Novel chiral fluorescent chemosensors for malate and acidic amino acids based on two-arm thiourea and amide

Article abstract of DOI:10.1139/V07-147

The charge neutral anthracene based chiral fluorescent receptors 4a and 4b containing thiourea and amide groups were synthesized by simple steps in good yields, and their enantioselective recognition for chiral dicarboxylic anions (L/D-malate, L/D-asparta

Full text of DOI:10.1139/V07-147

170
Novel chiral fluorescent chemosensors for malate
and acidic amino acids based on two-arm thiourea
and amide
Xiao-Huan Huang, Yong-Bing He, Zhi-Hong Chen, Chen-Guang Hu, and Guang-
Yan Qing
Abstract: The charge neutral anthracene based chiral fluorescent receptors 4a and 4b containing thiourea and amide
groups were synthesized by simple steps in good yields, and their enantioselective recognition for chiral dicarboxylic
1
anions (L/D-malate, L/D-aspartate, and L/D-glutamate) were examined by UV–vis, fluorescence, and H NMR spectros-
copy. The sensor 4a exhibited an excellent enantioselective recognition ability towards malate (Kass (L)/Kass (D) = 9.65).
Key words: enantioselective recognition, chiral chemosensor, fluorescence, malate.
Résumé : Faisant appel à une méthode n’impliquant que des étapes simples, on a effectué avec de bons rendements la
synthèse des récepteurs fluorescents chiraux liés à des anthracènes électriquement neutres, 4a et 4b, qui contiennent
des groupes amide et thiourée; faisant appel à la spectroscopie UV-visible, à la spectroscopie de fluorescence et à la
1
spectroscopie RMN du H, on a aussi évalué leur habilité à reconnaître d’une façon énantiosélective les anions dicar-
boxyliques chiraux (L/D-malate; L/D-aspartate et L/D-glutamate). Le senseur 4a possède une excellente habilité à recon-
naître d’une façon énantiosélective le malate (Kass (L)/Kass (D) = 9,65).
Mots–clés : reconnaissance énantiosélective, senseur chimique chiral, fluorescence, malate.
[Traduit par la Rédaction] Huang, et al. 176
Introduction
gen binding of these functional groups is directional in char-
acter, resulting in relatively strong complexes with various
dicarboxylate anions (5). Gunnlaugsson et al. (6) have
developed a series of anthracene based receptors for dicar-
boxylic acids and pyrophosphate, but the sensors for the
enantioselective recognition of chiral dicarboxylates are still
rare.
The development of molecule-based enantioselective fluo-
rescence receptors is receiving growing research attention
because such receptors can potentially provide a real time
technique to determine the enantiomeric composition of
chiral molecules and contribute to the understanding of bio-
chemical systems, offering new perspectives for the develop-
ment of pharmaceuticals, enantioselective sensors, and other
molecular devices (1). The molecular recognition of biologi-
cally important anions by simple synthetic receptors is a hot
topic in the field of supramolecular chemistry. Despite the
fact that several elegant examples of chiral anion receptors
have been reported over the years, these often involve the
synthesis of complex and challenging organic hosts from
scaffolds such as cholic acid (2a, 2b), calixarenes (2c), bin-
aphthyls (2d), cyclodextrins (2e), but the use of anthracene
based electroneutral chiral anion receptors has been less in-
vestigated (3).
To our best knowledge, some receptors have been reported
to bind and recognize the malate enantiomers. In our previ-
ous work, two sensors based on calix[4]arenes have been re-
ported (7a), which showed good enantioselectivity for
malate, but the structure is complex. Gonzalez-Alvarez et al.
(7b) synthesized a water-soluble receptor for malate, but it
does not exhibit a fluorescence response. Herein, we report
two chiral fluorescent receptors 4a and 4b bearing anthra-
cene, amino acid, and thiourea units, which were synthesized
by simple steps and in good yields. Their enantioselective
recognition of malate and acidic amino acids were studied
1
by fluorescence emission, UV–vis, and H NMR spectra.
The sensing and monitoring of dicarboxylates is of great
interest in areas of bioanalytical and biomedical research (4).
Thiourea and amide moieties have become the focus of the
development of neutral anion receptors, because the hydro-
Results and discussion
The synthesis of chiral fluorescent receptors 4a and 4b is
outlined in Scheme 1. 9,10-Bis (aminomethyl)anthracene
was prepared following the published procedure in ref. 6a.
The intermediate 2 was obtained by the reaction of 1 and
N-Boc-L-alanine in the presence of CDI, which was treated
with trifluoroacetic acid to obtain compound 3. Receptors
4a and 4b were synthesized by the reaction of p-
nitrophenylisothiocyanate or p-tolylisothiocyanate and 3 in
Received 13 August 2007. Accepted 4 December 2007.
Published on the NRC Research Press Web site at
canjchem.nrc.ca on 18 January 2008.
X.-H. Huang, Y.-B. He,1 Z.-H. Chen, C.-G. Hu, and
G.-Y. Qing. Department of Chemistry, Wuhan University,
Wuhan, Hubei 430072, P.R. China.
1Corresponding author (e-mail: ybhe@whu.edu.cn).
Can. J. Chem. 86: 170–176 (2008)
doi:10.1139/V07-147
© 2008 NRC Canada

Huang, et al.
171
Scheme 1.
O
H
N
NHB oc
B r
B r
NH2
H
NHBo c
COOH
1) Hexa me thylene
te traam in e, CHCl3
H3
C
2 ) HCl, EtOH, H2
O
CDI
NH2
N
H
NHBoc
O
1
2
95%
S
O
O
NH2
H
N
H
N
N
H
N
H
R
R
R
NCS
CF3 COOH/ CH2Cl2
H
N
H
N
N
H
N
H
NH2
O
O
S
4a R=NO 2 87 %
4b R=CH3 8 5%
3
Fig. 1. (a) Fluorescence spectra of receptor 4a (5 × 10–5 mol/L) with L-malate anion in DMSO. Anion equiv. 0→8.7. λex = 372 nm. In-
set: changes of fluorescence intensity of 4a at 429 nm upon addition of L-malate anion. The line is a fitted curve. The correlation coef-
ficient (R) of nonlinear curve fitting is 0.9986. (b) UV–vis absorption spectra of 4a (5 × 10–5 mol/L) upon the addition of various
amounts of L-malate in DMSO. Anion equiv. 0→9.2.
200
200
1.8
180
180
160
140
120
100
80
(a)
(b)
160
140
120
100
80
1.5
1.2
0.9
0.6
0.3
0.0
60
0
2
4
6
8
10
[G]/[H]
60
40
20
0
400
450
500
550
600
300
350
400
450
500
550
600
Wavelength (nm)
Wavelength (nm)
high yields. All of these compounds were characterized by
Scheme 2. Structures of the chiral dicarboxylates.
1
IR, H NMR, 13C NMR, MS, and elemental analysis.
NHBoc
*
NHBoc
COOH
OH
*
*
COOH
HOOC
COOH
HOOC
HOOC
Fluorescence and UV–vis spectra study
The chiral recognition properties of receptors 4a and 4b
were investigated for the enantiomers of malate, aspartate,
and glutamate (Scheme 2). The fluorescence and UV–vis
spectra were recorded from a solution of receptors 4a and 4b
(5.0 × 10–5 mol/L) in DMSO in the absence or presence of
various anions, and in each case the counter cations were
tetrabutylammonium.
Figures 1a and 1b show the fluorescence emission and
UV–vis spectra of 4a with different concentrations of
L-malate in DMSO. When gradually increasing the concen-
tration of the anions, the fluorescence emission intensities of
4a (5.0 × 10–5 mol/L) at 429 nm (λex = 372 nm) decreased,
while it gradually enhanced at 538 nm. A discernible
isoemissive point was observed at 510 nm (8). It was partic-
aspartate
glutamate
malate
ularly noteworthy that adding a small amount of L-malate
(0.5 equiv.) made the color of solution of receptor 4a change
from light yellow to orange-red, which could be easily ob-
served by the naked eye. When the receptor bound anions,
hydrogen bonds were constructed to form stable complexes,
and the electron density in the supramolecular system was
increased to enhance the charge-transfer interactions be-
tween the electron-rich donor nitrogen of the thiourea units
and electron-deficient p-nitrophenyl moieties, which resulted
in a visible color change (9). As shown in Fig. 1a, the intro-
duction of L-malate to the solution of receptor 4a resulted in
© 2008 NRC Canada

172
Can. J. Chem. Vol. 86, 2008
Fig. 2. (a) Fluorescence spectra of receptor 4a (5 × 10–5 mol/L) with D-malate anion in DMSO. Anion equiv. 0→8.3. λex = 372 nm.
Inset: changes of fluorescence intensity of 4a at 429 nm upon addition of L-malate anion. The line is a fitted curve. The correlation
coefficient (R) of nonlinear curve fitting is 0.9941. (b) UV–vis absorption spectra of 4a (5 × 10–5 mol/L) upon the addition of various
amounts of D-malate in DMSO. Anion equiv. 0→9.5.
200
180
160
140
120
100
80
200
180
160
140
120
100
80
1.8
1.5
1.2
0.9
0.6
0.3
0.0
(a)
(b)
60
0
2
4
6
8
60
[G]/[H]
40
20
0
400
450
500
550
600
300
350
400
450
500
550
600
Wavelength (nm)
Wavelength (nm)
quenching of the locally excited emission at 429 nm, while
enhancing the emission at 538 nm; the dual fluorescence
peaks at 429 and 538 nm may be due to the locally excited
(LE) state and charge transfer (CT) state in equilibrium, re-
spectively (10). As shown in the inset of Fig. 1a, the satis-
factory nonlinear fitting curve verified the formation of a 1:1
complex between 4a and L-malate.
Figure 1b shows the UV–vis spectra of 4a with different
concentrations of L-malate in DMSO. On gradual increase of
the concentration of L-malate, the intensity of the absorption
band at 375 nm decreased gradually, and a new absorption
band appeared with a maximum absorption at 470 nm. The
obvious color change can be observed from light yellow to
orange-red. The color change can be attributed to the ap-
pearance of a new long wavelength peak (9). When a protic
solvent such as methanol was added to the orange-red solu-
tion of 4a and L-malate in DMSO, the color of the solution
returned to colorless, which illustrates that the interaction
between 4a and the anions was in essence a hydrogen-
binding interaction.
Figures 2a and 2b show the fluorescence emission and
UV–vis spectra of 4a with different concentrations of
D-malate in DMSO. When gradually increasing the concen-
tration of the D-malate, the changes in fluorescence emission
and UV–vis spectra were similar but smaller than when add-
ing the equivalent L-malate into the solution of 4a. The color
change from light yellow to orange-red can also be ob-
served. The quenching efficiency was about 50% with the
addition of 2.0 equiv. of L-malate (Fig. 1a), while it was
30% with 2.0 equiv. of D-malate (Fig. 2a). The different
quenching efficiencies (∆IL/∆ID = 1.67) indicated that recep-
tor 4a has a good enantioselective recognition ability for L-
and D-malate. In addition, the association constants (Kass) are
different; the association constant of 4a with L-malate is
(3.62 0.25) × 104 (mol/L)–1, while that of 4a with D-malate
is (3.75 0.33) × 103 (mol/L)–1, and the enantioselectivity
(Kass(L)/Kass(D)) is 9.65 for malate. These obvious changes in
fluorescence and UV–vis spectra show that 4a has an excel-
lent chiral recognition ability towards the enantiomers of
malate. Similar but smaller variations in the fluorescence
and absorption spectra were obtained when adding L- or D-
aspartate and L- or D-glutamate into the solution of 4a in
DMSO, respectively (see Supplementary Data, parts 1 and
3).2 The corresponding association constants (Kass) and cor-
relation coefficients (R) of interaction between host and
guest are listed in Table 1.
Figure 3 exhibits the fluorescence change of receptor 4a
with L- or D-malate. Different fluorescent responses indicate
that 4a has good enantioselective recognition ability for
malate.
Figures 4a and 4b show the fluorescence emission spectra
of 4b with different concentrations of L- or D-malate in
DMSO. When gradually increasing the concentration of the
anions, the fluorescence emission intensities of 4b (5.0 ×
10–5 mol/L–1) at 429 nm (λex = 372 nm) decreased. The fluo-
rescence quenching of receptor 4b most likely arose from
the change in free energy (∆GPET) of electron transfer be-
tween the excited fluorophore and the receptor (11a). When
L- or D-malate interacted with receptor 4b, the reductive po-
tential of the amide group increased along with the ratio of
the electron transfer from the HOMO orbit of the receptors
to the excited anthracene group, which in turn leads to the
intramolecular PET (photo-induced electron transfer) pro-
cess being facilitated (11b), and therefore fluorescence
quenching was observed. The changes in the absorption
spectra of the anthracene moiety were only minor for 4b in
the presence of L- or D-malate (see Supplementary Data, part
4), which implies that a PET process occurred with anion
binding.2 Similar variations in the fluorescence and absorp-
tion spectra were observed when 4b interacted with L- or
D-aspartate and L- or D-glutamate (see Supplementary Data,
part 2), respectively.2 It was proposed that upon anion recog-
2 Supplementary data for this article are available on the journal Web site (canjchem.nrc.ca) or may be purchased from the Depository of Un-
published Data, Document Delivery, CISTI, National Research Council Canada, Ottawa, ON K1A 0R6, Canada. DUD 3704.
© 2008 NRC Canada

Huang, et al.
173
Table 1. Association constants (Kass) and correlation coefficients (R) of 4a and 4b with the chiral dicarboxylate anions in DMSO.
Receptor 4a
Receptor 4b
Aniona
Kass ((mol/L)–1)b
R
KL/KD
Kass ((mol/L)–1)b
R
KL/KD
L-malate
D-malate
L-aspartate
D-aspartate
L-glutamate
D-glutamate
(3.62 0.25c) × 104
(3.75 0.33c) × 103
(2.90 0.17c) × 104
(5.11 0.24c) × 103
(1.78 0.48c) × 104
(8.24 0.37c) × 103
0.9986
0.9941
0.9985
0.9970
0.9907
0.9949
9.65
(5.18 0.26c) × 103
(2.38 0.32c) × 103
(9.91 0.17c) × 103
(2.45 0.23c) × 103
(6.13 0.15c) × 103
(2.50 0.34c) × 103
0.9927
0.9945
0.9939
0.9975
0.9901
0.9911
2.18
5.68
2.16
4.04
2.45
aThe anions were used as their tetrabutylammonium salts.
bThe data were calculated from results of fluorescence titrations in DMSO.
cAll error values were obtained by the results of nonlinear curve fitting.
Fig. 3. Fluorescence intensity change of receptor 4a (5 × 10–5 mol/L)
with L- or D- malate in DMSO; the line is a fitted curve
X = X0+ (Xlim – X0)/2c0 {cH+cG+1/Kass
– [(cH+cG+1/Kass)2 –4cHcG]1/2
}
1.1
L
-malate
-malate
where X represents the fluorescence intensity, cH and cG rep-
resent the corresponding concentrations of host and guest.
The nonlinear curve fitting results of the fluorescence inten-
sity (at 429 nm) of the interaction between 4a or 4b with
L/D-malate, L/D-aspartate, and L/D-glutamate are shown in Ta-
ble 1. The satisfactory result (the correlation coefficient is
over 0.99) of the nonlinear curve fitting confirmed that the
1:1 complex between 4a or 4b and the chiral dicarboxylate
anions has been formed.
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
D
0
I
The data in Table 1 illustrates that the association con-
stants of 4a with the anions are much higher than for 4b.
The results demonstrated that the introduction of a p-
nitrophenyl group into the thiourea moiety provided an ef-
fective intromolecular charge transfer, conjugated with anion
binding and enhanced the hydrogen bond ability, resulting in
a strong anion binding. Receptor 4a revealed an excellent
enantioselective recognition to the enantiomers of the malate
anion (Kass (L)/Kass (d) = 9.65). Receptors 4a and 4b exhib-
ited good enantioselective recognition towards the L-enantiomer
of the chiral guests, which is probably due to the L-enantiomer
having a more complementary structure with receptors 4a
and 4b.
0
2
4
6
8
10
[G]/[H]
nition, the rate of the electron transfer from the HOMO orbit
of the anion-receptor complex to the anthracene excited state
enhanced, which caused the fluorescence emission to be
quenched, with a little change of UV–vis spectra in the
complexation.
The association constant of 4b with L-malate is (5.18
0.26) × 103 (mol/L)–1, while that of 4b with D-malate is
(2.38 0.32) × 103 (mol/L)–1, which corresponds to the L/D-
selectivity (Kass(L)/Kass(D)) of 2.18 for malate. Figure 5
shows the fluorescence change of receptor 4b with L- or D-
malate. Kass and R of interaction between 4b and aspartate
and glutamate are listed in Table 1.
1H NMR study
1H NMR experiments were undertaken to assess the
enantioselective recognition properties between host and
guest, because they can provide direct structural and dy-
namic information (14). Studies on the enantioselective rec-
ognition were carried out on a 300 MHz NMR spectrometer,
using the receptor 4a as a chiral solvating agent in DMSO at
room temperature (RT).
Continuous variation methods were employed to deter-
mine the stoichiometric ratio of the receptor 4a with
L/D-malate and 4b with L/D-aspartate. The total concentration
of host and guest was constant (1.0 × 10–4 mol/L–1) in DMSO,
Figure 7 shows the spectra of receptor 4a and its complex
with equimolar amounts of L-, D-, or racemic malate in
DMSO-d6. When treated with L-malate, the characteristic
peaks of thiourea (NH b and NH c) of 4a disappeared, while
the amide (NH a) had a downfield shift from 8.36 to
8.52 ppm; the singlet peak of the CH2 protons at 5.35 ppm
linking with anthracene cleaved into multiple peaks when
L-malate was added to the solution; when treated with
D-malate, the peak of the amide (NH a) shifted from 8.36 to
8.68 ppm, while thiourea (NH c) became broadened and
shifted from 10.41 to 10.65. When adding equimolar
amounts of the racemic malate, thiourea (NH b and NH c)
also disappeared, and the peak of the amide (NH a) shifted
with
a continuously variable molar fraction of host
([H] / ([H] + [G])). Figure 6 shows the Job plots of receptors
4a and 4b with chiral anions (at 429 nm). When the molar
fraction of the host was 0.50 the fluorescence intensity
reached a maximum, which demonstrated that receptors 4a
and 4b formed a 1:1 complex with L/D-malate and L/D-
aspartate, respectively (12).
Assuming that the complex stoichiometry was 1:1, the as-
sociation constant (Kass) can be calculated by the following
equation in Origin 7.0 (13),
© 2008 NRC Canada

174
Can. J. Chem. Vol. 86, 2008
Fig. 4. (a) Fluorescence spectra of receptor 4b (5 × 10–5 mol/L)
Fig. 5. Fluorescence intensity change of receptor 4b (5 × 10–5 mol/L)
with L-malate anion in DMSO. Anion equiv. 0→82.0. λex
372 nm. Inset: changes of fluorescence intensity of 4b at
=
with L- or D-malate in DMSO; the line is a fitted curve.
1.1
429 nm upon addition of L-malate anion. The line is a fitted
curve. The correlation coefficient (R) of nonlinear curve fitting is
0.9927. (b) Fluorescence spectra of receptor 4b (5 × 10–5 mol/L)
with D-malate anion in DMSO. Anion equiv. 0→90.2. λex = 372 nm.
Inset: changes of fluorescence intensity of 4b at 429 nm upon
addition of D-malate anion. The line is a fitted curve. The corre-
lation coefficient (R) of nonlinear curve fitting is 0.9945.
L
-malate
-malate
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
D
0
I
200
200
(a)
180
180
160
160
140
140
120
120
100
80
100
0
20
40
60
80
100
60
[G]/[H]
80
40
0
20
40
60
80
60
40
20
0
[G]/[H]
Fig. 6. Job plots of 4a with L- or D-malate and 4b with L- or D-
aspartate (at 429 nm). The total concentration of the host and
guest is 1.0 × 10–4 mol/L in DMSO. I0 is the fluorescence inten-
sity of 4a or 4b; I is the fluorescence intensity of 4a or 4b in
the presence of the guest.
-20
400
450
500
550
4a+
4a+
4b+
4b+
L
-Malate
-Malate
-Aspartate
-Aspartate
D
Wavelength (nm)
40
30
20
10
0
L
D
200
150
100
50
200
180
160
140
120
100
80
(b)
I
I
60
0
20
40
[G]/[H]
60
80
100
0.0
0.2
0.4
0.6
0.8
1.0
[H]/[H]+[G]
malate, while both 4a and 4b also shown good chiral recog-
nition abilities towards L/D-aspartate. The steric effect of the
receptors, structure-complementary with guest, and multiple
hydrogen binding may be responsible for the enantio-
selective recognition. Sensitive fluorescent response and
good enantioselective recognition ability reveal that 4a can
be used as fluorescent chemosensor for malate.
0
400
450
500
550
Wavelength (nm)
to 8.62 ppm. These results indicate that 4a has a stronger in-
teraction with L-malate than with D-malate. Notably, the sig-
nal change of the CH2 protons of 4a from singlet to multiple
peaks when adding L-malate, means that there was strong in-
teraction between 4a and L-malate.
Experimental section
General methods
CH2Cl2 and Et3N were dried and distilled from CaH2. All
other commercially available reagents were used without
further purification. Melting points were determined with a
Reichert 7905 melting-point apparatus and are uncorrected.
Optical rotations were taken on a PerkinElmer Model 341
polarimeter. IR spectra were obtained on a Nicolet 670 FT-
IR spectrophotometer. 1H NMR spectra were performed on a
Varian Mercury VX 300 MHz spectrometer in DMSO-d6.
13C NMR spectra were recorded on a Varian Inova Unity
Conclusion
The anthracene based chiral fluorescent receptors 4a and
4b containing thiourea and amide groups were synthesized.
The enantioselective recognition ability of 4a and 4b to-
wards a series of chiral dicarboxylates were evaluated by
1
fluorescence and H NMR spectra. Receptor 4a exhibits ex-
cellent chiral recognition ability towards the enantiomers of
© 2008 NRC Canada

Huang, et al.
175
1
Fig. 7. The H NMR spectra of 4a and its guest complex at 25 °C ([4a] = [guest] = 2.0 × 10–3 mol/L) in DMSO-d6 at 300 MHz.
(A) racemic malate, (B) receptor 4a, (C) receptor 4a + L-malate, (D) receptor 4a + D-malate, (E) receptor 4a + racemic malate.
600 MHz spectrometer. Mass spectra were recorded on a
Finnigan LCQ advantage mass spectrometer. Elemental
analysis was determined with a Carlo-Erba 1106 instrument.
Fluorescence spectra were obtained on a Shimadzu RF-5301
spectrometer. The UV–vis spectra were performed with a
TU-1901 spectrophotomer.
vacuo, giving the TFA salt of 3 as a green solid, which was
used directly without further purification. The green solid
and triethylamine (0.5 mL) were dissolved in dry CH2Cl2
(10 mL), and a solution of p-nitrophenylisothiocyanate
(0.18 g, 1.0 mmol) or p-tolylisothiocyanate (0.15 g,
1.0 mmol) was added slowly. The mixture was stirred vigor-
ously overnight under N2 protection at RT. The resulting
precipitate was filtrated off and purified by crystallization
from CHCl3, obtaining pure products 4a and 4b, respec-
tively.
Synthesis
Compounds 2
To a stirred and ice-cooled solution of N-Boc-L-alanine
(0.38 g, 2.0 mmol) in dry CH2Cl2 (10 mL) was added 1,1′-
carbonyldiimidazole (CDI) (0.39 g, 2.4 mmol), and the mix-
ture was stirred for 2 h. Then a solution of 9,10-biamino-
methylanthracene (0.24 g, 1.0 mmol) was added dropwise to
the stirred mixture. The mixture was stirred under N2 protec-
tion at RT for 18 h, and the yellow solid produced was fil-
tered off, washed with CHCl3 three times, and dried under
vacuum. Pure compound 2 (0.55g) was obtained as a yellow
solid in 95% yield, mp 175 to 177 °C. [α] = –7.5° (c 0.02,
DMSO). IR (KBr, cm–1) 3320, 2978, 2931, 1693, 1644,
Compound 4a
Yield 87%, mp 198 to 201 °C. [α] = +37.3° (c 0.02,
DMSO). IR (KBr, cm–1) 3323, 3056, 1655, 1597, 1509,
1
1329, 1302, 1253, 1180, 1112, 849, 732, 602, 567. H NMR
(DMSO-d6, ppm) δ: 10.42 (s, 2H, NHAr), 8.78 (br, 2H,
NHCS), 8.39–8.47 (m, 4H, AnH), 8.38 (d, J = 8.6Hz, 2H,
NHCO), 8.16 (d, J = 8.7Hz, 4H, ArH), 7.92 (d, J = 8.7Hz,
4H, ArH), 7.59–7.62 (m, 4H, AnH), 5.35 (s, 4H, AnCH2),
4.81–4.85 (m, 2H, CH), 1.26 (d, J = 6.6Hz, 6H, CH3). 13C
*
NMR (DMSO-d6, ppm) δ: 179.5, 172.1, 147.0, 142.6, 131.2,
130.6, 126.6, 125.8, 125.1, 121.0, 79.9, 53.1, 36.1, 19.7.
ESI-MS m/z (%): 739 (M+ + 1,100). Anal. calcd. for
C36H34N8O6S2: C 58.52, H 4.64, N 15.17; found: C 58.45, H
4.71, N 15.13.
1
1525, 1448, 1367, 1250, 1166, 1051, 754, 654. H NMR
(DMSO-d6, ppm) δ: 8.38–8.41 (m, 4H, AnH), 8.21 (bs, 2H,
CH2NH), 7.56–7.59 (m, 4H, AnH), 6.84 (bs, 2H, NHBoc),
*
5.28 (bs, 4H, AnCH2), 3.94–3.95 (m, 2H, CH), 1.30 (s,
*
18H, CH3), 1.08 (d, J = 7.5Hz, 6H, CHCH3). 13C NMR
(DMSO-d6, ppm) δ: 173.2, 155.6, 131.3, 130.4, 126.5,
125.8, 78.6, 50.3, 35.9, 19.1. ESI-MS m/z (%): 578 (M+,
100). Anal. calcd. for C32H42N4O6: C 66.40, H 7.33, N 9.68;
found: C 66.35, H 7.38, N 9.65.
Compound 4b
Yield 85%, mp 189 to 191 °C. [α] = +96.5° (c 0.02,
DMSO). IR (KBr, cm–1) 3284, 2924, 1645, 1514, 1448,
1
1338, 1242, 1206, 818, 756, 721, 657, 600, 505. H NMR
(DMSO-d6, ppm) δ: 9.68 (s, 2H, NHAr), 8.70 (br, 2H,
NHCS), 8.41–8.44 (m, 4H, AnH), 7.70 (d, J = 8.1Hz, 2H,
NHCO), 7.58–7.61(m, 4H, AnH), 7.29 (d, J = 8.1Hz, 4H,
ArH), 7.10 (d, J = 8.1Hz, 4H, ArH), 5.31 (br, 4H, AnCH2),
Compounds 4a and 4b
TFA (0.5 mL) was added to the solution of compound 2
(0.29 g, 0.5 mmol) in dry CH2Cl2 (10 mL). The mixture was
stirred at RT for 30 min to remove the Boc protecting
groups. Then the solvent and excess acid was removed in
*
4.82–4.85 (m, 2H, CH), 2.24 (s, 6H, ArCH3), 1.21 (d, J =
*
6.6Hz, 6H, CHCH3). 13C NMR (DMSO-d6, ppm) δ: 179.9,
© 2008 NRC Canada

176
Can. J. Chem. Vol. 86, 2008
X.Z. Yang. Chirality, 13, 595 (2001); (e) R. Corradini, A.
Dossena, R. Marchelli, A. Panagia, G. Sartor, M. Saviano, A.
Lombardi, and V. Pavone. Chem. Eur. J. 2, 373 (1996).
3. (a) A. Ojida, Y. Mito-oka, M. Inoue, and I. Hamachi. J. Am.
Chem. Soc. 124, 6256 (2002); (b) J.Y. Kwon, Y.J. Jang, S.K.
Kim, K.H. Lee, J.S. Kim, and J. Yoon. J. Org. Chem. 69, 5155
(2004).
4. (a) M.S. Goodman, A.D. Hamilton, and J. Weiss. J. Am.
Chem. Soc. 117, 8447 (1995); (b) B.R. Linton, M.S. Good-
man, E. Fan, S.A. van Arman, and A.D. Hamilton. J. Org.
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172.5, 137.2, 134.1, 131.2, 130.5, 129.7, 126.5, 125.8,
123.8, 53.1, 46.4, 36.0, 21.1, 20.1. ESI-MS m/z (%): 676.5
(M+, 100). Anal. calcd. for C38H40N6O2S2: C 67.43, H 5.96,
N 12.42; found: C 67.42, H 6.03, N 12.38.
Tetrabutylammonium salts
All tetrabutylammonium salts were prepared by adding
2 equiv. of tetrabutylammonium hydroxide in methanol to a
solution of the corresponding malic acid (1 equiv.) or N-
protected (by Boc) aspartic acid and glutamic acid (1 equiv.)
in methanol. The mixture was stirred at RT for 4 h and evap-
orated to dryness under reduced pressure. The resulting
syrup was dried at high vacuum for 24 h, checked by NMR,
and stored in a desiccator.
5. (a) D.H. Lee, K.H. Lee, and J.I. Hong. Org. Lett. 3, 5 (2001);
(b) P. Piatek and J. Jurczak. Chem. Commun. (Cambridge),
2450 (2002).
Binding studies
The studies on the binding properties of 4a and 4b were
carried out in DMSO. The fluorescence titration was per-
formed with a series of 5 × 10–5 mol/L solutions of receptors
4a and 4b containing different amounts of chiral anions. The
6. (a) T. Gunnlaugsson, A.P. Davis, E.J. O’Brient, and M. Glynn.
Org. Lett. 4, 2449 (2002); (b) T. Gunnlaugsson, A.P. Davis,
J.E. O’Brien, and M. Glynn. Org. Biomol. Chem. 3, 48 (2005).
7. (a) G.Y. Qing, Y.B. He, Z.H. Chen, X.J. Wu, and L.Z. Meng.
Tetrahedron: Asymmetry, 17, 3144 (2006); (b) A. Gonzalez-
Alvarez, I. Alfonso, P. Diaz, E. Garcia-Espana, and V. Gotor.
Chem. Commun. (Cambridge, U.K.), 1227 (2006).
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4552 (1993); (b) D.H. Lee, H.Y. Lee, K.H. Lee, and J.I. Hong.
Chem. Commum. (Cambridge), 1188 (2001).
1
excited wavelengths were both 372 nm, H NMR studies
were recorded after adding equivalent anions into receptors
(4 × 10–2 mol/L). Association constants were calculated by
means of a nonlinear least-square curve fitting method with
Origin 7.0 (Origin-Lab Corporation).
9. S. Nishizawa, R. Kato, T. Hayashita, and N. Teramae. Anal.
Acknowledgments
Sci. 14, 595 (1998).
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We thank the National Natural Science Foundation for fi-
nancial support (Grant No. 20572080).
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© 2008 NRC Canada