Article

pubs.acs.org/Macromolecules

Crystallization of Poly(2-isopropyl-2-oxazoline) in Organic Solutions

Natalia Oleszko, Alicja Utrata-Wesołek, Wojciech Wałach, Marcin Libera, Anna Hercog, Urszula Szeluga,
Marian Domański, Barbara Trzebicka, and Andrzej Dworak*
Centre of Polymer and Carbon Materials, Polish Academy of Sciences, ul. M. Curie - Skłodowskiej 34, 41-819 Zabrze, Poland
*
S Supporting Information

ABSTRACT: The crystallization of polymers from organic solvents is a common phenomenon. Poly(2-isopropyl-2-oxazoline)
(PIPOx) is known to crystallize in aqueous or aqueous/organic solvent solutions. This process is associated with the dehydration
of polymer chains above the polymer’s lower critical solution temperature (LCST). In this work, the ability of PIPOx to
crystallize in nonaqueous media is presented. The annealing of a solution of PIPOx in organic solvents, such as acetonitrile,
dimethyl sulfoxide, or propylene carbonate, leads to the precipitation of insoluble material. DSC and WAXS studies confirm the
formation of a crystalline phase in the solution, with the degree of crystallinity dependent on the solvent and the polymer
concentration. SEM analysis reveals micron-sized fibril structures of the PIPOx crystalline fraction. The glass transition
temperature (Tg) and the melting temperature (Tm) of PIPOx crystallized in organic solutions are equal to those of the polymer
crystallized in bulk. The enthalpy of melting (ΔH) of the PIPOx crystalline fraction versus its degree of crystallinity (χc) is
shown. The value of the enthalpy of melting for hypothetical, fully crystalline PIPOx (ΔH100%) is determined.

■ INTRODUCTION
(Co)polymers of 2-alkyl-2-oxazolines (POx) have recently
gathered great interest within the scientific community. POxs
are nontoxic polymers,1 opening a route toward their potential
application in medicine and biotechnology. For example, these
(co)polymers do not accumulate in tissue but are rapidly
cleared from the bloodstream.2 They can be conjugated to
protein and small-molecule drugs maintaining the activity of the
drug,3 grafted onto liposomal bilayers,4 formulated into micellar
carriers,5,6 or immobilized on a surface to make antifouling
devices7 or layers for cell sheet engineering.8 In addition, much
of the interest in these materials is a result of the unique
properties of oxazoline (co)polymers, such as the ease with
end-functionalization9,10 or the ability to form polymers with
different architectures.11,12 The nature of the side chains
determines the behavior of a polymer in water. Those with
short alkyl side chains (up to 3 carbon atoms) are soluble in
water and, except for poly(2-methyl-2-oxazoline), exhibit a
lower critical solution temperature (LCST).13 Those with side
chains measuring from 4 to 9 carbon atoms in length are
soluble in water:ethanol mixtures and exhibit an upper critical
solution temperature (UCST).14 Moreover, the length of the
side chains determines the ability of poly(2-alkyl-2-oxazolines)
to crystallize. Poly(2-alkyl-2-oxazolines) with three or more
atoms of carbon in the side chain are known to crystallize in
bulk.15 Two reasons have been given for this behavior. First, the
side chain of POx is located on a nitrogen atom that belongs to
an amide group. As a result, all of the attached groups are
coplanar, producing a high degree of symmetry. Second, there
are three atoms in each repeating unit of the polymer main
chain. In this case, the conformation requires that side chains lie
on alternate sides of the main chain to prevent substituent
crowding and to allow for easy and symmetric packing along
the chain.
However, some thermoresponsive POxs tend to crystallize in
aqueous or aqueous/organic solvent solutions. Crystallization
of polymers from solution is a common phenomenon that has
received increasing attention in recent years.16−19 In the case of
POx dissolved in aqueous media, the ability of the polymer to
crystallize is connected with the phase transition when heated
above the LCST20,21 or cooled below the UCST.22,23 Such
polymer solutions reach a liquid−liquid two-phase regime
Received: December 24, 2014
Revised: February 20, 2015

© XXXX American Chemical Society A DOI: 10.1021/ma502586x

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(polymer-poor phase and polymer-rich phase) at the transition
temperature. Usually, for temperature-responsive polymers, the
phase separation occurs reversibly; however, for some POxs,
this transition is a driving force for subsequent crystallization.
For the first time, Schlaad and co-workers showed that
thermoresponsive poly(2-izopropyl-2-oxazoline) (PIPOx) crys-
tallizes in dilute aqueous solutions above its LCST.20,21 The
long-term annealing of PIPOx solutions above the phase
transition results in the irreversible formation of coagulated
particles. The crystallization of PIPOx proceeds gradually. First,
nanofibers (composed of nanoribbons) are formed in a process
of slow directional crystallization. The nanofibers produce a
bicontinuous network that subsequently collapses into
individual fiber aggregates. In secondary crystallization, the
preformed fiber aggregates act as nucleation sites for the
formation of compact and isolated microspheres of uniform size
(1−2 μm in diameter), the so-called “wool balls”.24 The
proposed mechanism for the crystallization of PIPOx upon
heating above the phase separation temperature involves both
nonspecific hydrophobic interaction between the nonpolar
isopropyl groups and favorable dipolar interactions between
amide dipoles, leading to changes of conformation and finally
to ordering of the chain segments into the elementary cell.25
Crystallization has been observed for other PIPOx-based
polymers in aqueous solutions: PIPOx ended with charged 4-
(N-Boc-amino)piperidine21 or hydrophobic C18 groups,26
PIPOx grafted to polysaccharide (pullulan),27 or statistical
copolymers of 2-isopropyl-2-oxazoline and 3-butenyl-2-oxazo-
line modified with 3-mercaptopropionic acid, 3-mercaptoetha-
nol, and thioglycerol or with 1-thio-β-D-glucose and 1-thio-β-D-
galactose.28 It has been demonstrated that external conditions
such as the polymer concentration, temperature, and presence
of either a cosolvent or surfactant influence the crystallization
process and the morphology of the resultant particles.24 For
example, above the LCST, crystallization occurs faster with
increasing temperature. This has been explained as a result of
the lower polymer saturation and nucleation rates and slower
diffusion rate of polymer chains at lower temperatures. The
particles obtained at lower temperatures tend to be larger (up
to 5 μm) and more porous.24 Although the polymer
concentration appears to have a minor effect on the
crystallization rate, a more poorly developed spherical
morphology has been observed.24 A PIPOx crystalline phase
was also found in water in which either ethylene glycol or
tetrahydrofuran was used as a cosolvent. However, this crystal
portion consisted mostly of fibril structures, whereas spherical
particles were only a minority fraction.20
Crystallization forced by phase separation in aqueous
solutions has also been described for other thermoresponsive
poly(2-substitued-2-oxazoline). The annealing of an aqueous
solution of poly(2-ethyl-2-oxazoline) at a temperature above its
LCST for 45 days induced the formation of crystalline fibrils.29
The addition of various salts to the solution shortened the
crystallization process. In addition, the crystallization of poly(2-
isobutyl-2-oxazoline), poly(2-nonyl-2-oxazoline), and gradient
copolymers of 2-phenyl- and 2-nonyl-2-oxazoline was found to
occur below their UCST in water with the addition of
ethanol.22,23 The appearance of monodisperse spherical clusters
composed of either fibrils or lamellas with particular sizes and
morphologies depended on the polymer concentration,
temperature, and solvent composition.
Although the crystallization of POx (in aqueous or aqueous/
organic solvent solutions) associated with the phase separation
B DOI: 10.1021/ma502586x
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temperature is known, here, to the best of our knowledge for
the first time, we report the formation of poly(2-isopropyl-2-
oxazoline) crystallites in organic solvents. Because PIPOx does
not exhibit thermoresponsive behavior in organic solvents, we
demonstrate that phase separation is not a precondition for
PIPOx crystallization. For this work, the PIPOx crystallites were
analyzed using wide-angle X-ray scattering (WAXS), scanning
electron microscopy (SEM), and differential scanning calorim-
etry (DSC).
■
EXPERIMENTAL SECTION
Materials. 2-Isopropyl-2-oxazoline was synthesized as described
previously.30 Briefly, isobutyronitrile (99.6%, Aldrich) in the amount of
200 mL (2.231 mol) was added to 134 mL (2.231 mol) of 2-
aminoethanol (99%, Aldrich), and the mixture was heated under reflux
in the presence of cadmium acetate (>98%, Fluka) (2.46 g, 0.022 mol)
for 12 days at 100 °C and then distilled under a dry argon atmosphere.
Raw 2-isopropyl-2-oxazoline was dried over KOH, distilled under
reduced pressure, then dried over CaH2, and distilled again. A fraction
of 99.8% purity (checked by gas chromatography) was used for
polymerization. Acetonitrile (ACN) (for HPLC super gradient,
minimum 99.9%, POCH Gliwice) was dried over CaH2 and distilled
under a dry argon atmosphere. Methyl 4-nitrobenzenesulfonate (99%,
Aldrich), propylene carbonate (PC) (anhydrous, 99.7%, Aldrich), and
dimethyl sulfoxide (DMSO) (for HPLC, minimum 99.5%, POCH
Gliwice) were used as received. Acetone (99.5%, POCH Gliwice) and
deionized water were filtered before use.
Synthesis of Poly(2-isopropyl-2-oxazoline). Poly(2-isopropyl-
2-oxazoline) was synthesized via cationic ring-opening polymerization.
The assumed degree of polymerization (DP) was 175. 2-Isopropyl-2-
oxazoline (29.37 g, 0.257 mol) and methyl 4-nitrobenzenesulfonate
(0.322 g, 1.48 × 10−3 mol) were dissolved in acetonitrile (50 mL)
under an argon atmosphere. The mixture was degassed, and the
polymerization was carried out at 50 °C for 5 days until full conversion
of the monomer (checked by gas chromatography). After this time, the
living polymer chains were terminated by the addition of KOH
solution in methanol (equimolar with the initiator), then evaporated
from acetonitrile, dissolved in water, and lyophilized. The obtained
polymer was designated PIPOx.
Crystallization of PIPOx in Bulk. PIPOx was annealed at 190 °C
for 1 h and then cooled to room temperature at a rate of 10 °C/min.
The sample was named PIPOxbulk.
Crystallization of PIPOx in Water. PIPOx was dissolved in water
(5%, w/v) and held at 60 °C for 5 h, according to ref 24. After this
time, the precipitate formed in the mixture was decanted, washed with
water, dried under reduced pressure to a constant weight, and named
PIPOxH2O5%.
Crystallization of PIPOx in Organic Solutions. PIPOx was
dissolved in DMSO (5%, w/v), PC (5%, w/v), and ACN (5%, 10%,
30%, w/v) and held at 50 °C for 20 days. The obtained solid products
were purified by rinsing in DMSO, PC, or ACN, respectively, and then
were centrifuged and decanted. Then the products were rinsed in
water, centrifuged, and decanted. Finally, the products were rinsed in
acetone, decanted, and dried under reduced pressure.
The names of the PIPOx crystalline samples are present in Table 1.
Table 1. Names of the PIPOx Crystalline Samples Obtained
Using Different Solvents
solvent C [%, w/v] symbol of sample
H2O 5 PIPOxH2O5%
DMSO 5 PIPOxDMSO5%
PC 5 PIPOxPC5%
ACN 5 PIPOxACN5%
10 PIPOxACN10%
30 PIPOxACN30%
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Figure 1. DSC traces of PIPOx (A) and PIPOxbulk (B), at a heating rate of 10 °C/min. The violet line denotes the first run, and the red line is the
second run after quenching.
Figure 2. X-ray diffraction curves of PIPOx (A) and PIPOxbulk (B).
Measurements. The molar mass and molar mass dispersity of
PIPOx were determined using a GPC-MALLS system equipped with a
multiangle laser light scattering detector (DAWN EOS, Wyatt
Technologies, λ = 658 nm) and a refractive index detector (Δn-
1000 RI WGE DR Bures, λ = 620 nm). Two PL gel MIXED-C
columns (Polymer Laboratories) were used. Measurements were
carried out in DMF (with 5 mmol/L LiBr) with a nominal flow rate of
1 mL/min. The refractive index increment (dn/dc) was measured
independently using a refractometric detector SEC-3010 (WGE DR
Bures, λ = 620 nm) and was found to be 0.065 mL/g. The results were
evaluated using ASTRA software (Wyatt Technologies).
Transmittance measurements of 5% PIPOx solutions in water,
ACN, DMSO, and PC were performed using a Jasco V-530 UV−vis
spectrophotometer. The transmittance was monitored as a function of
temperature at a wavelength of λ = 500 nm.
Calorimetric measurements were carried out using a differential
scanning calorimeter DSC 2920 (TA Instruments) under nitrogen
(flow rate of 50 mL/min). Samples of 1.5 mg placed in aluminum pans
were heated from −40 to 260 °C (heating rate of 10 °C/min). Then,
the samples were quenched with liquid nitrogen to −40 °C, and a
second heating run to 260 °C was performed. The obtained results
were collected and then analyzed using Universal Analysis 2000
software. The melting point (Tm) was determined from the first
heating curve, and the enthalpy of melting (ΔH) was calculated as the
area under the peak, limited by the sigmoidal baseline. The glass
transition temperature (Tg) was determined as the inflection point of
the second heat flow curve.
The presence of a crystalline phase in the sample was measured by a
wide-angle X-ray diffractometer (WAXS) TUR-M62 equipped with a
C DOI: 10.1021/ma502586x
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HZG-3 goniometer, using Cu Kα radiation. X-ray diffraction curve
analysis (calculation of the intensities and peak positions) was carried
out with WAXSFIT software. The degree of sample crystallinity χc was
determined by integrating the intensities of the crystalline reflections
and amorphous halos and was calculated as the ratio of the area under
the diffraction peaks to the total area of the diffraction curve.
The morphology of all PIPOx samples was analyzed by scanning
electron microscopy. Water suspensions of PIPOx crystallites obtained
in different solvents (10 μL, 1 g/L) were placed on a mica surface and
lyophilized. SEM analysis was performed using the microscope ESEM
Quanta 250 FEG (FEI Co.), which was equipped with a large field
detector (LFD), low voltage high contrast detector (vCD), and
Everhart−Thornley detector (ETD).
■
RESULTS AND DISCUSSION
PIPOx Synthesis and Characterization. Poly(2-isoprop-
yl-2-oxazoline) was obtained via cationic ring-opening polymer-
ization initiated by methyl 4-nitrobenzenesulfonate.8 Linear
poly(2-isopropyl-2-oxazoline) with a low molar mass dispersity
(Mw/Mn = 1.01) and molar mass equal to 20 800 g/mol (good
agreement with a theoretical value of Mn = 20 000 g/mol) was
obtained (Supporting Information, Figure S1A). Transmittance
measurements of the PIPOx aqueous solution confirmed its
thermoresponsiveness. The cloud point (TCP) in water was
determined at 50% transmittance from the heating run, giving a
value of 37 °C (Supporting Information, Figure S1B).
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Crystallization of PIPOx in Bulk. The thermal properties
of bulk PIPOx were studied by DSC (Figure 1A).
In the first DSC run of the PIPOx sample, performed at a
heating rate of 10 °C/min (Figure 1A), an exothermic peak is
observed in the range from 130 to 190 °C with the maximum
located at 154 °C. The heat of the observed effect is attributed
to the crystallization of poly(2-isopropyl-2-oxazoline) and is
equal to 11 J/g. At the temperature of 205 °C, the endothermic
peak is related to the melting of the freshly crystallized sample.
The enthalpy of melting (ΔH = 11 J/g) is the same as the heat
of crystallization. This indicates that the initial PIPOx sample
was amorphous. During measurement, part of the PIPOx
sample crystallized and then melted.
Amorphous PIPOx was subjected to isothermal crystalliza-
tion in bulk. For this purpose, the PIPOx sample was annealed
in a vacuum dryer at 190 °C for 1 h and then cooled to room
temperature. A DSC trace of sample named PIPOxbulk is shown
in Figure 1B. No exothermic effect is observed, while melting of
the sample occurs between 203 and 205 °C. The enthalpy of
melting is equal to ΔH = 38 J/g, which is significantly higher
than the value observed for a previous example (Figure 1A),
indicating a higher degree of sample crystallinity.
After heating to 260 °C, the samples were quenched, and in
the second run, no thermal effects were observed. The glass
transition values for PIPOx and PIPOxbulk, as determined from
the second run, are in good agreement with the literature (Tg of
approximately 70 °C).20
To determine the percentage of the crystalline phase in the
samples, WAXS studies were performed. X-ray diffraction
curves of amorphous PIPOx and PIPOxbulk are presented in
Figure 2.
In the WAXS curve of PIPOx, no diffraction peaks are
present (Figure 2A). This confirms that the polymer is
amorphous, which is consistent with the results obtained
from the DSC measurements of PIPOx, as discussed above. In
the curve of PIPOxbulk, two major diffraction peaks are present
at 2θ = 7.84° (11.3 Å) and 18.08° (4.9 Å) as well as two smaller
peaks at 21.23° (4.2 Å) and 23.98° (3.7 Å) (Figure 2B).
Identical peak positions and intensities were observed in the
WAXS curves of PIPOx, and described by Schlaad and co-
workers.20
The degree of crystallinity χc of PIPOxbulk was calculated
from the ratio of the area under the diffraction peaks to the
total area of the diffraction curve, giving a value of
approximately 68%.
Crystallization of PIPOx in Water. A number of studies
on the crystallization of PIPOx in aqueous solutions have been
carried out.20,21,24−28 Crystallization in water is explained as
being induced by the so-called solubility gap, connected with
the polymer phase transition above the LCST of thermores-
ponsive PIPOx.20,21
The properties of PIPOx crystallized in water, PIPOxH2O5%,
have been studied by DSC and WAXS (Supporting
Information, Figure S2). Both the Tm and Tg found in this
work are similar to values described in the literature.20 The
enthalpy of melting ΔH is equal to 25 J/g. The degree of
crystallinity χc is approximately 49%, which is consistent with
the value obtained for PIPOx crystallized in water for 5 h.24
The highest degree of crystallinity, χc = 80%, was reported for
PIPOx annealed in water for 25 h.24
Crystallization of PIPOx in Organic Solutions. To
determine whether phase separation above the LCST is a
precondition for the formation of crystallites, we investigated
D DOI: 10.1021/ma502586x
Article
solutions of PIPOx that do not exhibit thermoresponsivity. The
solutions of PIPOx in polar solvents with dipole moments
higher than that of water (approximately 4 D) that were
investigated here included acetonitrile (ACN), dimethyl
sulfoxide (DMSO), and propylene carbonate (PC). PIPOx
was dissolved in DMSO or PC at concentrations of 5% and in
ACN at concentrations of 5, 10, and 30% (w/v). No change in
transmittance with increasing temperature was observed for any
of these organic solutions of PIPOx.
An example transmittance−temperature curve of PIPOx in
acetonitrile is presented in Figure 3.
Figure 3. Transmittance−temperature curve of PIPOx in ACN (UV−
vis, 5%, λ = 500 nm).
The solutions of PIPOx in DMSO, PC, and ACN were
further incubated at 50 °C for 20 days. During this time, the
mixtures became turbid, and the formation of a precipitate was
observed (Figure 4).
The solid products obtained in the organic solutions were
isolated, purified, and dried. The names for the products
obtained after purification and drying are given in Table 1. The
properties of these products were studied by DSC and WAXS.
Exemple DSC traces and X-ray diffraction curves of
PIPOxDMSO5% and PIPOxPC5% are shown in Figure 5 (curves
for the other samples are present in the Supporting
Information, Figure S3).
In the first DSC run of PIPOxDMSO5%, a narrow endothermic
peak is present at 209 °C (Figure 5A) and is related to the
melting of the crystalline sample. The enthalpy of melting is
equal to 35 J/g, which is close to the ΔH of PIPOxbulk (ΔH =
38 J/g), indicating that a similar fraction of the crystalline phase
is present in both samples.
A broad endothermic peak with a maximum of 209 °C is
present in the DSC trace of PIPOx crystallized in PC at the
same concentration (PIPOxPC5%, Figure 5B). The enthalpy of
melting for this sample is equal to 30 J/g, which is lower than
that for PIPOxDMSO5%.
In the case of PIPOxACN5% (Supporting Information, Figure
S3A), the enthalpy of melting ΔH = 20 J/g was lower than for
the samples described above. This indicates the lowest content
of crystalline phase, in comparison with the samples obtained in
DMSO and PC of the same concentrations.
A comparison of ΔH for the samples crystallized in ACN at
different concentrations (PIPOxACN5%, PIPOxACN10%, and
PIPOxACN30%) shows the influence of solution concentration
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Figure 4. Formation of a precipitate during the incubation of PIPOx in ACN at 50 °C (5%, w/v).

Figure 5. DSC traces (heating rate of 10 °C/min, the violet line is the first run, the red line is the second run after quenching) of PIPOxDMSO5% (A)
and PIPOxPC5%. (B) X-ray diffraction curves of PIPOxDMSO5% (C) and PIPOxPC5% (D).

on the degree of crystallinity. The crystalline fraction increases,
as expressed by the ΔH values: 20 J/g for 5%, 26 J/g for 10%,
and 41 J/g for 30% (Supporting Information, Figure S3).
It is noteworthy that the melting peaks recorded in the DSC
traces for all samples are not symmetric, possibly due to the
formation of imperfect crystals of various morphologies.31
The glass transition value for all samples, as determined from
the second run, is 70 °C. Both Tm and Tg of all samples of
PIPOx crystallized in organic solutions are similar to that of
PIPOxbulk (Figure 1B).
The X-ray diffraction curves were analyzed to calculate the
percentage of crystalline phase in PIPOx samples. In the WAXS
curve of PIPOxDMSO5% (Figure 5A), diffraction peaks at 2θ =
7.94° (11.1 Å) and 17.88° (5.0 Å) and two smaller peaks at
21.40° (4.2 Å) and 24.24° (3.7 Å) can be seen. Similar peaks
are also present in the diffraction curve of PIPOxPC5% (Figure
5B) at 2θ = 7.91° (11.2 Å), 18.73° (4.9 Å), 21.40° (4.2 Å),
E DOI: 10.1021/ma502586x
24.20° (3.7 Å) and for all samples obtained in ACN: the peaks
of PIPOxACN5% (Supporting Information, Figure S3A) are
present at 2θ = 7.93° (11.2 Å), 18.11° (4.9 Å), 21.45° (4.1 Å),
and 24.24° (3.7 Å), for PIPOxACN10% (Supporting Information,
Figure S3B), the peaks are at 2θ = 7.94° (11.2 Å), 17.97° (4.9
Å), 21.43° (4.2 Å), and 24.37° (3.7 Å), and finally for
PIPOxACN30% (Supporting Information, Figure S3C), the peaks
are at 2θ = 7.97° (11.1 Å), 17.94° (4.9 Å), 21.20° (4.2 Å), and
24.30° (3.7 Å).
The diffraction peaks of PIPOx crystallized in the various
organic solutions (ACN, DMSO and PC) are in agreement
with the WAXS curve of PIPOx crystallized in water, as
described by Schlaad and co-workers.20 This confirms that
these crystalline products have the same unit cell. According to
the PIPOx unit cell model proposed in ref 20 the main chain of
the polymer is oriented through the [001] direction, the
isopropyl groups are alternately aligned along the [100]
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direction to either side of the backbone, and the amide dipoles

are alternately oriented along the [010] direction.
The mechanism of conformational orientation of polymer
backbone leading to crystallization, accompanied by molecular
orbital calculations is extensively described by Winnik et al.25
According to this mechanism, the liquid−liquid phase
separation of the aqueous PIPOx solution at the LCST causes
crystallization in the polymer-rich liquid phase. Upon heating,
irreversible transition of the polymer backbone in the polymer-
rich liquid phase facilitates nucleation and crystal growth. The
mechanism of conformational changes, leading to crystallization
from organic solvents is most likely the same as described by
Winnik25 in water, as the same unit cell of the crystalline
fraction is reached.
However, the crystallization of PIPOx in organic solutions
proceeds at a significantly slower rate (days) than in water
(hours). As the liquid−liquid phase separation, leading to the
formation of polymer-rich phase does not occur in organic
Figure 6. Degree of crystallinity versus the enthalpy of melting of
solvents, the nucleation and crystal growth last much longer. PIPOx. The dotted line is given as a guideline for the eye.
The degree of crystallinity χc was calculated for all samples
from the ratio of the area under the diffraction peaks to the
total area of the diffraction curve. The highest degree of
crystallinity, χc = 68%, was obtained for PIPOxACN30%, and this
value is related to the highest value of enthalpy of melting,
recorded as ΔH = 41 J/g, in comparison with the samples
crystallized in the other organic solvents. The crystallinity of
PIPOxACN30% is the same as that recorded for PIPOxbulk. Lower
concentrations of PIPOx crystallized in acetonitrile, in the case
of PIPOxACN10% and PIPOxACN5%, resulted in lower degrees of
crystallinity of 55% and 45%, respectively, indicating that χc
depends slightly on the polymer concentration.
For PIPOx crystallized in the other organic solvents at 5%
(w/v), the percentages of crystalline phase are approximately
65% for PIPOxDMSO5% and 60% for PIPOXPC5%. Differences in
χc values of samples crystallized from various organic solvents at
the same concentration are due to the differences in
crystallization rate.
We observed that prolonged (60 days) annealing of 5%
PIPOx solution in ACN, DMSO, and PC leads to the same
degree of crystallinity of 65% for all solutions.
The presented WAXS and DSC data indicate the ability of
PIPOx to crystallize in organic solutions. This means that phase
separation connected with the LCST is not a precondition for
PIPOx crystallization in solution.
All values of χc received for crystalline PIPOx were correlated
with the DSC data. When plotting the degree of crystallinity Figure 7. SEM micrographs of PIPOxACN30% (A), PIPOxACN5% (B),
versus the enthalpy of melting (Figure 6), a linear relationship PIPOxDMSO5% (C), and PIPOxH2O5% (D).
is expected because the ΔH of the sample increases with sample
crystallinity.32 Approximating the positions of the points with a
linear dependence allowed for the calculation of the enthalpy of
melting of perfectly crystalline poly(2-isopropyl-2-oxazoline), The length of the fibrils ranged from a few to several microns,
ΔH100%, giving a value of 50 J/g. Basically, this value is with a width of approximately 50 nm. A dense, fibrillar network
impossible to be reached experimentally in macromolecules can also be observed in the SEM micrographs of PIPOx
because perfectly crystalline polymers are almost never crystallized in acetonitrile at lower concentrations: PI-
obtained.33 POxACN10% and PIPOxACN5% (Figure 7B), indicating that
To compare the morphology of PIPOx crystallized in the concentration has a minor effect on sample morphology. The
organic solutions and PIPOx crystallized in water, SEM analysis PIPOx crystalline structures formed in DMSO (Figure 7C) and
was performed (Figure 7). PC are similar to those obtained in ACN.
The morphology of PIPOx crystallized in organic solutions is However, the SEM micrograph of PIPOxH2O5% (Figure 7D)
different from the morphology of PIPOx crystallized in water. shows spherical, compact particles of regular diameter
In the SEM micrograph of PIPOxACN30% (Figure 7A), a (approximately 1 μm) and shape that are composed of fibers,
network-like structure is present. Within this network, separate as described in the literature (“wool balls”24). As it was
objects possessing a fibril-like morphology can be distinguished. explained in ref 24, the fibers wrap into microspheres as the
F DOI: 10.1021/ma502586x
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result of driving force to minimize the interfacial energy
between the crystalline particles and water.
As it was claimed in ref 24, the degree of crystallinity of
PIPOx microspheres crystallized in water reaches 80%. This
value is significantly higher than that obtained for fibrillar
PIPOx crystallites obtained in organic solutions (χc up to 68%).
This difference could be due to highly developed surface area of
the microspheres relative to that of the fibrils.
■
SUMMARY AND CONCLUSIONS
We demonstrated that PIPOx crystallization occurs not only in
aqueous media but also in organic solvents, including
acetonitrile, dimethyl sulfoxide, and propylene carbonate.
However, the crystallization time of PIPOx is significantly
shorter in water (hours) than in organic solutions (days). An
increase of PIPOx concentration speeds up the crystallization.
PIPOx does not crystallize in water below the LCST due to
the presence of solvation sphere, which prevents the polymer
chains from orienting favorably for crystallization. Above the
LCST, the solvation sphere is weaker, and intra- and interchain
interactions are dominant. Thus, phase separation associated
with the LCST is a driving force for polymer chains orientation
and crystallization.
Unlike water, ACN, DMSO, and PC do not form H-bonds
with the hydrophilic elements of PIPOx. As a consequence,
phase separation does not occur; therefore, the LCST is not a
precondition for PIPOx crystallization in organic solutions.
Both the type of organic solvent and the concentration of the
polymer solution influence the degree of crystallinity of the
obtained products. Annealing of PIPOx in acetonitrile of the
highest concentration for 20 days results in higher degree of
crystallinity (comparable with that for PIPOxbulk) than in the
case of PIPOx crystallized in ACN at lower concentrations.
Upon comparing the crystallization of 5% (w/v) PIPOx in
different organic solutions after 20 days, PIPOx crystallized in
either DMSO or PC was found to have a higher crystalline
content than PIPOx crystallized in ACN. The annealing
prolonged to 60 days leads to the same degree of crystallinity
for all solutions.
Identical peak positions and intensities were observed in the
WAXS curves of PIPOx crystallized in the various organic
solvents as well as in PIPOx crystallized in water, confirming
that all products the same unit cell.
The ΔH of the crystalline fraction of the sample increases
linearly with the degree of crystallinity. This dependence
allowed us to determine the value of enthalpy of melting for
hypothetical, perfectly crystalline PIPOx, ΔH100%, which was
found to be 50 J/g.
The morphology of PIPOx crystallized in nonaqueous media
differed from that observed when crystallized in water. The
micron-sized fibers were unable to form the so-called “wool
balls” observed by others in water.
■
ASSOCIATED CONTENT
*
S Supporting Information
SEC traces and transmittance−temperature curve of PIPOx as
well as DSC traces and X-ray diffraction curves of PIPOxH2O5%,
PIPOxACN5%, PIPOxACN10%, and PIPOxACN30%. This material is
available free of charge via the Internet at http://pubs.acs.org.
■
AUTHOR INFORMATION
Corresponding Author
*(A.D.) E-mail: adworak@cmpw-pan.edu.pl.
G DOI: 10.1021/ma502586x
Article
Notes
The authors declare no competing financial interest.
■
ACKNOWLEDGMENTS
This work was supported by the National Centre for Research
and Development, project POLYCELL PBS1/B9/10/2012,
and by the National Science Centre, project 2012/07/N/ST5/
00261.
■
REFERENCES
(1) Kronek, J.; Kronekova, Z.; Luston, J.; Paulovicova, E.;
Paulovicova, L.; Mendrek, B. J. Mater. Sci.: Mater. Med. 2011, 22,
1725−1734.
(2) Gaertner, F. C.; Luxenhofer, R.; Blechert, B.; Jordan, R.; Essler,
M. J. Controlled Release 2007, 119, 291−300.
(3) Tong, J.; Luxenhofer, R.; Yi, X.; Jordan, R.; Kabanov, A. V. Mol.
Pharmaceutics 2010, 7, 984−992.
(4) Fortig, A.; Jordan, R.; Graf, K.; Schiavon, G.; Purrucker, O.;
Tanaka, M. Macromol. Symp. 2004, 210, 329−338.
(5) Volet, G.; Chanthavong, V.; Wintgens, V.; Amiel, C. Macro-
molecules 2005, 38, 5190−5197.
(6) Trzebicka, B.; Koseva, N.; Mitova, V.; Dworak, A. Polymer 2010,
51, 2486−2493.
(7) Konradi, R.; Pidhatika, B.; Muehlebach, A.; Textor, M. Langmuir
2008, 24, 613−616.
(8) Dworak, A.; Utrata-Wesołek, A.; Oleszko, N.; Wałach, W.;
Trzebicka, B.; Anioł, J.; Sieroń, A. L.; Klama-Baryła, A.; Kawecki, M. J.
Mater. Sci.: Mater. Med. 2014, 25, 1149−1163.
(9) Park, J. S.; Akiyama, Y.; Winnik, F. M.; Kataoka, K.
Macromolecules 2004, 37, 6786−6792.
(10) Kempe, K.; Hoogenboom, R.; Jaeger, M.; Schubert, U. S.
Macromolecules 2011, 44, 6424−6432.
(11) Fijten, M.; Kranenburg, J.; Thijs, H.; Paulus, R.; van Lankvelt,
B.; de Hullu, J.; Springintveld, M.; Thielen, D.; Tweedie, C.;
Hoogenboom, R.; Vliet, K.; Schubert, U. S. Macromolecules 2007,
40, 5879−5886.
(12) Weberskirch, R.; Hettich, R.; Nuyken, O.; Schmaljohann, D.;
Voit, B. Macromol. Chem. Phys. 1999, 200, 863−873.
(13) Christova, D.; Velichkova, R.; Loos, W.; Goethals, E. J.; Du Prez,
F. Polymer 2003, 44, 2255−2261.
(14) Lambermont-Thijs, H.; van Kuringen, H.; van der Put, J.;
Schubert, U. S.; Hogenboom, R. Polymers 2010, 2, 188−199.
(15) Litt, M.; Rahl, F.; Roldan, L. G. J. Polym. Sci., Part A 1969, 7,
463−473.
(16) Aharoni, S. M.; Sanjeeva Murthy, N. Int. J. Polym. Mater. 1998,
42, 275−283.
(17) Zhang, M. Q.; Ning, K. J.; Li, T. Q.; Zeng, H. M. J. Polym. Sci.
1999, 74, 3376−3379.
(18) Kalika, D. S.; Gibson, D. G.; Quiram, D. J.; Register, R. A. J.
Polym. Sci., Polym. Phys. 1998, 36, 65−73.
(19) Gao, J.; Duan, L.; Yang, G.; Zhang, Q.; Yang, M.; Fu, Q. Appl.
Surf. Sci. 2012, 261, 528−535.
(20) Demirel, A. L.; Meyer, M.; Schlaad, H. Angew. Chem., Int. Ed.
2007, 46, 8622−8624.
(21) Meyer, M.; Antonietti, M.; Schlaad, H. Soft Matter 2007, 3,
430−431.
(22) Diehl, C.; Dambowsky, I.; Hoogenboom, R.; Schlaad, H.
Macromol. Rapid Commun. 2011, 32, 1753−1758.
(23) Hoogenboom, R.; Lambermont-Thijs, H.; Jochems, M.;
Hoeppener, S.; Guerlain, C.; Fustin, C.; Gohy, J. F.; Schubert, U. S.
Soft Matter 2009, 5, 3590−3592.
(24) Diehl, C.; Cernoch, P.; Zenke, I.; Runge, H.; Pitschke, R.;
Hartmann, J.; Tiersch, B.; Schlaad, H. Soft Matter 2010, 6, 3784−3788.
(25) Katsumoto, Y.; Tsuchiizu, A.; Qiu, X.; Winnik, F. M.
Macromolecules 2012, 45, 3531−3541.
(26) Obeid, R.; Tanaka, F.; Winnik, F. M. Macromolecules 2009, 42,
5818−5828.
Macromolecules XXXX, XXX, XXX−XXX
Macromolecules Article

(27) Morimoto, N.; Obeid, R.; Yamane, S.; Winnik, F. M.; Akiyoshi,
K. Soft Matter 2009, 5, 1597−1600.
(28) Diehl, C.; Schlaad, H. Chem.Eur. J. 2009, 15, 11469−11472.
(29) Guner, P. T.; Miko, A.; Schweinberger, F. F.; Demirel, A. L.
Polym. Chem. 2012, 3, 322−324.
(30) Witte, H.; Seeliger, W. Liebigs Ann. Chem. 1974, 996−1009.
(31) Sauer, B. B.; Kampert, W. G.; Blanchard, E. N.; Threefoot, S. A.;
Hsiao, B. S. Polymer 2000, 41, 1099−1108.
(32) Cerqueira, D. A.; Filho, G. R.; Assuncao, R. M. Polym. Bull.
2006, 56, 475−484.
(33) Elias, H. G. Macromolecules, 2nd ed.; Plenum Press: New York,
1984; Vol. 1, Chapter 5, pp 158−166.

H DOI: 10.1021/ma502586x
Macromolecules XXXX, XXX, XXX−XXX