Single-chain nanoparticles with well-defined structure via intramolecular crosslinking of linear polymers with pendant benzoxazine groups

Article abstract of DOI:10.1002/pola.25003

Controlled intramolecular collapse of linear polymer chains with crosslinkable groups is an efficient way to prepare single-chain nanoparticles in the size range of 5-20 nm. However, the nature of the crosslinking group is critical. In present study, poly

Full text of DOI:10.1002/pola.25003

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ARTICLE
Single-Chain Nanoparticles with Well-Defined Structure via
Intramolecular Crosslinking of Linear Polymers
with Pendant Benzoxazine Groups
Peng Wang, Hongting Pu, Ming Jin
Institute of Functional Polymers, School of Materials Science and Engineering, Tongji University, Shanghai 201804, China
Correspondence to: H. Pu (E-mail: puhongting@tongji.edu.cn)
Received 27 August 2011; accepted 9 September 2011; published online 26 September 2011
DOI: 10.1002/pola.25003
ABSTRACT: Controlled intramolecular collapse of linear polymer
chains with crosslinkable groups is an efficient way to prepare
single-chain nanoparticles in the size range of 5–20 nm. However,
the nature of the crosslinking group is critical. In present study,
poly(styrene-co-chloromethyl styrene) [P(St-co-CMS)] was synthe-
sized via reversible addition-fragmentation chain transfer (RAFT)
polymerization and then was converted into polystyrene azide
(PSAN3). Polystyrene containing benzoxazine side groups [P(St-
co-BS)], which can be used as the precusor for the later intramo-
lecular collapse, was obtained from PSAN3 and 3-(4-(prop-2-yny-
loxy)phenyl)-3,4-dihydro-2H-benzo [e][1,3]oxazine (P-APPE) via
the method of click chemistry. The sub-20 nm polymeric nano-
particles with well-defined structure via thermally intramolecular
crosslinking of P(St-co-BS) were prepared. The structure change
from the linear polymers to the single-chain nanoparticles was
confirmed by nuclear magnetic resonance (NMR), Fourier trans-
form infrared (FTIR), and gel permeation chromatography (GPC).
The morphology and the dimension of the nanoparticles were
characterized by using transmission electron microscope (TEM),
atomic force microscopy (AFM), as well as dynamic light scatter-
ing (DLS). The results reveal that the size of the nanoparticles can
be regulated by changing the molecular weight of the precursors
and the amount of pendant benzoxazine groups by the use of
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controlled polymerization techniques.
2011 Wiley Periodicals,
Inc. J Polym Sci Part A: Polym Chem 49: 5133–5141, 2011
KEYWORDS: benzoxazine; crosslinking; nanoparticles; reversible
addition fragmentation chain transfer (RAFT); single-chain
much byproducts.9 As a consequence, polymer nanoparticles
with size ranging from 20 to 200 nm can be effectively
obtained using these methods, but the preparation of smaller
nanoparticles is still challenging.
INTRODUCTION Polymer nanoparticles have attracted signifi-
cant attention in recent years due to their peculiar proper-
ties and key role in the implementation of nanotechnology.
Compared with inorganic nanoparticles, polymeric nanopar-
ticles as a kind of soft materials show better biocompatibil-
ity, biodegradability, and self-assembly performance. Thus,
functionalized polymer nanoparticles can be considered as
building blocks for a variety of nanotechnological applica-
tions, ranging from vectors for drug and DNA delivery sys-
tems1,2 to templating agents for nanoporous microelectronic
materials.3 Among the technologies developed to prepare
polymer nanoparticles, two types of methods are convention-
ally used. One is the dispersion of preformed polymers,
including microphase inversion,4 nanopreciptation,5 self-as-
sembly of block copolymers into micelles followed by chemi-
cal crosslinking (20–200 nm),6 as well as supramolecular
strategies to collapse nanoparticles.2,7 The other is the poly-
merization of monomers in dispersed medium, such as emul-
sion polymerization (50–200 nm), microemulsion technique
(20–50 nm),8 as well as the synthesis of discrete spherical
macromolecules like dendrimers (1–10 nm), which has the
disadvantages of complicated synthetic procedure and too
A strategy involving the collapse and intramolecular coupling
of polymeric single-chain to give discrete nanoparticle in the
size range of 5–20 nm has been proposed.10 Synthetically,
the preparation of these polymeric nanoparticles involves
two steps. The first involves the synthesis of crosslinkable
linear polymers. They can be the polymers with reactive
groups which can be thermally or chemically crosslinked
later. Up to date, this technique includes crosslinking of vinyl
functionalization,11 click chemistry,12 thermal crosslinking of
benzylcyclobutane,13 or sulfonyl azide,14 crosslinking of
alternate o-quinodimethane precursors,15 crosslinking of
copolymers containing pendent isocyanate functionality with
diamine,16 photo-crosslinking of cinnamoyl groups,17 to give
the single-chain nanoparticles. The second involves the prep-
aration of single-chain nanoparticles in ultra-dilute solution
(ca.10ꢀ5–10ꢀ6 M) to avoid intermolecular crosslinking reac-
tion. But this precludes the synthesis of these nanoparticles
in mass. In addition, even at this ultra-diluted solution
Additional Supporting Information may be found in the online version of this article.
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SCHEME 1 Synthesis of 3-(4-(prop-2-ynyloxy)phenyl)-3,4-dihydro-2H-benzo[e][1,3]oxazine.
RESULTS AND DISCUSSION
intermolecular crosslinking is still evident, which results in
poorly defined structure and even gelation in some cases. To
overcome this difficulty, a continuous dropwise addition
strategy for the successful synthesis of discrete nanoparticles
was proposed.13,14 In this way, intermolecular crosslinking
can be effectively eliminated even at high concentration (0.1
M), which makes it a practical technique for the large-scale
synthesis of well-defined nanoparticles.
Synthesis of Propargyl Ether Functionalized Benzoxazine
Propargyl ether functionalized benzoxazine, 3-(4-(prop-2-
ynyloxy)phenyl)-3,4-dihydro-2H-benzo[e][1,3]oxazine (P-APPE),
was synthesized from phenol, paraformaldehyde with p-ami-
nophenyl propargyl ether (APPE) by solventless method
according to Scheme 1. The chemical structure of P-APPE
(4) was confirmed by both FTIR and 1H NMR. The charac-
teristic absorption of benzoxazine structure appears at
1,217 cmꢀ1 due to the asymmetric stretching of CAOAC,
and the peaks at 954 and 1,506 cmꢀ1 are attributed to the
tri-substituted benzene ring. The propargyl group is evi-
denced by characteristic bands of HACBC and ACBCA
appeared at 3,286 and 2,121 cmꢀ1, respectively. 1H NMR
spectrum of P-APPE shows a triplet at 2.50 ppm and a dou-
blet at 4.55 ppm, which are assigned to HACB and CH2
(propargyl). Also, the protons on NACH2AO and NACH-Ar
of oxazine rings are detectable at 5.29 and 4.61 ppm.
To satisfy these demands, the nature of the crosslinking
group is critical. It must be selectively activated and react
rapidly, leading to the efficient formation of the intramolecu-
lar bonds. It is also important that this reaction is irreversi-
ble and leads to a bonded structure that is subsequently
unreactive under the reaction condition.13 However, most of
the crosslinking reactions are difficulty to be controlled and
have subsidiary reactions, which produce the nanoparticles
with complicated structure and wide dispersion.11,14,17 Ben-
zoxazines are heterocyclic compounds which can be poly-
merized via a thermally induced ring-opening polymerization
without using any catalyst and thus no other byproducts are
generated during the polymerization. Furthermore, benzoxa-
zine monomers can be easily prepared from inexpensive raw
materials like phenols, formaldehyde, and primary amines
(aliphatic or aromatic) either via solution or solventless
method.18 Accordingly, various types of benzoxazine mono-
mers can be synthesized using various phenols and amines
with different substituting groups attached. These substitut-
ing groups can provide additional polymerizable sites and
also affect the crosslinking process.19
Synthesis of Linear Polystyrene Containing Pendent
Benzoxazine Groups
For the synthesis of parent azide functionalized copolymers,
a series of poly(styrene-co-chloromethyl styrene) (P(St-co-
CMS)), 5 were first prepared via reversible addition-fragmen-
tation chain transfer (RAFT) polymerization of chloromethyl
styrene (CMS) and styrene (St) in the presence of S-ethoxy-
carbonyl phenylmethyl dithiobenzoate (ECPDB) and azobisi-
sobutyronitrile (AIBN) according to Scheme 2. The composi-
tion of the copolymer was determined using 1H NMR
spectroscopy. The mole fractions of CMS and St are calcu-
lated from the ratio of the peak area around 4.5 ppm, corre-
sponding to two protons of methylene in the side chain of
CMS, to the total area between 6.25 and 7.24 ppm, which is
attributed to the total aromatic protons. Then copolymer 5
with different mole fraction of chloromethyl groups (5–20
mol %) is quantitatively converted into polystyrene azide
(PSAN3) (6) in the presence of NaN3/N,N-dimethylforma-
mide (DMF) at room temperature. From 1H NMR spectrum
of 6 shown in Figure 1(A), it can be found that a new signal
appears at 4.25 ppm due to CH2 linked to azide groups
when the signal at 4.5 ppm, corresponding to the protons of
In this study, propargyl ether functionalized benzoxazine
monomer was synthesized and added to azide functionalized
polymers via the method of click chemistry to give the cross-
linkable linear polymers. These linear polymers can undergo
intramolecular collapse by ring-opening polymerization of
benzoxazine groups to give polymer nanoparticles with small
size. Furthermore, the polymer nanoparticles obtained from
this procedure are freely soluble in common solvents and do
not need any surfactant, during either the synthesis or the
subsequent stabilization of the resulting nanoparticle
solution.
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SCHEME 2 Synthesis of linear polymers containing pendent benzoxazine functionalities.
CH2-Cl in copolymer 5, disappears completely. The structure
of 6 is further supported by the observation from IR spec-
trum of the azide stretching band at 2,096 cmꢀ1 [Fig. 2(A)].
denced by nearly quantitative functionalization. Moreover,
general agreement between the molecular weight of the
clicked polymer 7 (Mn ¼ 53315) and that of the precursor
azide-polymer 6 (Mn ¼ 42618) obtained by GPC also con-
firms efficient coupling. The observed increase in the molec-
ular weight is due to the additional benzoxazine moiety
incorporated.
Click chemistry is an effective method to join small modular
units together.20 Thus polystyrene containing benzoxazine
side groups [P(St-co-BS)] can be obtained from PSAN3 and
P-APPE via the method of click chemistry, as shown in
Scheme 2. PSAN3 (6) was dissolved in DMF and reacted
with 4 in the presence of CuBr/N,N,N0,N00,N00-pentamethyldi-
ethylenetriamine (PMDETA) ligand at room temperature
under nitrogen. After removing the catalyst, the polymer was
precipitated and dried under vacuum. The extent of conver-
sion of the side azide moieties was monitored by 1H NMR
and by observing the disappearance of the protons of meth-
ylene adjacent to the azide group (N3ACH2Ph) at 4.25 ppm
as well as the appearance of the new protons of methylene
adjacent to the triazole ring at 5.36 ppm (triazole-CH2Ph)
[Fig. 1(B)]. Moreover, the band, corresponding to the AN3
group at 2,096 cmꢀ1, disappears completely [Fig. 2(B)].
Thus, the click reaction of the side group is efficient, as evi-
It is also important to confirm whether benzoxazine ring will
be preserved during the click reaction. The presence of signals
1
in H NMR spectra at 5.27 ppm and 4.55 ppm, corresponding
to NACH2AO and NACH2-Ar clearly, indicates the retention of
the benzoxazine ring during the click reaction [Fig. 1(B)].
Moreover, the characteristic absorption of benzoxazine struc-
ture appeares on copolymer 7 at 1,510, 1,226, 941 cmꢀ1 also
proves the existence of benzoxazine ring [Fig. 2(B)].
Preparation of the Single-Chain Nanoparticles via
Intramolecular Crosslinking
As the crosslinking group should be selectively activated and
react rapidly, an optimum reaction temperature to ensure
FIGURE 1 1H NMR spectra of (A) PSAN3, (B) P(St-co-BS), and
(C) nanoparticle 8.
FIGURE 2 FTIR spectra of (A) PSAN3, (B) P(St-co-BS), and (C)
nanoparticle 8.
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structure23 (-aromatic-CH2ANRACH2-aromatic-) as described
in Scheme 3. Moreover, the disappeared characteristic absorp-
tion of benzoxazine structure on nanoparticle 8 at 1,510,
1,226, 941 cmꢀ1, compared with that of polymer 7 also indi-
cates the complete reaction of benzoxazine ring [Fig. 2(C)].
Comparison of the GPC traces for the collapsed nanoparticles
versus the starting linear polymers is an efficient diagnostic
technique for demonstrating the volume change that will be
expected for the collapse of a linear polymer to give an intra-
molecularly crosslinked nanoparticle. As shown in Table 1,
GPC data of the crosslinked nanoparticles show that the
hydrodynamic volumes of the particles as measured by the
elution time are significantly smaller than those of the start-
ing linear polymers. The reduction in hydrodynamic volume
and low polydispersity index indicate that no significant
intermolecular crosslinking happens. For example, as shown
in Figure 5, a copolymer with 10 mol % benzoxazine and an
initial molecular weight Mn ¼ 53315 (PDI ¼ 1.38) gives a
nanoparticle with a molecular weight Mn ¼ 32522 (PDI ¼
1.30), which represents a reduction in hydrodynamic volume
of 39%. This result agrees with the expected decrease in the
size of the polymer due to the formation of the internal
covalent bonds. As shown in Table 1, for styrenic copolymers
containing 5, 10, 15, and 20 mol % benzoxazine-functional-
ized repeat units, a slightly increase in molecular weight is
observed when the relative percentage of benzoxazine
groups increases. After crosslinking, a systematic decrease in
the hydrodynamic volume of the nanoparticles is observed
on increasing the percentage of benzoxazine groups, which is
consistent with an increase in the level of intramolecular
bonding and a globular, three-dimensional (3D) structure.
For the copolymers with the same amount of benzoxazine
functionality, it can be found that the reduction in hydrody-
namic volume after crosslinking becomes more obvious as
the molecular weight of the linear polymers increases.
FIGURE 3 DSC thermogram of P(St-co-BS), 7.
efficient and fast intramolecular crosslinking is very impor-
tant. The DSC thermogram for copolymer 7 shown in Figure
3 reveals two exothermic peaks around 150 and 250 ꢁC. In
general, depending on the substituents and functional groups
present in the structure, the benzoxazine ring opens at the
temperature ranging between 210 and 250 ꢁC. Thus, the
exothermic peak at 250 ꢁC corresponds to the ring-opening
polymerization of benzoxazine moiety and results in the con-
sequent crosslinking of the polymer. In addition to this exo-
thermic peak, the thermogram shows an interesting feature
of lower temperature exothermic peak with maximum value
at 150 ꢁC. Ishida et al.21 attributed this phenomenon to the
contribution from the thermal coupling of the residual pro-
pargyl and azide end groups. But Yagci et al.22 gave the opin-
ion that it may be due to the transformation of 1,2,3-triazole
ring, because benzylic triazoles have the possibility to ther-
mally transform from 1,2,3 form to other triazoles. Actually,
there is limited information in the literature about the ther-
mal stability of 1,2,3-triazole rings, formed via click chemis-
try, at elevated temperature. But the decomposition of the
triazole ring by the evolution of nitrogen under 300 ꢁC is
impossible as no weight loss due to the nitrogen evolution
was observed in thermogravimetric analysis (TGA) of poly-
mer 7 (Fig. 4).
The Morphology and the Size of the Nanoparticles
Hydrodynamic radius (Rh) of the nanoparticles in tetra-
hydrofuran (THF) was determined by DLS. Examination
of the data in Table 1 reveals that the size is very small
Considering the above factors, the intramolecular collapse of
ꢁ
the single chain in dibenzyl ether at 250 C (Scheme 3) and
the dropwise technique described for benzocyclobutene13
and sulfonyl azide14 can be chosen. Under these conditions,
the continuous addition strategy of a concentrated solution
of the same linear polymer with a benzoxazine concentration
of 0.02 M gives a final crosslinking concentration of 0.008 M
in dibenzyl ether after addition.
The structure change from the random coil of linear polymers
to intramolecular collapsed nanoparticles is monitored by 1H
1
NMR and FTIR. The disappearance of signals in H NMR spec-
tra at 5.27 ppm and 4.55 ppm corresponding to NACH2AO
and NACH2-Ar clearly indicates the high-efficiency ring-open-
ing reaction of the benzoxazine group at 250 ꢁC [Fig. 1(C)],
and the appearance of methylene protons at 3.7 ppm in
Figure 1(C) proves the formation of the Mannich bridge
FIGURE 4 TGA-DTA thermogram of P(St-co-BS), 7.
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SCHEME 3 Schematic representation of the intramolecular collapse of linear polymer 7, to give nanoparticle 8.
(Rh ¼ 5.1–11.8 nm). This range of size, which is characteris-
tic of dendrimers and some micelles, has never been reached
before for a polymeric nanoparticle via emulsion polymeriza-
tion or self-assembly. Furthermore, the results also demon-
strate the inherent versatility of this approach in controlling
the size of the final nanoparticle. Not only can the size and
the crosslinking density of the nanoparticle be controlled by
the level of benzoxazine incorporated, but also the molecular
weight of the starting linear polymer plays a key role in
determining the hydrodynamic size of the final nanoparticle.
All these factors can be regulated by the use of controlled
polymerization techniques.
The 3D morphology of the polymeric nanoparticles on the
solid substrate was measured by atomic force microscopy
(AFM). The samples were dissolved in THF, and all solu-
tions were filtered with a Teflon filter (0.2 lm) to reduce
the amount of large dust particles and atmospheric
TABLE 1 Comparison of GPC and DLS Data for PSAN3, 6, P(St-co-BS), 7, and the Final
Nanoparticle, 8
Linear
Polymers
Precursors (PSAN3)
[P(St-co-BS)]
Nanoparticles
a
b
AN3 mol % (%)
Mn
PDI
Mn
PDI
Mn
PDI
Rh (nm)
5
22,474
23,093
23,441
25,100
41,533
42,618
44,382
44,654
71,580
73,497
1.22
1.27
1.29
1.33
1.21
1.23
1.19
1.37
1.24
1.41
25,782
28,618
32,210
38,465
46,932
53,315
60,433
64,620
80,269
91,283
1.31
1.37
1.33
1.46
1.33
1.38
1.31
1.48
1.45
1.62
21,156
19,475
17,265
16,924
36,484
32,522
24,365
22,838
52,174
46,513
1.25
1.27
1.31
1.39
1.22
1.30
1.21
1.38
1.31
1.44
6.6
6.1
10
15
20
5
5.7
5.1
8.7
10
15
20
5
7.8
7.1
6.8
11.8
10.6
10
a
Mole fraction of N3 units as measured by 1H NMR.
b
Hydrodynamic radius as measured by DLS in THF at the concentration of 0.1 mg/mL.
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height of the nanoparticle on the substrate will be smaller
than its unperturbed size.25 Further evaluation of the col-
lapsed nanoparticles with transmission electron microscope
(TEM) confirms the controlled crosslinking process of linear
precursors into defined 3D architectures with the mean di-
ameter of 8.7 6 1.5 nm (Fig. 8).
EXPERIMENTAL
Materials
N-(4-hydroxyphenyl)acetamide, tetrabutylammonium bro-
mide, paraformaldehyde, HCl solution (37%), CuBr, ethanol,
methanol, PMDETA, phenol, 1,4-dioxane, chloroform, toluene,
THF, DMF, diethyl ether, sodium hydroxide, anhydrous mag-
nesium sulfate, and sodium azide were all analytical grades
and purchased from Shanghai Chemical Reagent. Propargyl
bromide (ꢂ80 volume % in toluene), CMS (90%) and benzyl
ether (98%) were obtained from Aldrich. St and CMS were
distilled under reduced pressure before use. AIBN was
recrystallized from ethanol. THF was dried with sodium
using benzophenone as indicator. CuBr was purified by
washing with acetic acid and acetone alternately. The RAFT
agent ECPDB was prepared similar to the method described
in reference.26 All other reagents were used without further
purification.
FIGURE 5 GPC traces for (A) PSAN3, 6, (Mn ¼ 42618, PDI ¼
1.23), (B) P(St-co-BS), 7, (Mn ¼ 53315, PDI ¼ 1.38), and (C)
nanoparticle 8 (Mn ¼ 32522, PDI ¼ 1.30).
contaminants. The solution (concentration, 0.01 mg/mL) was
spin-coated at 2000 rpm for 40 s on the mica substrate. The
images shown in Figure 6 clearly demonstrate the uniformity
of the nanoparticles on the surfaces, and the narrow height
distribution provides evidence that only individual polysty-
rene nanoparticles are present and no agglomeration of
nanoparticles occurs. It is clear that the dimension of the
nanoparticles increases with increasing molecular weight of
the starting linear polymer.
Synthesis of APPE, 3
The synthesis of APPE is similar to the method described in
Ref. 22. In a 250-mL flask, N-(4-hydroxyphenyl)acetamide, 1,
(8.1 g, 50 mmol) was dissolved in 100-mL NaOH solution
As shown in Figure 7(A), the diameter of the nanoparticle
(12.5 6 1.5 nm) is much larger than its height (1.6 6 0.3
nm) on the mica surface. Thus, on the mica surface the
nanoparticle adopts a pancake-like shape as shown in the
inset of Figure 7(A). This pancake-like conformation is also
observed in dendrimer structure. It has been shown before
that both charged and uncharged dendrimers are adsorbed
to mica surface and form a flat disk structure.24 With a high
free energy surface like mica, the number of the repeat units
in contact with the surface will increase to gain adsorption
energy to reduce the conformational entropy, therefore, the
ꢁ
(0.4 N) and heated at 70 C until a clear solution was formed.
Then tetrabutylammonium bromide (1.6 g, 5 mmol) was added
as a phase transfer catalyst. A solution of propargyl bromide
(6.5 g, 55 mmol) in 50-mL toluene was added portion-wise to
ꢁ
the solution and stirred at 70 C for 24 h. Then, it was cooled
to get the solid product, and the toluene layer was separated,
washed repeatedly with water, and precipitated. The crude
product was dissolved in 1,4-dioxane and precipitated in water
(ca. 200 mL), and washed repeatedly with copious amount
of water to give N-(4-(prop-2-ynyloxy)phenyl)acetamide, 2,
FIGURE 6 AFM 3D images of nanoparticle 8, the image dimensions are both 5 ꢃ 5 lm. (A) 10 mol % benzoxazine, Mn ¼ 19475,
PDI ¼ 1.27; (B) 10 mol % benzoxazine, Mn ¼ 46513, PDI ¼ 1.44.
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FIGURE 7 Top-view of AFM images of nanoparticle 8 and the sectional analysis of the single nanoparticle; (A) 10 mol % benzoxa-
zine, Mn ¼ 19475, PDI ¼ 1.27; (B) 10 mol % benzoxazine, Mn ¼ 46513, PDI ¼ 1.44; The inset shows a pancake-like model.
(8.9 g, yield: 94 %). In a 250 mL flask, 2 (8.5 g, 45 mmol) was
dissolved in 70-mL ethanol, and then 70-mL HCl solution
(37%) was added. The mixture was stirred at 90 ꢁC for 3 h.
After neutralized with sodium hydroxide, the solution was
extracted with chloroform, and the organic layer was dried
over anhydrous MgSO4. Evaporation of chloroform gave a yel-
lowish brown viscous product. The crude product was purified
by distillation under reduced pressure (bp: 95 ꢁC, 10 mmHg)
to get a colorless and highly viscous liquid, which crystallized
into yellowish white crystals after a while in the flask to APPE,
3, (5.0 g, yield: 75 %, mp: 49–50 ꢁC). 1H-NMR (400 MHz,
CDCl3, d):2.50 (t, BCAH), 3.50 (br s, NH2), 4.60 (d, CH2, pro-
pargyl), 6.65–6.81 (d, d, 4H, Ar).
Synthesis of P-APPE, 4
Into a 20-mL vial APPE (1.47 g, 10 mmol), phenol (0.94 g,
10 mmol), and paraformaldehyde (0.90 g, 30 mmol) were
ꢁ
mixed together and heated at 120 C for 20 min. The crude
product after cooling was dissolved in 50-mL diethyl ether
and washed several times with 1 N sodium hydroxide solu-
tion and finally with distilled water. Then, the ether solution
was dried with anhydrous sodium sulfate, followed by evap-
oration of ether under vacuum to get pale yellow viscous
fluid. (1.59 g, yield: 60%). FTIR (m, cmꢀ1): 3,290, 3,041,
2,919, 2,121, 1,597, 1,506, 1,336, 1,236, 1,217, 1,034, 1,019,
954, 756, 690, 642. 1H NMR (400 MHz, CDCl3, d): 2.50 (t,
BCAH), 4.55 (s, CH2, oxazine), 4.61 (d, CH2, propargyl), 5.29
(s, CH2, oxazine), and 6.75–7.1 (8H, Ar).
Synthesis of P(St-co-CMS), 5
P(St-co-CMS) containing quantitative chloromethyl groups
was synthesized via RAFT polymerization of St and CMS in
the presence of ECPDB and AIBN. To a Schlenk tube
equipped with a magnetic stirring bar, styrene (1.8747 g,
18.0 mmol), CMS (0.3052 g, 2.0 mmol), ECPDB (0.0063 g,
FIGURE 8 TEM image of nanoparticle 8 (10 mol % benzoxazine,
Mn ¼ 46513, PDI ¼ 1.44).
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0.02 mmol), and AIBN (0.0016 g, 0.01 mmol) were added in
that order. The tube was degassed by three freeze-pump-
thaw cycles, left in vacuum, and placed in oil bath at 65 ꢁC
for 12 h. Subsequently, the mixture of the polymerization
was diluted with THF and precipitated in excess methanol.
The polymer was dried for 24 h in a vacuum oven at 25 ꢁC
to give 5, as a pink powder (1.00 g, yield: 45%). FTIR
(m, cmꢀ1): 3,050, 2,924, 1,601, 1,492, 1,452, 1,265, 757, and
699. 1H NMR (400 MHz, CDCl3, d): 7.24–6.25 (m, Ar), 4.50
(br s, CH2), 1.23–2.13 (m, CH2, CH).
7.24–6.23 (m, Ar), 5.39 (br s, CH2), 5.22 (br s, CH2), 3.77 (br
s, CH2), 2.21–1.22 (m, CH2, CH).
Characterization
1H NMR measurements were carried out on a Bruker AMX
300 spectrometer, CDCl3 as the solvent. FTIR analysis of the
samples was carried out on a thermo Bruker EQUINOXSS/
HYPERION 2000 spectrometer. GPC was performed in THF
on a Waters Alliance HPLC system. The molecular weight of
the polymers was calculated relative to linear polystyrene
standard. DSC of the polymers was performed on MDSC-
Q100 (TA) under a nitrogen atmosphere at a constant heat-
ing rate of 10 ꢁC/min. TGA was performed on a STA 449C
(NETZSCH Co.) instrument under a nitrogen atmosphere at a
constant heating rate of 20 ꢁC/min. TEM was performed
with a Hitachi H-600 TEM, operating with an acceleration
voltage of 200 KV. The TEM samples were prepared by plac-
ing one drop of the diluted dispersion of the nanoparticles
on a 200 mesh carbon coated copper grid and left in air to
dry. The height and distribution of the nanoparticles were
determined on tapping-mode AFM (SPA-300HV, Seiko Instru-
ments) under ambient condition in air. The standard silicon
tips were used. The average particle size of the nanoparticles
was also determined on Malvern Autosizer 4700 dynamic
light scattering (DLS) equipped with a solid-state laser (ILT
5500QSL, output power 100 mW at k ¼ 532 nm) as light
source.
Synthesis of PSAN3, 6
Copolymer 5 was dissolved in DMF, and then NaN3 (two
times excess to the mole of chloromethyl group of each co-
polymer) was added. The resulting solution was allowed to
ꢁ
stir at 25 C overnight and precipitated into methanol/water
mixture (1/1 by volume). After filtratiꢁon, the polymer was
dried for 24 h in a vacuum oven at 25 C to give 6, as a col-
orless powder (yield: 92%). FTIR (m, cmꢀ1): 3,026, 2,924,
2,096, 1,681, 1,601, 1,493, 1,452, 907, 757, and 699. 1H
NMR (400 MHz, CDCl3): d ¼ 7.24–6.23 (m, Ar), 4.25 (br s,
CH2), 2.21–1.22 (m, CH2, CH).
Synthesis of P(St-co-BS), 7
Copolymer 6 (0.5 g, 0.46 mmol AN3, Mn ¼ 42618, PDI ¼
1.23), and P-APPE (0.24 g, 0.92 mmol) were dissolved in 10-
mL DMF in a Schlenk tube and purged with nitrogen. CuBr
(0.26 g, 1.84 mmol) and PMDETA (0.31 g, 2 mmol) were
added, and the reaction mixture was degassed by three
freeze-pump-thaw cycles and left under nitrogen and stirred
at room temperature for 24 h. Subsequently, the polymer so-
lution was precipitated into methanol and then dissolved in
THF and passed through an alumina column to remove cop-
per salt. Finally, the polymer solution was concentrated and
precipitated in excess methanol, then filtered and dried
under vacuum to give 7, as beige powder (0.57 g, yield:
92%). FTIR (m, cmꢀ1): 3,026, 2,924, 1,601, 1,510, 1,493,
1,452, 1,226, 1,030, 941, 755, and 699. 1H NMR (400 MHz,
CDCl3, d): 7.38 (br s, CH¼¼C), 7.24–6.23 (m, Ar), 5.36 (br s,
CH2), 5.27 (br s, CH2), 5.12 (br s, CH2), 4.55 (br s, CH2),
2.21–1.22 (m, CH2, CH).
CONCLUSIONS
In summary, a new synthetic strategy for the controlled
intramolecular crosslinking of linear polymers with pendant
benzoxazine groups to give single-chain nanoparticles has
been demonstrated. It is found that the dimension of the
polymeric nanoparticles can be controlled in 5–20 nm by
varying the molecular weight and the amount of benzoxazine
groups for the starting linear polymers. It is also confirmed
that the nanoparticles adopt a pancake-like shape on a high
free energy surface. Furthermore, a wide range of benzoxa-
zine monomers with additional functionalities such as acety-
lene, nitrile, propargyl, and maleimide groups can be easily
prepared from inexpensive raw materials, this flexibility pro-
vides much possibility of incorporating benzoxazine group
into polymer to give the crosslinkable precursors to prepare
single-chain nanoparticles.
General Procedure for the Preparation
of the Nanoparticle
In a 100-mL three-necked flask equipped with an internal
thermometer, 25 mL of benzyl ether was heated at 250 ꢁC
under nitrogen. A solution of 0.5 g benzoxazine-functional-
ized linear copolymer 7 (Mn ¼ 53315, PDI ¼ 1.38, 10 mol %
benzoxazine) dissolved in 20 mL benzyl ether, was added
dropwise via a peristaltic pump at about 12 mL/h with vigo-
rously stirring. After addition, the reaction mixture was
heated for an additional 2.5 h, the polymer mixture was con-
centrated and precipitated in excess methanol. After filtra-
tion, the polymer was dried for 24 h in a vacuum oven at
The project is sponsored by Major Program for Fundamental
Research of Shanghai Science & Technology Commission
(09JC1414300) and Natural Science Foundation of China
(21144006)
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