate the properties of the chiral recog-
nition of 4a and 4b, Boc alanine and phenylalanine tet-
rabutylammonium salts (L-Ala anions, D-Ala anions,
L-Phe anions, and D-Phe anions) were chosen as the
guests, which could increase the reaction between the
receptor and guest by hydrogen bondings. The amino
group was protected by di-tert-butyldicarbonate.

S. Liu et al. / Tetrahedron: Asymmetry 16 (2005) 1527–1534
1529
Upon the addition of 500 equiv of the N-protected Ala
or Phe derivatives (not as tetrabutylammonium salts)
into a solution of 4a or 4b in CHCl3, the fluorescence
intensity of 4a or 4b was slightly quenched (about
10%) by both L- and D-amino acid derivatives. This indi-
cates that hydrogen bonding plays an important role in
the interaction between the host and guest and leads to
the easier signal transductions of chiral recognition by
fluorescence method.
200
180
160
140
120
100
200
150
100
50
0
50
100
150 200
[L-Ala anion]/[4a]
0
In the presence of amino acid anions, the fluorescence
quenching of receptors 4a and 4b most likely arises from
the change of the free energy (DGPET) of electron trans-
fer between the excited fluorophore and the receptor.13
When the anion was introduced into a solution of either
receptor 4a or 4b, the reductive potential of the amide
group increased along with the ratio of the electron
transfer from the HOMO orbit of the receptors to the
excited naphthalene group, which in turn leads to the
intramolecular PET (photo-induced electron transfer)
process being more easy.7a,14
400
500
600
700
Wavelength (nm)
Figure 1. Fluorescence spectra of receptor 4a (CHCl3,
5.0 · 10ꢀ5 mol Lꢀ1) upon the addition of various amounts of L-Ala
anions in CHCl3. Equivalents of L-Ala anions: 0, 2, 4, 6, 8, 10, 15, 20,
30, 50, 75, 100, 150, and 200. kex = 361 nm.
200
150
100
50
Assuming the complex stoichiometry was 1:1, then the
complexation of guest N-protected amino acid anions
(G) with host calix[4]arene derivatives (H) could be ex-
pressed by Eq. 1. The association constant (Kass) of
the complex was calculated from the changes in fluores-
cence intensity (I) of host upon stepwise addition of G to
the solution of host in CHCl3, using the nonlinear least
squares method.15
0
500
600
700
400
Wavelength (nm)
ꢀ
Ilim ꢀ I0
Figure 2. Fluorescence spectra of receptor 4a (CHCl3,
5.0 · 10ꢀ5 mol Lꢀ1) upon the addition of various amounts of D-Ala
anions in CHCl3. Equivalents of D-Ala anions: 0, 2, 4, 6, 8, 10, 20, 40,
60, 100, 150, 200, 250, and 300. kex = 361 nm.
I ¼ I0 þ
cH þ cG þ 1=Kass
2c0
ꢁ
h
i
1=2
2
ꢀ ðcH þ cG þ 1=KassÞ ꢀ 4cHcG
ð1Þ
where I represents the fluorescence intensity; I0 represents
the fluorescence intensity of pure host; cH and cG are the
corresponding concentrations of host and guest and Kass
is the association constant. The nonlinear curve fitting re-
sults of the fluorescence intensity (at 515 nm for 4a and
517 nm for 4b) of the interaction between 4a or 4b and
L-, D-amino acid anions are shown in Table 1. The fitting
curves all have large correlation coefficients (R >0.99),
which indicate that the 1:1 complex between 4a or 4b
and the amino acid anion has been formed.15,16 Accord-
ing to Table 1, both 4a and 4b have good enantioselectiv-
ities to Ala and Phe anions. Compound 4a gives an
enantioselectivity Kass( -Phe)/Kass( -Phe) = 10. The associa-
to a solution (5.0 · 10ꢀ5 mol Lꢀ1) of 4a, the enantiose-
lectivity fluorescence response was 2.5 (DIL/DID).
Similar phenomena were observed when L- or D-Ala
and Phe anions were added into a solution (5.0 ·
10ꢀ5 mol Lꢀ1) of 4b. The emission spectra of 4b ap-
peared at 517 nm when it was excited at 363 nm. The
quenching efficiencies of receptor 4b were 46% and
43% by 100 equiv of L-Ala and L-Phe anions with a
slight blue shift while 8% and 17% by D-Ala and D-
Phe anions with no blue shift in CHCl3. Enantioselective
fluorescence responses were observed, which gave DIL/
DID = 5.7 for Ala anions and DIL/DID = 2.5 for Phe
anions.
L
D
tion constants of 4a or 4b with L-amino acid anions are
much higher than that of 4a or 4b with D-amino acid
Table 1. Association constants Kass (Mꢀ1) of receptors 4a and 4b with amino acid anions
N-protected amino acid anions
4a
4b
Kass (Mꢀ1
)
R
Kass (Mꢀ1
)
R
L-Alaa
D-Alaa
L-Phea
D-Phea
(2.30 0.19 b) · 104
0.9941
(1.08 0.14b) · 103
0.9995
c
c
(1.32 0.14b) · 104
(1.01 0.13b) · 103
0.9904
0.9912
(1.94 0.15b) · 103
(0.73 0.06b) · 103
0.9938
0.9963
a The anions were used as their tetrabutylammonium salts.
b All error values were obtained by the results of nonlinear curve fitting.
c The association constants are too small to calculate.

1530
S. Liu et al. / Tetrahedron: Asymmetry 16 (2005) 1527–1534
1
2.3. H NMR study
anions, which is probably due to the L-amino acid anions
having a more complementary structure with receptors
4a and 4b. Due to the receptors having a good preorgani-
zation property and relative rigidity structure, receptors
4a and 4b showed a high enantioselective recognition
for L- and D-Ala anions.17 However because of the p–p
stack interactions of the aryl rings between the host and
the guest, 4a and 4b showed relatively lower enantioselec-
tive recognitions for L- and D-Phe anions. At the same
time, the association constants of 4a with amino acid an-
ions are higher than that of 4b. This is perhaps due to the
bigger steric hindrance of 4b over that of 4a.
Preliminary experiments were undertaken to confirm the
enantioselective recognition properties of receptors 4a
1
and 4b by H NMR in CDCl3 at room temperature.
The spectra of receptors 4a and its complex with equi-
molar amounts of racemic Ala or Phe anions are shown
in Figure 1. When treated with equimolar amounts of
receptor 4a, the CH proton of racemic Ala anion
cleaved into more complicated signals (Fig. 3C) with a
downfield shift (from d 3.91 to 4.04) while that of the
host with an upfield shift (from d 4.76 to 4.64). When
Figure 3. The 1H NMR spectra of receptor 4a and its guest complex at 25 ꢁC in CDCl3 at 300 MHz. (A) [4a] = 2.5 · 10ꢀ3 M; (B) [DL-Ala
anion] = 2.5 · 10ꢀ3 M; (C) [4a] = [DL-Ala anion] = 2.5 · 10ꢀ3 M; (D) [DL-Phe anion] = 2.5 · 10ꢀ3 M; (E) [4a] = [DL-Phe anion]=2.5 · 10ꢀ3 M. The
arrow indicates the CH proton of DL-Ala anion and DL-Phe anion.

S. Liu et al. / Tetrahedron: Asymmetry 16 (2005) 1527–1534
1531
adding equimolar amounts of the racemic Phe anion to
receptor 4a, the CH proton of the racemic Phe anion
cleaved into more complicated signals (Fig. 3E) with a
slight downfield shift (from d 4.20to 4.25) while that
of the host with an upfield shift (from d 5.04 to 4.60).
This confirmed further that the enantioselective recogni-
tion had happened between receptor 4a and the Ala or
Phe anion. Moreover, the signals of the NH proton of
with the addition of the guest. This indicated that the
interaction between the host and guest also happened
by multiple hydrogen bondings.
The similar phenomenon was observed when adding equi-
molar amounts of the racemic Ala or Phe anion to a solu-
tion of 4b (Fig. 4). The signals of the CH proton of
racemic Ala anion and Phe anion were observed with
Dd 0.12 and 0.10 downfield shift, respectively. The signal
of the CH of 4b had an upfield shift while the signals of the
hydrazide protons disappeared when the guest was added.
1
the hydrazide in the H NMR spectra of receptor 4a al-
most disappeared while the signals of other NH protons
in receptor 4a were shifted upfield (about Dd = 0.3 ppm)
Figure 4. The 1H NMR spectra of receptor 4b and its guest complex at 25 ꢁC in CDCl3 at 300 MHz. (A) [4b] = 2.5 · 10ꢀ3 M; (B) [DL-Ala
anion] = 2.5 · 10ꢀ3 M; (C) [4b] = [DL-Ala anion] = 2.5 · 10ꢀ3 M; (D) [DL-Phe anion] = 2.5 · 10ꢀ3 M; (E) [4b] = [DL-Phe anion] = 2.5 · 10ꢀ3 M. The
arrow indicates the CH proton of DL-Ala anion and DL-Phe anion.

1532
S. Liu et al. / Tetrahedron: Asymmetry 16 (2005) 1527–1534
3. Conclusion
chromatography on silica gel (eluant: CHCl3/
CH3CH2OH = 100:1 (v/v)) as a white powder (1.30 g)
in 93% yield; mp 120–122 ꢁC. IR (KBr/cmꢀ1) m: 3423,
3346, 2958, 1751, 1685, 1541, 1484, 1458, 1207, 1159,
Chiral calix[4]arenes containing hydrazide and dansyl
groups, were synthesized. The different fluorescence re-
sponses and the results of the H NMR confirm that
1
1
1125, 1039, 871; H NMR (CDCl3): dH 1.08 (s, 18H,
both 4a and 4b have a good enantiosensitive recognition
for L-Ala or Phe anions. The selectivity of 4a for amino
acid anions is better than that of 4b. It is clear that the
cooperative act of the hydrazide and amide in the bind-
ing amino acid anion by multiple hydrogen bonds in-
creases the ability of the chiral recognition of 4a and
4b. Receptors 4a and 4b are promising in their use as
fluorescence sensors for chiral anions.
But), 1.28 (s, 18H, But), 1.48 (d, J = 6.9 Hz, 6H,
CCH3), 3.43, (d, J = 13.5 Hz, 2H, ArCH2Ar), 3.47 (d,
J = 13.5 Hz, 2H, ArCH2Ar), 3.69 (s, 6H, OCH3), 4.16
(d, J = 13.5 Hz, 2H, ArCH2Ar), 4.31 (d, J = 13.5 Hz,
2H, ArCH2Ar), 4.53 (d, J = 15.3 Hz, 2H, OCH2CO),
4.67–4.75 (m, 4H, NCHCO and OCH2CO), 6.95 (d,
J = 5.1 Hz, 4H, ArH), 7.07 (d, J = 5.1 Hz, 4H, ArH),
7.97 (s, 2H, ArOH), 9.46 (d, J = 7.5 Hz, 2H, NH).
4.2.2. 5,11,17,23-Tetra-4-tert-butyl-25,27-bis(L-phenyl-
alaninemethylester-N-carbonylmethoxy)-26,28-dihydroxy-
calix[4]arene 2b. Pure product was obtained by column
chromatography on silica gel (eluant: CHCl3/
CH3CH2OH = 200:3 (v/v)) as a white powder (1.45 g)
in 89% yield; mp 100–102 ꢁC. IR (KBr/cmꢀ1) m: 3433,
3313, 3031, 2958, 1750, 1677, 1529, 1484, 1458, 1438,
1206, 1124, 1044, 871, 699; 1H NMR (CDCl3): dH
1.08 (s, 18H, But), 1.21 (s, 18H, But), 2.90–3.02 (m,
6H, ArCH2Ar and ArCH2 CH), 3.41 (d, 2H, ArCH2Ar),
3.54 (s, 6H, OCH3), 3.94–4.06 (m, 6H, OCH2CO and
ArCH2Ar), 4.92–5.02 (m, 4H, NCHCO and OCH2CO),
6.77–6.93 (m, 18H, ArH), 7.74 (s, 2H, ArOH), 9.46 (d,
J = 8.1 Hz, 2H, NH).
4. Experimental
4.1. General
Melting points were determined with a Reichert 7905
melting-point apparatus and are uncorrected. Optical
rotations were taken on a Perkin–Elmer Model 341
polarimeter. IR spectra were obtained on a Nicolet
670FT-IR spectrophotometer. 1H NMR spectra were
recorded in CDCl3, with Me4Si as the internal standard,
on a Varian Mercury VX-300 MHz spectrometer and
13C NMR spectra on a Varian Inova-600 MHz. Mass
spectra were recorded on a Finnigan LCQ advantage
mass spectrometer. Elemental analysis was determined
with a Carlo-Erba 1106 instrument. Fluorescence spec-
tra were obtained on a Shimadzu RF-5301 spectro-
meter. CHCl3 and Et3N were dried and distilled from
CaH2. All other commercially available reagents were
used without further purification. Compounds 1, amino
acid methyl ether hydrochloride and the N-protected
amino acid derivatives (by di-tert-butyldicarbonate)
were synthesized according to the methods reported in
the literature,18–20 respectively.
General procedure for preparing the hydrazide derivatives
3: To a solution (30mL) of 2a or 2b (1.5 mmol) in
CHCl3/CH3OH [1:2 (v/v)], hydrazine hydrate (4 equiv
for 2a or 2b) was added. The reaction was stirred for
24 h at room temperature. Then the solvent was evapo-
rated under reduced pressure and water (20mL) poured
into the residue. After filtration, the solid was dried in
vacuum to obtain pure product.
4.2.3. 5,11,17,23-Tetra-4-tert-butyl-25,27-bis(hydrazide-
L-alanine-N-carbonylmethoxy)-26,28-dihydroxycalix[4]ar-
ene 3a. The product was obtained as a white powder
4.2. Synthesis
General procedure for the synthesis of chiral calix[4]ar-
ene derivatives 2: To a solution of L-alanine methyl ether
hydrochloride or L-phenylalanine methyl ether hydro-
chloride (3 mmol) and triethylamine (4 equiv for each
amino acid methyl ether hydrochloride) in dry CHCl3
(30mL), 1 (0.5 equiv for each amino acid methyl ether
hydrochloride) in dry CHCl3 (20mL) was dropwise
added in ice brine bath under nitrogen atmosphere.
After addition, the reaction mixture was stirred at 0 ꢁC
for 1 h and then the ice brine bath was removed and
kept stirring overnight at room temperature. Then the
reaction solution was washed with a dilute aqueous
solution of hydrogen chloride (10%), sodium hydrogen
carbonate (10%), and brine, respectively. The organic
layer was collected and dried over anhydrous Na2SO4.
After filtration, the solvent was removed under reduced
pressure, and the residue purified by column chromato-
graphy on silica gel.
(1.22 g) in 87% yield; mp 144–146 ꢁC. IR (KBr/cmꢀ1
)
m: 3432, 3316, 2960, 1750, 1676, 1536, 1484, 1458,
1
1207, 871; H NMR (CDCl3): dH 1.04 (s, 18H, But),
1.18 (s, 18H, But), 1.28 (d, J = 6.3 Hz, 6H, CCH3),
3.23, (d, J = 13.8 Hz, 2H, ArCH2Ar), 3.42 (d,
J = 13.8 Hz, 2H, ArCH2Ar), 4.09 (d, J = 15.0Hz, 2H,
OCH2CO), 4.15–4.23 (m, 4H, ArCH2Ar), 4.64–4.69
(m, 2H, NCHCO), 5.16 (d, J = 15.0Hz, 2H, OCH 2CO),
6.87 (s, 4H, ArH), 6.96 (s, 4H, ArH), 8.24 (s, 2H,
ArOH), 8.67 (s, 2H, CONHN), 9.85 (d, J = 8.4 Hz,2H,
CONHC).
4.2.4. 5,11,17,23-Tetra-4-tert-butyl-25,27-bis(hydrazide-
L-phenylalanine-N-carbonylmethoxy)-26,28-dihydroxyca-
lix[4]arene 3b. The product was obtained as a white
powder (1.28 g) in 79% yield; mp 128–130 ꢁC. IR
(KBr/cmꢀ1) m: 3432, 3316, 2958, 1750, 1677, 1529,
1
1484, 1458, 1439, 1363, 1207, 1124, 871, 699; H NMR
(CDCl3): dH 1.13 (s, 18H, But), 1.21 (s, 18H, But),
2.80–3.02 (m, 4H, ArCH2 CH), 3.16 (d, J = 12.9 Hz,
2H, ArCH2Ar), 3.57, (d, J = 13.5 Hz, 2H, ArCH2Ar),
4.01 (d, J = 15.0Hz, 2H, OCH 2CO), 4.12 (d,
4.2.1.
5,11,17,23-Tetra-4-tert-butyl-25,27-bis(L-alani-
nemethylester-N-carbonylmethoxy)-26,28-dihydroxycalix-
[4]arene 2a. Pure product was obtained by column

S. Liu et al. / Tetrahedron: Asymmetry 16 (2005) 1527–1534
1533
J = 12.9 Hz, 2H, ArCH2Ar), 4.34, (d, J = 13.5 Hz, 2H,
ArCH2Ar), 4.80–4.84 (m, 2H, NCHCO), 5.23 (d,
J = 15.0Hz, 2H, OCH 2CO), 6.99–7.11 (m, 18H, ArH),
8.24 (br, 2H, CONHN), 8.45 (s, 2H, ArOH), 10.12 (d,
J = 9.0Hz, 2H, CONHC).
J = 14.7 Hz, 2H, OCH2CO), 5.03–5.05 (m, 2H,
NCHCO), 6.73–7.02 (m, 18H, ArH), 7.07 (d,
J = 7.8 Hz, 2H, H6-naph), 7.37 (t, 2H, H7-naph), 7.53
(t, 2H, H3-naph), 7.66 (s, 2H, ArOH), 8.28 (d,
J = 7.5 Hz, 2H, H2-naph), 8.43 (d, J = 7.8 Hz, 2H, H8-
naph), 8.63 (d, J = 7.5 Hz, 2H, H4-naph), 9.06 (s, 2H,
NNHS), 9.20(br, 2H, CONHN), 9.57 (d, J = 9.0Hz,
2H, CNHCO); 13C NMR (CDCl3): 171.7, 169.2, 149.9,
149.5, 147.8, 142.2, 135.9, 132.8, 132.7, 132.2, 131.5,
130.9, 129.7, 129.3, 128.6, 128.3, 126.9, 126.7, 126.1,
125.7, 124.9, 123.3, 115.2, 74.9, 50.0, 45.6, 38.9, 34.3,
34.0, 33.0, 32.5, 31.9, 31.3; ESI-MS m/z (%): 1551
(Mꢀ1, 100); Elemental analysis calcd. (%) for
C90H104N8O12S2: C, 69.55; H, 6.76; N, 7.21; S, 4.13.
Found: C, 69.48; H, 6.81; N, 7.18; S, 4.08.
General procedure for preparing 4: To a solution of 3a or
3b (1.5 mmol) and triethylamine (4 equiv) in dry CHCl3
(15 mL), dansyl chloride (2 equiv for 3a or 3b) in dry
CHCl3 (15 mL) was dropwise added. After addition,
the reaction mixture was stirred at room temperature
overnight and then washed with the aqueous solution
of citric acid (10%), sodium hydrogen carbonate
(10%), and brine, respectively. The organic layer was
collected and dried over anhydrous Na2SO4. After filtra-
tion, the solvent was removed under reduced pressure,
and the residue was purified by column chromatography
on silica gel.
4.3. Tetrabutylammonium salts
All tetrabutylammonium salts were prepared by adding
1 equiv of tetrabutylammonium hydroxide in methanol
to a solution of the corresponding N-protected (by
Boc) amino acid derivatives (1 equiv) in methanol. The
mixture was stirred at room temperature for 2 h and
evaporated to dryness under reduced pressure. The
resulting syrup was dried at high vacuum and 50 ꢁC
for 24 h, checked by NMR and stored in a desiccator.
4.2.5.
5,11,17,23-Tetra-4-tert-butyl-25,27-bis(N-(5-di-
methylaminonaphthalene-1-sulfonyl)hydrazide-N0-L-alan-
ine-N00-carbonylmethoxy)-26,28-dihydroxycalix[4]arene 4a.
Pure product (0.73 g) was obtained by column chroma-
tography
on
silica
gel
(eluant:
CHCl3/
CH3CH2OH = 100:3 (v/v)) as a yellow powder in 35%
20
D
yield; mp 200–202 ꢁC; ½aꢁ ¼ þ8:7 (c 0.5, CHCl3); IR
(KBr/cmꢀ1)m : 3428, 3290, 2958, 1655, 1484, 1458,
1
4.4. Binding studies
1341, 1203, 1166, 1148, 1047, 791; H NMR (CDCl3):
dH 0.80 (d, J = 6.3 Hz, 6H, CCH3), 1.08 (s, 18H, But),
1.20(s, 18H, Bu t), 2.69 (s, 12H, NCH3), 3.13, (d,
J = 15.3 Hz, 2H, OCH2CO), 3.22 (d, J = 14.1 Hz, 2H,
ArCH2Ar), 3.35 (d, J = 14.1 Hz, 2H, ArCH2Ar), 3.82–
3.93 (m, 4H, ArCH2Ar), 4.59 (d, J = 15.3 Hz, 2H,
OCH2CO), 4.74–4.79 (m, 2H, NCHCO), 6.86 (s, 2H,
ArH), 6.93 (s, 6H, ArH), 7.10(d, J = 7.5 Hz, 2H, H6-
naph), 7.41 (t, 2H, H7-naph), 7.60(t, 2H, H 3-naph),
7.70(s, 2H, ArOH), 8.31 (d, J = 7.2 Hz, 2H, H2-naph),
8.41 (d, J = 7.5 Hz, 2H, H8-naph), 8.62 (d, J = 7.2 Hz,
2H, H4-naph), 8.88 (br, 2H, CONHN), 9.35 (s, 2H,
NNHS), 9.54 (d, J = 8.4 Hz,2H, CNHCO); 13C NMR
(CDCl3): 171.5, 169.9, 149.9, 149.7, 147.9, 142.0,
133.2, 132.9, 132.7, 131.7, 131.4, 130.8, 129.6, 128.6,
127.0, 126.7, 125.7, 125.6, 125.2, 123.3, 115.2, 75.1,
46.3, 45.5, 34.3, 34.0, 32.5, 31.9, 31.3, 20.2; ESI-MS
m/z (%): 1399 (M-1, 100); Elemental analysis calcd.
(%) for C78H96N8O12S2: C, 66.82; H, 6.92; N, 7.99; S,
4.56. Found: C, 66.75; H, 7.02; N, 7.89; S, 4.54.
The studies on the binding properties of 4a and 4b were
carried out in CHCl3 or CDCl3. The fluorescence titra-
tion was performed with a series of 5 · 10ꢀ5 M solutions
of receptor 4a or 4b containing different amounts of chi-
ral anions (the excited wavelength was 361 or 363 nm,
the excitation slit width was 1.5 nm and the emission slit
1
width was 3 nm). H NMR studies were recorded as
adding equivalent racemic Ala or Phe anions into recep-
tors (2.5 · 10ꢀ2 M).
Acknowledgements
We thank the National Natural Science Foundation for
financial support (Grant No. 20372054).
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