Enantioselective fluorescent sensors for chiral carboxylates based on calix[4]arenes bearing an L-tryptophan unit

Article abstract of DOI:10.1002/ejoc.200600917

Two-armed chiral calix[4]arenes (3a-c) functionalized at the lower ring with L-tryptophan units have been prepared and the structures of these receptors characterized by IR, MS, ¹H, and ¹³C NMR spectroscopy and elemental analysis. The enantioselective recognition of these receptors has been studied by fluorescence titration and ¹H NMR spectroscopy. The receptors exhibited different chiral recognition abilities towards some enantiomers of chiral materials and formed 1:1 complexes between host and guest. Receptor 3a exhibits excellent enantioselective fluorescent recognition ability towards the N-Boc-protected alanine anion and 3b reveals good enantioselective recognition ability towards the enantiomers of mandelate. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.

Full text of DOI:10.1002/ejoc.200600917

FULL PAPER
DOI: 10.1002/ejoc.200600917
Enantioselective Fluorescent Sensors for Chiral Carboxylates Based on
Calix[4]arenes Bearing an -Tryptophan Unit
L
Guang-yan Qing,[a] Yong-bing He,*[a] Feng Wang,[a] Hai-juan Qin,[a] Chen-guang Hu,[a] and
Xi Yang[a]
Keywords: Calixarenes / Tryptophan / Fluorescence / Enantioselective recognition / Carboxylates / NMR spectroscopy
Two-armed chiral calix[4]arenes (3a–c) functionalized at the
lower ring with -tryptophan units have been prepared and
complexes between host and guest. Receptor 3a exhibits ex-
cellent enantioselective fluorescent recognition ability
towards the N-Boc-protected alanine anion and 3b reveals
good enantioselective recognition ability towards the
enantiomers of mandelate.
L
the structures of these receptors characterized by IR, MS, 1H,
and 13C NMR spectroscopy and elemental analysis. The
enantioselective recognition of these receptors has been
studied by fluorescence titration and 1H NMR spectroscopy.
The receptors exhibited different chiral recognition abilities
towards some enantiomers of chiral materials and formed 1:1
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
Introduction
used in the past few years as receptors to recognize a wide
variety of ions or inorganic and organic guest molecules,
forming host–guest or supramolecular complexes.[7] Al-
though many chiral calixarenes have been synthesized that
recognize a chiral guest,[1b,8] chiral calixarene receptors that
give a fluorescence response upon chiral recognition of a
guest are still rare.[9] In the synthesis of chiral receptors,
amino acids or peptides can be employed as chiral sources
in building the desired molecules because of their accessi-
bility and biological relevance.[10a] -Tryptophan is a natu-
ral amino acid that has both a fluorescent group and a
binding unit, it has been used in chiral recognition, and has
been shown to have a good fluorescence response.[10b]
The carboxylate group is an anionic entity of prime im-
portance in nature. Enzymes, antibodies, amino acids, and
metabolic intermediates contain a range of carboxylate
functionalities that account for their characteristic bio-
chemical behavior.[11] Enantioselective recognition of car-
boxylates is important in asymmetric synthesis and drug
discovery.[12] Amino acid esters and salts have been widely
researched owing to their important biochemical character-
istics.[13]
Chiral recognition of asymmetric compounds is an im-
portant subject not only in the field of supramolecular
chemistry, but also in the field of medicinal and biomedical
applications. In particular, supramolecular approaches to
rapid sensing of the absolute configurations of asymmetric
compounds are receiving increasing interest.[1]
The basis of any chiral recognition event is the formation
of diastereomeric complexes composed of a chiral receptor
and a chiral substrate possessing different stabilities.[2] The
crucial points in the molecular design of chemosensors are
how to achieve the specific recognition of a certain mole-
cule and how to transduce the recognition event into a sig-
nal.[3] Many tools are available for the study of the structure
and dynamics of multimolecular complexes with NMR
spectroscopy being perhaps the most suitable method for a
detailed examination of such complexes in solution.[4] The
use of fluorescent molecular sensors for the detection of
ions or molecules have attracted considerable interest in re-
cent years because of their high sensitivity and potential
applications in analytical, biological, clinical, and biochemi-
cal environments.[5] The development of molecular-based
enantioselective fluorescence receptors has received more
attention because such receptors potentially provide a real-
time technique that can be used to determine the enantio-
meric composition of chiral molecules.[6] Because of their
unique cavity-shaped architecture and preorganized binding
sites, calixarenes and their derivatives have been extensively
Herein, we describe the development of three novel, chi-
ral calix[4]arene derivatives bearing -tryptophan residues
that have similar two-armed structures; their chiral recogni-
tion ability towards chiral carboxylates, two amino acid
anions, and two amino alcohols have been explored by fluo-
1
rimetric titration and H NMR study. Obvious changes in
fluorescence and in NMR chemical shifts highlight the fact
that compounds based on chiral -tryptophan and calix[4]-
arene units have excellent chiral recognition ability towards
the enantiomers of the N-Boc-protected alanine anion or
mandelate.
[a] Department of Chemistry, Wuhan University,
Wuhan 430072, P. R. China
Fax: +86-27-68754067
E-mail: ybhe@whu.edu.cn
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
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Enantioselective Fluorescent Sensors for Chiral Carboxylates
FULL PAPER
1
structures of 3a–c were characterized by IR, MS, H, and
Results and Discussion
13C NMR spectroscopy and by elemental analysis.
Synthesis
The stereogenic centers of receptors 3a–c disturb the
The synthesis of calix[4]arene receptors 3a–c is outlined planar symmetry of the parent rings, which results in more
in Scheme 1. They are readily soluble in common organic aromatic carbon signals appearing in the 13C NMR spectra
solvents such as CHCl3, CH3OH, DMSO, and DMF. The of the receptors. This pattern is similar to that observed for
Scheme 1. Synthesis of receptors 3–c.
Eur. J. Org. Chem. 2007, 1768–1778
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G. Qing, Y. He, F. Wang, H. Qin, C. Hu, X. Yang
FULL PAPER
1
other chiral calix[4]arenes.[14] The H NMR spectra of 3a–
c show two sets of doublets due to the bridging methylene
protons and two sets of signals due to the tert-butyl groups.
This indicates that these receptors adopt a cone conforma-
1
tion in CHCl3. The H NMR spectra of 3a–c also exhibit
one set of doublets due to the ArOCH2 protons. This split-
ting pattern may be related to the introduction of chiral
moieties into the molecules, as observed in other chiral ca-
lix[4]arenes.[14]
Fluorescence Spectra Study
Fluorescence spectra of solutions of 3a–c were recorded
in the absence and presence of various chiral carboxylates,
such as mandelate, the α-phenylglycine anion, malate, and
tartrate; N-Boc-protected alanine anions (Ala anions) and
Figure 2. Fluorescence spectra of receptor 3a (5.0ϫ10–5 molL–1)
with the -Ala anion in DMSO. The anion equivalents are: 0, 4.0,
10.0, 20.0, 30.0, 40.0, 70.0, 90.0, 130.0, 155.0, 180.0, 210.0, 240.0,
N-Boc-protected phenylalanine anions (Phe anions) were 270.0, 300.0, 340.0, 380.0, 420.0, 460.0, and 500.0. λex = 295 nm
(EX: 5; EM: 10). Inset: changes in the fluorescence intensity of 3a
also examined as the guests. The amino groups were pro-
tected by the tert-butyloxycarbonyl functionality. In each
at 346 nm upon addition of the -Ala anion. The line shown is a
line-fitted curve. The correlation coefficient (R) of the nonlinear
case tetrabutylammonium was used as the counter cation.
curve fitting is 0.9982.
We also chose two amino alcohols, namely phenylglycinol
and phenylalaninol, as guests to compare the associated
abilities of the hosts to bind with neutral molecules. Con-
tion (1) from the Origin 7.0 software package,[15,16] where I
sidering the solubility of all the guests in various solvents,
represents the fluorescence intensity, CH and CG are the
DMSO was chosen as the solvent in which receptors 3a–c
host and guest concentrations, and C0 is the initial concen-
all have good fluorescence responses (see the Supporting
tration of the host. The association constants (Kass) and
Information).
correlation coefficients (R) obtained by a nonlinear least-
Figures 1 and 2 show the fluorescence emission spectra
squares analysis of I versus CH and CG are listed in Table 1.
of a mixture of 3a and different concentrations of the -
or -Ala anion in DMSO (λex = 295 nm), respectively. The
Ilim – I
I = I0 +
0{CH + CG + 1/Kass
–
fluorescence emission of 3a (at 346 nm) was slightly
quenched by about 10% upon addition of 155 equiv. of -
Ala anions (Figure 1). Figure 2 shows the change in fluores-
cence emission of 3a upon addition of -Ala anions; the
quenching efficiency (at 346 nm) was 48% for the addition
of 155 equiv. of -Ala anions. Satisfactory nonlinear curve
fitting (the correlation coefficient is Ͼ0.99) confirmed that
3a and the -Ala anion formed a 1:1 complex (see the inset
of Figure 2). For a complex of 1:1 stoichiometry, the associ-
ation constant (Kass) can be calculated by using Equa-
2C0
[(CH + CG + 1/Kass)2 – 4CHCG]1/2
} (1)
The association constant for the interaction of 3a with
the -Ala anion is 53.56 –1, whereas that for association
of 3a with the -Ala anion could not be calculated from
this equation owing to the weak response observed in the
fluorescence spectra. The dramatically different fluorescent
responses and quenching efficiencies observed for the two
enantiomers indicate that 3a has excellent enantioselective
fluorescent recognition ability towards the Ala anion. When
3a interacted with mandelate, no clear change in the fluo-
rescence spectra was observed. Similar phenomena to that
shown in Figure 2 were observed when other anion guests
were added to the solution of 3a (see the Supporting Infor-
mation). However, the association constants for the interac-
tion of 3a with guests were rather small [ranging from
3.70 –1 for -phenylalaninol to 249.13 –1 for -malate (see
Table 1)], which may be due to the rather weak hydrogen-
bonding interaction between the host and guest.
Figures 3 and 4 show the fluorescence spectra of receptor
3b (5.0ϫ10–5 molL–1) with different concentrations of -
or -mandelate in DMSO. Upon addition of -mandelate,
the fluorescence emission of 3b decreased gradually,
whereas addition of -mandelate to the solution of 3b led to
a small change in the fluorescence emission. The quenching
efficiency (at 345 nm) was 11% with 180.0 equiv. of -man-
Figure 1. Fluorescence spectra of receptor 3a (5.0ϫ10–5 molL–1)
with the -Ala anion in DMSO. The anion equivalents are: 0, 1.5,
5.5, 11.5, 35.0, 55.0, 85.0, 115.0, and 155.0. λex = 295 nm (EX: 5;
EM: 10).
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Enantioselective Fluorescent Sensors for Chiral Carboxylates
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Table 1. Association constants (Kass), correlation coefficients (R), enantioselectivities (Kass(D)/Kass(L)), Gibbs free energy changes (–∆G0),
and ∆∆G0 calculated from ∆G0 for the complexation of receptors 3a–c with / guests in DMSO at 25 °C.
Entry Host
Guest
Kass [–1][a,b]
R
Kass(d)/Kass(l)
–∆G0 [kJmol–1]
∆∆G0 [kJmol–1]
[c]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
-mandelate
-mandelate
[c]
-α-phenylglycine
-α-phenylglycine
-N-Boc-Ala[d]
-N-Boc-Ala[d]
-N-Boc-Phe[d]
-N-Boc-Phe[d]
-malate
94.88Ϯ7.76
0.9932
0.9972
11.285
13.499
231.84Ϯ9.64
2.44
–2.214
[c]
53.56Ϯ2.91
28.79Ϯ2.97
32.24Ϯ1.70
249.13Ϯ5.85
84.37Ϯ11.93
13.59Ϯ3.14
77.05Ϯ8.69
5.19Ϯ0.66
5.87Ϯ0.70
3.70Ϯ0.68
5.03Ϯ0.92
0.9982
0.9984
0.9991
0.9902
0.9913
0.9945
0.9926
0.9987
0.9983
0.9984
0.9956
9.867
8.329
8.609
13.678
10.994
6.468
10.769
4.082
4.387
3.243
4.004
1.12
0.34
5.70
1.13
–0.280
2.684
-malate
-tartrate
-tartrate
–4.301
–0.305
–0.761
-phenylglycinol
-phenylglycinol
-phenylalaninol
-phenylalaninol
1.36
Kass(d)/Kass(l)
[c]
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
3b
3b
3b
3b
3b
3b
3b
3b
3b
3b
3b
3b
3b
3b
3b
3b
-mandelate
-mandelate
(1.04Ϯ0.07)ϫ103
(1.04Ϯ0.05)ϫ104
(8.35Ϯ0.03)ϫ103
411.37Ϯ14.34
0.9928
0.9927
0.9957
0.9983
0.9910
0.9981
0.9966
0.9909
0.9928
0.9948
0.9908
0.9929
0.9921
0.9919
0.9907
17.220
22.928
22.384
14.921
19.813
16.575
16.149
23.647
26.185
22.879
22.413
10.255
10.426
12.838
13.044
-α-phenylglycine
-α-pPhenylglycine
-N-Boc-Ala[d]
-N-Boc-Ala[d]
-N-Boc-Phe[d]
-N-Boc-Phe[d]
-malate
0.80
7.20
0.84
2.78
0.83
1.07
0.544
–4.892
0.426
(2.96Ϯ0.22)ϫ103
801.51Ϯ23.63
674.99Ϯ33.19
(1.39Ϯ0.08)ϫ104
(3.87Ϯ0.15)ϫ104
(1.02Ϯ0.05)ϫ104
(8.45Ϯ0.06)ϫ103
62.63Ϯ8.44
-malate
-tartrate
-tartrate
–2.538
0.466
-phenylglycinol
-phenylglycinol
-phenylalaninol
-phenylalaninol
67.10Ϯ9.73
177.54Ϯ11.40
192.89Ϯ15.78
–0.171
–0.206
1.09
Kass(d)/Kass(l)
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
3c
3c
3c
3c
3c
3c
3c
3c
3c
3c
3c
3c
3c
3c
3c
3c
-mandelate
-mandelate
485.72Ϯ39.70
788.67Ϯ51.79
84.06Ϯ12.87
65.36Ϯ4.76
66.56Ϯ9.85
273.76Ϯ25.31
59.35Ϯ6.01
0.9910
0.9912
0.9928
0.9947
0.9918
0.9912
0.9947
0.9917
0.9927
0.9975
0.9908
0.9914
15.333
16.535
10.985
10.298
10.406
13.912
10.122
9.885
19.904
20.750
12.244
12.637
1.62
0.78
4.11
0.91
1.41
1.17
–1.202
0.687
-α-phenylglycine
-α-phenylglycine
-N-Boc-Ala[d]
-N-Boc-Ala[d]
-N-Boc-Phe[d]
-N-Boc-Phe[d]
-malate
–3.506
0.237
53.93Ϯ7.24
(3.07Ϯ0.23)ϫ103
(4.32Ϯ0.18)ϫ103
139.67Ϯ13.56
-malate
-tartrate
-tartrate
–0.846
–0.393
163.72Ϯ22.24
[e]
-phenylglycinol
-phenylglycinol
-phenylalaninol
-phenylalaninol
[e]
24.99Ϯ4.27
123.74Ϯ11.74
0.9913
0.9903
7.978
11.943
4.95
–3.965
[a] The data were calculated from results of fluorescence titrations in DMSO. [b] All error values were obtained from nonlinear curve
fitting. [c] The association constants could not be calculated precisely because the signal change was too small to provide reliable data
with tolerable error. [d] N-Boc-alanine and -phenylalanine tetrabutylammonium salts, the amino group was protected by a tert-butyloxy-
carbonyl function. [e] The association is too small to be calculated.
delate, whereas it was 88% with 165.0 equiv. of -mandel-
Receptor 3b also exhibits a good enantioselective fluores-
ate. The different quenching efficiencies (∆ID/∆IL = 8.0) cence response to the enantiomers of the Ala anion (see
indicate that 3b has a good enantioselective fluorescent re- Figures S3.9 and S3.10 of the Supporting Information).
cognition ability towards mandelate.
The fluorescence emission of 3b was quenched by about
Eur. J. Org. Chem. 2007, 1768–1778
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G. Qing, Y. He, F. Wang, H. Qin, C. Hu, X. Yang
FULL PAPER
In the absence of anions, photoinduced electron transfer
(PET) between the indole group and the electron-with-
drawing amide substituents might result in quenched fluo-
rescence. When anions were introduced into a solution of
either 3a or 3b, an anion–receptor complex was formed
through hydrogen bonding, the reductive potential of the
amide group increased along with electron transfer from the
HOMO orbital of the receptors to the excited indole group,
which in turn led to the intramolecular PET process being
easier.[5a,5b,17] Therefore fluorescence quenching was ob-
served.
Figures 5 and 6 show the fluorescence emission of recep-
tor 3c (5.0ϫ10–5 molL–1) with different concentrations of
the - or -Ala anion in DMSO. The fluorescence emission
of 3c (λex = 375 nm) gradually increased upon addition of
the - or -Ala anion. Satisfactory nonlinear curve fitting
(the correlation coefficient is Ͼ0.99) confirmed that recep-
tor 3c and the - or -Ala anion formed a 1:1 complex[15]
(see the insets in Figures 5 and 6). The association con-
stants for the interaction of 3c with the - or -Ala anion
are 66.56 or 273.76 –1, respectively, which correspond to a
/ selectivity [Kass(d)/Kass(l)] of 4.11 for the Ala anion and
a ∆∆G0 value of –3.506 kJmol–1.
Figure 3. Fluorescence spectra of receptor 3b (5.0ϫ10–5 molL–1)
with -mandelate in DMSO. The anion equivalents are: 0, 0.2, 0.4,
3.0, 20.0, 50.0, 100.0, 130.0, 180.0, 230.0, 330.0, and 430.0. λex
=
296 nm (EX: 5; EM: 10).
Figure 4. Fluorescence spectra of receptor 3b (5.0ϫ10–5 molL–1)
with -mandelate in DMSO. The anion equivalents are: 0, 1.0, 3.0,
6.5, 10.5, 15.0, 20.0, 28.0, 35.0, 40.0, 55.0, 65.0, 75.0, 85.0, 105.0,
125.0, 145.0, and 165.0. λex = 296 nm (EX: 5; EM: 10). Inset:
Changes in fluorescence intensity of 3b at 345 nm upon addition of
-mandelate. The line shown is a line-fitted curve. The correlation
coefficient (R) for the nonlinear curve fitting is 0.9928.
Figure 5. Fluorescence spectra of receptor 3c (5.0ϫ10–5 molL–1)
with the -Ala anion in DMSO. The anion equivalents are: 0, 1.5,
5, 12.0, 20.0, 35.0, 55.0, 75.0, 115.0, 145.0, 165.0, 200.0, 230.0,
260.0, and 290.0. λex = 375 nm (EX: 5; EM: 10). Inset: Changes in
the fluorescence intensity of 3c at 445 nm upon addition of the -
Ala anion. The line shown is a line-fitted curve. The correlation
coefficient (R) for the nonlinear curve fitting is 0.9918.
80% upon addition of 310 equiv. of -Ala anions, whereas
that of 3b was quenched by about 90% with only 115 equiv.
of -Ala anions. Satisfactory nonlinear curve fitting (the
correlation coefficient is Ͼ0.99) confirmed that receptor 3b
formed a 1:1 complex with the - and -Ala anion.[15] In
addition, the association constants (Kass) were different
(Kass(l) = 411.37 –1, ∆G0 = –14.921 kJmol–1; Kass(d)
=
Intriguingly, the emission spectra of 3c in DMSO are dif-
2.96ϫ103 –1, ∆G0 = –19.813 kJmol–1), yielding a / ferent to those of 3a and 3b: The emission peak of 3c is at
selectivity [Kass(d)/Kass(l)] of 7.20 for the Ala anion and a 445 nm, whereas those of 3a and 3b are both at 345 nm.
∆∆G0 value of –4.892 kJmol–1, demonstrating that 3b also Considering the similarities and differences in their struc-
has good chiral recognition ability towards the enantiomers tures, we presume that the more flexible ethylene chains of
of Ala anions.
3c enable the intramolecular two indole moieties to ap-
Compared with 3a, 3b has a more rigid structure and proach, resulting in the formation of an excimer. In con-
more amides that are good hydrogen-bonding donors as a trast, the much more rigid amide and hydrazine chains of
result of the introduction of hydrazine units into the ca- 3a and 3b prevent the two indole groups from stacking to-
lixarene arms, which causes the association constants for gether. Hence, only monomer emission peaks at 345 nm
the interaction of 3b with guests to be much higher than were observed. The monomer emission of 3c could also be
those of 3a, ranging from 62.63 –1 for -phenylglycinol to observed when the fluorescence of 3c was excited at 291 nm,
3.87ϫ104 –1 for -malate.
but the fluorescence intensity was much weaker than those
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Enantioselective Fluorescent Sensors for Chiral Carboxylates
FULL PAPER
phenylalaninol to 4.32ϫ103 –1 for -malate (see Table 1).
In particular, 3c has good enantioselective recognition abil-
ity towards phenylalaninol, the association constants (Kass
)
of 3c with - or -phenylalaninol being 24.99 and
123.74 –1, respectively, with a corresponding / selectivity
[Kass(d)/Kass(l)] of 4.95 for phenylalaninol and a ∆∆G0 value
of –3.965 kJmol–1 (Figure 7).
From the data reported above, we find that the associa-
tion constants for the interactions of 3b with guests are
larger than those of 3a or 3c, which maybe due to the more
rigid structure and stronger hydrogen-bonding interactions
between the host and guest (Figure 8). Receptor 3a only has
two amide groups and the NH group of indole that can
participate in the association, which limits the effective hy-
drogen bonding between the host and guest; the rather
small association constants confirm our conclusion. Com-
pared with 3b, receptor 3c has the same number of amide
groups and the NH group of indole, but the rigidity of the
structure of 3c is significantly lower owing to the flexibility
of the CH2CH2 link; the acidity of the amide groups is also
weakened by the separation of the two amide groups. These
differences result in small association constants for the in-
teraction of 3c with guests, but they are larger than those
of 3a. In spite of the differences in structure, these three
receptors all exhibit good chiral recognition ability towards
the enantiomers of the Ala anion, which indicates that the
Figure 6. Fluorescence spectra of receptor 3c (5.0ϫ10–5 molL–1)
with the -Ala anion in DMSO. The anion equivalents are: 0, 1.0,
5.0, 8.0, 14.0, 20.0, 26.0, 30.0, 40.0, 50.0, 75.0, 95.0, 120.0, 155.0,
190.0, and 220.0. λex = 375 nm (EX: 5; EM: 10). Inset: Changes in
the fluorescence intensity of 3c at 445 nm upon addition of the -
Ala anion. The line shown is a line-fitted curve. The correlation
coefficient (R) for the nonlinear curve fitting is 0.9912.
of 3a and 3b, which may be due to the formation of an
excimer causing a decrease in the emission of the monomer.
The monomer emission was gradually quenched upon ad-
dition of the - or -Ala anions; the association constants
calculated from the change in monomer emission is in ac-
cord with those calculated from the change in excimer emis-
sion (see Figures S3.25 and S3.26 of the Supporting Infor-
mation).
The increase in fluorescence intensity of the excimer
upon addition of the anion is similar to the anion-induced
fluorescence enhancement reported previously.[18] In the ab-
sence of anions, the photoinduced electron transfer between
the indole group and weak electron-withdrawing amide
substituents might result in decreased fluorescence intensity.
When anions were added to the solution, the interaction of
the anion with the receptor unit could erase this specific
PET process to increase fluorescence. Therefore anion-in-
duced fluorescence enhancement was observed.[18] Similar
phenomena were observed when other anions or neutral
amino alcohol guests were added to the solution of receptor
3c (see the Supporting Information). The association con-
stants for the interactions of 3c with the guests were smaller
Figure 8. Bar plots of the association constants (Kass) of receptors
3a–c with Ala, Phe, and mandelate anions. [The Kass(3a+l-Ala) (En-
try 1) and Kass(3b+l-mandelate) (Entry 9) could not be calculated owing
than those of 3b with guests, ranging from 24.99 –1 for - to the fluorescence response being too low.].
Figure 7. Structures of the guests.
Eur. J. Org. Chem. 2007, 1768–1778
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1773

G. Qing, Y. He, F. Wang, H. Qin, C. Hu, X. Yang
FULL PAPER
preorganized structure of the calix[4]arene unit and the chi-
ral center of -tryptophan play important roles in the enan-
tioselective recognition process.
The Phe anion has a structure similar to that of the Ala
anion, but the association constants for the association of
the receptors with the Phe anion are smaller than those for
the Ala anion, which could be attributed to the greater ste-
ric hindrance of the phenyl ring relative to the methyl
group. Interestingly, we found that the association constants
for the interactions of 3a–c with the  enantiomers were
generally larger than those for the  enantiomers, which is
probably due to the  enantiomers having a structure more
complementary to the hosts. Further research is still being
carried out to investigate these phenomena.
Figure 9. Job plots for receptors 3a–c with the - or -N-Boc-Ala
anion (X = mol fraction of the anion, ∆δ = chemical shift change
of the CH proton of the anion).
1H NMR Study
1H NMR experiments were undertaken to assess the chi-
1H NMR spectra of 3b in the absence and presence of
ral recognition properties between receptors 3a–c and chiral Ala anions are shown in Figure 10. When treated with equi-
anionic guests because NMR spectroscopy can provide molar amounts of 3b, the signal of the CH proton of the
structural and dynamic information directly.[9a,19] Chiral re- racemic Ala anion again fragmented into a more compli-
cognition studies were carried out with a 300 MHz NMR cated signal pattern (Figure 10c) with a downfield shift
spectrometer using compounds 3a–c as chiral solvating (changing from δ = 3.834 to 3.918 ppm) and the signal of
1
agents. CDCl3 is the most common solvent used in the H the *CH proton of the host also experienced a downfield
NMR study of chiral recognition, and herein we chose shift (changing from δ = 5.269 to 5.327 ppm). The 1H NMR
CDCl3 as the solvent instead of [D6]DMSO because of seri- spectra of 3b show clear changes in the presence of the Ala
ous problems relating to the superposition of the signals of anion. Upon addition of an equimolar amount of the - or
the chiral CH protons of guests (including N-Boc-protected -Ala anion to a solution of 3b, the characteristic amide
alanine and mandelate) with the diagnostic signal of [D6]- peaks [NH(a), NH(b)] nearly disappeared. But differences
DMSO or the signals of the hosts leading to difficulties in were found: The signal of the *CH proton of the host expe-
1
clarifying the interaction properties. The H NMR spectra rienced a downfield shift from δ = 5.269 to 5.318 or
of 3a–c interactions with anionic guests in [D6]DMSO are 5.330 ppm for the - or -Ala anion, respectively, and the
presented in the Supporting Information.
1H NMR titration illustrated that the change in chemical
1
The H NMR spectra of 3a–c and the - or -Ala anion shift of the NH(b) signal of 3b in the presence of the -Ala
in a variety of ratios in CDCl3 at a constant total concen- anion occurred more quickly than with the -Ala anion (see
tration of 4.0ϫ10–3  were recorded. It was found that the the Supporting Information). The signal of the amide group
CH proton signal of the Ala anion at δ = 3.834 ppm under- linked to the Boc moiety of the host was also clearly down-
went a downfield shift when the Ala anion was treated with field-shifted from δ = 7.924 to 8.270 or 8.276 ppm for the
the three receptors. Figure 9 shows the Job plots of ∆δX - or -Ala anion, whereas the signal of the amide group
versus the mol fraction X of the - or -Ala anion in the (NH) of the guest was upfield-shifted from δ = 5.977 to
mixture.[20] Maxima were observed at X = 0.5, indicating 5.919 or 5.950 ppm for the - or -Ala anion, respectively,
that the receptors 3a–c all formed 1:1 complexes with the which suggested that the interaction between host and
Ala anion under the conditions employed. Probably the guest mainly happened through multiple hydrogen
two-armed structure based on calix[4]arene could associate bonds.[14c,18a,18d,21] The above results indicate that 3b has a
with an anion effectively through multi-hydrogen-bonding stronger interaction with the -Ala anion than with its 
interactions, which have been observed in other similar sys- enantiomer.
tems.[8a,8b,8g,14c,21]
Similar phenomena were found when 3b interacted with
When treated with equimolar amounts of receptor 3a, mandelate (see the Supporting Information). The signals of
the signal of the CH proton of the racemic Ala anion frag- the single CH protons of - and -mandelate were shifted
mented into a more complicated signal pattern (see the Sup- downfield by about 0.071 and 0.038 ppm in the presence of
porting Information) with a downfield shift (changing from 3b, respectively. The signal intensities of the amide protons
δ = 3.834 to 4.270 ppm), whereas the signal of the *CH [NH(a), NH(b)] were much weaker; the signal of the amide
proton of the host experienced an upfield shift (changing group linked to the Boc moiety was also downfield-shifted
from δ = 5.092 to 5.081 ppm). The amide [NH(a)] of the when 3b interacted with - or -mandelate. In particular, a
host exhibited nearly no change; only the signal of the NH downfield shift of the signal of the chiral proton of 3b from
proton of the guest showed a small upfield shift from δ δ = 5.269 to 5.302 or 5.289 ppm was observed for - or -
= 5.977 to 5.924 or 5.905 ppm for the - or -Ala anion, mandelate, respectively, clearly indicating that the host’s chiral
respectively.
centre has participated in the chiral recognition process.
1774
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Eur. J. Org. Chem. 2007, 1768–1778

Enantioselective Fluorescent Sensors for Chiral Carboxylates
FULL PAPER
Figure 10. The 1H NMR spectra of 3b and its guest complexes at 25 °C ([3b] = [guest] = 2.0ϫ10–3 ) in CDCl3 at 300 MHz. A) Racemic
N-Boc-Ala anion; B) receptor 3b; C) receptor 3b + racemic N-Boc-Ala anion; D) receptor 3b + -N-Boc-Ala anion; E) receptor 3b + -
N-Boc-Ala anion.
Probably as a result of the flexibility of the CH2CH2
Conclusion
units, the 1H NMR spectra of 3c did not show such obvious
Three chiral fluorescent receptors (3a–c) were synthe-
changes as those of 3b on interaction with the Ala anion
sized and their enantioselective recognition was studied by
(see the Supporting Information). The signals of the amide
1
fluorescence titration and H NMR spectroscopy. Recep-
peaks [NH(a), NH(b), NH(c)] all have clear downfield
tors 3a–c exhibit different chiral recognition abilities
towards some enantiomers of chiral materials and form 1:1
complexes with the guest molecules. Receptor 3a exhibits
shifts, but no signal disappeared, whereas the amide signal
of the Ala anion was shifted upfield from δ = 5.977 to 5.917
or 5.902 ppm upon addition of the - or -Ala anion, sug-
excellent enantioselective fluorescent recognition ability
gesting that the amide group of the guest also participates
towards the N-Boc-protected alanine anion and 3b reveals
in the association process.
good enantioselective recognition ability towards the
We can draw similar conclusions from the 1H NMR
enantiomers of mandelate. It is clear that a relatively rigid
spectra of the interactions between hosts and anionic guests
structure, good structural preorganization, steric effects,
in [D6]DMSO: The interactions mainly occur through mul-
and multiple hydrogen bonds induce the enantioselective re-
tiple hydrogen bonds. Some differences were found, notably
cognition ability of 3a and 3b. The remarkably different flu-
orescent responses that result from complexation reveal that
that the phenolic hydroxy groups of the calix[4]arene par-
ticipates in the association process and exhibits different
3a and 3b could be used as fluorescent chemosensors for the
changes in chemical shifts upon addition of the  or  anion
N-Boc-protected alanine anion or mandelate in the future.
(see the Supporting Information).
1
The H NMR spectra show that all the calix[4]arene de-
rivatives retain the cone conformation in solution and we
Experimental Section
found it interesting that the amide groups of 3b show the
strongest acidity and the most obvious change on inter-
acting with the anions, whereas the other two receptors
General: Melting points were determined with a Reichert 7905
melting point apparatus and are uncorrected. Optical rotations
show relatively weak changes, which is consistent with data were measured with a Perkin-Elmer Model 341 polarimeter. IR
spectra were obtained with a Nicolet 670 FT-IR spectrophotome-
ter. H NMR spectra were recorded in CDCl3 or [D6]DMSO with
obtained from the fluorescence titrations. In order to clarify
the effect of the hydrazine amide groups of 3b, receptor 3c
with a rather flexible CH2CH2 unit was designed; results
indicate that the rigidity of a structure also has an impor-
tant role in the association process.
The above results illustrate that the nature of the recep-
tor, the structural rigidity, multiple hydrogen-bonding inter-
actions, and complementary chiral-centre interactions may
be responsible for the enantiomeric recognition of anionic
guests.[22]
1
a Varian Mercury VX spectrometer at 300 MHz. 13C NMR spectra
were recorded with a Varian Inova spectrometer at 600 MHz. Mass
spectra were recorded with a Finnigan LCQ advantage mass spec-
trometer. Elemental analyses were determined with a Carlo-Erba
1106 instrument. Fluorescence spectra were obtained with a Shim-
adzu RF-5301 spectrometer. The UV/Vis spectra were recorded
with a TU-1901 spectrophotometer. Ethylenediamine was distilled
before use. CHCl3 was washed with water and dried with CaCl2,
and Et3N was dried and distilled from CaH2. All other commer-
Eur. J. Org. Chem. 2007, 1768–1778
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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1775

G. Qing, Y. He, F. Wang, H. Qin, C. Hu, X. Yang
FULL PAPER
cially available reagents were used without further purification. The
anions were used as their tetrabutylammonium salts. Compounds
1a, 1b, 2a, and the N-protected (by the tert-butyloxycarbonyl func-
tionality) amino acid derivatives were synthesized according to a
literature method.[23]
was stirred at room temperature for 2 h. Then a solution of 2a
(0.58 g, 2.0 mmol) or 2c (0.64, 2.0 mol), Et3N (0.1 mL) and DMAP
[p-(dimethylamino)pydridine] (0.02 g) in dry CHCl3 (20 mL, for 2c
2 mL of DMF was added to increase the solubility) was added
dropwise to the above solution under argon. After addition, the
mixture was stirred at room temperature for 48 h and then at 55 °C
for 5 h. The reaction mixture was washed with brine and the or-
ganic layer was collected and dried with anhydrous Na2SO4. After
filtration, the solvent was removed under reduced pressure and the
residue purified by column chromatography on silica gel.
Synthesis of Compound 2b: NaOH (0.40 g, 10 mmol) and (Boc)2O
(2.62 g, 12 mmol) were added to a solution of 2a (2.55 g, 10 mmol)
in water/dioxane (1:1, 40 mL). The mixture was stirred at room
temperature for 24 h and then the pH was adjusted to 7.0 by adding
6  HCl. The product was extracted with CHCl3 (5ϫ30 mL) and
the solvent was evaporated under reduced pressure to give 2b
Compound 3a: Chromatographic eluent: CHCl3/CH3CH2OH =
200:1 (v/v). The pure product was obtained as a white powder
(0.70 g, 60.0%). M.p. 152–154 °C. [α]2D0 = +45.71 (c = 0.05, CHCl3).
(2.71 g, 89%) as a pale yellow solid. M.p. 151–152 °C. [α]2D0
+47.50 (c = 0.05, CHCl ). IR (KBr): ν = 3384, 3323, 2976, 1737,
=
˜
3
1693, 1523, 1447, 1369, 1295, 1221, 1169, 1081, 1015, 752,
692 cm–1. 1H NMR (CDCl3): δ = 1.36 (s, 9 H, Boc-tBu), 3.26–3.32
(m, 2 H, Indole-CH2), 3.64 (s, 3 H, OCH3), 4.58–4.60 (m, 1 H,
NC*HCO), 6.82 (s, 1 H, Indole-CH), 6.95 (s, 1 H, Indole-CH),
7.03–7.08 (m, 1 H, Indole-CH), 7.11–7.16 (m, 1 H, Indole-CH),
7.28 (d, J = 7.8 Hz, 1 H, Indole-CH), 7.52 (d, J = 7.8 Hz, 1 H,
Indole-NH), 8.06 (s, 1 H, NHBoc) ppm. 13C NMR ([D6]DMSO):
δ = 28.5, 29.2, 51.8, 54.5, 78.4, 110.8, 111.7, 118.8, 119.1, 121.5,
124.5, 127.7, 136.7, 155.8, 171.8 ppm. C17H22N2O4 (318.37): calcd.
C 64.13, H 6.97, N 8.80; found C 64.15, H 7.02, N 8.69.
IR (KBr): ν = 3420, 2958, 1746, 1666, 1540, 1484, 1439, 1362, 1207,
˜
1
1124, 1046, 873, 741, 669 cm–1. H NMR (CDCl3): δ = 0.91 (s, 18
H, tBu), 1.25 (s, 18 H, tBu), 2.67 (d, J = 12.9 Hz, 2 H, ArCH2Ar),
3.48 (d, J = 12.8 Hz, 2 H, ArCH2Ar), 3.60 (d, J = 11.4 Hz, 6 H,
OCH3), 3.68 (d, J = 12.9 Hz, 2 H, ArCH2Ar), 3.81 (d, J = 13.8 Hz,
2 H, ArCH2Ar), 3.99 (d, J = 15.3 Hz, OCH2CO), 4.81 (d, J =
15.3 Hz, 2 H, OCH2CO), 5.03 (s, 2 H, NC*HCO), 6.85–6.97 (m, 4
H, ArH), 7.07 (d, J = 3.3 Hz, 4 H, ArH), 7.55 (s, 2 H, ArOH), 9.35
(d, J = 7.2 Hz, CONHCH) ppm. 13C NMR (CDCl3): δ = 25.6,
28.5, 29.4, 29.5, 29.6, 31.5, 31.6, 49.9, 50.0, 72.5, 107.7, 108.6,
116.1, 116.8, 119.4, 120.0, 122.4, 122.9, 123.1, 124.1, 125.3, 129.8,
129.9, 133.5, 139.7, 145.3, 147.5, 166.8, 169.7 ppm. ESI-MS: m/z
(%) = 1187.6 (100) [M – 1 + Na]+. C72H84N4O10 (1165.48): calcd.
C 74.20, H 7.26, N 4.81; found C 74.15, H 7.31, N 4.78.
Synthesis of Compound 2c: Hydrazine hydrate (4 equiv. of 2b) was
added to a solution (20 mL) of 2b (0.64 g, 2 mmol) in CHCl3/
CH3OH (1:10, v/v). The reaction mixture was stirred at room tem-
perature for 24 h. Then the solvent was evaporated under reduced
pressure and water (40 mL) poured onto the residue. After fil-
tration, the solid was dried in vacuo to obtain a pure white product
Compound 3b: Chromatographic eluent: CHCl3/CH3CH2OH =
50:1 (v/v). The pure product was obtained as a white powder
(0.30 g, 22.0%). M.p. 172–176 °C. [α]2D0 = –13.87 (c = 0.05, CHCl3).
(0.63 g)
in
98.4%
yield.
M.p.
˜
159–161 °C.
[α]2D0 = –4.88 (c = 0.05, DMF). IR (KBr): ν = 3344, 2984, 2933,
IR (KBr): ν = 3423, 2962, 1687, 1484, 1384, 1365, 1234, 1192, 1168,
˜
1674, 1653, 1524, 1505, 1459, 1390, 1368, 1271, 1250, 1172, 1026,
1124, 1046, 1023, 871, 742 cm–1. 1H NMR (CDCl3): δ = 1.07 (s, 18
H, tBu), 1.29 (s, 18 H, tBu), 1.41 (s, 18 H, Boc-tBu), 3.29–3.31 (m,
4 H, Indole-CH2), 3.41 (d, J = 12.6 Hz, 2 H, ArCH2Ar), 3.43 (d,
J = 15.3 Hz, 2 H, ArCH2Ar), 4.13 (d, J = 12.9 Hz, 2 H, ArCH2Ar),
4.21 (d, J = 13.8 Hz, 2 H, ArCH2Ar), 4.62 (d, J = 13.8 Hz, 2 H,
OCH2CO), 4.72 (d, J = 14.1 Hz, 2 H, OCH2CO), 5.30 (br., 2 H,
NC*HCO), 6.95 (s, 4 H, ArH), 7.00 (s, 4 H, Indole), 7.03 (d, J =
8.4 Hz, 2 H, Indole), 7.10 (s, 4 H, ArH), 7.14 (d, J = 7.8 Hz, 2 H,
Indole), 7.60 (d, J = 7.2 Hz, 2 H, Indole-NH), 7.93 (d, J = 2.7 Hz,
2 H, NH-Boc), 8.01 (s, 2 H, ArOH), 8.98 (s, 2 H, CONHN), 10.94
(s, 2 H, CONHN) ppm. 13C NMR (CDCl3): δ = 25.5, 25.9, 28.6,
29.3, 29.9, 31.6, 31.8, 51.6, 64.7, 71.8, 77.9, 107.3, 108.8, 116.3,
117.0, 119.4, 121.5, 123.2, 123.4, 123.8, 124.0, 124.6, 124.8, 125.5,
129.9, 130.0, 133.6, 140.8, 146.1, 146.7, 147.1, 153.4, 163.7,
1
738, 641 cm–1. H NMR ([D6]DMSO): δ = 1.28 (s, 9 H, Boc-tBu),
2.82–3.01 (m, 2 H, Indole-CH2), 4.17 (m, 3 H, NC*HCO, NH2),
6.67 (d, J = 8.1 Hz, 1 H, Indole-CH), 6.91 (m, 1 H, Indole-CH),
6.99 (m, 1 H, Indole-CH), 7.09 (s, 1 H, Indole-CH), 7.27 (d, J =
8.1 Hz, 1 H, Indole-CH), 7.54 (d, J = 7.2 Hz, 1 H, Indole-NH),
9.07 (s, 1 H, NHBoc), 10.74 (s, 1 H, CONHNH2) ppm. 13C NMR
([D6]DMSO): δ = 28.4, 28.8, 54.3, 78.5, 110.8, 111.9, 118.8, 119.1,
121.5, 124.3, 127.9, 136.7, 155.7, 172.0 ppm. C16H22N4O3 (318.38):
calcd. C 60.36, H 6.96, N 17.60; found C 60.34, H 7.03, N 17.58.
Synthesis of Compound 2d: Excess ethylene-1,2-diamine (0.72 g,
12 mmol) was added to a solution (20 mL) of 2b (0.64 g, 2 mmol)
in CHCl3/CH3OH (1:10, v/v). The reaction mixture was stirred at
room temperature for 36 h. After evaporation of the solvent and
the residual ethylenediamine under reduced pressure, a pale yellow
solid (0.65 g) was obtained in 93.7% yield. M.p. 137–139 °C. [α]2D0
166.9 ppm. ESI-MS: m/z (%)
= 1363.6 (100) [M –
1]+.
C80H100N8O12 (1365.72): calcd. C 70.36, H 7.38, N 8.20; found C
70.29, H 7.41, N 8.18.
= +14.37 (c = 0.05, CHCl ). IR (KBr): ν = 3341, 2979, 2928, 1686,
˜
3
1649, 1526, 1385, 1367, 1327, 1249, 1173, 1109, 741, 640 cm–1. H
1
Compound 3c: Compound 1b (0.80 g, 1 mmol) in dry CHCl3
(20 mL) was added dropwise to a solution of 2d (0.69 g, 2 mmol)
and triethylamine (2 equiv.) in dry CHCl3 (25 mL) at 0 °C. After
addition, the reaction mixture was stirred at room temperature for
2 d and then washed successively with an aqueous solution of citric
acid (10%), sodium hydrogen carbonate (10%) and brine. The or-
ganic layer was collected and dried with anhydrous Na2SO4. After
filtration, the solvent was removed under reduced pressure and the
residue was purified by column chromatography on silica gel [elu-
ent: CHCl3/CH3CH2OH = 100:3 (v/v)]. The pure product was ob-
NMR (CDCl3): δ = 1.44 (s, 9 H, Boc-tBu), 3.08–3.18 (m, 4 H,
NCH2C), 3.29–3.36 (m, 2 H, Indole-CH2), 4.40 (d, J = 5.1 Hz, 2
H, NH2), 5.25 (s, 1 H, NC*HCO), 6.07 (s, 1 H, NHBoc), 7.07 (s,
2 H, Indole-CH), 7.10–7.15 (m, 1 H, Indole-CH), 7.18–7.23 (m, 1
H, Indole-CH), 7.09 (s, 1 H, Indole-CH), 7.35 (d, J = 8.1 Hz, 1 H,
Indole-CH), 7.65 (d, J = 7.8 Hz, 1 H, Indole-NH), 8.34 (s, 1 H,
CONHC) ppm. 13C NMR ([D6]DMSO): δ = 28.5, 29.0, 40.5, 41.6,
54.4, 78.5, 110.7, 111.9, 118.9, 119.2, 121.5, 124.3, 127.8, 136.7,
155.8, 171.6 ppm. C18H26N4O3 (346.43): calcd. C 62.41, H 7.56, N
16.17; found C 62.39, H 7.59, N 16.14.
tained as a white powder (0.26 g, 18.5%). M.p. 156–158 °C. [α]2D0
=
General Procedure for the Synthesis of Receptors 3a and 3b: DCC
(0.41 g, 2.0 mmol) was added to a stirred and ice-cooled solution
of 1a (0.76 g, 1.0 mmol) in dry CHCl3 (10 mL) and the mixture
+9.52 (c = 0.05, CHCl ). IR (KBr): ν = 3400, 2963, 1670, 1541,
˜
3
1484, 1458, 1365, 1245, 1193, 1169, 1125, 1098, 1046, 873,
741 cm–1. 1H NMR (CDCl3): δ = 1.08 (s, 18 H, tBu), 1.25 (s, 18
1776
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 1768–1778

Enantioselective Fluorescent Sensors for Chiral Carboxylates
FULL PAPER
Molenveld, J. F. J. Engbersen, D. N. Reinhoudt, Chem. Soc.
Rev. 2000, 29, 75–86.
a) Y. Murakami, J. I. Kikuchi, Y. Hisaeda, O. Hayashida,
Chem. Rev. 1996, 96, 721–758; b) D. Philp, J. F. Stoddart, An-
gew. Chem. Int. Ed. Engl. 1996, 35, 1155–1196.
a) W. H. Pirkle, T. C. Pochapsky, Chem. Rev. 1989, 89, 347–
362; b) T. J. Ward, . M. Hamburg, Anal. Chem. 2004, 76,
4635–4644; c) I. Stibor, P. Zlatuskova, Top. Curr. Chem. 2005,
255, 31–63.
a) For NMR determination of enantiomeric purity, see: D. Par-
ker, Chem. Rev. 1991, 91, 1441–1457; b) T. Wenzel, J. D. Wil-
cox, Chirality 2003, 15, 256–270.
a) A. P. de Silva, H. Q. N. Gunaratne, T. Gunnlaugsson,
A. J. M. Huxley, C. P. McCoy, J. T. Rademacher, T. E. Rice,
Chem. Rev. 1997, 97, 1515–1566; b) R. Martiner-Manez, F.
Sancenon, Chem. Rev. 2003, 103, 4419–4476; c) S. Arimori,
M. L. Bell, C. S. Oh, T. D. James, Org. Lett. 2002, 4, 4249–
4251.
H, tBu), 1.45 (s, 18 H, Boc-tBu), 3.10–3.28 (m, 8 H, NCH2C), 3.30–
3.35 (m, 4 H, Indole-CH2), 3.39 (d, J = 5.1 Hz, 2 H, ArCH2Ar),
3.44 (d, J = 6 Hz, 2 H, ArCH2Ar), 4.01 (d, J = 5.1 Hz, 2 H, Ar-
CH2Ar), 4.13 (d, J = 5.1 Hz, 2 H, ArCH2Ar), 4.45 (d, J = 7.2 Hz,
2 H, OCH2CO), 4.55 (d, J = 7.5 Hz, 2 H, OCH2CO), 5.31(br, 2 H,
NC*HCO), 6.23 (s, 2 H, NH-Boc), 6.83 (d, J = 10.2 Hz, 2 H, In-
dole), 6.96 (s, 4 H, ArH), 7.06 (s, 4 H, ArH), 7.10 (s, 4 H, Indole),
7.16 (m, 2 H, Indole), 7.38 (d, J = 8.1 Hz, 2 H, Indole), 7.63 (d, J
= 7.5 Hz, 2 H, Indole-NH), 8.07 (s, 2 H, ArOH), 9.00 (s, 2 H,
CONHC), 9.34 (s, 2 H, CONHC) ppm. 13C NMR (CDCl3): δ =
28.6, 28.9, 31.2, 31.7, 32.4, 34.1, 34.4, 38.5, 39.3, 55.6, 74.7, 80.2,
109.9, 111.7, 118.8, 119.6, 122.0, 124.3, 126.0, 126.5, 127.3, 127.7,
132.6, 136.5, 143.6, 148.8, 149.0, 149.3, 155.6, 169.3, 172.5 ppm.
FAB-MS: m/z (%) = 1443.8 (100) [M – 1 + Na]+. C84H108N8O12
(1421.83): calcd. C 70.96, H 7.66, N 7.88; found C 70.87, H 7.69,
N 7.85.
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Tetrabutylammonium Salts: The tetrabutylammonium salts were
prepared by adding 1 equiv. (for a monocarboxylic acid) or 2 equiv.
(for a dicarboxylic acid) of tetrabutylammonium hydroxide in
methanol to a solution of the corresponding carboxylic acid in
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and the solvent evaporated to dryness under reduced pressure. The
resulting syrup was dried under high vacuum for 24 h, analyzed by
NMR spectroscopy, and stored in a desiccator.
Fluorescent Response Study: The host compounds 3a–c were pre-
pared as stock solutions (5ϫ10–4 molL–1) in DMSO. All the
anions used in this study were in the form of the tetrabutylammo-
nium salt and stock solutions of the salts were prepared at concen-
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test solutions were prepared by adding different volumes of anion
solution to a series of test tubes and then the same amount of stock
solution of the host compound was added to each of the test tubes
and diluted to 3.5 mL with DMSO. After being shaken for several
minutes, the test solutions were analyzed immediately.
Job Plots: Stock solutions of the host (4 m) and the tetrabutylam-
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were filled with 400 µL solutions of host and guest (the total con-
centrations were 4.0ϫ10–3 ) in the following volume ratios:
40:360, 80:320, 120:280, 160:240, 200:200, 240:160, 280:120, 320:80,
and 360:40. The resulting mixtures were allowed to stand at room
[9]
[10]
[11]
[12]
1
temperature for 4 h before H NMR measurements were taken.
Supporting Information (see footnote on the first page of this arti-
cle): Characterization spectra, fluorimetric titration graphs of re-
1
ceptors 3a–c with guests in DMSO, and H NMR study of recep-
tors with the N-Boc-protected Ala anion or mandelate in CDCl3
and [D6]DMSO.
Acknowledgments
[13]
We thank the National Natural Science Foundation for financial
support (Grant No. 20572080). G. Q. would like to thank for the
support of Dr. Lei Fang and Shun-ying Liu in the explanation of
the PET mechanism.
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Received: October 19, 2006
Published Online: February 20, 2007
1778
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Eur. J. Org. Chem. 2007, 1768–1778