Meso-meso-linked porphyrin dimer as a novel scaffold for the selective binding of oligosaccharides

Article abstract of DOI:10.1039/b003365k

A meso-meso-linked porphyrin dimer 1 bearing four boronic acid groups shows high selectivity for maltotetraose (n = 4) among maltooligosaccharides (n = 1-7), indicating that this class of porphyrins acts as a novel scaffold to design oligosaccharide recep

Full text of DOI:10.1039/b003365k

Meso–meso-linked porphyrin dimer as a novel scaffold for the selective
binding of oligosaccharides†
Masato Ikeda,a Seiji Shinkai*a and Atsuhiro Osukab
a Department of Chemistry and Biochemistry, Graduate School of Engineering, Kyushu University, Fukuoka
812-8581, Japan. E-mail: seijitcm@mbox.nc.kyushu-u.ac.jp
b Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan
Received (in Cambridge, UK) 26th April 2000, Accepted 5th May 2000
Published on the Web 25th May 2000
A meso–meso-linked porphyrin dimer 1 bearing four boronic
acid groups shows high selectivity for maltotetraose (n = 4)
among maltooligosaccharides (n = 1–7), indicating that this
class of porphyrins acts as a novel scaffold to design
oligosaccharide receptors.
The specific interaction between phenylboronic acids and
saccharides or related compounds has been attracting increasing
attention as a novel force for sugar recognition in aqueous
systems.1–8 Since one phenylboronic acid reacts with two OH
groups to form a cyclic boronate ester, monosaccharides usually
bearing five OH groups tend to form 1+2 monosaccharide–
phenylboronic acid complexes.1,9–13 However, the stability
order of these complexes is always the same, which is governed
by the inherent structure of monosaccharides.2–4,14,15 Of such
monosaccharides, fructose has a high association constant
Scheme 1 Reagents and conditions [yields]: i, TFA, CH2Cl2, r.t. then
whereas glucose has a low association constant.14,15 In contrast,
chloranil, reflux [30%]; ii, Zn(OAc)2, CHCl3–MeOH, r.t. [88%]; iii,
diboronic acids which can react with four of the five OH groups
propane-1,3-diol, benzene, reflux [98%]; iv, AgPF6/MeCN, CHCl3, r.t.
[4%].
to form intramolecular 1+1 complexes show a different stability
order, which is related to the specific spatial position of two
boronic acid groups. This implies that one can recognise a
specific saccharide by appropriate manipulation of two boronic
acids in the same molecule and the concept may be extended to
the selective binding of oligosaccharides. This idea has been
The absorption spectrum of 1 showed a split Soret band
(412.0 and 448.0 nm) and a few Q bands (516.0, 560.0 and
594.5 nm). When maltooligosaccharides (Mn: a-1,4-linked
oligomers of
D-glucose) were added, the absorption spectra
tested with a few diboronic acid systems bearing a ‘long’
spacer: e.g. diphenyl-3,3A-diboronic acid, stilbene-3,3A-di-
boronic acid and cis-5,15-bis[2-(dihydroxyboronyl)phenyl]-
10,20-diphenylporphine show some selectivity for certain
disaccharides but the selectivity observed so far is not very
high.16–18 We thus considered that one should look for a ‘long’
and ‘rigid’ scaffold by which one might finely tune the distance
between two boronic acid groups. Recently, it was found that
the meso–meso coupling reaction of Zn(II) porphyrinates is
efficiently mediated by AgPF619 to yield oligomeric porphyrins.
These new compounds seem to satisfy the prerequisites
mentioned above. As a preliminary step to use these compounds
as scaffolds for saccharide recognition, we designed compound
1. Very interestingly, we have found that 1 shows a high affinity
with maltotetraose among maltooligosaccharides. To the best of
our knowledge, this is the first artificial saccharide receptor
which shows selectivity for oligosaccharides.
were scarcely changed, indicating that the skeleton of com-
pound 1 is fairly rigid. In the circular dichrosim (CD) spectra, on
the other hand, exciton-coupling-type CD bands appeared in the
Soret band region (Fig. 1). It is seen from Fig. 1 that the CD
spectra consist of two exciton-coupling bands: for the 1·M4
complex (Fig. 1), a negative band at higher wavelength and the
positive band at shorter wavelength. The strongest peak appears
at 417 nm where two CD bands overlap. The CD intensity at 417
nm is summarised in Table 1. It is seen from Table 1 that: (i) the
complex with -glucose (M1) is almost CD-silent, (ii) maltose
D
(M2) and maltotriose (M3) give a weak negative 417 nm peak
whereas maltotetrose and higher-order maltooligosaccharides
(M5–M7) all give a positive 417 nm peak and (iii) a particularly
strong CD band is observed for M4. The results indicate that (i)
Compound 1 was synthesised from 4-(1,3-dioxaborinan-
2-yl)benzaldehyde and dipyrrylmethane according to Scheme 1
1
and identified as its propane-1,3-diol-protected species by H
NMR and MALDI-TOF mass (m/z 1386.9) spectra and
elemental analysis.‡ Since 1H NMR spectroscopy showed that
the protecting groups are readily eliminated in aqueous media to
yield 1, it was used for the spectroscopic measurements without
deprotection treatment. From examination of Lambert–Beer
plots, we found that 1 tends to aggregate in water-rich solvents.
We thus chose a water (pH 10.5 with 50 mmol dm23 carbonate
buffer)–MeOH (2+3 v/v) mixture into which 1 was solubilised
discretely.
Fig. 1 CD spectrum of 1 (5.00 3 1026 mol dm23) with a 1 cm cell in the
presence of maltotetraose (50 mmol dm23) in a water (pH 10.5 with 50
mmol dm23 carbonate)–MeOH (2+3) mixture at 25 °C. A similar CD
spectral shape was also observed (although the intensity was different) in
the presence of other maltooligosaccharides.
† Electronic supplementary information (ESI) available (i) Fig. A and B
(Job plot for 1+M4 and possible binding mode for 1/M4, respectively). See
http://www.rsc.org/suppdata/cc/b0/b003365k/
DOI: 10.1039/b003365k
Chem. Commun., 2000, 1047–1048
This journal is © The Royal Society of Chemistry 2000
1047

Table 1 CD intensity at 417 nm and binding parameters obtained from
Hill’s plots and substitution methods
correlated with the CD intensity, (ii) the largest K is observed
for M4, which is 48- and 39-fold larger, respectively, than those
of M5 and M6 and (iii) the m values are smaller than 2.0,
indicating the weak positive allosterism and the presence of the
1+1 species in the low saccharide concentration region. This
novel binding mode implies that the binding of the first guest
which intramolecularly bridges two boronic acid groups
suppresses the rotational freedom of the porphyrin rings and
preorganises the two residual boronic acids so that they can
easily complex the second guest.
In conclusion, it was shown that the meso–meso-linked
porphyrin dimer is a useful scaffold to separate two boronic acid
groups so that they can show selectivity for oligosaccharides.
We believe that this study is very important in revealing boronic
acid–saccharide interactions toward selective recognition of
oligosaccharides.
CD intensitya/
mdeg
Kb/dm6
mol22
Kc/dm6
mol22
Saccharide
mb
Glucose (M1)
Maltose (M2)
0.2
20.5
20.2
6.8
1.9
1.4
—
—
—
—
—
—
1.7
1.8
1.8
1.5
2.5 3 103
1.5 3 103
Maltotriose (M3)
Maltotetraose (M4)
Maltopentaose (M5)
Maltohexaose (M6)
Maltoheptaose (M7)
2.0 3 103
6.3 3 105
1.3 3 104
1.6 3 104
2.0 3 103
—
—
—
—
1.7
a See caption of Fig. 1. b Determined from Hill’s plots. c The 1+2 to 1+2
substitution (e.g. from 1·(M4)2 to 1·(M1)2) is assumed for the calculation.
D-glucose is too small to bridge two boronic acid groups, (ii) the
two porphyrin planes are oriented in opposite directions for the
M2, M3 complexes and M4–M7 complexes, respectively, and
(iii) M4 forms a particularly stable complex with 1.
Notes and references
‡ In step iv (Scheme 1), by-products were detected in which the boronic acid
groups were substituted by OH groups. The raw yield of 1 estimated by
HPLC was ca. 20%.
§ Conformations with low potential energy encountered during a 100 ps
MD simulation at 300 K were selected. The system was minimised using
conjugate gradient and Newton–Raphson methods until convergence was
attained for a gradient of 0.01 kcal mol21 Å21. The force field used in this
study was the ESFF.
To obtain further insights into the binding mode, the complex
stoichiometries were estimated by a Job plot method for M4–M7
which show measurable CD intensity. A typical example for M4
is shown in Fig. A(ESI):† a maximum is observed at ([1]/[1] +
[M4]) = 0.33. This supports the view that 1 binds two M4 guests
to form the stable complex. Similar 1+2 stoichiometries were
also observed for M5, M6 and M7. The computational studies
(Discover 3/Insight II 98.0) predict that in the most stable
conformation the two porphyrin planes cross at 90°, in which
the distance between two boron atoms is 1.58 nm. This distance
is comparable with that between the 1,2-diol and 4,6-diol in the
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two terminal -glucose units of M4 (ca. 1.5–1.8 nm). One may
D
thus illustrate a binding mode for the 1+2 1/M4 complex as
shown in Fig. B(ESI).†§
The CD spectra measured as a function of M4–M7 concentra-
tions provided several isosbestic points. As typical examples,
plots of CD intensity at 417 nm vs. [M4] and [M5] are shown in
Fig. 2. The sigmoidal curvatures indicate that the 1+2
complexes are formed in a cooperative manner. Similar
sigmoidal dependences were also observed for M6 and M7. The
binding of the guest to 1 is cooperative. This cooperative guest
binding profile can be analysed with the Hill equation: log [y/(1
2 y)] = mlog[guest] + log K, where K and m are the association
constant and Hill coefficient, respectively, and y = K/
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using the linear portion at log [y/(1 2 y)] = 0–0.8 we obtained
K and m values for M4–M7. The determination of K values for
M1–M3 was difficult because of their weak CD intensity, but
measurements were obtained by a substitution method using the
1·M4 complex, that is, by the CD intensity decrease induced by
addition of M1–M3, and the results are summarised in Table 1.
Examination of Table 1 reveals that: (i) the magnitude of K is
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Fig. 2 Plots of CD intensity (417 nm) for 1 (5.00 3 1026 mol dm23) vs. [M4]
and [M5].
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Chem. Commun., 2000, 1047–1048