New amphiphilic polycarbonates with side functionalized cholesteryl groups as biomesogenic units: synthesis, structure and liquid crystal behavior

Article abstract of DOI:10.1039/c7ra00360a

The synthesis of four new amphipathic copolymers with side functionalized-cholesterol based aliphatic polycarbonates is described through the ring-opening polymerization and coupling reaction. The chemical structures, liquid crystal (LC) behavior, and thermal stability of the chiral monomers and copolymers obtained in this study were characterized using Fourier transform infrared (FT-IR) spectroscopy, proton nuclear magnetic resonance (¹H NMR) spectroscopy, gel permeation chromatography (GPC), polarizing optical microscopy (POM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and thermogravimetric analysis (TGA) measurements. The effect of the spacer length on the molecular interaction and mesophase of the chiral monomers and copolymers was investigated. It was found that chiral monomers with longer spacer seemed beneficial for the formation of mesophases, and the additional ordering on polymerization caused mesophases to be more ordered than for the corresponding monomers. The LC copolymers all revealed a smectic A phase with an interdigitated molecular arrangement. The results seemed to show a decreased tendency toward the glass transition temperature, and isotropic temperature for the LC copolymers by increasing the spacer length. In addition, four LC copolymers had a good thermal stability.

Full text of DOI:10.1039/c7ra00360a

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PAPER
New amphiphilic polycarbonates with side
functionalized cholesteryl groups as biomesogenic
units: synthesis, structure and liquid crystal
behavior†
Cite this: RSC Adv., 2017, 7, 14176
a
b
b
b
a
c
Xiaoxu Xu, Xiaofeng Liu, Qun Li, Jianshe Hu,* Qifan Chen,* Liqun Yang
d
and Yanhua Lu
The synthesis of four new amphipathic copolymers with side functionalized-cholesterol based aliphatic
polycarbonates is described through the ring-opening polymerization and coupling reaction. The chemical
structures, liquid crystal (LC) behavior, and thermal stability of the chiral monomers and copolymers
obtained in this study were characterized using Fourier transform infrared (FT-IR) spectroscopy, proton
1
nuclear magnetic resonance ( H NMR) spectroscopy, gel permeation chromatography (GPC), polarizing
optical microscopy (POM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and
thermogravimetric analysis (TGA) measurements. The effect of the spacer length on the molecular
interaction and mesophase of the chiral monomers and copolymers was investigated. It was found that
chiral monomers with longer spacer seemed beneficial for the formation of mesophases, and the
additional ordering on polymerization caused mesophases to be more ordered than for the corresponding
monomers. The LC copolymers all revealed a smectic A phase with an interdigitated molecular
arrangement. The results seemed to show a decreased tendency toward the glass transition temperature,
and isotropic temperature for the LC copolymers by increasing the spacer length. In addition, four LC
copolymers had a good thermal stability.
Received 10th January 2017
Accepted 22nd February 2017
DOI: 10.1039/c7ra00360a
rsc.li/rsc-advances
11.12
optical and bioactive materials.
As a kind of self-assembled
Introduction
functional so materials, LC compounds possess both order
In recent years, aliphatic polycarbonates have been found to be and mobility at molecular, supramolecular and macroscopic
1
3–16
promising biomaterials because of their good biodegradability levels.
and biocompatibility.
Moreover, LC compounds also can produce response or
1–5
Until now, many modication sensitively through the self-assembling ability under external
approaches have been used to obtain the desirable properties. stimuli such as temperature, pressure, and electromagnetic eld.
Among them, the incorporation of the bioactive or self-assembly In fact, LC compounds are also useful in biorelated elds because
functional compounds to the polymer chain has currently their self-organizing structures through non-covalent specic
6–10
17–20
become the most important modication strategies. As known, interactions are compatible with those in living systems.
liquid crystal (LC) materials have been widely used for display Recently, LC compounds in the elds of biomedical application
devices because their exible ordered structures can lead to such as controlled drug delivery and protein binding have been
21
systems displaying switchable optical modulation. Moreover, the demonstrated. Because of their dynamic nature, photochemi-
LC compounds can potentially be used as new functional mate- cally, thermally or mechanically induced structure changes of LC
rials for electron, ion, molecular transporting, sensory, catalytic, can be used for the construction of stimuli-responsive multi-
functional materials.
As an important structural component in mammalian cells,
cholesterol has high thermodynamic affinity toward cell
a
School of Chemical Engineering, Eastern Liaoning University, Dandong, P. R. China.
E-mail: qifan_C405@163.com
b
membrane and ability to change the uidity and permeability of
Center for Molecular Science and Engineering, College of Science, Northeastern
22
the membrane. Therefore, cholesterol can play important
roles in the functions of biological system and LC so matter
and become an interesting component with bioactive because
University, Shenyang 110819, P. R. China. E-mail: hujs@mail.neu.edu.cn
c
Key Laboratory of Reproductive Health and Medical Genetics, National Health and
Family Planning Commission, Shenyang, P. R. China
d
Key Laboratory of Functional Textile Materials, Eastern Liaoning University, of its universal effect, regardless of cell type and receptor map
Dandong, Liaoning, P. R. China
on the membrane. In recent years, cholesterol as a natural
biomesogen has also become an attractive candidate to
†
Electronic supplementary information (ESI) available. See DOI:
0.1039/c7ra00360a
1
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synthesize new smart, responsive and biodegradable LC poly- (DSC), X-ray diffraction (XRD), and thermogravimetric analysis
3,23–29
mer materials.
Stupp and coworkers rst reported the (TGA) measurements.
synthesis of cholesterol end functionalized oligo(L-lactic
3,23
24,25
26
acid).
Later, Cheng
and Yang et al. also reported cho-
Experimental
Materials
lesteryl end-capped aliphatic polycarbonates and dicholesteryl
end functionalized block poly(3-caprolactone), respectively, as
biodegradable polymers. These study results have shown that All chemicals were obtained from the indicated sources.
the cholesterol-functionalized biodegradable polycarbonate Cholesterol was purchased from Xiayi Beier Biological Products
block copolymers can play an important role in encapsulation Co., Ltd. (Xiayi, China). Adipic acid and sebacic acid were
of complex hydrophobic therapeutics for drug application. purchased from Shenyang Xinxing Chemical Reagent Plant
However, because the functionalized cholesteryl units are (Shenyang, China). Glycerol and benzaldehyde were purchased
located in the terminal groups of macromolecular chain, the from Tianjin Bodi Chemical Co., Ltd. (Tianjin, China). Succinic
copolymers obtained in these study show lower average anhydride and benzyl chloride were purchased from Shanghai
molecular weight, in other words, they are oligomers, which will Chemical Reagent Plant (Shanghai, China). Suberic acid, hex-
affect their application in drug delivery and tissue engineering. adecyl trimethylammonium bromide (HTAB), stannous octoate
2
Compared with the biodegradable polycarbonates with main [Sn(Oct) ], and methoxypolyethylene glycols (mPEG43) were
chain functionalized cholesteryl mesogenic groups, the poly- purchased from Sigma-Aldrich. Ethyl chloroformate was
carbonates based on side functionalized cholesteryl groups purchased from Xinyi Huili Fine Chemical Co., Ltd. (Xinyi,
have more advantage such as controlled multiple structure and China). Tetrahydrofuran (THF) was dried over potassium
molecular weight. However, to the best of our knowledge, little hydroxide and then distilled over sodium potassium alloy in
research on the biodegradable aliphatic polycarbonate based on argon atmosphere. Toluene was dried by treatment with Na and
9,10,30
cholesterol as side chain biomesogenic units is reported.
distilled before use. All other solvents and reagents used were
So, it is necessary to synthesize new biodegradable side chain puried by standard methods.
LC polycarbonate derived from cholesterol and study their
structure–property relationships and explore the potential Characterization
applications in drug delivery and tissue engineering templates.
FT-IR spectra were measured on a PerkinElmer spectrum One
In the present work, we designed and synthesized a series of
new side cholesterol-functionalized amphipathic copolymers
based aliphatic polycarbonates, and investigated their struc-
ture–mesomorphism relationships. A side chain functionalized
cholesterol with hydrophobic moiety was added onto the
amphiphilic block copolymers with polycarbonate and mPEG
backbone for the introduction of physicochemical function-
ality. The ability of side cholesterol groups to form mesophase
will be anticipated to provide a driving force for self-assembly
into nanostructure. Herein, we only discussed the synthesis,
LC properties, mesophase structure, and thermal stability of the
obtained copolymers with Fourier transform infrared (FT-IR)
1
(B) spectrometer (PerkinElmer, Foster City, CA). H NMR
spectra were obtained using a Bruker ARX 600 (Bruker, Ger-
many) high resolution NMR spectrometer, and chemical shis
were reported in ppm with tetramethylsilane (TMS) as an
internal standard. Gel permeation chromatographic (GPC)
measurements were carried out at room temperature on
a Waters 1515 instrument calibrated with a polystyrene stan-
dard, and using THF as an eluent. The phase transition
temperature was determined with a Netzsch 204 (Netzsch,
Hanau, Germany) differential scanning calorimetry (DSC)
equipped with a cooling system at a heating and cooling rate of
ꢀ
ꢁ1
1
0 C min in a nitrogen atmosphere. The optical texture was
1
spectrum, proton nuclear magnetic resonance ( H NMR) spec-
trum, gel permeation chromatographic (GPC), polarizing
optical microscopy (POM), differential scanning calorimetry
observed with a Leica DMRX (Leica, Wetzlar, Germany) polar-
izing optical microscopy (POM) equipped with a Linkam
THMSE-600 (Linkam, London, UK) cool and hot stage. The
Scheme 1 Synthetic route of cyclic monomer.
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0
N,N -Dicyclohexylcarbodiimide (DCC) (5.2 g, 0.025 mol) and
DMAP (1.2 g, 0.01 mol) were dissolved in dichloromethane (20
mL), and then added dropwise to the ask. Aer stirring for
0
.5 h, cholesterol (9.7 g, 0.025 mol), dissolved in 20 mL of
dichloromethane, was added dropwise to the above mixture.
ꢀ
The reaction mixture was stirred for 24 h at 30 C. The
resulting mixture was washed with 50 mL of water, and a solid,
0
N,N -dicyclohexyl urea, was precipitated and ltered off. The

ltrate was dried with anhydrous magnesium sulfate and
evaporated to dryness. The crude product was rst recrystal-
lized with ethanol, and then further puried by silica gel
column chromatography (petroleum ether/ethyl acetate ¼
ꢀ
3
: 1). A white solid was obtained. Yield: 65%, mp: 139.5 C. IR
Scheme 2 Synthetic route of chiral monomers.
ꢁ1
1
(
KBr, cm ): 2944, 2863 (–CH
2
–, –CH
3
); 1722, 1694 (C]O). H
NMR (d, ppm from TMS in CDCl
3
): 5.38–5.36 (d, 1H, J ¼ 6.0 Hz,
–
CH]C in cholesteryl); 4.66–4.57 (m, 1H, –COOCH in cho-
thermal decomposition temperature was measured under
nitrogen atmosphere with a Netzsch 209C thermogravimetric
2
lesteryl); 2.39 (m, 2H, –CH COO–); 2.35, 2.01 (m, 2H,
pCHCH C]C in cholesterol); 2.31 (m, 2H, –CH COOH); 1.99–
2
2
ꢀ
ꢁ1
analysis (TGA) at a heating rate of 20 C min . X-ray diffraction
XRD) measurements were performed with a nickel-ltered Cu-
0
.68 (m, 45H, rest of the protons from cholesteryl and
(
–
CH (CH ) CH COOH).
2
2 2
2
Ka radiation with a Bruker D8 Advance (Bruker, Germany)
powder diffractometer.
Synthesis of 8-cholesteroxy-8-oxooctanoic acid (M ). In a way
3
similar to the synthesis of M
accordingly prepared. Yield: 67%, mp: 129.5 C. IR (KBr, cm ):
2
, new cholesteryl derivative M
3
was
ꢀ
ꢁ1
1
Synthesis of cyclic monomer
2956, 2865 (–CH
from TMS in CDCl
cholesteryl); 4.64–4.60 (m, 1H, –COOCH in cholesteryl); 2.36–
2.34 (m, 2H, J ¼ 7.2 Hz, –CH COO–); 2.33–0.69 (m, 53H, rest of
the protons from cholesteryl and –CH (CH ) COOH).
2
3
–, –CH ); 1737, 1705 (C]O). H NMR (d, ppm
3
): 5.39–5.37 (d, 1H, J ¼ 4.8 Hz, –CH]C in
The cyclic monomer 5-(benzyloxy)-1,3-dioxan-2-one (BTMC),
shown in Scheme 1, was prepared according to the method re-
30
ꢀ
ꢁ1
2
ported by Hu et al. Yield: 43%, mp: 145.8 C. IR (KBr, cm ):
2
2 5
3
1
5
2
069 (]C–H); 2969, 2872 (–CH
2
–); 1746 (C]O); 1531, 1467 (Ph–),
192 (C–O). H NMR (d, ppm from TMS in CDCl ): 7.39–7.33 (m,
H, J ¼ 7.2, Ph–H); 4.66 (s, 2H, Ar–CH O–); 4.52–4.43 (m, 4H, J ¼
.4, pCHCH
O–); 3.91–3.89 (m, 1H, J ¼ 2.4, –CH).
1
Synthesis of 10-cholesteroxy-10-oxodecanoic acid (M
a way similar to the synthesis of M , new cholesteryl derivative
was accordingly prepared. Yield: 40%, mp: 117.3 C. IR (KBr,
4
). In
3
2
2
ꢀ
M
4
2
ꢁ
1
1
cm ): 2960, 2858 (–CH
d, ppm from TMS in CDCl
C in cholesteryl); 4.64–4.60 (m, 1H, –COOCH in cholesteryl);
COO–); 2.32–0.68 (m, 57H,
2
–, –CH
3
); 1737, 1707 (C]O). H NMR
(
3
): 5.38–5.36 (d, 1H, J ¼ 4.2 Hz, –CH]
Synthesis of chiral monomers
The synthetic route of the chiral monomers M
Scheme 2.
1
–M
4
is shown in 2.36–2.33 (m, 2H, J ¼ 7.8 Hz, –CH
2
rest of the protons from cholesteryl and –CH (CH ) COOH).
2 2 5
Synthesis of 4-cholesteroxy-4-oxobutanoic acid (M
cinic anhydride (10 g, 0.1 mol), 4-dimethylaminopyridine
DMAP) (1.2 g, 0.01 mol), and anhydrous dichloromethane (150
1
). Suc-
Synthesis of block copolymers
(
mL) were placed in a 500 mL three-neck ask with magnetic stir The synthetic route of the block copolymers is shown in Scheme 3.
bar. Aer stirring for 0.5 h, cholesterol (19.3 g, 0.05 mol), dis- Synthesis of mPEG43-b-PBTMC50. The block copolymer
solved in 70 mL of dichloromethane, was added dropwise to the mPEG43-b-PBTMC50 was synthesized by ring-opening polymer-
above mixture. The reaction mixture was stirred for 24 h at ization of the cyclic carbonate monomer BTMC and mPEG43 in
ꢀ
30
C. The resulting mixture was evaporated to dryness, the polymerization ask equipped with a sealing cap using Sn(Oct)
2
crude product was recrystallized with acetic acid, washed with as a catalyst. The general synthetic procedure for the copolymer
hot water, and then further puried by silica gel column chro- was described as follows: BTMC (8.32 g, 40 mmol), mPEG
matography (petroleum ether/ethyl acetate ¼ 3 : 1). A white (2.24 g, 1.18 mmol), and Sn(Oct) toluene solution (0.8 mL,
2
ꢀ
ꢁ1
ꢁ1
solid was obtained. Yield: 60%, mp: 180.1 C. IR (KBr, cm ): 0.1 mol L ) were placed in the glass ask, which was degassed
1
2949, 2862 (–CH
2 3
–, –CH ); 1731, 1710 (C]O). H NMR (d, ppm in a vacuum by several vacuum-purge cycles, and then sealed
from TMS in CDCl
3
): 5.39–5.37 (d, 1H, J ¼ 4.2 Hz, –CH]C in under argon atmosphere. The reaction was held for 24 h at
ꢀ
cholesteryl); 4.66–4.62 (m, 1H, –COOCH in cholesteryl); 2.69– 150 C in an oil bath. Aer completion of polymerization, the
2
.67 (t, 2H, J ¼ 6.6, HOOCCH
2
CH
2
–); 2.61–2.59 (t, 2H, J ¼ 6.6, crude polymer was puried by dissolving it in dichloromethane
HOOCCH
2
CH
2
–); 2.33–0.68 (m, 43H, rest of the protons from and precipitated in methanol, and then dried in a vacuum until
cholesteryl).
a constant sample mass was obtained. Yield: 90%. IR (KBr,
ꢁ
1
Synthesis of 6-cholesteroxy-6-oxocaproic acid (M ). Adipic cm ): 2961, 2872 (–CH –, –CH ); 1750 (C]O); 1496, 1454 (Ph–),
acid (14.6 g, 0.1 mol) and dichloromethane (200 mL) were 1239 (C–O). H NMR (d, ppm from TMS in CDCl
placed in a 500 mL three-neck ask with magnetic stir bar. Ph–H); 4.72–4.58 (m, Ph–CH O–); 4.31–4.21 (m, –OCH
2
2
3
1
3
): 7.32–7.26 (m,
–CH–
2
2
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Scheme 3 Synthetic route of block copolymers.
CH O–); 3.86–3.83 (m, –OCH –CH–CH O–); 3.67–3.62 (m, groups), dissolved in 5 mL of dichloromethane, was added
2
2
2
–
OCH – in mPEG).
dropwise to the above mixture. The reaction mixture was stirred
2
ꢀ
Synthesis of mPEG43-b-PHTMC50. mPEG43-b-PBTMC50 (8 g), for 24 h at 30 C. The resulting mixture was washed with 20 mL
0
Pd/C (0.04 g), Pd(OH)
2
(0.04 g, 10%), and 150 mL of methanol/ of water, and a solid, N,N -dicyclohexyl urea, was precipitated
tetrahydrofuran (1 : 1) were placed in a 250 mL three-neck ask and ltered off. The ltrate was dried with anhydrous magne-
with magnetic stir bar under argon atmosphere. The reaction sium sulfate and evaporated to dryness. The crude polymer was
ꢀ
mixture was stirred for 48 h at 25 C in hydrogen system. Aer puried by dissolving them in dichloromethane and precipi-
completion of reducing reaction, the Pd/C and Pd(OH) were tated in methanol, and then dried in a vacuum until a constant
2
ꢁ
1

ltered off, the ltrate was evaporated to dryness, and then sample mass was obtained. Yield: 32%. IR (KBr, cm ): 2940,
dried in a vacuum until a constant sample mass was obtained. 2966 (–CH –, –CH ); 1737 (C]O); 1653 (C]C); 1259 (C–O). H
1
2
3
ꢁ
1
Yield: 75%. IR (KBr, cm ): 3376 (–OH); 2961, 2904 (–CH
2
–, NMR (d, ppm from TMS in CDCl
); 1753 (C]O); 1256 (C–O). H NMR (d, ppm from TMS in cholesteryl); 5.29–5.26 (m, –OCH –CH–CH
DMSO-d ): 5.45 (m, –OH); 4.10–4.02 (m, –OCH –CH–CH
O–); –COOCH in cholesteryl); 4.36–4.21 (m, –OCH
.95–3.91 (m, –OCH –CH–CH O–); 3.50 (m, –OCH – in mPEG). 3.65 (m, –OCH – in mPEG); 2.67–2.60 (m, –COO(CH
Synthesis of mPEG43-b-P(TMC-M (4.7 g, 10 mmol) 2.32–0.68 (m, rest of the protons from cholesteryl).
and dichloromethane (50 mL) were placed in a 100 mL three- Synthesis of mPEG -b-P(TMC-M ) . The block copolymer
neck ask with magnetic stir bar. DCC (2.16 g, 10.5 mmol) mPEG -b-P(TMC-M ) was prepared by a procedure similar to
3
): 5.38–5.36 (t, –CH]C in
O–); 4.65–4.60 (m,
–CH–CH O–);
COO–);
1
–
CH
3
2
2
6
2
2
2
2
3
2
2
2
2
2 4
)
1 1
)50. M
4
3
2 50
4
3
2 50
and DMAP (0.12 g, 1 mmol) were dissolved in 5 mL of that for mPEG -b-P(TMC-M ) , using M instead of M . Yield:
4
3
1 50
2
1
ꢁ1
dichloromethane, and then added dropwise to the ask. Aer 45%. IR (KBr, cm ): 2932, 2857 (–CH
stirring for 0.5 h, mPEG43-b-PHTMC50 (1.6 g, 10 mmol for –OH 1643 (C]C); 1255 (C–O). H NMR (d, ppm from TMS in CDCl ):
3
2
–, –CH
3
); 1735 (C]O);
1
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5
.39–5.37 (t, –CH]C in cholesteryl); 5.28–5.25 (m, –OCH
2
–CH– Table 1 Yields and average molecular weight of the copolymers
CH O–); 4.61–4.55 (m, –COOCH in cholesteryl); 4.42–4.16 (m,
2
a
b
c
Copolymer
Yield/%
M
n
(kDa)
M
n
(kDa)
PDI
–
OCH –CH–CH O–); 3.65 (m, –OCH – in mPEG); 2.38–0.69 (m,
2 2 2
rest of the protons from PCL, cholesteryl and –COO(CH ) COO–).
2
4
mPEG43-b-PBTMC50
90
75
36
45
38
35
12.3
7.8
31.3
32.7
34.1
35.5
9.2
5.5
27.2
29.1
29.9
31.6
1.47
1.42
1.55
1.61
1.66
1.57
3
Synthesis of mPEG43-b-P(TMC-M )50. The block copolymer mPEG43-b-PHTMC50
mPEG43-b-P(TMC-M
3
)
50 was prepared by a procedure similar to mPEG43-b-P(TMC-M
mPEG43-b-P(TMC-M
1
2
3
4
)
50
)
50
)
50
)
50
1 3 1
that for mPEG43-b-P(TMC-M )50, using M instead of M . Yield:
ꢁ1
mPEG43-b-P(TMC-M
mPEG43-b-P(TMC-M
3
1
5
8%. IR (KBr, cm ): 2934, 2859 (–CH
2
–, –CH
647 (C]C); 1260 (C–O). H NMR (d, ppm from TMS in CDCl
.39–5.37 (t, –CH]C in cholesteryl); 5.28–5.26 (m, –OCH –CH–
3
); 1735 (C]O);
1
3
):
a
1
b
M
n
values calculated from H NMR.
M
n
values determined by GPC in
2
ꢁ1
c
THF using PS standards, g mol
.
PDI ¼ M /M
w
n
.
CH O–); 4.63–4.58 (m, –COOCH in cholesteryl); 4.38–4.20 (m,
2
–
OCH –CH–CH O–); 3.65 (m, –OCH – in mPEG); 2.39–0.68 (m,
2 2 2
rest of the protons from PCL, cholesteryl and –COO(CH
Synthesis of mPEG43-b-P(TMC-M 50. The block copolymer
mPEG43-b-P(TMC-M 50 was prepared by a procedure similar to
that for mPEG43-b-P(TMC-M 50, using M instead of M . Yield:
5%. IR (KBr, cm ): 2936, 2861 (–CH –, –CH ); 1739 (C]O);
2 6
) COO–).
macroinitiator with hydroxyl groups such as polyethylene
4
)
28,31
glycols.
In this investigation, the block copolymers were
4
)
synthesized according to the route shown in Scheme 3. First, the
copolymer mPEG43-b-PBTMC50 was prepared by the ring-
opening polymerization of cyclic monomer BTMC using
1
)
4
1
ꢁ
1
3
1
5
2
3
1
648 (C]C); 1263 (C–O). H NMR (d, ppm from TMS in CDCl ):
3
2
Sn(Oct) as a catalyst in the presence of mPEG43 under argon
.38–5.35 (t, –CH]C in cholesteryl); 5.27–5.25 (m, –OCH –CH–
2
atmosphere. The optimum reaction conditions were selected to
CH O–); 4.69–4.59 (m, –COOCH in cholesteryl); 4.35–4.09 (m,
2
ꢀ
be 24 h at 150 C, and the molar ratio of BTMC to Sn(Oct) was
2
2 2 2
–OCH –CH–CH O–); 3.60 (m, –OCH – in mPEG); 2.38–0.66 (m,
5
00 : 1. Second, mPEG43-b-PHTMC50 was obtained by hydro-
genolysis reaction to result in the deprotection of side benzyl
groups for mPEG43-b-PBTMC50 using Pd/C and Pd(OH)
composite catalyst. Third, four LC copolymers mPEG43-b-
P(TMC-M 50 were synthesized through esterication reaction
2 8
rest of the protons from PCL, cholesteryl and –COO(CH ) COO–).
2
Results and discussion
Synthesis and characterization of chiral monomers
n
)
between side hydroxyl group of mPEG43-b-PHTMC50 and
terminal carboxyl group of the cholesteryl derivatives M –M ,
To investigate the effect of spacer length on molecular interac-
tion and physical properties of the chiral monomers and block
copolymers obtained in this study, as shown in Schemes 2 and
1
4
respectively, using DCC as the condensation agent and DMAP as
the catalytic system in dry dichloromethane. The copolymers
obtained in this study were soluble in common organic solvents
such as TFF, dichloromethane, and toluene. Their molecular
3, a series of chiral LC monomers with two, four, six, and eight
methylene segments were synthesized. Their chemical struc-
1
tures were characterized by FT-IR and H NMR spectra. To
1
structures were conrmed by FT-IR and H NMR spectra. The
reduce the bulky steric hindrance, improve the reactivities of
cholesterol, and obtain mesophase of the cholesteryl deriva-
tives, the commercially available cholesterol was allowed to be
structurally modied. The cholesteryl derivatives with different
longer spacer and more reactive terminal carboxyl group were
successfully synthesized by reacting cholesterol with an excess
amount of succinic anhydride, adipic acid, suberic acid and
sebacic acid, respectively. The crude products were puried by
silica gel column chromatography to result in a white powder as
the monomers. FT-IR spectrum of the monomers M –M
n
number average molecular weight (M ) and the polydispersity
index (PDI) of the block copolymers were detected by GPC.
Yields and average molecular weight of the obtained copoly-
mers are summarized in Table 1. The degree of polymerization
and molecular composition of the obtained block copolymer
1
were estimated from the H NMR spectra by comparing the
integrated signals in the –CH
.62 ppm for mPEG43. Aer the polymerization, the signal peaks
of methylene proton at 4.52–4.43 ppm for BTMC shied to 4.31–
.21 ppm for mPEG43-b-PBTMC50, moreover, the peaks of the
2
O– regions located at 3.67–
3
1
4
ꢁ
4
1
showed characteristic bands at 2960–2858 and 1737–1694 cm
chemical shis corresponding to the polymer were broad and
attributable to the C–H and ester C]O stretching bands,
1
respectively. H NMR spectra of M
1 4
–M showed peaks at the
characteristic resonances values of 5.39–5.36, 4.66–4.57, and
a
Table 2 The phase transition temperatures of the monomers
2
.69–0.68 ppm corresponding to olenic, –COOCH, and –CH
2
–
ꢀ
and –CH protons, respectively. The spectrum was agreed well
Phase transition temperature ( C) and enthalpy changes
3
ꢁ
1
with the proposed molecular structure of M –M . As an
(J g )
1
4
1
example, the H NMR spectra of M are shown in Fig. S1.†
1
Monomer
Heating cycle
Cooling cycle
M
M
1
2
K180.1(36.5)I
K139.5(54.7)Ch147.7(2.7)I
K129.5(20.5)Ch132.6 (—)I
K117.3(37.2)Ch119.8 (—)I
I151.3(43.2)K
Synthesis and characterization of the copolymers
I146.0(3.6)Ch96.6(21.1)K
I120.3(1.2)Ch55.2(10.2)K
I115.0(3.7)Ch99.4(33.2)K
b
At present, it is known that the ring-opening polymerization is M3
b
M
4
an efficient method for the preparation of biodegradable
aliphatic polycarbonates. The ring-opening polymerization of
a
b
K ¼ crystal; Ch ¼ cholesteric phase; I ¼ isotropic. Isotropic
the cyclic carbonate could be carried out in the presence of temperature determined by POM.
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1 4
Fig. 1 DSC curves of M –M on heating (a) and cooling (b) cycles.
Fig. 2 Optical textures of M
2
. (a) Oily streak texture of cholesteric
ꢀ
phase on cooling to 136 C; (b) focal conic texture of cholesteric phase
ꢀ
on cooling to 134 C.
consistent with the expected polymer structure. In addition,
compared with mPEG43-b-PBTMC50, the proton signals of
mPEG43-b-PHTMC50 at 7.32–7.26 and 4.72–4.58 ppm for benzyl
2 4
groups completely disappeared, which indicated that the benzyl exothermic peaks on cooling process. However, M –M all
groups were complete removed by hydrogenolysis reaction. The showed two endothermic peaks and two exothermic peaks, and
typical proton signals of mPEG, polycarbonate chains, and side exhibited enantiotropic cholesteric phase. In general, the
1
cholesteryl units could be observed. H NMR spectra of mPEG - formation of mesophases may be affected by aspect ratio, ex-
4
3
32,33
b-PBTMC , mPEG -b-PHTMC , and mPEG -b-P(TMC-M )
1 50
ible spacer at the center, and polarity of the monomers.
As
5
0
43
50
43
are shown in Fig. S2–S4.†
shown in Table 2, the chiral monomer M
1
with shorter exible
Liquid crystal properties of chiral monomers
a
Table 3 Thermal properties of the copolymers
The thermal behaviour and optical texture of the chiral mono-
mers obtained in this study were investigated with DSC and
POM. The corresponding phase transition temperatures,
enthalpy changes and phase sequence of M –M , obtained
1 4
during rst cooling and second heating scans, are summarized mPEG43-b-P(TMC-M )
ꢀ
Copolymer
Phase transition temperature ( C)
mPEG43-b-PBTMC50
mPEG43-b-PHTMC50
g ꢁ20.5 I
g ꢁ28.3 I
1 50
g 26.6 SmA 198.8 (4.7) I
g 10.2 SmA 148.9 (3.3) I
g 4.9 SmA 139.5 (3.1) I
g 1.5 SmA 123.4 (3.8) I
in Table 2. Typical DSC curves of M –M are shown in Fig. 1(a mPEG43-b-P(TMC-M
2
3
4
)
50
)
50
)
50
1
4
mPEG43-b-P(TMC-M
mPEG43-b-P(TMC-M
and b).
According to DSC curves of the chiral monomers, M
1
only
a
showed an endothermic peak on heating process and an
g ¼ glass state; SmA ¼ smectic A phase; I ¼ isotropic.
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Fig. 3 DSC curves of block LC copolymers.
spacer length did not reveal any mesophase, which was also
conrmed by POM result. However, the chiral monomer M –M
2
4
with longer exible spacer length all showed enantiotropic
cholesteric phase during heating and cooling cycles. This sug-
gested that the exible spacer length had a considerable inu-
ence on the thermal behaviour, mesomorphism, and molecular
arrangements of the chiral monomers. As seen from the data
listed in Table 2, with increasing the number of the exible
m
methylene, the corresponding melting temperature (T )
ꢀ
ꢀ
decreased from 180.1 C for M to 117.3 C for M , while the
1
4
ꢀ
isotropic temperature (T ) decreased from 147.7 C for M to
ꢀ
19.8 C for M . POM showed that M1 did not exhibit any
4
i
2
1
mesophase texture, while M
streak and focal conic textures of cholesteric phase. The typical
optical textures of M are shown in Fig. 2(a and b).
2 4
–M all exhibited enantiotropic oily
2
ꢀ
Fig. 5 XRD curves of M
2
at 142 C (a) and mPEG43-b-P(TMC-M
2
)
50 at
Liquid crystal properties of the copolymers
ꢀ
1
00 C (b).
The transition temperatures of the synthesized copolymers are
listed in Table 3. Their DSC curves are presented in Fig. 3. As
shown in Fig. 3, the copolymers mPEG43-b-PBTMC50 and
mPEG43-b-PBTMC50 only showed a glass transition because they
did not contain any mesogenic units. However, four copolymers
with side functionalized cholesteryl groups all revealed a glass
transition at low temperature and a smectic a (SmA) to isotropic
phase transition at high temperature. Although the monomer
M did not exhibit LC property, the corresponding copolymer
1
showed a SmA phase, and the fan-shaped texture was observed
by POM. This indicated that the copolymer mPEG43-b-P(TMC-
M )50 had high interaction between side chain units leading to
1
the generation of mesophase. Moreover, this behavior could be
attributed to an increased density of the mesogenic units in side
34
chain. The data listed in Table 3 revealed that three copoly-
mers incorporating chiral monomer M –M shown cholesteric
2
4
phase all exhibited SmA phases, which could be further
conrmed by fan-shaped texture observed by POM. This indi-
cated in many cases that the mesophase of side chain LC
polymers formed by the additional ordering on polymerization
2 50
Fig. 4 Optical textures of mPEG43-b-P(TMC-M ) .
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2 50
Fig. 6 Schematic representation of the SmA molecular arrangement of the pendant LC groups for mPEG43-b-P(TMC-M ) .
was more ordered than that the corresponding monomers. The Mesophase structure
results also suggested that the polymer chains might hinder the
formation of a helical supermolecular mesogenic structure and
an ordered organization into the mesophase. As an example, the
optical texture of mPEG43-b-P(TMC-M )50 is shown in Fig. 4.
2
In general, the mesomorphic properties of side chain LC
polymers depend on the nature of polymer backbone, exible
As known, XRD measurement is a powerful tool for recognizing
the mesophase organization in LC materials. To further identify
the mesophase structure of the synthesized monomers and
copolymers, the variable-temperature XRD studies were carried
out. Fig. 5(a and b) shows the representative XRD patterns of M
2
ꢀ
ꢀ
at 142 C (a) and mPEG43-b-P(TMC-M )50 at 100 C, respectively.
2
spacer, and mesogenic units. For four LC copolymers mPEG43
b-P(TMC-M ) , their glass transition temperature (T ) and T
i
-
In general, a sharp reection, corresponding to the periodic
distance, is characteristic of a smectic phase in which the
molecules are stacked into layer with short-range order within
the layers. A broad and weak peak corresponds to the distance
of the local arrangement between the neighboring mesogenic
n 50
g
were mainly affected by the spacer length because of same
polycarbonate backbone and cholesteryl mesogenic units. As
can be seen in Table 3, the inuence of methylene segment as
the exible spacer on the phase transition temperatures of the
copolymers revealed same tendency as those mentioned above
side groups. The XRD patterns of M
2
–M
4
showed a broad peak
ꢀ
only at around 2q ¼ 17 , which a typical cholesteric character-
istic according to oily streak and focal conic texture observed
with POM. However, the XRD patterns of four LC copolymers
mPEG -b-P(TMC-M ) all revealed a sharp and intense peak at
for the chiral monomers, that is to say, T
g i
and T of four
copolymers mPEG43-b-P(TMC-M 50 all decreased with
n
)
increasing methylene segment spacer. Furthermore, the meso-
4
3
n 50
phase temperature ranges of the copolymers mPEG -b-P(TMC-
4
3
a low angle region and a weak and diffuse peak at a wide angle
region, respectively. As an example, the XRD pattern of mPEG43
b-P(TMC-M 50, shown in Fig. 5(b), revealed a sharp and strong
M ) were greater than those of the corresponding monomers,
n 50
-
which indicated the polymerization could further stabilize and
widen the mesophase ranges.
2
)
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Table 4 TGA data of the copolymers
Weight loss/%
a
d
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
Copolymer
T
/ C
200 C
250 C
300 C
350 C
400 C
mPEG43-b-PBTMC50
mPEG43-b-PHTMC50
279
195
303
288
286
312
2.0
6.9
—
1.4
—
2.9
59.2
—
2.1
2.0
—
11.8
68.8
4.6
6.1
6.2
89.3
71.9
42.2
32.3
20.8
12.8
97.5
84.2
95.6
79.8
77.4
61.2
mPEG43-b-P(TMC-M
mPEG43-b-P(TMC-M
mPEG43-b-P(TMC-M
mPEG43-b-P(TMC-M
1
)
50
)
50
)
50
)
50
2
3
4
—
4.0
a
Temperature at which 5% weight loss occurred.
ꢀ
peak at 2q ¼ 2.08 , corresponding to the layer d-spacing value of which easily result in the occurrence of thermal decomposi-
ꢀ
ꢀ
ꢀ
4
6.3 A at 100 C, implying a smectic structure of the copolymer. tion or degradation. However, the T
d
increased from 195 C
ꢀ
Furthermore, a fan-shaped texture, as shown in Fig. 4, was for mPEG43-b-PHTMC50 to 279 C for mPEG43-b-PBTMC50
clearly observed with POM, which is a characteristic texture of with side phenyl groups. This result indicated that the exis-
a SmA phase. According to the molecular modeling calculation tence of phenyl segments could increase the intermolecular
using ChemBio3D-Ultra, employing MM2 energy parameters, p–p interaction between side repeating units, form resonance
the estimated all-trans molecular length L of the most extended structures with the polycarbonate backbones to stabilize or
ꢀ
conformation of mPEG -b-P(TMC-M ) is about 26.1 A. A d/L deactivate the radical species, and enhance the resistance of
4
3
2 50
ratio of 1.79 (L < d < 2L) was calculated, indicating an inter- the polymers against thermal degradation. According to
digitated molecular arrangement of the mesogenic groups Fig. 7, four LC copolymers all had higher thermal stability,
within the smectic layers. This partial bilayer structure was moreover, the thermal weight loss or thermal degradation
similar to the SmA
results were also reported.
d
phase formed by polar mesogens. Similar showed a decreased tendency with increasing the exible
35,36
The schematic representation of spacer length of the side functionalized cholesteryl groups.
the molecular arrangement of the pendant LC groups (a) and The fast thermal decomposition of four LC copolymers
ꢀ
SmA arrangements model of the interdigitated SmA layer (b) for appeared between 300 and 400 C. When the temperature
ꢀ
mPEG -b-P(TMC-M ) are shown in Fig. 6.
increased to 400 C, the corresponding weight loss was 95.6%,
4
3
2 50
7
9.8%, 77.4%, and 61.2%, respectively. The results also sug-
Thermal stability
gested that the existence of the longer mesogenic side chain
might cause a strong interaction between the repeating units
and entanglement of the polymer chains, which lead to an
The thermal stability of the copolymers was also studied with
TGA under nitrogen atmosphere, and the corresponding
thermal decomposition and weight loss data are summarized in
Table 4. Fig. 7 shows TGA curves of six copolymers.
3
3,37
increase of thermal resistance.
As can be clearly seen in Table 4, the temperatures at which
Conclusions
5
1
% weight loss occurred (T
d
) of mPEG43-b-PHTMC50 was only
ꢀ
95 C due to the existence of side active hydroxyl groups,
Four new LC amphiphilic polycarbonates with side functional-
ized cholesteryl groups were synthesized and characterized. The
LC copolymers obtained in this study all exhibited an enantio-
tropic fan-shaped texture of a SmA phase, and showed an
interdigitated molecular arrangement of the mesogenic groups
within the smectic layers. Although these chiral monomers
showed the cholesteric phases, the corresponding copolymers
showed smectic phases. With increasing the exible spacer
length, the corresponding Tg and T all showed a decreased
i
tendency. Furthermore, the mesophase ranges of the copoly-
mers were greater than those of the chiral monomers. In
addition, four LC copolymers all had higher thermal stability,
and the thermal weight loss showed a decreased tendency with
an increase of the exible spacer length. In summary, the
amphiphilic LC copolymers based on polycarbonate backbone
revealed mesophase state below body temperature, which was
expected to be used clinically as a new self-assemble material
for applications in controlled drug delivery to specic tumor
site and so on.
Fig. 7 TGA curves of block copolymers.
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1
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