"On-demand" control of thermoresponsive properties of poly(N-isopropylacrylamide) with cucurbit[8]uril host-guest complexes

Article abstract of DOI:10.1039/c1cc11214g

The chain end complexation of a functional PNIPAM by a cucurbit[8]uril- viologen complex causes a shift in its lower critical solution temperature (LCST) by over 5°C. An instantaneous phase change of the thermally responsive polymer beyond its LCST can be

Full text of DOI:10.1039/c1cc11214g

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‘‘On-demand’’ control of thermoresponsive properties of
poly(N-isopropylacrylamide) with cucurbit[8]uril host–guest complexeswz
Urs Rauwald, Jesus del Barrio, Xian Jun Loh and Oren A. Scherman*
´
Received 1st March 2011, Accepted 28th March 2011
DOI: 10.1039/c1cc11214g
The chain end complexation of a functional PNIPAM by a
cucurbit[8]uril-viologen complex causes a shift in its lower
critical solution temperature (LCST) by over 5 1C. An
instantaneous phase change of the thermally responsive polymer
beyond its LCST can be induced by addition of the aqueous
cucurbituril host–guest complex. Subsequent decomplexation
upon addition of a competitive guest releases the PNIPAM
terminus and triggers complete reversibility.
masking effect of the cyclodextrins changes the hydrophobic
nature of the guest moieties.23,24 Pseudo-block copolymers
based on star-shaped PNIPAM with a b-cyclodextrin core
show tunable LCSTs depending on the complexation of
poly(ethylene glycol)s of different chain lengths to the cyclo-
dextrin bearing PNIPAM.25
The host cucurbit[8]uril (CB[8]) has been shown to form a
variety of strong, stable ternary complexes consisting of
a complementary pair of an electron-deficient aromatic compound
such as methyl viologen (M2V) and an electron-rich aromatic
compound such as naphthalene.26–29 Functionalising the chain
ends of polymers, peptides and proteins with such aromatic
moieties allows for the creation of a wide range of macro-
molecular architectures in water, which are held together by
the three-component host–guest complexes with CB[8].30–34
The highly tunable and addressable three-component nature
of the CB[8] system along with its high binding constants in
water make it particularly attractive to study its incorporation
into aqueous materials. Herein, we report the controllable
phase transition of an end-functional PNIPAM triggered by a
set of changes in temperature and host–guest complexation
(Fig. 1a). The doubly-charged binary complex of CB[8] and
Stimuli-responsive polymers exhibit reversible changes in their
properties according to environmental triggers such as pH,
light or temperature.1–3 Significant research aimed at developing
‘‘smart’’ polymer systems for a variety of promising applications,
such as controlled drug delivery, gene delivery, cell and
enzyme immobilisation, biosensor, and bioaffinity separation
has been carried out.4–15 In these applications, thermoresponsive
polymers are an important class of materials, which often
show strong and reversible phase transitions in response to
small temperature changes. The widely used poly(N-isopropyl-
acrylamide) (PNIPAM) features a sharp phase transition
behaviour in water with a lower critical solution temperature
(LCST) of ca. 32 1C.16
Several concepts have been developed to control LCST
behaviour of polymers. Conventional copolymerization of
N-isopropylacrylamide with hydrophilic or other amphiphilic
monomers has been reported.17–20 Alternatively, chain-end
modification using functional initiator routes or reactive end
groups has been employed to modify the thermoresponsive
properties of PNIPAM.21 In recent years, supramolecular
routes to alter the LCST have been studied as well. Metallo-
supramolecular complexes have been utilised to elongate
PNIPAM into diblock homopolymers which resulted in a
change of the LCST.22 Cyclodextrins have also been used to
modify the LCSTs of temperature-responsive polymers by
selective complexation of hydrophobic chain ends. The
Melville Laboratory for Polymer Synthesis, Department of Chemistry,
University of Cambridge, Lensfield Road, Cambridge, CB2 1EW,
United Kingdom. E-mail: oas23@cam.ac.uk; Fax: +44 1223 334866;
Tel: +44 1223 331508
w This article is part of a ChemComm ‘Supramolecular Chemistry’
web-based themed issue marking the International Year of Chemistry
2011.
Fig. 1 (a) Modification of the thermoresponsive properties of end
functional PNIPAM via supramolecular complexation/decomplexation.
(b) Chemical structures and schematic representations of the end
functionalized PNIPAM (P1), M2V C CB[8] and 1-aminoadamantane.
(c) Chain end complexation of P1 with M2V C CB[8] followed
by disruption of the ternary complex in the presence of
1-aminoadamantane.
z Electronic supplementary information (ESI) available: Experimental
Section, and Supporting Fig. S1–S6. See DOI: 10.1039/c1cc11214g
c
6000 Chem. Commun., 2011, 47, 6000–6002
This journal is The Royal Society of Chemistry 2011

M2V was used as a supramolecular end-group modification
unit for a PNIPAM terminated by a hydrophobic dibenzofuran
(DBF) end group, P1 (see Fig. 1b). The formed ternary
complex can be decomplexed by addition of a competitive
guest such as 1-aminoadamantane (Ad) (Fig. 1c), allowing for
control of the phase of P1 at a constant temperature above its
LCST via a series of host–guest complexations.
The existence of a DBF end group at the terminus of P1 has
a large effect on its LCST behaviour. An aqueous solution
of P1 shows an LCST of 24.5 1C, a temperature that is
significantly lower than that of unmodified P2 (32.6 1C)
(compare Fig. 2 and Fig. S4 in ESIz). This difference in LCST
between DBF-functional and control PNIPAM is a result of
the incorporation of a hydrophobic terminal group in P1.24 In
an effort to modify the cloud point behaviour of P1, its
LCST transition was probed in the presence and absence of
M2V C CB[8] (see Fig. 2). Upon addition of 1 equivalent of
M2V C CB[8], the LCST of the complexed P1 increased by
5.7 1C, from originally 24.5 1C for the neat polymer solution to
30.2 1C for the fully complexed polymer. This drastic shift in
the LCST can be attributed to the effect of chain-end
complexation with M2V C CB[8] which results in the
instantaneous switch from the hydrophobic DBF moiety to
the charged, hydrophilic ternary complex. To rule out
any non-specific binding effects, an aqueous solution of
unfunctionalised P2 was also subjected to 1 equivalent of
M2V C CB[8]. In this case, the same LCST was observed,
regardless of the presence of M2V C CB[8] (see Fig. S4 in
ESIz).
Scheme 1 summarises the synthesis of DBF-functionalised
P1 and unfunctionalised P2 which served as a control. The
polymers were prepared via reversible addition-fragmentation
chain transfer (RAFT) polymerisation, using 3-benzylsulfanyl
thiocarbonylsulfanyl propionic acid as the chain transfer agent
(CTA) in the synthesis of P2, or the functional CTA1 in the
synthesis of P1 (Scheme 1). CTA1 was obtained by an amidation
reaction between 3-benzylsulfanyl thiocarbonylsulfanyl
propionic acid and 3-amino-2-methoxydibenzofuran.32 Both
P1 and P2 were synthesised by polymerising N-isopropylacryl-
amide at 70 1C in the presence of the respective CTA and 2,20-
azobis(isobutyronitrile) (AIBN) as the source of the primary
radicals at a molar ratio of [monomer][CTA][AIBN] =
440 : 10 : 1 (target polymer molecular weight of B5000 g molꢀ1).
The polymers were isolated by precipitation in diethyl ether
1
and their chemical structures analysed by H NMR spectro-
While CB[8]-induced chain-end complexation of P1 can be
employed to modify the LCST of P1, the thermoresponsive
supramolecular assembly can also be exploited to exert
a higher level of control on the phase behaviour of a
PNIPAM-based system. As Fig. 3 illustrates, an aqueous
solution of P1 (0.2 mM) is turbid at 26 1C. The solution turns
clear instantaneously upon addition of an equimolar amount
of M2V C CB[8]. This feature is a result of chain end
complexation causing P1 to switch from a hydrophobic state
at 26 1C back to a hydrophilic state. The ternary complex
formation between P1 and M2V C CB[8] at 26 1C was
confirmed by 1H NMR (see Fig. S5 in ESIz). To the clear
solution of complexed P1 at 26 1C, Ad was then added in
3-fold molar excess. This induced an abrupt change in the
transmittance of the sample, from clear back to turbid (see
Fig. 3). The complexation of Ad inside CB[8] disrupts the
ternary complex, expelling both M2V and the DBF end group
scopy and gel permeation chromatography (GPC). The molecular
weights obtained by 1H NMR spectroscopic end-group
analysis for P1 and P2 were found to be Mn = 5000 g molꢀ1
and Mn = 5100 g molꢀ1, respectively. GPC analysis indicated
unimodal and narrow molecular weight distributions for both
polymers (Mw/Mn o 1 : 1).
The purpose of the DBF moiety at the terminus of P1 was to
allow for specific, noncovalent binding of the chain end with
M2V C CB[8], as illustrated in Fig. 1c. The expected ternary
complex formation of M2V and the DBF end group of P1
inside the cavity of the CB[8] host was confirmed by 1H NMR
measurements in D2O, exhibiting an upfield shift and
broadening of the signals corresponding to the resonance of
the aromatic protons of both DBF end group of P1 and M2V
(see Fig. S2 in ESIz). An immediate colour change from light
yellow to reddish purple upon addition of M2V C CB[8] to an
aqueous solution of P1 was a further indicator for ternary
complexation, which was also supported by UV/vis spectro-
scopy showing the existence of a strong charge-transfer
absorption band at 430 nm (see Fig. S3 in ESIz). In contrast,
an aqueous solution of P2 mixed with M2V C CB[8] did not
show any absorption band in the same region.
Fig. 2 Thermo-responsive phase transition of P1 (0.2 mM in water)
in the absence (black squares) and presence (red circles) of M2V C
CB[8]. Sample solutions were recorded at 600 nm and at a heating rate
of 1 1C /min.
Scheme 1 Synthesis of end functional PNIPAM P1 and control P2.
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 6000–6002 6001

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6002 Chem. Commun., 2011, 47, 6000–6002
This journal is The Royal Society of Chemistry 2011