Deprotection-Induced Micellization of Glycopolymers: Control of Kinetics and Morphologies

Article abstract of DOI:10.1021/acs.macromol.5b00572

In recent years, self-assembly of block or graft copolymers with sugar-containing component has drawn great attention. We just reported that protection-deprotection chemistry could initiate self-assembly of glycopolymers based on the high polarity change

Full text of DOI:10.1021/acs.macromol.5b00572

Article
pubs.acs.org/Macromolecules
Deprotection-Induced Micellization of Glycopolymers: Control of
Kinetics and Morphologies
Xiulong Wu, Lu Su, Guosong Chen,* and Ming Jiang
The State Key Laboratory of Molecular Engineering of Polymers, Collaborative Innovation Center of Polymers and Polymer
Composite Materials and Department of Macromolecular Science, Fudan University, Shanghai 200433, China
S
* Supporting Information
ABSTRACT: In recent years, self-assembly of block or graft copolymers with sugar-containing component has drawn great
attention. We just reported that protection−deprotection chemistry could initiate self-assembly of glycopolymers based on the
high polarity change induced by the deprotection. Considering that the protection−deprotection is so common and its variety in
glycochemistry, it is worth developing this finding into a new and general strategy of self-assembly of glyco-containing polymers.
For this purpose, this article focuses on the kinetics and morphology control of the assemblies of glyco-block copolymers induced
by the deprotection. Benzoyl (Bz) as the protective group was introduced, which has much lower deprotection rate than acetyl
group (Ac) reported previously. Thus, the detailed kinetic study of the self-assembly of Bz copolymer by means of in situ light
scattering and 1H NMR, etc., became possible. The morphologies of all of the resultant assemblies were observed by cryo-TEM.
Thus, we found that in the case of using an equivalent catalyst TBAOH, with the progress of deprotection of Bz, the copolymer
follows three-stage assembly, i.e., fast initiation, steady growth, and then fission/reorganization into stable state. In most
conditions, both Bz and Ac copolymers form stable vesicles, but the former is apparently larger than the latter. This is because
that the slow deprotection of Bz makes the resultant assemblies assume structures closer to equilibrium, and the fast reaction of
Ac makes the assemblies with more kinetic-trapped features.
preparation of the related monomers and polymers. For-
tunately, the protection−deprotection process developed in
glycochemistry succeeds in eliminating such interference.
Accompanying the deprotection, i.e., removal of the protective
groups, a significant polarity change of the glyco-block takes
place. However, the possible role of such change in self-
assemble of glyco-block-containing copolymers was neglected.
Recently, we first proposed and realized the protection−
deprotection strategy for self-assembly of a glyco-block-
containing copolymer leading to glyco-inside vesicles and
micelles.8
INTRODUCTION
■
Self-assembly of block copolymers containing bioactive species,
including peptides and sugars, has attracted more and more
attention due to their role in deepening one’s understanding of
the related processes in living systems and the promising
potential applications in biomedicine.1 However, until now, the
common strategies to self-assemble these biocopolymers in
solution have been limited. In the most common way, the
peptide/sugar-based blocks play the role of a hydrophilic block
to stabilize the obtained nanostructures in the self-assembly
processes which are induced by the hydrophobicity or
responsiveness of the other non-bio-block.2−7 Obviously, the
limitation on self-assembly strategy of glycopolymers slowed
down our footsteps on the exploration of new sweet materials
in biomedicine. Thus, it is demanding to develop new self-
assembly strategies. It is known that monosaccharides and
oligosaccharides are aldehydes or ketones with multiple
hydroxyl groups, which always interfere the reactions in
This deprotection-induced micellization can be regarded as a
significant advance of self-assembly of block copolymer induced
by chemical reactions. In this field, there are some well-known
Received: March 17, 2015
Revised: May 15, 2015
© XXXX American Chemical Society
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examples; chemical reaction-induced self-assembly of copoly-
mer chain of poly(phenylvinyl sulfoxide) (PVSO) and poly(4-
methylstyrene) (PMS) was first reported several years ago.9
Recently, for block copolymers consisting of a polystyrene (PS)
block and a photocleavable block, Gohy et al.10 realized its
micellization by the cleavage of O-nitrobenzyl esters. Compared
to the chemical interactions used in such examples, the
protection−deprotection is much more general and in some
extent indispensable in glycochemistry. Moreover, the well-
established carbohydrate chemistry provides many kinds of
protective groups with similar functionality but different
reactivity. So a broader scope of chemistry is available for
developing this macromolecular self-assembly. Therefore, the
strategy induced by this reaction is worth exploring more
extensively. On the basis of our previous exploration, in this
paper, we will introduce benzoyl (Bz) group to well-
characterized glycomonomer and glycopolymer. The self-
assembly of the latter will be induced by deprotection of the
Bz moiety. Strikingly, we found that starting from very similar
backbone removal of Bz group and acetyl (Ac) group induces
very different self-assembly kinetics and even different self-
assembled morphologies.
Scheme 1. Synthetic Route of Lactopyranomonomers Bz-2
and Ac-2 with Bz and Ac Protection, Respectively
a
a
Reagents: (a) benzoyl chloride, 4-(dimethylamino)pyridine
(DMAP), triethylamine (TEA); (b) hydrazine acetate, N,N-
dimethylformamide (DMF); (c) 1,8-diazabicyclo[5.4.0]undec-7-ene
(DBU), trichloroacetonitrile, dichloromethane (DCM); TMSOTf:
trimethylsilyl trifluoromethanesulfonate.
ization on the intermediates and monomers are shown in the
Supporting Information (Scheme S1).
RESULTS AND DISCUSSION
■
Design and Synthesis of Benzoyl-Containing Mono-
mer and Copolymers. In our previous study, Ac was
employed as the protective group to control the self-assembly
of glycopolymers.8 However, the Ac removal was so fast that
the corresponding self-assembly process could not be
monitored. In current research for exploring how is the
assembly directed by the deprotection chemistry, we tried to
find some other esters with moderate reactivity first. Thus,
model deprotection reactions on two disaccharides (S3 and S5,
Supporting Information) protected with benzoyl and acetyl,
respectively, were performed by using tetrabutylammonium
hydroxide (TBAOH), which was proved powerful to remove
Ac groups on polymer side chain in our previous study.8 As in
t h e r e a c t i o n T B A O H f o r m s e q u i v a l e n t ( n -
C4H9)4N+C6H5COO− for Bz, which will be discussed later;
strictly speaking, it serves a reactant rather than a catalyst. For
clarity, the number of equivalency of TBAOH used in this
paper is calculated according to the molar amount of protective
groups. As shown in Figure S1, TLC results showed that 2.5
equiv of TBAOH to Bz or Ac groups was capable to remove all
of the protective groups but the Bz removal was finished in 10
min while Ac in 5 min. Furthermore, 1.0 equiv amount of
TBAOH could remove all of Ac groups in about 15 min, but
only part of Bz groups could be removed even in much longer
time. This result of comparing the deprotection rate between
Bz and Ac is generally in agreement with that reported in the
literature,11 indicating that the Bz group could be a good
candidate for the kinetic study of the self-assembly of
glycopolymers.
1
Figure 1. H NMR spectra of monomers (a) Bz-2 and (b) Ac-2.
Reversible addition−fragmentation chain transfer (RAFT)
polymerization on monomer Bz-2 and Ac-2 was performed
with the RAFT macro chain transfer reagent (macroCTA) PS
(Scheme 2) in bulk at 70 °C. To each monomer, two
copolymers were synthesized with the same macroCTA, but
different degree of polymerization (DP) of glyco-monomers.
The polymerization was proved to be successful as the products
showed unimodal gel permeation chromatography (GPC)
curves in Figure 2 and the calculated polydispersity (PDI) was
low, around 1.2 (Table 1). As the chemical structure of our
glyco-block is very different from the PS standard in GPC
measurements, large errors in calculating molecular weight are
expected. So more believable molecular weights from GPC-
MALS, where absolute molecular weight was measured by
multiangle light-scattering (MALS) detector, are listed in Table
To compare the self-assembly behavior of Bz- and Ac-
protected glycopolymers, the corresponding monomers were
designed first. As shown in Scheme 1, glycosylation donors Bz-
1 and Ac-1 were prepared via three steps according the reaction
conditions reported in the literature.12 After glycosylation
reaction with the same acceptor S1, the vinyl group was
successfully coupled to Bz-1 and Ac-1, generating new
monomers Bz-2 and Ac-2. 1H NMR and 13C NMR
characterization of the two monomers are shown in Figure 1
and Figure S2, respectively. Synthetic details and character-
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a
Scheme 2. Synthetic Route of Glycopolymers PS-b-PLacR and the Deprotection To Form PS-b-PLac by Using TBAOH
a
Red for the lactopyranoside protected by Bz, blue for protected by Ac, and yellow for unprotected Lac.
Figure 2. GPC curves of (a) SbB5, SbB15 and (b) SbA7, SbA13 and the corresponding macro-CTA PS115 in DMF.
1. Meanwhile, the number-average molecular weight (Mn) from
1H NMR in Table 1 could be in a large error as the designed
length of glyco-block was quite short compared to that of PS
block. Table 1 lists the characterization data of four copolymers,
C
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1
Table 1. Molecular Weight Characterization on Copolymers Used in Deprotection Study by H NMR, GPC, and GPC-MALS
b
c
1H NMR
GPC-MALS
GPC
d
code
copolymer
PS115
Mn
Mw
Mw
Mn
PDI
ratio
0
12200
a
12200
19300
34000
18050
27610
10700
15800
19000
16600
19700
8900
13100
15700
14000
16300
1.20
1.21
1.21
1.19
1.21
SbB5
SbB15
SbA7
SbA13
PS115-b-PLacBz5
PS115-b-PLacBz15
PS115-b-PLacAc7
PS115-b-PLacAc13
0.23
0.68
0.32
0.59
a
18000
23100
a
b
c
Could not be measured due to low solubility. Mw measured from GPC-MALS. Mn, Mw, and PDI were calculated from GPC with PS as standard.
d
Calculated from the weight ratio of sugar block to PS block after deprotection.
Figure 3. (a) FT-IR spectra and (b) 1H NMR of SbB15 and SbL15. For FT-IR, after 10 min reaction and dialysis against water, the resultant powder
of the deprotected product was collected and used for the measurement.
i.e., PS115-b-PLacBz15, PS115-b-PLacAc13, and PS115-b-
PLacBz5, PS115-b-PLacAc7, where Lac represents the glyco-
block with disaccharide pendent group of lactopyranoside. For
clarity, the four copolymers are represented as SbB15, SbA13,
SbB5, and SbA7, respectively; accordingly, after being
completely deprotected, the four copolymers are called SbL15,
SbL13, SbL5, and SbL7. Details of the molecular weight
measurements are listed in the Supporting Information
(Figures S3−S15). Thus, we have two pairs of the copolymers.
In each pair, the Bz and Ac moieties have very similar DP
values. We found that all the four block copolymers could be
molecularly dissolved in THF by DLS measurements shown in
Figure S17.
7.16 ppm were assigned to the protons of Bz groups. Clearly,
after the reaction, the peaks associated with Bz completely
disappeared as a result of the full deprotection. However, the
peaks belonging to the protons of lactopyranoside disappeared
as well. This indicated that due to the solvophobicity of the
exposed hydroxyl groups of lactose in THF, the resultant
copolymer self-assembled into nanoparticles with glyco-inside
structure. In addition, it was worth noting that the peaks
around δ = 8.05 ppm and δ = 7.20 ppm generated after
deprotection were found to be associated with the soluble
structure of (n-C4H9)4N+C6H5COO−, which was confirmed by
ESI-MS (Figure S16). This means that TBAOH in fact reacted
with the Bz group equivalently. In short, combining the results
for Bz copolymers mentioned above and that for Ac
copolymers (Figure S18), we could conclude that both Bz or
Ac groups on the copolymer in THF could be removed with an
excess amount of TBAOH, and the deprotection reaction
induced their self-assembly to nanostructures with glyco-block
inside.
Self-Assembly of Bz and Ac Copolymers with an
Excess of Catalyst. In this section we discuss and compare
the self-assembly of the block copolymers with an excess of
TBAOH; i.e., the relative molar ratios of TBAOH to Bz and Ac
groups were 2.5 and 2.1, respectively. As shown in Figure 4a,
for both Bz and Ac copolymers, upon addition of TBAOH, the
average hydrodynamic radius ⟨Rh⟩ of the copolymer solution in
THF measured by dynamic light scattering (DLS) increased
very fast at first until reaching a plateau where the ⟨Rh⟩ no
longer changed, indicating formation of stable nanostructures,
which were named V-Bz-3 from SbB15 and V-Ac-3 from SbA13.
The results indicated that the self-assembly of both the Bz and
Ac copolymers follow the similar process. However, the
Analysis on Deprotection of Copolymers by FT-IR and
1H NMR. Deprotection reaction on the copolymers containing
Bz-protected disaccharides was studied by Fourier transform
infrared spectroscopy (FT-IR) and 1H NMR first. Deprotection
of SbB15 (1.25 mg/mL in THF) was performed by addition of
an excess, i.e., 2.5 equiv of aqueous TBAOH (10 μL, 40 wt %).
As shown in Figure 3a, compared to the FT-IR spectrum of
SbB15, the resultant copolymer showed complete disappearance
of the signal belonging to Bz groups at 1731 cm−1 (ν(CO))
and a great enhancement of the characteristic broad absorption
of hydroxyl groups at 3405 cm−1 (Figure 3a) as well,
demonstrating the successful removal of Bz groups and
1
formation of unprotected SbL15. H NMR was then employed
to confirm this process (Figure 3b). For the spectra of SbB15,
the peaks around δ 6.00−4.00 ppm belonged to the protons on
the pyranose ring of lactose, and those around δ 7.16−6.30
ppm showed the phenyl groups directly bonded to the
polymeric backbone. In addition, the peaks around δ 8.30−
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could be formed and frozen soon after addition of TBAOH,
and therefore formation of larger aggregates which required
more block molecules to get together by diffusion became
almost impossible. In contrast, Bz removal proceeded slower,
which enabled the copolymer molecules to have chance to
adjust their conformation and diffuse to close to each other
forming vesicles with a size close to its equilibrium structure. In
addition, it seems not surprising to find that for the current
copolymers with the low ratio of the unit number of the
solvophobic block (Bz15 and Ac13) to the solvophilic block
(PS115) forming vesicles instead of micelles, if the much larger
volume of the sugar repeating unit than that of PS unit is
considered.8
Self-assembly of the second pair of copolymers with the
shorter glyco-block, i.e., SbB5 and SbA7, by addition of excess of
TBAOH (13.3 μL, 4.0 equiv) in THF solutions (1.5 mL, 1.25
mg/mL) was performed as well. Full removal of Bz and Ac
group of the copolymers was proved by FT-IR and 1H NMR as
shown in Figures S19 and S20. Kinetic behavior of the assembly
for this pair was very similar to the pair with long Bz and Ac
blocks just discussed; i.e., the ⟨Rh⟩ increased very fast at first
and then remained stable (Figure 5a,b). However, as revealed
by cryo-TEM, the deprotection of SbB5 led to vesicles (V-Bz-
4) while SbA7 led to micelles (M-Ac-4) (Figure 5c,d). The size
difference between them was also striking, i.e. ⟨Rh⟩ of V-Bz-4
was around 140 nm, while that of M-Ac-4 was only around 14
nm. Similar with the above discussion for the pair of
copolymers with the long glyco-block, here the different
deprotection rate between Bz and Ac was attributed to the
apparent difference of the resultant assemblies because the
assemblies from Bz and Ac copolymers are in fact in different
degrees of kinetically trapped structures (Figure 5e,f).
Self-Assembly with Equivalent Catalyst. For the case of
using an excess catalyst, even for Bz copolymers with relatively
slow deprotection rate, the detail process of the assembly still
could not be followed by any available techniques. Therefore,
here an equivalent TBAOH was used to the solution of SbB15
and SbA13 (1.25 mg/mL) in THF. As shown in Figure 6a,
when 1.0 equiv of TBAOH (8 μL, 20 wt %) was added into the
THF solution of SbB15, it showed very different kinetics: ⟨Rh⟩
of the solution suddenly increased to 120 nm within 5 min
(stage I) followed by a slow increase (in about 45 min, stage II)
until a maximum value (⟨Rh⟩ = 270 nm) reached. Then ⟨Rh⟩
began to quickly decrease to and kept stable around 50 nm
within 15 min (stage III) forming the final stable nanostructure
V-Bz-5. By contrast, for SbA13, even only 1.0 equiv of TBAOH
(8 μL, 24 wt %) was used, the kinetic character was the same as
that for the excess catalyst: rapid formation of nanoparticles (V-
Ac-5, ⟨Rh⟩ = 22 nm) was observed, which became stable over a
long time. Moreover, cryo-TEM images proved the vesicle
morphology for the both (Figure 6b,c). And the ⟨Rg⟩/⟨Rh⟩
values of V-Bz-5 and V-Ac-5 were found to be 1.12 and 1.17
(Table 3), respectively, confirming their vesicular structure. But
V-Bz-5 was much larger than that of V-Ac-5 in weight; i.e., the
number of aggregation (Nagg) calculated from SLS of the
Figure 4. (a) Evolution of ⟨Rh⟩ during the self-assembly process
started from addition of excess amount of TBAOH (40 wt %, 10 μL)
into the THF solution of SbB15 and SbA13 (1.5 mL, 1.25 mg/mL). (b)
Rh distribution of V-Bz-3 and V-Ac-3. Cryo-TEM images of (c) V-Bz-
3 and (d) V-Ac-3. Cartoon scheme of self-assembly of (e) SbB15 and
(f) SbA13.
resultant assemblies are quite different in size: as shown in
Figure 4a,b, ⟨Rh⟩ of V-Bz-3 was around 58 nm, while that of V-
Ac-3 was only around 24 nm. Under cryogenic transmission
electron microscopy (cryo-TEM), both of the stabilized
nanostructures showed vesicular morphology but quite differ-
ent diameters in consistent to the results from DLS. Moreover,
the vesicle morphology was also supported by the values of
⟨Rg⟩/⟨Rh⟩, where ⟨Rg⟩ was obtained from static light scattering
(SLS), shown in Table 2. The number of aggregation (Nagg) of
935 for V-Bz-3 and 166 for V-Ac-3 calculated from SLS also
showed an apparent difference.
The apparent difference in size between V-Bz-3 and V-Ac-3
was unexpected as here an excess of catalyst was used capable
of removing all the protective groups, and therefore the
resultant copolymers from Bz and Ac copolymers should be the
same in chemistry. This difference clearly demonstrates the role
of process and kinetics of deprotection on the final size and
morphology. Although we could not follow the assembly
process in details by DLS for so quick process, it is reasonable
to think that Ac removal is so fast that the assembly structure
a
Table 2. Summary of ⟨Rh⟩, PDI, and Morphology of the Self-Assembled Structures in THF
starting copolymer
particle
TBAOH (equiv)
⟨Rh⟩ (nm)
PDI
⟨Rg⟩ (nm)
⟨Rg⟩/⟨Rh⟩
Nagg
morphology
SbB15
SbA13
V-Bz-3
V-Ac-3
2.5
2.1
58
24
0.11
0.13
63
29
1.09
1.21
935
166
vesicle
vesicle
a
Data were collected by DLS and SLS.
E
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1.25 mg/mL). As shown in Figure 7, the three groups show the
same kinetic characters: the ⟨Rh⟩ evolution follows the three-
stage pathway, i.e., fast initiation, steady growth to a turning
point, and then fast decrease to stable state. The corresponding
evolution of the Rh distribution profiles during the deprotection
shown in Figure 7d−f provided more information about the
assembly process: an abrupt right shift of the peak was observed
soon after addition of TBAOH, and then the peak shifted
slowly. These changes obviously correspond to the initial fast
and the slow increase of ⟨Rh⟩ value. Afterward, when ⟨Rh⟩
reached the turning point in Figure 7a−c, in the profiles, a small
peak at a low Rh value appeared leading to a bimodal
distribution of Rh (Figure 7d−f). Then the bimodal distribution
went back to unimodal one with the peak at the smaller Rh
value. So in the stage III, what happening could be fission of the
large aggregates and reorganization, which finally resulted in
smaller but stable aggregates. Furthermore, all the final three
stable structures were found to be vesicles (Figure 7g−i and
Table 4).
Meanwhile, removal of Bz group from the glyco-block was
monitored by 1H NMR during the whole deprotection process
(Figures S23−S25). After addition of TBAOH, a sharp peak
appeared around δ = 7.20 ppm associated with the removed Bz
group of (n-C4H9)4N+C6H5COO−, which was quantified via
internal standard tetraethylsilane and used as an indicator of the
degree of deprotection. Fully deprotected SbB15 was first
generated to give the possible total amount of free Bz peaks. As
shown in Figure 7a−c, generally, there is a fast initial removal
followed by a slow process, which generally corresponded to
the stage I and II of the assembly, respectively. So the results
clearly indicated that the assembly was driven by the
deprotection. It is interesting to find that the aggregation in
fact was initiated very soon after the catalyst was added where
the great amount of Bz groups still remained. So at this stage
the aggregation force due to the solvophobic character of the
resultant hydroxyl groups is not enough to form stable
assemblies. With increasing amount of removed Bz groups,
the aggregates grew to quite larger size around 200−400 nm
depending on the water amount added. Such large size was far
beyond the expected equilibrium values, so they were believed
to be loose and kinetically trapped aggregates. This opinion
found support from the morphology observation of the samples
collected from the solution at the stage I and stage II,
respectively, as being arrowed in Figure 7a. As shown in Figure
8b,c, the TEM images of both do not show any regular
structure of self-assemblies but just irregular aggregates.
Afterward, these unstable aggregates further fissioned and
reorganized into stable vesicles when the deprotection
proceeded slowly (Figure 8a).
Figure 5. (a) Evolution of ⟨Rh⟩ during the self-assembly process
started from addition of TBAOH (13.3 μL, 4.0 equiv) into the
solution of SbB5 and SbA7 (1.5 mL, 1.25 mg/mL) in THF. (b) Rh
distribution of V-Bz-4 and M-Ac-4. The cryo-TEM images of (c) V-
Bz-4 and (d) M-Ac-4. Cartoon scheme of self-assembly of (e) SbB5
and (f) SbA7.
former was 841, while that of the latter was only 146.
Moreover, the compositions of resulting vesicles were slightly
different; i.e., as shown in Figure S21, only a tiny amount of Ac
groups remained after deprotection, while more Bz groups did
so on the copolymer chain as demonstrated in Figure S22,
which will be discussed in detail below.
The complex kinetics of SbB15 with an equivalent catalyst
was further studied in detail. The results from three groups of
experiments are shown in Figure 7, where the same amount of
aqueous TBAOH (1.0 equiv) in different concentrations and
also with different amounts of water, i.e. 40 wt %, 4 μL; 20 wt
%, 8 μL; and 10 wt %, 16 μL (the middle case was just
mentioned) were added to the THF solution of SbB15 (1.5 mL,
Figure 6. (a) Evolution of ⟨Rh⟩ during the self-assembly process starting from addition of 8.0 μL of TBAOH (1.0 equiv) into the THF solution of
SbB15 (red line) and SbA13 (green line) (1.5 mL, 1.25 mg/mL). The cryo-TEM images of (b) V-Bz-5 and (c) V-Ac-5.
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a
Table 3. Summary of ⟨Rh⟩, PDI, and Morphology of the Self-Assembled Structures in THF
starting copolymer
particle
TBAOH (equiv)
⟨Rh⟩ (nm)
PDI
⟨Rg⟩ (nm)
⟨Rg⟩/⟨Rh⟩
Nagg
morphology
SbB15
SbA13
V-Bz-5
V-Ac-5
1.0
1.0
57
23
0.06
0.13
64
27
1.12
1.17
841
146
vesicle
vesicle
a
Data were collected by DLS and SLS.
Figure 7. Evolution of ⟨Rh⟩ (black line) and degree of deprotection (%, blue line) calculated from the peaks around δ = 7.20 ppm in 1H NMR during
the self-assembly process by addition of (a) 4 μL of TBAOH (40 wt %), (b) 8 μL of TBAOH (20 wt %), and (c) 16 μL of TBAOH (10 wt %) into
the THF solution of SbB15 (1.5 mL, 1.25 mg/mL). Corresponding Rh distribution changes (d, e, f) and cryo-TEM images of the stable self-
assembled structures (g, h, i). (a, d, g; b, e, h; and c, f, i are for the respective same conditions).
a
Table 4. Summary of ⟨Rh⟩, PDI, and Morphology of the Self-Assembled Structures in THF
TBAOH
starting copolymer
particle
μL
wt %
⟨Rh⟩ (nm)
PDI
⟨Rg⟩ (nm)
⟨Rg⟩/⟨Rh⟩
Nagg
SbB15
SbB15
V-Bz-6
V-Bz-5
V-Bz-7
4
8
40
20
10
52
57
84
0.09
0.06
0.10
60
64
94
1.17
1.12
1.12
740
841
b
SbB15
16
2060
a
b
Data were collected by DLS and SLS. The same as Table 3.
Comparing the three groups, it was clear that the larger
group remained on the copolymer, the larger the solvent-
phobicity, and consequently the larger the vesicles generated.
amount of water, the faster the assemblies reached the maxium
⟨Rh⟩ (100, 45, and 20 min for 4, 8, and 16 μL aqueous solution
of TBAOH, respectively), then faster turned to the stable state.
It seemed understandable as the small amount water served
cocatalyst accelerating the deprotection. Moreover, the final
degree of deprotection varied with the amount of water used,
i.e., 90%, 60%, and 55% removal of Bz for 4, 8, and 16 μL
aqueous TBAOH, respectively. The corresponding ⟨Rh⟩ of the
final vesicles were 52 nm (V-Bz-6), 57 nm (V-Bz-5), and 84
nm (V-Bz-7). This means that as the larger amount of the Bz
CONCLUSIONS
■
In this paper, removal of Bz group has been used to induce self-
assembly of glyco-block-containing copolymers for the first
time. Compared to Ac group, the slower deprotection speed of
Bz brought much more space and variations, which makes the
detail studies of kinetics and morphology control of the
deprotection-induced self-assembly possible. After careful
analysis on the data from DLS, SLS, in situ NMR, and cryo-
TEM, etc., we found that Bz removal always gave much larger
G
DOI: 10.1021/acs.macromol.5b00572
Macromolecules XXXX, XXX, XXX−XXX

Macromolecules
Article
Figure 8. (a) Proposed mechanism of the assembly process in Figure 7a. Cryo-TEM images of the assemblies collected at (b) state I and (c) state II
as arrowed in Figure 7a.
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ASSOCIATED CONTENT
■
S
* Supporting Information
Synthesis and characterization of monomer Bz-2 and Ac-2,
1
block copolymer SbB15, SbB5, SbA13, and SbA7, including H
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(c) Schumers, J.-M.; Bertrand, O.; Fustin, C.-A.; Gohy, J.-F. J.
Polym. Sci., Part A: Polym. Chem. 2012, 50, 599−608.
NMR as well as details of GPC-MALS, FT-IR, and SLS
measurements. The Supporting Information is available free of
charge on the ACS Publications website at DOI: 10.1021/
acs.macromol.5b00572.
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AUTHOR INFORMATION
Corresponding Author
*E-mail guosong@fudan.edu.cn; Tel +86 21 55664275 (G.C.).
Notes
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The authors declare no competing financial interest.
(12) (a) Sandbhor, M. S.; Soya, N.; Albohy, A.; Zheng, R. B.;
Cartmell, J.; Bundle, D. R.; Klassen, J. S.; Cairo, C. W. Biochemistry
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ACKNOWLEDGMENTS
■
Ministry of Science and Technology of China
(2011CB932503), National Natural Science Foundation of
China (Nos. 21474020, 91227203, 51322306, and GZ962), the
Shanghai Rising-Star Program (Grant 13QA1400600), and the
Innovation Program of the Shanghai Municipal Education
Commission are acknowledged for their financial support.
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DOI: 10.1021/acs.macromol.5b00572
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