Suzuki homo-coupling reaction based fluorescent sensors for monosaccharides

Article abstract of DOI:10.1039/c4ra07331b

Palladium catalysed, aryl boronic acid homocoupling, is explored as a fluorescence sensing regime for saccharides. The catalytic formation rate of fluorescent bi-aryls, under control of a palladium catalyst, is modulated by the presence of saccharides. The nature of the aryl group, rate of biaryl formation and limits of detection are investigated.

Full text of DOI:10.1039/c4ra07331b

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Suzuki homo-coupling reaction based fluorescent
sensors for monosaccharides†
Cite this: RSC Adv., 2014, 4, 35238
Su-Ying Xu, Hui-Chen Wang,a Stephen E. Flower,a John S. Fossey,b
a
*
c
a
*
*
Yun-Bao Jiang and Tony D. James
Received 11th June 2014
Accepted 29th July 2014
DOI: 10.1039/c4ra07331b
www.rsc.org/advances
Palladium catalysed, aryl boronic acid homocoupling, is explored as a saccharide sensing.5,9–11 Colorimetric and uorometric boronic
fluorescence sensing regime for saccharides. The catalytic formation acid based saccharide sensors rely on a linear response gener-
rate of fluorescent bi-aryls, under control of a palladium catalyst, is ated by saccharides interacting with a dened stoichiometry of
modulated by the presence of saccharides. The nature of the aryl boronic acid sensor, to elicit the colour or uorescence
group, rate of biaryl formation and limits of detection are investigated. responses they display. The synthesis of new sensor systems can
oen be challenging yet the search for more sensitive sensors
remains a highly active area of research. Indicator displacement
assays partially relieve synthetic effort since the signal reporter
Introduction
moiety does not need to be directly linked to the binding unit
Saccharide recognition is vital to the development and survival
(boronic acid moiety).12–14 Using a similar concept a boronic
of life and has attracted signicant interest.1–5 However, the
acid-modied quencher was used by Singaram et al.,15 in this
development of synthetic, saccharide recognition domains that
system binding between boronic acid (quencher) and saccha-
can compete with bulk water to recognise these heavily solvated
saccharide molecules remains a challenging problem.6–8 Aryl
boronic acids reversibly bind covalently with 1,2- and 1,3-diols
to form ve- and six-member boronate esters, respectively
ride released an anionic dye, resulting in signal recovery. While
saccharide selectivity oen requires multiple boronic acid
receptors, Jiang and co-workers have developed a series of
glucose-selective monoboronic acid derivatives using the non-
(Fig. 1).
covalent “linking” of boronic acid moieties to afford optimal
The reversible covalent binding of boronic acids with
binding conformation for D-glucose.16,17 However, the reversible
saccharides has been extensively explored in the area of direct
interaction between a boronic acid and diols typically allow
binding of sugar at mM or sub-mM levels. Thus a high
concentration of chemosensor is required to generate a
detectable signal.
New chemosensing strategies with enhanced sensitivity are
in great demand. In previous work by some of the authors
included in this report, the palladium catalysed formation of
biphenyl via a homocoupling of phenylboronic acid was used as
a probe to detect saccharide binding.18 The approach relies on
the catalytic formation of the reporter molecule, therefore the
Fig. 1 Binding scheme between boronic acid moiety and cis-diol.
sensitivity is not limited to the detection of the added probe
rather the formation of biphenyl giving enhanced opportunities
for sensitivity in colorimetric and uorometric sensing, since
the background and noise are minimised. In this system it is the
rate of probe formation that gives information on the concen-
tration of the saccharide analyte.
aDepartment of Chemistry, University of Bath, Bath BA2 7AY, UK. E-mail: suying.xu@
bath.edu; t.d.james@bath.ac.uk
bThe School of Chemistry, The University of Birmingham, Edgbaston, Birmingham, B15
2TT, UK
cDepartment of Chemistry, College of Chemistry and Chemical Engineering, and the
MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, Xiamen
University, Xiamen 361005, China. E-mail: ybjiang@xmu.edu.cn
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c4ra07331b
In a palladium catalysed Suzuki homo-coupling reaction the
nature of the boron species affects the rate of reaction. Boronic
esters react more slowly than boronic acids in these reactions;
therefore the formation of a boronic ester with a saccharide
35238 | RSC Adv., 2014, 4, 35238–35241
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slows bi-aryl formation. The boronic ester formed between an
aryl boronic acid moiety and probe saccharides slows the rate of
reaction towards Suzuki homo-coupling.
In the earlier work with phenylboronic acid (1a) as the
substrate for catalytic saccharide sensing, the product biphenyl
has excitation and emission wavelengths of 250 nm and 311
nm, respectively. These wavelengths are sub-optimal for prac-
tical sensing applications, since exogenous uorophores could
interfere and impair the accuracy of this sensing system. As
such alternative boronic acid substrates are required in order to
deliver output molecules with longer wavelength excitation and
emission proles to avoid interference from exogenous
uorophores.
Fig. 2 Illustration of the sensing mechanism.
Table 1 Comparison of limit of detection of different saccharides with
probe 1a and 1b, respectively
Limit of detection, mol Lꢀ1
Results and discussion
D-Fructose
D-Galactose
D-Glucose
In addition to the previously tested phenyl boronic acid (1a),
naphthalene-1-boronic acid (1b) and 1,4-phenyldiboronic acid
(1c), (Scheme 1), were selected as substrates for comparison in
the catalytic Suzuki homo-coupling based saccharide sensing
strategy (Fig. 2).
For naphthalene-1-boronic acid (1b) when the catalyst was
added, a new emission at 380 nm was observed along with the
disappearance of its intrinsic emission at 330 nm (S1†), which
was a very encouraging result since as well as extending the
wavelength, the system is now a ratiometric uorescence
sensing platform for saccharides. The reaction was monitored
using TLC and the binaphthyl product was veried using an
authentic sample of 1,10-binaphthyl (S2†). The optimum time
for each measurement to obtain the maximum difference
1a (I311 nm
1b (I380 nm/I330 nm
)
2.4 ꢁ 10ꢀ5
1.8 ꢁ 10ꢀ5
3.3 ꢁ 10ꢀ4
2.0 ꢁ 10ꢀ4
6.1 ꢁ 10ꢀ3
1.2 ꢁ 10ꢀ3
)
between the catalysed reaction with and without fructose was 25
minutes (S3†). The titration of 1b (Fig. 3) with D-fructose
revealed that 1 mM of D-fructose (4 mM in the case of the PBA
system, shown in S4†) was required to fully quench the reaction,
demonstrating that the sensitivity of the catalytic sensing
strategy can be modied by changing substrates. More impor-
tantly the ratiometric sensing observed could eliminate possible
interference in the system and also lead to a calibration free
system. Using the same protocol, saccharide titrations with D-
galactose and D-glucose were also investigated and the usual
saccharide order of affinities towards the boronic acid moiety
was observed (Table 1).19 The limit of detection (LOD) indicates
that an improved level of sensitivity was observed using the
naphthalene-1-boronic acid, compared with our previous work.
The improved sensitivity might be attributed to the establish-
ment of the internal calibration of this sensing system.
1,4-Phenydiboronic acid (1c) was also utilised under the
same conditions; in this system the uorescent intensity dis-
played an initial increase, but the intensity reduced over time.
We attributed this to poor water solubility of the resulting
polymer product, i.e. the uorescence decreases as the product
desolvates. However, a good linear relationship between uo-
rescent emission and the concentration of saccharide is
obtained before the uorescence intensity decreases. The D-
fructose titration was carried out by collecting uorescent
spectra aer six minutes at different concentrations of saccha-
rides. The 1,4-phenyldiboronic acid displayed a red-shied
maximum emission and quicker response, which might be due
to the extended conjugation of the generated products and also
the reactivity of the substrate towards Suzuki homo-coupling
reactions (Fig. 4).
It is worth noting that all the substrates were investigated
under the same experimental conditions as the previous work
without further optimisation toward each substrate for easier
comparison. Given the popularity of the Suzuki coupling reac-
tion and the multitude of boronic acid derivatives that are
Scheme 1 Structures of phenylboronic acid (1a), naphthalene-1-
boronic acid (1b) and 1,4-phenyldiboronic acid (1c) and their corre-
sponding homocoupling products (3a, 3b and 3c respectively).
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Experimental section
Reagents and solvents were purchased from Sigma-Aldrich and
Fisher, and were used directly without further purication.
Fluorescence spectra were recorded on a Perkin Elmer Lumi-
nescence Spectrophotometer LHB50 uorescence spectrometer
using a 1 cm quartz cell. Buffer solutions were 0.02 M NaHCO3–
Na2CO3, calibrated by Hanna Instruments HI 9321 Micropro-
cessor pH meter.
NaHCO3–Na2CO3 buffer solution was made up by dissolving
0.53 g Na2CO3 and 1.68 g NaHCO3 into 250 mL deionised water
($18.2 MU), with a pH value of 9.3. The stock solution of
palladium catalyst was 1.0 ꢁ 10ꢀ3 M, made from PdCl2 dis-
solved in MeOH. All the experiments were carried out at room
temperature.
Fig. 3 (a) Fluorescent spectra of 1b after 25 minutes in the presence of
different concentrations of D-fructose; [1b] ¼ 3 ꢁ 10ꢀ6 M, [Pd] ¼ 1 ꢁ
10ꢀ5 M, lex ¼ 280 nm (b) plot of the ratio fluorescent intensities
(I380 nm to I330 nm) against the concentrations of saccharide.
Acknowledgements
TDJ and SYX are grateful for nancial support from China
Scholarship Council (CSC) and University of Bath for a Full Fees
Scholarship. TDJ, JSF, YBJ and SYX thank the Royal Society-
NSFC International Exchanges Scheme: China cost-share pro-
gramme for funding exchanges between the UK and China. The
Catalysis And Sensing for our Environment (CASE) network is
thanked for promoting research exchange opportunities. TDJ
thanks Xiamen University for a guest professorship.
Notes and references
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concentration of fructose after six minutes under the catalysis of
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The magnitude of inhibition for all the boronic acids inves-
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saccharides toward the boronic acid moiety.19 This demon-
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