Shell-crosslinked nanostructures from amphiphilic AB and ABA block copolymers of styrene-alt-(maleic anhydride) and styrene: Polymerization, assembly and stabilization in one pot

Article abstract of DOI:10.1039/b504313a

Shell-crosslinked nanostructures having unusual rosette morphologies have been produced by a simple process from styrene and maleic anhydride. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b504313a

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Shell-crosslinked nanostructures from amphiphilic AB and ABA block
copolymers of styrene-alt-(maleic anhydride) and styrene:
polymerization, assembly and stabilization in one pot{
Simon Harrisson and Karen L. Wooley*
Received (in Cambridge, UK) 29th March 2005, Accepted 19th April 2005
First published as an Advance Article on the web 12th May 2005
DOI: 10.1039/b504313a
Shell-crosslinked nanostructures having unusual rosette
morphologies have been produced by a simple process from
styrene and maleic anhydride.
Nanoparticles formed by the regioselective crosslinking of the
outer regions of amphiphilic block copolymer micelles (by covalent
1–5
coupling of chain segments constituting the shell
or an
6,7
intermediary layer ) have attracted great interest in recent years
7
as well-defined nanoreactors, agents for encapsulation, trans-
3–5
3
4
duction, and drug delivery, among other potential applications.
The block copolymer precursors are programmed for multi-
molecular assembly into complex nanostructures based upon their
8
compositions and structures, which are controlled during
synthesis using living polymerization techniques and via post-
polymerization modifications. For physical and chemical compat-
ibility purposes, protecting groups are often utilized during
polymerization to establish the polymer structure and then are
removed to reveal polar, reactive functionalities to promote
9
supramolecular assembly and provide for covalent crosslinking.
Armes and coworkers have developed an approach towards
reducing the synthetic complexity of copolymer synthesis and
Scheme 1 Synthesis of di- and tri-block poly(styrene-alt-maleic anhy-
dride)-block-polystyrene copolymers and formation of micelles and shell-
crosslinked nanoparticles.
2,6,7
micelle formation,
whereby the direct production of micelles
from block copolymers was accomplished by aqueous atom
transfer radical polymerization of monomer units having pH- and
thermally-tunable degrees of hydrophilicity. In another approach,
the assembly of polymer mixtures into non-covalently crosslinked
micelles has been followed by shell-crosslinking to establish robust
structure and composition of the products and to study its
influence on the resulting assemblies and crosslinked
nanostructures.
10
nanomaterials by a block copolymer-free strategy. In this report,
we present an alternative synthetic simplification strategy, which
maintains the elegance of block copolymer assembly and utilizes a
one-pot formation of well-defined, regioselectively-crosslinked
nanostructures from commercially-available monomers.
In the first stage, the block copolymers were synthesized from
commodity monomers and without the need for sequential
monomer additions and post-polymerization modification, allow-
ing for significant cost and labor savings over current techniques
for the synthesis of similar nanostructures. The propensity of MA
and STY to form alternating copolymers regardless of their molar
To demonstrate this one-pot synthetic strategy, poly(maleic
anhydride-alt-styrene)-block-styrene AB and ABA block copoly-
mers were prepared from maleic anhydride (MA) and styrene
ratio is well-known. The living copolymerization of MA with STY
11,12
has been reported under RAFT
13,14
or nitroxide-mediated
(
STY) via radical addition fragmentation chain transfer (RAFT)
(NMRP)
polymerization conditions. Of these, RAFT was
11
polymerization, hydrolyzed and organized into micellar assem-
blies upon the addition of water, and crosslinked by addition of a
diamine in the presence of 1-[3-(dimethylamino)propyl]-3-ethyl-
carbodiimide hydrochloride (EDC), yielding shell-crosslinked
nanostructures (Scheme 1). Each step within the overall one-pot
methodology was performed independently to confirm the
selected, as it can be performed at temperatures lower than those
13
required for NMRP, allowing the formation of MA–STY
copolymers with structures much closer to the alternating
11,12
ideal.
The practical problems of synthesis, purification, and
storage, commonly associated with RAFT agents, were amelio-
rated by the use of crystalline and virtually odorless RAFT agents,
S-dodecyl S9-2-(2,2-dimethylacetic acid) trithiocarbonate, 1, and
2
{
Electronic supplementary information (ESI) available: Full experimental
details, AFM images and DLS correlation functions. See http://
15
,29-bis(propionic acid) trithiocarbonate, 2. Therefore, RAFT
copolymerization of MA and STY was conducted in the presence
of excess STY to afford an alternating copolymer initially, which
www.rsc.org/suppdata/cc/b5/b504313a/
*klwooley@artsci.wustl.edu
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Chem. Commun., 2005, 3259–3261 | 3259

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Table 1 Polymers synthesized in this study
a
b
c
d
STY : MA : RAFT : AIBN (initial ratios) Conv.
M
n
(theory)
n
M (GPC) PDI %STY Composition
e
250 : 50 : 1 : 0.2
3
4
5
6
a
93%
94%
86%
96%
29 200
29 100
35 700
20 200
b
23 100
29 800
35 400
20 600
1.08 77.7
1.09 56.3
1.10 68.3
1.08 69.3
(STY-alt-MA)52–STY118
(STY-alt-MA)117–STY25
(STY-alt-MA)109–STY113
(STY-alt-MA)28–STY63–(STY-alt-MA)28
c
e
200 : 100 : 1 : 0.2
e
300 : 100 : 1 : 0.2
f
150 : 50 : 1 : 0.2
1
Estimated by H NMR analysis of final reaction mixture. Calculated from conv. 6 ([STY] + [MA])/[RAFT]. From elemental analysis.
d
Ideal structure, calculated using %STY from elemental analysis, M
n
from GPC, assuming no transitional region between poly(STY-alt-MA)
e
and polySTY segments. RAFT 5 1. RAFT 5 2.
f
was then extended by a homopolystyrene block segment, once the
MA was exhausted. In this way, block copolymers were formed in
which the length of the first STY-alt-MA block was determined by
the ratio of MA to RAFT agent, while the length of the homo-
STY block was determined by the ratio of excess STY to RAFT
When observed by TEM, assemblies of 3–5 frequently appeared
to be composed of multiple subunits, arranged in a rosette pattern
(Fig. 1A–C). This ordering was evident particularly for the
structures formed from 5 (Fig. 1C) which were typically composed
of 4, 5 or 6 subunits arranged circularly. The diameters by TEM
(Table 2) were measured for the entire assemblies, rather than
individual subunits. The agreement between diameters measured
by DLS and by TEM suggests that these assemblies were present
in solution and not an artefact of substrate adsorption. Higher-
order assembly was not exhibited by 6, which formed much
smaller aggregates without visible microstructure (Fig. 1D).
AFM of the micelles confirmed the dimensions observed by
TEM and DLS. Higher-order structure was not observed by
AFM, suggesting that the images obtained by TEM reveal the
internal arrangement of polystyrene core domains in a continuous
poly(styrene-alt-maleic acid) matrix. Intricate, internal segregation
11,13,14
agent and the overall conversion.
Di- and triblock copolymers with a range of compositions were
conveniently prepared by dissolving appropriate amounts of
maleic anhydride, styrene, RAFT agent 1 or 2, respectively, and
2
,29-azobisisobutyronitrile (AIBN) in 20 mL dioxane and heating
for 21 h (reaching 75–96% conversion) (Table 1). The resulting
polymers exhibited two glass transition temperatures (T ) at 77
g
and 170 uC, of varying intensities depending on the relative
amounts of STY and MA, indicating the presence of microphase-
separated domains in the bulk. Molecular weight distributions
were unimodal and of narrow polydispersities, as observed by gel
permeation chromatography (GPC). The architecture of the ABA
17
patterns have been observed for microscopic assemblies and are
well known for block copolymers in the bulk, however, capture of
such uniform structures within assemblies that are tens of
nanometres in dimension is of significant interest.
1
6
triblock copolymer, 6, was confirmed by pyrolysis of the polymer
(30 min at 250 uC), which resulted in cleavage at the central
trithiocarbonate group to produce polymer chains having a
number-average molecular weight half that of 6, and a narrow
Crosslinking was obtained via carbodiimide-mediated amida-
tion,§ resulting in robust nanostructures. Dilution of the aqueous
solutions with 9 volumes of THF caused disassembly of the
noncrosslinked diblock copolymer assemblies, with the effect that
no light scattering was observed from these solutions by DLS. In
contrast, the crosslinked nanomaterials remained intact on dilution
with THF. While the micelles of the triblock copolymer 6 did not
dissociate completely on addition of THF, a clear difference was
observed between crosslinked and noncrosslinked samples, with
n
molecular weight distribution (M 5 11 100, PDI 5 1.12).
In the cases of isolated block copolymers, aggregates were
2
1
formed by slow addition (10 mL h ) of an equal volume of water
2
1
to a solution of copolymer in THF (2 mg mL ) in the presence of
a catalytic amount of triethylamine,{ followed by dilution to
2
1
0
.67 mg mL , dialysis against deionised water and, finally,
21
dilution to 0.5 mg mL . The resulting solutions varied in
appearance from colorless to bluish-white and were characterized
by transmission electron microscopy (TEM), atomic force
microscopy (AFM) and dynamic light scattering (DLS)
(Table 2).{ In solution, the assemblies of 3–5 were narrowly
distributed in size, while the size distribution of 6 was significantly
broader.
Table 2 Characterization of micellar assemblies formed by
polymers 3–6 before and after crosslinking to form shell-crosslinked
nanoparticles
Before crosslinking
After crosslinking
a
/nm Poly
a
b
H/nm D/nm
c
a
/nm Poly
a
b
H/nm) D/nm
c
D
h
D
h
3
4
5
6
a
41.2 (3) 0.06 (2) 50 (8) 49 (7) 84 (2) 0.19 (5) 48 (11) 38 (8)
45.0 (4) 0.06 (2) 39 (6) 38 (7) 100 (1) 0.125 (2) 49 (11) 36 (8)
58 (3) 0.05 (4) 56 (11) 53 (11) 102 (2) 0.10 (2) 62 (17) 47 (11)
30 (4) 0.19 (1) 23 (4) 27 (6) 44 (1) 0.14 (2) 32 (9) 22 (6)
h
Hydrodynamic volume (D ) and polydispersity (Poly) measured by
DLS. Numbers in parentheses represent standard error in the final
digits. Average height (and standard deviation) measured by AFM.
Average diameter (and standard deviation) measured by TEM.
b
c
Fig. 1 TEM images of 3 (A), 4 (B), 5 (C) and 6 (D), showing rosette-like
arrangements of subunits in assemblies of 5 (C). Scale bars are 100 nm.
3
260 | Chem. Commun., 2005, 3259–3261
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Washington University, St Louis, MO 63130, USA.
E-mail: klwooley@artsci.wustl.edu; Fax: +1 314 935 4481;
Tel: +1 314 935 7136
Notes and references
{
§
In the absence of triethylamine, precipitation occurred on water addition.
In a typical procedure, 1,2-ethylenedioxy bis(ethylamine) (10 mol%
relative to maleic anhydride units) was added to a micellar solution of
polymer. After stirring for 20 min, EDC was added (20 mol% relative to
maleic anhydride units). The solution was stirred overnight at RT, then
dialyzed for 3 days against deionised H
MA (0.5 g) and STY (1.5 g) were heated at 60 uC in the presence of 2.0 g
dioxane, 18 mg 1, and a trace of AIBN for a period of 16 h under N . The
2
O to remove the urea byproduct.
"
2
resulting mixture (conversion 5 89% by NMR) was dissolved in 1 L of
THF. 1,2-Ethylenedioxy bis(2-ethylamine) (18.9 mg, 10 mol% relative to
maleic anhydride) was added with vigorous stirring to a 250 mL aliquot of
this solution, followed immediately by 250 mL nanopure water. The THF
was removed by evaporation in vacuo (at RT) and the resulting micellar
solution was diluted to 1 L with nanopure water.
Fig. 2 Transmission electron micrographs of 3 (A), 4 (B), 5 (C), and 6
D), crosslinked to a nominal crosslink density of 20%. Scale bars
(
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the crosslinked nanostructures showing greater resistance to THF-
induced disassembly. Further confirmation of crosslinking was
provided by IR analysis of the lyophilized crosslinked structures,
3
2
1
which showed an amide carbonyl absorption band at 1636 cm
.
4
5
There was a significant increase in the hydrodynamic diameter and
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The structures formed from 3–5, as observed by TEM (Fig. 2),
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complexity of the microstructure (cf. Fig. 1). The mechanism of
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tion. The crosslinked morphologies from 6 were similar in
appearance to their noncrosslinked precursors.
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164 ¡ 2 nm, and a
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This material is based upon work supported by the National
Science Foundation under Grant No. 0301833. Mass spectrometry
was provided by the Washington University Mass Spectrometry
Resource, an NIH Research Resource (Grant No. P41RR0954).
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This journal is ß The Royal Society of Chemistry 2005
Chem. Commun., 2005, 3259–3261 | 3261