Fluorescent internal charge transfer (ICT) saccharide sensor

Article abstract of DOI:10.1016/S0040-4039(01)00767-5

An efficient internal charge transfer (ICT) fluorescent saccharide sensor 3 has been prepared from 2-formyl benzeneboronic acid and aniline. When saccharides interact with sensor 3 in aqueous solution at pH 8.21 the emission maxima at 404 nm shifts to 362

Full text of DOI:10.1016/S0040-4039(01)00767-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 4553–4555
Fluorescent internal charge transfer (ICT) saccharide sensor
Susumu Arimori, Laurence I. Bosch, Christopher J. Ward and Tony D. James*
Department of Chemistry, University of Bath, Bath BA2 7AY, UK
Received 10 April 2001; revised 30 April 2001; accepted 10 May 2001
Abstract—An efficient internal charge transfer (ICT) fluorescent saccharide sensor 3 has been prepared from 2-formyl ben-
zeneboronic acid and aniline. When saccharides interact with sensor 3 in aqueous solution at pH 8.21 the emission maxima at 404
nm shifts to 362 nm. © 2001 Elsevier Science Ltd. All rights reserved.
Saccharide receptors based on the covalent interactions
between phenylboronic acid and diols are becoming
increasingly important.1 The most common interactions
are with cis-1,2- or 1,3-diols of saccharides to form five-
or six-membered rings, respectively. These bonds are
rapidly and reversibly formed between a diol and boronic
acid (sp3-hybridized) in aqueous solution. Formation of
an sp3-hybridized boronic acid is possible in a basic pH
region (boronate anion) or by incorporation of a neigh-
bouring tertiary amine (BꢀN bond) at neutral pH.
The BꢀN bond has been successfully used in the devel-
opment of saccharide sensors. The interaction of the
neighbouring amine with the boronic acid is strengthened
on saccharide binding. The strength of this boronic
acid–tertiary amine interaction can be used to signal the
binding event. Many successful photoinduced electron
transfer (PET) sensors have been developed based on this
approach.2–4 Internal charge transfer (ICT) is an impor-
tant mechanism for fluorescent signalling. However,
there are still very few ICT sensors for neutral molecules.5
The Shinkai group have prepared an ICT fluorescent
sensor for saccharides.6 However, with compound 1 only
a small shift in emission wavelength and intensity of
emission on saccharide binding is observed. We were
convinced that the failure of the coumarin system did not
mean that an efficient fluorescent ICT system could not
be found. What the Shinkai result had shown was that
the coumarin ICT system compound 1 was insensitive to
saccharide binding.
HO
B
HO
OH
B
HO
N
N
H
N
O
O
1
We recently reported7 our work on a saccharide selective
N
ICT colour sensor, compound 2. The wavelength of the
HO
OH
N
azo dye 2 shifted by ca. 55 nm on binding with D-fructose;
B
the observed colour changed from purple to red. The
colour change was due to a change in the environment
of the anilinic nitrogen which leads to changes in the
energy levels of the n and p* orbitals of the azo
chromophore.
H
NO2
3
2
NH2
CHO
B(OH)2
B(OH)2
N
B(OH)2
i)
ii)
N
H
+
3
Scheme 1. Synthesis of fluorescence saccharide sensor 3. Reagent (yields): (i) EtOH/toluene; (ii) NaBH4, MeOH (15%; two steps).
* Corresponding author.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00767-5

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S. Arimori et al. / Tetrahedron Letters 42 (2001) 4553–4555
lated from the fluorescence intensity versus pH titra-
tion.9 The observed shift in pKa to lower values on
saccharide binding is in agreement with previous
work.1,3,4,10
Our success with the ICT colour sensor compound 2
led us to investigate the ICT fluorescent properties of a
related system, compound 3. We believed that if a
working ICT system could be prepared then the many
advantages of fluorescence could be used to develop
working saccharide sensors.5
The fluorescence titration of 3 (2.0×10−5 mol dm−3) with
different saccharides was carried out in methanolic
aqueous buffer solution [52.1 wt% methanol at pH 8.21
(KCl, 0.01000 mol dm−3; KH2PO4, 0.002752 mol dm−3;
Na2HPO4, 0.002757 mol dm−3)].11 The fluorescence
The fluorescence sensor 3 was prepared according to
Scheme 1 from readily available starting materials,
aniline and 2-formylbenzeneboronic acid.8
spectra of 3 in the presence of
D-fructose (0–0.1 mol
dm−3) are shown in Fig. 2. The fluorescence intensity of
3 increased and shifted from 404 to 362 nm with
increasing saccharide concentration; an isosbestic point
was observed at 377 nm. The observation of an isos-
bestic point indicates that fluorescence sensor 3 changes
from a single unbound species to a single saccharide
bound species. The stability constants (K) of fluores-
cence sensor 3 were calculated by fitting the emission
wavelength at 360 nm versus concentration of saccha-
ride.9 The curves are shown in Fig. 3 and the calculated
values are given in Table 1.
The fluorescence intensity versus pH profile of com-
pound 3 (1×10−5 mol dm−3) in the absence and presence
of
D
-fructose (0.05 mol dm−3) are shown in Fig. 1. The
pH was controlled using the minimum volumes of
sodium hydroxide and hydrochloric acid solutions. The
pKa of compound 3 was 10.21 0.01 and 7.92 0.06 in
the presence of
D
-fructose (0.05 mol dm−3), as calcu-
The observed order of stability constants (K) with
D
-fructose>
D
-galactose>D-glucose, is the expected
order for all monoboronic acids.1,3,4,10
In conclusion, with this system we have shown that it is
possible to prepare efficient ICT fluorescent sensors for
saccharides which display both a significant change in
Figure 1. Fluorescence intensity versus pH profile of 3 at
25°C; [3]=1×10−5 mol dm−3, 33.3 wt% methanolic aqueous
solution in the presence of [NaCl]=0.05 mol dm−3, (ꢀ)
without saccharide, (ꢁ) in the presence of
D-fructose (0.05
mol dm−3). uex=244 nm, uem=360 nm.
Figure 3. Relative fluorescence intensity versus saccharide
concentration profile of 3 with (ꢁ)
D-fructose, (ꢀ) D-glucose,
(") -galactose, (ꢂ) -mannose. The measurement condi-
D
D
tions are the same as those in Fig. 2. uex=274 nm, uem=360
nm.
Table 1. Stability constant K (coefficient of determination;
r2) for saccharide complexes of fluorescence sensor 3
D
-Fructose
D
-Glucose
D
-Galactose
D-Mannose
Figure 2. Fluorescence spectra change of 3 (2.0×10−5 mol
a
10697 (0.99)
1896 (0.98)
2794 (0.99)
–
dm−3) with different concentration of
D-fructose (0–0.1 mol
dm−3) in 52.1 wt% MeOH pH 8.21 phosphate buffer. uex=274
a The K could not be determined because of the small fluorescence
nm.
change.

S. Arimori et al. / Tetrahedron Letters 42 (2001) 4553–4555
1996, 281–288.
4555
the intensity and wavelength of the emission maxima.
We are currently developing other ICT fluorescent sen-
4. James, T. D.; Sandanayake, K. R. A. S.; Shinkai, S.
sors selective for other saccharides.
Angew. Chem., Int. Ed. 1996, 35, 1911–1922.
5. Desilva, A. P.; Gunaratne, H. Q. N.; Gunnlaugsson, T.;
Huxley, J. M.; McCoy, C. P.; Rademacher, J. T.; Rice, T.
E. Chem. Rev. 1997, 97, 1515–1566.
Acknowledgements
6. Sandanayake, K. R. A. S.; Imazu, S.; James, T. D.;
Mikami, M.; Shinkai, S. Chem. Lett. 1995, 139–140.
7. Ward, C. J.; James, T. D.; Patel, P.; Ashton, P. Chem.
Commun. 2000, 229–230.
8. Selected data for 3: mp: 125–129°C. Found: C, 74.70; H,
5.97; N, 6.63. C13H14BNO2–H2O requires C, 74.72; H,
5.80; N, 6.70%; lH (300 MHz; CD3OD) 4.21 (2H, s,
CH2), 6.6–6.7 (3H, m, ArH), 6.95–7.25 (6H, m, ArH); lC
(75 MHz; CD3OD) 51.6, 117.4, 121.5, 126.9, 127.9, 129.8,
130.2, 132.7, 146.0, 149.1; m/z (FAB) 497.3 ([M+2(3-
HOCH2C6H4NO2)−2H2O]+, 100%).
T.D.J. wishes to acknowledge the Royal Society, The
EPSRC, and Beckman-Coulter for support. S.A. wishes
to acknowledge Beckman-Coulter for support through
the award of a Postdoctoral Research Fellowship.
L.I.B. wishes to acknowledge Beckman-Coulter for
support through the award of a Studentship. C.J.W.
wishes to acknowledge the EPSRC and Avecia Limited
for support through the award of a Studentship. We
would also like to acknowledge the support of the
University of Bath.
9. The pKa and K were analysed in KaleidaGraph using
nonlinear (Levenberg–Marquardt algorithm) curve
fitting.12 The errors reported are the standard errors
obtained from the best fit.
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