A molecular colour sensor for monosaccharides

Article abstract of DOI:10.1039/a909204h

Boronic acid colour sensor 2 undergoes a large visible colour change, from purple to red in aqueous solution on the addition of monosaccharides.

Full text of DOI:10.1039/a909204h

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A molecular colour sensor for monosaccharides†
a
b
a
a
Christopher J. Ward, Prakash Patel, Peter R. Ashton and Tony D. James*
a
The University of Birmingham, School of Chemistry, Edgbaston, Birmingham, UK B15 2TT.
E-mail: tdjames@chemistry.bham.ac.uk
AVECIA Limited, Hexagon House, PO Box 42, Blackley, Manchester, UK M9 8ZS
b
Received (in Cambridge, UK) 22nd November 1999, Accepted 23rd December 1999
Boronic acid colour sensor 2 undergoes a large visible colour
change, from purple to red in aqueous solution on the
addition of monosaccharides.
Much recent attention has been paid to the development of
synthetic molecular receptors with the ability to recognise
neutral organic species, including saccharides. A large majority
of these systems have utilised hydrogen bonding interactions for
the purposes of recognition and binding of guest species.
However, there is still no designed, monomeric receptor which
can compete effectively with bulk water for low concentrations
of monosaccharide substrates.1
Boronic acids readily and reversibly form cyclic esters with
diols in aqueous basic media. Saccharides contain a linked array
of hydroxy groups ideal for binding to boronic acids. The most
common interaction is with 1,2- and 1,3-diols of saccharides to
form five- or six-membered rings respectively via two covalent
bonds. Lorand and Edwards determined the selectivity and first
The main drawback of this system is the relatively small
shifts in the absorption bands of the chromophore upon
saccharide binding. The aim with this research was to develop
a molecular ICT sensor, which produces a large visible colour
change on saccharide binding. If a system with a large colour
change can be developed it could be incorporated into a
stability trends of various polyols and saccharides towards
phenylboronic acid.2
The complex stability increases from ethylene glycol to -
D
diagnostic test paper for
indicator paper for pH. Such a system would make it possible to
measure -glucose concentrations without the need of specialist
D-glucose, similar to universal
fructose, i.e. from the simple acyclic diols to the rigid, vicinal
cis-diols of saccharides. This observed selectivity order is
common to all monoboronic acids, not just to phenylboronic
D
3
instrumentation. This would be of particular benefit to diabetics
in developing countries.
Dye molecule 2 was prepared in three steps in high yield.‡
The imine formed between comercial 2-formylphenylboronic
acid and m-toluidine was reduced using NaBH to give amine 3
4
in 75% yield. The final step is to couple 3 with the diazonium
acid. The suitability of the boronic acid functionality as a
receptor for saccharides has been established in both circular
dichroism and fluorescence detection studies. Indeed, a number
of fluorescent sensors have been reported in the literature.4
–6
A fairly recent development has been the study of the effect
of saccharides on the colour of dyes containing boronic acid
7
salt of 4-nitroaniline to give the boronic acid azo dye molecule
functionality. Russell synthesised a boronic acid azo dye from
2
in 74% yield. The m-methyl group of 3 ensures that only the
m-aminophenylboronic acid which was found to be sensitive to
saccharides. Nagasaki, Shinmori and Shinkai observed that
chromophores containing boronic acid moieties and which
aggregate in water, changed colour and deaggregated upon
14
p-isomer is obtained.
Absorption–pH titrations, from pH 2 to 12, of 2 in 0.05
2
3
mol dm NaCl in MeOH–H
2
O (1+2, w/w), were followed
8
9
using a UV-VIS spectrometer. The experiments were then
repeated with 0.05 mol dm
addition of saccharides. This year Strongin reported a system
based on resorcinarenes for the visual sensing of saccharides.
However, for a colour change to be observed the saccharide
must be heated (90 °C) in DMSO.
2
3
D
-fructose also present. The NaCl
present acts as an ionic buffer because small amounts of NaCl
are formed on adjustment of the pH with NaOH and HCl.
Because the titrations are carried out in a MeOH–H O mixture
2
rather than simply water, the concept of pH is not strictly
applicable to this situation. However, De Ligny and Rehbach
have shown that for solutions in 50% MeOH the pH is only
changed by 0.1 of a pH unit compared to a 100% water
solution.15
In 1994 Sandanayake and Shinkai reported ‘the first known
synthetic molecular colour sensor for saccharides’.10 This
designed molecular internal charge transfer (ICT) sensor, dye
molecule 1, was based on the intramolecular interaction
between the tertiary amine and the boronic acid group.11,12 The
electron-rich amine creates a basic environment around the
electron-deficient boron centre, which has the effect of inducing
a
The pK of compound 2 calculated from the absorption–pH
titrations16 was 10.2 and in the presence of 0.05 M fructose the
the boronic acid–saccharide interaction and reducing the
working pH of the sensor.13 Electronic changes associated with
value drops to 6.95. This shift on saccharide binding is in
agreement with previous work2
,3,5,6,10
and can be explained by
a
this decrease in the pK of the boronic acid moiety on saccharide
the decrease in oxygen–boron–oxygen bond angle upon
saccharide binding, which increases the acidity of the boron
centre.3
During these titrations it was noted that the UV–VIS
absorption maxima of 2 does not move to as long a wavelength
complexation were shown to be transmitted to the neighbouring
amine. This creates a spectral change in the connected ICT
chromophore, which can be detected spectrophotometrically.
a
The pK value associated with the boron–nitrogen interaction
shifted on saccharide addition.
at high pH with
phenomenon -fructose,
tions were performed at pH 11.32. The absorption spectra of the
-glucose titrations are shown in Fig 1.
D
-fructose present. To investigate this
D
D
-glucose and ethylene glycol titra-
†
Details of the colour changes upon addition of
D-glucose to 2 are available
as supplementary data, see http://www.rsc.org/suppdata/cc/a9/a909204h/
D
Chem. Commun., 2000, 229–230
This journal is © The Royal Society of Chemistry 2000
229

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In the absence of saccharide, at pH 11.32, the observed colour
is purple and in the presence of saccharide the colour is red.†
From previous work it is known that when saccharides form
cyclic boronate esters with boronic acids, the Lewis acidity of
the boronic acid is enhanced and therefore the Lewis acid–base
interaction between the boronic acid and the amine is strength-
ened.3 This stronger B–N interaction will favour the red
species over the equivalent saccharide bound purple species.
The reason for this can be understood by considering species 4
and 5 from Scheme 1. In the presence of saccharide the B–N
interaction in species 5 is stronger than that in species 4. The
increased B–N interaction of species 5 will make the N–H
proton of species 5 more acidic than the corresponding proton in
species 4. Therefore at higher pH, species 5 will deprotonate to
form the red species 7, whereas the weaker B–N bond in species
,12
4
is broken by hydroxide ion to form the purple coloured species
6.§
The colour change arises from the different electronic
2
5
Fig. 1 Absorption spectral changes of dye molecule 2 (5.66 3 10 mol
23
dm ) with increasing concentration of
D
-glucose at pH 11.32. pH 11.32
buffer: 0.01000 mol dm KCl, 0.002771 mol dm23 NaHCO
2
3
, 0.002771
environment of the anilinic nitrogen. The anilinic nitrogen is
conjugated to the azo chromophore. A change in the environ-
ment of this nitrogen leads to changes in the energy levels of the
n and p* orbitals of the azo chromophore and hence to a change
in the absorption energy and wavelength. The proposal of these
equilibrium species may also explain why dye molecule 1 did
not give a visible spectral shift on saccharide binding. Because
the anilinic nitrogen is tertiary in nature rather than secondary,
there is no possibility of deprotonation, so the high pH boron–
nitrogen bond cannot be formed. Hence there is no differ-
entiation between the equilibrium species at high pH and
consequently no spectral shift is observed.
3
23
mol dm Na
2
CO
3
2
in 52.1% MeOH–47.9% H O (ref. 23).
T. D. J. wishes to acknowledge the Royal Society for support
through the award of a University Fellowship. C. J. W. wishes
to acknowledge the EPSRC and AVECIA Limited for support
through the award of a Studentship.
Notes and references
+
‡
3
1
Selected data for 2: mp 120–122 °C (decomp.) (HRMS: Found: [M] ,
2
1
72.1381, C20
H17BN O
4 3
requires 372.1394); nmax(KBr)/cm
1602s,
H
518s and 1333s; d (300 MHz; CD
3
OD; Me Si) 2.63 (3 H, m), 4.45 (2 H,
4
br s), 6.52–6.58 (1 H, m), 6.99–7.04 (1 H, m), 7.18–7.40 (5 H, m), 7.63–7.72
1 H, m), 7.87–7.93 (1 H, m), 8.21–8.36 (2 H, m); d (125 MHz; CD OD;
Me Si) 18.1, 49.7, 113.2, 114.7, 118.3, 122.7, 123.6, 125.7, 127.6, 128.1,
(
C
3
4
+
1
H
29.8, 130.2, 132.8, 144.3; m/z (EI) 373 ([MH 2 H
2
O] , 66%), 222 ([M 2
+
2 2 6 4 2
O–N C H NO ] , 100).
§
Negative ion electrospray ionisation (ESI) mass spectrometry using a
Micromass LCT spectrometer confirmed the presence of the red species 7
(m/z 533).
1
A. P. Davis and R. S. Wareham, Angew. Chem., Int. Ed., 1999, 38,
978.
2
2
3
J. P. Lorand and J. O. Edwards, J. Org. Chem., 1959, 24, 769.
T. D. James, K. Sandanayake and S. Shinkai, Angew. Chem., Int. Ed.
Engl., 1996, 35, 1911.
Scheme 1
4
5
6
7
8
C. R. Cooper and T. D. James, Chem. Commun., 1997, 1419.
C. R. Cooper and T. D. James, Chem. Lett., 1998, 883.
T. D. James, P. Linnane and S. Shinkai, Chem. Commun., 1996, 281.
A. P. Russell, WO 91/04488, 1991.
N. Nagasaki, H. Shinmori and S. Shinkai, Tetrahedron Lett., 1994, 35,
2201.
The wavelength shifts by ca. 55 nm to shorter wavelength
upon guest complexation. The concentration of the guest
required to produce the change is different in each case, which
is due to the different stability constants of the binding species,
2
as mentioned earlier. The wavelength shift obtained with 2 on
9 C. J. Davis, P. T. Lewis, M. E. McCarroll, M. W. Read, R. Cueto and
R. M. Strongin, Org. Lett., 1999, 1, 331.
addition of diols is the largest observed to date. The stability
constants (logK) of the boronic acid dye–saccharide complexes
were calculated from UV–VIS absorption–concentration pro-
-fructose (3.75), -glucose (1.85) and
ethylene glycol (0.66) respectively.
Scheme 1 shows the species in equilibria responsible for the
observed colour change, consistent with the experimental
results. With dye molecule 1 Shinkai proposes that at inter-
mediate pH a boron–nitrogen interaction is prevalent, whereas
at high and low pH this bond is broken.10 What makes the
equilibria of dye molecule 2 more interesting is the presence of
the anilinic hydrogen, which can give rise to different species at
high pH. This apparently simple modification in the molecular
structure is responsible for the enhanced response of these dyes
relative to those previously reported.
1
0 K. Sandanayake and S. Shinkai, J. Chem. Soc., Chem. Commun., 1994,
1
083.
1 H. S. Snyder, M. S. Konecky and W. J. Lennarz, J. Am. Chem. Soc.,
958, 80, 3611.
1
files. The logK vales are
D
D
1
1
1
1
2 R. T. Hawkins and H. R. Snyder, J. Am. Chem. Soc., 1960, 82, 3863.
3 G. Wulff, Pure Appl. Chem., 1982, 54, 2093.
4 P. Gordon and P. Gregory, Organic Chemistry in Colour, Springer-
Verlag, Berlin, 1990.
15 C. S. De Ligny and M. Rehbach, Recl. Trav. Chim. Pays-Bas, 1960, 79,
727.
1
1
6 B. Valeur, J. Pouget, J. Bourson, M. Kaschke and N. P. Ernsting,
J. Phys. Chem., 1992, 96, 6545.
7 D. D. Perrin and B. Dempsey, Buffers for pH and Metal Ion Control,
Chapman & Hall, London 1974.
Communication a909204h
230
Chem. Commun., 2000, 229–230