Alkaline earth metal-sensing anthracene fluorophore-hosts

Article abstract of DOI:10.1039/a607688b

Novel anthracene fluorophore-hosts 1-4, bonding through an ester or ether linkage to a crown ether or polyether side-arm, have been synthesized. Addition of an alkaline earth metal cation to a host solution causes a unique fluorescence intensity change. That is, the hosts bonding through an ester linkage, compounds 1 and 3, give fluorescence quenching, whereas the hosts bonding through an ether linkage, compounds 2 and 4, give fluorescence enhancement. The host having a crown ether side-arm, compound 2, recognises calcium cations more strongly than barium cations, in contrast to the host having a polyether side-arm, compound 4, which prefers barium cations to calcium cations.

Full text of DOI:10.1039/a607688b

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Alkaline earth metal-sensing anthracene fluorophore-hosts
Satoru Iwata, Hideo Matsuoka and Kiyoshi Tanaka *
Faculty of Engineering, Seikei University, Musashino-shi, Tokyo 180, Japan
N ovel anthracene fluorophore-hosts 1–4, bonding through an ester or ether linkage to a crown ether or
polyether side-arm, have been synthesized. Addition of an alkaline earth metal cation to a host
solution causes a unique fluorescence intensity change. That is, the hosts bonding through an ester
linkage, compounds 1 and 3, give fluorescence quenching, whereas the hosts bonding through an ether
linkage, compounds 2 and 4, give fluorescence enhancement. The host having a crown ether side-arm,
compound 2, recognises calcium cations more strongly than barium cations, in contrast to the host having
a polyether side-arm, compound 4, which prefers barium cations to calcium cations.
Introduction
O
O
O
O
CO2H
O
O
Fluorescence sensing in molecular recognition systems is very
useful in biomimetic research, since the resulting fluorescence
can be highly sensitive so as to permit analysis. Recently, many
fluorophore-hosts were reported to sense a number of guests
such as alkali metals, alkaline earth metals, protons, transition
metals and sugar derivatives.1–5 Moreover, de Silva et al. created
a logical recognition system operated by changes in fluor-
escence intensity.6 In our previous paper, we reported a crown
ether-armed fluorophore, pyrido[1Ј,2Ј:1,2]imidazo[4,5-b]pyr-
azine (PIP), which was able to logically recognise two input sig-
nals, alkaline earth metal cations and thiocyanate anions, to
give a fluorescence-quenching output. This quenching char-
acter is explained by the photoinduced electron transfer (PET)
from the thiocyanate anion to the PIP ring. Here we describe
the metal-sensing ability of simple anthracene hosts bonding
through an ester or ether linkage to a crown ether or polyether
side-arm, as in structures 1–4.
i
1
Cl
O
O
O
O
O
ii
2
iii
MeO
O
OTs
MeO
O
OH
Results and discussion
iv
Novel anthracene hosts 1–4 were synthesized by the following
routes (Scheme 1). The ester linked hosts 1 and 3 were pre-
pared from anthracene-9-carboxylic acid and the correspond-
ing alcohols by 2-chloro-1,3-dimethylimidazolinium chloride
(DMC) dehydration, respectively. The ether linked hosts 2
and 4 were prepared by usual etherification methods.
O
O
O
OMe
5
v
MeO
O
OH
5
3
The UV–visible and fluorescence spectra of the crown ether
hosts 1 and 2 are shown in Figs. 1–4. The UV–visible spectra of
both compounds 1 and 2 indicate that there is little change in
absorption pattern and intensity by the addition of calcium or
sodium thiocyanate (Figs. 1 and 3). On the other hand, the
fluorescence intensity of the host is remarkably changed in
the presence of calcium thiocyanate; that is, fluorescence of the
ester linked host 1 was nearly quenched (Fig. 2); however,
that of the ether linked host 2 was substantially enhanced
(Fig. 4). The fluorescence intensity change caused by the add-
ition of alkaline earth metal and alkali metal thiocyanates, per-
chlorates, iodides and nitrates is summarised in Table 1. The
negative value shows fluorescence enhancement by the addition
of a salt, the positive value showing the fluorescence quenching.
These results indicate the following features. (a) All hosts 1–4
recognise alkaline earth metal salts more effectively than alkali
metal salts, bringing about the substantial fluorescence quench-
ing or enhancement. (b) Fluorescence of the ester linked
hosts 1 and 3 is quenched by alkaline earth metal salts while, on
the other hand, that of the ether linked hosts 2 and 4 is en-
hanced by the corresponding salts. (c) One of the ether linked
hosts, 2, recognises calcium salts preferentially in the presence
iii
O
O
OMe
5
vi
MeO
O
OTs
5
4
Scheme 1 Reagents: i, hydroxymethyl-12-crown-4, DMC, pyridine,
CH2Cl2; ii, hydroxymethyl-12-crown-4, NaH, THF; iii, TsCl, Et3N,
CH2Cl2; iv, tetraethylene glycol, ButOK, THF; v, anthracene-9-
carboxylic acid, DMC, pyridine, CH2Cl2; vi, 9-(hydroxymethyl)-
anthracene, ButOK, THF
of barium salts and, conversely the other host, 4, prefers
barium salts to calcium salts.
From the fact that sodium and potassium salts don’t affect
the fluorescence quenching, it is suggested that the quenching
of the hosts 1 and 3 is caused by the calcium and barium
cations trapped by the 12-crown-4 ether or polyether side-arm.
J. Chem. Soc., Perkin Trans. 1, 1997
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Table 1 Fluorescence intensity change (F0 Ϫ F)/F0 by addition of salt a
SCNϪ
Ca2ϩ
0.40
ClO4
Ca2ϩ
IϪ
NO3
Ϫ
Ϫ
Host
Ba2ϩ
Naϩ
Kϩ
Ba2ϩ
Naϩ
Ca2ϩ
Ba2ϩ
Ca2ϩ
Ba2ϩ
1
2
3
4
0.48
Ϫ0.91
0.78
0.03
Ϫ0.03
0.05
0.02
Ϫ0.03
0.05
0.29
Ϫ1.52
0.56
0.26
Ϫ0.80
0.79
0.02
Ϫ0.07
0.05
0.15
Ϫ2.40
0.79
0.19
Ϫ0.62
0.72
0.00
Ϫ1.05
0.37
0.06
Ϫ0.05
0.19
Ϫ1.49
0.53
Ϫ1.10
Ϫ1.36
Ϫ0.13
Ϫ0.17
Ϫ1.06
Ϫ2.16
Ϫ0.14
Ϫ0.22
Ϫ0.49
Ϫ0.56
Ϫ1.48
a
[Host] = 2 × 10Ϫ6 mol dmϪ3 in acetonitrile at 25 ЊC; F0 stands for fluorescence intensity without salt, F for fluorescence intensity with salt.
[Salt] = 2 × 10Ϫ4 mol dmϪ3; λex = 350 nm, λem = 457 nm.
Fig. 3 Absorption of compound 2 ([2] = 8.0 × 10Ϫ6 mol dmϪ3) in UV–
visible spectrum
Fig. 1 Absorption of compound 1 ([1] = 1.4 × 10Ϫ5 mol dmϪ3) in UV–
visible spectrum
Fig. 4 Intensity of fluorescence of compound 2 in fluorescence spec-
trum (λex = 350 nm)
Czarnik and de Silva reported that the fluorescence enhance-
ment in the anthracene hosts having an aza-crown ether or an
alkylamino group was caused by the metal chelating to the
nitrogen atom.5,8 The metal chelation decreases the reducing
ability of the nitrogen lone pair, which retards the electron
transfer to the anthracene photoexcited state. Therefore the
fluorescence enhancement effect of the ether linked hosts 2
and 4 could be ascribed to the weakened reducing ability of
the benzylic oxygen by the calcium or barium cation. To clarify
these relationships, quantum yields of some related anthracene-
Fig. 2 Intensity of fluorescence of compound 1 in fluorescence spec-
trum (λex = 350 nm)
Moreover, it should be added that the fluorescene quenching is
dependent on the counter anion and, in both hosts 1 and 3, the
nitrate anion relaxed the quenching. In host 1, the quenching
effect of the thiocyanate anion is notable and this is due to
PET occurring from the thiocyanate anion to the anthracene
ring, as discussed in the case of the PIP-host in our previous
paper.7
1358
J. Chem. Soc., Perkin Trans. 1, 1997

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Table 2 Fluorescence quantum yields of 9-substituted anthracene derivativesa
CH2OCH2-12-
Crown-4
2
CO2CH2-12-
Crown-4
1
Substituent
9-R
CH2OMe
0.10c
CH2OH
0.15
CH2OAc
0.21
Hb
CO2Me
0.26
CH2CO2Me
0.29
Quantum yield
0.10
0.23
0.26
a
In acetonitrile at 25 ЊC, λex = 260 nm. b Φstandard (calculated value on the basis of quantum yield Φ = 0.30 in ethanol). c Φ = 0.08 (methylcyclohexane),
see ref. 9.
9-carboxylic acid and -methanol derivatives were measured
(Table 2). The quantum yields were found to be fairly depend-
ent on the electronic effects of the 9-substituent. Electron-with-
drawing groups such as ester groups and ester-substituted
methyl groups increased the quantum yields. In contrast,
hydroxy- and alkoxy-methyl groups decreased the quantum
yields, the degree of which is determined by the electronic
effects of the substituent attaching to the alcohol oxygen; that
is, the electron-withdrawing acetyl group increases the quantum
yield whereas the electron-donating methyl group decreases it.
A 12-crown-4-ether-substituted methyl group should have an
effect equal to that of the methyl group.† These results confirm
that the quenching of anthracenemethanol derivatives is pro-
portional to the electron density of the benzylic oxygen. On the
other hand, according to computer-aided modelling, the ether
linked hosts 2 and 4 are holding calcium or barium cations not
only by the crown ether or polyether oxygen atoms but also the
linkage oxygen atom. Therefore, in the hosts 2 and 4, chelation
of calcium or barium cations decreases the reducing ability of
the linkage oxygen and brings about the fluorescence enhance-
ment.
The ether linked host 2 recognised calcium cations preferen-
tially in the presence of barium cations, in contrast to the host 4
which prefered barium cations to calcium cations; these prefer-
ences were not affected by the kind of counter anion. These
results may therefore be attributed to the size of cation. Thus
the calcium cation fits better in the holding cavity constructed
by the 12-crown-4 ether and the linkage oxygen atom and, con-
versely, the holding cavity in the host 4, which is constructed
with a flexible pseudo-crown ether of the polyether moiety, pre-
fers the barium cation, resulting in substantial fluorescence
enhancement.
was the highest quality from KOKUSAN Chemical Co. and
was used without purification.
Synthesis of (anthracen-9-ylcarboxymethyl)-12-crown-4 ether 1
To a suspension of dichloromethane (10 ml) containing
anthracene-9-carboxylic acid (0.69 g, 3.1 mmol) were added
hydroxymethyl-12-crown-4 ether (0.50 g, 2.4 mmol) and DMC
(0.53 g, 3.1 mmol). After the mixture had been stirred for 15
min at room temperature, pyridine (0.50 g, 6.3 mmol) was
added dropwise, and the mixture was stirred for 24 h at
room temperature. The solid was filtered off, and washed with
dichloromethane. The combined filtrates were washed succes-
sively with 1 M hydrochloric acid, water and brine, and the
organic layer was dried over anhydrous magnesium sulfate. The
solvent was evaporated off, and the residue was chromato-
graphed on silica gel (eluent, ethyl acetate) to give 0.16 g (16%)
of ester 1 as a yellowish oil; νmax(neat)/cmϪ1 3050 (CH of Ar),
1720 (C᎐O), 1205 and 1135 (C᎐O); δ 8.54 (1 H, s, 10-ArH),
᎐
H
8.14 (2 H, d, J 8.5, 1- and 8-ArH), 8.11 (2 H, d, J 7.3, 4- and 5-
ArH), 7.57–7.46 (4 H, m, 2-, 3-, 6- and 7-ArH), 4.72 (1 H, dd, J
4.4 and 11.7, CH2CH), 4.60 (1 H, dd, J 6.2 and 11.7, CH2CH),
4.08 (1 H, m, CH) and 3.94–3.85 (14 H, m, OCH2);
λmax(MeCN)/nm 382, 362, 346 and 252 (log ε/dm3 molϪ1 cmϪ1
3.68, 3.75, 3.60 and 4.95) (Found: C, 69.9; H, 6.4. C24H26O6
requires C, 70.2; H, 6.4%).
Synthesis of (anthracen-9-ylmethoxymethyl)-12-crown-4 ether 2
To a tetrahydrofuran (THF) solution of hydroxymethyl-12-
crown-4 ether (0.50 g, 2.4 mmol) and sodium hydride (0.18 g)
was added 9-(chloromethyl)anthracene (0.55 g, 2.4 mmol).
After being stirred for 6 h at room temperature, the reaction
mixture was extracted with ethyl acetate, and the organic layer
was washed successively with water and brine, dried over
anhydrous magnesium sulfate, and evaporated. The residue was
chromatographed on silica gel [eluent, hexane–ethyl acetate
(3:1)] to give 0.70 g (73%) of ether 2 as a yellowish oil;
νmax(neat)/cmϪ1 3050 (CH of Ar), 2860 (CH2), 1620 and 1520
(Ar) and 1100 (C᎐O); δH 8.40 (1 H, s, 10-ArH), 8.37 (2 H, d, J
10.0, 1- and 8-ArH), 7.95 (2 H, d, J 8.3, 4- and 5-ArH), 7.52–
7.40 (4 H, m, 2-, 3-, 6- and 7-ArH), 5.46 (2 H, s, CH2) and 3.74–
3.42 (17 H, m, OCH2 and CH); λmax(MeCN)/nm 384, 364, 346,
331 and 253 (log ε/dm3 molϪ1 cmϪ1 3.67, 3.72, 3.55, 3.26 and
4.91) (Found: C, 72.8; H, 7.0. C24H28O5 requires C, 72.7; H,
7.1%).
In conclusion, the anthracene hosts bonding through an ester
or ether linkage to 12-crown-4 ether or polyether side-arm 1–4
recognised calcium and barium cations, and the fluorescence of
the ester bonding hosts 1 and 3 or the ether bonding hosts 2 and
4 were quenched or enhanced, respectively, in the presence of
these cations. Calcium or barium cations were strongly recog-
nised by the 12-crown-4 ether or polyether side-armed host 2 or
4, respectively. These results are very useful for helping us build
a new type of host having a fluorescence output signal.
Experimental
Mps were measured on a MEL-TEMP II apparatus and are
uncorrected. IR Spectra were recorded on a JASCO Report-100
spectrometer. H NMR Spectra were taken on a JEOL JNM-
Preparation of 1-tosyloxy-3,6-dioxaheptane
To a dichloromethane (200 ml) solution of diethylene glycol
monomethyl ether (15.0 g, 0.13 mol) and toluene-p-sulfonyl
chloride (20.2 g, 0.11 mol) in an ice-bath was added triethyl-
amine (15.2 g, 0.15 mol) dropwise slowly over a 20 min period.
After the mixture had been stirred for 3 h, the solid was filtered
off, and washed with dichloromethane. The combined fil-
trates were washed successively with water and brine, and the
organic layer was dried over anhydrous magnesium sulfate. The
solvent was removed to give 13.5 g (47%) of 1-tosyloxy-3,5-
dioxaheptane as an oil and this product was used for the next
reaction without further purification.
1
GX270 (270 MHz) spectrometer for solutions in CDCl3. The
chemical shifts are given in δH (ppm) downfield from tetra-
methylsilane as the internal standard; J values are given in Hz.
The elemental analyses were measured with a Yanaco MT-3
instrument. The fluorescence spectra and quantum yields were
measured with a JASCO FP-777 spectrophotometer. UV–
Visible spectra were recorded with a JASCO Ubest-50 spectro-
photometer. The liquid chromatography purification was
carried out by LC-908 (Japan Analytical Industry, Co., Ltd.)
using JAI gel 1H (eluent, CHCl3). Acetonitrile for spectoscopy
Preparation of hexaethylene glycol monomethyl ether
To a THF (50 ml) solution of 1-tosyloxy-3,6-dioxaheptane
† For the low fluorescence of methoxymethylanthracene, consult ref. 9.
J. Chem. Soc., Perkin Trans. 1, 1997
1359

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(2.00 g, 7.3 mmol) and tetraethylene glycol (1.42 g, 7.3 mmol)
was added potassium tert-butoxide (0.82 g, 7.3 mmol). After
being refluxed for 17 h, the reaction mixture was cooled to
room temperature and the solid was filtered off, and washed
with THF. The combined filtrates were evaporated to give 2.24 g
of the crude hexaethylene glycol monomethyl ether, which was
used for the next reaction without further purification.
Synthesis of 1-(anthracen-9-ylmethoxy)-3,6,9,12,15,18-
hexaoxanonadecane 4
To a THF (4 ml) solution of 1-tosyloxy-3,6,9,12,15,18-hexa-
oxanonadecane (0.58 g) and 9-(hydroxymethyl)anthracene
(0.27 g, 1.3 mmol) was added potassium tert-butoxide (0.14 g,
1.3 mmol). After reflux of the mixture for 4 h, the solid was
filtered off, and washed with THF. The combined filtrates were
evaporated, the residue was chromatographed on silica gel (elu-
ent, ethyl acetate), and the crude product was further purified
by liquid chromatography to give 0.10 g (16%) of polyether 4 as
a yellowish oil; νmax(neat)/cmϪ1 3050 (CH of Ar), 2860 (CH2),
Synthesis of 1-(anthracen-9-ylcarboxy)-3,6,9,12,15,18-
hexaoxanonadecane 3
Hexaethylene glycol monomethyl ether (1.0 g) was dissolved in
dichloromethane (6 ml), and anthracene-9-carboxylic acid (0.75
g, 3.4 mmol) and DMC (0.57 g, 3.4 mmol) were added to the
solution. After the mixture had been stirred for 20 min, pyri-
dine (0.53 g, 6.7 mmol) was added to the mixture in an ice-bath.
After the mixture had been stirred at room temperature for 24
h, the solid was filtered off, and washed with dichloromethane.
The combined filtrates were evaporated to leave a residue, which
was chromatographed on silica gel (eluent, ethyl acetate). The
crude product was further purified with liquid chromatography
to give 0.18 g (12%) of polyether ester 3 as a yellowish oil;
νmax(neat)/cmϪ1 3050 (CH of Ar), 2870 (CH ), 1720 (C᎐O), 1520
1620 and 1520 (C᎐C and Ar), 1445 (OCH ) and 1100 (C᎐O); δ
᎐
3
H
8.44 (1 H, s, 10-ArH), 8.41 (2 H, d, J 8.8, 1- and 8-ArH), 7.99 (2
H, d, J 8.3, 4- and 5-ArH), 7.55–7.42 (4 H, m, 2-, 3-, 6- and 7-
ArH), 5.53 (2 H, s, CH2), 3.79–3.51 (24 H, m, OCH2) and 3.35
(3 H, s, OCH3); λmax(MeCN)/nm 384, 364, 346, 331 and 253 (log
ε/dm3 molϪ1 cmϪ1 3.81, 3.85, 3.69, 3.45 and 5.04) (Found: C,
68.8; H, 7.4. C28H38O7 requires C, 69.1; H, 7.9%).
References
1 A. P. de Silva, H. Q. N. Gunaratne and G. E. M. Maguire, J. Chem.
Soc., Chem. Commun., 1994, 1213.
2 T. D. James, K. R. A. S. Sandanayake and S. Shinkai, J. Chem. Soc.,
Chem. Commun., 1994, 477.
3 T. D. James, K. R. A. S. Sandanayake and S. Shinkai, Angew. Chem.,
Int. Ed. Engl., 1994, 33, 2207.
4 I. Aoki, Y. Kawahara, T. Sakaki, T. Harada and S. Shinkai, Bull.
Chem. Soc. Jpn., 1993, 66, 927.
᎐
2
(Ar), 1445 (OMe), 1205 and 1105 (C᎐O); δH 8.52 (1 H, s, 10-
ArH), 8.12 (2 H, d, J 8.8, 1- and 8-ArH), 8.01 (2 H, d, J 7.6, 4-
and 5-ArH), 7.56–7.45 (4 H, m, 2-, 3-, 6- and 7-ArH), 4.78 (2 H,
t, J 4.9, 1-H2), 3.93 (2 H, t, J 4.9, 2-H2), 3.72–3.50 (20 H, m,
OCH2) and 3.35 (3 H, s, OCH3); λmax(MeCN)/nm 382, 362,
346 and 252 (log ε/dm3 molϪ1 cmϪ1 3.88, 3.94, 3.80 and 5.15)
(Found: C, 67.6; H, 7.0. C28H36O8 requires C, 67.2; H, 7.25%).
5 A. W. Czarnik, Acc. Chem. Res., 1994, 27, 302.
6 A. P. de Silva, H. Q. N. Gunaratne and C. P. McCoy, Nature, 1993,
364, 42.
Preparation of 1-tosyloxy-3,6,9,12,15,18-hexaoxanonadecane
To a dichloromethane (3 ml) solution of the crude hexaethylene
glycol monomethyl ether (1.06 g) and toluene-p-sulfonyl chlor-
ide (0.68 g, 3.6 mmol) in an ice-bath was added triethylamine
(0.54 g, 5.4 mmol) slowly. After the mixture had been refluxed
for 2.5 h, the solid was filtered off, and washed with dichloro-
methane. The obtained filtrates were washed successively
with water and brine, and the organic layer was dried over
anhydrous magnesium sulfate and evaporated. The obtained
crude product was used for the next reaction without further
purification.
7 S. Iwata and K. Tanaka, J. Chem. Soc., Chem. Commun., 1995, 1491.
8 A. P. de Silva and S. A. de Silva, J. Chem. Soc., Chem. Commun.,
1986, 1709.
9 A. Castellan, J.-M. Lacoste and H. Bouas-Laurent, J. Chem. Soc.,
Perkin Trans. 2, 1979, 411.
Paper 6/07688B
Received 12th November 1996
Accepted 7th January 1997
1360
J. Chem. Soc., Perkin Trans. 1, 1997