A new water-soluble fluorescent dye based on 2-sulfanylhydroquinone dimers

Article abstract of DOI:10.1246/cl.130348

In this study, a new water-soluble fluorescent dye based on 2-sulfanylhydroquinone dimers was developed, and its physical properties were investigated.

Full text of DOI:10.1246/cl.130348

doi:10.1246/cl.130348
876
Published on the web May 29, 2013
A New Water-soluble Fluorescent Dye Based on 2-Sulfanylhydroquinone Dimers
Tomomi Nokubi, Kotaro Nasu, Ryusuke Watanabe, and Akio Kamimura*
Department of Applied Molecular Bioscience, Graduate School of Medicine, Yamaguchi University,
Ube, Yamaguchi 755-8611
(Received April 16, 2013; CL-130348; E-mail: ak10@yamaguchi-u.ac.jp)
In this study, a new water-soluble fluorescent dye based on
UV-vis region. Next, the deprotonation of 1a by treatment with
2-sulfanylhydroquinone dimers was developed, and its physical
properties were investigated.
potassium hydroxide in methanol was examined for conversion
to tetrapotassium salt 2a, which was then isolated by the removal
of methanol in vacuo (Scheme 1). Compound 2a was found to
be soluble in water and showed relatively strong fluorescence;
however, this decreased to zero within a second. It was
speculated that this decay was due to the oxidation of 2a by
an active oxidant in water, such as oxygen, resulting in its
conversion into quinone dimer 3a, which is not excited by UV
light at 365 nm.
This hypothesis prompted us to prepare a half-protected
hydroquinone dimer, which was expected to resist oxidation
to quinone derivatives. Compound 6 was therefore designed,
containing a monoprotected hydroxy group on each aromatic
nucleus (Scheme 2).22 The two hydroxy groups in hydroquinone
dimer 1a were protected by treatment with di-tert-butyldichloro-
silane in the presence of triethylamine, giving compound 4 in
58% yield. Protection of the other two hydroxy groups was
carried out using the Williamson ether synthesis, and compound
5 was prepared in almost quantitative yield. Deprotection of
di-tert-butylsilyl groups was achieved by treatment with TBAF,
giving compound 6 in 92% yield. Exposure of compound 6 to
one or two equivalents of potassium hydroxide gave salts 7 and
8, which were isolated by the evaporation of methanol.
Fluorescent dyes are recognized as important tools for
sensing or imaging of chemical, physical, and biological
processes. So far, a wide range of dyes have been developed,
and a number of these are already being applied to various
fields such as bioimaging1 and solar cells.2 Water solubility is
an important property of dyes, which is necessary for their
application to biochemical and environmental research.3 Some
dyes are originally water-soluble, but others require chemical
modification of the molecules. So far, many water-soluble
fluorescent dyes have been reported, including BODIPY-based
sulfides,4-7 fluorescein derivatives,8-11 rhodamines,12,13 boronic
acids,14,15 peptides,16 polyfluorene derivatives,17,18 and nano-
clusters.19,20 Recently, we reported a short protocol for the
synthesis of a quinone dimer bearing sulfur substituents.21 This
dimer exhibited relatively strong fluorescence in the visible light
region on UV irradiation. As this molecule contained four
phenolic hydroxy groups, it was expected to be a potential novel
water-soluble fluorescent dye on deprotonation of the hydroxy
groups. In this report, we describe the synthesis of a new type of
water-soluble fluorescent dye and its physical properties. We
also report an improvement in fluorescence.
OH
OH
O
O
OK
OK
Hydroquinone dimers 1a and 1b were prepared according
to a previously reported method.21 Oxidative coupling of 2-
sulfanylhydroquinone dimethyl ether, followed by deprotection
using boron tribromide, gave 1a and 1b in good yields. The
fluorescence on excitation by 328 nm UV light was measured in
methanol, and the resulting spectra are depicted in Figure 1,
where it can be seen that 1a showed almost three times stronger
fluorescence than 1b. Thus, it was deduced that the arylsulfanyl
group was necessary for obtaining strong fluorescence in the
RS
PhS
PhS
OH
O
O
OK
OK
KOH (4 equiv)
O
2 in water
MeOH
quant
SR
SPh
SPh
3a
1
2a
OH
1a, R = Ph
1b, R = C8H17
Scheme 1. Preparation of tetrapotassium salt 2a.
OH
Si
Si
PhS
O
O
OH
OH
PhS
HO
PhS
Si
O
O
Cl
Cl
NaH, MeI
THF, 99%
MeO
Et3
N
OH
1a
SPh
t-BuOH/CH3CN
reflux, 58%
SPh
SPh
OH
5
OMe
4
1a
1b
OMe
PhS
KOH (1 equiv)
MeOH
OMe
OH
OK
PhS
OH
TBAF
OH
SPh
THF
92%
7
OMe
OK
SPh
6
OMe
OMe
PhS
KOH (2 equiv)
MeOH
OK
SPh
8
OMe
Scheme 2. Synthesis of half-protected hydroquinone dimer 6
and its potassium salts.
Figure 1. Fluorescence spectra for 1a and 1b in methanol.
Chem. Lett. 2013, 42, 876-878
© 2013 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

877
(A)
Figure 3. Fluorescence of hydroquinone dimers. From left,
aqueous solution of 2a, methanolic solution of 8, aqueous
solution of 8, aqueous solution of 8 in the presence of an
iron(III) chloride solution.
(B)
Figure 4. Fluorescence spectra of compound 8 with and
without the addition of 5 equiv of Cu2+ and Fe3+, concentration
is 10¹6 M.
Figure 2. (A) Absorption and fluorescence spectra of com-
pounds 6, 7, and 8 in methanol. Absorption spectra: concen-
tration is 2 © 10¹5 M, fluorescence spectra: concentration is
10¹6 M. (B) Absorption and fluorescence spectra of compounds
peaks with almost the same intensity at approximately 472 nm
when irradiated with 360 nm UV light (Figure 2B).
7
and 8 in water. Absorption spectra: concentration is
5 © 10¹5 M, fluorescence spectra: concentration is 10¹6 M.
The quantum yields (ΦF) for these compounds were
measured on excitation at 360 nm. Compound 6 in methanol
showed the largest value, reaching 0.61. For compound 8, the
quantum yield in methanol was found to be 0.45; however, in
water, the value reached as low as 0.02, even though similar
fluorescence was observed in the two solvents. In this case,
no decay in fluorescence occurred. Thus, compound 8 showed
stable fluorescence in water on irradiation with 360 nm UV light.
This promising result indicated that compound 8 could serve as a
new, useful water-soluble fluorescent dye. Images depicting the
fluorescence of the dye under black light (365 nm) illumination
are shown in Figure 3.
The fluorescence of 8 in water was sensitive to the presence
of certain metallic cations. For example, the fluorescence
disappeared when an aqueous solution of Cu2+ or Fe3+ salt
was added (Figure 4), while most alkali metal cations did not
affect the fluorescence strength.
In conclusion, we have successfully developed a new water-
soluble fluorescent dye based on hydroquinone dimer 1. The
preparation process was simple, and half-protection of the
hydroxy groups was achieved efficiently. The present type of
water-soluble fluorescent dye is expected to be applicable as a
new chemical sensor in biological as well as environmental
chemistry. Further studies on this topic are underway in our
laboratory.
Table 1. Spectroscopic properties of compound 6, 7, and 8a
b
Compound Solvent
-max/nm log ¾
-em/nm ΦF
6
7
methanol
water
methanol
water
328
348
332
328
336
4.74
4.20
4.64
3.69
4.43
398
472
399
471
398
0.61
nd
nd
0.02
0.45
8
methanol
aUV-vis spectra: concentration is 2 © 10¹5 M for methanol
and 5 © 10¹5 M for water, fluorescence spectra: concentration
b
is 10¹6 M. Concentration is 10¹5 M, excited at 360 nm.
The absorbance and fluorescence of compounds 6, 7, and
8 were measured in both methanol and water (Figure 2 and
Table 1). Each compound can be seen to exhibit an absorption
peak around 330 nm. For example, compound 6 shows a strong
peak at 328 nm (solid red line), while the absorption of
compound 8 is relatively low (solid green line). Fluorescence
emission peaks for these compounds in methanol can be
observed around 400 nm. Interestingly, the fluorescence inten-
sities show a reverse trend toward absorbance, with dipotassium
salt 8 exhibiting the strongest fluorescence out of three (dotted
green line, Figure 2A). Compounds 7 and 8 were also soluble in
water. Their UV absorption spectra can be seen to be similar in
shape in this solvent, but their intensities are very different;
monopotassium salt 7 shows strong absorption at 348 nm, while
dipotassium salt 8 shows relatively weak absorption. On the
other hand, these two compounds give fluorescence emission
We are grateful to the financial aid provided by the
Sasagawa Scientific Research Grant (to T.N.). We also thank
Professor J. Kawamata, Yamaguchi University for help in
measuring the quantum yields of the compounds.
Chem. Lett. 2013, 42, 876-878
© 2013 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

878
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© 2013 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/