Thermally induced micelle to vesicle morphology transition for a charged chain end diblock copolymer

Article abstract of DOI:10.1039/b922289h

A quaternary amine end functionalised diblock copolymer (PtBuA-b-PNIPAM) has been synthesised using RAFT polymerisation and shown to undergo a thermally induced morphology transition from micelles to vesicles, as evidenced by TEM, AFM, SLS and DLS analyses.

Full text of DOI:10.1039/b922289h

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Thermally induced micelle to vesicle morphology transition for a charged
chain end diblock copolymerw
Adam O. Moughtona and Rachel K. O’Reilly*ab
Received (in Cambridge, UK) 26th October 2009, Accepted 1st December 2009
First published as an Advance Article on the web 16th December 2009
DOI: 10.1039/b922289h
A quaternary amine end functionalised diblock copolymer
(PtBuA-b-PNIPAM) has been synthesised using RAFT
polymerisation and shown to undergo a thermally induced
morphology transition from micelles to vesicles, as evidenced
by TEM, AFM, SLS and DLS analyses.
Precise morphological control over self-assembled polymers is
currently the subject of intense research interest with various
nanosized architectures being studied, including spherical
micelles, vesicles, cylinders, worm-like micelles and rods.1–3
Polymeric nanostructures are particularly attractive materials
since their size, structure and function can be readily tailored
to suit many desirable applications in nanoscience including
drug delivery and catalysis through careful selection of the
polymer structure and properties prior to self-assembly.4–8
Furthermore, research groups have been able to tune the
physical properties of the block copolymer building blocks
such that the morphology of the resultant self-assembled
system is responsive towards stimuli such as temperature
and pH.9–19
Fig. 1 Schematic of the stimuli induced change in the hydrophilic to
hydrophobic ratio of the target copolymer.
The diblock copolymer used in this study contains a thermo-
responsive polymer block (poly(N-isopropyl acrylamide) or
PNIPAM) located between a permanently hydrophobic block
and a permanently hydrophilic charged quaternary amine
‘headgroup’, Fig. 1.
The structure and properties of the diblock copolymer were
carefully chosen to enable a significant modification of p for
the diblock copolymer, upon changing the temperature of the
surrounding solution. It was proposed that the copolymer
would have a low p below the LCST of PNIPAM and
form smaller aggregates with higher interfacial curvature
(i.e. spherical micelles) and above the LCST the p value would
increase, thus forming larger aggregates with lower interfacial
curvature26 (i.e. vesicles), see Fig. 2.
Of particular interest is the ability for polymeric assemblies
to exhibit transitions between different morphologies (and
hence give rise to a change in physical properties) as a result
of an alteration in the packing parameter20 (p) of the consti-
tuent polymers in response to applied external stimuli.21–27
Recently, Grubbs and co-workers have investigated thermo-
responsive morphology transitions for triblock copolymers
which incorporate a thermoresponsive central block. Initial
studies on these systems (and those by Zhuo et al.) report that
the time taken for the triblock polymer assemblies to exhibit
this thermally induced transition can be in the order of
weeks.25,26 Herein, we report a thermally induced morphology
transition from micelles to vesicles for a diblock copolymer,
end functionalised with a permanently hydrophilic charged
group. We propose that this charged end group is a crucial
component in ensuring the stability of the diblock copolymer
in solution when self-assembled into a nanostructure.
The diblock copolymer used in this study was poly(tert-
butylacrylate-b-N-isopropylacrylamide), synthesised using a
quaternary amine functionalised RAFT CTA, 3, giving rise to
a well-defined permanently charged, end functionalised diblock
copolymer, PtBuA-b-PNIPAM, 5 (Mn (NMR) = 6600 Da,
Mn (GPC) = 5800 Da, Mw/Mn = 1.29), see Scheme 1.
The self-assembly of copolymer, 5, into micelles, 6,
proceeded via dissolution of the copolymer in tetrahydrofuran
(THF) at a concentration of 2 mg mLÀ1. Deionised nanopure
water was then added slowly to the stirred THF solution
followed by exhaustive dialysis into nanopure water to remove
the THF giving a final concentration of ca. 1 mg mLÀ1
.
Dynamic light scattering (DLS) of the resultant aggregates
at 25 1C showed the presence of exclusively micelles by volume
We synthesised an end functionalised diblock copolymer via
reversible addition fragmentation chain transfer (RAFT) poly-
merisation28 utilising a novel quaternary amine functionalised
chain transfer agent (CTA), see Fig. S1 and S2 (ESIw).29
a Department of Chemistry, University of Cambridge, Cambridge,
UK CB2 1EW
b Department of Chemistry, University of Warwick, Coventry,
UK CV4 7AL. E-mail: R.K.O-Reilly@warwick.ac.uk;
Fax: +44 (0)24765 24112; Tel: +44 (0)24765 23236
w Electronic supplementary information (ESI): Experimental details
and further characterisation data are available. See DOI: 10.1039/
b922289h
Fig. 2 Schematic representation of the thermally induced micelle to
vesicle morphology transition.
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Scheme 1 Synthesis of diblock copolymer, PtBuA-b-PNIPAM, 5,
utilising RAFT CTA, 3.
and number distributions with an average hydrodynamic
diameter (Dh) of 22 nm (PDI = 0.45). A small number of
larger aggregates could be observed in the DLS intensity data
(Dh = 105 nm). Analysis of a dried sample of the micelle
solution, 6, at 25 1C, by transmission electron microscopy
(TEM) stained with uranyl acetate, showed the presence of
spherical micelles Davg = 28 Æ 4 nm (see Fig. 4 and S13
(ESIw)), with a very small population of larger aggregates,
which could be the larger structures observable by DLS.
Upon heating and stirring a 1 mg mLÀ1 solution of the
micelles, 6, at 65 1C (above the LCST of PNIPAM at ca.
32 1C, and the glass transition temperature (Tg) of PtBuA at
40 1C), no significant change in the Dh (by DLS) of the
aggregates occurred over a period of 6 days. However, around
day 7, a dramatic change in the Dh of the aggregates was
observed, increasing from 22 nm to 147 nm (PDI = 0.47),
suggesting a possible morphology change, see Fig. 3. Longer
heating and stirring times (for a further 8 days) showed no
further increase in the size of the aggregates by DLS, although
the PDI by DLS decreased to 0.22. No precipitation or
discolouration of the clear solution occurred, indicating the
lack of an observable cloud point of the polymer in solution
(see Fig. S12, ESIw), which is consistent with other literature
reports for similar thermoresponsive systems.26 In a similar
method reported by Grubbs et al., we observed a broad LCST
Fig. 4 Representative TEM micrographs: (a) micelles, 6, at 25 1C
stained with uranyl acetate; (b) vesicles, 7, at 65 1C stained with
ammonium molybdate; (c) polydisperse micelles after cooling back the
vesicles, 7, to 25 1C, stained with uranyl acetate. Samples of 6 and 7
were drop cast from an aqueous solution (ca. 1 mg mLÀ1) at RT and
65 1C, respectively.
The average diameters of the vesicles by TEM were
observed to be lower than in solution by DLS measurements.
This is consistent with similar reports studying polymeric
vesicles via TEM in the dried state.19 The morphology of the
vesicles, 7, was explored further in the dried state by atomic
force microscopy (AFM), via drop deposition of 7 onto a mica
surface at 65 1C. Individual particles could be clearly identified
and they appeared to have a hollow morphology when
collapsed, with an average diameter, Davg of ca. 120 nm, which
agrees with DLS and TEM data. Although, as with TEM,
this was in the dried state and therefore showed a marked
reduction from their size in solution (as measured by DLS).
Fig. S15 (ESIw) shows representative AFM images for the
vesicles, 7, and highlights their hollow nature and also their
deformation from a uniform and spherical shape. Cross-
sectional AFM analysis of 7 supports this hypothesis.
1
at around 43 1C in the VT H NMR spectra of 5 in D2O.26
To confirm the existence of vesicles after heating for 7 days
at 65 1C, the solution was analysed by TEM. Upon deposition
of the sample (at 65 1C) and positive staining with ammonium
molybdate (selective for the positively charged outer shell),
much larger aggregates with Davg = 105 nm were observed
exclusively, which had a clearly definable bilayer structure and
showed fusion-like behaviour with each other, indicative of a
vesicle type morphology (see Fig. 4).
To further confirm their hollow nature, static light scattering
(SLS) measurements were performed on several samples of the
vesicles, 7, at 65 1C. This was done to determine the average
radius of gyration, Rg, of the vesicles, 7. The ratio Rg/Rh
(where Rh = 1/2 Dh) is useful for analyzing the structure of a
nanosized particle such as a vesicle, since Rg/Rh ratios close to
unity indicate that a hollow particle has been formed and
values close to 0.7 typically indicate a solid sphere-like particle,
such as a micelle.30 SLS measurements upon transformation
into vesicles, 7, at lower concentrations of 0.1–0.01 mg mLÀ1
(permitted for SLS analysis) proved successful, although the
micelle to vesicle transition yielded slightly larger vesicles than
at 1 mg mLÀ1, with Dh = 211 nm. However, morphology
transformations at 1 mg mLÀ1 also showed small amounts of
size variation. SLS measurements of 7 gave Rg = 116.8 for the
vesicles, which gave an Rg/Rh ratio of 1.11 (see Fig. S17 for the
Fig. 3 Change in hydrodynamic diameter, Dh (by number), of
copolymer 5 as a function of time upon heating at 65 1C at a
concentration of 1 mg mLÀ1
.
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Zimm plot, ESIw). Furthermore, vesicles formed at lower
concentrations were observable by TEM (see Fig. S14, ESIw).
This supports the theory of a thermally induced transformation
into hollow vesicles.
Ian Portman and Jane Green for assistance with TEM
measurements and Dr Ivan Prokes for the VT-NMR experiments.
Notes and references
To explore the reversibility of the micelle–vesicle transition,
a solution of vesicles, 7, at 1 mg mLÀ1 was cooled to room
temperature (with stirring) after being heated for 9 days. After
2 days of cooling, the mean Dh changed from ca. 155 nm to ca.
70 nm (PDI = 0.80) as observed by DLS measurements at
25 1C (see Fig. S10, ESIw). These structures were proposed to
be a polydisperse mixture of micelles and were observed by
TEM (see Fig. 4). Despite this morphology change back to
predominantly micelles, upon cooling the sample down, the
original well-defined micelles could not be solely re-isolated,
but could be observed by TEM in the presence of other
irregularly shaped nanostructures.
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