Translating Thermal Response of Triblock Copolymer Assemblies in Dilute Solution to Macroscopic Gelation and Phase Separation

Article abstract of DOI:10.1002/anie.201609360

The thermal response of semi-dilute solutions (5 w/w%) of two amphiphilic thermoresponsive poly(ethylene oxide)-b-poly(N,N-diethylacrylamide)-b-poly(N,N-dibutylacrylamide) (PEO₄₅-PDEAm_x-PDBAm₁₂) triblock copolymers, which

Full text of DOI:10.1002/anie.201609360

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Communications
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International Edition: DOI: 10.1002/anie.201609360
German Edition: DOI: 10.1002/ange.201609360
Self-Assembly
Translating Thermal Response of Triblock Copolymer Assemblies in
Dilute Solution to Macroscopic Gelation and Phase Separation
Zhe Sun, Ye Tian, Wendy L. Hom, Oleg Gang, Surita R. Bhatia, and Robert B. Grubbs*
Abstract: The thermal response of semi-dilute solutions (5 w/
w%) of two amphiphilic thermoresponsive poly(ethylene
oxide)-b-poly(N,N-diethylacrylamide)-b-poly(N,N-dibutyla-
crylamide) (PEO45-PDEAmx-PDBAm12) triblock copolymers,
which differ only in the size of the central responsive block, in
water was examined. Aqueous PEO45-PDEAm41-PDBAm12
solutions, which undergo a thermally induced sphere-to-worm
transition in dilute solution, were found to reversibly form soft
(G’ ꢀ 10 Pa) free-standing physical gels after 10 min at 558C.
PEO45-PDEAm89-PDBAm12 copolymer solutions, which
undergo a thermally induced transition from spheres to large
compound micelles (LCM) in dilute solution, underwent phase
separation after heating at 558C for 10 min owing to sedimen-
tation of LCMs. The reversibility of LCM formation was
investigated as a non-specific method for removal of a water-
soluble dye from aqueous solution. The composition and size
of the central responsive block in these polymers dictate the
microscopic and macroscopic response of the polymer solu-
tions as well as the rates of transition between assemblies.
of the polymer aggregates can change significantly. Several
examples of thermally responsive polymers that undergo
thermally induced morphological transitions between well-
defined structures in dilute solution have been reported.[5]
For example, poly(ethylene oxide)-block-poly(N-isopro-
pylacrylamide)-block-poly(isoprene) (PEO-PNIPAm-PI) tri-
block copolymers in dilute aqueous solution with specific
compositions form small spherical micelles at low temper-
atures that reassemble into large vesicles after heating above
the lower critical solution temperature (LCST) for three
weeks.[5a] More rapid transitions have been demonstrated
with polymers with lower-molecular-weight hydrophilic com-
ponents.[5d] We have hypothesized that, in addition to
molecular weight effects, interchain hydrogen bonding
between PNIPAm amide groups after dehydration above
the LCST can kinetically trap micelles and slow further
rearrangement. As evidence for this hypothesis, poly(ethy-
lene oxide)-block-poly(ethylene oxide-stat-butylene oxide)-
block-poly(isoprene) (PEO-P(EO/BO)-PI) triblock copoly-
mers were found to undergo a sphere-to-vesicle transition
upon heating above the P(EO/BO) LCST within several
hours.[5a]
Stimulus-responsive polymers have been exploited in appli-
cations including biomedicine, sensing, molecular actuation,
and separations.[1] With block copolymers, the introduction of
stimuli-responsive blocks[2] can strongly influence block
copolymer self-assembly and can allow triggered transforma-
tions between different assemblies.[3] The precise morphology
adopted by a given block copolymer mainly depends on the
relative volume fractions of the hydrophilic and hydrophobic
blocks and the interfacial energy associated with the block
junction,[3c,4] so if the degree of hydrophilicity of a given block
can be altered in response to external stimuli, the morphology
To further probe this hypothesis, we have investigated the
dilute solution behavior of poly(ethylene oxide)-block-
poly(N,N-diethylacrylamide)-block-poly(N,N-dibutylacryla-
mide) (PEO-PDEAm-PDBAm) copolymers synthesized by
reversible addition-fragmentation chain transfer (RAFT)
polymerization (Scheme 1),[6] in which the stimulus respon-
[*] Dr. Z. Sun, W. L. Hom, Prof. S. R. Bhatia, Prof. R. B. Grubbs
Department of Chemistry, Stony Brook University
Stony Brook, NY 11764-3400 (USA)
Scheme 1. Synthesis of PEO45-PDEAm89-PDBAm12 copolymers.
E-mail: robert.grubbs@stonybrook.edu
Dr. Y. Tian, Dr. O. Gang
sive block has an LCST in water similar to that of PNIPAm
but cannot form strong interchain hydrogen bonds. In the
course of these studies, we have identified two copolymers,
PEO45-PDEAm41-PDBAm12 (Mn = 5.2 kgmolÀ1; spherical to
worm-like micelle) and PEO45-PDEAm89-PDBAm12 (Mn =
11.3 kgmolÀ1; spherical to large compound micelle) that
undergo rapid transitions from spherical micelles to larger
aggregates upon heating (Scheme 1, Table 1). Herein, we
describe the solution behavior of these two copolymers in
water at higher concentrations (ꢁ 5.0 w/w%) before and after
heating above the PDEAm LCST.
Center for Functional Nanomaterials
Brookhaven National Laboratory
Upton, NY 11974 (USA)
Dr. O. Gang
Department of Chemical Engineering, Columbia University
New York, NY 10027 (USA)
and
Department of Applied Physics and Applied Mathematics
Columbia University
New York, NY 10027 (USA)
Supporting information, including experimental details, and the
ORCID identification number(s) for the author(s) of this article can
be found under:
Transmission electron microscopy (TEM) and dynamic
light scattering (DLS) studies of dilute aqueous PEO45-
http://dx.doi.org/10.1002/anie.201609360.
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Table 1: Molecular characteristics of PEO-PDEAm-PDBAm triblock
copolymers.
reversible over two heating/cooling cycles (Supporting Infor-
mation, Figure S5).
Copolymer[a]
Mn [kgmolÀ1 [a]
]
ꢀ[b]
fhydrophilic
[c]
TEM images of PEO45-PDEAm41-PDBAm12 samples
prepared from 0.1 w/w% solutions after heating at 558C for
10 min (Figure 1B), showed the spherical micelles had grown
into worm-like micelles. TEM images of PEO45-PDEAm89-
PDBAm12 solutions (0.1 w/w%) showed the formation of
large polydisperse spheres without any bilayer contrast after
heating at 558C for 10 min (Figure 1D). These spheres
resemble the large compound micelles (LCMs) reported
previously for amphiphilic block copolymers with very large
hydrophobic blocks.[9] The fast transformation rate from
spheres to worms or spheres to LCMs for PEO45-PDEAm89-
PDBAm12 block copolymers (ca. 10 min) supports the
hypothesis that the absence of strong interchain hydrogen
bonding in the thermally responsive block accelerates rear-
rangement of polymer assemblies.
PDEAm
total
258C
558C
PEO45-PDEAm41-PDBAm12
PEO45-PDEAm89-PDBAm12
5.2
11.3
9.4
15.5
1.29
1.34
0.75
0.84
0.20
0.13
[a] Mn values for PDEAm block and triblock copolymer in kg/mol as
determined from the polymerization conversions determined by
1H NMR of crude reaction mixtures and the molecular weight of the
PEO-CTA. [b] Dispersity (ꢀ) determined by SEC in THF calibrated with PS
standards. [c] Hydrophilic weight fraction calculated by the mass of the
hydrophilic block or blocks (PEO and PDEAm at 258C; PEO at 558C) to
the total mass of polymer.
Amphiphiles with worm-like micelle morphologies can
form gels at higher concentrations, even in the absence of
specific inter-worm interactions.[5g,10] Gelation in these cases
has been attributed to topological interactions and requires
that worms be sufficiently long and stiff to persist over the
time scales probed by rheology.[10c] The behavior of aqueous
solutions of PEO45-PDEAm41-PDBAm12 at higher concen-
trations (5–10 w/w%) was investigated to determine if the
thermally induced sphere-to-worm transition could result in
gelation.
A transparent aqueous solution of PEO45-
PDEAm41-PDBAm12 (5.0 w/w%) was heated at 558C. After
10 min the solution formed a soft free-standing physical gel
(Figure 1B). Visible degelation occurred within 30–40 s after
the sample was removed from the heating bath (Supporting
Information, Video S1). Repeated heating and cooling
experiments indicated that the gelation is completely ther-
moreversible. In contrast, phase separation was observed in
the PEO45-PDEAm89-PDBAm12 aqueous solutions (5.0 w/w
%) after heating at 558C for 10 min, as the concentrated large
compound micelles settled to the bottom of the solution
(Figure 1D).
Figure 1. TEM images of 0.1 w/w% aqueous solutions of A, B) PEO45-
PDEAm41-PDBAm12 C, D) and PEO45-PDEAm89-PDBAm12 at 258C and
after heating at 558C for 10 min. Inset images are photographs of vials
of 5.0 w/w% solutions of the indicated polymers at the given temper-
ature. Scale bar=200 nm (A–C); Scale bar=2 mm (D). Color image
available in the Supporting Information.
Oscillatory temperature sweep experiments (Figure 2)
confirm gelation; the storage modulus (G’) of 5.0 w/w%
PDEAmx-PDBAm12 solutions (0.10 w/w%; Figure 1A,C and
the Supporting Information, Figure S3) confirmed that both
triblock copolymers form spherical micelles in water at 258C
owing to their large hydrophilic weight fractions (f ꢁ 0.75).[7]
DLS data suggest that PEO45-PDEAm89-PDBAm12 appears
to assemble into slightly larger micelles (Dh = 26 nm) than
PEO45-PDEAm41-PDBAm12 (Dh = 24 nm), most likely result-
ing from the significantly larger central corona block in
PEO45-PDEAm89-PDBAm12 (Supporting Information, Fig-
ure S3c).
Heating dilute solutions of both polymers (0.28CminÀ1
;
Supporting Information, Figure S4) resulted in significant
increases in apparent Dh (DLS) above the LCST of the
PDEAm blocks (LCSTꢀ 418C for Mn = 4.7 kgmolÀ1; LCST
ꢀ 338C for Mn = 9.6 kgmolÀ1).[8] For PEO45-PDEAm41-
PDBAm12, Dh began to increase near 458C from 24 nm to
greater than 150 nm, while for PEO45-PDEAm89-PDBAm12,
Dh increased near 358C from 26 nm to almost 300 nm. For
both polymer solutions, the changes in apparent Dh were
Figure 2. Temperature sweep from 408C to 558C of 5.0 w/w% PEO45-
PDEAm41-PDBAm12 solutions/gels for G’ (filled squares) and G’’ (open
squares) at a fixed frequency of 1.0 Hz and 5.0% strain.
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aqueous PEO45-PDEAm41-PDBAm12 triblock copolymer sol-
undergo a spherical-to-large-compound micelle transition in
utions begins to exceed the loss modulus (G’’) at 498C,[10a]
which agrees well with the temperature (458C) at which the
onset of assembly growth is observed in dilute solutions.
Frequency sweeps at 558C clearly show a characteristic gel-
like response, with G’ relatively independent of frequency and
greater than G’’ over the entire range of measured frequen-
cies (Supporting Information, Figure S6).[10a,11] This can be
contrasted with the results from frequency sweeps taken at
258C and 458C (Supporting Information, Figure S6), in which
both G’ and G’’ show a frequency-dependence characteristic
of a viscoelastic liquid. The gel phase is fairly soft, with G’
increasing from 10–100 Pa as the polymer concentration was
raised from 5.0 to 10.0 w/w% (Supporting Information,
Figure S7).
dilute solution undergo phase separation at higher concen-
trations. The fast heating-induced growth rates (within
10 min), even faster transitions back to spherical micelles
upon cooling (within 1 min), and reversibility of the trans-
formations support our hypothesis that the absence of strong
interchain hydrogen bonding in the central thermally respon-
sive block facilitates rapid growth of smaller aggregates into
larger ones at the macroscopic as well as the microscopic
level. Further manipulation of block copolymer composition
and monomer functionality should allow the development of
control over gelation temperature and rate, as well as the
ability of large compound micelles to encapsulate hydrophilic
compounds.
The small dip in the value of G’’ that can be seen in the
temperature sweeps immediately after the gel transition (49–
528C) (Figure 2) is somewhat curious. This feature appears
reproducibly in temperature sweeps of various samples at
different concentrations (Supporting Information, Figure S7),
and likely results from two competing phenomena: 1) The
growth of worm-like micelles resulting from the thermally
induced change in polymer amphiphilicity, and 2) the
decrease in worm-like micelle length and relaxation time
that has been seen in surfactant-based worm-like micelles
with increasing temperature.[10c] As the temperature
increases, this competition would lead to a complex depend-
ence of the moduli on temperature near the gel transition.
Eventually the increasing length of the micelles dominates,
and gel formation is favored.
Acknowledgements
This research was supported by the National Science Foun-
dation (R.B.G.: DMR-1105622; S.R.B.: CBET-1335787) and
was partially carried out at the Center for Functional
Nanomaterials, a U.S. DOE Office of Science Facility, at
Brookhaven National Laboratory under Contract No. DE-
SC0012704.
Conflict of interest
The authors declare no conflict of interest.
Potential applications of large compound micelles have
not been widely explored. The presence of hydrophilic
domains within a large excluded phase suggests that the
reversible formation of large compound micelles could be of
use in the encapsulation and concentration of water-soluble
contaminants in water. The encapsulating ability of the large
compound micelles formed by PEO45-PDEAm89-PDBAm12
was investigated by dye-encapsulation experiments using the
hydrophilic dye rhodamine B (Supporting Information,
Table S1). An aqueous solution of PEO45-PDEAm89-
PDBAm12 (5.0 w/w %) and rhodamine B (ca. 2 ppm) was
heated at 558C to induce phase separation and the top
aqueous layer (ca. 0.4 ppm rhodamine B) was removed. A
small amount of water at a temperature of 558C that was
added atop the bottom polymer-rich layer remained clear
after 10 min at 558C with minimal extraction of rhodamine B
(ca. 0.08 ppm) from the polymer phase (Supporting Informa-
tion, Figure S8), indicating that rhodamine B was encapsu-
lated inside the large compound micelles. Cooling the bottom
layer down to 258C resulted in reformation of a transparent
micelle solution enriched with rhodamine B (ca. 2.7 ppm;
Supporting Information, Figure S9).
Keywords: block copolymers · gels · micelles · nanostructures ·
self-assembly
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Manuscript received: September 23, 2016
Revised: November 30, 2016
Final Article published: && &&, &&&&
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Angewandte
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Communications
Self-Assembly
Z. Sun, Y. Tian, W. L. Hom, O. Gang,
S. R. Bhatia,
R. B. Grubbs*
&&&& — &&&&
Translating Thermal Response of Triblock
Copolymer Assemblies in Dilute Solution
to Macroscopic Gelation and Phase
Separation
Midblock management: The size of the
central responsive block of an amphi-
philic triblock copolymer determines
structural changes upon heating and
affects whether gelation or phase sepa-
ration occurs in semi-dilute solution.
Angew. Chem. Int. Ed. 2016, 55, 1 – 5
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!