O R I G I N A L P A P E R
Synthesis of comb-type amphiphilic graft copolymers
derived from chlorinated poly(e-caprolactone) via click
reaction
Timur S¸anal1•I˙zzet Koc¸ak1•Baki Hazer1
Received: 12 November 2015 / Revised: 3 July 2016 / Accepted: 11 July 2016 / Published online: 23 July 2016
Ó Springer-Verlag Berlin Heidelberg 2016
Abstract This work refers to the synthesis of a series of novel chlorinated
poly(e-caprolactone) (PCL) for further functionalization of PCL. For this aim, chlorine gas was passed through into the chloroform solution to obtain chlorinated polycapro-lactone. The chlorine contents in chlorinated PCL were between 0.9 and 1.6 mol%.
The molecular weights of the polymers (Mn) changed from 4853 to 9497 g/mol. As
the amount of passing chlorine gas increases, the molecular weight of the chlori-nated PCL was found to decrease. Pendant chloride groups of PCL were reacted
with sodium azide to prepare PCL with pendant azide groups (PCL-N3).
Poly-(ethylene glycol) methyl ether (mPEG) was reacted with propargyl chloride to achieve alkynyl mPEG (mPEG-alkyn). Click reaction was then carried out by the
reaction between PCL-N3 and mPEG-alkyn to obtain PCL-g-PEG comb-type
amphiphilic graft copolymer. Interestingly, SEM images of the PCL-g-PEG comb-type amphiphilic graft copolymers showed the highly microporous structure. The
resulting products were characterized by 1H NMR, FT-IR, gel-permeation
chro-matography, SEM, surface tension, contact angle and water uptake measurements, differential scanning calorimeter and thermogravimetric analyses techniques.
Keywords Chlorinated polycaprolactone Porous polymer Click reaction
Amphiphilic copolymer Surface tension
Electronic supplementary materialThe online version of this article (doi:10.1007/s00289-016-1757-5) contains supplementary material, which is available to authorized users.
& Baki Hazer bkhazer@beun.edu.tr
1
Department of Chemistry, Bu¨lent Ecevit University, 67100 Zonguldak, Turkey DOI 10.1007/s00289-016-1757-5
Introduction
The preparation of well-defined macromolecular architectures, such as block, graft or star copolymers, has recently been one of the popular research areas of the polymer science. There has been a growing attention amongst the researchers towards the graft copolymers owing to their exceptional physical and chemical attributes. As there are also numerous types of polymer backbone and branches, it allows us to improve the properties of the corresponding material in wide range of
the polymer backbone [1–13].
These materials are, therefore, of potential interest in various areas, such as
polymeric biomaterials [14], nanocomposites [15, 16], drug delivery [17–19] and
tissue engineering [20,21] depending on the chemical nature of the backbone and
the side chains.
Amphiphilic graft copolymers containing hydrophobic and hydrophilic blocks are a class of functional polymers for the application in structural control of
materials interfaces [22–25].
The Cu (I)-catalyzed Huisgen 1,3-dipolar cycloaddition between terminal alkynes and azides is frequently used in click reaction. It has been widely used in the synthesis of the various types of block and graft copolymers, functionalized
polymers, telechelics and new macromonomers [26–31].
The click reaction has rapidly become one of the most popular reactions, because of its high selectivity, high yields, mild reaction conditions, little or no by-products and broad functional group tolerance. For these reasons, azide–alkyne coupling reactions have provided an appealing approach to the modification of biodegradable polyesters. Linear aliphatic polyesters and their copolymers also have outstanding features such as biodegradability, biocompatibility and excellent membrane forming ability, which allows to be used in biomedical applications, tissue engineering and
polymer-based biomaterials [32,33].
Poly(e-caprolactone) (PCL) is one of the linear aliphatic polyesters and has degradation and resorption kinetics, slower than other aliphatic polyester owing to
its high degree of crystallinity and hydrophobic character [34]. The introduction of
hydrophilic blocks into PCL chains enhances hydrophilicity and biodegradability. PEG can be used as a promising material for biomedical applications due to its low
toxicity, good hydrophilicity, excellent biocompatibility and biodegradability [35].
Over last decade, amphiphilic copolymers that possess PEG as hydrophilic block and biodegradable polyesters as hydrophobic block have widely been preferred by the researchers since their biomedical applications because of their excellent
biocompatibility, biodegradability and low toxicity [36–41]. PEG-b-PCL, and
mPEG-b-PCL block copolymers have been extensively investigated for use in
medical applications such as drug delivery systems [42–45].
We have recently reported the comb-type amphiphilic graft copolymers using
RAFT [46,47].
Williamson reaction [48], coordination polymerization [49], and thiol-ene photo
click reactions [50]. Similar procedures for the preparation of amphiphilic graft
polyesters were reported by Su et al. [51]. Polyester-g-PEG copolymers prepared using a,x-PEG-1100-monomethyl ether azide were reported by Parrish and
co-workers [52]. PCL-g-PEG copolymers were synthesized by combination of ROP
and Click chemistry by Zhang et al. [53].
We have recently modified poly-3-hydroxy alkanoates with pendant chlorides
[55,56]. Motivation of this work is to chlorinate biodegradable polyester, PCL, and
to modify the chlorinated polyester with polyethylene glycol to obtain the first amphiphilic comb-type graft copolymer. PCL-g-PEG2000 and PCL-g-mPEG2000 comb-type amphiphilic graft copolymers were obtained by click coupling reactions. In this manner, PCL with pendant azides obtained from its related chlorides was reacted with PEG2000 containing propargyl terminal group to obtain novel comb-type amphiphilic graft copolymers. Optic, thermal and physicochemical character-izations of the novel comb-type amphiphilic graft copolymers were performed in detail.
Experimental
MaterialsPoly(ethylene glycol) methyl ether (mPEG) (Mn: 2000, Aldrich) was purified by
re-crystallization in dichloromethane/diethyl ether system. Poly(ethylene glycol) 2000
(Merck) was dried in vacuum oven for 24 h. Poly(e-caprolactone) (Mn 70,000,
Aldrich), Sodium azide (Sigma), Propargylamine (98 %, Aldrich), CuBr (99.9 %, Aldrich) and Propargyl Chloride (70 wt% in toluene, Aldrich),
4-dimethylaminopy-ridine (DMAP, 99 %, Aldrich), 2,20-azobisisobutyronitrile (AIBN, Fluka A.G.),
n-hexane (Sigma-Aldrich), hydrochloric acid (37 %, Sigma-Aldrich) and potassium
permanganate (Sigma-Aldrich) were used as received. N,N,N0,N00,N00
-Pen-tamethyldiethylenetriamine (PMDETA, 99 %, Aldrich) was distilled over NaOH
prior to use. N,N0-Dicyclohexylcarbodiimide (DCC, 99 %, Aldrich tetrahydrofuran
(THF, C99.9 %, Sigma-Aldrich) was dried and distilled from benzophenone-Na. N,N-Dimethylformamide (DMF, 99.8 %, Sigma-Aldrich) was dried and distilled
under vacuum over CaH2. Dichloromethane (CH2Cl2, Sigma-Aldrich) was dried and
distilled over P2O5.
Instrumentation
Fourier-transform infrared spectroscopy (FT-IR) spectra were recorded using a
Perkin Elmer Pyris model FT-IR spectrometer.1H-nuclear magnetic resonance (1
H-NMR) spectra of the samples in CDCl3as the solvent, with tetramethylsilane as the
internal standard, were recorded using an Agilent Premium Compact, ultralong hold time 600 MHz NMR spectrometer. The molecular weights and molecular weight distributions were measured with a Malvern Viscotek gel-permeation chromatog-raphy (GPC) and OmniSEC 4.7 Software Systems with THF as the solvent at a flow
rate of 1 mL min-1. A calibration curve was generated with eight polystyrene
2.91 9 104, 5.87 9 103, and 955 g mol-1 of low polydispersity. The thermal properties of the polymers were characterized by thermogravimetric analysis and differential scanning calorimetry. Thermogravimetric analyses (TGA) of the polymers were carried out using an SIIQ TG/DTA 7200 model instrument to determine thermal degradation. Dried sample was heated under nitrogen atmosphere
from 25 to 600°C at a heating rate of 10 °C/min. Differential scanning calorimeter
(DSC) traces of the polymer samples were obtained using a Perkin Elmer Jade series thermal analysis system. Dried sample was heated under nitrogen from -50 to
100°C at a rate of 10 °C/min. The surface morphology of the freeze-dried samples
were analyzed by FEI-SEM Quanta 200F (Philips) at an accelerated voltage of 5 kV. Surface tension values of the copolymers were measured via Du Nouy method using PHYWE P2140500 set. Elemental analysis measurements were carried out using Leco Truspec Micro CHNS instrument. Contact angle measure-ments were obtained using a Canon 1D Mark IV camera and Canon 180 mm macroobjective.
Chlorination of polycaprolactone
10 g of Polycaprolactone (Mn: 70,000 g/mol) was dissolved in 100 mL of carbon
tetrachloride (CCl4). 100 mg of AIBN was added to the reaction mixture. After
stirring 1 h at room temperature, chlorine gas formed by the reaction of sulfuric acid with potassium permanganate was passed through the solution under sunlight with variable periods. The product was then precipitated by pouring into hexane dropwise. The obtained polymer was purified by two successive precipitations using THF as a solvent and hexane as a non-solvent and then dried under vacuum at room temperature for 24 h.
Synthesis of azide-terminated polycaprolactone (azide-PCL)
Chlorinated polycaprolactone (Mn: 11,057) (10 g, 0.85 mmol), sodium azide
(0.34 g, 5.3 mmol) and DMF (50 mL) were mixed and stirred at room temperature for 24 h. After removing DMF, the product dissolved with THF and then precipitated into hexane three times.
Preparation of alkynyl-terminated poly(ethylene glycol) (alkynyl-PEG) General procedure employed for the preparation of alkynyl-PEG was as follows
[36].
Poly(ethylene glycol) (2.0 g, 1 mmol) was dissolved in 20 mL of anhydrous THF, and then converted into sodium alkoxide by reaction with sodium hydride
(0.12 g, 3 mmol) at 30°C for 2 h. Propargyl chloride (70 wt% in toluene, 0.36 mL,
5 mmol) was added to the mixture, which was refluxed for 12 h. Then the solution concentrated and the product precipitated into diethyl ether three times. The same procedure was carried out using propargyl amine (2.97 mL, 28 mmol) in the same ratio.
Preparation of alkynyl-terminated poly(ethylene glycol) methyl ether (alkynyl mPEG)
The procedure applied for the synthesis of mPEG was followed as given in the
literature [54].
Briefly, mPEG (Mn: 2000) (2.0 g, 1 mmol) was dissolved in 20 mL of
dichloromethane. Propargyl amine (0.32 mL, 5 mmol) and DMAP (0.12 g, 1 mmol) were successively added to the reaction mixture. After stirring 30 min at
room temperature, a solution of DCC (1.03 g, 5 mmol) in 10 mL of CH2Cl2was
added to the reaction mixture and stirred overnight at room temperature. After filtration of salt, the solution was concentrated and the product was purified by
column chromatography over silica gel eluting with CH2Cl2/ethyl acetate mixture
(1:10). The same procedure was carried out using propargyl chloride (70 wt% in toluene) (0.53 mL, 5 mmol) in the same ratio.
Click reaction of PCL with mPEG or PEG2000
Click coupling reactions of azide-terminated polycaprolactone (PCL-N3) and
alkyne-terminated poly(ethylene glycol) (PEG-prpg) or poly(ethylene glycol) methyl ether (mPEG-prpg) were carried out using CuBr/PMDETA catalyst. mPEG-prpg (or PEG-prpg) (0.2 g, 0.08 mmol), PMDETA (230 lL, 1.1 mmol), DMF (7 mL) and PCL-N3 (0.5 g, 0.04 mmol) were added into a Schlenk tube. The mixture was degassed by three freeze–evacuate–thaw cycles and backfilled with Ar. 0.1 g CuBr was then added under argon and the Schlenk tube was sealed. The click reaction was carried out at room temperature for 36 h, and then the polymer solution was diluted with chloroform and passed through alumina column to remove copper salt. The polymer solution was concentrated and precipitated in cold diethyl ether, repeatedly two times.
Preparation of polymer films
0.5 g of copolymer was dissolved in 10 mL chloroform. The solution was poured into a Petri dish (/ = 5 cm) and paper sealed over the Petri dish. The solvent was allowed to evaporate leaving a thin polymer film and then dried under vacuum at room temperature for 24 h. The same procedure was repeated for all samples.
Results and discussion
Copolymer synthesis and discussion
In this study, we prepared for the first time a series of the chlorinated PCL to obtain amphiphilic graft copolymers and investigate the effects of structural alterations on their thermal and physicochemical behaviors. Primarily, a fixed amount of polycaprolactones is periodically reacted with chlorine gas. Then, chlorinated polycaprolactone is allowed to react with sodium azide to yield azide functionalized
polycaprolactone. On the other hand, mPEG was reacted with propargyl chloride to obtain alkynyl mPEG. Click reaction was then performed between modified PCL and mPEG to prepare amphiphilic graft copolymers. The same reaction was repeated using PEG2000 and propargyl amine to obtain amphiphilic comb-type graft copolymer. Synthetic routes employed for the preparation of PCL-g-PEG
amphiphilic graft copolymer are shown in Scheme1. The synthesis of the
alkynyl-terminated PEG using propargyl chloride was shown in supporting information (Figure S1). We believe that all chlorine is replaced with azide due to the fact that elemental analysis results obtained for nitrogen in azide functionalized PCL is found
to be quite consistent with1H NMR results.
Chlorinated PCL samples were obtained by passing the chlorine gas through the PCL solution with changing times under sunlight. The molecular weights of the
polymers (Mn) changed from 4853 to 9497 g/mol. As the amount of passing
chlorine gas increases, the molecular weight of the chlorinated PCL was found to decrease. The alteration of the molecular weights of the chlorinated polymers versus chlorine gas transition time and the percentage of chlorine is shown in supporting
information (Figure S2). Table1 summarizes results of the chlorination of
polycaprolactone under sunlight. The percentage of chlorine was calculated from
integration values by1H NMR spectra.
The chlorinated PCLs reacted with NaN3 to introduce azido units. Table2
summarizes results of the reaction of chlorinated polycaprolactone (PCL-Cl) with sodium azide (NaN3). The percentages of chlorine and nitrogen were calculated
from integration values by 1H NMR spectra which are shown in Figure S3 in
supporting information.
The introduction of chlorine and azido units were also confirmed both by 1H
NMR and FT-IR analysis, in agreement with the cited literature [55–57]. The
characteristic chlorine signal and azido unit were observed at 770 and 2106 cm-1,
respectively.
Figure1 shows the 1H NMR spectra of PCL, PCL-Cl and PCL-N3. The
characteristic chemical shift of the chloride units was observed at 3.5–3.8 ppm. The resonance of the methine close to the azido group was found at 3.6 ppm, supporting a
complete functionality transformation [40]. Because when NMR measurements for
Table 1 Chlorination of poly(e-caprolactone) under sunlight Run no. Chlorine gas transition
time (min) Mw Mn Chlorine (mol%) PCL-Cl-1 10 12,594 9497 0.9 PCL-Cl-2 40 11,904 9493 0.9 PCL-Cl-3 60 11,655 8919 1.0 PCL-Cl-4 90 10,790 8354 1.1 PCL-Cl-5 120 7066 4853 1.6
Table 2 Synthesis of alkyn-functionalized poly(ethylene glycol) or poly(ethylene glycol) methyl ether Run no. mPEG
(mmol) PEG2000 (mmol) Propargyl amine (mmol) Propargyl chloride (mmol) Mn (g/mol) Mw (g/mol) PDI Yield g wt% mPEG- prpg-amide-1 1.0 – 5.0 – 2472 2655 1.07 2.01 88 mPEG- prpg-ester-1 1.0 – – 5.0 2335 2586 1.10 2.18 92 PEG- prpg-amide-2 – 1.0 5.0 – 2216 2507 1.13 2.03 89 PEG- prpg-ester-2 – 1.0 – 5.0 2487 2636 1.06 2.19 92
chlorinated polymer are carried out, 8.6 % of chlorine is determined. Subsequent to chlorination process, we attempted to replace chlorine with azide functionality and the elemental analysis measurement of obtained azide functionalized polymer is performed. It was found that there is 8 % of nitrogen. These results can be considered as clear evidence for the transformation of chlorine to azide functionality.
Figure2shows the GPC chromatogram of the PCL, chlorinated polycaprolactone
and polycaprolactone with pendant azide group. GPC chromatograms were
unimodal. The molecular weights (Mn) were 70,000, 9497 and 9581 g/mol for
PCL, PCL-Cl-1 and PCL-N3-1, respectively.
In the second step of the work, poly(ethylene glycol), similarly poly(ethylene glycol) methyl ether were reacted with propargyl amine or propargyl chloride to obtain alkynyl-PEG or mPEG, respectively. The results of the reactions are
presented in Table2.
The introduction of propargyl units were also confirmed by both1H NMR and
FT-IR analysis, which is in good agreement with the cited literature [58–60].
Typical acetylene group (–C:CH) signal at 2118 cm-1and terminal acetylenic C–
H signal at 3324 cm-1appeared in alkynyl-PEG (or mPEG) samples, which verify
the expected chemical structure.1H-NMR spectrum exhibits structural
character-istics of acetylene unit. The signal of terminal acetylene proton (–C:CH), appears at 2.50 ppm, and the two protons of the propargyl part (–CH2–C:CH) were noted at 4.7 ppm.
Fig. 1 1H NMR spectrum of PCL, chlorinated polycaprolactone and polycaprolactone with pendant azide group
GPC chromatograms of the alkynyl poly(ethylene glycol) and poly(ethylene glycol) methyl ether were also found to be unimodal. The molecular weights of the
polymers (Mn) changed from 2216 to 2487 g/mol. GPC chromatograms of these
substances can be seen in the supporting information.
Click reaction was performed to obtain amphiphilic graft copolymer between azide-terminated polycaprolactone and alkyne-terminated poly(ethylene glycol) or poly(ethylene glycol) methyl ether, respectively. The results of the corresponding
reactions are presented in Table3. Graft copolymers were obtained with narrow
molecular weight distributions. In the studies made with propargyl amine, we have achieved results which were obtained in studies with propargyl chloride.
The structural characteristics of the graft copolymers were evaluated using1H
NMR spectrometry. Figure3shows 1H NMR spectrum of the PCL-g-PEG-2 graft
copolymer. The characteristic signals of each segments of the graft copolymer obtained were observed in this spectrum. Chemical shifts in PCL units can be assigned to the signal of independent methylene protons at 1.2–1.6 ppm, at 2.2 ppm to carboxyl group adjacent to methylene protons and at 4.0 ppm they can be assigned to oxygen atoms in acyloxy group adjacent to methylene protons, poly(ethylene glycol) were observed at 3.6 and 7.9 ppm for triazole protons.
The FT-IR spectrum of the g-PEG-2 was compared with those of PCL,
PCL-N3and PEG-prpg-1 in Fig.4. The characteristic signal of azido unit was observed at
2106 cm-1. Typical acetylene group (C:C) signal at 2118 cm-1 and terminal
acetylenic:C-H signal at 3324 cm-1appeared in alkynyl-PEG (or mPEG) samples,
which confirm the anticipated chemical structure [58]. Both of the characteristic peaks
of PCL and PEG (or mPEG) segments were observed in the spectra of diblock copolymers. The characteristic peaks of triazole unit were observed at 1625 and
1470 cm-1 [61, 62]. The peaks, which are related to PCL, as seen at 1721 and
1237 cm-1, respectively, belong to the carbonyl stretching peak and asymmetric C–O–
C stretching peak. Besides, C–H stretching vibration at 2866 cm-1, –OCH2CH2unit at
1107 cm-1and C–O–C stretching at 1065 cm-1prove the existence of PEG [63,64].
Tabl e 3 Syn thesis of PC L-g -mPEG or PCL-g -PEG amp hiphili c graft copol ymers Run no. PCL-N 3 PEG-pr pg CuBr (g) PM DETA (l l) Mn (g/mol) Mw (g/mol) PDI Yield (g) g M n mPEG-p rpg prpg-P EG-prpg Amide (g) Este r (g) Amide (g) Este r (g) PC L- g-mPEG-1 0.5 9581 0.2 – – – 0.1 230 22,0 22 31,1 46 1.41 0.61 PC L- g-mPEG-2 0.5 9581 – 0.2 – – 0.1 230 18,9 97 27,9 18 1.47 0.58 PC L- g-PEG -1 0.5 9581 – – 0.2 – 0.1 230 18,6 43 30,4 51 1.63 0.62 PC L- g-PEG -2 0.5 9581 – – – 0.2 0.1 230 16,1 70 26,9 06 1.66 0.60
Thermal analysis of PCL-g-mPEG and PCL-g-PEG amphiphilic graft copolymers
Thermogravimetric methods were employed to explore the thermal analysis
properties of PCL-g-mPEG and PCL-g-PEG amphiphilic graft copolymers. Tm
values generated from the DSC curves of the amphiphilic graft copolymers are
shown in Fig.5. Two very close melting transitions related to mPEG and PCL
blocks [65] were observed in DSC thermograms.
Tmvalues of mPEG and PEG are very close to each other (approximately 56°C).
No glass transition in the resulting graft copolymer was observed, which might be linked to their crystallizable ability.
TGA measurements were also carried out to explore thermal stability of the graft copolymers. In our work, the thermal decomposition stability of the amphiphilic graft copolymers were investigated by taking mass loss into account, arising from volatile substances generated as a consequence of increasing temperature. The temperature of thermal decomposition, the percentage of weight loss and the temperature at the maximum decomposition rate for the each amphiphilic graft
copolymers obtained from the TGA curves are shown in Fig.6. The similar TGA
curves were also obtained for the graft copolymers.
DSC and TGA curves of the PCL-g-mPEG-1, PCL-g-mPEG-2 and
PCL-g-PEG-1, PCL-g-PEG-2 in Table4 were studied in view of the thermal analysis.
The internal morphologies of the PCL-g-PEG or PCL-g-mPEG graft copolymers containing varying percentages of poly(ethylene glycol) were studied by SEM.
Figure7shows the SEM images of the cross-sectional view of the freeze-dried graft
copolymers. There was observed a distinct difference in pore size in each image. It was measured by the SEM device that the pore sizes of the polymers ranged between 350 and 400 nm.
All copolymer films have the microporous structure. PEG content in the film also affects the morphologies. As the PEG concentration increases, the pores and their size in the cross sections increase, which can be associated with the chain flexibility of the grafted polycaprolactone. Poly(ethylene glycol) or poly(ethylene glycol)
Fig. 5 DSC thermograms of the graft copolymers: a g-PEG-1, b g-PEG-2, c 1 and d PCL-g-mPEG-2
methyl ether may also have plasticization effect on polymer and its chain flexibility
[66].
The hydrophilic character of the graft copolymers was also explored by the water drops on the polymer films. 2 cm 9 2-cm-thick sections were taken from the 0.1-mm films of the copolymers. 1 drop of deionized water was dripped on the polymer and after 10 s its photo was taken from a fixed point with a professional camera. The
angle measurement was done with a goniometer on the captured images. Figure8
shows the photographs of the water drops on the graft copolymer films. Less than 90° contact angles for the graft copolymers indicates the increase in hydrophilicity,
while PCL have more than 90° contact angles due to hydrophobic nature [50,67].
As the percentage of PEG in the copolymer increases, the propagation velocity of the water droplets increases as well.
Water uptake studies of the graft copolymers were performed by dipping the polymer films into the water for 2 days. Water absorption values ranged from 19 to
53 %. The highest value of water absorption was obtained in the PCL95-g-PEG56-1
graft copolymer which was containing the maximum PEG.
Surface tension measurements were carried out at 20°C. Each value was given
as the average of three readings. The measurements of graft copolymers for surface
tension are shown in Table5. As the amount of PEG in the copolymer increases,
surface tension decreases (Table5). The maximum surface tension value was
observed in PCL95-g-mPEG52-2 which contains higher PEG blocks.
Fig. 6 TGA curves of PCL-g-mPEG or PCL-g-PEG graft copolymers (DT/Dt: 10°C/min under N2):
a PCL-g-mPEG-1, b PCL-g-mPEG-2, c PCL-g-PEG-1 and d PCL-g-PEG-2
Table 4 Tmand Tdvalues the
PCL-g-mPEG and PCL-g-PEG graft copolymers
Run no. Tm1 Tm2 Td(°C) Tonset(°C)
PCL-g-mPEG-1 56.1 57.7 411 340 PCL-g-mPEG-2 55.7 58.2 412 345
PCL-g-PEG-1 56.5 58.0 416 353
Fig. 7 SEM images of the fractured surfaces of the freeze-dried amphiphilic comb-type graft copolymers: PCL-g-mPEG-1 [bar 100 lm (a), 20 lm (b)]; PCL-g-mPEG-2 [bar 100 lm (c), bar 20 lm (d)]; PCL-g-PEG-1 [bar 100 lm (e), 20 lm (f)] and PCL-g-PEG-2 [bar 100 lm (g), 20 lm (h)]
Conclusions
Chlorination of PCL opens for new strategies for the functionality of the poly(e-caprolactone) such as click reaction. Well-defined amphiphilic comb-type graft copolymers composed of a PCL backbone and PEG or mPEG side chains were prepared by the click reactions. The hydrophilicity of the amphiphilic copolymers increases with increasing PEG content in the copolymer. Besides, it was illustrated that the contact angle decreases due to increasing PEG content. The average size of pores is found to be directly related to the PEG content in the copolymer. The porous amphiphilic polymers can be very promising biomaterials for drug delivery system.
Acknowledgments This work was supported by Bu¨lent Ecevit University Research Fund (#BEU-2012-10-03-13), TUBITAK (Grant # 211T016) and TUBITAK 2211—A National Scholarship Programme for Timur S¸anal (PhD Student).
References
1. Bates FS, Fredrickson GH (1990) Block copolymer thermodynamics: theory and experiment. Annu Rev Phys Chem 41:525–557
Table 5 Surface tension measurements of the graft copolymers
Run no. Surface tension (dyne/cm)
PCL95-g-mPEG55-1 22.8
PCL95-g-mPEG52-2 36.0
PCL95-g-PEG56-1 12.6
PCL95-g-PEG50-2 33.6
Fig. 8 Photographs of the water drops on the amphiphilic graft copolymer films: a PCL95
2. Hadjichristidis N, Iatrou H, Pispas S, Pitsikalis M (2000) Anionic polymerization: high vacuum techniques. J Polym Sci A Polym Chem 38:3211–3234
3. Hawker CJ, Bosman AW, Harth E (2001) New polymer synthesis by nitroxide mediated living radical polymerizations. Chem Rev 101:3661–3688
4. Hazer B (1990) Cationic polymerization of tetrahydrofuran initiated by difunctional initiators. Synthesis of block copolymers. Eur Polym J 26:1167–1170
5. Ito S, Goseki R, Manners I, Ishizone T, Hirao A (2015) Successive synthesis of multiarmed and multicomponent star-branched polymers by new iterative methodology based on linking reaction between block copolymer in-chain anion and a-phenylacrylate-functionalized polymer. Macromol Chem Phys 216:1523–1533
6. Kamigaito M, Ando T, Sawamoto M (2001) Metal-catalyzed living radical polymerization. Chem Rev 101:3689–3746
7. Kim JG, Cowman CD, LaPointe AM, Wiesner U, Coates GW (2011) Tailored living block copolymerization: multiblock Poly(cyclohexene carbonate)s with sequence control. Macromolecules 44:1110–1113
8. Lodge TP (2003) Block copolymers: past successes and future challenges. Macromol Chem Phys 204:265–273
9. Matyjaszewski K, Xia J (2001) Atom transfer radical polymerization. Chem Rev 101:2921–2990 10. Ruzette AV, Leibler L (2005) Block copolymers in tomorrow’s plastics. Nat Mater 4:19–31 11. Yildiz U, Hazer B, Tauer K (2012) Tailoring polymer architectures with macromonomer
azoinitia-tors. Polym Chem 3:1107–1118
12. Reddy KR, Sina BC, Ryua KS, Kimb JC, Chungc H, Leea Y (2009) Conducting polymer func-tionalized multi-walled carbon nanotubes with noble metal nanoparticles: synthesis, morphological characteristics and electrical properties. Synt Met 159:595–603
13. Reddy KR, Hassan M, Gomes VG (2015) Hybrid nanostructures based on titanium dioxide for enhancedphotocatalysis. Appl Catal A-Gen 489:1–16
14. Lee H, Zeng F, Dunne M, Allen C (2005) Methoxy poly(ethylene glycol)-block-poly(d-valerolac-tone) copolymer micelles for formulation of hydrophobic drugs. Biomacromolecules 6:3119–3128 15. Dao TD, Oh KM, Choi JT, Hi Lee, Jeong HM, Kim YS, Park SJ, Kim BK (2012) The effect of
oxidation on properties of graphene and its polycaprolactone nanocomposites. J Nanosci Nan-otechnol 12:8420–8430
16. Reddy KR, Lee KP, Kim JY, Lee Y (2008) Self-assembly and graft polymerization route to monodispersed Fe3O4@SiO2—polyaniline core-shell composite nanoparticles: physical properties. J Nanosci Nanotechnol 8:5632–5639
17. Hazer DB, Kılıc¸ay E, Hazer B (2012) Poly(3-hydroxyalkanoate)s: diversification and biomedical applications: a state of the art review. Mater Sci Eng C Mater Biol Appl 32:637–647
18. Kılıc¸ay E, Demirbilek M, Tu¨rk M, Gu¨ven E, Hazer B, Denkbas E (2011) Preparation and charac-terization of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHX) based nanoparticles for targeted cancer therapy. Eur J Pharm Sci 44:310–320
19. Zhang K, Tang X, Zhang J, Lu W, Lin X, Zhang Y, Tian Bi Yang H, He H (2014) PEG–PLGA copolymers: their structure and structure-influenced drug delivery applications. J Control Release 183:77–86
20. Carfı` Pavia F, La Carrubba V, Brucato V, Palumbo FS, Giammona G (2014) Synthesis, character-ization and foaming of PHEA–PLLA, a new graft copolymer for biomedical engineering. Mater Sci Eng C Mater Biol Appl 41:301–308
21. Hazer DB, Hazer B, Dinc¸er N (2011) Soft tissue response to the presence of polypropylene-G-poly(ethylene glycol) comb-type graft copolymers containing gold nanoparticles. J Biomed Biotechnol 2011:956169-1–956169-7. doi:10.1155/2011/956169
22. Li Z, Tan BH (2014) Towards the development of polycaprolactone based amphiphilic block copolymers: molecular design, self-assembly and biomedical applications. Mater Sci Eng C Mater Biol Appl 45:620–634
23. Lutz PJ, Peruch F (2012) Graft copolymers and comb-shaped homopolymers. In: Matyjaszewski K, Mo¨ller M (eds) Polymer science: a comprehensive reference. Elsevier, Amsterdam, pp 511–542 24. Maksym-Be˛benek P, Biela T, Neugebauer D (2014) Synthesis and investigation of monomodal
hydroxy-functionalized PEG methacrylate based copolymers with high polymerization degrees. Modification by ‘‘grafting from’’. React Funct Polym 82:33–40
25. Williams RJ, Pitto-Barry A, Kirby N, Dove AP, O’Reilly RK (2016) Cyclic Graft copolymer uni-molecular micelles: effects of cyclization on particle morphology and thermoresponsive behavior. Macromolecules 49:2802–2813
26. Golas PL, Matyjaszewski K (2010) Marrying click chemistry with polymerization: expanding the scope of polymeric materials. Chem Soc Rev 39:1338–1354
27. Iha RK, Wooley KL, Nystro¨m AM, Burke DJ, Kade MJ, Hawker CJ (2009) Applications of orthogonal ‘‘click’’ chemistries in the synthesis of functional soft materials. Chem Rev 109:5620–5686
28. Kolb HC, Finn MG, Sharpless KB (2001) Click chemistry: diverse chemical function from a few good reactions. Angew Chem Int Ed 40:2004–2021
29. Mansfeld U, Pietsch C, Hoogenboom R, Becer CR, Schubert US (2010) Clickable initiators, monomers and polymers in controlled radical polymerizations—a prospective combination in polymer science. Polym Chem 1:1560–1598
30. Rosen BM, Wilson CJ, Wilson DA, Peterca M, Imam MR, Percec V (2009) Dendron-mediated self-assembly, disself-assembly, and self-organization of complex systems. Chem Rev 109:6275–6540 31. Sumerlin BS, Vogt AP (2010) Macromolecular engineering through click chemistry and other
effi-cient transformations. Macromolecules 43:1–13
32. Dodds DR, Gross RA (2007) Chemicals from Biomass. Science 318:1250–1251
33. Mecking S (2004) Nature or petrochemistry? biologically degradable materials. Angew Chem Int Ed 43:1078–1085
34. Albertsson AC, Varma IK (2003) Recent developments in ring opening polymerization of lactones for biomedical applications. Biomacromolecules 4:1466–1486
35. Hazer B (2010) Amphiphilic Poly(3-hydroxy alkanoate)s: potential candidates for medical applica-tions. Int J Polym Sci. 2010:8. doi:10.1155/2010/423460
36. Dag A, Durmaz H, Demir E, Hizal G, Tunca U (2008) Heterograft copolymers via double click reactions using one-pot technique. J Polym Sci A Polym Chem 46:6969–6977
37. Gungor FS, Kiskan B (2014) One-pot synthesis of poly(triazole-graft-caprolactone) via ring-opening polymerization combined with click chemistry as a novel strategy for graft copolymers. React Funct Polym 75:51–55
38. Liang L, Astruc D (2011) The copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) ‘‘click’’ reaction and its applications. Coord Chem Rev 255:2933–2945
39. Wolinsky JB, Yohe ST, Colson YL, Grinstaff MW (2012) Functionalized hydrophobic poly(glycerol-co-e-caprolactone) depots for controlled drug release. Biomacromolecules 13:406–411
40. Zhao P, Yan Y, Feng X, Liu L, Wang C, Chen Y (2012) Highly efficient synthesis of polymer brushes with PEO and PCL as side chains via click chemistry. Polymer 53:1992–2000
41. Cai T, Li M, Neoh KG, Kang ET (2013) Surface-functionalizable membranes of polycaprolactone-click-hyperbranched polyglycerol copolymers from combined atom transfer radical polymerization, ring-opening polymerization and click chemistry. J Mater Chem B 1:1304–1315
42. Erdemli O¨ , Usanmaz A, Keskin D, Tezcaner A (2014) Colloids Surf B 117:487–496
43. Yang R, Meng F, Ma S, Huang F, Liu H, Zhong Z (2011) Galactose-decorated cross-linked biodegradable poly(ethylene glycol)-b-poly(e-caprolactone) Block copolymer micelles for enhanced hepatoma-targeting delivery of paclitaxel. Biomacromolecules 12:3047–3055
44. Yin G, Chen G, Zhou Z, Li Q (2015) Modification of PEG-b-PCL block copolymer with high melting temperature by the enhancement of POSS crystal and ordered phase structure. RSC Adv 5:33356–33363
45. Zhou S, Deng X, Yang H (2003) Biodegradable poly(e-caprolactone)-poly(ethylene glycol) block copolymers: characterization and their use as drug carriers for a controlled delivery system. Bio-materials 24:3563–3570
46. S¸anal T, Oruc¸ O, O¨ ztu¨rk T, Hazer B (2015) Synthesis of pH- and thermo-responsive poly (e-caprolactone-b-4-vinyl benzyl-g-dimethyl amino ethyl methacrylate) brush type graft copolymers via RAFT polymerization. J Polym Res 22:1–12
47. Toraman T, Hazer B (2014) Synthesis and characterization of the novel thermoresponsive conjugates based on poly(3-hydroxy alkanoates). J Polym Environ 22:159–166
48. Balcı M, Allı A, Hazer B, Gu¨ven O, Cavicchi K, Cakmak M (2010) Synthesis and characterization of novel comb-type amphiphilic graft copolymers containing polypropylene and polyethylene glycol. Polym Bull 64:691–705
49. Wu B, Lenz RW, Hazer B (1999) Polymerization of methyl methacrylate and its copolymerization with e-caprolactone catalyzed by isobutylalumoxane catalyst. Macromolecules 32:6856–6859
50. Hazer B (2015) Simple synthesis of amphiphilic poly(3-hydroxy alkanoate)s with pendant hydroxyl and carboxylic groups via thiol-ene photo click reactions. Polym Degrad Stabıl 119:159–166 51. Su RJ, Yang HW, Leu YL, Hua MY, Lee RS (2012) Synthesis and characterization of amphiphilic
functional polyesters by ring-opening polymerization and click reaction. React Funct Polym 72:36–44
52. Parrish B, Breitenkamp RB, Emrick TJ (2005) PEG- and peptide-grafted aliphatic polyesters by click chemistry. J Am Chem Soc 127:7404–7410
53. Zhang J, Song S, Zhang L, Wang L, Wu H, Pan D, Fan C (2006) Sequence-specific detection of femtomolar DNA via a chronocoulometric DNA sensor (CDS): effects of nanoparticle-mediated amplification and nanoscale control of DNA assembly at electrodes. J Am Chem Soc 128:8575–8580 54. Lin WJ, Flanagan DR, Linhardt RJ (1990) A novel fabrication of poly(e-caprolactone) microspheres
from blends of poly(e-caprolactone) and poly(ethylene glycol)s. Polymer 40:1731–1735
55. Arkin AH, Hazer B (2002) Chemical modification of chlorinated microbial polyesters. Biomacro-molecules 3:1327–1335
56. Arkin AH, Hazer B, Borcakli M (2000) Chlorination of poly(3-hydroxy alkanoates) containing unsaturated side chains. Macromolecules 33:3219–3223
57. Moody C, Wheelhouse R (2014) The medicinal chemistry of imidazotetrazine prodrugs. Pharma-ceuticals 7:797–838
58. Koz B, Kiskan B, Yagci Y (2008) Synthesis and characterization of polyacetylene with side-chain thiophene functionality. Int J Mol Sci 9:383–393
59. Lu C, Zhong W (2010) Synthesis of propargyl-terminated heterobifunctional poly(ethylene glycol). Polymers 2:407–417
60. Xu LQ, Jiang H, Neoh KG, Kang ET, Fu GD (2012) Poly(dopamine acrylamide)-co-poly(propargyl acrylamide)-modified titanium surfaces for ‘click’ functionalization. Polymer Chemistry 3:920–927 61. Li H, Zheng Q, Han C (2010) Click synthesis of podand triazole-linked gold nanoparticles as highly
selective and sensitive colorimetric probes for lead(ii) ions. Analyst 135:1360–1364
62. Zhai S, Ma Y, Chen Y, Li D, Cao J, Liu Y, Cai M, Xie X, Chen Y, Luo X (2014) Synthesis of an amphiphilic block copolymer containing zwitterionic sulfobetaine as a novel pH-sensitive drug carrier. Polym Chem 5:1285–1297
63. Reddy KR, Raghu AV, Jeong HM (2009) Synthesis and characterization of pyridine-based poly-urethanes. Des Monomers Polym 12:109–118
64. Reddy KR, Raghu AV, Jeong HM (2008) Synthesis and characterization of novel polyurethanes based on 4,40-{1,4-phenylenebis [methylylidenenitrilo]}diphenol. Polym Bull 60:609–616
65. Bock N, Woodruff MA, Hutmacher DW, Dargaville TR (2011) Electrospraying, a reproducible method for production of polymeric microspheres for biomedical applications. Polymers 3:131–149 66. Yuan J, Shang PS, Wu SH (2001) Effects of polyethylene glycol on morphology, thermomechanical properties and water vapor permeability of cellulose acetate free films. Pharm Technol 25:62–74 67. Bahrami AGKSH, Kochaksaraie AS (2012) Morphological, mechanical and biological properties of
