Li+ selective podand-type fluoroionophore based on a diphenyl sulfoxide derivative bearing two pyrene groups

Article abstract of DOI:10.3390/molecules16086844

New podand-type fluoroionophores having two pyrene moieties: 2,2′-bis(1-pyrenylacetyloxy)diphenyl sulfide (3), 2,2-bis(1- pyrenylacetyloxy)diphenyl sulfoxide (4), and 2,2-bis(1-pyrenylacetyloxy) diphenyl sulfone (5), have been synthesized by connecting two 1-pyrenecarbonylmethyl groups with the two hydroxy groups of 2,2-dihydroxydiphenyl sulfide, sulfoxide, and sulfone, respectively. Their complexation behavior toward alkali metal ions was examined by fluorescence spectroscopy. Among these fluoroionophores, compound 4, having a sulfinyl group, showed high selectivity toward Li⁺.

Full text of DOI:10.3390/molecules16086844

Molecules 2011, 16, 6844-6857; doi:10.3390/molecules16086844
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Li+ Selective Podand-Type Fluoroionophore Based on a
Diphenyl Sulfoxide Derivative Bearing Two Pyrene Groups
Yukihiro Nishimura 1,*, Tetsuo Takemura 2 and Sadao Arai 1
1
Department of Chemistry, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku,
Tokyo 160-8402, Japan; E-Mail: s-arai@tokyo-med.ac.jp
2
Department of Chemistry, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku,
Tokyo 162-8601, Japan; E-Mail: ttakemur@rs.kagu.tus.ac.jp
* Author to whom correspondence should be addressed; E-Mail: izumidai@tokyo-med.ac.jp;
Tel.: +81-3-3351-9069; Fax: +81-3-3351-9069.
Received: 11 July 2011; in revised form: 28 July 2011 / Accepted: 8 August 2011 /
Published: 10 August 2011
Abstract: New podand-type fluoroionophores having two pyrene moieties:
2,2´-bis(1-pyrenylacetyloxy)diphenyl sulfide (3), 2,2´-bis(1-pyrenylacetyloxy)diphenyl
sulfoxide (4), and 2,2´-bis(1-pyrenylacetyloxy)diphenyl sulfone (5), have been synthesized
by connecting two 1-pyrenecarbonylmethyl groups with the two hydroxy groups of
2,2´-dihydroxydiphenyl sulfide, sulfoxide, and sulfone, respectively. Their complexation
behavior toward alkali metal ions was examined by fluorescence spectroscopy. Among
these fluoroionophores, compound 4, having a sulfinyl group, showed high selectivity
toward Li+.
Keywords: fluoroionophore; podand; pyrene; fluorescence; lithium ion
1. Introduction
Design and synthesis of fluoroionophores for metal ions is a vigorous research area [1-6]. These
fluoroionophores have an ion recognition unit (such as a crown ether, calixarene or thiacalixarene) and
a fluorophore unit (such as dansyl, anthracenyl, and pyrenyl groups) connected by appropriate linkers.
When the ion recognition unit interacts with the target metal ions, chemical signals, such as absorbance
or fluorescence intensities, are typically generated or attenuated in the fluorophore unit.

Molecules 2011, 16
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Among alkali metal ions a number of fluoroionophores for Na+ and K+ have been reported because
these ions play particular roles in the regulation of many biological events. [7-9]. We have previously
reported a p-tert-butylcalix[4]arene derivative which is connected with p-tert-butylcalix[4]arene and
pyrene by a CH2CO linker [10]. This derivative shows an increase of pyrene monomer emission
and a decrease of pyrene excimer emission with increased Na+ concentration. Subsequently, we
have synthesized podand-type fluoroionophores, with two pyrene units 1 and 2 using
2,2´-dihydroxydiphenylmethane as a precursor of calix[4]arene and 2,2´-dihydroxydiphenyl ether,
respectively, and examined the binding abilities toward alkali metal ions [11]. Although 1 has only
slight affinity for alkali metal ions, 2 has good sensitivity for Na+ showing an increase of pyrene
mononer emission and a decrease of pyrene excimer emission with increased Na+ ion. The oxygen
atom between two phenyl groups in fluoroionophore 2 was found to play a crucial role in binding Na+.
This observation led us to construct novel podand-type fluoroionophores in which the oxygen atom
between the two phenyl groups in 2 is replaced by different types of atoms with binding abilities for
alkali metal ions other than Na+.
Fluoroionophores for Li+ have been developed recently with regard to their medical and clinical
applications for the treatment of manic-depressive psychosis [12-14]. However, relatively few studies
concerning fluoroionophores for Li+ have been reported compared with those for Na+ and K+. Here, we
report the synthesis of novel podand-type compounds 3–5 (Figure 1) having two pyrene units as a
fluorophore unit and a sulfur atom, sulfinyl group, or sulfonyl group as a binding site. Binding studies
of compounds 3–5 toward alkali metal ions (Li+, Na+, K+, Rb+, Cs+) have shown that compound 4,
which has a sulfinyl group, has a good binding ability for Li +.
Figure 1. Fluoroionophores 1, 2 and novel compounds 3, 4, and 5.
O
O
O
O
1: X = CH2
2 : X = O
X
3 : X = S
4 : X = SO
5 : X = SO2
2. Results and Discussion
The fluoroionophores 3–5 were synthesized by connecting two 1-pyrenecarbonylmethyl groups
with the two hydroxy groups of 2,2´-dihydroxydiphenyl sulfide, sulfoxide, or sulfone, respectively
(Scheme 1). First, 2,2´-dihydroxydiphenyl sulfoxide 6, sulfide 7, and sulfone 8 were synthesized using
4-bromophenol as a starting material according to a reported procedure [15]. Then, compounds 3, 4,
and 5, with two pyrene units, were synthesized by the reaction of 7, 6, and 8, respectively, with two
equivalents of 1-(bromoacetyl)pyrene in the presence of potassium carbonate in acetonitrile.
Furthermore, compounds 9, 10, and 11, with one pyrene unit, were synthesized as reference
compounds by the reaction of 7, 6, and 8, respectively, with one equivalent of 1-(bromoacetyl)pyrene

Molecules 2011, 16
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in the presence of sodium methoxide in acetonitrile. The structures of all the new fluoroionophores
were determined by FAB MS and NMR spectra.
Scheme 1. Synthetic routes of compounds 3, 4, and 5, with two pyrene units, and 9, 10,
and 11, with one pyrene unit.
OH
OH
OH
OH
OH
SO
SO
SOCl2 ,
AlCl3
Zn
ClCH2CH2Cl
KOH aq.
6
Br
Br
Br
CH3COOH
OH
Zn
OH
OH
OH
SO2
S
30 % H2O2
CH3COOH
8
7
COCH2Br
O
O
O
O
K2CO3, CH3CN
COCH2Br
OH
OH
X
3 : X = S
X
4 : X = SO
5 : X = SO2
7 : X = S
6 : X = SO
8 : X = SO2
O
O
NaOCH3, CH3CN
OH
X
9 : X = S
10 : X = SO
11 : X = SO2
Figure 2 shows the UV-Vis spectra of 10.0 µM chloroform solutions of compounds 3, 4, and 5. The
difference of binding site X does not significantly modify the absorption spectra, characterized by an
absorption maximum (λmax) at 366 nm and a shoulder at 393 nm.

Molecules 2011, 16
Figure 2. UV-Vis spectra of 3, 4, and 5 (10.0 µM in chloroform).
6847
Figure 3 shows the fluorescence spectra of 1.0 µM chloroform solutions of compounds 3, 4, and 5
under excitation at 360 nm. The pyrene monomer emission of compound 3 appeared at 380–440 nm,
and those of compounds 4 and 5 appeared at 380–485 nm. On the other hand, the pyrene excimer
emission of compounds 3, 4, and 5 appeared at different wavelengths: around 523 nm for 3, 534 nm
for 4, and 527 nm for 5. The fluorescence of pyrene in concentrated solutions shows dual emission
bands: pyrene monomer emission at 370–425 nm, and excimer emission at around 480 nm [16,17].
The pyrene monomer and excimer emission bands of compounds 3, 4, and 5 were shifted to longer
wavelengths than the corresponding emission bands of pyrene itself. These results can presumably be
attributed to the effect of the electron-withdrawing carbonyl group [18-21].
Figure 3. Fluorescence spectra of 3, 4, and 5 (1.0 µM in chloroform). Excitation
wavelength: 360 nm.

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It is noteworthy that the fluorescence intensity ratio (Ie/Im) for compound 4 (1.32) is greater than
that of compounds 3 (0.88) and 5 (0.69), where Ie and Im are the fluorescence intensities of the pyrene
excimer (at 523 nm for 3, 534 nm for 4, and 527 nm for 5) and monomer (at 419 nm for 3 and 438 nm
for 4 and 5), respectively. These results indicate that the two pyrene units in compound 4 would be in
closer proximity than those in compounds 3 and 5.
1
To examine the structures of compounds 3, 4, and 5 in detail, the H-NMR spectra of 3, 4, and 5
were compared with those of the corresponding compounds 9, 10, and 11, which have one pyrene
1
1
unit [22,23]. The H-NMR spectra of all compounds were examined in DMSO-d6 by H-1H COSY,
1H-13C COSY, and HMBC spectroscopy. The spectra of the pyrene unit are shown in Figure 4. The
chemical shifts (δ) of all compounds and the induced shifts (∆δ) are listed in Table 1.
1
Figure 4. H-NMR spectra of 3, 4, 5 (0.02 M in DMSO-d6) and 9, 10, 11 (0.04 M in
DMSO-d6).
c
b
a
d
O
O
O
O
O
O
e
f
i
OH
g
h
X
X
3 : X = S
9 : X = S
4 : X = SO
5 : X = SO2
10 : X = SO
11 : X = SO2
b,d,e,g,
b,d,e,g,
a
i
c
f
9
3
i
a
c
f
b,d,e,g
c
i
a
c
f h
1
4
b,d,e,g,
i
a
f
b,d,e,g,
i
a
c
f
1
b,d,e,g,
i
a
c
f
5
9.0
8.9
8.8
8.3
8.7 8.6 8.5 8.4
8.2 8.1 8.0 7.9

Molecules 2011, 16
Table 1. Chemical shift values (δ) of pyrene protons in compounds 3–5 and 9–11 and the
6849
induced shifts (∆δ) between the pyrene protons a–i in compounds 3–5, with two pyrene
units, and the corresponding pyrene protons in compounds 9–11, with one pyrene unit.
Protons (δ: ppm)
Compound
a
b
c
d
e
f
g
h
i
9
8.74
8.67
0.07
8.68
8.57
0.11
8.55
8.48
0.07
8.42
8.39
0.03
8.39
8.18
0.21
8.35
8.30
0.05
8.29
8.26
0.03
8.29
8.15
0.14
8.28
8.26
0.02
8.38
8.35
0.03
8.38
8.26
0.12
8.37
8.36
0.01
8.41
8.40
0.01
8.43
8.25
0.18
8.43
8.38
0.05
8.18
8.15
0.03
8.18
8.06
0.12
8.18
8.15
0.03
8.44
8.41
0.03
8.44
8.33
0.11
8.43
8.42
0.01
8.38
8.35
0.03
8.38
8.00
0.38
8.39
8.32
0.07
8.86
8.82
0.04
8.84
8.66
0.18
8.71
8.67
0.04
3
∆δ (9–3)
10
4
∆δ (10–4)
11
5
∆δ (11–5)
Table 1 shows that all the pyrene protons of 4 were shifted upfield compared to the corresponding
protons of compound 10. The ∆δ (10–4) values are larger than the corresponding values of ∆δ (9–3)
and ∆δ (11–5). These results suggest that both pyrene units in compound 4 are closer together than
those in 3 and 5, because it is well-established that π–π stacking interactions between two aromatic
rings shield the protons due to the anisotropy of the ring current effect [23,24].
To examine the alkali metal ion binding abilities of compounds 3, 4, and 5, we investigated the
absorption and fluorescent spectral changes in chloroform-acetonitrile (97:3, v/v). No alkali metal
ion-dependent changes in the UV-Vis spectra of 3, 4, and 5 were observed upon addition of 300 µM
Li+, Na+, K+, Rb+, and Cs+ (all metal ions as perchlorate salts, except for Rb+ as thiocyanate salt to
enhance solubility) to 1.0 µM 3, 4, and 5. On the other hand, pyrene monomer emissions of 4
(at 438 nm), and 5 (at 438 nm) were enhanced by the addition of some alkali metal ions. Figure 5
shows the relative fluorescence intensity (I–I0), where I and I0 are the fluorescence intensity in the
presence of 300 equiv. of each metal ion and the fluorescence intensity in the absence of metal ions,
respectively. The addition of Li+ to solution 4, which has a sulfinyl group, induced a remarkable
intensity change. In contrast, a moderate change in the fluorescence of compound 5, which has
sulfonyl group, was observed with the addition of Li+. For 3, which has a sulfur atom, no significant
changes were observed. It is noteworthy that compounds 3, 4, and 5 interact slightly with Na+
compared with compound 2 [11]. The oxygen atom(s) of the SO and SO2 groups in compounds 4 and
5, which bridge two phenyl groups, apparently have a crucial role in binding Li+, because even the
compound 5 showed a moderate affinity to Li+.
Figure 6 shows the change in fluorescence of compound 4 with various Li+ concentrations under
excitation at 360 nm. With the addition of Li+ in the range of 50–300 µM, the pyrene monomer
emission increased dramatically, and the pyrene excimer emission changed slightly. Similar
fluorescence changes were observed for compound 5 by the addition of Li+ (not shown).

Molecules 2011, 16
Figure 5. Effect of 300 µM alkali metal ions (Li+, Na+, K+, Rb+, Cs+) on the fluorescence
6850
spectra of compounds 3, 4, and 5 (1.0 µM) in chloroform-acetonitrile (97:3, v/v) at 419 nm
for 3 and 438 nm for 4 and 5. I0 and I are the fluorescence intensities of 3, 4, and 5 in the
absence and presence, respectively, of alkali metal ions.
160
140
120
100
80
60
40
20
5
0
4
Li+
Na+
3
K+
Alkali Metal Ions
Rb+
Cs+
Figure 6. Changes in fluorescence spectra of a 1.0 µM solution of 4 in chloroform-acetonitrile
(97:3, v/v) upon addition of LiClO4. Excitation wavelength: 360 nm.
As shown in Figure 7, the pyrene monomer emission of 10, with one pyrene unit, was unchanged
by the addition of Li+ in the range of 50–300 µM. This result clearly indicates that the increases in
pyrene monomer emissions of compound 4 with increasing Li+ concentration were caused by
interaction between the two pyrene units in 4. Namely, these interactions in 4 weaken with increasing
Li+ concentration.
To confirm the conformational changes in compound 4 caused by the addition of Li+, the chemical
shifts of pyrene protons in compound 4 in the absence and presence of Li+ were examined in

Molecules 2011, 16
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CDCl3-CD3CN (97:3, v/v) by 1H-NMR spectroscopy [7,25]. The spectra of the pyrene units in 4 in the
absence (4) and presence (4-Li+) of Li+ are shown in Figure 8. The chemical shifts (δ) and induced
shifts (∆δ) of pyrene protons are listed in Table 2. The signals for pyrene protons in 4-Li+ showed
downfield shifts relative to the corresponding protons in 4. These results indicate that the π–π stacking
interaction between the two pyrene units in 4 is weakened by the addition of Li+.
Figure 7. Changes in fluorescence spectra of a 1.0 µM solution of 10 in chloroform-acetonitrile
(97:3, v/v) upon addition of LiClO4. Excitation wavelength: 360 nm.
Figure 8. 1H-NMR spectra of a 0.10 mM solution of 4 in CDCl3-CD3CN (97:3, v/v) in the
absence (4) and presence (4-Li+) of Li+ (0.03 M).
b
f
a
g
d
e
h
c
4
i
8.
9. 9. 8. 8. 8. 8.
8. 8. 8. 8. 8. 7.
f
d h
a
g
b
e
c
4-Li+
i
8.
9. 9. 8. 8. 8. 8.
8. 8. 8. 8. 8. 7.

Molecules 2011, 16
6852
Table 2. Chemical shifts values (δ) of pyrene protons in 4 and 4-Li+, and the induced shifts
(∆δ) between the pyrene protons in 4 and 4-Li+.
Protons (δ: ppm)
Compound
A
B
C
D
E
F
G
H
I
4
8.18
8.34
−0.16
7.92
8.17
−0.25
7.90
8.09
−0.19
8.05
8.23
−0.18
8.10
8.26
−0.16
7.97
8.09
−0.12
8.14
8.30
−0.16
7.98
8.19
−0.21
8.87
9.04
4-Li+
∆δ (4-4-Li+)
−0.17
The fluorophotometric and NMR spectroscopic studies described above indicate that the two pyrene
units in compound 4 would be well separated in the presence of Li+ compared to their location in the
absence of Li+. Therefore, the pyrene monomer emission is expected to increase and excimer emission
is expected to decrease with increasing Li+ concentration. However, the pyrene excimer emission in 4
changed slightly with the addition of Li+, as shown in Figure 6. This is believed to be due to the small
fluorescence intensity ratio (Ie/Im) for compound 4 (1.32). In general, pyrene-functionalized
fluoroionophores having a large fluorescence intensity ratio (Ie/Im) before the addition of metal ions
show a great decrease in pyrene excimer emission with increasing metal ion concentration. For
example, two pyrene-functionalized calix[4]arenes having an (Ie/Im) ratio of about 4.16, as reported by
Jin et al., showed a great decrease in pyrene excimer emission with increasing Na+ concentration [26].
Even compound 2, with an (Ie/Im) ratio of 2.91, as we reported, showed a gradual decrease in pyrene
excimer emission with increasing Na+ concentration [10].
The stoichiometry of compound 4 and Li+ was confirmed by a Job plot (Figure 9) using fluorescent
titrations of 1.0 µM chloroform-acetonitrile (97:3, v/v) solutions of 4 with 1.0 µM chloroform-acetonitrile
(97:3, v/v) solutions of lithium perchlorate. Consequently, the Job plot represented the formation of a
1:1 complex.
Figure 9. Job plot for the binding of Li+ with 4.
Mole Fraction 4
Figure 10 shows plots of the relative fluorescence intensity (I/I0) for 4 at 438 nm against the added
Li+ concentration. The association constant of compound 4 for Li+ was calculated to be 1.14 × 103 M−1

Molecules 2011, 16
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on the basis of the Benesi–Hildebrand method by plotting 1/(F–F0) against 1/[Li+], where F0 and F are
the fluorescence intensities in the absence and presence, respectively, of Li+. By the same method, the
association constant of compound 5 for Li+ was calculated to be 2.83 × 102 M−1.
Figure 10. Relative fluorescence intensity (I/I0) of compound 4 (1 µM) in the absence and
presence (0–300 µM) of Li+. The fluorescence intensities were monitored at 438 nm by
excitation at 360 nm. I0 and I are the fluorescence intensity of 4 in the absence and
presence, respectively, of Li+.
3. Experimental
3.1. General
All melting points were determined using a Hansen & Co., Ltd. MEL-TEMP and were not corrected.
The fluorescence spectra were obtained by a Hitachi F-2500 fluorescence spectrophotometer. The
1H- and 13C-NMR spectra (at 300 MHz and 75 MHz, respectively) were measured using a
JEOL-JNM-ECP300 spectrometer. The chemical shifts were measured in ppm downfield from the
tetramethylsilane as an internal standard. The HRMS (FAB) spectra were measured by a JEOL
JMS-SX102A using glycerol or 3-nitrobenzyl alcohol as the matrix. All chemicals for the synthesis of
3–11 were commercially available and except for 1-(bromoacetyl)pyrene from Aldrich, were obtained
from Tokyo Chemical Industry Co., Ltd. All reagents and solvents were used without further
purification. Silica gel (70–230 mesh) came from Merck Ltd., Japan. Elemental analysis was
performed by Mitsui Chemical Analysis & Consulting Service Inc., Japan.
3.2. General Procedure for Fluorescent Study
Stock chloroform solutions of compounds 3–5 and 10 (1.03 µM) and acetonitrile solutions of alkali
metal salts LiClO4, NaClO4, KClO4, RbSCN, and CsClO4 (10 mM) were prepared by using
spectroscopic-grade solvent (Wako Pure Chemical Industries, Ltd., Japan). Test solutions were
prepared by mixing the stock solution (9.7 mL) of 3–5 and 10 and the alkali metal salt stock solution in

Molecules 2011, 16
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increments of 0.00 mL, 0.05 mL, 0.10 mL, 0.15 mL, 0.20 mL, 0.25 mL, and 0.30 mL, after which the
solution was diluted to 10.0 mL with acetonitrile.
3.3. General Procedure for the Preparation of 2,2´-Bis(1-pyrenylacetyloxy)diphenyl Compounds 3–5
2,2´-bis(1-Pyrenylacetyloxy)diphenyl sulfide (3): A mixture of 2,2´-dihydroxydiphenyl sulfide (1.52 mmol,
0.33 g) [15], 1-(bromoacetyl)pyrene (3.10 mmol, 1.00 g) and potassium carbonate (4.56 mmol, 0.63 g)
was refluxed in acetonitrile (300 mL) for 8 h. After evaporation of the solvent, the residue was
dissolved in chloroform (300 mL). The chloroform solution was washed with water, and the solvent
was evaporated. The residue was recrystallized from dichloromethane–hexane to afford compound 3.
Yield 83% (0.89 g) of yellow powder; mp 154–155 °C dec; 1H-NMR (DMSO-d6) δ 5.80 (s, 4H), 6.90
(td, J = 7.7 Hz, 1.1 Hz, 2H), 7.05 (dd, J = 7.7 Hz, 1.7 Hz, 2H), 7.06 (dd, J = 8.3 Hz, 1.1 Hz, 2H), 7.26
(td, J = 8.3 Hz, 1.7 Hz, 2H), 8.15 (t, J = 7.7 Hz, 2H), 8.26 (d, J = 9.1 Hz, 2H), 8.33–8.43 (m, 10H),
13
8.67 (d, J = 8.3 Hz, 2H), 8.82 (d, J = 9.3 Hz, 2H); C-NMR (DMSO-d6) δ 72.2, 112.6, 121.6, 122.1,
123.3, 124.0, 124.1, 124.3, 126.3, 126.7, 126.8, 127.0, 127.2, 128.4, 128.8, 128.9, 129.6, 129.7, 129.9,
130.5, 131.8, 133.7, 156.2, 198.6; HRMS (FAB): calcd for (M+H)/z: 703.1944. found (M+H)/z:
703.1943. Anal. calcd for C48H30O4S: C, 82.03; H, 4.30%; found: C, 81.87; H, 4.35%.
2,2´-bis(1-Pyrenylacetyloxy)diphenyl sulfoxide (4): This compound was prepared by the same
procedure given for the synthesis of compound 3 except that 2,2´-dihydroxydiphenyl sulfoxide [15]
(0.36 g) was used instead of 2,2´-dihydroxydiphenyl sulfide. Yield 67% (0.72 g) of yellow powder; mp
184–185 °C dec; 1H-NMR (CDCl3) δ 5.78 (d, J = 3.0 Hz, 4H), 7.10–7.16 (m, 4H), 7.46 (td, J = 8.5 Hz,
1.7 Hz, 2H), 7.58 (dd, J = 7.4 Hz, 1.7 Hz, 2H), 8.00 (d, J = 7.7 Hz, 2H), 8.06 (t, J = 7.7 Hz, 2H),
8.14–8.34 (m, 10H), 8.57 (d, J = 8.0 Hz, 2H), 8.66 (d, J = 9.6 Hz, 2H); 13C-NMR (DMSO-d6) δ; 72.2,
113.0, 121.6, 123.2, 123.9, 124.2, 126.0, 126.1, 126.6, 126.7, 126.9, 127.0, 128.1, 128.9, 129.6, 129.7,
129.8, 130.4, 132.4, 132.8, 133.7, 155.1, 197.6; HRMS (FAB): calcd for (M+H)/z: 719.1924. found
(M+H)/z: 719.1895. Anal. calcd for C48H30O5S: C, 80.20; H, 4.21%. found: C, 79.98; H, 4.04%.
2,2´-bis(1-Pyrenylacetyloxy)diphenyl sulfone (5): This compound was prepared by the same procedure
given for the synthesis of compound 3 except that 2,2´-dihydroxydiphenyl sulfone [15] (0.38 g) was
used instead of 2,2´-dihydroxydiphenyl sulfide. Yield 72% (0.80 g) of yellow powder; mp 221–222 °C
1
dec; H-NMR (CDCl3) δ 5.57 (s, 4H), 6.91 (t, J = 7.4 Hz, 2H), 7.24 (d, J = 8.0 Hz, 2H), 7.55 (td,
J = 8.5 Hz, 1.7 Hz, 2H), 7.90 (dd, J = 8.0 Hz, 1.7 Hz, 2H), 8.15 (t, J = 7.7 Hz, 2H), 8.26 (d, J = 9.0 Hz,
2H), 8.29–8.43 (m, 10H), 8.48 (d, J = 8.0 Hz, 2H), 8.67 (d, J = 9.3 Hz, 2H); 13C-NMR (DMSO-d6) δ;
72.5, 114.2, 120.3, 123.3, 123.9, 124.0, 124.2, 126.3, 126.7, 126.8, 127.0, 127.1, 128.5, 128.6, 128.8,
129.6, 129.7, 129.8, 130.5, 133.6, 135.0, 155.6, 197.2; HRMS (FAB): calcd for (M+H)/z: 735.1842.
found (M+H)/z: 735.1846. Anal. calcd for C48H30O6S: C, 78.46; H, 4.12%. found: C, 78.42; H, 4.12%.
3.4. General Procedure for the Preparation of 2-(1-Pyrenylacetyloxy)-2´-hydroxydiphenyl Compounds
9–11
2-(1-Pyrenylacetyloxy)-2´-hydroxydiphenyl sulfide (9): A mixture of 2,2´-dihydroxydiphenyl sulfide
(2.50 mmol, 0.54 g) [15] and sodium methoxide (2.91 mmol, 0.16 g) was refluxed in acetonitrile

Molecules 2011, 16
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(80 mL) for 30 min to completely monodeprotonate the 2,2´-dihydroxydiphenyl sulfide. A solution of
1-(bromoacetyl)pyrene (1.00 g, 3.10 mmol) in acetonitrile (300 mL) was then added to the reaction
mixture, followed by stirring at the reflux temperature for 6 h. The reaction mixture was neutralized
with a few drops of acetic acid, and the solvent was removed. The residue was purified by
recrystallization from chloroform to afford 9. Yield 70% (0.80 g) of yellow powder; mp 154–155 °C
1
dec; H-NMR (CDCl3) δ 5.85 (s, 2H), 6.79 (td, J = 7.8 Hz, 1.4, 1H), 6.80 (dd, J = 7.8 Hz, 1.7, 1H),
6.87 (td, J = 7.7 Hz, 1.1, 1H), 6.96 (dd, J = 8.0 Hz, 1.1, 1H), 7.07–7.24 (m, 4H), 8.18 (t, J = 7.7 Hz,
1H), 8.29 (d, J = 9.0 Hz, 1H), 8.32–8.45 (m, 5H), 8.74 (d, J = 8.3 Hz, 1H), 8.86 (d, J = 9.3 Hz, 1H),
9.89 (s, 1H); 13C-NMR (DMSO-d6) δ; 72.2, 79.2, 112.3, 115.7, 117.8, 119.9, 121.4, 123.4, 123.9,
124.0, 124.3, 126.3, 126.7, 126.9, 127.0, 127.2, 128.8 128.9, 129.0, 129.6, 129.8, 129.9, 130.6, 133.7,
134.1, 155.0, 157.2, 198.5; HRMS (FAB): calcd for (M+H)/z: 461.1212. found (M+H): 461.1206.
Anal. calcd for C30H20O3S: C, 78.20; H, 4.38%. found: C, 77.90; H, 4.29%.
2-(1-Pyrenylacetyloxy)-2´-hydroxydiphenyl sulfoxide (10): This compound was prepared by the same
procedure given for the synthesis of compound 9 except that 2,2´-dihydroxydiphenyl sulfoxide (0.59 g) [15]
was used instead of 2,2´-dihydroxydiphenyl sulfide. Yield 25% (0.29 g) of yellow powder; mp
1
168–169 °C dec; H-NMR (CDCl3) δ 5.76 (d, J = 17.3 Hz, 1H), 5.87 (d, J = 17.3 Hz, 1H), 6.89 (td,
J = 8.0 Hz, 0.84, 1H), 6.89 (dd, J = 7.4 Hz, 0.84, 1H), 7.16 (td, J = 7.4 Hz, 0.84, 1H), 7.20 (d,
J = 7.7 Hz, 1H), 7.32 (td, J = 8.0 Hz, 1.7, 1H), 7.38 (dd, J = 7.7 Hz, 1.7, 1H), 7.48 (td, J = 7.4 Hz, 1.7,
1H), 7.55 (dd, J = 7.7 Hz, 1.7, 1H), 8.18 (t, J = 7.7 Hz, 1H), 8.29 (d, J = 9.1 Hz, 1H), 8.36–8.45 (m,
13
5H), 8.68 (d, J = 8.0 Hz, 1H), 8.84 (d, J = 9.4 Hz, 1H), 10.38 (s, 1H); C-NMR (DMSO-d6) δ; 72.3,
113.1, 116.2, 119.5, 121.6, 123.3, 124.0, 124.1, 124.3, 126.1, 126.3, 126.5, 126.8, 126.9, 127.0, 127.2,
128.5 128.9, 129.4, 129.8, 129.9, 130.5, 132.0, 132.3, 132.4, 133.8, 155.2, 155.4, 197.8; HRMS
(FAB): calcd for (M+H)/z: 477.1161. found (M+H)/z: 477.1161. Anal. calcd for C30H20O4S: C, 75.61;
H, 4.23%. Found: C, 75.31; H, 4.12%.
2-(1-Pyrenylacetyloxy)-2´-hydroxydiphenyl sulfone (11): This compound was prepared by the same
procedure given for the synthesis of compound 9 except that 2,2´-dihydroxydiphenyl sulfone [15]
(0.63 g) was used instead of 2,2´-dihydroxydiphenyl sulfide. Yield 27% (0.34 g) of yellow powder; mp
178–179 °C dec; 1H-NMR (300 MHz CDCl3) δ 5.62 (s, 2H), 6.71 (td, J = 8.0 Hz, 0.84, 1H), 6.84 (dd,
J = 8.3 Hz, 0.84, 1H), 7.20 (t, J = 7.7 Hz, 1H), 7.21 (d, J = 8.5 Hz, 1H), 7.38 (td, J = 8.5 Hz, 1.7, 1H),
7.61 (td, J = 8.3 Hz, 1.7, 1H), 7.78 (dd, J = 8.0 Hz, 1.7, 1H), 8.06 (dd, J = 7.7 Hz, 1.7, 1H), 8.18 (t,
J = 7.7 Hz, 1H), 8.30 (d, J = 9.0 Hz, 1H), 8.32–8.45 (m, 5H), 8.55 (d, J = 8.0 Hz, 1H), 8.71 (d,
J = 9.4 Hz, 1H), 10.39 (s, 1H); 13C-NMR (DMSO-d6) δ; 72.3, 79.5, 114.0, 116.9, 118.0, 120.4, 123.3,
124.0, 124.1, 124.3, 126.1, 126.3, 126.8, 126.9, 127.1, 127.2, 128.5, 128.9, 129.7, 129.8, 129.9, 130.4,
130.5, 130.6, 133.7, 134.8, 135.0, 155.5, 155.7, 197.0; HRMS (FAB): calcd for (M+H)/z: 493.1110.
found (M+H)/z: 493.1105. Anal. calcd for C30H20O5S: C, 73.16; H, 4.09%. found: C, 72.86; H, 4.08%.
4. Conclusions
We have synthesized new podand-type fluoroionophores by connecting two pyrene units with
2,2´-dihydroxydiphenyl sulfide, sulfoxide, and sulfone. The fluorescent change upon addition of alkali

Molecules 2011, 16
6856
metal ions show that the difference in binding site affected metal ion selectivity and the
fluoroionophore having sulfinyl group is highly selective for Li+ ion over other alkali metal ions.
Although a number of fluoroionophores using calixarenes and crown ethers as ion recognition unit
have been reported, these results demonstrated that a podand-type fluoroionophore with a non-cyclic
binding site having sulfinyl group would be applicable as an effective Li+ ion fluorescence sensor.
Along these lines, we are examining the synthesis of new fluoroionophore that can be able to monitor
Li+ ion concentrations in aqueous samples.
Acknowledgments
This work was support by Tokyo Medical University.
Conflict of interests
The authors declare no conflict of interest.
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Sample Availability: Samples of the compounds are not available from the authors.
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