Tetrahedron Letters 52 (2011) 51925195

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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet

A new macrocyclic anion receptor utilizing amide, amine,

and 9-anthracenyl hydrogens
Sung Kyu Lee, Jongmin Kang
Department of Chemistry, Institute for Chemical Biology, Sejong University, Seoul 143-747, Republic of Korea

a r t i c l e

i n f o

a b s t r a c t

Article history:
Received 14 June 2011
Revised 26 July 2011
Accepted 3 August 2011
Available online 8 August 2011

We have developed a new macrocyclic anion receptor 2 utilizing two amide hydrogens, two amine hydrogens and 9-anthracenyl hydrogen to bind anions. As the binding cavity formed from these hydrogens is preorganized and its size is different from that of the previously reported receptor 1 due to its cyclization, the
afnity of the receptor 2 for the anion is somewhat different from that of the receptor 1. The receptor 2 binds
anions through hydrogen bonds with a selectivity of H2 PO4 > CH3 CO2 > F > C6 H5 CO2 > Cl > Br > I
while the receptor 1 binds anions with a selectivity of CH3 CO2 > H2 PO4 > C6 H5 CO2 > HSO4 > ClO4 >
NO3 .
2011 Published by Elsevier Ltd.

Keywords:
Macrocyclic anion receptor
Amide
Amine

biological, medical, environmental, and chemical sciences.1 In this

regard, macrocyclic polyamine2 and polyamide3 have drawn

The recognition and sensing of anions have become the focus of

considerable attention because anions play an important role in
O
NH HN

NO2

NH HN

NO2

NH2

NH2

Et3N
Br

Br

Br

Br

NH

HN

3/ NaHCO3
DMF

Methylene chloride

NH

HN

NH

HN

4
2
Scheme 1. The synthetic procedure for the anion receptor 2.

Corresponding author.
E-mail address: kangjm@sejong.ac.kr (J. Kang).
0040-4039/$ - see front matter 2011 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2011.08.022

S. K. Lee, J. Kang / Tetrahedron Letters 52 (2011) 51925195

Figure 1. The change of uorescence spectra over the course of titration of 40 lM

DMSO solutions of the receptor 2 when tetrabutylammonium dihydrogen phosphate was added.

Figure 2. The Job plots of receptor 2 with tetrabutylammonium dihydrogen

phosphate, tetrabutylammonium acetate and tetrabutylammonium chloride using
1
H NMR in DMSO-d6.

particular attention, as amide and amines are the most biologically

relevant groups.4 Therefore, incorporation of both amine and amide
as anion binding moiety has been a successful approach in designing

5193

Figure 4. The change of uorescence spectra over the course of titration of 40 lM

DMSO solutions of the receptor 2 when tetrabutylammonium acetate was added.

articial anion receptor.5 This strategy was also utilized by us on a

novel colorimetric receptor 1, which has two amide hydrogens
and two amine hydrogens anchored at 1,8-position of anthracene.
The receptor 1 was found to be a selective receptor for acetate and
dihydrogen phosphate and good naked eye detector for uoride
and pyrophosphate.6 As an extension of our work, we have designed
a new receptor 2. The new receptor 2 is macrocyclic version of the
receptor 1 and forms 18-membered ring. We expected delicate
change of conformation from the receptor 1 due to cyclization would
give change of anion selectivity. From the binding studies with uorescence spectra and 1H NMR, the receptor 2 was found to be a selective receptor for dihydrogen phosphate. In addition, the receptor 2
showed afnity for halides while the receptor 1 did not show any
afnity for halides.
The synthesis of the receptor 2 started from the reaction
between 1,8-diaminoanthracene 37 and bromoacetyl bromide,
which gave the compound 4 in 81% yields. Then the compound 4
was reacted with 1,8-diaminoanthracene again to give the desired
compound 2 in 52% yields8 (Scheme 1).
The receptor 2 displayed strong uorescence emission in DMSO
as shown in Figure 1. The excitation and emission wavelengths

Figure 3. 1H NMR spectra of 2 mM of 2 with increased amounts of tetrabutylammonium dihydrogen phosphate (03 equiv) in DMSO-d6.

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S. K. Lee, J. Kang / Tetrahedron Letters 52 (2011) 51925195

Figure 5. 1H NMR spectra of 2 mM of 2 with increased amounts of tetrabutylammonium acetate (04.5 equiv) in DMSO-d6.

were 392 and 484 nm, respectively. The association between the
receptor 2 and dihydrogen phosphate was investigated rst by uorescence titration. The intensity of emission spectrum from 40 lM
solution of the receptor 2 gradually decreased as the concentration
of tetrabutylammonium dihydrogen phosphate salts was increased
(18 equiv), which indicates the association between the receptor 2
and dihydrogen phosphate. The uorescence quenching effect was
possibly due to the photo-induced electron transfer (PET) process
between the anthracene moiety and the binding site.
The stoichiometry between the receptor 2 and dihydrogen
phosphate was determined by Job plot using 1H NMR, which
showed evident 1:1 stoichiometry (Fig. 2).9
A BenesiHildebrand plot10 by use of change at 484 nm in uorescence spectrum gave the association constants. From the experiments, the receptor 2 showed association constant 6.3  103 for
dihydrogen phosphate in DMSO.
This phenomenon could be conrmed by a 1H NMR titration. In
DMSO-d6, both amide NH hydrogen peak and amine NH hydrogen peak of receptor 2 showed downeld shifts upon addition of
dihydrogen phosphate ion. For example, the amide peak of the
receptor 2 appearing at 9.98 ppm showed downeld shift until
10.97 ppm and amine peak of the receptor 2 appearing at
7.0 ppm showed downeld shift until 8.42 ppm, indicating that
both amide and amine participate in the binding event through
hydrogen bonds. In addition, 9-H of the anthracene moiety appearing at 9.56 and 9.13 ppm showed downeld shift until 9.98 and
9.53 ppm, respectively, indicating that 9-H of anthracene moiety
also participates in hydrogen bonding with dihydrogen phosphate
(Fig. 3).
Many examples of receptors in which aromatic hydrogens participate in hydrogen bonding with anions have been reported.11
For titration, amide NH peak was used. Analysis of chemical shift
utilizing EQNMR12 gave the association constant of 5.8  103 M 1,
which is similar to the values obtained from uorescence
titrations.
With tetrabutylammonium acetate, a similar phenomenon was
observed. In uorescence titration, the intensity of emission spectrum from 40 lM solution of the receptor 2 gradually decreased as
the concentration of tetrabutylammonium acetate salts was
increased (Fig. 4) and Job plot showed 1:1 stoichiometry again. In

Table 1
The association constants (M

a
b

) of the receptor 2 with various anions in DMSO

Anion

Fluorescence (Ka)

NMR (Ka)

H2 PO4
HSO4
ClO4
CH3 CO2
PhCO2
NO3
F
Cl
Br
I

6.3  103
nbb
nb
3.3  103
9.0  102
nb
2.0  103
5.7  102
8.0  10
5.0  10

5.8  103a

3.1  103

1.1  103

Errors are less than 10%.

No binding.

Figure 6. Fluorescence quench ratio (I0 I)/I0 of the compound 2 (40 lM) with
various anions (n-Bu4N+ salts, 3 equiv) in DMSO at kex = 392 nm and kem = 484 nm.

addition, amide NH hydrogen, amine NH hydrogen and 9-H of

the anthracene moiety showed downeld shifts again (Fig. 5). From
these experiments, association constants for acetate were calculated
as 3.3  103 and 3.1  103 from the uorescence titration and 1H
NMR titrations, respectively.

S. K. Lee, J. Kang / Tetrahedron Letters 52 (2011) 51925195

5195

Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.08.022.
References and notes

Figure 7. The energy-minimized structure of receptor 2 and uoride (Cache 3.2

MOPAC calculation).

We also investigated association constants of other anions. The

results are summarized in Table 1. Among the anions investigated,
the receptor 2 showed good selectivity for dihydrogen phosphate.
The uorescence intensity changes were the most signicant with
dihydrogen phosphate (Fig. 6). From modeling, two hydrogens
from one amide and one amine in the receptor 2 bind one of two
oxygens in dihydrogen phosphate. The energy-minimized structure of receptor 2 and dihydrogen phosphate is shown in Figure
7 (Cache 3.2 MOPAC calculation). From modeling, the distance
between the NH hydrogens and oxygen in dihydrogen phosphate
fell in the range 2.092.22 .
However, among the anions with same geometry, the association constants simply reected basicities of anions. When we compare the receptors 1 and 2, both receptors showed strong
association with dihydrogen phosphate and acetate which have
strong basicity. However, the macrocyclic receptor 2 showed
stronger afnity for dihydrogen phosphate than acetate while the
receptor 1 showed stronger afnity for acetate than dihydrogen
phosphate. Probably the macrocyclic receptor 2 has more preorganized structure to accept dihydrogen phosphate than acetate. In
addition, while the receptor 1 did not show any afnity for halides,
the receptor 2 showed afnity for halides as the binding cavity of
the receptor 2 is smaller than the receptor 1 due to its cyclic
structure.
In summary, we have developed a new macrocyclic anion receptor 2 utilizing two amide hydrogens, two amine hydrogens and 9anthracenyl hydrogen to bind anions. As the binding cavity formed
from these hydrogens is preorganized and its size is different from
that of the receptor 1 due to its cyclization, the selectivity of the
receptor 2 for the anion is somewhat different from that of the receptor 1. The receptor 2 binds anions through hydrogen bonds with a
selectivity of H2 PO4 > CH3 CO2 > F > C6 H5 CO2 > Cl > Br > I
while the receptor 1 binds anions with a selectivity of CH3 CO2 >
H2 PO4 > C6 H5 CO2 > HSO4 > ClO4 > NO3 .
Acknowledgment
This research was supported by Basic Science Research Program
through the National Research Foundation of Korea (NRF) funded
by the Ministry of Education, Science and Technology (20100021333).

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