Thermoresponsive dendronized polymers with tunable lower critical solution temperatures

Article abstract of DOI:10.1039/b811464a

A series of first (PG1) and second generation (PG2) dendronized polymers were synthesized which exhibit fast and sharp phase transitions with negligible hystereses in aqueous solutions and apparent lower critical solution temperatures (LCSTs) in the range of 33-49 °C. The Royal Society of Chemistry.

Full text of DOI:10.1039/b811464a

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Thermoresponsive dendronized polymers with tunable lower critical
solution temperaturesw
¨
Wen Li,a Afang Zhang*ab and A. Dieter Schlutera
Received (in Cambridge, UK) 7th July 2008, Accepted 12th August 2008
First published as an Advance Article on the web 23rd September 2008
DOI: 10.1039/b811464a
A series of first (PG1) and second generation (PG2) dendronized
polymers were synthesized which exhibit fast and sharp phase
transitions with negligible hystereses in aqueous solutions and
apparent lower critical solution temperatures (LCSTs) in the
range of 33–49 1C.
stretched backbone in the interior. If the dendrons were
themselves thermoresponsive, they would be forced into close
proximity in such a polymer, and we set out to explore whether
this unique structural feature could lead to fast and sharp
transitions. Furthermore, the hydrophilicity–hydrophobicity
balance in dendronized polymers could in principle be easily
tuned by changing generation, interior, or peripheral groups.
We recently reported two examples of thermoresponsive den-
dronized polymers.8 Although they show fast and sharp
transitions around their LCSTs, the corresponding tempera-
tures (in the range of 63–65 1C) are too high to be attractive for
applications in bio-related fields.
Responsive behavior is rather typical for biomacromolecules
and has been mimicked in fields ranging from advanced
artificial devices, smart surfaces and sensors to medicine and
biomineralization.1 It presents a substantial scientific and
engineering challenge with a considerable application poten-
tial.2 An interesting class of stimuli-responsive materials are
thermoresponsive synthetic polymers.3 They start to collapse
close to their lower critical solution temperatures (LCSTs) due
to dehydration of the chains, and subsequently form aggre-
gates. The LCST of a polymer is not only dependent on the
balance of the hydrophilic and hydrophobic units, with the
more hydrophilic polymers commonly showing higher LCSTs
than the more hydrophobic ones, but also on how these units
are incorporated into the molecular structure. The most often
investigated thermoresponsive polymers contain polyethylene
glycol (PEG), oligoethylene glycol (OEG), or poly(N-isopro-
pylacrylamide) (PNiPAM) units.4 Their generally high bio-
compatibility makes them especially attractive research
targets. These structural motifs have not only been used in
homo- but also in more complex hybrid polymers.5 Much
attention has been paid recently to develop novel thermore-
sponsive macromolecules with dendritic, hyperbranched, and
star structures.6 The transitions of all these materials are often
broad and associated with considerable hystereses, which are
less attractive features as far as applications are concerned.
Therefore, developing novel thermoresponsive polymers with
sharp and fast transitions in both heating and cooling remains
an important challenge.
We here present the design and synthesis of a series of first
(PG1) and second generation (PG2) dendronized polymers
(Fig. 1) which comprises three structural variables that allow
tuning the LCST almost at will. They comprise the choice of
either a methoxy or an ethoxy terminal substituent, the length
of the outmost OEG segment (y = 1 or 2), and the dendron
generation (G1 or G2). The polymer structures were designed
based on the calculated hydrophilicity values (log P, with P =
[solute]n-octanol/[solute]water) by Ghose’s increment method,
whereby the smaller the log P, the more hydrophilic the
polymer should be.9
The synthetic procedures for the corresponding dendrons
and macromonomers are delineated in Scheme 1. First, the
methoxy-terminated dendrons and macromonomers will be
discussed. Williamson etherification of methyl gallate with
tosylated diethylene glycol monomethyl ether (Me-DEG-Ts)
Dendronized polymers are composed of a linear backbone
surrounded by dendrons at each repeating unit.7 The dendro-
nization reduces the attainable backbone conformations and,
in the extreme case, renders a random coil polymer into a
cylindrically shaped, rigid molecular object with a more or less
a Institute of Polymers, Department of Materials, ETH Zurich,
Wolfgang-Pauli-Strasse 10, HCI G 525, Zurich, 8093, Switzerland.
E-mail: zhang@mat.ethz.ch; Fax: (+41) 44-6331390
b School of Materials Science and Engineering, Zhengzhou University,
Daxue Beilu 75, Zhengzhou, 450052, China
w Electronic supplementary information (ESI) available: Experimental
procedures and details. NMR spectra of new compounds and poly-
mers. See DOI: 10.1039/b811464a
Fig. 1 Chemical structures of the dendronized polymers: PG1(MT)
and PG2(MT) reported in the earlier work,8 as well as PG1(MD),
PG2(MD), PG1(ET) and PG2(ET) from the present work. For the
log P values, see main text. For the nomenclature: MT, MD and ET
stands for methoxytriethyleneoxy, methoxydiethyleneoxy and ethoxy-
triethyleneoxy, respectively.
ꢀc
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Scheme 1 Synthesis procedures for G1 and G2 macromonomers 2c, 2f and 3c, 3f. Reagents and conditions: (a) Me-DEG-Ts or Et-TEG-Ts,
K2CO3, KI, DMF, 80 1C, 24 h (83–87%); (b) LAH, THF, À5 to 25 1C, 3 h (91–92%); (c) MAC, triethylamine (TEA), 4-dimethylaminopyridine
(DMAP), DCM, 0–25 1C, 3 h (92%); (d) KI, 15-crown-5, NaH, THF, r.t., 24 h (48–50%); (e) (i) N-methylmorpholine, ethyl chloroformate, THF,
À15 1C, 1 h; (ii) NaBH4, À5 to 25 1C, 4 h (81–82%); (f) MAC, TEA, DMAP, DCM, 0–25 1C, 5 h (83–85%).
gave 2a, whose reduction with lithium aluminum hydride
(LAH) furnished the corresponding dendron alcohol 2b, which
was reacted with 2g8 to give the G2 dendron acid 3a. From this
acid, 3b was obtained by its reduction according to Kokotos’
protocol.10 The corresponding G1 and G2 macromonomers 2c
and 3c were prepared by esterification of the respective
alcohols 2b and 3b with methacryloyl chloride (MAC). By
similar procedures, the ethoxy-terminated analogs 2f and 3f
were obtained from the corresponding dendron alcohols. All
macromonomers were obtained as completely colorless, water-
soluble liquids, whose fluidity is reminiscent of glycerol. The
high synthesis efficiency is illustrated by overall yields for 2c,
2f, 3c and 3f of 73, 70, 26 and 25%, respectively, starting from
higher molar masses than in DMF solution.8 Thus, DMF
seems to be an unfavorable solvent at first glance. However,
the polymerization of 2c always led to gelation in bulk or even
in concentrated DMF solution. Therefore, its polymerization
needed to be done in slightly dilute DMF solution (56 wt%)
and stopped at an early stage in order to avoid gelation. This is
the reason for the low conversion of 28%. The other poly-
merizations did not lead to gelation and bulk conditions,
which are advantageous for achieving high molar mass poly-
mers from macromonomers,11 could be applied.
All polymers are water-soluble at room temperature, but
collapse from water and their aqueous solutions turn turbid
when heated up to the LCST. The LCSTs were measured and
the thermoresponsive behavior investigated by turbidity mea-
surements using UV/Vis spectroscopy. Typical phase transi-
tion curves are shown in Fig. 2(a). For comparison, the
transition curves for PG1(MT) and PG2(MT) from ref. 8
are also included. It is interesting to note how strongly the
transitions depend on slight structural changes and how sharp
(r0.8 1C) they are in addition to their unprecedented rever-
sibility. Also, the hystereses are very small (r0.6 1C). Though
it would be tempting to correlate the transitions’ sharpness
with molecular structure, we feel that more examples are
needed before serious conclusions can be drawn.5c,6d The
1
methyl gallate. All new compounds were characterized by H
and 13C NMR spectroscopy, high resolution mass spectro-
metry, and correct values from combustion analysis. Typical
1H NMR spectra are shown in the supplementary information
to illustrate the high purities achieved.
The macromonomers were polymerized by conventional
free radical techniques, and the conditions and typical results
are summarized in Table 1. The molar masses were determined
by GPC using DMF (0.1 wt% LiBr) as eluent and universal
calibration. Polymerization of this kind of liquid macro-
monomers in bulk normally affords polymers with much
Table 1 Conditions for and results from the polymerization of the macromonomers 2c, 2f, 3c and 3f
Polymerization conditionsa GPC resultsd
e
Entries
Monomer
[Monomer]c/mol LÀ1
t/h
4.0
3.0
24.0
24.0
Yield (%)
10À5Mn
DPn
PDI
LCST/1C
1
2
3
4
a
2cb
2f
3c
3f
1.10
1.56
0.56
0.44
28
68
61
62
4.5
7.2
5.9
3.4
843
1023
303
1.90
3.15
2.63
3.14
43.3
33.2
48.5
36.0
c
139
b
All polymerizations were carried out at 60 1C in bulk with AIBN as initiator (concentration 0.5 wt% based on monomer). In DMF. The
d
values were obtained by calculation from the monomer density (1.1 g mLÀ1 for both G1 and G2 monomers). All GPC measurements were done
e
in DMF (0.1 wt% LiBr) as eluent at 45 1C. DPn = number-average degree of polymerization.
ꢀc
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Fig. 2 Plots of transmittance (a) and surface tension (b) vs. temperature for 0.25 wt% aqueous solutions of PG1(ET), PG2(ET), PG1(MD),
PG2(MD), PG1(MT) and PG2(MT). (c) LCST dependence of PG1(MD) and PG2(MD) on NaCl concentration in PBS (pH 7.0). The linear lines in
(b) and (c) are a guide to the eye.
LCSTs for PG1(ET), PG2(ET), PG1(MD), PG2(MD),
PG1(MT) and PG2(MT) are 33, 36, 43, 48, 63 and 64 1C,
respectively. The log P values for these polymers are qualita-
tively in line with this structure/LCST relation. The following
conclusions as to the dependence of LCST on structure can be
drawn: (i) LCSTs of PG1 are lower than the corresponding
PG2, (ii) ethoxy-substituted polymers have always lower
LCSTs than their methoxy counterparts, (iii) the OEG seg-
ments with y = 1 have lower LCSTs than those with y = 2.
The change of terminal groups from methoxy into ethoxy
shows a stronger effect on LCST than either alternation of
dendron generation or the length of OEG.
are thanked for their kind help with the surface tension and
GPC measurements, respectively. This work was supported by
ETH Research Grant ETH-1608-1. A. Z. thanks for the
financial support from the National Natural Science Founda-
tion of China (Nos. 20374047 & 20574062).
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Chem. Commun., 2008, 5523–5525 | 5525