Synthesis and characterization of physical crosslinking systems based on cyclodextrin inclusion/host-guest complexation

Article abstract of DOI:10.1002/pola.23771

New supramolecular assemblies based on cyclodextrin and adamantane were prepared. Two methacrylate monomers bearing cyclodextrin and adamantane were synthesized, and copolymerized with poly(ethylene glycol) methyl ether methacrylate, (PEGMA, 300 g/mol), by free radical polymerization. Copolymers bearing pendent cyclodextrin and adamantane were characterized by NMR, FTIR, TGA, SEC, Differential scanning calorimetry (DSC), and UV-visible spectrophotometer. All copolymers showed two distinct glass transitions. The specific interaction between pendent adamantyl and cyclodextrin was examined by ¹H-NMR. The viscoelastic properties of supramolecular assemblies were investigated with frequency and temperature sweep experiments. The specific host-guest interaction between pendent adamantyl and cyclodextrin lead to large increases of the viscosity; and depending on the concentration of these groups, also to gel formation.

Full text of DOI:10.1002/pola.23771

Synthesis and Characterization of Physical Crosslinking Systems Based
on Cyclodextrin Inclusion/Host-Guest Complexation
ETHEM KAYA, LON J. MATHIAS
Department of Polymer Science, University of Southern Mississippi, 118 College Drive #10076, Hattiesburg,
Mississippi 39406-0076
Received 29 June 2009; accepted 30 September 2009
DOI: 10.1002/pola.23771
Published online in Wiley InterScience (www.interscience.wiley.com).
ABSTRACT: New supramolecular assemblies based on cyclodex-
trin and adamantane were prepared. Two methacrylate mono-
mers bearing cyclodextrin and adamantane were synthesized,
and copolymerized with poly(ethylene glycol) methyl ether
methacrylate, (PEGMA, 300 g/mol), by free radical polymeriza-
tion. Copolymers bearing pendent cyclodextrin and adaman-
tane were characterized by NMR, FTIR, TGA, SEC, Differential
scanning calorimetry (DSC), and UV-visible spectrophotometer.
All copolymers showed two distinct glass transitions. The spe-
cific interaction between pendent adamantyl and cyclodextrin
was examined by 1H-NMR. The viscoelastic properties of
supramolecular assemblies were investigated with frequency
and temperature sweep experiments. The specific host-guest
interaction between pendent adamantyl and cyclodextrin lead
to large increases of the viscosity; and depending on the con-
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centration of these groups, also to gel formation. 2009 Wiley
Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 581–592,
2010
KEYWORDS: adamantane; cyclodextrin; gel formation; gels;
host-guest systems; physical crosslinking; radical polymeriza-
tion; supramolecular assemblies
INTRODUCTION Cyclodextrins (CDs) have been extensively
used for industrial applications in many fields from laundry
soap to food and pharmaceuticals. They also have been
investigated as building blocks for supramolecular chemistry
because they can form complexes with a number of different
molecules and polymers through host-guest interaction.1,2
The most widely used CDs are a-CD, b-CD, and c-CD, which
respectively, consist of six, seven, or eight D-glucopyranose
units. They possess truncated, cone-shaped hydrophobic cav-
ities in which the narrow end has primary and the wide end
secondary hydroxyl groups. Since the inner cavity does not
have any hydroxyl groups,3 it can bind a number of different
hydrophobic moieties. The driving forces for complex forma-
tion are the expulsion of high energy water from the cyclo-
dextrin cavity, the release of ring strain, van der Waals inter-
action, and hydrogen bonding.4
tion temperature can be varied by changing the solution
concentrations, the PEG content in the graft polymer, and the
stoichiometric ratio between guest and host molecules.
Yui and coworkers3 used both ionic and hydrophobic inter-
actions to obtain sol-gel systems with rapid phase transi-
tions. They modified poly(e-lysine) with b-CD to give biocom-
patible and biodegradable polymeric hosts (b-CDPL). The
guest, 3-trimethylsilylpropionic acid (TPA), containing both
hydrophobic and ionic groups, was chosen specifically to
provide dual interactions with the polymeric host and each
other. In this system, TPA is included into the CD cavity by
host-guest interaction to create physical crosslinks through
cooperative hydrophobic and ionic interactions. The system
showed a very rapid phase transition with small change in
temperature across the upper critical solution region.
Because of the ionic character, these systems are profoundly
affected by pH changes.
Several physical crosslinking systems have been reported uti-
lizing CDs. Yui and coworkers5 reported supramolecular
hydrogels based on inclusion complexation between a-cyclo-
dextrin and poly(ethylene glycol)-grafted dextran. a-Cyclo-
dextrin threaded poly(ethylene glycol) (PEG) chains come
together to form channel-type crystalline micro-domains.
These crystalline microphases create physical junctions
between dextran main chains. The sol–gel transition is based
on physical threading-dethreading of a-CDs with the poly-
meric guests. The process is strongly affected by tempera-
ture changes, making gelation thermoreversible. The transi-
A variety of hydrophobic groups interact strongly with CDs.
The interaction between adamantane and b-cyclodextrin was
reported to be very strong compared to other bulky groups
as studied by AFM.6 In recent years, there have been a num-
ber of reports published utilizing these strong host-guest
interactions.7–10 Harada et al. reported a use of these host-
guest interaction to obtain high molecular weight (Mn
¼
100,000) supramolecular polymers formed from a b-cyclo-
dextrin dimer and a guest dimer having adamantyl groups
linked by PEG.11
Correspondence to: L. J. Mathias (E-mail: lon.mathias@usm.edu)
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Supramolecular hydrogels resulting from host/guest interac-
tion or inclusion complexation obtained by cyclodextrin with
various hydrophobic moieties and polymers has been investi-
gated for biomedical application due to their possible poten-
tial in drug or cell deliveries.12–15 The use of this specific
interaction with guest molecules to design hydrogels sensi-
tive to temperature, light, and pH has been reported.16–19
Harada and coworkers20 prepared a photoresponsive hydro-
gel system using different molecular recognition of a ternary
mixture of dodecyl-modified poly(acrylic acid), a-cyclodex-
trin, 4,40-azodibenzoic acid. Davis and coworkers21,22 investi-
gated biocompatible linear cyclodextrin polymers and several
adamantane-terminated crosslinking agents for local gene
delivery. These supramolecular systems were shown to be
suitable for in vivo tissue repair applications.
(APM) was previously synthesized in our laboratory, and this
procedure was followed to obtain APM as a white powder.33
6-(6-Aminohexyl)amino-6-deoxy-b-cyclodextrin
(b-CD-HDA)
A 250 mL three-necked, round-bottom flask was charged
with 5.0 g (3.8 mmol) of mono-6-OTs-b-CD and excess HDA
34
(20 g, 172 mmol) in 25 mL of DMF.
The reaction was car-
ꢀ
ried out overnight at 80 C. After completion of the reaction,
the mixture was allowed to cool down to room temperature
and the product precipitated into excess acetone. After filtra-
tion, the product was dissolved in DMF and reprecipitated in
acetone. After several reprecipitation cycles, the crude prod-
uct was washed with diethyl ether and kept in vacuum oven
at room temperature for 24 h. b-CD-HDA (2.3068 g) was
obtained as white powder in 43% yield. 1H-NMR (300 MHz,
DMSO-d6): 7.98, 5.75, 4.84, 4.49, 3.63, 3.4, 3.32, 3–3.1, 2.8–
2.92, 2.64–2.74, 2.1, 1.35, 1.26 ppm. 13C-NMR (300 MHz,
DMSO-d6): 102, 81.5, 73, 72.4, 72, 60, 49.5, 37, 29.5, 29,
26.5, 26.3 ppm.
Polymers consisting of poly(ethylene glycol)methyl ether
methacrylate (PEGMA) have been investigated extensively
for biomedical applications due to PEG biocompatibility and
nonadhesive interactions to proteins.23 These polymers also
exhibit a lower critical solution temperature (LCST), which
may be useful for nanotechnology and biotechnology applica-
tions.24 Currently, several derivatives of PEGMA macromono-
mers with different molecular weights and chain ends such
as methoxy or hydroxyl are commercially available. They
have been copolymerized with a variety of monomers using
several different methods including atom transfer radical po-
lymerization,25,26 reversible addition-fragmentation chain
transfer (RAFT),27,28 and conventional free radical meth-
ods.29–31 Most of these copolymer systems have been studied
for synergistic effects of two different units; for instance, to
form pH and temperature sensitive copolymers.27,24
(1-Methacrylamidohexyl)amino-6-deoxy-b-cyclodextrin
A 100 mL three-necked round-bottom flask was charged
with methacrylic anhydride (MCD) (10 g, 64 mmol) and
20 mL of DMF. To this solution, b-CD-HDA (7.73 g, 6.3
mmol) in 20 mL of DMF was added dropwise under nitrogen
atmosphere. The solution was stirred overnight. The product
was precipitated into excess acetone. The solid powder was
dissolved in DMF and reprecipitated into acetone several
times. The final product was obtained as a white powder,
which was dried in a vacuum oven at 70 ꢀC overnight. The
yield was quantitative. 1H-NMR (300 MHz, DMSO-d6): 5.7,
5.6, 5.3, 4.8, 4.5, 4.2, 3.2–3.7, 3, 2, 1.6–1.9, 1.37, 1.15 ppm.
13C-NMR (300 MHz, DMSO-d6): 167.9, 140.2, 119.1, 102,
81.7, 73, 72.4, 72, 60, 30.8, 28.9, 26.1, 25.9, 19.1 ppm.
Here we report the synthesis of two novel monomers and
their polymers bearing adamantane and cyclodextrin pend-
ant groups, respectively. These monomers were copolymer-
ized with PEGMA at three different compositions (5, 10, 15
mol % feed ratio) by conventional free radical polymeriza-
tion techniques. The characterization of these copolymers
has been done using NMR, FTIR, TGA, SEC, and Differential
scanning calorimetry (DSC). In addition, the effect of the
comonomers on the LSCT of PEGMA copolymers was also
studied. Finally, the host-guest interactions between PEG and
adamantane units with pendent cyclodextrin units were
examined, and the viscoelastic properties of these new physi-
cal network forming systems were investigated with both
frequency and temperature sweep rheology experiments.
Synthesis of Copolymer (PEGMA-co-MCD)
A typical copolymerization is given for (PEGMA-15-MCD).
MCD (3.84 g, 2.9 mmol), PEGMA (4.9 g, 16 mmol), AIBN
(0.079 g, 0.49 mmol), and 32 mL DMF were charged to a 50
mL three-necked, round-bottom flask. Nitrogen was bubbled
through the solution for 15 min before heating at 45 ꢀC for
24 h. The mixture was then precipitated into ethyl ether. Af-
ter three reprecipitation cycles, the product was dried in a
ꢀ
vacuum oven for 12 h at 40 C. For further purification, the
polymer was dissolved in deionized water, placed in Spectra
Por dialysis tubing with a molecular cutoff of 12,000–14,000
and dialyzed against deionized water for 7 days. The final
polymer was freeze-dried to obtain a fiber-like, slightly yel-
lowish solid in ꢁ77% yield.
EXPERIMENTAL
Materials
b-CD was purchased from TCI and used without purification.
Poly(ethylene glycol) methyl ether methacrylate (PEGMA,
300 g/mol), p-toluenesulfonyl chloride (p-TsCl) and 1,6-hexa-
nediamine (HDA), were purchased from Aldrich Chemical
and used as received. Azobisisobutyronitrile (AIBN) was pur-
chased from Aldrich Chemical, and recrystallized from meth-
anol three times before use. 6-o-Monotosyl-6-deoxy-b-cyclo-
dextrin (mono-6-OTs-b-CD) was synthesized based on a
literature procedure.32 4-(1-Adamantyl)phenyl methacrylate
Synthesis of Copolymer (PEGMA-co-APM)
A typical copolymerization is given for (PEGMA-15-APM).
APM (1.33 g, 4.5 mmol), PEGMA (7.65 g, 25.5 mmol), AIBN
(0.098 g, 0.6 mmol), and 62 mL DMF were charged to a 100
mL three-necked, round-bottom flask, and bubbled with
nitrogen for 15 min before heating. The reaction was carried
ꢀ
out at 45 C for 24 h, and the mixture was then precipitated
into ethyl ether. After three reprecipitation cycles, the prod-
uct was dried in a vacuum oven for 12 h at 40 ꢀC. The
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The optical transmittances of polymer solutions were
recorded as a function of temperature on a UV-visible spec-
trophotometer (Shimadzu, UV-1601PC). A 2.5 wt % solution
of each polymer was prepared, and the samples were heated
at 2 ꢀC/min while transmittances were recorded. All poly-
mers showed a sharp transition for the LCST, which was
defined as the temperature on heating at which the solution
gave almost no transmittance.
Rheological Measurements
Viscoelastic characterization was conducted with an
Advanced Rheometerics Expansion System (ARES, Rheomet-
rics) equipped with two 25 and 40 mm diameter parallel
plates. A thin layer of low-viscosity silicone oil was applied
to the air/sample interface to inhibit water loss. Frequency
sweep experiments were conducted at two different temper-
atures (20 and 30 ꢀC) to obtain complex viscosity, storage,
and loss moduli over a wide range of frequencies. Tempera-
ture sweep experiments were conducted with a stress con-
trolled rheometer (TA Instruments AR-G2) in a 40 mm dou-
ble gap concentric cylinder system.
RESULTS AND DISCUSSION
The copolymers bearing cyclodextrin and adamantane pend-
ent groups were synthesized by free radical polymerization
as described in the experimental section. The general routes
for the synthesis of monomers and polymers are given in
Schemes 1 and 2.
Figure 1 shows a typical solution 13C-NMR spectrum for a
copolymer bearing APM moieties. P(PEGMA-co-15APM) was
chosen as an example, and the homopolymer of PEGMA is
given for comparison. All peaks are assigned based on the
expected structures of the polymers. For PEGMA monomer,
SCHEME 1 Synthesis of monomers.
copolymers were then dissolved in deionized water, placed
in Spectra Por dialysis tubing with a molecular cutoff of
12,000–14,000, and dialyzed against deionized water for 7
days. The final polymers were freeze-dried to obtain the final
products as transparent solids in about 55% yield. Only the
copolymer with 5 mol % APM (PEGMA-5-APM) was sticky;
all other were nonsticky materials.
Instrumental Analysis
NMR measurements were conducted on a Varian 300 MHz
NMR using DMSO-d6 and D2O as solvents. FTIR spectra were
obtained on a Nicholet 5DX using pressed KBr pellets. SEC
was performed on a system using a HP 1037A RI detector
with a constaMetric pump flowing THF at 100 mL/min
through five American Polymer Standards separation col-
umns with porosities ranging from 100 to 1,000,000 A. The
SEC runs were calibrated using polystyrene standards.
Copolymers were totally soluble in THF with no observed
turbidity.
DSC experiments were performed on a TA Instruments 2920
using pierced-lid crimped aluminum pans at a ramp rate of
10.0 ꢀC/min for both heating and cooling. Temperature and
heat capacity were calibrated with indium and sapphire
standards, respectively. Thermogravimetric analysis was cꢀon-
ducted on a TA instrument 2960 at a heating rate of 10 C/
min under nitrogen.
SCHEME 2 General route for synthesis of copolymers.
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JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
FIGURE
1
13C solution NMR of
P(PEGMA) (top) and P(PEGMA-co-
15APM) (bottom) in DMSO-d6.
the double bond peaks appear at 135.9 and 125.4 ppm, and
these are absent in the spectra of the homopolymer and
copolymers. A broad new peak appears around 44.4 ppm,
which is associated with the backbone carbons. In addition
to PEGMA peaks, those associated with APM units are also
observed for the copolymers. The aromatic peaks are located
at 125.7 and 120.3 ppm, while the adamantyl peaks (labeled
n, o, m, and p) appear at 42.8, 36.2, 35.4, and 28.2, respec-
tively. The carbonyl peak of PEGMA monomer is around 166
ppm and shifts to 177 ppm in the homo- and copolymers.
ture of the copolymers. Upon polymerization, the double
bond peaks of MCD observed at 119.1 and 140.2 ppm disap-
pear, whereas the carbonyl peak shifts from 167.9 to 175.8
ppm. The peaks associated with cyclodextrin units appear at
102.1, 81.4, 73–72, 59.8 ppm, whereas the peaks attributed
to the alkyl spacer between the methacrylamide and cyclo-
dextrin amine appear at 36.7, 28.8, and 25.6 ppm. The peaks
ascribed to PEGMA units in the copolymer were assigned
based on the 13C-NMR spectrum of the homopolymer from
Figure 1.
1
The solution H-NMR spectra of P(PEGMA) and P(PEGMA-co-
The solution 1H NMR spectrum of P(PEGMA-co-15MCD) is
given in Figure 4. The double bond peaks of PEGMA, which
appear at 5.64 and 6.03 ppm are under the cyclodextrin
peaks (2 and 3), whereas the double bond peaks of MCD
appear at 5.32 ppm and as a shoulder on the cyclodextrin
peaks (2 and 3) at 5.6 ppm. Upon polymerization, the double
bond peaks disappear. The peaks associated with O(6)H,
C(1)H, O(2)H, and O(3)H of cyclodextrin units appear at
4.50, 4.85, and 5.73 ppm, respectively. The other peaks
attributed to cyclodextrin units are under the proton peaks
of PEG units, and cannot be seen. The peaks associated with
PEGMA units are assigned based on the 1H spectrum of the
homopolymer of P(PEGMA) (Fig. 2).
15APM) are given in Figure 2. The double bond peaks of
PEGMA at 5.64 and 6.03 ppm disappear upon polymeriza-
tion, and the backbone peaks of the homopolymer appear
around 1.4–1.9 ppm. The PEG proton chemical shift is
observed at 3.5 ppm, whereas the methylene protons a and
b to the ester groups give two distinct peaks at 4.2 and 3.7
ppm, respectively, for PEGMA; these two peaks shift slightly
upfield upon polymerization. The methylene protons a to the
ester group of PEGMA are at 4 ppm, whereas the methylene
protons b to the ester group appear as a shoulder to PEG
protons at around 3.6 ppm. In addition to all peaks associ-
ated with PEGMA units, new peaks are observed in the 1H-
NMR spectra of the copolymers due to APM units. The peaks
at 7.02 and 7.4 ppm are attributed to the phenyl rings,
whereas three peaks at 1.76, 1.88, and 2.08 ppm due to ada-
mantyl hydrogens overlap the backbone peaks.
The molecular weights, Mw and Mn, and polydispersity as
estimated by SEC are given in Table 1. The copolymer com-
positions are calculated by the total area ratios of the spe-
cific peaks using 1H-NMR and are also given in Table 1. The
compositions of copolymers bearing APM were calculated
from the area ratios of protons in the phenyl-rings (assigned
as k, and l) and PEGMA protons a to the ester group
(assigned as e), using the equation m/n ¼ (A1/4)/(A2/2),
The copolymer series bearing MCD moieties was analyzed
for copolymer composition by solution 13C-NMR. The spec-
trum of P(PEGMA-co-15MCD) is given in Figure 3 as an
example. All peaks are assigned based on the expected struc-
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FIGURE
2
1H solution NMR of
P(PEGMA) (top) and P(PEGMA-co-
15APM) (bottom) in DMSO-d6.
where A1 and A2 are the total area under (k þ l) and e,
respectively. The composition of copolymers bearing MCD
was calculated from the area ratios of C1H protons of cyclo-
dextrin to PEGMA protons a to the ester group (assigned as
e), using the equation, m/n ¼ (A1/7)/(A2/2), where A1 and
A2 are the total area under C1H and e, respectively.
(Fig. 5). Since each spectrum is dominated by PEGMA units
(90 mol % in each copolymer), the FTIR spectra of the
homopolymer of PEGMA and the PEGMA monomer are also
given for comparison. The band observed at 1640 cmꢂ1
belonging to the double bond of the monomer disappears in
the homo- and copolymers, which indicates that no residual
monomer is present.35 The band associated with stretching
of the ester carbonyl group at 1720 cmꢂ1 for PEGMA shifts
to 1731 cmꢂ1 in the polymers. The peak observed around
The polymers were further characterized by FTIR, and the
FTIR spectra of P(PEGMA-co-10APM) and P(PEGMA-co-
10MCD) are given as examples of each series of copolymers
FIGURE
3
13C solution NMR of
P(PEGMA-co-15MCD) in DMSO-d6.
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JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
FIGURE
4
1H solution NMR of
P(PEGMA-co-15MCD) in DMSO-d6.
1133 cmꢂ1 is due to CAOAC stretching of ester and ether
groups of PEGMA. The FTIR spectrum of P(PEGMA-co-
10MCD) shows a broad distinct peak around 3384 cmꢂ1
associated with the hydroxyl groups of pendant CD, and
this peak is not observed for the PEGMA monomer, the
homopolymer of PEGMA and P(PEGMA-co-10APM).
temperature of PEG chains around ꢂ59 ꢀC,37 and the Tg of
P(PEGMA300) previously was given as ꢂ57 ꢀC.38 The Tg1
values, given in Table 2, are slightly higher than the Tg value
reported for PEG. However, Tg2 values of P(PEGMA-co-APM)
are much lower compared with the homopolymer of APM
synthesized in our laboratory with a reported Tg of 253 C.
Therefore, the two glass transitions are not due to com-
pletely phase separated blocks but to essentially random
copolymers with microdomains of pendent PEG groups. The
glass transitions of this series of copolymers continuously
increase with increasing APM ratio from 5 to 15 mol %.
The Tg values for the copolymer series having MCD units are
more or less in the same range of the APM series. The
glass transition temperatures of the copolymers are given in
Table 2.
39
ꢀ
DSC thermograms of selected copolymers are given in Fig-
ure 6. DSC curves of all copolymers have two distinct Tg
transitions, and no observed side chain crystallinity probably
due to the PEG side chains not being long enough to form
ordered structures. Observation of two Tg’s is generally an
indication of separate microphases. Similar transitions were
observed for various copolymer systems consisting of
PEGMA and n-butyl methacrylate.36 The PEGMA polymers
have a limiting Tg corresponding to the glass transition
TABLE 1 Mn, Mw, PDI, Compositions, and Yield of Copolymers
Feed (mol %)a
Mol %b
Mn
Mw
PDIc
Yield %
c
c
Sample
P(PEGMA-co-5APM)
P(PEGMA-co-10APM)
P(PEGMA-co-15APM)
P(PEGMA-co-5MCD)
P(PEGMA-co-10MCD)
P(PEGMA-co-15MCD)
5
10
15
5
6
8
20,600
18,200
55,100
42,300
21,700
52,800
128,000
127,000
278,000
165,000
50,000
6.2
7
75
80
55
74
76
77
17
2
5
3.8
2.3
5.4
10
15
3.4
10.2
287,000
a
Comonomer feed mol %.
b
Copolymer compositions estimated by 1H NMR.
Estimated by SEC.
c
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TABLE 2 Tg1 and Tg2 Values of Copolymers
Sample
Tg1
Tg2
P(PEGMA-co-5APM)
P(PEGMA-co-10APM)
P(PEGMA-co-15APM)
P(PEGMA-co-5MCD)
P(PEGMA-co-10MCD)
P(PEGMA-co-15MCD)
ꢂ51.84
ꢂ54.62
ꢂ48.49
ꢂ54.53
ꢂ53.52
ꢂ48.59
51.81
54.34
59.27
61.89
55.77
58.46
10 wt % loss for P(PEꢀGMA-co-15APM) and P(PEGMA-co-
5APM) are 290 and 280 C, respectively. These values are in
the same range as the homopolymer of PEGMA.40 The slight
increases may be due to incorporated APM units, which have
been reported to enhance thermal stabilities in copolymers.
The thermosensitive behaviors of solution of the copolymers
and the homopolymer of PEGMA were investigated using a
UV-visible spectrophotometer. The copolymer composition has
a great effect on LCST behavior of the polymers, since the
hydorphobicity-hydrophilicity balance changes with composi-
tion. In general, hydrophobic comonomers decrease the LCST,
whereas hydrophilic comonomers increase it.27 It was
expected that the copolymers with hydrophobic APM moieties
and hydrophilic MCD would show different thermoresponsive
behavior. The effect of these hydrophobic or hydrophilic como-
nomers on LCST of P(PEGMA) is summarized in Figure 8. All
polymers showed a sharp transition at the ꢀcloud point. The
LCST of the homopolymer of PEGMA was 63 C, which is close
to the LCST of 3 wt % solution of P(PEGMA) reported of
60.8 C. As expected, the cloud point continuously decreases
with increasing content of the hydrophobic APM units in the
copolymers. The decrease is as high as 14 ꢀC for the copoly-
mer with 17 mol % APM. On the other hand, there are slight
increases of observed cloud points with increasing MCD ratio
in copolymers.
FIGURE 5 FTIR spectra of (a) P(PEGMA-co-10MCD), (b)
P(PEGMA-co-10APM), (c) P(PEGMA), and (d) PEGMA.
Thermal stabilities of the copolymers were analyzed by TGA.
Figure 7 shows TGA thermograms of two copolymers of each
series with a heating rate of 10 ꢀC/min in N2. The copoly-
mers with MCD exhibit a two-step degradation process. The
onset of thermal decomposition of P(PEGMA-15MCD) is
much lower compared with other copolymers perhaps due
to the thermal degradation of pendant cyclodextrin units at
lower temperatures. Similar behavior was observed for the
copolymers having the highest feed ratio of MCD. The tem-
perature at 10 wt % loss for this polymer is 250 ꢀC. The
copolymers with 5 mol % APM and MCD give almost the
same thermograms. The onset of the thermal degradation for
the P(PEGMA-co-5MCD) is somewhat earlier because of the
less stable cyclodextrin pendant units. However, it is not as
pronounced as the onset of the thermal decomposition of
the copolymer with 15 mol % MCD. The temperature at
38
ꢀ
FIGURE 6 DSC thermograms of copolymers (a) P(PEGMA-co-
5APM), (b) P(PEGMA-co-10APM), (c) P(PEGMA-co-15APM), (d)
P(PEGMA-co-5MCD), (e) P(PEGMA-co-10MCD), (f) P(PEGMA-co-
15MCD).
FIGURE 7 TGA thermograms of copolymers (a) P(PEGMA-co-
5MCD), (b) P(PEGMA-co-15MCD), (c) P(PEGMA-co-5APM), (d)
P(PEGMA-co-15APM) in N2.
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JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
peaks. The spectrum has very broad peaks with no distinct
separation for the aromatic groups of APM consistent with
hydrophobic association. The spectral changes due to solvent
differences indicate structural rearrangement, and perhaps
pendent group association, of the amphiphilic polymer in
D2O. Similar observation has been reported for the amphi-
philic block copolymer of PEG with hydrophobic poly-(b-ben-
zyl L-aspartate) and poly [N-{o-(4-phenyl-4,5-dihydro-1,3-oxa-
zol-2-yl)phenyl}maleimide].41,42 In D2O, the hydrophobic
groups tend to aggregate and may form a micelle-like struc-
ture. Mobility decreases in micelle structures, and would cause
broadening of the APM peaks, as can easily be seen for the
peaks associated with the aromatic groups, and disappearance
of peaks associated with adamantane.
It is generally accepted that, unlike neat a-cyclodextrin, which
has been reported to form polyrotaxane type complexes with
PEG, neat b-cyclodextrin cannot form such stable complexes
with PEG.43–45 However, Ripmeester and coworkers46 did
report stable binding between PEG and neat b-cyclodextrin,
and this complexation was further investigated by Cosgrove
and coworkers47 In both cases, complexation of linear PEG
with free b-cyclodextrin was investigated. Here, on the other
hand, the mobilities of PEG and b-cyclodextrin units are re-
stricted by the main polymer chain. Therefore, the binding and
interactions of these groups would be expected to be different.
Considering expected compositions of copolymers with ada-
mantane and PEG units, three possibilities should be consid-
ered: (1) PEG units of the polymers can form stable complexes
with cyclodextrin; (2) PEG units do not form stable complexes
but inhibit interactions of adamantyl moieties with
FIGURE 8 Cloud point versus mol % of comonomers determined
by 1H-NMR in copolymers bearing MCD (~) and APM (*).
The copolymers having APM moieties are expected to show
amphiphilic properties due to combined hydrophobic and
hydrophilic segments. To explore the amphiphilic character
of the copolymer, 1H-NMR was used and the spectrum of
P(PEGMA-co-15APM) is given for two different solvents,
DMSO-d6 and D2O (Fig. 9). DMSO-d6 is a good solvent for the
copolymers, and with it, the adamantyl peaks can be easily
identified, plus there are two separate peaks associated with
the aromatic group of APM. On the other hand, the peaks of
the adamantyl groups totally disappear in D2O or they may
not be observed because of overlap with the backbone
FIGURE 10 1H-NMR analysis of inclusion complex formation
between P(PEGMA-co-10APM) with various concentration of
free cyclodextrin.
FIGURE 9 1H-NMR analysis of P(PEGMA-co-15APM) in D2O
(bottom) and DMSO-d6 (top).
588
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ARTICLE
FIGURE 11 Photograph and the schematic representation of gel formation as a result of inclusion complexation between adaman-
tyl and cyclodextrin pendent groups of copolymers.
cyclodextrin; and (3) only adamantane and cyclodextrin groups
form stable complexes. Another important factor, which will
influence the host-guest interaction between adamantyl and
cyclodextrin groups, may be the inter- and intramolecular self-
association of bulky adamantyl moieties, which may lead to in-
hibition of the host-guest complex formation between adaman-
tyl groups and CDs.
moieties may be disturbed upon addition of the cyclodextrin.
Figure 11 shows a schematic representation and photograph of
the gel formation. This gel was obtained with the 30 wt % of
the P(PEGMA-co-15APM)/P(PEGMA-co-15MCD) mixture. Ini-
tially, both solutions of 30 wt % of P(PEGMA-co-15APM) and
30 wt % of P(PEGMA-co-15MCD) were prepared; these solu-
tions were viscous liquids at these concentration. After mixing,
gel formation occurs rapidly, and is demonstrated by the test
tube inversion method as shown in the photograph.
1H-NMR analysis has been extensively used to probe inclu-
sion formation in similar complexes.48–50 The formation of
inclusion complexes between free cyclodextrin and adaman-
tyl moieties of P(PEGMA-co-10APM) was investigated here
using 1H-NMR. Figure 10 shows variation of the 1H proton
NMR spectra with increasing free CDs in solution (25% CD:
0.015 mmol CD and 0.25 g polymer in 2 mL D2O; 50% CD:
0.03 mmol CD and 0.25 g polymer in 2 mL D2O). The top
To investigate viscoelastic properties of supramolecular
assemblies, four 1:1 aqueous solution mixtures were pre-
pared: P(PEGMA-co-15APM)/P(PEGMA-co-15MCD), P(PEG-
MA-co-10APM)/P(PEGMA-co-10MCD), P(PEGMA-co-5APM)/
P(PEGMA-co-5MCD). Each pair was mixed together to
explore the effect of increasing associative group contents on
viscosity. An aqueous solution of P(PEGMA)/P(PEGMA-co-
10MCD) was used as the control to probe the interaction
between PEG units of P(PEGMA) and the pendent CDs
groups of P(PEGMA-co-10MCD). For consistency, all samples
were prepared as 10 wt % solutions in water, and the com-
plex viscosity, storage, and loss moduli as a function of angu-
lar frequency were determined in frequency sweep measure-
ments. The viscosities were measured for two different
1
spectrum is H-NMR spectrum of P(PEGMA-co-10APM) given
for comparison. The shifts of specific peaks in the polymer
spectrum result from the inclusion complexation between
adamantyl moieties and PEG units with added cyclodextrin.
1
Chemical shifts of adamantane moieties in H-NMR with vari-
ous concentrations of cyclodextrin can also be used to obtain
the association constant, Ka. Due to hydrophobicity of ada-
mantane moiety and its size, which perfectly matches the
cavity of b-cyclodextrin, the specific interaction of adaman-
tane and cyclodextrin has been shown to be very strong
with an association constant between 104 and 105 Mꢂ1
depending on the nature of the systems.51,52 The assosica-
tion constant of complex between P(PEGMA-co-10APM) with
neat b-cyclodextrin was determined, using Benesi-Hildebrand
ꢀ
temperatures, 20 and 30 C.
The complex viscosities of the mixtures of viscous liquids as a
function of angular frequency are given Figure 12. The complex
viscosities are almost independent of frequency for all four
samples for both temperatures. The viscosity values are dra-
matically higher for those samples with higher ratios of asso-
ciative groups in the copolymers. The 1:1 mixture of P(PEGMA-
co-15APM)/P(PEGMA-co-15MCD) and P(PEGMA-co-10APM)/
P(PEGMA-co-10MCD) show the highest viscosities, which indi-
cates that the solution properties of P(PEGMA) are tunable by
changing the associating comonomer contents. It is worth not-
ing that the temperature dependence of viscosity is stronger
for the samples with higher comonomer loading. Therefore, it
plots, to be 1.9 ꢃ 104 Mꢂ1
.
The downfield shift indicates that there is indeed host-guest
complex formation between pendant adamantane and cyclo-
dextrin and confirm that self-association of the amphiphilic
polymer does not inhibit this specific complexation between
two groups. In fact, the interaction between these two groups
is so strong that the association of hydrophobic adamantyl
SUPRAMOLECULAR ASSEMBLIES BASED ON CYCLODEXTRIN, KAYA AND MATHIAS
589

JOURNAL OF POLYMER SCIENCE: PART A: POLYMER CHEMISTRY DOI 10.1002/POLA
FIGURE 12 Angular frequency dependence on complex viscosity
for the mixture of 10 wt % P(PEGMA-co-5APM)/P(PEGMA-co-
5MCD) (n, h), P(PEGMA-co-10APM)/P(PEGMA-co-10MCD) (~,
~), P(PEGMA-co-15APM)/P(PEGMA-co-15MCD) (l, *), and
P(PEGMA)/P(PEGMA-co-10MCD) (^, ^) at 20 (filled symbols)
and 30 ꢀC (open symbols).
FIGURE 14 Viscosity dependence on temperature for the mix-
ture of P(PEGMA-co-10APM)/P(PEGMA-co-10MCD) (~) and
P(PEGMA-co-10MCD) (~) alone.
plexation once the adamantyl group reaches a certain upper
concentration.
can be concluded that the decrease in viscosity with tempera-
ture must be related with the supramolecular inclusion associa-
tion of adamantyl and cyclodextrin groups rather than the
interaction between PEG units with CDs. Another interesting
finding is the fact that the viscosity increases for the samples
bearing 5 mol % associative groups to 10 mol % associative
groups is significant, whereas there is no further increase for
the mixture of the copolymer bearing 15 mol % associative
groups. P(PEGMA-co-15APM) possesses more hydrophobic
groups, which enhance micelle formation and hydrophobic
associations, and then may limit or decrease the inclusion com-
The storage modulus, G0, and the loss modulus, G00, of the four
samples in 10 wt % solutions are given in Figure 13. The val-
ues of both G0 and G00 increase with increasing associative
groups in the copolymer compositions, and the magnitudes of
G00 is higher than that of G0 for all sample, which means vis-
cous flow dominates elastic response over the range of angu-
lar frequencies monitored. However, at low frequency, G00 is
almost equal to G0 for the samples bearing the highest asso-
ciative groups, P(PEGMA-co-15APM)/P(PEGMA-co-15MCD),
and the difference between G00 and G0 increases with angular
frequency. The data at Figure 13 indicates that P(PEGMA-co-
15APM)/P(PEGMA-co-15MCD) is at the gel boundry, and the
inclusion complexes are dissociated as viscous flow dominates
the elastic response with increasing angular frequency. This
observation is not surprising considering adamantyl/cyclodex-
trin inclusion complexation is in dynamic equilibrium, and the
fast exchange between free and complexed adamantyl moi-
eties may not maintain long-range connectivity.48 The data
indicates that both G0 and G00 are frequency dependent, and
that they increase with increasing applied frequency. Similar
observations were reported for G0 and G00 of cyclodextrin and
adamantyl-grafted chitosan, and the decrease of G0 and G00
with decreasing frequency was explained by network relaxa-
tion as a result of breaking and reforming of the crosslink
points.45
Temperature effects on host-guest complex formation were
further investigated for the 5 wt % aqueous solution of
P(PEGMA-co-10APM)/P(PEGMA-co-10MCD) via temperature
sweep measurement. The variation in viscosity as a function
of temperature is given in Figure 14. The viscosity change of
the 5 wt % aqueous solution of P(PEGMA-co-10MCD) with
temperature is also included in the same plot for compari-
son. As expected, the initial viscosity is significantly higher
for the P(PEGMA-co-10APM)/P(PEGMA-co-10MCD) mixture
FIGURE 13 Frequency dependence on storage (filled symbols).
and loss moduli (open symbols) for the mixture of 10 wt %
P(PEGMA-co-5APM)/P(PEGMA-co-5MCD) (n, h), P(PEGMA-co-
10APM)/P(PEGMA-co-10MCD) (~, ~), P(PEGMA-co-15APM)/
P(PEGMA-co-15MCD) (l, *), and P(PEGMA)/P(PEGMA-co-
10MCD) (^, ^) at 30 ꢀC.
590
INTERSCIENCE.WILEY.COM/JOURNAL/JPOLA

ARTICLE
8 Li, L.; Guo, X.; Wang, J.; Liu, P.; Prud’homme, R. K.; May, B.
due to host-guest inclusion complexation between adamantyl
and cyclodextrin pendent groups. However, the viscosity con-
stantly and drastically decreases with increasing temperature
since the inclusion complexation is enthalpy driven. That is,
temperature increases leads to decreases in the number of
inclusion complexes, which in turn result in lower apparent
molecular weight and decreased viscosity.8,53,54 This may
result in a thermoreversible gel system such as has been
reported by Hennick et al. for a star-shaped eight-arm PEG
which was end-modified with b-cyclodextrin and cholesterol
moieties. The storage (G0) and loss moduli (G00) of the hydro-
gel system formed by the mixture of b-cyclodextrin end-
capped PEG and cholesterol end-capped PEG decreased with
L.; Lincoln, S. F. Macromolecules 2008, 41, 8677–8681.
9 Koopmans, C.; Ritter, H. Macromolecules 2008, 41,
7418–7422.
10 Charlot, A.; Auzely-Velty, R. Macromolecules 2007, 40,
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11 Hasegawa, Y.; Miyauchi, M.; Takashima, Y.; Yamaguchi, H.;
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12 Daoud-Mahammed, S.; Grossiord, J. L.; Bergua, T.; Amiel,
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13 Li, J.; Ni, X.; LeongK. W. J Biomed Mater Res 2003, 65A,
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196–202.
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which leads to decreased viscosity may be increasing phase
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Methacrylate monomers bearing cyclodextrin and adaman-
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16 Ren, L.; He, L.; Sun, T.; Dong, X.; Chen, Y.; Huang, J.; Wang,
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1
with PEGMA by free radical polymerization. Both 13C and H
17 Zhang, J.; Xue, Y.; Gao, F.; Huang, S.; Zhuo, R. J Appl
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cyclodextrin units besides PEGMA units. Although micelle
formation (hydrophobic interaction of adamantyl groups)
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examined by 1H-NMR, these associations did not inhibit the
host-guest complex formation between pendent adamantyls
with free CD. The viscoelastic properties of supramolecular
assemblies were investigated with frequency and tempera-
ture sweep experiments. It was shown that PEG units did
not form stable complexes with pendent CD groups, while
the specific host-guest interaction between pendent adaman-
tyl and cyclodextrin moieties lead to large increases in vis-
cosity: It has thus been shown that the viscosity of these sys-
tems is tunable by varying the concentration of these groups
in water-soluble copolymers.
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