Cholic acid-based high sensitivity fluorescent sensor for α,ω-dicarboxylate: an intramolecular excimer emission quenched by complexation

Article abstract of DOI:10.1016/j.tet.2006.09.042

Fluorescent receptors (1 and 2) bearing two binding units on C3 and C24 and two signal display units on C7 and C12 of cholic acid, respectively, were designed and synthesized. Both 1 and 2 emit a much weaker fluorescence than that of the control compound

Full text of DOI:10.1016/j.tet.2006.09.042

Tetrahedron 62 (2006) 11687–11696
Cholic acid-based high sensitivity fluorescent sensor
for a,u-dicarboxylate: an intramolecular excimer
emission quenched by complexation
b
Shun-Ying Liu,a,b Yong-Bing He,a Wing Hong Chanb, and Albert W. M. Lee
*
aDepartment of Chemistry, Wuhan University, Hubei, China
bDepartment of Chemistry and Central Laboratory of the Institute of Molecular Technology for Drug Discovery and Synthesis,
Hong Kong Baptist University, Hong Kong, China
Received 21 July 2006; revised 13 September 2006; accepted 14 September 2006
Available online 17 October 2006
Abstract—Fluorescent receptors (1 and 2) bearing two binding units on C3 and C24 and two signal display units on C7 and C12 of cholic acid,
respectively, were designed and synthesized. Both 1 and 2 emit a much weaker fluorescence than that of the control compound 3 lacking of the
binding units reflecting that a PET process originated from the C-3 thiourea group to the plural pyrenyl pendant groups is operative. Addition
of terminal dicarboxylate anions to the CH3CN solution of 1 or 2 enhances the PET process, which leads to a significant and highly sensitive
fluorescence response, resulting in an almost complete quenching of the excimer emission of the signal units. To maximize the interaction of
the host and the guest, carboxylates of more than five carbon chains could penetrate through the space between the two pyrenyl pendants of the
host, triggering a considerable conformational change of the fluorophores. As a result, an enhancement of the monomer emission at the ex-
pense of the excimer emission will take place. The binding properties and mechanism of 1 and 2 to dicarboxylates in CH3CN were manifested
by the combined fluorescence, UV–vis, and 1H NMR spectroscopic method.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
The structural complementary between receptors and termi-
nal dicarboxylates (ꢀOOC(CH2)nCOOꢀ) plays a crucial role
in the selective recognition processes.8 To assemble selec-
tive artificial ditopic receptors for terminal dicarboxylates,
based on cyclopolyammonium,9 sapphyrin,10 and calix[4]-
arene,11 some classical molecular skeletons were rationally
designed and exquisitely synthesized. Charge neutral che-
mosensors, which are immune from cross pH interference are
particularly attractive. Gunnlaugsson and Davis12 reported
a neutral fluorescent PET sensor for glutarate while He’s
group developed two fluorescent sensors for adipate.13 Mei
and Wu reported a sensor containing a naphthalene group
as the signal unit for pimelate.14 However, most of these che-
mosensors exhibit good selectivity only for dicarboxylates
of a relatively short chain length (nꢁ3) and with moderate
binding constants of 105 Mꢀ1. It is very difficult to construct
a suitable receptor for a long-chain terminal dicarboxylate
using the classical molecular scaffolds such as polyazama-
crocycles and calixarenes. To our best knowledge, there is
no example of chemosensor, which can bind strongly with a
long-chain terminal dicarboxylate (n>5). In this paper, we
report the design and synthesis of two cholic acid-based fluo-
rescent sensors, which are amenable to the sensitive detec-
tion of long-chain terminal dicarboxylates (n¼6 and 8).
Anions play an important role in a wide range of chemical,
environmental, and biological processes.1 The quest for che-
mosensors capable of effecting the selective and sensitive
binding and sensing of negatively charged species through
visible, electrochemical, and optical responses has contin-
ued to attract considerable attention in scientific commu-
nity.2 Dicarboxylates are among the most attractive targets
for the study of anion recognition and sensing because of
their biological importance,3 such as their critical roles in
numerous metabolic processes.4 Therefore, their sensitive
detection is of great interest in a variety of areas in bioana-
lytical and biomedical researches.4b,5 The optical methods,
owing to their simplification of manipulation and sensitivity
of transduction of binding behaviors, are extensively adop-
ted in the investigation of molecular/ion recognition.6
Numerous endeavors have been particularly devoted to the
design and synthesis of ditopic anion receptors bearing opti-
cal signal display subunits (i.e., chromophore or fluoro-
phore) as sensing probes for dicarboxylates.7
Keywords: Cholic acid; Fluorescence; UV–vis spectroscopy; Dicarboxylate;
Chemosensor.
Pioneered by the seminal works of Davis and others, cholic
acid has recently emerged as a promising natural material to
* Corresponding author. Tel.: +852 3411 7076; fax: +852 3411 7348;
e-mail: whchan@hkbu.edu.hk
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.09.042

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S.-Y. Liu et al. / Tetrahedron 62 (2006) 11687–11696
construct supramolecular systems for molecular recogni-
tion.15 To achieve high affinity and selectivity to the
‘host’, the three axially oriented functionalities at the C3,
C7, and C12 of cholic acid could be modified and assembled
in such a way to confer cooperative binding interactions to
a specific guest anion. Recently, by incorporation of two
thiourea groups connected to an anthracene moiety at the
C3 and C24 as the signal subunit, we have created a fluores-
cent ditopic receptor possessing binding capability to dicarb-
oxylates even in aqueous media.16 Our findings represent
the first charge neutral chemosensor, which can be exploited
for binding dicarboxylates in aqueous conditions. However,
the fluorescent signal change of the sensor over a wide con-
centration range of the guest is only moderate. To further
improve the sensitivity and selectivity of the sensor, we
envisage that, if two pyrene moieties are introduced onto
the C7 and C12 as signal display units and two thiourea
receptive subunits were appended onto C3 and C24 of cholic
acid, upon association with dicarboxylates, a distinct fluo-
rescent response indicative of binding will be observed.
The two pendent proximate pyrenyl groups can display not
only a well-defined monomer emission at 370w430 nm but
also an efficient excimer emission at around 480 nm.17 To
effectively interact with the host, the terminal dicarboxylates
may penetrate through the space between the plural pyrenyl
pendants reaching the two receptive sites at the two ends of
the host. The binding event can trigger conformational
changes of the pyrene-appended signal display units, which
could upset the equilibrium between the monomer and the
excimer emissions. Besides, the fluorescence of the system
will be quenched by the formation of the complex via
a PET (photo-induced electron transfer) mechanism. In ad-
dition, appending bulky pyrenyl groups to the C7 and C12
of cholic acid can also create a bigger steric hindrance and
sharpen the selectivity of the sensor favoring the binding
between the host and long-chain terminal dicarboxylates.
Herein, we report the synthesis and structural characteriza-
tion of two new charge neutral fluorescent sensors 1 and 2
bearing two signal subunits at C7 and C12 and two binding
subunits at C3 and C24 of cholic acid, respectively. The
binding abilities of 1 and 2 to dicarboxylates were demon-
strated by fluorescence emission spectra, UV–vis spectra,
and 1H NMR method.
2. Results and discussion
2.1. Synthesis
Treatment of 1-pyrenyl acid or 1-pyrenebutyric acid with
sulfuryl dichloride in benzene afforded the corresponding
acid chlorides 5 and 6 in 100% yield, which could be directly
used for the subsequent condensation reaction (Scheme 1).
To overcome the high steric hindrance of introducing the
plural pyrenyl moieties on the C7 and C12 of the cholic
acid scaffold, we adopted the Maitra’s protocol by reacting
excess 5 or 6 with methyl 3-azidocholate (4)15c in a mixed
solvent of dichloromethane and xylene (1:10) using CaH2
as a base with a catalytic amount of benzyltriethylammo-
nium chloride, giving rise to 7 and 8 in ca. 40% yield, respec-
tively.18 Reduction of 7 (or 8) by zinc dust in acetic acid
followed by hydrazidation with hydrazine yielded amine
11 (or 12). Condensation reactions were performed between
11 (or 12) and 4-trifluoromethylphenylisothiocyanate in di-
chloromethane and the target compounds 1 and 2 were
OCH3
O
O
O
COCl
n(H2C)
O
C
(CH2)n
OH
H
O
OCH3
+
O
1. Zn / AcOH, r.t.
2. Et3N
CaH2, Cat
C
N3
(CH2)n
xylene/DCM, reflux
H
N3
OH
H
5: n=0
6: n=3
7: n=0
8: n=3
4
NHNH2
NHNH
OCH3
S
O
O
O
HN
O
O
O
O
O
O
C
C
C
O
O
O
trifluoromethyl
isothiocyanate
(CH2)n
•
NH2NH2 H2O
(CH2)n
(CH2)n
O
O
O
C
C
C
NH2
CH3OH/CH2Cl2
NH
NH
NH2
(CH2)n
(CH2)n
(CH2)n
DCM, r.t.
S
CF3
CF3
11: n=0
12: n=3
1: n=0
2: n=3
9: n=0
10: n=3
Scheme 1. Synthetic routes for receptors 1 and 2.

S.-Y. Liu et al. / Tetrahedron 62 (2006) 11687–11696
11689
obtained in ca. 30w50% over two steps. In order to investi-
gate the effect of binding behaviors on the fluorescence of
1 and 2, control compound 3 was synthesized from methyl
3a-acetyl-7a,12a-dihydroxy-5b-cholan-24-oate.19
of F3>F2>F1. Due to the more proximal thiourea groups
at the two pyrenyl units in receptor 1 than in receptor 2,
a more effective PET process was effectuated for 1.
To obtain insight into the binding properties of 1 and 2
toward dicarboxylate anions, we first investigated the fluo-
rescence change of the sensors upon addition of dicarboxy-
lates in CH3CN. With a gradual increase in the concentration
of dicarboxylate anions, malonate, succinate, glutarate,
adipate, suberate, and sebacate (all as tetrabutylammonium
salts), the monomer emission of 1 (1ꢂ10ꢀ5 M) can be
quenched ca. 50% and the excimer can be quenched as much
as >90%. Comparing with our previously reported anthra-
cene based carboxylate sensors,16 the extent of quenching
of the present systems caused by the guests is significantly
enhanced. Potentially, sensors 1 and 2 would be more sensi-
tive optical probes toward dicarboxylates. Typical fluores-
cence change of 1 and 2 modulated with different amounts
of suberate in CH3CN is showed in Figures 2 and 3, respec-
tively. The inset of the graph shows the change of the fluores-
cence intensity of the monomer and excimer upon addition
of suberate. Several interesting features of the plots are note-
worthy. Firstly, both sensors are ratiometric, which are more
superior systems in sensor design due to their ability to elim-
inate the sample matrix effect in the recognition process.
Both sensors operate complementarily to each other. As
the concentration of the guest increases, the IM/IE of 1 and
2 responds differently (i.e., the ratio of 1 decreases while
that of 2 increases, Supplementary data). It is noteworthy
that, when treated with different amounts of dicarboxylate
anions, the excimer of receptor 2 at 475 nm (1ꢂ10ꢀ5 M in
CH3CN) had shown a more sensitive fluorescence response
than that of receptor 1 and the excimer was almost com-
pletely quenched. The guest induced conformational change
of sensor 2 was implicated at the moderate concentration of
suberate as a slightly increase in the monomer peak was ob-
served. Expansion of Figure 3 in the range of 400–450 nm
allows the manifestation of an iso-emission point at around
421 nm (Supplementary data).
2.2. Binding properties
As expected, when excited at 352 nm in CH3CN, receptor 1
(1ꢂ10ꢀ5 M) displayed a monomer emission at 388 nm and
an excimer emission at 488 nm, with an intensity ratio of
monomer to excimer emission (IM/IE) as 2.42. Compared
to sensor 1, 2 (1ꢂ10ꢀ5 M) was excited in CH3CN at a shorter
wavelength (342 nm) and gave a monomer and an excimer
emission at 375 and 475 nm, respectively, the ratio of
IM/IE was found to be 0.21, which is substantially smaller
than that of 1. This indicated that, in comparison with 1,
the presence of the more flexible three carbon spacer in 2
between the pyrenyl groups and the C-7 and C-12 ester func-
tionalities enables a tighter excimer formation arising from
a stronger p–p stacking in receptor 2. In both 1 and 2, the
intensity of ratio of monomer to excimer is barely changed
in the concentration range of 10ꢀ7–10ꢀ4 M, implicating
that their excimer emissions result from an intramolecular
excimer but not from an intermolecular excimer (Supple-
mentary data).
To unravel the details of the interaction between the host and
the guest, compound 3 lacking the thiourea groups on the C3
and C24 served as the control was synthesized. Compared
with 1 and 2, 3 can emit relatively stronger emissions and
give a monomer emission at 388 nm and an excimer at
488 nm when excited at 352 nm. On this basis a higher
IM/IE ratio of 0.84 was obtained for 3 compared with the
value of 0.21 for 1, it is quite likely that the quenching effect
by the thiourea group is more pronounced to the excimer
than that to the monomer (Fig. 1). Apparently, the thiourea
groups not only affect the ratio of monomer to excimer emis-
sion but also quench the fluorescence of receptors 1 and 2.
This is conceivably attributable to the fact that the thiourea
groups take part in the PET process in which an electron is
transferred from a lone-pair electron of the sulfur atom to
two excited pyrenyl units of 1 and 2.20 The quantum yield
of 1, 2 and 3 were assessed using pyrene as the standard
and the results are tabulated in Table 1. The quantum yield
of 3 was much higher than that of 1 and 2 with the order
Regarding the nature of the guest–host interaction in the sen-
sor systems, the key question was: how do dicarboxylates
preorganize themselves in reaching the two binding sites of
the host? Could they penetrate through or just move around
the space between the pyrenyl pendent groups in the
OCH3
O
O
O
C
O
O
C
AcO
3
Figure 1. The fluorescence emission spectra of 1, 2, and 3 in CH3CN (1ꢂ10ꢀ6 M) (1 and 3 were excited at 352 nm, and 2 at 342 nm).

11690
S.-Y. Liu et al. / Tetrahedron 62 (2006) 11687–11696
Table 1. Absorption and fluorescence spectral data of 1, 2, and 3 in CH3CN
Sample
labs (nm)
3 (104 M ꢀ1 cmꢀ1 a
)
F313 nm
Pyrene
231/240/262/272/306/319/334
282/352/385
235/242/265/276/313/327/343
280/348/383
3.83/6.95/2.15/4.05/1.02/2.53/4.15
7.49/6.95/2.18
11.1/14.9/7.09/10.3/3.09/5.49/6.97
7.44/4.96/1.33
0.530b,d
0.877c,d
0.699c,d
0.592c,d
3
2
1
The concentration is 1ꢂ10ꢀ5 M.
a
b
c
d
Quantum yield was detected in EtOH and used as the standard.
Quantum yield was detected in CH3CN.
Quantum yield was determined with lex¼303 nm.
respective complexes? Treated with ca. 60 equiv of malo-
nate and succinate anions (i.e., short chain dicarboxylates),
the fluorescence response of 1 or 2 attained equilibrium,
while with only ca. 15 equiv of other longer chain dicarb-
oxylate anions an equilibrium could be observed. The exci-
mer emission is more sensitive to the dicarboxylates than the
monomer emission both in 1 and 2. With the increase of the
length of the dicarboxylate anion, the sensitivity of both 1
and 2 toward dicarboxylate increases. For long chain dicarb-
oxylates, there is a significant fluorescence response even at
the concentration at around 10ꢀ8 M (Supplementary data).
Sensor 2 has a more sensitive response to the same dicarb-
oxylate than 1 because of its two pyrenyl groups linked
with flexible spacers, which lead to a stronger excimer emis-
sion. Introducing dicarboxylates and other anions such as
AcOꢀ, Clꢀ, Brꢀ, and Iꢀ to the CH3CN solution of 3, there
is no change observed in the fluorescence spectra. This indi-
cated that the anions quenched the fluorescence intensity of
pyrenyl groups only by coordinating with thiourea groups
present in 1 and 2.
two pyrenyl units leading to the enhancement of the mono-
mer emission at the expense of the excimer peak (vide
supra). The observation appears to be consistent with this in-
teraction model. When treated with 100 equiv of AcOꢀ, the
monomer emission of 1 and 2 could be quenched ca. 50% as
the extent of quench caused by dicarboxylates (except malo-
nate and succinate) while both the excimer of 1 and 2 only
could be quenched at about 50% (Supplementary data).
Apparently, acetate due to its small size could not go through
the space of the two pendent groups. This observation
strongly supported that the long-chain dicarboxylates (n¼3,
4, 6, 8) went through rather than passed around the two pyr-
enyl units, which also contributed to a great quenching of the
excimer of 1 and 2 (i.e., from 50 to 90%). In response to the
combined electronic and conformational change effects trig-
gered by complex formation, an enhancing PET process
from thiourea groups to the pyrenyl groups and a decrease
of the p–p stack between the two pyrenyl groups take place.
Accordingly, the excimer emission can be quenched signif-
icantly, which creates a highly sensitive fluorescence respon-
sive system to dicarboxylates. While treated with 100 equiv
of other anions, spherical anions such as Clꢀ, Brꢀ, and Iꢀ,
only less than 10% quenching was observed in the fluores-
cence spectra of 1 and 2.
After binding the dicarboxylate anion, the electron-donating
power of either the aminothiourea or amidothiourea group in
the hosts can be enhanced, which leads to a stronger PET
process from the thiourea to the pyrenyl units (vide supra).
This possibly contributes to the quenching of the monomer
and excimer. At the same time, when the binding events oc-
curred, the dicarboxylate anion would go through the C-7
and C-12 pendent groups of the cholic acid derivatives.
Such type of interaction could destroy the p–p stack of the
Job plot21 showed that both 1 and 2 formed 1:2 complexes
with malonate and succinate (Fig. 4) and 1:1 complexes with
other dicarboxylate anions (Supplementary data). This result
is consistent with the phenomena observed in the fluores-
cence spectra (vide supra) and suggest that pyrenyl groups
on C7 and C12 not only act as signal units but also play
Figure 2. The fluorescence emission spectra of 1 (1ꢂ10ꢀ5 M) with suberate
in CH3CN, lex¼352 nm. Inset: the fluorescence intensity of 1 at 388 nm
(monomer) and 488 nm (excimer) with different amounts of suberate.
Figure 3. The fluorescence emission spectra of 2 (1ꢂ10ꢀ5 M) with suberate
in CH3CN, lex¼342 nm. Inset: the fluorescence intensity of 1 at 475 nm
with different amounts of suberate.

S.-Y. Liu et al. / Tetrahedron 62 (2006) 11687–11696
11691
For short chain dicarboxylates, the complex association con-
stants (log Ka) and the stoichiometry for 1:2 binding model
are calculated using the Benesi–Hildebrand equation25 and
are listed in Table 3. Both 1 and 2 gave the values of stoichio-
metry (n) with malonate and succinate close to 2, which
corroborated well with the results obtained from the Job plot
(vide supra).
To investigate the chiral discriminative power of the sensors,
L-, D-glutamate, and N-acetyl-L-glutamate (used as tetra-
butylammonium salts) were chosen to introduce into the
CH3CN solution of 1 and 2 (1ꢂ10ꢀ5 M). The corresponding
association constants are determined and are given in
Table 2. Within the experimental errors, the binding strength
of the hosts and glutamate was found to be slightly greater
than that of the hosts and glutarate. The possible H-bonding
between the a-amino group of glutamate and the oxygen of
the C-7/C-12 ester group of the host may contribute to the
additional binding interaction. Interestingly, comparing the
binding constants of the two antipodal forms of glutamate to
the hosts, enantioselective factors exhibited by 1 and 2 to
the guests were found to be 1.53 and 1.79, respectively. The
1H NMR also showed that, under the chiral influence of the
host 1, the splitting of the two b-proton signals of glutamate
centered at d 2.08 and 2.18 was evident. Reciprocally, the C-7
and C-12 protons of 1 at d 5.40 and 5.60 were split by the
racemic glutamate (Supplementary data).
Figure 4. Job plot for the complexation of 2 with succinate and glutarate in
CH3CN (the total concentration is 1ꢂ10ꢀ5 M).
important roles in complexing with terminal dicarboxylate
anions. Specifically, non-bonding repulsion between the host
and malonate (or succinate) precludes the formation of a 1:1
complex by passing through the bulky pyrenyl pendants. We
have reported for the first time that the flexible C17 side
chain of cholic acid derivatives can be exploited to provide
a binding unit onto the C2422 and the resulting fluorescent
sensor had demonstrated a fairly selective binding toward
adipate,16 which possesses a carbon chain of suitable length.
With the help of the flexible binding arm on C17 and the
steric constraint of the pendent groups on C7 and C12, 1
and 2 can show a selective recognition to some long-chain
terminal dicarboxylate anions.
To substantiate the binding interaction between the dicarb-
oxylates and the hosts, all titration experiments were per-
formed in CH3CN with UV–vis spectroscopic method. The
typical spectra of 1 and 2 (1ꢂ10ꢀ5 M) with different
amounts of suberate in CH3CN are shown in Figures 5 and
6, respectively. Sensor 1 has two characteristic peaks at
280 and 348 nm, with addition of suberate, the intensity of
both peaks was increased with a slight blue shift and a new
absorption band appeared at around 308 nm. At the same
time, in the first derivative of the UV titration curves, an iso-
sbestic peak at 269 nm could be easily identified.
On the basis of the change in fluorescent intensity associated
with the stepwise addition of guest dicarboxylates, the com-
plex association constants (Ka) for 1:1 binding model were
calculated using non-linear least-squares curve fitting23 and
are compiled in Table 2. Excellent relative coefficients
(R>0.99) were obtained and demonstrated that 1 and 2
formed 1:1 complexes with long-chain terminal dicarboxy-
late anions (n¼3, 4, 6, 8).24 The association constants of
1 and 2 to sebacate are much larger than those of other di-
carboxylates, suggesting that both 1 and 2 exhibit selective
recognition to sebacate. For all 1:1 binding models, 1 pre-
sumably due to its more rigid structure has a slightly weaker
binding ability to dicarboxylates than 2.
The free 2 gives a similar absorption with pyrene in CH3CN.
Adding suberate anion into the solution of 2, the charac-
teristic peak at 265 nm ascribed to the absorption of tri-
fluoromethylphenyl ring was increased discernibly. A new
absorption band appeared at the range of 283w323 nm and
an isosbestic point at 276 nm could be observed in the
first derivative of the corresponding UV-titration curves
Table 2. The association constants of 1 and 2 with dicarboxylates (1:1 binding model) in CH3CN
Anion
1
2
a
Ka
b
Ka
a
b
Ka
Ka
Glutaratec
(8.22ꢃ1.51)ꢂ105
(1.27ꢃ0.12)ꢂ106
(1.64ꢃ0.14)ꢂ106
(2.27ꢃ0.23)ꢂ107
(1.18ꢃ0.13)ꢂ106
(1.81ꢃ0.11)ꢂ106
(1.29ꢃ0.19)ꢂ106
(1.08ꢃ0.09)ꢂ106
(1.29ꢃ0.14)ꢂ106
(1.03ꢃ0.06)ꢂ106
(2.30ꢃ0.23)ꢂ107
(2.21ꢃ0.13)ꢂ106
(1.81ꢃ0.19)ꢂ106
(1.09ꢃ0.10)ꢂ106
(1.68ꢃ0.17)ꢂ106
(5.56ꢃ0.42)ꢂ106
(2.10ꢃ0.19)ꢂ107
>108d
(1.60ꢃ0.11)ꢂ105
(1.87ꢃ0.14)ꢂ107
(3.19ꢃ0.10)ꢂ107
>108d
Adipatec
Suberatec
Sebacatec
L-Glutamatec
D-Glutamatec
N-Acetyl-L-glutamatec
(2.35ꢃ0.11)ꢂ106
(4.21ꢃ0.23)ꢂ106
(1.63ꢃ0.21)ꢂ106
(2.03ꢃ0.22)ꢂ106
(5.23ꢃ0.11)ꢂ106
(8.35ꢃ1.30)ꢂ105
a
The values were calculated from the change of the fluorescence spectra.
The values were calculated from the change of the UV–vis spectra.
Anions were used as their tetrabutylammonium salts.
The value is too large to calculate.
b
c
d

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S.-Y. Liu et al. / Tetrahedron 62 (2006) 11687–11696
Table 3. The association constants of 1 and 2 with dicarboxylates (1:2 binding model) in CH3CN
Anion
1
2
na
log Ka
nb
log Ka
na
log Ka
nb
log Ka
a
b
a
b
Manolatec
Succinatec
1.84
1.96
8.07ꢃ0.59
8.76ꢃ0.61
1.75
2.13
7.93ꢃ0.14
8.87ꢃ0.26
2.02
2.11
9.01ꢃ0.15
9.47ꢃ0.13
2.2
2.09
8.85ꢃ0.09
8.67ꢃ0.12
a
The values were calculated from the change of the fluorescence spectra.
The values were calculated from the change of the UV–vis spectra.
Anions were used as their tetrabutylammonium salts.
b
c
1H NMR spectra also had been used to study the binding
properties of 1 and 2 toward dicarboxylates. When 1 was
treated with 1 equiv of adipate anion in DMSO-d6, the inten-
sity of the proton signals ascribed to the thiourea hydrogens
diminished significantly and at least one of these protons
recorded a downfield shift of 0.07 ppm, which is indicative
of H-bonding interaction between the host and the guest
(Supplementary data). The aromatic protons of the trifluoro-
methylphenyl ring of 1 underwent a clear upfield shift from
7.63 to 7.34 ppm after the thiourea groups were bound with
the anion.
3. Conclusion
Charge neutral fluorescent chemosensors 1 and 2 for dicarb-
oxylates have been rationally designed and synthesized.
Both 1 and 2, functionalized adequately at the C3, C7,
C12, and C24 of cholic acid, showed high affinities to di-
carboxylates resulting from multiple hydrogen bonding
interactions. A significant fluorescence response of the sen-
sors took place through an intramolecular excimer emission
quenched by complexation. The preorganization of 1 and 2
permits two points binding with the guests on C3 and C24
receptive sites under the cooperation of bulky signal groups
on C7 and C12 to produce highly selective affinities to long-
chain terminal dicarboxylates. Sensors 1 and 2 exhibit high
sensitive response to long-chain dicarboxylates (n¼6 and 8)
and the strong binding between the host and the guest ren-
dered the detection of dicarboxylates possible even at the
concentration of 10ꢀ8 M. Sensors 1 and 2 are promising
fluorescent sensors for suberate and sebacate. The recogni-
tion characteristics of the novel hosts developed in this work
are established unambiguously by the combined UV, fluores-
Figure 5. The absorption of 1 with different amounts of suberate in CH3CN.
Inset: the change of the absorption of 1 at 280 nm.
(Supplementary data). In contrast, the characteristic peaks
at 326 and 343 nm ascribed to the pyrenyl group seem to
be intact. This strongly suggested that the pyrenyl groups
in the ground state had not been involved in the interaction
with dicarboxylates. According to the change of absorption
during the titrations, the complex association constants are
calculated and are listed in Tables 2 and 3. The values of
the association constants are comparable with those obtained
from the fluorescence titration experiments.
1
cence, and H NMR spectroscopic methods. In addition,
the moderate chiral recognition ability of the host was also
demonstrated.
4. Experimental
4.1. General methods
Melting point was determined with a MEL-TEMPII melt-
ing-point apparatus (uncorrected). IR spectra were obtained
on a Nicolet MAGNA-IR 550 spectrophotometer. 1H NMR
spectra were recorded in DMSO-d6 or CDCl3, with Me4Si as
the internal standard, on a JEOL EX270 spectrometer and
13C NMR spectra on a Varian INOVA-400 FT NMR spec-
trometer. High-resolution mass spectra were recorded on a
Bruker Autoflex mass spectrometer (MALDI-TOF) or Elec-
trospray ionization high-resolution mass spectra on an API
Figure 6. The absorption of 2 with different amounts of suberate in CH3CN.
Inset: the change of the absorption of 2 at 313 nm.

S.-Y. Liu et al. / Tetrahedron 62 (2006) 11687–11696
11693
Qstar Pulsari mass spectrometer (ESI-TOF). Infrared spectra
were recorded on MAGNA-IR 550 spectrometer. Absorption
spectra were recorded on a Hewlett Packard 8453 UV–
vis spectrophotometer. Fluorescent emission spectra were
collected on a Photon Technology International (PTI) at
293 K. CH2Cl2 and xylene were dried and distilled from
CaH2, and benzene was dried and distilled from Na
freshly. THF was distilled under nitrogen in the presence
of sodium chips using benzophenone ketyl as the indicator.
All other commercially available reagents were used as
received.
34.5, 33.0, 32.8, 31.6, 31.2, 31.0, 29.0, 27.5, 27.1, 27.0,
26.8, 25.6, 23.3, 22.8, 17.9, 12.5; MALDI TOF HRMS:
calcd for C65H69N3O6, 987.5186; found, 987.5204.
4.5. General procedure for the synthesis of 9 and 10
Activated zinc powder (0.65 mg, 10 mmol) was added to a
solution of 7 or 8 (0.5 mmol) in glacial acetic acid (10 mL).
The mixture was stirred vigorously for 24 h. Acetic acid was
then completely removed under reduced pressure by adding
toluene for several times. The residue, acetate ammonium
salt of 9 or 10, was dissolved by saturated sodium chloride
solution (10 mL). Basification of the solution by excessive
triethylamine and extraction of it by ethyl acetate gave
amine 9 or 10 as the pure product. After drying by sodium
sulfate and removal of organic solvent, compound 9 or 10
was obtained.
4.2. General procedure for the synthesis of 7 and 8
To a mixture solution of 4 (0.45 g, 1 mmol) in xylene/
CH2Cl2 (10:1, 5 mL) were added calcium hydride (0.63 g,
15 mmol) and benzyltriethylammonium chloride (0.01 g,
0.04 mmol), and the mixture was refluxed for 10 min under a
nitrogen atmosphere. To the refluxing solution was added
a solution of freshly prepared 1-pyrenoyl chloride or 1-
pyrenebutanoyl chloride (3 mmol) in xylene (10 mL) and
refluxed for 24 h. The reaction mixture was filtered under
reduced pressure, diluted with ethyl acetate, and washed
with aq NaHCO3. The organic layer was dried over anhy-
drous Na2SO4, and volatiles were removed.
4.6. Methyl 3a-amino-7a,12a-dipyrenylcarbonyl-5b-
cholan-24-oate (9)
Compound 9 was obtained as yellow foam (0.44 g, 99%):
mp 122–124 ꢄC; IR (KBr, cmꢀ1): 3437, 2949, 2912, 2876,
1735, 1704, 1632, 1607, 1456, 1446, 1389, 1255, 1231,
1
1193, 1145, 1133, 1086, 849, 721; H NMR (270 MHz,
CDCl3): d 3.54 (s, 3H), 5.47 (br, 1H), 5.68 (br, 1H), 7.26–
8.56 (m, 16H), 9.24–9.30 (m, 2H); MALDI TOF HRMS:
calcd for C59H59NO6 (M+H)+, 878.4420; found, 878.4405.
4.3. Methyl 3a-azide-7a,12a-dipyrenylcarbonyl-5b-
cholan-24-oate (7)
The crude product was chromatographed on silica gel (230–
400 mesh) eluting first with 25% ethyl acetate/petroleum
ether (60–80 ꢄC) and then with pure dichloromethane to give
the pure product (0.33 g, 37%): mp 130 ꢄC; IR (KBr, cmꢀ1):
3438, 2948, 2871, 2089, 1736, 1705, 1596, 1446, 1389,
4.7. Methyl 3a-amino-7a,12a-di(1-pyrenebutanoyl)-5b-
cholan-24-oate (10)
Compound 10 was obtained as yellow foam (0.43 g, 90%):
mp 100–104 ꢄC; IR (KBr, cmꢀ1): 3436, 2948, 2914, 2876,
1735, 1705, 1632, 1607, 1457, 1448, 1389, 1255, 1231,
1
1255, 1229, 1145, 1133, 849, 710; H NMR (270 MHz,
1
CDCl3): d 0.88 (s, 3H), 0.96 (d, J¼8.91 Hz, 3H), 1.11 (s,
3H), 3.03 (m, 1H), 3.52 (s, 3H), 5.48 (br, 1H), 5.70 (br,
1H), 7.58–8.61 (m, 16H), 9.16–9.57 (m, 2H); 13C NMR
(100 MHz, CDCl3): 174.2, 167.5, 167.0, 134.0, 133.9,
131.1, 131.0, 130.3, 130.2, 129.6, 129.4, 127.6, 127.4,
126.9, 126.1, 124.8, 124.6, 124.4, 124.1, 76.2, 71.5, 60.5,
51.4, 47.8, 45.6, 44.0, 41.5, 40.0, 38.7, 37.3, 35.4, 35.1,
34.8, 34.7, 31.7, 31.0, 30.7, 29.6, 29.0, 28.5, 27.4, 26.9,
25.9, 25.6, 24.5, 23.3, 22.8, 21.6, 17.9, 17.8, 17.2, 12.5;
MALDI TOF HRMS: calcd for C59H57N3O6 (M+H)+,
903.4247; found, 903.4218.
1197, 1140, 1132, 1086, 846, 725; H NMR (270 MHz,
CDCl3): d 3.12–3.30 (m, 4H), 3.48 (s, 3H), 4.86 (br, 1H),
5.05 (br, 1H), 7.61–8.08 (m, 18H); MALDI TOF
HRMS: calcd for C65H71NO6 (M+H)+, 962.5359; found,
962.5392.
4.8. General procedure for the synthesis of 11 and 12
The mixture of 9 or 10 (0.5 mmol) and hydrazine (1.0 mL,
large excess) monohydrate in a mixture solution of metha-
nol/CH2Cl2 (10 mL, 2:1) was stirred under nitrogen at ambi-
ent temperature for 48 h. Then organic solvent and the
excess of hydrazine were removed under reduced pressure.
The residue was poured into 30 mL cold water and stirred
for 10 min. After filtration, the solid was washed with large
amount of cold water and dried in vacuum at 60 ꢄC. The
product was obtained as a yellow solid.
4.4. Methyl 3a-azide-7a,12a-di(1-pyrenebutanoyl)-5b-
cholan-24-oate (8)
The crude product was chromatographed on silica gel (230–
400 mesh) eluting first with 20% ethyl acetate/petroleum
ether (60–80 ꢄC) and then for the second time with pure di-
chloromethane to give the pure product (0.34 g, 35%): mp
90 ꢄC; IR (KBr, cmꢀ1): 3442, 2953, 2865, 2089, 1727,
4.9. 1-Hydrazide 3a-amino-7a,12a-dipyrenylcarbonyl-
5b-cholan-24-oate (11)
1
1638, 1456, 1384, 1251, 1182, 1094, 844, 716; H NMR
(270 MHz, CDCl3): d 0.75 (s, 3H), 0.81 (d, 3H), 0.94 (s,
3H), 3.10–3.28 (m, 4H), 3.57 (s, 3H), 5.02 (br, 1H), 5.17
(br, 1H), 7.68–8.19 (m, 18H); 13C NMR (100 MHz, CDCl3):
174.7, 173.1, 173.0, 135.8, 135.7, 131.6, 131.1, 130.2, 130.1,
129.0, 128.9, 128.6, 127.7, 127.6, 127.4, 127.0, 126.1, 125.3,
125.2, 125.1, 125.0, 124.9, 123.5, 123.4, 75.6, 71.0, 60.9,
51.7, 47.8, 45.4, 43.7, 41.5, 38.2, 35.4, 35.0, 34.7, 34.6,
Compound 11 was obtained as a yellow solid in a 76%
yield (0.33 g) and need no further purification for the next
reaction: mp>166 ꢄC (decomposed); IR (KBr, cmꢀ1):
3430, 2921, 2876, 1702, 1625, 1389, 1250, 1231, 1194,
1145, 1133, 1086, 849, 705; H NMR (270 MHz, CDCl3):
d 3.72 (br, 4H), 5.46 (br, 1H), 5.67 (br, 1H), 6.55 (br, 1H),
7.60–8.55 (m, 16H), 9.24–9.30 (m, 2H); MALDI TOF
1

11694
S.-Y. Liu et al. / Tetrahedron 62 (2006) 11687–11696
HRMS: calcd for C58H59N3O5 (M+H)+, 878.4532; found,
878.4519.
133.0, 131.2, 131.1, 131.0, 129.9, 129.8, 128.5, 127.7,
127.6, 127.3, 127.2, 127.0, 126.8, 126.7, 126.5, 126.1,
126.0, 125.2, 125.0, 124.9, 124.8, 124.7, 124.5, 124.3,
122.8, 116.9, 76.7, 75.4, 55.1, 47.3, 45.2, 43.4, 41.2, 37.9,
35.6, 35.2, 34.6, 34.5, 34.1, 32.3, 31.5, 31.1, 29.7, 29.0,
27.5, 27.2, 26.4, 25.4, 22.9, 22.6, 17.6, 12.2; MALDI TOF
HRMS: calcd for C80H79F6N5O5S2 (M+H)+, 1368.5505;
found, 1368.5400.
4.10. 1-Hydrazide 3a-amino-7a,12a-di(10-pyrenebuta-
noyl)-5b-cholan-24-oate (12)
Compound 12 was obtained as a yellow solid in a 80% yield
(0.38 g) and need no further purification for the next reaction:
mp>140 ꢄC (decomposed); IR (KBr, cmꢀ1): 3418, 2933,
2864, 1722, 1645, 1622, 1456, 1379, 1249, 1183, 1143,
4.13. Methyl 3a-acetyl-7a,12a-dipyrenylcarbonyl-5b-
cholan-24-oate (3)
1
1016, 844, 705; H NMR (270 MHz, CDCl3): d 3.26 (m,
4H), 3.70 (br, 4H), 4.97 (br, 1H), 5.14 (br, 1H), 6.35 (br,
1H), 7.72–8.19 (m, 18H); MALDI TOF HRMS: calcd for
C64H71N3O5 (M+H)+, 962.5471; found, 962.5495.
To a mixture solution of methyl 3a-acetyl-7a,12a-di-
hydroxy-5b-cholan-24-oate (0.46 g, 1 mmol) in xylene/
CH2Cl2 (10:1, 5 mL) were added calcium hydride (0.63 g,
15 mmol) and benzyltriethylammonium chloride (0.01 g,
0.04 mmol), and the mixture was refluxed for 10 min under
a nitrogen atmosphere. To the refluxing solution was added a
solution of freshly prepared 1-pyrenoyl chloride (0.79 g,
3 mmol) in xylene (10 mL) and refluxed for 24 h. The reac-
tion mixturewas filtered under reduced pressure, diluted with
ethyl acetate, and washed with aq NaHCO3. The organic
layer was dried over anhydrous Na2SO4, and volatiles were
removed. The crude product was chromatographed on silica
gel (230–400 mesh) eluting first with 10% ethyl acetate/
petroleum ether (60–80 ꢄC) and then for the second timewith
pure dichloromethane to give the pure product (0.25 g,
26%): mp 114–116 ꢄC; IR (KBr, cmꢀ1): 3446, 3042, 2932,
2873, 1735, 1705, 1559, 1449, 1393, 1254, 1231, 1145,
4.11. 1-[(40-Trifluoromethylphenyl)thioureido]hydra-
zide 3a-[(40-trifluoromethylphenyl)thioureido]-7a,12a-
dipyrenylcarbonyl-5b-cholan-24-oate (1)
To a solution of 11 (0.26 g, 0.3 mmol) in dried CH2Cl2
(10 mL), 4-trifluoromethylphenylisocyanate (0.15 g, 0.7 mmol)
was added and stirred at room temperature for 36 h under ni-
trogen. The reaction mixture was diluted with CH2Cl2. The
organic solution was first washed by saturated brine and then
dried by anhydrous sodium sulfate. Purification of the crude
by preparative TLC plate (SiO2) eluted by the solvent of
ethyl acetate/dichloromethane (20:100) gave the pure
product 1 as a yellow solid (0.20 g, 52%): mp 164–166 ꢄC;
IR (KBr, cmꢀ1): 3394, 2938, 2865, 1706, 1622, 1520,
1
1
1324, 1257, 1232, 1166, 1125, 1066, 850, 705; H NMR
1133, 1087, 1045, 848, 712; H NMR (270 MHz, CDCl3):
(270 MHz, DMSO-d6): d 0.81 (d, J¼8.1 Hz, 3H), 3.86 (m,
1H), 5.39 (br, 1H), 5.57 (br, H), 7.33–8.49 (m, 26H), 9.04–
9.25 (m, 4H), 9.70 (br, 1H); 13C NMR (100 MHz, DMSO-
d6): 179.0, 170.1, 170.0, 148.5, 134.1, 133.6, 133.4, 133.2,
130.9, 130.5, 130.1, 130.0, 129.8, 129.7, 129.6, 128.3,
127.6, 127.3, 127.1, 1265.8, 126.7, 126.4, 125.2, 124.6,
124.0, 123.3, 123.0, 121.1, 116.6, 76.3, 72.2, 53.9, 47.9,
45.2, 43.6, 41.1, 40.1, 37.7, 35.4, 34.5, 34.1, 31.3, 30.1,
28.8, 26.8, 26.3, 25.3, 23.6, 22.8, 22.5, 20.3, 17.7, 17.0,
12.1; ESI TOF HRMS: calcd for C74H67F6N5O5S2Na
(M+Na)+, 1306.4385; found, 1306.4436.
d 0.85 (s, 3H), 1.01 (d, J¼6.48 Hz, 3H), 1.11 (s, 3H), 3.54
(s, 3H), 4.55 (m, 1H), 5.47 (br, 1H), 5.72 (br, 1H), 7.26–
8.53 (m, 16H), 9.20–9.30 (m, 2H); 13C NMR (100 MHz,
CDCl3): 174.4, 170.4, 168.2, 168.0, 167.5, 133.9, 133.7,
133.5, 130.9, 130.8, 130.7, 130.2, 130.0, 129.5, 129.4,
129.2, 129.1, 128.9, 128.7, 127.6, 127.4, 127.2, 127.1,
127.0, 126.9, 126.8, 126.4, 126.3, 126.2, 126.0, 125.9,
125.4, 125.0, 124.8, 124.6, 124.4, 124.1, 123.7, 74.8, 74.3,
73.5, 72.0, 71.8, 68.2, 51.4, 47.9, 47.8, 46.7, 45.6, 44.0,
41.2, 41.0, 38.7, 34.8, 34.7, 34.6, 31.6, 31.5, 31.0, 30.7,
29.7, 28.2, 27.2, 26.9, 26.7, 25.9, 25.8, 23.2, 22.5,
22.4, 21.1, 17.8, 12.4; MALDI TOF HRMS: calcd for
C61H60O8Na (M+Na)+, 943.418; found, 943.4147.
4.12. 1-[(40-Trifluoromethylphenyl)thioureido]hydra-
zide 3a-[(40-trifluoromethylphenyl)thioureido]-7a,12a-
di(10-pyrenebutanoyl)-5b-cholan-24-oate (2)
4.14. Binding experiments
To a solution of 12 (0.29 g, 0.3 mmol) in dried CH2Cl2
(10 mL), 4-trifluoromethylphenylisocyanate (0.15 g, 0.7 mmol)
was added and stirred at room temperature for 36 h under
nitrogen. The reaction mixture was diluted with CH2Cl2.
The organic solution was first washed by saturated brine
and then dried by anhydrous sodium sulfate. Purification
of the crude by preparative TLC plate (SiO2) eluted by the
solvent of ethyl acetate/dichloromethane (10:100) gave the
pure product 2 as a yellow solid (0.20 g, 29%): mp 138–
140 ꢄC; IR (KBr, cmꢀ1): 3430, 3274, 2953, 2865, 1720,
1617, 1549, 1524, 1324, 1249, 1165, 1122, 1067, 850,
All dicarboxylate anions were obtained from the respective
dicarboxylic acid treated with 2.0 equiv of tetrabutylammo-
nium hydroxide in CH3OH and dried in vacuum at 60 ꢄC for
over night. The structures of these guest anions were verified
by 1H NMR.
All the host compounds 1, 2, and 3 were prepared as
2w5ꢂ10ꢀ4 mol/L stock solutions in acetonitrile. All anions
used in this report were in the form of tetrabutylammonium
salt. They were prepared to approximate 0.01 mol/L and
2w5ꢂ10ꢀ3 mol/L of stock solutions in acetonitrile. The
work solutions were prepared by adding different volumes
of anion stock solution to a series of test tubes followed by
dilution to 5 mL by acetonitrile. Then, the same amount of
stock solution of the host compound was added into each
of the test tube. After shaking for several minutes, the work
solutions could be measured immediately.
1
724; H NMR (400 MHz, CDCl3): d 0.69 (s, 3H), 0.78 (d,
J¼4.1 Hz, 3H), 0.96 (s, 3H), 3.0–3.26 (m, 4H), 4.00 (br,
1H), 5.06 (br, 1H), 5.19 (br, 1H), 6.49 (br, 1H), 6.61 (br,
1H), 7.00 (br, 1H), 7.48–8.24 (m, 18H), 8.87 (br, 1H), 9.82
(br, 1H); 13C NMR (100 MHz, CDCl3): 182.9, 178.9,
172.6, 172.3, 170.5, 140.9, 139.6, 136.5, 135.0, 134.8,

S.-Y. Liu et al. / Tetrahedron 62 (2006) 11687–11696
11695
3. Voet, D.; Voet, J. G. Biochemistry, 2nd ed.; Wiley: New York,
NY, 1995.
4. (a) Nohta, H.; Sonoda, J.; Yoshida, H.; Satozono, H.; Ishida, J.;
Yamaguchi, M. J. Chromatogr., A 2003, 1010, 37–44; (b) Miao,
H.; Rubakhin, S. S.; Sweedler, J. V. Anal. Chem. 2005, 77,
7190–7194.
5. (a) Cordek, J.; Wang, X.; Tan, W. Anal. Chem. 1999, 71, 1529–
1533; (b) Rossi, S.; Kyne, G. M.; Turner, D. L.; Wells, N. J.;
Kilburn, J. D. Angew. Chem., Int. Ed. 2002, 41, 4233–4236.
6. (a) Fabbrizzi, L.; Licchelli, M.; Rabaioli, M. G.; Tagllietai, A.
Coord. Chem. Rev. 2000, 205, 85–108; (b) Amendola, V.;
Boiocchi, M.; Fabbrizzi, L.; Palchetti, A. Chem.—Eur. J.
2005, 11, 5648–5660; (c) Qing, G.-Y.; He, Y.-B.; Zhao, Y.;
Hu, C.-G.; Liu, S.-Y.; Yang, X. Eur. J. Org. Chem. 2006,
1574–1580.
Association constants (1:1) of 1 and 2 with anions are
calculated by non-linear least square curve fitting using the
following equation in origin 7.0:
n
ꢀ
X ¼ X0 þ 0:5D3 cH þ cG þ 1=Kass ꢀ ðcH þ cG
o
ꢁ
1=2
2
þ 1=KassÞ ꢀ4cHcG
Association constants (1:2) of 1 and 2 with anions are calcu-
lated by Benesi–Hildebrand equation and linearly fitted in
origin 7.0:
log½ðX ꢀ X0Þ=ðXN ꢀ XÞꢅ ¼ nlog½Gꢅ þ log Ka
X0: fluorescent intensity or absorption of host without an-
ions; X: fluorescent intensity or absorption reaching a limita-
tion by adding excessive anions; cH: concentration of host
molecule; cG: concentration of anions added.
´
7. (a) Martınez-Manez, R.; Sancenon, F. Chem. Rev. 2003, 103,
4419–4476; (b) Pu, L. Chem. Rev. 2004, 104, 1687–1716;
ꢀ˜
ꢀ
ꢀ
(c) Vazquez, M.; Fabbrizzi, L.; Taglietti, A.; Pedrido, R. M.;
ꢀ
Gonzalez-Noya, A. M.; Bermejo, M. Angew. Chem., Int. Ed.
2004, 43, 1962–1965; (d) Gunnlaugsson, T.; Kruger, P. E.;
Jensen, P.; Tierney, J. J. Org. Chem. 2005, 70, 10875–
10878; (e) Peng, X.; Wu, Y.; Tian, M.; Han, K. J. Org.
Chem. 2005, 70, 10524–10531; (f) Ragusa, A.; Rossi, S.;
Hayes, J. M.; Stein, M.; Kilburn, J. D. Chem.–Eur. J. 2005,
11, 5674–5688.
Acknowledgements
The financial support of the work by grants from the Univer-
sity Grants Committee of the Hong Kong Special Adminis-
trative Region, China (AoE/P-10/01), and from the Hong
Kong Baptist University (FRG/04-05/II-18) is acknowl-
edged.
8. Hosseini, M. W.; Lehn, J.-M. Helv. Chim. Acta 1986, 69, 587–
603.
ꢀ
9. (a) Lara, K. O.; Godoy-Alcantar, C.; Rivera, I. L.; Eliseev,
A. V.; Yatsimirsky, A. K. J. Phys. Org. Chem. 2001, 14, 453–
462; (b) Boiocchi, M.; Bonizzoni, M.; Fabbrizzi, L.; Piovani,
G.; Taglietti, A. Angew. Chem., Int. Ed. 2004, 43, 3847–
3852; (c) Bonizzoni, M.; Fabbrizzi, L.; Piovani, G.; Taglietti,
A. Tetrahedron 2004, 60, 11159–11162.
Supplementary data
Synthesis and characterization spectra of 1 and 2, the
fluorometric titration experiment and the H NMR study,
the fluorescence intensity of 1 and 2 with different concen-
tration in CH3CN, Job plot of 1 and 2 with dicarboxylates.
Supplementary data associated with this article can be found
in the online version, at doi:10.1016/j.tet.2006.09.042.
1
ꢀ
10. Kral, V.; Andrievsky, A.; Sessler, J. L. J. Am. Chem. Soc. 1995,
117, 2953–2954.
11. Liu, S.-Y.; He, Y.-B.; Wu, J.-L.; Wei, L.-H.; Qin, H.-J.; Meng,
L.-Z.; Hu, L. Org. Biomol. Chem. 2004, 2, 1582–1586.
12. Gunnlaugsson, T.; Davis, A. P. Org. Lett. 2002, 4, 2449–
2452.
References and notes
13. (a) Zeng, Z.-Y.; He, Y.-B.; Wu, J.-L.; Wei, L.-H.; Liu, X.;
Meng, L.-Z.; Yang, X. Eur. J. Org. Chem. 2004, 2888–2893;
(b) Wu, J.-L.; He, Y.-B.; Zeng, Z.-Y.; Wei, L.-H.; Meng, Z.;
Yang, T.-X. Tetrahedron 2004, 60, 4309–4314.
14. Mei, M.; Wu, S. New J. Chem. 2001, 25, 471–475.
15. (a) Davis, A. P.; Joos, J. B. Coord. Chem. Rev. 2003, 240, 143–
1. (a) Schmidtchen, F. P.; Berger, M. Chem. Rev. 1997, 97,
1609–1646; (b) Beer, P. D.; Gale, P. A. Angew. Chem.,
Int. Ed. 2001, 40, 486–516; (c) Best, M. D.; Tobey, S. L.;
Anslyn, E. V. Coord. Chem. Rev. 2003, 240, 3–15; (d)
Supramolecular Chemistry of Anions; Bianchi, A., Bowman-
ꢀ
156; (b) Lawless, L. J.; Blackburn, A. G.; Ayling, A. J.; Perez-
Payan, M.; Davis, A. P. J. Chem. Soc., Perkin Trans. 1 2001,
ꢀ
´
James, K., Garcıa-Espan˜a, E., Eds.; Wiley-VCH: New York,
NY, 1997.
1329–1341; (c) Vijayalakshmi, N.; Maitra, U. Org. Lett.
2005, 7, 2727–2730; (d) Sisson, A. L.; Clare, J. P.; Davis,
A. P. Chem. Commun. 2005, 5263–5265.
2. (a) Shin-ichi, S.; Masaaki, M.; Koichiro, N.; Yoshito, T. J. Org.
Chem. 2000, 65, 275–289; (b) Sessler, J. L.; Davis, J. M. Acc.
Chem. Res. 2001, 34, 989–997; (c) Amendola, V.; Fabbrizzi, L.;
Monzani, E. Chem.—Eur. J. 2004, 10, 76–82; (d) Kristln, B. J.
Acc. Chem. Res. 2005, 38, 671–678; (e) Myiaji, H.; Kim, K. H.;
Sim, E. K.; Lee, C. K.; Cho, W. S.; Sessler, J. L.; Lee, C. H.
J. Am. Chem. Soc. 2005, 127, 12510–12512; (f) Sessler,
J. L.; Cho, W.-S.; Gross, D. E.; Shriver, D. E.; Lynch,
V. M.; Marquez, M. J. Org. Chem. 2005, 70, 5982–5986;
(g) Chmielewski, M. J.; Jurczak, J. Chem.—Eur. J. 2005,
11, 6080–6094; (h) Juewen, L.; Yi, L. Angew. Chem., Int.
Ed. 2006, 45, 90–94; (i) Massimiliano, T.; Salvatore, S.;
Andrew, P. W.; Francisco, M. R. J. Org. Chem. 2006, 71,
16. Liu, S.-Y.; Fang, L.; He, Y.-B.; Chan, W.-H.; Yeung, K.-T.;
Cheng, Y.-K.; Yang, R.-H. Org. Lett. 2005, 7, 5825–5828.
17. (a) Birks, J. B. Photophysics of Aromatic Molecules; Wiley-
Interscience: London, 1970; (b) Winnik, F. M. Chem. Rev.
1993, 93, 587–614; (c) Seiichi, N.; Yuichi, K.; Norio, T.
J. Am. Chem. Soc. 1999, 121, 9463–9464; (d) Akimitsu, O.;
Keiichiro, K.; Isao, S. J. Am. Chem. Soc. 2004, 126, 4820–
4827; (e) Vyacheslav, V. F.; Erik, B. P. J. Am. Chem. Soc.
2005, 127, 14849–14858.
18. Potluri, V. K.; Maitra, U. J. Org. Chem. 2000, 65, 7764–7769.
ꢀ
19. Davis, A. P.; Perez, P. M. N. Synlett 1999, 991–993.
20. Lee, S. H.; Kim, S. H.; Kim, S. K.; Jung, J. H.; Kim, J. S. J. Org.
Chem. 2005, 70, 9288–9295.
ꢀ
744–753; (j) Nieto, S.; Perez, J.; Riera, L.; Riera, V.;
Miguel, D. Chem.—Eur. J. 2006, 12, 2244–2251.

11696
S.-Y. Liu et al. / Tetrahedron 62 (2006) 11687–11696
21. (a) Job, A. Ann. De Chim. (Paris) 1928, 9, 133–157; (b)
Nishizawa, S.; Kato, R.; Hayashita, T.; Teramae, N. Anal.
Sci. 1998, 14, 595–597.
22. Fang, L.; Chan, W.-H.; He, Y.-B.; Kwong, D. W. J.; Lee,
A. W. M. J. Org. Chem. 2005, 70, 7640–7646.
23. Valeur, B.; Pouget, J.; Bourson, J. J. Phys. Chem. 1992, 96,
6545–6549.
24. (a) Bernard, V. Molecular Fluorescence: Principles and Appli-
cations; Wiley-VCH: Weinheim, Germany, 2002; (b) Wu,
F. Y.; Li, Z.; Wen, Z. C.; Zhou, N.; Zhao, Y. F.; Jiang, Y. B.
Org. Lett. 2002, 4, 3203–3205.
25. (a) Pocker, Y.; Ciula, J. C. J. Am. Chem. Soc. 1989, 111, 4728–
4753; (b) Bourson, J.; Pouget, J.; Valeur, B. J. Phys. Chem.
1993, 97, 4552–4557.