A sorbitol-selective fluorescence sensor

Article abstract of DOI:10.1016/j.tetlet.2005.03.121

A new anthracene derivative bearing two phenylboronic acid groups at the 1,8-positions was prepared and its binding properties towards sorbitol, xylitol, fructose, glucose and galactose have been studied using fluorescence analysis.

Full text of DOI:10.1016/j.tetlet.2005.03.121

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 3453–3456
A sorbitol-selective fluorescence sensor
K. M. K. Swamy,a Yun Jung Jang,a Min Sun Park,a Hwa Soo Koh,a
Sang Kil Lee,b Yeo Joon Yoona,* and Juyoung Yoona,*
aDepartment of Chemistry and Division of Nano Sciences, Ewha Womans University, 11-1 Daehyun-Dong,
Seodaemun-Ku, Seoul 120-750, Korea
bSchool of Chemical Engineering, Seoul National University, Seoul 151-742, Korea
Received 7 February 2005; revised 16 March 2005; accepted 18 March 2005
Available online 6 April 2005
Abstract—A new anthracene derivative bearing two phenylboronic acid groups at the 1,8-positions was prepared and its binding
properties towards sorbitol, xylitol, fructose, glucose and galactose have been studied using fluorescence analysis.
Ó 2005 Elsevier Ltd. All rights reserved.
A great amount of attention has been devoted to the
development of fluorescent chemosensors to recognize
ions.1 On the other hand, detection of neutral species
by a real-time fluorescence analysis in aqueous media
has been one of the major challenges in fluorescent
chemosensor-related research. Recently, by applying
boronic acid–saccharides interaction to the fluorescent
PET (photo-induced electron transfer) sensor, many
successful results have been reported during last
decade.2
We report herein a new fluorescent PET sensor for sac-
charides, which bears two phenylboronic groups at the
1,8-positions of anthracene. While 9,10-isomer (4) is
reported to recognize glucose,5b,c host 1 selectively senses
D-sorbitol in aqueous solution at physiological pH.
We prepared the host 1 by reaction of the 2-meth-
ylaminomethylphenylboronic acid 37 with 1,8-bis(bro-
momethyl)anthracene 2 as shown in Scheme 1. Our
synthesis began with 1,8-bis(hydroxymethyl)anthracene,
which was then transformed to 1,8-bis(bromomethyl)
anthracene 2 using the procedures of Nakagawa and
co-workers.8 2-Methylaminomethylphenylboronic acid
3 was obtained from the treatment of 2-formylphenyl
boronic acid and methylamine followed by the reduction
with sodium borohydride. Compound 1 was synthesized
by the addition of 3 to a mixture of 2, K2CO3 and
CHCl3 at room temperature (see Supporting
Information).
Even though boronic acid has been known for almost
50 years to have high affinity for diol-containing com-
pounds such as carbohydrates,3 Yoon and Czarnik
reported4 2-anthrylboronic acid as the first example of
fluorescent chemosensor in 1992, which displayed chela-
tion-enhanced fluorescent quenching (CHEQ) effects
upon the addition of polyols.
Most noticeably, the Sinkai group5 and James group6
have been leading the field in many regards. Sinkai
and his co-workers have reported new series of PET sen-
sors for saccharides bearing boronic acid unite as well as
benzyl amine unit.5 Recently, James group also reported
many noticeable results regarding boronic acid-based
fluorescent receptors for saccharides.6
OH
B
OH
B
B(OH)2
OH
HO
Br
Br
H
N
N
N
3
K2CO3/CHCl3
21%
Keywords: Fluorescent chemosensor; Carbohydrate sensing; Boronic
acid; Anthracene; Sorbitol detection.
2
*
Corresponding authors. Tel.: +82 2 3277 2400; fax: +82 2 3277 2384
(J.Y.); tel.: +82 2 3277 4082; fax: +82 2 3277 2384 (Y.J.Y.); e-mail
addresses: jyoon@ewha.ac.kr; joony@ewha.ac.kr
1
Scheme 1. Synthesis of compound 1.
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.03.121

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K. M. K. Swamy et al. / Tetrahedron Letters 46 (2005) 3453–3456
rescent sensors for anions and cations.12 Introduction
of ligands onto 1,8-positions of anthracene provided a
unique preorganized and rigid binding site compared
to 9,10-anthracene derivatives. Indeed, our host 1
displayed quite different binding properties towards
saccharides compared to host 4.
Cl
Cl
N
N
OH
N
B
B
B
HO
OH
OH
OH
OH
B
HO
OH
N
4
5
From the pH–fluorescence profile in unbuffered aqueous
media, pKa of compound 1 in the presence of 0.1 mM of
fructose, galactose and glucose were calculated as 4.22,
4.26 and 4.47, respectively. An observed fluorescence
dependence on pH is in keeping with the intramolecular
amine quenching mechanism.5a
HO
B
OH
O
HO
B(OH)2
B(OH)2
B
OH
N
In host 1, the interaction of boronic acid and benzyl
amine moiety can only partially inhibit the photo-in-
duced electron transfer (PET), however, this inhibition
of PET can be maximized upon the addition of saccha-
rides because the complexed form of boronic acid–
saccharide can lower the pKa of boronic ester. Conse-
quently, the anionic form of boronate can make a
stronger interaction with adjacent benzylic amine
moiety, which resulted in the fluorescent chelation-
enhanced fluorescent (CHEF) effect by blocking the
PET efficiently.5a
O
OH
H
7
6
OH
HO
B
B
8a:
8b:
OH
OH
N
N
N
All titration studies were conducted in 50% MeOH/
0.1 M aqueous phosphate buffer at pH 7.4 and using a
6 lM concentration of compound 1. Excitation wave-
length was 365 nm. From the fluorescent titrations, the
association constants for sorbitol, xylitol, fructose,
galactose and glucose were calculated as 1060, 440,
200, 81 and 12 MÀ1 (errors <10%), respectively (Figs.
2–6).13 Unlike host 4, host 1 displayed a selectivity for
sorbitol among the saccharides examined. The selectiv-
ity for sorbitol is almost 100 times that for glucose. To
confirm the selectivity, the association constant for sor-
bitol was redetermined in the presence of 1 mM glucose
(Ka = 1080 MÀ1): no decrease in observed association
constant resulted (see Supporting Information). The
fluorescence enhancements of chemosensor 1 with sorbi-
tol, xylitol, fructose, galactose and glucose were 2.2-,
1.9-, 3.9-, 2.9- and 2.3-fold, respectively.
N
Linker
O
O
OH
B
OH
B
OH
HO
N
N
9
Figure 1. Diboronic acid sensors for saccharides reported in the
literature.
As shown in Figure 1, few receptors as the diboronic
acid sensors have been reported by Shinkai and
co-workers (4),5b,c Norrild and co-workers (5),9 Drueck-
hammer and co-workers (6),10 Wang and co-workers
(8)11 and James and co-workers (7,6a 96f). These recep-
tors display selective binding for glucose over other car-
bohydrates. For example, sensor 4 exhibited a 12- and
25-fold selectivity for glucose over fructose and galac-
tose, respectively. Wang and co-workers reported that
8a also shows 43-fold selectivity for glucose over fruc-
tose.11 On the other hand, the binding constants of sen-
sor 8b for glucose, fructose and galactose were
determined as 178, 283 and 33 MÀ1, respectively. These
compounds differ in linker length and flexibility, which
might be the reason for the opposite selectivity of the
two sensors. On the other hand, host 7 is reported to
show a selectivity towards small saccharides such as D-
sorbitol, D-fructose, dulcitol, etc.6a
We have recently reported various anthracene deriva-
tives bearing binding units at the 1,8-positions as fluo-
Figure 2. Fluorescence spectra of 1 (6 lM) upon the addition of
D-sorbitol in 50% MeOH/0.1 M aqueous phosphate buffer at pH 7.4.

K. M. K. Swamy et al. / Tetrahedron Letters 46 (2005) 3453–3456
3455
Figure 6. Fluorescence titrations of 1 (6 lM) in 50% MeOH/0.1 M
aqueous phosphate buffer at pH 7.4 as
concentration.
a function of sugar
Figure 3. Fluorescence spectra of 1 (6 lM) upon the addition of xylitol
in 50% MeOH/0.1 M aqueous phosphate buffer at pH 7.4.
selectivity for sorbitol, which can be productively com-
pared to the selectivity of chemosensor 4.
In conclusion, new anthracene derivative 1, which con-
tains two boronic acid groups at 1,8-positions of anthra-
cene was prepared. The fluorescent chemosensor 1
displayed a selective binding with D-sorbitol at pH 7.4
among the saccharides examined. This work illustrates
that the selectivity of chemosensor bearing diboronic
acid groups can be modified by controlling the spacing
unit between two boronic acid groups and the rigidity
of this binding site. This result also demonstrated the
possibility of monitoring the concentration of biologi-
cally important saccharides, which are less abundant
than D-glucose, in a variety of industrial and biological
applications.
Figure 4. Fluorescence spectra of 1 (6 lM) upon the addition of
D-fructose in 50% MeOH/0.1 M aqueous phosphate buffer at pH 7.4.
Acknowledgements
This work was supported by the Korea Research
Foundation Grant (KRF-2004-005-C00093). K.M.K.S.
thanks for the Brain Pool Fellowship.
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2005.03.121. Experimental Sections including character-
izations of 1 are available.
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