Fabrication of soft submicrospheres by sequential boronate esterification and their dynamic behavior

Article abstract of DOI:10.1002/cplu.201100008

Pyridine-assisted sequential boronate esterification of benzene- 1,4-diboronic acid and 1,2,4,5-tetrahydroxybenzene has induced hierarchical molecular self-assembly, and in turn producing well-defined submicrospheres. Spectroscopic analyses such as FE-SEM, TEM, DLS, NMR, XRD, and IR absorption spectroscopy indicates that the particles are composed of lamellar structures of sp²-hybridized trigonal planar poly(dioxaborole). The spontaneous self-organization is ascribable to reactive layerby- layer assembly through sequential boronate esterification of the diboronic acid and the tetrahydroxybenzene whereby initially formed oligo(dioxaborole) may provide a platform for further reactions, thus resulting in the production of submicrospheres. It is interesting to note that the dynamic covalent functionality as a result of the dioxaborole linkage induced a stimuli-responsive change in morphology by not only a pH switch but also the exchange reaction with pentaerythritol. Further, a selective saccharide-induced change in the submicrosphere morphology was observed through a simple exchange reaction of dynamic covalent boronate esters with saccharides in THF; the selective change in morphology is visually detected through the color change in the solution. These findings can provide a useful insight into the design of stimuli-responsive hierarchical architectures based on boron-containing dynamic covalent bond.

Full text of DOI:10.1002/cplu.201100008

DOI: 10.1002/cplu.201100008
Fabrication of Soft Submicrospheres by Sequential
Boronate Esterification and Their Dynamic Behavior
Ryuhei Nishiyabu, Shiori Teraoka, Yusuke Matsushima, and Yuji Kubo*[a]
Pyridine-assisted sequential boronate esterification of benzene-
1,4-diboronic acid and 1,2,4,5-tetrahydroxybenzene has in-
duced hierarchical molecular self-assembly, and in turn produc-
ing well-defined submicrospheres. Spectroscopic analyses such
as FE-SEM, TEM, DLS, NMR, XRD, and IR absorption spectrosco-
py indicates that the particles are composed of lamellar struc-
tures of sp2-hybridized trigonal planar poly(dioxaborole). The
spontaneous self-organization is ascribable to reactive layer-
by-layer assembly through sequential boronate esterification
of the diboronic acid and the tetrahydroxybenzene whereby
initially formed oligo(dioxaborole) may provide a platform for
further reactions, thus resulting in the production of submicro-
spheres. It is interesting to note that the dynamic covalent
functionality as a result of the dioxaborole linkage induced a
stimuli-responsive change in morphology by not only a pH
switch but also the exchange reaction with pentaerythritol.
Further, a selective saccharide-induced change in the submi-
crosphere morphology was observed through a simple ex-
change reaction of dynamic covalent boronate esters with sac-
charides in THF; the selective change in morphology is visually
detected through the color change in the solution. These find-
ings can provide a useful insight into the design of stimuli-re-
sponsive hierarchical architectures based on boron-containing
dynamic covalent bond.
Introduction
Dynamic covalent chemistry[1] is an effective approach for pro-
ducing constitutional dynamics,[2] wherein molecules are en-
dowed with a thermodynamically reversible nature, thus facili-
tating self-control and self-correction. The use of boronic acid
complexation with diols and their congeners, such as cate-
chols, has great promise in developing reversible boron-con-
taining multicomponent systems wherein the boronate ester
linkage serves as the intercomponent bond of supramolecular
architectures.[3] The dynamic structure-directing potential has
led to not only well-defined self-organization involving macro-
cycles,[4] capsules,[5] and gels[6] but also reversible polymers[7]
and boronic-acid-attached polymers.[8] In the field of material
science, boronate-ester-linked periodic covalent organic frame-
works (COFs) with two-dimensional (2D)[9] and 3D[10] porous
crystals have been prepared. Moreover, boronic acids recog-
nize the diol motif through boronate esterification; such bor-
onic-acid-appended systems have been explored for use as
sensing protocols for diol derivatives such as saccharides.[11]
Despite the superior properties of boronic acids as structure-
directing functional groups in supramolecular chemistry, hier-
archical 3D self-organization, formed by sequential boronate
esterification, with a well-defined morphology and dynamic
functionality are unprecedented.
Figure 1. a) FE-SEM image of the submicrospheres formed by adding pyri-
dine to a solution of 1 and 2 in THF. b) the size distribution of 1000 particles
in the FE-SEM images. c) TEM image of the submicrospheres. Conditions:
[1]=[2]=[pyridine]=1.0ꢀ10À2 m in THF at room temperature. The resultant
solids were isolated by filtration after 15 minutes reaction time.
Herein, we report for the first time well-defined submicro-
spheres arising from sequential boronate esterification of ben-
zene-1,4-diboronic acid (1) with 1,2,4,5-tetrahydroxybenzene
(2), wherein spontaneously provided well-defined submicro-
spheres in ambient conditions in the presence of pyridine
(Figure 1). The result is of scientific significance because dehy-
dration under conditions proposed by Rambo and Lavigne[12]
resulted in an agglomeration with an ill-defined morphology
[a] Dr. R. Nishiyabu, S. Teraoka, Y. Matsushima, Prof. Y. Kubo
Department of Applied Chemistry,
Graduate School of Urban Environmental Science,
Tokyo Metropolitan University
Minami-ohsawa, Hachioji, Tokyo 192-0397 (Japan)
Fax: (+81)42-677-3134
E-mail: yujik@tmu.ac.jp
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/cplu.201100008.
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201

Y. Kubo et al.
(see Figure S1 in the Supporting Information). A pyridine-cata-
lyzed sequential boronate esterification enabled excellent mor-
phology and dimensionality control of the hierarchical archi-
tectures by using chemical stimuli such as a pH switch and ex-
change reaction of the building blocks. Further, we demon-
strate a selective saccharide-induced morphological change by
taking advantage of the dynamic covalent functionalities of
boronate esters; such an event is visually detectable through a
color change in the solution.
Figure 3. a) ATR-FT-IR spectra of 1, 2, and submicrospheres formed from 1
and 2. b) IR spectrum (KBr method) of submicrospheres. A characteristic in-
Results and Discussion
tense peak at 660 cmÀ1 ( ) was assigned to boronate esters.
*
The submicrospheres were easily obtained by the following
procedure: to a solution of 1 (1.0ꢀ10À2 m) and 2 (1.0ꢀ10À2 m)
in THF was added pyridine (1.0 equiv) to obtain a turbid sus-
pension after 15 minutes. It is interesting to note that well-de-
fined spherical particles were observed by field-emission scan-
ning electron microscopy (FE-SEM; Figure 1a) and transmission
electron microscopy (TEM; Figure 1c). Particle size distribution
was taken from about 1000 particles observed in the FE-SEM
images (see Figure S2); the histogram shows that the average
diameter of the submicrospheres was 870 nm with a standard
deviation of 100 nm (Figure 1b). These objects were formed in
the solution; the size distribution was determined by dynamic
light scattering (DLS) measurement (see Figure S3).
the ÀOH stretching frequencies was observed at 3277 and
3147 cmÀ1 (Figure 3a). A characteristic intense signal assigned
to boronate ester of 1 and 2 was also observed at 660 cmÀ1 to-
gether with a peak corresponding to BÀO stretch at 1359 cmÀ1
(Figure 3b; KBr method).[12] Although it is known that coordi-
nation of pyridine to boron facilitates not only boronate
esterification[14] but also formation of boroxines[15], the absence
of a characteristic signal at near 580 cmÀ1 corresponding to
boroxine structures indicates that boroxine structures were not
formed under the reaction conditions we employed.
Powder X-ray diffraction (PXRD) analysis led us to analyze
the nanostructures of the particles, which evinced the lamellar
alignment of poly(dioxaborole)s in the submicrospheres (Fig-
ure 4a). The observed peaks at 25.58 and 27.48 corresponding
to 3.49 and 3.25 ꢂ, which represent the distances between pol-
Analysis for components of the particles was carried out by
using NMR spectroscopy. When the isolated solid was dis-
1
solved in [D6]DMSO, the H NMR measurement exhibited sin-
glet signals at 7.72 and 6.20 ppm, which were assigned to the
aryl resonances of Ha and Hb, respectively (Figure 2a). The Ha
Figure 2. a) 1H and (b) 11B NMR spectra of the submicrospheres dissolved in
[D ]DMSO at 258C. A broad background peak ( ) in the 11B NMR spectrum is
*
6
assigned to boron nitride used in the NMR probe.
signal was found to integrate in a 2:1 ratio with respect to
that of Hb, thus implying that sequential boronate esterifica-
tion occurred between 1 and 2. Further assessment was made
by 11B NMR analysis in [D6]DMSO (Figure 2b) and a significant
signal was observed at 30.04 ppm, which is indicative of the
formation of sp2-hybridized trigonal planer boronate ester.[13]
Boronate ester formation between 1 and 2 in the objects
was also evidenced by infrared (IR) absorption spectroscopy
with an attenuated total reflection (ATR) apparatus capable of
avoiding the influence of water, wherein the disappearance of
Figure 4. a) PXRD pattern of the submicrospheres. b) Observation of the sur-
face of the submicrospheres by high-magnified FE-SEM and c) high-magni-
fied TEM image of the surface. d) Plausible structures of the submicrosphere;
lamellar structures composed of stacking structures of planar boronate ester
polymers are self-assembled into the submicrosphere.
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Supramolecular Chemistry
y(dioxaborole)s, and possibly result from interactions between
the vacant pz orbital of boron and the p orbital. Diffraction
peaks at 16.08 and 32.28 should represent lamellar packing of
the stacked poly(dioxaborole)s in the submicrospheres (d-spac-
ings of 5.53 ꢂ). This packing leads to the production of a pyri-
dine-free lamellar structure. Although this result was unexpect-
1
ed, the H NMR spectrum of the spheres that were dissolved in
[D6]DMSO exhibited a negligible amount of pyridine (Figure 2,
see above); this led us to consider that the plausible reaction
mechanism involves a conversion from pyridine-bound boro-
nate ester polymer to pyridine-free planar boronate ester poly-
mer (see below). From the PXRD data, one can estimate that
approximately 109 dioxaborole units might be contained in the
object having a diameter of 870 nm. Further assessment for
the characterization came from a high-magnified FE-SEM
image of the particles; the obtained particles were found to
possess wrinkled nanostructures at the surface (Figure 4b). In
addition, high-magnification TEM image on the edge of the
condensed flake structures shows stripe patterns (Figure 4c),
thus supporting the presence of nanostructures with a lamellar
periodicity (estimated by PXRD). All these findings together in-
dicate a plausible hierarchical supramolecular assembly of pol-
y(dioxaborole)s, which is illustrated schematically in Figure 4d.
The reaction mechanism for the formation of submicro-
spheres is an intriguing subject that is explored in this study.
This interest arises from the experiments carried out in THF at
reflux and led to ill-defined fibrous agglomerates (see Fig-
ure S4). Initially, we focused on the role of pyridine because
particle formation is initiated by adding pyridine into the solu-
tion of 1 and 2 in THF. An interaction between the boronic
acid and an amino base, also known as a B···N interaction, low-
ered the pKa value of boronic acid, thus allowing boronate
esterification to occur more easily than when under amine-free
conditions.[14] In fact, 2,6-di-tert-butylpyridine, which contained
sterically hindered tert-butyl groups that prevents the B···N in-
teraction, had a negligible effect on the solution (see Fig-
ure S5).
Figure 5. The basicity-dependence for the polymeric boronate esterification.
The FE-SEM images and PXRD patterns of the solid isolated from the mix-
tures of 1 and 2 in THF at room temperature after the addition of (a) pyri-
dine, (b) 3-picoline, (c) 4-methoxypyridine, (d) 4-dimethylaminopyridine, and
(e) triethylamine, respectively. The use of 3-cyanopyridine induced no aggre-
gation. Reaction conditions: [1]=[2]=[base]=1.0ꢀ10À2 m. The solids were
isolated from the mixture by filtration after 15 minutes reaction time.
resulted in agglomeration with no PXRD pattern (Figure 5e).
1
The H NMR spectra of the solid, being dissolved in [D6]DMSO
(see Figure S7), exhibited signals at 1.17 (CH2) and 3.08 ppm
(CH3) corresponding to the Et3NH+ ion. We thus reasoned that
Et3N could cause a deprotonation of 2 to assist boronate
esterification of 1 and 2. From these results, while an interac-
tion of pyridine with boronic acid part is significant to cause
sequential boronate esterification to form well-defined submi-
crospheres, thereby a strong interaction as well as strong base
led to an agglomeration.
We also found that the particle dispersity was sensitively af-
fected by the nature of the bulk solvent employed (Figure 6).
When we used 1,4-dioxane (ET(30)=36.0), which has a lower
The Lewis basicity dependence of pyridines in particle for-
mation was also investigated (Figure 5a–d). Although no reac-
tion occurred in the presence of a weak base such as 3-cyano-
pyridine, the use of 3-picoline allowed us to detect well-de-
fined and dispersed particles as seen in FE-SEM images and
PXRD patterns, and is almost identical to the result obtained in
the presence of pyridine. In contrast, on increasing the Lewis
basicity of the pyridines, 4-methoxypyridine and 4-dimethyla-
minopyridine led to ill-defined shapes. The insight into the
1
structure regulation came from H NMR measurement of the
solid derived with 4-dimethylaminopyridine (see Figure S6).
When the solid species was dissolved in [D6]DMSO and then
analyzed by using 1H NMR spectroscopy, the signals corre-
sponding to 4-dimethylaminopyridine appeared at 3.08, 6.83,
and 8.15 ppm as well as signals arising from 1 and 2, thus sug-
gesting the production of 4-dimethylaminopyridine-containing
species. It supports the observation that the pyridine-assisted
particle formation involves a step in which the pyridine can be
eliminated from the boronate ester. On the other hand, the
use of triethylamine with a strong Brønsted base (pKa =10.8)
Figure 6. Morphology of the isolated solids formed in (a) 1,4-dioxane
(b) THF, and (c) acetone. The ET(30) values of 1,4-dioxane, THF, and acetone
are 36.0, 37.4, and 42.2, respectively. Reaction conditions: [1]=[2]=[pyridi-
ne]=1.0ꢀ10À2 m at room temperature after 15 minutes reaction time.
polarity than THF (ET(30)=37.2), partially agglomerated
spheres were obtained, thus indicating that the morphology is
sensitive to the bulk solvent. The solvophobic effect caused
the integration of layers arising from polymeric boronate
esterification. However, the use of solvent with a higher polari-
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Y. Kubo et al.
Figure 7. Schematic illustration of a plausible mechanism for the formation of the submicrospheres by reactive layer-by-layer assembly.
ty such as acetone (ET(30)=42.2) resulted in agglomeration,
and is possibly due to the enhanced interfacial free energy be-
tween the aggregation and the bulk solvent. In addition, there
was no precipitate in DMSO (ET(30)=45.0) involving 1, 2, and
pyridine, thus indicating that good solvents for bis(dioxabor-
ole)s do not induce particle formation.
morphology would be affected by a pH switch in the solution
(Figure 9). The addition of concentrated hydrochloric acid into
a suspension of the isolated spheres in THF (Figure 9a) led to
a clear solution in 24 hours (Figure 9b). The negligible scatter-
ing in the DLS measurement of the resulting solution indicated
degradation of the submicroparticles based on cleavage of
boronate ester linkages under acidic conditions.[17] A lack of
particle formation was still observed after the solution under-
went neutralization with anhydrous sodium sulfate and dehy-
dration with molecular sieve 4 ꢂ (Figure 9c). However, subse-
quent addition of pyridine made the solution turbid again (Fig-
ure 9d). The DLS measurement of the solution showed strong
light scattering, thus declaring the presence of colloidal parti-
cles. From the number size distribution and the intensity size
distribution, the average diameter of the particles were deter-
mined to be (823.6Æ179.7) nm and (1147.2Æ261.5) nm, re-
spectively (see Figure S8). The FE-SEM image of the isolated
solid allowed us to detect submicrospheres whose size and
morphology was similar to that of the particles before degra-
dation (Figure 9d, also see Figure S9). This outcome means
that pyridine serves as a catalyst for the particle formation. In
this manner, the reversible formation of submicrospheres was
completed, thus leading to a system that is capable of self-as-
sembly in response to changes in pH value.
From all these observations, we propose a plausible mecha-
nism for the formation of the submicrospheres (Figure 7). This
mechanism is based on the reactive layer-by-layer assembly of
boronate ester-based polymers. It involves 1) coordination of
pyridine to 1 thereby promoting polymeric boronate esterifica-
tion with 2 to induce particle nucleation in the early stage,
and 2) the initially formed spherical aggregates serving as a
self-template for further boronate esterification, whereby pyri-
dine-coordinated boronate ester oligomers/polymers are con-
verted into planar structures via the elimination of pyridine,
which is interpreted as the planar state that is composed of
trigonal planar boronate ester, which is more thermodynami-
cally favorable than the pyridine-coordinated tetrahedral struc-
ture because of interactions such as phenyl–boron–phenyl
p stacking. Finally, the resulting polymers are spherical, which
allows formation for minimization of the interfacial free energy
between the particles and solvent used.[16] Our proposed reac-
tive layer-by-layer assembly is supported by the growth of the
particles as a function of time, as indicated by the FE-SEM
images (Figure 8). Note that small particles were produced
after 30 second after aging of 1 and 2 in the presence of pyri-
dine (Figure 8a). Time-dependent growth of the particles with
well-defined morphology may be ascribable to solvophobic
phenyl–boron–phenyl p-stacking interactions between poly(-
dioxaborole)s, thus resulting in the production of submicro-
spheres composed of denser flakes (Figure 8c).
It was anticipated that the exchange reaction, having multi-
functional diols on the boronate ester linkages, would induce
a change in morphology; we added pentaerythritol to a sus-
pension of submicrospheres of 1 and 2 in THF at room tem-
perature (Figure 10a). As a result, a slight change in the surface
morphology was observed after three days (Figure 10c). Fur-
thermore, after a few weeks the submicrospheres were finally
transformed into particles composed of larger and sparser
flakes (Figure 10e).
The dynamic covalent functionality of boronate ester linkag-
es in the particles drove us to investigate how the well-defined
The transformation was attributed to the replacement of 2
with pentaerythritol in the polymeric structures as inferred
from time-dependent PXRD patterns of the isolated solids at
different reaction times (Figure 11). In the PXRD patterns,
peaks at 16.0, 25.5 and 27.68 corresponding to the packing
structures of poly(dioxaborole)s of 1 and 2 (Figure 11a) de-
creased in the early stage (Figure 11b,c). Furthermore, four
new peaks at 16.8, 20.3, 26.1 and 30.08 appeared in the course
of the morphological changes (Figure 11d,e), thus indicating
that the resultant flake structures possesses different compo-
nents and packing structures from the original submicro-
spheres. In fact, boronate ester polymers separately prepared
Figure 8. The FE-SEM images of submicrospheres at varied reaction times
(a) 30 sec, (b) 1 min, and (c) 10 min. Reaction conditions: [1]=[2]=[pyridi-
ne]=1.0ꢀ10À2 m in THF at room temperature.
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Figure 10. Morphological transformation of the submicrospheres based on
constitutional dynamic functionality of boronate ester linkages. The FE-SEM
images of the submicrospheres of 1 and 2 (12.0 mg, 0.051 mmol[18]) upon
the addition of pentaerythritol (6.0 mg, 0.044 mmol) in THF (4.0 mL) at differ-
ent reaction times (before adding pentaerythritol (a), and 1 day (b), 3 days
(c), 12 days (d), and 22 days (e) after adding pentaerythritol, respectively).
Figure 9. Intensity size distributions from DLS spectra for pH-triggered rever-
sible formation of the submicrospheres. a) THF suspension of the submicro-
spheres, (b) after the addition of concentrated hydrochloric acid, (c) subse-
quent addition of anhydrous sodium sulfate and molecular sieve, and then
(d) pyridine addition. The total scattering intensities of samples for (a), (b),
(c), and (d) were 7.42ꢀ106, 4.24ꢀ104, 2.63ꢀ104, and 7.91ꢀ106 cps, respec-
tively.
from 1 and pentaerythritol in THF exhibit a similar diffraction
pattern (2q=18.9, 21.0, 25.0, and 30.08 in Figure 11 f) with that
1
of the final products of flake structures. The H NMR spectrum
of the polymer measured after 22 days, dissolved in D2O, re-
vealed approximately 80% of 2 was replaced by pentaerythri-
tol (see Figure S10). This result strongly indicates that reversi-
ble boronate esterification enables us to control the self-as-
sembly of the objects, thus leading to changes in the morphol-
ogy.
Figure 11. The XRD patterns of the submicrospheres of 1 and 2 (12.0 mg,
51.0 mmol[18]) in THF for different reaction times (before adding pentaerythri-
tol (a), and 1 day (b), 3 days (c), 12 days (d), and 22 days (e) after adding
pentaerythritol (6.0 mg, 44.0 mmol[18]), respectively) and boronate ester poly-
mers obtained from 1 and pentaerythritol in THF (f). Peaks marked with as-
terisks are assigned to insoluble residue of pentaerythritol.
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Y. Kubo et al.
Next, our interest turned to finding out whether the submi-
crospheres would have a morphological signaling capability
toward saccharides. This proposition is based on boronic acid–
saccharide covalent interactions that readily occur in a solu-
tion.[19]With this in mind, we separately added three kinds of
saccharides, phenyl-b-d-galactopyranoside (pGal), phenyl-b-d-
glucopyranoside (pGlc), and phenyl-b-d-xylopyranoside (pXyl),
to the dispersed THF solutions containing the submicrospheres
and aged these solutions for five days (Figure 12). Interestingly,
fibrous aggregates were observed in the FE-SEM images when
pGal was added, whereas the addition of pGlc or pXyl induced
almost no morphological change. As a control experiment,
when pGal was added to a solution of 1 in THF in the absence
of 2, similar fiberlike structures were obtained (see Figure S11).
This outcome strongly suggests that the morphological
changes from spherical to fiberlike structures upon the addi-
tion of pGal may be caused by the exchange reaction of build-
ing blocks between 2 and pGal.
CH(CH2OH) and diol groups (Figure 13a, also see Figure S12).
1
On the other hand, as shown in Figure 13b, the H NMR spec-
trum of the particles isolated from the corresponding solution
with pGlc was the same as that of the above-mentioned sub-
microspheres (Figure 2a). Such higher reactivity with pGal
The characterization of the fiberlike structures was evident
1
from the H NMR measurements; fibrous aggregates obtained
from the reaction of the submicrospheres with pGal were dis-
solved in [D6]DMSO. Subsequently, the 1H NMR and 1H–
1H NOESY spectra indicate the production of the (pGal)2·(1)
complex with a six-membered ring formed from a cis-CH(OH)-
1
Figure 13. The H NMR spectra of (a) the fibrous aggregates and (b) the par-
ticles in [D6]DMSO, which were isolated after aging with pGal and pGlc at
room temperature for five days, respectively.
compared to that with pGlc is consistent with the binding
strength of phenylboronic acid with these saccharides,[19] thus
suggesting that the submicrospheres could selectively react
with the saccharides.
Another interesting point is that after removing (by filtra-
tion) the fibrous aggregates composed of the (pGal)2·(1) com-
plex, the resultant solution was orange and showed an absorp-
1
tion band at 388 nm. The H NMR spectrum in [D6]DMSO clear-
ly indicates a singlet signal at 5.82 ppm, which arises from the
formation of 1,4-dihydroxy-p-benzoquinone (see Figure S13)
and is probably the oxidized product of 2 eliminated from the
particle by an exchange reaction with saccharide. Figure 14a
shows the absorption spectra of the submicrospheres-dis-
persed THF solution in the presence of 10 equivalents of pGal;
the absorption band at 388 nm gradually increased as a func-
tion of time. As inferred from Figure 14b, a specific response
towards pGal was obtained because other saccharides tested
here induced almost no change in the absorption spectra. This
result strongly suggests that the saccharide-induced morpho-
logical signaling of the particles can be translated into a color
change in the solution (see Figure S14).
Conclusion
Figure 12. Influence on the morphology of the submicrospheres (2.0 mg, 8.5
mmol[18]): (a) saccharide-free condition, (b) pGal (22.0 mg, 85.0 mmol) addi-
tion, (c) pGlc (22.0 mg, 85.0 mmol) addition, and (d) pXyl (19.0 mg, 85.0
mmol) addition in THF (2.0 mL) at room temperature for five days.
In conclusion, we have developed a simple method for fabri-
cating poly(dioxaborole) hierarchical soft particles by reactive
layer-by-layer assembly through sequential boronate esterifica-
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Supramolecular Chemistry
namic radius was calculated from Stokes-Einstein relationship with
the cumulant method. Intensity size distributions of the submicro-
spheres were calculated by the Marquardt method. The infrared
spectrum of the submicrospheres was recorded on a JASCO FT/IR-
5300 spectrometer by using the KBr pellet technique. To detect
peaks corresponding to OH stretch of 1, 2, and the submicro-
spheres, the infrared spectra were measured with a SHIMADZU
IRAffinity-1 equipped with an attenuated total reflection (ATR) ap-
paratus. The H, 11B, and H–1H NOESY NMR spectra were recorded
on a Bruker AVANCE-500 spectrometer using tetramethylsilane
(TMS) as internal standard (0 ppm) for 1H NMR analysis and
BF3·OEt2 as an external standard (0 ppm) for 11B NMR analysis. All
spectra were recorded at 298 K. Powder X-ray diffraction (PXRD)
data were collected by Rigaku RINT-TTR III X-ray diffractometer
with Cu Ka radiation. Absorption spectra were obtained on Shi-
madzu UV-3100PC spectrophotometer at 258C and a quartz cell
with 1 cm path length was used.
1
1
Figure 14. a) Absorption spectra of supernatant solution of submicrospheres
(4.0 mg, 17.0 mmol[18]) dispersed in THF (4.0 mL) in the presence of 10 equiv-
alents of pGal. Time-dependent absorption spectra were recorded (1, 2, 3, 4,
and 5 day). b) Absorption intensity at 388 nm of supernatant solution of
submicrospheres (4.0 mg; 17.0 mmol[18]) dispersed in THF (4.0 mL) in the
presence of 10 equivalents of pGal, pGlc, and pXyl, respectively. The data
were collected after aging the solution at room temperature for five days.
Materials
tion. By taking advantage of boron-based dynamic covalent
functionality, we demonstrated not only the reversible forma-
tion of the particles on pH switching but also the transforma-
tion in morphology using pentaerythritol. Furthermore, the
fact that the particles have a morphological signaling capabili-
ty toward saccharides is noteworthy; the recognition event
can be detected by the naked eye owing to the production of
1,4-dihydroxy-p-benzoquinone in the solution. The ready avail-
ability of boronic acids and catechols/diols allowed us to pre-
pare a variety of chemical stimuli-responsive 3D soft systems.
Additionally, the surface of this material is composed of Lewis
acidic sp2-hybridized trigonal planar boronate ester, which
opens up new possibilities for the use of scaffold entities in
various application fields that involve organic/inorganic hybrid
materials, polymer-supported catalysts, sensor particles, and
separation media. Further research in this regard is currently
underway in our laboratory.
Synthesis of 1,2,4,5-tetrahydroxybenzene (2) was performed ac-
cording to the literature as follows:[12,20] A suspension of 2,5-dixy-
droxy-1,4-benzoquinone (10.7 g, 76.7 mmol) and granular tin
(10.9 g) in concentrated hydrochloric acid (233 mL) was heated at
reflux in a 500 mL round-bottom flask equipped with a condenser.
After 1 h, the granular tin was removed by passage through a
glass filter and the reaction mixture was cooled to room tempera-
ture. The resultant brown needle crystal was collected and recrys-
tallization from THF twice afforded white platelike crystals (7.4 g,
1
68% yield). H NMR (500 MHz, [D6]DMSO, TMS): d=6.20 (s, 2H; ArÀ
H), 7.94 (s, 4H; OH). THF was distilled from sodium wire with ben-
zophenone before use. All other reagents were purchased from
commercial suppliers and used without further purification.
Preparation of submicrospheres
Benzene-1,4-diboronic acid (1, 16.6 mg, 0.10 mmol) and
2
(14.2 mg, 0.10 mmol) were dissolved in freshly distilled THF (5 mL),
respectively. To a mixture of the THF solutions was added pyridine
(7.9 mL, 0.10 mmol). The resultant mixture was then allowed to
stand for 15 min at RT. In this period, the reaction mixture became
a turbid suspension. The resultant solids were isolated by filtration
and used for further study (yield=18.4 mg). In the experiments for
the effect of steric hindrance and basicity-dependence of bases on
the polymeric boronate esterification, 2,6-di-tert-butylpyridine,
3-cyanopyridine, 3-picoline, 4-methoxypyridine, 4-dimethylamino-
Experimental Section
General procedures
Field-emission scanning electron microscopy (FE-SEM) and trans-
mission electron microscopy (TEM) were performed by JEOL JSM-
7500F (acceleration voltage of 5 kV), JEOL JEM-2000FX (accelera-
tion voltage of 200 kV), and JEOL JEM-3200FS (acceleration voltage
of 300 kV) electron microscopes, respectively. For FE-SEM measure-
ments, submicrospheres were collected on a PTFE membrane filter
(pore size of 0.1 mm; Advantec Toyo Kaisha, Ltd.) by filtration or on
a glass substrate by casting of the suspensions. These samples
were coated with Au on an EIKO IB3 ION COATER. For TEM meas-
urements, a suspension of submicrospheres in THF was placed on
pyridine, and triethylamine were used. To solutions of
1
(0.10 mmol) and 2 (0.10 mmol) in THF (10 mL) were separately
added pyridine derivatives (0.10 mmol) and then the reaction mix-
tures were allowed to stand for 15 min at RT. The solids formed by
the addition of 3-picoline, 4-methoxypyridine, 4-dimethylaminopyr-
idine and triethylamine were collected by filtration for SEM and
PXRD experiments. For the study on the effect of solvent on the
particle dispersity, boronate esterification was performed using 1,4-
dioxane, acetone, and DMSO in the same manner.
a
carbon-meshed copper grid (Elastic carbon substrate on
STEM100Cu grids; Okenshoji Co., Ltd.) and the solution was imme-
diately filtered by using a filtration paper. The resultant grid was
dried in vacuum and measured without staining. Determination of
average diameters of the submicrospheres from FE-SEM was calcu-
lated from the 1000 particles in the FE-SEM images. Dynamic light
scattering (DLS) was measured using an Otsuka Electronic ELSZ-2.
The scattering angle of the apparatus is 165.78 to collect light scat-
tering from near the surface of a sample cell. The values of viscosi-
ty (0.5505 cp), refractive index (1.4000) of THF were used. Hydrody-
pH-Triggered reversible formation
To a suspension of submicrospheres (70.0 mg) in THF (30 mL) was
added concentrated hydrochloric acid (0.22 mL). The resultant mix-
ture was allowed to stand at RT for 24 h until the solution became
clear. Degradation of submicrospheres into component monomers
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207

Y. Kubo et al.
[7] a) I. Nakazawa, S. Suda, M. Masuda, M. Asai, T. Shimizu, Chem. Commun.
2000, 881–882; b) W. Niu, C. O’Sullivan, B. M. Rambo, M. D. Smith, J. J.
Lavigne, Chem. Commun. 2005, 4342–4344.
was confirmed by DLS measurement of the resultant clear solution.
The degraded solution was dehydrated with anhydrous sodium
sulfate and molecular sieve (4 ꢂ) in a freezer for 12 h. To the dehy-
drated solution (2.5 mL) was added pyridine (2.0 mL). The resultant
mixture became turbid within minutes and the solids were isolated
by filtration for SEM observation.
[8] a) T. Nagasaki, T. Kimura, S. Arimori, S. Shinkai, Chem. Lett. 1994, 1495–
1498; b) H. Kobayashi, M. Amaike, J. H. Jung, A. Friggeri, S. Shinkai, D. N.
Reinhoudt, Chem. Commun. 2001, 1038–1039; c) H. Kobayashi, K. Kou-
moto, J. H. Jung, S. Shinkai, J. Chem. Soc. Perkin Trans. 2 2002, 1930–
1936; d) Y. Qin, V. Sukul, D. Pagakos, C. Cui, F. Jꢄkle, Macromolecules
2005, 38, 8987–8990; e) J. N. Cambre, D. Roy, S. R. Gondi, B. S. Sumerin,
J. Am. Chem. Soc. 2007, 129, 10348–10349; f) D. Roy, J. N. Cambre, B. S.
Sumerlin, Chem. Commun. 2008, 2477–2479; g) D. Roy, J. N. Cambre,
B. S. Sumerlin, Chem. Commun. 2009, 2106–2108; h) P. De, S. R. Gondi,
D. R. B. S. Sumerlin, Macromolecules 2009, 42, 5614–5621; i) C. Cui, E. M.
Bonder, Y. Qin, F. Jꢄkle, J. Polym. Sci. A: Polym. Chem. 2010, 48, 2438–
2445; j) F. Cheng, F. Jꢄkle, Polym. Chem. 2011, 2, 2122–2132.
Morphological transformation of submicrospheres
To a suspension of submicrospheres (12.0 mg, 51.0 mmol[18]) in THF
(4.0 mL) was added pentaerythritol (6.0 mg, 44.0 mmol) and the re-
sultant mixture was allowed to stand at RT. The solids were isolat-
ed by filtration at varied reaction times for SEM and PXRD experi-
ments. In the experiments using sugars as chemical stimuli,
phenyl-b-d-galactopyranoside (22.0 mg, 85.0 mmol), phenyl-b-d-
glucopyranoside (22.0 mg, 85.0 mmol); and phenyl-b-d-xylopyrano-
side (19.0 mg, 85.0 mmol) were separately added to the submicro-
spheres (2.0 mg, 8.5 mmol[18]) in THF (2.0 mL), respectively. The mix-
tures were allowed to stand at RT for five days and the solids were
collected on PTFE membrane filters by filtration for NMR and SEM
studies of the products.
[9] a) A. P. Cꢅtꢆ, A. I. Benin, N. W. Ockwig, M. O’Keeffe, A. J. Matzger, O. M.
Yaghi, Science 2005, 310, 1166–1170; b) R. W. Tilford, W. R. Gemmill, H.-
C. zur Loye, J. J. Lavigne, Chem. Mater. 2006, 18, 5296–5301; c) A. P.
Cꢅtꢆ, H. M. El-Kaderi, H. Furukawa, J. R. Hunt, O. M. Yaghi, J. Am. Chem.
Soc. 2007, 129, 12914–12915; d) R. W. Tilford, S. J. Mugavero III, P. J.
Pellechia, J. J. Lavigne, Adv. Mater. 2008, 20, 2741–2746; e) S. Wan, J.
Guo, J. Kim, H. Ihee, D. Jiang, Angew. Chem. 2008, 120, 8958–8962;
Angew. Chem. Int. Ed. 2008, 47, 8826–8830; f) S. S. Han, H. Furukawa,
O. M. Yaghi, W. A. Goddard, J. Am. Chem. Soc. 2008, 130, 11580–11581;
g) N. L. Campbell, R. Clowes, L. K. Ritchie, A. I. Cooper, Chem. Mater.
2009, 21, 204–206; h) S. Wan, J. Guo, J. Kim, H. Ihee, D. Jiang, Angew.
Chem. 2009, 121, 5547–5550; Angew. Chem. Int. Ed. 2009, 48, 5439–
5442; i) C. J. Doonan, D. J. Tranchemontagne, T. Grant Glover, J. R. Hunt,
O. M. Yaghi, Nat. Chem. 2010, 2, 235–238; j) E. L. Spitler, W. R. Dichtel,
Nat. Chem. 2010, 2, 672–677; k) J. W. Colson, A. R. Woll, A. Mukherjee,
M. P. Levendorf, E. L. Spitler, V. B. Shields, M. G. Spencer, J. Park, W. R.
Dichtel, Science 2011, 332, 228–231; l) X. Feng, L. Chen, Y. Dong, D.
Jiang, Chem. Br. Chem. Cummun. 2011, 47, 1979–1981; m) X. Ding, J.
Guo, X. Feng, Y. Honsho, J. Guo, S. Seki, P. Maitarad, A. Saeki, S. Nagase,
D. Jiang, Angew. Chem. 2011, 123, 1325–1329; Angew. Chem. Int. Ed.
2011, 50, 1289–1293; n) E. L. Spitler, M. R. Giovino, S. L. White, W. R.
Dichtel, Chem. Sci. 2011, 2, 1588–1593; o) S. Wan, F. Gꢃndara, A. Asano,
H. Furukawa, A. Saeki, S. K. Dey, L. Liao, M. W. Ambrogio, Y. Y. Botros, X.
Duan, S. Seki, J. F. Stoddart, O. M. Yaghi, Chem. Mater. 2011, 23, 4094–
4097; p) L. M. Lanni, R. W. Tilford, M. Bharathy, J. J. Lavigne, J. Am. Chem.
Soc. 2011, 133, 13975–13983; q) X. Ding, L. Chen, Y. Honsho, X. Feng,
O. Saengsawang, J. Guo, A. Saeki, S. Seki, S. Irle, S. Nagase, V. Parasuk,
D. Jiang, J. Am. Chem. Soc. 2011, 133, 14510–14513; r) E. L. Spitler, B. T.
Koo, J. L. Novotney, J. W. Colson, F. J. Uribe-Romo, G. D. Gutierrez, P.
Clancy, W. R. Dichtel, J. Am. Chem. Soc. 2011, 133, 19416–19421.
[10] a) H. M. El-Kaderi, J. R. Hunt, J. L. Mendoza-Cortꢆs, A. P. Cꢅtꢆ, R. E. Taylor,
M. O’Keeffe, O. M. Yaghi, Science 2007, 316, 268–272; b) H. Furukawa,
O. M. Yaghi, J. Am. Chem. Soc. 2009, 131, 8875–8883; c) D. Cao, J. Lan,
W. Wang, B. Smit, Angew. Chem. 2009, 121, 4824–4827; Angew. Chem.
Int. Ed. 2009, 48, 4730–4733.
Acknowledgements
This research was supported by a Grant-in-Aid for Scientific Re-
search from the Ministry of Education, Science, Sports and Cul-
ture of Japan (grant nos. 21550137, 23750167) and the Yamada
Science Foundation.
Keywords: boron
·
dynamic
covalent
chemistry
·
nanostructures · self-assembly · supramolecular chemistry
[1] a) S. J. Rowan, S. J. Cantrill, G. R. L. Cousins, J. K. M. Sanders, J. F. Stod-
dart, Angew. Chem. 2002, 114, 938–993; Angew. Chem. Int. Ed. 2002, 41,
898–952; b) P. T. Corbett, J. Leclaire, L. Vial, K. R. West, J.-L. Wietor,
J. K. M. Sanders, S. Otto, Chem. Rev. 2006, 106, 3652–3711; c) I. Huc, J.-
M. Lehn, Proc. Natl. Acad. Sci. USA 1997, 94, 2106–2110; d) J.-M. Lehn,
Chem. Eur. J. 1999, 5, 2455–2463; e) J.-M. Lehn, Proc. Natl. Acad. Sci.
USA 2002, 99, 4763–4768; f) J.-M. Lehn, Science 2002, 295, 2400–2403;
g) O. Ramstrçm, J.-M. Lehn, Nat. Rev. Drug Discovery 2002, 1, 26–36;
h) K. Severin, Chem. Eur. J. 2004, 10, 2565–2580.
[2] J.-M. Lehn, Chem. Soc. Rev. 2007, 36, 151–160.
[11] a) T. D. James, P. Linnane, S. Shinkai, Chem. Commun. 1996, 281–288;
b) T. D. James, S. Shinaki, Top. Curr. Chem. 2002, 218, 159–200; c) R.
Nishiyabu, Y. Kubo, T. D. James, J. S. Fossey, Chem. Commun. 2011, 47,
1106–1123.
[12] B. M. Rambo, J. J. Lavigne, Chem. Mater. 2007, 19, 3732–3739.
[13] M. T. Reetz, C. M. Niemeyer, K. Harms, Angew. Chem. 1991, 103, 1515–
1517; Angew. Chem. Int. Ed. Engl. 1991, 30, 1472–1474.
[14] a) G. Wulff, M. Lauer, H. Bçhnke, Angew. Chem. 1984, 96, 714–716;
Angew. Chem. Int. Ed. Engl. 1984, 23, 741–742; b) M. Lauer, H. Bçhnke,
R. Grotstollen, M. Salehnia, G. Wulff, Chem. Ber. 1985, 118, 246–260;
c) M. Lauer, G. Wulff, J. Chem. Soc. Perkin Trans. 2 1987, 745–749;
d) S. L. Wiskur, J. J. Lavigne, H. Ait-Haddou, V. Lynch, Y. H. Chiu, J. W.
Canary, E. V. Anslyn, Org. Lett. 2001, 3, 1311–1314; e) L. Zhu, S. H. Shab-
bir, M. Gray, V. M. Lynch, S. Sorey, E. V. Anslyn, J. Am. Chem. Soc. 2006,
128, 1222–1232; f) E. Sheepwash, V. Krampl, R. Scopelliti, O. Sereda, A.
Neels, K. Severin, Angew. Chem. 2011, 123, 3090–3093; Angew. Chem.
Int. Ed. 2011, 50, 3034–3037.
[3] a) N. Fujita, S. Shinkai, T. D. James, Chem. Asian J. 2008, 3, 1076–1091;
b) K. Severin, Dalton Trans. 2009, 5254–5264; c) A. L. Korich, P. M.
¨
Iovine, Dalton Trans. 2010, 39, 1423–1431; d) F. Jakle, Chem. Rev. 2010,
110, 3985–4022; e) R. Nishiyabu, Y. Kubo, T. D. James, J. S. Fossey, Chem.
Commun. 2011, 47, 1124–1150.
[4] a) V. Barba, R. Villamil, R. Luna, C. Godoy-Alcꢃntar, H. Hçpfl, H. I. Beltran,
L. S. Zamudio-Rivera, R. Santillan, N. Farfꢃn, Inorg. Chem. 2006, 45,
2553–2561; b) N. Christinat, R. Scopelliti, K. Severin, J. Org. Chem. 2007,
72, 2192–2200; c) N. Iwasawa, H. Takahagi, J. Am. Chem. Soc. 2007, 129,
7754–7755; d) H. Takahagi, N. Iwasawa, Chem. Eur. J. 2010, 16, 13680–
13688.
[5] a) K. Kataoka, S. Okuyama, T. Minami, T. D. James, Y. Kubo, Chem.
Commun. 2009, 1682–1684; b) K. Kataoka, T. D. James, Y. Kubo, J. Am.
Chem. Soc. 2007, 129, 15126–15127; c) N. Nishimura, K. Kobayashi, J.
Org. Chem. 2010, 75, 6079–6085; d) N. Nishimura, K. Yoza, K. Kobayashi,
J. Am. Chem. Soc. 2010, 132, 777–790; e) N. Nishimura, K. Kobayashi,
Angew. Chem. 2008, 120, 6351–6354, Angew. Chem. Int. Ed. 2008, 47,
6255–6258.
[15] a) J. Kua, M. N. Fletcher, P. M. Iovine, J. Phys. Chem. A 2006, 110, 8158–
8166; b) J. Kua, P. M. Iovine, J. Phys. Chem. A 2005, 109, 8938–8943;
c) E. K. Perttu, M. Arnold, P. M. Iovine, Tetrahedron Lett. 2005, 46, 8753–
8756.
[6] a) Y. Kubo, W. Yoshizumi, T. Minami, Chem. Lett. 2008, 37, 1238–1239;
b) L. He, D. E. Fullenkamp, J. G. Rivera, P. B. Messersmith, Chem.
Commun. 2011, 47, 7497–7499.
208
www.chempluschem.org
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemPlusChem 2012, 77, 201 – 209

Supramolecular Chemistry
[16] a) M. Oh, C. A. Mirkin, Nature 2005, 438, 651–654; b) T. Nakanishi, W.
Schmitt, T. Michinobu, D. G. Kurth, K. Ariga, Chem. Commun. 2005,
5982–5984; c) H. Maeda, M. Hasegawa, T. Hashimoto, T. Kakimoto, S.
Nishio, T. Nakanishi, J. Am. Chem. Soc. 2006, 128, 10024–10025; d) Y. Su,
Q. He, X. Yan, J. Fei, Y. Cui, J. Li, Chem. Eur. J. 2011, 17, 3370–3375.
[17] G. Springsteen, B. Wang, Tetrahedron 2002, 58, 5291–5300.
[18] The concentration was based on the monomer unit.
[20] P. R. Weider, L. S. Hegedus, H. Asada, S. V. D’Andreq, J. Org. Chem. 1985,
50, 4276–4281.
Received: September 25, 2011
Revised: December 24, 2011
[19] J. P. Lorand, J. O. Edwards, J. Org. Chem. 1959, 24, 769–774.
Published online on January 26, 2012
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